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

BMJ. 2019 Aug 28:366:l4894. doi: 10.1136/bmj.l4894.

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%.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / analysis
  • Blood Glucose / drug effects
  • Child
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / epidemiology*
  • Diabetic Nephropathies / etiology
  • Diabetic Retinopathy / blood
  • Diabetic Retinopathy / epidemiology*
  • Diabetic Retinopathy / etiology
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis*
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / complications*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Male
  • Registries / statistics & numerical data
  • Retrospective Studies
  • Risk Factors
  • Sweden / epidemiology
  • Young Adult

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents