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Aims/hypothesis The aim of this study was to assess the interaction between genetic risk and lifestyle intervention on the occurrence of gestational diabetes mellitus (GDM) and postpartum diabetes. Methods The RADIEL study is an RCT aimed at prevention of GDM and postpartum diabetes through lifestyle intervention. Participants with a BMI ≥30 kg/m2 and/or prior GDM were allocated to intervention and control groups before pregnancy or in early pregnancy. The study visits took place every 3 months before pregnancy, once in each trimester, and at 6 weeks and 6 and 12 months postpartum. We calculated a polygenic risk score (PRS) based on 50 risk variants for type 2 diabetes. Results Altogether, 516 participants provided genetic and GDM data. The PRS was associated with higher glycaemic levels (fasting glucose and/or HbA1c) and a lower insulin secretion index in the second and third trimesters and at 12 months postpartum, as well as with a higher occurrence of GDM and glycaemic abnormalities at 12 months postpartum (n = 356). There was an interaction between the PRS and lifestyle intervention (p=0.016 during pregnancy and p=0.024 postpartum) when analysing participants who did not have GDM at the first study visit during pregnancy (n = 386). When analysing women in tertiles according to the PRS, the intervention was effective in reducing the age-adjusted occurrence of GDM only among those with the highest genetic risk (OR 0.37; 95% CI 0.17, 0.82). The risk of glycaemic abnormalities at 12 months postpartum was reduced in the same group after adjusting additionally for BMI, parity, smoking and education (OR 0.35; 95% CI 0.13, 0.97). Conclusions/interpretation Genetic predisposition to diabetes modifies the response to a lifestyle intervention aimed at prevention of GDM and postpartum diabetes. This suggests that lifestyle intervention may benefit from being tailored according to genetic risk. Clinical trial registration ClinicalTrials.gov identifier: NCT01698385 Graphical abstract

Background To explore long-term cardiovascular prognosis after myocardial infarction (MI) among patients with type 1 diabetes. Methods Patients with type 1 diabetes surviving 90 days after MI (n = 1508; 60% male, mean age = 62.1 years) or without any type of diabetes (n = 62,785) in Finland during 2005–2018 were retrospectively studied using multiple national registries. The primary outcome of interest was a combined major adverse cardiovascular event (MACE; cardiovascular death, recurrent MI, ischemic stroke, or heart failure hospitalization) studied with a competing risk Fine-Gray analyses. Median follow-up was 3.9 years (maximum 12 years). Differences between groups were balanced by multivariable adjustments and propensity score matching (n = 1401 patient pairs). Results Cumulative incidence of MACE after MI was higher in patients with type 1 diabetes (67.6%) compared to propensity score-matched patients without diabetes (46.0%) (sub-distribution hazard ratio [sHR]: 1.94; 95% confidence interval [CI]: 1.74–2.17; p Conclusions Patients with type 1 diabetes have notably poorer long-term cardiovascular prognosis after an MI compared to patients without diabetes. These results underline the importance of effective secondary prevention after MI in patients with type 1 diabetes.

Graphical abstract It has been known for decades that social networks are causally related to disease and mortality risk. However, this field of research and its potential for implementation into diabetes care is still in its infancy. In this narrative review, we aim to address the state-of-the-art of social network research in type 2 diabetes prevention and care. Despite the diverse nature and heterogeneity of social network assessments, we can draw valuable lessons from the available studies. First, the structural network variable ‘living alone’ and the functional network variable ‘lack of social support’ have been associated with increased type 2 diabetes risk. The latter association may be modified by lifestyle risk factors, such as obesity, low level of physical activity and unhealthy diet. Second, smaller network size and less social support is associated with increased risk of diabetes complications, particularly chronic kidney disease and CHD. Third, current evidence shows a beneficial impact of social support on diabetes self-management. In addition, social support interventions were found to have a small, favourable effect on HbA1c values in the short-term. However, harmonisation and more detailed assessment of social network measurements are needed to utilise social network characteristics for more effective prevention and disease management in type 2 diabetes. Supplementary Information The online version contains a slideset of the figures for download available at 10.1007/s00125-021-05496-2.

BackgroundTo develop targeted and tailored interventions for addressing medication non-adherence, it is important to identify underlying factors.ObjectiveTo identify factors associated with non-adherence as well as subtypes of non-adherence to antihypertensive or antihyperlipidemic drugs among patients with type 2 diabetes in Indonesia.DesignAn observational multicenter cross-sectional survey.ParticipantsPatients with type 2 diabetes using either antihypertensive or antihyperlipidemic drugs in four regions in Indonesia.Main MeasuresNon-adherence and its subtypes of intentional and unintentional non-adherence were assessed using the Medication Adherence Report Scale. Necessity and concern beliefs were assessed with the Beliefs about Medicines Questionnaire. We applied binary and multinomial logistic regression to assess associations of medication beliefs, sociodemographic factors, and clinical-related factors to non-adherence and report odds ratios (OR) with 95% confidence intervals (CI).Key ResultsOf 571 participating patients (response rate 97%), 45.5% and 52.7% were non-adherent to antihypertensive and antihyperlipidemic drugs, respectively. Older age was associated with non-adherence to antihypertensive drugs (60–69 years) (OR, 5.65; 95% CI, 2.68–11.92), while higher necessity beliefs (OR, 0.92; 95% CI, 0.88–0.95) were associated with less non-adherence. Factors associated with non-adherence to antihyperlipidemic drugs were female gender (OR, 1.84; 95% CI, 1.03–3.27) and higher concern beliefs (OR, 1.10; 95% CI, 1.03–1.18), while higher necessity beliefs (OR, 0.89; 95% CI, 0.83–0.96) were associated with less non-adherence.ConclusionsThe main factors associated with non-adherence to antihypertensive and antihyperlipidemic drugs are modifiable. In general, beliefs about the necessity of the drug are important but for antihyperlipidemic drugs concerns are important as well. Healthcare providers should pay attention to identify and address medication beliefs during patient counselling.

Purpose: This literature review is aimed at examining the benefits of lifestyle modifications in preventing recurrent gestational diabetes (GDM). Worldwide GDM affects approximately 16.2% of all pregnancies with significant maternal, fetal and neonatal complications. Almost two thirds of pregnant women with GDM will develop type 2 diabetes mellitus (T2DM) in the years following pregnancy. The proportion of women affected by GDM is on the rise and reflects increasing trends in T2DM as well as adult and childhood obesity. Methods: Using predefined subject headings, we searched for relevant articles from the PubMed, Scopus, and Cochrane databases. Results: For high-risk women lifestyle modifications, such as dietary and exercise changes, are the mainstay of treatment to reduce negative outcomes for both women and their pregnancies. This includes reducing the incidence of recurrent GDM and future T2DM by intervening during pregnancy and in the postnatal period. Conclusion: This review provides an overview of the literature to date, discusses different targeted approaches and how these interventions can optimise their benefits, and where further research is required.

Background In stable patients with type 2 diabetes (T2D), insulin treatment is associated with elevated risk for major adverse cardiovascular events (MACE). Patients with acute coronary syndrome (ACS) and T2D are at particularly high risk for recurrent MACE despite evidence-based therapies. It is uncertain to what extent this risk is further magnified in patients with recent ACS who are treated with insulin. We examined the relationship of insulin use to risk of MACE and modification of that risk by apabetalone, a bromodomain and extra-terminal (BET) protein inhibitor. Methods The analysis utilized data from the BETonMACE phase 3 trial that compared apabetalone to placebo in patients with T2D, low HDL cholesterol, andACS. The primary MACE outcome (cardiovascular death, myocardial infarction, or stroke) was examined according to insulin treatment and assigned study treatment. Multivariable Cox regression was used to determine whether insulin use was independently associated with the risk of MACE. Results Among 2418 patients followed for median 26.5 months, 829 (34.2%) were treated with insulin. Despite high utilization of evidence-based treatments including coronary revascularization, intensive statin treatment, and dual antiplatelet therapy, the 3-year incidence of MACE in the placebo group was elevated among insulin-treated patients (20.4%) compared to those not-treated with insulin (12.8%, P = 0.0001). Insulin treatment remained strongly associated with the risk of MACE (HR 2.10, 95% CI 1.42–3.10, P = 0.0002) after adjustment for demographic, clinical, and treatment variables. Apabetalone had a consistent, favorable effect on MACE in insulin-treated and not insulin-treated patients. Conclusion Insulin-treated patients with T2D, low HDL cholesterol, and ACS are at high risk for recurrent MACE despite the use of evidence-based, contemporary therapies. A strong association of insulin treatment with risk of MACE persists after adjustment for other characteristics associated with MACE. There is unmet need for additional treatments to mitigate this risk. Trial registration ClinicalTrials.gov NCT02586155, registered October 26, 2015

Aims/hypothesis Diabetes is associated with an increased risk of dementia. We estimated the potential impact of trends in diabetes prevalence upon mortality and the future burden of dementia and disability in England and Wales. Methods We used a probabilistic multi-state, open cohort Markov model to integrate observed trends in diabetes, cardiovascular disease and dementia to forecast the occurrence of disability and dementia up to the year 2060. Model input data were taken from the English Longitudinal Study of Ageing, Office for National Statistics vital data and published effect estimates for health-state transition probabilities. The baseline scenario corresponded to recent trends in obesity: a 26% increase in the number of people with diabetes by 2060. This scenario was evaluated against three alternative projected trends in diabetes: increases of 49%, 20% and 7%. Results Our results suggest that changes in the trend in diabetes prevalence will lead to changes in mortality and incidence of dementia and disability, which will become visible after 10–15 years. If the relative prevalence of diabetes increases 49% by 2060, expected additional deaths would be approximately 255,000 (95% uncertainty interval [UI] 236,000–272,200), with 85,900 (71,500–101,600) cumulative additional cases of dementia and 104,900 (85,900–125,400) additional cases of disability. With a smaller relative increase in diabetes prevalence (7% increase by 2060), we estimated 222,200 (205,700–237,300) fewer deaths, and 77,000 (64,300–90,800) and 93,300 (76,700–111,400) fewer additional cases of dementia and disability, respectively, than the baseline case of a 26% increase in diabetes. Conclusions/interpretation Reducing the burden of diabetes could result in substantial reductions in the incidence of dementia and disability over the medium to long term.

Diabetes mellitus (DM) could cause pilot incapacitation and result in aviation fatalities. The mechanisms could be directly as a consequence of acute hypoglycemia/subacute diabetic ketoacidosis (DKA) or indirectly as an acute cardiovascular event by contributing to the development of atherosclerosis in coronary or carotid and cerebral arteries. In this study, DM-related fatal flight accidents in the US National Transport Bureau's database between years 2011-2016 were analyzed with special emphasis on postmortem (PM) glucose levels and correlation of toxicological reports with anamnestic information on DM. Additionally, autopsy results on coronary arteries were reviewed. In 43 out of 1491 (similar to 3%) fatal accidents pilots had DM. Postmortem glucose or glycated hemoglobin percentage (Hb1Ac) was measured in 12 of the 43 cases; while antidiabetic medication was found in 14 of the cases (only two of the cases had both glucose measurements and medication). With the increasing prevalence of DM, a possibility of pilot incapacitation due to DM or complications of DM should be actively studied, even if no anamnestic information of DM was available. While PM hypoglycemia is difficult to assess, we propose a systematic investigation based on measurement of glucose, Hb1Ac%, and ketone bodies, and documentation of atherosclerotic lesions in major arteries to identify or rule out DM as a cause of pilot incapacitation.

Aims/hypothesis This study aimed to assess the use of ambulatory BP monitoring (ABPM) to identify the presence of masked, nocturnal and white-coat hypertension in individuals with type 1 diabetes, patterns that could not be detected by regular office-based BP monitoring alone. We also analysed associations between BP patterns and arterial stiffness in order to identify individuals at cardiovascular risk. Methods This substudy included 140 individuals with type 1 diabetes from the Helsinki metropolitan area, who attended the Finnish Diabetic Nephropathy Study (FinnDiane) Centre in Helsinki between January 2013 and August 2017. Twenty-four hour ABPM and pulse wave analysis were performed simultaneously using a validated non-invasive brachial oscillometric device (Mobil-O-Graph). Definitions of hypertension were based on the European Society of Hypertension guidelines. Masked hypertension was defined as normal office BP (BP obtained using a standardised automated BP device) but elevated 24 h ABPM, and white-coat hypertension as elevated office BP but normal 24 h ABPM. Results A total of 38% of individuals were normotensive and 33% had sustained hypertension, while 23% had masked and 6% had white-coat hypertension. About half of the cohort had increased absolute levels of night-time BP, half of whom were untreated. In the ambulatory setting, central BP and pulse wave velocity (PWV) were higher in participants with masked hypertension than in those with normotension (p

Aims/hypothesis The aim of this study was to develop a core outcome set (COS) for trials and other studies evaluating the effectiveness of prepregnancy care for women with pregestational (pre-existing) diabetes mellitus. Methods A systematic literature review was completed to identify all outcomes reported in prior studies in this area. Key stakeholders then prioritised these outcomes using a Delphi study. The list of outcomes included in the final COS were finalised at a face-to-face consensus meeting. Results In total, 17 outcomes were selected and agreed on for inclusion in the final COS. These outcomes were grouped under three domains: measures of pregnancy preparation (n = 9), neonatal outcomes (n = 6) and maternal outcomes (n = 2). Conclusions/interpretation This study identified a COS essential for studies evaluating prepregnancy care for women with pregestational diabetes. It is advocated that all trials and other non-randomised studies and audits in this area use this COS with the aim of improving transparency and the ability to compare and combine future studies with greater ease. Electronic supplementary material The online version of this article (doi:10.1007/s00125-017-4277-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Urinary albumin excretion is an early sign of diabetic kidney disease, affecting every third individual with diabetes. Despite substantial estimated heritability, only variants in the GLRA3 gene have been genome-wide significantly associated (p-value −8) with diabetic albuminuria, in Finnish individuals with type 1 diabetes; However, replication attempt in non-Finnish Europeans with type 1 diabetes showed nominally significant association in the opposite direction, suggesting a population-specific effect, but simultaneously leaving the finding controversial. In this study, the association between the common rs10011025 variant in the GLRA3 locus, and albuminuria, was confirmed in 1259 independent Finnish individuals with type 1 diabetes (p = 0.0013), and meta-analysis of all Finnish individuals yielded a genome-wide significant association. The association was particularly pronounced in subjects not reaching the treatment target for blood glucose levels (HbA1c > 7%; N = 2560, p = 1.7 × 10−9). Even though further studies are needed to pinpoint the causal variants, dissecting the association at the GLRA3 locus may uncover novel molecular mechanisms for diabetic albuminuria irrespective of population background.

Background Maternal vitamin D status has been associated with both gestational diabetes mellitus (GDM) and fetal growth restriction, however, the evidence is inconsistent. In Finland, maternal vitamin D status has improved considerably due to national health policies. Our objective was to compare maternal 25-hydroxy vitamin D concentrations [25(OH)D] between mothers with and without GDM, and to investigate if an association existed between maternal vitamin D concentration and infant birth size. Methods This cross-sectional study included 723 mother-child pairs. Mothers were of Caucasian origin, and infants were born at term with normal birth weight. GDM diagnosis and birth size were obtained from medical records. Maternal 25(OH)D was determined on average at 11 weeks of gestation in pregnancy and in umbilical cord blood (UCB) at birth. Results GDM was observed in 81 of the 723 women (11%). Of the study population, 97% were vitamin D sufficient [25(OH)D ≥ 50 nmol/L]. There was no difference in pregnancy 25(OH)D concentration between GDM and non-GDM mothers (82 vs 82 nmol/L, P = 0.99). Regression analysis confirmed no association between oral glucose tolerance test results and maternal 25(OH)D (P > 0.53). Regarding the birth size, mothers with optimal pregnancy 25(OH)D (≥ 80 nmol/L) had heavier newborns than those with suboptimal pregnancy 25(OH)D (P = 0.010). However, mothers with optimal UCB 25(OH)D had newborns with smaller head circumference than those with suboptimal 25(OH)D (P = 0.003), which was further confirmed as a linear association (P = 0.024). Conclusions Maternal vitamin D concentration was similar in mothers with and without GDM in a mostly vitamin D sufficient population. Associations between maternal vitamin D status and birth size were inconsistent. A sufficient maternal vitamin D status, specified as 25(OH)D above 50 nmol/L, may be a threshold above which the physiological requirements of pregnancy are achieved. Trial registration The project protocol is registered in ClinicalTrials.gov in November 8, 2012 (NCT01723852). Electronic supplementary material The online version of this article (10.1186/s12884-017-1600-5) contains supplementary material, which is available to authorized users.

Aims/hypothesis The aim of this study was to evaluate the relationship among age at onset of diabetes, age at onset of menarche and risk of diabetic nephropathy and laser-treated retinopathy in type 1 diabetes. Methods Data related to age at menarche were collected through questionnaires and were available for 1,304 women who participated in the Finnish Diabetic Nephropathy Study (FinnDiane). A possible association between age at menarche and diabetic nephropathy and retinopathy was investigated. Results There was an inverse relationship between the age at onset of diabetes and age at menarche: the younger the age at onset of diabetes, the higher the age at menarche (p mean age+ 2 years) had a 2.30 (95% CI 1.27, 4.17; p

Background Microvascular disease is associated with a high risk of macrovascular events in patients with type 2 diabetes, but the impact of macrovascular disease on the risk of microvascular events remains unknown. We sought to evaluate the respective effects of prior microvascular and macrovascular disease on the risk of major outcomes, including microvascular events, in these patients. Methods Participants in the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) trial (n = 11,140) and the ADVANCE-ON post-trial study (n = 8494) were categorized into 4 groups at baseline: dual absence of microvascular or macrovascular disease (n = 6789), presence of microvascular disease alone (n = 761), macrovascular disease alone (n = 3196), and both (n = 394). Outcomes were all-cause mortality, major macrovascular events (MACE), and major clinical microvascular events. Results All-cause mortality, MACE, and major clinical microvascular events occurred in 2265 (20%), 2166 (19%), and 807 (7%) participants respectively, during a median follow-up of 9.9 (inter-quartile interval 5.6–10.9) years. The adjusted hazard ratios [95% CI] of death, MACE, and major clinical microvascular events were each greater in patients with baseline microvascular disease (1.43 [1.20–1.71], 1.64 [1.37–1.97], and 4.74 [3.86–5.82], respectively), macrovascular disease (1.43 [1.30–1.57], 2.04 [1.86–2.25], and 1.26 [1.06–1.51]) or both (2.01 [1.65–2.45], 2.92 [2.40–3.55], and 6.30 [4.93–8.06]) compared with those without these conditions. No interaction was observed between baseline microvascular and macrovascular disease for these events. The addition of microvascular disease (change in c-statistic [95% CI] 0.005 [0.002–0.008], p = 0.02) or macrovascular disease (0.005 [0.002–0.007], p

BACKGROUND: The reactive hyperemia peripheral artery tonometry (RH-PAT) is a newly developed method for non-invasive endothelial function assessment. OBJECTIVE: The goal of this study is to determine whether a significant difference in RH-PAT score is present between adolescents with type 1 diabetes (T1D) in comparison with controls. SUBJECTS AND METHODS: Thirty-four adolescents with T1D and 25 control subjects (age 12-20 years) underwent RH-PAT endothelial function testing after an overnight fast. Height, weight, body mass index (BMI), blood pressure (BP), fasting lipid profile, Tanner stage, and glucose level were determined in each child. RESULTS: Adolescents with T1D had significantly lower RH-PAT scores compared to healthy controls, and this difference remained significant when overweight cases were not considered (p < 0.05). This difference was also observed in the female subgroup (p = 0.005). The interindividual variability in RH-PAT observations in T1D cases was not explained by BMI standard deviation score (SDS), BP SDS, age, duration of T1D, hemoglobin A1c, triglycerides, and pubertal stage, respectively. CONCLUSIONS: The RH-PAT technique is used as a non-invasive test to assess for early vascular changes in high-risk patient groups. Endothelial dysfunction, measured by RH-PAT, was present in diabetic adolescent, especially in the female subgroup. Although additional longitudinal studies are required, early detection of this reversible process may have therapeutic and prognostic implications. ispartof: European Journal of Pediatrics vol:172 issue:8 pages:1017-1022 ispartof: location:Germany status: published

AIMS/HYPOTHESIS: The aim of this study was to examine the association of physical activity (PA) with all-cause mortality and incident and prevalent cardiovascular disease (CVD) among patients with type 1 diabetes. METHODS: The EURODIAB Prospective Complications Study is a cohort including 3,250 male and female patients with type 1 diabetes (mean age 32.7¿±¿10.2 years) from 16 European countries, of whom 1,880 participated in follow-up examinations. In analysis 1 (longitudinal), the association of baseline PA (based on the reported number of hours per week spent in mild, moderate and vigorous PA) with all-cause mortality and incident CVD was examined by performing survival analysis. In analysis 2 (cross-sectional), we focused on the association between PA at follow-up (data on sports, walking distance and regular bicycling) and prevalent CVD by performing logistic regression analysis. Adjustments were made for age, sex, BMI, smoking, consumption of alcohol, consumption of certain nutrients and diabetic complications. RESULTS: Analysis 1 (longitudinal): participation in moderate or vigorous PA once a week or more was borderline inversely associated with all-cause mortality (men and women combined) (HR 0.66, 95% CI 0.42, 1.03) and incident CVD (women only) (HR 0.66, 95% CI 0.40, 1.08). No association was found in men. Analysis 2 (cross-sectional): total PA (indexed by sports, walking, bicycling) and distance walked were inversely associated with prevalent CVD (OR(totalPA) 0.66, 95% CI 0.45, 0.97; and OR(walking) 0.61, 95% CI 0.42, 0.89). CONCLUSIONS/INTERPRETATION: PA showed a borderline inverse association with both all-cause mortality (both sexes) and incident CVD (women only) in patients with type 1 diabetes. Since this is an under-researched clinical population, future longitudinal studies with objective PA measurements are needed to expand on these results.

Prescribing quality assessment is increasingly used in improvement programs and pay-for-performance policies. Within the area of diabetes many quality indicators have been developed. Some measure prescribing on a general level, e. g. calculating percentages of patients prescribed any statins. Others are very specific, e. g. percentages of patients with an elevated LDL-cholesterol in whom lipid-lowering treatment is started unless contraindicated or return to control within 3 months. Although the latter seems more precise, we question how far one should go in developing such indicators. Using the example of diabetes treatment, we highlight the need, opportunities, and feasibility of assessing prescribing quality in the context of individualised treatment. We conclude that it is not realistic to develop indicators that take all possible aspects of therapy non-respons, intolerance and patient preferences into account. We do recommend further development of indicators that better address subpopulations in need of adjusted treatment, such as elderly or patients with comorbidity.

Aims/hypothesis In the past few years, several genes outside the MHC region have been described as new susceptibility genetic factors to type 1 diabetes. An association between CAPSL-rs1445898 and type 1 diabetes was reported in a large white population and corroborated in a genome-wide analysis, which also found an association with IL7R, which is located adjacent to CAPSL. The aim of this study was to replicate the aforementioned associations in independent cohorts. Methods We analysed two CAPSL (rs1010601 and rs1445898) and three IL7R (rs6897932, rs987106 and rs3194051) polymorphisms. All these single nucleotide polymorphisms (SNPs) were genotyped using TaqMan minor groove binder chemistry in 301 unrelated Spanish type 1 diabetes patients and 646 healthy controls. Additionally, the associated CAPSL SNP rs1445898 was genotyped in a Dutch cohort consisting of 429 type 1 diabetes patients and 720 healthy controls. Results The homozygous mutant genotype of the CAPSL SNP rs1445898 showed a trend towards a protective effect in the overall Spanish cohort (OR [95% CI] 0.70 [0.44-1.09]; p=0.09) and in the Dutch cohort (OR [95% CI] 0.74 [0.51-1.05]; p=0.09). Pooling of both cohorts was performed, yielding a statistically significant difference (Mantel-Haenszel OR 0.71; p=0.005). This protective effect was significantly different in early-onset vs late-onset Spanish patients (OR [95% CI] 0.26 [0.10-0.65]; p=0.001). Similarly, in the early-onset subgroup, the homozygous mutant genotype of the IL7R SNP rs6897932 showed a similar protective effect (OR [95% CI] 0.18 [0.02-0.94]; p=0.02). Conclusions/interpretation In summary, we describe an independent replication of the association between the CAPSL-IL7R locus and type 1 diabetes, especially for early-onset type 1 diabetes patients.

Objective: The objective of this study was to examine the association between diabetes, and both urinary bladder cancer (UBC) risk and mortality. Methods: We conducted a retrospective cohort study using data from the UK Clinical Practice Research Datalink (CPRD) linked to the Office of National Statistics (ONS). Patients diagnosed with diabetes mellitus type 1 or 2, or using antidiabetic drugs (ADDs), were compared to matched non-diabetic controls. Cox proportional hazards models were used to estimate the risk and mortality of UBC. We adjusted for age, sex, smoking status and body mass index. Results: The cohort included 329 168 patients using ADD, and 307 315 controls with 1295 and 1071 patients, respectively, diagnosed as having UBC during follow-up. The adjusted HRs of UBC were 0.77 (95% CI 0.57 to 1.05) and 1.04 (95% CI 0.96 to 1.14) for type 1 and 2 diabetes, respectively. These results were similar if we restricted our analysis to an inception cohort. We noticed a small increased risk during the first year after diagnosis (HR=1.26 (95% CI 1.05 to 1.52)), which could be explained by detection bias. There was no influence of the severity of diabetes as measured by the glycated haemoglobin. Mortality of UBC was not increased for patients with either type 1 (HR=0.95 (95% CI 0.39 to 2.34)) or type 2 diabetes (HR=1.16 (95% CI 0.91 to 1.46)). Conclusions: Neither the risk of UBC nor the mortality from UBC was increased in patients with type 1 and patients with type 2 diabetes in the CPRD data.

Background: Pregnancy in women with type 1 (T1DM) or type 2 diabetes (T2DM) is associated with increased risk. These conditions are managed similarly during pregnancy, and compared directly in analyses, however they affect women of different age, body mass index and ethnicity. Methods: We assess if differences exist in pregnancy outcomes between T1DM and T2DM by comparing them directly and with matched controls. We also analyze the effect of glycemic control on pregnancy outcomes and analyze predictive variables for poor outcome. Results: We include 323 women with diabetes and 660 glucose-tolerant controls. T2DM women had higher BMI, age and parity with a shorter duration of diabetes and better glycemic control. Preeclampsia occurred more in women with T1DM only. Rates of elective cesarean section were similar between groups but greater than in controls, emergency cesarean section was increased in women with type 1 diabetes. Maternal morbidity in T1DM was double that of matched controls but T2DM was similar to controls. Babies of mothers with diabetes were more likely to be delivered prematurely. Neonatal hypoglycemia occurred more in T1DM than T2DM and contributed to a higher rate of admission to neonatal intensive care for both groups. Adverse neonatal outcomes including stillbirths and congenital abnormalities were seen in both groups but were more common in T1DM pregnancies. HbA1C values at which these poor outcomes occurred differed between T1 and T2DM. Conclusions: Pregnancy outcomes in T1DM and T2DM are different and occur at different levels of glycemia. This should be considered when planning and managing pregnancy and when counseling women.

Aims/hypothesis Activating mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the K-ATP channels in pancreatic beta cells are a common cause of neonatal diabetes. One-third of patients also have developmental delay, which probably results from mutated K-ATP channels in muscle, nerve and brain. Sulfonylureas, which bind to the sulfonylurea receptor 1 subunit of the K-ATP channel, can replace insulin injections in patients with KCNJ11 mutations. The aim of this study was to investigate the long-term outcome and impact on neurological features of sulfonylurea treatment.Methods We report the response to sulfonylurea treatment in a boy with neonatal diabetes and marked developmental delay resulting from the KCNJ11 mutation V59M.Results Glibenclamide (glyburide) treatment was started at 23 months and resulted in insulin being discontinued, lower overall glycaemia, reduced glucose fluctuations and reduced hypoglycaemia. Good control (HbA(1c) 6.5%) was maintained 2 years after discontinuing insulin, despite a reduction in the glibenclamide dose (from 0.41 to 0.11 mg center dot kg(-1)center dot day(-1)). Within 1 month of starting glibenclamide there was marked improvement in motor function, resulting in the patient progressing from being unable to stand unaided to walking independently, but there was no improvement in mental function.Conclusions/interpretation This 2-year follow-up of a patient highlights that sulfonylurea treatment can result in prolonged, excellent glycaemic control and may improve motor features, but not mental features, associated with KCNJ11 mutations. This suggests that the neurological actions of sulfonylurea are initially principally on peripheral (nerve or muscle) rather than on central (brain) K-ATP channels. Early molecular diagnosis is important in patients with neonatal diabetes and neurological features.

PURPOSE: In subjects without underlying cardiac disease dobutamine is known to enhance systolic LV function and LV relaxation. As end-systolic (ES) and end-diastolic (ED) volumes (V) can be derived from gated SPECT we intent to study these volumes and their response to dobutamine in order to have a better understanding of the mechanism by which stroke volume (SV) increases during dobutamine infusion. We intent to do this in normal controls and in young diabetic subjects. METHODS: After injection of sestamibi, serial gated SPECT were obtained at baseline, and during low doses of dobutamine infusion in 12 asymptomatic type I diabetic patients, and in 12 age matched controls. LV EDV, ESV, SV and EF were calculated with the QGS program. RESULTS: Gated SPECT showed comparable LV EF and SV in both groups at rest. There was a significant increase in LVEF and SV during dobutamine infusion but in the diabetic patients the increase in SV was due to a decrease in ESV from 25+/-5 to 20+/-6 ml/m2 (p=0.002) and no change in EDV. In normal controls, the increase in EF was due to an increase in EDV from 69+/-10 to 73+/-12 ml/m2 (p=0.002) with no significant change in ESV. CONCLUSION: These data confirm the presence of subclinical abnormalities of diastolic function in asymptomatic type I diabetic patients and show differences in adaptation to inotropic stimulation in order to preserve the increase in stroke volume and LV ejection fraction.

Alleles of HLA class II genes DQB1, DQA1, and DRB1 in the MHC region are major determinants of genetic predisposition to type 1 diabetes (T1D). Several alleles of each of these three loci are associated with susceptibility or protection from disease. In addition, relative risks for some DR-DQ genotypes are not simply the sum or product of the single haplotype relative risks. For example, the risk of the DRB1*03-DQB1*02/DRB1*0401-DQB1*0302 genotype is often found to be higher than for the individual DRB1*03-DQB1*02andDRB1*0401-DQB1*0302 homozygous genotypes. It has been hypothesized that this synergy or epistasis occurs through formation of highly susceptible trans-encoded HLA-DQ(alpha1, beta1) heterodimers. Here, we evaluated this hypothesis by estimating the disease associations of the range of DR-DQ genotypes and their inferred dimers in a large collection of nuclear families. We determined whether the risk of haplotypes in DRB1*0401-DQB1*0302-positive genotypes relative to the DRB1*03-DQB1*02-positive genotypes is different from that of DRB1*01-DQB1*0501, which we used as a baseline reference. Several haplotypes showed a different risk compared to DRB1*01-DQB1*0501, which correlated with their ability to form certain trans-encoded DQ dimers. This result provides new evidence for the potential importance of trans-encoded HLA DQ molecules in the determination of HLA-associated risk in T1D.

Many diabetic patients in general practice do not achieve good glycaemic control. The aim of this study was to assess which characteristics of type 2 diabetes patients treated in primary care predict poor glycaemic control (HbA(1c) greater than or equal to7%). Data were collected from the medical records. 1641 patients were included who had mean HbA(1c) 7.1( SD 1.7)%, and 42% had HbA(1c) greater than or equal to7%. On univariate analysis younger age; longer duration of diabetes; higher levels of blood glucose at diagnosis; most recent fasting blood glucose (FBG), total cholesterol, and triglyceride; higher body mass index (BMI); treatment with oral hypoglycaemic agents (OHA); treatment with insulin; more GP-visits for diabetes in the last year; and lower educational level were associated with poor control. Both in multiple linear regression and in multiple logistic regression higher levels of FBG ( odds ratio ( OR): = 1.6, 95% confidence interval (CI): 1.49, 1.70), treatment with OHA OR: 2.1, 95% CI: 1.41, 3.04), treatment with insulin ( OR: 7.2, 95% CI: 4.18, 12.52), lower educational level ( OR: 1.26, 95% CI: 1.01, 1.56) were independently associated with poor levels of HbA(1c). When FBG levels were excluded from the model, higher blood glucose at diagnosis, higher values for triglyceride and total cholesterol, and younger age predicted poor glycaemic control, but these variables explained only 15% of the variation in HbA(1c). In conclusion prediction of poor glycaemic control from patient characteristics in diabetic patients in general practice is hardly possible. FBG appeared to be a strong predictor of HbA(1c), which underlines the usefulness of this simple test in daily diabetes care. The worse metabolic control in those treated with either OHA or insulin suggests that current treatment regimes might be not sufficiently applied to reach the targets of care. Providers of diabetes care should be attentive to patients with lower educational level.

Background Previous studies have shown that the carpal tunnel syndrome seems to occur more frequently in patients with diabetes mellitus and might be associated with the duration of diabetes mellitus, microvascular complications and degree of glycaemic control. Primary aim was to determine if type 2 diabetes can be identified as a risk factor for carpal tunnel syndrome after adjusting for possible confounders. Furthermore, the influence of duration of diabetes mellitus, microvascular complications and glycaemic control on the development of carpal tunnel syndrome was investigated. Methods Retrospective, case–control study using data from electronic patient charts from the Isala (Zwolle, the Netherlands). All patients diagnosed with carpal tunnel syndrome in the period from January 2011 to July 2012 were included and compared with a control group of herniated nucleus pulposus patients. Results A total of 997 patients with carpal tunnel syndrome and 594 controls were included. Prevalence of type 2 diabetes was 11.5% in the carpal tunnel syndrome group versus 7.2% in the control group (Odds Ratio 1.67 (95% confidence interval 1.16-2.41)). In multivariate analyses adjusting for gender, age and body mass index, type 2 diabetes was not associated with carpal tunnel syndrome (OR 0.99 (95% CI 0.66-1.47)). No differences in duration of diabetes mellitus, microvascular complications or glycaemic control between groups were detected. Conclusion Although type 2 diabetes was more frequently diagnosed among patients with carpal tunnel syndrome, it could not be identified as an independent risk factor. Electronic supplementary material The online version of this article (doi:10.1186/1471-2474-15-346) contains supplementary material, which is available to authorized users.

Aims/hypothesis Oxidative stress plays a key role in the development of type 2 diabetes mellitus. We previously showed that the circulating antioxidant peroxiredoxin 4 (Prx4) is associated with cardiometabolic risk factors. We aimed to evaluate the association of Prx4 with type 2 diabetes risk in the general population. Methods We analysed data on 7,972 individuals from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (49% men, aged 28–75 years) with no diabetes at baseline. Logistic regression models adjusted for age, sex, smoking, waist circumference, hypertension and family history of diabetes were used to estimate the ORs for type 2 diabetes. Results During a median follow up of 7.7 years, 496 individuals (288 men; 58%) developed type 2 diabetes. The median (Q1–Q3) Prx4 level was 0.84 (0.53–1.40) U/l in individuals who developed type 2 diabetes and 0.68 (0.43–1.08) U/l in individuals who did not develop type 2 diabetes. For every doubling of Prx4 levels, the adjusted OR (95% CI) for type 2 diabetes was 1.16 (1.05–1.29) in the whole population; by sex, it was 1.31 (1.14–1.50) for men and 1.03 (0.87–1.21) for women. Further adjustment for other clinical measures did not materially change the results. The addition of Prx4 to a validated diabetes risk score significantly improved the prediction of type 2 diabetes in men (p = 0.002 for reclassification improvement). Conclusions/interpretation Our findings suggest that elevated serum Prx4 levels are associated with a higher risk of incident type 2 diabetes. For men, taking Prx4 into consideration can improve type 2 diabetes prediction over a validated diabetes risk score; in contrast, there is no improvement in risk prediction for women. Electronic supplementary material The online version of this article (doi:10.1007/s00125-014-3278-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Background Abdominal obesity is a more important risk factor than overall obesity in predicting the development of type 2 diabetes and cardiovascular disease. From a preventive and public health point of view it is crucial that risk factors are identified at an early stage, in order to change and modify behaviour and lifestyle in high risk individuals. Methods Data from a community based study was used to assess the risk for type 2 diabetes, cardiovascular disease and prevalence of metabolic syndrome in middle-aged men. In order to identify those with increased risk for type 2 diabetes and/or cardiovascular disease sensitivity and specificity analysis were performed, including calculation of positive and negative predictive values, and corresponding 95% CI for eleven different cut-off points, with 1 cm intervals (92 to 102 cm), for waist circumference. Results A waist circumference ≥94 cm in middle-aged men, identified those with increased risk for type 2 diabetes and/or for cardiovascular disease with a sensitivity of 84.4% (95% CI 76.4% to 90.0%), and a specificity of 78.2% (95% CI 68.4% to 85.5%). The positive predictive value was 82.9% (95% CI 74.8% to 88.8%), and negative predictive value 80.0%, respectively (95% CI 70.3% to 87.1%). Conclusions Measurement of waist circumference in middle-aged men is a reliable test to identify individuals at increased risk for type 2 diabetes and cardiovascular disease. This measurement should be used more frequently in daily practice in primary care in order to identify individuals at risk and when planning health counselling and interventions.

Background Type 2 diabetes is an important preventable disease and a growing public health problem. Based on information provided by clinical trials, we know that Type 2 diabetes can be prevented or delayed by lifestyle intervention. In view of translating the findings of diabetes prevention research into real-life it is necessary to carry out community-based evaluations so as to learn about the feasibility and effectiveness of locally designed and implemented programmes. The aim of this project was to assess the effectiveness of an active real-life primary care strategy in high-risk individuals for developing diabetes, and then evaluate its efficiency. Methods/Design Cost-Effectiveness analysis of the DE-PLAN (Diabetes in Europe - Prevention using Lifestyle, physical Activity and Nutritional intervention) project when applied to a Mediterranean population in Catalonia (DE-PLAN-CAT). Multicenter, longitudinal cohort assessment (4 years) conducted in 18 primary health-care centres (Catalan Health Institute). Individuals without diabetes aged 45-75 years were screened using the Finnish Diabetes Risk Score - FINDRISC - questionnaire and a 2-h oral glucose tolerance test. All high risk tested individuals were invited to participate in either a usual care intervention (information on diet and cardiovascular health without individualized programme), or the intensive DE-PLAN educational program (individualized or group) periodically reinforced. Oral glucose tolerance test was repeated yearly to determine diabetes incidence. Besides measuring the accumulated incidence of diabetes, information was collected on economic impact of the interventions in both cohorts (using direct and indirect cost questionnaires) and information on utility measures (Quality Adjusted Life Years). A cost-utility and a cost-effectiveness analysis will be performed and data will be modelled to predict long-term cost-effectiveness. Discussion The project was intended to evidence that a substantial reduction in Type 2 diabetes incidence can be obtained at a reasonable cost-effectiveness ratio in real-life primary health care setting by an intensive lifestyle intervention. As far as we know, the DE-PLAN-CAT/PREDICE project represents the first assessment of long-term effectiveness and cost-effectiveness of a public healthcare strategy to prevent diabetes within a European primary care setting.

Infants of diabetic mothers are at risk of developing hypoglycemia postnatally. Strict control of blood glucose during pregnancy might result in adequate glucose homeostasis in the neonate. We followed 15 mother-infant pairs from the beginning of pregnancy until birth. Glucose kinetics in the infants were measured on the first day of life, using a stable isotope dilution technique. Furthermore, levels of alternative substrates, FFA, and ketone bodies were measured. All infants received i.v. glucose from birth onward at a rate of 3.4 +/- 0.7 mg/kg/min (mean +/- SD). There was no relationship between the parameters of control of the insulin-dependent diabetes mellitus in the mothers and glucose kinetics in their infants. Glucose turnover was 5.2 +/- 1.1 mg/kg/min, glucose production rate (GPR) was 1.8 +/- 1.1 mg/kg/min. GPR was significantly lower in the infants studied at the end of the first day of life (p < 0.01), irrespective of the glucose infusion rate. Furthermore, the lower GPR was associated with an increased concentration of ketone bodies, suggesting an increased production of ketone bodies in these infants. The relatively high GPR measured in the infants who were studied in the first hours postnatally may be the result of postnatal hormonal stimulation of glycogenolysis and/or gluconeogenesis. From this study, we conclude that glucose kinetics in infants of tightly controlled diabetic mothers appear to be normal. Interestingly, despite the near-optimal insulin therapy in the mothers, there is a relationship between the SD scores of birth weight and the mean 3rd-trimester blood glucose values.