Effects of thyroid hormone replacement on glycated hemoglobin levels in non diabetic subjects with overt hypothyroidism

Objective Glycated hemoglobin (HbA1c) may not accurately reflect the level of glycemia in conditions of altered erythrocyte turnover. Hypothyroidism is one condition associated with sluggish erythropoesis. To assess changes in HbA1c, independent of changes in plasma glucose after initiation of thyroxine replacement in patients with overt hypothyroidism. Materials and methods In this prospective longitudinal study carried out in a tertiary care centre, adult non-diabetic patients with overt hypothyroidism recruited between March 2012 to August 2013 were rendered euthyroid on thyroxine. They underwent testing for hemoglobin, HbA1c, reticulocyte count, thyroxine, thyrotropin and a standard oral glucose tolerance test, both before and at 3 months after restoration to the euthyroid state. Main outcome assessed was the change in HbA1c independent of the change in glucose parameters. Results Thirty eight patients (35 female and 3 male) aged 37.8 ± 10.2 years with overt hypothyroidism (thyroxine 12.6 ± 13.4 ng/mL and thyrotropin -98.1 ± 63.7 µIU/mL respectively) were recruited. While HbA1c fell from 5.8 ± 0.7% to 5.6 ± 0.5% (p = 0.009) at 3 months following the correction of hypothyroidism, there were no changes in the fasting and the 2 hr post oral glucose tolerance test glucose (p = 0.67 and 0.56 respectively). The number of patients with dysglycemia diagnosed by HbA1c (i.e HbA1c≥ 5.7%) fell from 25 (65.78%) to 17 (44.7%) after treatment (p = 0.008). There were 7 (18.4%) patients with HbA1c ≥ 6.5% at baseline, but this fell to just 4 (10.5%) (p < 0.001) after 3 months of euthyroidism. Conclusion HbA1c is not a reliable diagnostic test for diabetes in the presence of hypothyroidism.

研究背景与目的：糖化血红蛋白（glycated hemoglobin, HbA1c）在红细胞周转（erythrocyte turnover）异常的情况下，可能无法准确反映血糖水平。甲状腺功能减退症（hypothyroidism）是与红细胞生成迟缓相关的疾病之一。本研究旨在评估显性甲状腺功能减退症（overt hypothyroidism）患者接受甲状腺素替代治疗（thyroxine replacement）后，糖化血红蛋白的变化是否独立于血浆葡萄糖水平的变化。

材料与方法：本研究为一项在三级医疗中心开展的前瞻性纵向研究，纳入2012年3月至2013年8月期间招募的成年非糖尿病显性甲状腺功能减退症患者，予甲状腺素治疗使其恢复至甲状腺功能正常状态（euthyroid state）。分别于甲状腺功能恢复正常前及恢复后3个月，对所有受试者进行血红蛋白、糖化血红蛋白、网织红细胞计数（reticulocyte count）、甲状腺素、促甲状腺素（thyrotropin）以及标准口服葡萄糖耐量试验（standard oral glucose tolerance test）检测。本研究的主要评估结局为糖化血红蛋白的变化是否独立于血糖参数的变化。

结果：本研究共纳入38例患者（女性35例，男性3例），年龄为37.8±10.2岁，基线甲状腺素水平为12.6±13.4 ng/mL，促甲状腺素水平为98.1±63.7 µIU/mL。甲状腺功能纠正后3个月，受试者糖化血红蛋白从5.8±0.7%降至5.6±0.5%（p=0.009），但空腹血糖及口服葡萄糖耐量试验后2小时血糖均无显著变化（分别为p=0.67和0.56）。根据糖化血红蛋白诊断的血糖异常人群（即糖化血红蛋白≥5.7%）从基线的25例（65.78%）降至17例（44.7%）（p=0.008）。基线时有7例（18.4%）受试者糖化血红蛋白≥6.5%，甲状腺功能恢复正常3个月后仅余4例（10.5%）（p<0.001）。

结论：甲状腺功能减退症患者中，糖化血红蛋白并非可靠的糖尿病诊断检测手段。