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Aims: Alongside its metabolic implications, obesity and associated diabetes impair female reproductive function, causing infertility and polycystic ovarian syndrome (PCOS). Recently, gut hormones and their receptors have been identified in various reproductive organs indicating their potential regulatory effects on reproductive function. This review aims to give an overview of their potential effects. Methods: This review focuses on literature that outlines modifications during obesity, diabetes and related infertility with an emphasis on gut hormones and their therapeutic potential. Results: Evidence suggests that bariatric surgery has positive effects on fertility and PCOS where major alterations in metabolism occurs through restoration of gut hormone levels. This is thought to be due to the indirect effect weight loss and regulation of blood glucose has on the hypothalamic–pituitary–ovarian and hypothalamic–pituitary–adrenal axis influencing reproduction. Conclusions: Further research is required to elucidate the cellular mechanisms involved in the direct effects of gut hormone receptor activation on reproductive tissues. Current observations suggest a therapeutic role for gut hormones in infertility/PCOS associated with metabolic pathophysiology. [ABSTRACT FROM AUTHOR]

Obesity is a complex and multifactorial condition that poses significant health risks. Recent advancements in our understanding of obesity have highlighted the heterogeneity within this disorder. Identifying distinct subtypes of obesity is crucial for personalised treatment and intervention strategies. This review paper aims to examine studies that have utilised clinical biomarkers and genetic data to identify clusters or subtypes of obesity. The findings of these studies may provide valuable insights into the underlying mechanisms and potential targeted approaches for managing obesity‐related health issues such as type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: We report contemporary age‐related prevalence, characteristics and care of children and young people with type 2 diabetes in England. Methods: Individuals with a recorded diagnosis of type 2 diabetes between January 2019 and March 2020 were identified from a whole population register. Age, sex, ethnicity, deprivation quintile, weight, HbA1c and receipt of the nine National Institute for Health & Care Excellence (NICE) recommended annual care processes were extracted from electronic clinical records and analysed by pre‐specified age bands. Results: In total, 122,780 (4.6%) of 2,642,435 individuals in England with type 2 diabetes were aged under 40 years, comprising; 650 (0.5%) under 16 years, 910 (0.7%) aged 16–18 years, 8245 (6.7%) aged 19–25 and 112,975 (92%) aged 26–39 years. Compared to people with type 2 diabetes aged above 40 years, young people were significantly more likely to be from minority ethnic groups: 51% under 16 years, 41% 16–18 years, 38% 19–25 years, 38% 26–39 years, 27% 40–59 years and 15% 60–79 years were of Black or Asian ethnicity. In addition, those aged under 40 years were more likely to be obese, women, to live in the most‐deprived socioeconomic areas and less likely to receive the NICE recommended annual care processes or achieve target HbA1c. Interpretation: The substantial number of people under 40 years of age with type 2 diabetes, are more likely to have characteristics associated with inequalities and are less likely to achieve HbA1c targets and receive recommended care processes. These findings highlight the need to consider novel approaches to service provision for this high‐risk group. [ABSTRACT FROM AUTHOR]

Aims: No reports examine the relationship between in‐utero exposure to gestational diabetes mellitus (GDM), offspring epigenetic age acceleration (EAA), and offspring insulin sensitivity. Methods: Using data from a cohort study, we examined associations between GDM in‐utero exposure and offspring EAA at approximately 10 years of age, using separate regression models adjusting for offspring chronological age and sex. We also examined associations between EAA with updated homeostasis model assessment of insulin sensitivity and secretion (HOMA2‐S and HOMA2‐β) measured at approximately 10 and 16 years of age, using mixed linear regression models accounting for repeated measures after adjustment for offspring chronological age and sex. Results: Compared to unexposed offspring (n = 91), offspring exposed to GDM (n = 88) had greater EAA or older extrinsic age compared to chronological age (β‐coefficient 2.00, 95% confidence interval [0.71, 3.28], p = 0.0025), but not greater intrinsic EAA (β‐coefficient −0.07, 95% CI [−0.71, 0.57], p = 0.93). Extrinsic EAA was associated with lower insulin sensitivity (β‐coefficient −0.018, 95% CI [−0.035, −0.002], p = 0.03) and greater insulin secretion (β‐coefficient 0.018, 95% CI [0.006, 0.03], p = 0.003), and these associations persisted after further adjustment for measures of maternal and child adiposity. No associations were observed between intrinsic EAA and insulin sensitivity and secretion, before or after adjustment for measures of maternal and child adiposity. Conclusions: In this study, children exposed to GDM experience greater extrinsic EAA, which is associated with lower insulin sensitivity and greater insulin secretion. Further studies are needed to determine the directionality of these associations. [ABSTRACT FROM AUTHOR]

This personal account presents some glimpses into the clinical research processes which have made radical changes to our understanding of disease and treatment, and some characteristics of researchers, drawn from history and personal experiences around obesity and type 2 diabetes. Some summary messages emerge: The history of clinical diabetes research has shown how, perhaps through skilful leadership, combining very different personalities, skills and motivation can solve great challenges: Type 2 diabetes is a primary nutritional disease, secondary to the disease‐process of obesity, not a primary endocrine disease. Type 2 diabetes is a manifestation of the disease‐process of obesity, revealed by weight gain in people with underlying metabolic syndrome genetics/diathesis, mediated in large part at least by reversible ectopic fat accumulation impairing function of organs (liver, pancreas, brown adipose tissue). Treat overweight/obesity more seriously (defined as a disease‐process with multiple organ‐specific complications—not as a disease‐state or BMI cut‐off). Discuss the complications and risks of T2D openly: remission is as important as for cancers. Offer and support an optimal dietary weight management program as soon as possible from diagnosis, specifically aiming for remission: (a) Warn against non‐evidence‐based programs that look similar or claim to have similar potential: we have fully evidence‐based programs; (b) Target sustained loss of >15 kg for Europeans (possibly less, e.g. >10 kg for Asians?). Increase future research support to enhance long‐term weight loss maintenance. Several approaches need consideration: (a) Personalise diet compositions (recognising there is no intrinsic advantage from different carbohydrate/fat content). (b) Novel diet strategies (e.g. 5:2, time‐restricted, flexible diet compositions). (c) New pharmaceutical agents as adjuncts to diet if necessary. (d) Novel food supplements to increase endogenous GLP‐1 secretion. [ABSTRACT FROM AUTHOR]

Aims: Both lifestyle factors and genetic background contribute to the development of type 2 diabetes. Estimation of the lifetime risk of diabetes based on genetic information has not been presented, and the extent to which a normal body weight can offset a high lifetime genetic risk is unknown. Methods: We used data from 15,671 diabetes‐free participants of European ancestry aged 45 years and older from the prospective population‐based ARIC study and Rotterdam Study (RS). We quantified the remaining lifetime risk of diabetes stratified by genetic risk and quantified the effect of normal weight in terms of relative and lifetime risks in low, intermediate and high genetic risk. Results: At age 45 years, the lifetime risk of type 2 diabetes in ARIC in the low, intermediate and high genetic risk category was 33.2%, 41.3% and 47.2%, and in RS 22.8%, 30.6% and 35.5% respectively. The absolute lifetime risk for individuals with normal weight compared to individuals with obesity was 24% lower in ARIC and 8.6% lower in RS in the low genetic risk group, 36.3% lower in ARIC and 31.3% lower in RS in the intermediate genetic risk group, and 25.0% lower in ARIC and 29.4% lower in RS in the high genetic risk group. Conclusions: Genetic variants for type 2 diabetes have value in estimating the lifetime risk of type 2 diabetes. Normal weight mitigates partly the deleterious effect of high genetic risk. [ABSTRACT FROM AUTHOR]

Aims: Aim of this study is to describe changes in the utilization of basal insulins (glargine, detemir, degludec, neutral protamine Hagedorn [NPH]) among individuals with type 2 diabetes between 2003 and 2018 in the United Kingdom (UK). Materials and Methods: Using the UK Clinical Practice Research Datalink (CPRD) Aurum, we created three study cohorts of individuals with type 2 diabetes: (1) all users of antidiabetic drugs (n = 686,170); (2) initiators of antidiabetic drugs (n = 382,247); and (3) initiators of basal insulins (n = 85,369). Trends in prescription rates were determined using Poisson regression overall and stratified by sex, cardiovascular disease history, and obesity. Crude and adjusted Cox proportional hazards models were used to obtain hazard ratios (HRs) and confidence intervals (CI) comparing rates of treatment change between classes of basal insulins, with an intention‐to‐treat exposure definition. Results: During the study period, prescription rates of insulin analogues increased in the all‐user cohort from 118.3 (95% CI: 116.4, 120.2) prescriptions per 1000 person‐years in 2003 to 579.4 (95% CI: 576.9, 582.0) in 2018. Prescription rates of NPH decreased from 770.5 (95% CI: 765.0, 775.3) in 2003 to 457.7 (95% CI: 455.5, 460.0) in 2018. Compared to initiators of NPH, initiators of detemir were more likely to change treatment (adjusted HR: 1.31, 95% CI: 1.25, 1.37) while glargine initiators were less likely to change treatment (adjusted HR: 0.85, 95% CI: 0.82, 0.88). Conclusions: Basal insulin prescription evolved between 2003 and 2018. Our study provides insight into the evolving use of basal insulin among individuals with type 2 diabetes in the UK. [ABSTRACT FROM AUTHOR]

In the article, the authors discuss their study which examined the effects of body mass index (BMI) and age on the fasting serum glucose and glycosylated haemoglobin (HbA1c) in male and female maturity-onset diabetes of the young 2 (MODY2) and MODY3 probands. Topics include the methods used in the study like the Spearman's rank analysis and least linear square approach, and the results showing deteriorating fasting glucose in MODY2.

Diabetic peripheral neuropathy in people with type 2 diabetes is poorly managed because of its insidious onset, delayed diagnosis and more complex aetiology resulting from the contribution of not only hyperglycaemia, but also ageing, hyperlipidaemia, hypertension and obesity. Because there is no US Food and Drug Adminstration‐approved disease‐modifying therapy for diabetic peripheral neuropathy, the key to ameliorating it in type 2 diabetes has to be through earlier diagnosis and timely multi‐factorial risk factor reduction. The management of painful diabetic peripheral neuropathy also requires a detailed appraisal of the choice of therapy, taking into account efficacy, patient wishes, comorbidities, side effect profile and potential for abuse. What's new?: Neuropathy is a common and severe consequence of diabetes mellitus.Early diabetic neuropathy is difficult to diagnose.There are no disease‐modifying therapies for diabetic neuropathy.The diagnosis of diabetic neuropathy relies on clinical evaluation, which detects disease too late.More objective measures of diagnosing and assessing the severity of diabetic neuropathy are required.The diagnostic approach to diabetic neuropathy needs to change to identify early nerve damage, especially in type 2 diabetes.The management of diabetic neuropathy in type 2 diabetes requires a multifactorial approach and tailored pharmacotherapy. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the association between sarcopenic obesity and the decline in estimated GFR in people with type 2 diabetes. Methods: We enrolled 745 people with type 2 diabetes (mean age 64.6 years, 53.6% men). Body composition was evaluated using dual‐energy X‑ray absorptiometry. Skeletal muscle index, calculated as appendicular non‐fat mass (kg) divided by height squared (m2), was used to determine sarcopenia. Sarcopenic obesity was defined as the coexistence of sarcopenia and a ratio of android to gynoid fat mass greater than the median values in each gender. The association of sarcopenic obesity both with the annual rate of decline in estimated GFR and a >30% decline in estimated GFR was evaluated using multivariate linear regression models and Cox proportional hazard models, respectively. Results: Participants with sarcopenic obesity were at an increased risk of a high annual rate of decline in estimated GFR, even after adjustment for the confounding variables (standardized β = −0.228, P <0.001). Sarcopenic obesity was also significantly associated with risk of a >30% decline in estimated GFR (hazard ratio 4.52, 95% CI 2.16–9.47; P < 0.01) in multivariate model. Conclusions: Sarcopenic obesity evaluated by dual energy X‑ray absorptiometry is associated with a faster decline in renal function in people with type 2 diabetes. What's new?: People with sarcopenic obesity, defined as the coexistence of sarcopenia and obesity, were reported to have an extremely high risk of metabolic abnormalities including insulin resistance, metabolic syndrome and diabetes; however, the impact of sarcopenic obesity on decline in renal function has not been fully established.This study demonstrated that sarcopenic obesity was significantly associated with a high annual rate of estimated GFR (eGFR) decline and a >30% decline in eGFR in both men and women with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the percentage of women with untreated fasting hyperglycaemia in early pregnancy who develop gestational diabetes mellitus after 22 weeks' gestation, the determinants of gestational diabetes development in such women and the prognosis of early fasting hyperglycaemia according to whether the women go on to develop gestational diabetes. Methods: From a large cohort of women who delivered in our hospital between 2012 and 2016, we retrospectively selected all those who had untreated early fasting hyperglycaemia and separated them into a 'gestational diabetes' and a 'no‐gestational diabetes' group according to oral glucose tolerance test results after 22 weeks' gestation. We compared the incidence of a predefined composite outcome (preeclampsia or large‐for‐gestational‐age infant or shoulder dystocia or neonatal hypoglycaemia) in both groups. Results: A total of 268 women (mean fasting plasma glucose 5.3 ± 0.3 mmol/l at a mean ± sd of 10.2 ± 4.2 weeks' gestation) were included. Gestational diabetes developed in 134 women and was independently associated with early fasting plasma glucose ≥ 5.5 mmol/l [odds ratio 3.16 (95% CI 1.57, 6.33)], age ≥ 30 years [odds ratio 2.78 (95% CI 1.46, 5.31)], preconception obesity [odds ratio 2.12 (95% CI 1.11, 4.02)], family history of diabetes [odds ratio 1.87 (95% CI 1.00, 3.50)] and current employment [odds ratio 0.46 (95% CI 0.26, 0.83)]. Despite treatment, gestational diabetes induced a significant increase in the composite outcome as compared to no gestational diabetes (odds ratio 2.16 [95% CI 1.08, 4.34]). The association disappeared after adjustment for risk factors. Conclusions: Only half of the women with early fasting hyperglycaemia and no specific care subsequently developed gestational diabetes, and these women had a poor prognosis despite gestational diabetes treatment. Poor prognosis was mostly attributable to risk factors. Our results suggest that only women with certain risk factors should be screened for early fasting hyperglycaemia. What's new?: Guidelines recommend treatment of women with fasting plasma glucose levels ≥5.1 mmol/l during early pregnancy immediately after diagnosis; however approximately half of untreated women do not develop gestational diabetes mellitus after 24 weeks' gestation.Women with untreated early fasting hyperglycaemia have more risk factors and adverse outcomes if they develop gestational diabetes after 22 weeks' gestation (50%), and this occurs despite subsequent treatment.Only women with risk factors should be screened for early fasting hyperglycaemia during pregnancy. [ABSTRACT FROM AUTHOR]

Aims: To determine the prevalence and potential risk factors for diabetic peripheral neuropathy with a loss of protective sensation in Barbados. Methods: A representative population sample aged > 25 years with previously diagnosed diabetes or a fasting blood glucose ≥ 7 mmol/l or HbA1c ≥ 48 mmol/mol (6.5%) was tested by 10 g monofilament at four plantar sites per foot and a 28 Hz tuning fork and neurothesiometer at the hallux. Data were adjusted to the age structure of people with diabetes in Barbados. Multivariable logistic regression assessed associations with peripheral neuropathy with a loss of protective sensation. Results: Of 236 participants [74% response rate, 33% men, 91% black, median age 58.6 years, mean BMI 30.1 kg/m2, mean HbA1c 54 mmol/mol (7.1%)], 51% had previously diagnosed diabetes. Foot examination demonstrated that 25.8% (95% CI 20.2 to 31.5) had at least one insensate site with monofilament testing, 14.8% (95% CI 10.2 to 19.4) had an abnormal tuning fork test and 10.9% (95% CI 6.9 to 14.9) had a vibration perception threshold > 25 V. Peripheral neuropathy with a loss of protective sensation prevalence was 28.5% (95% CI 22.7 to 34.4) as indicated by monofilament with ≥ 1 insensate site and/or vibration perception threshold > 25 V. With previously diagnosed diabetes the prevalence was 36.4% (95% CI 27.7 to 45.2) with 98.4% of cases identified by monofilament testing. Increasing age, previously diagnosed diabetes, male sex and abdominal obesity were independently associated with peripheral neuropathy with a loss of protective sensation. Conclusions: Over a third of people with previously diagnosed diabetes had evidence of peripheral neuropathy with a loss of protective sensation. Monofilament testing alone may be adequate to rule out peripheral neuropathy with a loss of protective sensation. Monofilament and neurothesiometer stimuli are reproducible but dependent on participant response. What's new?: In Barbados, foot problems account for 89% of diabetes‐related hospital admissions, but in primary care only 41% had a foot examination over a 2‐year period. Peripheral neuropathy prevalence in a predominantly African descent Caribbean population with diabetes is unknown.In people with known and newly diagnosed diabetes, the prevalence of peripheral neuropathy with a loss of protective sensation was 28.5% (95% CI 22.7 to 34.4) as indicated by monofilament testing with ≥ 1 insensate site and/or vibration perception threshold > 25 V. Monofilament testing alone identified 98% of such cases in people with previously diagnosed diabetes.Monofilament testing alone may be adequate for screening for peripheral neuropathy with a loss of protective sensation. [ABSTRACT FROM AUTHOR]

Aim: Overweight and obesity are frequently reported in young persons with type 1 diabetes, however its relative magnitude in comparison to the general population is not well understood. This study compared the prevalence of overweight and obesity in young persons with type 1 diabetes to a reference population and explored possible associated factors, including gender, age, HbA1c, insulin regimen, age at diagnosis, diabetes duration, socio‐economic status and cardiovascular disease risk factors. Methods: A cross‐sectional review was undertaken of data collected from youth (3–17 years) in 2016 and young adults (18–30 years) in 2015 with a diagnosis of type 1 diabetes for > 3 months attending diabetes centres in Newcastle, Australia. Rates of overweight and obesity were compared with matched population survey results. Results: Data from 308 youth and 283 young adults were included. In girls, significantly higher prevalence of overweight and obesity were seen in the 5–8 (43% vs. 18%), 13–16 (41% vs. 27%), 18–24 (46% vs. 34%) and 25–30 (60% vs. 43%) years age groups; whereas in boys increased prevalence was observed in the 5–8 years age group only (41% vs. 18%). Rates of overweight and obesity increased with age across sexes. In youth, BMI standard deviation score was correlated with socio‐economic status, insulin regimen, blood pressure and blood lipids (P < 0.05). In adults, BMI was positively associated with blood pressure, and longer diabetes duration (P < 0.02). Conclusions: Overweight and obesity are over‐represented in young persons with type 1 diabetes, particularly girls. As overweight is associated with other cardiovascular disease markers early intervention is paramount. What's new?: Overweight and obesity are highly prevalent in young people with type 1 diabetes and are associated with increased cardiovascular disease risk factors.This study has shown that across a paediatric and adult service in a single geographic region in Australia, women with type 1 diabetes are significantly more overweight and obese compared with women from age matched groups in the general population.Overweight and obesity rates increase with age.This research suggests that interventions to prevent excessive weight gain should target girls with type 1 diabetes prior to teenage years. [ABSTRACT FROM AUTHOR]

Aims: To determine obstructive sleep apnoea prevalence in people with Type 2 or Type 1 diabetes in a national primary care setting, stratified by BMI category, and to explore the relationship between patient characteristics and obstructive sleep apnoea. Methods: Using the Royal College of General Practitioners Research and Surveillance Centre database, a cross‐sectional analysis was conducted. Diabetes type was identified using a seven‐step algorithm and was grouped by Type 2 diabetes, Type 1 diabetes and no diabetes. The clinical characteristics of these groups were analysed, BMI‐stratified obstructive sleep apnoea prevalence rates were calculated, and a multilevel logistic regression analysis was completed on the Type 2 diabetes group. Results: Analysis of 1 275 461 adult records in the Royal College of General Practitioners Research and Surveillance Centre network showed that obstructive sleep apnoea was prevalent in 0.7%. In people with Type 2 diabetes, obstructive sleep apnoea prevalence increased with each increasing BMI category, from 0.5% in those of normal weight to 9.6% in those in the highest obesity class. By comparison, obstructive sleep apnoea prevalence rates for these BMI categories in Type 1 diabetes were 0.3% and 4.3%, and in those without diabetes 1.2% and 3.9%, respectively. Obstructive sleep apnoea was more prevalent in men than women in both diabetes types. When known risk factors were adjusted for, there were increased odds ratios for obstructive sleep apnoea in people with Type 2 diabetes in the overweight and higher BMI categories. Conclusions: Obstructive sleep apnoea was reported in people with both types of diabetes across the range of overweight categories and not simply in the highest obesity class. What's new?: Links among Type 2 diabetes mellitus, obesity and obstructive sleep apnoea (OSA) have been established in secondary care clinic studies, but primary care population data are limited.From a national primary care network, we ascertained that people with Type 2 diabetes had an increased OSA prevalence in every excessive weight category, from overweight to obesity class 3. People with Type 1 diabetes had similar OSA prevalence rates as those without diabetes.Strategies to diagnose and manage OSA need to consider its increased prevalence in people with Type 2 diabetes who are overweight as well as those with obesity. [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]

Joint problems commonly occur in people with diabetes. Cheiroarthropathy affects the hands and results in painless limited finger joint extension, appearing to be associated with longer diabetes duration and the presence of microvascular complications. The prevalence of cheiroarthropathy seems to be falling, perhaps as a result of improvements in glycaemic management. Non‐enzymatic glycation of collagen results in abnormally crosslinked protein resistant to degradation with subsequent increased build‐up of collagen in joints. The management of cheiroarthropathy is predominantly conservative, with occupational and hand therapy at the forefront. Tendinopathy is more common in people with diabetes than those without, and is associated with obesity and insulin resistance. As with cheiroarthropathy, the exact causative mechanism of tendinopathy in diabetes is not known, but may be linked to inflammation, apoptosis and increased vascularity of affected tendons, driven by hyperinsulinaemia. Local fat pads have also been suggested to play a role in the pathogenesis of tendinopathy. What's new?: This study presents a comprehensive overview of the current state of play regarding cheiroarthropathy and tendinopathy in diabetes.In patients with microvascular complications of diabetes, the presence of cheiroarthropathy should be considered.Tendinopathy should be considered to be more than simply a structural problem. Dyslipidaemia, hyperinsulinaemia and Type 2 diabetes are strongly linked with tendinopathy; management of these factors may mitigate the risk of developing tendinopathy. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the interaction effects of gestational diabetes (GDM) with obesity on perinatal outcomes. Methods: A population‐based cohort study in Sweden excluding women without pre‐gestational diabetes with a singleton birth between 1998 and 2012. Logistic regression was performed to evaluate the potential independent associations of GDM and BMI with adverse perinatal outcomes as well as their interactions. Main outcome measures were malformations, stillbirths, perinatal mortality, low Apgar score, fetal distress, prematurity and Erb's palsy. Results: Some 1,294,006 women were included, with a GDM prevalence of 1% (n = 14,833). The rate of overweight/obesity was 67.7% in the GDM‐group and 36.1% in the non‐GDM‐group. No significant interaction existed. Offspring of women with GDM had significantly increased risk of malformations, adjusted odds ratio (aOR) 1.16 (95% confidence intervals 1.06–1.26), prematurity, aOR 1.86 (1.76–1. 98), low Apgar score, aOR 1.36 (1.10–1.70), fetal distress, aOR 1.09 (1.02–1.16) and Erb's palsy aOR 2.26 (1.79–2.86). No risk for stillbirth or perinatal mortality was seen. Offspring of overweight (BMI 25–29.9 kg/m2), obese (BMI 30–34.9 kg/m2) and severely obese women (BMI ≥ 35.0 kg/m2) had significantly increased risks of all outcomes including stillbirth 1.51 (1.40–1.62) to 2.85 (2.52–3.22) and perinatal mortality 1.49 (1.40–1.59) to 2.83 (2.54–3.15). Conclusions: There is no interaction effect between GDM and BMI for the studied outcomes. Higher BMI and GDM are major independent risk factors for most serious adverse perinatal outcomes. More effective pre‐pregnancy and antenatal interventions are required to prevent serious adverse pregnancy outcomes among women with either GDM or high BMI. What's new?: It is known that both gestational diabetes (GDM) and maternal overweight are associated with adverse perinatal outcomes.Excess maternal weight and GDM have comparable and independent effects on adverse perinatal outcomes.GDM is not associated with perinatal mortality and stillbirth in the Swedish population.There is a need for research on interventions that reduce the effects of hyperglycaemia and prevent/better manage overweight/obesity to be able to improve perinatal outcomes. [ABSTRACT FROM AUTHOR]

Aims To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes mellitus. Methods We recruited patients with Type 2 diabetes with a BMI ≥ 24 kg/m2, who visited the diabetes clinics of 60 hospitals in 21 cities in Guangdong Province, China from August 2011 to March 2012. Anthropometric measurements, biochemical tests and abdominal ultrasonography were performed for all the patients. Results The study included 3861 patients (1860 men) with a mean ± sd (range) age of 58.91 ± 13.06 (18-90) years. Non-alcoholic fatty liver disease was found in 1751 patients (45.4%), with a significantly higher prevalence among men than women (48.0 vs 42.9%). The peak of non-alcoholic fatty liver disease prevalence was in patients with a BMI of 34-35 kg/m2, those with a triglyceride/ HDL cholesterol ratio of 5.5-6.0, men aged < 30 years and women aged 40-50 years. Assessment using the BARD ( BMI, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score system showed that the prevalence of advanced fibrosis was 80.52% in all patients and that women had a higher prevalence than men (86.52 vs 74.16%). Multiple logistic regression analyses showed that dyslipidaemia, BMI and 2-h postprandial plasma glucose were independent risk factors for non-alcoholic fatty liver disease, while heart rate and female gender were protective factors. Conclusion The prevalence of non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes in South China is high. Multiple metabolic disorders were significantly associated with non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims To assess the non-linear relationship between BMI and mortality and to determine the BMI values with the lowest mortality risk in adults with and without diabetes. Methods This observational study assessed the relationship between BMI and mortality with flexible parametric survival models using data from the US National Health Interview Survey. Participants included 25 458 adults with diabetes and 315 939 adults without diabetes, aged 18-84 years at baseline surveys, conducted from 1997 to 2009. Mortality status data were obtained from the linked mortality data up to 2011. Results We observed a U-shaped relationship between BMI and mortality in both adults with and without diabetes. With the BMI 25-29.9 kg/m2 group as reference, hazard ratios (95% CI) of mortality for those with BMI < 18.5, 18.5-24.9, 30-34.9, 35-39.9 and ≥ 40 kg/m2 were 2.67 (2.12, 3.35), 1.26 (1.18, 1.35), 1.04 (0.98, 1.12), 1.12 (1.02, 1.22) and 1.37 (1.24, 1.51), respectively, for adults with diabetes, adjusting for age, sex, race and survey year. The corresponding hazard ratios for adults without diabetes were 2.97 (2.78, 3.17), 1.27 (1.23, 1.30), 1.07 (1.03, 1.12), 1.36 (1.27, 1.45), and 1.77 (1.62, 1.92), respectively. The BMI values associated with the lowest mortality were 29.1 kg/m2 for adults with diabetes and 26.7 kg/m2 for those without diabetes. Conclusions Regardless of the presence of diabetes, there is a U-shaped relationship between BMI and mortality. The BMI values associated with the lowest mortality were above the current 'normal' range for adults with and without diabetes. [ABSTRACT FROM AUTHOR]

Aim To explore barriers to and motivators for physical activity in a group of overweight and obese individuals with dysregulated Type 2 diabetes. Methods Data were collected from the Steno Diabetes Center's outpatient clinic in Denmark. Four focus groups were conducted including 28 individuals with Type 2 diabetes aged 39-71 years. The facilitators used open-ended questions and probes such as images, statements and quotations about physical activity to foster active participation and interaction among participants. Focus groups were recorded on video and the discussions were transcribed and analysed thematically. Results We identified four main themes: 1) the body as a barrier to physical activity because of functional limitations; 2) logistical challenges, including lack of time and awareness of where to exercise in the local area; 3) being physically active with others, providing a sense of mutual commitment and enjoyment; and 4) goal-setting and self-tracking, which was seen as an opportunity to track physical improvement over time. Conclusions The findings suggest that, once people are active, a high level of social interaction may help maintain their activity levels. Further research is needed to investigate the effect of combining individually tailored exercise plans with the establishment of customized and locally based exercise communities that offer enjoyment and support. Additionally, it is relevant to explore experiences of using self-tracking technologies to review short- and long-term goals. [ABSTRACT FROM AUTHOR]

Aim Although pedometer intervention is effective in increasing physical activity among adults with Type 2 diabetes, its impact on weight loss remains unclear. This meta-analysis was aimed to assess whether pedometer intervention promotes weight loss. Methods Three different databases were searched for randomized controlled trials (RCTs) published in English up to April 2015. Studies were included if they investigated the effects of pedometer intervention on weight loss, as measured by BMI or weight. Effect sizes were aggregated using a random-effects model. Subgroup and meta-regression analyses were used to identify potential moderators. Eleven RCTs with 1258 participants were included. All enrolled participants were overweight or obese. Results Pedometer intervention led to significantly decreased BMI [weighted mean difference (WMD) −0.15 kg/m2, 95% confidence interval (CI) −0.29 to −0.02 kg/m2] and reduced weight (WMD −0.65 kg, 95% CI −1.12 to −0.17 kg). Dietary counselling seemed to be a key predictor of the observed changes. However, none of the following variables had a significant influence: step goal setting, baseline age, BMI, weight, sex distribution, disease duration, intervention duration, and baseline values or change scores for total or moderate-to-vigorous physical activity. After completion of the pedometer intervention, non-significant declines in BMI and weight were observed during the follow-up periods. Conclusions Pedometer intervention promotes modest weight loss, but its association with physical activity requires further clarification. Future studies are also required to document dietary and sedentary behaviour changes to facilitate the use of pedometers for weight loss in overweight and obese adults with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aim Obesity is a well-established risk factor for developing Type 2 diabetes. Evidence suggests that sarcopenia, the age-related decline in muscle mass and strength, may exacerbate diabetes risk in obese individuals. The aim of this study was to determine the combined effect of obesity and low muscle strength, dynapenia, on the risk of incident Type 2 diabetes in older adults. Methods Participants were 5953 (1670 obese) men and women from the English Longitudinal Study of Ageing without known Type 2 diabetes at baseline and for whom handgrip strength, biochemical and other clinical data were collected. A diagnosis of Type 2 diabetes was recorded from self-reported physician diagnosis over 6 years. Results For each unit increase in grip strength, there was a reduction in diabetes risk (age-, sex- and BMI adjusted HR; 0.98; 95% CI 0.96-0.99). The risk of Type 2 diabetes was elevated in all obese participants, but was greatest in those with low handgrip strength (HR = 4.93, 95% CI 2.85, 8.53) compared with non-obese individuals with high handgrip strength. Eleven per cent of the sample met the threshold for weakness (handgrip strength: men < 26 kg; women < 16 kg) that was associated with elevated Type 2 diabetes risk in obese ( HR = 3.57, 95% CI 2.04, 6.24) but not in non-obese ( HR = 0.86, 95% CI, 0.44, 1.68) compared with normal/non-obese participants. Conclusion Dynapenic obesity, determined by high BMI and low handgrip strength, is associated with increased risk of incident Type 2 diabetes in older people. [ABSTRACT FROM AUTHOR]

Aims To explore the efficacy and acceptability of very low energy diets in overweight or obese adults with Type 2 diabetes. Methods Controlled trials and qualitative studies of individuals with Type 2 diabetes that compared very low energy diets with standard care, minimal interventions, other weight loss interventions, less intensive very low energy diet interventions and very low energy diets with additional components were eligible for inclusion. Meta-analyses of changes in weight, blood glucose levels and attrition rates were performed. Acceptability of very low energy diets was assessed by attrition rates, number and severity of side effects, and by qualitative evaluations of the interventions. Results Four randomized, five non-randomized controlled trials and no qualitative studies (21 references, 9 studies, 346 participants) were identified. Meta-analyses showed that very low energy diets induced greater weight losses than minimal interventions, standard care or low energy diets at 3 and 6 months. No conclusive evidence for differences in outcomes between very low energy diets and Roux-en-Y gastric bypass surgery was found. Greater differences in energy prescription between intervention and comparator arms were associated with greater differences in weight loss and fasting blood glucose levels at 3 months. Attrition rates did not differ between the very low energy diets and the comparator arms at any measurement point. Conclusions Very low energy diets are effective in substantial weight loss among people with Type 2 diabetes. Levels of adherence to very low energy diets in controlled studies appear to be high, although details about behaviour support provided are usually poorly described. [ABSTRACT FROM AUTHOR]

The article presents abstracts on diabetes in pregnancy topics which include the thin-fat fetal phenotype in pregnancies with gestational diabetes (GDM), analysis of placental G-protein coupled receptors (GPCRs) ligand secretome in mouse, and the association between sleep and glycaemic control.

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 Diabetes rates are high in Asia despite relatively low rates of obesity, which might be related to lower muscle mass. Muscle mass plays an important role in glucose metabolism. Peak muscle mass is obtained in late adolescence. We tested the hypothesis that pubertal testosterone is negatively associated with glucose metabolism mediated by muscle mass. Methods Participants aged 15 years (278 boys and 223 girls) were recruited from the Hong Kong's 'Children of 1997' birth cohort in 2012. Multivariable linear regression with multiple imputation and inverse probability weighting was used to examine the adjusted associations of pubertal testosterone with skeletal muscle index, body fat percentage, fasting glucose, insulin and homeostasis model of assessment - insulin resistance. Results Total testosterone was negatively associated with fasting glucose (−0.008, 95% confidence interval −0.015 to −0.002), insulin (−0.43, 95% confidence interval −0.56 to −0.30) and insulin and homeostasis model of assessment - insulin resistance (−0.09, 95% confidence interval −0.12 to −0.06) adjusted for sex, birth weight, highest parental education, mother's place of birth and physical activity. These associations were attenuated by additional adjustment for skeletal mass index or body fat percentage. Conclusions Adolescent glucose metabolism may be influenced by testosterone, perhaps partially via skeletal muscle mass. [ABSTRACT FROM AUTHOR]

Aims To examine the association between gestational diabetes mellitus ( GDM) and high maternal weight and the risk of development of chronic disease. Methods Women with singleton deliveries between April 1999 and March 2010 in Alberta, Canada, were categorized according to pre-pregnancy weight (overweight ≥ 91 kg) and GDM status. Obstetric and neonatal outcomes, as well as the long-term incidence of maternal diabetes, hypertension and cardiovascular disease were examined. Results Of 240 083 women, 213 765 (89%) had no GDM and were not overweight (reference group), 17 587 (7.3%) were overweight only, 7332 (3%) had GDM only and 1399 (0.6%) had GDM and were overweight. Significant differences in Caesarean section rates, induction rates and birthweight were observed across the four groups. During a median follow-up of 5.3 years, diabetes incidence was 36% in the GDM and overweight, 18.8% in the GDM only, 4.8% in the overweight only and 1.1% in the reference group. With respect to hypertension and cardiovascular disease, the GDM and overweight group had the highest rates (26.8% and 3.1%, respectively) and the reference group had the lowest rates (5.8% and 1.0%, respectively). However, rates were similar in the GDM only (14.9% and 1.9%, respectively) and overweight only groups (14.9% and 1.5%, respectively). Conclusions Not surprisingly, the presence of both high maternal weight and GDM compounds the risk of developing diabetes. However, the association between overweight alone and GDM alone and hypertension and cardiovascular disease appears similar suggesting a need for effective interventions to manage both these conditions to improve the health of these patients. [ABSTRACT FROM AUTHOR]

Aims Conventional definitions of obesity, e.g. body mass index ( BMI) ≥ 30 kg/m2 or waist circumference cut-points of 102 cm (men) and 88 cm (women), may underestimate metabolic risk in non-Europeans. We prospectively identified equivalent ethnicity-specific obesity cut-points for the estimation of diabetes risk in British South Asians, African-Caribbeans and Europeans. Methods We studied a population-based cohort from London, UK (1356 Europeans, 842 South Asians, 335 African-Caribbeans) who were aged 40-69 years at baseline (1988-1991), when they underwent anthropometry, fasting and post-load (75 g oral glucose tolerance test) blood tests. Incident Type 2 diabetes was identified from primary care records, participant recall and/or follow-up biochemistry. Ethnicity-specific obesity cut-points in association with diabetes incidence were estimated using negative binomial regression. Results Diabetes incidence rates (per 1000 person years) at a median follow-up of 19 years were 20.8 (95% CI: 18.4, 23.6) and 12.0 (8.3, 17.2) in South Asian men and women, 16.5 (12.7, 21.4) and 17.5 (13.0, 23.7) in African-Caribbean men and women, and 7.4 (6.3, 8.7), and 7.2 (5.3, 9.8) in European men and women. For incidence rates equivalent to those at a BMI of 30 kg/m2 in European men and women, age- and sex-adjusted cut-points were: South Asians, 25.2 (23.4, 26.6) kg/m2; and African-Caribbeans, 27.2 (25.2, 28.6) kg/m2. For South Asian and African-Caribbean men, respectively, waist circumference cut-points of 90.4 (85.0, 94.5) and 90.6 (85.0, 94.5) cm were equivalent to a value of 102 cm in European men. Waist circumference cut-points of 84.0 (74.0, 90.0) cm in South Asian women and 81.2 (71.4, 87.4) cm in African-Caribbean women were equivalent to a value of 88 cm in European women. Conclusions In prospective analyses, British South Asians and African-Caribbeans had equivalent diabetes incidence rates at substantially lower obesity levels than the conventional European cut-points. [ABSTRACT FROM AUTHOR]

Aims There is some confusion regarding which anthropometric measurement of adiposity should be used to indicate diabetes, especially for Asians. The present study was to evaluate different indicators of adiposity (BMI, waist circumference and body fat) with Type 2 diabetes risk among women with prior gestational diabetes mellitus. Methods We performed a cross-sectional survey in 1263 women with gestational diabetes at 1-5 years after delivery. Logistic regression models were used to estimate the association of BMI, waist circumference and body fat with Type 2 diabetes risk. Results BMI, waist circumference and body fat were all associated with an increased risk of Type 2 diabetes among women with prior gestational diabetes (all Ptrend < 0.001). After adjustment for waist circumference and body fat, the positive association of BMI with Type 2 diabetes risk became non-significant and reversed. There was a significantly positive association of waist circumference with Type 2 diabetes risk after adjustment for BMI, and a significantly positive association of body fat with Type 2 diabetes risk after adjustment for both BMI and waist circumference. When the joint effects were examined, the significantly positive associations of waist circumference or body fat with Type 2 diabetes risk were consistent among women with different levels of BMI, and the positive association of BMI and Type 2 diabetes risk was significant among women with gestational diabetes with a waist circumference of ⩾ 50% or body fat ⩾ 50%. Conclusions BMI, waist circumference and body fat were all associated with an increased risk of Type 2 diabetes, and waist circumference and body fat were better indicators than BMI for Type 2 diabetes risk among Chinese women with prior gestational diabetes. [ABSTRACT FROM AUTHOR]

Renal transplantation has important benefits in people with end-stage renal disease, with improvements in mortality, morbidity and quality of life. Whilst significant advances in transplantation techniques and immunosuppressive regimens have led to improvements in short-term outcomes, longer-term outcomes have not improved dramatically. New-onset diabetes after transplantation appears to be a major factor in morbidity and cardiovascular mortality in renal transplant recipients. The diagnosis of new-onset diabetes after renal transplantation has been hampered by a lack of clarity over diagnostic tests in early studies, although the use of the WHO criteria is now generally accepted. HbA1c may be useful diagnostically, but should probably be avoided in the first 3 months after transplantation. The pathogenesis of new-onset diabetes after renal transplantation is likely to be related to standard pathogenic factors in Type 2 diabetes (e.g. insulin resistance, b-cell failure, inflammation and genetic factors) as well as other factors, such as hepatitis C infection, and could be exacerbated by the use of immunosuppression (glucocorticoids and calcineurin inhibitors). Pre-transplant risk scores may help identify those people at risk of new-onset diabetes after renal transplantation. There are no randomized trials of treatment of new-onset diabetes after renal transplantation to determine whether intensive glucose control has an impact on cardiovascular or renal morbidity, therefore, treatment is guided by guidelines used in non-transplant diabetes. Many areas of uncertainty in the pathogenesis, diagnosis and management of new-onset diabetes after renal transplantation require further research. [ABSTRACT FROM AUTHOR]

Aims Thiazolidinediones reduce ectopic fat, increase adiponectin and reduce inflammatory adipokines, fatty acids and glucose in people with Type 2 diabetes. We aimed to measure these effects in people with impaired fasting glucose and/or impaired glucose tolerance. Methods After approximately 3.5 years of exposure to rosiglitazone 8 mg ( n = 88) or placebo ( n = 102), 190 DREAM trial participants underwent abdominal computed tomography and dual-energy X-ray absorptiometry scans. Visceral and subcutaneous adipose tissue areas, estimated hepatic fat content, total fat and lean mass were calculated and changes in levels of fasting adipokines, free fatty acids, glucose and post-load glucose were assessed. Results Compared with the placebo, participants on rosiglitazone had no difference in lean mass, had 4.1 kg more body fat ( P < 0.0001) and 31 cm2 more subcutaneous abdominal adipose tissue area ( P = 0.007). Only after adjusting for total fat, participants on rosiglitazone had 23 cm² less visceral adipose tissue area ( P = 0.01) and an 0.08-unit higher liver:spleen attenuation ratio (i.e. less hepatic fat; P = 0.02) than those on the placebo. Adiponectin increased by 15.0 μg/ml with rosiglitazone and by 0.4 μg/ml with placebo ( P < 0.0001). Rosiglitazone's effect on fat distribution was not independent of changes in adiponectin. Rosiglitazone's effects on fasting (-0.36 mmol/l; P = 0.0004) and 2-h post-load glucose (-1.21 mmol/l; P = 0.0008) were not affected by adjustment for fat distribution or changes in adiponectin or free fatty acids. Conclusions In people with impaired fasting glucose/impaired glucose tolerance, rosiglitazone is associated with relatively less hepatic and visceral fat, increased subcutaneous fat and increased adiponectin levels. These effects do not appear to explain the glucose-lowering effect of rosiglitazone. [ABSTRACT FROM AUTHOR]

Aim To examine the prediction of gestational diabetes in obese women using routine clinical measures and measurement of biomarkers related to insulin resistance in the early second trimester. Methods A total of 117 obese pregnant women participating in a pilot trial of a complex intervention of dietary advice and physical activity were studied. Blood samples were obtained at recruitment (15+0-17+6 weeks' gestation) and demographic, clinical history and anthropometric measures recorded. The biomarkers analysed were plasma lipids ( HDL cholesterol, LDL cholesterol, triglycerides), high-sensitivity C-reactive protein, alanine transaminase, aspartate transaminase, ferritin, fructosamine, insulin, adiponectin, tissue plasminogen activator, interleukin-6, visfatin and leptin. Univariate and logistic regression analyses were performed to determine independent predictors and area under the receiver-operating curve was calculated for the model. Results Of the 106 participants included in the analysis, 29 (27.4%) developed gestational diabetes. Participants with gestational diabetes were older ( P = 0.002), more often of parity ≥ 2, had higher systolic ( P = 0.02) and diastolic blood pressure ( P = 0.02) and were more likely to be black ( P = 0.009). Amongst the blood biomarkers measured, plasma adiponectin alone remained independently associated with gestational diabetes in adjusted models ( P = 0.002). The area under the receiver-operating curve for clinical factors alone (0.760) increased significantly (area under the curve 0.834, chi-square statistic (1) = 4.00, P = 0.046) with the addition of adiponectin. Conclusions A combination of routinely measured clinical factors and adiponectin measured in the early second trimester in obese women may provide a useful approach to the prediction of gestational diabetes. Validation in a large prospective study is required to determine the usefulness of this algorithm in clinical practice. (Clinical Trial Registry No: ISRCTN89971375) [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including Melanocortin-4 receptor (MC4R) genotypes as treatment for obese patient with type 2 diabetes, use of pedometer to monitor patients weight loss and risk of diabetes for obese persons.

The article presents abstracts related to non-islet biology including the deficiency on neuronal interleukin 6 (IL-6) receptor which excerbates glucose intolerance, the infusion of peptide that exacerbates metabolic dysfunction, and the brain glucokinase which is a glucose homeostasis determinant.

The article discusses the search for genes in type 2 diabetes. Topics include the hunt for type 2 diabetes genes, the mapping of the human genome and microarray-based technology, and the arrival of genome-wide association studies, which allowed hypothesis-free testing of the human genome. Other topics include the discovery of 60 or more loci robustly associated with Type 2 diabetes, and the discovery of the exome and whole-genome sequencing.