The role of metformin and statins in the incidence of epithelial ovarian cancer in type 2 diabetes: a cohort and nested case-control study.

OBJECTIVE: To obtain evidence of the effects of metformin and statins on the incidence of ovarian cancer in women with type 2 diabetes (T2D). DESIGN: A retrospective cohort study and nested case-control study. SETTING: The data were obtained from a diabetes database (FinDM) combining information from several nationwide registers. POPULATION: A cohort of 137 643 women over 40 years old and diagnosed with T2D during 1996-2011 in Finland. METHODS: In full cohort analysis Poisson regression was used to estimate the hazard ratios (HR) in relation to ever use of metformin, insulin other oral anti-diabetic medication or statins. In the nested case-control analysis 20 controls were matched to each case of ovarian cancer. Conditional logistic regression was used to estimate HRs in relation to medication use and cumulative use of different medications. The estimates were adjusted for age and duration of T2D. MAIN OUTCOME MEASURE: Incidence of ovarian cancer. RESULTS: In all, 303 women were diagnosed with ovarian cancer during the follow up. Compared with other forms of oral anti-diabetic medication, metformin (HR 1.02, 95% CI: 0.72-1.45) was not found to be associated with the incidence of ovarian cancer. Neither was there evidence for statins to affect the incidence (HR 0.99, 95% CI: 0.78-1.25). In nested case-control analysis the results were essentially similar. CONCLUSIONS: No evidence of an association between the use of metformin or statins and the incidence of ovarian cancer in women with T2D was found. TWEETABLE ABSTRACT: No evidence found for metformin or statins reducing the incidence of ovarian cancer.

Cause-specific mortality in endometrioid endometrial cancer patients with type 2 diabetes using metformin or other types of antidiabetic medication.

AIM: To obtain further evidence of the association between metformin or other types of antidiabetic medication (ADM) and mortality from endometrial cancer (EC) and other causes of death in patients with endometrioid EC and type 2 diabetes (T2D). MATERIALS AND METHODS: A retrospective cohort of women with existing T2D and diagnosed with endometrioid EC from 1998 to 2011, obtained from a nationwide diabetes database (FinDM), were included in the study. Cumulative mortality from EC and that from other causes was described by using the Aalen-Johansen estimator. Cause-specific mortality rates were analyzed by using Cox models, and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were estimated in relation to the use of different forms of ADM during the three-year period preceding EC diagnosis. RESULTS: From the FinDM cohort we identified 1215 women diagnosed with endometrioid EC, of whom 19% were metformin users, 12% were users of other types of oral antidiabetic medication, 25% used other types of oral antidiabetic medication plus metformin, 26% used insulin and 14% had no antidiabetic medication. Mortality from EC was not found to be different in women using metformin (HR 0.89, 95% Cl 0.52-1.54) but mortality from other causes was lower (HR 0.52, 95% Cl 0.31-0.88) compared with women using other types of oral ADM. CONCLUSIONS: Our findings are inconclusive as to the possible effect of metformin on the prognosis of endometrioid EC in women with T2D. However, use of metformin may reduce mortality from other causes.

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

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

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

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

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

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

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

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

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

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

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

AIMS/HYPOTHESIS: Subclinical inflammation confers an increased risk of type 2 diabetes, cardiovascular disease, neurodegenerative disorders and other age-related chronic diseases. Physical activity and diet can attenuate systemic immune activation, but it is not known which individual components of a comprehensive lifestyle intervention are most effective in targeting subclinical inflammation. METHODS: We used data from the baseline examination and the 1 year follow-up of a subsample of 406 of 522 participants of the Finnish Diabetes Prevention Study (DPS) to estimate the effect of individual components of lifestyle intervention on C-reactive protein (CRP) and IL-6 levels, which represent the best characterised proinflammatory risk factors for type 2 diabetes. Changes in metabolic markers, dietary patterns and exercise were analysed to determine which were most strongly associated with the anti-inflammatory effect of lifestyle changes. RESULTS: Lifestyle intervention reduced circulating levels of CRP (p < 0.001) and IL-6 (p = 0.060). Increases in fibre intake and moderate to vigorous leisure time physical activity (LTPA), but not total LTPA, predicted decreases in CRP and/or IL-6 and remained associated even after adjustment for baseline BMI or changes in BMI during the first year of the study. Changes in carbohydrate or fat intake were either weakly or not linked to reductions in CRP and IL-6. CONCLUSIONS/INTERPRETATION: The present study assessed the individual effects of dietary and physical activity measures on low-grade inflammation in individuals at high cardiometabolic risk. Our results underline the importance of moderate to vigorous LTPA and a diet rich in natural fibre, and this should be emphasised in lifestyle recommendations.

Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes.

Single nucleotide polymorphisms (SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in the Finnish Diabetes Prevention Study (DPS). We determined whether physical activity (PA), assessed annually with a questionnaire, modified the association of SNPs in SLC2A2 and ABCC8 with the conversion to T2D in the combined intervention and control groups of the DPS. Finnish overweight subjects with IGT (N = 479) were followed for an average of 4.1 yr. The interaction of the SNPs with the change in PA on the conversion to T2D was assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). The carriers of the common homozygous genotype of rs5393, rs5394, or rs5404 of SLC2A2 and rs3758947 of ABCC8 who were in the lower third of the change in moderate-to-vigorous PA during the follow-up had a 2.6- to 3.7-fold increased risk of developing T2D compared with the upper third, whereas the rare allele carriers seemed to be unresponsive to changes in moderate-to-vigorous PA (for the interaction of genotype with change in PA, P = 0.022-0.027 for the SNPs in SLC2A2, and P = 0.007 for rs3758947). We conclude that moderate-to-vigorous PA may modify the risk of developing T2D associated with genes regulating insulin secretion (SLC2A2, ABCC8) in persons with IGT.

Association of Long-Term Dietary Fat Intake, Exercise, and Weight with Later Cognitive Function in the Finnish Diabetes Prevention Study.

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.

Assessment of periodontal treatment needs among adults with diabetes in Finland.

OBJECTIVES: People with diabetes have a high risk for periodontal disease, which can be considered one of the complications of diabetes. We evaluated periodontal treatment needs using the Community Periodontal Index of Treatment Needs (CPITN) in relation to diabetes-related factors and oral hygiene. DESIGN: The sample consisted of 120 dentate diabetics, all of whom were regular patients at the Salo Regional Hospital Diabetes Clinic. The nurses, who interviewed the patients, collected data on duration and type of diabetes, complications, and HbA1c level. Clinical periodontal examination included identification of visible plaque, the presence of calculus and use of the CPITN. RESULTS: The CPITN score 3 was the most prevalent. According to the logistic regression model, poor metabolic control was significantly related to pathologic pockets. No significant association was found between diabetes-related factors and the highest individual CPITN score of 4, which was, in turn, significantly associated with extensive calculus. CONCLUSIONS: Excessive periodontal treatment needs found, indicate that current dental care may be insufficient in adults with diabetes. Oral health among high-risk groups, especially those with poor metabolic control, should be promoted by collaboration between dental and health care professionals involved in diabetes care.

Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

AIMS: Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). METHODS: DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. RESULTS: There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016). CONCLUSIONS: Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.

Association of sequence variations in the gene encoding adiponectin receptor 1 (ADIPOR1) with body size and insulin levels. The Finnish Diabetes Prevention Study.

AIMS/HYPOTHESIS: Adiponectin is a circulating peptide derived from adipose tissue. It mediates its insulin-sensitising and anti-atherogenic effects on target tissues through two known receptors, adiponectin receptors 1 and 2 (ADIPOR1; ADIPOR2), which are encoded by the genes ADIPOR1 and ADIPOR2. Our aim was to study the association of ADIPOR1 gene variations with body size and risk of type 2 diabetes in subjects with impaired glucose tolerance, who participated in the Finnish Diabetes Prevention Study (DPS). SUBJECTS AND METHODS: We selected seven single nucleotide polymorphisms (SNPs) of the ADIPOR1 gene to perform association studies with anthropometrics and metabolic parameters at baseline, and with the risk of type 2 diabetes during the 3-year follow-up in the DPS study population. Both single SNP analysis and haplotype effects were studied. RESULTS: Three out of seven markers studied (rs10920534, rs22757538 and rs1342387) were significantly associated with various body size measurements including weight, height, waist and hip circumference, sagittal diameter and body mass index. Furthermore, three markers (rs10920534, rs12045862 and rs7539542), of which two were different from those associating with body size, were linked to fasting and 2-h insulin levels, particularly in men at baseline. The haplotype analysis with five markers revealed seven major haplotypes in the DPS study population. The haplotype effects on body size measures were in line with those of single SNP analysis. However, none of the markers were associated with the risk of type 2 diabetes. CONCLUSIONS/INTERPRETATION: Our findings suggest that ADIPOR1 has a putative role in the development of body size, and that traits for central adiposity and insulin resistance may be dissociated from each other.

Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study.

OBJECTIVE: Genetic variation in leptin receptor (LEPR) gene has been reported to associate with insulin and glucose metabolism and adiposity in different study settings and various populations. We wanted to evaluate the association between LEPR polymorphisms, diabetes risk and body weight in Finnish subjects with impaired glucose tolerance (IGT). METHODS: We investigated the associations of the three LEPR polymorphisms (Lys109Arg, Gln223Arg, 3'UTR Del/Ins) with the conversion to type 2 diabetes and the changes in body weight in 507 individuals with IGT participating in the Finnish Diabetes Prevention Study. Participants were randomized to either an intensive diet and exercise intervention group or a control group. RESULTS: After 3 years, the odds ratio for the development of type 2 diabetes in individuals in the control group with the Lys109Lys genotype was 2.38-fold higher than in individuals with other genotype combinations (P=0.016). Irrespective of group individuals with the Gln223Gln genotype had higher conversion to type 2 diabetes (OR 2.01 (95% CI 1.03-3.93)) than the Arg223 allele carriers (P=0.042). The risk was more pronounced in the control group than in the intervention group. Individuals having the 3'UTR Del/Del genotype had a slightly higher body weight throughout the study than those with the insertion allele (P=0.020), although no difference in weight change was observed. CONCLUSION: Two polymorphisms (Lys109Arg, Gln223Arg) in the extracellular domain of the leptin receptor predicted the conversion to type 2 diabetes in high-risk individuals with IGT. The Del/Ins polymorphism in the 3'UTR of LEPR was associated with body weight.

Improved fibrinolysis by an intensive lifestyle intervention in subjects with impaired glucose tolerance. The Finnish Diabetes Prevention Study.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of lifestyle intervention on the levels of plasminogen activator inhibitor (PAI-1) and fibrinogen in subjects participating in the Finnish Diabetes Prevention Study (DPS). METHODS: In five DPS centres, 321 subjects with impaired glucose tolerance (intervention group, n=163; control group, n=158) had their PAI-1 and fibrinogen levels measured at baseline and at the 1-year follow-up. Additional 3-year follow-up assessments were carried out in a sample of 97 subjects in one of the DPS centres (Turku). The intervention programme included an intensive lifestyle intervention aiming at weight reduction, healthy diet and increased physical activity. RESULTS: During the first intervention year, PAI-1 decreased by 31% in the intervention group but showed no change in the control group (p<0.0001). In the Turku subgroup, the decrease in PAI-1 persisted throughout the 3-year follow-up. Changes in PAI-1 were associated with the number of lifestyle changes made during the first year (p=0.008). Weight reduction was the most important factor explaining the decrease in PAI-1. Changes in fibrinogen levels did not differ between the groups. CONCLUSIONS/INTERPRETATION: In addition to the previously reported reduction in the risk of type 2 diabetes in DPS participants with impaired glucose tolerance, the intensive dietary and exercise intervention had beneficial long-term effects on fibrinolysis as indicated by the reduced levels of PAI-1. These results suggest that elevated PAI-1 levels in obese subjects with impaired glucose tolerance are mostly reversible by lifestyle changes, especially those geared to weight reduction.

Oral self-care and periodontal health indicators among adults with diabetes in Finland.

We assessed the effects of oral self-care on periodontal health indicators among adults with diabetes. The sample consisted of 120 dentate individuals, all of whom were regular patients at the Salo Regional Hospital Diabetes Clinic in southwest Finland. Clinical periodontal examination included identification of visible plaque, the presence of calculus, and use of the Community Periodontal Index of Treatment Needs (CPITN). A questionnaire focused on self-treatment, self-prevention, and self-diagnosis of oral diseases, utilization of dental services, and patients' knowledge and attitudes towards oral health. The New Century model of oral health promotion was used as a theoretical framework for analysis of determinants of oral self-care. Although individuals aged 40 years or older were more frequent interdental cleaners, significantly better oral health indicators were found among younger patients. Women reported brushing their teeth more frequently, and differences in plaque and calculus indices were significantly lower than those of men. Self-reported good oral condition was strongly associated with frequent dental visits and less plaque and calculus. No missing teeth and age less than 40 years were predictors of lower plaque, calculus, and CPITN scores. A significant association was found only between frequent dental visits and reduced amount of calculus. Self-reported frequency of oral health habits among adults with diabetes seemed to have little effect on periodontal health indicators. Adults with diabetes should benefit from comprehensive oral self-care, and more attention is needed for improving the quality and outcome of these habits.

Common polymorphisms in the genes regulating the early insulin signalling pathway: effects on weight change and the conversion from impaired glucose tolerance to Type 2 diabetes. The Finnish Diabetes Prevention Study.

AIMS/HYPOTHESIS: Type 2 diabetes is a complex disorder with strong heritability. The aim of our study was to investigate whether common polymorphisms in the genes regulating the early insulin signalling pathway (insulin; A-23T, insulin-like growth factor 1 receptor [IGF-1R]; GAG1013GAA, plasma cell membrane glycoprotein 1 [PC-1]; K121Q, insulin receptor substrate [IRS-1]; G972R, insulin receptor substrate 2 [IRS-2]; G1057D and phosphatidylinositol 3-kinase p85 alpha [PI3K]; M326I) affect the weight change and development of Type 2 diabetes in the Finnish Diabetes Prevention Study. METHODS: We screened for the polymorphisms in 490 overweight subjects with impaired glucose tolerance whose DNA was available from the Finnish Diabetes Prevention Study. These subjects were randomly allocated into a control group and an intervention group characterised by intensive, individualised diet and exercise. RESULTS: In carriers of the GAA1013GAA genotype of IGF-1R, the R972 allele of IRS-1 and the D1057D genotype of IRS-2, lifestyle intervention did not lead to significant differences in weight loss between the intervention and control groups, implying a role of these risk genotypes in the regulation of body weight. We observed a statistically significant difference in the conversion rate from IGT to diabetes between the genotypes of the IGF-1R gene (GAG1013GAG: 18.6%, GAG1013GAA: 10.4%, GAA1013GAA: 19.5%, p=0.033). Common polymorphisms in the insulin, PC-1 and PI3K genes did not regulate weight change or conversion to diabetes. CONCLUSIONS/INTERPRETATION: The common polymorphisms of the IGF-1R, IRS-1 and IRS-2 genes may modify the weight change response to a lifestyle intervention but not the conversion from IGT to Type 2 diabetes, whereas IGF-1R may also regulate the risk of developing Type 2 diabetes.

Association between a deletion/insertion polymorphism in the alpha2B-adrenergic receptor gene and insulin secretion and Type 2 diabetes. The Finnish Diabetes Prevention Study.

AIMS/HYPOTHESIS: Impaired insulin secretion has a strong genetic component. In this study we investigated whether the 12Glu9 polymorphism in the gene encoding the alpha2B-adrenergic receptor ( ADRA2B) is associated with insulin secretion and/or the incidence of Type 2 diabetes in individuals with impaired glucose tolerance. METHODS: We investigated a total of 506 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study (DPS). Participants were randomly assigned to an intervention group or a control group. Anthropometric measurements and an oral glucose tolerance test were performed at baseline and at annual follow-up. In a subgroup of patients (n=83), a frequently sampled intravenous glucose tolerance test (FSIGT) was performed at baseline. RESULTS: All patients had similar anthropometric measurements and insulin and glucose levels at baseline. Multiple logistic regression analysis revealed significant interaction (p=0.003) between study group and genotype across the entire study population. In the control group, subjects with the Glu9 allele had an increased risk of developing Type 2 diabetes compared with subjects with the Glu12/12 genotype (odds ratio [OR]=2.68, 95% CI 1.02-7.09, p=0.047 for Glu12/12, and OR=5.17, 95% CI 1.76-15.21, p=0.003 for Glu9/9). This increased risk was not observed in the intervention group, who showed significant weight loss during the trial. In the subgroup who underwent the FSIGT, subjects with the Glu9/9 genotype showed the lowest acute insulin response (p=0.005 for trend). CONCLUSIONS/INTERPRETATION: The 12Glu9 polymorphism of ADRA2B is associated with impaired first-phase insulin secretion and may predict the development of Type 2 diabetes in subjects with impaired glucose tolerance who are not subjected to a lifestyle intervention.

Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.

BACKGROUND: Type 2 diabetes mellitus is increasingly common, primarily because of increases in the prevalence of a sedentary lifestyle and obesity. Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known. METHODS: We randomly assigned 522 middle-aged, overweight subjects (172 men and 350 women; mean age, 55 years; mean body-mass index [weight in kilograms divided by the square of the height in meters], 31) with impaired glucose tolerance to either the intervention group or the control group. Each subject in the intervention group received individualized counseling aimed at reducing weight, total intake of fat, and intake of saturated fat and increasing intake of fiber and physical activity. An oral glucose-tolerance test was performed annually; the diagnosis of diabetes was confirmed by a second test. The mean duration of follow-up was 3.2 years. RESULTS: The mean (+/-SD) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group (P<0.001 for both comparisons between the groups). The cumulative incidence of diabetes after four years was 11 percent (95 percent confidence interval, 6 to 15 percent) in the intervention group and 23 percent (95 percent confidence interval, 17 to 29 percent) in the control group. During the trial, the risk of diabetes was reduced by 58 percent (P<0.001) in the intervention group. The reduction in the incidence of diabetes was directly associated with changes in lifestyle. CONCLUSIONS: Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects.

Prevention of Type II diabetes in subjects with impaired glucose tolerance: the Diabetes Prevention Study (DPS) in Finland. Study design and 1-year interim report on the feasibility of the lifestyle intervention programme.

UNLABELLED: AIMS/HYPOTHESIS; The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet-exercise programme in preventing or delaying Type II (non-insulin-dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance. METHODS: A total of 523 overweight subjects with impaired glucose tolerance ascertained by two oral glucose tolerance tests were randomised to either a control or intervention group. The control subjects received general information at the start of the trial about the lifestyle changes necessary to prevent diabetes and about annual follow-up visits. The intervention subjects had seven sessions with a nutritionist during the first year and a visit every 3 months thereafter aimed at reducing weight, the intake of saturated fat and increasing the intake of dietary fibre. Intervention subjects were also guided individually to increase their physical activity. RESULTS: During the first year, weight loss in the first 212 study subjects was 4.7 +/- 5.5 vs 0.9 +/- 4.1 kg in the intervention and control group, respectively (p < 0.001). The plasma glucose concentrations (fasting: 5.9 +/- 0.7 vs 6.4 +/- 0.8 mmol/l, p < 0.001; and 2-h 7.8 +/- 1.8 vs 8.5 +/- 2.3 mmol/l, p < 0.05) were significantly lower in the intervention group after the first year of intervention. Favourable changes were also found in blood pressure, serum lipids and anthropometric indices in the intervention group. CONCLUSION/INTERPRETATION: The interim results show the efficacy and feasibility of the lifestyle intervention programme.