Risk-Factor Trajectories Preceding Diabetic Polyneuropathy: ADDITION-Denmark

OBJECTIVE To study cardiometabolic risk-factor trajectories (in terms of levels and changes over time) preceding diabetic polyneuropathy (DPN) 13 years after a screen-detected diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS We clinically diagnosed DPN in a nested case-control study of 452 people in the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION). By linear regression models, we estimated preceding risk-factor trajectories during 13 years. Risk of DPN was estimated by multivariate logistic regression models of each individual’s risk-factor trajectory intercept and slope adjusting for sex, age, diabetes duration, height, and trial randomization group. RESULTS Higher baseline levels of HbA 1c (odds ratio [OR] 1.76 [95% CI 1.37; 2.27] and OR 1.68 [95% CI 1.33; 2.12] per 1% and 10 mmol/mol, respectively) and steeper increases in HbA 1c over time (OR 1.66 [95% CI 1.21; 2.28] and OR 1.59 [95% CI 1.19; 2.12] per 1% and 10 mmol/mol increase during 10 years, respectively) were associated with DPN. Higher baseline levels of weight, waist circumference, and BMI were associated with DPN (OR 1.20 [95% CI 1.10; 1.31] per 5 kg, OR 1.27 [95% CI 1.13; 1.43] per 5 cm, and OR 1.24 [95% CI 1.12; 1.38] per 2 kg/m 2 , respectively). CONCLUSIONS Both higher levels and slopes of HbA 1c trajectories were associated with DPN after 13 years. Our findings indicate that the rate of HbA 1c increase affects the development of DPN over and above the effect of the HbA 1c level. Furthermore, this study supports obesity as a risk factor for DPN.