Effects of Insulin Deprivation and Treatment on Homocysteine Metabolism in People with Type 1 Diabetes

• Published in: The journal of clinical endocrinology and metabolism Vol. 91; no. 9; pp. 3344 - 3348
• Main Authors: Abu-Lebdeh, Haitham S, Barazzoni, Rocco, Meek, Shon E, Bigelow, Maureen L, Persson, Xuan-Mai T, Nair, K. Sreekumaran
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.09.2006
• Subjects: Adult; Amino Acids, Branched-Chain - blood; Biological and medical sciences; Blood Glucose - metabolism; Carbon Radioisotopes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fundamental and applied biological sciences. Psychology; Homocysteine - blood; Homocysteine - metabolism; Homocysteine - pharmacokinetics; Humans; Insulin - blood; Insulin - deficiency; Insulin - pharmacology; Male; Medical sciences; Methionine - blood; Methionine - metabolism; Methionine - pharmacokinetics; Middle Aged; Vertebrates: endocrinology; Sulfur containing aminoacid; Endocrinopathy; Immunopathology; Pancreatic hormone; Thiol; Treatment; Homocystein; Type 1 diabetes; Autoimmune disease; Metabolism; Insulin; Endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-0018

Context: Abnormal homocysteine metabolism may contribute to increased cardiovascular death in type 1 diabetes (T1DM). Amino acid metabolism is altered in T1DM. In vitro, insulin reduces hepatic catabolism of homocysteine by inhibiting liver transsulfuration. It remains to be determined whether methionine-homocysteine metabolism is altered in T1DM. Objective: We sought to determine whether insulin deficiency during insulin deprivation or high plasma insulin concentration after insulin treatment alters homocysteine metabolism in T1DM. Design: This was an acute interventional study with paired and comparative controls. Setting: The study was conducted at a general clinical research center. Patients and Intervention: We used stable isotope tracers to measure methionine-homocysteine kinetics in six patients with T1DM during insulin deprivation (I−) and also during insulin treatment (I+) and compared them with nondiabetic controls (n = 6). Main Outcome Measures: Homocysteine kinetics (transmethylation, transsulfuration, and remethylation) were from plasma isotopic enrichment of methionine and homocysteine and 13CO2. Results: T1DM (I−) had lower rates of homocysteine-methionine remethylation (P < 0.05 vs. control and I+). In contrast, transsulfuration rates were higher in I− than controls and I+ (P < 0.05). Insulin treatment normalized transsulfuration and remethylation (P < 0.05 vs. I− and P > 0.8 vs. control). Plasma homocysteine concentrations were lower in T1DM (P < 0.05 vs. control during both I− and I+), which may be explained by increased homocysteine transsulfuration. Thus, significant alterations of methionine-homocysteine metabolism occur during insulin deprivation in humans with T1DM. Conclusions: Insulin plays a key role in the regulation of methionine-homocysteine metabolism in humans, and altered homocysteine may occur during insulin deficiency in type 1 diabetic patients.