Long-term trajectories of sleep duration are associated with incident diabetes in middle-to-older-aged Black and White Americans.

AIMS/HYPOTHESIS: Both short and long sleep durations have been linked to higher diabetes risk. However, sleep duration may vary over time, and there has been limited research focusing on individual sleep trajectories and diabetes risk. There are substantial racial disparities in both sleep health and diabetes risk in the USA. Thus, it is important to understand the role of suboptimal sleep patterns in diabetes risk in different racial groups. METHODS: We assessed long-term trajectories of sleep duration and incident diabetes in 22,285 Black adults (mean age ± SD, 51.1 ± 8.2 years; 64.8% women) and 13,737 White adults (mean age ± SD, 54.4 ± 9.0 years; 63.8% women) enrolled in the Southern Community Cohort Study. Nine sleep trajectories were derived based on self-reported sleep duration at baseline and after a mean of 5 years of follow-up: normal-normal (reference), short-normal, normal-short, short-short, long-normal, normal-long, long-long, long-short and short-long. Diabetes was reported using a validated questionnaire. Multivariable-adjusted logistic regression was used to determine relationships between sleep trajectories and incident diabetes. RESULTS: When compared with the normal-normal trajectory, suboptimal sleep trajectories were associated with higher likelihoods of developing diabetes (OR; 95% CI: short-normal 1.19; 1.09, 1.31; normal-short 1.14; 1.02, 1.27; short-short 1.17; 1.07, 1.28; long-normal 1.13; 0.98, 1.30; normal-long 1.16; 1.00, 1.34; long-long 1.23; 1.02, 1.48; long-short 1.45; 1.19, 1.77; short-long 1.51; 1.28, 1.77). Stratified analyses by race and socioeconomic status (i.e. education and household income) showed that most suboptimal sleep trajectories were consistently associated with incident diabetes in all sociodemographic subgroups. We also noted potential interaction with race and education for several sleep trajectories (i.e. short-long and normal-short with race; long-long and short-short with education). CONCLUSIONS/INTERPRETATION: Adults with suboptimal sleep duration trajectories are more likely to develop incident diabetes. Future research is needed to study how sociodemographic factors modulate this relationship.

Very short sleep duration reveals a proteomic fingerprint that is selectively associated with incident diabetes mellitus but not with incident coronary heart disease: a cohort study.

BACKGROUND: The molecular pathways linking short and long sleep duration with incident diabetes mellitus (iDM) and incident coronary heart disease (iCHD) are not known. We aimed to identify circulating protein patterns associated with sleep duration and test their impact on incident cardiometabolic disease. METHODS: We assessed sleep duration and measured 78 plasma proteins among 3336 participants aged 46-68 years, free from DM and CHD at baseline, and identified cases of iDM and iCHD using national registers. Incident events occurring in the first 3 years of follow-up were excluded from analyses. Tenfold cross-fit partialing-out lasso logistic regression adjusted for age and sex was used to identify proteins that significantly predicted sleep duration quintiles when compared with the referent quintile 3 (Q3). Predictive proteins were weighted and combined into proteomic scores (PS) for sleep duration Q1, Q2, Q4, and Q5. Combinations of PS were included in a linear regression model to identify the best predictors of habitual sleep duration. Cox proportional hazards regression models with sleep duration quintiles and sleep-predictive PS as the main exposures were related to iDM and iCHD after adjustment for known covariates. RESULTS: Sixteen unique proteomic markers, predominantly reflecting inflammation and apoptosis, predicted sleep duration quintiles. The combination of PSQ1 and PSQ5 best predicted sleep duration. Mean follow-up times for iDM (n = 522) and iCHD (n = 411) were 21.8 and 22.4 years, respectively. Compared with sleep duration Q3, all sleep duration quintiles were positively and significantly associated with iDM. Only sleep duration Q1 was positively and significantly associated with iCHD. Inclusion of PSQ1 and PSQ5 abrogated the association between sleep duration Q1 and iDM. Moreover, PSQ1 was significantly associated with iDM (HR = 1.27, 95% CI: 1.06-1.53). PSQ1 and PSQ5 were not associated with iCHD and did not markedly attenuate the association between sleep duration Q1 with iCHD. CONCLUSIONS: We here identify plasma proteomic fingerprints of sleep duration and suggest that PSQ1 could explain the association between very short sleep duration and incident DM.

Impact of migration on diabetes burden: audit in the metropolitan area of Bologna, Italy.

PURPOSE: To investigate the impact of diabetes in immigrants on the Italian healthcare system, as well as their compliance with standard protocols of control and treatment. METHODS: The prevalence of immigrants with diabetes living in the metropolitan area of Bologna (about 1 million inhabitants) in 2019 was investigated using a database containing all subjects in active follow-up for diabetes, based on antidiabetic drug use, disease-specific copayment exemption, ICD-9 codes, continuous care in diabetes units. Country of origin was derived from fiscal code. RESULTS: The overall prevalence of diabetes (n = 53,941; 51.8% males, median age 64) was 6.1% in both Italy-born and immigrant cohorts. Immigrant prevalence was 12.4%, moderately higher than that observed in the total population (12.2%). Diabetes risk was increased in the whole immigrant cohort (odds ratio (OR) 1.74; 95% Confidence Interval (CI) 1.69-1.79). Among cases with incident diabetes, the proportion of immigrants (median age, 49 vs. 65 in Italy-born individuals) increased progressively from 11.7% to 26.5% from 2011 to 2019 (males, 8.9-21.0%; females, 14.9-32.8%) in all age groups, particularly in young adults, but also in older subjects. Metabolic control was lower in immigrants, as was adherence to shared diagnostic and therapeutic protocols, without systematic differences in antidiabetic drug use, but much lower use of drugs for comorbid conditions. CONCLUSIONS: The population with diabetes in the metropolitan area of Bologna is rapidly changing. Quality improvement initiatives are needed to reduce the burden for the universalistic Italian health care system generated by the rapidly-growing high-risk immigrant population.

Does COVID-19 Infection Increase the Risk of Diabetes? Current Evidence.

PURPOSE OF REVIEW: Multiple studies report an increased incidence of diabetes following SARS-CoV-2 infection. Given the potential increased global burden of diabetes, understanding the effect of SARS-CoV-2 in the epidemiology of diabetes is important. Our aim was to review the evidence pertaining to the risk of incident diabetes after COVID-19 infection. RECENT FINDINGS: Incident diabetes risk increased by approximately 60% compared to patients without SARS-CoV-2 infection. Risk also increased compared to non-COVID-19 respiratory infections, suggesting SARS-CoV-2-mediated mechanisms rather than general morbidity after respiratory illness. Evidence is mixed regarding the association between SARS-CoV-2 infection and T1D. SARS-CoV-2 infection is associated with an elevated risk of T2D, but it is unclear whether the incident diabetes is persistent over time or differs in severity over time. SARS-CoV-2 infection is associated with an increased risk of incident diabetes. Future studies should evaluate vaccination, viral variant, and patient- and treatment-related factors that influence risk.

Nomogram model and risk score to predict 5-year risk of progression from prediabetes to diabetes in Chinese adults: Development and validation of a novel model.

AIM: To develop a personalized nomogram and risk score to predict the 5-year risk of diabetes among Chinese adults with prediabetes. METHODS: There were 26 018 participants with prediabetes at baseline in this retrospective cohort study. We randomly stratified participants into two cohorts for training (n = 12 947) and validation (n = 13 071). The least absolute shrinkage and selection operator (LASSO) model was applied to select the most significant variables among candidate variables. And we further established a stepwise Cox proportional hazards model to screen out the risk factors based on the predictors chosen by the LASSO model. We presented the model with a nomogram. The model's discrimination, clinical use and calibration were assessed using the area under the receiver operating characteristic (ROC) curve, decision curve and calibration analysis. The associated risk factors were also categorized according to clinical cut-points or tertials to create the diabetes risk score model. Based on the total score, we divided it into four risk categories: low, middle, high and extremely high. We also evaluated our diabetes risk score model's performance. RESULTS: We developed a simple nomogram and risk score that predicts the risk of prediabetes by using the variables age, triglyceride, fasting blood glucose, body mass index, alanine aminotransferase, high-density lipoprotein cholesterol and family history of diabetes. The area under the ROC curve of the nomogram was 0.8146 (95% CI 0.8035-0.8258) and 0.8147 (95% CI 0.8035-0.8259) for the training and validation cohort, respectively. The calibration curve showed a perfect fit between predicted and observed diabetes risks at 5 years. Decision curve analysis presented the clinical use of the nomogram, and there was a wide range of alternative threshold probability spectrums. A total risk score of 0 to 2.5, 3 to 4.5, 5 to 7.5 and 8 to 13.5 is associated with low, middle, high and extremely high diabetes risk status, respectively. CONCLUSIONS: We developed and validated a personalized prediction nomogram and risk score for 5-year diabetes risk among Chinese adults with prediabetes, identifying individuals at a high risk of developing diabetes. Doctors and other healthcare professionals can easily and quickly use our diabetes score model to assess the diabetes risk status in patients with prediabetes. In addition, the nomogram model and risk score we developed need to be validated in a prospective cohort study.

The association between fatty liver index and onset of diabetes: secondary analysis of a population-based cohort study.

BACKGROUND: According to research, the fatty liver index (FLI) is associated with diabetes. However, few studies have been conducted to investigate the relationship between FLI and diabetes risk from various perspectives. This study comprehensively investigated the relationship between FLI and incident diabetes in a large Japanese population. METHODS: This retrospective cohort study included 14,280 participants from Murakami Memorial Hospital in Japan from 2004 to 2015. The independent and dependent variables are FLI and risk of type 2 diabetes mellitus (T2DM), respectively. To examine the link between FLI and incident T2DM, Cox proportional-hazards regression was employed. In addition, we performed a number of sensitivity studies to guarantee the validity of the results. Moreover, we conducted subgroup analyses. RESULTS: After adjusting covariates, the results showed that FLI was positively associated with the risk of T2DM (HR = 1.019, 95%CI: 1.012, 1.025). Additionally, the sensitivity analysis showed how reliable the outcomes were. And a stronger association between FLI and incident T2DM was observed in the regular exercisers (HR = 1.036, 95%CI: 1.019-1.053, P < 0.0001) and the population without ethanol consumption (HR = 1.028, 95%CI: 1.017-1.039, P < 0.0001). Besides, receiver operating characteristic (ROC) curve analysis showed that FLI was better than waist circumference, triglycerides, body mass index, and gamma-glutamyl transferase in predicting incident T2DM. CONCLUSION: FLI is positively associated with incident T2DM.

Associations of HIV and Depression with Incident Diabetes Mellitus: Veterans Aging Cohort Study.

BACKGROUND: Persons with HIV (PWH) are at increasingly higher risk for metabolic complications, including diabetes mellitus (DM). Additionally, depression is highly prevalent among PWH and has been associated with increased risk for DM in the general population. However, the association of HIV and depression with incident DM has not been well established. METHODS: Using the Veterans Aging Cohort Study (VACS), we selected adults with and without HIV who did not have DM at baseline. Prevalent depression was defined as having a Patient Health Questionnaire-9 (PHQ-9) score of ≥10. Incident DM was identified using validated Kelly's criteria. Basic clinical and demographic characteristics were collected, and cox proportional hazards regression models were run to test the association between depression and incident DM stratified by HIV serostatus. RESULTS: A total of 5,722 participants were analyzed, 2,886 (53%) had HIV and 1,124 (20%) had depression at baseline. 1,235 (22%) participants developed incident DM during follow-up, with 26% of HIV-negative participants developing DM compared to 17% of participants with HIV. Depression was significantly associated with increased risk of incident DM among HIV-negative participants (adjusted HR [aHR] = 1.31; p-value 0.003), but not among participants with HIV (aHR 1.09; p-value 0.44). However, among participants with HIV with baseline viral load < 500 copies/mL, we noted a stronger association between depression and incident DM. CONCLUSIONS: Incident DM in the VACS cohort is significantly higher for HIV-negative participants compared to veterans with HIV. A significant association between depression and incident DM was noted among HIV-negative participants but not among those with HIV.

Non-linear relationship between high-density lipoprotein cholesterol and incident diabetes mellitus: a secondary retrospective analysis based on a Japanese cohort study.

BACKGROUND AND OBJECTIVE: High-density lipoprotein cholesterol (HDL-C) may be directly involved in glucose metabolism by enhancing insulin sensitivity and insulin secretion. This current study aimed to explore the association between HDL-C and the risk of diabetes mellitus (DM) in Japanese population. METHODS: This retrospective cohort study was based on a publicly available DRYAD dataset. We enrolled 15,388 Japanese participants who received medical examinations from 2004 to 2015 at Murakami Memorial Hospital. Our study selected HDL-C at baseline and incident DM during follow-up as the target independent variable and the dependent variable, respectively. Cox proportional-hazards regression was used to investigate the association between HDL-C and DM, generalized additive models to identify non-linear relationships. RESULTS: After adjusting for the demographic and clinical covariates, the result showed low HDL-C levels were associated with increased risk for diabetes (HR = 0.54, 95%CI (0.35, 0.82)). The results remained robust in a series of sensitive analysis. A non-linear relationship was detected between HDL-C and incident DM with an inflection point of HDL-C at 1.72 mmol/L (Log-likelihood ratio test P = 0.005). Subgroup analysis showed that a stronger association could be found in ex-smokers and current-smokers. The same trend was also seen in the community with hypertension (P for interaction = 0.010, HR = 1.324). CONCLUSION: This study demonstrates a negative and non-linear relationship between HDL-C and diabetes in the Japanese population. There is a threshold effect between HDL-C and diabetes. When HDL-C is lower than 1.72 mmol/L, the decreased HDL-C levels were associated with an increased risk for diabetes.

Prognostic value of exercise capacity in incident diabetes: a country with high prevalence of diabetes.

BACKGROUND: Diabetes Mellitus (DM) is a fast-growing health problem that imposes an enormous economic burden. Several studies demonstrated the association between physical inactivity and predicting the incidence of diabetes. However, these prediction models have limited validation locally. Therefore, we aim to explore the predictive value of exercise capacity in the incidence of diabetes within a high diabetes prevalence population. METHODOLOGY: A retrospective cohort study including consecutive patients free of diabetes who underwent clinically indicated treadmill stress testing. Diabetic patients at baseline or patients younger than 18 years of age were excluded. Incident diabetes was defined as an established clinical diagnosis post-exercise testing date. The predictive value of exercise capacity was examined using Harrell's c-index, net reclassification index (NRI), and integrated discrimination index (IDI). RESULTS: A total of 8,722 participants (mean age 46 ± 12 years, 66.3% were men) were free of diabetes at baseline. Over a median follow-up period of 5.24 (2.17-8.78) years, there were 2,280 (≈ 26%) new cases of diabetes. In a multivariate model adjusted for conventional risk factors, we found a 12% reduction in the risk of incident diabetes for each METs achieved (HR, 0.9; 95% CI, 0.88-0.92; P < 0.001). Using Cox regression, exercise capacity improved the prediction ability beyond the conventional risk factors (AUC = 0.62 to 0.66 and c-index = 0.62 to 0.68). CONCLUSION: Exercise capacity improved the overall predictability of diabetes. Patients with reduced exercise capacity are at high risk for developing incidence diabetes. Improvement of both physical activity and functional capacity represents a preventive measure for the general population.

Perfluorinated compounds in adults and their association with fasting glucose and incident diabetes: a prospective cohort study.

BACKGROUND: The endocrine disruption of perfluorinated compounds is an emerging issue. We aimed to examine the association of serum perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels with incident diabetes and fasting serum glucose concentration. METHODS: This prospective cohort study was based on an urban-based cohort subpopulation from the Korean Genome and Epidemiology Study. Serum samples (600 µL) were received from 100 participants in the normoglycemic baseline survey (2004-2013), and concentrations of PFOA and PFOS were measured using mass spectrometry. The incidence of diabetes was tracked in the follow-up survey (2012-2016). RESULTS: The mean age was 56.4 years (men, 59%). The median serum PFOA and PFOS concentrations were 4.29 ng/mL and 9.44 ng/mL, respectively. PFOA and PFOS concentrations differed according to age, sex, and residential area. After 60 months, 23 patients had diabetes. Log-transformed PFOA (lnPFOA) and log-transformed PFOS (lnPFOS) were significantly higher in those who transitioned to diabetes than in those who did not (both p < 0.05). After multivariate adjustment, lnPFOA (coefficient = 6.98, 95% CI -0.04-14, p = 0.054) and lnPFOS (coefficient = 7.06, 95% CI -0.96-15.08, p = 0.088) predicted increased fasting glucose without statistical significance. In addition, lnPFOA, but not lnPFOS, significantly predicted incident diabetes (HR = 3.98, 95% CI 1.42-11.1, p < 0.01). CONCLUSION: Exposure to PFOA and PFOS may have a potential dysglycemic effect. In particular, exposure to PFOA increased the risk of diabetes. Further research with larger sample size is warranted.

Association of hypertension and incident diabetes in Chinese adults: a retrospective cohort study using propensity-score matching.

BACKGROUND: Reliable quantification of the relationship between hypertension and diabetes risk is limited, especially among Chinese people. We aimed to investigate the association between hypertension and the risk of diabetes in a large cohort of the Chinese population. METHODS: This was a retrospective propensity score-matched cohort study among 211,809 Chinese adults without diabetes at baseline between 2010 and 2016. The target independent and dependent variable were hypertension at baseline and incident diabetes during follow-up respectively. The propensity score matching using a non-parsimonious multivariable logistic regression was conducted to balance the confounders between 28,711 hypertensive patients and 28,711 non-hypertensive participants. The doubly robust estimation method was used to investigate the association between hypertension and diabetes. RESULTS: In the propensity-score matching cohort, diabetes risk increased by 11.0% among hypertensive patients (HR = 1.110, 95% confidence interval (CI): 1.031-1.195, P = 0.00539). And diabetes risk dropped to 8.3% among hypertensive subjects after adjusting for the propensity score (HR = 1.083, 95%CI: 1.006-1.166, P = 0.03367). Compared to non-hypertensive participants with low propensity score, the risk of incident diabetes increased by 2.646 times among hypertensive patients with high propensity score (HR = 3.646, 95%CI: 2.635-5.045, P < 0.0001). CONCLUSION: Hypertension was associated with an 11.0% increase in the risk of developing diabetes in Chinese adults. And the figure dropped to 8.3% after adjusting the propensity score. Additionally, compared to non-hypertensive participants with low propensity scores, the risk of incident diabetes increased by 2.646 times among hypertensive patients with high propensity scores.

Should leisure-time sedentary behavior be replaced with sleep or physical activity for prevention of diabetes?

The aim was to examine the effects of replacing self-reported leisure-time sedentary behavior with sleep, light-to-moderate physical activity, or vigorous physical activity on incident diabetes among Danish adults using isotemporal substitution modeling. Participants ≥25 years from the Danish Capital Region Health Survey 2007 (N = 69 800, response rate 52.3%), 2010 (N = 95 150, response rate 52.3%), and 2013 (N = 95 150, response rate 43.5%) were included. Information on daily sleep duration, leisure-time sedentary behavior, and movement behaviors was collected by questionnaire. Information on incident diabetes was obtained from National registers. Analyses included Cox proportional hazards regression models and isotemporal substitution analyses, with time (in years) from baseline to incident diabetes or censoring December 31, 2017. Potential confounders, sex, age, BMI, ethnicity, education, smoking, inflammatory joint disease, perceived stress, physical and mental component scale and work status, were included. Out of N = 87 339 in the final study sample, n = 3007 had incident diabetes during a mean follow-up time of 7.4 years. Adults with incident diabetes included more men, higher mean age, and higher BMI, compared to respondents without incident diabetes. Theoretically substituting 30 minutes of leisure-time sedentary behavior with light-to-moderate PA (HR: 0.96; 95% CI: 0.94; 0.98) or with vigorous PA (HR: 0.82; 95% CI: 0.72; 0.94) decreased the risk of incident diabetes. We found no change in incident diabetes risk of substituting sedentary time with sleep (HR: 1.00; 95% CI: 0.97; 1.02). Substituting 30 minutes per day of leisure-time sedentary behavior with light-to-moderate or vigorous PA may significantly reduce the risk of incident diabetes among adults.

Autoimmunity plays a role in the onset of diabetes after 40 years of age.

AIMS/HYPOTHESIS: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. METHODS: GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. RESULTS: GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. CONCLUSIONS/INTERPRETATION: Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.

Association of Triglyceride to high-density lipoprotein cholesterol ratio and incident of diabetes mellitus: a secondary retrospective analysis based on a Chinese cohort study.

BACKGROUND: Previous studies have revealed that triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) is one of major risk factors of insulin resistance and diabetes. However, study on the association between TG/HDL-C and diabetes mellitus (DM) risk is limited, especially in Chinese people. This study was undertaken to investigate the relationship between TG/HDL-C and incident of diabetes in a large cohort in Chinese population. METHODS: The present study was a retrospective cohort study. A total of 114,787 adults from Rich Healthcare Group in China, which includes all medical records for participants who received a health check from 2010 to 2016. The target independent variable and the dependent variable were triglyceride to high-density lipoprotein cholesterol ratio measured at baseline and incident of diabetes mellitus appeared during follow-up respectively. Covariates involved in this study included age, gender, body mass index, diastolic blood pressure, systolic blood pressure, fasting plasma glucose, total cholesterol, low density lipoprotein cholesterol, serum creatinine, smoking and drinking status and family history of diabetes. Cox proportional-hazards regression was used to investigate the association of TG/HDL-C and diabetes. Generalized additive models was used to identify non-linear relationships. Additionally, we also performed a subgroup analysis. It was stated that the data had been uploaded to the DATADRYAD website. RESULT: After adjusting age, gender, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low density lipoprotein cholesterol, serum creatinine, smoking and drinking status and family history of diabetes, result showed TG/HDL-C was positively associated with incident of diabetes mellitus (HR = 1.159, 95%CI (1.104, 1.215)). A non-linear relationship was detected between TG/HDL-C and incident of diabetes, which had an inflection point of TG/HDL-C was 1.186. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.718(1.433,2.060) and 1.049(0.981,1.120), respectively. Subgroup analysis showed, the stronger association can be found in the population with fasting plasma glucose (FPG) < 6.1 mmol/L (P for interaction< 0.0001; HR = 1.296 with FPG < 6.1 mmol/L vs HR = 1.051 with FPG ≥ 6.1 mmol/L).The same trend was also seen in the population with body mass index (BMI)(≥18.5, < 24 kg/m2) (P for interaction = 0.010,HR = 1.324) and family history without diabetes(P for interaction = 0.025, HR = 1.170). CONCLUSION: TG/HDL-C is positively associated with diabetes risk. The relationship between TG/HDL-C and incident of diabetes is also non-linear. TG/HDL-C was strong positively related to incident of diabetes when TG/HDL-C is less than 1.186.

Association between triglyceride-glucose index and risk of incident diabetes: a secondary analysis based on a Chinese cohort study : TyG index and incident diabetes.

BACKGROUND: Recent studies have suggested the triglyceride-glucose index (TyG index) may serve as a suitable substitute for insulin resistance. However, evidence for the relationship between TyG index and risk of diabetes remains limited. This study sought to explore the association of baseline TyG index with risk of developing diabetes in Chinese adults. METHODS: This retrospective cohort study was conducted using data from the health screening program in China. A total of 201,298 non-diabetic individuals were included. TyG index was calculated as Ln [fasting plasma glucose (mg/dL) × fasting triglyceride level (mg/dL) / 2]. Diabetes was defined as fasting plasma glucose ≥126 mg/dL and/or self-reported diabetes. Cox proportion-hazard model was employed to evaluate the independent impact of baseline TyG index on future diabetes risk. Sensitivity and subgroup analyses were implemented to verify the reliability of results. Notably, data were downloaded from the DATADRYAD website, and used only for secondary analyses. RESULTS: During an average follow-up of 3.12 years, among 201,298 individuals aged ≥20 years, 3389 subjects developed diabetes. After adjusting for potential confounders, elevated TyG index were independently correlated with greater risk of incident diabetes (hazard ratio (HR), 3.34; 95% confidence interval (CI), 3.11-3.60). Compared with the lowest quartile (Q1), increasing TyG index (Q2, Q3, and Q4) was related to increased HR estimates of incident diabetes [HR (95% CI), 1.83 (1.49-2.26); 3.29 (2.70-4.01), and 6.26 (5.15-7.60), respectively]. Moreover, a nonlinear relationship was observed between TyG index and risk of diabetes and the slope of the curve increased accompanying the rise of TyG index. Subgroup analysis revealed the positive association was stronger among subjects with age < 40 years, body mass index ≥18.5 kg/m2 and < 24 kg/m2, or systolic blood pressure < 140 mmHg, or in females. CONCLUSIONS: Elevated TyG index is independently correlated with increased risk of incident diabetes in Chinese adults, indicating it may represent a reliable predictor of diabetes in high-risk populations.

Association and risk factors of chronic kidney disease and incident diabetes: a nationwide population-based cohort study.

AIMS/HYPOTHESIS: Chronic kidney disease (CKD) is a known complication of diabetes mellitus, and insulin resistance is a well-known complication of CKD. However, there is no consensus in the published data on the association of CKD with incident diabetes. METHODS: A total of 15,403 people with CKD were identified from the Taiwan National Health Insurance Research Database to determine their risk of incident diabetes compared with that of 15,403 matched individuals without CKD. Fine and Gray regression models using death as a competing risk were performed to calculate adjusted HRs and 95% CIs. Risk factors for incident diabetes in people with CKD were also determined. RESULTS: The CKD cohort had a higher incidence rate of diabetes compared with the non-CKD cohort (11.23/1000 person-years vs 8.93/1000 person-years). In the fully adjusted model, CKD was a significant and independent predictor of incident diabetes (adjusted HR 1.204; 95% CI 1.11, 1.31). The influence of CKD on incident diabetes showed consistent results in three levels of sensitivity analysis. In the CKD cohort, the significant risk factors for incident diabetes included increased age, geographical location, hypertension, hyperlipidaemia and gout. Of these, hypertension was associated with the highest risk of developing incident diabetes (adjusted HR 1.682; 95% CI 1.47, 1.93). CONCLUSIONS/INTERPRETATION: People with CKD were at higher risk of developing incident diabetes. People with CKD and hypertension, hyperlipidaemia, increased age or gout and who lived in certain geographical regions of Taiwan were more likely to develop diabetes as a complication compared with people without those characteristics.

Association of C2, a derivative of the radial artery pressure waveform, with new onset of type 2 diabetes mellitus: the MESA study.

BACKGROUND: Although microvascular dysfunction is known to result from diabetes, it might also lead to diabetes. Lower values of C2, a derivative of the radial artery pressure waveform, indicate microvascular dysfunction and predict hypertension and cardiovascular disease (CVD). We studied the association of C2 with incident diabetes in subjects free of overt CVD. METHODS: Among multi-ethnic participants (n = 5214), aged 45-84 years with no diabetes, C2 was derived from the radial artery pressure waveform. Incident diabetes (N = 651) was diagnosed as new fasting glucose ≥ 126 mg/dL or antidiabetic medicine over ~ 10 years. The relative incidence density (RID) for incident diabetes per standard deviation (SD) of C2 was studied during ~ 10 years follow-up using four levels of adjustment. RESULTS: Mean C2 at baseline was 4.58 ± 2.85 mL/mmHg × 100. The RID for incident diabetes per SD of C2 was 0.90 (95% CI 0.82-0.99, P = 0.03). After adjustment for demographics plus body size, the corresponding RID was 0.81 (95% CI 0.73-0.89, P < 0.0001); body mass index (BMI) was the dominant covariate here. After adjustment for demographics plus cardiovascular risk factors, the RID was 0.98 (95% CI 0.89, 1.07, P = 0.63). After adjustment for all the parameters in the previous models, the RID was 0.87 (95% CI 0.78, 0.96, P = 0.006). CONCLUSIONS: In a multi-ethnic sample free of overt CVD and diabetes at baseline, C2 predicted incident diabetes after adjustment for demographics, BMI and CVD risk factors. Differences in arterial blood pressure wave morphology may indicate a long-term risk trajectory for diabetes, independently of body size and the classical risk factors.

Sugar-Sweetened Soda Consumption Increases Diabetes Risk Among Mexican Women.

BACKGROUND: Epidemiological evidence supports an association between sugar-sweetened soda consumption and diabetes. However, evidence regarding this association is limited in countries that have recently undergone a nutritional transition. OBJECTIVE: We estimated the association between sugar-sweetened soda consumption and incident diabetes. We also determined if the association between sugar-sweetened soda and diabetes differs as a result of early life factors and potential genetic susceptibility. METHODS: We used data from the Mexican Teachers' Cohort including 72,667 women aged ≥25 y, free of diabetes, cardiovascular disease, and cancer at baseline. We assessed sugar-sweetened soda consumption using a validated food frequency questionnaire (FFQ) at baseline. Diabetes was self-reported. We used Cox proportional hazard regression models to estimate the association between quintiles of sugar-sweetend soda and diabetes. We also estimated the associaiton by increasing one serving per day (355 mL) of sugar-sweetened soda. We conducted prespecified subgroup analysis by potential effect modifiers, namely markers of energy balance of early life factors, family history of diabetes, and Amerindian admixture. RESULTS: During a median follow-up of 2.16 y (IQR 0.75-4.50) we identified 3,155 incident cases of diabetes. The median consumption of sugar-sweetened soda was 1.17 servings per day (IQR 0.47- 4.00). In multivariable analyses, comparing extreme quintiles showed that higher sugar-sweetened soda consumption was associated with diabetes incidence (HR = 1.32; 95% CI: 1.17, 1.49), and each additional serving per day of sugar-sweetened soda was associated with an increase of 27% in diabetes incidence (HR = 1.27; 95% CI: 1.16, 1.38). The soda-diabetes association was stronger among women who experienced intrauterine and childhood over-nutrition (high birth weight, no short stature, higher adiposity in premenarche, and higher adiposity at age 18-20 y old). CONCLUSION: Sugar-sweetened soda consumption is associated with an increased risk of diabetes among Mexican women in a magnitude similar to that reported in other populations. The stronger association among individuals with markers of early life over-nutrition reinforce the need for early life interventions.

Diabetogenic Action of Statins: Mechanisms.

PURPOSE OF REVIEW: Observational studies and meta-analyses of randomized clinical trials data have revealed a 10-12% increased risk of new-onset diabetes (NOD) associated with statin therapy; the risk is increased with intensive treatment regimens and in people with features of the metabolic syndrome or prediabetes. The purpose of this review is to provide an updated summary of what is known about the potential mechanisms for the diabetogenic effect of statins. RECENT FINDINGS: Hydroxyl methyl glutaryl coenzyme A reductase (HMGCoAR) is the target of statin therapy and the activity of this key enzyme in cholesterol synthesis is reduced by statins in a partial and reversible way. Mendelian randomization studies suggest that the effect of statins on glucose homeostasis reflect reduced activity of HMGCoAR. In vitro and in vivo data indicate that statins reduce synthesis of mevalonate pathway products and increase cholesterol loading, leading to impaired ß-cell function and decreased insulin sensitivity and insulin release. While this effect has been thought to be a drug class effect, recent insights suggest that pravastatin and pitavastatin could exhibit neutral effects on glycaemic parameters in patients with and without diabetes mellitus. The mechanisms by which statins might lead to the development of NOD are unclear. The inhibition of HMGCoAR activity by statins appears to be a key mechanism. It is difficult to offer a comprehensive view regarding the diabetogenic effect of statins because our understanding of the most widely recognized potential mechanisms, i.e. underlying statin-induced reduction of insulin sensitivity and/or insulin secretion, is still far from complete. The existence of this dual mechanism is supported by the results of a study in a large group of non-diabetic men, showing that a 46% higher risk of NOD in statin users compared to non-users was accompanied by a significant 12% reduction in insulin secretion and a 24.3% increase in insulin resistance. Although statin therapy is associated with a modest increase in the risk of NOD (about one per thousand patient-years), patients should be reassured that the benefits of statins in preventing cardiovascular disease (CVD) events far outweigh the potential risk from elevation in plasma glucose.

The impact of hip and knee osteoarthritis on the subsequent risk of incident diabetes: a population-based cohort study.

AIMS/HYPOTHESIS: This study examined the relationship between hip/knee osteoarthritis and incident diabetes. We hypothesised that hip/knee osteoarthritis would be independently related to an increased risk of incident diabetes and that this relationship would be due, at least in part, to walking difficulty. We also hypothesised a stronger relationship with incident diabetes for knee than hip osteoarthritis because of the higher prevalence in the former of obesity/the metabolic syndrome. METHODS: A population cohort aged ≥55 years recruited from 1996 to 1998 was followed through provincial health administrative data to 2014. Participants with baseline diabetes were excluded. Hip/knee osteoarthritis was defined as swelling, pain or stiffness in any joint lasting 6 weeks in the past 3 months and indication on a joint homunculus that a hip/knee was 'troublesome'. Walking limitation was defined as self-reported difficulty standing or walking in the last 3 months (yes/no). Using Cox regressions, we examined the relationship of baseline hip/knee osteoarthritis with incident diabetes as defined from health administrative data, controlling for age, sex, BMI, income, prior hypertension, cardiovascular disease and primary care exposure. We tested whether the observed effect was mediated through walking limitation. RESULTS: In total, 16,362 participants were included: median age 68 years and 61% female. Of these, 1637 (10%) individuals met the criteria for hip osteoarthritis, 2431 (15%) for knee osteoarthritis and 3908 (24%) for walking limitation. Over a median follow-up of 13.5 years (interquartile range 7.3-17.8), 3539 individuals (22%) developed diabetes. Controlling for confounders, a significant relationship was observed between number of hip/knee joints with osteoarthritis and incident diabetes: HR for two vs no osteoarthritic hips 1.25 (95% CI 1.08, 1.44); HR for two vs no osteoarthritic knees 1.16 (95% CI 1.04, 1.29). From 37% to 46% of this relationship was explained by baseline walking limitation. CONCLUSIONS/INTERPRETATION: In a large population cohort aged ≥55 years who were free of diabetes at baseline, and controlling for confounders, the presence and burden of hip/knee osteoarthritis was a significant independent predictor of incident diabetes. This association was partially explained by walking limitation. Increased attention to osteoarthritis and osteoarthritis-related functional limitations has the potential to reduce diabetes risk.