No abstract

Plasma insulin and glucose concentrations were examined in man in a basal state from central venous samples taken at 1-min intervals for up to 2.5 h. Normal subjects have insulin oscillations of mean period 14 min (significant autocorrelation, p less than 0.0001) with changes in concentration of 40% over 7 min. The pulsation frequency was stable through cholinergic, endorphin, alpha-adrenergic or beta-adrenergic blockade, or small perturbations with glucose or insulin. Stimulation of insulin secretion by intravenous glucose, tolbutamide or sodium salicylate increased the amplitude of the insulin oscillations while the frequency remained stable. Patients with a truncal vagotomy or after Whipple's operation had longer-term oscillations of 33 and 37 min periodicity (autocorrelation: p less than 0.0001), with insulin-associated glucose swings four times larger than those of normal subjects. Type 2 (non-insulin-dependent) diabetic patients had a similarly increased insulin-associated glucose swing of six times that seen in normal subjects. The hypothesis is proposed that the 14-min cycle of insulin production is controlled by a 'pacemaker' which assists glucose homeostasis. The longer 33-37-min oscillations, seen in those with denervation, may arise from a limit-cycle of the feedback loop between insulin from the B cells and glucose from the liver. The vagus may provide hierarchical control of insulin release.

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 ...

The basal plasma insulin and glucose concentrations of 12 diet-treated maturity-onset diabetics were measured at minute intervals for 2 h. Brief, irregular oscillations (mean period 8.8 min) in plasma insulin were superimposed on longer term fluctuations (greater than 30 min). Time series analysis demonstrated a synchronous plasma glucose oscillation (mean amplitude 0.03 mmol/L) associated with short insulin cycles. The glucose changes seen in diabetic subjects were similar to the short plasma insulin cycles (less than 10 min) observed in normal subjects. In contrast, the longer plasma insulin cycles (greater than 10 min) of normal subjects were associated with a plasma glucose oscillation that rose before the end of the cycle. The demonstration of insulin oscillations independent of preceding plasma glucose changes in both normal and diabetic subjects suggests a pancreatic oscillating mechanism of "pacemaker". The associated glucose changes may reflect the entrainment, by the insulin cycles, of glucose production or utilization.

No abstract