Interdisciplinary Department of Medicine-Section of Internal Medicine, Geriatrics, Endocrinology, and Rare Diseases. University of Bari "Aldo Moro", School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Italy.
Endocr Metab Immune Disord Drug Targets. 2023;23(9):1240-1244. doi: 10.2174/1871530323666230227113252.
Insulin resistance (IR) and type 2 diabetes mellitus (T2D) are known to affect the progression of chronic heart failure (CHF), but little evidence exists about the impact of IR and T2D on right ventricular dysfunction and exercise tolerance. Insights from the T.O.S.C.A. Registry: Echocardiographic hallmarks and cardiopulmonary exercise test (CPET) results were evaluated at baseline and after an average time of 36 months. T2D patients exhibited a greater intraventricular septum (IVS) thickness (11 ± 2 mm, 10 ± 2 mm, 10 ± 2 mm, in T2D, IR, and EU, respectively; p<.05) and LV wall thickness (0.34 ± 0.1, 0.32 ± 0.1, and 0.32 ± 0.1, in T2D, IR, and EU, respectively; p<.05). Moreover, T2D patients exhibited worse LV filling dynamics with larger left atrial volume index compared to IR and EU. Right ventricle dysfunction, expressed as a lower TAPSE/PASP ratio, was found in T2D [0.52(0.32-0.72)] than in EU and IR [0.60(0.30-0.90); p<.05]. T2D patients showed a significantly lower VO2 max peak when compared to IR and EU patients (15.8 ± 3.8 vs. 16.5 ± 4.3 vs. 18.4 ± 4.3 ml/Kg/min; p<.003), with an inverse relationship between the HOMAIR classes and VO2 max. Right ventricle structure and function deteriorated more rapidly in T2D, as suggested by more relevant deterioration in TAPSE/PASP ratio (-10% in EU patients, -14% in IR patients, -21% in T2D; p<.05).
The study findings suggest that the right ventricle structure, function, and cardiopulmonary performance deteriorate with IR and, more evidently, due to chronic exposure to hyperglycemia in T2D. Impaired exercise tolerance, poor cardiorespiratory fitness, diastolic dysfunction, and left atrial enlargement predispose patients to poor quality of life, suboptimal adherence to physical activity, and an overall increase in the risk of all-cause and cardiovascular mortality. In addition, chronic hyperglycemia accelerates the progression of these alterations, especially in patients with poor glycemic control over time. Highly selective and even more non-selective sodium glucose transporter type 2 inhibitors and glucagon-like peptide 1 receptor agonists should be considered as the first-line therapy for improving CV outcomes in T2D and CHF. Further studies are needed to understand the role of these molecules in treating pre-clinical conditions, such as IR and metabolic syndrome.
胰岛素抵抗（IR）和 2 型糖尿病（T2D）已知会影响慢性心力衰竭（CHF）的进展，但关于 IR 和 T2D 对右心室功能障碍和运动耐量的影响的证据很少。T.O.S.C.A. 登记处的见解：在基线时和平均 36 个月后评估了超声心动图特征和心肺运动试验（CPET）结果。T2D 患者的室间隔（IVS）厚度更大（11±2mm、10±2mm、10±2mm，分别在 T2D、IR 和 EU 中；p<.05）和左心室壁厚度（0.34±0.1、0.32±0.1 和 0.32±0.1，分别在 T2D、IR 和 EU 中；p<.05）。此外，与 IR 和 EU 相比，T2D 患者的左心房容积指数更大，表明 LV 充盈动力学更差。T2D 患者的 TAPSE/PASP 比值较低，表明右心室功能障碍[0.52（0.32-0.72）]比 EU 和 IR[0.60（0.30-0.90）]差（p<.05）。与 IR 和 EU 患者相比，T2D 患者的 VO2 max 峰值明显更低（15.8±3.8 比 16.5±4.3 比 18.4±4.3ml/Kg/min；p<.003），且 HOMAIR 分级与 VO2 max 呈负相关。TAPSE/PASP 比值的恶化更明显（EU 患者恶化 10%、IR 患者恶化 14%、T2D 患者恶化 21%；p<.05），表明 T2D 患者的右心室结构和功能恶化更快。
研究结果表明，IR 会导致右心室结构、功能和心肺性能恶化，而在 T2D 中，由于长期暴露于高血糖，恶化更为明显。运动耐量受损、心肺适应性差、舒张功能障碍和左心房扩大使患者易患生活质量差、身体活动依从性不佳以及全因和心血管死亡率增加等问题。此外，慢性高血糖加速了这些改变的进展，尤其是在血糖控制不佳的患者中。高选择性甚至更非选择性钠葡萄糖转运蛋白 2 抑制剂和胰高血糖素样肽 1 受体激动剂应被视为改善 T2D 和 CHF 心血管结局的一线治疗药物。需要进一步研究以了解这些分子在治疗 IR 和代谢综合征等临床前疾病中的作用。
