Summary
Hypertriglyceridaemia, which is frequently seen in Type 2 (non-insulin-dependent) diabetes mellitus, is associated with insulin resistance. The connection between hypertriglyceridaemia and insulin resistance is not clear, but could be due to substrate competition between glucose and lipids. To address this question we measured glucose and lipid metabolism in 39 Type 2 diabetic patients with hypertriglyceridaemia, i. e. mean fasting serum triglyceride level equal to or above 2 mmol/l (age 59±1 years, BMI 27.4±0.5 kg/m2, HbA1c8.0±0.2%, serum triglycerides 3.2±0.2 mmol/l) and 41 Type 2 diabetic patients with normotriglyceridaemia, i. e. mean fasting serum triglyceride level below 2 mmol/l (age 58±1 years, BMI 27.0±0.7 kg/m2, HbA1c7.8±0.2 %, serum triglycerides 1.4±0.1 mmol/l). Insulin sensitivity was assessed using a 340 pmol·(m2)−1· min−1 euglycaemic insulin clamp. Substrate oxidation rates were measured with indirect calorimetry and hepatic glucose production was estimated using a primed (25 μCi)-constant (0.25 μCi/min) infusion of [3-3H]-glucose. Suppression of lipid oxidation by insulin was impaired in patients with hypertriglyceridaemia vs patients with normal triglyceride levels (3.5±0.2 vs 3.0±0.2μmol·kg−1· min−1; p<0.05). Stimulation of glucose disposal by insulin was reduced in hypertriglyceridaemic vs normotriglyceridaemic patients (27.0±1.3 vs 31.9±1.6 μmol·kg−1·min−1; p<0.05) primarily due to impaired glucose storage (9.8±1.0 vs 14.6±1.4μmol·kg−1·min−1; p<0.01). In contrast, insulinstimulated glucose oxidation was similar in patients with hypertriglyceridaemia and in patients with normal triglyceride concentrations (16.9±0.8 vs 17.2±0.7μmol·kg−1·min−1). Hepatic glucose production in the basal state and during the clamp did not differ between the two groups. We conclude therefore that oxidative substrate competition between glucose and lipids does not explain insulin resistance associated with hypertriglyceridaemia in Type 2 diabetes. The question remains whether the reduced nonoxidative glucose disposal observed in the patients with hypertriglyceridaemia is genetically determined or a consequence of increased lipid oxidation.
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Greenfield M, Kolterman O, Olefsky J, Reaven GM (1980) Mechanism of hypertriglyceridaemia in diabetic patients with fasting hyperglycaemia. Diabetologia 18: 441–446
Mancini MA, Rivellese A, Rubba P, Riccardi G (1980) Plasma lipoproteins in maturity onset diabetes. Nutr Metab 24: 65–71
Barret-Connor E, Grundy SM, Holdbrook MJ (1982) Plasma lipids and diabetes mellitus in adult community. Am J Epidemiol 115: 657–663
West KM, Ahuja MMS, Bennett PH et al. (1983) The role of circulating glucose and triglyceride concentrations and their interactions with other ‘risk factors’ as determinants of arterial disease in nine diabetic population samples from the WHO Multinational Study. Diabetes Care 6: 575–578
Laakso M, Vuotilainen H, Sarlund H, Aro A, Pyörälä K, Penttilä I (1985) Serum lipids and lipoproteins in middle-aged non-insulin-dependent diabetics. Atherosclerosis 56: 271–281
Taskinen M-R (1990) Hyperlipidemia in diabetes. In: Betteridge DJ (ed) Lipid and lipid disorders. Baillière's clinical endocrinology and metabolism, vol 4. Baillière Tindall, London Philadelphia Sydney Tokyo Toronto, pp 743–775
DeFronzo RA (1988) The triumvirate: β-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 37: 667–687
Steiner G, Morita S, Vranic M (1980) Reistance to insulin but not to glucagon in lean human hypertriglyceridemics. Diabetes 29: 899–905
Bazelmans J, Nestel PJ, Nolan C (1983) Insulin induced glucose utilization influences triglyceride metabolism. Clin Sci 64: 511–516
Reaven GM, Meheab K, Villaume C, Drouin P, Debry G (1983) Plasma glucose and insulin responses to oral glucose in nonobese subjects and patients with endogenous hypertriglyceridemia. Metabolism 32: 447–450
Yki-Järvinen H, Taskinen M-R (1988) Interrelationships among insulin's antilipolytic and glucoregulatory effects and plasma triglycerides in non-diabetic and diabetic patients with endogenous hypertriglyceridemia. Diabetes 37: 1271–1278
McKane WR, Stevens AB, Woods R, Andrews WJ, Henry RW, Bell PM (1990) The assessment of hepatic and peripheral insulin sensitivity in hypertriglyceridemia. Metabolism 39: 1240–1245
Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet I: 785–789
Ferrannini E, Barrett EJ, Bevilacqua S, DeFronzo RA (1983) Effect of fatty acids on glucose production and utilization in man. J Clin Invest 72: 1737–1747
Thiebaud D, DeFronzo RA, Jacot E et al. (1985) Effect of longchain triglyceride infusion on glucose metabolism in man. Metabolism 31: 1128–1136
Bevilacqua S, Buzzigoli G, Bonadonna R et al. (1990) Operation of Randle's cycle in patients with NIDDM. Diabetes 39: 383–389
Bonadonna R, Zych K, Boni C, Ferrannini E, De Fronzo RA (1989) Time dependence of the interation between lipid and glucose in humans. Am J Physiol 257: E49-E56
Boden G, Jadali F, White J et al. (1991) Effects of fat on insulinstimulated carbohydrate metabolism in normal men. J Clin Invest 88: 960–966
Alberti KGMM, Gries FA (1988) Management of non-insulindependent diabetes mellitus in Europe: a consensus view. Diabetic Med 5: 275–281
DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quanifying insulin secretion and resistance. Am J Physiol 237: E214-E223
Ferrannini E (1989) The theoretical basis for indirect calorimetry: a review. Metabolism 37: 287–301
Meriläinen PT (1987) Metabolic monitor. Int J Clin Monitor Comput 4: 167–177
Tappy L, Owen O, Boden G (1988) Effect of hyperinsulinemia on urea pool size and substrate oxidation rates. Diabetes 37: 1212–1216
Coleman TG, Manning RD Jr, Norman A Jr et al. (1972) Dynamics of water-isotope distribution. Am J Physiol 223: 1371–1375
Miles JR, Glasscock J, Aikens J, Gerich J, Haymond M (1983) A microfluorometric method for the determination of free fatty acids in plasma. J Lipid Res 24: 96–99
Radziuk J, Norwich KH, Vranic M (1978) Experimental validation of measurements of glucose turnover in nonsteady state. Am J Physiol 234: E84-E93
Cobelli C, Mari A, Ferrannini E (1987) Non-steady state: error analysis of Steele's model and development for glucose kinetics. Am J Physiol 252: E679-E689
Dixon WJ (ed) (1988) BMDP statistical software manual. University of California Press, Berkeley
Abbott, WGH, Lillioja S, Young AA et al. (1988) Relationships between plasma lipoprotein concentrations and insulin action in an obese hyperinsulinemic population. Diabetes 36: 897–904
Garg A, Helderman JH, Koffler M, Ayuso R, Rosenstock J, Raskin P (1988) Relationship between lipoprotein levels and in vivo insulin action in normal young white men. Metabolism 37: 982–987
Laakso M, Sarlund H, Mykkänen L (1990) Insulin resistance is associated with varying degrees of glucose tolerance. Arteriosclerosis 10: 223–231
Bieger WP, Michel G, Barwich D, Bhiel K, Wirth A (1984) Diminished insulin receptors on monocytes and erythrocytes in hypertriglyceridemia. Metabolism 33: 982–987
Grundy SM (1984) Pathogenesis of hypertriglyceridemia in man. In: Carlsson LA, Olsson AG (eds) Treatment of hyperlipoproteinemia. Raven Press, New York, pp 21–34
Groop L, Bonadonna R, Shand M, Petrides A, DeFronzo RA (1991) Role of free fatty acids and insulin in determining free fatty acid and lipid oxidation in man. J Clin Invest 87: 83–89
Wititsuwannakul D, Kim J (1977) Mechanism of palmityl coenzyme A inhibition of liver glycogen synthase. J Biol Chem 252: 7812–7817
Shen D-C, Fuh MTT, Shieh S-M, Chen Y-DI, Reaven GM (1991) Effect of gemfibrozil treatment in sulfonylurea-treated patients with non-insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 73: 503–510
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Widén, E., Ekstrand, A., Saloranta, C. et al. Insulin resistance in Type 2 (non-insulin-dependent) diabetic patients with hypertriglyceridaemia. Diabetologia 35, 1140–1145 (1992). https://doi.org/10.1007/BF00401367
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DOI: https://doi.org/10.1007/BF00401367