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Aims: Telemedicine has been promoted as an effective way of managing type‐2 diabetes (T2DM) in primary care. However, the effectiveness of telemedicine is unclear. We investigated the clinical and cost‐effectiveness of different telemedicine interventions for people with T2DM, compared to usual care. Methods: We searched Medline, Embase, Cochrane, CINHAL, ProQuest and EconLit for randomized controlled trials (RCTs) that examined the effectiveness of telemedicine interventions on clinical outcomes (HbA1c, body mass index [BMI], weight, diastolic blood pressure [DBP], systolic blood pressure [SBP], fasting blood glucose, high‐density lipoprotein [HDL] cholesterol, low‐density lipoprotein [LDL] cholesterol, total cholesterol and triglyceride) in adults with T2DM, published in English from inception until 31 December 2022. Meta‐analyses were conducted using random‐effects models pooling mean differences, heterogeneity was quantified using the I2 statistic. Publication bias was assessed using funnel plots, Egger tests and trim and fill. Subgroup analyses included type of telemedicine intervention, telemedicine mode of delivery and type of healthcare professionals. This study was registered with PROSPERO, CRD 42022375128. Results: Of the 4093 records identified, 21 RCTs, 10,732 participants from seven regions, were included. Reported interventions included telephone (k = 16 studies), internet‐based (k = 2), videoconference (k = 2) and telephone and emails (k = 1). We observed no statistically significant differences between synchronous or asynchronous telemedicine interventions compared to usual care for HbA1c (−0.08% (−0.88 mmol/mol); 95% CI: −0.18, 0.02), BMI (0.51 kg/m2; 95% CI: −0.21, 1.22), SBP (−1.48 mmHg; 95% CI: −3.22, 0.26), DBP (3.23 mmHg; 95% CI: −0.89, 7.34), HDL‐cholesterol (0.01 mmol/L; 95% CI: −0.03, 0.05), LDL‐cholesterol (0.08 mmol/L; 95% CI: −0.22, 0.37), triglycerides (−0.08 mmol/L, 95% CI: −0.31, −0.15), total cholesterol (−0.10 mmol/L; 95% CI: −0.25, 0.04) and weight (−0.50 kg; 95% CI: −1.21, 0.21). Conclusions: Telemedicine was as effective as usual care in improving health outcomes of people with T2DM. They can provide a safe solution in times of rising demands for primary healthcare services, or in extreme events, like a global pandemic. More high‐quality RCTs are needed on the cost evaluation of telemedicine. [ABSTRACT FROM AUTHOR]

Aim: To examine the preliminary effects of a culturally tailored, family‐supported, community‐based diabetes self management education and support (DSMES) programme for Ethiopian people with type 2 diabetes on glycosylated haemoglobulin (HbA1c), blood pressure, body mass index and lipid profiles. Methods: A two‐arm pilot randomised controlled trial (RCT) was conducted involving 76 participant–caregiver dyads from Western Ethiopia, which were randomly allocated to the intervention arm to receive 12 h of DSMES intervention guided by social cognitive theory on top of usual care, or to the control group, which received usual care. While HbA1c was a primary outcome, the blood pressure, body mass index and lipid profiles were secondary outcomes. Primary outcome was the change in HbA1c between baseline and 2‐month follow‐up between the groups. Generalised estimating equations was used to test the preliminary effect of the DSMES programme on the outcomes at baseline, post‐intervention and at 2‐month follow‐up for secondary outcomes. Cohen's d was used to estimate the between‐group effect sizes of the intervention. Results: The DSMES produced significant improvement in HbA1c with large effect size (β = −1.667, p < 0.001, d = −0.81) and triglycerides with medium effect size (d = −0.50). HbA1c in the intervention group was decreased by 12 mmol/mol (1.1%). Although nonsignificant, the DSMES also had small to moderate effects (d = −0.123 to 0.34) on blood pressure, body mass index, total cholesterol, low‐density and high‐density lipoproteins when compared with usual care. Conclusion: A culturally tailored, social cognitive theory‐guided, family‐supported, community‐based DSME programme could have a benefit on HbA1c and triglycerides. A full RCT is warranted to test the effectiveness of the DSMES programme. [ABSTRACT FROM AUTHOR]

Aims: Change in weight, HbA1c, lipids, blood pressure and cardiometabolic events over time is variable in individuals with type 2 diabetes. We hypothesised that people with a genetic predisposition to a more favourable adiposity distribution could have a less severe clinical course/progression. Methods: We involved people with type 2 diabetes from two UK‐based cohorts: 11,914 individuals with GP follow‐up data from the UK Biobank and 723 from Salford. We generated a 'favourable adiposity' genetic score and conducted cross‐sectional and longitudinal studies to test its association with weight, BMI, lipids, blood pressure, medication use and risk of myocardial infarction and stroke using 15 follow‐up time points with 1‐year intervals. Results: The 'favourable adiposity' genetic score was cross‐sectionally associated with higher weight (effect size per 1 standard deviation higher genetic score: 0.91 kg [0.59,1.23]) and BMI (0.30 kg/m2 [0.19,0.40]), but higher high‐density lipoprotein (0.02 mmol/L [0.01,0.02]) and lower triglycerides (−0.04 mmol/L [−0.07, −0.02]) in the UK Biobank at baseline, and this pattern of association was consistent across follow‐up. There was a trend for participants with higher 'favourable adiposity' genetic score to have lower risk of myocardial infarction and/or stroke (odds ratio 0.79 [0.62, 1.00]) compared to those with lower score. A one standard deviation higher score was associated with lower odds of using lipid‐lowering (0.91 [0.86, 0.97]) and anti‐hypertensive medication (0.95 [0.91, 0.99]). Conclusions: In individuals with type 2 diabetes, having more 'favourable adiposity' alleles is associated with a marginally better lipid profile long‐term and having lower odds of requiring lipid‐lowering or anti‐hypertensive medication in spite of relatively higher adiposity. [ABSTRACT FROM AUTHOR]

Aims: Microvascular complications' risk differs between people with latent autoimmune diabetes in adults (LADA) and people with type 2 diabetes. We aimed to investigate whether the prevalence of cardiac autonomic neuropathy, a life‐threatening complication of diabetes, also varies depending on diabetes type. Methods: In this cross‐sectional study, 43 adults with LADA, 80 with type 1 diabetes and 61 with type 2 diabetes were screened for cardiac autonomic neuropathy with recommended tests. Logistic regression models were used to test differences between diabetes types adjusting for confounders. Results: Cardiac autonomic neuropathy was diagnosed in 17 (40%) participants with LADA, 21 (26%) participants with type 1 diabetes and 39 (64%) participants with type 2 diabetes (p < 0.001). The odds ratio (OR) for cardiac autonomic neuropathy in type 1 diabetes and in type 2 diabetes compared to LADA were 0.54 (95% CI: 0.25–1.20, p‐value: 0.13) and 2.71 (95% CI: 1.21–6.06, p‐value 0.015) respectively. Smoking (adjOR 3.09, 95% CI: 1.40–6.82, p‐value: 0.005), HDL cholesterol (adjOR 0.29, 95% CI: 0.09–0.93, p‐value: 0.037) and hypertension (adjOR 2.11, 95% CI: 1.05–4.24, p‐value: 0.037) were independent modifiable risk factors for cardiac autonomic neuropathy. Differences among diabetes types did not change after correction for confounders. Conclusions: This is the first study offering a comparative evaluation of cardiac autonomic neuropathy among LADA, type 1 and type 2 diabetes, showing a lower risk of cardiac autonomic neuropathy in LADA compared to type 2 diabetes and similar compared to type 1 diabetes. This disparity was not due to differences in age, metabolic control or cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Aim: To examine the possible gene‐environment interactions between 32 single nucleotide polymorphisms and environmental factors that could modify the probability of chronic kidney disease. Methods: A case‐control study was conducted involving 600 people with type 2 diabetes (300 chronic kidney disease cases, 300 controls) who participated in The Malaysian Cohort project. Retrospective subanalysis was performed on the chronic kidney disease cases to assess chronic kidney disease progression from the recruitment phase. We genotyped 32 single nucleotide polymorphisms using mass spectrometry. The probability of chronic kidney disease and predicted rate of newly detected chronic kidney disease progression were estimated from the significant gene‐environment interaction analyses. Results: Four single nucleotide polymorphisms (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and five environmental factors (age, sex, smoking, waist circumference and HDL) were significantly associated with chronic kidney disease. Gene‐environment interaction analyses revealed significant probabilities of chronic kidney disease for sex (PPARGC1A rs8192678), smoking (eNOS rs2070744, PPARGC1A rs8192678 and KCNQ1 rs2237895), waist circumference (eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228) and HDL (eNOS rs2070744 and PPARGC1A rs8192678). Subanalysis indicated that the rate of newly detected chronic kidney disease progression was 133 cases per 1000 person‐years (95% CI: 115, 153), with a mean follow‐up period of 4.78 (SD 0.73) years. There was a significant predicted rate of newly detected chronic kidney disease progression in gene‐environment interactions between KCNQ1 rs2283228 and two environmental factors (sex and BMI). Conclusions: Our findings suggest that the gene‐environment interactions of eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895 and KCNQ1 rs2283228 with specific environmental factors could modify the probability for chronic kidney disease. What's new?: In parallel with genotyping advancement, the number of gene‐environment interaction studies has grown substantially.This study tries to elucidate the possible gene‐environment interactions between single nucleotide polymorphisms and environmental factors that could modify the probability for chronic kidney disease among people with type 2 diabetes where local data is scarce.This study suggests that four single nucleotide polymorphisms interact significantly with specific environments to modify the probability of chronic kidney disease. Based on the gene‐environment interaction findings, genotype‐targeted lifestyle modification might benefit specific subgroups of people with type 2 diabetes who have increased chronic kidney disease probability in specific environments. [ABSTRACT FROM AUTHOR]

Aim: To assess the relevance of lipoprotein‐associated phospholipase A2 activity as a diagnostic and prognostic marker for renal microvascular diseases. Methods: We analysed lipoprotein‐associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes‐Patients Follow‐up (DPV) registry at blood collection and on average 2.4 ± 1.3 years later at follow‐up. Relationships between lipoprotein‐associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression. Results: Lipoprotein‐associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow‐up. Lipoprotein‐associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein‐associated phospholipase A2 activity. Cross‐sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein‐associated phospholipase A2 activity with HbA1c and HDL‐cholesterol. Conclusions: Lipoprotein‐associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein‐associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro‐ and macrovascular diseases in Type 1 diabetes. What's new?: High levels of lipoprotein‐associated phospholipase A2 activity have been shown to be strong predictive markers for cardiovascular events and are associated with oxidative stress.In our cohort of adolescents with Type 1 diabetes, lipoprotein‐associated phospholipase A2 was not associated with albuminuria and lysophosphatidylcholine as surrogate markers of diabetic microvascular disease and oxidative stress.By contrast, lipoprotein‐associated phospholipase A2 activity was negatively correlated with HbA1c levels.This negative association of lipoprotein‐associated phospholipase A2 with HbA1c levels may limit its use as a cardiovascular risk marker in people with diabetes. [ABSTRACT FROM AUTHOR]

Aim: To determine the optimal cut‐points of visceral adipose tissue (VAT) areas at different anatomic levels to discriminate participants with cardiometabolic risk factors in a Chinese middle‐aged population. Methods: A total of 1744 individuals who underwent regular health checks in Nanjing BENQ Medical Center from January 2013 to December 2016 were included in this cross‐sectional study. VAT areas were measured by abdominal quantitative computed tomography at the L2/3 intervertebral disk and umbilicus levels. Cardiometabolic risk factors including serum triglycerides, HDL cholesterol levels, plasma glucose and blood pressure were defined using IDF 2005 criteria for metabolic syndrome. Results: The cut‐points for VAT area at the umbilicus level were 111 cm2 for men and 96 cm2 for women to identify people with one or more cardiometabolic risk factors. For VAT area at the L2/3 level, the optimal cut‐points were 142 cm2 for men and 115 cm2 for women. A VAT area at the L2/3 level of ≥ 142 cm2 for men or 115 cm2 for women significantly increased the prevalence of hyperglycaemia [odds ratio (OR) 3.18, 95% confidence interval (CI) 2.45–4.13], hypertension (OR 2.81, 95% CI 2.27–3.49) and dyslipidaemia (OR 4.37, 95% CI 3.50–5.45) after adjusting age. Conclusions: The optimal cut‐points for VAT area at the umbilicus level and L2/3 level were 111 cm2 and 142 cm2 for men and 96 cm2and 115 cm2 for women to identify participants with one or more cardiometabolic risk factors. What's new?: This study aimed to investigate the optimal cut‐points of visceral adipose tissue (VAT) areas by means of computed tomography (CT) scanning to discriminate participants with cardiometabolic risk factors in a Chinese middle‐aged population.The results showed that the optimal cut‐points for VAT area at the umbilicus level were 111 cm2 for men and 96 cm2 for women to identify participants with one or more cardiometabolic risk factors, which was 142 cm2 for men and 115 cm2 for women for VAT area at the L2/3 level.VAT area at the L2/3 level had comparable power with VAT area at the umbilicus level to identify participants with cardiometabolic risk factors.Such information of setting up ethnic‐ and sex‐specific cut‐points for VAT areas is of clinical and economic importance for risk assessment. [ABSTRACT FROM AUTHOR]

Aims: To examine the effect of pump vs injection therapy on the lipid profile of children with Type 1 diabetes mellitus. Methods: A cross‐sectional analysis of the lipid profile of children aged ≤ 18 years with Type 1 diabetes mellitus from SWEET, an international diabetes registry, was conducted with a focus on the effect of treatment regimen. Dyslipidaemia was defined as LDL cholesterol ≥2.6 mmol/l or non‐HDL cholesterol ≥3.1 mmol/l. LDL and non‐HDL cholesterol values among 14 290 children (52% boys, 51% receiving pump therapy) from 60 SWEET centres were analysed by linear and logistic regression analysis adjusted for sex, age, diabetes duration, HbA1c and BMI‐standard deviation score group, region, and common interactions between age, sex, HbA1c and BMI. Results: This study confirmed the established associations of increased lipids with female sex, age, diabetes duration, HbA1c and BMI. LDL and non‐HDL cholesterol levels were lower in the pump therapy group compared to the injection therapy group [LDL cholesterol: injection therapy 2.44 mmol/l (95% CI 2.42 to 2.46) vs pump therapy 2.39 mmol/l (95% CI 2.37–2.41), P<0.001; non‐HDL cholesterol: injection therapy 2.88 mmol/l (95% CI 2.86 to 2.90) vs pump therapy 2.80 mmol/l (95% CI 2.78–2.82), both P<0.0001]. Similarly, the odds ratios for LDL cholesterol ≥2.6 mmol/l [0.89 (95% CI 0.82–0.97)] and non‐HDL cholesterol ≥3.1 mmol/l [0.85 (0.78 to 0.93)] were significantly lower in the pump therapy group, even after all adjustments. Conclusions: Our results indicate that pump therapy is associated with a better lipid profile. What's new?: People with Type 1 diabetes mellitus have an increased risk of cardiovascular disease.Dyslipidaemia is one of the major factors contributing to cardiovascular morbidity.Pump treatment has been associated with lower cardiovascular mortality, but the association with lipids has not been investigated.In a large cohort of children with Type 1 diabetes, pump treatment was associated with a better lipid profile compared to injection treatment. This association remained significant even after adjustments for major confounding factors.The use of an insulin pump may independently lead to a better lipid profile and thus a lower cardiovascular risk in people with Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Diabetes is associated with increased cardiovascular disease (CVD) risk. Previous studies with statins have established that a 1 mmol/l reduction in LDL‐cholesterol reduces CVD events by 21% over 5 years in people with diabetes. More recently, trials in people with acute coronary syndromes showed that ezetimibe reduced CVD events by 6% at 5 years and achieved a LDL‐cholesterol of 1.6 mmol/l with better results in people with Type 2 diabetes. Several novel lipid‐lowering therapies have recently been developed. Most data have been accumulated with proprotein convertase subtilisin kexin‐9 (PCSK‐9) inhibitors, which reduce LDL‐cholesterol by 50–55%. A large CVD outcome trial with evolocumab, in which 40% of participants had diabetes, achieved a LDL‐cholesterol of 0.8 mmol/l and showed a consistent 20% relative risk reduction within 2 years, including in people with diabetes. Trials to increase HDL‐cholesterol using cholesterol ester transfer protein (CETP) inhibitors have generally underwhelmed. Although anacetrapib reduced coronary ischaemic events by 7% in a population with chronic CVD, more expansive CVD endpoints were not improved. The complex nature of CETP inhibitor trial outcomes means that these compounds are not being developed further. Trials targeting inflammation‐associated lipids have been generally unsuccessful but recent data on the interleukin‐1B receptor antagonist canakinumab have shown a reduction in acute coronary intervention, validating this target although at the cost of increased infections. The ability to achieve low LDL‐cholesterol with off‐patent medications and the costs of novel therapies will confine the use of novel agents to subgroups of people at highest risk of CVD. [ABSTRACT FROM AUTHOR]

Aims To describe factors associated with prevalence or absence of microvascular and macrovascular complications in people with Type 1 diabetes of very long duration and to investigate the risk factors associated with the incidence of such complications. Methods We included individuals with Type 1 diabetes who had been entered in the Swedish National Diabetes Register between 2002 and 2004 ( n = 18 450). First, risk factor distribution in people with diabetes duration of ≥ 50 years was compared between people with and without complications. Second, the incidence of complications during a 10-year follow-up period was studied in all individuals who had no complications at baseline. Results Among people with a diabetes duration of ≥ 50 years ( n = 1023), 453 (44%) had macrovascular disease, 534 (52%) had microvascular disease and 319 (31%) did not have either of the diagnoses. Factors that differed significantly between people with and without macrovascular disease were gender, age, HbA1c, BMI, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, albuminuria, antihypertensive medication and lipid-lowering medication. The same factors differed significantly between people with and without microvascular disease, with the exception of gender and HDL cholesterol. During the follow-up period, 6.1% of the study cohort were diagnosed with macrovascular disease and 19.6% with microvascular disease. Incidence of macrovascular disease was significantly associated with HbA1c levels. Hazard ratios decreased with longer diabetes duration. Conclusions People with Type 1 diabetes who have survived ≥ 50 years without complications are significantly younger, and have significantly lower HbA1c levels, BMI and triglyceride levels than survivors with complications. HbA1c level is a predictor of macrovascular disease, independently of diabetes duration. [ABSTRACT FROM AUTHOR]

Aims To examine the incidence of and risk factors for insulin resistance and β-cell dysfunction in a representative Iranian population over a median follow-up of 9.2 years. Methods In total, 3662 people (1528 men) without known diabetes with a baseline homeostasis model assessment of insulin resistance ( HOMA- IR) level < 75th percentile and, when β-cell dysfunction was the outcome of interest, 3664 people (1530 men) with a homeostasis model assessment of β-cell function (HOMA-β) level ≥ 25th percentile were included in the study ( HOMA- IR < 2.20 and HOMA-β ≥ 64.3 among men, and HOMA- IR < 2.39 and HOMA-β ≥ 81.7 among women). Results The incidence rates of insulin resistance and β-cell dysfunction were 56.3 and 33.6/1000 person-years among men and 48.6 and 50.3/1000 person-years among women, respectively. Applying multivariable Cox regression in both sexes, fasting insulin, triglyceride/ HDL cholesterol ratio and lower education were positive predictors of insulin resistance, whereas age was a negative predictor. Moreover, fasting plasma glucose, waist-to-height ratio, wrist circumference and lower hip circumference were significantly associated with incident insulin resistance only among women (all P < 0.05). Considering β-cell dysfunction in both sexes, age and fasting plasma glucose increased the risk, whereas 2-h post-challenge plasma glucose was a positive predictor only among men, and waist-to-height ratio and triglyceride/ HDL cholesterol ratio were negative predictors only among women (all P < 0.05). Conclusions Modifiable risk factors are related to the incidence of insulin resistance and β-cell dysfunction, which can be prevented with proper strategies although the difference between men and women should be taken into account. [ABSTRACT FROM AUTHOR]

Aims Higher levels of brain natriuretic peptide ( BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established. Methods N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance ( HOMA- IR), quantitative insulin sensitivity check index ( QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-pro BNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-pro BNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-pro BNP levels on insulin resistance. Results Lower NT-pro BNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors ( P < 0.001 for all four indices). Although the genetic score was strongly related to measured NT-pro BNP levels amongst European Americans ( F statistic = 71.08), we observed no association of genetically determined NT-pro BNP with insulin resistance ( P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-pro BNP). Conclusions In older adults, lower NT-pro BNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study. [ABSTRACT FROM AUTHOR]

Aim To investigate the safety and efficacy of insulin degludec/liraglutide ( IDegLira), a novel combination product, as add-on therapy for people with Type 2 diabetes uncontrolled on sulphonylurea therapy. Methods In this 26-week, double-blind trial, adults with Type 2 diabetes [HbA1c 53-75 mmol/mol (7.0-9.0%)] were randomized to IDegLira ( n = 289) or placebo ( n = 146) as add-on to pre-trial sulphonylurea ± metformin, titrating to a fasting glycaemic target of 4.0-6.0 mmol/l. Treatment initiation was at 10 dose steps, and maximum dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Results The mean HbA1c decreased from 63 mmol/mol (7.9%) to 46 mmol/mol (6.4%) with IDegLira and to 57 mmol/mol (7.4%) with placebo [estimated treatment difference -11 mmol/mol (95% CI -13; -10) or -1.02% (95% CI -1.18; -0.87); P < 0.001]. The HbA1c target of 53 mmol/mol (<7%) was achieved by 79.2% of participants in the IDegLira group vs 28.8% in the placebo group [estimated odds ratio 11.95 (95% CI 7.22; 19.77); P < 0.001]. Mean weight change was +0.5 kg with IDegLira vs -1.0 kg with placebo [estimated treatment difference 1.48 kg (95% CI 0.90; 2.06); P < 0.001]. Confirmed hypoglycaemia occurred in 41.7 and 17.1% of IDegLira- and placebo-treated participants, respectively, with rates of 3.5 vs 1.4 events/patient-years of exposure [estimated rate ratio 3.74 (95% CI 2.28; 6.13); P < 0.001]. IDegLira was generally well tolerated. The rates of serious adverse events were 20.3 and 8.0 per 100 patient-years of exposure with IDegLira and placebo, respectively, without obvious patterns in the type of events. Conclusions IDegLira can be used in people uncontrolled with sulphonylurea ± metformin to improve efficacy with a safety profile in line with previous DUAL trials. [ABSTRACT FROM AUTHOR]

Aims To investigate the incidence of pre-diabetes and its different phenotypes and the related risk factors during 9 years of follow-up. Methods A total of 5879 people (2597 men and 3282 women) aged ≥ 20 years, free of diabetes and pre-diabetes, took part in the study. Multivariable Cox proportional hazard models were used to evaluate hazard ratios ( HR) and 95% confidence intervals ( CI) for all potential risk factors. Results Overall, 853 men and 902 women developed pre-diabetes. Incidence rates of pre-diabetes were 46.1 per 1000 person-years in men and 36.8 per 1000 person-years in women, while isolated impaired fasting glucose had the highest incidence rate among all pre-diabetes phenotypes. In both sexes, age, family history of diabetes, fasting plasma glucose and 2-hour post-challenge plasma glucose were related to incident pre-diabetes. Among women, waist-to-height ratio [ HR: 1.02 (1.00-1.03)] and being divorced/widowed compared with married [ HR: 0.67 (0.52-0.87)] were significant predictors of pre-diabetes; whereas among men, community-based intervention [ HR: 0.79 (0.68-0.90)], higher level of education and being single [ HR: 0.77 (0.6-0.97)] were protective against progression to pre-diabetes. Moreover, hip circumference among women [ HR: 0.95 (0.93-0.98)] and current smoking among men [ HR: 1.69 (1.15-2.48)] were related to incident combined impaired fasting glucose and impaired glucose tolerance. Conclusion More than 4% of the Iranian population develop pre-diabetes each year, emphasizing the important role of socio-economic factors (marital status, education and smoking habits) and community-based intervention in progression to impaired glucose regulations. Thus, emergent intervention is necessary to halt the tsunami of pre-diabetes among the Iranian population. [ABSTRACT FROM AUTHOR]

Aim To investigate the distribution of and risk factors for dysglycaemia (Type 2 diabetes and prediabetes) in women with previous gestational diabetes mellitus in India. Methods All women ( n = 989) from two obstetric units in New Delhi and Hyderabad with a history of gestational diabetes were invited to participate, of whom 366 (37%) agreed. Sociodemographic, medical and anthropometric data were collected and 75-g oral glucose tolerance test were carried out. Results Within 5 years (median 14 months) of the pregnancy in which they were diagnosed with gestational diabetes, 263 (72%) women were dysglycaemic, including 119 (32%) and 144 (40%) with Type 2 diabetes and prediabetes, respectively. A higher BMI [odds ratio 1.16 per 1-kg/m2 greater BMI (95% CI 1.10, 1.28)], presence of acanthosis nigricans [odds ratio 3.10, 95% CI (1.64, 5.87)], postpartum screening interval [odds ratio 1.02 per 1 month greater screening interval 95% CI (1.01, 1.04)] and age [odds ratio 1.10 per 1-year older age 95% CI (1.04, 1.16)] had a higher likelihood of having dysglycaemia. The American Diabetes Association-recommended threshold HbA1c value of ≥ 48 mmol/mol (6.5%) had a sensitivity and specificity of 81.4 and 90.7%, respectively, for determining the presence of Type 2 diabetes postpartum. Conclusion The high post-pregnancy conversion rates of gestational diabetes to diabetes reported in the present study reinforce the need for mandatory postpartum screening and identification of strategies for preventing progression to Type 2 diabetes. Use of the American Diabetes Association-recommended HbA1c threshold for diabetes may lead to significant under-diagnosis. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to evaluate whether women with gestational diabetes mellitus could be screened using HbA1c for glucose metabolism status at 6-12 weeks post-partum. Methods We enrolled 699 pregnant women diagnosed with gestational diabetes mellitus from October 2005 to December 2013. A 75-g oral glucose tolerance test ( OGTT) and HbA1c measurement were performed at 6-12 weeks after delivery. Results The prevalence of overt diabetes and pre-diabetes were 5.2% ( n = 36) and 49.1% ( n = 343), respectively, when using the 75-g OGTT as the gold standard. HbA1c alone identified 2.9% ( n = 20) as having overt diabetes and 32.2% ( n = 225) as having pre-diabetes. When American Diabetes Association cut-offs were applied, the sensitivity and specificity for HbA1c to diagnose overt diabetes were 19.4% and 98.0%, respectively. Pre-diabetes, according to the HbA1c criterion, had 41.2% sensitivity and 72.2% specificity. The misclassifications identified 97 positive differences, 233 negative differences and 369 ties ( P < 0.05). The area under the receiver operating characteristic curves for detecting diabetes and pre-diabetes were 0.615 [95% confidence interval (95% CI), 0.515 to 0.716] and 0.588 (95% CI, 0.545 to 0.630), respectively. Conclusions HbA1c may not be sensitive enough for an accurate diagnosis, but it is highly specific for diagnosing overt diabetes at 6-12 weeks post-partum in women with previous gestational diabetes mellitus. [ABSTRACT FROM AUTHOR]

Aim To assess the relationship between plasma neutrophil gelatinase-associated lipocalin ( NGAL) levels and diabetic retinopathy in patients with Type 2 diabetes. Methods In total, 204 patients with Type 2 diabetes were investigated in this cross-sectional study. They were classified as having no diabetic retinopathy, non-proliferative diabetic retinopathy ( NPDR) or proliferative retinopathy ( PDR), according to the degree of diabetic retinopathy. Thus, diabetic retinopathy in the patients in this study was either NPDR or PDR. Results Plasma NGAL concentrations were significantly higher in patients with diabetic retinopathy than in those without. The mean plasma NGAL levels differed significantly according to the severity of diabetic retinopathy (no diabetic retinopathy, 120.8 ng/ml; NPDR, 217.8 ng/ml; PDR, 372.4 ng/ml; P for trend = 0.002) after adjustment for other covariates. In multivariable analysis, plasma NGAL levels were significantly associated with diabetic retinopathy (odds ratio for each standard deviation increase in the logarithmic value, 7.75; 95% confidence interval, 2.04-29.41, P = 0.003). Conclusion Plasma NGAL levels were positively associated with diabetic retinopathy in patients with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim To compare the effects of the basal insulin analogues glargine and detemir on endothelial function and adipocytokine levels in people with Type 2 diabetes. Methods We studied 32 people with Type 2 diabetes whose blood glucose control was unsatisfactory while receiving only oral hypoglycaemic drugs. Participants were randomized to either insulin glargine or detemir for 24 weeks and then crossed over to the other treatment without a washout period. Flow-mediated vasodilatation, adipocytokine levels (plasminogen activator inhibitor-1 and leptin/adiponectin ratio), and fasting ghrelin levels were monitored. Results HbA1c levels were significantly decreased by both basal insulin therapies. Body weight was significantly increased by glargine but not by detemir. The proportion of flow-mediated vasodilatation was significantly increased by detemir but not glargine (glargine: from 5.17 ± 0.69 to 5.94 ± 0.83%; detemir: from 4.89 ± 0.78 to 7.92 ± 0.69%). Plasminogen activator inhibitor-1 level was significantly decreased by only detemir (glargine: from 16.4 ± 1.8 to 17.3 ± 2.1; detemir: from 19.2 ± 2.8 to 16.0 ± 1.6 ng/ml). The leptin/adiponectin ratio was significantly increased only by glargine. Acyl ghrelin level was significantly decreased by glargine but not detemir. Conclusions These results suggest that the effect on endothelial function and adipocytokine profiles may differ between glargine and detemir in people with diabetes (Trial registration ID: UMIN000004973). [ABSTRACT FROM AUTHOR]

Aims The glycolysis-derived metabolite methylglyoxal has been linked to clinical microvascular complications, including diabetic nephropathy. We aimed to further investigate the hypothesis that methylglyoxal is involved in decline in renal function by assessing the associations between measures of renal function during a 6-year follow-up in 1481 people with screen-detected Type 2 diabetes, as part of the Danish arm of the ADDITION-Europe trial ( ADDITION- DK). Methods Biobank serum samples collected at ADDITION- DK baseline (2001-2006) and follow-up (2009-2010) were used in the current analysis of methylglyoxal. We assessed cross-sectional baseline and longitudinal associations between methylglyoxal and urinary albumin-to-creatinine ratio ( ACR) or estimated GFR ( eGFR), and between methylglyoxal and categories of albuminuria or reduced eGFR. Results Baseline methylglyoxal was positively associated with ACR at baseline (12% higher ACR per doubling in methylglyoxal levels), and change in methylglyoxal during 6 years of follow-up was inversely associated with change in eGFR (-1.6 ml/min/1.73 m2 per doubling in methylglyoxal change), in models adjusted for age, sex, HbA1c, systolic blood pressure, anti-hypertensive treatment, LDL-cholesterol, lipid-lowering treatment, C-reactive protein and smoking. Conclusions In a population of people with screen-detected Type 2 diabetes, we observed associations between methylglyoxal and markers of renal function: 6-year change in methylglyoxal was inversely associated with 6-year change in eGFR. Also, methylglyoxal at baseline was positively associated with ACR at baseline. Our study lends further support to a role for methylglyoxal in the pathogenesis of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Aim Diabetes is a known risk factor for hearing impairment. No study regarding the association of insulin resistance ( IR), β-cell dysfunction and impaired fasting glucose ( IFG) with hearing impairment has been reported in the population without diabetes. We examined these associations using a representative sample of the Korean population. Methods Participants included 1589 males and 2496 females, who were ≥ 20 years of age and without diabetes from the Korea National Health and Nutritional Examination Surveys of the Korean population (2010). Audiometric tests and laboratory examinations were performed. Homeostasis model assessments of IR and β-cell function ( HOMA- IR and HOMA-β) were calculated. Results The prevalence of both high- and low-/mid-frequency hearing impairment among subjects with IFG was higher compared with those with normal glycaemia (42.2% vs. 24.5%, 14.7% vs. 7.8%, respectively). After adjustment for age, HOMA- IR and HOMA-β showed significant association with high-frequency hearing impairment in males. In the multiple logistic regression analyses adjusting for confounding variables, the presence of IFG, higher HOMA- IR and lower HOMA-β remained as independent risk factors for high-frequency mild hearing impairment in males < 70 years [odds ratio ( OR) 1.441, 95% confidence interval (95% CI), 1.056 to 1.967; OR, 1.448, 95% CI, 1.039 to 2.101; and OR, 0.447, 95% CI, 0.274 to 0.729, P < 0.05, respectively). Conclusions IR, β-cell dysfunction and IFG are associated with high-frequency mild hearing impairment in the male population < 70 years before the onset of diabetes. [ABSTRACT FROM AUTHOR]

Aim The burden of Type 2 diabetes is alarmingly high in South Asia, a region that has many genetically diverse ethnic populations. Genome-wide association studies ( GWAS) conducted largely in European populations have identified a number of loci predisposing to Type 2 diabetes risk, however, the relevance of such genetic loci in many South Asian sub-ethnicities remains elusive. The aim of this study was to replicate 49 single nucleotide polymorphisms ( SNPs) previously identified through GWAS in Punjabis living in Pakistan. Methods We examined the association of 49 SNPs in 853 Type 2 diabetes cases and 1945 controls using additive logistic regression models after adjusting for age and gender. Results Of the 49 SNPs investigated, eight showed a nominal association ( P < 0.05) that also remained significant after controlling for the false discovery rate. The most significant association was found for rs7903146 at the TCF7L2 locus. For a per unit increase in the risk score comprising of all the 49 SNPs, the odds ratio in association with Type 2 diabetes risk was 1.16 (95% CI 1.13-1.19, P < 2.0E-16). Conclusion These results suggest that some Type 2 diabetes susceptibility loci are shared between Europeans and Punjabis living in Pakistan. [ABSTRACT FROM AUTHOR]

Aims The metabolic syndrome (MetS) is a clustering of low levels of HDL cholesterol, hyperglycaemia, high waist circumference, hypertension and elevated triglycerides, and is associated with cardiovascular disease. Calcified atherosclerotic plaque in the thoracic aorta ( TAC), measured by non-contrast cardiac computed tomography ( CT) scans, is a marker for atherosclerosis and relates to mortality. We sought to evaluate the independent association of MetS and TAC on cardiac CT scans. Methods We examined the relation of the MetS, and each of its components, to the prevalence of TAC, measured from 2000 to 2002 in 6778 white, Chinese, African-American and Hispanic participants in the Multi-Ethnic Study of Atherosclerosis ( MESA). Results Adjusting for age, gender, race, smoking, LDL cholesterol and lipid-lowering medications, relative risks and 95% confidence intervals ( CI) for a TAC score > 0 were: 1.19 (95% CI 1.11 to 1.28) for participants with MetS, 1.34 (95% CI 1.21 to 1.49) for those with diabetes and MetS, and 1.33 (95% CI 1.11, 1.58) for those with diabetes and no MetS compared with participants who were free of the MetS and diabetes. Associations were found for most of the components of the MetS with TAC. Conclusions We conclude that in adults without known heart disease, the MetS, most of its components and diabetes are associated with a higher prevalence of calcified atherosclerotic plaque in the thoracic arteries in a multi-ethnic population of men and women. [ABSTRACT FROM AUTHOR]

Aims HNF1A gene mutations are the most common cause of maturity-onset diabetes of the young ( MODY) in the UK. Persons with HNF1A- MODY display sensitivity to sulphonylurea therapy; however, the long-term efficacy is not established. There is limited literature as to the prevalence of micro- and macrovascular complications in this unique cohort. The aim of this study was to determine the natural progression and clinical management of HNF1A- MODY diabetes in a dedicated MODY clinic. Methods Sixty patients with HNF1A- MODY and a cohort of 60 BMI-, age-, ethnicity- and diabetes duration-matched patients with Type 1 diabetes mellitus participated in the study. All patients were phenotyped in detail. Clinical follow-up of the HNF1A- MODY cohort occurred on a bi-annual basis. Results Following a genetic diagnosis of MODY, the majority of the cohort treated with sulphonylurea therapy remained insulin independent at 84-month follow-up (80%). The HbA1c in the HNF1A- MODY group treated with sulphonylurea therapy alone improved significantly over the study period [from 49 (44-63) mmol/mol, 6.6 (6.2-7.9)% to 41 (31-50) mmol/mol, 5.9 (5-6.7)%; P = 0.003]. The rate of retinopathy was significantly lower than that noted in the Type 1 diabetes mellitus group (13.6 vs. 50%; P = 0.0001).There was also a lower rate of microalbuminuria and cardiovascular disease in the HNF1A- MODY group compared with the Type 1 diabetes mellitus group. Conclusions This study demonstrates that the majority of patients with HNF1A- MODY can be maintained successfully on sulphonylurea therapy with good glycaemic control. We note a significantly lower rate of micro- and macrovascular complications than reported previously. The use of appropriate therapy at early stages of the disorder may decrease the incidence of complications. [ABSTRACT FROM AUTHOR]

Aims We investigated the association between lipoprotein(a) [Lp(a)] level and new-onset chronic kidney disease ( CKD) in patients with Type 2 diabetes. Methods We conducted a prospective cohort study from March 2003 to December 2004 with a median follow-up time of 10.1 years. Patients aged 25-75 years with Type 2 diabetes and without CKD [estimated glomerular filtration rate ( eGFR) ≥ 90 ml/min/1.73 m2) were consecutively enrolled. The eGFR was measured at least twice every year , and new-onset CKD was defined as a decreased eGFR status of < 60 ml/min/1.73 m2 using a Chronic Kidney Disease Epidemiology Collaboration ( CKD- EPI) equation. Results Of the 862 patients who were enrolled, 560 (65.0%) completed the follow-up and 125 (22.3%) progressed to CKD. The mean age and duration of diabetes were 53.3 ± 9.6 and 7.5 ± 6.0 years, respectively. The baseline eGFR was 101.8 ± 11.3 ml/min/1.73 m2. After adjusting for multiple confounding factors, a Cox hazard regression analysis revealed that the third tertile of Lp(a) was significantly associated with the development of CKD during the observation period when compared with the first tertile [hazard ratio 2.12 (95% confidence interval 1.33-3.36); P = 0.001). Conclusions In this prospective, longitudinal, observational cohort study, we demonstrated that the Lp(a) level was an independent prognostic factor for the future development of CKD in patients with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims To investigate the risk prediction and the risk stratification performances of the Chronic Kidney Disease Epidemiology Collaboration ( CKD- EPI) equation and the Modification of Diet in Renal Disease ( MDRD) equation for estimated glomerular filtration rate ( eGFRCKD- EPI vs. eGFRMDRD) on heart failure in patients with Type 2 diabetes. Methods The study cohort included 12 258 White and 16 886 African American low-income patients with Type 2 diabetes who were 30-90 years old at baseline. Heart failure risk according to different eGFRCKD- EPI and eGFRMDRD categories was prospectively assessed. Results During a mean follow-up of 6.5 years, 5043 incident heart failure cases were identified. Multivariable-adjusted hazard ratios ( HRs) of heart failure associated with the eGFRCKD- EPI categories [≥ 90 (reference group), 75-89, 60-74, 30-59 and < 30 ml/min/1.73 m2] were 1.00, 1.11, 1.31, 1.75 and 2.93 ( Ptrend < 0.001) for African American patients, and 1.00, 1.11, 1.08, 1.59 and 2.92 ( Ptrend < 0.001) for White patients, respectively. The model with eGFRCKD- EPI and the other risk factors had significantly higher Harrell's C than the model with eGFRMDRD and other risk factors. Patients reclassified downward from eGFRMDRD 60-74 to eGFRCKD- EPI 30-59 and from eGFRMDRD 30-59 to eGFRCKD- EPI < 30 ml/min/1.73 m2 showed higher heart failure risk than those who were not reclassified. Conclusions Impaired kidney function (i.e. GFR < 60 ml/min/1.73 m2), and even mildly decreased GFR (60-74 ml/min/1.73 m2) estimated by both equations is associated with an increased risk of heart failure. Compared with GFR estimated using the MDRD equation, GFR estimated using the CKD- EPI equation added more predictive power to the model with the other risk factors. Also, eGFRCKD- EPI provided more accurate heart failure risk stratification than eGFRMDRD . [ABSTRACT FROM AUTHOR]

Aims To investigate whether serum complement C3 is related to the prevalence and incidence of prediabetes in an adult population. Methods A cross-sectional ( n = 10 206) and prospective cohort study ( n = 3333), with a mean (range; 95% CI) follow-up of 2.63 (1-6; 2.58-2.68) years, was conducted in people recruited from the Health Management Centre of Tianjin Medical University General Hospital in Tianjin, China. Measurement of serum C3 concentration, blood fasting glucose, oral glucose tolerance, HbA1c and other potential confounding factors was performed at baseline and each year during the follow-up. Prediabetes was defined according to the criteria of the American Diabetes Association. Adjusted logistic and Cox proportional hazards regression models were used to assess the relationships between C3 quintiles and prediabetes. Results The prevalence and incidence of prediabetes were 38.5% and 119 per 1000 person-years, respectively. In cross-sectional analysis, after adjustment for potential confounders, the odds ratios of prediabetes for increasing quintiles of C3 were 1.00 (reference), 1.32 (95% CI 1.14-1.53), 1.37 (95% CI 1.18-1.59), 1.75 (95% CI 1.51-2.03), 2.25 (95% CI 1.93-2.62; P for trend < 0.0001). In the cohort analysis, the multiple-adjusted hazard ratio of prediabetes in the highest quintile of baseline C3 was 1.43 (95% CI 1.15, 1.78; P for trend < 0.001), when compared with the lowest quintile. Conclusions These findings indicate that elevated serum C3 levels are significantly related to an increased risk of developing prediabetes in an adult population, suggesting that C3 can be used as a biomarker in high-risk individuals to improve primary prevention of prediabetes and diabetes. [ABSTRACT FROM AUTHOR]

Aim To investigate the prevalence of diagnosed Type 2 diabetes and its related complications in a nationally representative sample of older adults in the Republic of Ireland. Methods Cross-sectional analysis of a population-based sample of adults aged ≥ 50 years from the first wave of The Irish Longitudinal Study on Ageing ( TILDA), (2009-2011). Diagnosed Type 2 diabetes prevalence was estimated by self-report or the use of oral hypoglycaemic agents. The prevalence of microvascular and macrovascular complications was determined by self-report. Results Diagnosed Type 2 diabetes prevalence was 8.4% [95% confidence interval ( CI): 7.8-9.0%] and was higher among men [10.3% (95% CI: 9.4-11.2%)] than women [6.6% (95% CI: 5.9-7.5%)]; P ≤ 0.001. Among participants with diagnosed Type 2 diabetes, the overall prevalence of microvascular complications was 26.0% (95% CI: 22.4-30.0%) with no evidence of gender-specific differences ( P = 0.7). The overall prevalence of macrovascular complications was 15.1% (95% CI: 12.2-18.4%) and was higher among men [17.8% (95% CI: 14.3-23.1%)] than women [11.4% (95% CI: 7.7-16.4%)]; P ≤ 0.001. Conclusions In the absence of a national diabetes register, these findings provide a robust estimate of the national prevalence of diagnosed Type 2 diabetes and level of complications among adults aged 50 years and over in Ireland. [ABSTRACT FROM AUTHOR]

Aims Metformin is the most widely used oral anti-diabetes agent and has considerable benefits over other therapies, yet 20-30% of people develop gastrointestinal side effects, and 5% are unable to tolerate metformin due to the severity of these side effects. The mechanism for gastrointestinal side effects and their considerable inter-individual variability is unclear. We have recently shown the association between organic cation transporter 1 ( OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes. The aim of this study was to explore the association of OCT1 reduced-function polymorphisms with common metformin-induced gastrointestinal side effects in Type 2 diabetes. Methods This prospective observational cohort study included 92 patients with newly diagnosed Type 2 diabetes, incident users of metformin. Patients were genotyped for two common loss-of-function variants in the OCT1 gene ( SLC22A1): R61C (rs12208357) and M420del (rs72552763). The association of OCT1 reduced-function alleles with gastrointestinal side effects was analysed using logistic regression. Results Forty-three patients (47%) experienced gastrointestinal adverse effects in the first 6 months of metformin treatment. Interestingly, the number of OCT1 reduced-function alleles was significantly associated with over two-fold higher odds of the common metformin-induced gastrointestinal side effects (odds ratio = 2.31, 95% confidence interval 1.07-5.01, P = 0.034). Conclusions In conclusion, we showed for the first time the association between OCT1 variants and common metformin-induced gastrointestinal side effects. These results confirm recent findings related to the role of OCT1 in severe metformin intolerance, and suggest that high inter-individual variability in mild/moderate and severe gastrointestinal intolerance share a common underlying mechanism. These data could contribute to more personalized and safer metformin treatment. [ABSTRACT FROM AUTHOR]

Aims To assess young healthy men from rural India, who had normal or low birth weights, using magnetic resonance spectroscopy to determine the potential differences in ectopic fat storage between birth weight groups, and to determine if ectopic fat storage was associated with insulin resistance in this population. Methods A total of 54 lean men with normal birth weight and 49 lean men with low birth weight (age range 18-22 years) from rural India were recruited. All the men underwent anthropometry, magnetic resonance spectroscopy, a hyperinsulinaemic-euglycaemic clamp and a dual-energy X-ray absorptiometry. Results The median (interquartile range) values for hepatic cellular lipids, intramyocellular lipids and extramyocellular lipids, measured using magnetic resonance spectroscopy were 0.76 (0.1-1.8)%, 1.27 (1.0-2.3)% and 1.89 (1.3-3.2)%, respectively, for the normal birth weight group and 0.4 (0.1-1.3)%, 1.38 (0.9-2.2)% and 2.07 (1.2-2.8)%, respectively, for the low birth weight group ( P > 0.05). No difference in ectopic fat storage was observed between the low and normal birth weight groups, with or without adjustment for age and total fat percentage. Homeostatic model assessment of insulin resistance values were not associated with hepatic cellular, intramyocellular or extramyocellular lipid content in any of the groups. Total fat percentage was the only independent predictor of intramyocellular and extramyocellular lipid content. Conclusion Young and lean men from rural India with low birth weight were not observed to have ectopic fat storage in the liver or muscle, and the amount of liver and muscle fat was unrelated to insulin resistance. Older age and/or an urban affluent lifestyle may be required to show a potential role of ectopic fat storage on insulin resistance in Indian people with low or normal birth weight. [ABSTRACT FROM AUTHOR]

Aim To study prospectively the ethnic-specific risks of cardiovascular disease, end-stage renal disease and all-cause mortality in patients with Type 2 diabetes mellitus among native Asian subpopulations. Methods A total of 2337 subjects with Type 2 diabetes (70% Chinese, 17% Malay and 13% Asian Indian) were followed for a median of 4.0 years. Time-to-event analysis was used to study the association of ethnicity with adverse outcomes. Results Age- and gender-adjusted hazard ratios for cardiovascular disease in ethnic Malay and Asian Indian subjects were 2.01 (1.40-2.88; P<0.0001) and 1.60 (1.07-2.41; P=0.022) as compared with Chinese subjects. Adjustment for conventional cardiovascular disease risk factors, including HbA1c, blood pressure and lipid profile, slightly attenuated the hazards in Malay (1.82, 1.23-2.71; P=0.003) and Asian Indian subjects (1.47, 0.95-2.30; P=0.086); However, further adjustment for baseline renal function (estimated GFR) and albuminuria weakened the cardiovascular disease risks in Malay (1.48, 0.98-2.26; P=0.065) but strengthened that in Asian Indian subjects (1.81, 1.14-2.87; P=0.012). Competing-risk regression showed that the age- and gender-adjusted sub-distribution hazard ratio for end-stage renal disease was 1.87 (1.27-2.73; P=0.001) in Malay and 0.39 (0.18-0.83; P=0.015) in Asian Indian subjects. Notably, the difference in end-stage renal disease risk among the three ethnic groups was abolished after further adjustment for baseline estimated GFR and albuminuria. There was no significant difference in risk of all-cause mortality among the three ethnic groups. Conclusions Risks of cardiovascular and end-stage renal diseases in native Asian subjects with Type 2 diabetes vary substantially among different ethnic groups. Differences in prevalence of diabetic kidney disease may partially explain the ethnic disparities. [ABSTRACT FROM AUTHOR]

Aims Reduced aspirin efficacy has been demonstrated in people with Type 2 diabetes. Because increased platelet reactivity and/or turnover are postulated mechanisms, we examined whether higher and/or more frequent aspirin dosing might reduce platelet reactivity more effectively. Methods Participants with Type 2 diabetes ( n = 24) but without known cardiovascular disease were randomized in a three-way crossover design to 2-week treatment periods with aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily. The primary outcome was platelet reactivity, assessed using the VerifyNow™ ASA method. Relationships between platelet reactivity and aspirin dosing were examined using generalized linear mixed models with random subject effects. Results Platelet reactivity decreased from baseline with all doses of aspirin. Modelled platelet reactivity was more effectively reduced with aspirin 100 mg twice daily vs. 100 mg once daily, but not vs. 200 mg once daily. Aspirin 200 mg once daily did not differ from 100 mg once daily. Aspirin 100 mg twice daily was also more effective than once daily as measured by collagen/epinephrine-stimulated platelet aggregation and urinary thromboxane levels, with a similar trend measured by serum thromboxane levels. No episodes of bleeding occurred. Conclusions In Type 2 diabetes, aspirin 100 mg twice daily reduced platelet reactivity more effectively than 100 mg once daily, and numerically more than 200 mg once daily. Clinical outcome trials evaluating primary cardiovascular disease prevention with aspirin in Type 2 diabetes may need to consider using a more frequent dosing schedule. [ABSTRACT FROM AUTHOR]

Aims To evaluate C-reactive protein, insulin growth factor 1 and lipid levels during the follicular and luteal phases in adolescents with Type 1 diabetes. Methods Adolescents with Type 1 diabetes (N = 40) and healthy controls (C; N = 43) were studied during the follicular and luteal phases of their menstrual cycles. C-Reactive protein, insulin growth factor 1 and lipid levels were measured. Results Adolescents with Type 1 diabetes exhibited higher C-reactive protein levels than the C group during the follicular (P < 0.0001) and luteal phases (P < 0.01). The elevation of C-reactive protein levels was more pronounced in overweight adolescents with Type 1 diabetes than in adolescents in the C group. More adolescents with Type 1 diabetes were classified as having an elevated risk of cardiovascular disease (C-reactive protein > 3 mg/l) in the luteal phase than in the follicular phase (37.5% and 17.5%, respectively); half of the overweight adolescents with Type 1 diabetes in the luteal phase reached this level. BMI was the only significant factor affecting follicular and luteal phase C-reactive protein levels in adolescents with Type 1 diabetes. Lower insulin growth factor 1 levels were observed during both phases of the menstrual cycle in adolescents with Type 1 diabetes compared with controls. An elevation in insulin growth factor 1 levels in the luteal phase relative to the follicular phase was observed in controls, but not in adolescents with Type 1 diabetes. Luteal insulin growth factor 1 and C-reactive protein exhibited an inverse correlation (r = -0.4, P = 0.01). Conclusions Adolescents with Type 1 diabetes have higher C-reactive protein levels and lower insulin growth factor 1 levels relative to controls, especially during the luteal phase. Type 1 diabetes diminishes the natural elevation in insulin growth factor 1 levels observed during the luteal phase in controls. Excess weight exacerbates the subclinical inflammatory state observed during both phases of the menstrual cycle in adolescents with Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Aim Previous studies have reported that monocyte chemoattractant protein-1 (MCP-1) is involved in inflammatory and metabolic diseases. The purpose of this study is to investigate the role of MCP-1 in the pathogenesis of diabetic retinopathy (DR) in Han Chinese patients with Type 2 diabetes. Methods Serum levels of MCP-1 protein in patients classified as diabetic without retinopathy (DWR) and DR, including NPDR and PDR, were assayed by enzyme-linked immunosorbent assay. Genomic DNA from 198 DWR patients, 176 NPDR patients and 143 PDR patients were genotyped by using a PCR restriction fragment length polymorphism (PCR-RFLP) assay. Results MCP-1 serum levels were significantly higher in NPDR and PDR patients than in the DWR patients. The frequencies of the GG genotype and G allele of the single nucleotide polymorphism (SNP) were significantly increased in DR patients compared with DWR patients. Further subgroup analysis was performed to test whether there was an association between the PDR or NPDR and DWR groups. Significantly higher frequencies of the GG genotype and G allele were observed in PDR and NPDR patients compared with DWR patients. Furthermore, the 25 patients with PDR were divided into three groups according to the genotype of the tested SNP. The expression of the MCP-1 gene was higher in the GG genotype group compared with the other two groups. Conclusions The results suggested that the -2518 GG genotype and G allele of MCP-1 are associated with an increased risk of PDR in the Chinese Han population. This polymorphism may influence the expression of the MCP-1 gene, which may play an important role in the pathogenesis of DR. [ABSTRACT FROM AUTHOR]

Aim Lower limb amputation is a serious complication of diabetic foot disease and there are unexplained ethnic variations in incidence. This study investigates the risk of amputation among different ethnic groups after adjusting for demographic, socio-economic status and clinical variables. Methods We used primary care data from a large national multi-ethnic cohort of patients with Type 2 diabetes in New Zealand and linked hospital records. The primary outcome was time from initial data collection to first lower limb amputation. Demographic variables included age of onset and duration since diabetes diagnosis, gender, ethnicity and socio-economic status. Clinical variables included smoking status, height and weight, blood pressure, HbA1c, total cholesterol/HDL ratio and albuminuria. Cox proportional hazards models were used. Results There were 892 lower limb amputations recorded among 62 002 patients (2.11 amputations per 1000 personyears), followed for a median of 7.14 years (422 357 person-years). After adjusting for demographic and socio-economic variables and compared with Europeans, Maori had the highest risk [hazard ratio (HR) 1.84 (95% CI:1.54-2.19)], whereas East Asians [HR 0.18, (0.08-0.44)] and South Asians [HR 0.39 (0.22-0.67)] had the lowest risk. Adjusting for available clinical variables reduced the differences but they remained substantial [HR 1.61 (1.35-1.93), 0.23 (0.10-0.56) and 0.48 (0.27-0.83), respectively]. Conclusions Ethnic groups had significantly different risk of lower limb amputation, even after adjusting for demographic and some major clinical risk factors. Barriers to care should be addressed and intensive prevention strategies known to reduce the incidence of lower limb amputations could be prioritized to those at greatest risk. [ABSTRACT FROM AUTHOR]

Aims Salivary amylase gene (AMY1) copy number variations (CNVs) correlate directly with salivary amylase activity and serum amylase levels. Previously, individuals with high AMY1 CNVs exhibited low postprandial glucose levels and postprandial early insulin surge, suggesting that high AMY1 gene copy numbers may play a role in lowering the risk of insulin resistance. Methods We verified the relationship between AMY1 CNVs and homeostatic model assessment.insulin resistance (HOMA-IR) in a cohort of 1257 Korean men aged 20.65 years who visited two medical centres for regular health check-ups, and in subgroups of current smokers and regular alcohol drinkers. Individuals with fasting plasma glucose levels > 10.0 mmol/l, HbA1c ≤ 64 mmol/mol (8.0%) or who used oral hypoglycaemic agents or insulin were excluded. Results AMY1 CNVs correlated negatively with HOMA-IR even after adjusting for covariates (e.g. BMI, systolic blood pressure, triacylglycerol, alcohol consumption, smoking and physical activity). When the participants were divided according to current smoking and alcohol consumption habits, negative correlations between AMY1 CNVs and HOMAIR were more evident among non-smokers and regular drinkers and were non-significant among smokers and nonregular drinkers. Conclusions Low AMY1 CNVs correlated with high insulin resistance in asymptomatic Korean men, and such a relationship presented differently according to the status of smoking and alcohol consumption. [ABSTRACT FROM AUTHOR]

Aims Few studies have evaluated the effect of weight change from pre-pregnancy to post-partum with the risk of cardiometabolic diseases among women with a history of gestational diabetes mellitus. The aim of this study was to evaluate the association between weight change from pre-pregnancy to 1-5 years post-partum with metabolic syndrome among Chinese women with prior gestational diabetes mellitus. Methods We performed a retrospective cohort study in 1263 women with gestational diabetes mellitus at 1-5 years post-partum. Participants were divided into four groups based on their weight change from pre-pregnancy to 1-5 years post-partum: loss of ≥ 3 kg, ± 3 kg, gain of 3-7 kg and gain of ≥7 kg. Results The prevalence of metabolic syndrome was 12.1%, 16.2%, 26.0% and 44.3% among women with weight loss ≥ 3 kg, stable weight ( ± 3 kg), weight gain 3-7 kg and weight gain ≥ 7 kg from pre-pregnancy to post-partum, respectively. The positive association between weight change and metabolic syndrome was observed among women with pre-pregnancy normal weight ( BMI < 24 kg/m2), overweight ( BMI 24-27.9 kg/m2) and obesity ( BMI ≥ 28 kg/m2). The prevalence of metabolic syndrome was almost similar among pre-pregnancy normal weight women with weight gain ≥ 7 kg, pre-pregnancy overweight women with stable weight ( ± 3 kg) and pre-pregnancy obese women with weight loss ≥ 3 kg from pre-pregnancy to post-partum ( P = 0.62). Conclusions Women with gestational diabetes mellitus who had large weight gain from pre-pregnancy to post-partum were more likely to develop metabolic syndrome. Women who are pre-pregnancy overweight/obesity and also diagnosed as gestational diabetes mellitus during pregnancy need more weight control after delivery. [ABSTRACT FROM AUTHOR]

Aims To determine differences in predictors of albuminuria and decreased estimated GFR in Japanese people with Type 2 diabetes mellitus without chronic kidney disease. Methods This single-centre observational cohort study involved 1802 Japanese people with Type 2 diabetes with normoalbuminuria and estimated GFR ≥ 60 ml/min/1.73 m2 (740 women; mean ± sd age 58 ± 12 years). Two separate outcomes were evaluated: onset of albuminuria ( ≥ 30 mg/g creatinine, albuminuria cohort; n = 1655) and decrease in estimated GFR ( < 60 ml/min/1.73 m2; estimated GFR cohort; n = 1777). A Cox proportional hazards model was used to identify significant predictors for each outcome. Results During a median follow-up period of 6.9 years for the albuminuria cohort and 8.0 years for the estimated GFR cohort, 181 and 316 individuals reached the respective outcome. The 5-year cumulative incidence of albuminuria was 8.3%, and that of decreased estimated GFR was 10.4%. In the multivariate Cox model, greater urinary albumin-to-creatinine ratio, presence of diabetic retinopathy and higher HbA1c levels were associated with both outcomes. Unique risk factors for onset of albuminuria were male gender and higher uric acid levels; those for decreased estimated GFR were older age, greater systolic blood pressure, and lower baseline estimated GFR and HDL cholesterol levels. Conclusions Identification of both common and distinct predictive factors for onset of albuminuria and decreased estimated GFR support the hypothesis that both common and distinct pathophysiological mechanisms are involved in the development of these two manifestations of chronic kidney disease in diabetes. [ABSTRACT FROM AUTHOR]

Aims To examine the independent impacts of the homeostasis model assessment of insulin resistance ( HOMA- IR) and the updated model ( HOMA2- IR) on incident cardiovascular /coronary heart disease in a Middle Eastern population with a high prevalence of cardiovascular disease risk factors. Methods We examined 3777 Iranian people, aged ≥ 30 years, without history of cardiovascular disease and without use of antidiabetic medication at baseline. Both HOMA- IR and HOMA2- IR were log-transformed and categorized into quartiles. The multivariable Cox proportional hazard regression model, adjusted for traditional cardiovascular disease risk factors, was applied to examine the association between HOMA- IR/ HOMA2- IR with incident cardiovascular/coronary heart disease, considering the lowest quartile as reference. Results During a median follow-up of > 10 years, 197 cardiovascular disease and 181 coronary heart disease events occurred. Among the covariates, we found a significant interaction between hypertension and HOMA- IR/ HOMA2- IR for incident coronary heart/cardiovascular disease (all P ≤ 0.01). Among the population without hypertension, the risk of cardiovascular disease significantly increased in the second [hazard ratio 1.96 (95% CI 1.04-3.68)], third [hazard ratio 1.93 (95% CI 1.00-3.75)] and fourth [hazard ratio 2.34 (95% CI 1.15-4.75)] quartiles of HOMA- IR, and the risk of coronary heart disease increased significantly in the fourth quartile of HOMA- IR [hazard ratio 2.30 (95% CI 1.12-4.73)], but no significant association was detected between HOMA- IR and cardiovascular/coronary heart disease in the population with hypertension. Among the populations both with and without hypertension, no risk was found to be associated with HOMA2-IR quartiles however, a 1-unit increase in HOMA2- IR was associated with a significant risk of cardiovascular disease among the non-hypertensive group [hazard ratio 1.60 (95% CI 1.03-2.48); P = 0.03]. Conclusions The presence of hypertension modified the impact of HOMA- IR/ HOMA2- IR on incident cardiovascular/coronary heart disease. The presence of insulin resistance highlighted a significant and independent risk for cardiovascular disease/coronary heart disease only in the population without hypertension. [ABSTRACT FROM AUTHOR]

Aims To investigate the usefulness of the additional measurement of HbA1c, compared with performing only the oral glucose tolerance test ( OGTT), in identifying participants at increased cardiometabolic risk, in an urban Chinese population. Methods All participants from the fourth visit of the population-based Hong Kong Cardiovascular Risk Factors Prevalence Study, without known diabetes, were included. All had their glycaemic status assessed by OGTT and HbA1c, according to American Diabetic Association 2010 criteria. Results Based on OGTT criteria alone, 3.5% of the study cohort ( N = 1300) had diabetes and 19.2% had prediabetes. Based on HbA1c criteria only, 6.2% had diabetes and 61.2% had prediabetes. The measurement of HbA1c, in addition to the OGTT, increased the proportion of participants with diabetes to 7.8% and with prediabetes to 65.3%. Subjects with prediabetes having raised HbA1c but normal glycaemia ( N = 600) had waist circumference, systolic blood pressure, fasting glucose, insulin resistance index ( HOMA- IR), Gutt Index and Framingham 10-year cardiovascular risk scores intermediate between those with both normal HbA1c and glycaemia ( N = 350), and those with impaired fasting glucose and/or impaired glucose tolerance ( N = 249; all P < 0.01). Conclusion The measurement of HbA1c in our population, in addition to the OGTT, results in the detection of a large number of participants with prediabetes having raised HbA1c but normal glycaemia who have a cardiometabolic risk profile intermediate between impaired fasting glucose and/or impaired glucose tolerance and normal participants, and would benefit from early lifestyle intervention. [ABSTRACT FROM AUTHOR]

Aim To investigate the association between pulse pressure and risk of hospitalization for cardiovascular events among people with Type 2 diabetes. Methods A population-based case-control study was carried out using data from medical databases. A total of 588 people with Type 2 diabetes from 18 general practices in Cambridgeshire recorded a first hospitalization for a cardiovascular event between 2009 and 2011, and a total of 2920 age-matched, gender-matched and practice-matched control subjects with Type 2 diabetes were selected based on risk-set sampling. Pulse pressure was assessed before admission in 2008-2009. Further dose-response relationships between pulse pressure and risks were explored using spline models. Results There was a non-linear relationship between pulse pressure and the risk of hospitalization for a cardiovascular event ( P < 0.001 for linearity test). The pulse pressure associated with the lowest risk of hospitalization for a cardiovascular event was 61 (95% CI 57-63) mmHg. Conclusion In people with Type 2 diabetes, pulse pressure is a good predictor of risk of hospitalization for cardiovascular events. The risk is lowest with a pulse pressure of 57-63 mmHg. [ABSTRACT FROM AUTHOR]

Aim To examine the feasibility and potential health impact of a diabetes self-management education and support intervention involving peer support on glycaemic control and diabetes distress. Methods A total of 41 South-Asian adults with Type 2 diabetes were recruited for a 24-week diabetes self-management education and support pilot intervention involving peer support. The intervention consisted of six weekly education sessions co-facilitated by a certified diabetes educator and two peer leaders, followed by 18 weekly support sessions facilitated by two peer leaders. Education sessions were guided entirely by participants' self-management questions and also emphasized goal setting and action planning. Support sessions were based on empowerment principles and participants discussed self-management challenges, shared emotions, asked self-management questions, problem-solved in a group, set goals, and developed and evaluated action plans. Feasibility outcomes included recruitment and retention. Primary health-related outcomes included HbA1c levels and diabetes distress (measured at baseline, 6 and 24 weeks). Programme satisfaction was also assessed. Results Pre-established criteria for recruitment and retention were met. Paired t-tests showed no changes in HbA1c and diabetes distress at 6 weeks. At 24 weeks, HbA1c levels deteriorated [54 mmol/mol (7.1%) vs 61 mmol/mol (7.7%)] while diabetes distress scores improved (2.0 vs 1.7). Conclusions Although feasible, findings suggest this peer-support model may have a positive impact on diabetes distress, but not on HbA1c levels. Culturally responsive modifications (e.g. intervention location) to the pilot model are needed and could lead to more favourable health outcomes for this community. Such a re-designed peer-support model will require further investigation. [ABSTRACT FROM AUTHOR]

Aim To investigate whether previous physical activity levels are associated with blood glucose levels in individuals with impaired glucose tolerance in the context of an international pharmaceutical trial. Methods Data were analysed from the NAVIGATOR trial, which involved 9306 individuals with impaired glucose tolerance and high cardiovascular risk from 40 different countries, recruited in the period 2002-2004. Fasting glucose, 2-h post-challenge glucose and physical activity (pedometer) were assessed annually. A longitudinal regression analysis was used to determine whether physical activity levels 2 years (t-2) and 1 year (t-1) previously were associated with levels of glucose, after adjusting for previous glucose levels and other patient characteristics. Those participants with four consecutive annual measures of glucose and two consecutive measures of physical activity were included in the analysis. Results The analysis included 3964 individuals. Change in physical activity from t-2 to t-1 and activity levels at t-2 were both associated with 2-h glucose levels after adjustment for previous glucose levels and baseline characteristics; however, the associations were weak: a 100% increase in physical activity was associated with a 0.9% reduction in 2-h glucose levels. In addition, previous physical activity only explained an additional 0.05% of the variance in 2-h glucose over the variance explained by the history of 2-h glucose alone (R2 = 0.3473 vs. 0.3468). There was no association with fasting glucose. Conclusions In the context of a large international clinical trial, previous physical activity levels did not meaningfully influence glucose levels in those with a high risk of chronic disease, after taking into account participants' previous trajectory of glucose control. [ABSTRACT FROM AUTHOR]

Aims Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen-detected Type 2 diabetes (duration ~ 5.8 years). Methods The patients were well controlled with regard to HbA1c, lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy was assessed by vibration detection threshold ( n = 319), 10 g monofilament ( n = 543) and the Michigan Neuropathy Screening Instrument questionnaire ( n = 966). Painful diabetic neuropathy was assessed using the Brief Pain Inventory short form ( n = 882). Results No associations between methylglyoxal and cardiovascular autonomic reflex tests or any measures of diabetic peripheral neuropathy or painful diabetic neuropathy were observed. However, a positive association between methylglyoxal and several heart rate variability indices was observed, although these associations were not statistically significant when corrected for multiple testing. Conclusion Serum methylglyoxal is not associated with cardiovascular autonomic neuropathy, diabetic peripheral neuropathy or painful diabetic neuropathy in this cohort of well-treated patients with short-term diabetes. [ABSTRACT FROM AUTHOR]

Aims We investigated the risk of developing diabetes across various metabolic phenotypes by considering the presence of overall adiposity or abdominal adiposity and the number of metabolic abnormalities and aimed to clarify whether a 'healthy overweight' phenotype, that is, overweight with no metabolic abnormalities, was protective of the development of diabetes. Methods We studied 29 564 Japanese individuals without diabetes. The 5-year incidence of diabetes was assessed according to a combination of either overweight ( BMI ≥ 25.0 kg/m2) or abdominal obesity (waist circumference ≥ 90 cm in men and ≥ 80 cm in women) and the number of metabolic factors present (hypertension, elevated triglyceride concentration, low HDL cholesterol concentration and impaired fasting glucose). Results A total of 1188 individuals developed diabetes. Compared with normal weight individuals with none of the four metabolic abnormalities, in overweight individuals with none of the four abnormalities there was an odds ratio ( OR) of 2.32 [95% confidence interval ( CI) 1.50, 3.59] for diabetes; having any one metabolic abnormality increased the risk of developing diabetes among normal weight individuals [ OR 3.23 (2.55, 4.10)] and overweight individuals [ OR 5.00 (3.77, 6.63)]. Among overweight individuals, the presence of impaired fasting glucose alone substantially elevated the risk of diabetes by 8.98-fold (5.52, 14.6) in comparison with the absence of the four metabolic factors. Conclusions Being 'healthy overweight' was associated with a higher OR of developing future diabetes among Japanese individuals than normal weight individuals with no metabolic abnormalities, and being overweight with one or more abnormalities had a further elevated OR compared with 'healthy overweight' people. [ABSTRACT FROM AUTHOR]

Aims The molecular mechanisms by which muraglitazar (peroxisome proliferator-activated receptor γ/α agonist) improves insulin sensitivity in Type 2 diabetes mellitus are not fully understood. We hypothesized that muraglitazar would increase expression of 5′-monophosphate-activated protein kinase and genes involved in adiponectin signalling, free fatty acid oxidation and mitochondrial function in skeletal muscle. Methods Sixteen participants with Type 2 diabetes received muraglitazar, 5 mg/day ( n = 12) or placebo ( n = 4). Before and after 16 weeks, participants had vastus lateralis muscle biopsy followed by 180 min euglycaemic hyperinsulinaemic clamp. Results Muraglitazar increased plasma adiponectin (9.0 ± 1.1 to 17.8 ± 1.5 μg/ml, P < 0.05), while no significant change was observed with placebo. After 16 weeks with muraglitazar, fasting plasma glucose declined by 31%, fasting plasma insulin decreased by 44%, insulin-stimulated glucose disposal increased by 81%, HbA1c decreased by 21% and plasma triglyceride decreased by 39% (all P < 0.05). Muraglitazar increased mRNA levels of 5′-monophosphate-activated protein kinase, adiponectin receptor 1, adiponectin receptor 2, peroxisome proliferator-activated receptor gamma coactivator-1 alpha and multiple genes involved in mitochondrial function and fat oxidation. In the placebo group, there were no significant changes in expression of these genes. Conclusions Muraglitazar increases plasma adiponectin, stimulates muscle 5′-monophosphate-activated protein kinase expression and increases expression of genes involved in adiponectin signalling, mitochondrial function and fat oxidation. These changes represent important cellular mechanisms by which dual peroxisome proliferator-activated receptor agonists improve skeletal muscle insulin sensitivity. [ABSTRACT FROM AUTHOR]

Aims To assess geographic differences in the association between BMI, blood pressure and lipid levels with impaired glucose regulation among young adults from various geographical regions. Methods This was a cross-sectional study including data from 6987 participants aged ≤ 30 years from India, Singapore, Australia, Greenland, Kenya and Tanzania. Impaired glucose regulation was determined by the 75-g oral glucose tolerance test. For each geographical region, BMI, blood pressure and lipids were examined and compared between participants with normal glucose tolerance and those with impaired glucose regulation. Multiple logistic regression models were used to assess the association between risk factors and impaired glucose regulation. Results Indian and East African people had a higher prevalence of impaired glucose regulation compared with participants from other regions, despite their lower BMI. Compared with the other regions, blood pressure was lower among Indian and Singaporean people but higher in those from Greenland. Greenlanders had the highest, while Indian and East-African people, had the lowest level of HDL cholesterol. BMI was positively associated with impaired glucose regulation in all regions, and there were no statistically significant geographic differences. In the Indian, Singaporean and Australian participants, there was a positive association between blood pressure and impaired glucose regulation. Triglycerides were positively associated with and HDL cholesterol had no association with impaired glucose regulation in all geographical regions. Conclusions Higher BMI and triglyceride levels were positively associated with prevalent impaired glucose regulation in all geographical regions. There were geographic differences in the association between impaired glucose regulation and blood pressure and lipids, probably reflecting environmental and genetic factors. [ABSTRACT FROM AUTHOR]

The article presents abstracts of studies on adipocyte function presented at the Diabetes UK Professional Conference held in March 2015 including A. Adaikalakoteswari et al's Vitamin B12 deficiency for cholesterol biosynthesis, A. D. White et al's adipocyte mineralocorticoid receptor expression regulation and aldosterone secretion from protein kinase activators, and C. E. Hills and PE Squires' transforming glucose-evoked growth beta 1 modulate cell substrate.

Aim To analyse the effects of thyroid hormones on β-cell function and glucose metabolism in people with prediabetes who are euthyroid. Methods A total of 111 people who were euthyroid underwent 75-g oral glucose tolerance tests, of whom 52 were assigned to the normal glucose tolerance and 59 to the prediabetes groups. Homeostatic model assessment of β-cell function, insulinogenic index and areas under the curve for insulin and glucose were evaluated as indices of pancreatic β-cell function. Results In both groups, BMI, fasting insulin, homeostasis model assessment ratio and HDL cholesterol correlated significantly with all indices of pancreatic β-cell function. Free triiodothyronine correlated positively with all insulin secretion indices in the prediabetes group. Multiple linear regression analysis showed that free triiodothyronine was an independent variable that had a positive correlation with all indices of β-cell function in the prediabetes group. By contrast, no such correlation was found in the normal glucose tolerance group. Conclusions Free triiodothyronine is associated with both basal and glucose-stimulated insulin secretion in people with prediabetes who are euthyroid; therefore, the regulation of insulin secretion by thyroid hormones is a potentially novel therapeutic target for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

Aim To test the hypothesis that greater baseline insulin sensitivity would predict regression of albuminuria over 6 years in adults with Type 1 diabetes. Method We enrolled 81 people aged 30-48 years with albuminuria at baseline in the present study and re-examined them 6 years later. Urinary albumin excretion rate was measured and albuminuria was defined as urinary albumin excretion rate ≥ 20 μg/min. Regression of albuminuria was defined as normoalbuminuria (urinary albumin excretion rate < 20 μg/min) at follow-up. Predictors of regression of albuminuria were examined in stepwise logistic regression. The variables age, diabetes duration, sex, serum uric acid, HbA1c, systolic blood pressure, LDL cholesterol, HDL cholesterol, BMI, baseline albumin excretion rate, estimated insulin sensitivity at baseline, change in estimated insulin sensitivity from baseline to follow-up and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were considered for inclusion in the model. Results Estimated insulin sensitivity was significantly higher at both baseline (4.6 ± 1.2 vs 3.4 ± 1.7; P = 0.002) and follow-up (5.2 ± 1.9 vs. 3.5 ± 1.7; P < 0.0001) in people who had regression of albuminuria vs those who did not. HbA1c (odds ratio 0.4, 95% CI 0.2-0.8; P = 0.006), estimated insulin sensitivity (odds ratio 2.5, 95% CI 1.3-4.9; P = 0.006) at baseline and change in estimated insulin sensitivity from baseline to follow-up (odds ratio 2.7, 95% CI 1.4-5.3; P = 0.003) were independently associated with regression of albuminuria in a multivariable stepwise model. Conclusions In conclusion, over 6 years, higher baseline estimated insulin sensitivity and change in estimated insulin sensitivity independently predicted regression of albuminuria. Improving insulin sensitivity in people with Type 1 diabetes is a potential therapeutic target to increase rates of regression of albuminuria. [ABSTRACT FROM AUTHOR]

Aim To explore the gender differences, along with the relationships between BMI, glycaemic control, cardiovascular risk factors and the prevalence of diabetes complications, in a representative population-based group of people with Type 1 and Type 2 diabetes. Methods Data were obtained from general practices in Ayrshire and Arran, Scotland for 15 351 patients. Results In the cohort with Type 1 diabetes, after adjustment for age, men had a significantly lower BMI ( P = 0.007) and significantly lower total cholesterol ( P = 0.005), HDL-cholesterol ( P = 2.5*10-17) and HbA1c levels ( P = 0.003) than women. By contrast, men had higher blood pressure, both systolic ( P = 0.034) and diastolic ( P = 0.0003), and higher non-fasting triglyceride levels ( P = 0.001). Men with Type 1 diabetes had a higher prevalence of neuropathy ( P = 0.021). Among people with Type 2 diabetes, men had a significantly lower BMI ( P = 4.26*10-37), and significantly lower total cholesterol ( P = 2.96*10-62) and HDL-cholesterol levels ( P = 8.25*10-141) but higher non-fasting triglyceride levels ( P = 0.0002). In Type 2 diabetes, men had a higher prevalence of ischaemic heart disease ( P = 1.66*10-25), stroke ( P = 0.002) and peripheral vascular disease ( P = 1.68*10-12), while women were older ( P = 4.83*10-23), heavier and had a higher prevalence of hypertension ( P = 5.32*10-12). More people with Type 2 diabetes were on lipid-lowering treatment (84.7 vs 52.4%; P = 5.51*10-8) than were those with Type 1 diabetes. The prevalence of retinopathy was higher among non-smokers thank smokers in people with both Type 1 and Type 2 diabetes (Type 1, P = 0.016; Type 2, P = 0.001). Conclusions The study shows gender differences between Type 1 and 2 diabetes that are of clinical significance and require further investigation. Follow-up of the patients included in the present study should give us much greater understanding of the importance of gender in the development of metabolic abnormalities and diabetes complications. [ABSTRACT FROM AUTHOR]