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Metformin-associated lactic acidosis is not necessarily due to metformin accumulation; true type B (aerobic) lactic acidosis, i.e., without an apparent associated hypoxic factor, seems exceptional. Neither the severity of the clinical picture nor the degree of metformin accumulation predicted survival; rather, the prognosis was dependent upon the severity of the associated pathological conditions.

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-To assess the influence of initial diameter on the gender difference in flow-dependent dilatation (FDD) of the conduit artery, we measured radial artery internal diameter (echotracking), flow (Doppler) and total blood viscosity in 24 healthy (25 Ϯ 0.8 yr) men and women during reactive hyperemia (RH) and during a gradual hand skin heating (SH). At baseline, mean diameter (men, 2.76 Ϯ 0.09 vs. women, 2.32 Ϯ 0.07 mm, P Ͻ 0.05), flow (men, 21 Ϯ 4 vs. women, 10 Ϯ 1 ml/min, P Ͻ 0.05), and blood viscosity (men, 4.13 Ϯ 0.07 vs. women, 3.92 Ϯ 0.13 cP, P Ͻ 0.05) were higher in men but mean shear stress (MSS) was not different between groups. During RH, the percent increase in diameter was lower in men (men, 9 Ϯ 1 vs. women, 13 Ϯ 1%, P Ͻ 0.05). This difference was suppressed after correction for baseline diameter. During SH, the increase in diameter with flow was higher in women (P Ͻ 0.01). However, the increase in MSS was higher in women because of their smaller diameter at each level of flow (P Ͻ 0.01) and there was no difference between groups for the increase in diameter at each level of MSS. These results demonstrate in a direct manner that initial diameter influences the magnitude of FDD of conduit arteries in humans by modifying the value of the arterial wall shear stress at each level of flow and support the interest of the heating method in presence of heterogeneous groups. endothelium; shear stress; skin heating; vasodilatation CONDUIT ARTERY FLOW-DEPENDENT vasodilatation is a fundamental mechanism that regulates vascular conductance at rest and during exercise and maintains wall shear stress within physiological values (3,22,28). This vasodilatation is mainly mediated by the endothelium release of nitric oxide (NO) in response to shear stress (17,22). Postischemic hyperemia, by increase of artery flow, is currently used in clinical studies (1,6,11,17,20,23) for noninvasive evaluation of flowdependent dilatation and is considered (i.e., by comparison with the vasodilating effect of exogenous NO) an index of endothelium-derived NO bioavailability. Gender differences in flow-dependent dilatation have been reported with a higher magnitude of conduit artery flow response in nonmenopausal women when compared with age-matched men, an effect that was considered as a consequence of the positive effect of endogenous estrogens on the bioavailability of NO (11,21). However, despite the fact that numerous studies (2, 7, 12-14, 24, 26) support this positive effect of estrogens on NO bioavailability, when the initial value of arterial diameter is taken into consideration in the statistical analysis, the increase in diameter appears similar between men and women (21). This suggests that gender difference could be the consequence of the larger baseline diameter observed in the men (11,20,21). Indeed, for the same increase in flow, because of higher diameter in men, the increase in shear stress during hyperemia could have been smaller in men than in women and thus may explain these different results. Because of technical limit...