A Pre-Post Study of Vitamin D Supplement Effects on Urinary Megalin: The Emerging Predictive Role of Megalin in Diabetic Nephropathy Progression.

INTRODUCTION: Megalin is a renal proximal tubular protein that reabsorbs vitamin D from glomerular filtrates. Previous studies found significantly higher levels of urinary megalin in chronic microvascular complications of diabetes with associated metabolic derangements. This study aimed at testing the effect of vitamin D supplements on urinary megalin levels in diabetic nephropathy (DN) patients with vitamin D hypovitaminosis. METHODS: Sixty-three participants with vitamin D deficiency and diabetic nephropathy (DN) were enrolled in the pre-post study; urinary megalin levels with various clinical parameters and serum levels of vitamin D3 were measured and compared to the baseline at 3- and 6-month intervals. RESULTS: Interestingly, a supplementation related increase in serum vitamin D3 levels at 3- and 6- month interventions affected a constellation of ameliorations in the DN progression of clinical and metabolic factors. There was a decrease in ACR with a concomitant decrease in urinary megalin and a decrease in blood pressure, fasting plasma glucose (FPG), and low-density lipoprotein - cholesterol (LDL-C) - but an increase in glomerular filtration rate (GFR). Principally, pellet urinary megalin associated positively (p < 0.05) with vitamin D hypovitaminosis and the albumin-to-creatinine ratio (ACR) but negatively (p < 0.05) with Ca2+ and body mass index (BMI). CONCLUSION: Vitamin D supplementation could elucidate underlying pathophysiological mechanisms and a prognostic significance of urinary megalin association with DN, obesity/MetS-related dyslipidemia, and hyperglycemia modification. Megalin is a putative sensitive and precise predictive marker and an emerging therapeutic target of renal anomalies.

Serum level of insulin-like growth factor-I in type 2 diabetic patients: impact of obesity.

Background Insulin-like growth factor-I (IGF-I) is homologous to proinsulin and possesses glucose reducing activity. The association between the level of IGF-I and diabetes has been highlighted. However, this association is controversial due to the influence of different factors including obesity. The aim of the study was to evaluate serum level of IGF-I in type 2 diabetic patients compared to control subjects. Materials and methods A cross-sectional study involving 100 participants was conducted. Serum levels of IGF-I were measured using enzyme-linked immunosorbent assay (ELISA) and the fasting plasma glucose (FPG) levels were measured using the glucose oxidase method. Results IGF-I levels in the diabetic patients were significantly lower than in non-diabetic control subjects (105.13 ± 6.34 vs. 159.96 ± 9.62 ng/mL, p < 0.0001). Among the diabetic group, there was no significant difference in IGF-I levels between obese diabetic patients and non-obese diabetic patients, p = 0.18. Similarly, among the non-diabetic group, a non-significant difference was found in IGF-I levels between obese non-diabetic and non-obese non-diabetic subjects, p = 0.156. However, among the obese group, obese diabetic patients had significantly lower IGF-I serum levels compared to obese non-diabetic subjects (112.07 ± 7.97 vs. 147.07 ± 13.05 ng/mL, p = 0.02). Furthermore, among the non-obese group, the non-obese diabetic patients had significantly lower IGF-I serum levels compared to the non-obese non-diabetic subjects (91.66 ± 9.93 vs. 171.86 ± 13.86 ng/mL, p < 0.0001). No significant associations were observed between IGF-I level and any of the age, gender, body mass index (BMI), FPG levels, or the duration of diabetes. Conclusions Type 2 diabetes mellitus is associated with lower levels of IGF-I regardless to the presence or absence of obesity.

Cross-sectional correlates of increased IL-18 but reduced fetuin-A and oxytocin with adiposity and blood indices in metabolic syndrome patients with and without prediabetes.

BACKGROUND: Oxytocin (OXT), fetuin-A and interleukin-18 (IL-18) are involved in the development and progression of metabolic syndrome (MetS) and prediabetes (pre/T2DM). AIMS PARTICIPANTS AND METHODS: This study aimed to compare and correlate the plasma levels of OXT, fetuin-A and IL-18 with clinical parameters, haematological indices and adiposity indices in Jordanian MetS subjects. In a cross-sectional study, 30 normoglycaemic lean study participants (control), 30 MetS study participants, and 29 MetS pre/T2DM study participants were recruited. RESULTS: Median circulating levels of both OXT and fetuin-A were lower in MetS and MetS pre/T2DM versus control group. OXT (pg/ml; median interquartile range): MetS 1975.4 and MetS pre/T2DM 1403 versus control 4176.6 (p = 0.009 and p = 0.001, respectively). For fetuin-A (ng/ml), MetS (5784) and MetS pre/T2DM (2154) were lower versus control (6756.3) (p = 0.040 and p = 0.007, respectively). Neither biomarker was described as substantially different in MetS versus MetS pre/T2DM (p = 0.071 and p = 0.155, respectively). Conversely, a non-significant increase in IL-18 was observed in the MetS and MetS pre/T2DM groups compared to normoglycaemic lean controls (232 and 287.5, p > 0.05 versus 108 for both). In addition, conicity index (C-index), atherogenicity index (TG-HDL-C), waist to hip ratio, mean platelet volume (MPV; fl) and red cell distribution width (RDW-CV%) in both MetS and MetS pre/T2DM were significantly higher (p < 0.001) versus controls. However all above MetS-related indices were not ascribed any statistically marked variation in the MetS group when compared to the MetS pre/T2DM group. Both total study pool of recruits' fetuin-A (Spearman r = -2.66, p = 0.049) as well as MetS pre/T2DM group IL-18 (Spearman r = 0.380, p = 0.046) were inversely correlated with RDW-CV%. OXT in MetS inversely correlated with waist circumference/hip circumference ratio (Spearman r = -0.387, p = 0.038). No other pronounced associations between biomarkers could be detected in any study arm. CONCLUSION: These findings substantiate the clinical relevance and significance of OXT, fetuin-A and IL-18 as surrogate screening/prognostic tools and therapeutic targets to predict/prevent metabolic dysregularities and anomalies.