This column is about an open access article published online in Diabetologia 09 June 2011. I found it in my search for answers to questions I raised in #86, “Beta Cell Function and Insulin Sensitivity,” here. Unfortunately, I will not learn the answers from my new endo since he fired me as reported here in #87, “Optimal Blood Lipid Levels.” The Diabetologia article is “Reversal of type 2 diabetes: normalization of beta cell function in association with decreased pancreas and liver triacylglycerol.” The authors, E. L Lim, K. G Holingsworth, B. S. Aribisala, M. J. Chen, J. C. Mathers and R. Taylor, all of whom are associated with institutes at Newcastle University in the UK, begin their abstract thus:
“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.”
The plot thickens, however, with an exposition of this theme in the “Introduction,” from which I delete only footnotes:
“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 reverses type 2 diabetes by normalizing both the beta cell function and insulin sensitivity. We examined the restoration of first-phase and total insulin response as well as hepatic and peripheral insulin sensitivity. Additionally, to examine the mechanistic basis of observed outcomes, we quantified the changes in fat content in the pancreas and liver.”
This last paragraph is particularly notable for the word “alone,” and even more so when you consider the study participants’ diet. It was basically 2.1 MJ/day (510 kcal/day for non-Brits) of Optifast, which is a “liquid diet formula” manufactured by Nestlé Nutrition. This was supplemented with “three portions of non-starchy vegetables” such that total energy intake was about 2.5 MJ (600kcal)/day. The authors aver that “Nestlé UK provided the Optifast on request but had no other input into the research.” The authors declare “no duality of interest.” And I believe them.
Another reason why this is notable is that the formulation of Optifast used in this study was 46.4% carbohydrate, 32.5% protein and 20.1% fat. And that was before the 3 servings (0.4 MJ or +/-90 calories) of vegetables, essentially all carbs, was added. So the results of this study 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. Type 2s take note. The paradox is about to get 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. Key metrics were taken using state-of-art measurement techniques (e.g. magnetic resonance imaging) and study practices. All the protocols for exclusion, ethics, etc. were followed. The results (selected only to omit arcane statistics): “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.”
The implications of this are still reverberating in my brain. This paper is pretty “brainy” and certainly way above my pay grade, but I wonder why many others who are qualified to discuss it aren’t. Could it be a “duality of interest”? Or maybe our clinicians are too busy figuring out the latest medical reimbursement rules and insurance regulations. Who knows!!!