Overweight and obese but not normal weight women with PCOS are at increased risk of Type 2 diabetes mellitus-a prospective, population-based cohort study.

STUDY QUESTION: What are the respective roles of polycystic ovary syndrome (PCOS), long-term weight gain and obesity for the development of prediabetes or Type 2 diabetes mellitus (T2DM) by age 46 years? SUMMARY ANSWER: The risk of T2DM in women with PCOS is mainly due to overweight and obesity, although these two factors have a synergistic effect on the development of T2DM. WHAT IS KNOWN ALREADY: PCOS is associated with an increased risk of prediabetes and T2DM. However, the respective roles of PCOS per se and BMI for the development of T2DM have remained unclear. STUDY DESIGN, SIZE, DURATION: In a prospective, general population-based follow-up birth cohort 1966 (n = 5889), postal questionnaires were sent at ages 14 (95% answered), 31 (80% answered) and 46 years (72% answered). Questions about oligoamenorrhoea and hirsutism were asked at age 31 years, and a question about PCOS diagnosis at 46 years. Clinical examination and blood sampling were performed at 31 years in 3127 women, and at 46 years in 3280 women. A 2-h oral glucose tolerance test (OGTT) was performed at 46 years of age in 2780 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women reporting both oligoamenorrhoea and hirsutism at age 31 years and/or diagnosis of PCOS by 46 years were considered as women with PCOS (n = 279). Women without any symptoms at 31 years and without PCOS diagnosis by 46 years were considered as controls (n = 1577). The level of glucose metabolism was classified according to the results of the OGTT and previous information of glucose metabolism status from the national drug and hospital discharge registers. MAIN RESULTS AND THE ROLE OF CHANCE: PCOS per se significantly increased the risk of T2DM in overweight/obese (BMI ≥ 25.0 kg/m2) women with PCOS when compared to overweight/obese controls (odds ratio: 2.45, 95% CI: 1.28-4.67). Normal weight women with PCOS did not present with an increased risk of prediabetes or T2DM. The increase in weight between ages 14, 31 and 46 years was significantly greater in women with PCOS developing T2DM than in women with PCOS and normal glucose tolerance, with the most significant increase occurring in early adulthood (between 14 and 31 years: median with [25%; 75% quartiles]: 27.25 kg [20.43; 34.78] versus 13.80 kg [8.55; 20.20], P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The diagnosis of PCOS was based on self-reporting, and the questionnaire at 46 years did not distinguish between polycystic ovaries only in ultrasonography and the syndrome. Ovarian ultrasonography was not available to aid the diagnosis of PCOS. WIDER IMPLICATIONS OF THE FINDINGS: These results emphasize weight management already during adolescence and early adulthood to prevent the development of T2DM in women with PCOS, as the period between 14 and 31 years seems to be a crucial time-window during which the women with PCOS who are destined to develop T2DM by 46 years of age experience a dramatic weight gain. Furthermore, our results support the view that, particularly in times of limited sources of healthcare systems, OGTT screening should be targeted to overweight/obese women with PCOS rather than to all women with PCOS. STUDY FUNDING/COMPETING INTERESTS: Finnish Medical Foundation; North Ostrobothnia Regional Fund; Academy of Finland (project grants 104781, 120315, 129269, 1114194, 24300796, Center of Excellence in Complex Disease Genetics and SALVE); Sigrid Juselius Foundation; Biocenter Oulu; University Hospital Oulu and University of Oulu (75617); Medical Research Center Oulu; National Institute for Health Research (UK); National Heart, Lung, and Blood Institute (grant 5R01HL087679-02) through the STAMPEED program (1RL1MH083268-01); National Institute of Health/National Institute of Mental Health (5R01MH63706:02); ENGAGE project and grant agreement HEALTH-F4-2007-201413; EU FP7 EurHEALTHAgeing-277849 European Commission and Medical Research Council, UK (G0500539, G0600705, G1002319, PrevMetSyn/SALVE) and Medical Research Center, Centenary Early Career Award. The authors have no conflicts of interests. TRIAL REGISTRATION NUMBER: N/A.

Association of maternal smoking during pregnancy with aerobic fitness of offspring in young adulthood: a prospective cohort study.

OBJECTIVE: We evaluated the association of maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and maternal smoking with aerobic fitness in young men aged 19-20 years. DESIGN: A 19-year prospective cohort study. SETTING: Data from the Northern Finland Birth Cohort 1986 (NFBC 1986) and the Sodankylä Jaeger Brigade, Finland, in 2005-6. POPULATION: Mothers and the 508 offspring in the NFBC 1986 who entered military service at the Sodankylä Jaeger Brigade in 2005. METHODS: Associations of weight, 12-minute running test (Cooper test), and muscle fitness index (MFI) of offspring on entry to military service were evaluated with antenatal factors, including maternal smoking, pre-pregnancy BMI, and GWG. MAIN OUTCOME MEASURES: Aerobic and muscle fitness of the offspring were evaluated by the Cooper test and MFI. RESULTS: Maternal smoking during pregnancy was associated with lower aerobic fitness of male adolescents, measured by the Cooper test (2356 m; 95% confidence interval, 95% CI 2265-2446 m), compared with the offspring of mothers who did not smoke during pregnancy (2537 m, 95% CI 2499-2574 m). This association was independent of the BMIs of both the mother and the offspring, GWG, and the smoking and physical activity of offspring (regression coefficient -140.6 m, 95% CI -273.1 to -8.0 m). High maternal pre-pregnancy BMI and excessive GWG were also associated with lower aerobic fitness of the offspring; however, this association was mediated via the weight of the offspring. CONCLUSIONS: Maternal smoking during pregnancy may have a negative impact on the aerobic fitness of the offspring. TWEETABLE ABSTRACT: Study shows that young men have lower aerobic fitness if their mothers smoked during pregnancy.

Changes in glucose metabolism in people with different glucose metabolism disorders at baseline: follow-up results of a Finnish national diabetes prevention programme.

AIM: To examine changes in glucose metabolism (fasting and 2-h glucose) during follow-up in people with impaired fasting glucose in comparison with changes in people with isolated impaired glucose tolerance, people with impaired fasting glucose and impaired glucose tolerance combined and people with screening-detected Type 2 diabetes at baseline, among those who participated in a diabetes prevention programme conducted in Finland. METHODS: A total of 10 149 people at high risk of Type 2 diabetes took part in baseline examination. Of 5351 individuals with follow-up ≥ 9 months, 1727 had impaired glucose metabolism at baseline and completed at least one lifestyle intervention visit. Most of them (94.6%) were overweight/ obese. RESULTS: Fasting glucose decreased during follow-up among overweight/obese people in the combined impaired fasting glucose and impaired glucose tolerance group (P = 0.044), as did 2-h glucose in people in the isolated impaired glucose tolerance group (P = 0.0014) after adjustment for age, sex, medication and weight at baseline, follow-up time and changes in weight, physical activity and diet. When comparing changes in glucose metabolism among people with different degrees of glucose metabolism impairment, fasting glucose concentration was found to have increased in those with isolated impaired glucose tolerance (0.12 mmol/l, 95% Cl 0.05 to 0.19) and it decreased to a greater extent in those with screening-detected Type 2 diabetes (-0.54 mmol/l, 95% Cl -0.69 to -0.39) compared with those with impaired fasting glucose (-0.21 mmol/l, 95% Cl -0.27 to -0.15). Furthermore, 2-h glucose concentration decreased in the isolated impaired glucose tolerance group (-0.82 mmol/l, 95% Cl -1.04 to -0.60), in the combined impaired fasting glucose and impaired glucose tolerance group (-0.82 mmol/l, 95% Cl -1.07 to -0.58) and in the screening-detected Type 2 diabetes group (-1.52, 95% Cl -1.96 to -1.08) compared with those in the impaired fasting glucose group (0.26 mmol/l, 95% Cl 0.10 to 0.43). Results were statistically significant even after adjustment for covariates (P < 0.001 in all models). CONCLUSIONS: Changes in glucose metabolism differ in people with impaired fasting glucose from those in people with isolated impaired glucose tolerance, people with impaired fasting glucose and impaired glucose tolerance combined and people with screening-detected Type 2 diabetes.

Markers of cholesterol metabolism as biomarkers in predicting diabetes in the Finnish Diabetes Prevention Study.

BACKGROUND AND AIMS: We examined the effect of serum markers of cholesterol synthesis and absorption on the incidence of type 2 diabetes (T2D) in the randomized Finnish Diabetes Prevention Study (DPS). We also explored a possible interaction of ABCG8 rs4299376 on sterol levels and lifestyle intervention. METHODS AND RESULTS: We conducted a prospective cohort study including overweight, middle-aged people with impaired glucose tolerance at baseline who participated in the randomized DPS. The primary outcome of the DPS was the diagnosis of T2D based on repeated oral glucose tolerance tests (OGTTs). After active intervention (median of four years, 1994-2001), non-T2D participants were further followed until T2D diagnosis, dropout or the end of 2009. Of these, 340 participants who had ß-sitosterol, campesterol, lathosterol and desmosterol measured by gas chromatography-mass spectrometry during the active four-year follow-up and who were not using cholesterol lowering medications were analysed. Surrogate indexes of insulin sensitivity (IS) and secretion were calculated from an OGTT. In adjusted models, plant sterols during the four-year follow-up were associated with lower T2D incidence during the extended eight-year follow-up (HR for 1-SD change in ß-sitosterol and campesterol: 0.76 [0.63-0.92], and 0.81 [0.67-0.99], respectively). Lathosterol levels were associated with higher T2D incidence (HR: 1.35 [1.13-1.62]). These associations, though, were not independent of IS. There was an interaction between rs4299376 and study group on ß-sitosterol (p = 0.001) and campesterol (p = 0.004) levels during the follow-up. CONCLUSIONS: Markers of low absorption and high synthesis of cholesterol were associated with the risk of developing T2D, mostly ascribed to IS.

National diabetes prevention program (DEHKO): awareness and self-reported lifestyle changes in Finnish middle-aged population.

OBJECTIVES: The national development programme for the prevention and care of diabetes was carried out in Finland during 2000-2010. One of the programme goals was to raise awareness of diabetes and its risk factors in the whole population through various activities, e.g. media campaigns and health fares. In addition, a targeted implementation project on the prevention of type 2 diabetes, FIN-D2D, was carried out in selected districts during 2003-2008. The aim of this analysis was to examine the changes in overall awareness of the programme and its association with self-reported lifestyle changes within the adult population during the FIN-D2D project period in the FIN-D2D area compared with the area not participating in the FIN-D2D (the control area). STUDY DESIGN: Health behaviour and health among the Finnish Adult Population -postal survey. METHODS: The structured questionnaire mailed to a random population sample included questions on participants' sociodemographic background, medical history, health habits, and recent lifestyle changes. Awareness of the national diabetes programme was also enquired. Data (n = 10 831) from the 2004-2008 postal surveys were used for this investigation. RESULTS: In the FIN-D2D area, 25% (347/1384) of men and 48% (797/1674) of women reported being aware of the programme. In the control area, the proportions were 20% (702/3551) and 36% (1514/4222), respectively. The overall awareness increased among both genders and in all areas during the project period, but the level of awareness was consistently higher in the FIN-D2D area. Female gender and higher age were associated with increasing awareness of the programme in both areas. Self-reported lifestyle changes were more common among women, but associated with the level of awareness of the programme more often among men than women. CONCLUSIONS: The awareness of diabetes and its risk factors increased among men and women in both implementation and control areas during the FIN-D2D project period. The activities of the implementation project may at least partly explain the differences in lifestyle changes between areas, especially among men. The results suggest that health promotion campaigns increase the population awareness about the prevention of chronic diseases and as a result, especially men may be prompted to make beneficial lifestyle changes.

Light physical activity determined by a motion sensor decreases insulin resistance, improves lipid homeostasis and reduces visceral fat in high-risk subjects: PreDiabEx study RCT.

OBJECTIVE: To examine physical activity (PA) thresholds affecting glucose, insulin and lipid concentrations and body fat composition in high-risk patients for type 2 diabetes (T2D). INTERVENTION: A total of 113 subjects of both genders having abnormal glucose levels in the oral glucose tolerance test were contacted. A total of 78 subjects with age 58.8±10.4 years and body mass index 31.7±5.3 kg m(-2) were randomly assigned to intervention and control groups. INTERVENTION consisted of a supervised walking (60 min three times weekly) for 3 months. All the subjects received standard care for PA and weight reduction and wore an accelerometer during the whole wakeful time. RESULTS: Over 80% of the daily steps clustered at an acceleration level of 0.3-0.7 g (2-3 km h(-1) of walking) and were 5870 in the intervention and 4434 in the control group (P<0.029). Between 0 and 3 months no significant changes were observed in fasting and 2-h glucose, body weight or maximal oxygen uptake. In contrast, changes in fasting and 2-h insulin (-3.4 mU l(-1), P=0.035 and -26.6, P=0.003, respectively), homeostasis model assessment-estimated insulin resistance (-1.0, P=0.036), total cholesterol (-0.55 mmol l(-1), P=0.041), low-density lipoprotein (LDL) cholesterol (-0.36 mmol l(-1), P=0.008) and visceral fat area (-5.5 cm(2), P=0.030) were significantly greater in the intervention than in control subjects. The overall effects of PA were analyzed by quartiles of daily steps of all subjects. There were significant reductions in total and LDL cholesterol and visceral fat area between the highest (daily steps over 6520) and the lowest quartile (1780-2810 daily steps). The changes associated with PA remained significant after adjustments of baseline, sex, age and body weight change. CONCLUSION: Habitual and structured PAs with the acceleration levels of 0.3-0.7 g and daily steps over 6520, equivalent to walking at 2-3 km h(-1) for 90 min daily, standing for the relative PA intensity of 30-35% of the maximal oxygen uptake, are clinically beneficial for overweight/obese and physically inactive individuals with a high risk for T2D.

Improved lifestyle and decreased diabetes risk over 13 years: long-term follow-up of the randomised Finnish Diabetes Prevention Study (DPS).

AIMS/HYPOTHESIS: This study aimed to determine whether lifestyle intervention lasting for 4 years affected diabetes incidence, body weight, glycaemia or lifestyle over 13 years among individuals at high risk of type 2 diabetes. METHODS: Overweight, middle-aged men (n = 172) and women (n = 350) with impaired glucose tolerance were randomised in 1993-1998 to an intensive lifestyle intervention group (n = 265), aiming at weight reduction, dietary modification and increased physical activity, or to a control group (n = 257) that received general lifestyle information. The primary outcome was a diagnosis of diabetes based on annual OGTTs. Secondary outcomes included changes in body weight, glycaemia, physical activity and diet. After active intervention (median 4 years, range 1-6 years), participants still free of diabetes and willing to continue their participation (200 in the intervention group and 166 in the control group) were further followed until diabetes diagnosis, dropout or the end of 2009, with a median total follow-up of 9 years and a time span of 13 years from baseline. RESULTS: During the total follow-up the adjusted HR for diabetes (intervention group vs control group) was 0.614 (95% CI 0.478, 0.789; p < 0.001). The corresponding HR during the post-intervention follow-up was 0.672 (95% CI 0.477, 0.947; p = 0.023). The former intervention group participants sustained lower absolute levels of body weight, fasting and 2 h plasma glucose and a healthier diet. Adherence to lifestyle changes during the intervention period predicted greater risk reduction during the total follow-up. CONCLUSIONS/INTERPRETATION: Lifestyle intervention in people at high risk of type 2 diabetes induces sustaining lifestyle change and results in long-term prevention of progression to type 2 diabetes.

Lactation is associated with greater maternal bone size and bone strength later in life.

SUMMARY: The association between lactation and bone size and strength was studied in 145 women 16 to 20 years after their last parturition. Longer cumulative duration of lactation was associated with larger bone size and strength later in life. INTRODUCTION: Pregnancy and lactation have no permanent negative effect on maternal bone mineral density but may positively affect bone structure in the long term. We hypothesized that long lactation promotes periosteal bone apposition and hence increasing maternal bone strength. METHODS: Body composition, bone area, bone mineral content, and areal bone mineral density of whole body and left proximal femur were assessed using DXA, and cross-sectional area and volumetric bone mineral density of the left tibia shaft were measured by pQCT in 145 women (mean age 48 years, range 36-60 years) 16 to 20 years after their last parturition. Hip (HSI) and tibia strength indexes (TBSI) were calculated. Medical history and lifestyle factors including breastfeeding patterns and durations were collected via a self-administered questionnaire. Weight change during each pregnancy was collected from personal maternity tracking records. RESULTS: Sixteen to 20 years after the last parturition, women who had breastfed in total more than 33 months in their life, regardless of the number of children, had greater bone strength estimates of the hip (HSI = 1.92 vs. 1.61) and the tibia (TBSI = 5,507 vs. 4,705) owing to their greater bone size than mothers who had breastfed less than 12 months (p < 0.05 for all). The differences in bone strength estimates were independent of body height and weight, menopause status, use of hormone replacement therapy, and present leisure time physical activity level. CONCLUSION: Breastfeeding is beneficial to maternal bone strength in the long run.

Family history of diabetes and effectiveness of lifestyle counselling on the cardio-metabolic risk profile in individuals at high risk of Type 2 diabetes: 1-year follow-up of the FIN-D2D project.

AIMS: To investigate whether a positive family history of diabetes is associated with the effectiveness of lifestyle counselling on cardio-metabolic risk factors and glucose tolerance status in a 1-year follow-up in a cohort of Finnish men and women at high risk for Type 2 diabetes. METHODS: Altogether, 10,149 individuals who had high risk of Type 2 diabetes participated in the implementation programme of the national diabetes prevention programme at baseline. One-year follow-up data were available for 2798 individuals without diabetes. Family history of diabetes was based on self-report. Lifestyle interventions were individual or groups sessions on lifestyle changes. The effectiveness of lifestyle intervention was measured as changes in cardiovascular risk factors, glucose tolerance status and incidence of Type 2 diabetes. RESULTS: Family history was associated with the effectiveness of lifestyle intervention in men, but not in women. During the 1-year follow-up, body weight, BMI, systolic blood pressure, total cholesterol, LDL cholesterol and score for 10-year risk for fatal cardiovascular disease (SCORE) decreased and glucose tolerance status improved more in men without a family history of diabetes than in men with a family history of diabetes. Of the participating men and women, 10% and 5% developed Type 2 diabetes, respectively. Family history was not related to the incidence of Type 2 diabetes in either gender. CONCLUSIONS: Men without a family history of diabetes were more successful in responding to lifestyle counselling with regard to cardio-metabolic measurements and glucose tolerance than those with a family history of diabetes. Similar results were not seen in women. In keeping with findings from earlier studies, the prevention of Type 2 diabetes is not influenced by a family history of diabetes.

How does lifestyle intervention affect depressive symptoms? Results from the Finnish Diabetes Prevention Study.

AIMS: To assess the effect of lifestyle intervention on depressive symptoms during a 36-month randomized clinical trial designed to prevent Type 2 diabetes. METHODS: A total of 522 middle-aged participants, who were overweight or obese and had impaired glucose tolerance, were randomized to the lifestyle intervention or control group in the Finnish Diabetes Prevention Study. The intervention group received individualized counselling aimed at reducing weight and increasing physical activity. Depressive symptoms were measured using the Beck Depression Inventory among a subgroup of 140 participants. RESULTS: On study entry, the mean Beck Depression Inventory scores ± sd were 6.8 ± 5.6 in the intervention group and 6.7 ± 5.5 in the control group. Beck Depression Inventory scores reduced during the intervention study: the mean ± sd (95% CI) reduction was 0.90 ± 4.54 (-1.99 to -0.19) scores in the intervention group and 0.75 ± 4.47 (-1.80 to 0.31) in the control group, with no difference between the groups. In a stepwise linear multivariate regression analysis, the variables with the strongest associations with the change in Beck Depression Inventory scores were baseline Beck Depression Inventory scores, marital status, weight change and change of total energy intake (R(2) = 0.209, P < 0.001). CONCLUSIONS: Participation in the study lowered depression scores, with no specific group effect. Among the lifestyle changes, particularly successful reduction of body weight was associated with the greater reduction of depressive symptoms. Thus, regardless of the intensity of the treatment, the success in executing alterations in one's lifestyle and behaviour is associated with beneficial changes in mood.

HbA(1c) in diagnosing and predicting Type 2 diabetes in impaired glucose tolerance: the Finnish Diabetes Prevention Study.

AIMS: We analysed the Finnish Diabetes Prevention Study data in order to evaluate how the new HbA(1c) -based criterion compares with the oral glucose tolerance test in diagnosing Type 2 diabetes among high-risk individuals during a prospective average follow-up of 4 years. METHODS: In the Diabetes Prevention Study, 172 men and 350 women who were overweight and had impaired glucose tolerance at baseline were randomized into an intensive lifestyle intervention or a control group. The oral glucose tolerance test and HbA(1c) measurements were performed annually until the diagnosis of diabetes using the World Health Organization 1985 criteria. RESULTS: The sensitivity of the HbA(1c) ≥ 6.5% (≥ 48 mmol/mol) as a diagnostic criterion for Type 2 diabetes was 35% (95% CI 24%, 47%) in women and 47% (95% CI 31%, 64%) in men compared with diagnosis based on two consecutive oral glucose tolerance tests. The corresponding sensitivities for HbA(1c) ≥ 6.0% (≥ 42 mmol/mol) were 67% (95% CI 55%, 77%) and 68% (95% CI 51%, 82%). The participants with HbA(1c) ≥ 6.5% (≥ 48 mmol/mol) and diabetes based on the oral glucose tolerance test were more obese and had higher fasting glucose and 2-h glucose concentrations than those who had a diabetic oral glucose tolerance test but HbA(1c) < 6.5% (< 48 mmol/mol). There were no differences in the predictive performance of baseline fasting glucose, oral glucose tolerance test and HbA(1c) . CONCLUSIONS: Of those with diabetes diagnosis based on two oral glucose tolerance tests during the Diabetes Prevention Study follow-up, 60% would have remained undiagnosed if diagnosis had been based on HbA(1c) ≥ 6.5% (≥ 48 mmol/mol) criterion.

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

AIMS: The aim of this study was to investigate the prevalence of cardiovascular autonomic neuropathy in persons with previously diagnosed impaired glucose tolerance and to characterize associations between components of metabolic syndrome and cardiovascular autonomic neuropathy in the Finnish Diabetes Prevention Study cohort. METHODS: Two hundred and sixty-eight individuals with impaired glucose tolerance at baseline in the Finnish Diabetes Prevention Study, but not diagnosed with diabetes during follow-up, were studied for cardiovascular autonomic neuropathy. At the second annual follow-up visit after the end of lifestyle intervention, we performed deep-breathing and active orthostatic tests to detect possible parasympathetic and sympathetic dysfunction. To describe metabolic characteristics, anthropometric measurements, an oral glucose tolerance test and assessments for HbA(1c,) serum lipids and blood pressure were carried out. RESULTS: Prevalence of parasympathetic dysfunction was 25% and prevalence of sympathetic dysfunction was 6%, with no difference between the former intervention and control group participants or between men and women. Subjects with parasympathetic dysfunction were older, more obese (weight, waist circumference, body mass index) and had higher triglyceride concentration compared with those with normal parasympathetic function (P<0.01 for all). Parasympathetic dysfunction was not significantly associated with other characteristics of metabolic syndrome; for example, high cholesterol, glucose and insulin levels or HbA(1c) . Correlations between the Expiration/Inspiration (E/I) ratio (the longest heart beat duration in expiration divided by the shortest heart beat duration in inspiration) and measures reflecting obesity were statistically significant in the pooled population and in men but not in women. CONCLUSIONS: Cardiovascular autonomic neuropathy is common in persons with impaired glucose tolerance. Obesity, especially among men, seems to play an important role in the early pathogenesis of cardiovascular autonomic neuropathy.

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.

Parental predictors of fruit and vegetable consumption in treatment-seeking overweight children.

BACKGROUND: Information on the role of family dietary behaviours is needed to enable the design of effective interventions for treatment of childhood obesity. The present study aimed to analyse differences in consumption and predictors of fruit, berries and vegetables (FBV) between normal-weight and overweight treatment-seeking children and their parents. METHODS: Fifty-four treatment-seeking overweight and 65 normal-weight 8-year-old children and their parents participated in the present study. Children's and parent's consumption of FBV were assessed by a food frequency questionnaire. Availability of vegetables at home meals, child's preference for FBV and parent's control over portion size were determined. Weight and height were measured and the standardised body mass index of each child was calculated. Multiple linear regression analysis was performed to investigate the predictors of children's FBV consumption. RESULTS: Normal-weight children and parents ate FBV more frequently than overweight children. In the multiple linear regression analysis, mother's (ß = 0.476, P ≤ 0.001) and father's consumption of FBV (ß = 0.347, P = 0.001) and child's preference for eating vegetables (ß = 0.259, P = 0.002) were positively associated with the child's consumption of FBV. In overweight children, parent's consumption of FBV was the only predictor of the offspring's consumption of FBV (P = 0.002). CONCLUSIONS: Predictors related to FBV consumption appear to be the similar in normal-weight and treatment-seeking overweight children. The findings obtained in the present study highlight the importance of parental modelling in determining the consumption of FBV in their children.

The Prevalence of Frailty Using Three Different Frailty Measurements in Two Finnish Cohorts Born Before and After the Second World War.

OBJECTIVES: To study the prevalence of frailty and its relationship to mortality in cohorts born before and after the Second World War using three different frailty measures. METHODS: Cross-sectional data from two cohorts born in 1935 (n=593) and 1945 (n=714) were studied for frailty at the mean age of 70.7 (SD 1.8) years. Frailty was measured using the Frailty Phenotype (FP), the Frail Scale (FS) and the 74-item Frailty Index (FI>0.21 denoted frailty). Information on socioeconomic factors was obtained via a study questionnaire and the data on mortality were obtained from the Population Information System. RESULTS: The prevalence of frailty by FI was more common in the older 1935 cohort than in the 1945 cohort (p<0.001). The percentage of robust subjects was higher in both sexes in the 1945 cohort using both FI and FS. After adjusting for sociodemographic factors, the difference in the prevalence of frailty between the cohorts remained significant in women only (OR 1.9 (95% CI 1.3-2.9), p=0.001). The FI classified people as frail more often (30.2% in the 1935 cohort and 17.5% in the 1945 cohort) than the FS (13.1% and 8.8%) or FP (1.8% and 1.6%). Low financial satisfaction was associated significantly with frailty in both sexes. Low level of education was associated with frailty in women and being unmarried or divorced in men. Frailty was associated to increased mortality using all frailty definitions in the 1935 cohort with a longer follow-up time. CONCLUSIONS: Improved living conditions and health care may have resulted in the lower prevalence of frailty in the 1945 cohort. The present study further strengthens the association between frailty and mortality and poor economic status and frailty. Frailty definitions are in need of further study.

Prevalence and associated factors of restless legs in a 57-year-old urban population in northern Finland.

OBJECTIVE: We examined the prevalence and associated factors of restless legs syndrome (RLS) in a 57-year-old unselected urban population in northern Finland. METHODS: A health survey was conducted in 2002 that targeted persons born in 1945 and residing in the city of Oulu on 31 December, 2001. Their history of RLS, coronary heart disease (CHD), daytime sleepiness, depressive symptoms and snoring was assessed by means of questionnaires. RESULTS: Altogether 995 of 1332 eligible subjects (74%) participated (556 women, 439 men). The overall prevalence of RLS > or = 1 per week was 20% in women and 15% in men. In the fitted multiple logistic regression model, RLS was found to be associated with female gender (OR 1.64, 95% CI 0.98-2.72), CHD (OR 2.92, 95% CI 1.18-7.23), daytime sleepiness (OR 2.12, 95% CI 1.32-3.41), moderately elevated (31-45) or high (46-65) Zung sum scores (OR 1.95, 95% CI 1.09-3.48 and OR 3.67, 95% CI 1.71-7.90, respectively), antidepressant medication (OR 2.10, 95% CI 1.06-4.19) and arthropathy (OR 1.69, 95% CI 1.04-2.72). Insufficient evidence was found of an association between RLS and type 2 diabetes or impaired glucose regulation. CONCLUSIONS: Restless legs syndrome is fairly common in subjects aged 57 years. A particularly strong positive association was observed between RLS and depressive symptoms and CHD.

Serum ghrelin and the prediction of the development of impaired glucose regulation and Type 2 diabetes in middle-aged subjects.

BACKGROUND: Ghrelin is a peptide hormone which has been shown to associate with obesity, hypertension and Type 2 diabetes (T2DM) in cross-sectional studies. AIM: To study whether total ghrelin levels have predictive value for the incidence of impaired glucose regulation (IGR) or T2DM. SUBJECTS AND METHODS: The subjects of this prospective follow-up study (no.=201) belonged to a population-based cohort collected in Northern Finland. Oral glucose tolerance tests (OGTT) and measurements of fasting serum total ghrelin, lipids, blood pressure and body mass index were performed at the beginning and at the end of the study. The mean follow-up time was 5.1 yr. The subjects had normal glucose tolerance (NGT) at the beginning of the study. RESULTS: T2DM developed in 6 (3%), impaired fasting glucose (IFG) in 6 (3%) and impaired glucose tolerance (IGT) in 35 (17.4%) subjects. The baseline ghrelin concentrations did not differ between the two studied groups: median fasting serum total ghrelin concentration was 733 pg/ml (25th-75th percentiles: 571-961 pg/ml) among those who maintained NGT, and 661 pg/ml (25th-75th percentiles: 527- 878 pg/ml) among those who developed IGR (IFG and/or IGT) or T2DM (p=0.421). The baseline ghrelin concentrations did not explain the changes in the 0-h or 2-h blood glucose concentrations in regression models. CONCLUSIONS: Our findings suggest that fasting serum total ghrelin levels measured at one time point might not have predictive value for the development of abnormalities in glucose tolerance.

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

AIMS/HYPOTHESIS: Subclinical 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. METHODS: We 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. RESULTS: Lifestyle 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/INTERPRETATION: The 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.

Depressive symptoms predispose females to metabolic syndrome: a 7-year follow-up study.

OBJECTIVE: To evaluate the risk for developing metabolic syndrome when having depressive symptoms. METHOD: The prevalence of depressive symptoms and metabolic syndrome at baseline, and after a 7-year follow-up as measured with Beck depression inventory (BDI), and using the modified National Cholesterol Education Program--Adult Treatment Panel III criteria for metabolic syndrome (MetS) were studied in a middle-aged population-based sample (n = 1294). RESULTS: The logistic regression analysis showed a 2.5-fold risk (95% CI: 1.2-5.2) for the females with depressive symptoms (BDI >or=10) at baseline to have MetS at the end of the follow-up. The risk was highest in the subgroup with more melancholic symptoms evaluated with a summary score of the melancholic items in BDI (OR 6.81, 95% CI: 2.09-22.20). In men, there was no risk difference. CONCLUSION: The higher risks for MetS in females with depressive symptoms at baseline suggest that depression may be an important predisposing factor for the development of MetS.

High insulin levels are positively associated with peripheral nervous system function.

OBJECTIVE: The aim of this study was to analyze peripheral nervous system (PNS) function in overweight and obese individuals. MATERIALS AND METHODS: Forty-four adult non-diabetic overweight individuals were recruited. Peroneal motor nerve conduction and radial, sural, and medial plantar sensory nerve conduction were studied. Insulin and glucose levels were determined twice (over a 2- to 3-year period) with an oral glucose tolerance test (OGTT). Multiple stepwise linear regression models adjusted for age, height, weight, and skin temperature were used to analyze the data. RESULTS: Analysis revealed that baseline insulin levels measured 120 min after an OGTT explained 18% of the variation in peroneal F-wave minimum latency, 8% of peroneal F-wave maximum latency variation, 15% of sural sensory latency variation, 13% of sural sensory nerve conduction velocity (NCV) variation, and 10% of the variation in medial plantar sensory NCV. DISCUSSION AND CONCLUSION: Our study shows that serum insulin levels measured 120 min after an OGGT are positively associated with PNS function. High insulin levels without notably high glucose levels appear to be beneficial for the function of the PNS.