Evaluation of Early Markers of Nephropathy in Patients with Type 2 Diabetes Mellitus

Abstract

Aims. T2DM often remains undiagnosed for many years because hyperglycemia develops gradually and may not produce any symptoms. As patients with T2DM are at increased risk of microvascular and macrovascular complications, the preclinical diagnosis of the state is the key point of the disease management. Methods. We evaluated parameters such as GAGs/PGs, NAG, and NGAL in urine samples from 43 normoalbuminuric T2DM patients and 31 apparently healthy control subjects. Results. The total urinary GAG excretion showed no significant differences between patients and controls. The electrophoretic analysis evidenced the presence of UTI and its degradation products (LSC and SM-LSC), CS, and HS. We observed modifications of HS and total UTI (including UTI and its degradation products) relative contents in T2DM patients compared with controls whereas no differences in CS percentage were found. NGAL levels were significantly increased in T2DM patients and were positively correlated with both NAG (r = 0.606, p < 0.0001) and the presence of hypertension (r = 0.352, p < 0.05). Conclusions. These data suggest that the assessed molecules could represent useful markers to detect early renal impairment in patients with T2DM.

Defining reference intervals for a serum growth differentiation factor-15 (GDF-15) assay in a Caucasian population and its potential utility in diabetic kidney disease (DKD)

“…Several authors [16][17][18] have long noted the need for biomarkers in DM care that can improve patient outcomes, even at the individual level by identifying which patients will develop micro-or macro-vascular complications, respond to therapy or are eligible for inclusion in clinical trials [19]. These markers may facilitate cardiovascular risk stratification and the introduction of therapy at an earlier time point to reduce renal risk [20][21][22].…”

Retinal Vessel Analysis as a Novel Screening Tool to Identify Childhood Acute Lymphoblastic Leukemia Survivors at Risk of Cardiovascular Disease

“…[41][42][43] Additionally, CRP is also associated with albuminuria in individuals with diabetes, which is a known marker of diabetic nephropathy. [44][45][46] We hypothesise that inflammation may play an important role in late effects observed among CCS, although the exact pathophysiological mechanisms remain to be elucidated. Therapy-induced damage to normal cells may be associated with systemic chronic inflammation, leading to premature aging and late effects in CCS.…”

Levels of Urinary Trypsin Inhibitor and Structure of Its Chondroitin Sulphate Moiety in Type 1 and Type 2 Diabetes

“…Except for a few studies that report no change or even a reduced excretion of GAGs/PGs, a plethora of papers evidence an increased excretion as a whole (in most of them only a quantitative analysis was performed) and in particular of HS in both type 1 and 2 diabetes, often in association with diabetic nephropathy [ 48 ]. In the last years, we reported an association among UTI and both type 1 and 2 diabetes [ 31 – 35 ] suggesting UTI as a promising marker for the chronic inflammation resulting from diabetic condition [ 31 , 32 ]. Despite the numerous studies on both UTI structure and function, several aspects related to its structural modifications following inflammation and their relevance for a biological and diagnostic point of view remain to be elucidated.…”

“…Several studies reported that UTI/bikunin levels can increase up to 10-fold following both acute and chronic inflammatory diseases [ 22 ], bladder carcinoma [ 23 ], brain contusion [ 24 ], disseminated cancers [ 25 ], acute hepatitis [ 26 ], Fabry's disease [ 27 ], Crohn's disease, arthritis, pericarditis, deep vein thrombosis, fibromyalgia, asthmatiform bronchitis [ 28 , neoplasia, and kidney diseases [ 4 ]. Besides, we reported variations of UTI/GAGs levels in pathological conditions such as chronic glomerulonephritis [ 29 , 30 ], type 1 and 2 diabetes [ 31 – 35 ], systemic lupus erythematosus [ 36 ] and following kidney transplantation [ 37 ]. In human plasma, the concentration of bikunin is 4–7 μ M, of which only 2–10% is in free form, while in urine UTI levels are about 0.03–0.05 μ M [ 4 ].…”