#61 December 2018 Update on My T1D Management

This is a monthly update on my glycemic management of type 1 diabetes (T1DM) using Humalog and Lantus insulin injections with resistance exercise and a ketogenic whole-food diet as described in my book, The Ketogenic Diet for Type 1 Diabetes also available on Amazon in print. My other book, Conquer Type 2 Diabetes with a Ketogenic Diet, is also available on Amazon in print. I would appreciate anyone who has read and benefited from either of these books to leave a review on Amazon. The number and ratings of the reviews are used by Amazon to order the search results when people are looking for books on diabetes.

I have made several changes over the past five months in my attempt to further improve the glycemic control of my T1DM. These are the changes I made:

  1. Two meals per day: I continued eating breakfast at 7 AM and lunch at 3 PM. I like eating breakfast and given that my meal-time insulin requirements have always been greatest at breakfast, it makes me think that the breakfast Humalog dose is likely also contributing to compensating for the dawn phenomenon. Thus, eating later or skipping breakfast would likely result in morning hyperglycemia or require a larger basal insulin dose. Making my last meal at 3 PM immediately after weight training might help maintain my muscle mass according to some (not all) studies. But other reason to eat at that time is to allow for a 16-hour fasting period daily which might possibly have some metabolic benefits long-term. This also will probably never be formally studied, but I doubt it will hurt anything.
  2. In December, I tried taking Lantus three times daily at 7 AM, 3 PM and 11 PM (from December 1st through the 13th). The 3 PM and 11 PM doses ended up being very small (1-3 IU) and because I can’t measure it any more accurately than 0.25 IU with the insulin syringe, the % difference in dose (from say 1 IU to 1.25 IU i.e. a 25% increase) was rather large and not producing satisfactory result. So on December 14th, I changed to twice daily at 7 AM and 11 PM. So far, I am satisfied with this regimen and will continue it going forward.
  3. I will continue weighing my food on a kitchen scale. I plan to take it with me when I travel to maintain the consistency in food intake which I think is positively contributing to my glycemic control. Weighing food is no longer a bother now that I am seeing a benefit from it compared to years ago when I was using it to calculate carb intake which wasn’t helping at all. My breakfast macronutrient counts are: protein 63 grams, fat 60 grams, carbs 16 grams and lunch macronutrient counts are: protein 65 grams, fat 62 grams, carbs 28 grams. Daily macronutrient totals are: protein 129 grams (or 2.0 grams/kg/day), fat 125 grams, carbs 44 grams (of which 16 grams is fiber). The daily totals expressed as % of total calories are: 28% protein, 62% fat, 10% carbs.
  4. I continue taking metformin at 2,500 mg/day, 1,500 mg with breakfast and 1,000 mg with lunch. I have been tolerating this maximal dose without any side effects. I am convinced that even though I am relatively insulin sensitive, the metformin helps control post-meal BG by suppressing liver glucose production in response to meals and may be increasing muscle glucose uptake as well. These are the known mechanisms of metformin in helping to control BG in diabetes. I believe metformin is helping me because on the several occasions when I forgot to take the dose my post-meal BG was significantly elevated (by 30 – 40 mg/dl) compared to the previous days when I took the metformin. I forgot to take it for one meal in December and again noticed the unexpected rise in BG. It makes sense that metformin would help T1DM because exogenous insulin is at a relatively low concentration around the pancreatic alpha-cells compared to normal and thus glucagon secretion is chronically elevated and particularly elevated after meals since amino acids (from the protein in the meal) directly stimulate alpha-cell glucagon secretion. Glucagon in turn stimulates liver glucose production (and ketone production). Less liver glucose production by taking metformin in turn means either lower BG or since my BG is low already, means lower insulin doses. I think lower insulin doses while BG is controlled is beneficial in terms of prevention of insulin resistance (and therefore “double diabetes”), cardiovascular disease, high blood pressure, cancer, and Alzheimer’s dementia. These chronic conditions constitute the leading causes of death amongst Americans.
  5. In December, I obtained Humalog diluent from Eli Lilly (they kindly sent it to me for free) and I made a 5-fold diluted Humalog solution. This way I could accurately deliver Humalog in 0.1 IU increments or decrements which translates to 0.5 IU on my insulin syringe.

Glycemic Management Results for December 2018

My December glycemic results were improved in terms of mean blood glucose (BG) 97 mg/dl (97 mg/dl in October) and standard deviation (SD) 18 mg/dl (29 mg/dl in October). In fact, the SD of 18 mg/dl is a record low result. I just missed my desired BG goal of >70% of time spent with a BG value between 71 and 120 mg/dl.

The graphs below show the total daily insulin dose, and total Humalog and Lantus doses and my actual BG meter readings.

The graph below shows each Humalog and Lantus dose taken during the month.

The table below shows the mean BG, standard deviation (SD) of BG, coefficient of variation of BG (which is simply SD divided by mean BG expressed as a percentage).

The table below shows the % Time spent in three BG ranges and what the mean BG was during those times.

My Goals For 2019

I will continue to strive for normal BG values and my goals are to:

  1. Aim for a mean BG value of 96 mg/dl with a standard deviation of 12 mg/dl.
  2. Minimize or eliminate hypoglycemia i.e. BG < 71 mg/dl.
  3. Aim for % Time in the range of 71-120 mg/dl of > 80%.
  4. I realize these are lofty goals, but I believe if you aim low, you will likely get what you’re aiming for or conversely, if you aim high, you are more likely to hit the target you’re seeking.

How Will I Achieve These Goals

  1. I think estimating the Lantus insulin doses with the smaller 0.25 IU increments on my insulin syringes and diluting the Humalog 5-fold has helped get my resulting BG closer my target and I will continue doing this.
  2. I will continue Lantus dosing twice daily because that seems to be working.
  3. I am working on a mathematical method to predict my insulin doses based on prior responses. Haven’t found the right formula yet, but my search continues.

I hope these measures will result in additional improvements next month.

References

Efficacy and safety of metformin for patients with type 1 diabetes mellitus: a meta-analysis – here

A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults – here

Continuous Glucose Profiles in Healthy Subjects under Everyday Life Conditions and after Different Meals – here

Variation of Interstitial Glucose Measurements Assessed by Continuous Glucose Monitors in Healthy, Nondiabetic Individuals – here

Severe Hypoglycemia–Induced Lethal Cardiac Arrhythmias Are Mediated by Sympathoadrenal Activation – here

Advertisements

#60 The American Diabetes Association Has Shifted Its Stance On The Low-Fat Diet For Diabetes

I have just read the 2019 Standards of Medical Care in Diabetes (Ref. 1). This is a comprehensive document produced annually by the American Diabetes Association (ADA). I have read this document each year since 2008. To their credit, the ADA has gradually changed their dietary recommendations in the right direction, in my opinion. Yes, their changes have been exceedingly slow. And, yes, I believe they have not given any special credence to a very low carbohydrate ketogenic diet (VLCKD) for the treatment of both type 1 diabetes (T1DM) and type 2 diabetes (T2DM). To date, they haven’t mentioned that a low carbohydrate diet can place T2DM in remission. In this study (Ref. 2), 65% of participants were able to achieve a HbA1c < 6.5% with either no medications (25%) or metformin alone (35%). I believe this missing knowledge would motivate many to adopt the VLCKD as a lifestyle. Of course, I am biased in favor of the VLCKD. I am also aware that some persons with T1DM who follow a VLCKD to improve their glycemic control have received discouraging words from their health care provider (HCP) about this choice. In this study (Ref. 3), 20% of the participants felt that their HCP was not supportive of their choice to use a VLCKD.

However, I believe this latest 2019 ADA document makes it quite clear that a variety of dietary choices are acceptable as long as they result in improved glycemic control. Additionally, this is the first time that “shared decision making” has been emphasized. This represents a significant shift from the idea that the HCP knows best and dictates what the patient should do without any input from the patient. This document makes it clear that HCPs should listen to and respect the patients’ individual preferences regarding their own diabetes care including which diet they feel is best. Therefore, I think it is fair to refer this document to your HCP if they do not agree with your dietary choice.

Below I have listed quotes from the 2019 Standards of Medical Care in Diabetes rather than paraphrase or summarize their words. I have added bold lettering to some words and my own thoughts in brackets that are particularly relevant to those who follow the VLCKD for treatment of their diabetes.

  1. This document is an official ADA position, is authored by the ADA, and provides all of the ADA’s current clinical practice recommendations. 
  2. The field of diabetes care is rapidly changing as new research, technology, and treatments that can improve the health and well-being of people with diabetes continue to emerge.
  3. A new figure from the ADA-European Association for the Study of Diabetes (EASD) consensus report about the diabetes care decision cycle was added to emphasize the need for ongoing assessment and shared decision making to achieve the goals of health care and avoid clinical inertia. [Just to clarify: shared decision making means that your health care provider should be listening to your desires about your own medical care. Avoiding clinical inertia means the provider should stop just doing the same old thing and be more nimble by updating their medical knowledge. Were they to do so, they would see that the body of published research on the effectiveness of a VLCKD for improved glycemic control continues to grow which is the primary goal of both the patient and the provider.]
  4. Evidence continues to suggest that there is not an ideal percentage of calories from carbohydrate, protein, and fat for all people with diabetes. Therefore, more discussion was added about the importance of macronutrient distribution based on an individualized assessment of current eating patterns, preferences, and metabolic goals. [This is the ADA’s way of saying that their previously recommended low fat diet is clearly not the best choice for treating diabetes. This should alert physicians that the ADA no longer recommends the low fat diet as the best way to eat. Therefore, there is no reason to discourage a patient from following a VLCKD if he/she so chooses.]
  5. Additional considerations were added to the eating patterns, macronutrient distribution, and meal planning sections to better identify candidates for meal plans, specifically for low-carbohydrate eating patterns and people who are pregnant or lactating, who have or are at risk for disordered eating, who have renal disease, and who are taking sodium–glucose co- transporter 2 inhibitors. [see my notes in 14. below]
  6. There is not a one-size-fits-all eating pattern for individuals with diabetes, and meal planning should be individualized. 
  7. A recommendation was modified to encourage people with diabetes to decrease consumption of both sugar sweetened and nonnutritive-sweetened beverages and use other alternatives, with an emphasis on water intake. 
  8. The sodium consumption recommendation was modified to eliminate the further restriction that was potentially indicated for those with both diabetes and hypertension. 
  9. In addition, in response to the growing literature that associates potentially judgmental words with increased feelings of shame and guilt, providers are encouraged to consider the impact that language has on building therapeutic relationships and to choose positive, strength-based words and phrases that put people first. [This is applicable to any provider who reacts negatively about the patient’s choice to follow the VLCKD.]
  10. People with diabetes and those at risk are advised to avoid sugar-sweetened beverages (including fruit juices) in order to control glycemia and weight and reduce their risk for cardiovascular disease and fatty liver and should minimize the consumption of foods with added sugar that have the capacity to displace healthier, more nutrient-dense food choices. 
  11. Data on the ideal total dietary fat content for people with diabetes are inconclusive, so an eating plan emphasizing elements of a Mediterranean-style diet rich in monounsaturated and polyunsaturated fats may be considered to improve glucose metabolism and lower cardiovascular disease risk and can be an effective alternative to a diet low in total fat but relatively high in carbohydrates.
  12. Studies have demonstrated that a variety of eating plans, varying in macronutrient composition, can be used effectively and safely in the short term (1–2 years) to achieve weight loss in people with diabetes. This includes structured low-calorie meal plans that include meal replacements and the Mediterranean eating pattern as well as low-carbohydrate meal plans.
  13. Studies examining the ideal amount of carbohydrate intake for people with diabetes are inconclusive, although monitoring carbohydrate intake and considering the blood glucose response to dietary carbohydrate are key for improving postprandial glucose control.
  14. Providers should maintain consistent medical oversight and recognize that certain groups are not appropriate for low-carbohydrate eating plans, including women who are pregnant or lactating, children, and people who have renal disease or disordered eating behavior, and these plans should be used with caution for those taking SGLT2 inhibitors due to potential risk of ketoacidosis. [See the warnings from the Food and Drug Administration (FDA) (Ref. 4). I agree with avoiding the use of SGLT2 inhibitor drugs for those with T1DM or those with type 2 diabetes (T2DM) who require exogenous insulin especially if they follow a VLCKD. Although very few persons with T1DM would be prescribed any of these drugs since they are not FDA approved, doctors can prescribe them off-label at their discretion. In those with T2DM (not on insulin) who follow a VLCKD, caution should also be used if an SGLT2 inhibitor drug is prescribed. The rationale for this caution is that some persons with T2DM have an impaired ability to make insulin somewhat like a person with T1DM. Additionally, a VLCKD significantly reduces insulin requirements as does an SGLT2 inhibitor due to its ability to cause the kidney to excrete glucose. Therefore, combining the VLCKD with an SGLT2 inhibitor drug results in low insulin levels and increases the risk of euglycemic diabetic ketoacidosis (EDKA). During EDKA the same symptoms (abdominal pain, nausea, vomiting) develop, but the patient may not cognate that DKA is a possibility due to the normal or near-normal blood glucose level caused by the SGLT2 inhibitor. Thus, it is best to avoid SGLT2 inhibitor drugs while following a VLCKD.

As far as children with T1DM using a VLCKD, Dr. Richard Bernstein and numerous other physicians have been treating children with a low carb diet for many years. The facebook group, TYPEONEGRIT, has thousands of children using Dr. Bernstein’s approach, and a research study of this group has been published (Ref. 3).

I have read several case reports of pregnant women who developed ketoacidosis and reported following a low carb diet. However in each of these case reports, there was no careful analysis of what the women were eating prior to hospital admission, but more importantly each of them also had a superimposed illness that caused them to be unable to eat for several days. Thus, they likely had superimposed starvation ketoacidosis, not related to the prior low carb diet. I would argue that these case reports certainly do not settle the issue about using a low carb diet with pregnancy or lactation. That said, I do admit that the use of a low carb diet with pregnancy or lactation has hardly been studied. Thus, caution should be exercised in using a VLCKD during pregnancy or lactation.]

  1. There is inadequate research about dietary patterns for type 1 diabetes to support one eating plan over another at this time. 
  2. However, for special populations, including pregnant or lactating women, older adults, vegetarians, and people following very low-calorie or low-carbohydrate diets, a multivitamin may be necessary. [A well-formulated VLCKD should not require a multivitamin supplement IF one chooses whole, real (not processed) foods rich in micronutrients. I suggest using cronometer.com to calculate the micronutrient content of your VLCKD. IF after entering and adjusting your VLCKD foods in cronometer.com, you determine you cannot meet your micronutrient needs, then a multivitamin or individual supplement with the specific deficient micronutrient(s) is indicated. Although vitamin supplements in general can be useful, they are not regulated in the U.S. and likely other places around the world. That means you can never be sure that the supplement contains the vitamin/mineral you are needing, it may contain more or less than what the label states, or it may contain toxic substances not listed on the label. Also, real food likely contains other nutrients which have not necessarily been identified by nutrition science. Thus, you should really make the effort to get as many of your micronutrients (vitamins/minerals) from food rather than supplements if you can.]

I hope anyone contemplating or following a VLCKD can use the above information from the ADA to discuss their approach with their HCP without fear of criticism.

For more information about using the VLCKD to improve glycemic control for those with type 1 diabetes (T1DM) consider purchasing my book, The Ketogenic Diet for Type 1 Diabetes also available on Amazon in print. My other book, Conquer Type 2 Diabetes with a Ketogenic Diet, is also available on Amazon in print. I would appreciate anyone who has read and benefited from either of these books to leave a review on Amazon. The number and ratings of the reviews are used by Amazon to order the search results when people are looking for books on diabetes.

References

  1. American Diabetes Association, Standards of Medical Care in Diabetes, 2019 http://care.diabetesjournals.org/content/suppl/2018/12/17/42.Supplement_1.DC1
  2. Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study https://www.ncbi.nlm.nih.gov/pubmed/29417495
  3. Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet. http://pediatrics.aappublications.org/content/early/2018/05/03/peds.2017-3349.
  4. https://www.fda.gov/Drugs/DrugSafety/ucm446852.htm.

#59 November 2018 Update on My Type 1 Diabetes Management

This is a monthly update on my glycemic management of type 1 diabetes (T1DM) using Humalog and Lantus insulin injections with resistance exercise and a ketogenic whole-food diet as described in my book, The Ketogenic Diet for Type 1 Diabetes also available on Amazon in print. My other book, Conquer Type 2 Diabetes with a Ketogenic Diet, is also available on Amazon in print. I would appreciate anyone who has read and benefited from either of these books to leave a review on Amazon. The number and ratings of the reviews are used by Amazon to order the search results when people are looking for books on diabetes.

I have made several changes over the past four months in my attempt to further improve the glycemic control of my T1DM. These include:

  1. I returned to two meals per day on 8/8/2018, but now eating breakfast (7 AM) and lunch (2 PM) instead of breakfast (7 AM) and dinner (6 PM). This has allowed me to administer Humalog at 7 AM and 2 PM and Lantus at 6 PM separately rather than Humalog and Lantus together at 6 PM as I had been doing for many years. Turns out my basal Lantus dose was too high and my dinner-time Humalog dose was too low (many days I was not even taking Humalog at dinner-time). I did notice in November that although this improved my fasting BG readings, I was still have very different results with only tiny differences in the 6 PM Lantus doses. More on this shortly.
  2. I returned to weighing my food on a kitchen scale last month to more accurately balance the Humalog dose with food. The last time I did this was about 10 years ago when I was counting carbohydrates. I did it for two years with very unsatisfactory results. IMO carbohydrate counting does not work for T1DM (or for T2DM for that matter) primarily because eating a lot a carbs in those with diabetes does not work.
  3. Last month, I increased my dose of metformin to the maximum of 2,500 mg/day, 1,500 mg with breakfast and 1,000 mg with lunch. I have been tolerating this maximal dose without any side effects. I am convinced that even though I am relatively insulin sensitive, the metformin helps control post-meal BG by suppressing liver glucose production in response to meals and may be increasing muscle glucose uptake as well. These are the known mechanisms of metformin in helping to control BG in diabetes. I believe metformin is helping me because on the several occasions when I forgot to take the dose my post-meal BG was significantly elevated (by 30 – 40 mg/dl) compared to the previous days when I took the metformin. It makes sense that metformin would help T1DM because exogenous insulin is at a relatively low concentration around the pancreatic alpha-cells compared to normal and thus glucagon secretion is chronically elevated and particularly elevated after meals since amino acids (from the protein in the meal) directly stimulate alpha-cell glucagon secretion. Glucagon in turn stimulates liver glucose production (and ketone production). Less liver glucose production by taking metformin in turn means either lower BG or since my BG is low already, means lower insulin doses. I think lower insulin doses while BG is controlled is beneficial in terms of prevention of insulin resistance (and therefore “double diabetes”), cardiovascular disease, cancer, and Alzheimer’s dementia. These chronic conditions constitute the top causes of death amongst Americans.
  4. In November, I decided to try again to use smaller doses of my basal insulin, Lantus, given twice daily. But after three days, I decided to go ahead and try it three times a day which I have never tried before. This started just a few days ago (11/26/2018) so I will have to wait till next month to comment on the results. My rationale for this change was I had to change my weightlifting from the whole-body movements of olympic weightlifting (OWL) to bodybuilding type exercises on a machine due to a nagging hip discomfort that only occurs when standing up from a deep squat. However, OWL cannot be done without doing a deep squat. Interestingly I noticed that after the bodybuilding exercises, my BG was going up just as much as after OWL. These two types of exercises are completely different. The bodybuilding exercises, at least the way I have been doing them, are not at all intense. This made me suspect that the elevated BG values after both OWL and the easy bodybuilding exercises were more likely due to insufficient insulin onboard rather than release of stress hormones as I have thinking for quite a long time. This is why I decided to add a 7 AM morning Lantus dose to prevent the BG increase that occurs between 10:30 AM and 2 PM. After three days of twice daily Lantus, due to the above mentioned variation in fasting BG with small changes in the 6 PM Lantus dose, I decided to try giving the Lantus three times a day (at 7 AM, 2 PM, 10 PM) with smaller doses at 2 PM and 10 PM. I hope it works.

Glycemic Management Results for November 2018

My November glycemic results were about the same in terms of mean BG (97 mg/dl) and standard deviation (29 mg/dl) compared to October. Of course I was hoping for a reduction in standard deviation, but I did not achieve that. I did reach my desired BG goal of >70% of time spent with a BG value between 71 and 110 mg/dl and I had a reduced frequency of asymptomatic hypoglycemia. In November, my BG was calculated to be <71 mg/dl 10% of the time with a mean of 68 mg/dl during that time, 73% of the time BG was between 71 and 120 mg/dl with a mean of 89 mg/dl during that time, 17% were >120 mg/dl with a mean of 137 mg/dl during that time. No BG readings were in excess of 200 mg/dl. Preventing hypoglycemia is my top priority now so this reduction in asymptomatic hypoglycemia was encouraging.

The graphs below shows the total daily insulin doses of Humalog and Lantus and the total of both insulin doses and my actual BG readings.

The graph below shows each Humalog and Lantus dose taken during the month.

I had more fluctuations in insulin doses than I think is helpful. I think it reflects an impatience on my part to achieve normal BG as soon as possible.

My Goals For December 2018

I continue to strive for normal BG values and my goals are to:

  1. Achieve normal BG values including mean BG of 96 mg/dl with a standard deviation of 12 mg/dl or at least close to those values.
  2. Eliminate hypoglycemia i.e. BG < 71 mg/dl.
  3. In December, I am going to try my best to limit changing insulin doses to +/- 0.25-0.5 from one day to the next especially with the Lantus doses due to its longer half-life.

How Will I Achieve These Goals

  1. I think estimating insulin doses with the smaller 0.25 IU increments on my insulin syringes has helped get my resulting BG closer my target and I will continue doing that.
  2. I will try three times a day Lantus dosing to see if that helps.

I hope these measures will result in some improvements next month.

#58 October 2018 Update on My Type 1 Diabetes Management

This is a monthly update on my glycemic management of type 1 diabetes (T1DM) using Humalog and Lantus insulin injections with resistance exercise and a ketogenic whole-food diet as described in my book, The Ketogenic Diet for Type 1 Diabetes also available on Amazon in print. My other book, Conquer Type 2 Diabetes with a Ketogenic Diet, is also available on Amazon in print. I would appreciate anyone who has read and benefited from either of these books to leave a review on Amazon. The number and ratings of the reviews are used by Amazon to order the search results when people are looking for books on diabetes.

I have made several changes over the past three months to further improve the glycemic control of my T1DM. These include:

  • I returned to two meals per day on 8/8/2018, but now eating breakfast (8 AM) and late lunch (3 PM) instead of breakfast and dinner. This will allow me to administer Humalog at 8 AM and 3 PM and Lantus at 6 PM separately rather than Humalog and Lantus together at 6 PM as I had been doing for many years. Turns out my basal Lantus dose was too high and my dinner-time Humalog dose was too low (many days I was not even taking Humalog at dinner-time). I check my blood glucose (BG) five times a day at 8:00 AM (fasting i.e. before breakfast) and 11:00 AM, at noon I exercise, another BG check and lunch at 3 PM, another BG check at 6 PM and take my dose of Lantus, then check BG at 10 PM (bedtime).
  • I returned to weighing my food on a kitchen scale last month to more accurately balance the Humalog dose with food. The last time I did this was about 10 years ago when I was carbohydrate counting. I did it for two years with very unsatisfactory results. IMO carbohydrate counting does not work for T1DM (or for T2DM for that matter) primarily because eating a lot a carbs in those with diabetes does not work.
  • Last month, I increased my dose of metformin to the maximum of 2,500 mg/day, 1,500 mg with breakfast and 1,000 mg with lunch. I have been tolerating this maximal dose without any side effects. I am convinced that even though I am relatively insulin sensitive, the metformin helps control post-meal BG by suppressing liver glucose production in response to meals and may be increasing muscle glucose uptake as well. These are the known mechanisms of metformin in helping to control BG in diabetes. I believe metformin is helping me because on the several occasions when I forgot to take the dose my post-meal BG was significantly elevated (by 30 – 40 mg/dl) compared to the previous days when I took the metformin. It makes sense that metformin would help T1DM because as I reviewed in other articles on my website lowcarbdiabetesdoctor.com, exogenous insulin is at a relatively low concentration around the pancreatic alpha-cells compared to normal and thus glucagon secretion is chronically elevated and particularly elevated after meals since amino acids (from the protein in the meal) directly stimulate alpha-cell glucagon secretion. Glucagon in turn stimulates liver glucose production (and ketone production). Less liver glucose production by taking metformin in turn means either lower BG or since my BG is low already, means lower insulin doses. I think lower insulin doses while BG is controlled is beneficial in terms of prevention of insulin resistance (and therefore “double diabetes”), cardiovascular disease, cancer, and Alzheimer’s dementia. These chronic conditions constitute the top causes of death amongst Americans. See the section below about euglycemic diabetic ketoacidosis where exogenous insulin doses can be too low!
  • Last month, all of the above resulted in a reduction in total daily insulin dose from 24.5 IU/day on 8/8/2018 to 16 IU/day on 9/30/2018 as well as a reduction in body weight from 163.4 to 150.6 lb. (over a 10 week period). I am sure the reduction in body weight contributed greatly to the reduction in insulin dose. However, insulin dose is usually expressed as IU/kg body weight and when expressed this way it is a reflection of insulin sensitivity. In general the lower the dose, the more insulin sensitive (assuming BG control is the same) the person is. Expressed this way, my total daily insulin dose decreased from 0.33 IU/kg BW/day on 8/8/2018 to 0.23 IU/kg BW/day on 9/30/2018. Thus, my insulin sensitivity improved due to the weight reduction and the increase in metformin dose from 2,000 mg/day to 2,500 mg/day. This is the lowest dose of insulin I have taken since my diagnosis in 1998. Fortunately, my insulin doses remained just as low in October, on average 15.7 IU/day, and my weight declined slightly more as well to 147.3 lb. Thus, the total daily insulin dose based on body weight was 0.24 IU/kg/day which is almost one-fourth the amount I was taking prior to starting my low carb ketogenic diet.
  • The last change I made last month was to decrease the volume of vegetables I was eating. This was due to some GI disturbances after meals. I was really eating more than I needed in terms of getting my micronutrients and fiber. I am glad to report that the GI disturbances resolved completely in October.

Glycemic Management Results for October 2018

My October glycemic results were about the same in terms of mean BG (96 mg/dl) and standard deviation (30 mg/dl) compared to September. Of course, I was hoping for more improvement (a reduction in standard deviation), but I did not achieve that. I did reach my desired BG goal of about 70% of time spent with a BG value between 61 and 110 mg/dl. I had a reduced frequency of asymptomatic hypoglycemia this month compared to last month. In October, 8.4% of my BG meter readings were less than 61 mg/dl, 61.3% were between 61 and 110 mg/dl, 30.3% were between 111 and 200 mg/dl, and none were in excess of 200 mg/dl. Preventing hypoglycemia is my top priority now so this reduction is asymptomatic hypoglycemia was encouraging.

The graph below shows my actual BG readings and the total daily insulin doses of Humalog and Lantus insulin and the total of both insulin doses.

Post 58 BG Insulin Totals Graph

The graph below shows the BG readings and the Humalog doses given.

Post 58 BG Humalog Doses Graph

I had more fluctuations in insulin doses this month compared to prior months. Hopefully this will smooth out in November.

The graph below shows the % Time spent in different ranges of BG on each day of October.

Post 58 %Time in Range

The graph below shows the % Time my BG was low, in target, or high and the mean BG value in those intervals for the month of October.

Post 58 %Time BG Low, BG in Target, and BG High

The graph below shows the % of meter BG readings in three different ranges at each of the five times of day that I measure it for October.

Post 58 %BG in Range Different Times of Day

New Diet Regimen beginning October 2018

The table below shows my new diet menu.

Daily Menu

Note: the MCT oil is only to be used if my body weight falls below 66 kg or 145 lb. I haven’t needed to use it yet.

From the table above you can see I eat different breakfast menus on Sunday Tuesday Thursday Saturday (beef and egg) compared to Monday Wednesday Friday (salmon). The weight of food and macronutrients are almost identical. Pictures of the meals are shown below. I realize I am not a professional food photographer. LOL.

Breakfast Beef and Egg on STTSBreakfast Salmon on MWF

Below is lunch at 3 PM everyday.Lunch Beef and Egg Photo

The macronutrient counts are as follows:

Macronutrient Table

Note that I am consuming 2.1 grams of protein/kg body weight/day. This is more protein than many who follow a ketogenic diet might consume. I am doing this due my age and and athletic goals as I desire to hold on to as much lean muscle mass as I can as I age. Aging has been shown to create some resistance to dietary protein in promoting skeletal muscle synthesis as well as resistance to the muscle building effects of resistance exercise. Stuart M Phillips, PhD in the Department of Kinesiology, McMaster University, Hamilton, Canada, based on his meta-analysis of multiple studies recommends a dietary protein intake of 1.62 grams protein/kg/day. However the 95% confidence interval is 1.03 to 2.20 grams protein/kg/day,  so I decided to consume protein at the higher end of his recommendation since I have no contraindications to doing so. The paper is here for your reference. At this level of protein intake, my blood ketones last month on two occasions were 0.5 and 0.6 mM.

You may wonder if eating the same menu over and over each day is difficult. For me it is not. I realize not everyone would be satisfied with the monotony. However, I did pick foods that I really enjoy and secondly, for me anyway, the lack of hunger produced by a ketogenic diet eliminates all cravings for other foods. If the above diet will result in the type of BG control that I am seeking, then the lack of variety will be worth it. Additionally, I can change the menu in small ways from time to time as long as I do so infrequently.

The graph below is a pictorial version of the above macronutrient table.

Macronutrient Pie Chart without MCT Oil

The graph below shows the % of the RDA (Recommended Daily Allowances) of vitamins provided by my diet. This was to confirm that I am getting all the micronutrients in adequate amounts. So as not to make this post too long, I will skip for now the meaning of RDA. Turns out that the confidence one should place on the RDA amounts is not very high.

Percent of RDA for Vitamins

The graph below shows the % of the RDA (Recommended Daily Allowances) of minerals provided by my diet.

Percent of RDA for Minerals

I would like to give credit to cronometer.com as an easy to use application to enter foods and determine both the macronutrient and micronutrient components of a menu.

Side Bar Regarding Euglycemic Diabetic Ketoacidosis

I have written on this blog in a prior post about nutritional ketosis as apposed to diabetic ketoacidosis (DKA). I think nutritional ketosis is a desirable state in general, but that the ketone levels do not need to be particularly elevated and in fact probably should not be particularly elevated, e.g. > 4 mM. I recently heard a talk by Jake Kushner, MD (a pediatric endocrinologist) at the Low Carb Houston conference where he said that persons with T1DM using a ketogenic diet to help manage their BG should be aware that nutritional ketosis may in rare cases increase the likelihood of euglycemic diabetic ketoacidosis (EDKA). DKA and EKDA are both pathological and potentially life-threatening states where the liver is overproducing ketones due to a high glucagon to insulin ratio in the blood, but in contrast to DKA, in EDKA the BG is not particularly elevated (generally less than 200 mg/dl). The fact that the BG is not particularly elevated makes the person with T1DM not be on the lookout for DKA. This phenomenon of EDKA has become more prominent recently due to some persons with T1DM being prescribed an SGLT2 inhibitor drug (which include the following: canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance), empagliflozin/linagliptin (Glyxambi), empagliflozin/metformin (Synjardy), dapagliflozin/metformin (Xigduo XR)) off label to improve BG control and subsequently developed EDKA. SGLT2 inhibitors are FDA approved for T2DM and more commonly used for T2DM. The number of cases of EDKA has also increased in those with T2DM. Thus, this problem is not limited to just T1DM.

Dr. Kushner explained that nutritional ketosis has some physiological similarities to the effect of SGLT2 inhibitors. One is that SGLT2 inhibitors lead to chronically elevated glucagon levels and an elevated glucagon to insulin ratio. This elevated glucagon to insulin ratio occurs in those with T1DM (even not taking an SGLT2 inhibitor) because exogenous insulin does not adequately suppress alpha-cell glucagon production and I believe that nutritional ketosis and the resulting lower exogenous insulin doses probably magnifies this effect (although I don’t think it has been actually measured). So first, in my opinion, SGLT2 inhibitors should not be used in T1DM especially if a low carb ketogenic diet is being consumed. The second condition that can lead to an elevated glucagon to insulin ratio and the potential risk for EDKA in persons with T1DM is restriction of food intake either voluntarily (intentional fasting) or involuntarily due to an illness like gastroenteritis. The reduction in food intake requires a further (beyond what the low carb diet requires) reduction in exogenous insulin doses to avoid hypoglycemia. However, because as mentioned earlier exogenous insulin at very low doses does not adequately suppress alpha-cell glucagon production, the liver receives a signal (a high glucagon to insulin ratio) to overproduce ketones. This would not occur normally in a non-diabetic person who intentionally fasts or does not eat due to illness. So the take home message is that very low (or large reductions in) exogenous insulin doses in persons with T1DM should be a waving red flag. The blood ketone levels should be monitored along with BG and exogenous insulin doses need to be increased to keep blood ketones below, say 4 mM, even if that requires eating a significant amount of dietary carbohydrates. Obviously, illnesses can and do occur and cannot necessarily be avoided. However, voluntary fasting or significant reductions in caloric intake for the purpose of body fat loss, or other potential benefits (e.g. autophagy) can be moderated or avoided in those with T1DM. The benefits of fasting for autophagy and improvements in lifespan or health-span has only been studied in microorganisms and small animals, not in humans. Thus, implementing fasting for these purposes given the potential risks in those with T1DM is unwarranted in my opinion. As far as body fat loss is concerned, achieving a normal amount of body fat is important, but it must be achieved gradually with a modest caloric deficit (e.g. 100 – 200 kcal/day) to be safe in those with T1DM.

My Goals For November 2018 and Beyond

I am going to raise the bar further in terms of my glycemic management. I am not, by any means, sure that I will be able to achieve these lofty goals, but without goals, there is no direction to move toward. These are my goals:

  • Achieve near-normal BG values including mean BG of 96 mg/dl with a standard deviation as close to 12 mg/dl as possible.
  • Adjust my target BG range up from 61 – 110 mg/dl to 71 – 120 mg/dl and spend 80% of the day in this new higher range, 71 – 120 mg/dl. Honestly, with the elevation in BG that results from olympic weightlifting, this will be difficult to achieve. I do not feel the temporary elevation in BG that results from exercise is harmful. The elevation in BG is a normal response to exercise. The part that is not normal is that without exogenous insulin, the BG would remain elevated. This is why I eat lunch and take insulin right after I finish exercising. The main purpose of increasing the target BG range is to encourage me to avoid hypoglycemia. However, this elevation in BG after olympic weightlifting increases both the mean BG and the standard deviation. Thus, normalizing both of these parameters may not be compatible with olympic weightlifting.
  • Eliminate hypoglycemia or make it a rare event. I my case, my odds of developing long-term diabetic complications due to hyperglycemia are quite small, but I think my risk of having adverse effects of hypoglycemia are significantly higher. I want to eliminate that risk. This is my highest priority.

How Will I Achieve These Goals

In addition to the changes made in the past two months enumerated above, I am going make smaller adjustments in insulin doses by using 0.25 IU increments or decrements on my insulin syringes. This is because my total insulin doses are smaller than in the past and thus I need to have finer adjustments to the doses so the % change remains small. I have become aware that this applies to my basal insulin, Lantus, dose as well. I have noticed that changes in the Lantus dose have significant BG implications the following morning. I had been operating under the assumption that because it was “long-acting” it would take larger adjustments and require several days to have an effect. This is not the case. So any changes in my Lantus dose will be smaller than I have used in the past.

I hope next month I will have some improvements to report.

 

 

#57 September 2018 Update on My T1D Management

This is a monthly update on my glycemic management of type 1 diabetes (T1DM) using Humalog and Lantus insulin injections with resistance exercise and a ketogenic whole-food diet as described in my book, The Ketogenic Diet for Type 1 Diabetes also available on Amazon in print. My other book, Conquer Type 2 Diabetes with a Ketogenic Diet, is also available on Amazon in print. I would appreciate anyone who has read and benefited from either of these books to leave a review on Amazon. The number and ratings of the reviews are used by Amazon to order the search results when people are looking for books on diabetes.

I have made several changes over the past two months to further improve the glycemic control of my T1DM. These include:

  • I returned to two meals per day on 8/8/2018, but now eating breakfast (7:30-8 AM) and late lunch (3 PM) instead of breakfast and dinner. This will result in a 16 hr daily fast. It has also allowed me to administer Humalog and Lantus separately rather than together at dinner time. Turns out my basal Lantus dose was too high and my dinner-time Humalog dose was too low (many days I was not even taking Humalog at dinner-time). So now I take Humalog at breakfast (7:30-8 AM) and late lunch (3 PM) and take Lantus at 6 PM. I check my blood glucose (BG) five times a day at 7:30 AM (fasting i.e. before breakfast) and 10:30 AM, at noon I exercise, another BG check and lunch at 3 PM, check BG at 6 PM and take my dose of Lantus, then check BG at 10 PM (bedtime).
  • I returned to weighing my food on a kitchen scale to more accurately balance the Humalog dose with food. The last time I did this was about 10 years ago when I was carbohydrate counting. I did it for two years with very unsatisfactory results. IMO carbohydrate counting does not work for T1DM (or for T2DM).
  • I increased my dose of metformin to the maximum of 2,500 mg/day, 1,500 mg with breakfast and 1,000 mg with lunch. I am convinced that even though I am relatively insulin sensitive, the metformin helps control post-meal BG by suppressing liver glucose production in response to meals and may be increasing muscle glucose uptake. I know this because on the occasions when I forgot to take the dose my post-meal BG was significantly elevated compared to the previous days when I took the metformin. It makes sense that metformin would help T1DM because as I reviewed in other articles on my website lowcarbdiabetesdoctor.com, exogenous insulin is at a relatively low concentration around the pancreatic alpha-cells compared to normal and thus glucagon secretion is chronically elevated and particularly elevated after meals since amino acids (from the protein in the meal) directly stimulate alpha-cell glucagon secretion. Glucagon in turn stimulates liver glucose production. Less liver glucose production in turn means either lower BG or since my BG is low already, means lower insulin doses. I think lower insulin doses while BG is controlled is a benefit.
  • All of the above resulted in a reduction in total daily insulin dose from 24.5 IU/day on 8/8/2018 to 16 IU/day on 9/30/2018 as well as a reduction in body weight from 163.4 to 150.6 lb. I am sure the reduction in body weight contributed somewhat to the reduction in insulin dose. However, insulin dose is usually expressed as IU/kg body weight and when expressed this way it is a reflection of insulin sensitivity. The lower the dose, the better the insulin sensitivity (assuming BG control is the same). Expressed this way, my total daily insulin dose decreased from 0.33 IU/kg BW/day on 8/8/2018 to 0.23 IU/kg BW/day on 9/30/2018. Thus, my insulin sensitivity improved due to either the weight reduction or the small increase in metformin dose from 2,000 mg/day to 2,500 mg/day, or both combined. Either way, this is the lowest dose of insulin I have taken since my diagnosis in 1998.
  • The last change I made was to decrease the volume of vegetables I was eating. This was due to some GI disturbances after meals. I was really eating more than I needed, so hopefully the reduction will correct the GI problem. I will discuss this in more detail next month once I’m sure the GI problem has resolved (it is an intermittent problem so it will take some time to sort out). I will review my new diet menu and include the macronutrients and micronutrients next month. Since non-starchy vegetables are mainly composed of carbohydrates some of which are fiber as well as important vitamins and minerals, reducing them has resulted in a reduction in total carbohydrates which could additionally have contributed to the reduction in insulin requirements.

Glycemic Management Results for September 2018

My September glycemic results were somewhat improved compared to previous time periods. I reached my desired BG goal of >70% time spent with a BG value between 61 and 110 mg/dl. I had about the same frequency of asymptomatic hypoglycemia this month compared to last month. Preventing hypoglycemia is my top priority now. I think I can figure out a way to make it a rare event.

Below are my mean BG values, mean insulin doses, and BG frequency distribution for September 2018 compared to previous time periods. The predicted HbA1c uses the formula: AUC mean BG plus 88.55 divided 33.298. This formula is the least squares fit using my own personal mean BG versus measured HbA1c over many years. My particular HbA1c values are higher than many other individuals with the same mean BG. This is referred to as being a “high glycator.”

Post 57 Means Table

Below are my BG readings along with the Humalog (rapid-acting insulin) doses in September 2018. I adjust the breakfast (blue circles) and post-workout lunch (black circles), doses based on the pre-meal BG reading and take extra correction Humalog doses (red circles) for high BG readings as needed.

Post 57 BG Humalog Doses.png

The table below shows the BG variability results for current and previous time periods. The percentiles (10th, 25th, 75th, 90th) on the right show the spread of the BG readings about the median. The interquartile range, the difference between the 75th and 25th percentiles, is a measure of BG variability. In the middle of the table are the %Time in three BG ranges: %Time BG < 61 mg/dl (hypo) and the mean BG during that time, then %Time BG 61-110 mg/dl (target) and the mean BG during that time, and %Time BG > 110 mg/dl (hyper) and the mean BG during that time. Both the %Time with hypoglycemia and hyperglycemia are probably overestimates because they do not account for the corrections with glucose tablets for hypoglycemia or rapid-acting insulin (Humalog) for hyperglycemia. Measuring my BG more frequently than 5 times per day or using an accurate CGM would result in a more accurate estimate.

Post 57 Variability Table

The daily insulin dose totals started at 19 IU and ended the month at 16 IU with a bump up in the middle of the month. As mentioned above, 16 IU is the lowest dose since my diagnosis so I hope that continues and wasn’t just a fluke.

Post 57 BG Insulin Dose Totals

The daily insulin dose totals for 2018 are shown in the graph below. You can see a steady reduction in insulin doses since the peak at the beginning of January 2018. I outlined above the measures I have taken this year to reduce my insulin requirements. Included in that list is regular exercise which I continue daily.

Post 57 2018 Insulin Dose Totals

I will skip the section on my current diet because it is still being adjusted until my GI issue is resolved. I am experimenting with which and how much non-starchy vegetables I can tolerate and still come close to 100% of the RDA values for each nutrient.

That’s all folks…..

References

Efficacy and safety of metformin for patients with type 1 diabetes mellitus: a meta-analysis – here

A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults – here

Continuous Glucose Profiles in Healthy Subjects under Everyday Life Conditions and after Different Meals – here

Variation of Interstitial Glucose Measurements Assessed by Continuous Glucose Monitors in Healthy, Nondiabetic Individuals – here

Severe Hypoglycemia–Induced Lethal Cardiac Arrhythmias Are Mediated by Sympathoadrenal Activation – here

#56 August 2018 Update on My T1D Management

This is a monthly update on my glycemic management of type 1 diabetes (T1DM) using Humalog and Lantus insulin injections with resistance exercise and a ketogenic whole-food diet as described in my book, The Ketogenic Diet for Type 1 Diabetes also available on Amazon in print. My other book, Conquer Type 2 Diabetes with a Ketogenic Diet, is also available on Amazon in print. I would appreciate anyone who has read and benefited from either of these books to leave a review on Amazon. The number and ratings of the reviews are used by Amazon to order the search results when people are looking for books on diabetes.

I have posted the blog post on my new website lowcarbdiabetesdoctor.com and the new blog post is here.

Post-56-Variability-Table

#55 July 2018 Update on My T1DM Management

Dear Blog Followers, I am happy to reveal my new website, lowcarbdiabetesdoctor.com that also will house my blog posts. The purpose of the new website is to make it easier to find more information about using lifestyle changes including the low carb ketogenic diet and exercise for not only type 1 diabetes (T1DM), but also for many related metabolic conditions including insulin resistance, prediabetes, type 2 diabetes, dyslipidemia, cardiovascular disease, and many more.

Please sign up for the newsletter on the new website which is the mechanism by which I can announce new blog posts and new articles that I will be writing. I just started the new website about 6 weeks ago, so many of the articles I have planned are not written, but they will be forthcoming. Thanks for your interest and support. You can find my latest blog post here.

#54 June 2018 Update on My T1DM Management

Dear Blog Followers, I am happy to reveal my new website that also will house my blog posts. The purpose of the new website is to make it easier to find more information about using lifestyle changes including the low carb ketogenic diet and exercise for not only type 1 diabetes (T1DM), but also for many related metabolic conditions including insulin resistance, prediabetes, type 2 diabetes, dyslipidemia, cardiovascular disease, and many more.

You can find my latest blog post here. Please sign up for the newsletter which is the mechanism by which I can announce new blog posts and new articles that I will be writing. I just started the new website two weeks ago, so many of the articles I have planned are not written, but they will be forthcoming. Thanks for your interest and support.

#53 May 2018 Update on My T1D Management

This is a monthly update on my glycemic management of type 1 diabetes (T1DM) using Humalog and Lantus insulin injections with resistance exercise and a ketogenic whole-food diet as described in my book, The Ketogenic Diet for Type 1 Diabetes also available on Amazon in print. My other book, Conquer Type 2 Diabetes with a Ketogenic Diet, is also available on Amazon in print. I would appreciate anyone who has read and benefited from either of these books to leave a review on Amazon. The number and ratings of the reviews are used by Amazon to order the search results when people are looking for books on diabetes.

Although glycemic management in T1DM will always be challenging, the low carb ketogenic whole-food diet definitely improves it by reducing average blood glucose (BG) and variations in BG as well as insulin requirements. Many of the diseases (cardiovascular disease, cancer, Alzheimer’s, and many more) associated with T2DM and “double diabetes” as part of T1DM are due to insulin resistance and hyperinsulinemia. The low carbohydrate ketogenic whole-food diet directly improves both insulin resistance and endogenous hyperinsulinemia in T2DM and exogenous insulin requirements in T1DM (i.e. reduced insulin doses).

May 2018 was the third full month of taking metformin at a dose of 2000 mg/day (started that dose on Feb. 15, 2018). I am tolerating it without any side effects. As you may know metformin is the first-line medication for T2DM, but can also be useful for those with T1DM. Metformin acts on the liver to reduce glucose production by suppressing both gluconeogenesis and glycogenolysis. I think this may be useful for those with T1DM on a low carbohydrate diet because the reduction in dietary carbohydrate reduces insulin requirements which in turn stimulates glucagon secretion by the alpha cells in the pancreas which in turn increases glucose production by the liver. This increase in glucose production occurs primarily from increased gluconeogenesis, but also some increase in glycogenolysis is suggested in some studies. In addition, metformin stimulates muscle uptake of glucose independent of insulin. Hopefully over time, I will be able to determine if taking metformin either reduces my blood glucose (BG), insulin requirements, or both. I am estimating that I will need to take it for 6 months to be able to make a before and after comparison as far as the insulin dose comparison is concerned. There is a possibility that metformin could increase the incidence and severity of hypoglycemia while on a ketogenic diet, so caution should be exercised. A possible mechanism for this is the fact that gluconeogenesis plays a more important role in maintaining BG in those on a ketogenic diet than on a balanced macronutrient diet. If metformin reduces gluconeogenesis, then hypoglycemia could result if insulin doses are not appropriately reduced. 

Glycemic Management Results for May 2018

My May glycemic results were somewhat improved compared to previous time periods although I did not reach my desired BG goal of >70% time spent with a BG value between 61 and 110 mg/dl. I had less hypoglycemia this month, but one was symptomatic. This time I developed skin numbness while walking. I have had this particular symptom before and took two glucose tablets immediately and the symptom resolved in about 30 mins. This occurred when I was out of town. Travel usually adversely affects my glycemic control so I stay on high alert. Below are my mean BG values, mean insulin doses, and BG frequency distribution for May 2018 compared to previous time periods. The predicted HbA1c uses the formula: AUC mean BG plus 88.55 divided 33.298. This formula is the least squares fit using my own personal mean BG versus measured HbA1c over many years. My particular HbA1c values are higher than many other individuals with the same mean BG. This is referred to as being a “high glycator.”

Post 53 Mean BG Table

As discussed previously, exogenous insulin cannot mimic normal insulin secretion, so persons with T1DM should not expect to have truly normal BG values at all times. They just need to be low enough to prevent long-term complications and not so low as to cause unpleasant hypoglycemic symptoms or less common, yet more dangerous, consequences including brain damage, seizure, injury, coma, or death. I have set my target BG range at 61-110 mg/dl because values in this range are not likely to lead to harm or complications of T1DM. Your target BG range should be determined with your physician because one size does not fit all. Normal BG is 96 ± 12 mg/dl (mean ± standard deviation (SD)) and coefficient of variation is 13% which is the weighted mean from two studies of continuous glucose monitoring in healthy subjects (see references at the end). The standard deviation and coefficient of variation are measures of BG variability which I believe are important in T1DM. Clinical outcomes in T1DM (i.e. microvascular and macrovascular complications) have only been documented to correlate with measures of mean BG, particularly HbA1c. This does not mean that BG variability is not important, but it just has not been documented to correlate with outcomes and complications of T1DM. Achieving a normal standard deviation or coefficient of variation in T1DM would be difficult, if not impossible, with current exogenous insulin therapy (injected or pumped). Monitoring the standard deviation and/or coefficient of variation and finding ways to improve them to the best of one’s ability is desirable in my opinion. Following a low carbohydrate ketogenic diet is one such method of reducing BG variability, mean BG, insulin doses, and hypoglycemia. A ketogenic diet may also provide an alternate or additional brain fuel in the form of ketones to protect the brain when BG does go low. The alternative energy that ketones supply to the brain may prevent or blunt the sympathoadrenal response to hypoglycemia which in turn reduces or eliminates the symptoms of and harm from hypoglycemia. This hypothesis needs to be tested before it can be stated as fact. Having mild asymptomatic hypoglycemia adapts the brain to lower BG and reduces the symptoms of mild hypoglycemia and potentially the harm from hypoglycemia due to lack of activation of the sympathetic nervous system by reducing sympathoadrenal-induced fatal cardiac arrhythmia (see references at the end).

Below are my BG readings along with the Humalog (rapid-acting insulin) doses in May 2018. I adjust the breakfast (blue circles), post-workout lunch (black circles), and dinner (purple circles) meal-time doses based on the pre-meal BG reading and take extra correction Humalog doses (red circles) for high BG readings as needed. I continued my previous pattern of high BG readings after weightlifting which I correct with my lunch-time Humalog dose.

Post 53 Humalog Doses and BG graph

The table below shows the BG variability results for current and previous time periods. The percentiles (10th, 25th, 75th, 90th) on the right show the spread of the BG readings about the median. The interquartile range, the difference between the 75th and 25th percentiles, is a measure of BG variability. In the middle of the table are the %Time in three BG ranges: %Time BG < 61 mg/dl (hypo) and the mean BG during that time, then %Time BG 61-110 mg/dl (target) and the mean BG during that time, and %Time BG > 110 mg/dl (hyper) and the mean BG during that time. Both the %Time with hypoglycemia and hyperglycemia are probably overestimates because they do not account for the corrections with glucose tablets for hypoglycemia or rapid-acting insulin (Humalog) for hyperglycemia. Measuring my BG more frequently than 5 times per day or using an accurate CGM would result in a more accurate estimate.

Post 53 Variability BG Table

The daily insulin dose totals ranged from 23 to 33.5 IU/day in response to the BG readings and are shown in the graphs below for May 2018. You can see a fairly steady total daily insulin dose during the month with a 2 to 4 day intervals of increased insulin doses to address hyperglycemia. The basal insulin dose was more stable and ranged from 20 to 22 IU/day.

Post 53 Insulin Dose Totals and BG graph

The daily insulin dose totals for 2018 are shown in the graph below. You can see a steady reduction in insulin doses since the peak at the beginning of January 2018. The measures I have taken to reduce this variation in insulin dose have included keeping meals and exercise as constant as possible and adding metformin to suppress liver glucose production. Specifically, I try to keep all meals constant in terms of portion size, macronutrient composition and timing of my meals. In addition, I try to keep exercise constant including frequency (daily), type (the type of weightlifting exercises, mainly compound movements), intensity (gradually increasing weight over time as tolerated), and volume (repetitions). That said, keeping exercise intensity constant from day to day is quite difficult.

Post 53 Insulin Dose Totals 2018

The graph below illustrates the distribution of BG values in the ranges indicated at various times of day. This could be useful to point out problems (hypoglycemia and/or hyperglycemia) at different times of day.

Post 53 Percent BG values in Ranges at Times of Day

The graph below illustrates the percentage of time spent in three BG ranges for each day of the month of May. The numeric percentage is shown on top of the green bars for the % of time BG was between 61 and 110 mg/dl.

Post 53 Daily Time in Range

In June, I will continue olympic weightlifting every day with 3 exercises per day. I will also continue metformin 2000 mg daily (1000 mg every twelve hours).

My Thoughts About Management of Type 1 Diabetes With A Ketogenic Diet

My goal of glycemic management in T1DM with a ketogenic diet is to keep BG as close to normal i.e. 96 ± 12 mg/dl (mean ± SD) as is safely possible (i.e. avoiding hypoglycemia) to avoid diabetic complications, a reduction in lifespan, and unpleasant symptoms of as well as injury and death from hypoglycemia. For me, a well-formulated whole-food nutrient-dense ketogenic diet, daily exercise, frequent BG measurements, and lower insulin-analog doses (Humalog/Lantus) have improved my glycemic control, hypoglycemic reactions, and quality of life. My basic diet philosophy is to avoid processed foods especially those containing refined carbohydrates, sugar, and vegetable (seed) oils while enjoying whole foods (with just one ingredient) as close to their original state as possible. I think just knowing the guidelines in this paragraph would be a good start for those wanting to improve their diet. To treat diabetes, the additional step is to eliminate all foods with significant amounts of carbohydrate to keep the net carbohydrate total < 50 grams/day. Some may do better with < 30 grams/day, while others who exercise a lot may do well with < 100 grams/day.

My current version of ketogenic diet is as follows: 

What I Cook & Eat

  • Beef, grass-fed, including meat (85% lean), heart, liver, and kidney (liverwurst)
  • Fish, mainly wild Alaskan salmon
  • Lamb, Chicken & Turkey occasionally
  • Chicken Eggs (one per day)
  • Non-starchy vegetables (about 5% carbohydrate content by weight) including Cabbage (Red, Green, Napa), Kale, Collard Greens, Home-made Sauerkraut from Red Cabbage, Bok-Choy, Broccoli, Cauliflower, and some others.
  • Fruit – Avocado, Olives, lemon juice on fish
  • Nuts & Seeds – Pepitas, Macadamia, Brazil, Pecan, Walnut, Pistachio, Cashew.
  • Note: I developed an intolerance to milk prior to my diagnosis of T1D. I did try heavy whipping cream after starting my KLCHF diet, but am also intolerant of it. I do tolerate butter, but wanted to decrease my fat intake, so eliminated all dairy including cheese and yogurt.

What I Drink

Water (filtered by reverse osmosis), Unsweetened Tea & Coffee

What I Don’t Eat

  • Grains – Wheat, Corn, Rice, Oats (there are many more) or anything made from them, which is too numerous to list here. Gluten is a protein present in a number of grains (all varieties of wheat including spelt, kamut, and triticale as well as barley and rye.) which can cause a number of medical problems for a significant portion of the population with gluten sensitivity or celiac disease. In my case, I avoid them due to their carbohydrate content.
  • Starchy and most root vegetables – potatoes, sweet potatoes, yams
  • Legumes – peas, beans, lentils, peanuts, soybeans
  • High sugar fruits – includes most fruits except berries, see above.
  • Sugar and the fifty other names used to disguise sugar.
  • Vegetable Oils – Canola, Corn, Soybean, Peanut, Sunflower, Safflower, Cottonseed, Grape seed, Margarine & Butter substitutes, Shortening.
  • All Processed Foods.
  • I avoid restaurants except when traveling, and then order fish or steak with plain steamed non-starchy vegetables (no gravy or sauces that typically contain sugar, cornstarch, or flour) or salad.
  • Refined, but healthy, fats – Although there is nothing bad about including butter, coconut & olive oil in a ketogenic diet, I have eliminated refined fats from my diet to improve my body composition.

What I Don’t Drink

  • Colas (both sweetened and artificially sweetened).
  • Fruit Juice except small amounts of lemon juice occasionally.
  • Alcohol (can cause hyperglycemia or hypoglycemia in persons with diabetes).
  • No artificial sweeteners: I don’t enjoy them.

My exercise regimen often results in post-exercise hyperglycemia which is a normal response to intense exercise. However due to having T1DM, my body is unable to correct this without taking exogenous rapid-acting insulin (Humalog). The exercise I choose negatively affects my glycemic control to some extent. I’m sure I could find an exercise that has less impact on glycemia, but I enjoy weightlifting and feel it has health-span and life-span extending benefits which may compensate for the temporary increase in BG during/after exercise. Hopefully my BG values and variability as well as the relatively lower insulin doses that result from my ketogenic diet, exercise, and hopefully metformin (yet to be determined) are close enough to optimal to avoid any reduction in lifespan, diabetic complications, and harm from hypoglycemia, but only time will tell.

References

Efficacy and safety of metformin for patients with type 1 diabetes mellitus: a meta-analysis – here

A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults – here

Continuous Glucose Profiles in Healthy Subjects under Everyday Life Conditions and after Different Meals – here

Variation of Interstitial Glucose Measurements Assessed by Continuous Glucose Monitors in Healthy, Nondiabetic Individuals – here

Severe Hypoglycemia–Induced Lethal Cardiac Arrhythmias Are Mediated by Sympathoadrenal Activation – here

#52 Hypoglycemia in Diabetes: Mechanisms, Avoidance, and Treatment

Hypoglycemia is a very important topic for persons with diabetes to read and understand. This topic was covered in my book, The Ketogenic Diet for Type 1 Diabetes also available on Amazon in print. My other book, Conquer Type 2 Diabetes with a Ketogenic Diet, covers this topic for those with T2DM which is also available on Amazon in print. I would appreciate anyone who has read and benefited from either of these books to leave a review on Amazon. The number and ratings of the reviews are used by Amazon to order the search results when people are looking for books on diabetes.

Today, 5/15/2018, is my 58th birthday. You might be wondering how I am going celebrate this day. Cake? Champagne? No, this year I’m celebrating my CAC score results. What is a CAC score? It is short for coronary artery calcium score. I first learned about the usefulness of this noninvasive cardiac screening test from Dr. Jeffry Gerber, MD here soon after starting the ketogenic diet in 2012 when we were attending a medical meeting. Because I have had type 1 diabetes mellitus (T1DM) for 20 years and have been on the ketogenic diet for six years, I thought it was about time to take a look. As you can see below my score was zero!!!

Post 52 18-04-24 Keith Runyan CACS Report

That is good news, because cardiovascular disease is the most common cause of death for those with T1DM. One less thing to think about now. I honestly believe my whole food nutrient dense ketogenic diet is cardioprotective because it is improves my glycemic control, does not cause inflammation (my hsCRP was 0.8), and results in low levels of small-dense LDL, oxidized LDL, and glycated LDL which are thought to lead to coronary artery disease. Although, I have not measured these particles, the fact that my fasting triglycerides are 65 mg/dl, HDL-C is 90 mg/dl, VLDL-C is 12 mg/dl, and remnant cholesterol is 12 mg/dl are all indicators that these particles are low and my risk for cardiac disease is relatively low. The CAC score of zero, however, is the icing on the cake which I will be enjoying on my birthday and every day. As far as what I’m eating, that will remain the same: salmon, 85% lean hamburger, one egg, steamed cabbage with some tomato sauce (no sugar added), or similar non-starchy vegetables and 7 varieties of nuts and seeds. This stays pretty constant from day to day except I substitute liverwurst or beef for salmon at breakfast time and add in home-made fermented sauerkraut 3 days a week.

Now For Today’s Topic, Hypoglycemia.

Remember the following is not medical advice, but is information that you can use with your own physician’s advice. Hypoglycemia represents a significant potential problem for those with diabetes who require insulin or any of the insulin-secreting medications (reviewed below). However for those with T1DM, hypoglycemia is a more significant problem due to the complete loss of the pancreatic β-cells and their interaction with their neighboring alpha-cells as will be explained below.

What Is Hypoglycemia? Why Does It Occur?

Hypoglycemia can be defined as an abnormally low plasma glucose concentration that exposes the individual to potential harm. Since persons with diabetes use blood glucose meters that are calibrated to give results in line with plasma glucose concentrations, I will use the term blood glucose (BG) to be equivalent to plasma glucose. A single value of BG that defines hypoglycemia is actually difficult to justify. For example in persons with poorly controlled diabetes, a BG value of 120 mg/dl (6.7 mmol/l) may result in typical symptoms of hypoglycemia whereas in persons with excellent glycemic control and especially those following a ketogenic diet may not experience symptoms until the BG falls below 50 mg/dl (2.8 mmol/l). More on this below, but first we should discuss why are those with T1DM and type 2 diabetes mellitus (T2DM) at risk for hypoglycemia? 

In healthy humans BG is tightly regulated by numerous hormones and organs. Without getting too deep into the details, suffice it to say that the principle hormones that regulate BG are insulin, amylin, and glucagon and the principle organs that influence BG are the liver, muscle, and fat. Briefly, the β-cells in the pancreas secrete insulin and amylin in response to current BG and amino acid levels and are modified by other hormones including glucagon. Insulin is capable of reaching a high concentration around the neighboring alpha-cells to suppress glucagon secretion which cannot occur in persons with diabetes injecting exogenous insulin. Normally, insulin, also in high concentration, reaches the liver via the portal vein to suppress liver production of glucose. Again, high levels of insulin reaching the liver are not possible by taking exogenous insulin for diabetes. Normally, the suppression of glucagon by insulin also suppresses the production of glucose in the liver. All of these mechanisms are responsible for preventing hyperglycemia both after meals and while fasting. Conversely in healthy subjects if BG falls, for example, during fasting, insulin secretion by the β-cells in inhibited and thus glucagon secretion by the alpha-cells is stimulated both of which increase glucose production primarily by the liver, but also by the kidneys. The liver and kidneys can make glucose from amino acids (from lean tissues), glycerol (from fat), acetone (a ketone made from fat), and from lactate (from muscle, red blood cells, other tissues). Thus, in healthy subjects hypoglycemia is an unusual condition. The third mechanism that corrects hypoglycemia in the unlikely event that the reduction in insulin secretion and increase in glucagon secretion are not sufficient to raise BG, is the sympathetic nervous system which secretes epinephrine (adrenaline), norepinephrine (noradrenaline), and acetylcholine while the adrenal glands secrete epinephrine. Epinephrine and norepinephrine stimulate glucose production by the liver and also result in symptoms of hypoglycemia including increased heart rate, blood pressure, and palpitations. The sympathetic nervous system also secretes acetylcholine which causes sweating and anxiety as well as stimulating glucose production. However, in those with T1DM with complete β-cell destruction the first two mechanisms (decrease in insulin and increase in glucagon) mentioned above are not functioning and recovery from hypoglycemia is dependent on either the person’s own recognition of the problem prior to symptoms via a meter or CGM reading or from the hypoglycemic symptoms caused by the activation of the sympathoadrenal axis.

Hopefully this explains why hypoglycemia almost invariably occurs in persons with T1DM and in those with T2DM who require insulin and/or medications that stimulate insulin secretion and why hypoglycemia is the greatest barrier to achieving near-normal glycemia. In addition to insulin, other medications used for diabetes can also precipitate hypoglycemia. These medications will be reviewed below.

What Should Our Target BG Be To Both Avoid The Long-term Complications Of Diabetes And Avoid Hypoglycemia Which Can Be Fatal?

Achieving a degree of glycemic control that minimizes the risk of developing the long-term complications of diabetes is obviously desirable. These diabetic complications include, but are not limited to, both microvascular complications (neuropathy, retinopathy, diabetic nephropathy) and macrovascular complications (heart disease, stroke, peripheral vascular disease) which can result in blindness, kidney failure, amputations, and cause a reduction in health-span and life-span. However, believe it or not, there is no research that reveals what level of glycemic control is necessary to avoid these complications. 

The Diabetes Control and Complications Trial (DCCT) published on September 30, 1993 in the New England Journal of Medicine (ref 1) enrolled 711 persons with T1DM to the intensive insulin arm and 730 to the conventional arm of the study. They had two groups in each arm of the study, one without evidence of diabetic complications (the primary prevention group) and the other with evidence of diabetic complications (the secondary prevention group). The study showed that intensive insulin therapy was able to lower HbA1c from 9% to 7% by increasing doses of insulin, but no changes in diet, which significantly reduced the incidence and progression of diabetic retinopathy (by 76%), neuropathy (by 60%), and nephropathy (of albuminuria by 54%). This was the first large randomized clinical trial to demonstrate this benefit of improved glycemic control. However, this came at a price. The intensive insulin group suffered approximately three times as many episodes of severe hypoglycemia. Severe hypoglycemia is defined as an episode of hypoglycemia that requires the assistance of another person to recover from whether that comes in the form of someone giving the person with T1DM glucose tablets, a glucagon injection, calling 911, or requiring hospitalization (e.g. due to a seizure). Another complication in the DCCT was that at five years, patients receiving intensive insulin therapy gained a mean of 4.6 kg body weight more than patients receiving conventional therapy. Importantly, on secondary analysis, the DCCT could not identify any level of HbA1c that would maximize benefits (i.e. reduce complications) while at the same time minimizing risks (i.e. reduce hypoglycemia). 

I have to interject at this point that these limitations of intensive insulin therapy without dietary intervention is where the low carbohydrate ketogenic diet is a potential game changer because glycemic control can be improved significantly with reduced insulin doses (not increased insulin doses as in the DCCT). More on this in my next blog post #53 or see ref 21. 

In summary, the DCCT showed that improving HbA1c from 9% to 7% with increased insulin doses significantly reduced the incidence and progression of long-term diabetic complications, but also results in a marked three-fold increase in severe hypoglycemia and a mean 4.6 kg body weight gain.

Unfortunately, we are still left with the question of how low should average BG or HbA1c be to both minimize the risk of long-term diabetic complications and hypoglycemia. I hope it is apparent that the lower the target BG even while on a low carbohydrate ketogenic diet, the more likely hypoglycemia is to occur due to the inherent variability created by using exogenous insulin. A definitive answer will require a long-term clinical trial that utilizes a low carbohydrate ketogenic diet. Until that trial is done, I think each individual will need to determine his/her own glycemic target in consultation with their physician. This glycemic target should be as close to normal as is safely achievable. Now, we need to know what “normal” is and what “safe” is. 

What BG Value Is Normal?

This study (ref 2) of 21 healthy non-diabetic subjects wearing continuous glucose monitors (CGM) found that “the mean 24-hour interstitial glucose concentration under everyday life conditions was 89.3 ± 6.2 mg/dl (mean ± SD, where SD = standard deviation), and mean interstitial glucose concentrations at daytime and during the night were 93.0 ± 7.0 and 81.8 ± 6.3 mg/dl, respectively.”  Whereas this study (ref 3) of 74 healthy non-diabetic children, adolescents, and adults had a mean interstitial glucose of 98 ± 13.7 (mean ± SD) using a blinded CGM device for 3 to 7 days. A weighted mean of these 95 healthy persons from these two studies reveals that a normal BG is 96 ± 12 mg/dl (mean ± SD) and coefficient of variation is 12.5% (or 12/96 = 12.5%). A mean BG of 96 mg/dl represents, in my opinion, the minimum target BG value to aim for since these healthy subjects would not be expected to develop diabetic complications. Aiming for an average BG less than 96 mg/dl would only increase the risk of hypoglycemia without providing any benefits. If this BG target of 96 mg/dl results in frequent or severe hypoglycemia, then the target average BG should be increased to whatever value is necessary to minimize hypoglycemia. You then might ask, “Does the increased BG variability lead to the development of diabetic complications?” As you may know, BG does not stay in a narrow range in those with diabetes and this BG variability is easily measured by calculating the standard deviation (SD) of your BG readings. Unfortunately, no studies have examined the question: Does BG variability lead to diabetic complications?  I think everyone with diabetes is striving to keep their BG variability as low as possible, but actually doing it is difficult. My SD before the ketogenic diet was 54 mg/dl and during the past six years on the ketogenic diet has ranged from 35 to 51 mg/dl over 1 year periods. You can see this is quite high compared to normal at 12 mg/dl.

What Incidence Of Hypoglycemia Is Considered “Safe”?

I do not have the answer to this question, but certainly the lower the better is the best bet. Regrettably, it only takes one severe hypoglycemic episode to die. The lesson here is to not let the zeal of perfection defeat the whole purpose of the pursuit. Personally, I have been striving to keep my BG between 61 and 110 mg/dl more than 70% of time and in addition spending less than 10% of time < 61 mg/dl. Although I am close to that goal every month, it has been difficult for me to actually achieve it. I am working to improve it. For those who do not take insulin for diabetes, it may be difficult to understand how variable the glycemic results of taking insulin can be. For me, this has been the most frustrating part of having T1DM. For example, one day I may wake up with a BG of 90 mg/dl and take 3 units of Humalog with breakfast and get a postprandial BG of 110 mg/dl. The very next day, I may wake up with a BG of 97 mg/dl and take 3 units of Humalog with breakfast and get a postprandial BG of 67 mg/dl having eaten the same breakfast, lunch, dinner, and done very similar exercise type, intensity, and duration. This has happened virtually every day for the past 20 years. Thus, for me anyway, each dose of insulin is a guess and the BG results are unpredictable.

Have You Noticed A Reduction In Symptoms Of Hypoglycemia Since Starting The Ketogenic Diet?

This was the first change that I became aware of after starting the ketogenic diet on Feb. 8, 2012. This started me down a path of investigation to try to understand it better. I personally have had BG values in the 30s mg/dl without symptoms. Please do not confuse this last statement as an indication that asymptomatic hypoglycemia is an acceptable or desirable condition. In fact, this is one of the reasons I decided to write this blog post on hypoglycemia. I am simply stating the fact that since starting my low carbohydrate ketogenic diet, and never before, I have had a significant reduction in the symptoms of hypoglycemia. However, I do not know how much of this reduction in symptoms is due to hypoglycemia unawareness and how much is due to the brain being able to use ketones as a fuel by following a ketogenic diet. 

Hypoglycemia Unawareness

Hypoglycemia unawareness simply means that a person with diabetes who has an abnormally low BG is unaware of it because they are not experiencing any sympathetic symptoms. 

Additionally, when hypoglycemia is even more severe (< 50–55 mg/dl, < 2.8–3.0 mmol/l), persons with diabetes may not recognize their own neuroglycopenic symptoms including cognitive impairments, behavioral changes, and psychomotor abnormalities, and, at even lower BG levels, seizure and coma. The exact mechanism for hypoglycemia unawareness is still unknown. However, it is known to occur as a result of antecedent episodes of hypoglycemia. The brain somehow adapts to these episodes of hypoglycemia and does not perceive subsequent episodes as an emergency and thus does not activate the sympathetic nervous system and adrenal glands which are in place to correct hypoglycemia by secreting epinephrine (adrenaline), norepinephrine (noradrenaline), and acetylcholine. This adaption is considered by experts in the field to be a double-edged sword (ref 4) because on the positive side the brain does not perceive an emergency requiring secretion of epinephrine which is thought to be the most common cause of harm from hypoglycemia, i.e. lethal cardiac arrhythmias mediated by sympathoadrenal activation (ref 5). Another study (ref 6) in rats found that 3 days of recurrent moderate hypoglycemia resulted in 62–74% less brain cell death after a subsequent episode of severe hyperinsulinemic hypoglycemia (BG 10-15 mg/dl) and were protected from most of the deficits in spatial learning and memory disturbances caused by severe hypoglycemia compared to the control rats. On the negative side of this double-edged sword, the lack of symptoms is thought to lead to more episodes of hypoglycemia any one of which could be severe enough to result in death from neuroglycopenia i.e. not enough glucose for the brain to survive. It is this negative side that needs special attention because we know that depending on the study cited, between 4 and 10% of those with T1DM actually die from hypoglycemia. The majority of these persons die in their sleep which is a time when perception of hypoglycemia is additionally reduced. In addition to antecedent hypoglycemia and sleep, exercise and alcohol ingestion also lead to hypoglycemia unawareness. Although we can’t avoid sleep, and shouldn’t avoid exercise, we can avoid drinking alcohol and work to minimize hypoglycemic episodes. Like many of the followers of this blog, I am a person with T1DM who is highly motivated to achieve BG values as close to normal as is safely possible. However if any of us die or are seriously harmed from hypoglycemia, we have just defeated our own goal of living a normal life-span without diabetic complications. Thus, minimizing or avoiding hypoglycemia is of paramount importance. In fact, this is what I mean by “as is safely possible.” If a person with diabetes is having frequent hypoglycemia, then steps need to be taken to reduce them. I will cover those steps below. Also, be aware that the hypoglycemia unawareness due to recurrent hypoglycemia is completely reversible by avoiding hypoglycemia for 3-4 weeks (ref 7). Resolving hypoglycemia unawareness is an important strategy for preventing future hypoglycemia. 

However, at this point you may be asking “given that I follow a ketogenic diet and lack symptoms of hypoglycemia at levels of BG that previously caused symptoms, what value of BG do I use to define hypoglycemia?” Certainly, low BG values should not be accepted as “OK”, even if they occur without symptoms. The 2018 American Diabetes Association (ADA) Standards of Medical Care in Diabetes (ref 8) uses < 70 mg/dl as a threshold to define “hypoglycemia alert value” (see Table 6.3 from ref 8 shown below). This hypoglycemia alert value signals the need to take a fast-acting carbohydrate (glucose tablet(s)) and to adjust the dose of glucose-lowering therapy. I use both of these recommendations on a daily basis since each and every insulin dose I take is adjusted based on my BG results in the previous several days in the context of physical activity. The difficult part of diabetes control is that these previous results can vary significantly from day to day such that each dose is in effect, a guess. Several years ago, I arbitrarily chose < 61 mg/dl (3.4 mmol/l) to define hypoglycemia for myself since I had to choose a value to calculate the frequency of and time during a 24 hour period spent with hypoglycemia to be able to report my results on this blog. However, that does not mean I feel a BG in the 60s mg/dl requires no treatment or no insulin dose adjustment.

Post 52 ADA Table 6.3 Classification of Hypoglycemia

As everyone who follows this blog knows, I am not entirely successful at keeping my BG above 60 mg/dl. However, the purpose of starting this blog was to show the actual results of a highly motivated person doing high-intensity resistance exercise and following a ketogenic diet. Despite my lack of complete success, I want everyone to know that I think hypoglycemia is serious and potentially fatal and should be avoided as much as possible.

Can Nutritional Ketosis Provide An Alternate Brain Fuel And Protect Us From Hypoglycemia?

Another topic of research that needs to be done is to measure the degree to which ketones created by the liver by following a ketogenic diet can act as a brain fuel and lead to a reduction in or lack of symptoms of hypoglycemia in those with T1DM. We know from the study done by Drenick et. al. (ref 9) that in non-diabetic obese persons who fasted for 2 months and achieved blood beta-hydroxybutyrate (BHB) levels of 8 mM when given a single dose of insulin to induce severe hypoglycemia suffered no symptoms despite BG values as low as 9 mg/dl (0.5 mmol/l). However, the applicability of this study to those with diabetes following a ketogenic diet is questionable given that the BHB levels are typically in the 0.5 to 3 mM range from nutritional ketosis. Another study (ref 10) in rats found that the cerebral metabolic rate of glucose decreased by 9% for each 1 mmol/l increase in total plasma ketone body concentration in ketotic rats induced by 3 weeks of a ketogenic diet. “The brain’s ability to switch from glucose oxidation towards ketone bodies requires a type of ‘cerebral metabolic adaptation’. This process is not well understood but is thought to be highly associated with the duration and level of ketosis. Ketones are considered to supply up to 70% of the total energy demands once maximal metabolic adaptation occurs.” Another study (ref 11) of 8 healthy male students found that mental alertness was significantly reduced by moderate hypoglycemia (40 mg/dl or 2.2 mmol/l) after an overnight fast while similar hypoglycemia did not reduce mental alertness after a 72 hour fast. BHB levels were not reported in the abstract (I did not purchase the full article). Finally in this study (ref 12), the effect of hyperketonemia on counter-regulatory hormone responses to hypoglycemia was examined in six healthy subjects. The peak adrenaline (epinephrine) response to hypoglycemia fell from 7.97 to 2.6 nmol/l during ketone infusion and the peak noradrenaline, cortisol and growth hormone responses were also significantly lower during ketone infusion at a rate of 3 mg/min/kg body weight which resulted in a 0.58 mmol/l BHB concentration which as you know is achievable with nutritional ketosis. In addition, the study found that the BG required to elicit the counter-regulatory hormone response was lower during the ketone infusion (BG was 2.5 mmol/l (45 mg/dl) during ketone infusion compared to 3.0 (54 mg/dl) mmol/l without ketones). 

These data are quite suggestive that keto-adaption at levels of blood ketones achievable with nutritional ketosis may, in fact, be providing the brain with an alternate source of fuel making hypoglycemia less symptomatic and less dangerous. Of course, formal studies of persons with T1DM following a ketogenic diet long-term need to be done to confirm this potential beneficial effect of the ketogenic diet.

How To Handle Glycemic Fluctuations During Illness

All patients with diabetes need to know how to manage BG during illness. The most common illnesses that lead to glycemic fluctuations include infections (most common are pneumonia and urinary tract infections) and gastrointestinal illnesses (some of which are caused by viruses) which often result in nausea, vomiting, reduced food and fluid intake, and diarrhea. These acute illnesses are a stress to the body which responses by secreting cortisol, growth hormone, glucagon, and epinephrine all of which increase BG. Occasionally, patients with diabetes are prescribed corticosteroid medications (e.g. prednisone, methylprednisolone) for various medical conditions. These medications are synthetic versions of the stress hormone, cortisol, and will increase BG often dramatically. Reduced food intake may modify the changes in BG as well. In the setting of illness, the goal is avoid both severe increases in hyperglycemia which can result in diabetic ketoacidosis (DKA) and to avoid hypoglycemia from overly aggressive increases in insulin doses by trying to maintain near-normal BG. The increases in stress hormones often require increased doses of insulin to control hyperglycemia, but accepting mild hyperglycemia during a short illness is much preferred to developing hypoglycemia from overly aggressive increases in insulin doses. Therefore when treating hyperglycemia during illness, it is best to maintain your usual basal insulin dose and use rapid-acting insulin doses to treat hyperglycemia. Rapid-acting insulin typically has a duration of action of 4-5 hours, so dosing them more frequently than every 4-5 hours should be avoided. This 4-5 hour window also varies with the person, so if you have measured BG repeatedly after taking your rapid-acting insulin and know when your BG has stabilized, you could use that time period instead. Taking rapid-acting insulin more frequently that this time period, is called insulin-stacking and can result in hypoglycemia as can an excess dose of rapid-acting insulin. Keeping BG in the 100-200 mg/dl (5.6-11.1 mmol/l) range during an illness should be adequate enough to prevent DKA. Obviously, mildly elevated BG during an illness will have no impact on long-term complications of diabetes. However, overly aggressive insulin doses during an illness can and has caused death from hypoglycemia. On the flip side, a patient with insulin-requiring diabetes who is unable to eat during an illness sometimes severely reduces their insulin doses or just stops insulin altogether. Remember even while fasting (not eating at all), humans need insulin at some basal rate to prevent hyperglycemia. Add to that the stress hormones of illness, and you can see that severely reducing or stopping basal insulin is also a mistake that can result in DKA.

Finally, If you do not feel you are getting control of your BG with the above guidelines, do not hesitate to seek medical attention (calling your physician or going to the emergency room). Developing either severe hypoglycemia or DKA during an illness is life-threatening and both are preventable in the hospital setting.

Additional medications other than insulin are used to improve glycemic control in those with T1DM and T2DM. Some of these medications can increase the incidence of hypoglycemia. These medications are reviewed below.

Sulfonylureas

The first sulfonylurea was discovered in 1942. The first-generation sulfonylureas include chlorpropamide (Diabinese), tolazamide (Tolinase), and tolbutamide (Orinase). The second generation sulfonylureas include gliclazide (Diamicron), glipizide (Glucotrol), glyburide (also known as glibenclamide) (Micronase, Diabeta, Glynase). Glimepiride (Amaryl) is a third generation sulfonylurea. They are the most prescribed medication for T2DM, probably due to their low cost. Sulfonylureas work primarily by stimulating pancreatic β-cells to secrete insulin and by reducing hepatic clearance of insulin as well as by some other mechanisms. Consequently they are effective only when residual pancreatic β-cells are present (typically only in T2DM). This stimulation of insulin secretion, however, is independent of the BG level which can lead to hypoglycemia. In the settings of an excessive dosage of these drugs, hypoglycemia can last many hours and is prolonged in those with renal failure requiring hospitalization. Sulfonylureas over time can exhaust the β-cells leading to progressive β-cell dysfunction and worsening of insulin secretion (secondary failure). Thus, despite better glycemic control in the short term, diabetes could worsen in the long term. Because sulfonylureas increase β-cell insulin secretion in the setting of insulin resistance, the fat cells are encouraged to store fat and these drugs often cause body weight/fat gain. Finally, sulfonylureas are associated with higher rates of cardiac ischemic events and cardiac deaths compared to metformin in multiple different studies. The FDA issued a special warning on this increased risk of cardiac mortality based on the older studies of tolbutamide. The mechanism for this association is currently unknown. Sulfonylureas are effective in most patients and are low cost, but do have the side-effects of hypoglycemia and weight gain. Sulfonylureas are not used for T1DM since there are no β-cells to stimulate.

Meglitinides 

Meglitinides work by stimulating the pancreas to release insulin in response to a meal. It closes ATP-dependent potassium channels in functioning β-cells. This blockade of potassium channels depolarizes the beta cells leading to opening of calcium channels and resulting in influx of calcium. Increased intracellular calcium induces insulin secretion. This release of insulin occurs independent of the current BG level and thus can lead to hypoglycemia, although less so than with the sulfonylureas. Drugs in this class include repaglinide (Prandin) and nateglinide (Starlix). Like sulfonylureas, weight gain is another side-effect. Meglitinides are not used for T1DM since there are no β-cells to stimulate.

Pramlintide (Symlin)

Pramlintide is an analog of the peptide hormone amylin. Amylin is co-secreted with insulin from pancreatic β-cells and acts centrally to slow gastric emptying, suppress postprandial glucagon secretion, and decrease food intake. These actions complement those of insulin to regulate BG levels. Amylin is relatively deficient in patients with T2DM, depending on the severity of β-cell secretory failure, and is essentially absent in patients with T1DM. One trial showed pramlintide reduced postprandial BG, with modest reductions in overall glycemia (HbA1c ≈ 0.33%), but another randomized controlled trial was unable to detect any benefit at 6 months in patients with T1DM (ref 14). Pramlintide also induces modest weight loss through control of appetite centers in the brain. Pramlintide can cause hypoglycemia if meal-time insulin doses are not appropriately reduced. The most common side-effect of pramlintide is nausea which tends to decrease with continued use.

Metformin (Glucophage, Glumetza, Fortamet)

Metformin is the first-line medication for T2DM, but may also be useful for those with T1DM. From this paper (ref 13), “In the diabetic state, there is inadequate suppression of postprandial glucagon secretion (hyperglucagonemia) resulting in elevated hepatic glucose production. Importantly, exogenously administered insulin is unable both to restore normal postprandial insulin concentrations in the portal vein and to suppress glucagon secretion [by the alpha-cells] through a paracrine effect. This results in an abnormally high glucagon-to-insulin ratio that favors the release of hepatic glucose. These limits of exogenously administered insulin therapy are well documented in individuals with type 1 or type 2 diabetes and are considered to be important contributors to the postprandial hyperglycemic state characteristic of diabetes.”

So far, researchers have not discovered a way to inhibit this excess glucagon production or to block glucagon receptors. For another helpful review of glucagon in T1DM, check (ref 14). But, this is where metformin may be helpful. Metformin acts on the liver to reduce glucose production by suppressing both gluconeogenesis and glycogenolysis. I speculate that metformin may be especially useful for those with T1DM on a low carbohydrate ketogenic diet because the reduction in dietary carbohydrate reduces insulin requirements. This in turn might stimulate glucagon secretion by the alpha-cells in the pancreas even more than that caused by the diabetic state. This would lead to chronic overproduction of glucose by the liver and contribute to hyperglycemia. However, hyperglycemia does not suppress glucagon production without the accompanying physiologic increase in insulin secretion which does not occur in T1DM. The use of metformin for T1DM while following a ketogenic diet also needs a clinical trial that has yet to be done. Metformin also stimulates muscle uptake of glucose independent of insulin. Although uncommon in those not following a ketogenic diet, metformin might cause hypoglycemia if meal-time insulin doses are not appropriately reduced in those following a ketogenic diet. A meta-analysis (ref 15) of metformin use in those with T1DM not following a ketogenic diet found the following:

“RESULTS: In total, eight randomized controlled trials were included. Metformin was associated with a reduction in daily insulin dosage, body weight, total cholesterol level, low-density lipoprotein level, and high-density lipoprotein level but an increase in risk of gastrointestinal adverse effects compared with placebo treatment in T1DM patients. No significant difference was found between the metformin group and the placebo group in HbA1c level, FPG level, or triglycerides level. No significant difference was found between the metformin group and the placebo group in the risk of severe hypoglycemia or diabetic ketoacidosis.”

Thiazolidinediones

Thiazolidinediones are peroxisome proliferator-activated receptor gamma (PPARg) agonists with multiple actions that lead to improved insulin sensitivity.  Drugs in this class include pioglitazone (Actos) and rosiglitazone (Avandia). This class of drugs is used for T2DM where insulin resistance and carbohydrate resistance are the primary defects. Serious side-effects include fluid retention (edema) and hypertension especially when combined with exogenous insulin, upper respiratory tract infections, and headaches. Rosiglitazone was found to increase the risk of myocardial ischemia and heart failure which led Europe and the UK to remove it from the market. Pioglitazone was linked to an increased risk of bladder cancer in one study, but the strength of the data did not warrant removal of the drug from the market. I could find only one small pilot study done in new-onset T1DM which showed pioglitazone did not preserve β-cell function when compared to placebo. (ref 16). 

GLP-1 (glucagon-like peptide 1) receptor agonists

GLP-1 is an incretin peptide that is produced and secreted by intestinal enteroendocrine L-cells and certain neurons in the brainstem upon food consumption. The medications in this class have small amino acid substitutions in GLP-1 that bind to and activate the GLP-1 receptor with longer durations of action. They include albiglutide (Tanzeum), dulaglutide (Trulicity), lixisenatide (Lyxumia/Adlyxin), liraglutide (Victoza), semaglutide (Ozempic), and exenatide (Byetta/Bydureon). They are administered by subcutaneous injection. They are most commonly used in T2DM wherein they stimulate insulin secretion in a glucose-dependent fashion, but may be used for T1DM wherein they inhibit glucagon secretion and may inhibit appetite to assist with losing excess body fat. Two trials of GLP-1 receptor agonists for T1DM showed a reduction in insulin requirements without an increase in hypoglycemia (ref 14). GLP-1 receptor agonists have not been studied in those who follow a ketogenic diet.

DPP-4 (dipeptidyl peptidase 4) Inhibitors

DPP-4 is an enzyme that degrades endogenous GLP-1. By inhibiting DPP-4, DPP-4 inhibitors potentiate the activity of GLP-1 or the GLP-1 receptor agonists (see above). This class of diabetes medications include sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), vildagliptin (Galvus, Zomelis), saxagliptin/metformin extended release (Janumet XR, Kombiglyze XR), and vildagliptin/metformin (Eucreas). In T2DM, HbA1c decreased by 0.5 – 1.4% depending on the clinical trial and duration of therapy. The most common side-effects include nasopharyngitis, upper respiratory tract infection, and headache. In a meta-analysis of clinical trials regarding treatment with sitagliptin and vildagliptin, there was no increased incidence of hypoglycemic events compared with the control group. Two small clinical trials of sitagliptin and vildagliptin for T1DM showed not only improvement in glucagon levels, but also a modest reduction in HbA1c (ref 14), but a larger longer trial showed no differences (ref 17).

SGLT-2 (sodium/glucose cotransporter) inhibitors

The sodium/glucose cotransporter in the renal tubule of the kidneys functions to reabsorb filtered glucose. Normally, this transporter prevents any glucose from reaching the urine. However in uncontrolled diabetes (T1DM or T2DM), so much glucose is filtered that the transporter cannot keep pace and glucose spills out into the urine (glycosuria). The medications in this class inhibit this transporter and reduces the reabsorption of filtered glucose such that glucose spills out into the urine depending on the BG level. Thus, less glucose appears in the urine when BG is normal which minimizes the potential for hypoglycemia. Because these drugs do not stimulate insulin secretion, exhaustion of β-cells does not occur. They are not effective in the setting of impaired kidney function. This class of medications include ertugliflozin (Steglatro), empagliflozin (Jardiance), canagliflozin (Invokana), and dapagliflozin (Farxiga). They are the newest class of diabetes medications used primarily for T2DM and are not commonly used for T1DM. When used off-label for T1DM, they should be used with caution not only because they could lead to hypoglycemia if insulin doses are not reduced sufficiently, but also because they can cause euglycemic diabetic ketoacidosis (EDKA). The reduction in BG causes both a reduction in insulin secretion (or insulin dosage in T1DM) and an increase in glucagon secretion. Therefore, in both T1DM and T2DM the decrease in the insulin/glucagon ratio, in some instances, can signal the liver to make excessive amounts of ketones leading to diabetic ketoacidosis, but with a normal or only mildly elevated BG i.e. EDKA. Since BG alone is typically measured, the patient may be unaware of the impending problem until they become ill from EDKA. Twenty cases of EDKA were reported to the FDA and 101 cases of EDKA worldwide as of 2015, the majority of whom had a diagnosis of T2DM and were taking exogenous insulin. The FDA also identified potential triggering factors such as intercurrent illness, reduced food and fluid intake, excessively reduced insulin doses, and a history of alcohol intake. Additionally, some cases of insulin-treated T2DM may have been mislabeled and they actually had T1DM. Other side-effects include genital yeast infections, urinary tract infections, dehydration, hypotension, hyperkalemia, and kidney failure. SGLT-2 inhibitors are effective in improving glycemic control, but the above precautions and risks need to be understood.

α-Glucosidase inhibitors

Alpha-Glucosidase inhibitors work by blocking the action of enzymes that normally begin to break down certain carbohydrates in the upper part of the small intestine, thus delaying the absorption of carbohydrates from the intestine. They are used primarily to improve post-prandial hyperglycemia in T2DM. The oral drugs in this class include acarbose (Precose), miglitol (Glyset), and voglibose (Volix). Side-effects include bloating, nausea, diarrhea, and flatulence. Usually, these side effects can be minimized by starting therapy with a small dose and slowly working up to the most effective dose. They do not cause hypoglycemia by themselves, but can slow the absorption of simple carbohydrates other than glucose used to treat hypoglycemia. Thus, pure glucose should be used to treat hypoglycemia. They may be used or either T1DM or T2DM. For those following a very low carbohydrate ketogenic diet, I would not expect these drugs to add any benefit.

Dopamine-2 agonist

Bromocriptine is a sympatholytic D2-dopamine agonist that has been approved for the treatment of type 2 diabetes. Based on animal and human studies, timed bromocriptine administration within 2 hours of awakening is believed to augment low hypothalamic dopamine levels and inhibit excessive sympathetic tone within the central nervous system (CNS), resulting in a reduction in postprandial BG levels due to enhanced suppression of hepatic glucose production. Bromocriptine has not been shown to augment insulin secretion or enhance insulin sensitivity in peripheral tissues (muscle). Addition of bromocriptine to poorly controlled type 2 diabetic patients treated with diet alone, metformin, sulfonylureas, or thiazolidinediones produces a 0.5–0.7% decrement in HbA1c. Bromocriptine also reduces fasting and postprandial plasma free fatty acid (FFA) and triglyceride levels. In a 52 double-blind, placebo-controlled study in type 2 diabetic patients, bromocriptine reduced the composite cardiovascular end point by 40%. The mechanism of the drug’s beneficial effect on cardiovascular disease remains to be determined. Drugs in this class include bromocriptine (Parlodel) and a timed-release bromocriptine mesylate (Cycloset). Side-effects that occurred more commonly in Cycloset versus placebo were nausea (26 vs. 5%), asthenia (15 vs. 8%), constipation (11 vs. 4%), dizziness (11 vs. 6%), and rhinitis (8 vs. 5%). In general, these side effects were mild and transient. Thirteen percent of Cycloset-treated subjects withdrew because of adverse events compared with 3–5% of placebo-treated subjects (P < 0.01). There was no increase in serious adverse events in the Cycloset compared with placebo groups (2.4 vs. 4.3%, respectively). There was no difference in the incidence of hypoglycemia between the Cycloset and placebo-treated groups in any trial. The mechanism(s) via which timed bromocriptine reduces cardiovascular events in type 2 diabetic patients by 40% remains to be defined. Based on the composite cardiovascular outcome, 79 diabetic patients need to be treated for 1 year to avoid one cardiovascular event.

Steps That Should Be Taken To Improve Glycemic Control and Avoid Hypoglycemia

From the discussion reviewed above, the exact target BG that will both maximize benefit (lowest risk of long-term complications) and minimize risk (lowest risk of hypoglycemia) is NOT known. Each person with diabetes needs to discuss with their physician what their target BG value should be to first minimize the number and severity of hypoglycemic episodes. This is a safety-first approach. Once the number of hypoglycemic episodes is minimized, then one can begin to lower the target BG towards a normal average BG reading of 96 mg/dl. If the number/severity of hypoglycemic episodes increases, then the target BG should be increased to a higher value. Thus, the target BG should be titrated down toward 96 mg/dl (but not below) while minimizing the number/severity of hypoglycemic episodes.

When trying to reduce the number and severity of hypoglycemic episodes, one needs to look carefully at several variables. First and most importantly, the basal and/or bolus insulin doses need to be reduced especially when using a low carbohydrate ketogenic diet. Remember that basal insulin (or the basal rate in those who use an insulin pump) covers one’s insulin needs between meals and overnight. The basal insulin dose is determined primarily by the fasting BG results. Fasting hypoglycemia, especially occurring on more than one day, will require a reduction in the basal insulin dose. The meal-time bolus insulin dose is determined primarily by the post-meal BG results. Post-meal hypoglycemia will likely require a reduction in the meal-time insulin dose (assuming similar meal and exercise). The different basal and bolus insulin preparations and methods of administering and adjusting doses are covered in detail in our books mentioned at the beginning of this blog post.

Keeping one’s meals as consistent as possible from day to day will greatly improve the consistency of the BG response to one’s meals. Thus, I for example, attempt to keep the quantity and types of food I eat at each meal consistent from day to day so that the grams of protein, carbs, fat, and fiber remain relatively constant. Similarly, I try to keep my exercise type, duration, intensity, and time of day that I exercise, consistent as well. Exercise has a very significant effect on one’s insulin sensitivity and therefore on the BG response to exogenous insulin.

Exercise and Hypoglycemia

Followers of this blog may know that my interest in the ketogenic diet had its origins when I was trying to improve my glycemic control to complete an ironman distance triathlon in 2012. I started training in swimming, cycling, and running in August 2007 and did my first sprint triathlon on Dec. 8, 2007. I progressively increased the distance each year completing my first olympic distance triathlon Nov. 9, 2008, and my first half ironman distance triathlon on Nov. 8, 2009. As the distance of training increased, I started having hypoglycemia which I did not like so much that I started using sports nutrition products (sugar essentially) preemptively to the point that I was developing hyperglycemia. On Sept. 18, 2009, I had the highest HbA1c ever at 7.9% which I felt was due to this practice of using sports nutrition products. In 2011 I was hoping to complete an ironman distance triathlon, but felt the amount of time required to complete it (around 15 hrs) would require a better approach. I was concerned about both hypoglycemia and hyperglycemia occurring during the event, but hypoglycemia could have resulted in more dire consequences had I been unable to recognize the symptoms. I discovered through listening to two podcasts, IM Talk and Jimmy Moore’s Livin’ La Vida Low Carb, about Dr. Richard K. Bernstein, Dr. Stephen Phinney and Dr. Jeff Volek and the ketogenic diet. I implemented it on Feb. 8, 2012. This was a game changer for me, not only for my life in general, but specifically my need for carbohydrate during exercise and the swings in BG were dramatically reduced. Rather than taking carbohydrate at the beginning of exercise, I measured my BG every hour during exercise and supplemented with carbohydrate on an as needed basis. I stopped having hypoglycemia during exercise which gave me the confidence to complete the ironman distance triathlon on Oct. 20, 2012 in 15.5 hours. This was not a competitive time, but I was just happy to have been able to do it without hypoglycemia and a BG less than 200 mg/dl for the majority of the time. From this experience, I am convinced that the lower insulin doses and fat-adaptation that result from a ketogenic diet allow for improved glycemic control during endurance exercise. The endurance exercise also contributed to improved insulin sensitivity which allowed for additional lowering of insulin doses. One problem I noticed, however, was that the long endurance training did require a day or two of rest to recover which resulted in varying insulin sensitivity from day to day. So I noticed I was adjusting insulin doses more so than what I was doing prior to starting regular exercise. After completing the ironman distance triathlon in 2012, I was so excited about the accomplishment that I continued pushing my training and signed up for another ironman event in April 2013. However, soon before the event all that training finally caught up to me and I was having both knee and foot pains from iliotibial band syndrome and plantar fasciitis. I continued exercising with a lot of swimming and short bike rides. As you might guess I also increased the distance of the swims and did two 5 kilometer swims. These swims were completed on the ketogenic diet so I was not worried so much about hypoglycemia and had none to boot. I never did another triathlon and it took almost 3 years for the plantar fasciitis to finally go away. In Dec. 2014, I started weightlifting mainly to address recurrent low back pain which I been having for years precipitated by lifting things, cycling, and chores that involved bending over. I started with powerlifting: deadlift, squat, bench press. After 3 months, I was again developing overuse injuries, now in my elbows and I had flared up a preexisting injury in my left shoulder doing the bench press. So I switched to olympic weightlifting in March 2015 and over time, my central back pain with radiculopathy consistent with a herniated disc did resolve. It took several years to figure out how much exercise I could do without overtraining and in the process figured out that exercising daily had the most stabilizing effect on my glycemic control. With a few exceptions, I found that olympic weightlifting which I would describe as high-intensity resistance exercise almost invariably increases my BG. The elevation has ranged from mild to rather extreme (an increase of about 120 mg/dl at most). I have accepted these increases as a normal consequence of the type of exercise that I enjoy. It is caused by release of the stress hormones cortisol, epinephrine, growth hormone, and glucagon which serve to release glucose from the liver and fatty acids from fat to supply energy to exercising muscles. This stress hormone effect definitely did not happen during my endurance training exercise since I was doing long-slow training, i.e. no sprinting. Initially, I took small doses of rapid-acting insulin to correct the BG elevations after exercise. Up to that point, I had been avoiding eating lunch for 17 years so as to avoid having to take insulin and thus avoid the chance of hypoglycemia after lunch. So I added a small protein-containing lunch (1/4 lb. hamburger patty and one egg) after my weightlifting session since I was taking insulin most days anyway in the hopes of adding some additional muscle. So far, my muscle mass seems rather stable, but if I can prevent it from declining that will be a victory. If I stop exercising which sometimes happens due to an injury or travel, I develop hyperglycemia using the same insulin doses and thus require increases in insulin doses progressively each day that I do not exercise. After two weeks of no exercise, the insulin doses stabilize at a new higher dose. Several years ago this occurred and I had to increase my total daily insulin dose from 30 IU/day to 42 IU/day. This represents a 40% increase in insulin dosage due to the reduced insulin sensitivity from the cessation of exercise.

All this is a long way of saying that I have had a lot of experience with exercising with T1DM as an endurance athlete on both a high-carb and low-carb ketogenic diet and with high-intensity resistance training on a low-carb ketogenic diet. The lessons I have learned and the reading I have done on the topic include the following:

  1. Hypoglycemia almost invariably occurred with endurance exercise when not consuming sports nutrition products (sugar) while on a high-carb diet. Longer duration exercise was more likely to result in hypoglycemia.
  2. Hyperglycemia commonly occurred with endurance exercise when consuming sports nutrition products (sugar) while on a high-carb diet.
  3. There were days when my BG was well controlled with endurance exercise when consuming sports nutrition products (sugar) while on a high-carb diet, but it seemed to be the minority of the time.
  4. If I had a CGM, I think I could have done a better job controlling my BG. I have spoken to other T1DM athletes who had a positive experience with a CGM.
  5. If I had an insulin pump, reducing the basal rate prior to exercise may have allowed for controlled BG during endurance exercise without consuming much sports nutrition products (sugar) while on a high-carb diet, but that is speculation. I have spoken to other T1DM athletes who had a positive experience with this and others for whom it did not work.
  6. I had much better glycemic control during and after endurance exercise after starting the ketogenic diet. My HbA1c was 5.6% after the ironman distance triathlon. I used very little sports nutrition products (sugar) as a result of the ketogenic diet possibly due to the improved ability to burn fat as a fuel while taking less insulin. I would use glucose tablets instead of sports nutrition products on an as needed basis were I to do it again.
  7. Post-exercise hypoglycemia can and does occur in many persons with T1DM. For me, this usually occurred after dinner (9 pm) and I learned to reduce my rapid-acting insulin doses at dinner-time to improve it. However, post-exercise hypoglycemia can and does occur in many persons with T1DM during the night while sleeping (nocturnal hypoglycemia). Making sure BG is in your target range before going to sleep and setting an alarm to check your BG or using a CGM with an alarm is a good idea until you can understand your glycemic pattern after exercise. For me, nocturnal hypoglycemia was a problem when taking NPH insulin as my basal insulin and for a period of 3 months (March – May 2008) when I didn’t realize that my BG meter was reading falsely high. On June 6, 2008, my HbA1c was 5.3% (lowest ever on a high-carb diet) with many hypoglycemic episodes. With the combination of glargine (Lantus) insulin and getting the Freestyle Freedom Lite glucose meter, my nocturnal hypoglycemia stopped.
  8. Intense exercise of any type (resistance, running, cycling, swimming, etc.) can result in hyperglycemia due to the normal stress hormone response to exercise. Normally, insulin is released to control the degree of hyperglycemia during exercise and to normalize the BG after exercise which does not occur in those with diabetes especially T1DM (ref 18).
  9. In my personal experience, high-intensity resistance exercise on a ketogenic diet usually, but not always, leads to some degree of hyperglycemia (BG > 110 mg/dl). Since this rise in BG occurs in normal athletes, I simply correct it with a dose of rapid-acting insulin after measuring the BG. A larger basal insulin dose might prevent the post-exercise hyperglycemia, but would in turn result in fasting and or nocturnal hypoglycemia which is dangerous. Could I find an exercise that would not affect my BG very much? Probably, but at some point, one should take their enjoyment of physical activity into account. I really like weightlifting.🏋️‍♀️

Here is a short article on the glycemic response to various types of exercise in those with diabetes (except for the ketogenic part) (ref 19). 

Treating Hypoglycemia

One of the most frequent questions I get is whether treating hypoglycemia with glucose tablets/liquid or food for that matter will interfere with ketosis. First, I hope I made it clear above that treating hypoglycemia is essential for one’s own safety. So whether ketosis is affected or not is irrelevant. Hypoglycemia should be treated immediately with anything that is available at the moment. Ideally, every person with diabetes, particularly T1DM, should be carrying glucose tablets/liquid with them at all times. These sources of pure glucose are best for rapidly raising BG and resolving any symptoms of hypoglycemia as quickly as possible. The longer the symptoms last, in addition to being unpleasant, the more potential for more serious complications as well as overcorrection by consuming too much food or sugar. I would like to explain that sugar is sucrose which is a compound composed of one glucose and one fructose molecule. The fructose can be converted to glucose primarily in the liver, but the process is slow compared to the immediate absorption and utilization of glucose. This study (ref 20) found the mean conversion rate from fructose to glucose was 41% ± 10.5 (mean ± SD) in 3–6  hours after ingestion. Thus, sugar is not equivalent to or as good as glucose for correcting hypoglycemia in persons with T1DM (only use it if pure glucose is not available). To treat symptomatic hypoglycemia, take 2-4 glucose tablets (contains 8-16 grams glucose) and wait about 15 mins to see if symptoms are improving. If symptoms are not improving take 2-4 more tablets and seek additional help (e.g. glucagon injection) and/or medical attention. Note that the ADA (ref 8) recommends using 15-20 grams of glucose initially. However, I found this usually results in hyperglycemia. Thus, each person needs to determine their own glucose dose because their body weight and insulin sensitivity will affect the dose of glucose needed to correct hypoglycemia. Taking excessive amounts of food, sugar, or even glucose tablets can result in hyperglycemia which will need to be treated with one or more additional insulin doses. This has and likely will happen to each and every person with T1DM, but these episodes can be minimized by following the above guidelines. Finally, glucose tablets are also best for correcting mild asymptomatic hypoglycemia. I typically use 1/2 or 1 glucose tablet (2-4 grams of glucose). The tablets are scored and easy to break in half. Liquid glucose can be used as well. Finally, recheck BG with your meter to confirm that the hypoglycemia has been corrected especially before driving a car or going to sleep.

Now for the question about what happens to ketosis in those following a ketogenic diet after treating hypoglycemia with glucose tablets. Taking just a few glucose tablets is not likely to affect ketosis at all. In fact because hypoglycemia in those with T1DM is a hyperinsulinemic hypoglycemia, the excess insulin itself is more likely to have already inhibited ketosis if it has been affected at all. You see, insulin inhibits the rate-limiting enzyme, HMG CoA synthase, required to make ketones. Treating hypoglycemia with glucose tablets will effectively use up the excess insulin and may restore ketone synthesis. Thus treating hyperinsulinemic hypoglycemia with glucose tablets will either improve nutritional ketosis or not affect it at all.

Stay tuned for the next blog post #53 on a study (ref 21) just published in the journal Pediatrics where I was one of the participants in the study.

References

  1. The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. https://www.nejm.org/doi/pdf/10.1056/NEJM199309303291401
  2. Continuous Glucose Profiles in Healthy Subjects under Everyday Life Conditions and after Different Meals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769652/pdf/dst-01-0695.pdf
  3. Variation of Interstitial Glucose Measurements Assessed by Continuous Glucose Monitors in Healthy, Nondiabetic Individuals. http://care.diabetesjournals.org/content/diacare/33/6/1297.full.pdf
  4. Hypoglycemia-Associated Autonomic Failure in Diabetes: Maladaptive, Adaptive, or Both?  http://diabetes.diabetesjournals.org/content/64/7/2322
  5. Severe Hypoglycemia–Induced Lethal Cardiac Arrhythmias Are Mediated by Sympathoadrenal Activation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781452/
  6. Recurrent Moderate Hypoglycemia Ameliorates Brain Damage and Cognitive Dysfunction Induced by Severe Hypoglycemia. https://www.ncbi.nlm.nih.gov/pubmed/20086229
  7. Reversal of hypoglycemia unawareness, but not defective glucose counterregulation, in IDDM here https://www.ncbi.nlm.nih.gov/pubmed/7958494
  8. Standards of Medical Care in Diabetes – 2018.  http://care.diabetesjournals.org/content/diacare/suppl/2017/12/08/41.Supplement_1.DC1/DC_41_S1_Combined.pdf
  9. Resistance to Symptomatic Insulin Reactions after Fasting. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC332976/
  10. Ketosis proportionately spares glucose utilization in brain. https://www.ncbi.nlm.nih.gov/pubmed/23736643
  11. Mental alertness in response to hypoglycaemia in normal man: the effect of 12 hours and 72 hours of fasting. https://www.ncbi.nlm.nih.gov/pubmed/3315761
  12. Ketone infusion lowers hormonal responses to hypoglycaemia: evidence for acute cerebral utilization of a non-glucose fuel. https://www.ncbi.nlm.nih.gov/pubmed/1653662
  13. Glucose Metabolism and Regulation: Beyond Insulin and Glucagon. http://spectrum.diabetesjournals.org/content/17/3/183
  14. Alpha cell function in type 1 diabetes. http://www.bjd-abcd.com/index.php/bjd/article/view/12/37
  15. Efficacy and safety of metformin for patients with type 1 diabetes mellitus: a meta-analysis. https://www.ncbi.nlm.nih.gov/pubmed/25369141
  16. Effect of Pioglitazone on the Course of New-Onset Type 1 Diabetes Mellitus. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890222/ 
  17. Effect of Sitagliptin on Post-Prandial Glucagon and GLP-1 Levels in Patients With Type 1 Diabetes: Investigator-Initiated, Double-Blind, Randomized, Placebo-Controlled Trial. http://journals.aace.com/doi/abs/10.4158/EP12100.OR
  18. Differences in the metabolic and hormonal response to exercise between racing cyclists and untrained individuals. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1308956/
  19. Blood Glucose Responses to Type, Intensity, Duration, and Timing of Exercise. https://digitalcommons.odu.edu/cgi/viewcontent.cgi?article=1048&context=hms_fac_pubs
  20. Fructose metabolism in humans – what isotopic tracer studies tell us. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533803/pdf/1743-7075-9-89.pdf 
  21. Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet. http://pediatrics.aappublications.org/content/early/2018/05/03/peds.2017-3349