Effect of sulphonylurea administration on insulin secretion and amino acid metabolism in non-insulin-dependent diabetic patients.

Sulphonylureas lower blood glucose but other metabolic effects have been little studied. In an assessment of carbohydrate and amino acid metabolism in 9 patients with non-insulin-dependent diabetes mellitus (NIDDM) before and after 3 months' therapy with gliclazide, glycaemic control was improved (mean +/- S.D. glycosylated haemoglobin 13.8 +/- 1.9% before therapy, 10.2 +/- 2.1% after therapy (p less than 0.01], but fasting amino acid levels were not altered. In contrast, postprandial levels of branched chain amino acids (BCAA) were significantly reduced: total BCAA (valine, leucine, and isoleucine) 120 mins following a standard test meal fell from 717 +/- 71 mumol/l before therapy to 600 +/- 90 mumol/l after 3 months' therapy (p less than 0.01). This finding implies an increased action of endogenous insulin on skeletal muscle to promote uptake of BCAA postprandially and, in accord with this, peripheral insulin levels were significantly increased following drug treatment (peak insulin level 55.6 +/- 20.2 mU/l before therapy, 91.3 +/- 17.9 mU/l after therapy (p less than 0.01]. Sulphonylurea drugs therefore do not simply have a hypoglycaemic action but also affect amino acid metabolism in NIDDM patients.

Dissociation of adrenarche and gonadarche in diabetes mellitus.

Serum concentrations of testosterone and dehydroepiandrosterone sulphate (DHAS) have been measured in 10 stable insulin-dependent diabetic (IDD) males (chronological age (CA) range 13.0-17.5 years). Their results have been compared with those of a control population of 69 non-diabetic males who presented with mild constitutional growth delay and whose skeletal maturity and pubertal development were similar to the diabetic subjects. Within bone ages (BA) 11.0-14.5 years no significant difference was observed between the serum testosterone concentrations of the diabetic patients and controls: diabetic males, 8.2 (0.3-25) nmol/l (median and range); controls, 7.0 (less than 0.3-23) nmol/l. In contrast, within BA 11.0-14.5 years, the diabetic males had significantly lower serum DHAS concentrations: diabetic males, 1.1 (0.7-4.2) mumol/l; controls, 3.7 (0.7-5.6) mumol/l (P less than 0.001). The serum DHAS concentrations of the diabetic males were also significantly lower than the controls when matched separately for pubic hair and genital development, testicular volume and serum testosterone, (in each comparison P less than 0.02). Serum DHAS concentrations of the diabetic males did not correlate significantly with CA, BA, BA delay (CA-BA), age of onset of diabetes, duration of diabetes, or glycosylated haemoglobin (GHb), but significant correlation was observed between BA delay and duration of diabetes, r = 0.65, P less than 0.05. We conclude that gonadarche appears to proceed despite delayed adrenarche in IDD males. This study presents further evidence in favour of adrenarche and gonadarche being independent physiological events. The causes and clinical significance of low serum DHAS concentrations in adolescent diabetic males remain to be established.

Effects of diabetic control and biosynthetic human insulin on blood rheology in established diabetics.

Blood rheology (blood viscosity, haematocrit, plasma viscosity, erythrocyte sedimentation and deformability) was measured in 22 diabetics in a study to compare animal insulins with biosynthetic human insulin. All rheological variables were significantly abnormal in the diabetics when compared with matched normal controls, and were not influenced by the type of insulin injected. However, blood rheology was related to diabetic control, as judged by glycosylated haemoglobin levels; when diabetic control was worst (mean glycosylated haemoglobin 11%), blood viscosity was significantly higher and red cell deformability significantly lower than when control was at its best (mean glycosylated haemoglobin 9.5%). A similar correlation between mean red cell deformability and mean glycosylated haemoglobin was found when individual diabetics were compared (r = 0.66; p less than 0.001). The occurrence of abnormal blood viscosity and red cell deformability during periods of poor diabetic control may contribute to the development of diabetic vascular complications.

Changes in glycosylated haemoglobin after oral glucose load.

To study the relation between hyperglycaemia and a change in the concentration of glycosylated haemoglobin (HbA1) blood glucose and HbA1 concentrations were measured during an oral glucose tolerance test and for 120 days afterwards in 20 normal subjects. These measurements showed that a minor degree of hyperglycaemia led to a significant increase in lycosylated haemoglobin concentrations. The increase appeared 10 days after the test, and values remained raised until 30 days and returned to normal 60 days after the test. If such a minor fluctuation of blood glucose can lead to a significant increase in HbA1 concentrations the test may be too sensitive as an index of long-term blood glucose control in diabetics.

Blood viscosity in young male diabetics with and without retinopathy.

Blood viscosity (shear rates 100s-1 and 0.94s-1) and several of its major determinants (haematocrit, plasma fibrinogen and plasma viscosity) have been measured in 38 male insulin-treated diabetics, aged 18-50 years, and in 38 non-diabetic control subjects matched for age and smoking habit. Diabetics without fundoscopic retinopathy (n=20) had higher mean blood viscosity than controls at the high shear rate (7.07 cP vs 6.75 cP, p < 0.05) and the low shear rate (21.2 cP vs 18.7 cP, p < 0.025). These differences persisted after correction of blood viscosity to a standard haematocrit, and were associated with increased plasma viscosity (1.41 cP vs 1.34 cP, p < 0.025) and plasma fibrinogen (2.9 g/L vs. 2.5 g/L, p < 0.025). Diabetics with retinopathy (n = 18) had higher mean blood viscosity than diabetics without retinopathy at the high shear rate (7.53 cP vs 7.07 cP, p < 0.05) and the low shear rate (24.3 cP vs. 21.2 cP, p < 0.05), associated with a higher haematocrit (p < 0.05). Blood viscosity and haematocrit correlated with the duration of diabetes (r > 0.32, p < 0.05).

Effect of carbohydrate restriction on lipoprotein abnormalities in maturity-onset diabetes mellitus.

Hyperlipoproteinemia occurs commonly in diabetics and may contribute to early atherosclerosis in these patients. The effect of dietary carbohydrate restriction on lipid abnormalities has been examined in 42 newly diagnosed maturity-onset diabetics, in whom plasma lipoproteins were measured before treatment was started and at regular intervals during ten months of dietary therapy. Twenty-four patients (57%) had abnormal lipids when diabetes was first diagnosed. Nine were classed as Type II and 15 as Type IV hyperlipoproteinemia. Plasma lipids reverted to normal in half these patients after dietary treatment for one month. Only 8 diabetics (19%) showed persistent lipid abnormality after ten months' treatment: all had been unable to diet satisfactorily as judged by persisting obesity and hyperglycemia. The common lipoprotein abnormalities of maturity-onset diabetes can usually be returned to normal by the simplest possible carbohydrate-restricted diet, if patients adhere to this. Specialized and complex diets or lipid-lowering drugs are unncessary in the majority of patients.

Lipoprotein concentrations in untreated adult onset diabetes mellitus and the relationship of the fasting plasma triglyceride concentration to insulin secretion.

Plasma lipoprotein concentrations in 64 untreated adult onset diabetics were compared to the lipoprotein levels found in non diabetics. No significant difference was found. The relationship of the fasting plasma triglyceride concentration to the plasma immunoreaction insulin response to 50 g glucose orally was investigated. Using correlation analysis a significant and insulin response in the non diabetics but not in the diabetics.

Occupational absorption of tellurium: a report of two cases.

Industrial uses of tellurium are limited, and reported cases of tellurium absorption of occupational origin are rare. Two such cases are reported here. Both showed typical signs and symptoms of intoxication; in particular, the stench of sour garlic was noted on breath and from excreta. An unusual feature was the bluish-black discoloration of the webs of the fingers and streaks on the face and neck. Full hospital investigation was negative. No permanent damage resulted and each patient made a spontaneous recovery without treatment.

Continuous intravenous infusion of small doses of insulin in treatment of diabetic ketoacidosis.

Continuous intravenous infusion of small amounts of insulin has been used in the management of a series of patients with diabetic ketoacidosis. In 13 patients with a plasma glucose level on admission of 725 mg/100 ml (+/- 80 S.E. of mean) and an arterial pH of 7.07 +/- 0.05 a mean loading dose of 6.5 +/- 0.82 units of soluble insulin was administered intravenously, and thereafter a sustaining infusion of 6.5 +/- 0.82 U/hr was continued until ketosis was corrected and the plasma glucose fell below 300 mg/100 ml. The total insulin dose needed to achieve this was 39.2 +/- 6.6 units given over a 3 to 10-hour period. Plasma insulin was measured in patients who had not previously received insulin and the mean level at an infusion rate of 4 U/hr was 75.6 +/- 8.0 muU/ml. Plasma glucose fell at a regular rate of 101 +/- 11 mg/100 ml/hr, and ketosis improved in parallel. Plasma potassium was well maintained throughout treatment. This regimen of treatment was clinically effective and simple to follow.

Evolution of an examination: M.R.C.P. (U.K.).

Recent changes in the structure of the examination for M.R.C.P. (U.K.) have prompted a review of these together with a historical outline of the examinations which preceded it at the Royal Colleges of Physicians of Edinburgh, Glasgow, and London.Part I of the examination continues to fulfil its role as a screen and a slight change in the marking system appears to have improved its discriminating powers still further. The major change in part II is the substitution of a more objective written test in place of the essay papers.

Mycoplasmas and recurrent oral ulceration.

A controlled cultural and serological investigation of mycoplasmas in recurrent oral ulceration was undertaken. No evidence for an aetiological relationship between oral mycoplasmas and this condition was obtained.Mycoplasmas, principally M. orale, were frequently recovered from the oral cavities of individuals with natural teeth, but rarely from edentulous subjects.