Effects of insulin deprivation and treatment on homocysteine metabolism in people with type 1 diabetes.
BACKGROUND
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.


METHODS
This was an acute interventional study with paired and comparative controls.


METHODS
The study was conducted at a general clinical research center.


METHODS
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).


METHODS
Homocysteine kinetics (transmethylation, transsulfuration, and remethylation) were from plasma isotopic enrichment of methionine and homocysteine and (13)CO(2).


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.
Abu-Lebdeh
Haitham S
HS
Endocrine Research Unit, Mayo Clinic, 200 First Street SW, Joseph 5-194, Rochester, Minnesota 55905, USA.
Barazzoni
Rocco
R
Meek
Shon E
SE
Bigelow
Maureen L
ML
Persson
Xuan-Mai T
XM
Nair
K Sreekumaran
KS
D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002250:Carbon Radioisotopes; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D005260:Female; D006710:Homocysteine / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D007328:Insulin / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology; D008297:Male; D008715:Methionine / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D008875:Middle Aged
D000597:Amino Acids, Branched-Chain; D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D006710:Homocysteine; D008715:Methionine