Abstract

The study aims to investigate the effect of vitamin D (VD) combined with pioglitazone hydrochloride (PIO) on bone mineral density (BMD) and bone metabolism in patients with Type 2 diabetic nephropathy (T2DN). T2DN patients were selected and assigned into mild, moderate, and severe groups. In each group, three therapy regimens (VD, PIO, and VD plus PIO) were administered. X-ray absorptiometry was used to measure BMD. Intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D3 (25-OH-VD3) were measured by chemiluminescence meter. ELISA was applied to detect levels of osteoprotegerin (OPG), bone gla protein (BGP), C-terminal telopeptides of type I collagen (β-CTX), procollagen type I N-propeptide (PINP), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Compared with the mild group, T2DN patients in the moderate and severe groups had longer course of disease and higher levels of total cholesterol (TC), triglyceride (TG), serum phosphorus, fasting plasma glucose (FPG), glycosylated hemoglobin (HbAlc) and creatine (Cr), and lower blood calcium. The BMD in different parts increased among the mild, moderate, and severe groups, and the highest BMD was found after VD plus PIO treatment. OPG, iPTH, BGP, β-CTX, Pyr/Cr, and D-Pyr/Cr levels were reduced, while 25-OH-VD3 and PINP levels were elevated among three groups after different treatments, and the most obvious change was observed after VD plus PIO treatment. Our findings indicate that VD combined with PIO may be more effective in improving BMD and bone metabolism than VD or PIO alone in the treatment of T2DN patients, especially for T2DN patients with mild disease.

Highlights

  • Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, with a proportion of 90% in diagnosed DM cases globally, and is featured by insulin resistance and insulin secretion disorders [1]

  • The course of disease, total cholesterol (TC), serum phosphorus, fasting plasma glucose (FPG), glycosylated hemoglobin (HbAlc), and Cr were enhanced, but blood calcium was declined in the severe group as compared with the moderate group

  • One of the results demonstrates that bone mineral density (BMD) in patients with Type 2 diabetic nephropathy (T2DN) is increased after vitamin D (VD) plus pioglitazone hydrochloride (PIO) treatment

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Summary

Introduction

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, with a proportion of 90% in diagnosed DM cases globally, and is featured by insulin resistance and insulin secretion disorders [1]. It is noted that approximately 40% DM (including T1DM and T2DM) develops from diabetic nephropathy (DN) [2]. Type 2 diabetic nephropathy (T2DN) is a severe vascular complication of DM and is recognized as the principle cause of chronic kidney disease and death in DM patients [3]. T2DM evolution to T2DN originally begins from a slight increase in urinary albumin excretion (micro-albuminuria) to macro-albuminuria with higher and higher glomerular filtration rate (GFR), and eventually deteriorates into advanced renal disease that is pathologically characterized by glomerulosclerosis and tubulointerstitial fibrosis [4]. To the best of our knowledge, kidney is closely linked with changes in bone and mineral metabolism, and patients with nephrotic syndrome are found to have a predisposition to bone disease such as osteoporosis, which considerably results from metabolic imbalances of calcium and vitamin D (VD) [5]. VD and pioglitazone hydrochloride (PIO) have become a new and popular research field, as impact factors of DM [6]

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