In September 2016 since I did so well with glycemic control last month, I decided to raise the bar a bit further. By that I mean, to narrow the blood glucose (BG) range that I am aiming for from 51-120 mg/dl to 61-110 mg/dl. Doing so will increase both the number of hypoglycemic and hyperglycemic BG values. I also reexamined what a normal BG is in non-diabetic healthy individuals. I have been using 83 mg/dl as a normal BG which is found in many different sources. However, that value is usually based on fasting or between meals and does not take into account the excursions due to meals or exercise. By aiming for 83 mg/dl, I have what I consider to be excessive numbers of low BG readings despite the fact that they are either asymptomatic or minimally so. If meal and exercise related BG excursions are taken into account, the “normal” value would definitely be higher. So I searched for studies that measured BG over the entire 24 hours in a day in those without diabetes. I found only one study which I will present below. If anyone finds other such studies please let me know via comment or email. Addendum: A blog follower directed me to another study that measured continuous interstitial glucose in nondiabetic healthy children and adults. For adults >= 45 years of age, the mean interstitial glucose +/- SD was 95 +/- 12.4 mg/dl with a coefficient of variation of 13%. Thanks for that Adam B.
Below are my BG values using the new target ranges mentioned above for September 2016. From the last row for September, the mean BG was 85 mg/dl at a slightly higher insulin dose, 31.5 IU/day compared to 30.4 IU/day last month. The percentage of BG values < 61 mg/dl increased from 15% to 25%. That’s on average one hypoglycemic value per day and despite the fact that they are asymptomatic or minimally so is more than I am comfortable with.
As presented in blog post #15 exogenous insulin cannot mimic normal insulin secretion, so persons with type 1 diabetes should not expect to have truly normal BG values. They just need to be low enough to prevent long-term complications and not so low as to cause unpleasant symptoms, brain damage, seizure, injury, coma, or death. What those values are varies from one person to the next and are contextual based on one’s recent level of glycemic control. Aiming for normal 90-95 ± 7-12 mg/dl (mean ± SD) is desirable as long as hypoglycemia is minimized. Following a low carbohydrate ketogenic diet may provide additional brain fuel in the form of ketones to protect the brain when BG does go low. I will also present another study below that shows that hypoglycemic mortality is reduced in rats with recurrent iatrogenic hypoglycemia.
Below are my BG readings along with exercise type and time so you can see how the type and duration of exercise affected my glycemic control.
The table below shows the summary of current and previous BG variability results. Most of the results were improved compared to previous months and years with improvement in the following variability measures: mean daily BG range = 62, mean time of hyperglycemia = 3.8 hr/day, interquartile BG range = 41. The measures of BG variability were defined and explained in blog post #10.
The actual daily insulin doses and daily insulin dose totals are shown in the graphs below.
The Ketonix breath ketone (acetone) monitor results beginning June 2015 are shown below (see blog post #19 for more details). I have been in continuous nutritional ketosis due to my low carbohydrate ketogenic diet. There is a noticeable gradual decline in the readings. I would guess this is related to either a gradual increase in carbohydrate intake from nuts and seeds or that I am able to utilize the ketones more effectively. I have added MCT oil 2 tbsp./day beginning 9/27/2016 to my diet which may increase the breath acetone values.
The graphs below show the change in BG that results from mealtime rapid-acting insulin. On the x-axis is the Breakfast and Dinner mealtime insulin dose (Humalog) plotted against the change in BG, i.e. Post meal BG minus Pre meal BG on the y-axis. Thus positive values represent an increase in BG and negative values represent a decrease in BG after the meal. Also, note that I removed 14 of 30 Breakfast points and 13 of 30 Dinner points from the graphs where the Post meal BG was not in the range of 61-110 mg/dl. The rationale for this is to eliminate graphing mealtime doses that were “incorrect” so to speak. This way the graph shows both that larger doses of insulin reduce BG more (obvious), but more importantly even when the resulting Post BG was in an acceptable range, that there is a wide variation in the amount of BG reduction for any given dose of insulin. This variation can be due to varying absorption of injected insulin, variation in insulin sensitivity from exercise, or variation in food consumed during the meal from one day to the next. Reducing this variation is an important goal of mine.
The first study I want to review briefly is titled, Continuous Glucose Profiles in Healthy Subjects under Everyday Life Conditions and after Different Meals.
Continuous interstitial glucose measurement was performed under everyday life conditions (2 days) and after ingestion of four meals with standardized carbohydrate content (50 grams), but with different types of carbohydrates and variable protein and fat content. Twenty-four healthy volunteers (12 female, 12 male, age 27.1 ± 3.6 years) participated in the study. The mean 24-hour interstitial glucose trace under everyday life conditions is shown in Figure 2 [shown below]. The mean 24-hour interstitial glucose concentration was 89.3 ± 6.2 mg/dl (range 79.2–101.3 mg/dl), with a mean glucose concentration of 93.0 ± 7.0 mg/dl at daytime (7 am to 11 pm) and 81.8 ± 6.3 mg/dl during the night (11pm to 7am). The mean 24-hour capillary blood glucose concentration was 90.9 ± 6.8 mg/dl (16 values per 24 hours), and mean blood glucose concentrations at daytime and during the night were 92.7 ± 6.9 mg/dl (14 values per day) and 78.1±7.9 mg/dl (2 values per night).
Thus, a better BG target to aim for is 90.9 ± 6.8 mg/dl rather than 83 mg/dl. By doing so, I should have fewer hypoglycemic values while still having little chance of diabetic complications.
The second study to review briefly is titled, Severe Hypoglycemia–Induced Lethal Cardiac Arrhythmias Are Mediated by Sympathoadrenal Activation. The abstract and two figures from the paper are shown below.
For people with insulin-treated diabetes, severe hypoglycemia can be lethal, though potential mechanisms involved are poorly understood. To investigate how severe hypoglycemia can be fatal, hyperinsulinemic, severe hypoglycemic (10–15 mg/dL) clamps were performed in Sprague-Dawley rats with simultaneous electrocardiogram monitoring. With goals of reducing hypoglycemia-induced mortality, the hypotheses tested were that: 1) antecedent glycemic control impacts mortality associated with severe hypoglycemia; 2) with limitation of hypokalemia, potassium supplementation could limit hypoglycemia-associated deaths; 3) with prevention of central neuroglycopenia, brain glucose infusion could prevent hypoglycemia-associated arrhythmias and deaths; and 4) with limitation of sympathoadrenal activation, adrenergic blockers could prevent hypoglycemia-induced arrhythmic deaths. Severe hypoglycemia–induced mortality was noted to be worsened by diabetes, but recurrent antecedent hypoglycemia markedly improved the ability to survive an episode of severe hypoglycemia. Potassium supplementation tended to reduce mortality. Severe hypoglycemia caused numerous cardiac arrhythmias including premature ventricular contractions, tachycardia, and high-degree heart block. Intracerebroventricular glucose infusion reduced severe hypoglycemia–induced arrhythmias and overall mortality. β-Adrenergic blockade markedly reduced cardiac arrhythmias and completely abrogated deaths due to severe hypoglycemia. Under conditions studied, sudden deaths caused by insulin-induced severe hypoglycemia were mediated by lethal cardiac arrhythmias triggered by brain neuroglycopenia and the marked sympathoadrenal response. Diabetes 62:3570–3581, 2013
As discussed in this paper, hypoglycemia is both maladaptive and adaptive.
Hypoglycemia attenuates sympathoadrenal and symptomatic responses to the same level of subsequent hypoglycemia and thus causes hypoglycemia-associated autonomic failure (HAAF) in diabetes… On the other hand, HAAF appears to be adaptive in that it reduces the most devastating effect of severe hypoglycemia—death.
If blood ketones are sufficiently high during nutritional ketosis to prevent neuroglycopenia during hypoglycemia, then a ketogenic diet ± MCT oil supplementation ± exogenous ketone supplementation might prevent death from hypoglycemia in persons taking insulin for type 1 diabetes by preventing neuroglycopenia. Second, those with type 1 diabetes who are seeking close to normal glycemic control will likely experience multiple hypoglycemic episodes despite their efforts to avoid them. This study suggests that these recurrent hypoglycemic episodes may actually blunt the sympathoadrenal response and thus reduce the likelihood of death from cardiac arrhythmia. Thus, not having the sympathoadrenal-mediated symptoms during hypoglycemia whether that is due to either hypoglycemia unawareness or to brain utilization of ketones may actually reduce the risk of death. Just to be clear, I am not suggesting that it is okay to have hypoglycemia. Rather, I am saying that hypoglycemia does occur in type 1 diabetes despite one’s best efforts to avoid it and nutritional ketosis from a ketogenic diet may reduce the likelihood of hypoglycemia–induced lethal cardiac arrhythmias. Hopefully, this will be studied in humans in the near future.
In October, I will continue weightlifting and aerobic exercise on alternate days. I have added back two additional exercises: deadlifts and jerks from the rack. My olympic weightlifting takes about 2 hours to complete including warmup, cool down, and stretching to maintain mobility. The aerobic exercise consists of swimming or cycling at low intensity for ≈ 0.5 – 2 hours. The goal is to exercise consistently to maintain insulin sensitivity while avoiding injury and overtraining.
The goal of glycemic management in type 1 diabetes is to keep BG as close to normal (≈ 90 mg/dl) as is safely possible (i.e. avoiding hypoglycemia) to avoid both diabetic complications, a reduction in lifespan, and injury and death from hypoglycemia. For me, a nutrient-dense real-food low carbohydrate ketogenic diet (see blog post #9 for more details) combined with insulin analogs (Humalog/Lantus) have been the best tools so far in accomplishing this goal. I also feel, but cannot prove, that this eating plan and the resulting nutritional ketosis reduces the symptoms of hypoglycemia and protects the brain from the consequences of mild degrees of hypoglycemia (see blog post #12 for more details). Exercise with its resulting varying insulin sensitivity and hormonal changes actually makes glycemic management more difficult, but I both enjoy it and feel exercise has other health and lifespan extending benefits. Hopefully, my BG values and insulin doses are close enough to normal to avoid both a reduction in lifespan and diabetic complications. Only time will tell.
Till next time ….