Pleiotropic effects of vitamin D in an early stage of chronic kidney disease—effect on insulin resistance

Disturbances of carbohydrate metabolism are common in patients with chronic kidney disease (CKD). Possible pathogenetic mechanisms involve unresponsiveness of insulin receptor and/or a bland response of the beta cell at the stimulus of hyperglycaemia. It is known that vitamin D has an important role in the endocrine function of the pancreas, particularly in the insulin release process, and is one of the determinants of insulin resistance [1]. This metabolic complication may be implicated in the accelerated atherosclerotic process and is common in CKD. The aim of our study was to investigate the effect of vitamin D treatment on insulin resistance in patients with CKD stage 3. We included in our study 37 (25 men/12 women, age 51 ± 13 years old) non-diabetic patients with CKD stage 3 (eGFR 30–59 mL/min/1.73 m2 calculated with the Modification of Diet in Renal Disease formula). Patients with history of diabetes mellitus and previous therapy with vitamin D were excluded. The underlying kidney disease was obstructive nephropathy, secondary focal segmental glomerulosclerosis, membranous glomerulonephritis and unknown cause of CKD. In all patients, CKD–mineral and bone disorder (CKD–MBD) was established. All patients were treated at the beginning with dietary phosphorous restriction, phosphate-binding agents and calcium supplements. If intact parathyroid hormone (iPTH) values were persistently >70 pg/mL, administration of 1-alpha-hydroxyvitamin D3 in a single daily dose of 0.25 μg was initiated. Fasting glucose concentration, insulin levels, HbA1c, iPTH, Ca, P and insulin resistance evaluated by homeostasis model assessment index [HOMA index, calculated as: fasting glucose (mmol/L) × insulin (mU/mL) / 22.5] were measured before (T0) and 12 weeks after (T1) initiation of treatment. In all patients, an oral glucose tolerance test (OGTT) with an oral dose of 75 g of glucose was performed. No patient was under treatment with corticosteroids or erythropoietin for anaemia. Plasma levels of fasting glucose and insulin levels were comparable before (T0) and after (T1) treatment with vitamin D (Table 1). The HOMA index was statistically higher in time T0 than T1 indicating that insulin resistance was improved. Mean glucose OGTT levels were higher in T0. There was no statistical difference in calcium, phosphorous, HbA1c, pre- and post-treatment concentration, although the T1 calcium concentration was higher than T0. Table 1 Plasma levels of fasting glucose and insulin levels before and after treatment with vitamin D Vitamin D insufficiency is correlated with increased risk of all-cause and cardiovascular (CV) mortality in patients with stage 3 and 4 CKD [2]. Studies demonstrate a link between abnormalities in vitamin D metabolism and insulin resistance, a very common condition in patients with CKD. It is proven that insulin resistance is an independent predictor of morbidity and mortality for CV causes in non-diabetic patients with end-stage renal disease [3]. A few works have investigated the effect vitamin D has on insulin resistance in early stages of CKD. Our study has shown a beneficial effect of vitamin D supplementation in patients with CKD stage 3 on insulin resistance. The HOMA index and OGTT mean glucose plasma levels have significantly decreased after 1-alpha-hydroxyvitamin D3 treatment. Changes in PTH, a factor implicated in insulin resistance, were not significant during the study period and were not correlated with the amelioration of the HOMA index. Our conclusion was that vitamin D affected insulin metabolism directly and not through reduction of PTH in patients with stage 3 CKD. Insulin resistance is present in early stages of CKD and is associated with vitamin D metabolism. According to our data, treatment with vitamin D in patients with CKD stage 3 has a beneficial effect on insulin resistance assessed with the HOMA index. Of course, further randomized controlled large-scale studies are needed in order to assess long-term benefits in morbidity and mortality of those patients. Conflict of interest statement. None declared.