Very Low Calorie Diet: a Quick Therapeutic Tool to Improve Beta Cell Function in Morbidly Obese Patients With Type 2 Diabetes Mellitus

In obese patients with type 2 diabetes mellitus, lifestyle modifications resulting in weight loss improve or even normalize blood glucose. This beneficial effect on glucose control is accounted for by improvements in both insulin secretion and insulin sensitivity. However, the metabolic effects of caloric restriction per se may be, at least in part, independent of body weight reduction. Furthermore, improved control of blood glucose in type 2 diabetes by very low calorie diet (VLCD) for 40 days was documented during the first 10 days of caloric restriction, when weight loss was still trivial. When caloric intake was increased after weight reduction, plasma glucose increased in spite of no weight rebound. The mechanism(s) underlying these early improvements caused by a VLCD in patients with type 2 diabetes have been assessed only in a few studies. Thus, a fall in hepatic glucose production and a modest increase in insulin sensitivity were reported as early as 7 days after a very low calorie diet. A subsequent study replicated the effects of short term VLCD on hepatic glucose production, but not on whole body insulin sensitivity.

As to beta cell function, earlier studies reported an apparent improvement in insulin secretion rate during the oral glucose tolerance test (OGTT), after short-term application of a VLCD. However, no formal investigation of beta cell sensitivity to glucose was performed, and, since glucose was given per os, other factors (e.g. incretins, ghrelin) might have been involved. One study reported an improvement of beta cell response during hyperglycemic clamps, i.e. excluding gut related factors, after 8 weeks of a VLCD and during a weight stabilization period, i.e. in the absence of the negative energy balance signal. Furthermore, by study design, it did not explore the first phase secretory response to glucose.

Quite recently, Lim and coll. reported that, in patients with type 2 diabetes, a VLCD markedly improved glucose control in a few days, and that ameliorations of both liver insulin sensitivity and beta cell sensitivity to glucose were the mechanisms primarily involved. Prolongation of the VLCD for 8 weeks led to an apparent remission of diabetes. This and most of earlier mechanistic studies were performed in patients with BMI around 30-35, in whom, according to most current guidelines, metabolic surgery should not be considered a treatment option. In patients with type 2 diabetes undergoing bariatric surgery, improvements in glucose control and in beta cell function are detectable before a significant weight loss occurred, and there is a strong suggestion that intestinal bypass procedures may have metabolic effects (e.g. on beta cell) that are independent of their effect on body weight, possibly involving the incretin axis. Furthermore, remission rates of type 2 diabetes following bariatric surgery as high as 70-80% have been reported.

Thus, it would be important to know whether in severely obese patients with type 2 diabetes, who are potential candidates for metabolic surgery, a short term VLCD exerts effects similar to those reported in less obese patients.

The investigators therefore performed a preliminary proof-of-concept study to assess whether in severely obese patients with type 2 diabetes 7 days of VLCD affect glucose control through changes in either beta cell function or insulin sensitivity or both.