Abstract
INTRODUCTION: There is conflicting evidence regarding optimal glycaemic targets to reflect the legacy effect of hyperglycaemia in people with type 2 diabetes (T2D). We examined the risks of microvascular complications and hospital admission with glycated haemoglobin (HbA1c) levels from the diagnosis of T2D. METHODS: We identified individuals with incident T2D from 1998 to 2007 from the Clinical Practice Research Datalink and Hospital Episode Statistics. A composite microvascular outcome was defined as a new diagnosis of neuropathy, nephropathy or retinopathy. A multivariate time-varying Cox regression analysis was performed to assess the risk of microvascular disease associated with HbA1c at five different levels (1.0% (11 mmol/mol) intervals). HbA1c 6.5%-7.5% (48.0-58.9 mmol/mol) was defined as the reference. RESULTS: N = 172,869 (mean age 62.6 ± 14.0 years, 54.6% female) were analysed. Average follow-up was 11.2 years. The risk of microvascular disease increased with higher HbA1c levels, the highest risk in the ⩾9.6% (⩾81 mmol/mol; hazard ratio (HR): 1.29, 95% confidence interval (CI): 1.11-1.51) and the lowest in the <6.5% (<48.0 mmol/mol; HR: 0.94, 95% CI: 0.83-1.08). The risk of hospital admission suggested a U-shaped association with HbA1c, highest risk in the lowest (<6.5% (<48.0 mmol/mol); HR: 1.04, 95% CI: 1.01-1.07) followed by HbA1c groups (8.6%-9.6% (70.0-81.0 mmol/mol); HR: 1.02, 95% CI: 0.97-1.08) while the lowest risk for hospital admission was observed for targets with the reference group (target between 6.5% and 7.5%, (48.0-58.9 mmol/mol)). CONCLUSION: The risk of microvascular complications was lowest when HbA1c levels were within the non-diabetic range and increased with higher HbA1c levels. The risk of hospital admission was significantly elevated in individuals with HbA1c levels below 6.5%, suggesting a potential U-shaped association, although the increased risk at higher HbA1c levels did not reach statistical significance. This highlights the importance of maintaining individualised HbA1c targets in the management of T2D from diagnosis to prevent these complications.