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

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-(3)H]-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 (HbA(1c) 10.9 +/- 0.4%, age 50 +/- 3 years, BMI 30 +/- 2 kg/m(2)) 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.

• Authors: Preeti Kishore, Julia Tonelli, Sudha Koppaka, Corina Fratila, Anita Bose, Do-Eun Lee, Kalpana Reddy, Meredith Hawkins
• Journal: Diabetes (Diabetes) Vol. 55 Issue 6 Pg. 1761-8 (Jun 2006) ISSN: 0012-1797 [Print] United States
• PMID: 16731840 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Fatty Acids, Nonesterified
• Niacin
• Sodium Chloride
• Glycerol

Topics

• Adolescent
• Adult
• Aged
• Blood Glucose (metabolism)
• Diabetes Mellitus, Type 2 (metabolism, pathology, physiopathology)
• Fatty Acids, Nonesterified (metabolism, physiology)
• Glucose Clamp Technique
• Glycerol (metabolism)
• Humans
• Hyperglycemia (metabolism, pathology, prevention & control)
• Middle Aged
• Niacin (administration & dosage, pharmacology)
• Sodium Chloride (administration & dosage, pharmacology)
• Time Factors