Markers of the progression of complications in patients with type 2 diabetes: a one-year longitudinal study

Abstract

Hyperglycemia induces tissue damage and complications by mechanisms that produce advanced glycation end-products (AGEs) and inflammation.To investigate the factors associated with the progression of complications in Type 2 diabetes patients.We recruited 157 patients (110 women and 47 men) with diabetes for more than 5 years who were non-smokers and did not have current infections or chronic diseases. Patients were grouped according to neuropathy, nephropathy, and retinopathy status: without (I), slight or moderate (II), and severe complications (III). We measured glucose, lipids and HbA1c, low molecular weight AGEs (LMW AGEs), high sensitivity C-reactive protein (CRP), TNF-α, IL-6, and malondialdehyde (MDA). Patients were re-evaluated 1 year later.Patients were 52.2±6.8 years old with 11.0±4.9 years since diagnosis. After 1 year, circulating AGEs increased (p<0.0001) and eGFR decreased (p<0.0007) in groups II and III. IL-6 and MDA decreased in groups I and II. CRP (p<0.029) and AGEs (p<0.0001) increased in group II. At baseline in group I, TNF-α levels were higher (p<0.002) in patients who later developed complications. In group II, TNF-α levels (p<0.015) and microalbuminuria (p<0.00004) were higher in patients whose complications progressed. Logistic regression analysis showed that complication progress was significantly associated with log(albuminuria) (p<0.004) and log(TNF-α) (p<0.008). In the total group, AGEs were associated with age (p<0.024) and HbA1c (p<0.026).Our results suggest that baseline TNF-α is an important predictor of complication progression in Type 2 diabetes patients. AGEs also increased during the deterioration of renal function after 1 year of follow-up observation.