HbA1c 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%.

Fig 1

Adjusted odds ratios (95% confidence intervals) for retinopathy and nephropathy for 10 mmol/mol increase in glycated haemoglobin (HbA_1c) area under curve. y axis is on logarithmic scale. Proliferative diabetic retinopathy/laser photocoagulation and macroalbuminuria adjusted only for age and sex owing to small number of events; other outcomes adjusted for age, sex, mean systolic and mean diastolic blood pressure, mean body mass index, mean high and mean low density lipoprotein cholesterol, mean cholesterol, mean triglycerides, and smoking. PPDR=preproliferative diabetic retinopathy; PDR=proliferative diabetic retinopathy. Whiskers represent 95% confidence intervals

Fig 2

Estimated cumulative probability for preproliferative diabetic retinopathy or worse (PPDR), proliferative diabetic retinopathy (PDR), and laser photocoagulation for different area under the curve (AUC) glycated haemoglobin (HbA_1c) values allowing for non-linear relation using spline functions for follow-up cohorts. Shaded areas represent 95% confidence intervals