Hyperamylinemia is associated with hyperinsulinemia in the glucose-tolerant, insulin-resistant offspring of two Mexican-American non—insulin-dependent diabetic parents

Abstract

Several investigations have presented evidence that amylin inhibits insulin secretion and induces insulin resistance both in vitro and in vivo. However, basal and postmeal amylin concentrations proved similar in non—insulin-dependent diabetes mellitus (NIDDM) patients and controls. Since hyperglycemia may alter both amylin and insulin secretion, we examined basal and glucose-stimulated amylin secretion in eight glucose-tolerant, insulin-resistant Mexican-American subjects with both parents affected with NIDDM (offspring) and correlated the findings with the insulin sensitivity data acquired by an insulin clamp. Eight offspring and eight Mexican-Americans without any family history of diabetes (controls) underwent measurement of fat free mass ( 3H 2O dilution method); 180-minutes, 75-g oral glucose tolerance test (OGTT), and 40-mU/m 2, 180-minute euglycemic insulin clamp associated with 3H-glucose infusion and indirect calorimetry. Fasting amylin was significantly increased in offspring versus controls (11.5 ± 1.4 v 7.0 ± 0.8 pmol/L, P < .05). After glucose ingestion, both total (3,073 ± 257 v 1,870 ± 202 pmol · L −1 min −1, P < .01) and incremental (1,075 ± 170 v 518 ± 124 pmol · L −1 · min −1, P < .05) areas under the curve (AUCs) of amylin concentration were significantly greater in offspring. The amylin to insulin molar ratio was similar in offspring and controls at all time points. Basal and postglucose insulin and C-peptide concentrations were significantly increased in the offspring. No correlation was found between fasting amylin, postglucose amylin AUC or IAUC, and any measured parameter of glucose metabolism during a euglycemic-hyperinsulinemic clamp (total glucose disposal, 7.21 ± 0.73 v 11.03 ± 0.54, P < .001; nonoxidative glucose disposal, 3.17 ± 0.59 v 6.33 ± 0.56, P < .002; glucose oxidation, 4.05 ± 0.46 v 4.71 ± 0.21, P = NS; hepatic glucose production, 0.29 ± 0.16 v 0.01 ± 0.11, P = NS; all mg · min −1 · kg −1 fat-free mass, offspring v controls). In conclusion, these data do not support a causal role for amylin in the genesis of insulin resistance in NIDDM.