Dataset Information

Mean and visit-to-visit variability of glycated hemoglobin, and the risk of non-alcoholic fatty liver disease.

ABSTRACT:

Aims/introduction

We aimed to determine whether mean and visit-to-visit glycated hemoglobin (HbA1c) variability independently increase the incidence of non-alcoholic fatty liver disease (NAFLD) across the diabetic continuum from normal glucose tolerance (NGT) to established diabetes.

Materials and methods

In a longitudinal cohort study, 21,123 participants underwent five or more annual health screening checkups. Participants were categorized into diabetes (n = 1,635), prediabetes (n = 6,650) and NGT (n = 12,838) groups. Mean, standard deviation (SD) and coefficient of variation data on HbA1c were obtained from three consecutive measurements. The associations between those data and incident NAFLD were analyzed using Cox regressions.

Results

Over a median follow-up period of 57 months, 3,860 (18.3%) participants developed NAFLD. The risk of NAFLD increased continuously, with the mean HbA1c beginning at 4.9%, even in the NGT group. We found a significant association between increasing HbA1c variability and incident NAFLD (coefficient of variation, adjusted hazard ratio 1.14, 95% confidence interval 1.01-1.29; standard deviation, adjusted hazard ratio 1.19, 95% confidence interval 1.05-1.36) in the diabetes group, but not in the NGT or prediabetes group. Consistent findings were observed when NAFLD patients with a low possibility of fibrosis were excluded. The association between the coefficient of variation of HbA1c and incident NAFLD in the diabetes group was significant only in those with an increasing trend of post-baseline HbA1c (adjusted hazard ratio 1.24, 95% confidence interval 1.01-1.52).

Conclusions

Increased mean HbA1c levels elevated the risk of incident NAFLD, even with NGT. Increases in visit-to-visit variability of HbA1c independently elevated the risk of incident NAFLD, but only in the diabetes group.

SUBMITTER: Yoo JH

PROVIDER: S-EPMC8264391 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundVisit-to-visit variability (VVV) of glycated hemoglobin (HbA1c) levels have been found to be associated with prognosis of diabetes. However, little is known about whether or to what extent sex and age may modify the effects of VVV.MethodsTo investigate age- and sex-specific rates of mortality from all causes and relative hazards of mortality in association with VVV of HbA1c levels, 47,145 patients with diabetes and prescription of any antidiabetic agents >6 months were identified from outpatient visits of a tertiary medical center in northern Taiwan during 2003-2018. VVV of HbA1c was measured by quartiles of standard deviation (SD), coefficient of variation (CV), and average real variability (ARV), respectively. The study subjects were linked to Taiwan's National Death Registry to identify all-cause mortality. The person-year approach with the Poisson assumption was used to assess the all-cause mortality rates, and Cox proportional hazard regression model was used to evaluate the relative hazards of all-cause mortality concerning various levels of VVV of HbA1c.ResultsThe lowest all-cause mortality rate was found in either the first or second quartile of various measures for VVV of HbA1c, but the highest mortality rate was consistently observed in the fourth quartile of VVV, regardless of SD, CV, or ARV across ages and sexes. Increased hazards of overall all-cause mortality were noticed from the second to fourth quartile of VVV of HbA1c. In detailed age- and sex-stratified analyses, elevated risk of mortality was seen in the fourth quartile of those aged <50 years while in those aged >69 years, increased risk of mortality was noticed in the third and fourth quartiles of any VVV of HbA1c irrespective of sex. In those aged 50-69 years, incremental increased hazards of mortality were consistently observed in the second to fourth quartiles of VVV of HbA1c.ConclusionHbA1c variability whether it was SD, CV, or ARV could strongly predict the risks of all-cause mortality. The extent of the relationship between VVV of HbA1c and all-cause mortality in different age groups was comparable between both sexes. Given the importance of long-term glucose fluctuation, the inclusion of HbA1c variability calculated from the standardized method should be considered by clinical guideline policymakers as part of the biochemical panel in daily diabetes management.

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