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Exp Clin Endocrinol Diabetes 2004; 112(1): 44-51
DOI: 10.1055/s-2004-815726
Article

J. A. Barth Verlag in Georg Thieme Verlag Stuttgart · New York

Plasma Homocysteine after Insulin Infusion in Type II Diabetic Patients with and without Methionine Intolerance

P. Ventura 1 , R. Panini 2 , S. Emiliani 2 , G. Salvioli 2
  • 1Department of Internal Medicine, Chair of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy
  • 2Department of Internal Medicine, Chair of Geriatrics and Gerontology, University of Modena and Reggio Emilia, Modena, Italy
Further Information

Publication History

Received: January 9, 2003 First decision: March 13, 2003

Accepted: April 22, 2003

Publication Date:
03 February 2004 (online)

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Abstract

Background

A high prevalence of hyperhomocysteinemia has been reported in type II diabetic patients with documented vascular disease; hence the hypothesis that hyperhomocysteinemia may contribute to overall mortality in diabetic patients. The link between insulin and homocysteine metabolism has not been completely clarified yet; in particular, only few data are available on the effects of insulin in vivo on homocysteine metabolism in the presence of abnormalities of sulphur amino acid metabolism (methionine intolerance).

Materials and Methods

To establish whether methionine intolerance and which of its determinants could influence total plasma homocysteine in response to insulin infusion in vivo in type II diabetic patients, we submitted 18 patients (Group A) with normal and 18 patients with abnormal (hyperhomocysteinemia) (Group B) response to oral methionine load to a glucose/clamp study. At time 0, and 30, 60 and 120 minutes after hyperinsulinemia, homocysteine and methionine plasma levels were assessed. In order to evaluate the cause of methionine intolerance, all patients were assayed for fasting homocysteine-cysteine ratio (as a marker of suspected heterozygosis for cystathionine-β-synthase deficit), MTHFR C677T status and homocysteine-related vitamin status (serum vitamin B6 [PLP], vitamin B12 and folate).

Results

After hyperinsulinemia, plasma methionine was reduced (by about - 30 % at 120 minutes vs. basal values) within both groups, whereas tHcy tend to decrease in group A following insulin administration (up to - 6.6 ± 3.6 % vs. basal values at 120 minutes) with a significantly higher variability, while in patients with “methionine intolerance” (group B) tHcy tended to increase (up to + 29.05 ± 8.3 % vs. basal values at 120 min from the clamp). Serum folic acid (7.45 ± 2.8 vs. 4.82 ± 2.5 nmol/L, p < 0.05), Vit. B12 (348 ± 78 vs. 242 ± 65 pmol/L, p < 0.05) and PLP (84.1 ± 23.6 vs. 50.6 ± 32.4 nmol/L; p < 0.01) were significantly higher in group A than in group B; PLP levels significantly correlated with homocysteine after 4 h methionine load (n = 36; r = - 0.327, p < 0.05); group A showed also a significantly lower prevalence of suspected heterozygosis for cystathionine-β-synthase deficit (1/18 [11.1 %] vs. 5/18 [33.3 %], p < 0.05) and MTHFR T allele presence (4/18 [22.2 %] vs. 11/18 [61.1 %], p < 0.01).

A stepwise regression analysis with tHcy plasma level variations (event A = reduction; event B = increase) as the dependent variable showed that low serum folate and PLP levels and presence of MTHFR T allele were the variables associated with insulin-induced tHcy increase.

Conclusions

Methionine intolerance may influence the effect of insulin administration on plasma homocysteine in patients affected by type 2 diabetes. To prevent a possible acute (and repeated) hyperhomocysteinemia due to insulin administration in cases of methionine intolerance, it may be useful to assess the presence of methionine intolerance (tHcy after oral methionine loading) and Hcy-related vitamin status in all patients due to be subjected to insulin therapy.

Key words

Homocysteine - methionine intolerance - diabetes - transsulfuration - homocysteine/cysteine ratio - vitamin B6 - insulin

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M. D. Paola Ventura

Dipartimento di Medicina Interna e Specialità Mediche · Cattedra di Medicina Interna II · University of Modena and Reggio Emilia

Via del Pozzo 71 - Policlinico di Modena

Modena

Italy

Phone: + 0594222807

Fax: + 05 94 22 43 63

Email: paoloven@unimo.it