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Aims: To investigate the sex‐specific associations between predicted skeletal muscle mass index (pSMI) and incident type 2 diabetes in a retrospective longitudinal cohort of Chinese men and women. Materials and Methods: We enrolled Chinese adults without diabetes at baseline from WATCH (West chinA adulT health CoHort), a large health check‐up‐based database. We calculated pSMI to estimate skeletal muscular mass, and measured blood glucose variables and assessed self‐reported history to identify new‐onset diabetes. The nonlinear association between pSMI and incident type 2 diabetes was modelled using the penalized spline method. The piecewise association was estimated using segmented linear splines in weighted Cox proportional hazards regression models. Results: Of 47 885 adults (53.2% women) with a median age of 40 years, 1836 developed type 2 diabetes after a 5‐year median follow‐up. In women, higher pSMI was associated with a lower risk of incident type 2 diabetes (Pnonlinearity = 0.09, hazard ratio [HR] per standard deviation increment in pSMI: 0.79 [95% confidence interval {CI} 0.68, 0.91]). A nonlinear association of pSMI with incident type 2 diabetes was detected in men (Pnonlinearity < 0.001). In men with pSMI lower than 8.1, higher pSMI was associated with a lower risk of incident type 2 diabetes (HR 0.58 [95% CI 0.40, 0.84]), whereas pSMI was not significantly associated with incident diabetes in men with pSMI equal to or greater than 8.1 (HR 1.08 [95% CI 0.93, 1.25]). Conclusions: In females, a larger muscular mass is associated with a lower risk of type 2 diabetes. For males, this association is significant only among those with diminished muscle mass. [ABSTRACT FROM AUTHOR]

Seung Ho Yang, Jihyun Yoon, Yong-Jae Lee, Byoungjin Park, Dong-Hyuk Jung Department of Family Medicine, Yonsei University College of Medicine, Seoul, Republic of KoreaCorrespondence: Dong-Hyuk Jung; Byoungjin Park, Department of Family Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeondae-ro, Giheung-gu, Yongin-si, Gyeonggi-do, 16995, Republic of Korea, Tel +82-31-5189-8762 ; +82 31 5189 8763, Fax +82-31-5189-8567, Email balsan2@yuhs.ac; bjpark96@yuhs.acPurpose: The lipid accumulation product (LAP) has been a potential indicator of central lipid accumulation status. This study aimed to assess the longitudinal association between LAP index and incident type 2 diabetes among non-obese Korean adults using a large, community-based Korean cohort observed over 12 years.Patients and Methods: This study included 4281 non-diabetic adults without generalized obesity and abdominal obesity and aged 40– 69 years from the Korean Genome and Epidemiology Study. The participants were divided into four groups according to LAP index quartiles, calculated as (waist circumference [cm] - 65) x (triglycerides [mmol/L]) in men and (waist circumference [cm] - 58) x (triglycerides [mmol/L]) in women. We prospectively assessed hazard ratios (HRs) with 95% confidential intervals (CIs) for incident type 2 diabetes using multivariate Cox proportional hazard regression models.Results: Overall, 608 (14.2%) participants developed type 2 diabetes during the follow-up period. HRs for incident type 2 diabetes in the second, third, and fourth LAP quartile were 1.32 (95% CI: 0.97– 1.79), 1.51 (95% CI: 1.11– 2.06), and 2.14 (95% CI: 1.56– 2.94), respectively, after adjusting for age, sex, body mass index, smoking status, alcohol intake, physical activity, mean arterial blood pressure, family history of diabetes, and impaired glucose tolerance.Conclusion: A high LAP index can be an additional indicator for new-onset T2DM among middle-aged and elderly non-obese Koreans.Keywords: lipid accumulation product index, prospective cohort study, incident type 2 diabetes, Koreans

Recent attempts to classify adult-onset diabetes using only six diabetes-related variables (GAD antibody, age at diagnosis, BMI, HbA1c, and homeostatic model assessment 2 estimates of b-cell function and insulin resistance (HOMA2-B and HOMA2-IR)) showed that diabetes can be classified into five clusters, of which four correspond to type 2 diabetes (T2DM). Here, we classified nondiabetic individuals to identify risk clusters for incident T2DM to facilitate the refinement of prevention strategies. Of the 1167 participants in the population-based Iwaki Health Promotion Project in 2014 (baseline), 868 nondiabetic individuals who attended at least once during 2015–2019 were included in a prospective study. A hierarchical cluster analysis was performed using four variables (BMI, HbA1c, and HOMA2 indices). Of the four clusters identified, cluster 1 (n = 103), labeled as "obese insulin resistant with sufficient compensatory insulin secretion", and cluster 2 (n = 136), labeled as "low insulin secretion", were found to be at risk of diabetes during the 5-year follow-up period: the multiple factor-adjusted HRs for clusters 1 and 2 were 14.7 and 53.1, respectively. Further, individuals in clusters 1and 2 could be accurately identified: the area under the ROC curves for clusters 1and 2 were 0.997 and 0.983, respectively. The risk of diabetes could be better assessed on the basis of the cluster that an individual belongs to. [ABSTRACT FROM AUTHOR]

Abstract Background Endothelin-1 (ET-1) and adrenomedullin (ADM) are commonly known as vasoactive peptides that regulate vascular homeostasis. Less recognised is the fact that both peptides could affect glucose metabolism. Here, we investigated whether ET-1 and ADM, measured as C-terminal-proET-1 (CT-proET-1) and mid-regional-proADM (MR-proADM), respectively, were associated with incident type 2 diabetes. Methods Based on the population-based Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium data, we performed a prospective cohort study to examine associations of CT-proET-1 and MR-proADM with incident type 2 diabetes in 12,006 participants. During a median follow-up time of 13.8 years, 862 participants developed type 2 diabetes. The associations were examined in Cox proportional hazard models. Additionally, we performed two-sample Mendelian randomisation analyses using published data. Results CT-proET-1 and MR-proADM were positively associated with incident type 2 diabetes. The multivariable hazard ratios (HRs) [95% confidence intervals (CI)] were 1.10 [1.03; 1.18], P = 0.008 per 1-SD increase of CT-proET-1 and 1.11 [1.02; 1.21], P = 0.016 per 1-SD increase of log MR-proADM, respectively. We observed a stronger association of MR-proADM with incident type 2 diabetes in obese than in non-obese individuals (P-interaction with BMI

Background: Endothelin-1 (ET-1) and adrenomedullin (ADM) are commonly known as vasoactive peptides that regulate vascular homeostasis. Less recognised is the fact that both peptides could affect glucose metabolism. Here, we investigated whether ET-1 and ADM, measured as C-terminal-proET-1 (CT-proET-1) and mid-regional-proADM (MR-proADM), respectively, were associated with incident type 2 diabetes. Methods: Based on the population-based Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium data, we performed a prospective cohort study to examine associations of CT-proET-1 and MR-proADM with incident type 2 diabetes in 12,006 participants. During a median follow-up time of 13.8 years, 862 participants developed type 2 diabetes. The associations were examined in Cox proportional hazard models. Additionally, we performed two-sample Mendelian randomisation analyses using published data. Results: CT-proET-1 and MR-proADM were positively associated with incident type 2 diabetes. The multivariable hazard ratios (HRs) [95% confidence intervals (CI)] were 1.10 [1.03; 1.18], P = 0.008 per 1-SD increase of CT-proET-1 and 1.11 [1.02; 1.21], P = 0.016 per 1-SD increase of log MR-proADM, respectively. We observed a stronger association of MR-proADM with incident type 2 diabetes in obese than in non-obese individuals (P-interaction with BMI < 0.001). The HRs [95%CIs] were 1.19 [1.05; 1.34], P = 0.005 and 1.02 [0.90; 1.15], P = 0.741 in obese and non-obese individuals, respectively. Our Mendelian randomisation analyses yielded a significant association of CT-proET-1, but not of MR-proADM with type 2 diabetes risk. Conclusions: Higher concentrations of CT-proET-1 and MR-proADM are associated with incident type 2 diabetes, but our Mendelian randomisation analysis suggests a probable causal link for CT-proET-1 only. The association of MR-proADM seems to be modified by body composition. [ABSTRACT FROM AUTHOR]

Rationale: Obstructive sleep apnea (OSA) is associated with cardiovascular disease and incident type 2 diabetes (T2DM). Seven OSA phenotypes, labeled on the basis of their most distinguishing polysomnographic features, have been shown to be differentially associated with incident cardiovascular disease. However, little is known about the relevance of polysomnographic phenotypes for the risk of T2DM. Objectives: To assess whether polysomnographic phenotypes are associated with incident T2DM and to compare the predictive value of baseline polysomnographic phenotypes with the Apnea-Hypopnea Index (AHI) for T2DM. Methods: The study included 840 individuals without baseline diabetes from a multisite observational U.S. veteran cohort who underwent OSA evaluation between 2000 and 2004, with follow-up through 2012. The primary outcome was incident T2DM, defined as no diagnosis at baseline and a new physician diagnosis confirmed by fasting blood glucose >126 mg/dL during follow-up. Relationships between the seven polysomnographic phenotypes (1. mild, 2. periodic limb movements of sleep [PLMS], 3. non-rapid eye movement and poor sleep, 4. rapid eye movement and hypoxia, 5. hypopnea and hypoxia, 6. arousal and poor sleep, and 7. combined severe) and incident T2DM were investigated using Cox proportional hazards regression and competing risk regression models with and without adjustment for baseline covariates. Likelihood ratio tests were conducted to compare the predictive value of the phenotypes with the AHI. Results: During a median follow-up period of 61 months, 122 (14.5%) patients developed incident T2DM. After adjustment for baseline sociodemographics, fasting blood glucose, body mass index, comorbidities, and behavioral risk factors, hazard ratios among persons with "hypopnea and hypoxia" and "PLMS" phenotypes as compared with persons with "mild" phenotype were 3.18 (95% confidence interval [CI], 1.53-6.61] and 2.26 (95% CI, 1.06-4.83) for incident T2DM, respectively. Mild OSA (5 ⩽ AHI < 15) (vs. no OSA) was directly associated with incident T2DM in both unadjusted and multivariable-adjusted regression models. The addition of polysomnographic phenotypes, but not AHI, to known T2DM risk factors greatly improved the predictive value of the computed prediction model. Conclusions: Polysomnographic phenotypes "hypopnea and hypoxia" and "PLMS" independently predict risk of T2DM among a predominantly male veteran population. Polysomnographic phenotypes improved T2DM risk prediction comared with the use of AHI. [ABSTRACT FROM AUTHOR]

Reduced lung function is associated with type 2 diabetes (T2D), but there are limited data in East Asian populations on the relationship between them. For this reason, this study investigated the longitudinal relationship of lung function with incident T2D in Korean adults. The study included 7583 non-diabetic adults aged 40–69 years from the Korean Genome and Epidemiology Study. Participants were divided into four groups according to gender-specific quartiles (Q1–Q4) of %PFVC and %PFEV 1. Also, HRs with 95% CIs for incident T2D were prospectively analyzed as per American Diabetes Association criteria using multivariate Cox proportional-hazards regression models. During a 12-year follow-up, 1403 (18.5%) participants presented with newly developed T2D. HRs (95% CIs) of incident T2D in Q1 vs. Q4 (reference) of %PFVC were 1.67 (1.35–2.07) for men and 1.77 (1.39–2.24) for women and, of %PFEV 1 , 1.58 (1.28–1.95) for men and 1.61 (1.27–2.03) for women, after adjusting for age, waist circumference, smoking status, alcohol intake, regular exercise, education levels, monthly household income, family history of diabetes, HOMA-IR, triglycerides, HDL cholesterol and high-sensitivity C-reactive protein levels. Reduced lung function precedes and significantly predicts the future development of T2D independently of obesity, smoking and inflammation in community-dwelling middle-aged and elderly people. [ABSTRACT FROM AUTHOR]

Backgrounds and Aims: Limited evidence is available on whether serum γ-glutamyltransferase (GGT) has value as a predictor of type 2 diabetes in East Asian populations. We investigated the causal relationship between serum GGT level and incident type 2 diabetes in Korean adults.Methods and Results: A total of 7739 nondiabetic adults aged 40-69 years from the Korean Genome and Epidemiology Study were studied. We divided the population into four groups according to sex-specific quartiles by serum GGT levels. Hazard ratios (HRs) with 95% Confidence intervals (CIs) for incident type 2 diabetes were prospectively analyzed using multivariate Cox proportional hazards regression models. A total of 1432 (18.5%) participants developed type 2 diabetes over 12 years of follow-up. The higher the serum GGT group quartile, the higher the cumulative type 2 diabetes incidence over 12 years with significance in both sexes (log-rank test P < 0.001). HRs (95% CIs) for incident type 2 diabetes for the highest quartile versus referent lowest quartile for serum GGT levels were 2.55 (1.86-3.51) for men and 1.90 (1.40-2.58) for women after adjusting for confounding variables.Conclusions: Higher serum GGT levels preceded and positively associated with incident type 2 diabetes among community-dwelling middle-aged and older Korean adults. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: This work examined the role of physical activity in the course of diabetes using data spanning nearly three decades. Our first aim was to examine the long-term association of moderate and vigorous physical activity with incidence of type 2 diabetes. Our second aim was to investigate the association of moderate-to-vigorous physical activity post-diabetes diagnosis with subsequent risk of all-cause and cardiovascular disease mortality. Methods: A total of 9987 participants from the Whitehall II cohort study free of type 2 diabetes at baseline (1985–1988) were followed for incidence of type 2 diabetes, based on clinical assessments between 1985 and 2016 and linkage to electronic health records up to 31 March 2017. We first examined the association of moderate and vigorous physical activity measured by questionnaire in 1985–1988 (mean age 44.9 [SD 6.0] years; women, 32.7%) with incident type 2 diabetes, using the interval-censored, illness–death model, a competing risk analysis that takes into account both competing risk of death and intermittent ascertainment of diabetes due to reliance on data collection cycles (interval-censored). The second analysis was based on individuals with type 2 diabetes over the follow-up period where we used Cox regression with inverse probability weighting to examine the association of moderate-to-vigorous physical activity after diagnosis of type 2 diabetes with risk of all-cause and cardiovascular disease mortality. Results: Of the 9987 participants, 1553 developed type 2 diabetes during a mean follow-up of 27.1 (SD 6.3) years. Compared with participants who were inactive in 1985–1988, those who undertook any duration of moderate-to-vigorous physical activity had a lower risk of type 2 diabetes (HR 0.85 [95% CI 0.75, 0.97], p = 0.02; analysis adjusted for sociodemographic, behavioural and health-related factors). In 1026 participants with a diagnosis of type 2 diabetes over the follow-up period, data on moderate-to-vigorous physical activity after diabetes diagnosis were available; 165 all-cause deaths and 55 cardiovascular disease-related deaths were recorded during a mean follow-up of 8.8 (SD 6.1) years. In these participants with diabetes, any duration of moderate-to-vigorous physical activity was associated with lower all-cause mortality (HR 0.61 [95% CI 0.41, 0.93], p = 0.02) while the association with cardiovascular mortality was evident only for physical activity undertaken at or above recommendations (≥2.5 h per week of moderate-to-vigorous physical activity or ≥1.25 h per week of vigorous physical activity; HR 0.40 [95% CI 0.16, 0.96], p = 0.04) in fully adjusted models. Conclusions/interpretation: Moderate-to-vigorous physical activity plays an important role in diabetes, influencing both its incidence and prognosis. A protective effect on incidence was seen for durations of activity below recommendations and a marginal additional benefit was observed at higher durations. Among individuals with type 2 diabetes, any duration of moderate-to-vigorous physical activity was associated with reduced all-cause mortality while recommended durations of physical activity were required for protection against cardiovascular disease-related mortality. Data availability: Whitehall II data, protocols and other metadata are available to the scientific community. Please refer to the Whitehall II data sharing policy at https://www.ucl.ac.uk/epidemiology-health-care/research/epidemiology-and-public-health/research/whitehall-ii/data-sharing. [ABSTRACT FROM AUTHOR]

Abstract Background The role of an individual’s social network satisfaction (SNS) in the association of social isolation or living alone and incident type 2 diabetes (T2D) is unclear. We assessed the association of SNS with incident T2D and analysed potential modifications of the SNS-T2D association by social isolation or living alone. Methods The study population (N = 6839 aged 25–74 years without diabetes at baseline) derived from the prospective population-based MONICA/KORA study (1989–2009). Social network satisfaction was assessed by a single item. Cox regression was used to estimate hazard ratios (HR) for SNS separately in men and women. Results In men with low SNS, risk for incident T2D increased significantly (HR: 2.15, 95% CI: 1.33–3.48, p value 0.002). After additional adjustments for social isolation or living alone, the risk for incident T2D was still significant, albeit less pronounced (HRs 1.85 or 2.05, p values 0.001 or 0.004). The interaction analysis showed an increased T2D risk effect for low SNS compared to high SNS in women living in a partnership (HR: 2.11, 95% CI: 1.00–4.44, p value for interaction: 0.047) and for moderate SNS compared to high SNS in socially connected women (1.56, 1.01–2.39, 0.010). Conclusions Further research is needed to address the complexities of the perception of social relationships and social interactions, or interdependence, especially when another major public health issue such as T2D is concerned.

Abstract Background Refined grains and white rice have been associated with elevated risk of type 2 diabetes mellitus (T2DM). In this study, we sought to quantify the effect of white rice intake on incident T2DM in two prospective population-based cohort studies from Iran, where white rice is one of the main staple. Methods We used follow-up data from 9,182 participants from Golestan Cohort Study (GCS, 2004–2007, conducted mainly in rural areas) and 2,173 from Tehran Lipid and Glucose Study (TLGS, 2004–2006) who did not have T2DM and other chronic diseases at baseline. Diet was assessed using validated food frequency questionnaires. Multivariable logistic regression models were used to estimate adjusted odds ratios (ORs) for incident T2DM. Results We documented 902 new cases of T2DM in GCS and 81 in TLGS. Age-standardized cumulative incidence of T2DM was 9.9% in Golestan and 8.0% in Tehran. Daily white rice intake was significantly higher among residents of Tehran compared to Golestan (median daily intake: 250 vs. 120 grams; P-value 250 grams/day to those with

Summary: The pathophysiological influence of gene‐lifestyle interactions on the risk to develop type 2 diabetes (T2D) is currently under intensive research. This systematic review summarizes the evidence for gene‐lifestyle interactions regarding T2D incidence. MEDLINE, EMBASE, and Web of Science were systematically searched until 31 January 2019 to identify publication with (a) prospective study design; (b) T2D incidence; (c) gene‐diet, gene‐physical activity, and gene‐weight loss intervention interaction; and (d) population who are healthy or prediabetic. Of 66 eligible publications, 28 reported significant interactions. A variety of different genetic variants and dietary factors were studied. Variants at TCF7L2 were most frequently investigated and showed interactions with fiber and whole grain on T2D incidence. Further gene‐diet interactions were reported for, eg, a western dietary pattern with a T2D‐GRS, fat and carbohydrate with IRS1 rs2943641, and heme iron with variants of HFE. Physical activity showed interaction with HNF1B, IRS1, PPARγ, ADRA2B, SLC2A2, and ABCC8 variants and weight loss interventions with ENPP1, PPARγ, ADIPOR2, ADRA2B, TNFα, and LIPC variants. However, most findings represent single study findings obtained in European ethnicities. Although some interactions have been reported, their conclusiveness is still low, as most findings were not yet replicated across multiple study populations. [ABSTRACT FROM AUTHOR]

Background: The relationship between OSA and glucose metabolism remains controversial. This retrospective study investigated the relationship between OSA and incident type 2 diabetes (T2D) in a clinic cohort of Chinese adults in Hong Kong, and the effect of long-term CPAP treatment.Methods: Data for diagnosis of incident T2D and CPAP usage were obtained from the territory-wide electronic health administration system and records of protocolized evaluation of CPAP adherence at the sleep clinic. The relationship between baseline OSA and incident T2D and the effect of CPAP therapy were examined by Cox regression models. Risk of incident T2D over the continuum of apnea-hypopnea index was examined with cubic spline analysis.Results: Of 1,206 subjects with overnight sleep studies and clinical assessment in 2006 through 2013, 152 developed diabetes (median follow-up, 7.3 years). In fully adjusted models, untreated moderate or patients with severe OSA had higher risk of developing diabetes, hazard ratios 2.01 (95% CI, 1.06-3.81) and 2.62 (95% CI, 1.40-4.93) respectively, with a trend to plateau in those with severe OSA. No interaction was demonstrated between OSA and obesity. Regular CPAP use, which was attained in about one-third of subjects with moderate-severe OSA, was associated with reduction of diabetes incidence from 3.41 to 1.61 per 100 person-years, and of adjusted hazard risk to that of non-OSA.Conclusions: OSA severity independently predicted incident diabetes. Regular long-term CPAP use was associated with reduced risk of incident T2D, after adjustment for various baseline metabolic risk factors and subsequent body weight change. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Information on the associations of long-term exposure to fine particulate matter (with an aerodynamic diameter less than 2.5 μm; PM2.5) with the development of type 2 diabetes is scarce, especially for south-east Asia, where most countries are experiencing serious air pollution. This study aimed to investigate the long-term effects of exposure to ambient PM2.5 on the incidence of type 2 diabetes in a population of Taiwanese adults. Methods: A total of 147,908 participants without diabetes, at least 18 years of age, were recruited in a standard medical examination programme between 2001 and 2014. They were encouraged to take medical examinations periodically and underwent at least two measurements of fasting plasma glucose (FPG). Incident type 2 diabetes was identified as FPG ≥7 mmol/l or self-reported physician-diagnosed diabetes in the subsequent medical visits. The PM2.5 concentration at each participant's address was estimated using a satellite-based spatiotemporal model with a resolution of 1 × 1 km2. The 2 year average of PM2.5 concentrations (i.e. the year of and the year before the medical examination) was treated as an indicator of long-term exposure to ambient PM2.5 air pollution. We performed Cox regression models with time-dependent covariates to analyse the long-term effects of exposure to PM2.5 on the incidence of type 2 diabetes. A wide range of covariates were introduced in the models to control for potential effects, including age, sex, education, season, year, smoking status, alcohol drinking, physical activity, vegetable intake, fruit intake, occupational exposure, BMI, hypertension and dyslipidaemia (all were treated as time-dependent covariates except for sex). Results: Compared with the participants exposed to the first quartile of ambient PM2.5, participants exposed to the second, third and fourth quartiles of ambient PM2.5 had HRs of 1.28 (95% CI 1.18, 1.39), 1.27 (95% CI 1.17, 1.38) and 1.16 (95% CI 1.07, 1.26), respectively, for the incidence of type 2 diabetes. Participants who drank occasionally or regularly (more than once per week) or who had a lower BMI (<23 kg/m2) were more sensitive to the long-term effects of exposure to ambient PM2.5. Conclusions/interpretation: Long-term exposure to ambient PM2.5 appears to be associated with a higher risk of developing type 2 diabetes in this Asian population experiencing high levels of air pollution. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA, fasting insulin and HOMA-IR with incident type 2 diabetes mellitus. Methods: The study population included 1349 participants aged 50-75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations. Results: After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA, 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA with incident diabetes were non-linear, rising more steeply at higher values. Conclusions/interpretation: FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA, HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers. [ABSTRACT FROM AUTHOR]

Background: The role of an individual's social network satisfaction (SNS) in the association of social isolation or living alone and incident type 2 diabetes (T2D) is unclear. We assessed the association of SNS with incident T2D and analysed potential modifications of the SNS-T2D association by social isolation or living alone.Methods: The study population (N = 6839 aged 25-74 years without diabetes at baseline) derived from the prospective population-based MONICA/KORA study (1989-2009). Social network satisfaction was assessed by a single item. Cox regression was used to estimate hazard ratios (HR) for SNS separately in men and women.Results: In men with low SNS, risk for incident T2D increased significantly (HR: 2.15, 95% CI: 1.33-3.48, p value 0.002). After additional adjustments for social isolation or living alone, the risk for incident T2D was still significant, albeit less pronounced (HRs 1.85 or 2.05, p values 0.001 or 0.004). The interaction analysis showed an increased T2D risk effect for low SNS compared to high SNS in women living in a partnership (HR: 2.11, 95% CI: 1.00-4.44, p value for interaction: 0.047) and for moderate SNS compared to high SNS in socially connected women (1.56, 1.01-2.39, 0.010).Conclusions: Further research is needed to address the complexities of the perception of social relationships and social interactions, or interdependence, especially when another major public health issue such as T2D is concerned. [ABSTRACT FROM AUTHOR]

Background: Refined grains and white rice have been associated with elevated risk of type 2 diabetes mellitus (T2DM). In this study, we sought to quantify the effect of white rice intake on incident T2DM in two prospective population-based cohort studies from Iran, where white rice is one of the main staple.Methods: We used follow-up data from 9,182 participants from Golestan Cohort Study (GCS, 2004-2007, conducted mainly in rural areas) and 2,173 from Tehran Lipid and Glucose Study (TLGS, 2004-2006) who did not have T2DM and other chronic diseases at baseline. Diet was assessed using validated food frequency questionnaires. Multivariable logistic regression models were used to estimate adjusted odds ratios (ORs) for incident T2DM.Results: We documented 902 new cases of T2DM in GCS and 81 in TLGS. Age-standardized cumulative incidence of T2DM was 9.9% in Golestan and 8.0% in Tehran. Daily white rice intake was significantly higher among residents of Tehran compared to Golestan (median daily intake: 250 vs. 120 grams; P-value < 0.001). After adjustment for potential confounders, there was no significant association between daily white rice intake and incident T2DM in GCS. In TLGS, the adjusted OR (95% confidence interval (CI)) was 2.1 (1.1, 3.9) comparing participants with daily white rice intake of >250 grams/day to those with <250.Conclusions: We observed an increased lieklihood of T2DM associated with high white rice intake among residents of Tehran and no association in Golestan. Our findings, if further supported by other studies, have important public health implications especially for countries where white rice is a major staple and diabetes is increasing rapidly incidence is high. Further research is needed to investigate lack of an association between lower levels of white rice intake and T2DM. [ABSTRACT FROM AUTHOR]

Abnormal alanine aminotransferase level (ALT) levels might be associated with type 2 diabetes, but whether higher ALT levels within the normal range predict the risk is unknown. Methods: We followed a community-based cohort of 3446 individuals who were ≥35 years old without diabetes and hepatitis B or C in southern Taiwan for 8 years (1997–2004) to study the risk for type 2 diabetes with different normal ALT levels. Results: Among the 337 incident diabetes cases, 16.0% were from those with ALT levels

Aims/hypothesis: The relevance of the OGTT in predicting type 2 diabetes is unclear. We assessed the performance of 14 OGTT glucose traits in type 2 diabetes prediction. Methods: We studied 2,603 and 2,386 Europeans from the Botnia study and Malmö Prevention Project (MPP) cohorts with baseline OGTT data. Over a follow-up period of 4.94 years and 23.5 years, 155 (5.95%) and 467 (19.57%) participants, respectively, developed type 2 diabetes. The main outcome was incident type 2 diabetes. Results: One-hour plasma glucose (1h-PG) was a fair/good predictor of incident type 2 diabetes in the Botnia study and MPP (AUC for receiver operating characteristic [AUC] 0.80 [0.77, 0.84] and 0.70 [0.68, 0.73]). 1h-PG alone outperformed the prediction model of multiple clinical risk factors (age, sex, BMI, family history of type 2 diabetes) in the Botnia study and MPP (AUC 0.75 [0.72, 0.79] and 0.67 [0.64, 0.70]). The same clinical risk factors added to 1h-PG modestly increased prediction for incident type 2 diabetes (Botnia, AUC 0.83 [0.80, 0.86]; MPP, AUC 0.74 [0.72, 0.77]). 1h-PG also outperformed HbA in predicting type 2 diabetes in the Botnia cohort. A 1h-PG value of 8.9 mmol/l and 8.4 mmol/l was the optimal cut-point for initial screening and selection of high-risk individuals in the Botnia study and MPP, respectively, and represented 30% and 37% of all participants in these cohorts. High-risk individuals had a substantially increased risk of incident type 2 diabetes (OR 8.0 [5.5, 11.6] and 3.8 [3.1, 4.7]) and captured 75% and 62% of all incident type 2 diabetes in the Botnia study and MPP. Conclusions/interpretation: 1h-PG is a valuable prediction tool for identifying adults at risk for future type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Recent evidence links the soluble urokinase plasminogen activator receptor (suPAR), a stable biomarker of systemic immune activation, to several chronic diseases, including type 2 diabetes. suPAR is also associated with adiposity and smoking. We hypothesised that this biomarker would be linked to incident type 2 diabetes in individuals with impaired glucose regulation and that this association would be modified by smoking and body weight status. Methods: The study included 1,933 participants with impaired glucose regulation, who were drawn from the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION) and for whom data on suPAR, BMI and smoking were available. Logistic regression analysis was used to estimate the odds for incident type 2 diabetes per twofold increase in suPAR levels. Interactions between both smoking and body weight status and suPAR were tested. Results: During a 3-year follow-up (599 incident diabetes cases), there was a 48% overall increase in the odds of developing type 2 diabetes per twofold increase in suPAR ( p = 0.006). This association was modified by body weight status in overweight, but not in obese individuals (OR 2.36, 95% CI 1.48, 3.76 in overweight group), and by smoking status (OR 2.05, 95% CI 1.20, 3.51 in non-smokers). After adjustment for other diabetes risk factors, the association between suPAR and type 2 diabetes was attenuated in the whole sample and among non-smokers, but remained robust among overweight participants. Conclusions/interpretation: suPAR may be a good novel biomarker for systemic sub-clinical inflammation and immune activation linked to incident type 2 diabetes risk in overweight individuals and non-smokers. The observed interactions with adiposity and smoking should be investigated further. [ABSTRACT FROM AUTHOR]

Background/Purpose: Abnormal alanine aminotransferase level (ALT) levels might be associated with type 2 diabetes, but whether higher ALT levels within the normal range predict the risk is unknown. Methods: We followed a community-based cohort of 3446 individuals who were ≥35 years old without diabetes and hepatitis B or C in southern Taiwan for 8 years (1997–2004) to study the risk for type 2 diabetes with different normal ALT levels. Results: Among the 337 incident diabetes cases, 16.0% were from those with ALT levels <10 IU/L, 44.5% with ALT levels 10–19 IU/L, 30.0% with ALT levels 20–39 IU/L, and only 9.5% with ALT levels ≥40 IU/L. A cumulative hazard function test showed that the higher the ALT levels, the greater the cumulative incidence rate of diabetes (p < 0.001, log-rank test). A multiple Cox proportional hazards analysis showed that increasing age, lower educational levels, higher body mass index levels (≥25 vs. <25), and higher ALT levels (vs. the reference group, ALT <10 IU/L), from hazard ratio (HR) = 1.8, for ALT = 10–19, HR = 3.7 for ALT = 20–39, to HR = 4.5 for ALT ≥40, were significant factors for developing diabetes (p < 0.001). The hazard ratios of higher ALT levels in the participants without alcohol consumption were similar to or higher than those in the total cohort. Conclusion: Higher ALT levels, even within the normal range, are strong predictors of type 2 diabetes independently of body mass index levels with a dose–response relationship. [Copyright &y& Elsevier]

Background: Studies since the early 1990s have shown that birth size can be a predictor of the development of Type 2 diabetes mellitus (T2DM). In the present study, we evaluated changes in the strength of associations between T2DM and birth size and maternal weight with age. Methods: In 1993–1994 ( t0), 509 men and women (mean age 46 years) who had been born in Holdsworth Memorial Hospital were screened for diabetes, with increased diabetes risk identified in those who were shorter at birth and those born to heavier mothers. Ten years later ( t10), the screening was repeated in 266 subjects who were non-diabetic at t0 (70% of survivors). Results: At t10, 56 new cases of diabetes were found. The incidence of diabetes decreased with increasing birth length (odds ratio (OR) = 0.90, 95% confidence interval (CI) 0.84–0.97/cm birth length; P = 0.006) after adjustment for sex, age, socioeconomic status, family history, and current body mass index. Overall, there were no significant differences in OR for the association between birth length and diabetes at t0 compared with t10, but limiting analysis to subjects with normal glucose tolerance at t0 resulted in a stronger association at t10 (OR = 0.71, 95% CI 0.58–0.87) than at t0 (OR = 0.95, 95% CI 0.86–1.05; P = 0.015 for the difference). There was a positive correlation between maternal weight and incident disease at t0 (OR = 1.08, 95% CI 1.03–1.14; P = 0.001), but not at t10 (OR = 0.98/kg, 95% CI 0.92–1.05; P = 0.6; P = 0.02 for the difference). Conclusions: Short birth length remains a risk factor for diabetes. Changes in the effects of birth length and maternal weight on diabetes risk with age may indicate different causal pathways. These findings require replication in studies with more accurate dating of the onset of diabetes. [ABSTRACT FROM AUTHOR]

Previous studies have shown an inverse association between soluble thrombomodulin (sTM) and incident CHD, but there is a lack of data on the association between sTM and type 2 diabetes. Since CHD and type 2 diabetes share many risk factors, the aim of this study was to assess whether elevated sTM levels are associated with a lower incidence of type 2 diabetes. A case–cohort study was performed in initially healthy middle-aged men and women based on data from the Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg (MONICA/KORA) studies conducted between 1984 and 1998. Levels of sTM were measured with an ELISA in serum samples from 138 men and 86 women who developed type 2 diabetes during follow-up (cases) and 534 men and 446 women who did not develop type 2 diabetes (non-cases). An inverse association was found between sTM and type 2 diabetes risk after multivariable adjustment for diabetes risk factors, including several other markers of inflammation and endothelial dysfunction. Markers of inflammation and endothelial dysfunction were particularly strong confounders of the observed association. In the fully adjusted model, a 1 SD increase in sTM was associated with a 27% decrease in the risk of type 2 diabetes (hazard ratio = 0.73, 95% CI 0.58–0.91) in the total study population. We did not observe significant risk differences between men and women. These data suggest that, in initially healthy middle-aged men and women, levels of sTM are inversely associated with the risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Rationale: Obstructive sleep apnea (OSA) is associated with cardiovascular disease and incident type 2 diabetes (T2DM). Seven OSA phenotypes, labeled on the basis of their most distinguishing polysomnographic features, have been shown to be differentially associated with incident cardiovascular disease. However, little is known about the relevance of polysomnographic phenotypes for the risk of T2DM. Objectives: To assess whether polysomnographic phenotypes are associated with incident T2DM and to compare the predictive value of baseline polysomnographic phenotypes with the Apnea-Hypopnea Index (AHI) for T2DM. Methods: The study included 840 individuals without baseline diabetes from a multisite observational U.S. veteran cohort who underwent OSA evaluation between 2000 and 2004, with follow-up through 2012. The primary outcome was incident T2DM, defined as no diagnosis at baseline and a new physician diagnosis confirmed by fasting blood glucose >126 mg/dL during follow-up. Relationships between the seven polysomnographic phenotypes (1. mild, 2. periodic limb movements of sleep [PLMS], 3. non-rapid eye movement and poor sleep, 4. rapid eye movement and hypoxia, 5. hypopnea and hypoxia, 6. arousal and poor sleep, and 7. combined severe) and incident T2DM were investigated using Cox proportional hazards regression and competing risk regression models with and without adjustment for baseline covariates. Likelihood ratio tests were conducted to compare the predictive value of the phenotypes with the AHI. Results: During a median follow-up period of 61 months, 122 (14.5%) patients developed incident T2DM. After adjustment for baseline sociodemographics, fasting blood glucose, body mass index, comorbidities, and behavioral risk factors, hazard ratios among persons with "hypopnea and hypoxia" and "PLMS" phenotypes as compared with persons with "mild" phenotype were 3.18 (95% confidence interval [CI], 1.53-6.61] and 2.26 (95% CI, 1.06-4.83) for incident T2DM, respectively. Mild OSA (5 ⩽ AHI < 15) (vs. no OSA) was directly associated with incident T2DM in both unadjusted and multivariable-adjusted regression models. The addition of polysomnographic phenotypes, but not AHI, to known T2DM risk factors greatly improved the predictive value of the computed prediction model. Conclusions: Polysomnographic phenotypes "hypopnea and hypoxia" and "PLMS" independently predict risk of T2DM among a predominantly male veteran population. Polysomnographic phenotypes improved T2DM risk prediction comared with the use of AHI.

Abstract: Objective: Leukocyte telomere length shortening has recently been associated with type 2 diabetes mellitus (T2D). Whether this observation was modulated by genetic variation within the telomere-pathway genes remains elusive. To date, no prospective epidemiological data on the relationship of telomere-pathway gene variation with T2D are available. Methods: The association between 150 tagging-SNPs (tSNPs) of 11 telomere-pathway genes (TERC, UCP1, TERT, POT1, TNKS, TERF1, TNKS2, TEP1, ACD, TERF2 and TERF2IP) and incident T2D was investigated in 22,715 Caucasian female participants of the prospective Women''s Genome Health Study. All were free of known cardiovascular disease, cancer and diabetes at baseline. During a 13-year follow-up period, 1445 participants developed an incident T2D. Multivariable Cox regression analysis was performed to investigate the relationship between genotypes and T2D risk assuming an additive genetic model. Haplotype block analysis was also performed. Results: A total of eleven tSNPs within TERF1, TNKS, TEP1, ACD, and TERF2 were associated with T2D risk (all p-uncorrected <0.050). Further investigation using the haplotype-block analysis again revealed an association of several prespecified haplotypes of TERF1, and TEP1 with T2D risk (all p-uncorrected <0.040). Conclusion: If corroborated in other prospective studies, the present findings suggest that genetic variation within the telomere-pathway gene loci examined may be useful predictor for T2D risk assessment. [Copyright &y& Elsevier]

Aim: To determine the pooled association between variations of prolactin serum levels within the physiological range and the risk of type 2 diabetes mellitus (T2D).Methods: Pubmed, Scopus, Web of Science, and grey literature were searched for studies investigating the association between variations of prolactin serum levels in the normal range and the risk of T2D in adults. The risk of prevalent and incident T2D was summarized as the odds ratio or relative risk according to the quartile of prolactin serum concentration, using random-effects meta-analysis.Results: Of 2,014 articles identified, 6 met the inclusion criteria. Data were pooled from cross-sectional studies including 6,670 subjects and longitudinal studies involving 13,203 subjects. Men with prolactin levels in the fourth quartile versus those in the first quartile had decreased risk of prevalent T2D (OR 0.52; 95%CI 0.35-077). The same association was seen in women (OR 0.46; 95%CI 0.30-0.73). Conversely, prolactin levels in the fourth versus first quartile were not associated with the risk of incident T2D in men (RR 1.21; 95%CI 0.79-1.87) or women (RR 0.77; 95%CI 0.48-1.22).Conclusion: Higher prolactin serum levels within the normal range were associated with reduced risk of prevalent but not incident T2D. Further studies are necessary to address whether this association is causal, but these findings raise the discussion regarding the optimal level of prolactin suppression in subjects undergoing therapy with dopaminergic agonists. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Glycaemic markers and fasting insulin are frequently measured outcomes of intervention studies. To extrapolate accurately the impact of interventions on the risk of diabetes incidence, we investigated the size and shape of the associations of fasting plasma glucose (FPG), 2 h post-load glucose (2hPG), HbA 1c , fasting insulin and HOMA-IR with incident type 2 diabetes mellitus., Methods: The study population included 1349 participants aged 50-75 years without diabetes at baseline (1989) from a population-based cohort in Hoorn, the Netherlands. Incident type 2 diabetes was defined by the WHO 2011 criteria or known diabetes at follow-up. Logistic regression models were used to determine the associations of the glycaemic markers, fasting insulin and HOMA-IR with incident type 2 diabetes. Restricted cubic spline logistic regressions were conducted to investigate the shape of the associations., Results: After a mean follow-up duration of 6.4 (SD 0.5) years, 152 participants developed diabetes (11.3%); the majority were screen detected by high FPG. In multivariate adjusted models, ORs (95% CI) for incident type 2 diabetes for the highest quintile in comparison with the lowest quintile were 9.0 (4.4, 18.5) for FPG, 6.1 (2.9, 12.7) for 2hPG, 3.8 (2.0, 7.2) for HbA 1c , 1.9 (0.9, 3.6) for fasting insulin and 2.8 (1.4, 5.6) for HOMA-IR. The associations of FPG and HbA 1c with incident diabetes were non-linear, rising more steeply at higher values., Conclusions/interpretation: FPG was most strongly associated with incident diabetes, followed by 2hPG, HbA 1c , HOMA-IR and fasting insulin. The strong association with FPG is probably because FPG is the most frequent marker for diabetes diagnosis. Non-linearity of associations between glycaemic markers and incident type 2 diabetes should be taken into account when estimating future risk of type 2 diabetes based on glycaemic markers.

Objective: Determine the incidence of major diabetes risk factors over time in patients prescribed chronic statin therapy., Methods: Retrospective observational chart review of adult patients without diabetes in primary care who initiated statin therapy between 2005 and 2010. Presence of diabetes risk factors were determined 1 year prior to statin initiation and continued up to a maximum of 7 years. Diabetes risk factors included impaired fasting glucose, body mass index (BMI) ≥30 kg/m(2), hemoglobin A1c >6% and metabolic syndrome. Descriptive statistics were used to describe the incidence of diabetes risk factors over time., Results: A total of 98 patients met study criteria; mean age was 57 ± 13 years, 43% were men and 71% self-identified as Caucasian/white. Mean baseline values were A1c of 5.97%, fasting glucose of 104 mg/dl and BMI of 28 kg/m(2). There were zero diabetes risk factors over time in 54% ± 7% of patients. The incidence over time of 1 risk factor was 25 ± 9%, 2 risk factors was 17 ± 5% and 3 risk factors was 3 ± 2%. A total of 12 patients were diagnosed with type 2 diabetes during the course of the study period., Conclusion: The incidence of diabetes risk factors did not change over time in an ambulatory adult population prescribed chronic statin therapy. Larger population studies assessing the incidence of and change in diabetes risk factors in patients on chronic statin therapy may help assess the association between statin therapy and presence of such risk factors.