Impaired glucose tolerance and insulin insensitivity in primary hyperparathyroidism.

Objective: A high prevalence of diabetes mellitus has been shown in patients with primary hyperparathyroidism (PHPT). However, it is unclear whether this is related to the metabolic abnormalities in PHPT or to the presence of other risk factors for glucose intolerance in these patients. The aim of our study was to determine whether glucose intolerance and insulin insensitivity occur in subjects with PHPT who do not have other risk factors for diabetes mellitus.

Prednisolone enhances beta-cell function independently of ambient glycemic levels in type II diabetes.

This study examined the changes in beta-cell response and insulin sensitivity induced by a single overnight dose of 15 mg prednisolone in eight type II diabetic subjects, seven nondiabetic normal controls, and eight subjects with a first-degree type II diabetic relative who were therefore at risk of developing diabetes. beta-Cell secretion was assessed by use of the hyperglycemic clamp technique, and insulin sensitivity was assessed with the clamp and the Continuous Infusion of Glucose with Model Assessment (CIGMA) technique. Subjects were studied in random order on two occasions, after placebo and after prednisolone administration.

Diet treatment of newly presenting type 2 diabetes improves insulin secretory capacity, but has no effect on insulin sensitivity.

Fifteen newly diagnosed obese Type 2 diabetic subjects were treated with diet alone for 3 months with a median 1.5 kg weight loss. Each had a Continuous Infusion of Glucose with Model Assessment (CIGMA) test, at diagnosis and at 3 months, measuring insulin and C-peptide responses, and deriving mathematically modelled measures of beta-cell function and insulin sensitivity.

The physiological action of gliclazide: beta-cell function and insulin resistance.

There is continuing debate about the physiological mechanisms of the action of sulphonylureas in man. In those patients taking sulphonylureas insulin secretion can be demonstrated to be higher, but there are also data which have been interpreted as evidence that these drugs may cause an alteration in peripheral insulin sensitivity. The physiological effects of the sulphonylurea gliclazide in diabetic subjects has been examined using a variety of experimental protocols to address this question: an intravenous gliclazide infusion, experiments using glucose clamping, mathematical modelling of the insulin and glucose data from subjects on and off gliclazide therapy, and the infusion of amino acids and glucose separately or in combination.

Application of structural model of glucose-insulin relations to assess beta-cell function and insulin sensitivity.

A structural mathematical model of glucose-insulin relationships based on known quantitative responses of the major organs involved with glucose metabolism has been computed. Different degrees of beta-cell function and insulin sensitivity can be included, and the effect of their interaction assessed (i) in a steady state, basal homeostasis after an overnight fast and (ii) in response to a glucose infusion. By comparing a patient's basal plasma glucose and insulin (or C-peptide) concentrations with the predictions of a basal homeostatic model, the degree of impairment of beta-cell function and insulin sensitivity can be assessed.

Similar reduction of first- and second-phase B-cell responses at three different glucose levels in type II diabetes and the effect of gliclazide therapy.

To characterize the abnormal B-cell response to glucose in type II diabetes, five diet-treated diabetic and six weight-matched non-diabetic subjects were studied using the hyperglycemic clamp technique on three separate days at glycemic levels of 7.5, 10 and 15 mmol/L for 150 minutes with assessment of plasma insulin and C-peptide responses. To reduce possible secondary effects of hyperglycemia, diabetic subjects on a weight-maintaining diet were chosen who had only a slight elevation of the fasting plasma glucose, mean 6.

Unbiased and flexible iterative computer program to achieve glucose clamping.

Glucose clamping has become a widely used test for assessing insulin sensitivity and beta-cell function. We present a new method of achieving a reliable and unbiased clamp using an iterative computer program. After initial parameter estimation, the program uses no fixed algorithm or physiological preconceptions but makes predictions according to previous glycemic responses to infusion rates.

Suppression of insulin secretion by falling plasma glucose levels is impaired in type 2 diabetes.

The ability of Type 2 diabetic patients to suppress islet B-cell secretion in response to falling plasma glucose levels has been studied with two different protocols. (1) Five diet-treated diabetic patients and 6 normal subjects were studied after the termination of a hyperglycaemic clamp at 15 mmol l-1 for 150 min, with the plasma glucose levels then being allowed to fall and the glucose clamp re-established at 10 mmol l-1. The plasma insulin levels fell in normal subjects from 178 +/- 141 (+/- SD) mU l-1 at the end of the 15 mmol l-1 clamp to 147 +/- 97 mU l-1 (p less than 0.

The glucose stimulus-response curve of the beta-cell in physically trained humans, assessed by hyperglycemic clamps.

In order to examine the effect of habitual exercise on beta-cell responses over a wide range of plasma glucose levels, plasma insulin and C-peptide responses to 2 1/2-hour hyperglycemic clamps at 7.5, 10, and 15 mmol/L glucose were assessed in six trained athletes and six age- and weight-matched sedentary controls. Athletes were significantly fitter than controls (estimated maximal oxygen uptake [VO2 max] mean 44 v 30 mL.

The beta cell glucose stimulus-response curve in normal humans assessed by insulin and C-peptide secretion rates.

Insulin and C-peptide secretion rates have been measured and compared in 12 nondiabetic subjects to characterize the glucose stimulus-response of B cell secretion in man. On three different days, glucose concentrations were clamped for 150 minutes at 7.5, 10, and 15 mmol/L, respectively.

Does adding fibre to a low energy, high carbohydrate, low fat diet confer any benefit to the management of newly diagnosed overweight type II diabetics?

The effect of supplementing a low energy (roughly 5.0 MJ), high carbohydrate (180 g), low fat (roughly 25 g) diet with 10-15 g of either cereal fibre or guar gum was investigated in 24 newly diagnosed overweight non-insulin-dependent (type II) diabetics. The patients were divided into three treatment groups: one received a low fibre control diet throughout the study period of 20 weeks and the other received two supplements of cereal fibre and guar gum in a crossover manner.

Insulin secretion to glucose infusion in gestational diabetes subjects with differing DNA polymorphisms flanking the insulin gene.

Glucose-stimulated insulin secretion was assessed in relation to the DNA polymorphism flanking the insulin gene in 16 women who had had gestational diabetes. When not pregnant they were studied by a Constant Glucose Infusion for 1 hr with Model Assessment (CIGMA). The patients with either heterozygous 1/3 alleles or homozygous 1/1 or 3/3 alleles in the 5' flanking region of the insulin gene had similar plasma insulin and C-peptide concentrations and similar estimates of beta-cell function.

Pancreatic islet amyloid and elevated proinsulin secretion in familial maturity-onset diabetes.

Quantitative morphometry of immunostained pancreatic islet cells in a surgical specimen from a maturity-onset diabetic (MOD) patient (A) has been combined with a study of beta-cell secretion in him and his MOD son (B). The morphometry showed intra-islet amyloid deposits in 24% of islet sections which is a similar distribution to that found in 7 other MODs, (median 24%, range 0-95%). The distribution of islet cells in the pancreas from A was similar to the 7 MODs and 9 age matched non-diabetic subjects (mean beta-cell area per exocrine area, A, 2%; MODs, 1.

Beta-cell dysfunction, rather than insulin insensitivity, is the primary defect in familial type 2 diabetes.

Continuous infusion of glucose with model assessment was used to measure glucose tolerance, beta-cell function, and insulin sensitivity in 154 first-degree relatives of 55 patients with type-2 diabetes. The plasma glucose achieved at 1 h was normally distributed in normal control subjects, but 31 (20%) of relatives of type-2 diabetics had values above the normal distribution mean +2 SD. Insulin secretion, assessed from the first or second phase plasma-C-peptide responses, was significantly lower in the glucose-intolerant relatives than in normoglycaemic relatives of similar sex, age, and obesity.

Sulphonylurea therapy doubles B-cell response to glucose in type 2 diabetic patients.

The effect of sulphonylurea therapy for 3 weeks on glucose-stimulated insulin secretion and insulin resistance was studied in Type 2 diabetic patients. The fasting plasma insulin and C-peptide concentrations on diet alone were compared with each subject's fasting concentrations on sulphonylurea treatment at a lower fasting plasma glucose and at the original diet-alone glycaemic level obtained by the hyperglycaemic clamp technique. At this isoglycaemic level (mean 11 mmol/l), plasma insulin levels increased from 6.

Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.

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 beta-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 beta-cell function to the fasting hyperglycaemia (homeostasis model assessment, HOMA).

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

Continuous infusion of glucose with model assessment (CIGMA) is a new method of assessing glucose tolerance, insulin resistance and beta-cell function. It consists of a continuous glucose infusion 5 mg 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.

Transient, selective factor X deficiency and acute liver failure following chest infection treated with erythromycin BP.

A 57-year-old man developed symptoms of a respiratory tract infection which was treated with erythromycin BP. He subsequently went into acute liver failure. Investigation of a very prolonged prothrombin time revealed a marked, selective factor X deficiency (1% of normal activity).

Communicating hydrocephalus in the intellectual deterioration of diabetes mellitus.

Atherosclerosis of cerebral vessels (Grunnet 1963) and hypoglycaemia (Bale 1973) are thought to be involved in the premature intellectual deterioration which occurs in some diabetics. Two diabetics are now reported who, in the course of their investigation for intellectual deterioration, were found to have communicating hydrocephalus.

Insulin treatment of newly-presenting ketotic diabetic patients into the honeymoon period.

Newly-presenting, ketotic juvenile-onset diabetics initially need full insulin replacement, and this has been attempted with ultralente insulin, including a loading dose, to provide the basal insulin requirement, and twice-daily soluble insulin to cover main meals. A simple method has been developed for the patient to reduce the basal and meal-related insulin doses during the stabilisation period, during which insulin production recovers and administered insulin needs fall. The method was applied to 12 patients, whose mean insulin dose was reduced over 4 weeks, from 62 to 33 units/day, with maintenance of good control.