TY - JOUR
T1 - Effect of Mild Physiologic Hyperglycemia on Insulin Secretion, Insulin Clearance, and Insulin Sensitivity in Healthy Glucose-Tolerant Subjects
AU - Merovci, Aurora
AU - Tripathy, Devjit
AU - Chen, Xi
AU - Valdez, Ivan
AU - Abdul-Ghani, Muhammad
AU - Solis-Herrera, Carolina
AU - Gastaldelli, Amalia
AU - Defronzo, Ralph A.
N1 - Publisher Copyright:
© 2020 by the American Diabetes Association.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - The aim of the current study was to evaluate the effect of sustained physiologic increase of ∼50mg/dLinplasma glucose concentration on insulin secretion in normal glucose-tolerant (NGT) subjects. Twelve NGT subjects without family history of type 2 diabetes mellitus (T2DM; FH-) and 8 NGT with family history of T2DM (FH+) received an oral glucose tolerance test and two-step hyperglycemic clamp (100 and 300 mg/dL) followed by intravenous arginine bolus before and after 72-h glucose infusion. Fasting plasma glucose increased from 94 ± 2 to 142 ± 4 mg/dL for 72 h. First-phase insulin secretion (0–10 min) increased by 70%, while second-phase insulin secretion during the first (10–80 min) and second (90–160 min) hyperglycemic clamp steps increased by 3.8-fold and 1.9-fold, respectively, following 72 h of physiologic hyperglycemia. Insulin sensitivity during hyperglycemic clamp declined by 30% and ∼55% (both P < 0.05), respectively, during the first and second hyperglycemic clamp steps. Insulin secretion/insulin resistance (disposition) index declined by 60% (second clamp step) and by 62% following arginine (both P < 0.005) following 72-h glucose infusion. The effect of 72-h glucose infusion on insulin secretion and insulin sensitivity was similar in subjects with and without FH of T2DM. Following 72 h of physiologic hyperglycemia, metabolic clearance rate of insulin was markedly reduced (P < 0.01). These results demonstrate that sustained physiologic hyperglycemia for 72 h 1) increases absolute insulin secretion but impairs β-cell function, 2) causes insulin resistance, and 3) reduces metabolic clearance rate of insulin.
AB - The aim of the current study was to evaluate the effect of sustained physiologic increase of ∼50mg/dLinplasma glucose concentration on insulin secretion in normal glucose-tolerant (NGT) subjects. Twelve NGT subjects without family history of type 2 diabetes mellitus (T2DM; FH-) and 8 NGT with family history of T2DM (FH+) received an oral glucose tolerance test and two-step hyperglycemic clamp (100 and 300 mg/dL) followed by intravenous arginine bolus before and after 72-h glucose infusion. Fasting plasma glucose increased from 94 ± 2 to 142 ± 4 mg/dL for 72 h. First-phase insulin secretion (0–10 min) increased by 70%, while second-phase insulin secretion during the first (10–80 min) and second (90–160 min) hyperglycemic clamp steps increased by 3.8-fold and 1.9-fold, respectively, following 72 h of physiologic hyperglycemia. Insulin sensitivity during hyperglycemic clamp declined by 30% and ∼55% (both P < 0.05), respectively, during the first and second hyperglycemic clamp steps. Insulin secretion/insulin resistance (disposition) index declined by 60% (second clamp step) and by 62% following arginine (both P < 0.005) following 72-h glucose infusion. The effect of 72-h glucose infusion on insulin secretion and insulin sensitivity was similar in subjects with and without FH of T2DM. Following 72 h of physiologic hyperglycemia, metabolic clearance rate of insulin was markedly reduced (P < 0.01). These results demonstrate that sustained physiologic hyperglycemia for 72 h 1) increases absolute insulin secretion but impairs β-cell function, 2) causes insulin resistance, and 3) reduces metabolic clearance rate of insulin.
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U2 - 10.2337/db20-0039
DO - 10.2337/db20-0039
M3 - Article
C2 - 33033064
AN - SCOPUS:85099073162
SN - 0012-1797
VL - 70
SP - 204
EP - 213
JO - Diabetes
JF - Diabetes
IS - 1
ER -