Exercise training with dietary counselling increases mitochondrial chaperone expression in middle-aged subjects with impaired glucose tolerance.

BACKGROUND: Insulin resistance and diabetes are associated with increased oxidative stress and impairment of cellular defence systems. Our purpose was to investigate the interaction between glucose metabolism, antioxidative capacity and heat shock protein (HSP) defence in different skeletal muscle phenotypes among middle-aged obese subjects during a long-term exercise and dietary intervention. As a sub-study of the Finnish Diabetes Prevention Study (DPS), 22 persons with impaired glucose tolerance (IGT) taking part in the intervention volunteered to give samples from the vastus lateralis muscle. Subjects were divided into two sub-groups (IGTslow and IGTfast) on the basis of their baseline myosin heavy chain profile. Glucose metabolism, oxidative stress and HSP expressions were measured before and after the 2-year intervention. RESULTS: Exercise training, combined with dietary counselling, increased the expression of mitochondrial chaperones HSP60 and glucose-regulated protein 75 (GRP75) in the vastus lateralis muscle in the IGTslow group and that of HSP60 in the IGTfast group. In cytoplasmic chaperones HSP72 or HSP90 no changes took place. In the IGTslow group, a significant positive correlation between the increased muscle content of HSP60 and the oxygen radical absorbing capacity values and, in the IGTfast group, between the improved VO2max value and the increased protein expression of GRP75 were found. Serum uric acid concentrations decreased in both sub-groups and serum protein carbonyl concentrations decreased in the IGTfast group. CONCLUSION: The 2-year intervention up-regulated mitochondrial HSP expressions in middle-aged subjects with impaired glucose tolerance. These improvements, however, were not correlated directly with enhanced glucose tolerance.

Determinants for the effectiveness of lifestyle intervention in the Finnish Diabetes Prevention Study.

OBJECTIVE: Intensive lifestyle intervention significantly reduced diabetes incidence among the participants in the Finnish Diabetes Prevention Study. We investigated whether and to what extent risk factors for type 2 diabetes and other baseline characteristics of the study participants modified the effectiveness of the lifestyle intervention. RESEARCH DESIGN AND METHODS: Overweight, middle-aged volunteers with impaired glucose tolerance were randomly assigned to intensive lifestyle intervention (n = 265) or to a control group (n = 257) for a median of 4 years. Diabetes status was ascertained annually with repeated oral glucose tolerance testing. Incidence rates of diabetes and hazard ratios (HRs) comparing the intervention group with the control group were calculated by sex and baseline tertiles of age, BMI, waist circumference, plasma glucose concentration at fasting and 2 h after a glucose load, fasting serum insulin and insulin resistance index, and categories of composite baseline Finnish Diabetes Risk Score (FINDRISC). Interactions between the intervention assignment and baseline risk factors on diabetes risk were analyzed. RESULTS: The intervention was most effective among the oldest individuals (HRs 0.77, 0.49, and 0.36 by increasing age tertiles, respectively; P(interaction) = 0.0130) and those with a high baseline FINDRISC (HRs 1.09, 0.84, 0.34, and 0.22 by increasing risk score category, respectively; P(interaction) = 0.0400). The effect of the intervention on diabetes risk was not modified by other baseline characteristics or risk factors. CONCLUSIONS: The FINDRISC may be useful in identifying high-risk groups most likely to benefit from intensive lifestyle intervention to prevent type 2 diabetes.

Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome: The Finnish Diabetes Prevention Study.

Single nucleotide polymorphisms (SNPs) in the ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL genes were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D) in the Finnish Diabetes Prevention Study (DPS). In this study, we determined whether polymorphisms in these genes modified the effect of changes in physical activity (PA) on the risk of T2D in the DPS. Moreover, we assessed whether the polymorphisms modified the effect of changes in PA on changes in measures of body fat, serum lipids, and blood pressure during the first year of the follow-up of the DPS. Overweight subjects with IGT (n = 487) were followed for an average of 4.1 years, and PA was assessed annually with a questionnaire. The interactions of the polymorphisms with changes in total and moderate-to-vigorous PA on the conversion to T2D during the 4.1-year follow-up were assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). Univariate analysis of variance was used to assess interactions on changes in continuous variables during the first year of the follow-up. No interaction between the polymorphisms and PA on the conversion to T2D was found. The Leu72Met (rs696217) polymorphism in GHRL modified the effect of moderate-to-vigorous PA on changes in weight and waist circumference, the -501A/C (rs26802) polymorphism in GHRL modified the effect of total and moderate-to-vigorous PA on change in high-density lipoprotein cholesterol, and the Lys109Arg (rs1137100) polymorphism in LEPR modified the effect of total PA on change in blood pressure. In conclusion, genetic variation may modify the magnitude of the beneficial effects of PA on characteristics of the metabolic syndrome in persons with IGT.

Effect of lifestyle intervention on the occurrence of metabolic syndrome and its components in the Finnish Diabetes Prevention Study.

OBJECTIVE: The aim of this secondary analysis of the Finnish Diabetes Prevention Study was to assess the effects of lifestyle intervention on metabolic syndrome and its components. RESEARCH DESIGN AND METHODS: A total of 522 middle-aged overweight men and women with impaired glucose tolerance were randomized into an individualized lifestyle intervention group or a standard care control group. National Cholesterol Education Program criteria were used for the definition of metabolic syndrome. RESULTS: At the end of the study, with a mean follow-up of 3.9 years, we found a significant reduction in the prevalence of metabolic syndrome in the intervention group compared with the control group (odds ratio [OR] 0.62 [95% CI 0.40-0.95]) and in the prevalence of abdominal obesity (0.48 [0.28-0.81]). CONCLUSIONS: The results suggest that lifestyle intervention may also reduce risk of cardiovascular disease in the long run.

SNPs in PPARG associate with type 2 diabetes and interact with physical activity.

PURPOSE: To study the associations of seven single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor gamma (PPARG) gene with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D), and the interactions of the SNPs with physical activity (PA). METHODS: Overweight individuals with IGT who participated in the Finnish Diabetes Prevention Study (DPS) (N = 479) were followed, on average, 4.2 yr. PA was assessed yearly with a 12-month validated questionnaire. RESULTS: In Cox regression analyses, the rare alleles of rs17036314 and rs1801282 (Pro12Ala) predicted conversion to T2D (P = 0.038 and 0.037, respectively), but only rs17036314 predicted T2D after adjustment for baseline fasting glucose (P = 0.030). The change in the total amount of PA, stratified by median, modified the association of rs17036314 and rs1801282 with the risk of T2D during the intervention (P = 0.002 and 0.031, respectively, for interaction between PA change and genotype); an increase in PA seemed to remove the effect of the risk alleles. The distinct rs1152003 polymorphism interacted with the study group on the conversion to T2D (P = 0.027) and tended to increase the risk of T2D in the intervention group (P = 0.050). No interaction between rs1152003 and the change in PA was found. CONCLUSIONS: The rs17036314, rs1801282 (Pro12Ala), and rs1152003 were associated with the risk of T2D in the DPS. Increased PA seemed to decrease the effect of the risk alleles of rs17036314 and rs1801282 on the conversion to T2D. The effect of rs1152003 was modified by other lifestyle changes or the lifestyle intervention as a whole.

Use of secondary preventive medications after the first attack of acute coronary syndrome.

BACKGROUND: It is not well-known to what extent evidence-based medications, such as beta-blockers, hypolipidemic medications, and angiotensin-converting enzyme inhibitors, are prescribed after an attack of acute coronary syndrome in the general healthcare setting and what is the compliance of patients with these prescriptions. DESIGN: We conducted a countrywide record linkage study. METHODS: We used record linkage of the National Hospital Discharge Register, Causes of Death Register, and Social Insurance Institution's drug reimbursement records to identify drug purchases of patients aged 35-74 years hospitalized for the first nonfatal acute coronary syndrome in Finland during 1995-2003 (n=53 353). RESULTS: In 2003 about 28 and 15% of the patients did not receive hypolipidemic medications or beta-blockers, respectively, after their acute coronary syndrome and a further 6 and 10% discontinued the use about 3 months later. Patients aged 65-74 years were less likely to receive hypolipidemic medications [odds ratio (OR) 0.55; 95% confidence interval (CI), 0.53-0.58] and beta-blockers (OR 0.77; 95% CI, 0.74-0.81) than younger patients. Diabetic patients received less hypolipidemic medications (OR 0.82; 95% CI, 0.78-0.86) and were more likely to discontinue the medication (OR 1.15; 95% CI, 1.05-1.26) than nondiabetic patients. In proportional hazards regression analyses the regular use of hypolipidemic medication or beta-blockers was associated with lower risk of cardiovascular death: adjusted hazard ratios 0.47 (95% CI, 0.41-0.53) and 0.54 (95% CI, 0.49-0.60), respectively. CONCLUSIONS: Our study showed that the evidence-based use of medications after acute coronary syndrome was suboptimal in Finland, particularly in elderly and diabetic patients. Consistent use of these medications, however, was associated with a better prognosis.

Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study.

BACKGROUND: Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes, at least as long as the intervention continues. In the extended follow-up of the Finnish Diabetes Prevention Study, we assessed the extent to which the originally-achieved lifestyle changes and risk reduction remain after discontinuation of active counselling. METHODS: Overweight, middle-aged men (n=172) and women (n=350) with impaired glucose tolerance were randomly assigned to intensive lifestyle intervention or control group. After a median of 4 years of active intervention period, participants who were still free of diabetes were further followed up for a median of 3 years, with median total follow-up of 7 years. Diabetes incidence, bodyweight, physical activity, and dietary intakes of fat, saturated fat, and fibre were measured. FINDINGS: During the total follow-up, the incidence of type 2 diabetes was 4.3 and 7.4 per 100 person-years in the intervention and control group, respectively (log-rank test p=0.0001), indicating 43% reduction in relative risk. The risk reduction was related to the success in achieving the intervention goals of weight loss, reduced intake of total and saturated fat and increased intake of dietary fibre, and increased physical activity. Beneficial lifestyle changes achieved by participants in the intervention group were maintained after the discontinuation of the intervention, and the corresponding incidence rates during the post-intervention follow-up were 4.6 and 7.2 (p=0.0401), indicating 36% reduction in relative risk. INTERPRETATION: Lifestyle intervention in people at high risk for type 2 diabetes resulted in sustained lifestyle changes and a reduction in diabetes incidence, which remained after the individual lifestyle counselling was stopped.

Association between ghrelin gene variations and blood pressure in subjects with impaired glucose tolerance.

BACKGROUND: Ghrelin is a gut-brain hormone, which stimulates food intake and controls energy balance. Recently, it has been shown that ghrelin may also play a role in the regulation of blood pressure (BP) by acting at the sympathetic nervous system. In the present study we genotyped six variants of the ghrelin gene and its promoter, and tested whether these single nucleotide polymorphisms (SNPs) were associated with BP levels in participants of the Finnish Diabetes Prevention Study. METHODS: The Finnish Diabetes Prevention Study was a longitudinal study where 522 subjects with impaired glucose tolerance were randomized into either an intervention or control group. DNA was available from 507 subjects (mean body mass index [BMI] 31.2+/-4.5 kg/m2, age 55+/-7 years). All six SNPs were screened by the restriction fragment length polymorphism method. RESULTS: Subjects with the most common genotype combination of the following four SNPs, -604G/A, -501A/C, Leu72Met, and Gln90Leu, had the lowest systolic (131+/-11 v 137+/-13 mm Hg, P=.003) and diastolic BP levels (79+/-7 v 83+/-7 mm Hg, P=.004) at the baseline of the study and during 3 years of follow-up compared to all other genotypes. Adjustments for age, gender, antihypertensive medication, BMI, waist circumference, and alcohol intake did not change this association. CONCLUSIONS: Several ghrelin gene variations were associated with BP levels in subjects with impaired glucose tolerance.

Systemic immune mediators and lifestyle changes in the prevention of type 2 diabetes: results from the Finnish Diabetes Prevention Study.

The Finnish DPS (Diabetes Prevention Study) demonstrated that lifestyle intervention, aimed at increasing physical activity, improving diet, and decreasing body weight, reduced the incidence of type 2 diabetes in individuals with overweight and impaired glucose tolerance by 58%. Here, we studied which immunological markers at baseline predicted subsequent type 2 diabetes and whether there are immunologically defined subsets of subjects who are more or less responsive to the protective effects of lifestyle intervention. We randomly assigned 522 participants to a control group (n = 257) or a lifestyle intervention group (n = 265). Immunological parameters at baseline included high-sensitivity C-reactive protein (CRP), serum amyloid A, interleukin-6, regulated on activation normal T-cell expressed and secreted (RANTES), macrophage migration inhibitory factor (MIF), and soluble intercellular adhesion molecule. In the control group, CRP was the best immunological predictor for progression to overt type 2 diabetes. In the intervention group, progression to type 2 diabetes was significantly higher in subjects with the highest RANTES concentrations and was lower in subjects with the highest MIF levels. Ratios of RANTES to MIF in the upper tertile were highly predictive of incident type 2 diabetes in the intervention group (P = 0.006), whereas the association was less pronounced in the control group (P = 0.088). Thus, systemic concentrations of immune mediators appear to be associated with the progression to type 2 diabetes and the prevention of type 2 diabetes by lifestyle changes.

The effects of type 1 diabetes and its long-term complications on physical and mental health status.

OBJECTIVE: To analyse how type 1 diabetes mellitus (DM) and the symptoms of its chronic long-term complications correlate with health status domains in the adult population in Finland. METHODS: A representative sample of patients with type 1 DM was selected randomly from the Finnish drug reimbursement registry. Participants reported symptoms, diagnoses and treatments indicating the presence and time of appearance of long-term complications, and completed the RAND 36 questionnaire. A principal component analysis was performed to compress the eight RAND 36 dimensions into composite domains of health status. The results were validated with split-sample analysis. Regression analyses were used to estimate the effects of age, sex, symptoms of long-term complications and comorbidities on the component T-scores. RESULTS: Of the 752 (70.8%) responders, 592 fulfilled the criteria of type 1 DM. Of these, 82.6% fully completed the RAND 36 questionnaire. Principal component analysis of our data supports the theory of the 2-factor model of health, as physical and mental health domains were reflected unambiguously by different RAND 36 dimensions. The regression results show that the symptoms of long-term complications correlate more strongly with the physical than the mental domain of health status. CONCLUSION: Type 1 DM, and especially the symptoms of its long-term complications, correlate mainly with the physical domain of health, although the mental domain is also affected. The prevalence of long-term complications with type 1 DM is sufficiently high within the Finnish population to substantially influence the health status of people with type 1 DM.

Polymorphisms in the SLC2A2 (GLUT2) gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study.

Impaired insulin secretion is a fundamental defect in type 2 diabetes. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the genes regulating insulin secretion (SLC2A2 [encoding GLUT2], GCK, TCF1 [encoding HNF-1alpha], HNF4A, GIP, and GLP1R) are associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in participants of the Finnish Diabetes Prevention Study. With the exception of SLC2A2, other genes were not associated with the risk of type 2 diabetes. All four SNPs of SLC2A2 predicted the conversion to diabetes, and rs5393 (AA genotype) increased the risk of type 2 diabetes in the entire study population by threefold (odds ratio 3.04, 95% CI 1.34-6.88, P = 0.008). The risk for type 2 diabetes in the AA genotype carriers was increased in the control group (5.56 [1.78-17.39], P = 0.003) but not in the intervention group. We conclude that the SNPs of SLC2A2 predict the conversion to diabetes in obese subjects with IGT.

Trends in fatal and nonfatal strokes among persons aged 35 to > or =85 years during 1991-2002 in Finland.

BACKGROUND AND PURPOSE: Declining trends in the incidence and mortality of stroke have been observed in Finland since the beginning of the 1980s until 1997. In this study we analyzed the trends in fatal and nonfatal strokes in Finland during 1991-2002. METHODS: The Finnish Hospital Discharge Register was linked to the National Causes of Death Register to produce a Cardiovascular Disease Register, which includes data on 410 760 cerebrovascular events (International Statistical Classification of Diseases, 10th Revision [ICD-10] codes I60-I69) in patients aged > or =35 years in 1991-2002. RESULTS: Age-standardized incidence of first-ever stroke (ICD-10 codes I60-I64, excluding I63.6) per 100 000 persons declined during 1991-2002 annually by 2.2% (95% CI, -2.4% to -1.9%) among men and 2.5% (-2.8% to -2.2%) among women aged 35 to 74 years. In patients aged 75 to 84 years, the change in the incidence of first-ever stroke was -2.6% per year (-3.0% to -2.2%) among men and -3.2% per year (-3.5% to -2.9%) among women. A similar trend was observed also in the oldest age group, in patients aged > or =85 years. Among patients aged 35 to 74 years, the 28-day case fatality of first-ever stroke declined annually by 3.2% (-3.9% to -2.5%) among men and by 3.0% (-3.8% to -2.2%) among women. A significant decrease was found in the 28-day case fatalities of all subtypes of stroke in this age group. CONCLUSIONS: The favorable development in stroke incidence, mortality, and case-fatality has continued in Finland during 1991-2002.

Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study.

Clinical trials have demonstrated that lifestyle changes can prevent type 2 diabetes, but the importance of leisure-time physical activity (LTPA) is still unclear. We carried out post hoc analyses on the role of LTPA in preventing type 2 diabetes in 487 men and women with impaired glucose tolerance who had completed 12-month LTPA questionnaires. The subjects were participants in the Finnish Diabetes Prevention Study, a randomized controlled trial of lifestyle changes including diet, weight loss, and LTPA. There were 107 new cases of diabetes during the 4.1-year follow-up period. Individuals who increased moderate-to-vigorous LTPA or strenuous, structured LTPA the most were 63-65% less likely to develop diabetes. Adjustment for changes in diet and body weight during the study attenuated the association somewhat (upper versus lower third: moderate-to-vigorous LTPA, relative risk 0.51, 95% CI 0.26-0.97; strenuous, structured LTPA, 0.63, 0.35-1.13). Low-intensity and lifestyle LTPA and walking also conferred benefits, consistent with the finding that the change in total LTPA (upper versus lower third: 0.34, 0.19-0.62) was the most strongly associated with incident diabetes. Thus increasing physical activity may substantially reduce the incidence of type 2 diabetes in high-risk individuals.

Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. The Finnish Diabetes Prevention Study.

Type 2 diabetes is caused by defective insulin secretion and impaired insulin action. We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study. The 1273AGA allele of the SUR1 gene was associated with a 2-fold risk of type 2 diabetes [odds ratio (OR), 2.00; 95% confidence interval (CI), 1.19-3.36; P = 0.009]. This silent polymorphism was in linkage disequilibrium with three promoter polymorphisms (G-2886A, G-1561A, and A-1273G), and they formed a high-risk haplotype having a 2-fold risk of type 2 diabetes (OR, 1.89; 95% CI, 1.09-3.27; P = 0.023). Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004). We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene.

Return to work after first myocardial infarction in 1991-1996 in Finland.

BACKGROUND: A substantial number of myocardial infarctions (MI) occur at working age. It is, however, insufficiently well known how many of these patients return to work after their MI. METHODS: Sources of information were the Hospital Discharge Register, the Causes of Death Register and the registers for social security benefits. Availability for the labour market was used as the return to work criterion. Altogether 10,244 persons (8,733 men, 1,511 women) aged 35-59 years had their first MI or coronary death during 1991-1994 in Finland. Persons who survived for 28 days and were not on pension at the time of MI were included in a two-year follow-up. RESULTS: Twenty-nine per cent of patients were already pensioned at the time of their first MI. Of the patients not pensioned at the time of their MI, 4,929 were alive two years after the event. Of them, 38% of men and 40% of women received disability pension, 3% of both genders were on sick leave and 1% of both genders were on unemployment pension. The remainder, 58% of men and 56% of women, did not receive any of these benefits, thus, being available to the labour force. CONCLUSIONS: Nearly one-third of persons having their first MI at working age were already out of the labour force at the time of their MI. Of those who were not pensioned and who survived the event, slightly more than half were available to the labour market two years later.

Prevalence of the metabolic syndrome and its components: findings from a Finnish general population sample and the Diabetes Prevention Study cohort.

OBJECTIVE: To assess the prevalence of the metabolic syndrome (MetS) in two independent Finnish study cohorts. RESEARCH DESIGN AND METHODS: The prevalence of the MetS by modified World Health Organization criteria was analyzed in different categories of glucose tolerance in a cross-sectional, population-based sample of 2,049 individuals (FINRISK) aged 45-64 years and in 522 participants of the Finnish Diabetes Prevention Study (DPS) with impaired glucose tolerance (IGT). RESULTS: In the FINRISK cohort, the MetS was present in 38.8% of the men and 22.2% of the women. The prevalence was 14.4 and 10.1% in subjects with normal glucose tolerance, 74.0 and 52.2% in subjects with impaired fasting glucose, 84.8 and 65.4% in subjects with IGT, and 91.5 and 82.7% in subjects with type 2 diabetes in men and women, respectively. Among women, the prevalence of the MetS increased with increasing age. In the DPS cohort, the MetS was present in 78.4% of the men and 72.2% of the women with IGT. CONCLUSIONS: The MetS was extremely common in middle-aged subjects The high prevalence in men was mostly due to their high waist-to-hip ratio. The prevalence of the MetS increased in both sexes with deterioration in glucose regulation. Approximately 75% of the subjects with IGT had the MetS. Because the syndrome includes the major risk factors for atherosclerotic vascular diseases and is the major antecedent for type 2 diabetes, concerted preventive action should be targeted to control all the features of the MetS.

The G-250A promoter polymorphism of the hepatic lipase gene predicts the conversion from impaired glucose tolerance to type 2 diabetes mellitus: the Finnish Diabetes Prevention Study.

In population-based studies, dyslipidemia related to insulin resistance (high triglyceride level and low high-density lipoprotein cholesterol level) is a risk factor for type 2 diabetes. Therefore, variants in genes regulating lipid and lipoprotein metabolism are potential candidate genes for diabetes. We investigated whether the G-250A polymorphism of the hepatic lipase gene (LIPC) predicts the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. This study randomized subjects to either the intervention group (lifestyle modification aimed at weight loss, such as changes in diet and increased physical exercise) or the control group. Genotyping at position -250 of the LIPC gene was performed with PCR amplification, DraI enzyme digestion, and gel electrophoresis in 490 subjects with IGT whose DNA was available. In the entire study population, the conversion rate to type 2 diabetes was 17.8% among subjects with the G-250G genotype and 10.7% among subjects with the -250A allele (P = 0.032). In univariate analysis, the odds ratio for the G-250G genotype to predict the conversion from IGT to type 2 diabetes was 1.80 (95% confidence interval, 1.05-3.10; P = 0.034). In multivariate logistic regression analysis, the G-250G genotype predicted the conversion to diabetes independently of the study group (control or intervention), gender, weight, waist circumference at baseline, and change in weight and waist circumference. In the intervention group, 13.0% of subjects with the G-250G genotype and 1.0% of the subjects with the -250A allele converted to diabetes (P = 0.001). We conclude that the G-250G genotype of the LIPC gene is a risk factor for type 2 diabetes. Therefore, genes regulating lipid and lipoprotein metabolism may be potential candidate genes for type 2 diabetes.

Trends in fatal and non-fatal coronary heart disease events in Finland during 1991-2001.

OBJECTIVE: To analyse the trends in fatal and non-fatal coronary heart disease (CHD) events in Finland during an 11-year period 1991-2001. DESIGN: Data on hospitalizations due to CHD in the Hospital Discharge Register were linked to the National Causes of Death Register in order to produce a Cardiovascular Disease Register including data on 271,771 events in 234,244 individuals. RESULTS: The annual average decline in the age-standardized CHD mortality rate was 5.2% (95% CI, -5.6, -4.8%) among men and 6.1% (-6.6, -5.6%) among women. The incidence of first myocardial infarction declined annually on average by 5.5% (-5.9, -5.1%) from 1991 to 1997 and by 2.4% (-3.0, -1.7%) from 1998 to 2001 among men. The respective changes among women were -5.9% (-6.5, -5.2%) and -1.7% (-2.7, -0.6%). The number of hospitalizations due to unstable angina pectoris increased between 1991 and 1996 (p = 0.0002) and remained stable for the rest of the study period. CONCLUSIONS: The Cardiovascular Disease Register is a powerful tool for epidemiological monitoring of cardiovascular diseases in Finland.

Prevention of diabetes mellitus in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study: results from a randomized clinical trial.

Type 2 diabetes mellitus is increasing worldwide largely as a result from increasing obesity and sedentary lifestyle. The Finnish Diabetes Prevention Study (DPS) is the first individually randomized controlled clinical trial to test the feasibility and efficacy of lifestyle modification in high-risk subjects. We randomly assigned 522 (172 men, 350 women) middle-aged (mean age 55 yr), overweight (mean body mass index 31 kg/m(2)) subjects with impaired glucose tolerance either to the lifestyle intervention or control group. Each subject in the intervention group received individualized counseling aimed at reducing weight and intake of total and saturated fat, and increasing intake of fiber and physical activity. An oral glucose tolerance test was performed annually to detect incident cases of diabetes and to measure changes in metabolic parameters. The mean (+/- SD) weight reduction from baseline to year 1 and to year 2, respectively, was 4.2 +/- 5.1 kg and 3.5 +/- 5.5 in the intervention group and 0.8 +/- 3.7 kg and 0.8 +/- 4.4 in the control group (P < 0.001 between the groups). At the time of first analysis of the outcome data the mean duration of follow-up was 3.2 yr. The risk of diabetes was reduced by 58% (P < 0.001) in the intervention group compared with the control group. The reduction in the incidence of diabetes was directly associated with number and magnitude of lifestyle changes made. In conclusion, the DPS is the first controlled trial demonstrating that type 2 diabetes can be prevented by changes in lifestyle in high-risk subjects.