R. J. Jarrett

Diabetes mellitus · A

Inledning Randomiserade studier har styrkt betydelsen av god glukoskontroll både vid typ 1och typ 2-diabetes för att förhindra främst mikrovaskulära komplikationer (1). Även hjärt-kärlsjukdomar förhindras om än i mindre grad (2). Nyligen har stora randomiserade studier som inkluderat personer med typ 2-diabetes och hög risk för hjärtkärlsjukdomar visat att SGLT-2-hämmare (natrium-glukos-kotransportör 2-hämmare) (empagloflozin och kanagliflozin) och GLP-1-agonister (glucagon-like polypeptide 1-agonister) (liraglutid och semaglutid) minskar risken för återinsjuknade och död i hjärt-kärlsjukdom (3, 4, 5, 6, 7, 8). Vid typ 2-diabetes har den multifaktoriella riskfaktorbehandlingen starkt stöd (9, 10). Strikt blodtryckskontroll och behandling med statiner förebygger njurskador. Blodtrycksbehandling som enda behandling förebygger hjärt-kärlsjuklighet och död (11, 12, 13, 14). Sammantaget talar detta för att vid diabetes förhindras eller fördröjs både mikrooch makrovaskulära komplikationer av intensifierad behandling något som tillsammans med förändring till hälsosammare levnadsvanor är högt prioriterat i de Nationella riktlinjerna för diabetesvård.

Plasma lipid and coagulation factor concentrations in insulin dependent diabetics with microalbuminuria.

OBJECTIVE--To determine whether insulin dependent diabetics with microalbuminuria have significant abnormalities in concentrations of lipoproteins, apolipoproteins AI and B, fibrinogen, and clotting factor VII which could result in increased cardiovascular risk. DESIGN--Case-control study. SETTING--Outpatient department of a metabolic ward. PATIENTS--Group of 20 insulin dependent diabetics with urinary albumin excretion rates greater than 30 micrograms/min (microalbuminuria) and 20 individually matched insulin dependent diabetics with normal urinary albumin excretion rates (below 30 micrograms/min) matched for age, sex, and duration of diabetes. INTERVENTIONS--Fasting venous blood samples were taken for determination of concentrations of glucose, glycated haemoglobin, lipoproteins, apolipoproteins AI and B, fibrinogen, and factor VII. Height, weight, arterial pressure, and usual insulin dose were recorded, and each patient was given a dietary questionnaire to be completed at home. END POINT--Comparison of blood pressure and concentrations of lipoproteins, apolipoproteins AI and B, and fibrinogen in the diabetics with microalbuminuria and the controls. MEASUREMENTS AND MAIN RESULTS--Patients with microalbuminuria had significantly higher concentrations of low density lipoprotein cholesterol (mean 3.33 (SE 0.20) v 2.84 (0.12) mmol/l) and very low density lipoprotein cholesterol (0.30 (0.05) v 0.17 (0.03) mmol/l) than controls but significantly lower concentrations of high density lipoprotein 2 subfraction cholesterol (0.32 (0.04) v 0.54 (0.04) mmol/l). Concentrations of total triglyceride (1.11 (0.14) v 0.68 (0.08) mmol/l), very low density lipoprotein triglyceride (0.56 (0.10) v 0.30 (0.05) mmol/l), apolipoprotein B (0.88 (0.06) v 0.67 (0.03) g/l) and fibrinogen (2.2 (0.1) v 1.9 (0.1) g/l), and diastolic arterial pressure (80 (2) v 74 (2) mm Hg), were also higher in patients with microalbuminuria. CONCLUSIONS--Cardiovascular risk factors--namely, disturbances in lipoprotein and apolipoprotein concentrations, increased fibrinogen concentration, and increased arterial pressure--are already present in insulin dependent diabetics with microalbuminuria. The increased risk of coronary heart disease in patients with clinical proteinuria may result from prolonged exposure to these risk factors, which are present before any impairment of renal function.

Diurnal Variation in Oral Glucose Tolerance: Blood Sugar and Plasma Insulin Levels Morning, Afternoon, and Evening

Twenty-four subjects received three oral glucose tolerance tests, in the morning, afternoon, and evening of separate days. The mean blood sugar levels in the afternoon and evening tests were similar, and they were both significantly higher than those in the morning test. Plasma immunoreactive insulin levels, however, were highest in the morning test. The pattern of insulin levels during the afternoon and evening tests resembled that described as typical of maturity-onset diabetes.

DIURNAL VARIATION IN INSULIN SENSITIVITY

Abstract Intravenous insulin-tolerance tests were performed on the same subjects on two occasions, once in the morning and once in the afternoon. The fall in blood-sugar was consistently and significantly greater in the morning. If there is a similar diurnal variation in the sensitivity to endogenous insulin, it would partly explain the phenomenon of diurnal variation in oral-glucose tolerance.

Treatment of borderline diabetes: controlled trial using carbohydrate restriction and phenformin.

A five-year therapeutic trial of carbohydrate restriction with or without phenformin (50 mg/day) was performed in men with borderline diabetes. The aim of treatment was to diminish the enhanced risk of cardiovascular disease and deterioration of glucose tolerance. Cardiovascular morbidity and mortality were not significantly affected by any form of treatment, alone or in combination. The predominant risk factor for cardiovascular morbidity and mortality and for overall mortality was the initial blood pressure level. The baseline plasma cholesterol concentration significantly predicted the onset of intermittent claudication. One implication of the results is that hypotensive treatment, supplemented when necessary with hypolipidaemic treatment, may be more effective in preventing the progression of arterial disease in people with mild to moderate glucose intolerance than conventional antidiabetic therapy.

Borderline diabetics and their response to tolbutamide.

Publisher Summary This chapter presents a study of borderline diabetics. In the study, it was found that treatment of a group of mildly hyperglycemic diabetic individuals with tolbutamide appeared to protect them against the manifestations of arterial disease over a five-year period as compared to a closely similar group treated, double-blind, with an indistinguishable placebo. The 248 borderline diabetics involved in this study were newly detected in the Bedford population survey of 1962 and were defined as having capillary blood sugar values between 120 and 199 mg/100 ml 2 h after 50 gm of oral glucose. Shortly after their detection, the 248 subjects were randomly allocated to tolbutamide or placebo treatment groups, each of which was further randomly divided into approximately equal-sized carbohydrate-restricted and placebo diet subgroups.

Physical activity and prevalence of diabetes

Dear Sir, It has recently been suggested that in Type I (insulin-dependent) diabetes, mebendazole improves glycaemic control and increases Cpeptide secretion [1]. We have conducted a study in 12 poorly controlled Type 1 diabetic patients (Table1). Mebendazole (Vermox, Janssen Pharmaceuticals, Beerse, Belgium) was administered orally at a dose of 200mg/day for 3 days, and, thereafter, at 100mg/day throughout the 30-day study period. All patients continued their usual diet, ranging from 1500 to 2000 calories/day (carbohydrate 50%, fat 30%, protein 20%) and their usual mixtures of shortand long-acting insulin. At the beginning of the study and at the end of the 30-day treatment period, after an overnight fast, all patients attended the outpatient clinic for measurement of glycaemic profiles, 24-h urinary glucose, total glycosylated haemoglobin (HbA 0 and C-peptide levels. The results are shown in Table I. Although there was a trend towards a decrease in blood glucose levels at day 30, this decrease was not significant. Mean HbAI levels did not decrease and no changes in 24-h urinary glucose output were demonstrated. Fasting and post-prandial C-peptide levels did not change following the 30-day treatment period. In a sub-group of patients (n = 5), who demonstrated C-peptide secretion (fasting C-peptide ~>0.15pmol/ml and post-prandial Cpeptide i>0.30 pmol/ml), similar non-significant decreases in both mean fasting and post-prandial plasma glucose levels were observed. Although Lefebvre and Luyckx [2] demonstrated an imidazole-related increase in insulin secretion in dogs in 1971 and Kameda et al. [3] postulated that the imidazole derivative DG 5128 could stimulate glucose-induced insulin secretion in 1982, the recent report by Caprio et al. [1] was the first to outline some clinical effects of this compound in diabetes. However, our results do not confirm the findings of their preliminary study.

Biosynthetic Human Insulin: Effect in Healthy Men on Plasma Glucose and Non-Esterified Fatty Acids in Comparison with Highly Purified Pork Insulin

Biosynthetic human insulin (BHI) produced by recombinant DNA technology was administered subcutaneously and intravenously at two dose levels to two groups, each consisting of six normal men. Responses were compared with those for purified pork insulin (PPI) given by the same routes at the same dose levels to the same two groups. The glycemic response to the insulins was similar with a suggestion (seen both with intravenous and subcutaneous administration) that the glycemic depression with BHI was slightly greater at low dose and less at high dose. No significant difference between insulin types was found in the depression of non-esterified fatty acid (NEFA) concentrations, although significant differences between types with low-dose subcutaneous injection emerged during the later phases of the experiment. After termination of high-rate infusion with both insulins, NEFA concentrations rose more rapidly with some overshoot, suggesting that the rate and depth of blood glucose fall in these experiments might have triggered a brisker counterregulatory response. The small differences found between human and pork insulins, although in some cases significant, are unlikely to be of clinical importance.

Exercise and diabetes

Physical activity activates has acute and chronic effects on glucose, lipid and protein metabolism. In type 1 diabetic subjects, the lack of the physiological inhibition of insulin secretion during exercise results in a potential risk of hypoglycemia. On the other hand, exercise-induced activation of counterregulatory hormones might trigger an acute metabolic derangement in severe insulin-deficient subjects. Thus, diabetic patients, before starting exercise sessions, must be carefully educated about the consequences of physical activity on their blood glucose and the appropriate modifications of diet and insulin therapy. Long-term effects of regular exercise are particularly advantageous for type 2 diabetic patients. Regular aerobic exercise reduces of visceral fat mass and body weight without decreasing lean body mass, ameliorates insulin sensitivity, glucose and blood pressure control, lipid profile and reduces the cardiovascular risk. For these reasons, regular aerobic physical activity must be considered an essential component of the cure of type 2 diabetes mellitus. In this regard, individual behavioral strategies have been documented to be effective in motivating sedentary type 2 diabetic subjects to the adoption and the maintenance of regular physical activity.