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Journal of Clinical Endocrinology & Metabolism Vol. 66, No. 5 979-986
doi:10.1210/jcem-66-5-979
Copyright © 1988 by the Endocrine Society.
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Secretion and Hepatic Extraction of Insulin After Weight Loss in Obese Noninsulin-Dependent Diabetes Mellitus*

R. R. HENRY, G. BRECHTEL and K. GRIVER

Department of Medicine, University of California-San Diego La Jolla, California 00000
The San Diego Veterans Administration Medical Center San Diego California 92161

Address requests for reprints to: Robert R. Henry, M.D., Veterans Administration Medical Center, Research Service (V-111G), 3350 La Jolla Village Drive, San Diego, California 92161.

We assessed the effects of weight loss on pancreatic secretion and hepatic extraction of insulin in 11 obese subjects with noninsulin-dependent diabetes mellitus. Weight loss of 15.4 ± 2.0 kg (mean ± SE) resulted in decreased fasting insulin [20.2 ± 2.5 to 9.8 ± 2.5 µU/mL (145 ± 18 to 70 ± 18 pmol/L); P < 0.02] and C-peptide (850 ± 80 to 630 ± 110 pmol/L; P < 0.05) levels. The plasma glucose response to oral glucose and iv glucagon was improved with unchanged peripheral insulin levels. When plasma glucose levels were matched to those before weight loss, peripheral serum insulin and plasma C-peptide responses to iv glucagon were increased and similar to those in obese nondiabetic subjects studied at euglycemia. The total insulin response (area under the curve) to iv glucagon was reduced 30% (P < 0.005), while the total C-peptide response area did not change after weight loss. At matched hyperglycemia, the total response area was enhanced 72% for insulin (P < 0.002) and 64% for C-peptide (P < 0.001). Incremental (above basal) response areas after weight loss did not change for insulin, but increased 66% for C-peptide (P < 0.05). The incremental areas were augmented nearly 2-fold (196%) for insulin (P < 0.01) and 1.7-fold (173%) for C-peptide (P < 0.01) when assessed at matched hyperglycemia. Both basal (7.3 ± 0.5 to 14.1 ± 1.8; P < 0.01) and total stimulated (6.1 ± 0.4 to 8.8 ± 1.4; P < 0.05) C-peptide to insulin molar ratios increased after weight loss.

We conclude that after weight loss in noninsulin-dependent diabetes mellitus, 1) insulin secretion is decreased in the basal state but increased after stimulation; 2) changes in insulin secretion are reflected by peripheral levels of C-peptide but not insulin, due in part to enhanced hepatic insulin extraction; and 3) at matched levels of hyperglycemia insulin secretion is markedly increased and similar to that in obese nondiabetic subjects studied at euglycemia.

* This work was supported in part by Grant PHS RR-00827 from the General Clinical Research Branch, Division of Research Resources, NIH, and the Advanced Healthcare Division of Avadyne, Inc.

Received September 1, 1987.




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