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Summary Background Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes, at least as long as the intervention continues. In the extended follow-up of the Finnish Diabetes Prevention Study, we assessed the extent to which the originally-achieved lifestyle changes and risk reduction remain after discontinuation of active counselling. Methods Overweight, middle-aged men (n=172) and women (n=350) with impaired glucose tolerance were randomly assigned to intensive lifestyle intervention or control group. After a median of 4 years of active intervention period, participants who were still free of diabetes were further followed up for a median of 3 years, with median total follow-up of 7 years. Diabetes incidence, bodyweight, physical activity, and dietary intakes of fat, saturated fat, and fibre were measured. Findings During the total follow-up, the incidence of type 2 diabetes was 4·3 and 7·4 per 100 person-years in the intervention and control group, respectively (log-rank test p=0·0001), indicating 43% reduction in relative risk. The risk reduction was related to the success in achieving the intervention goals of weight loss, reduced intake of total and saturated fat and increased intake of dietary fibre, and increased physical activity. Beneficial lifestyle changes achieved by participants in the intervention group were maintained after the discontinuation of the intervention, and the corresponding incidence rates during the post-intervention follow-up were 4·6 and 7·2 (p=0·0401), indicating 36% reduction in relative risk. Interpretation Lifestyle intervention in people at high risk for type 2 diabetes resulted in sustained lifestyle changes and a reduction in diabetes incidence, which remained after the individual lifestyle counselling was stopped.

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

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

The aim of this study was to assess the performance of the Finnish Diabetes Risk Score as a screening tool for undetected type 2 diabetes (T2D), abnormal glucose tolerance (AGT) and metabolic syndrome in the general population. In a cross-sectional, population-based survey, a total of 4, 622 subjects aged 45–74 years were invited to a health examination that included an oral glucose tolerance test. Full data with risk score estimate and glucose tolerance status were available for 2, 966 subjects without a prior history of diabetes. The risk score was associated with the presence of previously undiagnosed T2D, AGT, metabolic syndrome and cardiovascular risk factors. The area under the receiver operating curve for the prevalence of undiagnosed diabetes was 0.72 in men and 0.73 in women. The sensitivity using a cutoff risk score of 11 to identify undiagnosed diabetes was 66% in men and 70% in women; the corresponding false-positive rates were 31% and 39%, respectively. The area under the receiver operating curve for detecting the metabolic syndrome was 0.72 in men and 0.75 in women. The Finnish Diabetes Risk Score can be used as a self-administered test to screen subjects at high risk for T2D. It can also be used in the general population and clinical practice to identify undetected T2D, AGT and the metabolic syndrome.

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

Currently, in many European countries more than half the adult population is overweight; it hass become ‘abnormal’ to be of ‘normal weight’. The risk of type 2 diabetes, CVD, hypertension and certain forms of cancer increase with increasing weight. Biological evolution has produced body-fat-regulating mechanisms that are more powerful in protecting against weight loss than against weight gain. The current environment offers constant availability of affordable palatable energy-rich foods, with no need to consume the energy through physical activity. The ‘obesogenic’ environment is to some extent a political issue, but it has been shown that the healthcare system can also have a role in preventing obesity-related morbidity. The Finnish Diabetes Prevention Study was the first controlled randomised study to show that individualised lifestyle counselling of individuals with high risk of developing type 2 diabetes can influence diet, physical activity and body weight, and that type 2 diabetes can be prevented, or at least postponed. Most importantly, lifestyle changes do not have to be extreme. If the population would adopt a lifestyle in line with the official nutrition recommendations, the obesity and diabetes trend could at least be stabilised.

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

No previous studies on the association between salt intake and the risk of type 2 diabetes have been reported. The aim of this study was to assess whether high salt intake, measured by 24-h urinary sodium excretion, is an independent risk factor for type 2 diabetes.We followed prospectively 932 Finnish men and 1,003 women aged 35-64 years with complete data on 24-h urinary sodium and potassium excretion and other study parameters. Hazard ratios for the incidence of type 2 diabetes were estimated for different levels of 24-h urinary sodium and potassium excretion.During a mean follow-up of 18.1 years, there were 129 incident cases of type 2 diabetes. The multivariate-adjusted (age, sex, study year, body mass index, physical activity, systolic blood pressure, antihypertensive drug treatment, education, smoking and coffee, alcohol, fruit, vegetable, sausage, bread and saturated fat consumption) hazard ratio for diabetes for the highest vs combined lower quartiles of 24-h urinary sodium excretion was 2.05 (95% CI, 1.43-2.96). This positive association persisted in non-obese and obese subjects, in normotensive and hypertensive subjects, as well as in men and women. Potassium excretion was not associated with the risk of type 2 diabetes.High sodium intake predicted the risk of type 2 diabetes, independently of other risk factors including physical inactivity, obesity and hypertension. These results provide direct evidence of the harmful effects of high salt intake in the adult population, although the confounding effect of other dietary factors cannot be fully excluded.

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

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

As the global epidemic of type 2 diabetes continues unabated with the associated increasing socioeconomic burden, attention is increasingly turning to the important issue of prevention. Type 2 diabetes is one part of the broader medical paradigm associated with cardiovascular disease—the metabolic syndrome. Population-directed prevention is aimed at reducing the risk factor burden in both the general population and susceptible communities or ethnic groups. To date, there has been limited attention paid to dealing with the foreseen epidemic of type 2 diabetes. Targeted prevention involves higher intensity intervention strategies aimed at subjects with impaired glucose tolerance and impaired fasting glucose (prediabetes). There are now four major studies investigating lifestyle intervention in subjects with impaired glucose tolerance and all have shown significant reduction in progression to type 2 diabetes. Over the last 20 years there have been a number of targeted pharmacological intervention studies in subjects reported, with mixed results. Recently troglitazone, acarbose, and metformin have been shown to reduce progression to diabetes. There are now large targeted studies underway, examining the possible prevention of diabetes with ramipril, rosiglitazone, nateglinide, valsartan, and insulin. Whether lifestyle strategies or pharmacological intervention will also reduce cardiovascular outcomes is unknown. Possible but speculative mechanisms for diabetes prevention with pharmacological interventions are discussed. Many other issues remain to be addressed and these are the following: (1) How best to implement risk factor reduction (behavioral modification) in the population at large, in susceptible communities and ethnic groups? (2) How to achieve and maintain lifestyle changes targeted at prediabetic subjects? (3) What is the long-term value and safety of pharmacological treatment of otherwise asymptomatic prediabetic subjects? (4) Are there benefits of combination therapies with lifestyle and pharmacological interventions in prediabetic individuals? (5) What are the socioeconomic costs and benefits, including cardiovascular protection, of implementing diabetes prevention programs? Keywords: type 2 diabetes; diabetes prevention; lifestyle factors; pharmacotherapy; prevention trials; cardiovascular risk reduction

To describe the 1) lifestyle intervention used in the Finnish Diabetes Prevention Study, 2) short- and long-term changes in diet and exercise behavior, and 3) effect of the intervention on glucose and lipid metabolism.There were 522 middle-aged, overweight subjects with impaired glucose tolerance who were randomized to either a usual care control group or an intensive lifestyle intervention group. The control group received general dietary and exercise advice at baseline and had an annual physician's examination. The subjects in the intervention group received additional individualized dietary counseling from a nutritionist. They were also offered circuit-type resistance training sessions and advised to increase overall physical activity. The intervention was the most intensive during the first year, followed by a maintenance period. The intervention goals were to reduce body weight, reduce dietary and saturated fat, and increase physical activity and dietary fiber.The intervention group showed significantly greater improvement in each intervention goal. After 1 and 3 years, weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group, respectively. Measures of glycemia and lipemia improved more in the intervention group.The intensive lifestyle intervention produced long-term beneficial changes in diet, physical activity, and clinical and biochemical parameters and reduced diabetes risk. This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system.

Lifestyle interventions reduce the incidence of type 2 diabetes among individuals with impaired glucose tolerance (IGT). However, it is unknown whether this is due to improved insulin sensitivity or insulin secretion. We investigated at baseline insulin sensitivity and insulin secretion applying frequently sampled intravenous glucose tolerance test (FSIGT) in 87 of 101 obese middle-aged subjects with IGT randomized into an intervention or a control group in the Finnish Diabetes Prevention Study. FSIGT was repeated after 4 years in 52 people. There were no significant differences in any of the baseline anthropometric or metabolic characteristics between the groups. The 4-year weight and waist circumference decreases were greater in the intervention than in the control group (P = 0.043 and P = 0.025, respectively). At 4-year examination, insulin sensitivity (Si) tended to be higher in the intervention group (the difference between the mean values 36%; P = 0.067, and P = 0.136 after adjustment for age, sex, BMI, and baseline Si value). There was strong correlation between the 4-year changes in Si and weight (r = -0.628 and r = -0.710, for intervention and control groups; P0.001 for both). In the entire group, Si improved by 64% in the highest tertile of weight loss but deteriorated by 24% in those who gained weight (lowest tertile). Acute insulin response declined significantly in the control group. In conclusion, Si markedly improved by weight reduction during the 4-year follow-up of individuals with IGT. Insulin secretion remained constant for years in individuals with IGT who were able to lose weight.

High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The -308A allele of the TNF-alpha gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05-3.09; P = 0.034). Subjects with both the A allele of the TNF-alpha gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02-4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the -308A allele of the promoter polymorphism (G-308A) of the TNF-alpha gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene.

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

Type 2 diabetes (T2D) is a devastating disease with multiple complications affecting many tissues, most notably the cardiovascular system. To be able to prevent a chronic disease such as T2D, certain requirements have to be met. Knowledge about its natural history with a preclinical phase, modifiable risk factors, effective and simple screening tools 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 under a clinical trial setting. Several major lifestyle intervention trials have been successfully carried out, with consistent results: the risk of T2D in high-risk subjects can be halved, the effect of lifestyle changes is rapid, and benefits are similar in different ethnic groups. Thus, the prevention of T2D is possible in most high-risk subjects, but how to achieve this at the population level remains a major challenge.

Interventions to prevent type 2 diabetes should be directed toward individuals at increased risk for the disease. To identify such individuals without laboratory tests, we developed the Diabetes Risk Score.A random population sample of 35- to 64-year-old men and women with no antidiabetic drug treatment at baseline were followed for 10 years. New cases of drug-treated type 2 diabetes were ascertained from the National Drug Registry. Multivariate logistic regression model coefficients were used to assign each variable category a score. The Diabetes Risk Score was composed as the sum of these individual scores. The validity of the score was tested in an independent population survey performed in 1992 with prospective follow-up for 5 years.Age, BMI, waist circumference, history of antihypertensive drug treatment and high blood glucose, physical activity, and daily consumption of fruits, berries, or vegetables were selected as categorical variables. Complete baseline risk data were found in 4435 subjects with 182 incident cases of diabetes. The Diabetes Risk Score value varied from 0 to 20. To predict drug-treated diabetes, the score valueor=9 had sensitivity of 0.78 and 0.81, specificity of 0.77 and 0.76, and positive predictive value of 0.13 and 0.05 in the 1987 and 1992 cohorts, respectively.The Diabetes Risk Score is a simple, fast, inexpensive, noninvasive, and reliable tool to identify individuals at high risk for type 2 diabetes.

The association of the Pro12Ala polymorphism of the PPAR-γ2 gene with the incidence of type 2 diabetes was investigated in 522 subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study. Subjects were randomized to either an intensive diet and exercise group or a control group. By 3 years of intervention, the odds ratio of the development of type 2 diabetes for subjects with the Ala12 allele was 2.11-fold compared with that for subjects with the Pro12Pro genotype (95% CI 1.20–3.72). The risk for type 2 diabetes increased also in subjects who gained weight or belonged to the control group. In the intervention group, subjects with the Ala12Ala genotype lost more weight during the follow-up than subjects with other genotypes (Pro12Pro vs. Ala12Ala P = 0.043), and none of subjects with the Ala12Ala genotype developed type 2 diabetes in this group. In conclusion, the Ala12 allele may predispose to the development of type 2 diabetes in obese subjects with IGT. However, beneficial changes in diet, increases in physical activity, and weight loss may reverse, to some extent, the diabetogenic impact of the Ala12 allele, possibly due to an improved insulin sensitivity.

To the Editor: In an extensive review Buyken and coauthors discussed the optimal dietary approaches for the prevention of type 2 diabetes [1]. The topic is of utmost importance because of the alarming increase in obesity, cardiometabolic syndrome and type 2 diabetes, the modern worldwide epidemic. The authors very briefly bypass the evidence coming from two lifestyle intervention trials, the Diabetes Prevention Study (DPS) [2] from Finland and the Diabetes Prevention Program (DPP) [3] from the USA, which showed a marked reduction in the incidence of diabetes both during the active intervention and the subsequent follow-up of up to 10 years [4, 5]. The authors then extensively discuss alternative diets that supposedly might be helpful in the prevention of type 2 diabetes. However, two major concerns remain after having read this review. First, the authors do not give major emphasis to evidence-based medical nutrition. In this regard, randomised controlled trials with onset of diabetes as an endpoint give the strongest evidence. But we do not yet have a definite answer to the question ‘what kind of diet is the best to prevent type 2 diabetes’, or even if such a universally superior diet exists. What we do know is that weight reduction and physical activity are the cornerstones of prevention. Weight reduction, however, is only possible with the reduction of total energy intake by dietary changes or increasing physical activity. As for the hard endpoint, the above-mentioned randomised prevention trials give the best (class A) evidence we have at the moment evidence and deserve to be cited appropriately. As for the quality of diet, we in the DPS study group originally decided to follow the general dietary recommendations for Nordic countries, with minor modifications. Information on the diets recommended and achieved in the DPS, as well as on how the goals were translated to practical dietary advice has been presented in detail [6]. The goal of total fat intake was 30% of energy (E%; intake up to 35 E% was acceptable if the surplus was monounsaturated fat), which can be considered a ‘moderate’ rather than a ‘low’ fat intake. Baseline total fat intake was 36–37 E% and intake of saturated fat 16–17 E%. After 1 and 3 years of the active intervention there was a 3.4–4.7 E% reduction in M. Uusitupa Institute of Public Health and Clinical Nutrition, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland

Objective We studied associations between the type of feeding in infancy and the incidence of insulin-dependent diabetes mellitus (IDDM). Research Design And Methods We studied 103 newly diagnosed diabetic children Results The risk of IDDM was decreased (P < 0.05) among children breast-fed for at least 7 mo (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.24–0.85) or exclusively breast-fed for at least 3 (OR 0.33, 95% CI 0.13–0.84) or 4 (OR 0.43, 95% CI 0.22–0.84) mo. Also, children who were ≥4 mo old at the time of introduction of supplementary milk feeding had a lower risk of diabetes (OR 0.48, 95% CI 0.26–0.91). Conclusions The protective effects of a long duration of breast-feeding and a late introduction of dairy products on the risk of IDDM remained significant after adjusting for the mother's education.

Background Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic effects. Two receptors for adiponectin, ADIPOR1 and ADIPOR2, have been characterized that mediate effects of adiponectin in various tissues. We examined whether genetic variation in ADIPOR2 predicts the development of cardiovascular disease (CVD) and/or Type 2 Diabetes (T2DM) in individuals with impaired glucose tolerance (IGT) participating the Finnish Diabetes Prevention Study (DPS). Methods CVD morbidity and mortality data were collected during a median follow-up of 10.2 years (range 1-13 years) and conversion from IGT to T2DM was assessed during a median follow-up of 7 years (range 1-11 years). Altogether eight SNPs in the ADIPOR2 locus were genotyped in 484 participants of the DPS. Moreover, the same SNPs were genotyped and the mRNA expression levels of ADIPOR2 were determined in peripheral blood mononuclear cells and subcutaneous adipose tissue samples derived from 56 individuals participating in the Genobin study. Results In the DPS population, four SNPs (rs10848554, rs11061937, rs1058322, rs16928751) were associated with CVD risk, and two remained significant (p = 0.014 for rs11061937 and p = 0.020 for rs1058322) when all four were included in the same multi-SNP model. Furthermore, the individuals homozygous for the rare minor alleles of rs11061946 and rs11061973 had increased risk of converting from IGT to T2DM. Allele-specific differences in the mRNA expression levels for the rs1058322 variant were seen in peripheral blood mononuclear cells derived from participants of the Genobin study. Conclusions Our results suggest that SNPs in the ADIPOR2 may modify the risk of CVD in individuals with IGT, possibly through alterations in the mRNA expression levels. In addition an independent genetic signal in ADIPOR2 locus may have an impact on the risk of developing T2DM in individuals with IGT. Trial registration number ClinicalTrials.gov NCT00518167

Background Adiponectin, secreted mainly by mature adipocytes, is a protein with insulin-sensitising and anti-atherogenic effects. Human adiponectin is encoded by the ADIPOQ gene on the chromosomal locus 3q27. Variations in ADIPOQ are associated with obesity, type 2 diabetes (T2DM) and related phenotypes in several populations. Our aim was to study the association of the ADIPOQ variations with body weight, serum adiponectin concentrations and conversion to T2DM in overweight subjects with impaired glucose tolerance. Moreover, we investigated whether ADIPOQ gene variants modify the effect of lifestyle changes on these traits. Methods Participants in the Finnish Diabetes Prevention Study were randomly assigned to a lifestyle intervention group or a control group. Those whose DNA was available (n = 507) were genotyped for ten ADIPOQ single nucleotide polymorphisms (SNPs). Associations between SNPs and baseline body weight and serum adiponectin concentrations were analysed using the univariate analysis of variance. The 4-year longitudinal weight data were analysed using linear mixed models analysis and the change in serum adiponectin from baseline to year four was analysed using Kruskal-Wallis test. In addition, the association of SNPs with the risk of developing T2DM during the follow-up of 0-11 (mean 6.34) years was analysed by Cox regression analysis. Results rs266729, rs16861205, rs1501299, rs3821799 and rs6773957 associated significantly (p < 0.05) with body weight at baseline and in the longitudinal analyses. The rs266729 C allele and the rare minor alleles of rs2241766 and rs2082940 were associated with an increased adjusted hazard ratio of developing T2DM. The differences in baseline serum adiponectin concentrations were seen according to rs16861210, rs17366568, rs2241766, rs6773957 and rs2082940 and differences in the change of serum adiponectin levels from baseline to the four year examination were seen according to rs16861205, especially in subjects who were able to lose weight during the first year of intervention. Conclusions These results from the Finnish Diabetes Prevention Study support the concept that genetic variation in ADIPOQ locus contributes to variation in body size and serum adiponectin concentrations and may also modify the risk of developing T2DM. Trial registration number ClinicalTrials.gov NCT00518167

Background We explored the associations of three variants in the uncoupling protein 2 (UCP2) gene, one variant in the UCP2-UCP3 intergenic region and five variants in the uncoupling protein 3 (UCP3) gene with obesity and diabetes related traits in subjects with impaired glucose tolerance participating in Finnish Diabetes Prevention Study. Altogether 507 overweight individuals (body mass index: 31.2 ± 4.5 kg/m2, age: 55 ± 7 years) for whom DNA was available were randomized to either an intensified diet and physical activity group or to a conventional care control group. Methods We analysed the data from the baseline and annual follow-up visits from years 1, 2 and 3. Measurements of anthropometry, plasma glucose and serum insulin in oral glucose tolerance test, serum total cholesterol, HDL-cholesterol and triglycerides were included. The median follow-up time for type 2 diabetes incidence was 7 years. Genetic variants were screened by restriction fragment length polymorphism or Illumina method. Results UCP3 gene variant rs3781907 was associated with increased serum total and LDL-cholesterol levels, at baseline and during the follow-up period. The same variant was associated with a higher risk of type 2 diabetes. Variants rs1726745, rs11235972 and rs1800849 in the UCP3 gene associated with serum total and LDL-cholesterol at baseline. Haploblock including variants rs659366, rs653529, rs15763, and rs1726745 was associated with measures of abdominal obesity at baseline and in the longitudinal analysis. The haplotype comprising alleles rs659366-G, rs653529-A, rs15763-G and rs1726745-A was associated with higher waist-to-hip ratio, and haplotype comprising alleles rs3781907-G, rs11235972-A, and rs1800849-T was associated with increased serum total and LDL-cholesterol concentrations. Conclusion Genetic variation in the UCP2-UCP3 gene cluster may act as a modifier increasing serum lipid levels and indices of abdominal obesity, and may thereby also contribute to the metabolic aberrations observed in obesity and type 2 diabetes.

In our recent publication (1), we showed that among participants in the Finnish Diabetes Prevention Study, a diabetes prevention trial using lifestyle intervention, those who had the highest baseline composite diabetes risk as measured by the Finnish Diabetes Risk Score (FINDRISC) achieved the largest risk reduction during the lifestyle intervention. We appreciate the comment written by Schulze. However, the major part of the comment addresses our earlier publication (3) describing the development and validation of the risk prediction model using two large, population-based cohorts. In that paper, we extensively discussed the issues raised by …

Background Sedentary lifestyle, obesity, and impaired glucose regulation are associated with the risk of type 2 diabetes. However, the joint associations of these risk factors are not known. Methods We prospectively followed up 2017 Finnish men and 2352 Finnish women aged between 45 and 64 years without a history of known or newly diagnosed diabetes at baseline. Single and joint associations of physical activity, body mass index (BMI), and blood glucose levels with risk of type 2 diabetes were examined using Cox proportional hazards models. Results During a mean follow-up of 9.4 years, there were 120 incident cases of type 2 diabetes. After adjustment for confounding factors (age, study year, sex, systolic blood pressure, smoking, and education), physical activity was found to be inversely associated with the risk of type 2 diabetes. This association was persistent in subjects with (1) both obesity and impaired glucose regulation, (2) either obesity or impaired glucose regulation, and (3) a normal BMI and glucose regulation. Similarly, the multivariate-adjusted positive association between BMI and risk of type 2 diabetes was consistently observed. Obesity in subjects who reported being inactive and had normal glucose levels was associated with an increased risk of diabetes compared with a normal BMI in subjects who reported being active and had impaired glucose regulation. Conclusions Increasing physical activity can reduce the risk of type 2 diabetes. The protective effect of physical activity was observed in subjects with an excessive BMI and elevated glucose levels. Physical activity and weight control are critical factors in diabetes prevention in subjects with both normal and impaired blood glucose regulation.

Only a few studies of coffee consumption and diabetes mellitus (DM) have been reported, even though coffee is the most consumed beverage in the world.To determine the relationship between coffee consumption and the incidence of type 2 DM among Finnish individuals, who have the highest coffee consumption in the world.A prospective study from combined surveys conducted in 1982, 1987, and 1992 of 6974 Finnish men and 7655 women aged 35 to 64 years without history of stroke, coronary heart disease, or DM at baseline, with 175 682 person-years of follow-up. Coffee consumption and other study parameters were determined at baseline using standardized measurements.Hazard ratios (HRs) for the incidence of type 2 DM were estimated for different levels of daily coffee consumption.During a mean follow-up of 12 years, there were 381 incident cases of type 2 DM. After adjustment for confounding factors (age, study year, body mass index, systolic blood pressure, education, occupational, commuting and leisure-time physical activity, alcohol and tea consumption, and smoking), the HRs of DM associated with the amount of coffee consumed daily (0-2, 3-4, 5-6, 7-9,or =10 cups) were 1.00, 0.71 (95% confidence interval [CI], 0.48-1.05), 0.39 (95% CI, 0.25-0.60), 0.39 (95% CI, 0.20-0.74), and 0.21 (95% CI, 0.06-0.69) (P for trend.001) in women, and 1.00, 0.73 (95% CI, 0.47-1.13), 0.70 (95% CI, 0.45-1.05), 0.67 (95% CI, 0.40-1.12), and 0.45 (95% CI, 0.25-0.81) (P for trend =.12) in men, respectively. In both sexes combined, the multivariate-adjusted inverse association was significant (P for trend.001) and persisted when stratified by younger and older than 50 years; smokers and never smokers; healthy weight, overweight, and obese participants; alcohol drinker and nondrinker; and participants drinking filtered and nonfiltered coffee.Coffee drinking has a graded inverse association with the risk of type 2 DM; however, the reasons for this risk reduction associated with coffee remain unclear.

The importance of overall diet in modifying circulating lipoprotein particles and fatty acids during pregnancy is unclear. We examined the relationships of diet quality as assessed by the validated Healthy Food Intake Index (HFII) with serum HDL, LDL and VLDL particle concentrations and sizes and proportions of serum fatty acids in pregnant women at high risk for gestational diabetes mellitus (GDM). Overall, 161 women with a BMI of ≥30 kg/m2and/or a history of GDM were drawn from the Finnish Gestational Diabetes Prevention Study, which is a dietary and exercise intervention trial to prevent GDM. At baseline, the HFII score was inversely related to concentrations of HDL particles (P=0·010) and MUFA (P=0·010) and positively related to concentrations ofn-3 (Pn-6 (P=0·003) PUFA. The significance for MUFA disappeared after adjustments. An increase in the HFII score from the first to second trimester of pregnancy correlated with reduced VLDL particle size (r−0·16, 95 % CI −0·31, −0·01), decreased MUFA concentrations (r−0·17, 95 % CI −0·31, −0·01) and elevatedn-6 PUFA concentrations (r0·16, 95 % CI 0·01, 0·31). In the maximum-adjusted model, the results remained significant except for VLDL particle size. These findings suggest that higher diet quality as defined by the HFII is related to a more favourable serum fatty acid profile, whereas the relationship with serum lipoprotein profile is limited in pregnant women at increased GDM risk.

Background The aim was to develop and validate a food-based diet quality index for measuring adherence to the Nordic Nutrition Recommendations (NNR) in a pregnant population with high risk of gestational diabetes (GDM). Methods This study is a part of the Finnish Gestational Diabetes Prevention Study (RADIEL), a lifestyle intervention conducted between 2008 and 2014. The 443 pregnant participants (61 % of those invited), were either obese or had a history of GDM. Food frequency questionnaires collected at 1st trimester served for composing the HFII; a sum of 11 food groups (available score range 0–17) with higher scores reflecting higher adherence to the NNR. Results The average HFII of the participants was 10.2 (SD 2.8, range 2–17). Factor analysis for the HFII component matrix revealed three factors that explained most of the distribution (59 %) of the HFII. As an evidence of the component relevance 9 out of 11 of the HFII components independently contributed to the total score (item-rest correlation coefficients

Introduction: Lifetime exposure to occupational complexity is linked to late-life cognition, and may affect benefits of preventive interventions. Methods: In the 2-year multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated, through post hoc analyses (N = 1026), the association of occupational complexity with cognition. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. Results: Higher levels of occupational complexity were associated with better baseline cognition. Measures of occupational complexity had no association with intervention effects on cognition, except for occupational complexity with data, which was associated with the degree of intervention-related gains for executive function. Discussion: In older adults at increased risk for dementia, higher occupational complexity is associated with better cognition. The cognitive benefit of the FINGER intervention did not vary significantly among participants with different levels of occupational complexity. These exploratory findings require further testing in larger studies. publishedVersion

English summary

The aim of the Finnish Diabetes Prevention Study is to assess the efficacy of an intensive diet–exercise programme in preventing or delaying type 2 diabetes in individuals with impaired glucose tolerance (IGT) and to evaluate the effect of the programme on the risk factors of atherosclerotic vascular diseases and the incidence of cardiovascular events. In this ongoing study, a total of 523 overweight subjects with IGT based on two oral glucose tolerance tests were randomized to either an intervention group or a control group. The main measure in the intervention group is individual dietary advice aimed at reducing weight and intake of saturated fat and increasing intake of dietary fibre. The intervention subjects are individually guided to increase their level of physical activity. The control group receives general information about the benefits of weight reduction, physical activity and healthy diet in the prevention of diabetes. A pilot study began in 1993, and recruitment ended in 1998. By the end of April 1999 there were 65 new cases of diabetes, 34 drop-outs and one death. The weight reduction was greater (-4.6 kg) at 1 year in the intervention group (n = 152) than in the control group (n = 143, -0.9 kg, P < 0.0001), and this difference was sustained in the second year of follow-up. At 1 year 43.4 % and at 2 years 41.8 % of the intervention subjects had achieved a weight reduction of at least 5 kg, while the corresponding figures for the control subjects were 14.0 and 12.0 % (P < 0.001 between the groups). At 1 year the intervention group showed significantly greater reductions in 2 h glucose, fasting and 2 h insulin, systolic and diastolic blood pressure, and serum triglycerides. Most of the beneficial changes in cardiovascular risk factors were sustained for 2 years. These interim results of the ongoing Finnish Diabetes Prevention Study demonstrate the efficacy and feasibility of the lifestyle intervention programme.

Background Compelling evidence has been accumulated to support the effectiveness of intensive lifestyle intervention in delaying progression to Type 2 diabetes even in people identified as being at high risk determined by the Finnish diabetes risk score. The DE-PLAN-CAT project (diabetes in Europe-prevention using lifestyle, physical activity and nutritional intervention–Catalonia) evidenced that intensive lifestyle intervention was feasible and cost-effective on a short scale in real-life primary care settings, at least over 4 years. However, transferring such lifestyle interventions to society remains the major challenge of research in the field of diabetes prevention. Methods/design The derived DP-TRANSFERS (diabetes prevention-transferring findings from European research to society) is a large scale national programme aimed at translating a tailored lifestyle intervention to the maximum of primary care centres where feasible through a core proposal agreed with all the partners. The method is built upon a 3-step (screening, intervention and follow-up) real-life, community-wide structure on the basis of a dual intensity lifestyle intervention (basic and continuity modules) and supported by a 4-channel transfer strategy (institutional relationships, facilitators’ workshops, collaborative groupware and programme WEB page). Participation will initially cover nine health departments (7 million inhabitants) through nine coordinating centres located in metropolitan (3.2 million), semi-urban (2.9 million) and rural (0.9 million) areas from which it is expected accessing 25 % of all primary care settings, equivalent to 90 associated centres (1.6–1.8 million people) with an estimate of 0.32 million participants aged 45–75 years at high risk of future development of diabetes. To ascertain sustainability, effect, satisfaction and quality of the translation programme statistical analyses will be performed from both the entire population (facilitators and participants) and a stratified representative sample obtained by collecting data from at least 920 participants. Discussion The DP-TRANSFERS will use a strategy of approach to society consistent with the impact of the disease and the fast accessibility provided by primary care settings in Catalonia. Both the widespread effect of the lifestyle intervention and the translational process itself could be assessed.

In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.

This study investigated barriers towards health behaviours (physical activity, limiting sedentary behaviour and healthy dietary habits) experienced by young European families living in vulnerable areas, from multiple perspectives (parents, teachers, local community workers). Focus groups were conducted in six European countries (Belgium, Bulgaria, Finland, Hungary, Greece and Spain). In each country, three focus groups were conducted with parents, one with teachers and one with local community workers. Data were analysed using a deductive framework approach with a manifest content analysis using the software NVivo. The present study identified barriers on four levels (individual, interpersonal, organisational and macro level) of a socio-ecological model of health behaviour. From parents’ perspectives, both general barriers (e.g., financial limitations and lack of time) and country-specific barriers (e.g., organisational difficulties and inappropriate work environment) were identified. Additional barriers (e.g., lack of parental knowledge and lack of parental skills) were provided by other stakeholders (i.e., teachers and local community workers). The results of this study demonstrate the additional value of including multiple perspectives when developing a lifestyle intervention aiming to prevent type 2 diabetes in vulnerable groups. Future lifestyle interventions are recommended to include multiple components (family, school, and community) and could be implemented across European countries if country-specific adaptations are allowed.