Is regulation of postabsorptive endogenous glucose production (egp) abnormal in people with n1ddm?

S. D. Wja, M. F. Niclsen, A. Basu, D. Turk, A. Alzaid, R. A. Rizza

Research output: Contribution to journalArticlepeer-review

Abstract

Controversy exists as to whether regulation of EGP is abnormal in NIDDM in the postabsorptivc state. To address this question, EGP measured in 14 NIDDM subjects following an overnight fast was compared to that in l 5 nondiabetic subjects matched for age, gender, and body mass index. To avoid the confounding effects of hyperglycemia, insulin was infused overnight so that postabsorptive glucose concentrations were comparable in the diabetic and nondiabetic subjects (5.4 ±0.1 vs. 5.0 ±0.1 mmol/L). This resulted in higher (p < 0.01) plasma insulin concentrations in the diabetic than in the nondiabetic subjects (143 ±8 vs 48±6 pmol/L) but no differences in glucagon concentrations (92 ±1 vs. 97 ±4 ng/L). Despite euglycemia and hyperinsulinemia, EGP remained higher (p < 0.001} in the diabetic than in the nondiabetic subjects (940 ±41 vs, 713 ±35 nmol/min). To determine whether the differences in EGP persist when endogenous hormone secretion is inhibited by somatostatin, EGP measured in 17 additional NIDDM subjects was compared to that in 19 matched nondiabetic subjects. Glucagon and growth hormone were intravenously replaced. Sufficient insulin was infused in both the diabetic and nondiabetic subjects so as to maintain euglycemia (5.1 ±0.1 vs. 5.1 ±0.1 mmol/L).. Once again, this resulted in higher (p <0.01) plasma insulin concentrations (134 ±15 vs. 85 ±7 pmol/L) in the diabetic than nondiabetic subjects; C-pcptide (0.03 ±0.01 vs. 0.04±0.01 nmol/L) and glucagon (106±4 vs. 109 ± 5 ng/L) concentrations were the same in both groups. In contrast to what was observed in the absence of somatostatin, the higher insulin concentrations were now associated with rates of EGP that were no longer higher in the diabetic than in the nondiabetic subjects (805 ±30 vs. 846 ±29 mol/min). We conclude that a) EGP is elevated in NIDDM independent of the confounding effects of hyperglycemia , b) the elevation in EGP is no longer evident when endogenous hormone secretion is inhibited by somatostatin and insulin is infused peripherally ; however c) the higher circulating insulin concentrations in the NIDDM subjects indicate that insulin resistance persists despite the comparable rates of EGP, and d) these alterations in EGP cannot be solely due to differences in plasma glucagon concentrations since they are comparable in both groups, both in the presence and absence of somatostatin. Thus, regulation of EGP is abnormal in people with NIDDM in the postabsorptive state.

Original languageEnglish (US)
Pages (from-to)223a
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - 1996

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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