Diabetes Prevention Study Research Articles

Reducing The Impact Of Diabetes: Is Prevention Feasible Today, Or Should We Aim For Better Treatment?

Type 2 diabetes prevention studies have shown that the onset of the disease can be delayed or prevented, chiefly by weight loss. But the current efforts to establish community-based lifestyle modification programs will not be very effective in preventing diabetes, largely because most overweight or obese people cannot maintain weight loss over time. A complex environment is driving greater food consumption along with less energy expenditure, making maintenance of weight loss extremely difficult. To improve the likelihood of achieving populationwide success in reducing the obesity pandemic, we need a better understanding of the biological processes that underlie the balance between intake and expenditure of energy. In the meantime, once diabetes develops, we can greatly reduce the likelihood of serious complications through early detection and proper medical management.

A framework convention on obesity control?

1 Tuomilehto J, Lindstrom J, Eriksson JG, et al, for the Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343–50. 2 Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403. 3 Umpierre D, Ribeiro PA, Kramer CK, et al. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA 2011; 305: 1790–99. 4 Bravata DM, Smith-Spangler C, Sundaram V, et al. Using pedometers to increase physical activity and improve health: a systematic review. JAMA 2007; 298: 2296–304. 5 Church TS, Blair SN, Cocreham S, et al. Eff ects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: a randomized controlled trial. JAMA 2010; 304: 2253–62. The legalisation of global health issues otherwise left in the political domain has the additional disadvantages of prioritising process over outcomes, consensus over diversity, generality over specifi city, states over non-state actors, and lawyers over health researchers. International law is often vague on specifi c commitments, slow to be implemented, hard to enforce, and diffi cult to update. It constrains future decision-making and crowds out alternative ap proaches. Confusing patchworks of issue-specifi c laws might also deepen challenges in global governance for health. Non-binding “soft laws” such as WHO’s codes on breastmilk and health worker migration could have similar eff ects, fewer costs, stronger language, and greater coverage. Before embarking on new solitary initiatives, research is needed on the full range of legal and other normative approaches and on how they can be integrated with existing mechanisms to avoid the proliferation of new governance platforms.

Associations of hip circumference and height with incidence of type 2 diabetes: the Isfahan diabetes prevention study

The aim of this study was to determine the effects of hip circumference (HC) and height on diabetes incidence in non-diabetic first-degree relatives (FDRs) of patients with type 2 diabetes. A total of 1,092 (254 men and 838 women) non-diabetics FDRs ≥ 30 years old in 2003-2005 were followed through 2010 for the occurrence of type 2 diabetes. At baseline and through follow-ups, participants were underwent a standard 75 g 2-h oral glucose tolerance test. The incidence of type 2 diabetes was 17.0 (95% CI: 13.7, 20.2) (13.0 men and 18.1 women) per 1,000 person-year based on 6,015 person-years of follow-up. Height was inversely associated with diabetes incidence. The age-, gender-, and waist-adjusted relative risk (95% CI) of diabetes was 0.54 (0.31, 0.93) for highest quartile of height and 0.59 (0.25, 1.37) for highest quartile of HC compared with lowest quartile. These data indicate that height was inversely associated with diabetes incidence, independently of gender among FDRs of patients with type 2 diabetes.

Fatty acids in serum and diet – a canonical correlation analysis among toddlers

Fatty acid concentrations in blood are potential biomarkers of dietary fat intake, but methodological studies among children are scarce. The large number of fatty acids and their complex interrelationships pose a special challenge in research on fatty acids. Our target was to assess the interrelationships between the total fatty acid profiles in diet and serum of young children. The study subjects were healthy control children from the birth cohort of the Type 1 Diabetes Prediction and Prevention Study. A 3-day food record and a frozen serum sample were available from 135 children at the age of 1 year, from 133 at 2 years, and from 92 at 3 years. The relationship between dietary and serum fatty acid profiles was analysed using canonical correlation analysis. The consumption of fatty milk correlated positively with serum fatty acids, pentadecanoic acid, palmitic acid and conjugated linoleic acid (CLA) at all ages. Correlations between dietary and serum eicosapentaenoic and/or docosahexaenoic acid were observed at 2 and 3 years of age. Serum linoleic acid was positively associated with the consumption of infant formula at the age of 1 year, and with the consumption of vegetable margarine at 2 and 3 years. The results indicate a high quality of the 3-day food records kept by parents and other caretakers of the children, and suitability of non-fasting, un-fractioned serum samples for total fatty acid analyses. The correlation between intake of milk fat and serum proportion of CLA is a novel finding.

The importance of type 2 diabetes prevention: The Norfolk Diabetes Prevention Study

Many large studies have investigated the prevention of type 2 diabetes in people at high risk of the condition, usually with changes in diet and physical activity levels. It is estimated that 2.25 million people in the UK have type 2 diabetes, with significant personal and healthcare costs, and the value of preventative measures in tackling this enormous public health challenge are well described. The Norfolk Diabetes Prevention Study (Norfolk DPS) will screen 10,000 people at risk of type 2 diabetes over five years, randomising 950 people with ‘pre-diabetes’ into a 36-month randomised controlled trial (three-armed study) of a novel diet and lifestyle intervention. The Norfolk DPS team is multidisciplinary and the intervention will be delivered by healthcare professionals in group settings. One arm will be part delivered by lay mentors who have existing type 2 diabetes. There is no UK-validated diet and lifestyle intervention for the prevention of type 2 diabetes in high risk groups that has been tested in a controlled trial, and an intervention delivered by those with existing type 2 diabetes has not been studied. The Norfolk DPS will provide further evidence in these areas.

The current state of lifestyle intervention implementation research: where do we go next?

In the USA, the prevalence of obesity is 33.8% [1] and type 2 diabetes is 27% [2]. The landmark Diabetes Prevention Program (DPP) showed that a lifestyle intervention facilitating a 7% weight loss had a significantly greater impact on diabetes risk than placebo or metformin with a risk reduction of 58% over 3 years [3]. Similar findings were reported in diabetes prevention studies in Finland and China [4, 5]. The impact of lifestyle interventions appears to be long term [3, 4]. In the 10-year follow-up of the DPP, the incidence of diabetes in the placebo and metformin groups (who had been offered the lifestyle intervention following the initial intervention period) fell to equal that of the lifestyle group; however, the cumulative incidence of diabetes remained lowest in the lifestyle group [6]. The China Da Qing Study revealed reduced incidence of diabetes from a lifestyle intervention at 20-year follow-up [5]. Widespread availability of lifestyle interventions could have a tremendous impact on public health.

Comparison of two insulin assays for first-phase insulin release in type 1 diabetes prediction and prevention studies

BackgroundDetection of below-threshold first-phase insulin release or FPIR (1+3 minute insulin concentrations during an intravenous glucose tolerance test [IVGTT]) is important in type 1 diabetes prediction and prevention studies including the TrialNet Oral Insulin Prevention Trial. We assessed whether an insulin immunoenzymometric assay (IEMA) could replace the less practical but current standard of a radioimmunoassay (RIA) for FPIR. MethodsOne hundred thirty-three islet autoantibody positive relatives of persons with type 1 diabetes underwent 161 IVGTTs. Insulin concentrations were measured by both assays in 1056 paired samples. A rule classifying FPIR (below-threshold, above-threshold, uncertain) by the IEMA was derived and validated against FPIR by the RIA. ResultsThe insulin IEMA-based rule accurately classified below- and above-threshold FPIRs by the RIA in 110/161 (68%) IVGTTs, but was uncertain in 51/161 (32%) tests for which FPIR by RIA is needed. An uncertain FPIR by the IEMA was more likely among below-threshold vs above-threshold FPIRs by the RIA (64% [30/47] vs. 18% [21/114], respectively; p<0.05). ConclusionsAn insulin IEMA for FPIR in subjects at risk for type 1 diabetes accurately determined below- and above-threshold FPIRs in 2/3 of tests relative to the current standard of the insulin RIA, but could not reliably classify the remaining FPIRs. TrialNet is limiting the insulin RIA for FPIR to the latter given the practical advantages of the more specific IEMA.

P2-125 Incidence of type 2 diabetes by HbA1c and OGTT: the Isfahan diabetes prevention study

AimsThe aim of this study was to estimate the incidence of type 2 diabetes using newly proposed haemoglobin A1C (HbA1c) and current oral glucose tolerance test (OGTT) definition in an...

Translating research evidence to service provision for prevention of type 2 diabetes: development and early outcomes of the ‘New life, New you’ intervention

We report the development and early outcomes of an innovative intervention, directed to people at risk of type 2 diabetes, delivered by fitness trainers in leisure and community settings in Middlesbrough, UK. Men and women aged 45 to 65, living in socio-economically disadvantaged areas were assessed for risk of type 2 diabetes and recruited to the intervention. Weight, height, waist circumference and physical activity were measured at baseline and six months. A social marketing campaign attracted 217 recruits. Baseline means (standard deviation; SD) were as follows: age 53.1(5.9) years, FINDRISC-score (a questionnaire-based prospective risk score to predict development of type 2 diabetes) 13.2 (3.3), body mass index 32.9 kgm2 (6.0), physical activity level 49.2 (6.4) self-report metabolic equivalent tasks (MET)-hours/day. Follow-up was completed by 144 participants with mean (SD) reduction in weight −2.2 kg (4.3) (95% confidence interval (CI) −3.0 to −1.5) and waist circumference −5.5 cm (4.5) (95% CI −6.6 to −4.5); increase in physical activity level +5.5 (5.4) (95% CI 4.5–6.4) self report MET-hours/day and variety +1.4 (1.2) (95% CI 1.1–1.6) activity types. High retention and positive outcomes at six months are indications of initial success. The interim results of this real-world intervention are comparable to early intermediate health outcomes in the European Diabetes Prevention Study (EDIPS)-Newcastle randomised controlled trial suggesting potential for translation of lifestyle intervention into practice. Longer term follow-up and controlled evaluation are warranted.

One-Year Results of a Community-Based Translation of the Diabetes Prevention Program

OBJECTIVEAlthough the Diabetes Prevention Program (DPP) and the Finnish Diabetes Prevention Study (FDPS) demonstrated that weight loss from lifestyle change reduces type 2 diabetes incidence in patients with prediabetes, the translation into community settings has been difficult. The objective of this study is to report the first-year results of a community-based translation of the DPP lifestyle weight loss (LWL) intervention on fasting glucose, insulin resistance, and adiposity.RESEARCH DESIGN AND METHODSWe randomly assigned 301 overweight and obese volunteers (BMI 25–40 kg/m2) with fasting blood glucose values between 95 and 125 mg/dL to a group-based translation of the DPP LWL intervention administered through a diabetes education program (DEP) and delivered by community health workers (CHWs) or to an enhanced usual-care condition. CHWs were volunteers with well-controlled type 2 diabetes. A total of 42.5% of participants were male, mean age was 57.9 years, 26% were of a race/ethnicity other than white, and 80% reported having an education beyond high school. The primary outcome is mean fasting glucose over 12 months of follow-up, adjusting for baseline glucose.RESULTSCompared with usual-care participants, LWL intervention participants experienced significantly greater decreases in blood glucose (−4.3 vs. −0.4 mg/dL; P < 0.001), insulin (−6.5 vs. −2.7 μU/mL; P < 0.001), homeostasis model assessment of insulin resistance (−1.9 vs. −0.8; P < 0.001), weight (−7.1 vs. −1.4 kg; P < 0.001), BMI (−2.1 vs. −0.3 kg/m2; P < 0.001), and waist circumference (−5.9 vs. −0.8 cm; P < 0.001).CONCLUSIONSThis translation of the DPP intervention conducted in community settings, administered through a DEP, and delivered by CHWs holds great promise for the prevention of diabetes by significantly decreasing glucose, insulin, and adiposity.

Innovation in rural health: Sound the trumpet!

The first three articles of this edition of the Australian Journal of Rural Health address important innovations in rural health. Gardner et al.1 review what is known about the challenges of implementing quality improvement programs and draws on data from a systematic continuous quality improvement project in remote communities in Australia and Fiji, known as Audit and Best practice for Chronic Disease (ABCD), to synthesise lessons and discuss the potential for broader application in low and middle income countries, including Pacific Island countries and territories. They argue that the participatory action research approach supports innovation and broad-based change and the evidence it has produced extends the current knowledge base and facilitates the translation of knowledge into action, both for policy and practice. Reddy and colleagues2 describe two real world diabetes prevention programs, one in Montana based on US Diabetes Prevention Program, the other in Australia based on the Finnish Diabetes Prevention Study – the two landmark randomised control trials. Using qualitative research, they sought to determine whether there were specific rural context issues involved in implementation in Montana and Victoria Australia. They conclude that there were some rural issues but overall diabetes prevention programs can be implemented in any setting urban or rural without major adaptation. Humphreys and Wakerman3 review what factors seem to contribute to successful and sustainable health systems in rural and remote communities drawing on evidence from Australia, Canada and the USA. They identify good governance, leadership and management, adequate funding infrastructure and service linkages as crucial for optimal workforce recruitment. Needs must – workforce shortages and other factors frequently lead to innovation in rural health simply because necessity is the mother of invention.4 These papers cover the two great questions of rural health – how much can we explain the disparity by understanding risk factors for chronic diseases and how much of the disparity is the result of poor access to services?5 The authors of these papers have made a substantial contribution to our understanding of how we can improve rural health. The Australian government has policies to reduce rural and remote health disparities. Medical Schools are funded to ensure that 25% of students complete 50% of their clinical training in rural areas. Eleven University Departments of Rural Health around the country have been established by the Government to improve the health, health services and workforce of rural and remote Australia. Disparities in health due to rurality are well recognised internationally but the causes and consequences are incompletely understood.5 What is it about rurality that explains increased morbidity and mortality? We still need to see a comparative study of risk factors that takes into account socioeconomic circumstances such as education, income and occupation to separate out the explanation for rural excess morbidity and mortality. We are fortunate to have the publicly funded infrastructure to be able to undertake research into rural health, health services and workforce. We have also come of age. In the first round of Centres for Research Excellence in Primary Health Care funded by the Australian Primary Health Care Research Institute, rural and remote researchers performed outstandingly.6 One centre is looking at accountable and equitable primary health care provision in rural and remote Australia, a second is looking at building quality, governance, performance and sustainability in primary health care, and the third looks at indigenous primary care interventions in chronic disease. Two of the centres are rurally or remotely based and the third has a large rural component. By comparison with University Departments of General Practice, University Departments of Rural Health are well represented including Broken Hill, Centre for Remote Health, Greater Green Triangle and the School of Rural Health Bendigo. Rural health research in Australia has come of age. A new model of rural research is emerging. Each of the Centres is a multisite collaboration frequently involving metropolitan colleagues with distinguished track records in research. The next five years will see a flourishing of rural and remote research particularly since the centres have a role in building capacity at the postdoctoral level. Sound the trumpet!

Impact of Intranasal Insulin on Insulin Antibody Affinity and Isotypes in Young Children With HLA-Conferred Susceptibility to Type 1 Diabetes

OBJECTIVEDespite promising results from studies on mouse models, intranasal insulin failed to prevent or delay the development of type 1 diabetes in autoantibody-positive children with HLA-conferred disease susceptibility. To analyze whether the insulin dose was inadequate to elicit an immunomodulatory response, we compared the changes observed in insulin antibody (IA) affinity and isotypes after treatment with nasal insulin or placebo.RESEARCH DESIGN AND METHODSNinety-five children (47 in the placebo group and 48 in the insulin group of the total of 224 children randomized for the trial) with HLA-conferred susceptibility to type 1 diabetes derived from the intervention arm of the Finnish Type 1 Diabetes Prediction and Prevention study were included in these analyses. Blood samples drawn before or at the beginning of the treatment and after treatment for 3 and 6 months were analyzed for IA affinity and isotype-specific IAs (IgG1–4, IgA, IgM, and IgE).RESULTSIgG3- and IgA-IA levels (P = 0.031 and 0.015, respectively) and the number of IgG3-IA–positive subjects (P = 0.022) were significantly higher at 6 months after the initiation of the treatment in the insulin group. No significant differences were observed between the two groups in IA affinity or other IA isotypes.CONCLUSIONSThe insulin dose administered induced a modest change in the IA isotype profile. The lack of impact of nasal insulin on IA affinity implies that the immune response of study subjects was already mature at the beginning of the intervention.

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

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. 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. 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. 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.

Long-Term Benefits From Lifestyle Interventions for Type 2 Diabetes Prevention

The potential to prevent type 2 diabetes in high-risk individuals by lifestyle intervention was established in several clinical trials. These studies had a strong focus on increased physical activity and dietary modification as well as weight reduction among overweight participants. The key issue seems to be a comprehensive approach to correct several risk factors simultaneously. Furthermore, long-term follow-up studies of lifestyle interventions lasting for a limited time period seem to have a long-lasting carry-over effect on risk factors and diabetes incidence (Table 1). View this table: Table 1 Long-term effectiveness of diabetes prevention trials The research evidence has inspired national and local authorities and health care providers all over the world to start programs and activities to prevent type 2 diabetes and its complications. Based on the experiences from the clinical trials, as well as from the “real world” implementation programs, the IMAGE (Development and Implementation of a European Guideline and Training Standards for Diabetes Prevention) Study Group collated information in a systematic manner. The IMAGE deliverables include a European evidence-based guideline for the prevention of type 2 diabetes, a toolkit for the prevention of type 2 diabetes in Europe, and the quality indicators for the prevention of type 2 diabetes in Europe. What is needed now is political support to develop national action plans for diabetes prevention. The prerequisites for successful prevention activities include involvement of a number of stakeholders on the governmental and nongovernmental level as well as on different levels of health care. Furthermore, structures to identify high-risk individuals and manage intervention, follow-up, and evaluation have to be established. Observational studies have provided firm evidence that multiple lifestyle-related factors either increase or decrease the risk of type 2 diabetes. Thus, in type 2 diabetes prevention, it is important to pay attention not only to one single factor such as obesity but …

Incidence of type 2 diabetes by HbA1c and OGTT: the Isfahan Diabetes Prevention Study

The aim of this study was to estimate the incidence of type 2 diabetes using newly proposed hemoglobin A(1C) (HbA(1c)) and current oral glucose tolerance test (OGTT) definition in an Iranian non-diabetic population. A total of 923 non-diabetic first-degree relatives (FDRs) of patients with type 2 diabetes 30-70 years old in 2003-2005 were followed through 2009 for the occurrence of type 2 diabetes. At baseline and through follow-ups, participants underwent a standard 75 g 2-h OGTT and HbA(1c) measurements. Prediction of progression to type 2 diabetes by OGTT-defined or HbA(1c)-defined diabetes was assessed with area under the receiver operating characteristic (ROC) curves based upon measurement of fasting plasma glucose, 2-h post-load glucose values, and HbA(1c). The prevalence of type 2 diabetes was 9.2% (95% CI: 8.2, 10.2) by OGTT-defined diabetes and 7.9% (95% CI: 6.9, 9.0) by HbA(1c) ≥ 6.5. The incidence of type 2 diabetes was 2.0% (95% CI: 1.6, 2.4) (1.8% men and 2.1% women) per year by the current OGTT definition, whereas the incidence rates were 1.7% (95% CI: 1.3, 2.0) (1.6% men and 1.7% women) per year by HbA(1c) ≥ 6.5%. Of those diagnosed with type 2 diabetes by OGTT, 69.6% had HbA(1c) <6.5% and therefore would not have been classified as having type 2 diabetes. The incidence and prevalence of diabetes using newly proposed HbA(1c) threshold in this FDRs of patients with type 2 diabetes were slightly lower than using current OGTT definition.

Receptor for advanced glycation end-products (RAGE) provides a link between genetic susceptibility and environmental factors in type 1 diabetes

This group of studies examines human genetic susceptibility conferred by the receptor for advanced glycation end-products (RAGE) in type 1 diabetes and investigates how this may interact with a western environment. We analysed the AGER gene, using 13 tag SNPs, in 3,624 Finnish individuals from the FinnDiane study, followed by AGER associations with a high risk HLA genotype (DR3)-DQA1*05-DQB1*02/DRB1*0401-DQB1*0302 (n = 546; HLA-DR3/DR4), matched in healthy newborn infants from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study (n = 373) using allelic analysis. We also studied islets and circulating RAGE in NODLt mice. The rs2070600 and rs17493811 polymorphisms predicted increased risk of type 1 diabetes, whereas the rs9469089 SNP was related to decreased risk, on a high risk HLA background. Children from the DIPP study also showed a decline in circulating soluble RAGE levels, at seroconversion to positivity for type 1 diabetes-associated autoantibodies. Islet RAGE and circulating soluble RAGE levels in prediabetic NODLt mice decreased over time and were prevented by the AGE lowering therapy alagebrium chloride. Alagebrium chloride also decreased the incidence of autoimmune diabetes and restored islet RAGE levels. These studies suggest that inherited AGER gene polymorphisms may confer susceptibility to environmental insults. Declining circulating levels of soluble RAGE, before the development of overt diabetes, may also be predictive of clinical disease in children with high to medium risk HLA II backgrounds and this possibility warrants further investigation in a larger cohort.

Impact of Positive Family History and Genetic Risk Variants on the Incidence of Diabetes

OBJECTIVEWe 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 METHODSA 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.RESULTSThe 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.CONCLUSIONSThese 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.

Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the Finnish Diabetes Prevention Study.

BackgroundAdiponectin, 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.MethodsParticipants 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.Resultsrs266729, 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.ConclusionsThese 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 numberClinicalTrials.gov NCT00518167

Normal fasting plasma glucose and risk of prediabetes and type 2 diabetes: the Isfahan Diabetes Prevention Study.

To determine the association of fasting plasma glucose (FPG) level within normal range and the risk of prediabetes and type 2 diabetes in an Iranian population. A total of 806 first-degree relatives (FDRs) of patients with type 2 diabetes who had FPG levels less than 5.6 mmol/l (100 mg/dl) in 2003 to 2005, and who did not have diabetes or impaired fasting glucose (IFG), were followed through 2010 for the occurrence of prediabetes or type 2 diabetes. At baseline and through follow-ups, participants underwent a standard 75 g 2-hour oral glucose tolerance test (OGTT). The incidence of type 2 diabetes, impaired glucose tolerance (IGT), and IFG was 9.6 (95% confidence interval (CI): 6.8-12.4), 28.7 (23.8-33.6), and 33.0 (27.7-38.2) per 1,000 person-years based on 4,489 person-years of follow-up, respectively. FPG was associated with the incidence of diabetes, IGT, and IFG. The multivariate-adjusted hazard ratios (95% CI) for diabetes, IGT, and IFG were 1.36 (1.01-1.84), 1.45 (1.10-1.91) and 1.31 (1.00-1.71), for the highest quintile of FPG compared with the lowest quintile, respectively. An increase in FPG in the normal range is associated with an increase in the incidence of IGT, IFG, and type 2 diabetes. These results prove FPG in the normal range to be useful in identifying apparently healthy FDRs of patients with type 2 diabetes at risk of developing prediabetes and diabetes.

HbA1c in diagnosing and predicting Type 2 diabetes in impaired glucose tolerance: the Finnish Diabetes Prevention Study

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. 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. 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) . 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.