Continuous infusion of glucose with model assessment: measurement of insulin resistance and ?-cell function in man

Abstract

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 ...

Comparison of insulin sensitivity tests across a range of glucose tolerance from normal to diabetes

“…Following basal sampling (±15, ±10, ±5 and 0 min), intravenous glucose was given at 0 min, then sampling followed at 3, 4, 5, 6, 8, 10, 12, 14, 16 and 19 min; at 20 min, insulin infusion was given, while sampling continued at 22,24,26,28,30,33,36,40,50,60,70,80, 100, 120, 140, 160, 180. Radioimmunoassay insulin and glucose were assayed on all samples.…”

“…Assessment of the glucose and insulin concentrations in each person allows evaluation of the combination of deficient beta-cell function and impaired insulin sensitivity that are present. The simplest application is assessing the basal homeostasis by measuring fasting glucose and insulin concentrations with HOMA [24,27]. Since the basal concentrations of glucose and insulin are low and require precise and sensitive assays, the alternative method evaluates the near-steady state glucose/insulin concentrations after 2 h of a low dose, constant glucose infusion that induces plasma glucose and insulin concentrations similar to postprandial concentrations (modelled with CIGMA) [23, 25±27].…”

“…Since the basal concentrations of glucose and insulin are low and require precise and sensitive assays, the alternative method evaluates the near-steady state glucose/insulin concentrations after 2 h of a low dose, constant glucose infusion that induces plasma glucose and insulin concentrations similar to postprandial concentrations (modelled with CIGMA) [23, 25±27]. Homeostasis model assessment and CIG-MA have been validated against independent measures of insulin sensitivity and beta-cell function, including clamp-derived measures [23,24] and are more practical, cheaper and less invasive than FSIVGTT. The short ITT is a simple direct estimate of in vivo insulin action, validated against the euglycaemic clamp, that measures the decrease in plasma glucose following an insulin bolus in the fasting state [23].…”

Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes

“…Parents of probands willing to undergo studies were studied with a continuous infusion of glucose (CIGMA) test [12]. This The fpg and apg concentrations after the 1-h CIGMA test (apg) are shown as Z scores, the deviation in SD from the mean of an age and BMI-matched normal population Fasting plasma glucose (fpg) and achieved plasma glucose (apg) are shown as Z age-and BMI-matched normal population scores, the deviation in SD from the mean of an consisted of a continuous intravenous infusion of 5 mg glucose.…”

Higher Serum Insulin Concentrations Positively Influence the Bone Mineral Density in African American Adolescents

“…Whole-body insulin sensitivity was calculated as proposed by Matsuda et al [24], where WBISI = 10,000/ √ (fasting glucose × fasting insulin) × (mean glucose × mean insulin during OGTT). The homeostatic model assessment of basal insulin resistance (HOMA-IR) was calculated using the formula: HOMA-IR = [fasting insulin (μU/ml) × fasting glucose (mmol/L)] / 22.5 [25,26]. Post-MMTT area under the curve (AUC) and incremental AUC for insulin and glucose were calculated using the trapezoidal method.…”