The beneficial effect of metformin on ß-cell function in non-obese Chinese subjects with newly diagnosed type 2 diabetes.

AIM: Studies with metformin suggest a favourable change in ß-cell function over sulphonylureas in the early course of obese type 2 diabetes mellitus (T2DM), but it remains unclear whether a similar effect is observed in non-obese individuals. Here we investigated the effects of metformin or glipizide gastrointestinal therapeutics system extended-release formulation (GITS) on ß-cell function in non-obese patients with newly diagnosed T2DM. METHODS: A total of 160 newly diagnosed patients with fasting glucose 7.0-13.0 mmol/L and body mass index <30 kg/m(2) from five centres in China were randomized to metformin or glipizide GITS for 24 weeks. Early insulin secretion [the ratio of area under the curve (AUC) of insulin to glucose during 0-30 min (InsAUC30 /GluAUC30 )] and insulin sensitivity [Matsuda index (ISIM )] were assessed during the standard meal tolerance test before and after therapy. Plasma glucagon-like peptide-1(GLP-1) and glucagon levels were also measured. RESULTS: Metformin improved InsAUC30 /GluAUC30 significantly (from 8.1 ± 0.6 pmol/mmol to 10.7 ± 0.7 pmol/mmol, p < 0.05), comparable to results with glipizide GITS. In the metformin-treated lean (body mass index < 25 kg/m(2) ) subgroup, the increase in ISIM was not significant, but the improvement in InsAUC30 /GluAUC30 was of great magnitude. Increased GLP-1 responses during meal tolerance test and decreased fasting glucagon level were observed after metformin treatment. Correlation analysis showed that the improvement of InsAUC30 /GluAUC30 was associated with the changes in HbA1c (r = -0.374, p = 0.000), ISIM (r = 0.356, p = 0.001), and ΔGLP-10-30 (r = 0.225, p = 0.02). CONCLUSIONS: Metformin improved ß-cell function in non-obese subjects with newly diagnosed T2DM, which was partly independent of the change in insulin sensitivity in these subjects. This study provides evidence-based data to support metformin use in non-obese patients with T2DM as the first-line agent, which can improve both insulin sensitivity and ß-cell function.

Correlated increase of omentin-1 and adiponectin by exenatide, avandamet and dietary change in diet-induced obese rats.

Adipokines omentin-1 and adiponectin have been reported to improve insulin resistance. It is known that insulin sensitizers exenatide, avandamet, or diet change from high-fat to normal chow ameliorate metabolic disorders. However, whether these treatments increase omentin-1 levels in high fat-diet animals and the relationship between omentin- 1 and adiponectin remain largely unknown. We investigated the effect of insulin sensitizers exenatide and avandamet, and of dietary change on these adipokine levels, body weight, and insulin sensitivity in diet-induced obese rats. Obesity was induced in rats by high-fat diet feeding for 8 weeks, and then the rats were given exenatide, avandamet and diet change to normal chow, respectively, for additional 8 weeks. Compared to the high-fat control group, exenatide and avandamet treatment significantly induced adipose gene expression and elevated the circulation levels of omentin-1 and adiponectin, whereas they decreased the leptin gene expression and circulation level, which is associated with improvement of systemic insulin sensitivity and the glucose and lipid profile. Notably, there was a significant positive correlation between omentin-1 and adiponectin in the above regimens, suggesting that omentin-1 and adiponectin may contribute to the insulin-sensitizing effect of exenatide and avandamet.