Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes

J Clin Invest. 1995 Sep;96(3):1261-8. doi: 10.1172/JCI118160.


It was the aim of this study to determine whether FFA inhibit insulin-stimulated whole body glucose uptake and utilization in patients with non-insulin-dependent diabetes. We performed five types of isoglycemic (approximately 11mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin; (c) with insulin plus glycerol; (d) with saline; (e) with saline plus fat/heparin and two types of euglycemic (approximately 5mM) clamps: (a) with insulin; (b) with insulin plus fat/heparin. During these studies, we determined rates of glucose uptake, glycolysis (both with 3[3H] glucose), glycogen synthesis (determined as glucose uptake minus glycolysis), carbohydrate oxidation (by indirect calorimetry) and nonoxidative glycolysis (determined as glycolysis minus carbohydrate oxidation). Fat/heparin infusion did not affect basal glucose uptake, but inhibited total stimulated (insulin stimulated plus basal) glucose uptake by 40-50% in isoglycemic and in euglycemic patients at plasma FFA concentration of approximately 950 and approximately 550 microM, respectively. In isoglycemic patients, the 40-50% inhibition of total stimulated glucose uptake was due to near complete inhibition of the insulin-stimulated part of glucose uptake. Proportional inhibition of glucose uptake, glycogen synthesis, and glycolysis suggested a major FFA-mediated defect involving glucose transport and/or phosphorylation. In summary, fat produced proportional inhibitions of insulin-stimulated glucose uptake and of intracellular glucose utilization. We conclude, that physiologically elevated levels of FFa could potentially be responsible for a large part of the peripheral insulin resistance in patients with non-insulin-dependent diabetes mellitus.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Analysis of Variance
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism*
  • Emulsions
  • Fat Emulsions, Intravenous / administration & dosage
  • Fat Emulsions, Intravenous / pharmacology*
  • Fatty Acids, Nonesterified / blood
  • Female
  • Glucagon / blood
  • Glucose / metabolism*
  • Glucose Clamp Technique
  • Heparin / pharmacology
  • Humans
  • Infusions, Intravenous
  • Insulin, Isophane / administration & dosage
  • Insulin, Isophane / blood
  • Insulin, Isophane / pharmacology*
  • Male
  • Middle Aged
  • Phospholipids
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / pharmacology
  • Safflower Oil
  • Soybean Oil


  • Blood Glucose
  • Emulsions
  • Fat Emulsions, Intravenous
  • Fatty Acids, Nonesterified
  • Phospholipids
  • Recombinant Proteins
  • safflower oil, soybean oil, phospholipid emulsion
  • Insulin, Isophane
  • Soybean Oil
  • Safflower Oil
  • Heparin
  • Glucagon
  • Glucose