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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 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 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 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]

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]

Aims The addition of the 1-h plasma glucose concentration measure from an oral glucose tolerance test to prediction models of future Type 2 diabetes has shown to significantly strengthen their predictive power. The present study examined the relationship between severity of depressive symptoms and hyperglycaemia, focusing on the 1-h glucose concentration vs. fasting and 2-h glucose measures from the oral glucose tolerance test. Methods Participants included 140 adults with the metabolic syndrome and without diabetes who completed a baseline psychobiological assessment and a 2-h oral glucose tolerance test, with measurements taken every 30 min. Depressive symptoms were assessed using the Beck Depression Inventory. Results Multivariate linear regression revealed that higher levels of depressive symptoms were associated with higher levels of 1-h plasma glucose concentrations after adjusting for age, gender, ethnicity, BMI, antidepressant use and high-sensitivity C-reactive protein. Results were maintained after controlling for fasting glucose as well as for indices of insulin resistance and secretion. Neither fasting nor 2-h plasma glucose concentrations were significantly associated with depressive symptoms. Conclusions Elevated depressive symptoms in persons with the metabolic syndrome were associated with greater glycaemic excursion 1-h following a glucose load that was not accounted for by differences in insulin secretory function or insulin sensitivity. Consistent with previous findings, this study highlights the value of the 1-h plasma glucose measurement from the oral glucose tolerance test in the relation between depressive symptoms and glucose metabolism as an indicator of metabolic abnormalities not visible when focusing on fasting and 2-h post-oral glucose tolerance test measurements alone. [ABSTRACT FROM AUTHOR]

Aim's The aim was to To study the relationship between BMI and hospitalization for heart failure in people with Type 2 diabetes. Methods We identified 83 021 individuals with Type 2 diabetes from the Swedish National Diabetes Registry during 1998-2003, who were followed until hospitalization for heart failure, death or end of follow-up on 31 December 2009. Cox regression analyses were performed, adjusting for age, sex, HbA1c, blood pressure, diabetes duration, smoking, microalbuminuria, cardiac co-morbidities, glucose-lowering and anti-hypertensive medications. Results During a median follow-up of 7.2 years, 10 969 patients (13.2%) were hospitalized with heart failure. By categories of BMI, with BMI 20 to < 25 kg/m2 as the reference, hazard ratios for patients during follow-up were 1.07 (95% CI 0.91-1.26) for a mean BMI of < 20 kg/m2, 1.04 (95% CI 0.98-1.11) for BMI 25 to < 27.5 kg/m2, 1.22 (95% CI 1.15-1.30) for BMI 27.5 to < 30 kg/m2, 1.54 (95% CI 1.45-1.63) for BMI 30 to < 35 kg/m2, 2.16 (95% CI 2.00-2.33) for BMI 35 to < 40 kg/m2 and 3.22 (95% CI 2.88-3.60) for BMI 40 kg/m2 or higher. There was a significant interaction between BMI and sex ( P = 0.0006), with numerically higher hazard ratios for hospitalization for heart failure within each BMI category for men than for women. Conclusions Obesity is strongly related to hospitalization for heart failure in people with Type 2 diabetes, and the relationship is somewhat stronger for men than for women. Preventing weight gain and promoting weight loss may be crucial in reducing the incidence of future hospitalizations for heart failure in this population. [ABSTRACT FROM AUTHOR]

Background Although allergic reactions to insulin are uncommon, they can be difficult to diagnose and management may be very difficult in subjects with Type 1 diabetes with severe allergy. Access to allergists and specialist diagnostic tests is limited and few diabetes specialists are familiar with desensitization as a means of treating allergy. People with diabetes may develop symptoms which mimic insulin allergy but are attributable to other conditions. Case reports Here we describe three cases of insulin allergy. One patient presented with severe, albeit localized, urticarial reactions at injection sites. The most severe case was a woman with recent-onset Type 1 diabetes who presented with grade 2 anaphylaxis. The third patient presented with generalized urticaria and angioedema. Insulin allergy was confirmed in all three cases. Methods Assessment involved measurement of immunoglobulin and anti-insulin antibody levels. Skin testing was performed in two cases. Treatments included desensitization in one case, alternative insulin preparations, antihistamines and continuous subcutaneous insulin infusion. In all three cases of insulin allergy there has been successful resolution of symptoms. Conclusions The clinical assessment and investigation in cases of suspected insulin allergy is described, along with detailed algorithms for skin testing and desensitization. This case series demonstrates an approach to challenging cases of suspected insulin allergy which will be helpful for diabetes specialists. [ABSTRACT FROM AUTHOR]

Clinical metabolic studies have demonstrated that insulin action declines progressively with age in humans. In addition to its close association with Type 2 diabetes, which reduces life expectancy in older people, age-related insulin resistance is implicated in pathogenesis of several highly prevalent disorders for which ageing is a major risk factor. These include atherosclerotic cardiovascular disease, dementia, frailty and cancer. Accordingly, insulin resistance may be viewed as biomarker of age-related ill health and reduced lifespan. The rapidly rising number of older people, coupled with a high prevalence of insulin resistance resulting from obesity and sedentary lifestyles, presents unprecedented public health and societal challenges. Studies of centenarians have shown that preserved whole-body sensitivity to insulin is associated with longevity. The mechanisms through which insulin action is associated with age-related diseases remain unclear. Changes in body composition, i.e. sarcopenia and excess adiposity, may be more potent than age per se. Moreover, the impact of insulin resistance has been difficult to disentangle from the clustering of vascular risk factors that co-segregate with the insulin resistance-hyperinsulinaemia complex. Potentially modifiable mediators of age-related changes in insulin sensitivity include alterations in adipocytokines, impaired skeletal myocyte mitochondrial function and brown fat activity. The hypothesis that improving or maintaining insulin sensitivity preserves health and extends lifespan merits further evaluation. Practical non-pharmacological interventions directed against age-related insulin resistance remain underdeveloped. Novel metabolically active pharmacological agents with theoretical implications for some age-related disorders are entering clinical trials. However, recent adverse experiences with the thiazolidinediones suggest the need for a cautious approach to the use of insulin sensitizing drugs in older people. This could be particularly important in the absence of diabetes where the risk to benefit analysis may be less favourable. [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 presents abstracts on medical topic which include targeted screening for glucokinase mutations in pregnancy, prediction of gestational diabetes in obese pregnant women, and exposure to potentially harmful medications among pregnant women with diabetes.

Diabet. Med. 30, 318-325 (2013) Abstract Aims To evaluate whether homeostasis model assessment and high-sensitivity C-reactive protein improve the prediction of isolated post-load hyperglycaemia. Methods The subjects were 1458 adults without self-reported diabetes recruited between 2006 and 2010. Isolated post-load hyperglycaemia was defined as fasting plasma glucose < 7 mmol/l and 2-h post-load plasma glucose ≥ 11.1 mmol/l. Risk scores of isolated post-load hyperglycaemia were constructed by multivariate logistic regression. An independent group ( n = 154) was enrolled from 2010 to 2011 to validate the models' performance. Results One hundred and twenty-three subjects (8.28%) were newly diagnosed as having diabetes mellitus. Among those with undiagnosed diabetes, 64 subjects (52%) had isolated post-load hyperglycaemia. Subjects with isolated post-load hyperglycaemia were older, more centrally obese and had higher blood pressure, HbA1c, fasting plasma glucose, triglycerides, LDL cholesterol, high-sensitivity C-reactive protein and homeostasis model assessment of insulin resistance and lower homeostasis model assessment of β-cell function than those without diabetes. The risk scores included age, gender, BMI, homeostasis model assessment, high-sensitivity C-reactive protein and HbA1c. The full model had high sensitivity (84%) and specificity (87%) and area under the receiver operating characteristic curve (0.91), with a cut-off point of 23.81; validation in an independent data set showed 88% sensitivity, 77% specificity and an area under curve of 0.89. Conclusions Over half of those with undiagnosed diabetes had isolated post-load hyperglycaemia. Homeostasis model assessment and high-sensitivity C-reactive protein are useful to identify subjects with isolated post-load hyperglycaemia, with improved performance over fasting plasma glucose or HbA1c alone. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, e117-e120 (2012) Abstract Introduction Circulating pigment epithelium-derived factor, or serine protease inhibitor F1, is upregulated during adipogenesis, contributing to obesity-induced insulin resistance. Furthermore, pigment epithelium-derived factor is abundant in stage I melanosomes and has been reported to increase pigment granules and the appearance of mature melanosomes in retinal pigment epithelium. As acanthosis nigricans is a well-recognized clinical marker of insulin resistance, we hypothesized that increased pigment epithelium-derived factor might be associated with the generation of acanthosis nigricans. Methods Acanthosis nigricans, anthropometric measurements, circulating total PEDF and metabolic profiles were assessed in 28 obese adolescents in a hospital-based obesity clinic. Results Subjects with acanthosis nigricans ( n = 10) showed greater plasma levels of pigment epithelium-derived factor (PEDF) than those without [geometric mean 23.55 (range 15.2-40.2) vs. 9.01 (range 5.5-18.7) μg/ml; P < 0.001]. Although pigment epithelium-derived factor was positively correlated with the homeostasis model assessment for insulin resistance (HOMA-IR) ( r = 0.779, P < 0.001; 95% CI 0.573-0.892), as previously reported, for the same degree of insulin resistance, those with acanthosis nigricans exhibited a 2.1-fold (95%CI 2.0-2.3) higher level of pigment epithelium-derived factor. Conclusions While acanthosis nigricans is undoubtedly associated with insulin resistance, its appearance is not ubiquitous in patients at any given level of HOMA-IR. The higher levels of pigment epithelium-derived factor in those with acanthosis nigricans compared with those without, with similar levels of resistance, suggest that pigment epithelium-derived factor levels are associated with acanthosis nigricans. [ABSTRACT FROM AUTHOR]