Recent data provided by the EURODIAB ACE study group have confirmed wide variation in the incidence of insulin-dependent diabetes mellitus (IDDM) across Europe. The aim of this report is to compare age-specific incidence and seasonality at clinical onset of IDDM between study regions. Using a uniform methodology, the EURODIAB ACE framework ascertained 3,168 newly-diagnosed cases of IDDM in children under the age of 15 years during 1989-1990. Eighteen percent of the cases were age 0-4 years at diagnosis, 34 % were age 5-9 years and 48 % were age 10-14 years. Poisson regression analysis suggested that there were highly significant statistical differences in incidence between the three age groups and between the 24 regions. Although incidence rates in the 0-4 year and 5-9 year age groups varied from region to region in a similar fashion, the pattern of variation in the older age group was different. Seasonality of diagnosis conformed to a sinusoidal model with a peak occurring in winter, a feature which was consistently observed in both sexes and in all age groups. However, a statistically significant heterogeneity in the seasonal distribution was present among regions, those in Scandinavia showing the smallest relative amplitude. The first insulin injection was given the same day or the day after diagnosis in 93 % of the cases for whom data were available.

OBJECTIVE - Care guidelines for people with non-insulin-dependent diabetes mellitus (NIDDM) emphasize the importance of weight loss in reducing mortality risk. However, existing evidence regarding the relationship between weight and mortality and the effects of weight change is conflicting. We examined these relationships in the World Health Organization Multinational Study of Vascular Disease in Diabetes.RESEARCH DESIGN AND METHODS - This was a cohort study of 1,416 men and 1,544 women. Baseline examinations were performed in 1975 through 1977, a morbidity follow-up was performed in 1983, and a mortality follow-up continued until 1988. Data were analyzed according to geographical groups: Europeans, East Asians, and Native Americans. The relationship between weight change and mortality was analyzed for Europeans only.RESULTS - Generally, body mass index (BMI) was positively associated with age, blood pressure, and cholesterol but was negatively associated with duration of diabetes, prevalence of retinopathy, and use of insulin. There was no clear relationship between BMI and mortality across the geographical groups. In Europeans, weight loss in the leanest subjects at baseline (BMI < 26 kg/m(2)) was associated with a threefold increase in mortality risk compared with those who had maintained a steady weight (relative risk [RR] 3.05, 95% confidence interval [CI] 1.26-7.36). Only in the most obese group was weight loss associated with a reduction in mortality risk (BMI > 29 kg/m(2), RR 0.84, 95% CI 0.40-1.74).CONCLUSIONS - The positive association of BMI with age, blood pressure, and cholesterol and the negative association with duration of diabetes, retinopathy, and use of insulin may explain why there is no strong relationship between BMI and mortality in NIDDM. Weight loss, particularly in the relatively lean diabetic person, may be associated with an increased mortality risk.

OBJECTIVE Strict glycemic control in people with insulin-dependent diabetes mellitus (IDDM) reduces the risk of microvascular complications, but improvementsin control are also associated with weight gain. Fears about the mortality risks of obesity may limit the acceptability of tight control. Therefore, we examined morbidity and mortality risks associated with body weight in people with IDDM. RESEARCH DESIGN AND METHODS This was a cohort study of 644 men and 576 women with IDDM from nine centers worldwide. Baseline examinations were performed in 1975–1977, and mortality follow-up continued until 1988. RESULTS Body weight was positively associated with blood pressure and, in men, with cholesterol. Fasting blood glucose was higher in the most obese groups in women only. There were 204 deaths among the men and 148 among the women. There was a reverse J-shaped relationship between body weight and all-cause mortality, with the highest mortality rates occurring in the leanest body mass index (BMI) category. The age-, duration-, and center-adjusted mortality rate ratio (95% confidence interval) comparing BMI category < 20 kg/m2 with BMI category ≥22 and <24 kg/m2 was 2.64 (1.59–4.38) in men and 1.54 (0.77–3.06) in women. Additional adjustment for smoking, blood pressure, glucose, cholesterol, and proteinuria did not qualitatively alter these findings. CONCLUSIONS We conclude that except in very lean people with IDDM, body weight is not significantly associated with mortality. Thus, efforts to improve glycemic control should not be restricted by concerns about the effects of weight gain on mortality.

The aim of the study was to compare the immunogenicity of semisynthetic human and porcine monocomponent (MC) insulin Novo during--5-year observation. Thirty-one diabetic patients, never previously treated with insulin were randomly allocated to treatment with one of the two coded insulin preparations in a double blind trial. 15 patients aged 20-58 years (mean age--36 years) were treated with human insulin and 16 diabetics aged 19-61 years (mean age--34 years) with MC pork insulin. The insulin was injected twice a day (Actrapid plus Monotard). Serum insulin-binding antibodies were determined according to Christiansen (radioimmunoelectrophoretic method). The development of insulin-binding antibodies during the first year of observation was more rapid in patients treated with MC pork insulin but thereafter it was similar in the two studied groups. After 5 years of treatment with human insulin serum insulin-binding antibodies were found in 14 patients. The level of antibodies was very low (< 0.130 mU/ml) in 5 subjects, low (0.171-0.401 mU/ml) in 6 patients and relatively high (0.885; 1.186; 5, 162 mU/ml) in 3 patients. In the group of diabetics treated with MC pork insulin after 5 years of observation serum insulin-binding antibodies were found in 12 patients. The level of antibodies was low (0.131-0.576 mU/ml) in 9 subjects and relatively high (1.034; 3.954; 5.639 mU/ml) in 3 patients. The results obtained after 2-5 years of the study did not differ significantly (Wilcoxon's test, p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

In 1986 a register of insulin-dependent diabetes mellitus (IDDM) was set up which comprised the population of 3 cities in Poland (1.7 million people aged between 0-29 yr). In 1988 we joined the Eurodiab Study, and in 1990 the Diamond Study. All registered patients had to fulfil the following criteria - had IDDM diagnosed according to the National Diabetes Data Group (NDDG) recommendation - had onset of diabetes at an age between 0 and 29 yr after 31 Dec. 1985 - had to be resident in the selected areas. The register originates from 3 independent sources, primary data source has been provided by provincial outpatient clinics, by respective medical academies, pediatrics and internal medical departments or parallel town hospital wards, and a retrospective review was performed on the basis of hospital records. From 1986-1991 mean annual incidence rate was 5.3 (3.3-7.7 range) with the confidence-interval level 95%. From 1985 to Sept 1986, randomised population studies were performed in subjects aged 25 to 74 yr inhabiting the Old City in Wroclaw. The sample population, i.e. 5.3% of the whole population comprised 1,169 men and 1,351 women. Diabetes mellitus was diagnosed using NDDG criteria. The incidence of diagnosed diabetes was 3.59% in men and 3.94% in women, including known diabetes in 2.31% of men and 2.51% of women - therefore ''unknown'' diabetes made up about 35% of all cases. Carbohydrate intolerance was found in 2.48% of men and 3.32% of women. We found a close relationship between the incidence of diabetes, carbohydrate intolerance, age and obesity. In comparison with Eurodiab Data the incidence rate of IDDM in Poland is one of the lowest, although prevalence of NIDDM is comparable to other European countries.

The oral ethanol loading test (0.5 g per kg b.m. given as 40% solution) was carried out in 5 groups, each of 10 patients with non-insulin-dependent (type 2) diabetes before and after 10 days of treatment with one of the following sulphonylurea derivatives: tolbutamide 0.5 t.i.d., chlorpropamide 0.5 once daily morning, glibornuride 0.025 t.i.d, glibenclamide 0.005 t.i.d. and glipizide 0.005 t.i.d. The response to alcohol (facial flush, heart rate, blood pressure) were compared, and blood concentration of ethanol, acetaldehyde, pyruvate, lactate, carbonates as well as blood pH, pO2 and pCO2 were determined in fasting state and during 6 hours after alcohol ingestion. In all patients the family history of diabetes and the presence and degree of vascular complications were registered. Evident flushing phenomenon was observed in 6 patients treated with chlorpropamide, in 3 treated with tolbutamide, in 2 treated with glibenclamide, in one receiving glibornuride and in none treated with glipizide. All drugs caused a greater rise of blood ethanol and acetaldehyde levels in relation to the control tests, but the difference reached statistical significance only in the group receiving chlorpropamide. Moreover, patients (pooled) with positive thermographic response had also significantly higher blood levels of ethanol and acetaldehyde during the second test. The ratio of acetaldehyde to ethanol concentration in blood (mumol:mmol) was not significantly changed in any group indicating parallel impairment of both steps of ethanol metabolism. All studied drugs intensified to a similar degree the alcohol-induced hypoglycaemia, but had no significant effect on the decrease of blood pyruvate level neither on the increase of blood lactate level. They didn't change the post-alcohol decrease of blood bicarbonate and pH, and didn't modify the behaviour of partial gas pressure. There was also no difference between pooled groups of patients with positive and negative thermographic reaction with respect to family history of diabetes and frequency and intensity of vascular complications. It is concluded that in patients with non-insulin-dependent (type 2) diabetes the second generation sulphonylurea derivatives are associated with lower risk of alcohol intolerance in case of its incidental ingestion in small amounts. The hypothesis of association of positive thermographic reaction to alcohol during treatment with sulphonylurea derivatives with more frequent occurrence of diabetes in family members and lower tendency to vascular complications was not confirmed.

A group of 15 patients with controlled insulin-independent diabetes (Type 2) were workloaded submaximally by a 15-minute load on a cycle ergometer and 2-3 days later same workload was repeated, but this time 5-patient groups were administered before the workload: 0.1 j.m. of insulin/kg of body mass i.v., 1.0 g tolbutamide sodium i.v. and 150 mg of phenformin orally one hour before the load. The patients who were injected insulin or tolbutamide were also administered glucose solution (intravenously) so as to keep the same level of glycaemia as in the follow-up examination. The time of metabolic observation after workload was 90 min., so the whole examination took 105 minutes. In the first (follow-up) examination, all the probands had in the venous blood an increase in alanine, lactate, pyruvate and the relation lactate: pyruvate (L/P), a decrease in pH, bicarbonates and pO2 (in capillary afterialized blood). The administration of insulin and tolbutamide eliminated or reduced after-effort alaninaemia increase, whereas the administration of phenformin increased the concentration of this amino acid in the blood after effort. Insulin resulted in a greater increase in after-effort lactacidaemia; besides, insulin and tolbutamide increased the relation L/P during and after effort. The influence of antidiabetic drugs on the behaviour of other biochemical parameters after effort was insignificant. The results obtained show that antidiabetic drugs modify the increase in alaninaemia after effort in patients with controlled insulin-independent diabetes (Type 2), the direction of the modification depending on a specific influence of particular drugs on the metabolism of this amino acid. While evaluating the influence of effort on the concentration of alanine in the blood in patients with this type of diabetes one should consider not only the present demand for this gluconeogenes substrate but also a specific influence of the kind of therapy applied at the time.

In 9 of the 14 national samples of diabetic patients assembled for the WHO Multinational Study of Vascular Disease in Diabetes additional laboratory data made it possible to relate manifestations of macrovascular disease to blood glucose concentrations as well as to diabetes duration and to other potential determinants. In five of the samples, serum triglyceride concentrations were also measured and were included in simple and multivariate analyses. Ischemic heart disease defined from Minnesota-coded EKGs and standardized WHO questionnaires was more strongly associated with serum triglyceride concentrations than with serum cholesterol concentrations, an association less notable in non-insulin-dependent diabetic patients. Ischemic heart disease was not related to the single fasting plasma glucose estimated for this study. Stroke and amputation were much more strongly related to the known duration of diabetes than was ischemic heart disease, and they were both related to blood glucose concentration measured at the time of study. Despite major variation in arterial disease prevalence rates between collaborating centers, risk for diabetic women appeared to equal that for diabetic men. The major variation in arterial disease prevalence between national groups could be accounted for only in part by the risk factors studied. Other factors, genetic or more likely environmental, are likely to contribute to the variation in arterial disease susceptibility and, if definable, may be potentially preventable.

In three groups of healthy subjects (n = 56) changes in blood lactate, pyruvate and bicarbonate concentrations and pH were determined during three different loading tests. These were an oral ethanol load (0.5 g/kg body wt), an IV fructose load (1 g/kg body wt over 60 min), and a 15 min submaximal exercise load. The same tests were repeated after administration of biguanides for 3 days in the following doses: phenformin 150 mg, buformin 300 mg and metformin 2.55 g daily. All three derivatives induced a significant rise in blood lactate level as well as a significant increase in blood [lactate]/[pyruvate] ratio in relation to control tests. The differences in the effect of individual biguanides were minimal. It was observed, on the other hand, that increments in blood lactate concentrations depended markedly on the type of load given. The highest rise in blood lactate level was found after fructose loading; in the 60th minute of the test after phenformin it was 1.60±1.29 (SD), after buformin 1.32±0.79, and after metformin 1.31±0.64 mmol/1. The smallest rise of lactate was observed after oral ethanol loading: in the 1st hour of the test the respective values were 0.41±0.24, 0.52 ±0.18, and 0.91±0.86 mmol/1. In the exercise test the highest increment of the blood lactate level was observed 15 min after the end of the exercise, being 1.06±0.37, 1.21±0.25 and 1.26±0.33 mmol/1, respectively. The results of these investigations show that all three biguanide derivatives used in treatment of diabetes — phenformin, buformin and metformin — are risk factors which may induce lactic acidosis under suitable conditions.