Myocardial fibrosis in Type 2 Diabetes is associated with functional and metabolomic parameters.

AIMS: To identify biomarkers of cardiomyopathy in patients with type 2 diabetes mellitus (T2DM) using cardiovascular magnetic resonance (CMR) and to identify associations between functional status, metabolomic profile and myocardial fibrosis. METHODS: In this prospective case control study, patients (n = 49) with T2DM without significant coronary artery disease, and matched controls (n = 18) underwent CMR, cardiopulmonary exercise testing, and plasma metabolomic analyses. RESULTS: Patients with T2DM (n = 49, median [interquartile range] age 61 [56-63] years, 61% male, diabetes duration 11 [7-20] years), historical HbA1c 7.6% (60 mmol/mol) (6.9-8.6) and matched controls (n = 18) were examined. Study patients had increased myocardial extracellular volume (ECV) (26.9 [23.8-30.0] vs 23.4 [22.4-25.5) %, p < 0.001). Increased ECV was associated with male sex (p = 0.04), time with T2DM (p = 0.02), reduced peak VO2 (R2 = 0.48, p = 0.01), increased circulating choline (p = 0.002) and cysteamine (p = 0.002) both of which were also associated with reduced peak VO2 (p < 0.025 and 0.014 respectively). CONCLUSIONS: Patients with well-controlled T2DM without significant coronary disease exhibit focal and diffuse myocardial fibrosis and diffuse myocardial fibrosis is associated with reduced exercise tolerance and metabolites. Plasma metabolites may provide mechanistic insights into diffuse myocardial fibrosis, and cardiopulmonary fitness.

Screening, assessment and management of type 2 diabetes mellitus in children and adolescents: Australasian Paediatric Endocrine Group guidelines.

INTRODUCTION: The incidence of type 2 diabetes mellitus has increased in children and adolescents due largely to the obesity epidemic, particularly in high risk ethnic groups. ß-Cell function declines faster and diabetes complications develop earlier in paediatric type 2 diabetes compared with adult-onset type 2 diabetes. There are no consensus guidelines in Australasia for assessment and management of type 2 diabetes in paediatric populations and health professionals have had to refer to adult guidelines. Recent international paediatric guidelines did not address adaptations to care for patients from Indigenous backgrounds. MAIN RECOMMENDATIONS: This guideline provides advice on paediatric type 2 diabetes in relation to screening, diagnosis, diabetes education, monitoring including targets, multicomponent healthy lifestyle, pharmacotherapy, assessment and management of complications and comorbidities, and transition. There is also a dedicated section on considerations of care for children and adolescents from Indigenous background in Australia and New Zealand. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINES: Published international guidelines currently exist, but the challenges and specifics to care for children and adolescents with type 2 diabetes which should apply to Australasia have not been addressed to date. These include: recommendations regarding care of children and adolescents from Indigenous backgrounds in Australia and New Zealand including screening and management; tighter diabetes targets (glycated haemoglobin, ≤ 48 mmol/mol [≤ 6.5%]) for all children and adolescents; considering the use of newer medications approved for adults with type 2 diabetes under the guidance of a paediatric endocrinologist; and the need to transition adolescents with type 2 diabetes to a diabetes multidisciplinary care team including an adult endocrinologist for their ongoing care.

A Novel Early Pregnancy Risk Prediction Model for Gestational Diabetes Mellitus.

INTRODUCTION: Accurate early risk prediction for gestational diabetes mellitus (GDM) would target intervention and prevention in women at the highest risk. We evaluated novel biomarker predictors to develop a first-trimester risk prediction model in a large multiethnic cohort. METHODS: Maternal clinical, aneuploidy and pre-eclampsia screening markers (PAPP-A, free hCGß, mean arterial pressure, uterine artery pulsatility index) were measured prospectively at 11-13+6 weeks' gestation in 980 women (248 with GDM; 732 controls). Nonfasting glucose, lipids, adiponectin, leptin, lipocalin-2, and plasminogen activator inhibitor-2 were measured on banked serum. The relationship between marker multiples-of-the-median and GDM was examined with multivariate regression. Model predictive performance for early (< 24 weeks' gestation) and overall GDM diagnosis was evaluated by receiver operating characteristic curves. RESULTS: Glucose, triglycerides, leptin, and lipocalin-2 were higher, while adiponectin was lower, in GDM (p < 0.05). Lipocalin-2 performed best in Caucasians, and triglycerides in South Asians with GDM. Family history of diabetes, previous GDM, South/East Asian ethnicity, parity, BMI, PAPP-A, triglycerides, and lipocalin-2 were significant independent GDM predictors (all p < 0.01), achieving an area under the curve of 0.91 (95% confidence interval [CI] 0.89-0.94) overall, and 0.93 (95% CI 0.89-0.96) for early GDM, in a combined multivariate prediction model. CONCLUSIONS: A first-trimester risk prediction model, which incorporates novel maternal lipid markers, accurately identifies women at high risk of GDM, including early GDM.

Age, age at diagnosis and diabetes duration are all associated with vascular complications in type 2 diabetes.

BACKGROUND: Type 2 diabetes (T2DM) is increasingly diagnosed in younger patients. The trajectory of complications in patients diagnosed at a younger or older age is not well understood. We examine the associations between age, age at diagnosis and diabetes duration and vascular complications in patients with T2DM. METHODS: A cross-sectional study of pre-specified demographic and clinical data, from 3419 adults with T2DM participating in the Australian National Diabetes Audit (2015). Factors associated with diabetes complications were analysed using logistic regression. RESULTS: Mean (±SD) current age was 62.9±12.5years, age at diagnosis was 49.4±12.3years and mean diabetes duration was 13.5±9.4years. Macrovascular complications were more prevalent in patients who were older at diabetes diagnosis whereas microvascular complications were more prevalent in patients who were younger at diabetes diagnosis. Age, age at diagnosis and diabetes duration were all independently associated with increased risk of macrovascular complications after adjustment for sex, smoking, BMI and microvascular complications (all p<0.001). In contrast, only diabetes duration was independently associated with microvascular complications after adjustment for sex, smoking, BMI and macrovascular complications (p<0.001). CONCLUSIONS: Age, age at diagnosis, and diabetes duration were all independently associated with macrovascular complications whereas only diabetes duration was independently associated with microvascular complications.

A first trimester prediction model for gestational diabetes utilizing aneuploidy and pre-eclampsia screening markers.

OBJECTIVE: We examined whether first trimester aneuploidy and pre-eclampsia screening markers predict gestational diabetes mellitus (GDM) in a large multi-ethnic cohort and the influence of local population characteristics on markers. METHODS: Clinical and first trimester markers (mean arterial pressure (MAP), uterine artery pulsatility index (UtA PI), pregnancy associated plasma protein A (PAPP-A), free-ß human chorionic gonadotropin (free-hCGß)) were measured in a case-control study of 980 women (248 with GDM, 732 controls) at 11 to 13 + 6 weeks' gestation. Clinical parameters, MAP-, UtA PI-, PAPP-A-, and free-hCGß-multiples-of-the-median (MoM) were compared between GDM and controls; stratified by ethnicity, parity, and GDM diagnosis <24 versus ≥24 weeks' gestation. GDM model screening performance was evaluated using AUROC. RESULTS: PAPP-A- and UtA PI-MoM were significantly lower in GDM versus controls (median ((IQR) PAPP-A-MoM 0.81 (0.58-1.20) versus 1.00 (0.70-1.46); UtA PI-MoM 1.01 (0.82-1.21) versus 1.05 (0.84-1.29); p < .05). Previous GDM, family history of diabetes, south/east Asian ethnicity, parity, BMI, MAP, UtA PI, and PAPP-A were significant predictors in multivariate analysis (p < .05). The AUC for a model based on clinical parameters was 0.88 (95%CI 0.85-0.92), increasing to 0.90 (95%CI 0.87-0.92) with first trimester markers combined. The combined model best predicted GDM <24 weeks' gestation (AUC 0.96 (95%CI 0.94-0.98)). CONCLUSIONS: Addition of aneuploidy and pre-eclampsia markers is cost-effective and enhances early GDM detection, accurately identifying early GDM, a high-risk cohort requiring early detection, and intervention. Ethnicity and parity modified marker association with GDM, suggesting differences in pathophysiology and vascular risk.

The imperative to prevent diabetes complications: a broadening spectrum and an increasing burden despite improved outcomes.

Diabetes mellitus and its complications are common; the complications are, of themselves, a major reason to manage diabetes. Recent data from Australia and similar developed health care systems overseas indicate that morbidity and mortality outcomes relating to diabetes complications are improving. However, these benefits are offset by increasing numbers of people diagnosed with diabetes, resulting in an increased disease burden with significant health care implications. Thus the imperative to prevent diabetes and diabetes complications has never been greater. Furthermore, the recognised spectrum of diabetes complications is broadening, especially complications relating to lipid levels, insulin resistance and the metabolic syndrome. Clinicians now need to be aware of both traditional complications (eg, nephropathy and cardiovascular disease) and non-traditional complications (eg, polycystic ovary syndrome, non-alcoholic fatty liver disease, some cancers and eating disorders). Complications outcomes could be further improved by decreasing the evidence-treatment gap - for example, by increasing personalisation of care in managing diabetes complications.

Ethnic specific differences in survival of patients with type 2 diabetes: analysis of data collected from an Australian multi-ethnic cohort over a 25 year period.

AIMS: To examine the survival of patients with type 2 diabetes from 7 ethnic groups, living in the shared environment of an Australian city. METHODS: Hazard ratio of death (HR) after diagnosis of diabetes was compared between Anglo-Celtic (n=5433), Indigenous Australian (n=439), Pacific Islander (n=354), Mediterranean (n=3138), Arabic (n=768), Indian (n=702) and Chinese (n=1632) patients who live in metropolitan Sydney. Mortality was ascertained by data-linkage with the Australian National Death Index. The modulating effects of glycaemic control, diabetes/vascular complications and risk factors, year of diabetes diagnosis and duration of diabetes on ethnic differences were analysed by Cox regression. Socio-economic status and competence in English were also examined. RESULTS: There were significant differences in survival between the ethnic groups; the Indigenous Australians had the highest HR for death (2.3, 95% CI 1.7-3.0) and the Chinese the lowest (0.4, 95% CI 0.4-0.5). The survival of the Anglo-Celtics (HR 1) was surprisingly poorer than for Indian (0.6, 95% CI 0.5-0.8), Arab (0.7, 95% CI 0.6-0.8) and Mediterranean groups (0.8, 95% CI 0.7-0.9). Prevalence of smoking and albuminuria were strongly associated with HR. The better survival of Chinese and Arab and the worse survival of Indigenous Australians remained after adjustment of risk factors. Need for an interpreter was a favourable risk factor for survival. CONCLUSIONS: Ethnicity is a significant determinant of survival in type 2 diabetes and this is substantially but not completely mediated by smoking and vascular risk factors. The favourable impact associated with less competence in English may represent a Healthy-migrant effect.

Timing is everything: age of onset influences long-term retinopathy risk in type 2 diabetes, independent of traditional risk factors.

OBJECTIVE: To test the hypothesis that age of type 2 diabetes onset influences inherent susceptibility to diabetic retinopathy, independent of disease duration and degree of hyperglycemia. RESEARCH DESIGN AND METHODS: Retinopathy data from 624 patients with a type 2 diabetes duration of 20-30 years (group A) were analyzed by stratifying patients according to age of onset of diabetes and glycemic control. Retinopathy status was scored clinically as per a modified Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. To obviate possible bias due to a higher attrition from comorbidities in those with later-onset diabetes and retinopathy, 852 patients with type 2 diabetes of shorter duration (10-12 years, group B) were similarly studied. RESULTS: Prevalence and severity of retinopathy was significantly higher in the younger-onset, group A patients. When further stratified according to mean A1C, retinopathy risk remained increased in younger-onset patients. The greatest impact was seen in those with a mean A1C >9% (odds ratio [OR] for retinopathy 16.6, 7.5, and 2.7 for age of diagnosis <45, 45-55, and >55 years, respectively, P = 0.003). By logistic regression, earlier type 2 diabetes onset is associated with increased retinopathy risk, independent of traditional risk factors (OR of retinopathy 1.9, 1.1, and 1 for age of onset <45, 45-55, and >55 years, respectively). Similar results were found in group B patients. CONCLUSIONS: These data suggest an increased inherent susceptibility to diabetic retinopathy with earlier-onset type 2 diabetes. This further supports the importance of delaying development of diabetes and also implies a need for more stringent metabolic targets for younger individuals.