Type 2 Diabetes: Etiology and Reversibility

Roy Taylor, MD, FRCP

Disclosures

Diabetes Care. 2013;36(4):1047-1055. 

In This Article

Reversal of Type 2 Diabetes by Diet Alone

If the rapid changes in metabolism following bariatric surgery are a consequence of the sudden change in calorie balance, the defects in both insulin secretion and hepatic insulin sensitivity of type 2 diabetes should be correctable by change in diet alone. To test this hypothesis, a group of people with type 2 diabetes were studied before and during a 600 kcal/day diet.[21] Within 7 days, liver fat decreased by 30%, becoming similar to that of the control group, and hepatic insulin sensitivity normalized (Fig. 2). The close association between liver fat content and hepatic glucose production had previously been established.[20,22,23] Plasma glucose normalized by day 7 of the diet.

Figure 2.

Effect of a very-low-calorie diet in type 2 diabetes on fasting plasma glucose level (A), basal hepatic glucose production (HGP) (B), and hepatic triacylglycerol content (C). For comparison, data for a matched nondiabetic control group are shown as ◯. Reproduced with permission from Lim et al.21 FFM, fat-free mass.

During this 8-week study, β-cell function was tested by a gold standard method that used a stepped glucose infusion with subsequent arginine bolus.[21] In type 2 diabetes, the glucose-induced initial rapid peak of insulin secretion (the first phase insulin response) typically is absent. This was confirmed at baseline in the study, but the first phase response increased gradually over 8 weeks of a very-low-calorie diet to become indistinguishable from that of age- and weight-matched nondiabetic control subjects. The maximum insulin response, as elicited by arginine bolus during hyperglycemia, also normalized. Pancreas fat content decreased gradually during the study period to become the same as that in the control group, a time course matching that of the increase in both first phase and total insulin secretion (Fig. 3). Fat content in the islets was not directly measured, although it is known that islets take up fat avidly[24] and that islet fat content closely reflects total pancreatic fat content in animal models.[25] Although a cause-and-effect relationship between raised intraorgan fat levels and metabolic effect has not yet been proven, the time course data following the dietary intervention study are highly suggestive of a causal link.[21]

Figure 3.

Effect of an 8-week very-low-calorie diet in type 2 diabetes on arginine-induced maximal insulin secretion (A), first phase insulin response to a 2.8 mmol/L increase in plasma glucose (B), and pancreas triacylglycerol (TG) content (C). For comparison, data for a matched nondiabetic control group are shown as ◯. Replotted with permission from Lim et al.21

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