Summary.The steady-state basal plasma glucose and insulin concentrations are determined by their interaction in a feedback loop. A computer-solved model has been used to predict the homeostatic concentrations which arise from Varying degrees of/3-cell deficiency and insulin resistance. Comparison of a patient's fasting values with the model's predictions allows a quantitative assessment of the contributions of insulin resistance and deficient r-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA). The accuracy and precision of the estimate have been determined by comparison with independent measures of insulin resistance and /3-cell function using hyperglycaemic and euglycaemic clamps and an intravenous glucose tolerance test. The estimate of insulin resistance obtained by homeostasis model assessment correlated with estimates obtained by use of the euglycaemic clamp (R~=0.88, p<0.0001), the fasting insulin concentration (P~ = 0.81, p < 0.0001), and the hyperglycaemic clamp, (Rs=0.69,p< 0.01). There was no correlation with any aspect of insulin-receptor binding. The estimate of deficient/3-cell function obtained by homeostasis model assessment correlated with that derived using the hyperglycaemic clamp (R~ = 0.61, p< 0.01) and with the estimate from the intravenous glucose tolerance test (R~ = 0.64, p < 0.05). The low precision of the estimates from the model (coefficients of variation: 31% for insulin resistance and 32% for/3-cell deficit) limits its use, but the correlation of the model's estimates with patient data accords with the hypothesis that basal glucose and insulin interactions are largely determined by a simple feed back loop.

Summary. Continuous infusion of glucose with model assessment (CIGMA) is a new method of assessing glucose tolerance, insulin resistance and r-cell function. It consists of a continuous glucose infusion 5mg 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 r-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 Type2 diabetic) the r-cell function measured by CIGMA correlated with steady-state plasma insulin levels during hyperglycaemic clamp at 10 mmol/1 (Rs = 0.64, p< 0.002). The CIGMA coefficient of variability was 21% for resistance and 19% for r-cell function. CIGMA is a simple, non-labour-intensive method for assessing insulin resistance and r-cell function in normal and Type 2 diabetic subjects who do not have glycosuria during the test.Key words: Insulin resistance, fl-cell function, mathematical model, glucose infusion, Type 2 diabetes, plasma insulin, plasma glucose.Patients with Type 2 diabetes are usually characterised by the severity of their hyperglycaemia, as assessed by glucose tolerance tests or by fasting plasma glucose measurements. The methods available for assessing the extent to which both/q-cell function and insulin resistance contribute to this hyperglycaemia are not suitable for routine use, and in most diabetic subjects pathophysiology is not assessed. If insulin resistance and deficient/q-cell function could be readily differentiated, it might be possible to predict an individual patient's response to diet, sulphonylurea or insulin therapy.The feed-back loop between the glucose stimulation of/3-cell secretion and insulin regulation of glucose turnover in the liver, muscle and fat, plays a major r6le in the regulation of fuel supply [1]. Although this is basically a very simple homeostatic system, the interactions are sufficiently complex that the glucose and insulin responses to clinical tests are not easy to assess. Thus, interpretations of the r61es of insulin resistance and r-cell deficiency in maturity-onset diabetic subjects vary [2,3]. With the aid of mathematical models, the effects of different combinations of insulin resistance and/q-cell deficiency can be predicted [4,5].We have investigated a new method which aims to give a near-physiological stimulus and to interpret the endogenous insulin and glucose responses. A standard, constant, low-dose glucose ...

Insulin insensitivity is present in PHPT even in the absence of hypertension and obesity, and may be the cause of glucose intolerance and diabetes. PHPT subjects with reduced beta-cell function are more likely to develop glucose intolerance.

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