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Context Circulating branched-chain amino acids (BCAAs) are associated with the risk of type 2 diabetes (T2D). Objective We examined to what extent lifestyle intervention aiming to prevent T2D interacts with this association and how BCAA concentrations change during the intervention. Methods We computed trajectory clusters by k-means clustering of serum fasting BCAAs analyzed annually by mass spectrometry during a 4-year intervention. We investigated whether baseline BCAAs, BCAA trajectories, and BCAA change trajectories predicted T2D and whether BCAAs predicted T2D differently in the intervention (n = 198) and control group (n = 196). Results Elevated baseline BCAAs predicted the incidence of T2D in the control group (hazard ratio [HR] 1.05 per 10 μmol/L, P = 0.01), but not in the intervention group. BCAA concentration decreased during the first year in the whole cohort (mean −14.9 μmol/L, P Conclusion Lifestyle intervention modified the association of the baseline BCAA concentration and BCAA trajectories with the incidence of T2D. Our study adds to the accumulating evidence on the mechanisms behind the effect of lifestyle changes on the risk of T2D.

Background The aim of this paper is to present the development of the Feel4Diabetes Healthy Diet Score and to evaluate its clinical validity. Methods Study population consisted of 3268 adults (63% women) from high diabetes risk families living in 6 European countries. Participants filled in questionnaires at baseline and after 1 year, reflecting the dietary goals of the Feel4Diabetes intervention. Based on these questions the Healthy Diet Score was constructed, consisting of the following components: breakfast, vegetables, fruit and berries, sugary drinks, whole-grain cereals, nuts and seeds, low-fat dairy products, oils and fats, red meat, sweet snacks, salty snacks, and family meals. Maximum score for each component was set based on its estimated relative importance regarding T2DM risk, higher score indicating better quality of diet. Clinical measurements included height, weight, waist circumference, heart rate, blood pressure, and fasting blood sampling, with analyses of glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides. Analysis of (co) variance was used to compare the Healthy Diet Score and its components between countries and sexes using baseline data, and to test differences in clinical characteristics between score categories, adjusted for age, sex and country. Pearson’s correlations were used to study the association between changes from baseline to year 1 in the Healthy Diet Score and clinical markers. To estimate reproducibility, Pearson’s correlations were studied between baseline and 1 year score, within the control group only. Results The mean total score was 52.8 ± 12.8 among women and 46.6 ± 12.8 among men (p Conclusion The Feel4Diabetes Healthy Diet Score is a reproducible method to capture the dietary information collected with the Feel4Diabetes questionnaire and measure the level of and changes in the adherence to the dietary goals of the intervention. It gives a simple parameter that associates with clinical risk factors in a meaningful manner. Trial registration Clinicaltrials.gov NCT02393872. Registered March 20, 2015.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes., Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Aims: /hypothesis. To determine the best cut-off threshold value of the Finnish Diabetes Risk Score (FIN-DRISC) for the detection of diabetes and non-diabetic hyperglycaemia in people 35 years or older at primary health care settings in Europe. Methods: Cross-sectional study in 11,444 adults from primary health care centres using community and opportunistic screening approaches. All participants completed the FIN-DRISC questionnaire and underwent a 2-hour oral glucose tolerance test (OGTT). The FIN-DRISC performance was assessed by the area under the curve (AUC) using receiver operating characteristics (ROC) analysis. The sensitivity, specificity, Youden acute accent s index, posi-tive and negative prediction values for different FINDRISC cut-offs were calculated. Results: The optimal FINDRISC value for detecting both diabetes or glucose impairment in the community -screened sample was 14 point with the associated AUC 0.75,5 (95 %CI 0.73,7-0.77,3). The optimal score in the opportunistic screening sample was 16 with the associated AUC only 0.60,4 (95% CI 0.56, 4-0.64, 4). Conclusions/interpretation: The FINDRISC is a non-invasive tool useful for detecting people with unknown diabetes and glucose impairment in people visiting primary health centres in Europe. (c) 2021 Elsevier B.V. All rights reserved.

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.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

The Feel4Diabetes program was comprised of a community-based screening and a two-year intervention phase aiming to prevent type 2 diabetes (T2D) in families at risk for diabetes across Europe. The current work aimed to identify the socio-demographic characteristics and body weight perceptions of participants who benefitted the most, achieving at least a 5% reduction in body weight, waist circumference and glycaemic indices (fasting plasma glucose, insulin, glycosylated haemoglobin levels), over two-year period. Following a two-stage screening procedure, 2294 high-risk parents were randomly allocated to standard care or more intensive intervention. The participants who benefitted most were living in Southern (OR 2.39&ndash, 3.67, p &lt, 0.001) and Eastern Europe (OR 1.55&ndash, 2.47, p &lt, 0.05), received more intensive intervention (OR 1.53&ndash, 1.90, p = 0.002) and were younger (&lt, 40 years old) adults (OR 1.48&ndash, 1.51, p &lt, 0.05). Furthermore, individuals with tertiary education (OR 2.06, p &lt, 0.001), who were unemployed (OR 1.62&ndash, 1.68, p &lt, 0.05) and perceived their body weight to be higher than normal (OR 1.58&ndash, 3.00, p &lt, 0.05) were more likely to benefit from the program. Lastly, males were more likely to show improvements in their glycaemic profiles compared to females (OR 1.40, p = 0.024). These findings point out the regions in Europe and the sociodemographic profile of individuals that benefitted the most in the current study, highlighting the need to prioritise regions in greater need for such interventions and also tailor future interventions to the characteristics and perceptions of the target populations.

Aims: To compare the quality of diabetes care among type 2 diabetes patients with and without mental disorders during six-year follow-up in North Karelia, Finland. Methods: All type 2 diabetes patients (n = 10190) were analysed using the electronic health records data from 2011-12 to 2015-16. The diabetes care was evaluated using the measurement activity and the achievement of the treatment targets for HbA1c and LDL. Results: Monitoring of HbA1c and LDL levels improved among all patient groups, except the dementia patients. The proportion of those achieving the HbA1c target declined and those achieving the LDL target improved in all patient groups. Differences in the changes of achievement of the target HbA1c level among patients with dementia and depression were observed when compared with those having only type 2 diabetes. Conclusions: This study highlights the challenge of glucose level management as the age and comorbidities of the patients related to the care and achievements of the treatment targets. Mental disorders that are likely to affect patients' adherence to medication and other treatments should be taken into account and more support for self-care should be provided to such patients. Improvement in the achievement of LDL target address the progress in the prevention of macrovascular complications. (C) 2020 The Authors. Published by Elsevier B.V.

Glycaemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycaemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated haemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.

Introduction: The Finnish Diabetes Risk Score (FINDRISC) is a tool that was initially developed to predict the risk of developing type 2 diabetes mellitus in adults. This tool is simple, quick to apply, non-invasive, and low-cost. The aims of this study were to perform a translation and cultural adaptation of the original version of FINDRISC into Brazilian Portuguese and to assess test-retest reliability. Methodology: This work was done following the ISPOR Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes Measures. Once the final Brazilian Portuguese version (FINDRISC-Br) was developed, the reliability assessment was performed using a non-random sample of 83 individuals attending a primary care health center. Each participant was interviewed by trained registered dieticians on two occasions with a mean interval of 14 days. The reliability assessment was performed by analyzing the level of agreement between the test-retest responses of FINDRISC-Br using Cohen’s kappa coefficient and the intraclass correlation coefficient (ICC). Results: The steps of ISPOR guidelines were consecutively followed without major problems. Regarding the reliability assessment, the questionnaire as a whole presented adequate reliability (Cohen’s kappa = 0.82, 95%CI 0.72 - 0.92 and ICC = 0.94, 95%CI 0.91 - 0.96). Conclusion: FINDRISC was translated into Brazilian Portuguese and culturally adapted following standard procedures. FINDRISC-Br has thus become available for use and has potential as a screening tool in different Brazilian settings and applications. RESUMO: Introdução: O Escore Finlandês de Risco de Diabetes (FINDRISC) é um instrumento que inicialmente foi desenvolvido para predizer o risco de desenvolver diabetes mellitus tipo 2 em adultos. Esse instrumento é simples, rápido de aplicar, não invasivo e de baixo custo. Os objetivos deste estudo foram descrever o processo de tradução e adaptação transcultural do FINDRISC para o português do Brasil e avaliar a sua confiabilidade teste-reteste. Metodologia: O projeto foi conduzido de acordo com as recomendações dos Princípios de Boas Práticas para o Processo de Tradução e Adaptação Transcultural de Medidas de Resultados Relatados pelo Paciente desenvolvidas pela ISPOR. Uma vez desenvolvida a versão final em português brasileiro (FINDRISC-Br), realizou-se a avaliação da confiabilidade usando uma amostra não aleatória de 83 indivíduos atendidos em uma unidade de atenção básica. Cada participante foi entrevistado por nutricionistas registradas treinadas em duas ocasiões com intervalo médio de 14 dias. A avaliação da confiabilidade foi realizada por meio da análise do nível de concordância entre as respostas do teste-reteste, utilizando-se o coeficiente kappa de Cohen e o coeficiente de correlação intraclasse (CCI). Resultados: As etapas das diretrizes da ISPOR foram seguidas consecutivamente sem maiores problemas. Em relação à avaliação da confiabilidade do teste-reteste, o questionário como um todo apresentou confiabilidade adequada (kappa de Cohen = 0,82; IC95% 0,72 - 0,92 e CCI = 0,94; IC95% 0,91 - 0,96). Conclusão: O FINDRISC foi traduzido e adaptado transculturalmente para o português do Brasil seguindo procedimentos padronizados. O FINDRISC-Br já está disponível para uso e tem potencial para ser usado como ferramenta de rastreamento em diferentes cenários brasileiros.

Objectives To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes. Methods Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial. Participants Males and females aged 45–74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey Intervention Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function Results One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%. Conclusions ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with prediabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes, All the funding or sources of support received during this specific study: - European Commission, FP7 EC-GA No. 279074 - Merck- Serono, Germany - Boeringher Ingelheim, Germany (IIS Program. Grant number 1218.166) - Instituto de Salud Carlos III, Spain PI11/01653

Diabetes mellitus and other noncommunicable diseases (NCDs) represent an emerging global public health challenge. In Germany, about 6.7 million adults are affected by diabetes according to national health surveys, including 1.3 million with undiagnosed diabetes. Complications of diabetes result in an increasing burden for individuals and society as well as enormous costs for the health care system. In response, the Federal Ministry of Health commissioned the Robert Koch Institute (RKI) to implement a diabetes surveillance system and the Federal Center for Health Education (BZgA) to develop a diabetes prevention strategy. In a two-day workshop jointly organized by the RKI and the BZgA, representatives from public health institutes in seven countries shared their expertise and knowledge on diabetes prevention and surveillance. Day one focused on NCD surveillance systems and emphasized both the strengthening of sustainable data sources and the timely and targeted dissemination of results using innovative formats. The second day focused on diabetes prevention strategies and highlighted the importance of involving all relevant stakeholders in the development process to facilitate its acceptance and implementation. Furthermore, the effective translation of prevention measures into real-world settings requires data from surveillance systems to identify high-risk groups and evaluate the effect of measures at the population level based on analyses of time trends in risk factors and disease outcomes. Overall, the workshop highlighted the close link between diabetes prevention strategies and surveillance systems. It was generally stated that only robust data enables effective prevention measures to encounter the increasing burden from diabetes and other NCDs.

To assess the long-term effectiveness of a pragmatic public healthcare strategy to prevent type 2 diabetes within primary care setting. In the extended follow-up of the DEPLANCAT project, we explored whether the originally-achieved risk reduction remains after discontinuation of active lifestyle intervention. Middle-aged men (n=184) and women (n=368) with Finnish Diabetes Risk Score (FINDRISC)>14 and/or prediabetes (WHO rules for fasting or 2-h glucose) were allocated not randomly but sequentially to standard care control (CG) or intensive lifestyle intervention (IG) group. After a median of 4.2 y of active intervention, participants who were still free of diabetes were further followed-up without any additional specific intervention for a median of 5.8 y (median total follow-up of 10.01 y) via computerized health-care records or direct personal contact with invitation to 2h-glucose retest. The primary outcome was the development of diabetes. During the active intervention, diabetes was diagnosed in 124 participants (22.5%): 63 (28.8%) in the CG and 61 (18.3%) in the IG. After 10 y, 27 people (4.9%) had died. Among the remaining 401 individuals, 34 diabetes diagnoses were traced using the health-care records. Additionally, among the 191 people (47.6%) who agreed to blood re-test (66 in the CG and 125 in the IG) 16 new cases were found. During the post-intervention follow-up the total number of new cases of diabetes was 16 in the CG and 34 in the IG. The absolute incidences of diabetes during the overall follow-up were 6.1 (95% CI 5.2-6.9) and 5.1 (4.4-5.8) per 100 person-years, respectively (p=0.019 log-rank). The corresponding HR was 0.59 (0.43-0.81) with a relative risk reduction of 16.6%. The NNT to prevent one case of diabetes was 10. Intensive lifestyle intervention in a primary care setting substantially reduces diabetes incidence among high-risk individuals. Risk reduction can persist for at least 10 years. Disclosure F. Barrio: None. B. Costa: None. F. Cos: None. J. Cabre: None. A. Martinez: None. S. Mestre: None. C. Castell: None. J. Lindstrom: None. Funding Institute of Health Carlos III, Spanish Ministry of Health and the European Regional Development Fund (PI14/00122, PI14/00124); La Marató de TV3 Foundation (73-201609.10); Spanish Diabetes Society; Department of Health, Generalitat de Catalunya; Pla Estratègic de Recerca i Innovació en Salut (SLT002/16/00045, SLT002/16/00154, SLT002/16/00093)

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

The Feel4Diabetes intervention was a school and community-based intervention aiming to promote healthy lifestyle and tackle obesity and obesity-related metabolic risk factors for the prevention of type 2 diabetes (T2D) among families at risk of developing this disease. The current study aims to present the results on lifestyle behaviors obtained from parents during the first year of the Feel4Diabetes intervention. This multicomponent intervention had a cluster randomized design and was implemented in Belgium, Bulgaria, Finland, Greece, Hungary and Spain over two years (2016&ndash, 2018). Standardized protocols and procedures were used by the participating centers in all countries to collect data on parents&rsquo, lifestyle behaviors (diet, physical activity, sedentary behavior). The Feel4Diabetes intervention was registered at clinicaltrials.gov (registration number: NCT02393872). In total, 2110 high-risk parents participated in the baseline and 12-month follow-up examination measurements. Participants allocated to the intervention group reduced their daily consumption of sugary drinks (p = 0.037) and sweets (p = 0.031) and their daily screen time (p = 0.032), compared with the control group. In addition, participants in the intervention group in Greece and Spain increased their consumption of breakfast (p = 0.034) and fruits (p = 0.029), while in Belgium and Finland they increased their water intake (p = 0.024). These findings indicate that the first year of the Feel4Diabetes intervention resulted in the improvement of certain lifestyle behaviors in parents from high-risk families.

A healthy diet prevents type 2 diabetes but is often difficult to adhere to. This cross-sectional study aimed to investigate whether eating competence is associated with diet or risk factors and prevalence of type 2 diabetes in individuals screened for type 2 diabetes risk. Eating competence is an indicator of food acceptance, positive attitudes, internal regulation and contextual skills related to food and eating. In total, 3147 Finnish adults aged 18&ndash, 74 at an increased risk for type 2 diabetes identified via online risk screening participated in the baseline examinations of the Stop Diabetes (StopDia) study. The participants filled out the digital questionnaire on food intake, physical activity and sleep, and the Satter Eating Competence Inventory 2.0TM (ecSI 2.0TM). In addition, anthropometric and laboratory measurements were performed at primary healthcare centres. Eating competent individuals (37%, classified by ecSI 2.0TM) had a better quality of diet (p &lt, 0.05 for all). Additionally, eating competence was associated with a lower prevalence of previously undiagnosed type 2 diabetes, abdominal obesity, metabolic syndrome and hypertriglyceridaemia, and with better insulin sensitivity (p &lt, 0.05 for all). However, these associations, except for metabolic syndrome, were at least partly mediated by body mass index. Eating competence is associated with a healthy diet and could, thus, in the long term, support the prevention of type 2 diabetes.

We recently reported using non-targeted metabolic profiling that serum indolepropionic acid (IPA), a microbial metabolite of tryptophan, was associated with a lower likelihood of developing type 2 diabetes (T2D). In the present study, we established a targeted quantitative method using liquid chromatography with mass spectrometric detection (HPLC-QQQ-MS/MS) and measured the serum concentrations of IPA in all the participants from the Finnish Diabetes Prevention Study (DPS), who had fasting serum samples available from the 1-year study follow-up (n = 209 lifestyle intervention and n = 206 control group). Higher IPA at 1-year study was inversely associated with the incidence of T2D (OR [CI]: 0.86 [0.73–0.99], P = 0.04) and tended to be directly associated with insulin secretion (β = 0.10, P = 0.06) during the mean 7-year follow-up. Moreover, IPA correlated positively with dietary fiber intake (g/day: r = 0.24, P = 1 × 10−6) and negatively with hsCRP concentrations at both sampling (r = − 0.22, P = 0.0001) and study follow-up (β = − 0.19, P = 0.001). Thus, we suggest that the putative effect of IPA on lowering T2D risk might be mediated by the interplay between dietary fiber intake and inflammation or by direct effect of IPA on β-cell function.

Lifestyle interventions in type 2 diabetes (DM2) prevention implementation studies can be effective and lasting. Long-term weight loss maintenance enhances the intervention effect through a significant decrease in diabetes incidence over time. Our objective was to identify factors predicting long-term successful weight reduction maintenance achieved during a DM2 prevention program in patients with high DM2 risk in primary health care. Study participants (n = 263), middle-aged, slightly obese with baseline increased DM2 risk (Finnish Diabetes Risk Score (FINDRISC)>14), but no diabetes were invited to receive 11 lifestyle counselling sessions, guided physical activity sessions and motivational support during 10-months. The study participants had three clinical examinations during the study (baseline, one and three years). Stepwise regression analysis was used to determine demographic, clinical, and lifestyle predictors of weight reduction maintenance two years after the discontinuation of the intervention. Out of 105 patients who completed all three examinations (baseline age 56.6 (standard deviation (SD) = 10.7), body mass index 31.1 kg/m2 (SD = 4.9), FINDRISC 18.6 (SD = 3.1)), 73 patients (70%) showed weight loss during the intervention (mean weight loss 4.2 kg, SD = 5.1). The total weight loss achieved in the maintainers (27 of 73 study participants) two years after the intervention had finished was 6.54 kg (4.47 kg+2.0 kg). The non-maintainers, on the other hand, returned to their initial weight at the start of the intervention (+0.21 kg). In multivariable analysis baseline history of increased glucose (odds ratio (OR) = 3.7; 95% confidence interval (CI) 1.0-13.6) and reduction of total fat in diet during follow-up (OR = 4.3; 95% CI 1.5-12.2) were independent predictors of successful weight loss. Further studies exploring predictors of weight loss maintenance in diabetes prevention are needed to help health care providers to redesign interventions and improve long-term outcomes of real life interventions.

Background: DP-TRANSFERS(Diabetes Prevention-Transferring findings from European research to society) is a large scale national program aimed at translating a lifestyle diabetes prevention intervention (DE-PLAN-CAT) in primary care centers in Catalonia. Methods: Multidisciplinary committee evaluated the programme. Participants without diabetes aged 45-75 years (FINDRISC>11 and/or prediabetes) were posible candidates. Implementation was a 4-channel transfer approach (institutional relationships, facilitator WS, collaborative groupware, programme website) and built upon a 3-step (screening, intervention, follow-up) real-life strategy. The 2-year lifestyle intervention program included an initial 9-hour and 15-hour continuity module, 6 and 10 sessions respectively. A 3-level (centre, professionals and participants) descriptive analysis was conducted using cluster sampling by contributing centres to assess results and barriers identified one year after implementation. Results: Between June2016 and July2017, 103 PHCC 1.4 million inhabitants (27.9% of all centres), 5professionals agreed to participate. After 1 year,83 centres (80.6%) remained active and 3professionals (60.3%) were involved. Implementation was not feasible in 20 centres (19.4%) 5 main barriers: lack of staff support; discontinuity of the initial effort; increase of workload; shift in professional status and lack of acceptance. Overall, 1819 people were screened and 1458 (80.1%) followed the lifestyle intervention, with 1190 (81.6% or 65.4% of those screened) participating in the basic module and 912 in the continuity (62.5% or 50.1%, respectively). Conclusions: Large-scale lifestyle intervention in primary care can be properly implemented using existing public health resources. Regrettably, one fifth of the centres and more than one third of the professionals showed substantial resistance to performing these additional activities. Disclosure B. Costa: None. S. Mestre: None. F. Barrio: None. J. Cabre: None. F. Cos: Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation. Advisory Panel; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Sanofi Pasteur. Speaker's Bureau; Self; Sanofi Pasteur. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Research Support; Self; Eli Lilly and Company. S. Aguilar: None. C. Sole: None. C. Castell: None. V. Arija: None. J. Lindstrom: None.

Background Type 2 diabetes is linked with cognitive dysfunction and dementia in epidemiological studies, but these observations are limited by lack of data on the exact timing of diabetes onset. We investigated diabetes, dysglycaemia, and cognition in the Finnish Diabetes Prevention Study, in which the timing and duration of diabetes are well documented. Methods The Finnish Diabetes Prevention Study comprised middle-aged, overweight participants with impaired glucose tolerance but no diabetes at baseline (n = 522), randomized to lifestyle intervention or a control group. After an intervention period (mean duration 4 years) and follow-up (additional 9 years), cognitive assessment with the CERAD test battery and Trail Making Test A (TMT) was executed twice within a 2-year interval. Of the 364 (70%) participants with cognitive assessments, 171 (47%) had developed diabetes. Results Cognitive function did not differ between those who developed diabetes and those who did not. Lower mean 2-h glucose at an oral glucose tolerance test (OGTT) and HbA1C during the intervention period predicted better performance in the TMT (p = 0.012 and 0.024, respectively). Those without diabetes or with short duration of diabetes improved in CERAD total score between the two assessments (p = 0.001) whereas those with long duration of diabetes did not (p = 0.844). Conclusions Better glycemic control among persons with baseline impaired glucose tolerance predicted better cognitive performance 9 years later in this secondary analysis of the Finnish Diabetes Prevention Study population. In addition, learning effects in cognitive testing were not evident in people with long diabetes duration. Copyright © 2015 John Wiley & Sons, Ltd.

OBJECTIVE To assess whether gestational diabetes mellitus (GDM) can be prevented by a moderate lifestyle intervention in pregnant women who are at high risk for the disease. RESEARCH DESIGN AND METHODS Two hundred ninety-three women with a history of GDM and/or a prepregnancy BMI of ≥30 kg/m2 were enrolled in the study at RESULTS A total of 269 women were included in the analyses. The incidence of GDM was 13.9% in the intervention group and 21.6% in the control group ([95% CI 0.40–0.98%]; P = 0.044, after adjustment for age, prepregnancy BMI, previous GDM status, and the number of weeks of gestation). Gestational weight gain was lower in the intervention group (−0.58 kg [95% CI −1.12 to −0.04 kg]; adjusted P = 0.037). Women in the intervention group increased their leisure time physical activity more and improved their dietary quality compared with women in the control group. CONCLUSIONS A moderate individualized lifestyle intervention reduced the incidence of GDM by 39% in high-risk pregnant women. These findings may have major health consequences for both the mother and the child.

Objectives: To investigate associations of long-term nutrient intake, physical activity and obesity with later cognitive function among the participants in the Finnish Diabetes Prevention Study, in which a lifestyle intervention was successful in diabetes prevention. Design: An active lifestyle intervention phase during middle age (mean duration 4 years) and extended follow-up (additional 9 years) with annual lifestyle measurements, followed by an ancillary cognition assessment. Setting: 5 research centers in Finland. Participants: Of the 522 middle-aged, overweight participants with impaired glucose tolerance recruited to the study, 364 (70%) participated in the cognition assessment (mean age 68 years). Measurements: A cognitive assessment was executed with the CERAD test battery and the Trail Making Test A on average 13 years after baseline. Lifestyle measurements included annual clinical measurements, food records, and exercise questionnaires during both the intervention and follow-up phase. Results: Lower intake of total fat (p=0.021) and saturated fatty acids (p=0.010), and frequent physical activity (p=0.040) during the whole study period were associated with better cognitive performance. Higher BMI (p= 0.012) and waist circumference (p= 0.012) were also associated with worse performance, but weight reduction prior to the cognition assessment predicted worse performance as well (decrease vs. increase, p= 0.008 for BMI and p= 0.002 for waist). Conclusions: Long-term dietary fat intake, BMI, and waist circumference have an inverse association with cognitive function in later life among people with IGT. However, decreases in BMI and waist prior to cognitive assessment are associated with worse cognitive performance, which could be explained by reverse causality.

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.

Type 2 diabetes prevalence is rising globally, and varies by socio-economic position. Amongst other factors, rising prevalence may reflect increasing incidence. Worldwide, few studies have examined population-level longitudinal trends in incident type 2 diabetes, and reports on secular trends in diabetes incidence by socio-economic measures such as educational attainment are lacking. Finland has a long-standing, comprehensive disease surveillance infrastructure. Using data collected over four decades from serial FINRISK surveys, the National Drug Reimbursement Register and the National Causes of Death Register, we examined secular trends in type 2 diabetes incidence in Finland from the 1970s to 2007. The diabetes status of 38,689 FINRISK participants aged 30–59 years at baseline assessment and without diagnosed diabetes at the time was followed for 10 years. Among men, incidence of diagnosed, pharmacologically managed type 2 diabetes increased over time. Compared with men surveyed in the 1970s, diabetes incidence was higher among men in the 1980s (adjusted HR 1.44, 95 % CI 1.13–1.84) and 1990s (adjusted HR 1.72, 1.32–2.24). Body mass index explained some, but not all of this variation. Increases occurred predominantly among men with low (adjusted HR 1980s: 2.07, 95 % CI 1.28–3.35; adjusted HR 1990s: 2.12, 95 % CI 1.28–3.53) and middle (adjusted HR 1980s: 1.30, 95 % CI 0.85–1.99; adjusted HR 1990s: 1.65, 95 % CI 1.05–2.60) educational attainment. No secular changes were apparent among women. This rising diabetes incidence among men over recent decades has occurred despite Finland’s sustained health promotion efforts. Renewed public health campaigns are urgently required. In addition to population-level initiatives, lower educational strata should be specifically targeted.

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.

Obesity increases the risk of low 25-hydroxyvitamin D (25(OH)D) concentrations and gestational diabetes (GDM). We explored whether the association between GDM and change in 25(OH)D concentrations measured in the first (7-18 wk) and second (20-27 wk) trimesters of pregnancy is dependent on maternal BMI. The study was a prospective study of 219 women with BMI of ≥30 kg/m2, a history of GDM, or both. The participants were stratified by first-trimester BMI: BMI of

Background: The effects of obesity surgery on serum and adipose tissue fatty acid (FA) profile and FA metabolism may modify the risk of obesity-related diseases. Methods: We measured serum (n=122) and adipose tissue (n=24) FA composition and adipose tissue mRNA expression of genes regulating FA metabolism (n=100) in participants of the Kuopio Obesity Surgery Study (KOBS, age 47.2±8.7 years, BMI 44.6±6.0, 40 men, 82 women) before and one year after obesity surgery. As part of the surgery protocol, all the subjects were instructed to add sources of unsaturated fatty acids, such as rapeseed oil and fatty fish, into their diet. The results were compared with changes in serum FA composition in 122 subjects from the Finnish Diabetes Prevention study (DPS) (age 54.3±7.1 years, BMI 32.2±4.6, 28 men, 94 women). Results: The proportion of saturated FAs decreased and the proportion of n-3 and n-6 FAs increased in serum triglycerides after obesity surgery (all P, published version, peerReviewed

Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of β-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity., published version, peerReviewed

AIMS This study assessed type 2 diabetes treatment outcomes and process indicators using a comprehensive type 2 diabetes patient cohort in North Karelia, Finland, from 2011 to 2016. METHODS Data from all diagnosed type 2 diabetes patients (n = 8429) living in North Karelia were collated retrospectively from regional electronic patient records. We assessed whether HbA1c and low-density lipoprotein (LDL) were measured and managed as recommended. RESULTS The HbA1c measurement rate improved (78% vs 89%) during 2011-2012 and 2015-2016, but a gradual deterioration in glycaemic control (HbA1c

Healthcare systems do not fit well with the "modern" patient, who has a right to autonomy and self-determination. The services that are designed and delivered in policy contexts are not prone to encourage innovation. National Diabetes Plans, defined as "any formal strategy for improving diabetes policy, services and outcomes that encompass structured and integrated or linked activities which are planned and co-ordinated nationally and conducted at the national, regional, and local level", may hold a great potential not only to improve prevention and care for type 2 diabetes, but also for transforming healthcare delivery. Today, changes to adapt healthcare delivery tend to be implemented within existing provider structures, with limited understanding of specific context, structures, processes and potential for change. National Diabetes Plan can be a diagnostic tool for barriers, can be a driver for planning the change, and can help develop capacities and competences that are needed to strengthen healthcare systems to better address health promotion and chronic diseases.

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.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.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.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.

The aim of this study was to find the association between adherence to the Nordic Nutrition Recommendations (NNR) and glucose metabolism. Participants were 137 pregnant obese women or women with a history of gestational diabetes (GDM) from the Finnish Gestational Diabetes Prevention Study. Adherence to the NNR was assessed by the Healthy Food Intake Index (HFII) calculated from the first trimesters' food frequency questionnaires. Higher HFII scores reflected higher adherence to the NNR (score range 0-17). Regression models with linear contrasts served for the main analysis. The mean HFII score was 10.0 (s.d. 2.8). The odds for GDM decreased toward the higher HFII categories (P=0.067). Fasting glucose (FG) and 2hG concentrations showed inverse linearity across the HFII categories (P(FG)=0.030 and P(2hG)=0.028, adjusted for body mass index, age and GDM/pregnancy history). Low adherence to the NNR is associated with higher antenatal FG and 2hG concentrations and possibly GDM.

About 500,000 people suffer from diabetes in Finland, a number which is predicted to increase within the next decades. At the moment, diabetes can neither be prevented nor cured. Diabetes is associated with microvascular (kidney, eye and peripheral nerves) and macrovascular complications (coronary heart disease, stroke). These complications affect the quality of life of patients and account for a substantial proportion of healthcare costs in Finland. The.current guidelines offer recommendations for the diagnosis, screening, prevention and treatment of diabetes and its complications.

The prevalence as well as actual number of people with type 2 diabetes has been increasing in Finland during the past decades, in parallel with an increase in overweight and obesity. Besides obesity, population aging is among the main drivers of increasing numbers of diabetic patients. Type 2 diabetes brings along complications, most importantly cardiovascular diseases, and increasing type 2 diabetes prevalence has also been suggested to lead to a new upward turn in cardiovascular diseases. Therefore, it is important to implement activities to prevent type 2 diabetes. We present the trial evidence for the prevention of type 2 diabetes with emphasis on the Finnish Diabetes Prevention Study findings. Furthermore, we discuss the practical implementation of screening of individuals for high type 2 diabetes risk and prevention of type 2 diabetes in Finland at the population level and describe how they have contributed to European level initiatives.HighlightsT2D is increasing and predisposes to serious complications.On population level, T2D trends follow the obesity trends.The risk of T2D can be markedly reduced by lifestyle intervention.High-risk individuals can be identified with FINDRISC, a simple T2D risk score.Finnish national T2D program has lead the way to many international initiatives.

Group Authors : DIAGRAM Consortium MUTHER Consortium variants influencing fasting glycemic traits and insulin resistance Seuls les 100 premiers auteurs ont été conservés dans la publication. La liste complète des auteurs et des des affiliations est disponible sur la publication https://www.nature.com/articles/ng.2274.pdf p. 667-669.; International audience; Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

To assess the feasibility and effectiveness of an active real-life primary care lifestyle intervention in preventing type 2 diabetes within a high-risk Mediterranean population.A prospective cohort study was performed in the setting of Spanish primary care. White-European individuals without diabetes aged 45-75 years (n = 2,054) were screened using the Finnish Diabetes Risk Score (FINDRISC) and a subsequent 2 h OGTT. Where feasible, high-risk individuals who were identified were allocated sequentially to standard care, a group-based or an individual level intervention (intensive reinforced DE-PLAN [Diabetes in Europe-Prevention using Lifestyle, Physical Activity and Nutritional] intervention). The primary outcome was the development of diabetes according to WHO criteria. Analyses after 4-year follow-up were performed based on the intention-to-treat principle with comparison of standard care and the combined intervention groups.The standard care (n = 219) and intensive intervention (n = 333) groups were comparable in age (62.0/62.2 years), sex (64.4/68.2% women), BMI (31.3/31.2 kg/m(2)), FINDRISC score (16.2/15.8 points), fasting (5.3/5.2 mmol/l), 2 h plasma glucose (7.1/6.9 mmol/l) and self-reported interest to make lifestyle changes at baseline. Diabetes was diagnosed in 124 individuals: 63 (28.8%) in the standard care group and 61 (18.3%) in the intensive intervention group. During a 4.2-year median follow-up, the incidences of diabetes were 7.2 and 4.6 cases per 100 person-years, respectively (36.5% relative risk reduction, p0.005). The number of participants needed to be treated by intensive intervention for 4 years to reduce one case of diabetes was 9.5.Intensive lifestyle intervention is feasible in a primary care setting and substantially reduces diabetes incidence among high-risk individuals.ClinicalTrial.gov NCT01519505.Commission of the European Communities, Institute of Health Carlos III, Spanish Ministry of Health and Department of Health, Generalitat de Catalunya.

A cluster of variants in the fat mass and obesity-associated (FTO) gene are associated with the common form of obesity. Well-documented dietary data are required for identifying how the genetic risk can be modified by dietary factors. The objective of the present study was to investigate the associations between the FTO risk allele (rs9939609) and dietary intake, and to evaluate how dietary intake affects the association between FTO and BMI in the Finnish Diabetes Prevention Study during a mean follow-up of 3·2 years. A total of 479 (BMI >25 kg/m2) men and women were genotyped for rs9939609. The participants completed a 3 d food record at baseline and before every annual study visit. The average intakes at baseline and during the years 1, 2 and 3 were calculated. At baseline, the FTO variant rs9939609 was not associated with the mean values of total energy intake, macronutrients or fibre. At baseline, a higher BMI by the FTO risk genotype was detected especially in those who reported a diet high in fat with mean BMI of 30·6 (sd 4·1), 31·3 (sd 4·6) and 34·5 (sd 6·2) kg/m2 for TT, TA and AA carriers, respectively (P =0·005). Higher BMI was also observed in those who had a diet low in carbohydrates (P =0·028) and fibre (P =0·015). However, in the analyses adjusted for total energy intake, age and sex, significant interactions between FTO and dietary intakes were not found. These findings suggest that the association between the FTO genotype and obesity is influenced by the components of dietary intake, and the current dietary recommendations are particularly beneficial for those who are genetically susceptible for obesity.

During the past decade, improved understanding of the pathophysiological mechanisms of diabetes development has resulted in advances in therapeutic concepts, but has also supported the potential for diabetes prevention through nonpharmacological means. At the beginning of the century, we experienced a shift in paradigm, as landmark studies have shown that diabetes mellitus is preventable with lifestyle intervention; moderate changes in diet and physical activity produce a substantial and sustained reduction in the incidence of type 2 diabetes mellitus (T2DM) for individuals with impaired glucose tolerance. This evidence must now be translated into clinical and public-health practice, but translational studies have varied in their ability to replicate the results of clinical trials. This variation reflects a number of challenging barriers for diabetes prevention in real-world clinical practice, which makes it necessary to focus on identifying efficient intervention methods and delivery mechanisms. Research is now focusing on these mechanisms, as well as on developing efficient screening and risk-identification strategies and realistic scenarios for public-health policy to implement diabetes prevention programs. In this Review, we will discuss these mechanisms and will consider the implications of diabetes prevention for public-health strategy and policy.

OBJECTIVE We investigated the effect of early-phase insulin secretion on the incidence of type 2 diabetes in individuals with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). We examined how a lifestyle intervention affected early-phase insulin secretion (ratio of total insulin area under the curve [AUC] and total glucose AUC [AIGR] from 0 to 30 min) during a 4-year follow-up intervention trial and whether AIGR0–30 response was modified by insulin sensitivity (IS) and obesity. RESEARCH DESIGN AND METHODS A total of 443 participants with IGT originally randomized to a lifestyle intervention or control group were studied. IS and AIGR0–30 were estimated from an oral tolerance glucose test administered annually during the 4-year follow-up trial and were related to the risk of diabetes onset over a 6-year follow-up. RESULTS Lifestyle intervention resulted in higher IS (P = 0.02) and lower unadjusted AIGR0–30 (P = 0.08) during the 4-year follow-up. A higher IS and a lower BMI during the follow-up were associated with a lower unadjusted AIGR0–30 during the follow-up, independently of study group (P < 0.001). A greater increase in IS on the median cutoff point of a 0.69 increase was associated with higher IS-adjusted AIGR0–30 during the follow-up (P = 0.002). In multivariate models, IS and IS-adjusted AIGR0–30 were both inversely associated with diabetes incidence (P < 0.001). Participants who progressed to type 2 diabetes were more obese and had lower IS and Matsuda IS index-AIGR0–30 than nonprogressors. CONCLUSIONS Our results indicate that the reduction in the risk of developing type 2 diabetes after lifestyle intervention is related to the improvement of IS along with weight loss. Improved IS may also have beneficial effects on preservation of β-cell function.

Diabet. Med. 28, 1234–1237 (2011) Abstract Aim To investigate changes in the prevalence of diabetes and pre-diabetes by shifting from 2-h plasma glucose and/or fasting plasma glucose diagnostic criteria to the proposed new HbA1c-based criteria when applied to a Mediterranean population detected to have a high risk of Type 2 diabetes. Methods Individuals without diabetes aged 45–75 years (n = 2287) were screened using the Finnish Diabetes Risk Score questionnaire, a 2-h oral glucose tolerance test plus HbA1c test. Prevalence and degree of diagnostic overlap between three sets of criteria (2-h plasma glucose, fasting plasma glucose and HbA1c) and three diagnostic categories (normal, pre-diabetes and diabetes) were calculated. Results Defining diabetes by a single HbA1c measurement resulted in a dramatic decrease in prevalence (1.3%), particularly in comparison with diabetes defined by 2-h plasma glucose (8.6%), but was also significant with regard to fasting plasma glucose (2.8%). A total of 201 screened subjects (8.8%) were classified as having diabetes and 1023 (44.7%) as having pre-diabetes based on at least one of these criteria; among these, the presence of all three criteria simultaneously classified only 21 and 110 individuals respectively, about ten percent of each group. The single overlap index between subjects diagnosed as having diabetes by 2-h plasma glucose/fasting plasma glucose vs. HbA1c was 13.9/28%. Similarly, the single overlap index regarding pre-diabetes was 19.2/27.1%. Conclusions A shift from the glucose-based diagnosis to the HbA1c-based diagnosis for diabetes will reduce diabetes prevalence with a low overall or single degree of overlap between diagnostic categories in this high-risk Spanish population.

Diabet. Med. 28, 699–704 (2011) Abstract 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 HbA1c, 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

OBJECTIVE We aimed to investigate the influence of positive family history (FH+) of diabetes and 19 known genetic risk loci on the effectiveness of lifestyle changes and their predictive value on the incidence of type 2 diabetes in the Finnish Diabetes Prevention Study (DPS). RESEARCH DESIGN AND METHODS A total of 522 subjects with impaired glucose tolerance (IGT) were randomized into the control (n = 257) and intervention (n = 265) groups. The mean follow-up was 6.2 years (median 7 years), and the lifestyle intervention, aimed at weight reduction, healthy diet, and increased physical activity, lasted for 4 years (range 1–6 years). An oral glucose tolerance test (OGTT) and assessment of basic clinical variables were performed annually. RESULTS The effect of intervention on the incidence of diabetes was almost similar in subjects with FH+ compared with subjects with a negative family history (FH−) of diabetes during the entire follow-up. In the Cox model, including FH, genetic risk SNPs, and randomization group, and adjusted for the effects of age, sex, BMI, and study center, only lifestyle intervention had a significant effect (hazard ratio 0.55, 95% CI 0.41–0.75, P < 0.001) on the incidence of diabetes. Further analyses showed that in addition to the baseline glucose and insulin values, 1-year changes in 2-h glucose and 2-h insulin achieved by lifestyle intervention had a significant effect on the incidence of diabetes. CONCLUSIONS These results emphasize the effectiveness of lifestyle intervention in reducing the risk of diabetes in high-risk individuals independently of genetic or familial risk of type 2 diabetes.

Diabet. Med. 28, 36–42 (2011) Abstract Aims We analysed the Finnish Diabetes Prevention Study data in order to evaluate how the new HbA1c-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 HbA1c measurements were performed annually until the diagnosis of diabetes using the World Health Organization 1985 criteria. Results The sensitivity of the HbA1c≥ 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 HbA1c≥ 6.0% (≥ 42 mmol/mol) were 67% (95% CI 55%, 77%) and 68% (95% CI 51%, 82%). The participants with HbA1c≥ 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 HbA1c

Background: The aim of this study was to investigate the association of socio-economic status (SES) with dysglycemia and the lifestyle-related risk factors, and to analyze to which extent known risk factors explain socio-economic differences in diabetes risk. Methods: Two population-based cross-sectional surveys in Finland including 1696 men and 1946 women aged 45–64 years who participated in a health examination in 2004 or 2007. Dysglycemia was determined by an oral glucose tolerance test. Total type 2 diabetes (including previously known and screen-detected type 2 diabetes), impaired glucose tolerance and impaired fasting glucose formed the category of total dysglycemia. Questionnaires and clinical examination were completed to assess risk factors for dysglycemia. SES was defined by education and household income. Results: In both genders, the prevalence of total dysglycemia differed statistically significantly between educational groups. Low education was statistically significantly associated with higher risk of total type 2 diabetes in women. The household income level was inversely associated with total type 2 diabetes in women and with total dysglycemia in men. Obesity, unhealthy diet and smoking were all inversely related to SES in both men and women. The observed association between education and dysglycemia was slightly attenuated after adjustment for obesity and other risk factors for diabetes. Conclusions: Low education was associated with an increased risk of dysglycemia more strongly than the low household income. Risk factors, especially obesity, explained only partly the observed associations between dysglycemia and education.