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      The assessment of insulin resistance in man.

      Diabetic Medicine

      Blood Glucose, metabolism, Diabetes Mellitus, Type 2, diagnosis, physiopathology, Glucose Clamp Technique, methods, Homeostasis, physiology, Humans, Insulin, analogs & derivatives, Insulin Resistance

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          Abstract

          Insulin resistance exists when a normal concentration of insulin produces a less than normal biological response. The ability to measure insulin resistance is important in order to understand the aetiopathology of Type 2 diabetes, to examine the epidemiology and to assess the effects of intervention. We assess and compare methods of measurement and have undertaken a literature review from 1966 to 2001. Quantitative estimates of insulin resistance can be obtained using model assessments, clamps or insulin infusion sensitivity tests. There is considerable variation in the complexity and labour intensity of the various methods. The most well-established methods are the euglycaemic clamp, minimal model assessment and homeostatic model assessment (HOMA). No single test is appropriate under all circumstances. There are a number of well-established tests used to measure insulin resistance: the choice of method depends on the size and type of study to be undertaken. Although the so-called 'gold-standard' test, the euglycaemic clamp, is useful for intensive physiological studies on small numbers of subjects, a simpler tool such as HOMA is more appropriate for large epidemiological studies. It is important to be aware that most techniques measure stimulated insulin resistance whereas HOMA gives an estimate of basal insulin resistance. Caution should be exercised when making comparisons between studies due to variations in infusion protocols, sampling procedures and hormone assays used in different studies.

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          Most cited references 20

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          Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity

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            A model-based method for assessing insulin sensitivity from the oral glucose tolerance test.

            Available insulin sensitivity (IS) methods based on the oral glucose tolerance test (OGTT) are empirical. We used a glucose-insulin model to derive an OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts glucose clearance in a glucose clamp. We validated OGIS against clamp data. OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0, 2, and 3 h (3-h OGTT) or at 0, 1.5, and 2 h (2-h OGTT). The formula includes six constants optimized to match the clamp results. For this purpose, 15 lean nondiabetic subjects (BMI 25 kg/m2), and 38 subjects with type 2 diabetes randomly underwent an OGTT and a 120 mU x min(-1) x m(-2) insulin infusion euglycemic clamp. Glucose clearance (Cl CLAMP), calculated as the ratio of glucose infusion to concentration during the last hour of the clamp, was compared with OGIS. OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance (IGT). OGIS and Cl CLAMP were correlated in the whole group (R = 0.77, P < 0.0001), in the subgroups (lean: R = 0.59; obese: R = 0.73; type 2 diabetes: R = 0.49; P < 0.02), and in the independent IGT group (R = 0.65, P < 0.02). Reproducibility of OGIS and Cl CLAMP were similar (coefficients of variation: OGIS 7.1%, Cl CLAMP 6.4%). OGIS was as effective as Cl CLAMP in discriminating between groups (for OGIS, lean vs. obese: 440 +/- 16 vs. 362 +/- 11 ml x min(-1) x m(-2), p < 0.001; lean vs. type 2 diabetes: 440 +/- 16 vs. 239 +/- 7, P < 0.0001; obese vs. type 2 diabetes: 362 +/- 11 vs. 239 +/- 7, P < 0.0001; results were similar for Cl CLAMP). The relationships between IS and BMI, fasting plasma insulin, and insulin secretion (calculated from the OGTT insulin concentration) were examined. OGIS yielded results similar to Cl CLAMP and fully consistent with established physiological principles. The performance of the index for the 3-h and 2-h OGTT was similar. OGIS is an index of IS in good agreement with the clamp. Because of its simplicity (only three blood samples required), this method has potential use for clinical investigation including large-scale epidemiological studies.
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              Homeostasis model assessment as a clinical index of insulin resistance in type 2 diabetic patients treated with sulfonylureas.

               H. Morii,  Y Okuno,  H Kanda (1999)
              To investigate whether the insulin resistance index (IR) assessed by homeostasis model assessment (HOMA) is associated with the insulin resistance index assessed by euglycemic-hyperinsulinemic clamp (clamp IR) in type 2 diabetic patients who received sulfonylureas (SUs), as well as in those treated by diet alone. Retrospectively, the association between HOMA IR and clamp IR was analyzed in 80 type 2 diabetic subjects (53 subjects treated with SUs and 27 subjects treated with diet alone). The 80 subjects, selected because they had not received insulin therapy, were among 111 diabetic participants in a clamp study for evaluation of insulin resistance from May 1993 to December 1997 in Osaka City University Hospital. The HOMA IR showed a hyperbolic relationship with clamp IR. The log-transformed HOMA IR (all subjects, r = -0.725, P 0.05; intercept, 6.566 vs. 5.478, P > 0.05). Stepwise multiple regression analyses demonstrated that the log-transformed HOMA IR was the strongest independent contributor to clamp IR (R2 = 0.640, P < 0.0001). The HOMA IR strongly correlated with the clamp IR in type 2 diabetic patients treated with SUs as well as in those treated with diet alone.
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