Effect of Subclinical Hypothyroidism on the Association between Hemoglobin A1c and Reduced Renal Function: A Prospective Study

Subclinical hypothyroidism (SCH) was reported to be associated with accelerating endothelial dysfunction, which is recognized as one of the upstream mechanisms that leads to glomerular injury (lower glomerular filtration rate (GFR)). SCH was also reported to be associated with hyperglycemia, which is associated with higher hemoglobin A1c (HbA1c) levels and induces endothelial dysfunction. Therefore, SCH status could influence the association between HbA1c and reduced eGFR. To clarify those associations, we conducted a prospective study of 1580 Japanese individuals who participated in an annual health check-up in 2014 with 2.8 years of follow-up. All participants had free triiodothyronine (T3) and free thyroxine (T4) levels in the normal range. Among study participants, 88 were diagnosed as having SCH. Even though no significant correlation was observed between HbA1c and annual change in estimated GFR among participants without SCH (multi-adjusted standardized parameter estimate (beta) = 0.03, p = 0.250), a significant inverse association was observed among participants with SCH (beta = -0.26, p = 0.014). When those analyses were performed among participants who were not taking glucose lowering medication, the observed associations were essentially the same: beta = 0.03, p = 0.266 for participants without SCH and beta = -0.32, p = 0.006 for participants with SCH, respectively. Therefore, SCH status could influence the association between HbA1c and renal function.