Weight gain in type 2 diabetes mellitus

Objective: To investigate the potential causes of weight gain using insulin and combination therapy in type 2 diabetes. Design and Methods: This was an open-label prospective study of 6-month duration. Randomization was performed to insulin monotherapy, insulin and pioglitazone 30 mg daily, or insulin and metformin up to 2000 mg daily. Fifty-seven subjects with poorly controlled type 2 diabetes were enrolled. The goal was to achieve a normal haemoglobin A1c (HbA1c) (< 5.6%). Weight, resting energy expenditure (REE), reported energy intake and total energy expenditure, HbA1c, glycosuria, plasma leptin, ghrelin and adiponectin levels, and body fat were measured. Results: A total of 49 subjects completed the study. At baseline, weight was 89.4 +/- 22.9 kg and HbA1c was 11.1 +/- 1.5%. Weight increased by 7.46, 7.60 and 7.12 kg in the monotherapy, metformin and pioglitazone groups, respectively [p = 0.98 between and < 0.0001 within the groups by repeated measures-analysis of variance (RM-anova)]. HbA1c dropped to 7.8 +/- 0.9% in the monotherapy arm, 7.6 +/- 1.0% in the metformin arm and 7.2 +/- 1.2% in the pioglitazone arm. Reported energy intake decreased. Glycosuria decreased but was not correlated with weight gain, while HbA1c changes were correlated with weight gain. REE per lean mass decreased (p = 0.04 by RM-anova). The subcutaneous fat areas in the insulin monotherapy and pioglitazone arms showed increases (p = 0.02 and 0.004 respectively). Conclusions: Weight gain was probably not due to an increase in food intake, while REE per lean body mass decreased, suggesting a role for increased efficiency in fuel usage due to improved glycaemic control. A drop in glycosuria probably also contributed to weight gain. In the monotherapy and pioglitazone arms, the subcutaneous fat areas increased.