The recent report by Ryan et al. (1) demonstrated that in newly diagnosed type 2 diabetes, a short course of intensive insulin therapy successfully laid a foundation for long-term good glycemic control and suggested that the only predictors that could be maintained on diet alone in the long term were those concerned with the ease with which glycemic control could be achieved. We agree with their strategy of short-term intensive insulin therapy to restore β-cell insulin secretion and/or insulin action that is impaired by glucose toxicity in cases of severe newly diagnosed type 2 diabetes.
Glucose toxicity has two different aspects: impaired insulin secretion (2) and decreased insulin action (3). In their report, however, the authors did not precisely discuss which mechanism (insulin secretion or action) was predominantly recovered or not rescued in better responders (diet-alone group) and lesser responders (oral hypoglycemic agent [OHA]/insulin group) with intensive insulin therapy in a short period. According to their results, both the area under the curve (AUCi) (their Fig. 1B) and the insulin-to-glucose ratios at the 30-min point in a post–insulin therapy oral glucose tolerance test (OGTT) were not different between the diet-success and diet-failure groups, suggesting that restoration of insulin secretion was similar in both groups. Although the authors selected newly diagnosed type 2 diabetic subjects with similar hyperglycemia, it is important to assess whether the disease duration after onset of diabetes was the same in both groups, because duration of diabetes may be a key predictor of the reserve of insulin secretion.
With regard to insulin resistance, the authors did not provide the clinical parameters of insulin resistance such as homeostasis model assessment of insulin resistance (HOMA-IR). They showed that with the post–insulin therapy OGTT, the fasting insulin-to-glucose ratio was higher in the diet-failure group, despite a higher fasting glucose level (fasting insulin level was not shown), than in the diet-success group, meaning greater insulin resistance in the diet-failure group. The BMI values of each group before insulin therapy were similar, but it is possible that a type II error was present because of very small sample numbers. Moreover, the BMI in the diet-only group was significantly reduced at 6 months, while that in the OHA/insulin group did not change throughout the study. Taken together with their results, we consider that insulin sensitivity or resistance rather than insulin secretion may deeply influence the need for OHAs or insulin after short-term intensive insulin therapy in their study. Additional larger prospective studies are needed to use intensive insulin therapy in clinical practice in newly diagnosed type 2 diabetes.
