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Notes: Summary Variations in the coding regions of the insulin receptor substrate-1 (IRS-1) gene have recently been suggested to contribute to the susceptibility of non-insulin-dependent diabetes mellitus (NIDDM). The purpose of this study was to examine the role of the IRS-1 missense mutations at codons 972 (glycine to arginine) and 513 (alanine to proline) in two diverse populations from South India and Finland at high risk for NIDDM. DNA was amplified and digested with restriction enzymes BstN1 to detect the codon 972 mutation and Dra III to detect the codon 513 mutation. The codon 513 mutation was not found in the study subjects. The codon 972 mutation was present in 10.3% of 126 middle-aged NIDDM subjects and 5.3% of 95 matched control subjects in the South Indians (p=0.17). In elderly Finnish subjects the frequency of the mutation was 7.5% in 40 NIDDM subjects and 7% in 42 matched control subjects. The frequency of codon 972 mutation in the South Indian NIDDM subjects was very similar to the two previously published studies in Danish and French subjects although each study individually fails to reach conventional levels of significance. The data from all four ethnic groups were analysed together after ascertaining that significant heterogeneity did not exist between the studies. Overall, the frequency of the codon 972 mutation is found in 10.7% NIDDM subjects and 5.8% control subjects (p = 0.02). These studies suggest that the codon 972 mutation of the IRS-1 gene might act as a susceptibility gene predisposing to NIDDM in certain ethnic groups.

Notes: Summary We studied the association of glucose intolerance with total and cause-specific mortality during a 5-year follow-up of 637 elderly Finnish men aged 65 to 84 years. Total mortality was 276 per 1000 for men aged 65 to 74 years and 537 per 1000 for men aged 75 to 84 years. Five-year total mortality adjusted for age was 364 per 1000 in diabetic men, 234 per 1000 in men with impaired glucose tolerance and 209 per 1000 in men with normal glucose tolerance. The relative risk of death among diabetic men was 2.10 (95% confidence interval 1.26 to 3.49) and among men with impaired glucose tolerance 1.17 (95% confidence interval 0.71 to 1.94) times higher compared with men with normal glucose tolerance. Cardiovascular disease was the most common cause of death in every glucose tolerance group. The multivariate adjusted relative risk of cardiovascular death was increased (1.55) in diabetic patients, albeit non-significantly (95% confidence interval 0.84 to 2.85). Diabetes resulted in an increased risk of cardiovascular mortality among men aged 65–74 years but not among the 75–84-year-old men. Relative risk of death from non-cardiovascular causes was slightly increased among diabetic subjects. In conclusion, diabetes mellitus is a significant determinant of mortality among elderly Finnish men.

Notes: Summary Variations in the coding regions of the insulin receptor substrate-1 (IRS-1) gene have recently been suggested to contribute to the susceptibility of non-insulin-dependent diabetes mellitus (NIDDM). The purpose of this study was to examine the role of the IRS-1 missense mutations at codons 972 (glycine to arginine) and 513 (alanine to proline) in two diverse populations from South India and Finland at high risk for NIDDM. DNA was amplified and digested with restriction enzymes BstN1 to detect the codon 972 mutation and Dra III to detect the codon 513 mutation. The codon 513 mutation was not found in the study subjects. The codon 972 mutation was present in 10.3 % of 126 middle-aged NIDDM subjects and 5.3 % of 95 matched control subjects in the South Indians (p = 0.17). In elderly Finnish subjects the frequency of the mutation was 7.5 % in 40 NIDDM subjects and 7 % in 42 matched control subjects. The frequency of codon 972 mutation in the South Indian NIDDM subjects was very similar to the two previously published studies in Danish and French subjects although each study individually fails to reach conventional levels of significance. The data from all four ethnic groups were analysed together after ascertaining that significant heterogeneity did not exist between the studies. Overall, the frequency of the codon 972 mutation is found in 10.7 % NIDDM subjects and 5.8 % control subjects (p = 0.02). These studies suggest that the codon 972 mutation of the IRS-1 gene might act as a susceptibility gene predisposing to NIDDM in certain ethnic groups. [Diabetologia (1995) 38: 481–486]

Notes: Summary To elucidate the role of hypertension as part of the insulin resistance syndrome, the longitudinal relationships of hypertension and overweight with hyperinsulinaemia and glucose tolerance were examined in the Dutch and Finnish cohorts of the Seven Countries Study (Zutphen, and east and west Finland). Three cohorts of men, born between 1900 and 1919, were first examined in 1959/1960. At the 30-year follow-up survey a 2-h glucose tolerance test was carried out on 619 of the surviving men, and fasting insulin was also measured. Blood pressure and body mass index (BMI) were measured several times during the entire 30-year follow-up period. In cross-sectional analyses, men with diabetes and impaired glucose tolerance at the 30-year follow-up examination had a significantly higher systolic blood pressure and a higher prevalence of hypertension than men with normal glucose tolerance, independent of age, cohort and BMI (p 〈 0.01). These differences had already been seen 5, 20 and 30 years earlier. Subjects with hyperinsulinaemia (fasting insulin ≥ 9.2 mU/l) had a higher BMI and a higher prevalence of hypertension. This cross-sectional association with hypertension was independent of age, cohort and BMI. BMI levels of men with hyperinsulinaemia had been shown to be higher 5, 20 and 30 years earlier, but blood pressure levels had not. These results indicate that hypertension is independently associated with glucose tolerance and insulin resistance in three Caucasian cohorts. Changes in blood pressure precede abnormal glucose tolerance but not hyperinsulinaemia; therefore, glucose tolerance appears to be a stronger correlate of hypertension than hyperinsulinaemia. [Diabetologia (1995) 38: 839–847]

Notes: Summary The antihypertensive effect of a new sustained-release matrix formulation of verapamil 200 mg was investigated in a dose-response study in patients with mild to moderate essential hypertension. Noninvasive ambulatory blood pressure measurements were recorded over 24 h in 6 patients with diastolic blood pressure ≥100 mmHg. The patients received sustained-release verapamil 200 mg once daily and twice daily in a randomized order. Each medication period lasted 2 weeks. Verapamil 200 mg twice daily had a better antihypertensive effect than the same dose once daily. After a 6-week placebo period 27 patients with a diastolic blood pressure ≥100 mmHg were included in a double-blind clinical trial. The patients received sustained release verapamil 200 mg once daily and twice daily in a randomized crossover manner. Each medication period lasted 6 weeks, with an intervening 6-week placebo period. A diastolic blood pressure of ≤95 mmHg was achieved in 6 patients with the once-daily regimen and in 14 with the twice-daily regimen. The mean fall in diastolic blood pressure was 4 and 9 mmHg, respectively (p〈0.05). We conclude that sustained-release verapamil 200 mg once daily gives a satisfactory blood pressure response only in a minority of patients, while 200 mg twice daily has a significantly better antihypertensive effect. Both doses were well tolerated.

Notes: Abstract The utilisation of antidiabetic drugs reflects both the prevalence of diabetes and the different therapeutic traditions of physicians. A questionnaire survey to study attitudes to the use of oral antidiabetic drugs amongst physicians and possible changes in treatment habits was carried out in a representative sample of Finnish physicians (n=454) in 1992 and the results were compared with those of a similar survey carried out in 1985, and with drug utilisation statistics. The mean fasting blood glucose level at which a physician would start pharmacological treatment was 8.7 mmol·l−1, which was significantly lower than in the 1985 survey. The responses to various case histories suggested a more active approach to pharmacological treatment compared to the 1985 survey. Insulin treatment especially seems to have gained in popularity. This change in attitude was paralled by an increase in the consumption of antidiabetic drugs in Finland during the observation period. The increase in use of oral drugs was steeper in Finland than in Norway and Sweden. Whether this active approach will improve the metabolic control and prognosis of patients with Type 2 diabetes, remains to be demonstrated.

Notes: Summary A double-blind comparison of the β-blockers metoprolol, alprenolol and oxprenolol was carried out to evaluate their antihypertensive effect and tolerability. 105 patients with previously untreated hypertension entered the trial and 71 completed it. Side-effects were infrequent and were never the reason for drop-out. All three drugs caused a statistically significant reduction in blood-pressure at the lower of the two doses used during a dose-finding period. At the higher dose employed in this period, metoprolol caused a significantly greater reduction in diastolic blood-pressure than did alprenolol or oxprenolol. All three drugs caused a significant reduction in heart rate. During the follow-up period, the β-blockers were supplemented if necessary with hydrochlorothiazide. This was required less frequently in the metoprolol group than in the other two groups.

Notes: Reliable models are required to assess the impacts of climate change on forest ecosystems. Precise and independent data are essential to assess this accuracy. The flux measurements collected by the EUROFLUX project over a wide range of forest types and climatic regions in Europe allow a critical testing of the process-based models which were developed in the LTEEF project. The ECOCRAFT project complements this with a wealth of independent plant physiological measurements. Thus, it was aimed in this study to test six process-based forest growth models against the flux measurements of six European forest types, taking advantage of a large database with plant physiological parameters.The reliability of both the flux data and parameter values itself was not under discussion in this study. The data provided by the researchers of the EUROFLUX sites, possibly with local corrections, were used with a minor gap-filling procedure to avoid the loss of many days with observations.The model performance is discussed based on their accuracy, generality and realism. Accuracy was evaluated based on the goodness-of-fit with observed values of daily net ecosystem exchange, gross primary production and ecosystem respiration (gC m−2 d−1), and transpiration (kg H2O m−2 d−1). Moreover, accuracy was also evaluated based on systematic and unsystematic errors. Generality was characterized by the applicability of the models to different European forest ecosystems. Reality was evaluated by comparing the modelled and observed responses of gross primary production, ecosystem respiration to radiation and temperature. The results indicated that: Accuracy. All models showed similar high correlation with the measured carbon flux data, and also low systematic and unsystematic prediction errors at one or more sites of flux measurements. The results were similar in the case of several models when the water fluxes were considered. Most models fulfilled the criteria of sufficient accuracy for the ability to predict the carbon and water exchange between forests and the atmosphere. Generality. Three models of six could be applied for both deciduous and coniferous forests. Furthermore, four models were applied both for boreal and temperate conditions. However, no severe water-limited conditions were encountered, and no year-to-year variability could be tested. Realism. Most models fulfil the criterion of realism that the relationships between the modelled phenomena (carbon and water exchange) and environment are described causally. Again several of the models were able to reproduce the responses of measurable variables such as gross primary production (GPP), ecosystem respiration and transpiration to environmental driving factors such as radiation and temperature. Stomatalconductance appears to be the most critical process causing differences in predicted fluxes of carbon and water between those models that accurately describe the annual totals of GPP, ecosystem respiration and transpiration.As a conclusion, several process-based models are available that produce accurate estimates of carbon and water fluxes at several forest sites of Europe. This considerable accuracy fulfils one requirement of models to be able to predict the impacts of climate change on the carbon balance of European forests. However, the generality of the models should be further evaluated by expanding the range of testing over both time and space. In addition, differences in behaviour between models at the process level indicate requirement of further model testing, with special emphasis on modelling stomatal conductance realistically.