School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Graduate School of Public Health and Health Policy, City University of New York, New York, United States.
EBioMedicine. 2022 Oct;84:104259. doi: 10.1016/j.ebiom.2022.104259. Epub 2022 Sep 27.
Hemoglobin A1c (HbA1c) is used for diabetes diagnosis and management. HbA1c also represents iron-related erythrocyte properties which differ by sex. We investigated erythrocyte properties on HbA1c and glucose, and whether corresponding consequences for mortality differed by sex.
In this two-sample Mendelian randomization study using the largest publicly available European descent summary statistics, we assessed sex-specific associations of iron (n=163,511) and hemoglobin (188,076 women/162,398 men) with HbA1c (185,022 women/159,160 men) and fasting glucose (73,089 women/67,506 men), of fasting glucose with HbA1c and diabetes (cases=6,589 women/10,686 men, controls=187,137 women/155,780 men), and of fasting glucose (n=140,595), HbA1c (n=146,806) and liability to diabetes (74,124 cases/824,006 controls) with parental attained age (412,937 mothers/415,311 fathers).
Iron and hemoglobin were inversely associated with HbA1c but not fasting glucose. Fasting glucose was more strongly associated with HbA1c and diabetes in women (1.65 standard deviation (SD) per mmol/L [95% confidence interval 1.58, 1.72]; odds ratio (OR) 7.36 per mmol/L [4.12, 10.98]) than men (0.89 [0.81, 0.98]; OR 2.79 [1.96, 4.98]). The inverse associations of HbA1c and liability to diabetes with lifespan were possibly stronger in men (-1.80 years per percentage [-2.77, -0.42]; -0.93 years per logOR [-1.23, -0.59]) than women (-0.80 [-2.69, 0.66]; -0.44 [-0.62, -0.26]).
HbA1c underestimates fasting glucose in men compared with women, possibly due to erythrocyte properties. Whether HbA1c and liability to diabetes reduce lifespan more in men than women because diagnostic and management criteria involving HbA1c mean that glycemia in men is under-treated compared to women needs urgent investigation.
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血红蛋白 A1c（HbA1c）用于糖尿病的诊断和管理。HbA1c 还代表红细胞的铁相关特性，这些特性因性别而异。我们研究了 HbA1c 和葡萄糖与红细胞特性之间的关系，以及这些特性对死亡率的影响是否因性别而异。
在这项使用最大的公开的欧洲血统汇总统计数据的两样本孟德尔随机化研究中，我们评估了铁（n=163511）和血红蛋白（188076 名女性/162398 名男性）与 HbA1c（185022 名女性/159160 名男性）和空腹血糖（73089 名女性/67506 名男性）、空腹血糖与 HbA1c 和糖尿病（病例=6589 名女性/10686 名男性，对照=187137 名女性/155780 名男性）、空腹血糖（n=140595）、HbA1c（n=146806）和糖尿病易感性（74124 例/824006 例对照）与父母达到的年龄（412937 名母亲/415311 名父亲）之间的性别特异性关联。
铁和血红蛋白与 HbA1c 呈负相关，但与空腹血糖无关。在女性中，空腹血糖与 HbA1c 和糖尿病的相关性更强（每 mmol/L 增加 1.65 个标准差[95%置信区间 1.58，1.72]；每 mmol/L 增加 7.36 个比值比[4.12，10.98]），而在男性中，相关性较弱（每 mmol/L 增加 0.89[0.81，0.98]；每 mmol/L 增加 2.79[1.96，4.98]）。HbA1c 和糖尿病易感性与寿命的负相关关系在男性中可能比女性更强（每增加 1%HbA1c 降低 1.80 年[-2.77，-0.42]；每增加一个 logOR 降低 0.93 年[-1.23，-0.59]），而在女性中则较弱（每增加 1%HbA1c 降低 0.80 年[-2.69，0.66]；每增加一个 logOR 降低 0.44 年[-0.62，-0.26]）。
与女性相比，男性的 HbA1c 低估了空腹血糖，这可能是由于红细胞特性所致。HbA1c 和糖尿病易感性是否会使男性的预期寿命比女性缩短更多，是否因为涉及 HbA1c 的诊断和管理标准意味着男性的血糖治疗不足，需要紧急调查。
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