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 ...

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An amperometric glucose-measuring 25 gauge (0.5 mm diameter) needle-type sensor has been developed using a glucose oxidase and dimethyl ferrocene paste behind a semi-permeable membrane situated over a window in the needle. Electron transfer results in direct current generation. Sensors have been tested subcutaneously in the abdomen both in anaesthetized rats (40 sensors, 11 rats) and in normal, conscious man (20 sensors, 10 subjects). In rats the blood glucose was modulated by glucose and by insulin infusion. In man the glucose concentrations were rapidly changed by use of a glucose clamp at 12 mmol/l plasma concentration for 2 h, after which the glucose returned to normal. In rats the median correlation between glucose change was 0.83 with an interquartile range from 0.70 to 0.92, and in man the median correlation was 0.80 with an interquartile range 0.67 to 0.86. Hysteresis, a measure of the accuracy on the upswing and downswing, was not a problem and cross-correlation showed no phase-lag. There were quantitative differences between in vitro calibration and the performance in vivo, reflecting the different conditions of use. The current in response to a glucose concentration was stable over 6.0 h in rats and 4.5 h in man.

ADP-induced platelet aggregation was measured in 15 Type 1 (insulin-dependent) diabetic patients, 15 Type 2 (non-insulin-dependent) diabetic patients and in 15 non-diabetic control subjects. Simultaneous measurements were made of fasting blood glucose, glycosylated haemoglobin, serum insulin, total plasma cholesterol, cholesterol in the lipoprotein subfractions, total triglycerides and platelet phospholipid fatty acid levels. Regression analysis of aggregation against the biochemical variables within the three groups revealed that there was no significant difference in the associations with aggregation between the groups. When the data was pooled, blood glucose (p less than 0.01) and glycosylated haemoglobin (p less than 0.05) demonstrated significant associations with aggregation. Multiple regression analysis was then applied; only blood glucose (p less than 0.05) had an independent effect on aggregation. Platelet aggregation in diabetic patients and non-diabetic patients appears to be related directly only to blood glucose levels.

NIDDM has a strong genetic component, as evidenced by the high level of concordance between identical twins. The nature of the genetic predisposition has remained largely unknown. Recently, the glucokinase gene locus on chromosome 7p has been shown to be linked to a subtype of NIDDM known as MODY in French and British pedigrees, and glucokinase mutations have been identified. To study the relationship between the glucokinase gene and NIDDM, we performed a linkage analysis in 12 Caucasian pedigrees ascertained through a proband with classical NIDDM. The LINKAGE program was used under four models, including autosomal dominant and recessive, with individuals with glucose intolerance counted as either affected or of unknown status. Linkage was significantly rejected with the dominant models (LOD scores -4.65, -4.25), and was unlikely with the recessive model when glucose intolerance was considered as affected (LOD score -1.38). These findings suggest that mutations in or near the glucokinase gene are unlikely to be the major cause of the inherited predisposition to NIDDM in Caucasian pedigrees, but do not exclude a role for this locus with a polygenic model, or a major role in some pedigrees.

Previous studies have shown that vessels from diabetics produce less prostacyclin in vitro than those from normal controls. To determine whether this decreased production is related to complications elective biopsy of a superficial forearm vein was performed on 12 insulin-dependent male diabetics, six with nil or minimal and six with proliferative retinopathy, and seven male controls. Vein segments from the diabetics and controls produced similar amounts of prostacyclin in vitro (medians 011 and 0 19 ng/mg tissue respectively), but the segments from the diabetics with nil or minimal retinopathy produced less than those from the diabetics with proliferative retinopathy (medians 0 09 and 0-18 ng/mg respectively). Preoperative plasma immunoreactive concentrations of 6-keto-prostaglandin F,0x were not significantly different between the controls and the diabetics (medians 101 and 116 pg/ml respectively). In a separate study, however, 11 diabetics with duration of disease of over 10 years and nil or minimal retinopathy had significantly lower concentrations than a matched group of 16 with background or proliferative retinopathy (medians 79 and 121 pg/ml respectively).These results do not support an association between reduced prostacyclin production and diabetic retinopathy.

The aggregometer monitors changes in light transmission through stirred suspensions of aggregation platelets. Arbitrary measurements from aggregometer recorder tracings have been used to investigate platelet aggregation without regard to mechanisms involved. To determine the applicability of particle collision theory to assessment of in vitro platelet sensitivity to proaggregating agents, platelet-rich plasma (PRP) from five volunteers was used to obtain recorder tracings after addition of ADP in five doses (0.4-4.0 mumol/l PRP) to aliquots of PRP stirred and incubated in an aggregometer. Using the equation describing light transmission through particulate suspensions, particle collision theory, and s (the probability of particle union after collision), a subject- and dose-independent relationship between aggregation rate (dn/dt) and particle number (n) at the recorder tracing inflection point was found (dn/dt = -k X s X n1.56, where k is a constant dependent on particle size and speed and on the proportion of unreactive particles). Determinations of mean particle size at the tracing inflection point indicated that k was also dose independent. Dose-response curves of ADP added vs. s could therefore be constructed. This methodology provides conveniently obtainable quantitative information concerning in vitro platelet "stickiness."

The aim of the study was to evaluate the precision and accuracy of the ExacTech home blood glucose meter when used with either capillary or venous blood and to compare this with a reference whole blood glucose assay. Non-fasting glucose measurements were used since a validation study showed no capillary-venous differences between fasting and post-prandial states. In a cross-sectional study, blood was taken from 182 patients and measured in duplicate on three batches of strips. Altogether we analysed 1089 readings. The regression of the data from capillary blood samples (meter vs reference method) had a correlation coefficient, of 0.93, and a mean bias of 0.2 mmol l-1. The corrected 90% confidence interval was +/- 1.5 mmol l-1 overall, and +/- 0.9 mmol l-1 for readings under 7.0 mmol l-1. Regression of the data from venous blood samples (meter vs reference method) had a correlation coefficient of 0.93 and a slope of x 1.1. The corrected 90% confidence interval was +/- 1.7 mmol l-1. Thus venous blood may be used even though the meter is calibrated for capillary samples but the value must be corrected by dividing by 1.1. Error-grid analysis showed that day-to-day clinical decisions could be made on the basis of ExacTech readings, although a diagnosis of borderline diabetes may not be possible.