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Aims/hypothesis: We aimed to assess associations between cord blood metabolic markers and fetal overgrowth, and whether cord markers mediated the impact of maternal adiposity on neonatal anthropometric outcomes among children born to Indigenous and Non-Indigenous Australian women with normal glucose tolerance (NGT), gestational diabetes mellitus (GDM) and pregestational type 2 diabetes mellitus. Methods: From the Pregnancy and Neonatal Outcomes in Remote Australia (PANDORA) study, an observational cohort of 1135 mother–baby pairs, venous cord blood was available for 645 singleton babies (49% Indigenous Australian) of women with NGT (n = 129), GDM (n = 419) and type 2 diabetes (n = 97). Cord glucose, triacylglycerol, HDL-cholesterol, C-reactive protein (CRP) and C-peptide were measured. Multivariable logistic and linear regression were used to assess the associations between cord blood metabolic markers and the outcomes of birthweight z score, sum of skinfold thickness (SSF), being large for gestational age (LGA) and percentage of body fat. Pathway analysis assessed whether cord markers mediated the associations between maternal and neonatal adiposity. Results: Elevated cord C-peptide was significantly associated with increasing birthweight z score (β 0.57 [95% CI 0.42, 0.71]), SSF (β 0.83 [95% CI 0.41, 1.25]), percentage of body fat (β 1.20 [95% CI 0.69, 1.71]) and risk for LGA [OR 3.14 [95% CI 2.11, 4.68]), after adjusting for age, ethnicity and diabetes type. Cord triacylglycerol was negatively associated with birthweight z score for Indigenous Australian women only. No associations between cord glucose, HDL-cholesterol and CRP >0.3 mg/l (2.9 nmol/l) with neonatal outcomes were observed. C-peptide mediated 18% (95% CI 13, 36) of the association of maternal BMI with LGA and 11% (95% CI 8, 17) of the association with per cent neonatal fat. Conclusions/interpretation: Cord blood C-peptide is an important mediator of the association between maternal and infant adiposity, across the spectrum of maternal glucose tolerance. [ABSTRACT FROM AUTHOR]

Background: In Australia's Northern Territory, 33% of babies are born to Indigenous mothers, who experience high rates of hyperglycemia in pregnancy. We aimed to determine the extent to which pregnancy outcomes for Indigenous Australian women are explained by relative frequencies of diabetes type [type 2 diabetes (T2DM) and gestational diabetes (GDM)].Methods: This prospective birth cohort study examined participants recruited from a hyperglycemia in pregnancy register. Baseline data collected were antenatal and perinatal clinical information, cord blood and neonatal anthropometry. Of 1135 women (48% Indigenous), 900 had diabetes: 175 T2DM, 86 newly diagnosed diabetes in pregnancy (DIP) and 639 had GDM. A group of 235 women without hyperglycemia in pregnancy was also recruited.Results: Diabetes type differed for Indigenous and non-Indigenous women (T2DM, 36 vs 5%; DIP, 15 vs 7%; GDM, 49 vs 88%, p < 0.001). Within each diabetes type, Indigenous women were younger and had higher smoking rates. Among women with GDM/DIP, Indigenous women demonstrated poorer birth outcomes than non-Indigenous women: large for gestational age, 19 vs 11%, p = 0·002; neonatal fat 11.3 vs 10.2%, p < 0.001. In the full cohort, on multivariate regression, T2DM and DIP were independently associated (and Indigenous ethnicity was not) with pregnancy outcomes.Conclusions: Higher rates of T2DM among Indigenous women predominantly contribute to absolute poorer pregnancy outcomes among Indigenous women with hyperglycemia. As with Indigenous and minority populations globally, prevention or delay of type 2 diabetes in younger women is vital to improve pregnancy outcomes and possibly to improve the long-term health of their offspring. [ABSTRACT FROM AUTHOR]

Objectives: To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers. Design: 6-month randomized, placebo-controlled trial. Participants: Ninety-five adults with serum 25-hydroxyvitamin D [25(OH)D] ≤55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score ≥15) were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45). Intervention: Daily calcium carbonate (1,200 mg) and cholecalciferol [2,000–6,000 IU to target 25(OH)D >75 nmol/L] or matching placebos for 6 months. Measurements: Insulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and β-cell function (Matsuda index x AUC for C-peptide) derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-α; IL-6; adiponectin; total and undercarboxylated osteocalcin. Results: Participants were middle-aged adults (mean age 54 years; 69% Europid) at risk of type 2 diabetes (48% with prediabetes). Compliance was >80% for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group (91% achieved >75 nmol/L), but remained unchanged in controls. There were no significant changes in insulin sensitivity, insulin secretion and β-cell function, or in inflammatory and metabolic markers between or within the groups, before or after adjustment for potential confounders including waist circumference and season of recruitment. In a post hoc analysis restricted to participants with prediabetes, a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity (HOMA%S and Matsuda) was observed. Conclusions: Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes. However, in participants with prediabetes, supplementation with vitamin D and calcium may improve insulin sensitivity. Trial Registration: Australian New Zealand Clinical Trials Registry [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine whether serum 25-hydroxyvitamin D (25OHD) and dietary calcium predict incident type 2 diabetes and insulin sensitivity. RESEARCN DESIGN AND METHODS--A total of 6,537 of the 11,247 adults evaluated in 1999--2000 in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study, returned for oral glucose tolerance test (OGTT) in 2004-2005. We studied those without diabetes who had complete data at baseline (n = 5,200; mean age 51 years; 55% were women; 92% were Europids). Serum 25OHD and energy-adjusted calcium intake (food frequency questionnaire) were assessed at baseline. Logistic regression was used to evaluate associations between serum 25OHD and dietary calcium on 5-year incidence of diabetes (diagnosed by OGTT) and insulin sensitivity (homeostasis model assessment of insulin sensitivity [HOMA-S]), adjusted for multiple potential confounders, including fasting plasma glucose (FPG). RESULTS--During the 5-year follow-up, 199 incident cases of diabetes were diagnosed. Those who developed diabetes had lower serum 25OHD (mean 58 vs. 65 nmol/L; P < 0.001) and calcium intake (mean 881 vs. 923 mg/day; P = 0.03) compared with those who remained free of diabetes. Each 25 nmol/L increment in serum 25OHD was associated with a 24% reduced risk of diabetes (odds ratio 0.76 [95% CI 0.63-0.92]) after adjusting for age, waist circumference, ethnicity, season, latitude, smoking, physical activity, family history of diabetes, dietary magnesium, hypertension, serum triglycerides, and FPG. Dietary calcium intake was not associated with reduced diabetes risk. Only serum 25OHD was positively and independently associated with HOMA-S at 5 years. CONCLUSIONS--Higher serum 25OHD levels, but not higher dietary calcium, were associated with a significantly reduced risk of diabetes in Australian adult men and women. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To evaluate A1C for screening and diagnosis of undiagnosed type 2 diabetes defined by oral glucose tolerance testing in clinical and general populations. RESEARCH DESIGN AND METHODS-- A1C cut offs (≤5.5% to rule out diabetes; ≥7.0% to rule in diabetes) were derived from a clinical group (Melbourne Pathology [MP] group: n = 2,494; undiagnosed diabetes 34.6%) and then evaluated in a population-based sample (AusDiab group: n = 6,015; undiagnosed diabetes 4.6%). RESULTS -- For diabetes in the MP and AusDiab groups, A1C at 5.5% gave sensitivities of 98.7 and 83.5%, while A1C at 7.0% gave specificities of 98.2 and 100%, respectively. Many (61.9-69.3%) with impaired A1C (5.6-6.9%) in both populations had abnormal glucose status. CONCLUSIONS -- A1C ≤5.5% and ≥7.0% predicts absence or presence of type 2 diabetes, respectively, while at A1C 6.5-6.9% diabetes is highly probable in clinical and population settings. A high proportion of people with impaired A1C have abnormal glucose status requiring follow-up. [ABSTRACT FROM AUTHOR]

Aims: To determine among First Nations and Europid pregnant women the cumulative incidence and predictors of postpartum type 2 diabetes and prediabetes and describe postpartum cardiovascular disease (CVD) risk profiles.Methods: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Ethnic-specific rates of postpartum type 2 diabetes and prediabetes were reported for women with diabetes in pregnancy (DIP), gestational diabetes (GDM) or normoglycaemia in pregnancy over a short follow-up of 2.5 years (n = 325). Pregnancy characteristics and CVD risk profiles according to glycaemic status, and factors associated with postpartum diabetes/prediabetes were examined in First Nations women.Results: The cumulative incidence of postpartum type 2 diabetes among women with DIP or GDM were higher for First Nations women (48%, 13/27, women with DIP, 13%, 11/82, GDM), compared to Europid women (nil DIP or GDM p < 0.001). Characteristics associated with type 2 diabetes/prediabetes among First Nations women with GDM/DIP included, older age, multiparity, family history of diabetes, higher glucose values, insulin use and body mass index (BMI).Conclusions: First Nations women experience a high incidence of postpartum type 2 diabetes after GDM/DIP, highlighting the need for culturally responsive policies at an individual and systems level, to prevent diabetes and its complications. [ABSTRACT FROM AUTHOR]