Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes.
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.


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-translormed 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 micromol/l, P < 0.0001; log tHcy, 1.040 +/- 0.021 vs. 0.920 +/- 0.016 micromol/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 (beta = -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 (beta = -0.438, R2 = 0.561, P < 0.001).


CONCLUSIONS
Insulin resistance and renal function are independent determinants of tHcy levels in patients with type 2 diabetes.
Emoto
M
M
Second Department of Internal Medicine, Institute of Geriatrics and Medical Science, Osaka City University Medical School, Japan. memoto@med.osaka-cu.ac.jp
Kanda
H
H
Shoji
T
T
Kawagishi
T
T
Komatsu
M
M
Mori
K
K
Tahara
H
H
Ishimura
E
E
Inaba
M
M
Okuno
Y
Y
Nishizawa
Y
Y
D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003404:Creatinine / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000097:blood* / Q000503:physiopathology; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012044:Regression Analysis; D014527:Uric Acid / Q000097:blood
D001786:Blood Glucose; D003404:Creatinine; D006442:Glycated Hemoglobin; D006710:Homocysteine; D007328:Insulin; D014527:Uric Acid