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.


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.
Jacob
A N
AN
Department of Internal Medicine, University of Texas Southwestern Medical Center in Dallas, Dallas, TX 75390-8858, USA.
Salinas
K
K
Adams-Huet
B
B
Raskin
P
P
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D004359:Drug Therapy, Combination; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006029:Glycosuria / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood; D000077205:Pioglitazone; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use; D015430:Weight Gain / Q000502:physiology*
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D008687:Metformin; D036361:Peptide Hormones; D000077205:Pioglitazone; D045162:Thiazolidinediones