Abstract:
:Although hyperhomocysteinemia, an independent cardiovascular risk factor, is common in type 2 diabetes with nephropathy, the mechanism(s) of this alteration is not known. In healthy humans, hyperinsulinemia increases methionine transmethylation, homocysteine transsulfuration, and clearance. No such data exist in type 2 diabetes either in the fasting state or in response to hyperinsulinemia. To this purpose, seven male type 2 diabetic patients with albuminuria (1.2 +/- 0.4 g/day, three with mild to moderate renal insufficiency) and seven matched control subjects were infused for 6 h with L-[methyl-(2)H(3), 1-(13)C]methionine. Methionine flux, transmethylation, and disposal into proteins as well as homocysteine remethylation, transsulfuration, and clearance were determined before and after euglycemic hyperinsulinemia (approximately 1,000 pmol/l). In type 2 diabetic subjects, homocysteine concentration was twofold greater (P < 0.01) and methionine transmethylation and homocysteine clearance lower (from approximately 15 to >50% and from approximately 40 to >100%, respectively; P < 0.05) than in control subjects. The insulin-induced increments of methionine transmethylation, homocysteine transsulfuration, and clearance were markedly reduced in type 2 diabetic subjects (by more than threefold, P < 0.05 or less vs. control subjects). In contrast, methionine methyl and carbon flux were not increased in the patients. In conclusion, pathways of homocysteine disposal are impaired in type 2 diabetes with nephropathy, both in postabsorptive and insulin-stimulated states, possibly accounting for the hyperhomocysteinemia of this condition.
journal_name
Diabetesjournal_title
Diabetesauthors
Tessari P,Coracina A,Kiwanuka E,Vedovato M,Vettore M,Valerio A,Zaramella M,Garibotto Gdoi
10.2337/diabetes.54.10.2968subject
Has Abstractpub_date
2005-10-01 00:00:00pages
2968-76issue
10eissn
0012-1797issn
1939-327Xpii
54/10/2968journal_volume
54pub_type
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