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

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%.