Low C-peptide together with high GADA levels predict progression to insulin dependence in LADA. The HUNT study.

AIMS: Progression to insulin dependence is variable in latent autoimmune diabetes in adults (LADA). Few studies have investigated factors behind progression. We looked for risk factors that could predict progression in LADA and compared them to those of type 2 diabetes.

MATERIALS AND METHODS: This study included 175 participants with LADA (autoantibody positive, without insulin treatment ≥1 year after diagnosis) and 2331 participants with type 2 diabetes (autoantibody negative, without insulin treatment ≥1 year after diagnosis) from the HUNT2 and HUNT3 surveys. We used Cox regression models and receiver operating characteristic curve analysis to identify predictive factors on progression to insulin dependency within 10 years.

RESULTS: Low C-peptide levels (<0.3nmol/l) predicted progression to insulin dependency within 10 years in both LADA (HR 6.40 [95% CI, 2.02-20.3]) and type 2 diabetes (HR 5.01 [95% CI, 3.53-7.10]). In addition, high GADA level (HR 5.37 [95% CI, 1.17-24.6]) predicted progression in LADA. Together these two factors had a discriminatory power between non-progressors and progressors of AUC 0.86 [95% CI, 0.80-0.93]. In type 2 diabetes, younger age at diagnosis (<50 years: HR 2.83 [95% CI, 1.56-5.15]; 50-69 years: HR 2.11 [95% CI, 1.19-3.74]), high HbA1c levels (≥53 mmol/mol, HR 2.44 [95% CI, 1.72-3.46]), central obesity (HR 1.65 [95% CI, 1.06-2.55]) and BMI >30kg/m2 (HR 1.73 [95% CI, 1.23-2.41]) were independent predictors. Together with C-peptide they reached an AUC of 0.79 [95% CI, 0.76-0.82].

CONCLUSION: Factors predicting progression to insulin dependence are partly similar, partly dissimilar between LADA and type 2 diabetes. A constellation of low C-peptide and high GADA levels identify LADA patients likely to progress to insulin dependence. This article is protected by copyright. All rights reserved.