Summary
Insulin resistance is present in patients suffering from lipoatrophic syndromes long before the onset of diabetes mellitus. Thus, the decreased peripheral glucose disposal may not be the only mechanism of hyperglycaemia. The kinetic parameters of glucose homeostasis were evaluated in six young females aged 15, 16, 18, 19 and 24 years with generalized lipoatrophy; one patient was studied both at 12 and 15 years. Insulin resistance was evaluated in vivo by the hyperinsulinaemic euglycaemic clamp (3–4 insulin infusion rates from 1 to 100 mU/kg · min). All patients showed a rightward shift of the dose-response curve, indicating decreased insulin sensitivity. In two patients, maximal glucose disposal was moderately decreased, while in five patients it was dramatically reduced (3.6–6.9 mg/kg · min). Fasting plasma glucose was variable (4.3–18.3 mmol/l) and did not correlate with peripheral glucose disposal rates. Hepatic glucose production, measured by infusion of [6,6-2H] glucose, varied from 1.7 to 8.3 mg/kg · min and was significantly correlated with fasting plasma glucose. The overproduction of glucose despite basal hyperinsulinism suggested hepatic insulin resistance, which was confirmed by the abnormal response to constant unlabelled glucose infusion (2 mg/kg · min) in five patients. In conclusion, impaired glucose tolerance seems to develop in generalized lipoatrophy with aggravated peripheral insulin resistance. The present data show that fasting hyperglycaemia is mainly the consequence of increased hepatic glucose production.
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Lawrence RD (1946) Lipodystrophy and hepatomegaly with diabetes, lipaemia, and other metabolic disturbances: a case throwing light on the action of insulin. Lancet I: 724–731
Kahn CR, Flier JS, Bar RS et al. (1976) The syndromes of insulin resistance and acanthosis nigricans. N Engl J Med 294: 739–745
Oseid S (1973) Studies in congenital generalized lipodystrophy (Seip-Berardinelli syndrome). Acta Endocrinol 72: 475–494
Bowen HF, Moorhouse JA (1973) Glucose turnover and disposal in maturity-onset diabetes. J Clin Invest 52: 3033–3045
De Fronzo RA (1988) The triumvirate: β-cell, muscle, liver. A collusion responsible for IDDM. Diabetes 37: 667–687
Campbell PJ, Mandarino LJ, Gerich JE (1988) Quantification of the relative impairment in actions of insulin on hepatic glucose production and peripheral glucose uptake in non-insulin-dependent diabetes mellitus. Metabolism 37: 15–21
Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37: 1595–1607
Ruvalcaba RH, Samols E, Kelley VC (1965) Lipoatrophic diabetes. I. Studies concerning endocrine function and carbohydrate metabolism. Am J Dis Child 109: 279–286
Samaan NA, Craig JW (1969) Serum insulin and growth hormone in lipoatrophic diabetes. Metabolism 18: 460–468
Senior B, Loridan L (1969) Fat cell function and insulin in a patient with generalized lipoatrophy. J Pediatr 47: 972–975
Naito C, Togawa K (1974) A possible role of circulating lipoprotein-triglycerides in the increase in concentration of free fatty acids and in insulin resistance in “total” lipodystrophy. J Clin Endocrinol Metab 39: 1030–1037
Huseman C, Johanson A, Varma M, Blizzard RM (1978) Congenital lipodystrophy: an endocrine study in three siblings. I. Disorders of carbohydrate metabolism. J Pediatr 93: 221–226
Keenan BS, Kirkland RT, Garber AJ et al. (1980) The effect of diet upon carbohydrate metabolism, insulin resistance, and blood pressure in congenital total lipoatrophic diabetes. Metabolism 29: 1214–1224
Beylot M, Sautot G, Laville M, Cohen R (1988) Metabolic studies in lipoatrophic diabetes: mechanisms of hyperglycemia and evidence of resistance to insulin of lipid metabolism. Diabete Métab 14: 20–24
Tsukahara H, Kikuchi K, Kuzuya H et al. (1988) Insulin resistance in a boy with congenital generalized lipodystrophy. Pediatr Res 24: 668–672
Cohen P, Harel C, Bergman R et al. (1990) Insulin resistance and acanthosis nigricans: evidence for a postbinding defect in vivo. Metabolism 39: 1006–1011
Robert JJ, Magre J, Reynet C, Darmaun D, Picard J, Capeau J (1990) In vivo and in vitro characterization of insulin resistance in three cases of lipoatrophic diabetes. Diabète Métab 16: 240–247
Rizza RA, Mandarino LJ, Gerich JE (1981) Dose-response characteristics for effects of insulin on production and utilization of glucose in man. Am J Physiol 240: E630-E639
Bier DM, Arnold KJ, Sherman WR, Holland WH, Holmes WF, Kipnis DM (1977) In vivo measurement of glucose and alanine metabolism with stable isotopic tracer. Diabetes 26: 1005–1015
Wolfe RR, Allsop JR, Burke JF (1979) Glucose metabolism in man: responses to intravenous glucose infusion. Metabolism 28: 210–219
Darmaun D, Cirillo D, Koziet J, Chauvet D, Young VR, Robert JJ (1988) Whole body glucose kinetics in type I diabetes studied with (6,6-2H) and (U-13C) glucose and the artificial B-cell. Metabolism 37: 491–498
Magre J, Reynet C, Capeau J, Blivet MJ, Picard J (1988) In vitro studies of insulin resistance in six patients with lipoatrophic diabetes: evidence for heterogeneous post-binding defects. Diabetes 37: 421–428
Magre J, Grigorescu F, Reynet C et al. (1989) Tyrosine-kinase defect of the insulin receptor in cultured fibroblasts from patients with lipoatrophic diabetes. J Clin Endocrinol Metab 69: 142–150
Van der Vorm ER, Kuipers A, Bonenkamp JW et al. (1993) Patients with lipodystrophic diabetes mellitus of the Seip-Berardinelli type, express normal insulin receptors. Diabetologia 36: 172–174
Desbois C, Magré J, Amselem S, Goossens M, Capeau J, Besmond C (1993) Lipoatrophic diabetes: exclusion of the insulin-receptor gene. Exp Clin Endocrinol 101 [Suppl]: 352–354
Klip A, Pâquet MR (1990) Glucose transport and glucose transporters in muscle and their metabolic regulation. Diabetes Care 13: 228–243
Farese RV, Standaert ML, Arnold T et al. (1992) The role of protein kinase C in insulin action. Cellular Signalling 4: 133–143
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Robert, J.J., Rakotoambinina, B., Cochet, I. et al. The development of hyperglycaemia in patients with insulin-resistant generalized lipoatrophic syndromes. Diabetologia 36, 1288–1292 (1993). https://doi.org/10.1007/BF00400807
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DOI: https://doi.org/10.1007/BF00400807