medwireNews: Aiming for the lowest international targets in glycated hemoglobin (HbA1c) levels may not protect against retinopathy and nephropathy in patients with type 1 diabetes, research suggests.
The Swedish registry study of 10,398 children and adults with type 1 diabetes found no statistically significant reduced risk for these microvascular complications among individuals with a mean HbA1c below 6.5% (48 mmol/mol) compared with a reference group who had a mean of 6.5% to 6.9% (48–52 mmol/mol) during a follow-up of between 8 and 20 years, after adjusting for other factors.
However, individuals in the lower HbA1c group were a significant 1.34 times more likely to experience severe hypoglycemia than the reference group. Indeed, each 1% (10 mmol/mol) increase in mean HbA1c was associated with a significant 21% reduction in the risk for severe hypoglycemia.
Study participants were a mean age of 14.7 years at registration, had lived with type 1 diabetes for a mean of 1.3 years, and had a mean HbA1c during follow-up of 8.0% (63.4 mmol/mol).
Milder complications increased with HbA1c levels above 7.0% (53 mmol/mol) such that, compared with the reference group, mean HbA1c levels of 7.0% to 7.4% (53–57 mmol/mol) were significantly associated with a 1.31-fold increased risk for any type of retinopathy and a 1.55-fold increased risk for microalbuminuria.
Severe diabetic complications in the form of proliferative retinopathy and macroalbuminuria first became evident with a mean HbA1c greater than 8.6% (70 mmol/mol), with the risk raised a significant 5.98 and 3.43 times, respectively, in these patients compared with the reference group.
Interestingly, preproliferative diabetic retinopathy or worse occurred in seven participants with the lowest HbA1c of less than 6.5% (48 mmol/mol), which Marcus Lind (University of Gothenburg, Sweden) and co-workers note was “an increased risk of borderline significance” versus the reference group.
Reporting in The BMJ, they write: “It seems unlikely that low HbA1c levels indicating glucose levels close to normal should be harmful in themselves; however, preclinical studies have indicated that microvascular complications might be promoted by frequent hypoglycaemia.”
The researchers suggest that “clinicians should be extra vigilant about ensuring people with diabetes do not spend considerable time in hypoglycaemia and that treatment is related to good quality of life at HbA1c levels below 6.5% (<48 mmol/mol) or else aim at higher levels of 6.5–6.9% (48–52 mmol/mol).”
As such, they conclude: “Other measures, including time in range, time in hypoglycaemia, and variation in glycaemia will be essential complementary measures to HbA1c in clinical practice and future studies.”
By Anita Chakraverty
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