Father of Insulin Resistance – Gerald Reaven

Dr Gerald Reaven of Stanford Medicine, may be my new hero. Dr Reaven:

Jerry is credited with developing the insulin suppression test, the first quantitative method to measure insulin-mediated glucose uptake in humans. Using this technique, he established the importance of insulin resistance in human disease, and importantly, in type 2 diabetes.

[Added 2017-11-30]: Dr Reaven delivered the seminal paper on the subject of Insulin Resistance at the Banting Lecture in 1988 (Role of Insulin Resistance in Human Disease).

And –

Dr. Reaven challenged the then prevailing theory that defective insulin secretion adequately explained the hyperglycemia of T2DM, postulating that insulin resistance might be as, or more, important.

He is a prolific writer of studies. Here’s just one (All obese individuals are not created equal: insulin resistance is the major determinant of cardiovascular disease in overweight/obese individuals) of his papers.

[Added 2017-11-30]: Another hero is Dr Kraft.

Related to the Kraft Test (Kristine Faerch, Adam Hulman, Thomas P.J. Solomon. Heterogeneity of Pre-diabetes and Type 2 Diabetes: Implications for Prediction, Prevention and Treatment Responsiveness. Current Diabetes Reviews, Volume 12 , Issue 1 , 2016).

We aimed to examine heterogeneity in glucose response curves during an oral glucose tolerance test with multiple measurements and to compare cardiometabolic risk profiles between identified glucose response curve groups. We analyzed data from 1,267 individuals without diabetes from five studies in Denmark, the Netherlands and the USA. Each study included between 5 and 11 measurements at different time points during a 2-h oral glucose tolerance test, resulting in 9,602 plasma glucose measurements. Latent class trajectories with a cubic specification for time were fitted to identify different patterns of plasma glucose change during the oral glucose tolerance test. Cardiometabolic risk factor profiles were compared between the identified groups. Using latent class trajectory analysis, five glucose response curves were identified. Despite similar fasting and 2-h values, glucose peaks and peak times varied greatly between groups, ranging from 7–12 mmol/L, and 35–70 min. The group with the lowest and earliest plasma glucose peak had the lowest estimated cardiovascular risk, while the group with the most delayed plasma glucose peak and the highest 2-h value had the highest estimated risk. One group, with normal fasting and 2-h values, exhibited an unusual profile, with the highest glucose peak and the highest proportion of smokers and men. The heterogeneity in glucose response curves and the distinct cardiometabolic risk profiles may reflect different underlying physiologies. Our results warrant more detailed studies to identify the source of the heterogeneity across the different phenotypes and whether these differences play a role in the development of type 2 diabetes and cardiovascular disease.

An Association Study Against LCHF

There is one study that looks bad for LCHF. It looks bad mostly based on the name of the study rather than the science (American Journal of Epidemiology, Volume 134, Issue 6, 15 September 1991, Pages 590–603. High-Fat, Low-Carbohydrate Diet and the Etiology of Non-Insulin-dependent Diabetes Mellitus: The San Luis Valley Diabetes Study. Julie A. Marshall Richard F. Hamman Judith Baxter).

The study (1990) suggests that High Fat diets are associated with onset of non-insulin dependent diabetes mellitus.

The findings support the hypothesis that high-fat, low-carbohydrate diets are associated with the onset of non-insulin-dependent diabetes mellitus in humans.

The problem is that, at least in the abstract, there’s no evidence that the people were on anything at all related to a Low Carbohydrate diet. That was inferred based on the High Fat. But you don’t need to go any farther than your local McD’s to know that french fries are both high in fat and high in carbs.

When you look close you can see that the study was an association study not a Randomized Control Trial. Association does not prove causation. Just because people who got diabetes at lower carb/higher fat diets doesn’t mean that the diet caused the diabetes.

This paper (Risk Factors for Non-Insulin Dependent Diabetes. Marian Rewers, MD, PhD, and Richard F. Hamman, MD, DrPH) lists quite a few studies on this subject (Table 9.6) and includes a helpful comment:

There are substantial methodological problems in measuring exposure to behavioral factors such as physical inactivity and diet pp 179-181. Most studies have used a single recording of activity or diet as a measure of exposure. While it is assumed that such point estimates are correlated with habitual exercise or intake, it is uncertain what period of time is necessary to obtain the most valid estimates

 

Status 2016-08-24

Saw an unbelievable sight when I woke up at 5 AM. My blood glucose reading was 100. I can’t remember ever seeing 100 when I was pumping Insulin.

Weight is down a couple of lbs in the past couple of days. Wish I had started tracking from the start. I am down 16 lbs from Aug 5th. My rough guess is about 20 lbs so far since I started IF on July 31.

My blood sugar readings average in the past 3 days has been 115. That’s down from my previous 7 day average of 125. Also, I did switch to the Bayer Contour Next and it reads a bit higher than the OneTouch UltraLink I was using before.

So, all of the trends are good. I’ve been trying hard on the diet to eat higher fat and lower protein. Seems to be paying off. Combining LCHF with IF looks to me to be the cure-all for Type 2 Diabetes. At least in me. Your mileage, as they say, may vary.

Still taking Metformin 2x, 625 mg. Stopped taking  Avorstatin. Considering stop taking Niacin since it is listed as raising blood sugar when taken in combination with Metformin.

 

Caloric Restriction vs Intermittent Fasting

A 2011 Meta-Analysis (Obes Rev. 2011 Jul;12(7):e593-601. Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss? Varady KA.) looked at the difference between calorie restriction and Intermittent Fasting. The study looked at 18 trials and examined the results across each of them. 11 of the trials were for Caloric Restriction alone and 7 were for Intermittent Fasting.

The study termed both diets as Calorie Restriction because they both result in less net calories. The fast day wasn’t an actual fast, but a caloric restriction to 25% of a normal day. The difference is on the feed day the subjects could eat whatever they wanted to eat.

The conclusion was interesting.

In sum, intermittent CR and daily CR diets appear to be equally as effective in decreasing body weight, fat mass, and potentially, visceral fat mass. However, intermittent restriction regimens may be superior to daily restriction regimens in that they help conserve lean mass at the expense of fat mass. These findings add to the growing body of evidence showing that intermittent CR may be implemented as another viable option for weight loss in overweight and obese populations.

Another great result for Intermittent Fasting!

I know as a dieter which I would prefer. If you told me I had to diet every other day and could eat what I want on the other day and that I would do just as well as if I had dieted every day that doesn’t sound like a hard choice at all.

Another study reached similar conclusions (Am J Clin Nutr. 2009 Nov;90(5):1138-43. Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and cardioprotection in obese adults. Varady KA1, Bhutani S, Church EC, Klempel MC.).

Here’s a third study on Alternate Day Fasting (Journal of Diabetes & Metabolic Disorders201312:4 The effects of modified alternate-day fasting diet on weight loss and CAD risk factors in overweight and obese women. Samira Eshghinia and Fatemeh Mohammadzadeh).

This is a great look at the evidence in favor of Intermittent Fasting (SA JOURNAL OF DIABETES & VASCULAR DISEASE. Intermittent fasting: a dietary intervention for prevention of diabetes and cardiovascular disease? James E Brown,Michael Mosley, Sarah Al).

The conclusion is worth reading:

The use of intermittent fasting offers the potential to improve weight loss and enhance the cardiovascular health of overweight and obese individuals with type 2 diabetes and reduces cardiovascular risk. This type of intervention is cost-effective and associated with a low risk of adverse events.

 

Alcohol and LCHF+IF (Aug 23, 2016)

Lost my taste for alcohol and haven’t wanted one in a couple of days. Haven’t had one either. Wanted to want to have a beer last night and I know that the low calories I had eaten for dinner would leave me hungry so I tried to talk myself into going and getting a beer. Couldn’t do it.

Not sure if it is my desire to keep down carbs or just not enjoying the taste as much when I am on ketosis.

Surprised that it is noon and I am not feeling particularly hungry since my dinner was just a double paddy burger without a bun at Five Guys last night.

Starting to enjoy being in ketosis.

 

One Week Off Insulin (Aug 23, 2016)

I’ve been off Insulin for a full week now.

So why am I still alive? After all, I needed 100 units a day on the average just one month ago. But here I am. Still Alive!

So did I just decide to ignore my Blood Glucose levels and am I on the edge of dying? Hardly. I’m still checking multiple times a day – mostly now in disbelief at how well my blood sugar is being regulated by my body. My high today was 124 and my low so far today is 109. I never got numbers like that before day after day on Insulin.

For dinner last night I took the kids out to Five Guys Burgers and Fries. I skipped the fries. I ate a bunch of peanuts and more importantly had my burger “bunless”. The choice to replace the bun with lettuce was a good one since it took away about 40 grams of carbs and left about 1 gram. The fat ratio was good and the jalapenos, etc didn’t add much to the carb count but they did add to the flavor.

All of that made my Blood Sugar at 103 around bedtime.

Addendum : Still taking Metformin. Not out of the T2D woods yet.

Weight Loss Numbers

Weight Loss on LC-HF+IF is a very strange thing. It goes in real spurts. Yesterday I dropped two lbs. Last week I had two days in a row where I lost five lbs each day. Most days I am about the same or down just a fraction of a lb.

I am down 14 lbs from a couple of week ago. I didn’t weigh myself at the start so I don’t know what weight I was to start with. I think I weighted 292 on the work scale (clothed of course).

Two or Five meals a day?

There’s a lot of hype around the eat less but eat more often, i.e., “eat five meals a day” concept. But is there science behind it?

Here’s an interesting comparison of two meals a day vs five meals a day in overweight women (Treatment of “Refractory Obesity” with a Diet of Five Meals a Day).

The study took women who had trouble losing weight and put them on a five meal a day eating plan. Sounds great, who would not want such a plan? And the women who had previously plateaued lost weight.

New headline “Eat Five Meals a Day and Lose Weight”.

Let’s look at the details.

The five meals a day were five meals of 200 calories per meal. Hardly a meal for most people. Not much more than a snack.

And the adherence was very poor. Although the diet was only 12 weeks long four of the 39 women dropped out and 21 of the patients admitted they were not able to adhere to the diet. Only 14 of the women could adhere to the diet.

The study notes that

A Man With Two Clocks – Measuring Blood Sugar

They say that a man with two clocks never knows what time it is. That’s because two clocks never agree.

Well I am in that situation. I own three Blood Glucose meters. One I leave at work and one I carry around with me, the OneTouch(R) UltraLink(R). I leave the one at work, the OneTouch(R) UltraMini(R), just in case I forget to bring the one I carry around. I like the one I carry around better since it had wireless to my pump. But now that I am not using the Insulin pump it really doesn’t matter which one I use.

The problem with the one for the pump is that, while it is wireless, it is only wireless between itself and the pump. The meter I use at work is small but not wireless.

Enter my third meter, Bayer Contour Next USB, and my current confusion about my Blood Glucose numbers. I got the Contour meter when I got my recent pump replacement. The Contour meter has a USB connector so I was thinking about changing over to that meter. But I measured my Blood Glucose this morning and the number was relatively high (still a great number for being off the pump but larger than the UltraLink number I had just measured. I re-measured with both meters. The UltraLink got a number that was close to its first number and the Contour got the exact same number (never had that happen with the UltraLink).

The UltraLink had 124 and the Contour had 141. Not a huge difference but enough to make me scratch my head. I didn’t have my work meter with me for a third measurement. Wish I had.

I will compare the three meters later today.

The ISO standard is pretty fat for meters (Evaluation of 12 Blood Glucose Monitoring Systems for Self-Testing: System Accuracy and Measurement Reproducibility):

In DIN EN ISO 15197:2003, system accuracy is defined as closeness of agreement between a measurement result and the accepted reference value determined by the manufacturer’s measurement procedure. According to this norm, at least 95% of the system measurement results shall fall within ±15 mg/dL of the results of the manufacturer’s measurement procedure at BG concentrations <75 mg/dL and within ±20% at BG concentrations ≥75 mg/dL. In the recently published revision ISO 15197:2013,5 criteria for system accuracy are more stringent, with at least 95% of the system measurement results within ±15 mg/dL of the results of the manufacturer’s measurement procedure at BG concentrations <100 mg/dL and within ±15% at BG concentrations≥100 mg/dL.

So if the true value was 130 it could be 15% higher or lower on the meter of 19.5 units off. (149.5 high and 101.5 low). Wow, that’s a pretty big range.

Looking at the test results, all of the meters tended to show higher numbers than the true number. This itself is reassuring. They didn’t have the same models that I use, but similar models from the same manufacturer show:

This makes me conclude that the meter manufacturers design their products for safety. They’d rather give a higher number than a lower number. If they gave too low a number someone might correct too much. Unfortunately, that strategy may be working against T2DM folks who are on the pump. They may end up giving too much of a correction.

Looking at the Bayer vs the OneTouch without actually crunching the numbers the Bayer looks like it produces tighter bunched results. I think I will switch over.

Comparison of Various Diets

A two-year long comparison of three diets was done in Israel (N Engl J Med 2008; 359:229-241. Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet. Iris Shai, R.D., Ph.D., Dan Schwarzfuchs, M.D., Yaakov Henkin, M.D., Danit R. Shahar, R.D., Ph.D., Shula Witkow, R.D., M.P.H., Ilana Greenberg, R.D., M.P.H., Rachel Golan, R.D., M.P.H., Drora Fraser, Ph.D., Arkady Bolotin, Ph.D., Hilel Vardi, M.Sc., Osnat Tangi-Rozental, B.A., Rachel Zuk-Ramot, R.N., et al., for the Dietary Intervention Randomized Controlled Trial (DIRECT) Group). Although the focus was on weight loss they looked at other lipids, etc. The participants were:

We conducted the trial between July 2005 and June 2007 in Dimona, Israel, in a workplace at a research center with an on-site medical clinic. Recruitment began in December 2004. The criteria for eligibility were an age of 40 to 65 years and a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of at least 27, or the presence of type 2 diabetes (according to the American Diabetes Association criteria) or coronary heart disease, regardless of age and BMI.

the mean age was 52 years and the mean BMI was 31. Most participants (86%) were men.

Patients were assigned one of three diets, Low-Carb, Mediterranean, and Low-Fat.

So, what happened to their weight?

The overall weight changes among the 322 participants at 24 months were −2.9±4.2 kg for the low-fat group, −4.4±6.0 kg for the Mediterranean-diet group, and −4.7±6.5 kg for the low-carbohydrate group.

Other measurements were

The waist circumference decreased by a mean of 2.8±4.3 cm in the low-fat group, 3.5±5.1 cm in the Mediterranean-diet group, and 3.8±5.2 cm in the low-carbohydrate group (P=0.33 for the comparison among groups).

Didn’t eating all that fat, meat and cheese cause them a cholesterol ratio problem? Not so much. Again LC came out on top since their HDL (good) number went up.

HDL cholesterol (Figure 3A) increased during the weight-loss and maintenance phases in all groups, with the greatest increase in the low-carbohydrate group (8.4 mg per deciliter [0.22 mmol per liter], P<0.01 for the interaction between diet group and time), as compared with the low-fat group (6.3 mg per deciliter [0.16 mmol per liter]).

Overall, the ratio of total cholesterol to HDL cholesterol (Figure 3D) decreased during both the weight-loss and the maintenance phases. The low-carbohydrate group had the greatest improvement, with a relative decrease of 20% (P=0.01 for the interaction between diet group and time), as compared with a decrease of 12% in the low-fat group.

The conclusions followed:

In this 2-year dietary-intervention study, we found that the Mediterranean and low-carbohydrate diets are effective alternatives to the low-fat diet for weight loss and appear to be just as safe as the low-fat diet. In addition to producing weight loss in this moderately obese group of participants, the low-carbohydrate and Mediterranean diets had some beneficial metabolic effects, a result suggesting that these dietary strategies might be considered in clinical practice and that diets might be individualized according to personal preferences and metabolic needs.

And.

The similar caloric deficit achieved in all diet groups suggests that a low-carbohydrate, non–restricted-calorie diet may be optimal for those who will not follow a restricted-calorie dietary regimen. The increasing improvement in levels of some biomarkers over time up to the 24-month point, despite the achievement of maximum weight loss by 6 months, suggests that a diet with a healthful composition has benefits beyond weight reduction.

As a note:

Labeling the “low-carbohydrate” diet as such is questionable, since 40 to 42% of calories were from carbohydrates from month 6 to month 24, and data regarding ketosis support this view.

Here is another great study on the same subject (N Engl J Med 2003; 348:2074-2081. A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity. Frederick F. Samaha, M.D., Nayyar Iqbal, M.D., Prakash Seshadri, M.D., Kathryn L. Chicano, C.R.N.P., Denise A. Daily, R.D., Joyce McGrory, C.R.N.P., Terrence Williams, B.S., Monica Williams, B.S., Edward J. Gracely, Ph.D., and Linda Stern, M.D.).

 

Metallic Taste in your Mouth?

If you have done a Low Carb High Fat (LCHF) diet for more than a few days you entered ketosis and likely experienced that metallic taste in your mouth.  That taste is acetone. It is the marker that you are in ketosis. It’s being produced in your lungs (Acetone as biomarker for ketosis buildup capability–a study in healthy individuals under combined high fat and starvation diets).

Using a Fisher LDS pair-wise comparison, higher significant levels of acetone buildup were found for diets with 79% fat content and 90% fat content vs. 29% fat content (with p = 0.00159**, and 0.04435**, respectively), with no significant difference between diets with 79% fat content and 90% fat content.

Also,

In addition, independent of the diet, a significantly higher ketone buildup capability of subjects with higher resting energy expenditure (R(2) = 0.92), and lower body mass index (R(2) = 0.71) was observed during FK.