MASSIVE WEIGHT-LOSS DOES NOT RESTORE NORMAL INSULIN SECRETORY PULSES IN OBESE PATIENTS WITH TYPE-2 (NON-INSULIN-DEPENDENT) DIABETES-MELLITUS

To study the effects of massive weight loss on insulin secretion, we a nalysed the oscillations of fasting peripheral insulin levels in obese patients who underwent vertical banded gastroplasty as treatment for morbid obesity. Patients were studied before and 6 months after surger y. Serial measurements of plasma free insulin levels were obtained in duplicates from 0 to 60 min at one-minute intervals. Insulin levels we re then analysed by autocorrelation and Fourier transformation. In nor mal controls and obese patients, the first oscillatory insulin compone nt was detected between 10 and 14 min. Compared to obese controls (n = 4), overt Type 2 diabetic patients (n = 4) had reduced amplitudes of insulin pulses and no oscillatory component. These defects were not as pronounced in patients with impaired glucose tolerance (IGT) after an oral glucose tolerance test (OGTT) (n = 5). When detected, the period icity of the oscillations occurred at different periods. In 3/5 [GT pa tients, the first positive peak of correlation was found at 13.3 +/- 2 .3 min. Weight loss (mean +/- SD) after 6 months was 24.3 +/- 3.7 for subjects with normal glucose tolerance (NGT), 37.9 +/- 9 for those wit h [GT and 29.8 +/- 5 kgs for Type 2 diabetic subjects. After weight lo ss, insulin oscillatory activity was detected in 4/5 IGT patients, wit h a period of 13 +/- 3 min. Weight loss did not reverse the defects ob served in obese diabetic patients despite a significant reduction in p eripheral insulin levels from 28.6 +/- 6 to 15.6 +/- 6 mU/l (p < 0.05) . insulin values remained higher than in obese controls (7.82 +/- 2, p < 0.05), and Type 2 patients remained mildly hyperglycaemic. These fi ndings indicate that beta-cell activity is abnormal in Type 2 diabetic patients. The absence of modification after weight loss suggests that inherent beta-cell defects may contribute to hyperglycaemia.