Impaired Glucose Tolerance Is Associated with Impaired Rise in Basal Insulin Secretion during Sustained Hyperglycemia

Presentation Number: MON 591
Date of Presentation: April 3rd, 2017

Ron T. Varghese*1, Nana Esi Nkuma Kittah1, James C. Andrews1, Chiara Dalla Man2, Robert A Rizza1, Claudio Cobelli2, Aleksey Matveyenko1 and Adrian Vella1
1Mayo Clinic, Rochester, MN, 2University of Padova, Padova, Italy

Abstract

Insulin is secreted in a pulsatile manner into the portal circulation. Diabetes and aging are conditions associated with alterations in pulse amplitude and frequency. Whether the frequency or mass of insulin pulses is altered in people with prediabetes in the fasting or hyperglycemic state is unknown. As part of a series of experiments examining the mechanisms underlying prediabetes, we studied 33 nondiabetic subjects whom 15 had isolated Impaired Glucose tolerance (IGT). The remainder had normal glucose tolerance status (NGT). The groups were matched for age, sex and fasting glucose. After an inpatient, overnight fast, a hepatic vein catheter was placed to allow sampling of hepatic vein insulin at 2 minute intervals. During the latter phase of the experiment glucose was maintained at 150mg/dL during a hyperglycemic clamp. Splanchnic blood flow was measured using indocyanine green. Inter-pulse secretion i.e. basal secretion did not differ during fasting (3.6 ± 0.7 vs. 4.6 ± 0.4 pmol/L/min, p = 0.25, NGT vs. IGT respectively). Similarly, pulse interval (6.7 ± 0.4 vs. 6.4 ± 0.3 min, p = 0.57) and amplitude (15.1 ± 2.5 vs. 17.3 ± 3.3 pmol/L/min, p = 0.60) did not differ between groups during fasting. However, in response to hyperglycemia, basal secretion increased significantly in the NGT group compared to the IGT group (193 ± 9 vs. 141 ± 16, (symmetrical % change, p = 0.01). The net contribution of basal insulin secretion increased in the NGT but not IGT group. This was accompanied by a reciprocal increase in pulse mass in the IGT group (131 ± 13 vs. 109 ± 15, symmetrical % change, p = 0.42). Taken together this data would suggest that the IGT does not alter insulin pulse frequency. However, the amount of basal (inter-pulse) insulin secretion is impaired during sustained hyperglycemia. Future studies will be needed to ascertain the nature of the insulin secretory defect in IGT in response to hyperglycemia.

 

Nothing to Disclose: RTV, NENK, JCA, CD, RAR, CC, AM, AV