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 following 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 T1DM during insulin deprivation (I-) and also during insulin treatment (I+) and compared them to non-diabetic 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.

Conclusion: Insulin plays a key role in the regulation of methionine-homocysteine metabolism in humans and altered homocysteine may occur during insulin deficiency in type I diabetic patients.