Risk Of Incident Type 2 Diabetes Research Articles

Long-term lifestyle change and risk of mortality and Type 2 diabetes in patients with cardiovascular disease.

To quantify the relationship between self-reported, long-term lifestyle changes (smoking, waist circumference, physical activity, and alcohol consumption) and clinical outcomes in patients with established cardiovascular disease (CVD). Data were used from 2011 participants (78% male, age 57 ± 9 years) from the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease cohort who returned for a re-assessment visit (SMART2) after ∼10 years. Self-reported lifestyle change was classified as persistently healthy, improved, worsened, or persistently unhealthy. Cox proportional hazard models were used to quantify the relationship between lifestyle changes and the risk of (cardiovascular) mortality and incident Type 2 diabetes (T2D). Fifty-seven per cent of participants was persistently healthy, 17% improved their lifestyle, 8% worsened, and 17% was persistently unhealthy. During a median follow-up time of 6.1 (inter-quartile range 3.6-9.6) years after the SMART2 visit, 285 deaths occurred, and 99 new T2D diagnoses were made. Compared with a persistently unhealthy lifestyle, individuals who maintained a healthy lifestyle had a lower risk of all-cause mortality [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.36-0.63], cardiovascular mortality (HR 0.57, 95% CI 0.38-0.87), and incident T2D (HR 0.46, 95% CI 0.28-0.73). Similarly, those who improved their lifestyle had a lower risk of all-cause mortality (HR 0.52, 95% CI 0.37-0.74), cardiovascular mortality (HR 0.46, 95% CI 0.26-0.81), and incident T2D (HR 0.50, 95% CI 0.27-0.92). These findings suggest that maintaining or adopting a healthy lifestyle can significantly lower mortality and incident T2D risk in CVD patients. This study emphasizes the importance of ongoing lifestyle optimization in CVD patients, highlighting the potential for positive change regardless of previous lifestyle habits.

Circulating organochlorine pesticide levels, genetic predisposition and the risk of incident type 2 diabetes

Persistent organochlorine pesticide (OCP) has been associated with type 2 diabetes (T2D), and genetic polymorphism might modify such an association. However, prospective evidence remains scarce. We conducted a nested case-control study comprising 1006 incident diabetic cases and 1006 matched non-diabetic controls [sex and age (±5 years)] from 2008 to 2013 (mean follow-up period: ∼4.6 years) based on the Dongfeng-Tongji cohort in Shiyan City of China, determined baseline levels of nineteen OCPs, and examined the associations of circulating OCPs, both individually and collectively, with incident T2D risk. We also constructed overall genetic risk score (GRS) based on 161 T2D-associated variants and five pathway-specific cluster GRSs based on established variants derived from the Asian population. Compared with the first quartile of serum β-BHC levels, the multivariable-adjusted ORs (95% CIs) of incident T2D risk in the second, third, and fourth quartiles were 0.98 (0.70–1.39), 1.43 (0.99–2.07), and 1.75 (1.14–2.68), respectively (FDR-adjusted Ptrend = 0.03). A positive association was observed between serum OCP mixture and incident T2D risk and can be largely attributed to β-BHC. Furthermore, serum β-BHC and p,p’-DDE showed significant interactions with the GRS for lipodystrophy, a T2D-related pathway representing fat redistribution to viscera, on T2D risk (Pinteraction < 0.05). In conclusion, higher circulating OCP levels were independently associated with an increased risk of T2D, with β-BHC possibly being the major contributor. Genetic predisposition to T2D-related morbidity, such as visceral adiposity, should be considered when assessing the risk of T2D conferred by OCPs.

Association between dietary carbohydrate intake and risk of type 2 diabetes: a systematic review and meta-analysis of cohort studies.

Previous meta-analyses have assessed the relationship between carbohydrate intake and type 2 diabetes (T2D) risk; however, they included few studies of Asian populations who have a higher carbohydrate intake and lower insulin secretory capacity than non-Asians. Since the publication of the previous meta-analyses, three further studies of Asian populations have been conducted. Based on this background, the present study aimed to perform an updated systematically examine observational studies concerning the link between dietary carbohydrate intake and T2D risk. We conducted a systematic search for cohort studies that investigated the target association. For each analyzed study, parameter-adjusted risk ratios were used to compare the lowest and highest carbohydrate-intake groups in terms of their risk of incident T2D. The risk ratios were calculated using a random-effects model. Ten publications were analyzed. Overall, carbohydrate intake was found not to be associated with increased risk ratios of incident T2D (risk ratio [RR] = 1.07; 95% confidence interval [95% CI] = 0.94, 1.21; P < 0.01, I2 = 61.9%). However, studies of Asian populations reported that high carbohydrate intake is significantly associated with this risk (RR = 1.29; 95% CI 1.15, 1.45; P = 0.59, I2 = 0.0%). This updated meta-analysis showed that, overall, carbohydrate intake is not associated with the risk of T2D; nevertheless, a significant association exists among Asian populations. To confirm the association between dietary carbohydrate intake and T2D risk observed in this study, further evidence from long-term observational studies of Asian populations is required. The online version contains supplementary material available at 10.1007/s13340-023-00642-0.

1376-P: Dietary Sodium Intake and Risk of Incident Type 2 Diabetes

Background: Type 2 Diabetes (T2D) and hypertension often coexist and share many common risk factors. High dietary sodium intake is a well-established risk factor for hypertension, whereas few studies have assessed the relation between dietary sodium intake and type 2 diabetes (T2D). In this study, we aimed to evaluate the association between the frequency of adding salt to foods, a surrogate marker for evaluating the long-term sodium intake, and incident T2D risk. Methods: A total of 402,982 participants from UK biobank, who were free of diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline, and had completed information on adding salt were analyzed in this study. Cox proportional hazards models were used to estimate the association between the frequency of adding salt to foods and incident T2D. Results: During a median of 11.8 years of follow-up, 13,120 incident T2D were documented. Compared with participants who Never/Rarely added salt to foods, the adjusted Hazard Ratios (95% confidence interval) were 1.13 (1.08, 1.17), 1.20 (1.14, 1.26), and 1.39 (1.30, 1.49) across the groups of Sometimes, Usually, and Always, respectively (P-trend&amp;lt;0.001). We did not find significant interactions between the frequency of adding salt to foods and baseline hypertension status and other covariates on the risk of incident T2D. The observed positive association was partly mediated by body mass index (BMI), waist to hip ratio, and C-reactive protein, with a significant mediation effect of 32.9%, 36.6% and 7.0%, respectively. The significant mediation effect of BMI was largely driven by the body fat mass rather than the body fat-free mass. Conclusions: Our findings for the first time indicate that higher frequency of adding salt to foods, a surrogate marker for a person’s long-term salt taste preference and intake, is associated with a higher T2D risk. Disclosure X.Wang: None. H.Ma: None. R.Tang: None. Q.Xue: None. X.Li: None. Y.Heianza: None. L.Qi: None.

Gene-environment interaction in long-term effects of polychlorinated biphenyls exposure on glucose homeostasis and type 2 diabetes: The modifying effects of genetic risk and lifestyle

The longitudinal relationships of polychlorinated biphenyls (PCBs) exposure with glucose homeostasis and type 2 diabetes (T2D) risk among Chinese population have not been assessed, and interactions of PCB exposure with genetic susceptibility and lifestyle are unclear. In this prospective cohort study, fasting plasma glucose (FPG) and insulin (FPI) and seven serum indicator-PCBs were measured for each participant. We constructed polygenic risk score (PRS) of T2D and healthy lifestyle score. Each 1-unit increment of ln-transformed PCB-118 was related with a 0.141 mmol/L, 11.410 pmol/L, 0.661, and 74.5% increase in FPG, FPI, homeostasis model assessment of insulin resistance, and incident T2D risk over 6 years, respectively. Each 1-unit increment in T2D-PRS was related with a 0.169 mmol/L elevation of FPG and 65.5% elevation of incident T2D risk during 6 years. Compared with participants who had low T2D-PRS and low PCB-118, participants with high T2D-PRS and high PCB-118 showed a significant increase in FPG (0.162 mmol/L; P for interaction <0.001) and incident T2D risk [hazard ratio (HR)= 2.222]. Participants with low PCB-118, low PRS, and healthy lifestyle had the lowest incident T2D risk (HR=0.232). Our findings highlighted the significance of reducing PCB exposure and improvement in lifestyle for T2D prevention and management, especially for individuals with higher genetic risk of T2D.

Mediation of metabolic syndrome in the association between long-term co-exposure to road traffic noise, air pollution and incident type 2 diabetes

ObjectivesRecent studies have linked exposure to road traffic noise or air pollution with incident type 2 diabetes (T2D), but investigation on their co-exposure was limited and underlying mechanisms remain unclear. We hypothesized that long-term co-exposure to road traffic noise and air pollution increases the risk of incident T2D via the development of metabolic syndrome (MetS). MethodsThis prospective study included 390,834 participants in UK Biobank. Cumulative risk index (CRI), the health-based weighted levels of multiple exposures, was applied to characterize the co-exposure to 24-hour road traffic noise (Lden), particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5), and nitrogen dioxide (NO2). Lden was modeled by the Common Noise Assessment Methods in Europe and air pollutant levels were measured by the Land Use Regression model at participants’ residential addresses. Incident T2D was ascertained through linkages to inpatient hospital records. MetS was defined by five (central obesity, triglycerides, HDL cholesterol, glucose, and blood pressure) or six factors (C-reactive protein additionally). Cox proportional hazard models were used to assess the association between environmental exposures and incident T2D, and mediation analyses were applied to investigate the role of MetS. ResultsAfter a median of 10.9 years of follow-up, 13,214 (3.4%) incident T2D cases were ascertained. The exposure to Lden, PM2.5, and NO2, as well as their co-exposure, were significantly associated with an elevated risk of incident T2D, with HRs of 1.03 (95%CI: 1.00, 1.05) per 3.5 dB(A) increase in Lden, 1.05 (95%CI: 1.01, 1.10) per 1.3 μg/m3 increase in PM2.5, 1.07 (95%CI: 1.02, 1.11) per 9.8 μg/m3 increase in NO2, and 1.06 (95%CI: 1.02, 1.09) per interquartile range increase in CRI. MetS significantly mediated 43.5%− 54.7% of the CRI-T2D relationship. ConclusionsLong-term co-exposure to road traffic noise and air pollution is associated with an elevated risk of incident T2D, which may partly be mediated by MetS.

Diurnal Cortisol Features and Type 2 Diabetes Risk in Patients With Hypertension and Obstructive Sleep Apnea: A Cohort Study.

The hypothalamic-pituitary-adrenal (HPA) axis may be associated with type 2 diabetes (T2D); however, whether HPA axis dysfunction is associated with incident T2D remains unclear in patients with hypertension and obstructive sleep apnea (OSA). To investigate the relationship between the diurnal cortisol features and the risk of incident T2D in patients with hypertension and OSA. Participants with cortisol rhythm test at baseline in the Urumqi Research on Sleep Apnea and Hypertension cohort were enrolled. The Cox regression model was used to evaluate the relationship between ln-transformed diurnal cortisol features and T2D risk. Stratified and sensitivity analyses were also performed. A total of 1478 patients with hypertension and OSA were enrolled in this study. During a median follow-up of 7.0 years, 196 participants developed T2D. Overall, a steep diurnal cortisol slope (DCS) was significantly associated with decreased T2D risk (per SD increase, HR 0.88, 95% CI 0.79-0.97, P = .014). Midnight cortisol was positively associated with increased T2D risk (per SD increase, HR 1.25, 95% CI 1.08-1.45, P = .003). Sensitivity analyses showed similar results. Neither DCS nor midnight cortisol was associated with incident T2D in the women's subgroup or participants with mild OSA. Steeper DCS and higher midnight cortisol levels are associated with lower and higher T2D risks in patients with hypertension and OSA, respectively, at least in men or participants with moderate to severe OSA. Diurnal cortisol features may represent an early prevention target for diabetes in this population.

A polygenic and family risk score are both independently associated with risk of type 2 diabetes in a population-based study

The availability of polygenic scores for type 2 diabetes (T2D) raises the question, whether assessing family history might become redundant. However, family history not only involves shared genetics, but also shared environment. It was the aim of this study to assess the independent and combined effects of one family risk score (FamRS) and a polygenic score (PGS) on prevalent and incident T2D risk in a population-based study from Germany (n = 3071). The study was conducted in 2004/2005 with up to 12 years of follow-up. The FamRS takes into account not only the number of diseased first grade relatives, but also age at onset of the relatives and age of participants. 256 prevalent and additional 163 incident T2D cases were recorded. Prevalence of T2D increased sharply for those within the top quantile of the PGS distribution resulting in an OR of 19.16 (p < 2 × 10–16) for the top 20% compared to the remainder of the population, independent of age, sex, BMI, physical activity and FamRS. On the other hand, having a very strong family risk compared to average was still associated with an OR of 2.78 (p = 0.001), independent of the aforementioned factors and the PGS. The PGS and FamRS were only slightly correlated (r2Spearman = 0.018). The combined contribution of both factors varied with varying age-groups, though, with decreasing influence of the PGS with increasing age. To conclude, both, genetic information and family history are relevant for the prediction of T2D risk and might be used for identification of high risk groups to personalize prevention measures.

Abstract 66: Clonal Hematopoiesis of Indeterminate Potential and Incident Type 2 Diabetes Risk

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is an aging-related accumulation of somatic mutations in hematopoietic stem cells, leading to clonal expansion. CHIP presence has been implicated in elevated risks for coronary heart disease (CHD) and death, but its association with incident type 2 diabetes (T2D) is unknown. Hypothesis: We hypothesized that CHIP is associated with elevated risk of incident T2D. Methods: CHIP was derived from whole genome sequencing of blood DNA in NHLBI Trans-omics for Precision Medicine (TOPMed) cohorts. We analyzed 17,637 participants without prior T2D, cardiovascular disease, or cancer at blood draw, with prospective follow-up for incident T2D. We evaluated baseline prevalence of CHIP vs. no CHIP with incident T2D risk using Cox regression. We also investigated CHIP variants previously related to CHD: DNMT3A , TET2 , ASXL1 , JAK2 , and TP53 . We estimated multivariable-adjusted hazard ratios and 95% confidence intervals (HR [CI]) adjusted for age, sex, body mass index, smoking, alcohol, and education. We combined cohort estimates via fixed effects meta-analysis. Results: On average, participants were age 63.4 years (SD=11.5) and 76% female. Prevalence of CHIP was 6.0% (1,055) at baseline. There were 2,467 incident T2D cases over mean=9.8 years follow-up. Compared to those without a mutation, having CHIP was associated with a 23% higher T2D risk, both overall (combined HR=1.23; 95% CI=1.04, 1.45), and among those with CHD-related CHIP mutations (87% of total CHIP): HR=1.23 (1.03, 1.46). Although those with CHIP mutations of TET2 (HR=1.48; 1.05, 2.08) and ASXL1 (HR=1.76; 1.03, 2.99) had larger elevations in T2D risk, and DNMT3A was suggestive of increased T2D risk (HR=1.15; 0.93, 1.43), statistical power was limited for JAK2 and TP53 mutation analyses. Conclusions: CHIP was associated with higher incidence of T2D. CHIP mutations located on loci previously implicated in aging and CHD were also related to T2D, suggesting shared pathology of atherosclerosis and T2D.

Abstract P346: Adherence to the French Dietary Guidelines and Type 2 Diabetes Risk: The E3n-Epic Prospective Cohort Study

Background: Recently, a dietary index reflecting adherence to the 2017 French food-based dietary guidelines, the Programme National Nutrition Santé - guidelines score 2 (PNNS-GS2), has been developed, but evidence on its level of adherence and incident type 2 diabetes (T2D) risk is limited. Objective: We aimed to investigate the association between adherence to the simplified PNNS-GS2 (sPNNS-GS2) and the risk of incident T2D in a French cohort of women. Methods: Between 1993 and 2014, 71,450 women aged over 18 years were examined, and thereafter followed up for the occurrence of T2D within the E3N-EPIC prospective cohort. Dietary data were collected at baseline via a food frequency questionnaire, and the sPNNS-GS2 was derived for each participant. Multivariable Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of T2D for continuous and quintile groups of the sPNNS-GS2. Effect modification by body mass index (BMI) and mediation by BMI and waist-hip ratio (WHR) were explored. Results: The mean age was 52.9 years (SD 6.7). During a mean follow-up of 19 years, 3679 incident T2D cases were identified and validated. There was a linear association between adherence to sPNNS-GS2 and T2D risk (P non-linear = 0.85). In the fully adjusted model, each 1-SD increase in the sPNNS-GS2 was associated with a 8% decrease risk of T2D [HR (95% CI), 0.92 (0.89, 0.95)]. Compared to those with the lowest adherence (first quintile), the third [HR (95% CI), 0.91 (0.82, 1.00)] up to the fifth quintile group [HR (95% CI), 0.79 (0.71, 0.88)] had a lower T2D risk. There was a sPNNS-GS2 x BMI interaction on T2D risk (P interaction &lt; 0.01) but not with WHR. The overall association was partly mediated by BMI (18%) and WHR (59%). Conclusion: Higher adherence to the 2017 French food-based dietary guidelines was associated with a lower risk of T2D in women. Furthermore, our mediation analysis suggests that the lower risk of T2D in women associated with adherence to the sPNNS-GS2 is partly mediated by obesity measured by BMI or WHR.

Abstract P152: Joint Association of Sugar- and Artificially-Sweetened Beverage Consumption and Physical Activity and Risk of Type 2 Diabetes in US Adults

Background: Consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) and physical activity are independently associated with type 2 diabetes (T2D) risk; however, it is unknown whether there is an interaction of SSB/ASB intake and physical activity on risk of T2D. Methods: We examined the independent and joint associations between habitual SSB/ASB intake and physical activity with incident T2D risk among 196,101 women and men from the Nurses’ Health Study (NHS, 1980-2016), NHSII (1991-2017), and Health Professional’s Follow-up Study (HPFS, 1986-2016), who were free from chronic diseases at baseline. Cox proportional hazards regressions were used to estimate hazard ratios and 95% confidence intervals (HR; CI), adjusting for demographic and lifestyle T2D risk factors. Results: There were 20,430 incident T2D cases over follow-up of 36, 26, and 30 years in NHS, NHSII, and HPFS, respectively. In multivariable-adjusted models, we confirmed that participants with higher SSBs, ASBs and lower physical activity were independently at higher T2D risk, compared to lower intakes and higher activity levels. In joint analyses for these exposures, participants who did not meet physical activity guidelines and consumed gt 2 servings/day of SSBs had a significantly higher risk of T2D than those who met physical activity guidelines and never/rarely consumed SSBs (1.51; 1.43, 1.60); we observed similar findings for ASBs: 1.29; 1.23, 1.36). Among participants who met physical activity guidelines, those who consumed gt 2 servings/day of SSBs had a HR of 1.23 (1.16, 1.30); the HR for ASBs was 1.07 (1.02, 1.13). Consistent results were observed for women and men. Conclusions: Long-term habitual intake of SSBs or ASBs combined with lower physical activity was associated with higher risk of T2D in three large prospective cohort studies. These findings suggest that even when individuals are physically active, higher consumption of SSBs is associated with a higher risk of T2D. Our results support recommendations and policies to limit the intake of SSB and increase physical activity levels.

Adherence to the EAT-Lancet diet, genetic susceptibility, and risk of type 2 diabetes in Swedish adults

Background and aimsIn 2019, the EAT-Lancet Commission proposed a mainly plant-based diet that nurtures human health and supports environmental sustainability. However, its association with type 2 diabetes (T2D) has not been widely studied, and it remains unclear whether genetic susceptibility for T2D can modify this association. The aim was therefore to investigate the association between the EAT-Lancet diet and risk of T2D and assess whether the association differs by the genetic predisposition to T2D. MethodsA total of 24,494 participants from the Malmö Diet and Cancer study were analyzed. Dietary intake was assessed using a modified diet history methodology, and an EAT-Lancet diet index (range from 0 to 42 points) was constructed based on the EAT-Lancet reference diet. National and local registers were used to identify T2D cases during follow-up. Cox proportional hazards regression model was applied to estimate the association between the EAT-Lancet diet index and risk of T2D. Genetic predisposition to T2D was captured based on 116 single nucleotide polymorphisms. ResultsDuring a median of 24.3 years of follow-up, 4197 (17.1 %) T2D cases were documented. Compared with those with the lowest adherence to the EAT-Lancet diet (≤13 points), participants who had the highest adherence (≥23 points) showed an 18 % (95 % CI: 4 %–30 %) lower risk of T2D (P for trend <0.01). There was no significant multiplicative interaction between genetic predisposition to T2D and the EAT-Lancet diet index (P = 0.59). Also, no significant additive interaction between the genetic risk and the EAT-Lancet diet was seen (P = 0.44). The highest risk was observed among the 22.9 % of the individuals with high genetic risk and low EAT-Lancet diet score (HR = 1.79; 95 % CI: 1.63, 1.96). ConclusionsOur findings indicate that high adherence to the EAT-Lancet diet was associated with decreased risk of incident T2D among people with different genetic risks.

Associations of residential green space with incident type 2 diabetes and the role of air pollution: A prospective analysis in UK Biobank

BackgroundGreen space is a newly modifiable environmental factor which would bring health benefits, and identifying potential pathways is important to better promote public health. Nowadays, limited evidence is available on residential green space and risk of incident type 2 diabetes (T2D). To evaluate the longitudinal association between residential green space and incident T2D, and further illustrate the role of air pollution, we conducted a prospective analysis in UK Biobank. MethodsIncident cases of T2D were ascertained through medical linkage of hospital admissions. Residential green space indicated by percentage of green space at 300 m buffer was estimated using land use data. Annual average air pollution was modelled using Land Use Regression model. Cox proportional hazard regression models were used to determine the association between the exposure and incident T2D. Effect modification of air pollution was assessed using log-likelihood tests. Casual mediation analysis including interaction of green space and air pollution was used to quantity pure natural indirect effect of air pollution. ResultsOf 379,238 participants at baseline, 15564 incident T2D cases were identified with 12.4 years of follow-up. In main models, individuals who exposed to residential green space at 300 m buffer in high level (≥75 %) had 14.4 % (95 % CI: 8.0 %, 20.3 %) lower risk of incident T2D compared with those in low level (<25 %). This association was modified by NO2, with green space indicating higher protective effect in low NO2 level (Pinteraction = 0.098). PM2.5 had a high mediation effect of 37.0 % in the association. ConclusionElevated residential green space level was associated with lower risk of incident T2D, and air pollution played an important role in this association. These findings would contribute to policy making and healthy city construction to take air pollution into consideration while planning green space, which would maximize public health benefits.

Dairy intake and risk of type 2 diabetes: results of a large prospective cohort.

Background and aims: Previous studies of primarily Western populations have consistently documented a lower risk of type 2 diabetes (T2D) among people with a higher yogurt intake, but an inconsistent association with milk intake. However, little is known about the association between dairy intake and risk of T2D among Chinese adults who consume considerably less dairy (mainly milk and yogurt) compared with Western populations. The aim is to investigate the associations of dairy intake with the risk of incident T2D in the general adult population in China. Methods: This cohort study consisted of 22 843 participants without prevalent cardiovascular disease, cancer, or diabetes at the baseline. Dietary data were collected using a validated food frequency questionnaire at the baseline (2013-2018); dairy intake was categorized into tertiles after zero consumers were taken as the reference. Incident T2D was ascertained by medical examinations and self-report of physician-diagnosed diabetes during follow-up visits. Cox proportional hazards models were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: In total, 735 incident T2D cases were recorded over a median follow-up of 4.0 years. Relative to zero consumers, the HRs (95% CIs) for incident T2D among participants in the highest tertiles were 0.70 (0.57, 0.87) for total dairy, 0.73 (0.60, 0.90) for milk, and 0.81 (0.66, 1.00) for yogurt. Such associations were slightly attenuated by additional adjustment for the body mass index. In addition, such inverse associations were robust in sensitivity analyses and consistent in most of the subgroups defined by baseline characteristics. Conclusion: Higher intakes of total dairy, milk, and yogurt were all associated with a lower risk of T2D among Chinese adults.

Circulating FGF21 Concentration, Fasting Plasma Glucose, and the Risk of Type 2 Diabetes: Results From the PREVEND Study.

Fibroblast growth factor 21 (FGF21) is a peptide hormone synthesized by several organs and regulates, among others, energy homeostasis. In obesity, insulin resistance and type 2 diabetes (T2D), higher circulating FGF21 concentrations have been found. Temporal analyses in murine studies demonstrate that FGF21 increases before insulin resistance occurs. The current study aims to investigate in time-to-event analyses whether FGF21 may be an early biomarker in the development of T2D. Circulating FGF21 was measured using an immunoassay of the Mesoscale U-PLEX assay platform. The study outcome was incident T2D. Associations of circulating FGF21 concentration with T2D were quantified using Cox proportional hazards models with adjustments for potential confounders. We included 5244 participants aged 52 ± 12 years, of whom 50% were male. Median [interquartile range] circulating FGF21 concentration was 860 [525-1329] pg/mL. During 7.3 [6.1-7.7] years of follow-up, 299 (5.7%) participants developed T2D. In fully adjusted analyses, higher circulating FGF21 concentration was associated with an increased risk of incident T2D (hazard ratio per doubling: 1.26 [95% CI, 1.06-1.51]; P = 0.008), with effect modification by fasting plasma glucose, consistent with strengthening of the association at lower fasting glucose (interaction coefficient: -0.12; P = 0.022). Higher circulating FGF21 concentrations are independently associated with an increased risk of incident T2D in participants with a low fasting plasma glucose, making circulating FGF21 concentration a potential early biomarker for type 2 diabetes.

Remnant Cholesterol Is an Independent Predictor of Type 2 Diabetes: A Nationwide Population-Based Cohort Study.

Although the atherogenic effect of remnant cholesterol (remnant-C) has been widely recognized, the relationship between remnant-C and glucose metabolism remains unclear. This retrospective, longitudinal study investigated the relationship between remnant-C and incident type 2 diabetes (T2D) in a nationwide cohort of Korean adults. A total of 8,485,539 Korean adults without diabetes participated in the national health screening in 2009 and were followed up until 2019. The relationship between remnant-C quartiles and incident T2D was examined by Cox regression models. The risk of incident T2D over the continuum of remnant-C was examined with cubic spline analysis. During the median follow-up period of 9.28 years, 584,649 individuals (6.8%) developed T2D. In multivariable-adjusted analyses, participants in the upper quartile of remnant-C had a higher risk of T2D, with hazard ratios of 1.25 (95% CI 1.24-1.27) in the second quartile, 1.51 (95% CI 1.50-1.53) in the third quartile, and 1.95 (95% CI 1.93-1.97) in the fourth quartile, compared with the lowest quartile. The increase in the risk of T2D owing to high remnant-C concentration was more profound in individuals with fewer traditional T2D risks, such as women, and absence of metabolic abnormalities, including impaired fasting glucose, hypertension, and atherogenic dyslipidemia. Moreover, the magnitude of the increased risk for incident T2D in individuals with higher remnant-C quartiles was higher in younger participants than older participants. These findings indicate that remnant-C profiles provide additional information in predicting future progression of T2D, independent of the conventional lipid parameters.

Vegetable, but Not Potato, Intake Is Associated With a Lower Risk of Type 2 Diabetes in the Danish Diet, Cancer and Health Cohort.

To examine the relationship between intake of vegetables/potatoes and incident type 2 diabetes (T2D) and explore whether the relationship between vegetable intake and incident T2D is mediated by baseline BMI. Cross-sectional associations between exposure (baseline intake of total vegetables, vegetable subgroups, and potatoes) and baseline BMI were assessed by multivariable-adjusted linear regression models. Associations between exposure and incident T2D were examined by multivariable-adjusted Cox proportional hazards models. Mediation by BMI was quantified through exploration of natural direct and indirect effects. Among 54,793 participants in the Danish Diet, Cancer and Health cohort, 7,695 cases of T2D were recorded during a median follow-up of 16.3 years. Participants in the highest total vegetable intake quintile (median 319 g/day) had a 0.35 kg/m2 (95% CI -0.46, -0.24) lower BMI and a 21% (95% CI 16, 26%) lower risk of incident T2D after multivariable adjustment compared with those in the lowest quintile (median 67 g/day). Baseline BMI mediated ∼21% of the association between vegetable intake and incident T2D. Participants in the highest compared with the lowest (median 256 vs. 52 g/day) potato intake quintile had a 9% (95% CI 2, 16%) higher risk of T2D after multivariable adjustment, with no association found after accounting for underlying dietary pattern. Of the vegetable subclasses, higher intake of green leafy and cruciferous vegetables was associated with a statistically significantly lower risk of T2D. The findings provide evidence that a higher vegetable, but not potato, intake might help mitigate T2D risk, partly by reducing BMI.

Cumulative Consumption of Sulfur Amino Acids and Risk of Diabetes: A Prospective Cohort Study

Cross-sectional studies have suggested that consumption of sulfur amino acids (SAAs), including methionine and cysteine, is associated with a higher risk of type 2 diabetes (T2D) in humans and with T2D-related biomarkers in animals. But whether higher long-term SAA intake increases the risk of T2D in humans remains unknown. We aimed to investigate the association between long-term dietary SAA intake and risk of T2D. We analyzed data collected from 2 different cohorts of the Framingham Heart Study, a long-term, prospective, and ongoing study. The Offspring cohort (1991-2014) included participants from fifth through ninth examinations, and the Third-Generation cohort (2002-2011) included participants from first and second examinations. After excluding participants with a clinical history of diabetes, missing dietary data, or implausible total energy intake, 3222 participants in the Offspring cohort and 3205 participants in the Third-Generation cohort were included. Dietary intake was assessed using a validated FFQ. The relations between energy-adjusted total SAA (methionine and cysteine) intake or individual SAA intake (in quintiles) and risk of incident T2D were estimated via Cox proportional hazards models after adjusting for dietary and nondietary risk factors. Associations across the 2 cohorts were determined by direct combination and meta-analysis. During the 23 y of follow-up, 472 participants reported a new diagnosis of T2D in the 2 cohorts. In the meta-analysis, the HRs of T2D comparing the highest with the lowest intake of total SAAs, methionine, and cysteine were 1.8 (95% CI: 1.3, 2.5), 1.7 (95% CI: 1.2, 2.3), and 1.4 (95% CI: 1.0, 2.1), respectively. The association of SAA intake with T2D was attenuated after adjusting animal protein intake in sensitivity analyses. Our findings show that excess intake of SAAs is associated with higher risk of T2D. Dietary patterns that are low in SAAs could help in preventing T2D.

Whole fresh fruit intake and risk of incident diabetes in different glycemic stages: a nationwide prospective cohort investigation

PurposeFruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities.MethodsThe present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose–response relation.ResultsDuring a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949–0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766–0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957–4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368–0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762–1.023]).ConclusionThese findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

Stair climbing, genetic predisposition, and the risk of incident type 2 diabetes: A large population-based prospective cohort study

BackgroundCross-sectional evidence and small-scale trials suggest positive effects of stair climbing on cardiometabolic disease and glucose regulation. However, few studies have examined the long-term association between stair climbing and the incidence of type 2 diabetes (T2D). We aimed to prospectively evaluate the association of stair climbing with T2D and assess modifications by genetic predisposition to T2D. MethodsWe included 451,699 adults (mean age = 56.3 ± 8.1 years, mean ± SD; 55.2% females) without T2D at baseline in the UK Biobank and followed up to March 31, 2021. Stair climbing information was collected through the touchscreen questionnaire. Genetic risk score for T2D consisted of 424 single nucleotide polymorphisms. ResultsDuring a median follow up of 12.1 years, 14,896 T2D cases were documented. Compared with participants who reported no stair climbing, those who climbed stairs regularly had a lower risk of incident T2D (10–50 steps/day: hazard ratio (HR) = 0.95, 95% confidence interval (95%CI): 0.89–1.00; 60–100 steps/day: HR = 0.92, 95%CI: 0.87–0.98; 110–150 steps/day: HR = 0.86, 95%CI: 0.80–0.91; >150 steps/day: HR = 0.93, 95%CI: 0.87–0.99, p for trend = 0.0007). We observed a significant interaction between stair climbing and genetic risk score on the subsequent T2D risk (p for interaction = 0.0004), where the risk of T2D showed a downward trend in subjects with low genetic risk and those who reported stair climbing activity of 110–150 steps/day appeared to have the lowest overall T2D risk among those with intermediate to high genetic risk. ConclusionA higher number of stairs climbed at home was associated with lower T2D incidence risk, especially among individuals with a low genetic predisposition to T2D. These findings highlight that stair climbing, as incidental physical activity, offers a simple and low-cost complement to public health interventions for T2D prevention.