HbA1c level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes: Swedish population based cohort study

Marcus Lind, Aldina Pivodic, Ann-Marie Svensson, Arndis F Ólafsdóttir, Hans Wedel, Johnny Ludvigsson, Marcus Lind, Aldina Pivodic, Ann-Marie Svensson, Arndis F Ólafsdóttir, Hans Wedel, Johnny Ludvigsson

Abstract

Objective: To evaluate if the lowest target level for glycated haemoglobin (HbA1c) 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 HbA1c.

Results: Mean age of participants was 14.7 years (43.4% female), mean duration of diabetes was 1.3 years, and mean HbA1c 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 HbA1c <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 HbA1c levels 6.5-6.9%, HbA1c 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 HbA1c levels >8.6% (>70 mmol/mol). The risk for severe hypoglycaemia was increased at mean HbA1c <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 HbA1c levels <6.5% but increased for severe hypoglycaemia compared with HbA1c levels 6.5-6.9%. The risk for severe complications mainly occurred at HbA1c levels >8.6%, but for milder complications was increased at HbA1c levels >7.0%.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: ML has received grants from AstraZeneca, Dexcom, Novo Nordisk, and Pfizer, and consulting fees from AstraZeneca, Dexcom, Eli Lilly, MSD, Novo Nordisk, and Rubin Medical; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Fig 1
Fig 1
Adjusted odds ratios (95% confidence intervals) for retinopathy and nephropathy for 10 mmol/mol increase in glycated haemoglobin (HbA1c) 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
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 (HbA1c) values allowing for non-linear relation using spline functions for follow-up cohorts. Shaded areas represent 95% confidence intervals

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