Separate contribution of diabetes, total fat mass, and fat topography to glucose production, gluconeogenesis, and glycogenolysis

Amalia Gastaldelli, Yoshinori Miyazaki, Maura Pettiti, Emma Buzzigoli, Srikanth Mahankali, Ele Ferrannini, Ralph A. DeFronzo

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


The contribution of increased gluconeogenesis (GNG) to the excessive rate of endogenous glucose production (EGP) in type 2 diabetes (T2DM) is well established. However, the separate effects of obesity (total body fat), visceral adiposity, and T2DM have not been investigated. We measured GNG (by the 2H2O technique) and EGP (with 3-3H-glucose) after an overnight fast in 44 type 2 diabetic and 29 gender/ethnic-matched controls. Subjects were classified as obese (body mass index 30 kg/m2 or greater) or nonobese (body mass index < 30 kg/m2); diabetic subjects were further subdivided according to the severity of fasting hyperglycemia [fasting plasma glucose (FPG) < 9 mM or ≥ 9 mM]. EGP was similar in nondiabetic conirols and T2DM with FPG less than 9 mM but was increased in T2DM with FPG ≥ 9 mM (P < 0.001). Within the diabetic groups, obesity had an independent effect to further increase basal EGP (P < 0.01). In both nonobese diabetic groups, both the percent GNG and gluconeogenic flux were increased, compared with nonobese nondiabetic controls. In both diabetic groups, obesity further increased both percent GNG and gluconeogenic flux. In obese and nonobese T2DM, the increase in gluconeogenic flux was not accompanied by a reciprocal decrease in glycogenolysis, indicating a loss of hepatic autoregulation. By multivariate analysis, gluconeogenic flux was positively correlated with percent body fat, visceral fat, and the fasting plasma free fatty acid and glucose concentrations (all P ≤ 0.02). We conclude that obesity per se, and visceral fat accumulation in particular, as well as poorly controlled diabetes are potent stimuli to augment gluconeogenic flux.

Original languageEnglish (US)
Pages (from-to)3914-3921
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number8
StatePublished - Aug 2004

ASJC Scopus subject areas

  • Biochemistry, medical
  • Endocrinology
  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism


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