Incident T2DM Research Articles

Protective Effect of High Adherence to Mediterranean Diet on the Risk of Incident Type-2 Diabetes in Subjects with MAFLD: The Di@bet.es Study.

Background/Objectives: Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) increases the risk of Type-2 Diabetes (T2DM). The Mediterranean diet (MD) has shown advantages in the management of MAFLD and preventing co-morbidities; however, its relationship with T2DM development in MAFLD has been less investigated. We aimed to evaluate the association of MD adherence with the risk of incident T2DM in the Spanish adult population with MAFLD and according to their weight gain at 7.5 years follow-up. Methods: A cohort of 714 participants (without weight increment: 377; with weight increment: 337) from the Di@bet.es cohort study with MAFLD and without T2DM at baseline were investigated. Anthropometric, sociodemographic, clinical data, and a survey on habits were recorded. OGTT and fasting blood biochemistry determinations were made. Baseline adherence to MD was estimated by the adapted 14-point MEDAS questionnaire and categorized as high and low adherence. Results: In total, 98 people developed T2DM at follow-up. The high adherence to MD was inversely associated with the development of T2DM in both the overall population (0.52 [0.31-0.87]) and subjects without weight gain at follow-up (0.35 [0.16-0.78]). Conclusions: Our results suggest the protective effect of high adherence to MD regarding the risk of T2DM in subjects with MAFLD, with this health benefit being more evident in men with the absence of weight gain. These results support the recommendations for MD use in these patients.

Risk of incident type 2 diabetes in male NAFLD and NAFLD-free smokers: a 7-year post-cessation study

BackgroundWe aimed to investigate the post-cessation T2DM risk in male NAFLD and NAFLD-free smokers in a 7-year cohort study.MethodsThe study population was male adults who underwent annual health checkups in a 7-year cohort study. Recent quitters were categorized into four groups based on their weight gain during follow-up: < 0 kg, 0–1.9 kg, 2.0–3.9 kg, and ≥ 4.0 kg. Cox proportional hazard models, adjusted for various variables, were used to estimate hazard ratios (HRs) for the association between post-cessation weight gain and incident T2DM in NAFLD and NAFLD-free individuals.ResultsAt baseline, we included 1,409 NAFLD and 5150 NAFLD-free individuals. During a total of 39,259 person-years of follow-up, 222 (15.8%) NAFLD patients and 621 (12.1%) NAFLD-free participants quit smoking, with the corresponding means (standard deviations) of post-cessation weight gain being 2.24 (3.26) kg and 1.15 (3.51) kg, respectively. Among NAFLD individuals, compared to current smokers, the fully adjusted HRs (95% CI) for incident T2DM were 0.41 (0.06–3.01), 2.39 (1.21–4.70), 4.48 (2.63–7.63), and 6.42 (3.68–11.23) for quitters with weight gains < 0 kg, 0.0–1.9 kg, 2.0–3.9 kg, and ≥ 4.0 kg, respectively. For NAFLD-free individuals, we only observed a significant association between post-cessation weight gain ≥ 4.0 kg and the risk of incident T2DM (P < 0.001). Further analysis revealed that the impact of post-cessation weight gain on T2DM risk was not affected by alcohol consumption or obesity status at baseline.ConclusionsMild post-cessation weight gain significantly increased the risk of T2DM in male NAFLD patients but not in male NAFLD-free individuals. Therefore, it is recommended that individuals with NAFLD manage their weight after quitting smoking.

Trends in the incidence of type 1 diabetes and type 2 diabetes in children and adolescents in North Rhine-Westphalia, Germany, from 2002 to 2022

AimsThe objective of this study was to assess overall and segmented trends in the incidence of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in children and adolescents younger than 20 years, from 2002 to 2022. MethodsThis study used registry data on physician-diagnosed T1DM or T2DM from primary and secondary sources, covering the German federal state of North Rhine-Westphalia with 18 million inhabitants. The ages at T1DM and T2DM onset ranged from 0 to 19 and 10–19 years, respectively. The main outcomes were direct age- and/or sex-standardized incidence rates per 100,000 person-years (PYs) and trends estimated as annual percentage changes (APCs), both with 95 % confidence intervals. The segmented trends for subperiods were based on joinpoint regression models. ResultsFrom 2002–2022, 17,470 and 819 persons had incident T1DM and T2DM, respectively. The total number of PYs was 73,743,982 for T1DM and 39,210,453 for T2DM, with a mean coverage rate of 98 % for T1DM and 90 % for T2DM. The standardized T1DM incidence increased from 17.6 [16.3;18.9} in 2002 to 33.2 [31.3;35.1] in 2022, with an APC of 2.7 % [2.3 %;3.1 %]. The standardized T2DM incidence increased from 1.3 [0.8;1.7] in 2002 to 2.8 [2.0;3.6] in 2022, with an APC of 6.4 % [4.9 %;8.0 %]. There were four different segmented trends for T1DM and T2DM, with the incidence peaking in 2021 and subsequently declining. ConclusionsThe incidence rates of T1DM and T2DM have increased over the past 20 years, with a wave-like pattern during the Covid-19 pandemic.

Weight change and risk of incident type 2 diabetes: short, medium and long-term follow-up in tehran lipid and glucose study

BackgroundDespite the high burden of obesity and Type 2 diabetes (T2DM) in the Middle East/West Asia region, the effect of weight change on the development of T2DM is poorly addressed. Therefore, we aimed to assess the impact of 3-year body weight change on incident of T2DM over 3-, 6-, and 9-year periods among Iranian adults.MethodsA total of 6930 participants (men = 2567) aged ≥ 20 years free of T2DM or cancer at baseline were included. Weight measurements were taken at baseline (2002–2005) and approximately 3 years later. Participants were categorized based on their weight change ratio into ≥ 5% loss, stable (± 5%), and ≥ 5% gain. Generalized estimating equations (GEE), adjusted with age, sex, education levels, baseline measurements of fasting plasma glucose, weight, waist circumference, triglycerides to high-density lipoprotein cholesterol ratio, family history of diabetes, current smoker, hypertension, and prevalent cardiovascular disease were applied to estimate the Odds ratios (ORs) and 95% confidence intervals (CIs) of weight change categories for incident T2DM, considering stable weight as a reference.ResultsDuring median follow-ups of 3-, 6-, and 9-year, 295, 505, and 748 cases of T2DM occurred, respectively. Weight gain of ≥ 5%, as compared to stable weight group (± 5%), was associated with increased T2DM risk, with ORs of 1.58 (95% CI 1.16–2.14), 1.76 (1.41–2.20), and 1.70 (1.40–2.05) for the 3-, 6-, and 9-year follow-ups, respectively, in multivariable analysis; corresponding values for weight loss ≥ 5% were 0.48 (0.29–0.80), 0.57 (0.40–0.81), and 0.51 (0.38–0.68), respectively. This association persisted even after adjusting for attained weight. Subgroup analysis showed consistent associations across age, gender, and body mass index categories.ConclusionWeight gain and loss of ≥ 5% were associated with increased and decreased risks of incident T2DM, respectively, regardless of attained weight. This association was consistent over various follow-up durations among the Iranian population as recommended by guidelines.

Hip fracture is associated with a reduced risk of type 2 diabetes: A retrospective cohort study

ObjectivesType 2 diabetes mellitus (T2DM) shares a complex relationship with bone metabolism and few studies investigated the effect of impaired bone health on the risk of T2DM. This study was conducted to investigate the association between hip fractures and the risk of incident T2DM. MethodsThis is a retrospective cohort study using data from the real-world hip fracture cohort. Hong Kong Chinese patients aged ≥ 65 years without T2DM who were admitted to public hospitals due to a fall between 2008 and 2015 were included in the study. Patients who sustained falls with and without hip fractures were matched by propensity score (PS) at a 1:1 ratio. Competing risk regression was used to evaluate the association between hip fracture and incident T2DM, with death being the competing event. ResultsA total of 23,314 hip fracture cases were matched to 23,314 controls. The median follow-up time was 5.09 years. The incidence rate of T2DM was 11.947 and 14.505 per 1000 person-years for the hip fracture and control group respectively. After accounting for the competing risk of death, the hip fracture group had a significantly lower risk of developing T2DM (HR: 0.771, 95% CI: 0.719–0.827). Similar results were observed in all subgroups after stratification by age and sex. ConclusionsHip fracture was found to be associated with a reduced risk of T2DM. These findings provide insight into the topic of bone and glucose metabolism and prompt further research in evaluating the role of bone health in the management of T2DM.

Long-term changes in frailty and incident type 2 diabetes: A prospective cohort study based on the UK Biobank.

To estimate the association between long-term changes in frailty and the risk of incident type 2 diabetes (T2DM) and to evaluate the effect of preventing the worsening of frailty on the risk of T2DM. We included 348 205 participants free of baseline T2DM and with frailty phenotype (FP) data from the UK Biobank; among them, 36 175 had at least one follow-up assessment. According to their FP score, participants were grouped into nonfrailty, prefrailty and frailty groups. Frailty assessed at baseline and at follow-up was used to derive the trajectory of frailty (ΔFP). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Compared with those in the nonfrailty group at baseline, the HRs of T2DM for the prefrailty and frailty groups were 1.38 (95% CI 1.33-1.43) and 1.69 (95% CI 1.59-1.79), respectively (both p < 0.001), in the multivariable-adjusted model. During a median follow-up of 5.4 years after the final assessment, data for 472 T2DM patients were recorded. A 1-point increase in the final FP was associated with a 25% (95% CI 1.14-1.38; p < 0.001) increased risk of T2DM. For the trajectory of frailty, each 0.5-point/year increase in ΔFP was associated with a 52% (95% CI 1.18-1.97; p < 0.001) greater risk of T2DM, independent of the FP score at baseline. Compared with those that remained in the nonfrailty group, the greatest risk of T2DM over time was prefrailty aggravation (HR 3.03, 95% CI 2.00-4.58; p < 0.001). Using the frailty index did not materially change the results. Long-term changes in frailty were associated with the risk of incident T2DM, irrespective of baseline frailty status. Preventing the worsening of frailty may reduce T2DM risk.

Association between cardiovascular disease risk and incident type 2 diabetes mellitus in individuals with prediabetes: A retrospective cohort study

AimsIn this study, we aimed to evaluate the impact of overall cardiovascular disease (CVD) risk on the development of incident T2DM in patients with prediabetes. MethodsWe retrospectively enrolled 5,908 subjects with prediabetes who underwent health check-ups at the Asan Medical Center. CVD risk was estimated using the Framingham Risk Score (FRS). We compared moderate- to high-risk groups with low-risk controls based on the FRS. Cox proportional hazards regressions were conducted to estimate the time-to-develop incident T2DM. ResultsAmong the 5908 subjects with prediabetes, 3031 (51.8 %) were identified to have either moderate or high CVD risk scores. During a median follow-up of 5.2 years, 278 (9.2 %) patients from the moderate- to high-risk group and 171 (5.9 %) from the low-risk group were diagnosed with T2DM. The covariate-adjusted hazard ratio for the incident T2DM was 1.30 (95 % CI, 1.06–1.60, p = 0.011) in the moderate- to high-risk group compared to the low-risk controls. ConclusionAmong patients with prediabetes, those with high CVD risk were more likely to develop incident T2DM, as determined by the FRS. CVD risk factors should be properly evaluated and managed in individuals with prediabetes to reduce the risk of both incident T2DM and associated cardiovascular complications.

Should dolutegravir always be withheld in people with HIV on dolutegravir with incident diabetes mellitus? a case report

Dolutegravir (DTG), an integrase strand transfer inhibitor is currently the recommended first and second line anti-retroviral therapy (ART) anchor agent by the World Health Organization due to its favorable side effect profile, high efficacy and genetic barrier to resistance.Despite its very good side effect profile, there have been multiple case reports of ART experienced patients developing hyperglycemia within weeks to a few months after switching to DTG preceded by weight loss. At population level, however, DTG as well as other integrase inhibitors have been demonstrated to have a reduced risk of incident diabetes mellitus (T2DM) compared to other HIV drug classes.Following multiple similar reports of accelerated hyperglycemia in Uganda during the first pilot year of DTG use, the Uganda Ministry of Health recommended withholding dolutegravir in all patients who develop diabetes. Whether this recommendation should be applied to all patients with incident T2DM remains to be demonstrated.We present a clinical case of an HIV positive ART naïve man who was diagnosed with T2DM after 36 weeks on DTG. We describe changes in blood glucose, glycated hemoglobin, insulin resistance and pancreatic beta cell function before and after withholding DTG. We demonstrated that he was phenotypically different from the reported cases of accelerated hyperglycemia and he continued to have worsening insulin resistance despite withholding DTG. His blood glucose improved with dietary T2DM management. It is possible he had an inherent risk of developing T2DM independent of his exposure to DTG. This put in question whether DTG should universally be withheld in PLHIV with incident T2DM in Uganda.

The severity of menopausal symptoms is associated with diabetes, and cardiometabolic risk factors in middle-aged women.

Ovarian senescence is associated with increased cardiovascular risk. We aimed to evaluate the association between menopausal symptoms and cardiometabolic risk factors in a cohort of apparently healthy middle-aged women. The cohort included 2793 peri- and postmenopausal women not on menopausal hormone therapy. Demographic/anthropometric and biochemical/hormonal data were assessed. The severity of menopausal symptoms was evaluated by the Greene Climacteric Scale (GCS). GCS-Total Score was associated with BMI (b=0.12, 95% CI: 0.04 to 0.20), T2DM (b=2.10, 95% CI: 0.06 to 4.15), and late-postmenopause (b=-1.24, 95% CI: -2.17 to -0.33). GCS-psychological score was associated with BMI (b=0.06, 95% CI: 0.00 to 0.11). GCS-Physical Score was associated with BMI (b=0.06, 95% CI: 0.03 to 0.09), central obesity (b=0.18, 95% CI: 0.02 to 0.34), and postmenopause (early-/late-postmenopause vs. perimenopause, b=-0.36, 95% CI: -0.59 to -0.13 and b=-0.65, 95% CI: -0.97 to -0.34, respectively). All GCS-scores were negatively associated with age. GCS-Sexual Score was associated with early-postmenopause (incidence rate ratio (IRR)=1.53, 95% CI: 1.21 to 1.94), central obesity (IRR=1.18, 95% CI: 1.00 to 1.39), smoking, diastolic blood pressure, age. Cox-regression analysis showed that incident T2DM was positively associated with increasing age, BMI, daily alcohol consumption, moderate-to-severe vasomotor symptoms (VMS, OR=1.045, 95% CI: 1.011 to 1.079), and negatively with moderate-to-strenuous physical activity. These associations persisted in lean but not in obese women. The severity of menopausal symptoms is associated with T2DM, obesity, and smoking in a cohort of peri-/postmenopausal women. VMS were associated with incident T2DM, especially in lean women. These associations must be considered in implementing primary and secondary prevention strategies.

A simpler definition of MAFLD precisely predicts incident metabolic diseases: a 7-year cohort study.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel definition proposed in 2020 with a relatively complex set of criteria. Thus, simplified criteria that are more applicable are required. This study aimed to develop a simplified set of criteria for identifying MAFLD and predicting MAFLD-related metabolic diseases. We developed a simplified set of metabolic syndrome-based criteria for MAFLD, and compared the performance of the simplified criteria with that of the original criteria in predicting MAFLD-related metabolic diseases in a 7-year follow-up. In the 7-year cohort, a total of 13,786 participants, including 3372 (24.5%) with fatty liver, were enrolled at baseline. Of the 3372 participants with fatty liver, 3199 (94.7%) met the MAFLD-original criteria, 2733 (81.0%) met the simplified criteria, and 164 (4.9%) were metabolic healthy and met neither of the criteria. During 13,612 person-years of follow-up, 431 (16.0%) fatty liver individuals newly developed T2DM, with an incidence rate of 31.7 per 1000 person-years. Participants who met the simplified criteria had a higher risk of incident T2DM than those who met the original criteria. Similar results were observed for incident hypertension, and incident carotid atherosclerotic plaque. The MAFLD-simplified criteria are an optimized risk stratification tool for predicting metabolic diseases in fatty liver individuals.

Abstract #1405175: Temporal Association Between Nonalcoholic Fatty Liver Disease and Type 2 Diabetes: Observational and Mendelian Randomization Study

Nonalcoholic fatty liver disease and diabetes are both chronic multi-system disease and their prevalence are emerging every year, causing considerable clinical and health burden worldwide. Previous epidemiological studies have found a bidirectional relationship between them but the actual causal effect remained unknown. We aim to verify this bidirectional association and find out the exact causal relationship between these two diseases. The study consisted of two datasets. The SPECT-China dataset included 2099 participants who attended SPECT-China 2014 and SPECT-China2 2019 simultaneously, and the UK Biobank dataset included 502414 participants aged 37-73 years across the UK. SNPs were extracted from IEU OPEN GWAS PROJECT. Logistic regression model and cox regression model were used to analyze the association between NAFLD and T2DM. Bidirectional mendelian randomization analysis were conducted to investigate the causal effects. During the follow-up, 129 cases of diabetes and 263 cases of NAFLD were observed in the SPECT-China dataset, and 30274 cases of diabetes and 4896 cases of NAFLD happened in the UK Biobank dataset. Baseline NAFLD is associated with an increased risk of incident T2DM in both datasets while baseline diabetes is only associated with incident NAFLD in the UK Biobank dataset. Bidirectional MR analysis found a causal relationship from NAFLD to T2DM. (OR: 1.05, 95%CI :1.03-1.07, P< 0.001) We found a potentially causal NAFLD→T2DM relationship, therefore public awareness should be raised in maintaining an optimal glycemic profile, especially in those with NAFLD.

External validation of the American prediction model for incident type 2 diabetes in the Iranian population

BackgroundThe primary aim of the present study was to validate the REasons for Geographic and Racial Differences in Stroke (REGARDS) model for incident Type 2 diabetes (T2DM) in Iran.MethodsPresent study was a prospective cohort study on 1835 population aged ≥ 45 years from Tehran lipids and glucose study (TLGS).The predictors of REGARDS model based on Bayesian hierarchical techniques included age, sex, race, body mass index, systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and fasting plasma glucose. For external validation, the area under the curve (AUC), sensitivity, specificity, Youden’s index, and positive and negative predictive values (PPV and NPV) were assessed.ResultsDuring the 10-year follow-up 15.3% experienced T2DM. The model showed acceptable discrimination (AUC (95%CI): 0.79 (0.76–0.82)), and good calibration. Based on the highest Youden’s index the suggested cut-point for the REGARDS probability would be ≥ 13% which yielded a sensitivity of 77.2%, specificity 66.8%, NPV 94.2%, and PPV 29.6%.ConclusionsOur findings do support that the REGARDS model is a valid tool for incident T2DM in the Iranian population. Moreover, the probability value higher than the 13% cut-off point is stated to be significant for identifying those with incident T2DM.

The Association of Specific Dietary Patterns with Cardiometabolic Outcomes in Women with a History of Gestational Diabetes Mellitus: A Scoping Review

Gestational diabetes mellitus is associated with a significantly increased risk of later type 2 diabetes (T2DM) and cardiovascular disease (CVD). Post-natal interventions aim to reduce this risk by addressing diet and lifestyle factors and frequently focus on restricting energy or macronutrient intake. With increased interest in the role of complete dietary patterns in the prevention of cardiometabolic disease, we sought to evaluate what is known about the role of dietary patterns in reducing cardiometabolic risk in women with previous GDM. A systematic search was conducted to identify studies relating to dietary pattern and cardiometabolic parameters in women with a history of GDM. The search criteria returned 6014 individual studies. In total, 71 full texts were reviewed, with 24 studies included in the final review. Eleven individual dietary patterns were identified, with the Alternative Health Eating Index (AHEI), Mediterranean diet (MD), and low glycaemic index (GI) as the most commonly featured dietary patterns. Relevant reported outcomes included incident T2DM and glucose tolerance parameters, as well as several cardiovascular risk factors. Dietary patterns which have previously been extensively demonstrated to reduce the risk of cardiovascular and metabolic disorders in the general population, including AHEI, MD, and DASH, were found to be associated with a reduction in the incidence of T2DM, hypertension, and additional risk factors for cardiometabolic disease in women with a history of GDM. Notable gaps in the literature were identified, including the relationship between dietary patterns and incident CVD, as well as the relationship between a low GI diet and the development of T2DM in this population.

Atherosclerosis indexes and incident T2DM in middle-aged and older adults: evidence from a cohort study

BackgroundType 2 diabetes mellitus (T2DM) is an expanding global health problem, requiring effective methods for predicting and diagnosing in its early stages of development. Previous studies reported the prognostic value of the atherosclerosis indexes in both cardiovascular diseases and T2DM. However, the predictive performance of Non-HDL-C, AI, AIP, TG/HDL-C and LCI indexes on the risk of T2DM remains unclear. This study aims to compare the five atherosclerosis indexes for predicting T2DM in middle-aged and elderly Chinese.MethodsData are collected from wave 2011 and wave 2015 of China Health and Retirement Longitudinal Study (CHARLS). Multi-variate logistic regression models were used to estimate odds ratio (OR) with 95% confidence interval (CI) of incident T2DM with five atherosclerosis indexes, and the restricted cubic splines were used to visualize the dose–response relationships. Receiver operating characteristic (ROC) curve was drawn and the areas under the curve (AUC) were used to compare the performance of the five atherosclerosis indexes in predicting T2DM.ResultsA total of 504 (10.97%) participants had T2DM. Multi-variate logistic regression analysis showed that five atherosclerosis indexes were associated with T2DM, with adjusted ORs (95% CIs) of 1.29 (1.15–1.45), 1.29 (1.18–1.42), 1.45 (1.29–1.62), 1.41 (1.25–1.59) and 1.34 (1.23–1.48) for each IQR increment in Non-HDL-C, TG/HDLC, AI, AIP and LCI, respectively. Restricted cubic spline regression showed a nonlinear correlation between five atherosclerosis indexes and the risk of T2DM (p for nonlinear < 0.001). According to the ROC curve analysis, LCI had the highest AUC (0.587 [0.574–0.600]).ConclusionWe found that LCI, compared with other indexes, was a better predictor in the clinical setting for identifying individuals with T2DM in middle-aged and elderly Chinese. LCI monitoring might help in the early identification of individuals at high risk of T2DM.

Two Distinct Groups Are Shown to Be at Risk of Diabetes by Means of a Cluster Analysis of Four Variables.

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.

U-shaped association between triglyceride and risk of incident diabetes in normoglycemic males with NAFLD: A population-base cohort study.

Background: Serum triglyceride (TG) was an important biomarker for nonalcoholic fatty liver disease (NAFLD), and the association between TG and incident type 2 diabetes mellitus is still under debate with some studies suggesting that elevated TG increase the risk of incident T2DM while others indicative of a negative relationship. These controversial findings may be partially due to the inclusion of the participants with NAFLD. The association between TG and incident type 2 diabetes mellitus in people with NAFLD remained unclear. Therefore, this study aimed to characterize the relationship between the baseline TG levels and incident type 2 diabetes mellitus in a male Japanese cohort with NAFLD. Methods: A total of 1221 males with NAFLD were enrolled from the Nagala (NAFLD in the Gifu Area Longitudinal analysis) study conducted from 2004 to 2015. Cox proportional hazards models were performed to examine the relationship between baseline TG concentration and incident type 2 diabetes mellitus. A two-piecewise linear regression model was explored to evaluate the threshold effect of the baseline TG levels on type 2 diabetes mellitus incidence by using a smoothing function. Results: During a median follow-up of 6.05 years, 39 males with NAFLD at baseline developed type 2 diabetes mellitus. The risk of incident type 2 diabetes mellitus was significantly associated with baseline TG concentration in males with NAFLD after fully adjustment for confounders, with per 10 mg/dl elevation in TG levels increasing the risk of incident diabetes by 8.5% (HR=1.085, CI=1.039-1.132; P<0.001). However, no typical dose-dependent positive association between type 2 diabetes mellitus incidence and the TG levels was observed across the TG tertiles. Interestingly, a U-shaped association between TG concentration and risk of incident type 2 diabetes mellitus was revealed by the two-piecewise linear regression analysis. Baseline TG concentration lower than the threshold values (TG <53mg/dl) were negatively associated with risk of incident type 2 diabetes mellitus. With each 10mg/dl increase in baseline TG levels, the risk of incident type 2 diabetes mellitus decreased by nearly 59% (HR=0.413, 95% CI=0.220-0.778). In contrast, when TG levels were higher than the threshold values (TG>53mg/dl), the risk of incident diabetes increased 9.1% with every 10mg TG elevation (HR=1.091, 95% CI=1.046-1.137). Conclusions: A U-shaped relationship was observed between baseline TG levels and incident type 2 diabetes mellitus in a male normoglycemic Japanese population with NAFLD, although extrapolation of the finding to other populations should be made with caution.

PS-C01-4: ASSOCIATIONS OF ARTERIAL STIFFNESS ONSET AGE WITH TYPE 2 DIABETES RISK: A LARGE-SCALE CHINESE COHORT STUDY

Objective: To explore the associations between arterial stiffness (AS) onset age and type 2 diabetes (T2DM) risk. Design and Method: This study enrolled 22,588 participants free of T2DM at baseline. All participants take an annual physical examination from 2012 to 2016, with fasting blood glucose and brachial-ankle pulse wave velocity measurements. Cox proportional model was used to investigate the association between AS onset age and T2DM risk. Sex specific analysis was also performed, as well as examining the association between early vascular aging (EVA), normal vascular aging (NVA), supernormal vascular aging (SUPERNOVA) onset age, and diabetes risk. Results: Totalling 757 (3.4%) participants were diagnosed with T2DM. Compared with participants free of AS in each specific age group, the earlier AS onset age was more strongly associated with T2DM risk, especially for the middle age, with the fully adjusted hazard risk (HR) and 95% confidence interval (CI) of 4.63 (2.79, 7.67) for AS onset age at 50. Similar results were observed both in males and females, with the fully adjusted HR and 95% CI of 4.54 (2.60, 7.93) for males and 4.86 (1.48, 16.01) for females, with AS onset age at 50. Such association was also observed in the exploration of EVA, NVA, and SUPERNOVA onset age and incident T2DM risk. Conclusions: This study revealed that middle-aged onset of AS was more significantly associated with a higher risk of T2DM. Early screening of AS, especially in middle age, may assist in T2DM detection and postpone diabetic vascular complications developing.

Association Between Handgrip Strength and Type 2 Diabetes: A Prospective Cohort Study and Systematic Review With Meta-analysis.

Both absolute (kg) and relative (kg per kg of body weight) handgrip strength (HGS) have been used as indicators of HGS. Multiple studies have explored HGS associations with type 2 diabetes (T2DM); however, prognostic values were inconsistent. We aimed to examine the associations between both absolute and relative HGS and incident T2DM. A total of 12,957 participants aged 40 years and older (mean age 51.0 years, 58.4% men) were followed and enrolled in the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) Cohort Study. Cox proportional hazards regression models were used to examine the association of HGS with incident T2DM. Other prospective studies on HGS and risk of T2DM were identified by searching several electronic databases up to November 31, 2021. Meta-analysis was performed by combining the results from the TCLSIH study and previous prospective cohort studies. From the TCLSIH Cohort study, after adjustment, relative HGS was inversely associated with T2DM (hazard ratio per 0.1 higher relative HGS 0.667, 95% confidence interval [CI] 0.616, 0.722). However, no significant association between absolute HGS and incident T2DM was found. The meta-analyses showed that per 5 kg higher HGS was associated with a 5% (95% CI 2%, 8%) lower risk of T2DM and each 0.1 higher relative HGS was associated with a 22% (95% CI 14%, 29%) lower risk of T2DM. The results from our cohort study and meta-analysis suggest that relative HGS was better than absolute HGS in predicting incident T2DM. Adiposity was an important factor that mediates the association between HGS and T2DM.

Bidirectional temporal relationships between uric acid and insulin and their joint impact on incident diabetes

Background and aimsThis study aims to examine the temporal relationship between uric acid (UA) and insulin and their joint impact on T2DM in middle-aged adults. Methods and resultsThe cohort consisted of 1351 non-diabetic adults who had serum UA and insulin measured twice at baseline and follow-up over 7.7 years on average, and incidence of T2DM in the outcome survey12.2 years later.After adjusting for covariates, the path coefficient from baseline UA to follow-up insulin was 0.082 (p < 0.001); the path from baseline insulin to follow-up UA was 0.060 (p = 0.030). In the mediation model with baseline UA as the predictor, total effect of baseline UA on incident T2DM was 0.089 (p = 0.016). The mediation effect through follow-up insulin on the UA-T2DM association was 28.1%. The direct effect of baseline UA on T2DM (0.064) became nonsignificant (p = 0.078). In the mediation model with baseline insulin as the predictor, total effect of baseline insulin on T2DM was 0.218 (p < 0.001). The mediation effect through follow-up UA on the insulin-T2DM association was 5.5%. The direct effect of baseline insulin on T2DM (0.206) remained significant (p < 0.001). The baseline hyperinsulinemia-follow-up hyperuricemia group showed the highest incidence rate of T2DM (27.9%). ConclusionsThe bidirectional temporal relationship suggests that UA and insulin influence each other in non-diabetic individuals, and the directionality plays pathogenic roles in the development of T2DM.

Fatty liver index as a predictor for incident type 2 diabetes in community-dwelling adults: longitudinal findings over 12 years

BackgroundDiagnosing fatty liver and identifying disease status are important for fatty liver related-diseases prevention. The fatty liver index (FLI), which can be easily available in clinical practice, can be very useful for managing fatty liver and preventing related diseases.No large-scale and long-term follow-up prospective studies have investigated the relationship between FLI and incident type 2 diabetes (T2DM) independent of baseline insulin resistance status. Therefore, this study aimed to evaluate the association between FLI and incident T2DM and to determine whether FLI could be used as an indicator of T2DM using a large-sample, community-based Korean cohort over 12 years.MethodsAmong the 10,030 total participants, 7,777 (3,676 men and 4,101 women) without diabetes were selected from the Korean Genome and Epidemiology Study (KoGES). FLI grade, which ranged from 0 to 100, was categorized into three groups: low, FLI (< 30); intermediate, FLI (30–59); and high, FLI (≥ 60). The hazard ratios (HRs) with 95% confidence intervals (CIs) for incident T2DM were calculated using multivariate Cox proportional hazards regression models after adjusting for potentially confounding variables.ResultsIn total, 1,490 individuals (19.2%) developed T2DM during follow-up. Compared to the reference FLI (< 30), the HRs of incident T2DM for the FLI (30–59), and FLI (≥ 60) increased after adjusting for potentially confounding variables, including the HOMA-IR marker.ConclusionsFLI grade at baseline could be a future indicator of T2DM even when prior glucose or insulin (HOMA-IR) levels are normal.