Time-dependent effects of free fatty acids on glucose effectiveness in type 2 diabetes

Preeti Kishore, Julia Tonelli, Sudha Koppaka, Corina Fratila, Anita Bose, Do Eun Lee, Kalpana Reddy, Meredith Hawkins

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Impaired effectiveness of glucose to suppress endogenous glucose production (EGP) is an important cause of worsening hyperglycemia in type 2 diabetes. Elevated free fatty acids (FFAs) may impair glucose effectiveness via several mechanisms, including rapid changes in metabolic fluxes and/or more gradual changes in gene expression of key enzymes or other proteins. Thus, we examined the magnitude and time course of effects of FFAs on glucose effectiveness in type 2 diabetes and whether glucose effectiveness can be restored by lowering FFAs. Glucose fluxes ([3-3H]-glucose) were measured during 6-h pancreatic clamp studies, at euglycemia (5 mmol/l glucose, t = 0-240 min), and hyperglycemia (10 mmol/l, t = 240-360 min). We studied 19 poorly controlled subjects with type 2 diabetes (HbA1c 10.9 ± 0.4%, age 50 ± 3 years, BMI 30 ± 2 kg/m2) on at least two occasions with saline (NA- group) or nicotinic acid (NA group) infusions for 3, 6, or 16 h (NA3h, NA6h, and NA16h groups, respectively) to lower FFAs to nondiabetic levels. As a reference group, glucose effectiveness was also assessed in 15 nondiabetic subjects. There was rapid improvement in hepatic glucose effectiveness following only 3 h of NA infusion (NA3h = 31 ± 6% suppression of EGP with hyperglycemia vs. NA- = 8 ± 7%; P < 0.01) and complete restoration of glucose effectiveness after 6 h of NA (NA6h = 41 ± 8% suppression of EGP; P = NS vs. nondiabetic subjects). Importantly, the loss of hepatic glucose effectiveness in type 2 diabetes is completely reversible upon correcting the increased FFA concentrations. A longer duration of FFA lowering may be required to overcome the chronic effects of increased FFAs on hepatic glucose effectiveness.

Original languageEnglish (US)
Pages (from-to)1761-1768
Number of pages8
JournalDiabetes
Volume55
Issue number6
DOIs
StatePublished - Sep 11 2006

Keywords

  • EGP
  • Endogenous glucose production
  • FFA
  • Free fatty acid

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Kishore, P., Tonelli, J., Koppaka, S., Fratila, C., Bose, A., Lee, D. E., Reddy, K., & Hawkins, M. (2006). Time-dependent effects of free fatty acids on glucose effectiveness in type 2 diabetes. Diabetes, 55(6), 1761-1768. https://doi.org/10.2337/db05-0988