Feature ranking of type 1 diabetes susceptibility genes improves prediction of type 1 diabetes

Aims/hypothesis

More than 40 regions of the human genome confer susceptibility for type 1 diabetes and could be used to establish population screening strategies. The aim of our study was to identify weighted sets of SNP combinations for type 1 diabetes prediction.

Methods

We applied multivariable logistic regression and Bayesian feature selection to the Type 1 Diabetes Genetics Consortium (T1DGC) dataset with genotyping of HLA plus 40 SNPs within other type 1 diabetes-associated gene regions in 4,574 cases and 1,207 controls. We tested the weighted models in an independent validation set (765 cases, 423 controls), and assessed their performance in 1,772 prospectively followed children.

Results

The inclusion of 40 non-HLA gene SNPs significantly improved the prediction of type 1 diabetes over that provided by HLA alone (p?=?3.1?×?10^?25), with a receiver operating characteristic AUC of 0.87 in the T1DGC set, and 0.84 in the validation set. Feature selection identified HLA plus nine SNPs from the PTPN22, INS, IL2RA, ERBB3, ORMDL3, BACH2, IL27, GLIS3 and RNLS genes that could achieve similar prediction accuracy as the total SNP set. Application of this ten SNP model to prospectively followed children was able to improve risk stratification over that achieved by HLA genotype alone.

Conclusions

We provided a weighted risk model with selected SNPs that could be considered for recruitment of infants into studies of early type 1 diabetes natural history or appropriately safe prevention.     

Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring

Aims/hypothesis

We evaluated the intake of vitamin D by pregnant Finnish women and examined associations between maternal intake of vitamin D and the development of advanced beta cell autoimmunity and type 1 diabetes in their offspring.

Methods

The research was carried out within the Diabetes Prediction and Prevention study (DIPP), which is a population-based birth cohort of infants at genetic risk of type 1 diabetes. Mothers of 3,723 infants born between 1997 and 2002 completed a validated 181-item food frequency questionnaire, which included questions on dietary supplements. The offspring were observed at 3 to 12 month intervals for the appearance of autoantibodies associated with type 1 diabetes and for the development of clinical type 1 diabetes.

Results

Maternal mean daily intake of vitamin D was 5.1 µg from food and 1.3 µg from supplements. The maternal intake of vitamin D, either from food or from supplements, was not associated with the risk of advanced beta cell autoimmunity/type 1 diabetes in offspring (HR [95% CI] for intake of vitamin D from food 1.25 [0.80–1.95], for vitamin D intake from supplements 1.05 [0.95–1.16]), or with the risk of type 1 diabetes alone (HR [95% CI] for intake of vitamin D from food 0.84 [0.41–1.72], for vitamin D intake from supplements 1.09 [0.99–1.20]).

Conclusions/interpretation

Maternal intake of vitamin D either from food or supplements during pregnancy is not associated with advanced beta cell autoimmunity/type 1 diabetes or with type 1 diabetes alone in Finnish offspring carrying increased genetic susceptibility to type 1 diabetes.     

Associations of maternal type 1 diabetes with childhood adiposity and metabolic health in the offspring: a prospective cohort study

Aims/hypothesis

Exposure to an intrauterine hyperglycaemic environment has been suggested to increase the offspring’s later risk for being overweight or having metabolic abnormalities, but conclusive evidence for pregnancies affected by maternal type 1 diabetes is still lacking. This study aims to analyse the relationship between maternal type 1 diabetes and the offspring’s metabolic health and investigate whether birthweight and/or changes in the offspring’s metabolome are in the potential pathway.

Methods

We analysed data from 610 and 2169 offspring having a first-degree relative with type 1 diabetes from the TEENDIAB and BABYDIAB/BABYDIET cohorts, respectively. Anthropometric and metabolic outcomes, assessed longitudinally at 0.3–18 years of age, were compared between offspring of mothers with type 1 diabetes and offspring of non-diabetic mothers but with fathers or siblings with type 1 diabetes using mixed regression models. Non-targeted metabolomic measurements were carried out in 500 individuals from TEENDIAB and analysed with maternal type 1 diabetes and offspring overweight status.

Results

The offspring of mothers with type 1 diabetes had a higher BMI SD score (SDS) and an increased risk for being overweight than the offspring of non-diabetic mothers (e.g. OR for overweight status in TEENDIAB 2.40 [95% CI 1.41, 4.06]). Further, waist circumference SDS, fasting levels of glucose, insulin and C-peptide, and insulin resistance and abdominal obesity were significantly increased in the offspring of mothers with type 1 diabetes, even when adjusted for potential confounders and birthweight. Metabolite patterns related to androgenic steroids and branched-chain amino acids were found to be associated with offspring’s overweight status, but no significant associations were observed between maternal type 1 diabetes and metabolite concentrations in the offspring.

Conclusions/interpretation

Maternal type 1 diabetes is associated with offspring’s overweight status and metabolic health in later life, but this is unlikely to be caused by alterations in the offspring’s metabolome.

     

Predicting major outcomes in type 1 diabetes: a model development and validation study

Aims/hypothesis

Type 1 diabetes is associated with a higher risk of major vascular complications and death. A reliable method that predicted these outcomes early in the disease process would help in risk classification. We therefore developed such a prognostic model and quantified its performance in independent cohorts.

Methods

Data were analysed from 1,973 participants with type 1 diabetes followed for 7 years in the EURODIAB Prospective Complications Study. Strong prognostic factors for major outcomes were combined in a Weibull regression model. The performance of the model was tested in three different prospective cohorts: the Pittsburgh Epidemiology of Diabetes Complications study (EDC, n?=?554), the Finnish Diabetic Nephropathy study (FinnDiane, n?=?2,999) and the Coronary Artery Calcification in Type 1 Diabetes study (CACTI, n?=?580). Major outcomes included major CHD, stroke, end-stage renal failure, amputations, blindness and all-cause death.

Results

A total of 95 EURODIAB patients with type 1 diabetes developed major outcomes during follow-up. Prognostic factors were age, HbA_1c, WHR, albumin/creatinine ratio and HDL-cholesterol level. The discriminative ability of the model was adequate, with a concordance statistic (C-statistic) of 0.74. Discrimination was similar or even better in the independent cohorts, the C-statistics being: EDC, 0.79; FinnDiane, 0.82; and CACTI, 0.73.

Conclusions/interpretation

Our prognostic model, which uses easily accessible clinical features can discriminate between type 1 diabetes patients who have a good or a poor prognosis. Such a prognostic model may be helpful in clinical practice and for risk stratification in clinical trials.     

Fertility in people with childhood-onset type 1 diabetes

Aims/hypothesis

To assess the number of live births in a population-based, retrospective cohort of women and men with childhood-onset type 1 diabetes, and matched controls.

Methods

The reproductive histories of people in a Finnish cohort of 2,307 women and 2,819 men with type 1 diabetes and two matched controls (for each case) were obtained from National Population Register data. All persons with diabetes were diagnosed with the disease in 1965–1979 at the age of 17 or under. A proportional hazards model was used to model the association between the rate of live births as a function of the age of an individual and the observed covariates (sex and age at onset of diabetes).

Results

Both women and men with diabetes had a smaller number of live births than the controls; the HR of having a first child for diabetic women compared with controls was 0.66 (95% CI 0.62, 0.71) and for men was 0.77 (95% CI 0.72, 0.83). In women, a birth cohort effect was detected; in more recent birth cohorts, the difference between diabetic women and controls as regards having children was significantly smaller than in earlier cohorts. Later age at onset of diabetes was associated with a higher rate of having a first child among men (p?=?0.04) and having a second live birth among women (p?=?0.002).

Conclusions/interpretation

Type 1 diabetes affects the number of live births in both women and men. The age at onset of diabetes is associated with the pattern of reproduction in both diabetic women and men.     

Confirmation of novel type 1 diabetes risk loci in families

Aims/hypothesis

Over 50 regions of the genome have been associated with type 1 diabetes risk, mainly using large case/control collections. In a recent genome-wide association (GWA) study, 18 novel susceptibility loci were identified and replicated, including replication evidence from 2,319 families. Here, we, the Type 1 Diabetes Genetics Consortium (T1DGC), aimed to exclude the possibility that any of the 18 loci were false-positives due to population stratification by significantly increasing the statistical power of our family study.

Methods

We genotyped the most disease-predicting single-nucleotide polymorphisms at the 18 susceptibility loci in 3,108 families and used existing genotype data for 2,319 families from the original study, providing 7,013 parent–child trios for analysis. We tested for association using the transmission disequilibrium test.

Results

Seventeen of the 18 susceptibility loci reached nominal levels of significance (p?p?=?0.055). When we allowed for multiple testing, ten of the 17 nominally significant loci reached the required level of significance (p??3). All susceptibility loci had consistent direction of effects with the original study.

Conclusions/interpretation

The results for the novel GWA study-identified loci are genuine and not due to population stratification. The next step, namely correlation of the most disease-associated genotypes with phenotypes, such as RNA and protein expression analyses for the candidate genes within or near each of the susceptibility regions, can now proceed.     

Use of class I and class II HLA loci for predicting age at onset of type 1 diabetes in multiple populations

Aims/hypothesis

The study aimed to assess, in multiple populations, the role of HLA alleles on early and late age at onset of type 1 diabetes.

Methods

Stepwise linear regression models were used to determine which HLA class I and class II risk alleles to include. High-resolution genotyping data for patients from the Type 1 Diabetes Genetics Consortium (T1DGC) collection (n?=?2,278) and four independent cohorts from Denmark, Sardinia and the USA (Human Biological Data Interchange [HBDI] and Joslin Diabetes Center) (n?=?1,324) (total n?=?3,602) were used to assess the role of HLA variation on age of onset and predict early onset (age ≤5?years) and late onset (age ≥15?years) of type 1 diabetes.

Results

In addition to carriage of HLA class I alleles A*24:02, B*39:06, B*44:03 and B*18:01, HLA class II DRB1-DQB1 loci significantly contributed to age at onset, explaining 3.4% of its variance in the combined data. HLA genotypes, together with sex, were able to predict late onset in all cohorts studied, with AUC values ranging from 0.58 to 0.63. Similar AUC values (0.59–0.70) were obtained for early onset for most cohorts, except in the Sardinian study, in which none of the models tested had significant predictive power.

Conclusions/interpretation

HLA associations with age of onset are consistent across most white populations and HLA information can predict some of the risk of early and late onset of type 1 diabetes. Considerable heterogeneity was observed between Sardinian and other populations, particularly with regard to early age of onset.     

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

Aims/hypothesis

Enterovirus (e.g. Coxsackie B virus serotypes [CVBs]) infections may be associated with development of type 1 diabetes. Studies conducted in several European countries have, however, shown an inverse correlation between the incidence of type 1 diabetes and the prevalence of enterovirus infections. These findings could in part be explained by an extension of the poliovirus hypothesis, suggesting that the absence of maternally transferred antibodies protecting offspring from early infection increases the risk for diabetes development. Experimental evidence supporting this hypothesis in type 1 diabetes is, however, lacking. As maternally transferred protection from infection is a crucial component of the extended poliovirus hypothesis, we here tested the hypothesis that previously infected females transfer protection against infection and diabetes to offspring.

Methods

The induction of CVB-specific maternal antibodies and transfer of protection from virus infection, replication and development of virus-induced diabetes to offspring was assessed using NOD and Socs1-transgenic NOD mice.

Results

Infected mice produced neutralising antibodies to CVB. Offspring from infected females were positive for neutralising antibodies and were strongly protected from both infection and experimental diabetes.

Conclusions/interpretation

Our study shows that maternally transferred antibodies protect offspring from enterovirus infection and virus-induced diabetes. This suggests that the absence of maternally provided protection increases the risk for severe outcomes after an enterovirus infection in offspring. Moreover, our findings may have implications for the design of prospective studies aimed at investigating the possible role of enterovirus infections in the aetiology of human type 1 diabetes.     

Risks of asphyxia-related neonatal complications in offspring of mothers with type 1 or type 2 diabetes: the impact of maternal overweight and obesity

Aims/hypothesis

We aimed to compare the risks of severe asphyxia-related neonatal complications in the offspring of mothers with type 1 or type 2 diabetes, and to assess the impact of maternal overweight/obesity on these risks.

Methods

This was a population-based study of 1,343,751 live-born singleton infants in Sweden between 1997 and 2011, including 5941 and 711 infants of mothers with type 1 and type 2 diabetes, respectively. ORs with 95% CIs were calculated for low Apgar score (0–6) at 5 min after birth, hypoxic ischaemic encephalopathy and neonatal seizures.

Results

The rates of a low Apgar score were 0.9%, 2.6% and 2.1% in the offspring of mothers without diabetes or with type 1 or type 2 diabetes, respectively. After controlling for maternal confounders (including BMI), the risk of a low Apgar score increased in the offspring of mothers with type 1 diabetes (OR 2.67, 95% CI 2.23, 3.20) but not in the offspring of mothers with type 2 diabetes (OR 1.25, 95% CI 0.66, 2.35). The ORs of hypoxic ischaemic encephalopathy or neonatal seizures were increased in the offspring of mothers with type 1 diabetes (OR 3.41, 95% CI 2.58, 4.49) and type 2 diabetes (OR 2.54, 95% CI 1.13, 5.69). Maternal overweight/obesity was a risk factor for asphyxia-related neonatal complications and low Apgar scores in the offspring of mothers with type 1 diabetes and mothers without diabetes.

Conclusions/interpretation

The risks of a low Apgar score and severe asphyxia-related neonatal complications are increased in the offspring of mothers with type 1 or type 2 diabetes. Maternal overweight/obesity is an important contributing factor.

     

Behandlung des Typ-2-Diabetes beim alten Patienten

Background

Type 2 diabetes is a disease which occurs more frequently with increasing age and is particularly influenced by the lifestyle of those affected in addition to a genetic disposition and age-related alterations.

Aim

The purpose of this article is to discuss the evidence for special characteristics of the therapy of type 2 diabetes in elderly patients.

Material and methods

The study is based on a literature survey and the guidelines of the“Deutsche Diabetes-Gesellschaft” (DDG, German Diabetes Society).

Results

There is increasingly more awareness of diabetes in advanced age not least due to the expected demographic changes. The therapeutic options in older patients with diabetes must be assessed depending on the achievable targets of therapy and comorbidities, in particular limited renal function.     

Associations between longevity of parents and glucose regulation in their offspring: the KORA S4/F4 Study

Aims

Type 2 diabetes was less prevalent in studies of the offspring of centenarians and a separate study of nonagenarian siblings. We examined whether this reduction would also be found when less extreme criteria of parental longevity (a lifespan of at least 80 years) were applied. Moreover, we looked for an association between parental longevity and incidence of dysglycaemia, which has not yet been reported for a population-based study group.

Methods

Baseline and 7-year follow-up data on 55–74-year-old participants in the population-based German Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort study were used for the analyses. Participants whose parents had died from traumatic causes were excluded. Diabetes was assessed by validated physician diagnosis or OGTTs. Using logistic regression models, adjusted OR and 95% CIs were calculated for the associations between parental longevity and the prevalence or incidence of dysglycaemia, which was defined as including either type 2 diabetes or prediabetes (defined in this study as comprising impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]).

Results

In age- and sex-adjusted models, the prevalence of type 2 diabetes was lower in individuals with one (OR 0.63, 95% CI 0.43, 0.93) or two (OR 0.46, 95% CI 0.25, 0.85) long-lived parents. Among participants with normal glucose tolerance at baseline, the odds of incident dysglycaemia were lower in those with one (OR 0.65, 95% CI 0.40, 1.03) or two long-lived parents (OR 0.46, 95% CI 0.22, 0.96) after adjustment for age and sex.

Conclusions/interpretation

This study showed that longevity of the parents, defined by a lifespan of at least 80 years, was associated with a lower prevalence and incidence of dysglycaemia in their offspring in an older German population.     

The type 1 diabetes protective HLA DQB1*0602 allele is less frequent in gestational diabetes mellitus

Aims/hypothesis

We tested whether gestational diabetes mellitus (GDM) is associated with HLA-DQ genotypes.

Methods

A total of 764 mothers with non-autoimmune (GAD65, insulinoma-associated protein 2 [IA-2] and insulin autoantibody-negative) GDM were ascertained between September 2000 and August 2004 in the population-based Diabetes Prediction in Skåne (DiPiS) study. HLA-DQB1 genotypes were determined in these mothers and in 1191 randomly selected non-diabetic control mothers also negative for islet autoantibodies. The data were analysed in relation to maternal age, country of birth, number of pregnancies/siblings and pregnancy weight gain.

Results

The frequency of type 1 diabetes high-risk HLA-DQ alleles (DQB1*0201, DQB1*0302) did not differ between GDM mothers and controls. In contrast, the low-risk DQB1*0602 allele was less prevalent (OR 0.64, 95% CI?=?0.51–0.80, p?=?0.0006) in GDM than in control mothers. The difference in DQB1*0602 frequency between GDM mothers and controls remained after multiple logistic regression analysis correcting for maternal age, country of birth, number of pregnancies/siblings and weight gain during pregnancy (OR 0.67, 95% CI 0.51–0.88, p?=?0.009).

Conclusions/interpretation

The negative association between mothers who have non-autoimmune GDM and HLA-DQ*0602 suggest that this allele may protect not only from type 1 diabetes but also from GDM.

     

Prevalence of retinopathy in patients with type 1 diabetes diagnosed before and after puberty

Aims

There is conflicting evidence to support the concept that the years with diabetes preceding puberty may not contribute to the development of vascular complications. In this paper, duration-related prevalence of retinopathy was compared in patients who developed type 1 diabetes before and after pubertal age.

Methods

Retrospective analysis of prospectively collected data of 1,483 patients was screened for retinopathy in 1991–2010, with diabetes onset at age ≤29, who were on insulin treatment and aged ≤60. Prepubertal age was defined as 0–12 in males and 0–11 in females.

Results

A total of 647 patients had developed diabetes before and 836 after puberty. Cumulative prevalence of retinopathy was initially lower among those with prepubertal onset diabetes but rates became superimposable after 20-year duration. Patients with prepubertal onset diabetes had higher lifetime HbA1c and lower blood pressure than those who became diabetic after puberty.

Conclusions/interpretation

Retinopathy is infrequent during childhood and develops later than in patients with post-pubertal onset diabetes. After 20-year duration, however, retinopathy becomes just as prevalent suggesting that, in the long term, prepubertal years do contribute to the development of retinopathy. In this series, higher blood pressure may have played a role in the earlier appearance of retinopathy in patients with diabetes onset after puberty, whereas worse metabolic control may have contributed to the late “catch-up” effect in those with prepubertal onset disease.     

Maternal smoking during pregnancy and the risk of childhood type 1 diabetes in Western Australia

Aims/hypothesis

The aim of this study was to investigate the association between maternal smoking during pregnancy and type 1 diabetes in the offspring, using complete population data sources available in Western Australia.

Methods

A prospective cohort study was undertaken with cases defined as children born in Western Australia between 1998 and 2008 who were diagnosed with type 1 diabetes at <15 years of age up to 31 December 2010. Eligible cases were identified from the prospective, population-based Western Australian Children’s Diabetes Database. Record linkage was performed to identify perinatal records of cases from the Western Australian Midwives’ Notification System, which contains data on >99% of all births in Western Australia. Cox regression was used to analyse the data and adjust for recognised risk factors such as birthweight, gestational age, maternal age and socioeconomic status.

Results

The unadjusted HR for babies born to mothers who smoked during pregnancy being diagnosed with childhood type 1 diabetes was 0.70 (95% CI: 0.50, 0.97). After adjustment, the confidence interval widened but the point estimate remained relatively unchanged at 0.76 (95% CI: 0.54, 1.08).

Conclusions/interpretation

Analyses of data from this population-based study indicate that maternal smoking during pregnancy may be associated with a reduced risk of childhood type 1 diabetes. Further investigation in larger populations with more detailed smoking data could lead to novel hypotheses regarding mechanisms that influence the immunopathogenesis of type 1 diabetes in early life.     

HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus

Aims/hypothesis

In this study the involvement of oxidative stress in type 1 diabetes mellitus autoimmunity and the possible association with rheumatoid arthritis (RA) was investigated. We tested the hypothesis that oxidative stress induced by chronic hyperglycaemia triggers post-translational modifications and thus the formation of neo-antigens in type 1 diabetes, similar to the ones found in RA.

Methods

Collagen type II (CII), a known autoantigen in RA, was treated with ribose and various reactive oxygen species (ROS). Levels of antibodies specific to native and ROS-modified CII (ROS-CII) were compared in type 1 diabetes, type 2 diabetes and healthy controls, and related to the HLA genotype.

Results

Significantly higher binding to ROS-CII vs native CII was observed in type 1 diabetic patients possessing the HLA-DRB1*04 allele irrespective of variables of glucose control (blood glucose or HbA_1c). Type 1 diabetic patients carrying a DRB1*04 allele with the shared epitope showed the highest risk for ROS-CII autoimmunity, while the DRB1*0301 allele was protective. Conversely, native CII autoimmunity was not associated with any specific DRB1 allele. Positive and inverse seroconversion rates of response to ROS-CII were high in DRB1*04-positive type 1 diabetic patients.

Conclusion

Hyperglycaemia and oxidative stress may trigger genetically controlled autoimmunity to ROS-CII and may explain the association between type 1 diabetes mellitus and RA.     

Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data

Aims/hypothesis

We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes.

Methods

Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies.

Results

Data were available for 29 predominantly European studies (five cohort, 24 case–control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01–1.11]; p?=?0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04–1.19]; p?=?0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00–1.06]; p?=?0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings.

Conclusions/interpretation

Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.     

Association between maternal folate concentrations during pregnancy and insulin resistance in Indian children

Aims/hypothesis

In an Indian birth cohort, higher maternal homocysteine concentration in pregnancy was associated with lower birthweight of the offspring. Lower maternal vitamin B12 and higher folate concentrations were associated with higher offspring insulin resistance. Disordered one-carbon metabolism during early development may increase later metabolic risk. We explored these associations in another birth cohort in India at three age points.

Methods

We measured plasma vitamin B12, folate and homocysteine concentrations at 30?±?2 weeks’ gestation in 654 women who delivered at one hospital. Neonatal anthropometry was recorded, and the children’s glucose and insulin concentrations were measured at 5, 9.5 and 13.5 years of age. Insulin resistance was estimated using HOMA of insulin resistance (HOMA-IR).

Results

Maternal homocysteine concentrations were inversely associated with all neonatal anthropometric measurements (p?<?0.05), and positively associated with glucose concentrations in the children at 5 (30 min; p?=?0.007) and 9.5 years of age (120 min; p?=?0.02). Higher maternal folate concentrations were associated with higher HOMA-IR in the children at 9.5 (p?=?0.03) and 13.5 years of age (p?=?0.03). Maternal vitamin B12 concentrations were unrelated to offspring outcomes.

Conclusions/interpretation

Maternal vitamin B12 status did not predict insulin resistance in our cohort. However, associations of maternal homocysteine and folate concentrations with birth size, and with childhood insulin resistance and glycaemia in the offspring, suggest a role for nutritionally driven disturbances in one-carbon metabolism in fetal programming of diabetes.     

N-terminal pro-brain natriuretic peptide and risk of cardiovascular events in older patients with type 2 diabetes: the Edinburgh Type 2 Diabetes Study

Aims/hypothesis

The aim of this study was to investigate the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with traditional cardiovascular risk factors and incident cardiovascular events in older people with type 2 diabetes.

Methods

In the prospective phase of the Edinburgh Type 2 Diabetes Study, 1066 men and women aged 60 to 75 years with type 2 diabetes mellitus were followed for 4 years; 112 participants had an incident cardiovascular event. At baseline, cardiovascular risk factors, pre-existing cardiovascular disease and levels of NT-proBNP were evaluated.

Results

Raised plasma NT-proBNP levels were associated with these classical cardiovascular risk factors: increased duration of diabetes, use of insulin, raised BMI, reduced HDL-cholesterol, reduced renal function and use of lipid-lowering and anti-hypertensive medication (all p?Conclusions/interpretation In older people with type 2 diabetes, NT-proBNP is associated with the development of coronary and cerebrovascular events, independent of a wide range of other vascular and metabolic risk factors, and may prove a useful addition to current vascular risk scores in diabetes populations.