Copeptin Plasma Levels are Associated with Decline of Renal Function in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Chronic kidney disease (CKD) is a leading complication of type 2 diabetes mellitus (T2DM) and is considered as a public health problem. Copeptin is a surrogate marker of arginine vasopressin (AVP) system and is proposed as a biomarker of decline renal function. OBJECTIVE: Evaluate whether plasma copeptin levels may be used as a biomarker of decline renal function in patients with T2DM. RESEARCH DESIGN AND METHODS: A total of 480 patients with T2DM and different stages of CKD were included. Plasma levels of copeptin, cystatin-C, and other biochemical parameters were measured. The correlation between copeptin and glomerular filtration rate (GFR), estimated based on plasma cystatin-C levels, was investigated. RESULTS: Plasma copeptin levels were gradually increased from the stage 1-5 of CKD in the patients with T2DM. In univariate linear regression analysis, high plasma levels of copeptin were associated with lower GFR (Standardized ß = -0.535, R2 = 0.287, p <0.0001). This association remained significant even after being adjusted for glucose levels and years of T2DM diagnosis, mean blood pressure, pharmacological treatment, gender, and age. CONCLUSIONS: The results show that high plasma copeptin levels are associated with the decline of renal function in patients with T2DM and, therefore, copeptin may be considered as a biomarker of renal function. Further evaluation of plasma copeptin levels to predict morbidity and mortality of T2DM patients, with or without CKD, has been taken into our consideration.

The eukaryotic translation initiation factor 3f (eIF3f) interacts physically with the alpha 1B-adrenergic receptor and stimulates adrenoceptor activity.

BACKGROUND: eIF3f is a multifunctional protein capable of interacting with proteins involved in different cellular processes, such as protein synthesis, DNA repair, and viral mRNA edition. In human cells, eIF3f is related to cell cycle and proliferation, and its deregulation compromises cell viability. RESULTS: We here report that, in native conditions, eIF3f physically interacts with the alpha 1B-adrenergic receptor, a plasma membrane protein considered as a proto-oncogene, and involved in vasoconstriction and cell proliferation. The complex formed by eIF3f and alpha 1B-ADR was found in human and mouse cell lines. Upon catecholamine stimulation, eIF3f promotes adrenoceptor activity in vitro, independently of the eIF3f proline- and alanine-rich N-terminal region. CONCLUSIONS: The eIF3f/alpha adrenergic receptor interaction opens new insights regarding adrenoceptor-related transduction pathways and proliferation control in human cells. The eIf3f/alpha 1B-ADR complex is found in mammals and is not tissue specific.

[Angiotensin-1 converting enzyme insertion/deletion gene polymorphism in a Mexican population with diabetic nephropathy]. / Polimorfismo inserción/deleción del gen de la enzima de conversión de la angiotensina en una población mexicana con nefropatía diabética.

BACKGROUND AND OBJECTIVE: Diabetic nephropathy is a polygenic and multifactorial disease. Studies of familial clustering and genetic predisposition suggest that genetic factors are involved. Among candidate genes, the coding for angiotensin-converting enzyme (ACE) polymorphism has been described. Our objective was to investigate the association ACE gene insertion/deletion (I/D) polymorphism with the development of diabetic nephropathy in a Mexican population. PATIENTS AND METHOD: In a cross-sectional study, we evaluated 204 patients with type 2 diabetes: 43 with incipient diabetic nephropathy, 45 with established diabetic nephropathy and 116 without diabetic nephropathy. Diabetic nephropathy was defined according the American Diabetes Association criteria. The ACE I/D gene polymorphism was detected by polymerase chain reaction. RESULTS: Patients with type 2 diabetes with both incipient diabetic nephropathy and established diabetic nephropathy significantly differed from controls with respect to variables that determined kidney damage (P<.0001) and serum lipids ( P<.01). The genotype DD was strongly associated with the development of incipient diabetic nephropathy (odds ratio [OR] adjusted = 2.83; 95% confidence interval, 1.74-4.59; P<.0001) and established diabetic nephropathy (OR adjusted = 2.95; 95% CI, 1.83-4.73; P<.0001). CONCLUSIONS: The ACE DD genotype is associated with the development of incipient diabetic nephropathy and established diabetic nephropathy in a Mexican population.

[Implications of the Renin-Angiotensin system in diabetic nephropathy]. / Implicaciones de sistems renina-angiotensina en la nefropatía diabética.

In the last decades, the incidence of type 2 diabetes has increased alarmingly worldwide including Mexico, and particularly among Mexican-Americans. The etiology of type 2 diabetes is multiple, in which there is a complex interaction between environmental and genetic risk factors. The kidney is a target organ that is damaged when type 2 diabetes occurs. The genetic predisposition for kidney disease in type 2 diabetes patients is the end result of the cumulative effects of multiple genetic and environmental factors. The components of the renin-angiotensin system and its genetic polymorphisms represent an area of intense research due to its association with kidney disease. Early identification of genetic risk factors for developing kidney disease could lead to timely treatment and may influence the response of the patients to drug therapy and diet recommendations.