Use and Abuse of HOMA Modeling
Tóm tắt
Homeostatic model assessment (HOMA) is a method for assessing β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. It has been reported in >500 publications, 20 times more frequently for the estimation of IR than β-cell function.
This article summarizes the physiological basis of HOMA, a structural model of steady-state insulin and glucose domains, constructed from physiological dose responses of glucose uptake and insulin production. Hepatic and peripheral glucose efflux and uptake were modeled to be dependent on plasma glucose and insulin concentrations. Decreases in β-cell function were modeled by changing the β-cell response to plasma glucose concentrations. The original HOMA model was described in 1985 with a formula for approximate estimation. The computer model is available but has not been as widely used as the approximation formulae. HOMA has been validated against a variety of physiological methods.
We review the use and reporting of HOMA in the literature and give guidance on its appropriate use (e.g., cohort and epidemiological studies) and inappropriate use (e.g., measuring β-cell function in isolation). The HOMA model compares favorably with other models and has the advantage of requiring only a single plasma sample assayed for insulin and glucose.
In conclusion, the HOMA model has become a widely used clinical and epidemiological tool and, when used appropriately, it can yield valuable data. However, as with all models, the primary input data need to be robust, and the data need to be interpreted carefully.
Từ khóa
Tài liệu tham khảo
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419, 1985
Bergman R, Ider Y, Bowden C, Cobelli C: Quantitative estimation of insulin sensitivity. Am J Physiol 236:E667–E677, 1979
Turner RC, Holman RR, Matthews D, Hockaday TD, Peto J: 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, 1979
Turner RC, Oakley NW, Nabarro JD: Control of basal insulin secretion, with special reference to the diagnosis of insulinomas. Br Med J 2:132–135, 1971
Turner RC, Grayburn JA, Newman GB, Nabarro JD: Measurement of the insulin delivery rate in man. J Clin Endocrinol Metab 33:279–286, 1971
Bergman RN, Bucolo RJ: Interaction of insulin and glucose in the control of hepatic glucose balance. Am J Physiol 227:1314–1322, 1974
Matthews DR, Rudenski AS, Burnett MA, Darling P, Turner RC: The half-life of endogenous insulin and C-peptide in man assessed by somatostatin suppression. Clin Endocrinol Oxf 23:71–79, 1985
Reichard GAJ, Jacobs AG, Kimbel P, Hochella NJ, Weinhouse S: Blood glucose replacement rates in normal and diabetic humans. J Appl Physiol 16:789–795, 1961
Forbath N, Hetenyi GJ: Glucose dynamics in normal subjects and diabetic patients before and after a glucose load. Diabetes 15:778–789, 1966
Insel PA, Liljenquist JE, Tobin JD, Sherwin RS, Watkins P, Andres R, et al.: Insulin control of glucose metabolism in man: a new kinetic analysis. J Clin Invest 55:1057–1066, 1975
Rowe GG, Maxwell GM, Castillo CA, Freeman DJ, Crumpton CW: A study in man of cerebral blood flow and cerebral glucose, lactate and pyruvate metabolism before and after eating. J Clin Invest 38:2154–2158, 1959
Morgan HE, Henderson MJ, Regan DM, Park CR: Regulation of glucose uptake in muscle. J Biol Chem 236:253–261, 1961
Daniel PM, Love ER, Pratt OE: Insulin-stimulated entry of glucose into muscle in vivo as a major factor in the regulation of blood glucose. J Physiol 247:273–288, 1975
Berger M, Hagg S, Ruderman NB: Glucose metabolism in perfused skeletal muscle. Interaction of insulin and exercise on glucose uptake. Biochem J 146:231–238, 1975
Levy JC, Matthews DR, Hermans MP: Correct homeostasis model assessment (HOMA) evaluation uses the computer program (Letter). Diabetes Care 21:2191–2192, 1998
Rudenski AS, Matthews DR, Levy JC, Turner RC: Understanding “insulin resistance”: both glucose resistance and insulin resistance are required to model human diabetes. Metabolism 40:908–917, 1991
Wallace TM, Levy JC, Matthews DR: An increase in insulin sensitivity and basal beta-cell function in diabetic subjects treated with pioglitazone in a placebo-controlled randomised study. Diabet Med In press
Robbins DC, Andersen L, Bowsher R, Chance R, Dineson B, Frank B, Gingerich R, Goldstein D, Widemeyer HM, Haffner S, Hales CN, Jarett L, Polonsky K, Porte D, Skyler J, Webb G, Gallagher K: Report of the American Diabetes Association’s task force on standardization of the insulin assay. Diabetes 45:242–256, 1996
Levy J, Morris R, Hammersley M, Turner R: Discrimination, adjusted correlation, and equivalence of imprecise tests: application to glucose tolerance. Am J Physiol (United States) 2:E365–E375, 1999
Bonora E, Targher G, Alberichie M, Bonadonna RC, Saggianni F, Zenere MB, Monauni T, Muggeo M: Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity. Diabetes Care 23:57–63, 2000
Emoto M, Nishizawa Y, Maekawa K, Hiura Y, Kanda H, Kawagishi T, Shoji T, Okuno Y, Morii H: Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas. Diabetes Care 22:818–822, 1999
Garcia-Estevez DA, Araujo-Vilar D, Fiestras-Janeiro G, Saavedra-Gonzalez A, Cabezas-Cerrato J: Comparison of several insulin sensitivity indices derived from basal plasma insulin and glucose levels with minimal model indices. Horm Metab Res 35:13–17, 2003
Hosker JP, Matthews DR, Rudenski AS, Burnett MA, Darling P, Bown EG, Turner RC: Continuous infusion of glucose with model assessment: measurement of insulin resistance and beta-cell function in man. Diabetologia 28:401–411, 1985
Hermans MP, Levy JC, Morris RJ, Turner RC: Comparison of tests of β-cell function across a range of glucose tolerance from normal to diabetes. Diabetes 48:1779–1786, 1999
UKPDS Group: U.K. Prospective Diabetes Study 16: Overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes 44:1249–1258, 1995
Haffner SM, Kennedy E, Gonzalez C, Stern MP, Miettinen H: A prospective analysis of the HOMA model: the Mexico City Diabetes Study. Diabetes Care 19:1138–1141, 1996
Wagenknecht LE, Mayer EJ, Rewers M, Haffner S, Selby J, Borok GM, Henkin L, Howard G, Savage PJ, Saad MF, Bergman RN, Hamman R: The Insulin Resistance Atherosclerosis Study (IRAS) objectives, design, and recruitment results. Ann Epidemiol 5:464–472, 1995
Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MI: Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 85:2402–2410, 2000
Katsuki A, Sumida Y, Gabazza EC, Murashima S, Furuta M, Araki-Sasaki R, Hori Y, Yano Y, Adachi Y: Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes. Diabetes Care 24:362–365, 2001
Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Jarvinen H, Van Haeften T, Hori Y, Yano Y, Adachi Y: Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 23:295–301, 2000
Hermans MP, Levy JC, Morris RJ, Turner RC: Comparison of insulin sensitivity tests across a range of glucose tolerance from normal to diabetes. Diabetologia 42:678–687, 1999
Levy JC, Rudenski A, Burnett M, Knight R, Matthews DR, Turner RC: Simple empirical assessment of beta-cell function by a constant infusion of glucose test in normal and type 2 (non-insulin-dependent) diabetic subjects. Diabetologia 34:488–499, 1991
Haffner SM, Miettinen H, Stern MP: The homeostasis model in the San Antonio Heart Study. Diabetes Care 20:1087–1092, 1997
Matsumoto K, Miyake S, Yano M, Ueki Y, Yamaguchi Y, Akazawa S, Tominaga Y: Glucose tolerance, insulin secretion, and insulin sensitivity in nonobese and obese Japanese subjects. Diabetes Care 20:1562–1568, 1997
Strazzullo P, Iacone R, Siani A, Cappuccio FP, Russo O, Barba G, Barbato A, D’Elia L, Trevisan M, Farinaro E: Relationship of the Trp64Arg polymorphism of the beta3-adrenoceptor gene to central adiposity and high blood pressure: interaction with age: cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study. J Hypertens 19:399–406, 2001
Dabelea D, Pettitt DJ, Hanson RL, Imperatore G, Bennett PH, Knowler WC: Birth weight, type 2 diabetes, and insulin resistance in Pima Indian children and young adults. Diabetes Care 22:944–950, 1999
Levy JC, Atkinson AB, Bell PM, McCance DR, Hadden DR: Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study. Diabet Med 15:290–296, 1998
Rosenblatt S, Miskin B, Glazer NB, Prince MJ, Robertson KE: The impact of pioglitazone on glycemic control and atherogenic dyslipidemia in patients with type 2 diabetes mellitus. Coron Artery Dis 12:413–423, 2001
Costa A, Rios M, Casamitjana R, Gomis R, Conget I: High prevalence of abnormal glucose tolerance and metabolic disturbances in first degree relatives of NIDDM patients: a study in Catalonia, a Mediterranean community. Diabetes Res Clin Pract 41:191–196, 1998
Pickavance L, Tadayyon M, Widdowson PS, Buckingham RE, Wilding JP: Therapeutic index for rosiglitazone in dietary obese rats: separation of efficacy and haemodilution. Br J Pharmacol 128:1570–1576, 1999