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The prevention of children being overweight/obese is of utmost importance. Parental characteristics play a pivotal role in shaping offspring weight status. This study aimed to examine associations between parental obesity and children's overweight/obesity status, and whether other parental type 2 diabetes (T2D) risk factors can predict children's obesity status.Logistic regression and receiver operating characteristic (ROC) analyses were conducted, using cross-sectional data from a European cohort of 20 151 adults (10 967 mothers; 9184 fathers) and children (n = 10 967) participating in the Feel4Diabetes study. Anthropometric measurements were conducted in children, and overweight/obesity was defined according to the International Obesity Task Force criteria. Parents' T2D risk was assessed applying the Finnish Diabetes Risk Score (FINDRISC).After adjusting for all other FINDRISC variables, region and maternal/parental education, maternal (adjusted odds ratio [aOR]: 2.64; 95% confidence interval [CI], 2.18-3.20) and parental (aOR: 3.21; 95% CI, 2.65-3.91) obesity, maternal (aOR: 1.46; 95% CI, 1.23-1.74) and parental (aOR: 1.59; 95% CI, 1.32-1.92) high waist circumference, as well as maternal (aOR: 1.60; 95% CI, 1.27-2.01) and parental (aOR: 1.87; 95% CI, 1.58-2.21) high FINDRISC score, were associated with child overweight/obesity status. Maternal (area under the curve- ROC: 0.638; 95% CI, 0.628-0.647) and paternal body mass index (BMI; area under the curve-ROC: 0.632; 95% CI, 0.622-0.642) were the most accurate in predicting child overweight/obesity status.Among parental risk factors for T2D, maternal/parental overweight/obesity status, central obesity, and high FINDRISC score were the main predictors of childhood overweight/obesity status, with BMI the most accurate. Maternal or paternal BMI is simple to use, and might be useful for the early identification of children at risk of being overweight/obese rather than other T2D factors.

Aim To assess the diagnostic accuracy of the FINDRISC for undiagnosed type 2 diabetes mellitus (T2DM) and dysglycaemia (i.e. the presence of prediabetes or T2DM) among early middle-aged adults from vulnerable groups in a large-scale European cohort. Methods Participants were recruited from low-socioeconomic areas in high-income countries (HICs) (Belgium-Finland) and in HICs under austerity measures (Greece-Spain) and from the overall population in low/middle-income countries (LMICs) (Bulgaria-Hungary). Study population comprised of 2116 parents of primary-school children from families identified at increased risk of T2DM, based on parental self-reported FINDRISC. Sensitivity (Se), specificity (Sp), area under the receiver operating characteristic curves (AUC-ROC) and the optimal cut-offs of FINDRISC that indicate an increased probability for undiagnosed T2DM or dysglycaemia were calculated. Results The AUC-ROC for undiagnosed T2DM was 0.824 with optimal cut-off ≥14 (Se = 68%, Sp = 81.7%) for the total sample, 0.839 with optimal cut-off ≥15 (Se = 83.3%, Sp = 86.9%) for HICs, 0.794 with optimal cut-off ≥12 (Se = 83.3%, Sp = 61.1%) for HICs under austerity measures and 0.882 with optimal cut-off ≥14 (Se = 71.4%, Sp = 87.8%) for LMICs. The AUC-ROC for dysglycaemia was 0.663 with optimal cut-off ≥12 (Se = 58.3%, Sp = 65.7%) for the total sample, 0.656 with optimal cut-off ≥12 (Se = 54.5%, Sp = 64.8%) for HICs, 0.631 with optimal cut-off ≥12 (Se = 59.7%, Sp = 62.0%) for HICs under austerity measures and 0.735 with optimal cut-off ≥11 (Se = 72.7%, Sp = 70.2%) for LMICs. Conclusion FINDRISC can be applied for screening primarily undiagnosed T2DM but also dysglycaemia among vulnerable groups across Europe, considering the use of different cut-offs for each subpopulation.

SummaryMetabolic dysregulation in multiple tissues alters glucose homeostasis and influences risk for type 2 diabetes (T2D). To identify pathways and tissues influencing T2D-relevant glycemic traits (fasting glucose [FG], fasting insulin [FI], two-hour glucose [2hGlu] and glycated hemoglobin [HbA1c]), we investigated associations of exome-array variants in up to 144,060 individuals without diabetes of multiple ancestries. Single-variant analyses identified novel associations at 21 coding variants in 18 novel loci, whilst gene-based tests revealed signals at two genes, TF (HbA1c) and G6PC (FG, FI). Pathway and tissue enrichment analyses of trait-associated transcripts confirmed the importance of liver and kidney for FI and pancreatic islets for FG regulation, implicated adipose tissue in FI and the gut in 2hGlu, and suggested a role for the non-endocrine pancreas in glucose homeostasis. Functional studies demonstrated that a novel FG/FI association at the liver-enriched G6PC transcript was driven by multiple rare loss-of-function variants. The FG/HbA1c-associated, islet-specific G6PC2 transcript also contained multiple rare functional variants, including two alleles within the same codon with divergent effects on glucose levels. Our findings highlight the value of integrating genomic and functional data to maximize biological inference.Highlights23 novel coding variant associations (single-point and gene-based) for glycemic traits51 effector transcripts highlighted different pathway/tissue signatures for each traitThe exocrine pancreas and gut influence fasting and 2h glucose, respectivelyMultiple variants in liver-enriched G6PC and islet-specific G6PC2 influence glycemia

Background: The transcription factor 7-like 2 gene (TCF7L2) is the strongest locus associated by the variant rs7903146 with type 2 diabetes (T2D) identified to date. Whether diet/lifestyle intervention modifies genetic effect of TCF7L2 variant on glucose homeostasis and adiposity is still controversial. Objective: To quantify the modification effects of the diet/lifestyle interventions on genetic association of TCF7L2 variant rs7903146 with glycemic control and adiposity changes in randomized controlled trials (RCTs). Design A large collaborative analysis of individual-participant data from seven RCTs. Setting RCTs conducted in adults reporting changes in glycemic traits, body weight, or waist circumference by TCF7L2 rs7903146 after dietary/lifestyle-based interventions. Gene-treatment interaction models were fitted to individual participant data from all studies, using allele dose coding for genetic effects and a common set of covariates. Results: We included seven eligible RCTs for the joint analysis (n=4,114 participants). Overall, a significant interaction between TCF7L2 rs7903146 and diet/lifestyle interventions on decrease in fasting glucose was observed. Compared with control, diet/lifestyle interventions reduced fasting glucose by -0.17 (95% CI, -0.32 to -0.02) mmol/L (test for heterogeneity: I2=45.1%, p

Aims The aim of this report is to describe the application of the FINDRISC in clinical practice within the DE-PLAN project as a step to screen for Type 2 diabetes. Methods Nine out of 24 possible centers were included. Six centers used opportunistic screening methods for participant recruitment whereas three centers provided study participants of a random population sample. Men ( n = 1621) and women ( n = 2483) were evaluated separately. In order to assess the prevalence of abnormal glucose tolerance (AGT) disorders across different risk categories, the FINDRISC was used. Anthropometric measurements included blood pressure, height, weight, and waist circumference. Blood lipids and an oral glucose tolerance test were performed in all participants. The primary outcome was identified risk of AGT and type 2 diabetes. Results There was no difference in the prevalence of smoking between the FINDRISC categories, people with a FINDRISC below 15 points tend to be more physically active and to eat more frequently fruits and vegetables. Men with a FINDRISC from 15 to 19 points had a prevalence of abnormal glucose tolerance of approximately 60% and women 50%. The prevalence for men and women with a FINDRISC >20 points was 80%. 30% of men and 20% of women with a FINDRISC between 15 and 19 points had Type 2 diabetes. Among people with a FINDRISC more than 20 points, 50% had previously undiagnosed Type 2 diabetes. Conclusions The FINDRISC may be a practical tool to be used in primary health-care systems throughout the European population.

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 β-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 β-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 β-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.

We studied cognition in the Finnish Diabetes Prevention Study (DPS), a trial of lifestyle intervention that prevented diabetes in persons with impaired glucose tolerance. Cognition was similar in the randomization arms 9 years after the intervention in 364 participants, suggesting that the intervention did not benefit cognition.

Summary Background Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies. In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a proof-of-concept randomised controlled trial, we aimed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population. Methods In a double-blind randomised controlled trial we enrolled individuals aged 60–77 years recruited from previous national surveys. Inclusion criteria were CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. We randomly assigned participants in a 1:1 ratio to a 2 year multidomain intervention (diet, exercise, cognitive training, vascular risk monitoring), or a control group (general health advice). Computer-generated allocation was done in blocks of four (two individuals randomly allocated to each group) at each site. Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation. The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery (NTB) Z score. Analysis was by modified intention to treat (all participants with at least one post-baseline observation). This trial is registered at ClinicalTrials.gov, number NCT01041989. Findings Between Sept 7, 2009, and Nov 24, 2011, we screened 2654 individuals and randomly assigned 1260 to the intervention group (n=631) or control group (n=629). 591 (94%) participants in the intervention group and 599 (95%) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis. Estimated mean change in NTB total Z score at 2 years was 0·20 (SE 0·02, SD 0·51) in the intervention group and 0·16 (0·01, 0·51) in the control group. Between-group difference in the change of NTB total score per year was 0·022 (95% CI 0·002–0·042, p=0·030). 153 (12%) individuals dropped out overall. Adverse events occurred in 46 (7%) participants in the intervention group compared with six (1%) participants in the control group; the most common adverse event was musculoskeletal pain (32 [5%] individuals for intervention vs no individuals for control). Interpretation Findings from this large, long-term, randomised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population. Funding Academy of Finland, La Carita Foundation, Alzheimer Association, Alzheimer's Research and Prevention Foundation, Juho Vainio Foundation, Novo Nordisk Foundation, Finnish Social Insurance Institution, Ministry of Education and Culture, Salama bint Hamdan Al Nahyan Foundation, Axa Research Fund, EVO funding for University Hospitals of Kuopio, Oulu, and Turku and for Seinajoki Central Hospital and Oulu City Hospital, Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare, and af Jochnick Foundation.

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.

We used data from the Finnish Diabetes Prevention Study to analyze the effectiveness of lifestyle intervention according to educational attainment. The effect of intervention on lifestyle changes and diabetes incidence was independent of education. The prevention of type 2 diabetes by lifestyle intervention is effective regardless of participants' educational attainment.

Purpose: We have reported that the genetic variation of the tenomodulin gene (TNMD) is associated with the risk of type 2 diabetes (T2DM), central obesity, and impaired glucose metabolism and the TNMD mRNA levels correlate with serum and mRNA levels of inflammatory markers. Our objective was to investigate the genetic associations of the single nucleotide polymorphisms of the TNMD gene with the serum levels of systemic immune mediators. Methods: Seven single nucleotide polymorphisms were genotyped from 507 participants of the Finnish Diabetes Prevention Study. All subjects had body mass index >25 and impaired glucose tolerance. Results: The sequence variation of tenomodulin was consistently associated with the serum concentrations of acute phase reactants, macrophage migration inhibitory factor, and CCR5 receptor ligands. The genotype effects were modified by status of glucose metabolism and central obesity. Markers associated with increased risk of T2DM in our previous study were associated with serum concentrations of acute phase proteins in men so that the subjects possessing the genotypes associated with increased risk of T2DM had higher serum concentrations of acute phase reactants. Conclusions: These results indicate that the genetic variation of TNMD is associated with low-grade inflammation. The putative link between TNMD and T2DM could be mediated through the effects on systemic immune mediators.

Knowledge about the natural history of type 2 diabetes (T2D) with a preclinical phase, modifiable risk factors, an effective and simple screening tool to identify high-risk subjects and effective intervention that is affordable and acceptable are necessary. In addition, the efficacy of the intervention has to be proven in a clinical trial setting. Such proof for lifestyle prevention of T2D from randomised clinical trials has accumulated as several major lifestyle intervention trials have been successfully carried out. The results are consistent: the risk of T2D in high-risk subjects can be halved; the effect of lifestyle changes is rapid; the magnitude of lifestyle changes required to achieve a significant risk reduction does not have to be drastic, and benefits are similar in different ethnic groups.

We carried out a double-blind, placebo-controlled cross-over trial to evaluate changes in nutrient intake during acarbose therapy and short-term changes in metabolic control in Finnish patients with non-insulin dependent diabetes mellitus. The efficacy and tolerability of acarbose was also assessed during this short 8-week treatment period. Patients were treated either with diet only (18 subjects) or with diet and sulphonylurea (9 subjects) prior to entering this trial. The nutrient intake was assessed using food records kept during the last 2-5 days of each treatment period. Treatment with acarbose did not affect body weight or the intake of energy and carbohydrates, but it was associated with a slight decrease in the dietary fat intake. Both fasting and 2-h postprandial blood glucose levels fell continuously during acarbose but the change did not reach statistical significance during the 8-week treatment period. The 2-h serum insulin response was not affected. The results were similar in patients treated with acarbose alone and in those receiving acarbose together with sulphonylurea regimen. The acarbose regimen was relatively well tolerated although mild gastrointestinal side-effects were observed in many patients. In conclusion, treatment with acarbose has no major effects on nutrient intake in diabetic patients. To monitor changes in metabolic control after the introduction of acarbose to the treatment regimen a longer than 8-week period is needed.