ABSTRACT
AIM: The purpose of our study is to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1R agonists) on early markers of kidney damage in patients with type 1 diabetes mellitus (DM). MATERIALS AND METHODS: The study included 27 patients with type 1 diabetes with normo- (n=16) and microalbuminuria (n=11) on intensive insulin injection regimen with insulin analogs. Patients were divided into two groups: 15 patients continued insulin therapy throughout the follow-up period, 12 patients were given 1.2 mg GLP-1R agonist (Liraglutide) once a day in addition to the insulin therapy for 6 months. HbA1c, lipid profile, classic markers of kidney damage (albuminuria, creatinine, glomerular filtration rate); plazma (neutrophilic gelatinase-associated lipoxalin - NGAL, molecule renal damage of type 1 - KIM-1, cystatin C, osteopontin) and urinary kidney biomarkers (nephrin, podocyne, uromodulin, NGAL, KIM-1, collagen type IV, cystatin C) were evaluated prior and in dynamics at 6 months. Kidney biomarkers levels were assessed by the enzyme-linked immunosorbent assay (ELISA). RESULTS: We observed a significant decrease in the urinary excretion of type IV collagen, cystatin C, increased uromodulin excretion and decrease in the plasma levels of osteopontin, NGAL and cystatin C in the group of combined insulin and GLP-1R agonist therapy. CONCLUSION: Changes in the level of sensitive kidney biomarkers indicate a possible renoprotective effect of GLP-1R agonist therapy in patients with type 1 diabetes at an early stages of kidney damage.
Subject(s)
Diabetes Mellitus, Type 1 , Kidney , Albuminuria , Biomarkers/metabolism , Biomarkers/urine , Diabetes Mellitus, Type 1/drug therapy , Glucagon-Like Peptide 1 , Glucagon-Like Peptide Receptors/antagonists & inhibitors , Humans , Hypoglycemic Agents , Kidney/drug effects , Kidney/physiopathologyABSTRACT
AIM: To estimate the urinary excretion of markers for podocyte injury, to specify their value for the early diagnosis of diabetic nephropathy (DN), and to access the risk of its progression in patients with diabetes mellitus (DM) with varying degrees of albuminuria/proteinuria. SUBJECT AND METHODS: Seventy-four diabetic patients (30 with type 1 DM and 44 with type 2 DM) were examined and divided into 3 groups according to the urinary concentration in one urinary portion: 1) 41 patients with normal albuminuria (NAU) (<20 mg/l); 2) 13 patients with microalbuminuria (MAU) (20-200 mg/l); 3) 20 patients with proteinuria (PU) (>200 mg/l). A control group included 10 healthy individuals. The urinary levels of the podocyte structural proteins nephrin and podocin were determined by enzyme immunoassay. RESULTS: Nephrinuria (NU) was detected in 63, 77, and 80% of the patients with NAU, MAU, and PU, respectively. Podocinuria (PDU) was found in 78, 54, and 83% of those with NAU, MAU, and PU, respectively. NU in DN with PU was significantly higher than that in DM with NAU. In the NAU, MAU, and PU subgroups, podocin excretion was equally higher and did not differ between the types of DM. There was a direct correlation of NU with albuminuria, which was stronger in the MAU subgroup. In the patients with DM with varying degrees of albuminuria, the values of NU and PDU correlated directly to serum creatinine levels and inversely with glomerular filtration rate. NU directly correlated with glycated hemoglobin levels in the patients with types 1 and 2 DM of less than 5 years' duration and a direct significant correlation of systolic blood pressure with NU was found in those with type 2 DM. CONCLUSION: Determination of urinary nephrin and podocin levels may be used for the early preclinical diagnosis of DN and the monitoring of the glomerular apparatus in DM.
ABSTRACT
AIM: To investigate the nonglycemic effects of incretins in patients with type 1 diabetes mellitus (DM1) of long duration (for more than 20 years) and chronic kidney disease. MATERIAL AND METHODS: Seventy-five patients with varying degrees of diabetic nephropathy (DN) and without this condition, including patients receiving renal replacement therapy with programmed hemodialysis and those who had undergone kidney transplantation were examined. The levels of phosphorus-calcium metabolic indicators (calcium, phosphorus, parathyroid hormone, vitamin D, and fibroblast growth factor 23 (FGF-23)), the cardiac damage marker atrial natriuretic peptide, the proinflammatory markers monocyte chemoattractant protein 1 (MCP-1) and C-reactive protein (CRP) and the fibrotic marker transforming growth factor-ß, as well as those of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were estimated in addition to conventional examination methods. All the patients underwent cardiac multislice spiral computed tomography, by calculating the Agatston index (calcium index (CI)) reflecting the degree of coronary artery calcification. RESULTS: The investigation revealed no relationship of GLP-1 and GIP levels to the presence and degree of DN in the patients of the study groups. GLP-1 was noted to be inversely related to patient age, indicating the diminished secretion of this peptide in older people. There was evidence that GLP-1 positively affected blood lipid composition (total cholesterol: r=-0,320; p<0.05) and the magnitude of coronary artery calcification (CI: r=-0.308; p<0.05). GIP showed a differently directed effect on the proinflammatory factors: fibrinogen (r=-0.264; p<0.05), CRP (r=-0.626; p<0.05), and FGF-23 (r=-0.341; p<0.05). CONCLUSION: The investigation has demonstrated the nonglycemic effects of incretins that favorably affect the pathogenetic processes underlying the late complications of DM1. The findings point to the potential efficacy of incretin-based drugs in preventing and treating the late complications of DM, which necessitates the conduction of larger investigations.
ABSTRACT
Comparative analysis of the data of immunological examination of pregnant women with markers of genitourinary infections (GUI), by taking into account the etiological factor, has established unidirectional changes in the levels cytokines and neopterin (NP). At the same time, the level of NP in all the groups of examinees with GUI was higher than that of cytokines. The highest content of NP in blood and cervical canal mucus (CCM) was noted in pregnant women with GUI of viral etiology. The changes in NP levels in infections caused by various viruses were similar. The study of the levels of cytokines and NP in the peripheral blood and CCM samples yielded information on the functional activity of different types of immunocompetent cells, the magnitude of an inflammatory process, its transition to the systemic level, and on the prediction of infection development.
