ABSTRACT

The two major abnormalities in both insulin-dependent diabetes mellitus (IDDM, type 1) and noninsulin-dependent diabetes mellitus (NIDDM, type 2) are hyperglycemia and dyslipidemia.

I. Introduction ...................................................................................................................... 1145 II. Fatty Acid Composition of Tissue Lipids ......................................................................... 1147 III. Metabolic Effects of Dietary Fatty Acids in Diabetes ...................................................... 1149 A. Unsaturated Fatty Acids .............................................................................................. 1149 B. ω-6 Fatty Acids ........................................................................................................... 1150 C. ω-3 Fatty Acids and Fish Oils .................................................................................... 1151 D. Saturated Fatty Acids .................................................................................................. 1154 E. Trans Fatty Acids ........................................................................................................ 1154 F. Free Fatty Acids .......................................................................................................... 1155 IV. Metabolism of Fatty Acids in Diabetes ............................................................................ 1156 A. Desaturation ................................................................................................................ 1156 B. Elongation ................................................................................................................... 1159 C. Oxidation of Fatty Acids in Diabetes ......................................................................... 1159 D. Binding Proteins and Fatty Acid Oxidation ................................................................ 1160 E. Conversion of EFAs to Eicosanoids ........................................................................... 1161 F. Hormones, Eicosanoids, and Platelet Aggregation in Diabetes .................................. 1163 V. Hormonal Control of Fatty Acid Metabolism in Diabetes ............................................... 1164 VI. Effect of Treatment of Diabetes on Fatty Acid Metabolism ............................................. 1168 A. Diet and Exercise ........................................................................................................ 1168 B. Oral Hypoglycemic Agents ........................................................................................ 1169 C. Oral Agents to Treat Lipid Disorders ......................................................................... 1170 a. Insulin Sensitizers .................................................................................................. 1170 b. Fatty Acid Oxidation Inhibitors ............................................................................. 1171 c. Inhibitors of Lipolysis ...............................................................................................1171 d. Lipid Lowering Agents .............................................................................................1171 D. Metal Ions ................................................................................................................... 1172 a. Chromium .............................................................................................................. 1172 b. Vanadium ............................................................................................................... 1172 c. Molybdenum .............................................................................................................1172 E. Other Agents ............................................................................................................... 1172 VII. Conclusions and Areas for Further Study ......................................................................... 1173 References ................................................................................................................................. 1175

In normal as well as many pathological conditions, the metabolism of carbohydrates, especially glucose, is closely linked to the metabolism of lipids. Insulin is intimately involved in the control of carbohydrate and lipid metabolism. There is either an absolute (in IDDM) or relative (in NIDDM) de< ciency of insulin in diabetes or peripheral resistance to insulin, particularly in obese NIDDM subjects. Thus, in untreated as well as poorly controlled diabetic subjects, hyperlipidemia is often associated with hyperglycemia. Close relationship has also been reported for fasting plasma glucose and fasting and meal-stimulated free fatty acid (FFA) levels (Coates et al., 1994). Newgard and McGarry (1995) recently advanced the concept that important signal for insulin secretion may reside at the linkage between glucose and lipid metabolism, namely the generation of malonyl coenzyme A (CoA) that promotes fatty acid esteri< cation and inhibits oxidation. The treatment of hyperglycemia by both diet and exercise, oral agents (sulfonylureas, biguanides, thiazolidinediones), or insulin often also results in the partial reduction of hyperlipidemia.