Impact of Insulin Resistance and Nephropathy on Homocysteine in Type 2 Diabetes
- Masanori Emoto, MD1,
- Hiroyuki Kanda, MD1,
- Tetsuo Shoji, MD1,
- Takahiko Kawagishi, MD1,
- Miyoko Komatsu, MD1,
- Katsuhito Mori, MD1,
- Hideki Tahara, MD1,
- Eiji Ishimura, MD1,
- Masaaki Inaba, MD1,
- Yasuhisa Okuno, MD2 and
- Yoshiki Nishizawa, MD1
- 1Second Department of Internal Medicine and the
- 2Department of Cardiovascular Medicine, Institute of Geriatrics and Medical Science, Osaka City University Medical School, Osaka, Japan
Abstract
OBJECTIVE—To assess the impacts of insulin resistance and renal function on plasma total homocysteine (tHcy) levels in patients with type 2 diabetes with a wide range of nephropathy.
RESEARCH DESIGN AND METHODS—Plasma tHcy levels were measured using the enzyme immunoassay method in 75 patients with type 2 diabetes and compared with those in 54 healthy control subjects. Insulin sensitivity indexes were assessed in patients with type 2 diabetes by hyperinsulinemic-euglycemic clamp using artificial pancreas.
RESULTS—Plasma tHcy levels and their log-transformed values (log tHcy) were significantly higher in all patients with diabetes than in control subjects (tHcy, 12.0 ± 0.7 [SE] vs. 8.7 ± 0.3 μmol/l, P < 0.0001; log tHcy, 1.040 ± 0.021 vs. 0.920 ± 0.016 μmol/l, P < 0.0001). Plasma tHcy levels in patients with diabetes were significantly increased according to degree of nephropathy (P < 0.0001). On simple regression analyses, log tHcy correlated with insulin sensitivity indexes (r = –0.319, P = 0.005) as well as creatinine clearance (r = 0.634, P < 0.0001) in all patients with diabetes. Multiple regression analyses showed that insulin sensitivity indexes (β = –0.245) as well as creatinine clearance were independent contributors to log tHcy in all patients with diabetes (R2 = 0.750, P < 0.0001). For the 59 patients with diabetes with creatinine clearance >60 ml/min, insulin sensitivity indexes were also shown to be a significant contributor to log tHcy (β = –0.438, R2 = 0.561, P < 0.001).
CONCLUSION—Insulin resistance and renal function are independent determinants of tHcy levels in patients with type 2 diabetes.
- CBS, cystathione β-synthase
- MTHFR, 5,10-methylenetetrahydrofolate reductase
- tHcy, total homocysteine
- SSPI, plasma insulin level during the steady state
- UAE, urinary albumin excretion
Footnotes
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Address correspondence and reprint requests to Masanori Emoto, MD, Second Department of Internal Medicine, Osaka City University Medical School, 1-4-3, Asahi-machi, Abeno-ku, Osaka, Japan, 545-8585. E-mail: memoto{at}med.osaka-cu.ac.jp.
Received for publication 31 July 2000 and accepted in revised form 15 November 2000.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
