Associations of Serum Folate and Vitamin B<sub>12</sub> Levels With Cardiovascular Disease Mortality Among Patients With Type 2 Diabetes

Liu, Yujie; Geng, Tingting; Wan, Zhenzhen; Lu, Qi; Zhang, Xuena; Qiu, Zixin; Lin, Li; Zhu, Kaiheng; Liu, Liegang; Pan, An; Lv, Gang

doi:10.1001/jamanetworkopen.2021.46124

Cited by 86 publications

(56 citation statements)

References 45 publications

(74 reference statements)

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“…Notably, we found a protective effect of genetically predicted folate levels on the risk of T2DM, which further indicate the association in the observational study was causal. Several researches of folate supplementation reducing the incidence of T2DM also support this causal relationship ( 20 , 21 , 38 ). A clinical trial that included 6,185 diabetic patients found that folate supplementation in T2DM patients resulted in lower hcy levels and better glycemic control ( 39 ).…”

Section: Discussionmentioning

confidence: 79%

Circulating homocysteine and folate concentrations and risk of type 2 diabetes: A retrospective observational study in Chinese adults and a Mendelian randomization analysis

Cheng

Wang

Zhang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundThe relation between circulating homocysteine (hcy) and folate concentrations and risk of type 2 diabetes mellitus (T2DM) has been evaluated in several observational studies with inconsistent results; and it is unclear about their causal relationships. Our aim was to assess the causality association between circulating hcy or folate concentrations and the development of T2DM using Mendelian randomization (MR) analysis, based on results of an observational study in Chinese adults.MethodsWe conducted an observational study of 370 patients with T2DM and 402 controls after routine physical examination who consulted at the Zhongnan Hospital of Wuhan University between March 2021 and December 2021. Correlations between hcy and folate and the incidence of T2DM were quantified using logistic regression models. Two-sample MR analysis was conducted using summary statistics of genetic variants gained from 2 genome-wide association studies (GWAS) on circulating hcy and folate concentrations in individuals of European ancestry and from an independent GWAS study based on DIAMANTE meta-analysis.ResultsIn the observational study, after logistic regression with multiple adjustment, lower hcy and higher folate levels were identified to be associated with the risk of T2DM, with OR (95% CI) for hcy of 1.032 (1.003–1.060); while 0.909 (0.840–0.983) for folate. In the MR analysis, the OR for T2DM was 1.08 (95% CI: 0.95, 1.21; P = 0.249) for each SD unit increase in genetically predicted homocysteinemia and the OR for T2DM per SD increase in genetically predicted folate elevation was 0.80 (95% CI: 0.60, 1.00, P = 0.026).ConclusionsWe discovered that high circulating hcy and low folate concentrations were related with an increased risk of developing T2DM in Chinese adults. Moreover, MR analysis provided genetic evidence for a possible causal relationship between serum folate and the risk of T2DM.

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Section: Discussionmentioning

confidence: 79%

Circulating homocysteine and folate concentrations and risk of type 2 diabetes: A retrospective observational study in Chinese adults and a Mendelian randomization analysis

Cheng

Wang

Zhang

et al. 2022

Front. Cardiovasc. Med.

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“…In total, 2833 adults with diabetes aged ≥ 20 were enrolled in the NHANES III (1988)(1989)(1990)(1991)(1992)(1993)(1994). The ascertainment of diabetes included a self-report of physician diagnosis, fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/ dL), 75-g oral glucose tolerance test result ≥ 11.1 mmol/L (200 mg/dL), or glycated hemoglobin A1c (HbA1c) level ≥ 6.5% (48 mmol/mol) [19][20][21]. Participants without data on serum thyroid hormone levels (n = 615), TSH and total thyroxine (TT 4 ) levels outside the reference range (n = 266), those with a history of thyroid disease at baseline (n = 110), those lost to follow-up (n = 4), and those who self-reported as being pregnant (n = 8) were excluded from the study.…”

Section: Study Populationmentioning

confidence: 99%

TSH levels within the normal range and risk of cardiovascular and all-cause mortality among individuals with diabetes

Zhu

Lao

Chen

et al. 2022

Cardiovasc Diabetol

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Background Evidence regarding thyroid-stimulating hormone (TSH) levels within the normal range and mortality in adults with diabetes is scarce. This study aimed to identify the association between TSH levels and cardiovascular disease (CVD) and all-cause mortality among euthyroid patients with diabetes. Methods This prospective cohort study included 1830 adults with diabetes from the Third National Health and Nutrition Examination Survey III. Mortality outcomes were ascertained by linkage to National Death Index records through December 31, 2019. Participants were categorized by tertiles of TSH levels (low-normal, 0.39–1.30 mIU/L; medium-normal, 1.30–2.09 mIU/L; high-normal, 2.09–4.60 mIU/L). Multivariable Cox proportional hazards models were used to explore the association between TSH levels within the normal range and overall and CVD mortality. Furthermore, restricted cubic spline analyses were used to determine the nonlinear relationship between TSH levels and mortality. Results During a median follow-up of 17.1 years, 1324 all-cause deaths occurred, including 525 deaths from CVD. After multivariate adjustment, a U-shaped relationship was observed between TSH levels in euthyroid status and all-cause or CVD mortality among patients with diabetes (both P < 0.05 for nonlinearity). Compared with participants with medium-normal TSH levels, those with high-normal TSH levels had a significantly higher risk of all-cause (hazard ratio, 1.31; 95% confidence interval, 1.07–1.61) and CVD (1.52; 1.08–2.12) mortality. Similarly, low-normal TSH levels also increased all-cause (1.39; 1.12–1.73) and CVD (1.69; 1.17–2.44) mortality risk. In stratum-specific analyses, we found that high-normal TSH levels were associated with higher mortality risk in younger (< 60 years) patients with diabetes but not in older (≥ 60 years) participants. Conclusion Low- and high-normal serum TSH levels were associated with increased all-cause and CVD mortality in euthyroid adults with diabetes. Further studies are needed to confirm the present observation in a wider population.

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“…In the Original Investigation titled “Associations of Serum Folate and Vitamin B 12 Levels With Cardiovascular Disease Mortality Among Patients With Type 2 Diabetes,” 1 published January 31, 2022, there were errors in panel B of the Figure; the unit of measure for serum B 12 should be picograms per milliliter. There was an error in the title of Table 3; the years of the National Health and Nutrition Examination Survey should be from 1999 through 2014.…”

mentioning

confidence: 99%

“…There was an error in the title of Table 3; the years of the National Health and Nutrition Examination Survey should be from 1999 through 2014. This article has been corrected …”

mentioning

confidence: 99%

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2022

JAMA Netw Open

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Associations of Serum Folate and Vitamin B₁₂ Levels With Cardiovascular Disease Mortality Among Patients With Type 2 Diabetes

Cited by 86 publications

References 45 publications

Circulating homocysteine and folate concentrations and risk of type 2 diabetes: A retrospective observational study in Chinese adults and a Mendelian randomization analysis

Circulating homocysteine and folate concentrations and risk of type 2 diabetes: A retrospective observational study in Chinese adults and a Mendelian randomization analysis

TSH levels within the normal range and risk of cardiovascular and all-cause mortality among individuals with diabetes

Errors in Figure and Table

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Associations of Serum Folate and Vitamin B12 Levels With Cardiovascular Disease Mortality Among Patients With Type 2 Diabetes

Cited by 86 publications

References 45 publications

Circulating homocysteine and folate concentrations and risk of type 2 diabetes: A retrospective observational study in Chinese adults and a Mendelian randomization analysis

Circulating homocysteine and folate concentrations and risk of type 2 diabetes: A retrospective observational study in Chinese adults and a Mendelian randomization analysis

TSH levels within the normal range and risk of cardiovascular and all-cause mortality among individuals with diabetes

Errors in Figure and Table

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Associations of Serum Folate and Vitamin B₁₂ Levels With Cardiovascular Disease Mortality Among Patients With Type 2 Diabetes