P.‐O. Bitzén

Norlund A, Apelqvist J, Bitzén P.‐O, Nyberg P, Scherstén (Swedish Council on Technology Assessment in Health Care, Stockholm; and University Hospital; and Dalby/Lund, University of Lund, Lund, Sweden) Cost of illness of adult diabetes mellitus underestimated if comorbidity is not considered. J Intern Med 2001; 250: 57–65. Objective. To determine costs of illness for adult diabetes mellitus (DM), including complications caused by DM. Design. A population‐based multicentre cross‐ sectional study including an interview and a physical examination of patients identified as having DM. The patients’ medical records were analysed regarding diagnoses and complications attributable to DM. Setting. Eight health care centres of six primary care districts in Southern Sweden. Subjects. 1677 adults aged 25+, cared for at the health care centres, entered the study. Main outcome measures. Utilization of health care and care from relatives and the municipality, absence of short‐ and long‐term sickness, cost of illness. Results. The average annual direct and indirect costs for an adult with DM were calculated to be 61 700 Swedish Kronor (SEK) or 2.5 times higher than earlier estimates. The incremental cost of DM was 34 100 SEK. The cost distribution was 28% for health care, 31% for the municipality and relatives and 41% lost productivity. Conclusions. Calculations for the cost of illness of DM are underestimated if comorbidity caused by DM is not considered. When DM‐related complications are included to identify the actual burden of disease to society, the cost of illness as a result of DM in Sweden is substantially higher than previously estimated.

A selective and sensitive gas chromatographic technique was used to measure the steady-state serum concentrations of tolbutamide and chlorpropamide in 97 patients with maturity-onset diabetes mellitus who had been taking these drugs (37 tolbutamide, 60 chlorpropamide) for at least a year. No other antidiabetic agents had been given. The serum tolbutamide concentrations varied widely between the patients (from close to zero to 370 mumol/l (100 mug/ml)), yet the variation in dosage was only sixfold (0.5-3.9 g daily). The serum chlorpropamide concentrations varied even more widely (from close to zero to 882 mumol/l (244 mug/ml)), though the dosage variation was fourfold (125-500 mg daily). There was no systematic relation between dosage and serum concentrations of the drugs.Only 2 (5.4%) of the tolbutamide-treated patients and 10 (16.7%) of the chlorpropamide-treated patients had normal fasting blood glucose concentrations (below 5.5 mmol/l (99 mg/100 ml)), and fewer than half had values below 8.0 mmol/l (144 mg/100 ml). In most cases, therefore, the treatment was insufficient.There was no significant difference in mean fasting blood glucose concentrations between the two treatment groups. The mean steady-state concentration of chlorpropamide, however, was significantly higher than that of tolbutamide. Thus, contrary to common belief, the intrinsic activity of chlorpropamide is apparently not greater than that of tolbutamide. The alleged greater potency of chlorpropamide seems to be related wholly to kinetic differences, such as the less extensive metabolic degradation and slower elimination of the drug.We conclude that treatment with sulphonylureas in conventional dosage is far from optimal and that monitoring the concentrations of these drugs in the blood may help to improve their efficacy.

Metformin and glibenclamide were compared in a randomized, double-blind trial in patients with non-insulin-dependent diabetes mellitus (NIDDM) using a parallel group design. The study was performed in primary health care, and the main purpose was to assess combination therapy with the two drugs as primary treatment versus conventional oral therapy. After a 2 months diet period patients were randomized to commence treatment with either metformin, glibenclamide or the combination of both. Patients randomized to monotherapy received the alternative drug in addition if the maximal dose i.e. 3 g metformin or 14 mg glibenclamide was insufficient to normalize the fasting blood glucose concentration (FBG). Randomization and dose escalation occurred at FBG greater than or equal to 6.7 mmol/l. The titrated dose was continued for 6 months, whereafter placebo was given for 2 weeks. Seventy-two patients were randomized to either the metformin group (n = 38) or the glibenclamide group (n = 34). Fifty-six completed 6 months treatment, twenty-eight in each randomized group. Glycaemic control was unchanged after diet alone in all groups. The improvement during drug treatment was highly significant (p less than 0.001), mean FBG difference (+/- SEM) 3.2 +/- 0.4 mmol/l and mean HbA1c difference (+/- SEM) 1.5 +/- 0.2% (n = 56). There were no significant differences between patients treated solely with metformin (n = 16) and glibenclamide (n = 17) or between patients treated with a combination of glibenclamide added to metformin (n = 12) and metformin added to glibenclamide (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)

The efficacy of dietary regulation was examined in 38 consecutive primary health care patients with hyperglycaemia detected on screening. Ten weeks of dietary regulation reduced overall mean fasting blood glucose from 8.2 to 6.5 mmol l-1. Fasting blood glucose fell more (from 12.3 to 7.6 mmol l-1 and from 8.4 to 6.6 mmol l-1) in the two quartiles initially above the median (7.15 mmol l-1), than in the lower quartiles (6.7 to 6.1 mmol l-1 and 5.7 to 5.8 mmol l-1), even though weight reduction was similar. The reduction in blood glucose correlated (r = 0.87) with the degree of fasting hyperglycaemia before treatment. Sixteen patients (42%) reached or maintained fasting blood glucose less than or equal to 6.0 mmol l-1, and they had a milder degree of glucose intolerance, a higher insulin response to a meal and a greater reduction in weight than the 22 patients (58%) who did not reach less than or equal to 6.0 mmol l-1. Nine patients (24%) maintained fasting blood glucose less than or equal to 6.0 mmol l-1 for greater than 5 years, and showed a considerable improvement of insulin action. Dietary regulation improved glucose control mainly by reducing fasting hyperglycaemia; neither the delay in early insulin release nor the associated elevation and prolongation of the post-prandial glucose excursions were reduced.