The Impact of Age and Sex on Fasting Plasma Glucose and Glycated Haemoglobin (HbA1c) in the Non-diabetes Population.

introductionWe previously reported sex differences in the distribution of glycated haemoglobin (HbA1c) for men/women aged < 50 years vs older individuals, with implications for delayed diabetes diagnosis. Here, we explored whether this pattern was also seen in matched fasting plasma glucose (FPG) levels.

methodsWe extracted data on same-day, paired HbA1c and FPG levels from clinical biochemistry laboratory databases from Mersey and West Lancashire Teaching Hospitals NHS Trust (n = 10,153) and Cambridge University Hospitals NHS Foundation Trust (n = 10,022) between Jan 2019 and Dec 2023. Only cases with a single, general-practice HbA1c test were utilised to minimise the risk of including non-diagnostic tests and tests from specialist care (e.g. endocrinology, antenatal services; final dataset: n = 17,271). We examined the links of HbA1c and FPG levels to age and sex.

resultsMedian HbA1c levels were 1 mmol/mol lower in women aged < 45 years compared to men aged < 45 years but not in those aged ≥ 45 years. This pattern was not seen with FPG, where median levels in women were 0.1-0.2 mmol/L lower across all ages. The HbA1c:FPG ratio was significantly higher in women than men in the 45-54 and ≥ 55 years age groups (p = 0.004, Z-score = 2.9 and p =  < 0.001, Z-score = 8.9, respectively) but not in the < 45 years age group (p = 0.649, Z-score = 0.5). We confirmed our previous finding that median HbA1c levels in women aged ≥ 55 years and 45-55 years were the same as those in men (39 and 37 mmol/mol, respectively) and that for women aged < 45 years, the median HbA1c (34 mmol/mol) was 1 mol/mol lower than for men (35 mmol/mol). This is reflected in the Z-scores, which showed the largest deviation from zero in the < 45 years age group (- 9.1) and the smallest in the older age group (- 2.9).

conclusionWe showed differences in HbA1c and FPG patterns with age between men and women, with implications for the diabetes diagnostic threshold for HbA1c in pre-menopausal women, the underdiagnosis of type 2 diabetes in younger women, and missed opportunities for intervention. We propose that a suggested change to HbA1c reference ranges in this group warrants serious consideration and detailed evaluation.