Reproductive factors, genetic susceptibility and risk of type 2 diabetes: A prospective cohort study.

AIM: To explore the relationships of multiple reproductive factors with type 2 diabetes mellitus (T2DM) risk and the joint effects of reproductive factors and genetic susceptibility. METHODS: We included 262,368 women without prevalent T2DM from the UK biobank. Cox proportional hazards regression models were employed to estimate the relationships of reproductive factors with T2DM risk and the joint effects of reproductive factors and genetic susceptibility. RESULTS: During a mean follow-up of 12.2 years, 8,996 T2DM cases were identified. Early menarche (< 12 years, hazard ratio (HR) 1.08 [95% confidence interval (CI) 1.02;1.13]), late menarche (≥ 15 years, HR 1.11 [1.04;1.17]), early menopause (< 45 years, HR 1.20 [1.12;1.29]), short reproductive lifespan (< 30 years, HR 1.25 [1.16;1.35]), hysterectomy (1.31, HR [1.23;1.40]), oophorectomy (HR 1.28 [1.20;1.36]), high parity (≥ 4, HR 1.25 [1.17;1.34]), early age at first live birth (< 20 years, HR 1.23 [1.16;1.31]), miscarriage (HR 1.13 [1.07;1.19]), stillbirth (HR 1.14 [1.03;1.27]), and ever used hormonal replacement therapy (HR 1.19 [1.14;1.24]) were related to a higher T2DM risk, while ever used oral contraceptives (HR 0.93 [0.89;0.98]) was related to a lower T2DM risk. Furthermore, women with reproductive risk factors and high genetic risk had the highest T2DM risk compared to those with low genetic risk and without reproductive risk factors. CONCLUSION: Our findings show that multiple reproductive factors are related to T2DM risk, particularly in women with high genetic risk.

Association between essential metals, adherence to healthy lifestyle behavior, and ankle-brachial index.

BACKGROUND: Ankle-brachial index (ABI) is a noninvasive diagnostic method for peripheral arterial disease (PAD) and a predictor of cardiovascular events. OBJECTIVE: The present study aimed to evaluate the association between individual or combined essential metals and ABI, as well as assess the collective impact of essential metals when coupled with healthy lifestyle on ABI. METHODS: A total of 2865 participants were recruited in Wuhan Tongji Hospital between August 2018 and March 2019. Concentrations of essential metals in urine were measured by inductively coupled plasma mass spectrometer. RESULTS: The results of general linear regression models demonstrated that after adjusting for confounding factors, there was a positive association between ABI increase and per unit increase of log 10-transformed, creatinine-corrected urinary Cr (ß (95 % CI): 0.010 (0.004, 0.016), PFDR = 0.007), Fe (ß (95 % CI): 0.010 (0.003, 0.017), PFDR = 0.018), and Co (ß (95 % CI): 0.013 (0.005, 0.021), PFDR = 0.007). The WQS regression revealed a positive relationship between the mixture of essential metals and ABI (ß (95 % CI): 0.006 (0.003, 0.010), P < 0.001), with Cr and Co contributing most to the relationship (weighted 45.48 % and 40.14 %, respectively). Compared to individuals with unfavorable lifestyle and the lowest quartile of Cr, Fe and Co, those with favorable lifestyle and the highest quartile of Cr, Fe and Co exhibited the most increase in ABI (ß (95 % CI): 0.030 (0.017, 0.044) for Cr, ß (95 % CI): 0.027 (0.013, 0.040) for Fe, and ß (95 % CI): 0.030 (0.016, 0.044) for Co). CONCLUSION: In summary, our study indicates that adequate essential metal intake together with healthy lifestyle behaviors perform crucial roles in PAD protection.

Association of exposure to multiple metals with hemoglobin levels in Chinese children and adolescents.

BACKGROUND: Previous studies have linked single metal to hemoglobin levels in children and adolescents; however, studies with regards to metal mixtures are still limited. OBJECTIVE: We aimed to investigate the associations of single metal and metal mixtures with hemoglobin levels in children and adolescents. METHODS: We conducted a cross-sectional study of 2064 children and adolescents aged 6 to 19 years in Liuzhou, China in 2018. The concentrations of 15 metals in urine were determined by inductively coupled plasma mass spectrometry. Generalized linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of single metal and metal mixtures with hemoglobin levels, respectively. RESULTS: The multivariable-adjusted ß-values for the highest versus the first quartiles of urinary metal concentrations were - 1.57 (95 % confidence interval [CI]: -3.01, -0.13) for chromium, -2.47 (95 % CI: -3.90, -1.05) for nickel and 1.88 (95 % CI: 0.49, 3.28) for copper. In addition, we found a significant negative association between the WQS index and hemoglobin levels (adjusted ß = -0.93, 95 % CI: -1.69, -0.19), with nickel contributing the most to the WQS index at 59.0 %. Subgroup analyses showed that exposure to urinary nickel or metal mixtures were associated with decreased hemoglobin levels in adolescents, but not in children (all Pinteration < 0.001). CONCLUSION: Among children and adolescents, urinary chromium and nickel concentrations were associated with decreased hemoglobin levels, while copper showed a positive relationship. Moreover, a negative association was observed between exposure to metal mixtures and hemoglobin levels. These findings need to be further validated in prospective studies.

Association between hemoglobin A1c trajectory during pregnancy and adverse birth outcomes among non-gestational diabetic women.

AIMS: Previous studies have shown that higher hemoglobin A1c (HbA1c) levels within the normal range during pregnancy can increase the risk of adverse birth outcomes. However, the effects of the longitudinal HbA1c trajectory during pregnancy on adverse birth outcomes among non-gestational diabetic women are poorly characterized. We aimed to identify HbA1c trajectory during pregnancy among non-gestational diabetic women and to estimate their associations with adverse birth outcomes. METHODS: Data was extracted from the Information System of Guangdong Women and Children Hospital, China, from January 2017 to July 2022. This study involved 13,979 women who did not have gestational diabetes mellitus and underwent repeated HbA1c measurements during pregnancy. Latent mixture modeling was used to identify HbA1c trajectory groups. Logistic regression was applied to explore the associations between HbA1c trajectory groups and adverse birth outcomes, including preterm delivery, low birth weight, macrosomia, small for gestational age, and large for gestational age (LGA). RESULTS: Three HbA1c trajectory groups were identified: low-stable (range 4.0% [20 mmol/mol]-4.4% [25 mmol/mol]), moderate-stable (range 4.6% [27 mmol/mol]-5.1% [32 mmol/mol]), and elevated-increasing (range 5.0% [31 mmol/mol]-5.6% [38 mmol/mol]). Compared with the low-stable HbA1c group, the elevated-increasing group had a higher risk of preterm delivery and LGA. The adjusted OR (95% CIs) were 1.67 (1.13, 2.49) and 1.47 (1.01, 2.12) for preterm delivery and LGA, respectively. CONCLUSIONS: Among non-gestational diabetic women, the elevated-increasing HbA1c trajectory group was associated with a higher risk of preterm delivery and LGA. This finding emphasizes the importance of maintaining optimal HbA1c levels throughout pregnancy.

Exposure to organochlorine pesticides and polychlorinated biphenyls, adherence to an ideal cardiovascular health, and arterial stiffness among Chinese adults.

This study aimed to assess the relationships between exposure to individual organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and their mixture and arterial stiffness and explore whether adherence to an ideal cardiovascular health (CVH) could mitigate these associations. The cross-sectional study enrolled 1437 Chinese adults between March and May 2019 in Wuhan, China. OCPs and PCBs concentrations were measured using solid phase extraction coupled with gas chromatography-tandem mass spectrometry. Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). CVH was determined by three behavioral and four biological metrics and categorized as ideal, intermediate, and poor CVH. We applied generalized linear model and weighted quantile sum (WQS) regression to evaluate the associations of exposure to individual OCPs or PCBs and their mixture with baPWV, respectively. We found that participants with detectable levels of heptachlor epoxide, PCB-153, and PCB-180 had higher baPWV (ß: 34.25, 95% CI 14.28-54.22; ß: 27.64, 95% CI 7.90-47.38; and ß: 30.51, 95% CI 10.68-50.35) than those with undetectable levels. In WQS regression, the mixture of OCPs and PCBs was related to a higher baPWV (ß: 24.93, 95% CI 2.70-47.15). Compared with participants with ideal CVH and undetectable OCPs or PCBs levels, those with poor CVH and detectable OCPs or PCBs levels had the highest increase in baPWV (heptachlor epoxide: ß: 147.94, 95% CI 112.52-183.55; PCB-153: ß: 150.22, 95% CI 115.40-185.04; PCB-180: ß: 147.02, 95% CI 111.66-182.38). Our findings suggested that individual OCPs, PCBs, and their mixture exposure were positively associated with arterial stiffness, and adherence to an ideal CVH may mitigate the adverse effect.

Associations of polychlorinated biphenyl and organochlorine pesticide exposure with hyperuricemia: modification by lifestyle factors.

Recent research has reported positive associations of exposure to polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) with hyperuricemia. However, most of these studies have primarily focused on the individual effects of PCB/OCP exposure. We aimed to explore the associations of both individual and combined PCB/OCP exposure with hyperuricemia and examine whether such associations could be modified by lifestyle factors. The cross-sectional study recruited 2032 adults between March and May 2019 in Wuhan, China. Logistic regression and weighted quantile sum (WQS) regression were applied to explore the relationship of individual and combined PCB/OCP exposure with hyperuricemia, while considering the modified effects of lifestyle factors. Of the 2032 participants, 522 (25.7%) had hyperuricemia. Compared with the non-detected group, the detected groups of PCB153 and PCB180 exhibited a positive association with hyperuricemia, with OR (95% CIs) of 1.52 (1.22, 1.91) and 1.51 (1.20, 1.90), respectively. WQS regression showed that PCB/OCP mixture was positively associated with hyperuricemia (OR: 1.31, 95% CI: 1.08, 1.58). PCB153/PCB180 exposure, combined with an unhealthy lifestyle, has a significant additive effect on hyperuricemia. Overall, PCB/OCP mixture and individual PCB153/PCB180 exposure were positively associated with hyperuricemia. Adherence to a healthy lifestyle may modify the potential negative impact of PCBs/OCPs on hyperuricemia.

Association between female-specific reproductive factors and leukocyte telomere length.

STUDY QUESTION: What are the associations between female-specific reproductive factors and leukocyte telomere length (LTL)? SUMMARY ANSWER: Early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of oral contraceptives (OCs) and hormone replacement therapy (HRT) were associated with shorter LTL. WHAT IS KNOWN ALREADY: Reproductive factors have been associated with age-related diseases, but their associations with cellular aging, as indicated by LTL, are unclear. STUDY DESIGN, SIZE, DURATION: This population-based study included 224 965 women aged 40-69 years from the UK Biobank between 2006 and 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 40-69 were included. Female-specific reproductive factors, including age at menarche, age at natural menopause, reproductive lifespan, number of live births, age at first live birth, history of stillbirth, history of miscarriage, and use of OCs and HRT were self-reported. LTL was measured using a validated polymerase chain reaction method. Multiple linear regression and restricted cubic spline models were applied to explore the association between each reproductive factor and LTL. MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for potential confounders, early menarche (<12 years; percent change, per unit change in LTL Z score: -1.29%, 95% CI: -2.32%, -0.26%), early menopause (<45 years; percent change: -7.18%, 95% CI: -8.87%, -5.45%), short reproductive lifespan (<30 years; percent change: -6.10%, 95% CI: -8.14%, -4.01%), multiparity (percent change: -3.38%, 95% CI: -4.38%, -2.37%), early age at first live birth (<20 years; percent change: -4.46%, 95% CI: -6.00%, -2.90%), and use of OCs (percent change: -1.10%, 95% CI: -2.18%, -0.02%) and HRT (percent change: -3.72%, 95% CI: -4.63%, -2.80%) were all significantly associated with shorter LTL. However, no significant association was found for history of miscarriage and stillbirth. We observed nonlinear relationships of age at menarche, age at natural menopause, reproductive lifespan, and age at first live birth with LTL (Pnonlinear < 0.05). LIMITATIONS, REASONS FOR CAUTION: Considering that the participants were predominantly of European ethnicity, the findings may not be generalizable to women of other ethnic backgrounds. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that early menarche, early menopause, short reproductive lifespan, early age at first birth, multiparity, and use of OCs and HRT were associated with shorter LTL, which has been linked to various chronic diseases. The accelerated shortening of telomeres may potentially contribute to the development of chronic diseases related to reproductive factors. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Natural Science Foundation of China (82003479, 82073660), Hubei Provincial Natural Science Foundation of China (2023AFB663), and the China Postdoctoral Science Foundation (2019M662646, 2020T130220). The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Sex-specific associations of single metal and metal mixture with handgrip strength: a cross-sectional study among Chinese adults.

Metallic elements are ubiquitous in the natural environment and always collaborate to affect human health. The relationship of handgrip strength, a marker of functional ability or disability, with metal co-exposure remains vague. In this study, we aimed to investigate the effect of metal co-exposure on sex-specific handgrip strength. A total of 3594 participants (2296 men and 1298 women) aged 21 to 79 years recruited from Tongji Hospital were included in the present study. Urinary concentrations of 21 metals were measured by inductively coupled plasma mass spectrometer (ICP-MS). We used linear regression, restricted cubic spline (RCS) model, and weighted quantile sum (WQS) regression to evaluate the association of single metal as well as metal mixture with handgrip strength. After adjusting for important confounding factors, the results of linear regression showed that vanadium (V), zinc (Zn), arsenic (As), rubidium (Rb), cadmium (Cd), thallium (Tl), and uranium (U) were adversely associated with handgrip strength in men. The results of RCS showed a non-linear association between selenium (Se), silver (Ag), and nickel (Ni) with handgrip strength in women. The results of WQS regression revealed that metal co-exposure was inversely related to handgrip strength for men (ß = -0.65, 95% CI: -0.98, -0.32). Cd was the critical metal in men (weighted 0.33). In conclusion, co-exposure to a higher level of metals is associated with lower handgrip strength, especially among men, and Cd may contribute most to the conjunct risk.

Association of metal exposure with arterial stiffness in Chinese adults.

BACKGROUND: Arterial stiffness is an important indicator of cardiovascular aging. However, studies assessing the association between metal exposure and arterial stiffness are limited. OBJECTIVE: The aim of this study was to investigate the independent and joint associations of metal exposure with arterial stiffness. METHODS: This cross-sectional study recruited 2982 Chinese adults from August 2018 to March 2019 in Wuhan, China. The concentrations of 20 urinary metals were determined using inductively coupled plasma mass spectrometer. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). We used generalized linear model (GLM) to estimate the association of single metal exposure with baPWV. We used weighted quantile sum (WQS) regression to estimate the association of metal mixture with baPWV. RESULTS: In GLM regression analysis, each doubling of urinary copper (Cu) and chromium (Cr) concentrations were associated with 6.48 (95 % CI: 2.51-10.45) cm/s and 3.78 (95 % CI: 0.42-7.14) cm/s increase in baPWV, respectively. In WQS regression analysis, each unit increase in WQS index of the metal mixture was associated with a 9.10 (95 % CI: 2.39-15.82) cm/s increase in baPWV. Cu, Zn, and Cr were the dominant urinary metals associated with baPWV. CONCLUSION: Metal exposure, both individually and in mixture, was associated with an increased risk of arterial stiffness. Our findings may provide a target for preventative strategies against cardiovascular aging.

Exposure to Metal Mixtures and Overweight or Obesity Among Chinese Adults.

Previous research has investigated the association between individual metal exposure and overweight/obesity (OW/OB). However, there is limited data about metal mixture exposure and OW/OB. This study aimed to explore the individual and joint effects of 21 metals on OW/OB and its metabolic phenotypes. A total of 4042 participants were enrolled in our study, and 51.0% of them were overweight/obese. We quantified 21 metal levels in the urine sample. OW/OB was defined as BMI ≥ 24 kg/m2, while the metabolic phenotypes, including metabolic unhealthy overweight/obesity (MUOW/OB) and metabolic health overweight/obesity (MHOW/OB), were determined by BMI and metabolic state. We used logistic regression to analyze the effect of individual metal exposure on OW/OB and its metabolic phenotypes. Quantile g-computation was applied to evaluate the joint effect of metal exposure on OW/OB and its metabolic phenotypes. In logistic regression, zinc (Zn) was positively associated with OW/OB, with the odds ratio (OR) in the highest quartiles of 2.19 (95% confidence interval (CI), 1.74, 2.77; P trend < 0.001), while arsenic (As) and cadmium (Cd) were negatively associated with OW/OB (OR = 0.70 (0.56, 0.87) and 0.61 (0.48, 0.78), respectively). After adjustment for age, gender, education, cigarette smoking, alcohol drinking, physical activity, meat intake, and vegetable intake, Zn was positively associated with MUOW/OB, while As, Cd, nickel (Ni), and strontium (Sr) were negatively associated with MUOW/OB (all P trend < 0.05). Quantile g-computation showed a significantly negative association between metal mixture exposure and MUOW/OB. Our study suggested that metal mixture exposure might be negatively associated with OW/OB, particularly with MUOW/OB. Zn, As and Cd contributed most to the effect of the mixture. More prospective studies are warranted to confirm these findings and reveal the underlying mechanisms.