BACKGROUND: The plasma concentrations of total homocysteine (tHcy) and total cysteine (tCys) are determined by intracellular metabolism and by renal plasma clearance, and we hypothesized that glomerular filtration is a major determinant of plasma tHcy and tCys. We studied the relationships between the glomerular filtration rate (GFR) and plasma tHcy and tCys in populations of diabetic patients with particularly wide ranges of GFR. METHODS: We measured GFR, urine albumin excretion rate (UAER), plasma tHcy, tCys, methionine, vitamin B12, folate, C-peptide, and routine parameters in 50 insulin-dependent diabetes mellitus (IDDM) and 30 non-insulin-dependent diabetes mellitus (NIDDM) patients. All patients underwent intensive insulin treatment and had a serum creatinine concentration below 115 micromol/liter. RESULTS: Mean plasma tHcy in diabetic patients (0.1 micromol/liter) was lower than in normal persons (11.1 micromol/liter, P = 0.0014). Mean plasma tCys in diabetic patients (266.1 micromol/liter) was also lower than in normal persons (281.9 micromol/liter, P = 0.0005). Seventy-three percent of the diabetic patients had relative hyperfiltration. Plasma tHcy and tCys were closely and independently associated with GFR, serum folate, and serum B12. However, plasma tHcy was not independently associated with any of the 22 other variables tested, including age, serum creatinine concentration, UAER, total daily insulin dose, and glycemic control. CONCLUSIONS: Glomerular filtration rate is an independent determinant of plasma tHcy and tCys concentrations, and GFR is rate limiting for renal clearance of both homocysteine and cysteine in diabetic patients without overt nephropathy. Declining GFR explains the age-related increase in plasma tHcy, and hyperfiltration explains the lower than normal mean plasma tHcy and tCys concentrations in populations of diabetic patients.
BACKGROUND: The plasma concentrations of total homocysteine (tHcy) and total cysteine (tCys) are determined by intracellular metabolism and by renal plasma clearance, and we hypothesized that glomerular filtration is a major determinant of plasma tHcy and tCys. We studied the relationships between the glomerular filtration rate (GFR) and plasma tHcy and tCys in populations of diabeticpatients with particularly wide ranges of GFR. METHODS: We measured GFR, urine albumin excretion rate (UAER), plasma tHcy, tCys, methionine, vitamin B12, folate, C-peptide, and routine parameters in 50 insulin-dependent diabetes mellitus (IDDM) and 30 non-insulin-dependent diabetes mellitus (NIDDM) patients. All patients underwent intensive insulin treatment and had a serum creatinine concentration below 115 micromol/liter. RESULTS: Mean plasma tHcy in diabeticpatients (0.1 micromol/liter) was lower than in normal persons (11.1 micromol/liter, P = 0.0014). Mean plasma tCys in diabeticpatients (266.1 micromol/liter) was also lower than in normal persons (281.9 micromol/liter, P = 0.0005). Seventy-three percent of the diabeticpatients had relative hyperfiltration. Plasma tHcy and tCys were closely and independently associated with GFR, serum folate, and serum B12. However, plasma tHcy was not independently associated with any of the 22 other variables tested, including age, serum creatinine concentration, UAER, total daily insulin dose, and glycemic control. CONCLUSIONS: Glomerular filtration rate is an independent determinant of plasma tHcy and tCys concentrations, and GFR is rate limiting for renal clearance of both homocysteine and cysteine in diabeticpatients without overt nephropathy. Declining GFR explains the age-related increase in plasma tHcy, and hyperfiltration explains the lower than normal mean plasma tHcy and tCys concentrations in populations of diabeticpatients.
Authors: Arpita Basu; Alicia J Jenkins; Julie A Stoner; Suzanne R Thorpe; Richard L Klein; Maria F Lopes-Virella; W Timothy Garvey; Timothy J Lyons Journal: Atherosclerosis Date: 2014-07-15 Impact factor: 5.162
Authors: A Giannattasio; M G Calevo; G Minniti; D Gianotti; M Cotellessa; F Napoli; R Lorini; G d'Annunzio Journal: J Endocrinol Invest Date: 2010-10-15 Impact factor: 4.256
Authors: Bertram L Kasiske; Teresa Anderson-Haag; Hassan N Ibrahim; Todd E Pesavento; Matthew R Weir; Joseph M Nogueira; Fernando G Cosio; Edward S Kraus; Hamid H Rabb; Roberto S Kalil; Andrew A Posselt; Paul L Kimmel; Michael W Steffes Journal: Am J Kidney Dis Date: 2013-03-22 Impact factor: 8.860
Authors: Karsten Suhre; Christa Meisinger; Angela Döring; Elisabeth Altmaier; Petra Belcredi; Christian Gieger; David Chang; Michael V Milburn; Walter E Gall; Klaus M Weinberger; Hans-Werner Mewes; Martin Hrabé de Angelis; H-Erich Wichmann; Florian Kronenberg; Jerzy Adamski; Thomas Illig Journal: PLoS One Date: 2010-11-11 Impact factor: 3.240