1,25-Dihydroxyvitamin D3 corrects insulin and lipid abnormalities in uremia

Abstract

The effect of intravenous 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] therapy on insulin and lipid metabolism was examined in patients on maintenance hemodialysis (HD). Eight patients (Group I, 19 +/- 1 years old) were studied before and after four weeks of intravenous 1,25 (OH)2D3 therapy (1.8 +/- 0.3 micrograms), during which time the serum parathyroid hormone (PTH) concentrations did not change. Another eight patients (Group II, 18 +/- 1 years old) were studied before and after four weeks of oral dihydrotachysterol (0.8 +/- 0.1 mg). Serum PTH also did not change in Group II. Serum glucose concentrations during an oral glucose tolerance test (OGTT) were higher in Group I before 1,25(OH)2D3 compared with controls and these normalized following four weeks of intravenous 1,25(OH)2D3. Serum glucose concentrations during OGTT were also higher in Group II before DHT compared with controls and did not change following four weeks of oral DHT. Insulin sensitivity during euglycemic clamp studies in Group I before 1,25(OH)2D3 (223 +/- 20 mg/m2/min; P < 0.01) was low compared with controls (320 +/- 26 mg/m2/min) and was normalized following therapy (315 +/- 25 mg/m2/min). Insulin sensitivity was also low in Group II at the beginning of the study and did not change at the end of the four week period. Both early-phase and late-phase insulin secretion were low in Group I before 1,25(OH)2D3 compared with controls and normalized following intravenous 1,25(OH)2D3 therapy. Both early-phase and late-phase insulin secretion were also low in Group II at the beginning of the study and did not change at the end of the four week period of DHT treatment. Plasma triglycerides were elevated in Group I patients before treatment (198 +/- 16 mg/dl; P < 0.01) compared with controls (139 +/- 12 mg/dl) and were normalized (148 +/- 13 mg/dl) following intravenous 1,25(OH)2D3 therapy. Plasma total cholesterol and high density lipoprotein cholesterol were normal before treatment compared with controls and did not change following Intravenous 1,25(OH)2D3 therapy. Plasma triglycerides, total cholesterol and high density lipoprotein cholesterol did not change in Group II during the study period. Thus, intravenous 1,25(OH)2D3 therapy corrected glucose intolerance, insulin resistance, hypoinsulinemia as well as hypertriglyceridemia in patients on HD, in the absence of PTH suppression.