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.

Factors Associated with Higher Pro-Inflammatory Tumor Necrosis Factor-α Levels in Young Women with Type 1 Diabetes

“…Further, they found that higher levels of TNF-α were associated with both more advanced stages of retinopathy and albuminuria, as well as the presence of cardiovascular disease. This is further supported by a longitudinal study, though in type 2 diabetes, that found baseline TNF-α levels were positively associated with progression of complications over one year [34]. In light of our data indicating that higher C-peptide may predict lower TNF-α levels years later, and data from the DCCT demonstrating that higher residual C-peptide levels were associated with lower incidence rates of microvascular complications [35], TNF-α may be not only a marker for higher risk of complications, but may play a pathophysiological role in the progression of hypertension or microalbumiuria.…”

Local and Systemic Inflammatory Biomarkers of Diabetic Retinopathy: An Integrative Approach

“…18,19 Baseline circulating TNFa was a predictor of DR incidence, 20 as well as of diabetic complications progression. 21 In addition, a strong correlation between plasma levels of TNF-a and PDR has been reported. 22,23 However, Klein et al 24 reported that this correlation was mediated by the presence of kidney disease.…”

Socioeconomic Deprivation Independently Predicts Painful Diabetic Neuropathy in Type 2 Diabetes

“…Further, patient education to achieve understanding of the importance of adhering to what can be a complex preventive strategy [19], willingness, motivation and the domestic and workplace-related circumstances, may also be adversely affected by lower socio-economic status [18]. Identification of markers of progression of diabetes neuropathy is a critical area of research with impact on outcomes for many patients [20,21]. We also studied drug prescription patterns for painful neuropathy in our study population.…”