Ruggenenti Piero, Cattaneo Dario, Loriga Giacomina, Ledda Franca, Motterlini Nicola, Gherardi Giulia, Orisio Silvia, Remuzzi Giuseppe
Mario Negri Institute for Pharmacological Research, Via Gavazzeni 11, Bergamo, Italy.
Hypertension. 2009 Sep;54(3):567-74. doi: 10.1161/HYPERTENSIONAHA.109.132522. Epub 2009 Jul 20.
Insulin resistance, a key component of the metabolic syndrome, is a risk factor for diabetes mellitus and cardiovascular disease. Acetyl-L-carnitine infusion acutely ameliorated insulin sensitivity in type 2 diabetics with insulin resistance. In this sequential off-on-off pilot study, we prospectively evaluated the effects of 24-week oral acetyl-L-carnitine (1 g twice daily) therapy on the glucose disposal rate (GDR), assessed by hyperinsulinemic euglycemic clamps, and components of the metabolic syndrome in nondiabetic subjects at increased cardiovascular risk a priori segregated into 2 groups with GDR < or =7.9 (n=16) or >7.9 (n=16) mg/kg per minute, respectively. Baseline GDR and systolic blood pressure were negatively correlated (n=32; P=0.001; r=-0.545), and patients with GDR < or =7.9 mg/kg per minute had higher systolic/diastolic blood pressure than those with higher GDR. Acetyl-L-carnitine increased GDR from 4.89+/-1.47 to 6.72+/-3.12 mg/kg per minute (P=0.003, Bonferroni-adjusted) and improved glucose tolerance in patients with GDR < or =7.9 mg/kg per minute, whereas it had no effects in those with higher GDRs. Changes in GDR were significantly different between groups (P=0.017, ANCOVA). Systolic blood pressure decreased from 144.0+/-13.6 to 135.1+/-8.4 mm Hg and from 130.8+/-12.4 to 123.8+/-10.8 mm Hg in the lower and higher GDR groups, respectively (P<0.05 for both; P<0.001 overall) and progressively recovered toward baseline over 8 weeks posttreatment. Total and high molecular weight adiponectin levels followed specular trends. Diastolic blood pressure significantly decreased only in those with higher GDRs. Treatment was well tolerated in all of the patients. Acetyl-L-carnitine safely ameliorated arterial hypertension, insulin resistance, impaired glucose tolerance, and hypoadiponectinemia in subjects at increased cardiovascular risk. Whether these effects may translate into long-term cardioprotection is worth investigating.
胰岛素抵抗是代谢综合征的关键组成部分，是糖尿病和心血管疾病的危险因素。静脉输注乙酰左旋肉碱可急性改善伴有胰岛素抵抗的2型糖尿病患者的胰岛素敏感性。在这项序贯性开-关-开的初步研究中，我们前瞻性评估了为期24周的口服乙酰左旋肉碱（每日2次，每次1 g）治疗对葡萄糖处置率（GDR）的影响，GDR通过高胰岛素正常血糖钳夹技术评估，同时还评估了心血管疾病风险增加的非糖尿病受试者的代谢综合征组分，这些受试者事先被分为两组，GDR分别≤7.9（n = 16）或＞7.9（n = 16）mg/kg每分钟。基线GDR与收缩压呈负相关（n = 32；P = 0.001；r = -0.545），GDR≤7.9 mg/kg每分钟的患者的收缩压/舒张压高于GDR较高的患者。乙酰左旋肉碱使GDR从4.89±1.47提高至6.72±3.12 mg/kg每分钟（P = 0.003，经邦费罗尼校正），并改善了GDR≤7.9 mg/kg每分钟患者的糖耐量，而对GDR较高的患者无影响。两组间GDR的变化有显著差异（P = 0.017，协方差分析）。较低和较高GDR组的收缩压分别从144.0±13.6降至135.1±8.4 mmHg和从130.8±12.4降至123.8±10.8 mmHg（两者P均<0.05；总体P<0.001），且在治疗后8周逐渐恢复至基线水平。总脂联素和高分子量脂联素水平呈现相反趋势。仅GDR较高的患者的舒张压显著降低。所有患者对治疗耐受性良好。乙酰左旋肉碱可安全改善心血管疾病风险增加的受试者的动脉高血压、胰岛素抵抗、糖耐量受损和低脂联素血症。这些作用是否能转化为长期心脏保护作用值得研究。
