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INTRODUCTION: The evidence remains contradictory regarding the optimal glycaemic targets needed to address the long-term effects of hyperglycaemia in people with diabetes mellitus (T2DM). We examined the association between HbA1c levels and the risk of individual microvascular complications among people with T2DM. METHODS: We used the Clinical Practice Research Datalink (CPRD) GOLD database for a prospective cohort study, following patients ≥18 years old from diagnosis of T2DM between January 2007 and December 2017. Neuropathy included foot ulcers, peripheral arterial disease, gangrene, and amputation. Nephropathy was classified by chronic kidney disease stages, and retinopathy included blindness and macular oedema. The risk of each complication in five HbA1c intervals 1.0% intervals compared to 48.0-57.9 mmol/mol (6.5-7.5%) was assessed using a multivariate time-varying Cox regression adjusted by various patients' characteristics. Subgroup analyses were performed according to age, hypertension, and the use of antihypertensive medications. RESULTS: Our study included 172,869 patients (mean age 62.6 years and, 54.6% women). The risks were the highest in HbA1c levels >81.0 mmol/mol (>9.6%) (HR 1.27, 95%CI 1.17-1.39 for nephropathy; 1.55, 1.27-1.47 for neuropathy; 1.66, 1.41-1.96 for retinopathy). The lowest risks observed in levels 48.0-57.9 mmol/mol (6.5-7.5%) for nephropathy and in levels <48.0 mmol/mol (<6.5%) for neuropathy (0.98, 0.88-1.09) and for retinopathy (0.89, 0.79-0.99). In the subgroup analysis, higher HbA1c levels were associated with an increased risk of nephropathy, particularly in individuals over 60, those with hypertension, and those using antihypertensive medications. For neuropathy, being over 60 was associated with an increased risk across all HbA1c levels. In retinopathy, hypertension and the use of antihypertensive medications were associated with lower risk across all HbA1c levels, while individuals under 60 were associated with higher risks at elevated HbA1c levels compared to those over 60. CONCLUSION: The risk of retinopathy and neuropathy was lowest in individuals with HbA1c levels within the non-diabetic range <48.0 mmol/mol (<6.5%) and increased progressively with higher HbA1c levels. In contrast, the lowest risk of nephropathy was observed in individuals with HbA1c levels between 48.0 and 57.9 mmol/mol (6.5-7.5%). These findings underscore the importance of a personalized approach to diabetes management that considers multiple risk factors and incorporates novel therapeutic strategies beyond glucose control.
Aldafas et al. (Wed,) studied this question.