Effect of Hyperketonemia on Myocardial Function in Patients with Heart Failure and Type 2 Diabetes

IF 6.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes Pub Date : 2024-10-24 DOI:10.2337/db24-0406
Carolina Solis-Herrera, Yuejuan Qin, Henri Honka, Eugenio Cersosimo, Curtis Triplitt, Sivaram Neppala, Jemena Rajan, Francisca M. Acosta, Alexander J. Moody, Patricio Iozzo, Peter Fox, Geoffrey Clarke, Ralph A. DeFronzo
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Abstract

We examined the effect of increased plasma ketones on left ventricular (LV) function, myocardial glucose uptake (MGU), and myocardial blood flow (MBF) in type 2 diabetes (T2DM) patients with heart failure (HF). Three groups (I,II,III) of T2DM (12 per group) with LV ejection fraction ≤50% received incremental infusions of β-OH-B for 3-6 hours to raise plasma β-OH-B concentration throughout the physiologic (Groups I and II) and pharmacologic (Group III) range. Cardiac MRI was performed at baseline and after each β-OH-B infusion to provide measures of cardiac function. On a separate day, Group II also received NaHCO3 infusion, thus serving as their own control for time, volume, and pH. Additionally, Group II underwent positron emission tomography study with 18F-fluoro-2-deoxyglucose to examine effect of hyperketonemia on MGU. Groups I, II, III achieved plasma β-OH-B levels of 0.7±0.3, 1.6±0.2, 3.2±0.2 mmol/L, respectively. Cardiac output, LVEF, and stroke volume increased significantly during β-OH-B infusion in Groups II (CO, 4.54 to 5.30; EF, 39.9 to 43.8; SV, 70.3 to 80.0) and III (CO, 5.93 to 7.16; EF, 41.1 to 47.5; SV, 89.0 to 108.4) and did not change with NaHCO3 infusion in Group II. The increase in LVEF was greatest in Group III (p<0.001 vs Group II). MGU and MBF were not altered by β-OH-B. In T2DM patients with LVEF≤50%, increased plasma β-OH-B significantly increased LV function dose-dependently. Since MGU did not change, the myocardial benefit of β-OH-B resulted from providing an additional fuel for the heart without inhibiting MGU.
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高酮血症对心力衰竭和 2 型糖尿病患者心肌功能的影响
我们研究了血浆酮体增加对心力衰竭(HF)2 型糖尿病(T2DM)患者左心室(LV)功能、心肌葡萄糖摄取量(MGU)和心肌血流量(MBF)的影响。三组(I、II、III 组)左心室射血分数≤50%的 T2DM 患者(每组 12 人)在 3-6 小时内逐步输注β-OH-B,以提高血浆β-OH-B 浓度,使其达到生理浓度(I 组和 II 组)和药物浓度(III 组)范围。在基线和每次输注β-OH-B后进行心脏核磁共振成像,以测量心脏功能。在另一天,II 组也接受了 NaHCO3 输注,从而在时间、容量和 pH 值上作为自己的对照。此外,第二组还接受了 18F 氟-2-脱氧葡萄糖正电子发射断层扫描研究,以检查高酮血症对 MGU 的影响。I、II、III组的血浆β-OH-B水平分别为0.7±0.3、1.6±0.2、3.2±0.2 mmol/L。第二组(CO,4.54 至 5.30;EF,39.9 至 43.8;SV,70.3 至 80.0)和第三组(CO,5.93 至 7.16;EF,41.1 至 47.5;SV,89.0 至 108.4)的心输出量、LVEF 和每搏容量在输注 β-OH-B 时显著增加,而第二组在输注 NaHCO3 时没有变化。第三组 LVEF 的增幅最大(p<0.001 vs 第二组)。β-OH-B不会改变MGU和MBF。在 LVEF≤50% 的 T2DM 患者中,血浆 β-OH-B 的增加可显著增加左心室功能,且呈剂量依赖性。由于 MGU 没有发生变化,β-OH-B 对心肌的益处来自于为心脏提供额外的燃料,而不抑制 MGU。
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来源期刊
Diabetes
Diabetes 医学-内分泌学与代谢
CiteScore
12.50
自引率
2.60%
发文量
1968
审稿时长
1 months
期刊介绍: Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.
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