Search

Aim To confirm whether serum bilirubin is an independent risk factor of type 2 diabetes mellitus (T2DM) onset in patients with impaired fasting glycemia (IFG) and impaired glucose tolerance (IGT). Methods This was a prospective cohort study carried out at the Diabetic Identification Center of Tianjin Metabolic Diseases Hospital. Serum total bilirubin (TBIL) was measured at baseline and the patients were grouped according to baseline bilirubin quartiles. The outcome was the confirmation of T2DM by oral glucose tolerance test (OGTT) during the 3-year follow-up. Logistic regression was used to determine the risk factors for T2DM development and whether bilirubin levels are independently associated with T2DM development. Results Finally, 523 patients were analyzed. After 3 years, 310 participants were diagnosed with diabetes based on OGTT. Baseline quartiles of total bilirubin were inversely associated with diabetes risk, even after multivariable adjustment. The adjusted ORs for diabetes were 1.0 (reference), 0.83 (95% CI 0.74–0.96), 0.78 (95% CI 0.68–0.90), 0.74 (95% CI 0.64–0.87) for the 1st, 2nd, 3rd, and 4th quartiles of baseline serum total bilirubin, respectively (P Conclusion In patients with IFG or IGT, low levels of serum total bilirubin were associated with a significantly increased risk of T2DM.

Aims To compare OGTT-derived estimates of β-cell function between youth and adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes after treatment discontinuation in RISE. Methods Youth (n = 89) and adults (n = 132) were randomized to 3 months glargine followed by 9 months metformin (G/M) or 12 months metformin (MET). Insulin sensitivity and β-cell responses were estimated from 3-hour OGTTs over 21 months. Linear mixed models tested for differences by time and age group within each treatment arm. Results After treatment withdrawal, HbA1c increased in both youth and adults with a larger net increase in G/M youth vs. adults at 21 months. Among youth, β-cell function decreased starting at 12 months in G/M and 15 months in MET. Among adults, β-cell function remained relatively stable although insulin secretion rates decreased in G/M at 21 months. At 21 months vs. baseline β-cell function declined to a greater extent in youth vs. adults in both the G/M and MET treatment arms. Conclusions After treatment withdrawal youth demonstrated progressive decline in β-cell function after stopping treatment with either G/M or MET. In contrast, β-cell function in adults remained stable despite an increase in HbA1c over time. ClinicalTrials.gov Identifier: NCT01779375 and NCT01779362 at clinical trials.gov.

Aims The objective of this study was to compare the islet cell function, insulin sensitivity, and incretin axis between Asian-Indian subjects with either impaired fasting glucose (IFG), or impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). Materials and methods Prediabetes subjects underwent a mixed meal tolerance test(MMTT) after overnight fasting. Samples for glucose, insulin, glucagon, and glucagon-like peptide-1 (GLP-1) were collected at 0, 30, 60, and 120 min. Insulin secretion sensitivity index -2 (ISSI-2) for beta-cell function and Matsuda index for insulin sensitivity were assessed. Alpha cell function was assessed by measuring the area under the curve (AUC) 0-120 glucagon/AUC0-120 glucose. Results A total of sixty subjects were recruited with 20 in each group. The beta-cell function represented by ISSI-2 was impaired in prediabetes subjects as compared to NGT group (IFG: 2.09 ± 0.44 vs. NGT: 3.04 ± 0.80, P Conclusion Asian-Indian prediabetes subjects have reduced beta-cell function with lesser glucagon secretion during MMTT as compared to normal healthy controls.

Aims We investigated the risk of type 2 diabetes in the Japanese population with prediabetes, focusing on prediabetes categories, age- and sex-related differences, and plasma glucose levels during a 75-g oral glucose tolerance test. Methods This retrospective cohort study included 11,414 participants (5330, 2560, 1501, and 2023 with normal fasting glucose/normal glucose tolerance, isolated impaired fasting glucose [IFG], isolated impaired glucose tolerance [IGT], and IFG plus IGT, respectively). The risk of type 2 diabetes was stratified by age and sex. Moreover, prediabetes was subdivided according to fasting plasma glucose (FPG) and 1-h post-load glucose levels. Results Over a mean 6.3-year follow-up period, 1002 participants developed type 2 diabetes. The risk of type 2 diabetes was higher in isolated IFG than isolated IGT in elderly participants, but not in middle-aged participants. A higher risk was evident in isolated IFG in women, but not men. Moreover, about a 27- and 29-fold difference exists in men and women, respectively, in the risk of type 2 diabetes among the subdivided prediabetes categories. Conclusion The assessment of age and sex-differences and subdivided prediabetes categories based on FPG and 1-h post-load glucose levels may effectively evaluate the risk of type 2 diabetes, which displays marked diversity.

Secular trends in diabetes prevalence vary globally. We compared the prevalence of diabetes in two surveys 15 years apart in rural Australia.Two cross-sectional household surveys and clinics (biomedical assessments including oral glucose tolerance tests (OGTTs)) in 2001-2003 (Crossroads) and 2016-2018 (Crossroads-II).Four rural Victorian towns.Residents of randomly selected households (Crossroads (n = 5258), Crossroads-II (n = 2649)) with nested clinic assessments for randomly selected participants (n = 1048 and 736 respectively). Response rate 61%.Self-reported diagnosed diabetes, screening history, and diabetes defined by OGTT.The age standardised prevalence of diagnosed diabetes increased from 5.0(4.4-5.7)% to 7.7(6.7-8.6)%, with crude prevalence increasing overall (5.4 to 10.4% p 0.001), in the smaller towns (5.4 to 11.1% p = 0.001) and, the regional centre (4.1 to 7.3% p 0.001). Screening for diabetes over the previous two years increased (rural towns 49.8 to 63.8%; regional centre 44.9 to 63.6%; both p 0.001). The proportion of undiagnosed diabetes was 23.2% in 2003 and 13.7% in 2018. The age and sex adjusted change in total diabetes was (1.15(0.84-1.59)). Central obesity (adjusted odd ratio 1.28(1.00-1.64)) but not overall obesity (adjusted odd ratio 1.17(0.95-1.46)) increased over time.Over 15 years, the crude prevalence of diagnosed diabetes increased while the age and sex adjusted total diabetes prevalence did not change significantly. The epidemic may be slowing in some settings.

Background Post- transplantation diabetes mellitus (PTDM) in children is a serious metabolic complication that can endanger both graft and patient survival. These complications can be partially reduced by early diagnosis & prompt treatment of impaired glucose tolerance. The aim of this study was to assess glucose tolerance & insulin resistance among a cohort of kidney transplanted children. Methods Thirty consecutive pediatric kidney transplant recipients were subjected to basal evaluation of plasma glucose and insulin then underwent oral glucose tolerance test (OGTT). Results Abnormal glucose metabolism was detected in 7 (23.3%) patients; 3 (10%) patients with PTDM; 3 (10%) patients with impaired fasting glucose (IFG) and 1 (3.3%) patient with IFG and impaired glucose tolerance (IGT). Four (13.3%) patients had high Homeostatic model assessment of insulin resistance (HOMA-IR). Patients with abnormal glucose metabolism had significantly higher tacrolimus trough levels and higher maintainence steroid doses (p values = 0.003,0.026). Significant positive correlation existed between pre-transplantation glucose level and post-transplantation fasting glucose (p = 0.001, r = 0.69), glucose at 120 min (p = 0.018, r = 0.429) and HOMA-IR (p = 0.008, r = 0.47). Conclusion Abnormalities in glucose metabolism (IFG, IGT &PTDM) are frequent in Egyptian pediatric kidney transplant recipients. OGTT is the gold standard for assessment of abnormalities in glucose metabolism.

Aim The aim of the study is to investigate whether adiposity markers, insulin resistance and prediabetes are associated with cognitive performance in middle-aged men and women without diabetes. Methods Cross-sectional study with 11,115 adults without diabetes (34–64 years old). Cognitive performance was tested by word-list learning, word-list delayed recall, word recognition tests, semantic and phonemic verbal fluency tests and trail making test B. Linear regression models and generalized linear regression with logarithmic links between the cognitive tests and anthropometric indicators (body mass index [BMI]), insulin resistance (Homeostasis Model Assessment for Insulin Resistance [HOMA-IR]), and prediabetes (impaired glucose tolerance) were stratified by sex. The results were adjusted for age, education, comorbidities, health-related behaviors, waist circumference, and lipids. Results Among women, higher BMI was associated with poorer performance on phonemic verbal fluency test (β-0.02 [−0.04; −0.01]) and memory tests (β-0.05 [−0.07; −0.02]). Higher HOMA-IR was associated with poorer cognitive performance in memory (β-0.11 [−0.19; −0.01]) and phonemic verbal fluency tests (β-0.12 [−0.20; −0.04]). In men, HOMA-IR (β-0.15 [−0.25; −0.04]) and prediabetes (β-0.35 [−0.69; -0.03]) were associated with poorer performance on memory tests. Conclusions We found a significant association of BMI and HOMA-IR with cognitive performance in young and middle-aged adult women without diabetes. In men, we found an association between HOMA-IR and prediabetes and poorer performance on memory tests.

Aims To quantify short and long-term outcomes of Gestational Diabetes Mellitus (GDM) among South Asians. Methods Prospective cohort-study in Gampaha District, Sri Lanka following a community-prevalence study (WHO 1999 criteria). All women with GDM (exposed) and within sample non-GDM (non-exposed) were recruited. Data was gathered at selected intervals until one-year post-partum by interviewer-administered questionnaire, anthropometry, blood pressure, post-partum 75gOGTT and cholesterol. Two groups were compared for pregnancy outcomes; and age, parity, first-trimester BMI adjusted odds ratios (aOR) calculated. Results GDM and non-GDM (n = 194 each) had 169 (87.1%) and 178 (91.8%) responders respectively. Significant differences in outcomes: Antenatal/Perinatal – obstetric and/or medical complications (aOR = 1.8; 95% CI = 1.1–2.7), pregnancy induced hypertension (aOR = 3.1; 95% CI = 1.5–6.5), birth-weight ≥ 3.5 kg (aOR = 2.8; 95% CI = 1.4–5.5), special baby-care for prematurity (aOR = 4.1; 95% CI = 1.1–15.1), low mean POA at delivery (p = 0.005), vaginal moniliasis (aOR = 4.9; 95% CI = 1.4–17.4) and breast-engorgement (aOR = 2.6; 95% CI = 1.02–6.4). Two months postpartum: impaired glucose tolerance (IGT) (aOR = 6.1; 95% CI = 2.7–13.8) and abnormal glucose tolerance [AGT = diabetes, impaired fasting glucose (IFG) and IGT collectively] (aOR = 9.1; 95% CI = 4.3–19.1). One-year postpartum (participation rate = 39.7%): exclusive breastfeeding for six months (aOR = 0.3; 95% CI = 0.1–0.7), diabetes mellitus (aOR = 4.1; 95% CI = 1.1–15.7), IGT (aOR = 5.8; 95% CI = 1.5–21.8), AGT (aOR = 7.7; 95% CI = 2.9–20.6). Conclusions Hyperglycaemia in Pregnancy detected and followed up in a sub-urban community setting in Sri Lanka, had significantly worse pregnancy outcomes with a high risk of maternal pre-diabetes/diabetes in first post-partum year.

Aims The aim of this study is to investigate the effect of platelet count on the incidence of type 2 diabetes mellitus (DM) in the overall Korean adults and in participants with impaired glucose tolerance (IGT) at baseline. Methods A total of 7502 participants (3528 men and 3974 women) aged 40–69 years were enrolled in this study. The study population was divided into tertiles (T) of serum platelet counts. We used Cox regression to analyse the relationship between baseline platelet count and new-onset type 2 DM. Results A total of 602 (8.0%) subjects developed type 2 DM during a mean follow-up of 8.4 years. Compared to the lowest tertile, the hazard ratio (95% confidence interval [CI]) for the incidence of type 2 DM was 1.28 (1.04–1.57) for T3 after adjusting for possible confounding factors. In subjects with IGT at baseline, the hazard ratio (95% CI) for the incidence of type 2 DM in T3 compared with T1 was 1.45 (1.05–2.00) after adjusting for the same confounders. Conclusion This prospective longitudinal study demonstrated that the incidence of type 2 DM increased as the serum platelet count at baseline increased within the normal range. This positive association was more prominent in subjects with IGT.

Aims Women with a history of gestational diabetes mellitus (GDM) are likely to develop postpartum diabetes mellitus (DM). We examined women in the early stages of pregnancy who were at high risk of postpartum DM progression to establish a follow-up method for early detection. Methods We performed the oral glucose tolerance test (OGTT) and identified predictive factors for postpartum impaired glucose tolerance (IGT) or DM in 77 women after GDM, for 2 years after delivery, retrospectively. Cutoff values for each factor were determined. We classified these women with GDM into four groups using these predictive factors and evaluated postpartum glucose intolerance (GI) in each group. Results In total, 44.1% of the women with a GDM history had developed postpartum GI within 2 years. We determined three risk factors for postpartum GI: elevated glucose level 120 min after a 75-g OGTT (Glu120), elevated glycated hemoglobin (HbA1c) level at diagnosis, and perinatal complications. The cutoff Glu120 and the HbA1c level were 155 mg/dl and 5.3% (34 mmol/mol), respectively. Type 2 DM developed in 53.8% of women, and IGT developed in 38.5% of women within 2 years in groups with high Glu120 and high HbA1c. Conclusions High-risk groups require careful follow-up observation.

Introduction Since the year 2000, IDF has been measuring the prevalence of diabetes nationally, regionally and globally. Aim To produce estimates of the global burden of diabetes and its impact for 2017 and projections for 2045. Methods A systematic literature review was conducted to identify published studies on the prevalence of diabetes, impaired glucose tolerance and hyperglycaemia in pregnancy in the period from 1990 to 2016. The highest quality studies on diabetes prevalence were selected for each country. A logistic regression model was used to generate age-specific prevalence estimates or each country. Estimates for countries without data were extrapolated from similar countries. Results It was estimated that in 2017 there are 451 million (age 18–99 years) people with diabetes worldwide. These figures were expected to increase to 693 million) by 2045. It was estimated that almost half of all people (49.7%) living with diabetes are undiagnosed. Moreover, there was an estimated 374 million people with impaired glucose tolerance (IGT) and it was projected that almost 21.3 million live births to women were affected by some form of hyperglycaemia in pregnancy. In 2017, approximately 5 million deaths worldwide were attributable to diabetes in the 20–99 years age range. The global healthcare expenditure on people with diabetes was estimated to be USD 850 billion in 2017. Conclusion The new estimates of diabetes prevalence, deaths attributable to diabetes and healthcare expenditure due to diabetes present a large social, financial and health system burden across the world.

MODY is a monogenic, autosomal dominant form of diabetes mellitus. MODY can be caused by mutations in several genes; glucokinase (GCK) accounts for 30-50% of the cases. The diagnosis can be suspected in early-onset diabetes with atypical features for type 1/type 2. Treatment is usually not recommended. A 5-year-old girl came to our attention for occasional episodes of hyperglycaemia. She was born at term, her birth weight was small for gestational age. At the beginning of her pregnancy, her mother was already on insulin therapy for impaired fasting glucose levels, detected before conception and confirmed in the first weeks of gestation. She was treated with insulin until the childbirth without further investigations. The patient was asymptomatic and in good clinical condition. Basal blood tests have shown a fasting plasma glucose of 125 mg/dl, an HbA1c of 6.5%. Antibodies against islet cells, anti-GAD and anti-ZNT8 antibodies were all negative. A 2-h oral glucose tolerance test was performed and underlined an impaired glucose tolerance. HLA haplotypes were screened, excluding susceptibility. GCK Sanger Sequencing identified a novel heterozygous variant. It is not described as a classical mutations. The analysis has been extended to the parents, finding out the same variant in her mother. To our knowledge this mutation has not been described previously; we believe that this variant is responsible for MODY2 due to FBG and Hb1Ac of all the affected members of family. We suggest high suspicion of an underlying GCK variant in SGA children with hyperglycaemia born to a diabetic mother.

Aims C1q/TNF-related protein-9 (CTRP9) is a novel adipokine that has been shown to promote lipid metabolism, enhance insulin sensitivity and protect against cardiovascular disease. However, previous studies in humans have produced controversial results regarding the association between CTRP9 and insulin resistance. The objective of this study was to evaluate the relationships between CTRP9 and insulin resistance in Chinese population. Methods Subjects with normal glucose tolerance (NGT, n = 108), impaired glucose tolerance (IGT, n = 92), and newly diagnosed type 2 diabetes mellitus (nT2DM, n = 106) were recruited to determining the circulating CTRP9 and adiponectin levels by enzyme linked immunosorbent assay. Anthropometric and biochemical measurements related to insulin resistance, adiposity and lipid profile were examined for all participants. Oral glucose tolerance test was performed in healthy subjects (17 male and 17 female). Results Circulating CTRP9 level was significantly higher in both IGT and nT2DM than in individuals with NGT. Overweight/obese subjects had much higher CTRP9 levels than lean individuals, and in all subjects, females also had higher CTRP9 levels than males. In addition, circulating CTRP9 level was positively correlated with markers of obesity and insulin resistance, including body mass index, fasting blood glucose, insulin, HbA1c, homeostasis model assessment of insulin resistance and low-density lipoprotein-cholesterol, while was inversely correlated with high-density lipoprotein-cholesterol and adiponectin. Moreover, hyperglycemia during an oral glucose challenge increased circulating CTRP9 concentrations. Conclusions We conclude that CTRP9 was strongly associated with insulin resistance, suggesting that CTRP9 might be important in the development of type 2 diabetes.

Aims In humans, noncoding variants of PCSK2, the gene encoding prohormone convertase 2 (PC2), have been previously associated with risk for and age of onset of type 2 diabetes (T2D). The aims of this study were to identify coding variants in PCSK2; to determine their possible association with glucose handling; and to determine functional outcomes for coding variants in biochemical studies. Methods Exome-wide genotyping was performed on 1725 Old Order Amish (OOA) subjects. PCSK2 coding variants were tested for association with diabetes-related phenotypes. In vitro analyses using transfected human PC2-encoding constructs were performed to determine the impact of each mutation on PC2 activity. Results We identified 10 rare missense coding variants in PCSK2 in various genomic databases. R430W (rs200711626) is greatly enriched in the OOA population (MAF 4.3%). This variant is almost twice as common (MAF 7.4%) in OOA individuals with T2D as in OOA individuals with normal or with normal/impaired glucose tolerance (MAF 3.9% and 2.9%, respectively; p = 0.25 and p = 0.10). In vitro experiments revealed a broadening of the pH optimum for the R430W variant, which may result in increased activity against PCSK2 substrates. Conclusions Although the association of the R430W variation with T2D in the OOA population did not reach significance, based upon the broadened pH profile of R430W PC2, we speculate that the presence of this substitution may result in altered processing of PCSK2 substrates, ultimately leading to increased conversion to diabetes.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy among women during reproductive age. PCOS is characterised by hyperandrogenaemia, hyperinsulinaemia, and deranged adipokines secretion from the adipose tissue. In addition to the reduced insulin sensitivity, PCOS women exhibit β-cell dysfunction as well. Low birth weight and foetal exposure to androgens may contribute to the development of the PCOS phenotype during life. Further metabolic complications lead to dyslipidaemia, worsening obesity and glucose tolerance, high prevalence of metabolic syndrome, and greater susceptibility to diabetes. PCOS women show age-related existence of hypertension, and subtle endothelial and vascular changes. Adverse reproductive outcomes include anovulatory infertility, and unrecognised potentiation of the hormone-dependent endometrial cancer. The main therapeutic approach is lifestyle modification. Metformin is the primary insulin-sensitising drug to be used as an adjuvant therapy to lifestyle modification in patients with insulin resistance and impaired glucose tolerance, as well as in those referred to infertility treatment. Thiazolidinediones should be reserved for women intolerant of or refractory to metformin, while glucagon-like peptide 1 analogues has a potential therapeutic use in obese PCOS women. Randomised clinical trials and repetitive studies on different PCOS phenotypes for the preventive actions and therapeutic options are still lacking, though.

To assess the effect of saxagliptin monotherapy on blood glucose and islet β-cell function in obese patients with newly diagnosed pre-diabetes and abnormal fat metabolism.A 24-week, randomized controlled trial was conducted involving 25 obese subjects with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) (mean age 45years) to receive lifestyle intervention only (control group) or combined with saxagliptin 2.5mg or 5mg daily (S2.5 or S5 group), metformin 1500mg daily (Met group). Anthropometrics, body fat and biochemical parameters were measured before and after 4, 12 and 24weeks intervention.S5 group and Met group showed a significant decrease in fasting plasma glucose (FPG) and HbA1c compared with the control group (all P0.05) after 24-week intervention. However, the decrease in 2h postprandial plasma glucose levels (2hPPG) in S5 group were greater compared with control group (P0.01). Insulin resistance (HOMA-IR) was reduced in S5 group, Met group and control group (P0.05), and the β-cell function (HOMA-β) was improved in all groups (P0.05). However, the changes in obesity-related indicators including waist circumference, hip circumference, weight, BMI, body fat, percentage of body fat and waist-to-hip fat ratio were greate in Met group (all P0.05) compared with other groups (P0.05).Saxagliptin monotherapy may prevent or delay the progression of IGT or IFG to type 2 diabetes mellitus in obese patients with newly diagnosed pre-diabetes. ClinicalTrials.gov: NCT01960205.

The objective of this systematic review was to assess available scientific data on the efficacy and safety of medicinal food plants for the treatment of impaired glucose tolerance. We included randomized controlled trials (RCTs) with a minimum follow-up period of 6weeks. The diagnosis was determined by fasting plasma glucose values after two-hour oral glucose tolerance testing (OGTT). Two authors independently extracted data and evaluated bias. The Cochrane tool of risk of Bias Tool was used. This review included ten trials. Most studies were highly biased as data were incomplete or reporting was selective. The two-hour fasting plasma glucose after the curcumin extract intervention showed statistical significance after 3, 6 and 9months: p

Aims In recent years, the prevalence of pregestational diabetes (PGDM) and the concern about the possibility of adverse pregnancy outcomes in affected women have been increasing. Routinely collected health data represent a timely and cost-efficient approach in PGDM epidemiological research. This study aims to evaluate the reliability of hospital discharge (HD) coding to identify a population-based cohort of pregnant women with PGDM and to assess trends in prevalence in two provinces of Northern Italy. Methods We selected all deliveries occurred in the period 1997–2010 with ICD-9-CM codes for PGDM in HD record and we matched up to 5 controls from mothers without diabetes. We used Diabetes Registers (DRs) as the gold standard for validation analysis. Results We selected 3800 women, 653 with diabetes and 3147 without diabetes. The agreement between HD records and DRs was 90.7%, with K = 0.58. We detected 350 false positives and only 1 false negative. Sensitivity was 99.3%, specificity 90.0%, positive predictive value 46.4% and negative predictive value 99.9%. Of the false positives, 48.6% had gestational diabetes and 2.3% impaired glucose tolerance. After the validation process, PGDM prevalence decreased from 4.4 to 2.0 per 1000 deliveries. Conclusions Our results show that HD facilitate detection of almost all PGDM cases, but they also include a large number of false positives, mainly due to gestational diabetes. This misclassification causes a large overestimation of PGMD prevalence. Our findings require accuracy evaluation of ICD-9-CM codes, before they can be widely applied to epidemiological research and public health surveillance related to PGDM.

Aims To provide global estimates of diabetes prevalence for 2019 and projections for 2030 and 2045. Methods A total of 255 high-quality data sources, published between 1990 and 2018 and representing 138 countries were identified. For countries without high quality in-country data, estimates were extrapolated from similar countries matched by economy, ethnicity, geography and language. Logistic regression was used to generate smoothed age-specific diabetes prevalence estimates (including previously undiagnosed diabetes) in adults aged 20–79 years. Results The global diabetes prevalence in 2019 is estimated to be 9.3% (463 million people), rising to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045. The prevalence is higher in urban (10.8%) than rural (7.2%) areas, and in high-income (10.4%) than low-income countries (4.0%). One in two (50.1%) people living with diabetes do not know that they have diabetes. The global prevalence of impaired glucose tolerance is estimated to be 7.5% (374 million) in 2019 and projected to reach 8.0% (454 million) by 2030 and 8.6% (548 million) by 2045. Conclusions Just under half a billion people are living with diabetes worldwide and the number is projected to increase by 25% in 2030 and 51% in 2045.

To examine whether high-sensitivity C-reactive protein (hs-CRP) can predict all-cause death in Chinese adults with hyperglycemia.All the 237 diabetes and 49 prediabetes recruited in the study were evolved from the participants with impaired glucose tolerance in the original Da Qing Diabetes Study. Blood hs-CRP level was measured at 2006. Ten-year outcome of death was traced from 2006 to 2016. Cox model was used to analyse the association between hs-CRP level and the risk of all-cause death occurred over the subsequent 10 years.During the follow-up, death occurred in 36 (37.9%) subjects in the highest hs-CRP tertile group (hs-CRP 2.16 mg/L) and 19 (20.0%) in the lowest hs-CRP tertile group (hs-CRP 0.82 mg/L, p 0.05). The corresponding incidence of all-cause death (per 1,000 person-years) was 44.7 (95% CI 30.1-59.3) and 21.6 (95% CI 11.9-31.3) in the two groups respectively (p 0.0001). The highest hs-CRP tertile was associated with the increased risk of all-cause death significantly (hazard ratio 1.88, 95% CI 1.07-3.32) after controlling for traditional risk factors.Serum hs-CRP was predictive of 10-year all-cause death in Chinese adults with hyperglycemia, suggesting the impact of low-grade inflammation on mortality deserves more attention.

Objective To determine the association of genetic variants rs7901695, rs7903146, rs7895340, rs11196205, rs12255372 of transcription factor 7 like 2 (TCF7L2) gene and its coherence with metabolic parameters in Lithuanian (Kaunas district) women population with previously diagnosed gestational diabetes mellitus (GDM) and to compare the prevalence of TCF7L2 single nucleotide polymorphism (SNP) results to general population. Methods Women with previously diagnosed GDM participated in the study. Anthropometric measurements were taken. Carbohydrate and fat metabolism were evaluated. TCF7L2 SNP common variants (rs7901695, rs7903146, rs7895340, rs11196205, rs12255372) were set. The prevalence of TCF7L2 the same SNP alleles were also evaluated for women of the general population. The results were compared to the main study group (women with previously diagnosed GDM). The results were calculated in a ratio of 1:2. General population group comprised 300 women who were selected from the random sample of the Kaunas city population. Statistical analysis was made with the statistical package IBM SPSS Statistics version 21. Quantitative parametric variables presented as mean and standard deviation, qualitative variables – as absolute numbers and percentage. ANOVA test was used, for the comparison between three or more groups. Quantitative variables were compared using Student’s t-test. Categorical variables were compared using chi-square test. Correlation analysis of parametrical data was performed by Pearson’s correlation. Odds ratios (OR) with 95% CIs were presented. The results were considered statistically significant at p Results 158 women with previously (15–47 years ago) diagnosed GDM participated in the study. The mean age of participants was 53.0 ± 8.2 years and 60.2 ± 7.5 years (p 0.05). Carbohydrate dysmetabolism was set for 57.6% women with previously diagnosed GDM: 11 (7.0%) were diagnosed with impaired fasting glycemia (IFG), 14 (8.9%) with impaired glucose tolerance (IGT), type 2 Diabetes Mellitus (DM) was diagnosed for 58 (36.7%), DM type 1 for 7 (4.4%), MODY2 (maturity onset diabetes of the young) – 1 (0.6%) patients. TCF7L2 SNPs in women with previously diagnosed GDM and various carbohydrate metabolism groups did not differed (p > 0.05). Body weight, body mass index (BMI), waist and hip circumference in GDM group participants with different TCF7L2 SNP alleles did not differ (p > 0.05). There was no statistically significant difference in fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) results, cholesterol levels and different TCF7L2 SNP alleles in GDM group (p > 0.05). We found higher prevalence of TCF7L2 SNP rs7901695 CC/CT, rs7903146 CT/TT and rs12255372 GT/TT alleles in women previously diagnosed GDM compared to general population women‘s group. The OR of being in GDM group with TCF7L2 SNP: rs7901695 CC/CT alleles, was 1.703 (95% CI 1.153–2.515); rs7903146 CT/TT – 1.708 (95% CI 1.149–2.538); rs12255372 GT/TT – 1.575 (95% CI 1.058–2.343). Conclusions No statistically significant difference in glucose, cholesterol levels and different TCF7L2 SNP alleles in GDM group was found. TCF7L2 SNPs did not differed in women with previously diagnosed GDM and various carbohydrate metabolism groups, though a significantly higher incidence of TCF7L2 rs7901695 SNP CC/CT, rs7903146 SNP CT/TT, rs12255372 GT/TT alleles in study subjects compared to the general population women were observed.

BACKGROUND Heart failure is a fatal complication of type 2 diabetes but little is known about its incidence in patients with impaired glucose tolerance (IGT). We used Acarbose Cardiovascular Evaluation (ACE) trial data to identify predictors of hospitalisation for heart failure (hHF) or cardiovascular (CV) death in patients with coronary heart disease (CHD) and IGT randomized to acarbose 50mg TID or placebo. METHODS Independent hHF or hHF/CV death risk factors were determined using Cox proportional hazards models, with participants censored at first hHF event, CV death, or end of follow-up. Baseline variables evaluated included age, sex, body mass index, smoking, plasma creatinine, prior CV events, fasting and 2-hour post-load glucose, and HbA1c. Those with nominal univariate associations (PRESULTS During median 5 years follow-up, hHF/CV death occurred in 393 (6.0%) ACE participants (triggered by 138 hHF events and 255 CV deaths). Significant hHF/CV death multivariate predictors were higher age and plasma creatinine, as well as prior heart failure (HF), myocardial infarction (MI), atrial fibrillation (AF) and stroke. Acarbose, compared with placebo, did not reduce hHF/CV death (hazard ratio [HR] 0.89, 95% CI 0.64–1.24, P=0.48) or hHF (HR 0.90, 95% CI 0.74–1.10, P=0.32). Forty of the 138 participants who experienced hHF had ³2 admissions, and 58 died. No significant effect of acarbose, compared with placebo, was seen for recurrent hHF (HR 1.19, 95% CI 0.92-1.55, p=0.19), or for all-cause mortality (odds ratio 1.49, 95% CI 0.75-2.95, p=0.25).CONCLUSIONS Patients with CHD and IGT at greater risk of hHF/CV death were older with higher plasma creatinine, and had prior HF, MI, AF or stroke. Addition of acarbose to optimized CV therapy did not reduce the risk of hHF/CV death or hHF. Clinical Trial Registration: ClinicalTrials.gov, number NCT00829660, and the International Standard Randomised Controlled Trial Number registry, number ISRCTN91899513.

AIMS: To compare dysglycaemia prevalence (impaired fasting glucose (IFG) impaired glucose tolerance (IGT) or diabetes) in HIV-infected persons stratified by antiretroviral therapy (ART) with a community-based survey (CBS) in Cape Town South Africa. METHODS: Three groups of HIV-infected adults without known diabetes were conveniently sampled from community healthcare centres; ART-naive first-line ART (non-nucleoside reverse transcriptase inhibitor (NNRTI) plus dual NRTIs) and second-line ART (lopinavir/ritonavir-boosted protease inhibitor plus dual NRTIs). The CBS recruited a representative cross-sectional sample from urban townships. Participants reporting ART use or known diabetes were excluded. All participants underwent oral glucose tolerance testing. Multiple logistic regression determined independent associations with dysglycaemia. RESULTS: The samples comprised ART-naive first-line ART second-line ART and CBS participants (n=393 439 108 and 880 respectively). Mean age was 34-40years. Dysglycaemia prevalence was as follows: CBS 18.0% ART-naive 21.6% first-line ART 26.0% and second-line ART 37.0%. Diabetes was similar across groups but IGT was 3-4-fold higher in second-line ART and CBS compared with ART-naive and first-line ART groups. In contrast IFG was 14.3-21.2% across HIV groups but only 1.5% in the CBS. Increased risk of dysglycaemia was associated with older age female gender and HIV status (ART-naive: OR 2.31 95% CI 1.65-3.24; first-line ART: OR 2.47 95% CI 1.80-3.38; second-line ART: OR 4.10 95% CI 2.54-6.61). Diabetes family history and central obesity were not related to dysglycaemia. CONCLUSIONS: In view of the increased risk of dysglycaemia in HIV-infected participants screening for diabetes should be instituted in ART programmes. Copyright (c) 2016. Published by Elsevier Ireland Ltd.

We examined the prevalence of metabolic syndrome (MetS), glucose tolerance categories and risk factors of cardiovascular-disease (CVD) in the general Spanish population. We studied 3844 randomly sampled subjects (46% males) aged 35-74 years. Glucose tolerance categories were defined according to the 2003 ADA and MetS according to the Harmonized Consensus Criteria with waist circumference (WC) cut-off-points previously reported in Spanish population (≥94.5/≥89.5cm for males/females). The prevalences of normoglycemia (NG), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG and IGT considered together (IFG/IGT), and diabetes mellitus (DM) were 67.6/16.6/5.0/3.3, and 7.5%, respectively. The overall prevalence of MetS was 31.2%. In subjects with NG, IFG, IGT, IFG/IGT, and DM the MetS prevalence's were 16.3/57.1/31.5/66.1, and 74.4% (p

We addressed whether endothelin-1, a marker of endothelial dysfunction, predicts impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in a population study in south-western Sweden. Follow-up after 9.7 years showed an association between circulating endothelin-1 levels at baseline and development of IGT/T2DM in women but not in men.

Aims Weight loss improves insulin sensitivity and glucose tolerance in obese subjects with impaired glucose tolerance (IGT), but the long term dynamic effects on blood metabolites other than glucose during an oral glucose tolerance test (OGTT), are largely unknown. Here, we studied changes in OGTT-elicited metabolite patterns in obese subjects during a diet-induced weight loss study. Methods Blood samples from 14 obese individuals with IGT were collected at 0, 30 and 120 min during a standard 75 g OGTT at baseline (BMI 44 ± 2 kg/m2), after weight loss (BMI 36 ± 2 kg/m2) and after weight maintenance (BMI 35 ± 2 kg/m2). Serum metabolite levels were analyzed by gas chromatography/mass spectrometry and compared to a lean glucose tolerant group. Results Changes in the OGTT-elicited metabolite patterns occurred differentially during weight loss and weight maintenance. Enhanced suppression of aromatic amino acids were associated with decreased insulinogenic index observed after weight loss (tyrosine: r = 0.72, p = 0.013; phenylalanine: r = 0.63, p = 0.039). The OGTT-elicited suppression and/or lack of increase in levels of glutamate, glutamine, isoleucine, leucine, and the fatty acids laurate, oleate and palmitate, improved towards the lean profile after weight maintenance, paralleling an improvement in glucose tolerance. The greater heterogeneity in the response before and after weight loss in the obese, compared to lean subjects, was markedly reduced after weight maintenance. Conclusions Diet-induced weight loss followed by weight maintenance results in changes in metabolite profiles associated with either hepatic insulin sensitivity or peripheral glucose tolerance. Our results highlight the importance of evaluating the effects of weight loss and weight maintenance separately.

Cystic fibrosis related diabetes (CFRD) is associated with a decrease in pulmonary function and nutritional status. We investigated the clinical significance of impaired glucose tolerance (IGT) in cystic fibrosis (CF) patients.Fifty-five CF patients (aged 22.8 ± 9.2 years, 29 males, mean FEV1 67.9 ± 22% predicted, mean BMI-SDS -0.23 ± 1.1) underwent a 2-h Oral Glucose Tolerance Test (OGTT) with 30-min interval measurements of glucose and insulin. Additional clinical and laboratory data were obtained from the medical charts.Thirty-eight participants (69%) had normal glucose tolerance (NGT), 13 (23.7%) had IGT, and 4 (7.3%) had newly diagnosed CFRD. Compared to patients with NGT, patients with IGT had significantly lower BMI-SDS (-1.1 ± 0.8 vs. 0.1 ± 1.1, p0.001), mean FEV1 (57 ± 19 vs. 74 ± 21% predicted, p0.01), and albumin (3.9 ± 0.3 vs. 4.3 ± 0.2g/dl, p=0.004), and higher fibrinogen (376 ± 56 vs. 327 ± 48 g/dl, p=0.02). Patients with IGT had impaired β-cell function, with reduced first phase insulin secretion, a delayed insulin peak, and significantly lower total insulin secretion, HOMA-%B and insulinogenic index. Seven patients had HbA1c in the "diabetic" range (≥6.5%; 47.5 mmol/mol), however, HbA1c was not a sensitive or specific marker of glucose tolerance status.IGT in CF patients is associated with increased inflammation and decreased nutritional status and pulmonary function.

We describe a two-step screening approach using non-invasive risk assessment and glycated hemoglobin (HbA1c) to identify participants for a diabetes prevention trial.A total of 6030 non-diabetic persons of 35-55 years were screened using risk assessment for diabetes. Those with three or more risk factors were screened using point of care HbA1c test. For this study, participants in HbA1c categories of 6.0% (42.1 mmol/mol)-6.4% (46.4 mmol/mol) were selected and their characteristics were analyzed.Among 6030 persons, 2835 (47%) had three or more risk factors for diabetes. Among those screened with HbA1c, 43.2% (1225) had HbA1c values of6.0% (42.1 mmol/mol), 46.8% (1327) had HbA1c values between 6.0% (42.1 mmol/mol) and ≤ 6.4% (46.4 mmol/mol) and 10% (283) had undiagnosed diabetes with ≥6.5% (47.5 mmol/mol). Positive family history was present in 53.2%, 81.7% were obese and 14.8% were overweight.Opportunistic screening using a two-step approach: diabetes risk profile and HbA1c measurement detected a large percentage of individuals with prediabetes. Prediabetic persons recruited to the trial had higher percentage of obesity and presence of positive family history than those who had lower HbA1c values. Outcomes from this trial will enable comparisons with the previous prevention studies that used blood glucose levels as the screening criteria.

Prediabetes (intermediate hyperglycemia) consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) detected by a standardized 75-gram oral glucose tolerance test (OGTT). Individuals with isolated IGT or combined IFG and IGT have increased risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). Diagnosing prediabetes early and accurately is critical in order to refer high-risk individuals for intensive lifestyle modification. However, there is currently no international consensus for diagnosing prediabetes with HbA1c or glucose measurements based upon American Diabetes Association (ADA) and the World Health Organization (WHO) criteria that identify different populations at risk for progressing to diabetes. Various caveats affecting the accuracy of interpreting the HbA1c including genetics complicate this further. This review describes established methods for detecting glucose disorders based upon glucose and HbA1c parameters as well as novel approaches including the 1-hour plasma glucose (1-h PG), glucose challenge test (GCT), shape of the glucose curve, genetics, continuous glucose monitoring (CGM), measures of insulin secretion and sensitivity, metabolomics, and ancillary tools such as fructosamine, glycated albumin (GA), 1,5- anhydroglucitol (1,5-AG). Of the approaches considered, the 1-h PG has considerable potential as a biomarker for detecting glucose disorders if confirmed by additional data including health economic analysis. Whether the 1-h OGTT is superior to genetics and omics in providing greater precision for individualized treatment requires further investigation. These methods will need to demonstrate substantially superiority to simpler tools for detecting glucose disorders to justify their cost and complexity.

Prediabetes has a high prevalence, with early detection essential to facilitate optimal management to prevent the development of conditions such as type 2 diabetes and cardiovascular disease. Prediabetes can include impaired fasting glucose, impaired glucose tolerance and elevated HbA1c. This position statement outlines the approaches to screening and management of prediabetes in primary care. There is good evidence to implement intensive, structured lifestyle interventions for individuals with impaired glucose tolerance. The evidence for those with impaired fasting glucose or elevated HbA1c is less clear, but individuals should still be provided with generalised healthy lifestyle strategies. A multidisciplinary approach is recommended to implement healthy lifestyle changes through education, nutrition and physical activity. Individuals should aim to lose weight (5-10% of body mass) using realistic and sustainable dietary approaches supported by an accredited practising dietitian, where possible. Physical activity and exercise should be used to facilitate weight maintenance and reduce blood glucose. Moderate-vigorous intensity aerobic exercise and resistance training should be prescribed by an accredited exercise physiologist, where possible. When indicated, pharmacotherapy, metabolic surgery and psychosocial care should be considered, in order to enhance the outcomes associated with lifestyle change. Individuals with prediabetes should generally be evaluated annually for their diabetes status.

Aims To evaluate the effect of metformin on various parameters of exercise capacity [oxygen consumption (VO2), peak oxygen consumption (VO2peak), heart rate (HR), exercise test duration, respiratory exchange ratio (RER), rating of perceived exertion (RPE), lactate and ventilatory anaerobic threshold (VAT)]. Methods Studies reporting change in VO2 or VO2peak after metformin administration were included. Subgroup analyses were performed as applicable. Mean difference with 95% CIs were pooled using random-effects model [RevMan (v5.3)]. Results There were no changes in VO2 and VO2peak in the overall population [VO2: n = 388, mean difference: −0.12 ml/kg/min, 95% CI: −0.74, 0.51, p = 0.71 (i2 = 0%, p = 0.99); VO2peak: n = 345, mean difference: 0.41 ml/kg/min, 95% CI: −0.51, 1.33, p = 0.38 (i2 = 0%, p = 0.89)], healthy volunteers and patients (type 2 diabetes mellitus, insulin resistance, impaired glucose tolerance/impaired fasting glucose and metabolic syndrome). For patients with insulin resistance, there was a decrease in VO2peak, but not VO2. In the overall population, there was a significant decrease in HR and RER, a significant increase in RPE, and no changes in exercise test duration and VAT. In addition, there was an increased VAT in the healthy volunteers. Conclusions In the overall population, metformin did not affect VO2, VO2peak, exercise test duration and VAT, although it significantly decreased HR, RER and increased RPE.

Aim We investigated the association of impaired glucose metabolism with tooth loss in adults in the Northern Finland Birth Cohort Study 1966 (NFBC1966). Methods We examined 4394 participants from the 46-year follow-up of the NFBC1966. Self-reported number of teeth as well as insulin and glucose values, taken during a standard oral glucose tolerance test (OGTT), served as the primary study variables. A multinomial logistic regression model served to analyse (unadjusted, smoking-adjusted and fully adjusted) the association between number of teeth (0–24, 25–27, 28–32) and glucose metabolism in women and men. Results Among women, type 2 diabetes – whether previously known or detected during screening – pointed to a higher likelihood of 0–24 teeth (fully adjusted OR = 2.99, 95%CI = 1.54–5.80) and 25–27 teeth (OR = 1.91, 95%CI = 1.18–3.08) than did normal glucose tolerance. Similarly, impaired fasting glucose and impaired glucose tolerance together indicated a higher likelihood of 0–24 teeth (OR = 1.71, 95%CI = 1.09–2.69) than did normal glucose tolerance. A similar, statistically non-significant, pattern emerged among men. Number of teeth associated with OGTT insulin and glucose curves as well as with the Matsuda index in both women and men. Conclusions Tooth loss strongly associated with impaired glucose metabolism in middle-aged Finnish women.

Aims To describe the roles of intra-abdominal fat and its change in the remission of impaired glucose tolerance (IGT) to normal glucose tolerance (NGT). Methods We followed 157 Japanese Americans with IGT at baseline for 10–11 years without external intervention. We measured intra-abdominal and abdominal subcutaneous fat area (IAFA and ASFA) by computed tomography at baseline and at 5–6 years of follow-up. Change in IAFA and ASFA (ΔIAFA and ΔASFA) were calculated by subtracting baseline fat area from 5–6 year follow-up fat area. Glucose and insulin at fasting and during a 75-g oral glucose tolerance test, insulinogenic index (IGI [Δinsulin/Δglucose (30–0 min)]) and homeostasis model assessment for insulin resistance (HOMA-IR) were measured at baseline. Results Fourty-four subjects remitted to NGT. Among those with lower IAFA (≤median 91.31 cm2) and the lowest tertile of ΔIAFA, 45% remitted, while with higher IAFA (>91.31 cm2) and the highest tertile of ΔIAFA, only 12.5% remitted. ΔIAFA was significantly associated with remission to NGT (multiple-adjusted odd ratio [1-SD decrease] 1.93, 95% CI 1.10–3.36) independent of IAFA, ASFA, ΔASFA, IGI, HOMA-IR, age, sex, and family history of diabetes. Conclusions In the natural history of IGT, change in intra-abdominal fat was associated with remission to NGT.

Aims To investigate whether continuous glucose monitoring (CGM) reveals patterns of glycaemic behaviour, the detection of which might improve early diagnosis of dysglycaemia. Methods A total 1521 complete days of valid CGM data were recorded under real-life conditions from a healthy sample of a Spanish community, as were matching FPG and HbA1C data. No participant was pregnant, had a history of kidney or liver disease, or was taking drugs known to affect glycaemia. Results CGM and fingerstick measurements showed a mean relative absolute difference of 6.9 ± 2.2%. All subjects were normoglycaemic according to FPG and HbA1C except 21% who were prediabetic. The normoglycaemic subjects had a 24-hour mean blood glucose concentration (MBG) of 5.7 ± 0.4 mmol/L, spending a median of 97% of their time within the target range (3.9–7.8 mmol/L). 73% of them experienced episodes with blood glucose levels above the threshold for impaired glucose tolerance, and 5% levels above the threshold for diabetes. These normoglycaemic participants with episodes of high glycaemia had glycaemic variabilities similar to those of prediabetic subjects with episodes of similar intensity or combined duration. Conclusions CGM is a better indicator of possible early dysglycaemia than either FPG or HbA1c.

The aims of this study were: (1) to assess the association of adiponectin, leptin and interleukin-6 (IL-6) with incidence of type 2 diabetes (T2DM) in Asian Indian men with impaired glucose tolerance (IGT) and (2) to evaluate the additional contribution of these with the well-established glycaemic marker HbA1c.This is an ancillary analyses of a nested case-control study derived from a prospective, prevention trial in India. All the participants had IGT at baseline. For this subanalysis a total of 147 (T2DM: 71; nondiabetic: 76) participants were selected based on the final glycemic outcomes. Association of these selected adipokines with T2DM were assessed using logistic regression analyses. Clinical usefulness of adding adipokine markers with HbA1c on prediction of T2DM was assessed using the area under the curve (AUC) of the receiver operating characteristics.Baseline levels of adiponectin were lower and the levels of IL-6 were higher in T2DM cases when compared with non-diabetic cases (P0.05). Levels of leptin were similar in both groups. In fully adjusted models, adiponectin (odds ratio (OR): 0.55 [95%CI: 0.33-0.91]; P=0.019) and IL-6 (OR: 2.27 [95%CI: 1.40-3.691]; P=0.001) were associated with diabetes. Addition of adiponectin to HbA1c improved the AUC (ΔAUC: 0.0619; P=0.0251), whereas addition of IL-6 did not improve the predictive power of HbA1c alone.Adiponectin and IL-6 are independently associated with incident diabetes. However, they are unlikely to serve as simple tools to predict future risk of diabetes but may have a role in understanding the pathogenesis.

We studied cognition in the Finnish Diabetes Prevention Study (DPS), a trial of lifestyle intervention that prevented diabetes in persons with impaired glucose tolerance. Cognition was similar in the randomization arms 9 years after the intervention in 364 participants, suggesting that the intervention did not benefit cognition.

Fibroblast growth factor 21 (FGF21) has been well-recognized as a metabolic hormone and a promising target for treatment of metabolic diseases. The level of endogenous FGF21 is elevated in patients with impaired glucose tolerance and progressively increased from patients with overt type 2 diabetes to those with micro- and macro-vascular complications, presumably as a compensation or response to the deterioration of metabolic imbalance. A few exploratory in vivo studies, including a recent clinical trial, showed that exogenous FGF21 mimetics targeting FGF21 signaling can attain beneficial metabolic effects not with-standing the already elevated ambient FGF21 levels. In addition, some clinically available pharmacologic agents such as fenofibrates and metformin may modulate energy and macronutrients metabolism by acting through FGF21. This review mainly focuses on the role of FGF21 in development, progression and treatment of type 2 diabetes from a clinical perspective.

Aims Individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) have an increased risk of progression to Type 2 diabetes mellitus. The objective of this review was to quantify the effectiveness of lifestyle, pharmacological and surgical interventions in reducing the progression to Type 2 diabetes mellitus in people with IFG or IGT. Methods A systematic review was carried out. A network meta-analysis (NMA) of log-hazard ratios was performed. Results are presented as hazard ratios and the probabilities of treatment rankings. Results 30 studies were included in the NMA. There was a reduced hazard of progression to Type 2 diabetes mellitus associated with all interventions versus standard lifestyle advice; glipizide, diet plus pioglitazone, diet plus exercise plus metformin plus rosiglitazone, diet plus exercise plus orlistat, diet plus exercise plus pedometer, rosiglitazone, orlistat and diet plus exercise plus voglibose produced the greatest effects. Conclusions Lifestyle and some pharmacological interventions are beneficial in reducing the risk of progression to Type 2 diabetes mellitus. Lifestyle interventions require significant behaviour changes that may be achieved through incentives such as the use of pedometers. Adverse events and cost of pharmacological interventions should be taken into account when considering potential risks and benefits.

Aims To compare the diabetes prevention impact and cost of several screening scenarios for diabetes prevention programs with the scenario which included an oral glucose tolerance test (OGTT). Methods We included 4864 participants of the Australian Diabetes, Obesity and Lifestyle study who were aged ≥40 years, did not have known diabetes at baseline, and attended the five year follow-up. The proportions of participants eligible or ineligible for diabetes prevention program were estimated for each scenario. The costs of screening and diabetes prevention programs were also estimated. Results Screening with OGTT alone identified 21% of participants as eligible for diabetes prevention. While 3.1% of the cohort were identified as high risk and developed diabetes after five years, 1.0% of the cohort were identified as low risk and developed diabetes. The population prevention potential (i.e. sensitivity) for OGTT alone was 76.5%. Screening all Australian adults aged ≥40 years in 2015 by OGTT would have cost a total of AU$2025 million (AU$1031 million on screening and AU$994 million on prevention programs). The total costs of screening and prevention were substantially lower when AUSDRISK was used alone or in combination with a blood test. However, the population prevention potentials were also lower (ranged from 20.1% to 50.7%). Conclusions A blood test post non-invasive risk assessment is a worthwhile step in the process of enrolling participants in a diabetes prevention program. Nevertheless, there will be ineligible individuals who proceed to diabetes.

Although impaired glucose tolerance (IGT) is a definite risk factor for type 2 diabetes mellitus (T2DM), there is limited information about the risk stratification for incident T2DM within IGT group. Thus, we aimed to evaluate the incidental risk for T2DM according to 2-h plasma glucose (2-h PG) level of oral glucose tolerance test (OGTT) and phenotype of IGT.7654 Korean participated in the Korean Genome and Epidemiology Study (KoGES) were stratified by 2-h PG levels of OGTT, and followed up for 63,665 person-years. Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidential interval (CI) for T2DM according to 2-h PG levels of OGTT with adjustment for multiple covariates. Subgroup analysis was performed by gender and the presence of impaired fasting glucose (IFG) or not.Within IGT, the adjusted HRs for T2DM significantly increased proportionally to 2-h PG level [140mg/dL: reference, 140-159mg/dL: 3.07 (2.67-3.54), 160-179mg/dL: 5.44 (CI 4.66-6.34), 180-199mg/dL: 7.91 (CI 6.53-9.59)]. IGT combined with IFG had the profoundly increased HRs than isolated IFG. Even within normal glucose tolerance (NGT), 2-h PG level≥120mg/dL had the higher risk for T2DM than other NGT groups. These associations were more dominant in male than female.The highest level of 2h-PG (180-199mg/dL) in IGT and IGT with IFG were strong predictor for T2DM. 2-h PG of 120-139mg/dL was more significantly associated with T2DM within NGT, and male was more susceptible for T2DM than female.

The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes.We recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3-6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7-6.4%, 39-46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated.Eighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥ 165 mg/dL and a 30-min C-peptide5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98-26.16) of developing diabetes than other prediabetic subjects.In Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population.

Aims To examine the properties of HbA1c to detect diabetes and IGT in adult Brazilian Xavante Indians, a high risk population for diabetes. Methods The survey was carried out between October 2010 and January 2012 and based on a 75 g oral glucose tolerance test (OGTT). Basal and 2 h capillary glycaemia were measured by HemoCue Glucose 201+; HbA1c using an automated high-performance liquid chromatography analyzer (Tosoh G7). Results 630 individuals aged ≥20 years were examined and 80 had a previous diagnosis of diabetes. Sensitivity, specificity and accuracy for HbA1c ≥ 6.5% (≥48 mmol/mol) were 71.3%, 90.5% and 87.2%. The areas under the ROC curve (AUC) was 0.88 (95%CI: 0.83–0.93). To identify IGT, HbA1c values between 5.7% and 6.4% (39–47 mmol/mol) presented sensitivity, specificity and accuracy of 87.2%, 24.7% and 51.4%, with an AUC of 0.62 (95%CI: 0.57–0.67). Conclusions The ADA/WHO proposed cut-off of 6.5% (48 mmol/mol) for HbA1c was adequate to detect diabetes among the Xavante. However, the performance of the ADA proposed cut-off points for pre-diabetes, when used to detect IGT was inadequate and should not be recommended.