Summary
Continuous infusion of glucose with model assessment (CIGMA) is a new method of assessing glucose tolerance, insulin resistance and β-cell function. It consists of a continuous glucose infusion 5 mg glucose/kg ideal body weight per min for 60 min, with measurement of plasma glucose and insulin concentrations. These are similar to postprandial levels, change slowly, and depend on the dynamic interaction between the insulin produced and its effect on glucose turnover. The concentrations can be interpreted using a mathematical model of glucose and insulin homeostasis to assess insulin resistance and β-cell function. In 23 subjects (12 normal and 11 with Type 2 (non-insulin-dependent diabetes) the insulin resistance measured by CIGMA correlated with that measured independently by euglycaemic clamp (Rs = 0.87, p < 0.0001). With normal insulin resistance defined as 1, the median resistance in normal subjects was 1.35 by CIGMA and 1.39 by clamp, and in diabetic patients 4.0 by CIGMA and 3.96 by clamp. In 21 subjects (10 normal and 11 Type 2 diabetic) the β-cell function measured by CIGMA correlated with steady-state plasma insulin levels during hyperglycaemic clamp at 10 mmol/l (Rs=0.64, p < 0.002). The CIGMA coefficient of variability was 21% for resistance and 19% for β-cell function. CIGMA is a simple, non-labour-intensive method for assessing insulin resistance and β-cell function in normal and Type 2 diabetic subjects who do not have glycosuria during the test.
Article PDF
Similar content being viewed by others
References
Turner RC, Matthews DR (1984) Insulin secretion in Type I and Type II diabetes. Front Diabetes 4: 36–54
Reaven G, Bernstein R, Davies B, Olefsky JM (1976) Non-ketotic diabetes mellitus: insulin deficiency or insulin resistance? Am J Med 60: 80–88
Rizza RA, Mandarino LJ, Gerich JE (1981) Mechanism and significance of insulin resistance in non-insulin-dependent diabetes mellitus. Diabetes 30: 990–995
Bergman RN, Phillips LS, Cobelli C (1981) Physiologic evaluation of factors controlling glucose tolerance in man. J Clin Invest 68: 1456–1467
Turner RC, Holman RR, Matthews D, Hockaday TDR, Peto J (1979) Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations. Metabolism 28: 1086–1096
DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237: E214–223
Metropolitan Life Assurance Co (1959) Net weight standard for men and women. Stat Bull Metrop Life Found 40: 1–4
Turner RC, Matthews DR, Holman RR, Peto J (1982) Relative contributions of insulin deficiency and insulin resistance in maturity-onset diabetes. Lancet 1: 596–598
Rowe GG, Maxwell GM, Castillo GA, Freeman DJ, Crumpton CW (1959) A study of cerebral blood flow and cerebral glucose metabolism before and after eating. J Clin Invest 38: 2154–2158
Daniel PM, Love ER, Pratt OE (1975) Insulin stimulated entry of glucose into muscle in vivo as a major factor in the regulation of blood glucose. J Physiol 247: 273–288
Kolterman OG, Gray RS, Griffin J, Burstein P, Insel J, Scarlett JA, Olefsky JM (1981) Receptor and postreceptor defects contribute to the insulin resistance in non-insulin-dependent diabetes mellitus. J Clin Invest 68: 957–969
Ciaraldi TP, Kolterman OG, Olefsky JM (1981) Mechanism of the postreceptor defect in insulin action in human obesity. J Clin Invest 68: 875–880
Bergman RN, Bucolo RJ (1974) Interaction of insulin and glucose in the control of hepatic glucose balance. Am J Physiol 227: 1314–1322
Felig P, Wahren J (1971) Influence of endogenous insulin secretion on splanchnic glucose and amino acid metabolism in man. J Clin Invest 50: 1702–1711
DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J, Felber JP (1981) The effect of insulin on the disposal of intravenous glucose. Diabetes 30: 1000–1007
Blackard WG, Nelson NC (1970) Portal and Peripheral vein immunoreactive insulin concentrations before and after glucose infusion. Diabetes 19: 302–306
Turner RC, Grayburn JA, Newman GB, Nabarro JDN (1971) Measurement of insulin delivery rate in man. J Clin Endocrinol Metab 33: 279–286
Lerner RL, Porte D (1972) Acute and steady-state insulin responses to glucose in non-obese diabetic subjects. J Clin Invest 51: 1624–1631
Cerasi E, Luft R, Efendic S (1971) Decreased sensitivity of the pancreatic beta cells to glucose in prediabetic and diabetic subjects. A glucose dose-response study. Diabetes 21: 224–234
Turner RC, Harris E, Ounsted M, Ponsford C (1979) Two abnormalities of glucose-induced insulin secretion: dose-response characteristics and insulin sensitivity. Acta Endocrinol 92: 148–165
Grodsky GM (1972) A threshold distribution hypothesis for packet storage of insulin and its mathematical modelling. J Clin Invest 51: 2047–2059
Matthews DR, Lang DA, Burnett MA, Turner RC (1983) Control of pulsatile insulin secretion in man. Diabetologia 24: 231–237
Matthews DR, Hosker JP (1984) An unbiased, flexible computer programme for glucose clamping, with graphics and running statistics. Diabetologia 27: 308–309 A
Albano JDM, Ekins RP, Maritz G, Turner RC (1972) A sensitive, precise, radioimmunoassay of serum insulin relying on charcoal separation of bound and free hormone moities. Acta Endocrinol 70: 487–509
Harano Y, Ohgaku S, Hidaka H, Haneda K, Kikkaw R, Shigeta Y, Abe H (1977) Glucose, insulin and somatostatin infusion for the determination of insulin sensitivity. J Clin Endocrinol Metab 45: 1124–1127
Felig P, Wahren J, Hendler R, Brundin T (1974) Splanchnic glucose and amino acid metabolism in obesity. J Clin Invest 53: 582–590
DeFronzo RA, Ferrannini E, Hendler R, Felig P, Wahren J (1983) Regulation of splanchnic and peripheral glucose uptake by insulin and hyperglycaemic in man. Diabetes 32: 35–45
World Health Organisation (1980) Expert Committee on Diabetes Mellitus. Technical Report Series 646, Geneva
Shen SW, Reaven GM, Farquhar JW (1970) Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes. J Clin Invest 49: 2151–2160
Scarlett JA, Gray RS, Griffin J, Olefsky JM, Kolterman OG (1982) Insulin treatment reverses the insulin resistance of type II diabetes mellitus. Diabetes 5: 353–363
Ginsberg H, Rayfield EJ (1981) Effect of insulin therapy on insulin resistance in type II diabetic subjects. Diabetes 30: 739–745
Greenfield MS, Doberne L, Kraemer F, Tobey T, Reaven G (1981) Assessment of insulin resistance with the insulin suppression test and the euglycaemic clamp. Diabetes 30: 387–392
Muller WA, Faloona GF, Unger RH (1971) The influence of antecedent diet upon glucagon and insulin secretion. New Engl J Med 285: 1450–1454
Matthews DR, Hosker JP, Rudenski A, Bown EG, Naylor BA, Treacher D, Turner RC (1985) Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia: 412–419
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hosker, J.P., Matthews, D.R., Rudenski, A.S. et al. Continuous infusion of glucose with model assessment: measurement of insulin resistance and β-cell function in man. Diabetologia 28, 401–411 (1985). https://doi.org/10.1007/BF00280882
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00280882