[Show abstract][Hide abstract] ABSTRACT: This review presents an analysis of clinical and experimental studies related to post-transplantation diabetes mellitus (PTDM) - a specific complication after solid organ transplantation. A search of the databases eLibrary, PubMed and Scopus using the keywords ≪posttransplantation diabetes mellitus≫, ≪new onset diabetes after transplantation≫, ≪transplantation≫ and ≪immunosuppression≫ yielded in 523 results, including four from Russian literature (one original research manuscript). The analysis included original research, reviews, meta-analyses and monographs published not before 2005 in Russian and English. A total of 60 relevant original researches and reviews were included in this review. Diagnostic criteria, disease risk factors and potential pathogenic mechanisms were all considered. The mechanisms of the diabetogenic effect of modern immunosuppressive drugs were analysed. The principles of pre- and post-transplantation screening for PTDM and optimal management strategies for patients with PTDM are presented. The current controversial issues concerning the various aspects of PTDM are discussed.
[Show abstract][Hide abstract] ABSTRACT: Genetic susceptibility plays an important role in the risk of developing chronic complications in patients with type 2 diabetes mellitus (T2DM). Aims: In this study, we evaluated the possible association of the polymorphic variants that encode key renal damage mediators (endothelial dysfunction, lipid metabolism and insulin secretion/sensitivity) with the risk of chronic kidney disease (CKD) in patients with T2DM. Materials and Methods: We enrolled 435 patients with T2DM using case-control study design. In 253 patients, we used non-overlapping criteria to form groups with/without CKD (defined as GFR<60 ml/min/1.73 m2) according to the duration of T2DM (≤5 years/≥10 years) (n=75 and 178, respectively) and analysed the following 4 polymorphic markers: I/D in ACE, ecNOS4a/4b in NOS3, I/D in APOB and e2/e3/e4 in APOE genes. We then divided 182 patients in groups with/without CKD (n=38 and 144, respectively) regardless of the duration of diabetes and studied pro12ala in PPARG2, rs5219 in KCNJ11, rs12255372 in TCF7L2 and rs13266634 in SLC30A8 genes. Statistical analysis was performed using the X2 test, and data were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Values of p <0.05 indicated statistical significance. Results: Four genes were found to have a significant association with CKD occurrence. For the eNOS3 the allele 4a and 4a/4a genotype was associated with a twofold CKD risk (OR=2.2/9.88) and the allele 4b and 4b/4b polymorphism were protective regarding CKD development (OR=0.44/0.45). For APOB I/D, the genotype DD was associated with lower risk of CKD [OR for DD=0.2 (95% CI: 0.05-0.88)]. In the second group, genotype TT of TCF7L2 predisposed to CKD (OR=3.03, 95% CI: 1.07-8.58). For KCNJ11 group genotype AA predisposed to CKD (OR=2.25, 95% CI: 1.02-4.97) compared to the allele G (OR=0,57, 95% CI: 0.34-0.96). Conclusions: In conclusion, our findings indicate a significant role of functional genetic variants associated with genes of endothelial factors (NOS3), lipid metabolism (APOB), and insulin secretion factors (KCNJ11, TCF7L2) in modulating the risk of CKD and their significant involvement in the mechanism of kidney damage in patients with T2DM.
[Show abstract][Hide abstract] ABSTRACT: Expansion of diabetic population (predominantly due to type 2 diabetes mellitus) with chronic kidney disease (CKD) comorbidity constitutes one of the major challenges in modern medicine. Throughout the course of diabetes nephropathy development, from its debut to the terminal stage, survival rate and quality of life are lower than those of other categories of patients. This indicates crucial role of hyperglycemia in accelerated metabolic degradation typical of CKD. Renal disease severely narrows the spectrum of available glucose-lowering agents. Concurrent treatment for hypertension and dyslipidemia, as well as anti-platelet therapy and stimulation of erythropoiesis becomes a complex issue. A creative and patient-oriented approach with clear metabolic and cardiovascular goals should be instrumental in its solution.
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular complications, a major cause for disability and morbidity in diabetes mellitus (DM), constitute the greatest threat of the diabetes epidemic. Glycemic stability within the therapeutic targets is a prerequisite to prevention of micro- and macrovascular complications of DM. Traditional therapies are aimed at cardinal defects determining development of type 2 diabetes mellitus (T2DM). Unfortunately even in combination they fail to deliver long-term glycemic control without stimulation of weight gain and increase in hypoglycemic risks with negative cardial, renal and hepatic impact. Preservation of β-cell secretion capacity is also hardly attainable. Incretin-based therapy is a novel, actively developed approach that influences gut hormone physiology for better glycemic control. So far research efforts have yielded two classes of drugs: GLP-1 mimetics and DPP-4 inhibitors. Both are regarded nowadays for a number of important benefits, including β-cell function improvement, adjusted to human physiology (i.e. stimulation of insulin secretion «as needed» by the body, - hence low hypoglycemic risk). They also feature positive cardiovascular and body weight effects, thereby taking an important position in complex DM treatment.
[Show abstract][Hide abstract] ABSTRACT: The program of renoprotection in patients with diabetes mellitus (DM) is based on a conceptual model of development and progression of diabetic kidney disease, which is the result of combined impact of genetically modulated metabolic and hemodynamic factors. Compensation of carbohydrate metabolism, which is crucial at the clinical debut of nephropathy, becomes problematic at the late stages of chronic kidney disease (CKD). ADA (American Diabetes Association) and EASD (European Association for the Study of Diabetes) recommendations formalized in a consensus on the treatment of patients with type 2 diabetes (T2D) should only be extrapolated to patients with CKD with great prudence. Incretin-based drugs gain reputation as promising and perspective therapy for metabolic control in patients with type 2 DM and CKD. There is an obvious need for large-scale, long-term studies involving patients with various severity of renal disease and related complications to assess the potential of this new diabetes therapy trend.
[Show abstract][Hide abstract] ABSTRACT: During latest decade, as threat of acute complications of diabetes mellitus was surmounted, cardiovascular complications became leading cause of death. Clinical manifestation of coronary, brachiocephalic and renal atherosclerosis is quite dramatic in diabetes mellitus, which determines extent of dissemination and intensity of lesions. Combination of these mutually confounding conditions is a characteristic problem of patients with diabetes mellitus. Presence of 2+ risk factors (one of which is diabetes mellitus in itself) requires active examination in order to rule out coronary, brachiocephalic, peripheral and renal artery lesions. Aggressive care is necessary in order to control progression of disease and administer adequate conservative and endovascular treatment with account of high risk of combination of lesions.
[Show abstract][Hide abstract] ABSTRACT: The second isoform of the PPARgamma2 is specific for adipose tissue. In adipocytes, this isoform is involved in the regulation of adipogenesis and lipid storage, insulin and glucose metabolism. Pro12Ala, a missense mutation in exon 2 of PPARG, reduces transcriptional activity of PPARgamma2 and is shown to be associated with increased insulin sensitivity and protection from T2D. Previously, this polymorphism has never been assessed in a Russian population for its relationship to T2D, insulin resistance, and diabetes-related metabolic traits. In this study, we tested 588 Russian T2D patients and 597 normoglycaemic controls. Carriers of the Pro12 allele and subjects homozygous for Pro/Pro had significantly increased risk of developing T2D (OR 1.43 and 2.04, respectively). In Pro/Pro homozygotes, adjustment for potential confounding risk factors resulted in reducing the OR value from 2.04 to 1.69, but the association remained significant (p=0.046).The Pro/Pro genotype also showed association with increased levels of fasting insulin (p=0.019) in non-diabetic controls and elevated serum triglycerides (p=0.019) in T2D patients. Compared with other genotypes, non-diabetic and diabetic subjects homozygous for Pro/Pro had a significantly higher HOMA-IR score and reduced ISI value. This observation strongly supports the implication of the PPARG Pro12Ala in insulin resistance and T2D in a Russian population.
Full-text · Article · Jan 2010 · Diabetes & Vascular Disease Research