Insulin Resistance

Himsworth HP . Diabetes mellitus: Its differentiation into insulin sensitive and insulin insensitive types. Lancet 1936; i: 127–30.

Himsworth HP Kerr RB . Insulin-sensitive and insulin-insensitive types of diabetes mellitus. Clin Sci 1939; 4: 119–52.

National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979; 28: 1039–57.

World Health Organization Expert Committee on Diabetes Mellitus. Second Report. Technical Report Series 646. Geneva: World Health Organization, 1980.

Yalow RS Berson SA . Immunoassay of endogenous plasma insulin in man. J Clin Invest 1960; 39: 1157–75.

Yalow RS Berson SA . Plasma insulin concentration in nondiabetic and early diabetic subjects—determination by a new sensitive immunoassay technique. Diabetes 1960; 9: 254–60.

Goldstein BJ . Syndromes of extreme insulin resistance. In: Kahn CR Weir GC , eds. Joslin's Diabetes Mellitus 13th ed. Philadelphia: Lea & Febiger, 1994; 282–99.

Shen S-W Reaven GM Farquhar JW . Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes. J Clin Invest 1970; 49: 2151–60.

Reaven GM . Insulin resistance in noninsulin-dependent diabetes mellitus—does it exist and can it be measured? Am J Med 1983; 74 (suppl 1A): 3–17.

Reaven GM . Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–607.

Kahn CR . Insulin resistance, insulin insensitivity, and insulin unresponsiveness: A necessary distinction. Metabolism 1978; 27: 1893–902.

Hollenbeck C Reaven GM . Variation in insulin-stimulated glucose uptake in healthy individuals with normal glucose tolerance. J Clin Endocrinol Metab 1987; 64: 1169–73.

Yki-Järvinen H. Role of insulin resistance in the pathogenesis of NIDDM. Diabetologia 1995; 38: 1378–88.

Moller DE Flier JS . Insulin resistance—mechanisms, syndromes and implications. N Engl J Med 1991; 325: 938–48.

Sobey WJ Beer SF Carrington CA Clark PMS Frank BH Gray IP Sensitive and specific two-site immunoradiometric assays for human insulin, proinsulin, 65–66 split and 32–33 split proinsulins. Biochem J 1989; 260: 535–41.

Rhodes CJ Alarcón C. What β-cell defect could lead to hyperproinsulinaemia in NIDDM? Some clues from recent advances made in understanding the proinsulin-processing mechanism. Diabetes 1994; 43: 511–7.

Gerich JE . Is muscle the major site of insulin resistance in type 2 (noninsulin-dependent) diabetes mellitus? Diabetologia 1991; 34: 607–10.

DeFronzo RA Bonadonna RC Ferrannini E. Pathogenesis of NIDDM. A balanced overview. Diabetes Care 1992; 15: 318–68.

DeFronzo RA Ferrannini E Simonson DC . Fasting hyperglycaemia in noninsulin-dependent diabetes mellitus: Contribution of excessive hepatic glucose production and impaired tissue glucose uptake. Metabolism 1989; 38: 387–95.

Beck-Nielsen H Hother-Nielsen O Vaag A Alford F. Pathogenesis of type 2 (noninsulin-dependent) diabetes mellitus: The role of skeletal muscle glucose uptake and hepatic glucose production in the development of hyperglycaemia. A critical comment. Diabetologia 1994; 37: 217–21.

Reaven GM . The fourth musketeer—from Alexandre Dumas to Claude Bernard. Diabetologia 1995; 38: 3–13.

Olefsky J Farquhar JW Reaven GM . Relationship between fasting plasma insulin level and resistance to insulin-mediated glucose uptake in normal and diabetic subjects. Diabetes 1973; 22: 507–13.

Matthews DR Hosker JP Rudenski AS Naylor BA Treacher DF Turner RC . Homeostasis model assessment: Insulin resistance and β-cell function from plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–9.

Phillips DIW Clark PM Hales CN Osmond C. Understanding oral glucose tolerance: Comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med 1994; 11: 286–92.

Wareham NJ Phillips DIW Byrne CD Hales CN . The 30 minute insulin incremental response in an oral glucose tolerance test as a measure of insulin secretion. Diabet Med 1995; 12: 931.

Galvin P Ward G Walters J Pestell R Koschmann M Vaag A A simple method for quantitation of insulin sensitivity and insulin release from an intravenous glucose tolerance test. Diabet Med 1992; 9: 921–8.

Bergman RN Ider Y Ziya Bowden CR Cobelli C. Quantitative estimation of insulin sensitivity. Am J Physiol 1979; 236: E667–77.

Bergman RN Phillips LS Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: Measurement of insulin sensitivity and β cell glucose sensitivity from the response to intravenous glucose. J Clin Invest 1981; 68: 1456–67.

Hosker JP Matthews DR Rudenski AS Burnett MA Darling P Bown EG Continuous infusion of glucose with model assessment: Measurement of insulin resistance and β-cell function in man. Diabetologia 1985; 28: 401–1.

DeFronzo RA Tobin JD Andres R. Glucose clamp technique: A method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214–23.

Mitrakou A Vuorinen-Markkola H Raptis G Toft I Mokan M Strumph P Simultaneous assessment of insulin secretion and insulin sensitivity using a hyperglycaemic clamp. J Clin Endocrinol Metab 1992; 75: 379–82.

Harano Y Ohgaku S Hidaka H Haneda K Kikkawa R Shigeta Y Glucose, insulin and somatostatin infusion for the determination of insulin sensitivity. J Clin Endocrinol Metab 1977; 45: 1124–7.

Nagulesparan M Savage PJ Unger RH Bennett PH . A simplified method using somatostatin to assess in vivo insulin resistance over a range of obesity. Diabetes 1979; 28: 980–3.

Proietto J Harewood M Aitken P Nankervis A Caruso G Alford F. Validation of a practical in vivo insulin dose-response curve in man. Metabolism 1982; 31: 354–61.

Groop LC Bonnadonna RC DelPrato S Ratheiser K Zyck K Ferrannini E Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus—evidence for multiple sites of insulin resistance. J Clin Invest 1989; 84: 205–13.

Schade DS Eaton RP . Dose-response to insulin in man: Differential effects on glucose and ketone body regulation. J Clin Endocrinol Metab 1977; 44: 1038–53.

Saccà L Sherwin R Hendler R Felig P. Influence of continuous physiologic hyperinsulinaemia on glucose kinetics and counterregulatory hormones in normal and diabetic humans. J Clin Invest 1979; 63: 849–57.

Hale PJ Black E Nattrass M. Metabolic effects of low-dose incremental insulin infusion in diabetic man. Horm Metab Res 1986; 18: 129–33.

Akinmokun A Selby PL Ramaiya K Alberti KGMM . The short insulin tolerance test for determination of insulin sensitivity: A comparison with the euglycaemic clamp. Diabet Med 1992; 9: 432–7.

Bonora E Moghetti P Zancanaro C Cigolini M Querena M Cacciatori V Estimates of in vivo insulin action in man: Comparison of insulin tolerance tests with euglycaemic and hyperglycaemic glucose clamp studies. J Clin Endocrinol Metab 1989; 68: 374–8.

Polonsky KS Given BD Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest 1988; 81: 442–8.

Lang DA Matthews DR Peto J Turner RC . Cyclic oscillation of basal plasma glucose and insulin concentrations in human beings. N Engl J Med 1979; 301: 1023–7.

Hollenbeck CB Chen Y-DI Reaven GM . Relationship between the plasma insulin response to oral glucose and insulin-stimulated glucose utilisation in normal subjects. Diabetes 1984; 33: 460–3.

Steil GM Murray J Bergman RN Buchanan TA . Repeatability of insulin sensitivity and glucose effectiveness from the minimal model. Implications for study design. Diabetes 1994; 43: 1365–71.

Groop LC Widén E Ferrannini E. Insulin resistance and insulin deficiency in the pathogenesis of type 2 (non-insulin-dependent) diabetes mellitus: Errors of metabolism or of methods? Diabetologia 1993; 36: 1326–31.

Czech M. The nature and regulation of the insulin receptor: Structure and function. Ann Rev Physiol 1985; 47: 357–81.

Kolterman OG Gray RS Griffin J Burstein P Insel J Scarlett JA Receptor and postreceptor defects contribute to the insulin resistance in noninsulin-dependent diabetes. J Clin Invest 1981; 68: 957–69.

Shia MA Pilch PF . The beta-subunit of the insulin receptor is an insulin-activated protein kinase. Biochemistry 1983; 22: 717–21.

Kahn CR White MF . The insulin receptor and the molecular mechanism of insulin action. J Clin Invest 1988; 82: 1151–6.

Sun XJ Rothenberg P Kahn CR Backer JM Araki E Wilden PA Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 1991; 352: 73–7.

Araki E Lipes MA Patti ME Bruning JC Haag B 3rd Johnson RS Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 1994; 372: 186–90.

Koch CA Anderson D Moran MF Ellis C Pawson T. SH2 and SH3 domains: Elements that control interactions of cytoplasmic signalling proteins. Science 1991; 252: 668–74.

Tanti JF Grémeaux T Van Obberghen E Le Marchand-Brustel Y. Insulin receptor substrate 1 is phosphorylated by the serine kinase activity of phosphatidylinositol 3-kinase. Biochem J 1994; 304: 17–21.

Lavan BE Lienhard GE . Insulin signalling and the stimulation of glucose transport. Biochem Soc Trans 1994; 22: 676–80.

Denton RM Tavare JM . Does mitogen-activated-protein kinase have a role in insulin action? The cases for and against. Eur J Biochem 1995; 227: 597–611.

Lee C-H Li W Nishimura R Zhou M Batzer AG Myers MG Jr Nck associates with the SH2 domain docking protein IRS-1 in insulin-stimulated cells. Proc Natl Acad Sci USA 1993; 90: 11713–7.

Cheatham B Kahn CR . Insulin action and the insulin signalling network. Endocr Rev 1995; 16: 117–42.

White MF . The insulin signalling system and the IRS proteins. Diabetologia 1997; 40 (Suppl 2): S2–17.

Yamauchi T Tobe K Tamemoto H Ueki K Kaburagi Y Yamamoto-Honda R Insulin signalling and insulin actions in the muscles and livers of insulin-resistant, insulin receptor substrate 1-deficient mice. Mol Cell Biol 1996; 16: 3074–84.

Thorens B. Glucose transporters in the regulation of intestinal, renal, and liver glucose fluxes. Am J Physiol 1996; 270: G541–53.

Kahn BB . Lilly lecture 1995. Glucose transport: Pivotal step in insulin action. Diabetes 1996; 45: 1644–54.

Yang J Clarke JF Ester CJ Young PW Kasuga M Holman GD . Phosphatidylinositol 3-kinase acts at an intracellular membrane site to enhance GLUT4 exocytosis in 3T3-L1 cells. Biochem J 1996; 313: 125–31.

Marshall S Garvey WT Traxinger RR . New insights into the metabolic regulation of insulin action and insulin resistance: Role of glucose and amino acids. FASEB J 1991; 5: 3031–6.

Karam JH . Reversible insulin resistance in noninsulin-dependent diabetes mellitus. Horm Metab Res 1996; 28: 440–4.

Krook A O'Rahilly S. Mutant insulin receptors in syndromes of insulin resistance. Baillière's Clin Endocrinol Metab 1996; 10: 97–122.

King GL Kahn CR Rechler MM Nissley SP . Direct demonstration of separate receptors for growth and metabolic activities of insulin and multiplication-stimulating activity (an insulin-like growth factor) using antibodies to the insulin receptor. J Clin Invest 1980; 66: 130–40.

Taylor SI . Receptor defects in patients with extreme insulin resistance. Diabetes Metab Rev 1985; 1: 171–202.

Geffner ME Golde DW . Selective insulin action on skin, ovary and heart in insulin resistant states. Diabetes Care 1988; 11: 500–5.

Boyns DR Crossley JN Abrams ME Jarrett RJ Keen H. Oral glucose tolerance and related factors in a normal population sample. I. Blood sugar, plasma insulin, glyceride and cholesterol measurements and the effects of age and sex. BMJ 1969; i: 595–8.

Welborn TA Stenhouse NS Johnstone CG . Factors determining serum insulin response in a population sample. Diabetologia 1969; 5: 263–6.

Hale PJ Wright JV Nattrass M. Differences in insulin sensitivity between normal men and women. Metabolism 1985; 34: 1133–8.

Yki-Järvinen H. Sex and insulin sensitivity. Metabolism 1984; 33: 1011–5.

Amiel SA Sherwin RS Simonson DC Lauritano AA Tamborlane WV . Impaired insulin action in puberty—a contributory factor to poor glycaemic control in adolescents with diabetes. N Engl J Med 1986; 315: 215–9.

Rowe JW Minaker KL Pallotta JA Flier JS . Characterization of the insulin resistance of aging. J Clin Invest 1983; 71: 1581–7.

Fink RI Kolterman OG Griffin J Olefsky JM . Mechanisms of insulin resistance of aging. J Clin Invest 1983; 71: 1523–35.

Coon PJ Rogus EM Drinkwater D Muller DC Goldberg AP . Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age. J Clin Endocrinol Metab 1992; 75: 1125–32.

Kohrt WM Kirwan JP Staten MA Bourey RE King DS Holloszy JO . Insulin resistance in aging is related to abdominal obesity. Diabetes 1993; 42: 273–81.

Boden G Chen X DeSantis RA Kendrick Z. Effects of age and body fat on insulin resistance in healthy men. Diabetes Care 1993; 16: 728–733.

Lohmann D Liebold F Heilmann W Senger H Pohl A. Diminished insulin response in highly trained athletes. Metabolism 1978; 27: 521–4.

King DS Dalsky GP Clutter WE Young DA Staten MA Cryer PE Effects of lack of exercise on insulin secretion and action in trained subjects. Am J Physiol 1988; 254: E537–42.

Devlin JT Horton ES . Effects of prior high-intensity exercise on glucose metabolism in normal and insulin-resistant men. Diabetes 1985; 34: 973–9.

Devlin JT Hirshman M Horton ED Horton ES . Enhanced peripheral and splanchnic insulin sensitivity in NIDDM men after single bout of exercise. Diabetes 1987; 36: 434–9.

Bogardus C. Insulin resistance in the pathogenesis of NIDDM in Pima Indians. Diabetes Care 1993; 16 (Suppl 1): 228–31.

Banerji MA Lebovitz HE . Insulin-sensitive and insulin-resistant variants in NIDDM. Diabetes 1989; 38: 784–92.

Dowling HJ Pi-Sunyer FX . Race-dependent health risks of upper body obesity. Diabetes 1993; 42: 537–43.

Dowling HJ Fried SK Pi-Sunyer FX . Insulin resistance in adipocytes of obese women: Effect of body fat distribution and race. Metabolism 1995; 44: 987–95.

McKeigue PM Marmot MG Court YD Syndercombe Cottier DE Rahman S Riemersma RA . Diabetes, hyperinsulinaemia, and coronary risk factors in Bangladeshis in East London. Br Heart J 1988; 60: 390–6.

McKeigue PM Shah B Marmot MG . Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet 1991; 337: 382–6.

Haffner SM Stern MP Hazuda HP Mitchell BD Patterson JK . Increased insulin concentration in nondiabetic offspring of diabetic parents. N Engl J Med 1988; 319: 1297–301.

Gelding SV Coldham N Niththyananthan R Anyaoku V Johnston DG . Insulin resistance with respect to lipolysis in non-diabetic relatives of European patients with type 2 diabetes. Diabet Med 1995; 12: 66–73.

Migdalis IN Zachariadis D Kalogeropoulou K Nounopoulos C Bouloukos A Samartzis M. Metabolic abnormalities in offspring of NIDDM patients with a family history of diabetes mellitus. Diabet Med 1996; 13: 434–40.

Vaag A Alford F Beck-Nielsen H. Intracellular glucose and fat metabolism in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM): Acquired versus genetic metabolic defects? Diabet Med 1996; 13: 806–15.

Osei K Cottrell DA Orabella MM . Insulin sensitivity, glucose effectiveness and body fat distribution pattern in nondiabetic offspring of parents with NIDDM. Diabetes Care 1991; 14: 890–6.

Keys A Fidanza F Karvonen MJ Kimura N Taylor HL . Indices of relative weight and obesity. J Chron Dis 1972; 25: 329–43.

Kolterman OG Insel J Saekow M Olefsky JM . Mechanism of insulin resistance in human obesity. Evidence for receptor and postreceptor defects. J Clin Invest 1980; 65: 1272–84.

Prager R Wallace P Olefsky JM . In vivo kinetics of insulin action on peripheral glucose disposal and hepatic glucose output in normal and obese subjects. J Clin Invest 1986; 78: 472–81.

Laakso M Edelman SV Brechtel G Baron AD . Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. J Clin Invest 1990; 85: 1844–52.

Bakir SM Jarrett RJ . The effects of a low-dose intravenous insulin infusion upon plasma glucose and non-esterified fatty acid levels in very obese and non-obese human subjects. Diabetologia 1981; 20: 592–96.

Meylan M Henny C Temler E Jequier E Felber JP . Metabolic factors in the insulin resistance in human obesity. Metabolism 1987; 36: 256–61.

Hale PJ Singh BM Crase J Baddeley RM Nattrass M. Following weight loss in massively obese patients correction of the insulin resistance of fat metabolism is delayed relative to the improvement in carbohydrate metabolism. Metabolism 1988; 37: 411–7.

Robertson DA Singh BM Nattrass M. Effect of obesity on circulating intermediary metabolite concentrations in the absence of impaired glucose tolerance. Int J Obes 1991; 15: 635–45.

Robertson DA Singh BM Hale PJ Nattrass M. Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as measured by low-dose insulin infusion. Metabolism 1992; 41: 604–12.

Hollenbeck CB Chen Y-DI Reaven GM . A comparison of the relative effects of obesity and noninsulin-dependent diabetes mellitus on in vivo insulin-stimulated glucose utilisation. Diabetes 1984; 33: 622–6.

Firth R Bell P Rizza R. Insulin action in noninsulin-dependent diabetes mellitus: The relationship between hepatic and extrahepatic insulin resistance and obesity. Metabolism 1987; 36: 1091–5.

Ludvik B Nolan JJ Baloga J Sacks D Olefsky J. Effect of obesity on insulin resistance in normal subjects and patients with NIDDM. Diabetes 1995; 44: 1121–5.

Bogardus C Lillioja S Mott DM Hollenbeck C Reaven GM . Relationship between degree of obesity and in vivo insulin action in man. Am J Physiol 1985; 248: E286–91.

Campbell PJ Gerich JE . Impact of obesity on insulin action in volunteers with normal glucose tolerance: Demonstration of a threshold for the adverse effect of obesity. J Clin Endocrinol Metab 1990; 70: 1114–8.

Vague J. The degree of masculine differentiation of obesities: A factor determining predisposition to diabetes, atherosclerosis, gout and uric calculous disease. Am J Clin Nutr 1956; 4: 20–34.

Kissebah AH Vydelingum N Murray R Evans DJ Hartz AJ Kalkhoff RK Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab 1982; 54: 254–60.

Krotkiewski M Björntorp P Sjöström L Smith U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest 1983; 72: 1150–62.

Evans DJ Hoffmann RG Kalkhoff RK Kissebah AH . Relationship of body fat topography to insulin sensitivity and metabolic profiles in premenopausal women. Metabolism 1984; 33: 68–75.

Peiris AN Struve MF Mueller RA Lee MB Kissebah AH . Glucose metabolism in obesity: Influence of body fat distribution. J Clin Endocrinol Metab 1988; 67: 760–7.

Landin K Krotkiewski M Smith U. Importance of obesity for the metabolic abnormalities associated with an abdominal fat distribution. Metabolism 1989; 38: 572–6.

Haffner SM Karhapää P Mykkänen L Laakso M. Insulin resistance, body fat distribution and sex hormones in men. Diabetes 1994; 43: 212–9.

Landin K Lönnroth P Krotkiewski M Holm G Smith U. Increased insulin resistance and fat cell lipolysis in obese but not lean women with a high waist/hip ratio. Eur J Clin Invest 1990; 20: 530–5.

Björntorp P. Metabolic implications of body fat distribution. Diabetes Care 1991; 14: 1132–43.

Krentz AJ Singh BM Nattrass M. Impaired glucose tolerance is characterized by multiple abnormalities in the regulation of intermediary metabolism. Diabet Med 1991; 8: 848–54.

Swislocki ALM Chen Y-DI Golay A Chang M-D Reaven GM . Insulin suppression of plasma free fatty acid concentration in normal individuals and patients with type 2 (non-insulin-dependent) diabetes. Diabetologia 1987; 30: 622–6.

Singh BM Palma M Nattrass M. Multiple aspects of insulin resistance—comparison of glucose and intermediary metabolite response to incremental insulin infusion in IDDM subjects of short and long duration. Diabetes 1987; 36: 740–8.

Yki-Järvinen H. Glucose toxicity. Endocr Rev 1992; 13: 415–31.

Ferrannini E DeFronzo RA Sherwin RJ . Transient hepatic response to glucagon in man: Role of insulin and hyperglycaemia. Am J Physiol 1982; 242: E73–81.

Kotzmann H Linkesch M Ludvik B Clodi M Luger A Schernthaner G Effect of danazolinduced chronic hyperglucagonaemia on glucose tolerance and turnover. Eur J Clin Invest 1995; 25: 942–7.

Lembo G Capaldo B Rendina V Iaccarino G Napoli R Guida R Acute noradrenergic activation induces insulin resistance in human skeletal muscle. Am J Physiol 1994; 266: E242–7.

Marangou AG Alford FP Ward G Liskaser F Aitken PM Weber KM Hormonal effects of norepinephrine on acute glucose disposal in humans: A minimal model analysis. Metabolism 1988; 37: 885–91.

Capaldo B Napoli R Di Marino L Saccà L. Epinephrine directly antagonizes insulin-mediated activation of glucose uptake and inhibition of free fatty acid release in forearm tissues. Metabolism 1992; 41: 1146–9.

Walters JM Ward GM Kalfas A Best JD Alford FP . The effect of epinephrine on glucose-mediated and insulin-mediated glucose disposal in insulin-dependent diabetes. Metabolism 1992; 41: 671–7.

Gerich JE Lorenzi M Bier DM Tsalikian E Schneider V Karam JH Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin. J Clin Invest 1976; 57: 875–84.

Rizza RA Mandarino LJ Gerich JE . Effects of growth hormone on insulin action in man. Mechanism of insulin resistance, impaired suppression of glucose production, and impaired stimulation of glucose utilisation. Diabetes 1982; 31: 663–9.

Foss MC Saad MJA Paccola GMGF Paula FJA Piccinato CE Moreira AC . Peripheral glucose metabolism in acromegaly. J Clin Endocrinol Metab 1991; 72: 1048–53.

Rizza RA Mandarino LJ Gerich JE . Cortisol-induced insulin resistance in man: Impaired suppression of glucose production and stimulation of glucose utilisation due to a postreceptor defect of insulin action. J Clin Endocrinol Metab 1982; 54: 131–8.

Yasuda K Hines E III Kitabchi AE . Hypercortisolism and insulin resistance: Comparative effects of prednisone, hydrocortisone and dexamethasone on insulin binding of human erythrocytes. J Clin Endocrinol Metab 1982; 55: 910–5.

Sandler MP Robinson RP Rabin D Lacy WW Abumrad NN . The effect of thyroid hormones on gluconeogenesis and forearm metabolism in man. J Clin Endocrinol Metab 1983; 56: 479–85.

Bratusch-Marrain PR Komsati M Waldhäusl WK . Glucose metabolism in noninsulin-dependent diabetic patients with experimental hyperthyroidism. J Clin Endocrinol Metab 1985; 60: 1063–8.

Foss MC Paccola GMGF Saad MJA Pimenta WP Piccinato CE Iazagi N. Peripheral glucose metabolism in human hyperthyroidism. J Clin Endocrinol Metab 1990; 70: 1167–72.

Shen D-C Davidson MB Kuo S-W Sheu WH-H. Peripheral and hepatic insulin antagonism in hyperthyroidism. J Clin Endocrinol Metab 1988; 66: 565–9.

Randin J-P Tappy L Scazziga B Jequier E Felber JP . Insulin sensitivity and exogenous insulin clearance in Graves' disease. Measurement by the glucose clamp technique and continuous indirect calorimetry. Diabetes 1986; 35: 178–81.

Harris PE Walker M Clark F Home PD Alberti KGMM . Forearm muscle metabolism in primary hypothyroidism. Eur J Clin Invest 1993; 23: 585–8.

Kim H Kalkhoff RK Costrini NV Cerletty JM Jacobson M. Plasma insulin disturbances in primary hyperparathyroidism. J Clin Invest 1971; 50: 2596–605.

Ginsberg H Olefsky JM Reaven GM . Evaluation of insulin resistance in patients with primary hyperparathyroidism. Proc Soc Exp Biol Med 1975; 148: 942–5.

Flier JS Eastman JC Minaker K Matteson D Rowe JW . Acanthosis nigricans in obese women with hyperandrogenism. Characterization of an insulin-resistant state disinct from the type A and B syndromes. Diabetes 1985; 34: 101–7.

Chang RJ Nakamura RM Judd HC Kaplan SA . Insulin resistance in nonobese patients with polycystic ovary disease. J Clin Endocrinol Metab 1983; 57: 356–9.

Stuart CA Peters EJ Prince MJ Richards G Cavallo A Meyer WJ III . Insulin resistance with acanthosis nigricans: The role of obesity and androgen excess. Metabolism 1986; 35: 197–205.

Barbieri RL Smith S Ryan KS . The role of hyperinsulinaemia in the pathogenesis of ovarian hyperandrogenism. Fertil Steril 1988; 50: 197–212.

Dunaif A Green G Futterweit W Dobrjansky A. Suppression of hyperandrogenism does not improve peripheral or hepatic insulin resistance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1990; 70: 699–704.

Diamanti-Kandarakis E Mitrakou A Hennes MM Platanissiotis D Kaklas N Spina J Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary syndrome. Metabolism 1995; 44: 525–31.

Nestler JE Barlascini CO Matt DW Steingold KA Plymate SR Clore JN Suppression of serum insulin by diazoxide reduces serum testosterone levels in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 1989; 68: 1027–32.

Dunaif A Scott D Finegood D Quintana B Whitcomb R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996; 81: 3299–306.

Rosenbaum D Haber RJ Dunaif A. Insulin resistance in polycystic ovary syndrome: Decreased expression of GLUT-4 glucose transporters in adipocytes. Am J Physiol 1993; 264: E197–202.

Hugh-Jones PA . Diabetes in Jamaica. Lancet 1955; ii: 891–7.

Modan M Halkin H Almog S Lusky A Eshkol A Shefi M Hyperinsulinaemia—a link between hypertension, obesity and glucose intolerance. J Clin Invest 1985; 75: 809–17.

Lind L Lithell H Pollare T. Is it hyperinsulinaemia or insulin resistance that is related to hypertension and other metabolic cardiovascular risk factors? J Hypertens 1993; 11 (Suppl 4): S11-6.

Ferrari P Weidmann P Shaw S Giachino D Riesen W Allemann Y Altered insulin sensitivity, hyperinsulinaemia and dyslipidaemia in individuals with a hypertensive parent. Am J Med 1991; 91: 589–96.

Zavaroni I Mazza S Dall'Aglio E Gasparini P Passeri M Reaven GM . Prevalence of hyperinsulinaemia in patients with high blood pressure. J Intern Med 1992; 231: 235–40.

Pollare T Lithell H Berne C. Insulin resistance is a characteristic feature of primary hypertension independent of obesity. Metabolism 1990; 39: 167–74.

Pontiroli AE Alberetto M Pozza G. Patients with insulinoma show insulin resistance in the absence of arterial hypertension. Diabetologia 1992; 35: 294–5.

Vettor R Mazzonetto P Macor C Scandellari C Federspil G. Effect of endogenous organic hyperinsulinaemia on blood pressure and serum triglycerides. Eur J Clin Invest 1994; 24: 350–4.

Saad MF Knowler WC Pettitt DJ Nelson RG Mott DM Bennett PH . Insulin and hypertension—relationship to obesity and glucose intolerance in Pima Indians. Diabetes 1990; 39: 1430–5.

Saad MF Lillioja S Nyomba BL Castillo C Ferraro R DeGregorio M Racial differences in the relation between blood pressure and insulin resistance. N Engl J Med 1991; 324: 733–9.

Muller DC Elahi D Pratley RE Tobin JD Andres R. An epidemiological test of the hyperinsulinaemia—hypertension hypothesis. J Clin Endocrinol Metab 1993; 76: 544–8.

Laakso M Pyörälä K Voutilainen E Marniemi J. Plasma insulin and serum lipids and lipoproteins in middle-aged noninsulin-dependent diabetic and nondiabetic subjects. Am J Epidemiol 1987; 125: 611–21.

Taskinen M-R Helve E Nikkila EA Yki-Järvinen H. Insulin therapy induces antiatherogenic changes in lipoproteins of type 2 diabetics. Diabetes 1987; 36 (suppl): 81A.

Lindström T Arnqvist HJ Olsson AG . Effects of different insulin regimens on plasma lipoprotein and apolipoprotein concentrations in patients with noninsulin-dependent diabetes mellitus. Atherosclerosis 1990; 81: 137–44.

Scarlett JA Gray RS Griffin J Olefsky JM Kolterman OG . Insulin treatment reverses the insulin resistance of type II diabetes mellitus. Diabetes Care 1982; 5: 353–63.

Davis CE Gordon D LaRosa J Wood PDS Halperin M. Correlation of plasma high density lipoprotein cholesterol levels with other plasma lipid and lipoprotein concentrations. The Lipid Research Clinics Program Prevalence Study. Circulation 1980; 62 (suppl IV): IV-24–30.

Karhapää P Malkki M Laakso M. Isolated low HDL-cholesterol: An insulin resistant state. Diabetes 1994; 43: 411–7.

Olefsky JM Farquhar JW Reaven GM . Reappraisal of the role of insulin in hypertriglyceridaemia. Am J Med 1974; 57: 551–60.

Bernstein RM Davis BM Olefsky JM Reaven GM . Hepatic insulin responsiveness in patients with endogenous hypertriglyceridaemia. Diabetologia 1978; 14: 249–53.

Steiner G Morita S Vranic M. Resistance to insulin but not to glucagon in lean human hypertriglyceridaemics. Diabetes 1980; 29: 899–905.

Widén E Ekstrand A Saloranta C Franssila-Kallunki A Eriksson J Schalin-Jäntti C Insulin resistance in type 2 (non-insulin dependent) diabetic patients with hypertriglyceridaemia. Diabetologia 1992; 35: 1140–5.

McKane WR Stevens AB Woods R Andrews WJ Henry RW Bell PM . The assessment of hepatic and peripheral insulin sensitivity in hypertriglyceridaemia. Metabolism 1990; 39: 1240–5.

Eckel RH . Lipoprotein lipase—a multifunctional enzyme relevant to common metabolic diseases. N Engl J Med 1989; 320: 1060–8.

Yki-Järvinen H Taskinen M-R. Interrelationships among insulin's antilipolytic and glucoregulatory effects and plasma triglycerides in nondiabetic and diabetic patients with endogenous hypertriglyceridaemia. Diabetes 1988; 37: 1271–8.

Reaven GM . Pathophysiology of insulin resistance in human disease. Physiol Rev 1995; 75: 473–86.

Kaplan NM . The deadly quartet—upper body obesity, glucose intolerance, hypertriglyceridaemia and hypertension. Arch Intern Med 1989; 149: 1514–20.

Ferrannini E Haffner SM Mitchell BD Stern MP . Hyperinsulinaemia: The key feature of a cardiovascular and metabolic syndrome. Diabetologia 1991; 34: 416–22.

DeFronzo RA Ferrannini E. Insulin resistance—a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerotic cardiovascular disease. Diabetes Care 1991; 14: 173–94.

Ingelfinger JA Bennett PH Liebow IM Miller M. Coronary heart disease in the Pima Indians. Diabetes 1976; 25: 561–5.

Neel JV . Diabetes mellitus: A ‘thrifty’ genotype rendered detrimental by ‘progress’? Am J Hum Genet 1962; 14: 353–62.

Zimmet P. Hyperinsulinaemia—how innocent a bystander? Diabetes Care 1993; 16 (suppl 3): 56–70.

Wendorf M Goldfine ID . Archaeology of NIDDM. Excavation of the ‘thrifty’ genotype. Diabetes 1991; 40: 161–5.

Barker DJP . The Wellcome Foundation Lecture 1994: The fetal origins of adult disease. Proc Roy Soc Lond (series B) 1995; 262: 37–43.

Barker DJP Hales CN Fall CHD Osmond C Phipps K Clark PMS . Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): Relation to reduced fetal growth. Diabetologia 1993; 36: 62–7.

Phillips DIW Barker DJP Hales CN Hirst S Osmond C. Thinness at birth and insulin resistance in adult life. Diabetologia 1994; 37: 150–4.

Stern M. Diabetes and cardiovascular disease. The ‘Common Soil’ hypothesis. Diabetes 1995; 44: 369–74.

Zavaroni I Bonora E Pagliari M Dall'Aglio E Lucchetti L Buonanno G Risk factors for coronary artery disease in healthy persons with hyperinsulinaemia and normal glucose tolerance. N Engl J Med 1989; 320: 702–6.

Haffner SM Valdez RA Hazuda HP Mitchell BD Morales PA Stern MP . Prospective analysis of the insulin resistance syndrome (syndrome X). Diabetes 1992; 41: 715–22.

Stout RW . Diabetes and atherosclerosis—the role of insulin. Diabetologia 1979; 16: 141–50.

Stout RW . Insulin and atheroma—an update. Lancet 1987; i: 1077–9.

Jarrett RJ . Is insulin atherogenic? Diabetologia 1988; 31: 71–5.

Jarrett RJ . In defence of insulin: A critique of syndrome X. Lancet 1992; 340: 469–71.

Widén EIM Eriksson JG Groop LC . Metformin normalises nonoxidative glucose metabolism in insulin-resistant normoglycaemic first-degree relatives of patients with NIDDM. Diabetes 1992; 41: 354–8.

Bailey CJ . Biguanides and NIDDM. Diabetes Care 1992; 15: 755–72.

Schoonjans K. Staels B Auwerx J . The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta 1996; 1302: 93–109.

Kolaczynski JW Nyce MR Considine RV Boden G Nolan JJ Henry R Acute and chronic effects of insulin on leptin production in humans: Studies in vivo and in vitro . Diabetes 1996; 45: 699–701.

Segal KR Landt M Klein S. Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes 1996; 45: 988–91.

de Courten M Zimmet P Hodge A Collins V Nicolson M Staten M Hyperleptinaemia: The missing link in the metabolic syndrome? Diabet Med 1997; 14: 200–8.

Considine RV Sinha MK Heiman ML Kriauciunas A Stephens TW Nyce MR Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292–5.

Rosenbaum M Nicolson M Hirsch J Heymsfield SB Gallagher D Chu F Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab 1996; 81: 3424–7.

Ofei F Hurel S Newkirk J Sopwith M Taylor R. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycaemic control in patients with NIDDM. Diabetes 1996; 45: 881–5.

Young A Pittner R Gedulin B Vine W Rink T. Amylin regulation of carbohydrate metabolism. Biochem Soc Trans 1995; 23: 325–31.

Bennet WM Smith DM Bloom SR . Islet amyloid polypeptide: Does it play a pathophysiological role in the development of diabetes? Diabet Med 1994; 11: 825–9.

Eriksson JW Lönnroth P Posner BI Shaver A Wesslau C Smith UPG . A stable peroxovanadium compound with insulin-like action in human fat cells. Diabetologia 1996; 39: 235–42.

Cohen N Halberstam M Shlimovich P Chang CJ Shamoon H Rossetti L. Oral vanadyl sulfate improves hepatic and peripheral insulin sensitivity in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1995; 95: 2501–9.

Boden G Chen X Ruiz J van Rossum GD Turco S. Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus. Metabolism 1996; 45: 1130–5.

Buemann B Tremblay A. Effects of exercise training on abdominal obesity and related metabolic complications. Sports Med 1996; 21: 191–212.