HbA 1c level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes: Swedish population based cohort study

Abstract

Objective To evaluate if the lowest target level for glycated haemoglobin (HbA 1c) of <6.5% is associated with lower risk for retinopathy and nephropathy than less tight control in children and adults with type 1 diabetes. Design Population based cohort study. Setting Swedish National Diabetes Registry, 1 January 1998 to 31 December 2017. Participants 10 398 children and adults with type 1 diabetes followed from diagnosis, or close thereafter, until end of 2017. Main outcome measures Relative risk (odds ratios) for retinopathy and nephropathy for different mean levels of HbA 1c. Results Mean age of participants was 14.7 years (43.4% female), mean duration of diabetes was 1.3 years, and mean HbA 1c level was 8.0% (63.4 mmol/mol). After adjustment for age, sex, duration of diabetes, blood pressure, blood lipid levels, body mass index, and smoking, the odds ratio for mean HbA 1c <6.5% (<48 mmol/mol) compared with 6.5-6.9% (48-52 mmol/mol) for any retinopathy (simplex or worse) was 0.77 (95% confidence interval 0.56 to 1.05, P=0.10), for preproliferative diabetic retinopathy or worse was 3.29 (0.99 to 10.96, P=0.05), for proliferative diabetic retinopathy was 2.48 (0.71 to 8.62, P=0.15), for microalbuminuria or worse was 0.98 (0.60 to 1.61, P=0.95), and for macroalbuminuria was 2.47 (0.69 to 8.87, P=0.17). Compared with HbA 1c levels 6.5-6.9%, HbA 1c levels 7.0-7.4% (53-57 mmol/mol) were associated with an increased risk of any retinopathy (1.31, 1.05 to 1.64, P=0.02) and microalbuminuria (1.55, 1.03 to 2.32, P=0.03). The risk for proliferative retinopathy (5.98, 2.10 to 17.06, P<0.001) and macroalbuminuria (3.43, 1.14 to 10.26, P=0.03) increased at HbA 1c levels >8.6% (>70 mmol/mol). The risk for severe hypoglycaemia was increased at mean HbA 1c <6.5% compared with 6.5-6.9% (relative risk 1.34, 95% confidence interval 1.09 to 1.64, P=0.005). Conclusions Risk of retinopathy and nephropathy did not differ at HbA 1c levels <6.5% but increased for severe hypoglycaemia compared with HbA 1c levels 6.5-6.9%. The risk for severe complications mainly occurred at HbA 1c levels >8.6%, but for milder complications was increased at HbA 1c levels >7.0%.