Nisoldipine improves the impaired erythrocyte deformability correlating with elevated intracellular free calcium-ion concentration and poor glycaemic control in NIDDM.
OBJECTIVE
To explore the mechanisms underlying the impaired erythrocyte deformability (RBC-df) in diabetic patients, the relationship between erythrocyte intracellular free calcium-ion concentration ([Ca2+]i) and RBC-df, and the effects of Ca2+-channel blocker on [Ca2+]i and RBC-df were evaluated.


METHODS
Forty-eight patients with NIDDM and 24 control subjects were enrolled in this study. [Ca2+]i was determined using fura-2, and RBC-df by filtration method expressed as Deformability Index (DI). Erythrocytes were treated with nisoldipine to evaluate the effects of a Ca2+-channel blocker.


RESULTS
[Ca2+]i was significantly higher (82.6 (78.0-87.2) vs 76.6 (74.3-81.2) nmol lRBC-1, P<0.001), and DI was significantly lower (0. 14 (0.09-0.28) vs 0.22 (0.16-0.28), P<0.01) in NIDDM than in controls. There was a significant correlation between HbA1c and [Ca2+]i (r=0.38, P<0.01), between HbA1c and DI (r=-0.51, P<0.01), and between [Ca2+]i and DI (r=-0.42, P<0.01). Stepwise multiple regression analysis revealed HbA1c and [Ca2+]i as independent determinants for the impaired RBC-df. Nisoldipine treatment in vitro significantly decreased [Ca2+]i, and significantly improved RBC-df.


CONCLUSIONS
These data indicate that the impaired RBC-df in NIDDM may at least partly be attributed to the elevated [Ca2+]i and poor glycaemic control. In addition, favorable effects of a Ca2+-channel blocker on both [Ca2+]i and RBC-df have been demonstrated.
Fujita
J
J
Department of Metabolism and Clinical Nutrition, Kyoto University Graduate School of Medicine, Japan.
Tsuda
K
K
Takeda
T
T
Yu
L
L
Fujimoto
S
S
Kajikawa
M
M
Nishimura
M
M
Mizuno
N
N
Hamamoto
Y
Y
Mukai
E
E
Adachi
T
T
Seino
Y
Y
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004909:Erythrocyte Indices / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D015737:Nisoldipine / Q000494:pharmacology*
D001786:Blood Glucose; D002118:Calcium; D002121:Calcium Channel Blockers; D006442:Glycated Hemoglobin; D015737:Nisoldipine