Epidemiology/Health Services Research

Vitamin B12 and risk of diabetes: new insight from cross-exclusive and longitudinal analyses of the Prc Stroke Main Prevention Trial (CSPPT)

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  1. Lishun Liu1,
  2. Xiao Huang2,
  3. Binyan Wangthree,4,five,
  4. Yun Songane,
  5. Tengfei Linone,
  6. Ziyi Zhoui,
  7. Zhuo Wangi,
  8. Yaping Wei1,
  9. Huiyuan Guoone,
  10. Ping Chenhalf-dozen,
  11. Yan Yang7,eight,
  12. Wenhua Ling8,nine,
  13. Youbao Li3,
  14. Xianhui Qin3,4,
  15. Genfu Tang4,
  16. Chengzhang Liufive,
  17. Jianping Liten,
  18. Yan Zhang10,
  19. Pierre A Zalloua11,
  20. Xiaobin Wang12,
  21. Yong Huo10,
  22. http://orcid.org/0000-0003-4148-1739Hao Zhangane,
  23. Xiping Xu1,iii
  1. 1 Beijing Advanced Innovation Heart for Food Diet and Human being Health, College of Food Science and Nutritional Engineering, Cathay Agricultural Academy, Beijing, China
  2. 2 Department of Cardiology, Nanchang University Second Affiliated Hospital, Nanchang, Jiangxi, People's republic of china
  3. iii National Clinical Research Study Center for Kidney Illness, the Country Fundamental Laboratory for Organ Failure Research, Renal Partition, Southern Medical Academy Nanfang Hospital, Guangzhou, Guangdong, People's republic of china
  4. iv Institute of Biomedicine, Anhui Medical University, Hefei, Anhui, China
  5. v Shenzhen Evergreen Medical Institute, Shenzhen, China
  6. half-dozen Higher of Pharmacy, Jinan University, Guangzhou, Guangdong, Communist china
  7. 7 School of Public Health (Shenzhen), Sun Yat-Sen University, Guangzhou, Guangdong, People's republic of china
  8. viii Guangdong Technology Technology Middle of Diet Transformation, Guangzhou, Prc
  9. 9 Section of Nutrition, Schoolhouse of Public Wellness, Lord's day Yat-Sen Academy, Guangzhou, China
  10. 10 Department of Cardiology, Peking University Showtime Hospital, Beijing, Mainland china
  11. 11 School of Medicine, Lebanese American University, Beirut, Lebanon
  12. 12 Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg Schoolhouse of Public Health, Baltimore, Maryland, United states of america
  1. Correspondence to Dr Hao Zhang; zhcau2019{at}126.com ; Dr Xiping Xu; xipingxu126{at}126.com

Abstruse

Introduction Previous studies in more often than not Western populations accept yielded conflicting findings on the clan of vitamin B12 with diabetes risk, in office due to differences in study design and population characteristics. This study sought to examine the vitamin B12–diabetes association in Chinese adults with hypertension by both cantankerous-exclusive and longitudinal analyses.

Research design and methods This written report included a total of 16 699 participants from the China Stroke Principal Prevention Trial, with pertinent baseline and follow-up information. Diabetes mellitus was divers equally either physician-diagnosed diabetes, use of glucose-lowering drugs, or fasting claret glucose (FBG) ≥seven.0 mmol/L. New-onset diabetes was defined as any new case of onset diabetes during the follow-up period or FBG ≥7.0 mmol/L at the exit visit.

Results At baseline, there were 1872 (11.2%) patients with diabetes; less than 1.v% had clinical vitamin B12 deficiency (<148.0 pmol/L). Over a median follow-up period of 4.5 years, there were 1589 (x.7%) cases of new-onset diabetes. Cantankerous-sectional analyses showed a positive association betwixt baseline vitamin B12 levels and FBG levels (β=0.18, 95% CI 0.15 to 0.21) and diabetes (OR=1.16, 95% CI one.10 to 1.21). Nevertheless, longitudinal analyses showed no clan between baseline vitamin B12 and new-onset diabetes or changes in FBG levels. Among a subset of the sample (n=4366) with both baseline and exit vitamin B12 measurements, we found a positive clan between an increase in vitamin B12 and an increase in FBG.

Conclusions In this big Chinese population of patients with hypertension mostly sufficient with vitamin B12, parallel cross-sectional and longitudinal analyses provided new insight into the alien findings of previous studies, and these results underscore the need for future studies to consider both baseline vitamin B12 and its longitudinal trajectory in society to better elucidate the function of vitamin B12 in the development of diabetes. Such findings would have important clinical and public health implications.

  • vitamin B12
  • diabetes mellitus, type 2
  • longitudinal studies
  • hypertension

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This is an open up access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC Past-NC 4.0) license, which permits others to distribute, remix, conform, build upon this work non-commercially, and license their derivative works on different terms, provided the original piece of work is properly cited, appropriate credit is given, any changes made indicated, and the use is not-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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  • vitamin B12
  • diabetes mellitus, type ii
  • longitudinal studies
  • hypertension

Significance of this study

What is already known almost this subject?

  • Conflicting findings were derived from previous studies on B12 and diabetes using either cross-exclusive or longitudinal design. Some cantankerous-sectional studies institute that B12 was positively associated with diabetes, while others reported the opposite results. Several longitudinal studies showed no meaning relationship between B12 and DM).

  • To appointment, the relationship between B12 and DM has remained elusive.

What are the new findings?

  • This is the first and largest written report of a Chinese population of patients with hypertension (n=16 699) to delineate cantankerous-sectional and longitudinal associations between plasma vitamin B12 and diabetes take chances.

  • The cross-sectional analyses showed a positive association between baseline vitamin B12 levels and diabetes; however, longitudinal analyses revealed no association. Among a subset of sample (due north=4366) with both baseline and exit B12 levels, we found a positive association between an increment in B12 and an increment in fasting claret glucose.

How might these results change the focus of research or clinical practice?

  • Findings from our cross-sectional and longitudinal analyses underscore the need for future studies to consider both baseline vitamin B12 and its longitudinal trajectory in gild to ameliorate elucidate the part of vitamin B12 in the development of diabetes.

  • Such findings, if farther confirmed, have important clinical and public health implications.

Introduction

Diabetes mellitus (DM) is a chronic metabolic disorder that has reached epidemic levels around the world.1 In Red china, there has been a abrupt increase in diabetes prevalence in the past few decades, and currently eleven.iv million people have diabetes.ii From both clinical and public health perspectives, there is a critical demand to develop cost-effective strategies to foreclose diabetes. Vitamin B12 is a coenzyme in the one-carbon metabolic pathway involved in the synthesis of methionine and pyrimidine and purine bases. Deficiencies in vitamin B12 and associated Dna damage and subsequent faulty repair are known to contribute to the development of vascular diseases, cancer, and some nascence defects, and can lead to hyperhomocysteinemia. Often related to folic acrid deficiency, vitamin B12 has been identified as a risk cistron for both hypertension and atherosclerosis.3

To date, nearly studies on vitamin B12 and DM have been centered on vitamin B12 deficiency among existing patients with diabetes. The association between metformin apply and low vitamin B12 levels has been supported by various levels of evidence.4 Considering ileal vitamin B12 absorption is a calcium-dependent process, and metformin is known to have an effect on calcium-dependent membrane activity, patients with type 2 diabetes normally developed a marked reduction in serum vitamin B12 while existence treated with metformin.5 Even so, the risks and benefits of vitamin B12 on future hazard of DM are not clear due to inconsistent results of previous studies. A cantankerous-sectional report in a Southward Indian population showed that college vitamin B12 levels decreased the risk of DM.half dozen Another longitudinal randomized control trial study showed no difference in the incidence of type two diabetes mellitus between the vitamin B12-supplemented group equally compared with the non-supplemented control group.7 The current study addresses an of import withal controversial topic of whether vitamin B12 is associated with DM.

This current study was motivated past the findings of the US National Health and Diet Examination Survey (NHANES)8 which showed that vitamin B12 levels in patients with DM without metformin were significantly higher than those in the general population. However, the NHANES is a cantankerous-sectional written report, and in order to address whether vitamin B12 levels that are higher than the optimal range are a risk factor for developing DM, a prospective cohort study would be required to appraise the temporal and dose–response human relationship.

In this report, we analyzed a total of sixteen 699 participants with hypertension from the China Stroke Primary Prevention Trial (CSPPT), with pertinent baseline data and a mean follow-up of iv.v years. Our primary objective is to perform both cross-sectional and longitudinal analyses with the aim of determining whether the findings of the NHANES could be replicated in a Chinese population, and furthermore whether in that location is a prospective and dose–response clan betwixt baseline vitamin B12 levels and gamble of new-onset DM. Amid a subset of the sample (north=4366) with both baseline and exit vitamin B12 measurements, we further analyzed the relationship between the alter in vitamin B12 levels and the change in fasting blood glucose (FBG) levels from baseline to the get out visit as the secondary objective.

Research design and methods

Participants and trial pattern

All participants provided written, informed consent. A total of xx 702 eligible participants, stratified past the methylenetetrahydrofolate reductase (MTHFR) C677T genotypes (CC, CT, or TT), were randomly assigned, in a 1:one ratio, to one of two treatment groups: a daily oral dose of i tablet containing 10 mg enalapril and 0.8 mg folic acid (the enalapril-folic acid group), or a daily oral dose of 1 tablet containing 10 mg enalapril only (the enalapril group). Participants were engaged in follow-up visits every 3 months.

A detailed description and the primary results of the CSPPT take been reported elsewhere.nine–11 Briefly, the CSPPT was a multicommunity, randomized, double-bullheaded, controlled trial conducted between May 19, 2008 and August 24, 2013 in 32 communities in Prc. Eligible participants were men and women aged 45–75 years with hypertension, defined every bit seated, resting systolic blood pressure level (SBP) ≥140 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg at both the screening and recruitment visit, or who were taking antihypertensive medication. The major exclusion criteria included history of physician-diagnosed stroke, myocardial infarction (MI), heart failure, postcoronary revascularization, or congenital heart affliction. Co-ordinate to the CSPPT written report protocol people who had long-term B-group vitamin supplementation were excluded, and other B-group vitamins should not exist supplemented during the study catamenia.

This study included 16 699 men and women with hypertension from the CSPPT with baseline vitamin B12 information and pertinent baseline and follow-up information on diabetes condition and covariables. Every bit illustrated in the menstruum nautical chart (online supplementary figure S1), the final analyses excluded participants with missing values for baseline vitamin B12, baseline FBG, go out FBG and with any missing data on the follow-upwards questionnaire. We also randomly selected a subset of the population (north=4366) to find changes in vitamin B12 at the exit visit (online supplementary table S1).

Supplemental material

Outcomes

Patients were classified as diabetic if they self-reported a doc diagnosis, or were using glucose-lowering medication, or when their FBG ≥seven.0 mmol/L at baseline.12 New-onset diabetes was defined equally a self-reported physician diagnosis, or utilize of glucose-lowering drugs during the follow-upwards menstruation, or when FBG changed from <7.0 mmol/50 at baseline to ≥7.0 mmol/L at the last report (exit) visit.

Covariables

Covariables included known or suspected factors associated with vitamin B12 and/or DM based on existing literature, including our ain studies in the CSPPT, specifically age, sexual practice, MTHFR factor C677T polymorphisms, SBP and DBP at baseline, mean SBP and DBP during the treatment period, trunk mass index (BMI), study heart, serum concentrations of folate, total homocysteine (tHcy), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), smoking status, alcohol consumption status, self-reported meat consumption and medication employ. Information on meat consumption was cocky-reported at baseline using a simple abbreviated semiquantitative Food Frequency Questionnaire. Participants were asked to study how oft, on boilerplate, they eat meat every week. Possible response categories included 'never', 'ane–ii times/week', '3–5 times/week' and 'every mean solar day'. Vitamin B12 deficiency was defined as vitamin B12 <148.0 pmol/Fifty.thirteen

Laboratory assays

For biochemical analyses, 20 mL claret samples were collected betwixt 7:00 and 9:00 later on an overnight fast (at to the lowest degree 8 hours). Serum samples were separated, aliquoted and after stored at –80°C until analysis. Plasma vitamin B12 at baseline and folate at baseline and the go out visit were measured using a chemiluminescent immunoassay at the commercial lab (New Industrial, Shenzhen, China). tHcy, fasting lipids and FBG at baseline and the exit visit were measured using automated clinical analyzers (Beckman Coulter, California, USA) at the core lab of the National Clinical Research Eye for Kidney Disease (Nanfang Infirmary, Guangzhou, China).

Statistical analysis

Descriptive data are presented as mean (SD) or median values with IQR in parentheses or proportions, equally advisable, for population characteristics according to baseline vitamin B12 quartiles. The significance of differences in population characteristics between groups was computed using two-sample t-tests, signed-rank tests, or χtwo tests for continuous and categorical variables.

Logistic regression models were used to estimate the ORs and their 95% CIs of diabetes, given the exact onset of diabetes was not known and many new-onset DM cases were detected by fasting glucose levels at the exit visit. All analyses were conducted with adjustments for covariables. Finally, subgroup analyses were performed to evaluate possible effect modifications by the covariables on the clan between vitamin B12 and DM, including sex activity (male person vs female), age (<60 vs ≥threescore years), MTHFR C677T polymorphism (CC vs CT vs TT), SBP (<160.0 vs ≥160.0 mm Hg), DBP (<90 vs ≥90 mm Hg), hateful SBP during the treatment period (<140.0 vs ≥140.0 mm Hg), mean DBP during the treatment catamenia (<90 vs ≥90 mm Hg), BMI (<25 vs ≥25 kg/one thousandii), written report heart (Anqing vs Lianyungang), folate (<eight vs ≥8 ng/mL), tHcy (<12.5 vs ≥12.5 μmol/50), TC (<v.v vs ≥v.5 mmol/L), TG (<1.five vs ≥1.5 mmol/L), HDL-C (<1.iii vs ≥1.3 mmol/50) and treatment grouping (enalapril vs enalapril-folic acid). A ii-tailed p<0.05 was considered significant in all analyses. All statistical analyses were performed using R software, V.three.6.0 (http://world wide web.R-project.org/, accessed April 26, 2019).

Results

Report participants and baseline characteristics

Study participants had an average age of 60.0 years (SD vii.4), 6713 were male (40.2%) and 9986 were female (59.8%) (online supplementary table S2). Participants had an average vitamin B12 level of 295.9 pmol/L (SD 91.5), 257 (1.five%) participants had vitamin B12 deficiency, while 10 468 (63.3%) participants did not consume meat. The hateful FBG level was 5.eight mmol/L (SD 1.vii) at baseline, and the leave mean FBG level was 6.3 mmol/L (SD ii.0). At baseline, 1872 (eleven.two%) participants had DM, and at the exit visit there were 1589 (x.7%) cases of new-onset DM. When stratified by baseline vitamin B12 quartiles, FBG levels were the highest (6.0 mmol/Fifty (SD 2.1)) in the fourth quartile (Q4). Tabular array 1 shows that the average age and BMI of the participants in Q4 were lower than those of the other groups, merely TC and TG levels were higher than the other quartiles.

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Table 1

Baseline and follow-upwards characteristics of the written report participants by baseline B12 quartiles

Cantankerous-sectional analysis on baseline vitamin B12 and DM

From the cross-exclusive analysis, vitamin B12 was establish to exist positively associated with DM (OR=1.35, 95% CI 1.26 to i.44, p<0.001) at baseline (table 2). After stratifying past vitamin B12 quartiles, participants in Q4 were institute to have the highest risk (OR=ane.68, 95% CI i.43 to ane.98, p<0.001). Also, in that location was a positive clan between vitamin B12 and FBG (β=0.14, 95% CI 0.11 to 0.17, p<0.001) (table iii). Afterward stratifying by relevant covariables, we discovered interactions between sex, TC levels and vitamin B12 with baseline DM and FBG (online supplementary figure S2, online supplementary figure S3). No interaction was found betwixt vitamin B12 and plasma folic acid or tHcy.

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Table 2

Cross-sectional and longitudinal association between baseline vitamin B12 levels and diabetes (DM) and new-onset DM

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Table 3

Cross-sectional and longitudinal association betwixt baseline vitamin B12 and baseline FBG, get out FBG and modify in FBG (ΔFBG)

Longitudinal analyses on baseline vitamin B12 and new-onset DM

Longitudinal analyses did non show an association between baseline vitamin B12 and new-onset DM (OR=0.97, 95% CI 0.90 to ane.04, p=0.346) (tabular array 2), alter in FBG (β=−0.01, 95% CI −0.04 to 0.02, p=0.602), or exit FBG (β=−0.01, 95% CI −0.04 to 0.02, p=0.602) subsequently making additional adjustments for baseline FBG (table 3). After stratifying by relevant covariables, no interaction was plant between vitamin B12 with new-onset DM, exit FBG or change in FBG (online supplementary figure S2, online supplementary effigy S3).

Longitudinal analyses on modify in vitamin B12 levels and change in FBG levels

Amongst a subset of the sample (due north=4366) with both baseline and exit vitamin B12 measurements, we further analyzed the relationship between modify in vitamin B12 levels and change in FBG levels from the baseline to the exit visit. We found a dose–response human relationship between change in vitamin B12 and modify in FBG levels (table four, effigy one).

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Tabular array 4

Longitudinal analyses on change in vitamin B12 (ΔB12) and change in' FBG (ΔFBG) from baseline to exit visit*

Figure 1

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Effigy 1

Multivariable-adjusted smoothing curves of alter in vitamin B12 and change in FBG in a subsample that included a total of 4366 subjects with both baseline and go out FBG and vitamin B12 measurements. Adjusted for age, sexual activity, MTHFR gene C677T polymorphisms, SBP and DBP at baseline, mean SBP and DBP during the treatment period, body mass index, study centre, baseline serum concentrations of folate, homocysteine, FBG, vitamin B12, total cholesterol, triglycerides, and high-density lipoprotein cholesterol, treatment group, smoking status, and alcohol consumption condition. DBP, diastolic claret pressure; FBG, fasting blood glucose; MTHFR, methylenetetrahydrofolate reductase; SBP, systolic blood pressure.

Give-and-take

This is the first time that the human relationship between vitamin B12 and DM has been explored in a Chinese population of patients with hypertension via both cross-sectional and longitudinal analyses. We confirmed the findings of the NHANES, showing a cross-sectional positive association between vitamin B12 and DM at baseline in this Chinese population. Furthermore, our longitudinal analyses demonstrated that at that place was no association between baseline vitamin B12 levels and new-onset DM chance. Our study has contributed new insights on the vitamin B12 and DM association and has helped to explain inconsistent findings in previous studies.

Vitamin B12 and DM association depends on population characteristics

Most previous studies on the clan of vitamin B12 and DM were centered on vitamin B12 deficiency amidst existing patients with DM with the use of metformin. The association betwixt metformin apply and low vitamin B12 levels has been supported by various levels of bear witness.4 Most of those studies were conducted in older populations, where vitamin B12 deficiency is more likely.eight In dissimilarity, our study was conducted in a Chinese population of patients with hypertension who were relatively immature (45–75 years at baseline), mostly free from DM at baseline, and mostly vitamin B12 sufficient. Only six.9% of the written report participants with DM reported using metformin (online supplementary figure S4).

Vitamin B12 and DM association depends on the study blueprint and type of analyses

In a Mendelian randomization study, Moen et alxiv found that vitamin B12 may have a causal effect on fasting glucose and one potential mechanism could be an effect of vitamin B12 on jail cell cycle and proliferation of pancreatic β cells, resulting in improved insulin secretion amongst individuals with higher vitamin B12 concentrations. Withal, in other cantankerous-sectional analyses, Jayashri et al6 institute that the levels of vitamin B12 decreased with increasing severity of glucose tolerance. Margalit et al15 establish no significant difference in claret sugar between the vitamin B12-deficient grouping and the non-deficient group. In longitudinal analyses and randomized trials, Looker et al16 found that vitamin B12 was positively associated with all-cause mortality and death from diabetes/nephropathy. Song et al7 plant that daily supplementation with folic acid and vitamins Bhalf-dozen and B12 did not reduce the risk of developing type 2 diabetes among women at high risk for cardiovascular diseases (CVD). Kwok et al17 found that vitamin B12 supplementation did not prevent cerebral reject in older patients with diabetes with borderline vitamin B12 status. In a systematic review, Rafnsson et alxviii plant that current data do non support vitamin B12 supplementation in reducing the risk of cardiovascular diseases or diabetes.

Our study was the first to perform and written report findings from both cross-sectional and longitudinal analyses in the same population. In the cross-exclusive analysis, nosotros plant an independent, positive association between baseline vitamin B12 levels and DM and FBG. These results persisted even after we adjusted for relevant covariables. This finding is consistent with the NHANES study.viii In the longitudinal analyses, we did not find any clan between baseline vitamin B12 and new-onset DM risk. This finding is consistent with the Women's Antioxidant and Folic Acid Cardiovascular Study, where women aged ≥forty years with a history of cardiovascular disease, who were free of DM at baseline, were supplemented with either a combination pill consisting of folic acrid, pyridoxine and vitamin B12, or a placebo. Later on a median follow-up of 7.3 years, no difference in incident blazon two diabetes mellitus was establish betwixt the ii groups.7 Another longitudinal study19 in Japan also reported like zippo results. Taken together, our longitudinal analyses and that of others did not support an association between vitamin B12 and new-onset DM. These findings underscore that cross-sectional associations demand to exist confirmed by prospective studies and clinical trials, because the former is more probable to be discipline to many drawbacks, including reverse causality.

Clinical implications of findings

The part of vitamin B12 in DM varied by patient characteristics. About previous studies accept shown that vitamin B12 supplementation is necessary in elderly patients with diabetes with low vitamin B12 levels or in patients with diabetes with long-term metformin utilise.viii 17 20 Our report, along with other longitudinal studies, however, does not support the routine utilize of vitamin B12 supplementation to reduce the risk of new-onset DM18 in relatively young patients with no show of vitamin B12 deficiency. Moreover, a meta-assay by Valdés-Ramos et al21 indicated no recommendation for the apply of vitamin supplements in patients with type ii diabetes mellitus. Of note, the research of Looker et alxvi showed that vitamin B12 was positively associated with all-cause mortality and death from diabetes/nephropathy, and previous data as well indicated that elevated serum vitamin B12 levels are a predictive factor for mortality in elderly patients with cancer.22 Salles et al23 and Hemmersbach-Miller et al24 reported that college vitamin B12 levels might also exist a marking to assess a higher hazard of mortality in elderly patients. Vitamin B12 can too accelerate refuse in renal function and increase the risk of cardiovascular events in patients with impaired renal function.25 26 Zeitlin et al27 also suggest that for elderly people, vitamin B12 supplementation should not exist routinely provided unless there are clear indications for doing so (a deficiency state), and and so to simply replace enough vitamin B12 to correct the deficiency. Through our research and assay, we found that vitamin B12 may still have a correlation with blood glucose or DM, and the disappearance of this correlation in the longitudinal analysis may be due to the relative changes in the observation age, the subtract in vitamin B12 levels and the increment in FBG levels over time. Therefore, the relationship between the changes in indicators needs to be observed to reflect real results. We plant that the change in vitamin B12 levels and the alter in FBG levels showed a positive vitamin B12–FBG clan in the subsample. In addition, we repeated the previous analysis with this subsample and found the results were consistent with those of the previous analysis (online supplementary table S3).

The present report had some limitations. First, this study focused on Chinese adults with hypertension, and then the generalizability of the results to other populations remains to be adamant. Second, new-onset DM was not a primary outcome or a prespecified outcome of the CSPPT. We did not obtain FBG measurements at the scheduled follow-upwardly visits, nor did nosotros measure hemoglobin A1c or perform glucose tolerance tests at baseline or during the follow-up visits. Therefore, it is possible that we have underestimated the incidence of new-onset DM in the CSPPT. Nevertheless, nosotros believe that any potential underestimation of new-onset DM should be non-differential, and therefore should not significantly affect the results. Finally, we only measured vitamin B12 levels on a small subset (n=4366) of the population at the get out visit and were unable to examine vitamin B12 dynamics during the follow-up flow of the CSPPT.

Decision

Among a population of adults with hypertension in China without a history of stroke or MI, who were mostly vitamin B12-sufficient, at that place was a dose–response clan of vitamin B12 levels with the risk of DM based on cross-sectional analyses at baseline. There was no prospective relationship between baseline vitamin B12 and new-onset DM in the longitudinal analyses. However, in a subsample, a positive vitamin B12–FBG association was shown by the alter in vitamin B12 levels and the change in FBG levels. This upshot indicates that at that place may be a potential correlation betwixt B12 and diabetes. Our findings illustrate a articulate discrepancy in results from the cross-exclusive and longitudinal analyses even from the same study population, and underscore the need to consider both baseline and longitudinal changes between vitamin B12 and FBG in society to better elucidate the role of vitamin B12 in the development of diabetes. If further studies confirm such findings, this volition have an important impact on clinical and public health.

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