Sirkka Aunola

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.

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.

Ten-year mortality and cardiovascular morbidity in the Finnish Diabetes Prevention Study - secondary analysis of the randomized trial

Background The Finnish Diabetes Prevention Study (DPS) was a randomized controlled trial, which showed that it is possible to prevent type 2 diabetes by lifestyle changes. The aim of the present study was to examine whether the lifestyle intervention had an effect on the ten-year mortality and cardiovascular morbidity in the DPS participants originally randomized either into an intervention or control group. Furthermore, we compared these results with a population-based cohort comprising individuals of varying glucose tolerance states. Methods and Findings Middle-aged, overweight people with IGT (n = 522) were randomized into intensive intervention (including physical activity, weight reduction and dietary counseling), or control “mini-intervention” group. Median length of the intervention period was 4 years and the mean follow-up was 10.6 years. The population-based reference study cohort included 1881 individuals (1570 with normal glucose tolerance, 183 with IGT, 59 with screen-detected type 2 diabetes, 69 with previously known type 2 diabetes) with the mean follow-up of 13.8 years. Mortality and cardiovascular morbidity data were collected from the national Hospital Discharge Register and Causes of Death Register. Among the DPS participants who consented for register linkage (n = 505), total mortality (2.2 vs. 3.8 per 1000 person years, hazard ratio HR = 0.57, 95% CI 0.21–1.58) and cardiovascular morbidity (22.9 vs. 22.0 per 1000 person years, HR = 1.04, 95% CI 0.72–1.51) did not differ significantly between the intervention and control groups. Compared with the population-based cohort with impaired glucose tolerance, adjusted HRs were 0.21 (95% CI 0.09–0.52) and 0.39 (95% CI 0.20–0.79) for total mortality, and 0.89 (95% CI 0.62–1.27) and 0.87 (0.60–1.27) for cardiovascular morbidity in the intervention and control groups of the DPS, respectively. The risk of death in DPS combined cohort was markedly lower than in FINRISK IGT cohort (adjusted HR 0.30, 95% CI 0.17–0.54), but there was no significant difference in the risk of CVD (adjusted HR 0.88, 95% CI 0.64–1.21). Conclusions Lifestyle intervention among persons with IGT did not decrease cardiovascular morbidity during the first 10 years of follow-up. However, the statistical power may not be sufficient to detect small differences between the intervention and control groups. Low total mortality among participants of the DPS compared with individuals with IGT in the general population could be ascribed to a lower cardiovascular risk profile at baseline and regular follow-up. Trial Registration ClinicalTrials.gov NCT00518167

Anti-inflammatory effect of lifestyle changes in the Finnish Diabetes Prevention Study.

AbstractAims/hypothesisSubclinical inflammation confers an increased risk of type 2 diabetes, cardiovascular disease, neurodegenerative disorders and other age-related chronic diseases. Physical activity and diet can attenuate systemic immune activation, but it is not known which individual components of a comprehensive lifestyle intervention are most effective in targeting subclinical inflammation.MethodsWe used data from the baseline examination and the 1 year follow-up of a subsample of 406 of 522 participants of the Finnish Diabetes Prevention Study (DPS) to estimate the effect of individual components of lifestyle intervention on C-reactive protein (CRP) and IL-6 levels, which represent the best characterised proinflammatory risk factors for type 2 diabetes. Changes in metabolic markers, dietary patterns and exercise were analysed to determine which were most strongly associated with the anti-inflammatory effect of lifestyle changes.ResultsLifestyle intervention reduced circulating levels of CRP (p < 0.001) and IL-6 (p = 0.060). Increases in fibre intake and moderate to vigorous leisure time physical activity (LTPA), but not total LTPA, predicted decreases in CRP and/or IL-6 and remained associated even after adjustment for baseline BMI or changes in BMI during the first year of the study. Changes in carbohydrate or fat intake were either weakly or not linked to reductions in CRP and IL-6.Conclusions/interpretationThe present study assessed the individual effects of dietary and physical activity measures on low-grade inflammation in individuals at high cardiometabolic risk. Our results underline the importance of moderate to vigorous LTPA and a diet rich in natural fibre, and this should be emphasised in lifestyle recommendations. Trial registration: ClinicalTrials.gov NCT00518167 Funding: The study was funded by the European Foundation for the Study of Diabetes, the German Federal Ministry of Health, the Ministry of Innovation, Science, Research and Technology of the State of North Rhine-Westphalia, the German Diabetes Foundation (Deutsche Diabetes-Stiftung), the Department of Internal Medicine II—Cardiology at the University of Ulm, the Academy of Finland, the Juho Vainio Foundation, the Finnish Ministry of Education, the Novo Nordisk Foundation, the Yrjö Jahnsson Foundation, the Finnish Diabetes Research Foundation and EVO funds from Tampere and Kuopio University Hospital.

Effects of aerobic and strength exercise on motor fatigue in men and women with multiple sclerosis: a randomized controlled trial

Objective: To investigate the effects of aerobic and strength exercise on motor fatigue of knee flexor and extensor muscles in subjects with multiple sclerosis (MS). Design: A randomized controlled trial. Setting: At Masku Neurological Rehabilitation Centre, Masku, and the Social Insurance Institution, Research Department, Turku, Finland. Subjects: Ninety-five MS patients with mild to moderate disability were randomized into exercise group (n = 47) and a control group (n = 48). Intervention: Participants in the exercise group attended in a supervised exercise period of three weeks, which was followed by a home exercise programme lasting for 23 weeks. Patients in the control group continued with their normal living. Outcome measures: Motor fatigue of knee flexor and extensor muscles was measured during a static 30-s maximal sustained muscle contraction. The decline in force (Nm) during the 30 s was recorded, and a fatigue index (FI) was calculated. Subjective fatigue was measured by using the Fatigue Severity Scale (FSS). The Ambulatory Fatigue Index (AFI) was calculated on the basis of a 500-m walking test. Assessment took place at baseline, at the third week (not for the control group) and at the 26th week. All outcome variables were analysed, men and women together, and some interesting contrasts were analysed by gender. Results: Associations were observed with changes in extension FI and Expanded Disability Status Scale (EDSS) score and mean extension torque (Nm), but not with changes in FI and aerobic or strength exercise activity, mean AFI, mean FSS or in mean knee flexion torque. AFI was decreased in all subject groups (p = 0.007). Motor fatigue was reduced in knee flexion (p = 0.0014) and extension (ns) among female but not in male exercisers after six months of exercise. The exercise activity of women was 25% higher than that of the men. Conclusions: Six months of exercise reduced motor fatigue in women, but not in men.

SLEEP DURATION, LIFESTYLE INTERVENTION AND INCIDENCE OF TYPE 2 DIABETES IN IMPAIRED GLUCOSE TOLERANCE. THE FINNISH DIABETES PREVENTION STUDY.

OBJECTIVE Both short and long sleep duration have frequently been found to be associated with an increased risk for diabetes. The aim of the present exploratory analysis was to examine the association between sleep duration and type 2 diabetes after lifestyle intervention in overweight individuals with impaired glucose tolerance in a 7-year prospective follow-up. RESEARCH DESIGN AND METHODS A total of 522 individuals (aged 40–64 years) were randomly allocated either to an intensive diet-exercise counseling group or to a control group. Diabetes incidence during follow-up was calculated according to sleep duration at baseline. Sleep duration was obtained for a 24-h period. Physical activity, dietary intakes, body weight, and immune mediators (C-reactive protein and interleukin-6) were measured. RESULTS Interaction between sleep duration and treatment group was statistically significant (P = 0.003). In the control group, the adjusted hazard ratios (HRs) (95% CI) for diabetes were 2.29 (1.38–3.80) and 2.74 (1.67–4.50) in the sleep duration groups 9–9.5 h and ≥10 h, respectively, compared with for that of the 7–8.5 h group. In contrast, sleep duration did not influence the incidence of diabetes in the intervention group; for sleep duration groups 9–9.5 h and ≥10 h, the adjusted HRs (95% CI) were 1.10 (0.60–2.01) and 0.73 (0.34–1.56), respectively, compared with that in the reference group (7–8.5 h sleep). Lifestyle intervention resulted in similar improvement in body weight, insulin sensitivity, and immune mediator levels regardless of sleep duration. CONCLUSIONS Long sleep duration is associated with increased type 2 diabetes risk. Lifestyle intervention with the aim of weight reduction, healthy diet, and increased physical activity may ameliorate some of this excess risk.

Leisure-Time Physical Activity and the Metabolic Syndrome in the Finnish Diabetes Prevention Study

OBJECTIVE To assess the effects of leisure-time physical activity (LTPA) and resistance training on metabolic syndrome (MetS) and its components in a post hoc analysis of the Finnish Diabetes Prevention Study, a randomized controlled lifestyle counseling trial. RESEARCH DESIGN AND METHODS A cohort of 486 middle-aged overweight men and women with impaired glucose tolerance were followed for an average of 4.1 years. The intervention and control groups were combined in the analyses. LTPA was assessed by questionnaires, dietary intake by food records, and features of the MetS by anthropometric and biochemical measures annually. Resistance training sessions were documented for 137 participants. RESULTS Increased moderate-to-vigorous LTPA, even after adjustments for changes in dietary intakes of total and saturated fat, fiber, and energy, and change in BMI was associated with a greater likelihood for resolution (29.7 vs. 19.1%; P = 0.004 in the upper versus lower third of change) and a lesser likelihood for development (23.5 vs. 44.7%; P = 0.041) of the MetS. Of the components of the MetS, the increase in moderate-to-vigorous LTPA was associated most strongly with improvement of glycemia. Among the 137 participants who participated in resistance training, MetS components were favorable in individuals who were in the upper third of participation rate (median 51 times/year) compared with individuals in the lowest third (median 8.5 times/year). CONCLUSIONS Increased moderate-to-vigorous LTPA was associated with a decreased likelihood of developing the MetS and an increased likelihood of its resolution in individuals at high risk for type 2 diabetes.

Assessment of muscle strength and motor fatigue with a knee dynamometer in subjects with multiple sclerosis: a new fatigue index

Objective: To measure muscle strength and motor fatigue with a knee dynamometer and to assess the intra-rater reliability of measurements for maximal isometric extensor and flexor torques and the reliability of a new fatigue index (FI) in patients with mild to moderate multiple sclerosis (MS). Design: Repeated assessments with one-week intervals. Setting: The Masku Neurological Rehabilitation Centre, Masku, and the Social Insurance Institution, Research Department, Turku, Finland. Subjects: Twenty-eight MS patients. Outcome measures: Maximal isometric torque during 5 s and fatigue of knee flexors and extensors during isometric contractions of 30 s were assessed. A new FI was established and compared with the two previously used indices (FI1 and FI2). All three indices are based on the calculated area under the force versus time curve (AUFC), with FI1 using the 30-s recording time in its entirety and F2 omitting the initial 5 s in the calculation. In the new fatigue index (FI3), the time point of maximum (TPM) torque achieved by the subject is used as the starting point in the calculation. The patients subjective fatigue was measured by Fatigue Severity Scale (FSS). Results: The intraclass correlation coefficient (ICC) was 0.97 in maximal isometric torque measurements. FI3 showed good intra-rater reliability (ICC 0.68-0.86). None of the fatigue indices correlated with FSS. Conclusions: Maximal isometric torque and motor fatigue of knee flexor and extensor muscles can be reliably measured using a knee dynamometer in MS patients. The new FI proved to be a reliable model for MS patients.

Cardiovascular autonomic dysfunction is associated with central obesity in persons with impaired glucose tolerance

Diabet. Med. 28, 699–704 (2011)

Association of the FTO gene variant (rs9939609) with cardiovascular disease in men with abnormal glucose metabolism – The Finnish Diabetes Prevention Study

BACKGROUND AND AIM The common single nucleotide polymorphism (SNP) in the FTO (fat mass and obesity associated) gene has been consistently associated with an increased risk of obesity. We investigated whether the SNP rs9939609 (T/A) of the FTO is associated with risk factors of cardiovascular diseases (CVD), including serum levels of C - reactive protein (CRP), the chemokine RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted; CCL5), and serum and lipoprotein lipids in the Finnish Diabetes Prevention Study (DPS). Furthermore, we examined whether the rs9939609 increased the CVD risk in the DPS and if these results could be replicated in a larger cross-sectional population-based random sample of Finnish men (the METSIM). METHODS AND RESULTS In the DPS, altogether 490 (BMI≥25kg/m(2)) subjects with impaired glucose tolerance were genotyped for rs9939609. Cardiovascular morbidity and mortality data were collected during the median follow-up of 10.2 years. The replication study was a population-based cross-sectional study of 6214 men. In the DPS, the AA genotype of rs9939609 was associated, independently of BMI, with increased RANTES (p=0.002) and decreased HDL cholesterol concentrations (p=0.007) in men. During the follow-up, the AA genotype was associated with an adjusted 2.09-fold risk (95% CI 1.17-3.73, p=0.013) of CVD in men. In the METSIM Study, the association with a history of myocardial infarction was replicated in the subgroup of men with type 2 diabetes. CONCLUSION We suggest that the variation in the FTO gene may contribute to the development of CVD in men with an abnormal glucose metabolism.