Tuesday, May 14, 2019

Retrospective #88: “Reversal of Type 2 Diabetes”

“Reversal of type 2 diabetes: normalization of beta cell function in association with decreased pancreas and liver triacylglycerol,” appeared in the ADA’s online Diabetologia on 09 June 2011. The authors are all with Newcastle University (UK). The corresponding author is R. Taylor. The Abstract, Introduction and Conclusions follow:
Aims/hypothesis: Type 2 diabetes is regarded as inevitably progressive with irreversible beta cell failure. The hypothesis was tested that both beta cell failure and insulin resistance can be reversed by dietary restriction of energy intake.”
“Introduction: Type 2 diabetes has long been regarded as a chronic progressive condition, capable of amelioration but not cure. A steady rise in plasma glucose occurs irrespective of the degree of control or type of treatment. Beta cell function declines linearly with time, and after 10 years more than 50% of individuals require insulin therapy. The underlying changes in beta cell function have been well described, and beta-cell mass decreases steadily during the course of type 2 diabetes. Overall, there is strong evidence that type 2 diabetes is inexorably progressive, with a high likelihood of insulin therapy being eventually required to maintain glycaemic control.
However, type 2 diabetes is clearly reversible following bariatric surgery. The normalization of plasma glucose concentration follows within days of surgery, long before major weight loss has occurred, and it has become widely assumed that the protective effects of gastrointestinal surgery are mediated by altered secretion of incretin hormones. Improved control of blood glucose in type 2 diabetes by moderate energy restriction has been demonstrated by others. We have hypothesized that the profound effect of a sudden negative energy balance on the metabolism could explain the post-bariatric surgery effect and, specifically, that the decrease in the intracellular fatty acid concentrations in the liver would lead to a lower export of lipoprotein triacylglycerol [i.e., TG or triglycerides] to the pancreas, with the release of beta cells from the chronic inhibitory effects of excess fatty acid exposure. This study was designed to test the hypothesis that acute negative energy balance alone [emphasis added] reverses type 2 diabetes by normalizing both the beta cell function and insulin sensitivity.”
The study design is notable for the use of the word “alone” – especially when you consider the participants’ diet. It was 1 MJ/day (510 kcal/day for non-Brits) of Optifast, which is a “liquid diet formula” by Nestlé Nutrition. This was supplemented with “three portions of non-starchy vegetables.” Total energy intake was 2.5 MJ (600kcal)/day.
This is notable I think because the formulation of Optifast used in this study was 46.4% carbohydrate, 32.5% protein and 20.1% fat. Those macro percents do not include the 3 servings (0.4 MJ or +/-90 calories) of vegetables, essentially all carbs. So, the results are all the more striking since the participants during the 8-week duration of the program ate a high carb, high protein, low fat, mostly liquid diet. And the paradox is about to get even starker.
“Eleven people with type 2 diabetes (aver. age 49.5, BMI 33.6) were studied before and after 1, 4, and 8 weeks. An age-, sex-, and weight-matched group of eight non-diabetic participants was studied also. “After 1 week of restricted energy intake, fasting plasma glucose normalized in the diabetic group from 9.2 to 5.9mmol/l (166 to 106mg/dl US). Insulin suppression of hepatic glucose output improved from 43% to 74% vs. 68% for the control group. Hepatic triacylglycerol (TG) content fell from 12.8% in the diabetic group to 2.9% by week 8; The first-phase insulin response increased during the study period…and approached control values; Maximal insulin response became supernormal at 8 weeks vs. controls; pancreatic triacylglycerol decreased from 8.0% to 6.2%, compared to 6.0% in the control group.”
Conclusions/interpretation: Normalization of both beta cell function and hepatic insulin sensitivity in type 2 diabetes was achieved by dietary energy restriction alone (emphasis mine). This was associated with decreased pancreatic and liver triacylglycerol stores. The abnormalities underlying type 2 diabetes are reversible by reducing dietary energy intake.”
Hmmm. Calorie Restriction alone can reverse Type 2 diabetes. This paper is pretty “brainy” and certainly above my pay grade, but I wonder why others who are qualified to discuss it aren’t.  I am confident that there is no “duality of interest” here. Maybe the answer is our clinicians are too busy learning about the latest pill or injection to treat Type 2 diabetes, or maybe they’re trying to figure out the current reimbursement rules and insurance regulations.

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