Risk Of Incident Type 2 Diabetes Mellitus Research Articles

Gamma-Glutamyl Transferase and the Risk of Type 2 Diabetes Mellitus: A Review

The relationship between gamma-glutamyl transferase (GGT) levels and risk factors for type 2 diabetes mellitus (T2DM) and the risk of incident T2DM was assessed using a narrative review of available evidence. Higher circulating levels of GGT are associated with an increased risk of type 2 diabetes mellitus, suggesting GGT as a risk predictor of T2DM. The incidence of type 2 diabetes and its association with GGT elevation could be explained by oxidative stress in cells followed by subclinical inflammation and fatty liver, leading to impaired insulin secretion and insulin resistance. A strong correlation is evident between BMI and GGT, in which hepatic steatosis and insulin resistance are proposed to be the intermediate connecting characteristics.

Alanine transferase levels (ALT) and triglyceride-glucose index are risk factors for type 2 diabetes mellitus in obese patients

AimsThe role of liver steatosis and increased liver enzymes (ALT) in increasing incident type 2 diabetes mellitus (T2DM) is debated, because of their differential effects on different ethnicities and populations. The aim of this study was to evaluate the role of elevated ALT in the development of T2DM in non-diabetic obese subjects receiving routine medical treatment.MethodsA total of 1005 subjects [296 men and 709 women, aged 45.7 ± 13.12 years, body mass index (BMI) 39.5 ± 4.86 kg/m2] were followed for a mean period of 14.3 ± 4.44 years. Subjects were evaluated for several metabolic variables, including the triglyceride-glucose index and the presence of metabolic syndrome (IDF 2005 definition), and were subdivided into ALT quartiles.ResultsT2DM developed in 136 subjects, and the difference was significant between the first and the fourth ALT quartile (p = 0.048). Both at univariate analysis and at stepwise regression, ALT quartiles were associated with incident T2DM. Traditional risk factors for T2DM coexisted, with a somehow greater predictive value, such as triglyceride-glucose index, age, arterial hypertension, LDL-cholesterol, and metabolic syndrome.ConclusionsThese data suggest an association between elevated ALT levels and the risk of incident T2DM in obesity.

Resting heart rate and the risk of incident type 2 diabetes mellitus among non-diabetic and prediabetic Iranian adults: Tehran lipid and glucose study

BackgroundResting heart rate (RHR) has been found to be a potential risk factor for developing type 2 diabetes mellitus (T2DM), with a highly significant heterogeneity among previous studies. Therefore, we examined the association of RHR and risk of incident T2DM among non-diabetic and prediabetic adults.MethodsThe study population included 2431 men and 2910 women aged ≥ 20 years without T2DM at baseline (2001–2005). Participants were followed for incident T2DM by about 3-year intervals up to April 2018. The multivariable Cox proportional models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The models were adjusted for age, body mass index, waist circumference, educational level, physical activity, smoking, hypertension, family history of diabetes, triglycerides/ high-density lipoprotein cholesterol ratio, and fasting plasma glucose.ResultsDuring a median follow-up of 12.2 years, 313 men and 375 women developed T2DM. Interestingly, a significant sex-difference was found (all P-values for sex interaction < 0.025). Among men, compared to the first quintile (< 68 bpm: beats per minute), those who had RHR of over 84 bpm were at higher T2DM risk with a HR (95%CI) of 1.69 (1.16–2.47). Furthermore, considering RHR as a continuous variable, an increase of 10 bpm caused 17% significantly higher risk among men with a HR of 1.17 (1.05–1.30). However, among women, there was no significant association between incident T2DM and RHR. Moreover, among prediabetic participants at baseline, the association of RHR and risk of T2DM progression was generally similar to the general population, which means higher RHR increased the risk of T2DM development only among men with a HR of 1.26 (1.09–1.46) for 10 bpm increase.ConclusionsAmong men, being either non-diabetic or prediabetic at baseline, higher RHR can be associated with incident T2DM; however, women didn’t show a significant association. Further studies are needed to determine the added value of RHR as a potential modifiable risk factor in screening and risk prediction of incident T2DM.

A U-shaped association between the triglyceride to high-density lipoprotein cholesterol ratio and the risk of incident type 2 diabetes mellitus in Japanese men with normal glycemic levels: a population-based longitudinal cohort study.

Several studies have verified that a high baseline TG/HDL-C ratio is a risk factor for incident type 2 diabetes mellitus (T2DM). However, for low baseline TG/HDL-C levels, the findings were inconsistent with ours. In addition, the association between baseline TG/HDL-C ratio and the risk of incident T2DM in Japanese men with normal glycemic levels is unclear. As a result, our study further investigated the relationship between baseline TG/HDL-C and the risk of incident T2DM in Japanese men with normal glycemic levels. This was a secondary longitudinal cohort study. We selected 7,684 male participants between 2004 and 2015 from the NAGALA database. A standardized Cox regression model and two piecewise Cox regression models were used to explore the relationship between the baseline high-density lipoprotein cholesterol ratio (TG/HDL-C) and incident T2DM. During a median follow-up of 2,282 days, 162 men developed incident T2DM. In the adjusted model, the baseline TG/HDL-C ratio was strongly associated with the risk of incident T2DM, and no dose-dependent positive association was observed between the baseline TG/HDL-C ratio and incidence of T2DM throughout the baseline TG/HDL-C quartiles. Two-piecewise linear regression analysis showed a U-shaped association between baseline TG/HDL-C ratio and incidence of incident T2DM. A baseline TG/HDL-C ratio below 1.188 was negatively associated with incident T2DM (H.R. = 0.105, 95% CI = 0.025, 0.451; P = 0.002). In contrast, a baseline TG/HDL-C ratio >1.188 was positively associated with incident T2DM (H.R. = 1.248, 95% CI = 1.113, 1.399; P<0.001). The best TG/HDL-C threshold for predicting incident T2DM was 1.8115 (area under the curve, 0.6837). A U-shaped relationship between baseline TG/HDL-C ratio and incident T2DM in Japanese men with normal glycemic levels was found.

The serum creatinine to cystatin C to waist circumference ratios predicts risk for type 2 diabetes: A Chinese cohort study.

There is a lack of research regarding the relationship between creatinine to cystatin C to waist circumference ratio (CCR/WC ratios) and the development of type 2 diabetes mellitus (T2DM). We aimed to evaluate the association between CCR/WC ratios and incident T2DM in Chinese adults. This prospective study was from the China Health and Retirement Longitudinal Study (2011, 2013, 2015, and 2018). The participants were divided into three groups by tertiaries of the CCR/WC ratios. Cox proportional-hazards models were used to identify the relationship between CCR/WC and T2DM. Overall, 5938 participants were included for analysis, 766 of whom developed T2DM between 2011 and 2018. Risk of incident T2DM was decreased with tertiaries 2, 3 versus tertiary 1 of the CCR/WC index (adjusted hazard ratio [HR] 0.772 [95% confidence interval 0.647-0.921] and 0.724 [0.596-0.880], p for trend = .001 across tertiaries of the CCR/WC index). The results were consistent excluding participants with T2DM in the first 2 years. This study demonstrated that CCR/WC was negatively correlated with the risk of T2DM in Chinese adults. Early detection is necessary to control the development of T2DM in Chinese with low CCR/WC levels.

Weight-adjusted waist index is not superior to conventional anthropometric indices for predicting type 2 diabetes: a secondary analysis of a retrospective cohort study.

Weight-adjusted waist index (WWI) is a new anthropometric indicator to assess adiposity. Current knowledge regarding its association with type 2 diabetes mellitus (T2DM) is limited. This present study aims to evaluate the association of WWI with the risk of T2DM in the Japanese population, and to compare its predictive ability with body mass index (BMI) and waist circumference (WC). This was a secondary analysis of a retrospective cohort study involving 15,464 participants. Participants were divided into quartiles based on baseline WWI levels. Cox regression model, Kaplan-Meier curve, and smooth curve fitting were used to explore the relationship between WWI and T2DM. The discriminative ability of obesity indices in predicting T2DM was compared by the receiver operating characteristic (ROC) curve. After a mean follow-up of 6.05 years, 373 participants were diagnosed with T2DM. In fully adjusted models, the risk of incident T2DM was 1.96 times higher for each 1-unit increment in WWI levels (95% CI: 1.61-2.39, P < 0.001). Smooth curve fitting analysis showed a linear positive association between baseline WWI and new-onset T2DM. Subgroup analysis showed consistent results which subjects in the 4th WWI quartile had the highest risk of developing T2DM in different age, gender, and BMI groups. WWI did not exhibit better predictive ability compared with BMI and WC in the results of ROC curve. WWI, a new metabolic index, can be used to predict new-onset T2DM in the Japanese population. However, its predictive capability was not superior to conventional anthropometric indices.

Association of frailty with the incidence risk of cardiovascular disease and type 2 diabetes mellitus in long-term cancer survivors: a prospective cohort study

BackgroundComorbidities among cancer survivors remain a serious healthcare burden and require appropriate management. Using two widely used frailty indicators, this study aimed to evaluate whether frailty was associated with the incidence risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) among long-term cancer survivors.MethodsWe included 13,388 long-term cancer survivors (diagnosed with cancer over 5 years before enrolment) free of CVD and 6101 long-term cancer survivors free of T2DM, at the time of recruitment (aged 40–69 years), from the UK Biobank. Frailty was assessed by the frailty phenotype (FP_Frailty, range: 0–5) and the frailty index (FI_Frailty, range: 0–1) at baseline. The incident CVD and T2DM were ascertained through linked hospital data and primary care data, respectively. The associations were examined using Cox proportional hazards regression models.ResultsCompared with non-frail participants, those with pre-frailty (FP_Frailty [met 1–2 of the components]: hazard ratio [HR]=1.18, 95% confidence interval [CI]: 1.05, 1.32; FI_Frailty [0.10< FI ≤0.21]: HR=1.51, 95% CI: 1.32, 1.74) and frailty (FP_Frailty [met ≥3 of the components]: HR=2.12, 95% CI: 1.73, 2.60; FI_Frailty [FI >0.21]: HR=2.19, 95% CI: 1.85, 2.59) had a significantly higher risk of CVD in the multivariable-adjusted model. A similar association of FI_Frailty with the risk of incident T2DM was observed. We failed to find such an association for FP_Frailty. Notably, the very early stage of frailty (1 for FP_Frailty and 0.1-0.2 for FI_Frailty) was also positively associated with the risk of CVD and T2DM (FI_Frailty only). A series of sensitivity analyses confirmed the robustness of the findings.ConclusionsFrailty, even in the very early stage, was positively associated with the incidence risk of CVD and T2DM among long-term cancer survivors, although discrepancies existed between frailty indicators. While the validation of these findings is required, they suggest that routine monitoring, prevention, and interventive programs of frailty among cancer survivors may help to prevent late comorbidities and, eventually, improve their quality of life. Especially, interventions are recommended to target those at an early stage of frailty when healthcare resources are limited.

The relationship between the ratio of gamma-glutamyltransferase to high-density lipoprotein cholesterol and the risk of diabetes mellitus using publicly available data: a secondary analysis based on a longitudinal study in Japan

BackgroundThe ratio of gamma-glutamyltransferase to high-density lipoprotein cholesterol (GGT/HDL-C) has been highlighted in nonalcoholic fatty liver disease (NAFLD) by previous studies. However, there have been fewer investigations into the correlation between the GGT/HDL-C ratio and type 2 diabetes mellitus (T2DM) incidence. Our secondary analysis used published data from a Japanese population and aimed to investigate the role of the GGT/HDL-C ratio in the incidence of T2DM.MethodsThe research was a longitudinal cohort study completed by Okamura, Takuro et al. We obtained the data from the DATADRYAD website and used it for secondary analysis only. The participants recruited from a medical program called the NAGALA database received regular medical examinations and standardized questionnaires to obtain the baseline variables. Abdominal ultrasound was used to diagnose fatty liver disease. The participants were followed up, and the duration and occurrence of T2DM were documented. The GGT/HDL-C ratio evaluated at baseline served as the independent variable, while the occurrence of diabetes served as the dependent variable.ResultsA total of 15,453 cases (8,419 men and 7,034 women) were included in our study. After adjusting for age, sex, BMI, DBP, SBP, ALT, AST, TG, TC, HbA1C, FPG, drinking status, smoking status, exercise status, and fatty liver, we observed that the GGT/HDL-C ratio was positively associated with the incidence of T2DM (hazard ratio = 1.005, 95% confidence interval: 1.000 to 1.010, P = 0.0667). The results were consistent when the GGT/HDL-C quartile was used as a categorical variable (P for trend < 0.00396). A curvilinear relationship with a threshold effect was identified between the GGT/HDL-C ratio and the risk of incident T2DM. On the left of the point, a one-unit increase in the GGT/HDL-C ratio was associated with a 1.5-fold increase in the risk of incident T2DM (hazard ratio 2.57, 95% confidence interval 1.20 to 5.49). On the right of the point, when GGT/HDL-C was greater than 6.53, their relationship became saturated.ConclusionThe GGT/HDL-C ratio correlated with the incidence of T2DM in a curvilinear form with a threshold effect. Their positive relationship could be observed when GGT/HDL-C was less than 6.53.

Association of cumulative monocyte to high-density lipoprotein ratio with the risk of type 2 diabetes: a prospective cohort study

BackgroundRecent studies have established that monocyte-derived inflammation plays a central role in the pathogenesis of type 2 diabetes mellitus (T2DM). It is unclear whether chronic metabolic inflammation, reflected by the cumulative monocyte to high-density lipoprotein ratio (CumMHR), predisposes the general population to T2DM.MethodsThis study included 40,813 participants without diabetes from a real-life, community-based cohort (the Kailuan Study) attending a 2-year cycle of health survey since 2006. Cumulative exposure was obtained from 2006/2007 to 2010/2011. Follow-up started at 2010/2011 and through 2020. Multivariable-adjusted Cox regression models were used to calculate the CumMHR-associated risk of incident T2DM.ResultsOver a median follow-up period of 7.98 (IQR: 5.74–8.87) years, 4,848 T2DM cases occurred. The CumMHR was positively associated with the risk of incident T2DM after adjusting for age, sex, smoking, drinking habits, physical activities, BMI, triglyceride-glycemia index, log(leukocyte count), log(hsCRP), blood pressure, renal function, and medication uses with adjusted HRs of 1.0 (ref.), 1.18 (1.05‒1.25), 1.17 (1.07‒1.27), 1.38 (1.26‒1.50), respectively, in CumMHR Quartiles 1, 2, 3 and 4. When follow-up ended at 2014/2015, the short-term (4‒year) adjusted T2DM risks in CumMHR Quartiles 2, 3, and 4 were 1.14 (1.01‒1.29), 1.17 (1.04‒1.32), 1.40 (1.25‒1.58), respectively, relative to Quartile 1. A significant interaction between CumMHR and cumulative high-sensitivity C-reactive protein (CumCRP) was observed (P-interaction: 0.0109). The diabetic risk in the highest quartile of CumMHR was higher (1.53 [1.28‒1.84]) when CumCRP < 1 mg/L, attenuated with increasing CumCRP levels (1 ~ 10 mg/L) and disappeared in CumCRP ≥ 10 mg/L. Hypertension, overweight, or smoking habits further modified the CumMHR-associated diabetic risk.ConclusionsCumulative MHR may be a promising supplement to hsCRP for more comprehensively assessing the influence of metabolic inflammation on T2DM susceptibility. For primary prevention, targeting high CumMHR, especially in cases at low risk of diabetes defined by traditional risk factors, may further help reduce the diabetic risk.

Triglyceride Glucose-Body Mass Index and Risk of Incident Type 2 Diabetes Mellitus in Japanese People With Normal Glycemic Level: A Population-Based Longitudinal Cohort Study.

BackgroundIt has been proved that triglyceride glucose-body mass index (TyG-BMI) is a readily available and clinically significant indicator of insulin resistance (IR). Nevertheless, the association between TyG-BMI and incident Type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to study the relationship between TyG-BMI and T2DM and explore the predictive characteristics of TyG-BMI.MethodsOur study was conducted as a longitudinal cohort study. 8,430 men and 7,034 women were enrolled and analyzed. They were both non-diabetic subjects with normal glycemic levels. Follow-up lasted for 13 years, from 1994 to 2016. To make the number of TyG-BMI in each group similar, the subjects were divided into four groups with 3866 subjects in each group.ResultsDuring the 13-year follow-up period, 373 subjects were diagnosed with incident T2DM. Our multivariate Cox regression analysis revealed that TyG-BMI was an independent predictor of incident T2DM. In addition, our research identified four specific groups, young people (18-44 years old), women, the non-hypertensive population and non-drinkers were at significantly higher risk of developing TyG-BMI-related diabetes (P-interaction< 0.05). The best threshold TyG-BMI for predicting incident T2DM was 197.2987 (area under the curve 0.7738).ConclusionsOur longitudinal cohort study demonstrated the positive correlation between baseline TyG-BMI and risk of incident T2DM in Japanese with normal glycemic levels, and this risk was significantly higher in the young people, women, the non-hypertensive population and non-drinkers.

Association between cardiovascular health metrics and risk of incident type 2 diabetes mellitus: the Rural Chinese Cohort Study.

The evidence for association between cardiovascular health (CVH) metrics and type 2 diabetes mellitus (T2DM) in Chinese population is limited. We explored the association between the number of ideal CVH metrics and risk of incident T2DM in a rural Chinese population. A total of 12,150 rural Chinese participants (median age 51years) were enrolled. A Cox proportional-hazards model was used to assess the association between the number of ideal CVH metrics and risk of incident T2DM by using hazard ratios (HRs) and 95% confidence intervals (CIs). We another conducted multiplicative and additive interaction effect between the number of ideal CVH metrics and sex or age on incident T2DM, and subgroup analyses of the association were also conducted by sex and age. During a median of 6.01years of follow-up, 840 incident cases of T2DM occurred. The number of ideal CVH metrics was negatively associated with risk of incident T2DM (per unit increase: HR = 0.76, 95% CI 0.70-0.82). We also observed both multiplicative and additive interaction effect between lower number of ideal CVH metrics and sex on incident T2DM, and multiplicative interaction effect between lower number of ideal CVH metrics and age on incident T2DM was observed. The association remained statistically significant for both men and women, or participants with age < 65years. Increasing number of ideal CVH metrics was associated with reduced risk of incident T2DM, which presented age- and sex-related differential associations.

Association Between Triglyceride-Glucose Index and the Risk of Type 2 Diabetes Mellitus in an Older Chinese Population Aged Over 75 Years.

BackgroundThe association between the triglyceride–glucose (TyG) index and type 2 diabetes mellitus (T2DM) in older adults has not been fully understood. This research aims to explore the association between the TyG index and the incidence of T2DM in an older Chinese population aged over 75 years.MethodsThis longitudinal analysis study was performed based on a database from a health check screening program in China. The participants were stratified based on the quintile ranges of the TyG index (Q1 to Q5 groups). T2DM was defined as fasting plasma glucose (FPG) ≥ 7.00 mmol/L and/or self-reported T2DM. The cumulative incidences of T2DM in various quintile groups were estimated by the Kaplan–Meier method. The Cox proportional hazard model was used to examine the independent impact of the TyG index on the risk of T2DM during the follow-up period. Subgroup analysis was performed by gender and BMI to further validate the credibility of the results.ResultsDuring the follow-up period, a total of 231 new-onset T2DM cases were recorded among the 2,571 individuals aged over 75 years. After adjusting confounding factors, elevated TyG index independently indicated a higher risk of T2DM (HR = 1.89; 95% CI, 1.47–2.44; p < 0.01). Higher TyG index quintile groups (Q3 to Q5) also presented with a higher risk of T2DM (hazard ratio (HR) = 1.36, 1.44, and 2.12, respectively) as compared with the lowest quintile group (Q1). Subgroup analysis showed that increased TyG index led to a higher risk of T2DM with HR = 2.35 (95% CI, 1.73–3.19), 1.90 (95% CI, 1.27–2.83), 2.95 (95% CI, 1.94–4.50), and 1.72 (95% CI, 1.25–2.35) in male subgroup, female subgroup, BMI < 24 kg/m2 subgroup, and BMI ≥ 24 kg/m2 subgroup, respectively.ConclusionsTriglyceride–glucose index independently correlated with the risk of incident T2DM in Chinese adults aged over 75 years. The TyG index might be useful in monitoring T2DM in the older populations.

Creatinine-to-body weight ratio is a predictor of incident diabetes: a population-based retrospective cohort study

PurposeCreatinine to body weight (Cre/BW) ratio is considered the independent risk factor for incident type 2 diabetes mellitus (T2DM), but research on this relationship is limited. The relationship between the Cre/BW ratio and T2DM among Chinse individuals is still ambiguous. This study aimed to evaluate the correlation between the Cre/BW ratio and the risk of T2DM in the Chinese population.MethodsThis is a retrospective cohort study from a prospectively collected database. We included a total of 200,658 adults free of T2DM at baseline. The risk of incident T2DM according to Cre/BW ratio was estimated using multivariable Cox proportional hazards models, and a two-piece wise linear regression model was developed to find out the threshold effect.ResultsWith a median follow-up of 3.13 ± 0.94 years, a total of 4001 (1.99%) participants developed T2DM. Overall, there was an L-shaped relation of Cre/BW ratio with the risk of incident T2DM (P for non-linearity < 0.001). When the Cre/BW ratio (× 100) was less than 0.86, the risk of T2DM decreased significantly as the Cre/BW ratio increased [0.01 (0.00, 0.10), P < 0.001]. When the Cre/BW ratio (× 100) was between 0.86 and 1.36, the reduction in the risk of developing T2DM was not as significant as before [0.22 (0.12, 0.38), P < 0.001]. In contrast, when the Cre/BW ratio (× 100) was greater than 1.36, the reduction in T2DM incidence became significantly flatter than before [0.73 (0.29,1.8), P = 0.49].ConclusionThere was an L-shaped relation of Cre/BW ratio with incidence of T2DM in general Chinese adults. A negative curvilinear association between Cre/BW ratio and incident T2DM was present, with a saturation effect predicted at 0.86 and 1.36 of Cre/BW ratio (× 100).

Cardiometabolic risk factors in obese individuals and the risk of incident diabetes mellitus in 12-year prospective study

Aim of the study was to investigate the risk of developing type 2 diabetes mellitus (T2DM) in individuals with metabolically healthy and unhealthy obesity phenotypes (MHO and MUO) and evaluate the contribution of metabolic syndrome (MS) components to the 12-year risk of developing T2DM according to a prospective study.Material and methods. The study included 1958 people with a BMI ≥30 kg/m² and no T2DM, from among those examined at the baseline screening in 2003– 2005 of the HAPPIE project. New cases of T2DM were diagnosed between 2003 and 2018 according to the register of diabetes mellitus and repeated screenings. The median follow-up period was 12.1 years. Were used to define MHO: criteria of the NCEPATP III, 2001 and IDF, 2005.Results. The incidence of T2DM in the MHO group according to all studied criteria is on 1,5 times lower than in persons with MUO, p&lt;0,001. According to the results of Cox regression multivariate analysis, the risk of developing T2DM in individuals with MHO is 2.3 times lower according to the IDF criteria, 2005 and 2,2 times lower according to the NCEP ATP III, 2001 criteria, compared with persons with MUO. The risk of developing T2DM increases in direct proportion to the number of MS components: 3 components—OR = 3,1 (95% CI: 1.0; 9.9), p = 0.048, 4 components—OR = 4.4 (95% CI: 1.4; 14.0), p = 0.011. However, the presence of obesity in a person with one risk factor does not lead to the development of T2DM within 12 years, p&gt;0.05. When analyzing obese individuals who had abdominal obesity (AO), the risk of developing T2DM is 2 times higher compared to individuals with normal waist circumference (WC), and people without AO demonstrate no risk of developing T2DM, with an increase in the number of MS components, p&gt; 0.05.Conclusions. The incidence of first-­onset T2DM during 12 years in the MHO group by any used criteria is on 1.5 times lower than in the MUO group. In individuals with obesity, regardless of its phenotype, the most significant independent predictors of the risk of incident T2DM are AO and fasting hyperglycaemia. In individuals without AO, the risk of developing T2DM does not increase, even with an increase in the number of MS components. In the presence of AO, the risk of developing T2DM increases 2 times already with the appearance of any other component.

Circulating osteocalcin levels were not significantly associated with the risk of incident type 2 diabetes mellitus in elderly Japanese men: The Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Cohort Study.

Cross-sectional studies have shown that patients with type 2 diabetes mellitus (T2DM) have low circulating levels of osteocalcin (OC) and undercarboxylated OC (ucOC). This longitudinal study aimed to examine whether low OC or ucOC levels at baseline are associated with the risk of incident T2DM. We examined 1700 community-dwelling Japanese men (≥65years) after excluding those with history of diseases (other than T2DM) or medications that affect bone and glucose metabolism. T2DM was defined as fasting plasma glucose (FPG) ≥126mg/dl or glycated hemoglobin A1c (HbA1c) ≥6.5%. Participants without prevalent T2DM at baseline were invited to follow-up surveys 5 and 10years after baseline. Among the participants, 309 with prevalent T2DM showed significantly lower serum OC and ucOC levels at baseline than those without. After excluding these participants, 46 and 57 participants with incident T2DM were identified in the first and second follow-up surveys, respectively. These participants did not show significantly different OC and ucOC levels at baseline relative to those without T2DM, although their FPG and HbA1c levels at baseline were significantly higher compared to those without incident T2DM. Increase in glycemic indices preceded decrease in OC and ucOC levels. OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM identified in the follow-up surveys. OC and ucOC levels at baseline were not significantly associated with the risk of incident T2DM. Our results do not support the findings of animal studies that ucOC is a hormone regulating glucose metabolism.

Association of metabolic score for insulin resistance and its 6-year change with incident type 2 diabetes mellitus.

The evidence for the association between metabolic score for insulin resistance (METS-IR) and type 2 diabetes mellitus (T2DM) is limited. We aimed to explore the association of METS-IR and its 6-year change with risk of incident T2DM in a rural Chinese population. We analyzed data for 12 107 participants (mean age 50.48 years). A Cox proportional-hazard model was used to estimate the association of METS-IR with incident T2DM by using hazard ratios (HRs) and 95% confidence intervals (CIs); a logistic regression model was used to assess the association of 6-year METS-IR change with incident T2DM by using odds ratios (ORs) and 95% CIs. We used subgroup analyses of the association of METS-IR and its 6-year change with incident T2DM by sex, age, and baseline fasting plasma glucose (FPG) level as well as restricted cubic splines to describe the dose-response association. The association of METS-IR and 6-year METS-IR change with incident T2DM was significant (per SD unit increase: HR=1.80, 95% CI: 1.60-2.02 for METS-IR, OR=1.42, 95% CI: 1.28-1.57 and OR=1.59, 95% CI: 1.44-1.76 for relative and absolute METS-IR change). The significant association remained on subgroup analyses by sex, age, and baseline FPG level. Dose-response analysis demonstrated that the probability of incident T2DM was significantly increased with increasing METS-IR and 6-year METS-IR change. Increased METS-IR and 6-year METS-IR change were positively associated with risk of incident T2DM in a rural Chinese population. METS-IR may be a vital indicator for identifying T2DM.

Association of mitochondrial DNA copy number with prevalent and incident type 2 diabetes in women: A population-based follow-up study

Mitochondrial dysfunction is an important factor of the aging process and may play a key role in various diseases. Mitochondrial DNA copy number (mtDNA-CN) is an indirect measure of mitochondrial dysfunction and is associated with type 2 diabetes mellitus (T2DM); however, whether mtDNA-CN can predict the risk of developing T2DM is not well-known. We quantified absolute mtDNA-CN in both prevalent and incident T2DM by well-optimized droplet digital PCR (ddPCR) method in a population-based follow-up study of middle aged (50–59 years) Swedish women (n = 2387). The median follow-up period was 17 years. Compared to those who were free of T2DM, mtDNA-CN was significantly lower in both prevalent T2DM and in women who developed T2DM during the follow-up period. Mitochondrial DNA-copy number was also associated with glucose intolerance, systolic blood pressure, smoking status and education. In multivariable Cox regression analysis, lower baseline mtDNA-CN was prospectively associated with a higher risk of T2DM, independent of age, BMI, education, smoking status and physical activity. Moreover, interaction term analysis showed that smoking increased the effect of low mtDNA-CN at baseline on the risk of incident T2DM. Mitochondrial DNA-copy number may be a risk factor of T2DM in women. The clinical usefulness of mtDNA-CN to predict the future risk of T2DM warrants further investigation.

The Risk of Type 2 Diabetes Mellitus in a Russian Population Cohort According to Data from the HAPIEE Project.

The aim of this study is to investigate the 14-year risk of type 2 diabetes mellitus (T2DM) and develop a risk score for T2DM in the Siberian cohort. A random population sample (males/females, 45–69 years old) was examined at baseline in 2003–2005 (Health, Alcohol, and Psychosocial Factors in Eastern Europe (HAPIEE) project, n = 9360, Novosibirsk) and re-examined in 2006–2008 and 2015–2017. After excluding those with baseline T2DM, the final analysis included 7739 participants. The risk of incident T2DM during a 14-year follow-up was analysed using Cox regression. In age-adjusted models, male and female hazard ratios (HR) of incident T2DM were 5.02 (95% CI 3.62; 6.96) and 5.13 (95% CI 3.56; 7.37) for BMI ≥ 25 kg/m2; 4.38 (3.37; 5.69) and 4.70 (0.27; 6.75) for abdominal obesity (AO); 3.31 (2.65; 4.14) and 3.61 (3.06; 4.27) for fasting hyperglycaemia (FHG); 2.34 (1.58; 3.49) and 3.27 (2.50; 4.26) for high triglyceride (TG); 2.25 (1.74; 2.91) and 2.82 (2.27; 3.49) for hypertension (HT); and 1.57 (1.14; 2.16) and 1.69 (1.38; 2.07) for family history of diabetes mellitus (DM). In addition, secondary education, low physical activity (PA), and history of cardiovascular disease (CVD) were also significantly associated with T2DM in females. A simple T2DM risk calculator was generated based on non-laboratory parameters. A scale with the best quality included waist circumference >95 cm, HT history, and family history of T2DM (area under the curve (AUC) = 0.71). The proposed 10-year risk score of T2DM represents a simple, non-invasive, and reliable tool for identifying individuals at a high risk of future T2DM.

Hypertriglyceridemic Waist Phenotype and Lipid Accumulation Product: Two Comprehensive Obese Indicators of Waist Circumference and Triglyceride to Predict Type 2 Diabetes Mellitus in Chinese Population.

Purpose To determine whether hypertriglyceridemic waist (HTGW) and high lipid accumulation product (LAP) preceded the incidence of type 2 diabetes mellitus (T2DM), and to investigate the interactions of HTGW and LAP with other components of metabolic syndrome on the risk of T2DM. Methods A total of 15,717 eligible participants without baseline T2DM and aged 35 and over were included from a Chinese rural cohort. Cox proportional hazards regression models were used to estimate the association of HTGW and LAP with the incidence of T2DM, and the restricted cubic spline model was used to evaluate the dose-response association. Results Overall, 867 new T2DM cases were diagnosed after 7.77 years of follow-up. Participants with HTGW had a higher hazard ratio for T2DM (hazard ratio (HR): 6.249, 95% confidence interval (CI): 5.199-7.511) after adjustment for potential confounders. The risk of incident T2DM was increased with quartiles 3 and 4 versus quartile 1 of LAP, and the adjusted HRs (95% CIs) were 2.903 (2.226-3.784) and 6.298 (4.911-8.077), respectively. There were additive interactions of HTGW (synergy index (SI): 1.678, 95% CI: 1.358-2.072) and high LAP (SI: 1.701, 95% CI: 1.406-2.059) with increased fasting plasma glucose (FPG) on the risk of T2DM. Additionally, a nonlinear (P nonlinear < 0.001) dose-response association was found between LAP and T2DM. Conclusion The subjects with HTGW and high LAP were at high risk of developing T2DM, and the association between LAP and the risk of T2DM may be nonlinear. Our study further demonstrates additive interactions of HTGW and high LAP with increased FPG on the risk of T2DM.

Historical exposure to non-persistent environmental pollutants and risk of type 2 diabetes in a Spanish sub-cohort from the European Prospective Investigation into Cancer and Nutrition study

BackgroundEnvironmental factors are believed to account for a substantial burden of type 2 diabetes mellitus (T2DM). Non-persistent environmental pollutants (npEPs) are a group of widely-used chemicals identified as endocrine/metabolic disrupting chemicals and obesogens. The aim of this study was to analyse the potential associations of serum levels of three groups of npEPs with the risk of incident T2DM. MethodsThis is a longitudinal study within a sub-sample of Granada EPIC-Spain cohort (n = 670). We quantified serum concentrations of 7 npEPs: four parabens (Methylparaben (MP) ethylparaben (EP), propylparaben (PP) and butilparaben (BP); two benzophenones: Benzophenone 1 (BP1), Benzophenone 3 (BP3); and Bisphenol A (BPA). Exposure was assessed by means of chemical analyses of serum samples collected at recruitment, and information on potential confounders was gathered by using validated questionnaires at baseline. Follow-up was performed by review of patients’ clinical records. Cox Proportional Hazards Models were used for the statistical analyses. ResultsMedian follow-up time was 23 years. There were 182 (27%) incident T2DM diagnoses in our sub-cohort. MP was the most frequently detected npEP, 88.42% samples above the limit of detection, and BP showed the lowest percentage of detection (19.21%). Those individuals within the fourth PP quartile (0.53–9.24 ng/ml) showed a statistically significant increased risk of T2DM (HR = 1.668 p = 0.012), while BP1 concentrations showed an inverse non-significant trend with the risk. ConclusionsWe evidenced a potential contribution of npEP exposure on T2DM, but no clear trend was observed. However, limitations in relation to exposure estimation might influence our findings and further research is warranted to confirm our results.