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Diabetes Care 24:969-970, 2001
© 2001 by the American Diabetes Association, Inc.

Letters: Comments and Responses
Letter

Low Total Plasma Homocysteine Concentrations in Patients With Type 1 Diabetes

Mario Cotellessa, MD1, Giuseppe Minniti, MS1, Roberto Cerone, MD1, Francesca Prigione, MD1, Maria Grazia Calevo, MS2 and Renata Lorini, MD1

1 Department of Pediatrics
2 Service of Epidemiology and Biostatistics-Scientific Direction, University of Genoa, G. Gaslini Institute, Genoa, Italy

We read with great interest the recent article by C. Pavia et al. (1) on total homocysteine (tHcy) and its modifying vitamin factors (folates and vitamins B12 and B6) in adolescents with type 1 diabetes. The authors studied the possible relationship between hyperhomocysteinemia in type 1 diabetes and duration of disease, degree of metabolic control, presence of microalbuminuria, alterations in fundus oculi, and chronic lymphocytic thyroiditis.

Numerous studies clearly demonstrate that mild hyperhomocysteinemia is strongly related to vascular diseases (2,3). Patients with diabetes often develop premature vascular disease. In type 2 diabetes, increased plasma concentrations of tHcy were found to be significantly associated with macroangiopathy, whereas there are only limited data on tHcy concentrations in patients with type 1 diabetes, especially children and/or adolescents (4,5). Increased plasma tHcy concentrations were found in diabetic patients with clinical signs of nephropathy (6), probably caused by reduced renal function (7), whereas plasma tHcy does not seem to play a major role in diabetic retinopathy (8).

C. Pavia et al. (1) reported no differences in tHcy concentrations between patients and control subjects; this observation suggests that the detection of no hyperhomocysteinemia in adolescents with type 1 diabetes has no predictive value for cardiovascular disease.

In our experience, we obtained similar results. We compared plasma tHcy concentrations in a group of type 1 diabetic patients attending the Genoa Pediatric Diabetologic Center and in 123 healthy control subjects matched for sex and age. Plasma tHcy concentrations (µmol/l) were measured with the high-performance liquid chromatography method and fluorescence detection (9). The patient group consisted of 112 subjects (63 males and 49 females) aged 17.6 years (range 4.4–33.9) with diabetes duration ranging from 0.7 to 3.0 years (mean 9.4); diabetes duration was >10 years in 65 patients. Plasma tHcy concentrations in type 1 diabetic patients were significantly lower (P < 0.001) than in sex- and age-matched control subjects (females <14 years, 3.24 vs. 7.90 µmol/l; males <14 years, 3.27 vs. 8.66 µmol/l; fe-males >14 years, 4.27 vs. 7.10 µmol/l; males >14 years, 5.03 vs. 8.40 µmol/l, respectively). Moreover, plasma tHcy levels increased with age (P < 0.001) and with diabetes duration (P < 0.05) in type 1 diabetic patients. No sex-related difference was found in plasma tHcy concentrations between type 1 diabetic patients >14 years of age with or without microvascular complications. Serum folate concentrations were higher in type 1 diabetic patients than in control subjects.

We confirm, as other authors have (4), that in children and adolescents with type 1 diabetes, hyperhomocysteinemia is not detected and therefore not predictive of microvascular lesions. Further studies are needed to define the role of tHcy levels and of latent hyperhomocysteinemia in type 1 diabetic patients. Currently, the methionine loading test may identify >50% of subjects with hyperhomocysteinemia, and it is a valuable adjunct to fasting tHcy (10).

FOOTNOTES

Address correspondence to Renata Lorini, MD, Department of Pediatrics, University of Genoa, G. Gaslini Institute, Genoa, Italy. Gaslini Children’s Hospital, Largo G. Gaslini, 5 I-16147 Genova, Italy. E-mail: renatalorini{at}ospedale-gaslini.ge.it.

References

  1. Pavia C, Ferrer I, Valls C, Artuch R, Colome C, Vilaseca MA: Total homocysteine in patients with type 1 diabetes. Diabetes Care 23:84–87, 2000[Abstract]
  2. Senaratne MP, Griffiths J, Nagendram J: Elevation of plasma homocysteine levels associated with acute myocardial infarction. Clin Invest Med 23:220–226, 2000[Medline]
  3. Hankey GJ, Eikelboom JW: Homocysteine and vascular disease. Lancet 354:407–413, 1999[Medline]
  4. Cronin CC, McPartlin JM, Barry DG, Ferriss JB, Scott JM, Weir DG: Plasma homocysteine concentrations in patients with type 1 diabetes. Diabetes Care 21:1843–1847, 1998[Abstract]
  5. Vilaseca MA, Moyano D, Artuch R, Ferrer I, Pineda M, Cardo E, Campistol J, Pavia C, Camacho JA: Selective screening for hyperomocysteinemia in pediatric patients. Clin Chem 44:662–664, 1998[Free Full Text]
  6. Agardh CD, Agardh E, Andersson A, Hultberg B: Lack of association between plasma homocysteine levels and microangiopathy in type 1 diabetes mellitus. Scand J Clin Lab Invest 54:637–641, 1994[Medline]
  7. Cerone R, Minniti G, Boeri D, Maiello M, Campanella D, Piana A, Armani U, Lorini R: Homocysteine pathway: oxidative stress and endothelial metabolism in Wistar rats with streptozotocin-diabetes. J Inherit Metab Dis 23(Suppl. 1):64, 2000
  8. Hultberg B, Agardh CD, Agardh E, Lovestam-Adrian M: Poor metabolic control, early age at onset, and marginal folate deficiency are associated with increasing levels of plasma homocysteine in insulin-dependent diabetes mellitus: a five-year follow-up study. Scand J Lab Invest 57:595–600, 1997
  9. Minniti G, Piana A, Armani U, Cerone R: Determination of plasma and serum homocysteine by high-performance liquid cromatography with fluorescence detection. J Chromatogr A 828:401–405, 1998[Medline]
  10. Bostom AG, Jacques PF, Nadeau MR, Williams RR, Ellison RC, Selhub J: Post-methionine load hyperhomocysteinemia in persons with normal fasting total plasma homocysteine: initial results from the NHLBI Family Heart Study. Atherosclerosis 116:147–151, 1995[Medline]

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