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Diabetes Care 26:1948, 2003
© 2003 by the American Diabetes Association, Inc.

Letters: Comments and Responses
Letter

Diabetic Retinopathy Possibly Results From Poor Blood Sugar Control Associated With MTHFR Gene Polymorphism in Type 2 Diabetic Patients

Response to Yoshioka et al.

Makiko Maeda, MS1, Isamu Yamamoto, MD1, Masakatsu Fukuda, MD, PHD2, Mari Nishida, BS1, Junko Fujitsu, MS1, Shinpei Nonen, MS1, Tsuyoshi Igarashi, MD, PHD3, Takashi Motomura, MD, PHD3, Makiko Inaba, MD3, Yasushi Fujio, MD, PHD1 and Junichi Azuma, MD1

1 Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
2 Department of Ophthalmology, NTT West Japan Osaka Hospital, Osaka, Japan
3 Second Department of Internal Medicine, NTT West Japan Osaka Hospital, Osaka, Japan

We appreciate the comments of Dr. Yoshioka et al. (1). As described previously (2), we excluded the patients with >133 µmol/l serum creatinine level. In addition, the patients with >300 mg/dl urinary protein levels did not participate in our study. We considered that these exclusions must elucidate the effects of the methylenetetrahydrofolate reductase (MTHFR) gene polymorphism, not the effects of nephropathy, on the progression of diabetic retinopathy (DR) in type 2 diabetic patients. We agree with their comment that we analyzed the correlation with a smaller number of subjects. However, we cannot help referring to the difference in the backgrounds of the subjects between the two studies. In our study, the subjects had a mean age of 59.4 years, a mean diabetes duration of 10.8 years, a mean HbA1c of 8.1%, and a mean serum creatinine of 0.76 mg/dl. The noteworthy difference between the two studies is the mean HbA1c level (8.1 vs. 7.3%). The discrepancy may be attributable to this difference.

To support this hypothesis, the subjects with >9.8% HbA1c level were excluded from the previous analysis (2) to get the mean HbA1c level down to 7.3%, and then the data were analyzed again. As a result, there was no significant difference in the relationship between the MTHFR gene polymorphism and DR (n = 124, {chi}2 test, P = 0.08). Fong et al. (3) described that epidemiological analysis of the U.K. Prospective Diabetes Study data showed a continuous relationship between the risk of microvascular complications and glycemia, such that for every percentage point decrease in HbA1c (e.g., from 8 to 7%), there was a 35% reduction in the risk of microvascular complications. Based on this description, improved control of blood glucose may mask the retinopathic background derived from the MTHFR gene polymorphism. Thus, in this letter, we propose that the MTHFR gene polymorphism contributes to the progression of DR synergistically with impaired blood glucose control. In other words, blood glucose control could override the effects of the MTHFR gene polymorphism in type 2 diabetic patients.

Prospective cohort studies are required to understand the influence of the MTHFR gene polymorphism on the progression of DR. We thank Yoshioka et al. again for their comment, which has illuminated that blood glucose control may be associated with the effect of the MTHFR gene polymorphism on DR.

Footnotes

Address correspondence to Junichi Azuma, Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamadaoka, Suita, Osaka, Japan. E-mail: azuma{at}phs.osaka-u.ac.jp

References

  1. Yoshioka K, Yoshida T, Takakura Y, Kogure A, Umekawa T, Toda H, Yoshikawa T: No association between the MTHFR gene polymorphism and diabetic retinopathy in type 2 diabetic patients without overt nephropathy (Letter). Diabetes Care 26: 1947–1948, 2003[Free Full Text]
  2. Maeda M, Yamamoto I, Fukuda M, Nishida M, Fujitsu J, Nonen S, Igarashi T, Motomura T, Inaba M, Fujio Y, Azuma J: MTHFR gene polymorphism as a risk factor for diabetic retinopathy in type 2 diabetic patients without serum creatinine elevation (Letter). Diabetes Care 26: 547–548, 2003[Free Full Text]
  3. Fong DS, Aiello L, Gardner TW, King GL, Blankenship G, Cavallerano JD, Ferris FL, Klein R: Diabetic retinopathy (Position Statement). Diabetes Care 26: 226–229, 2003[Free Full Text]

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This Article
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