Department of Endocrinology, Akershus University Hospital, Lørenskog, Norway.
Department of Endocrinology, Campus Akershus University Hospital, Lørenskog, 1478, Norway.
Cardiovasc Diabetol. 2024 Aug 3;23(1):284. doi: 10.1186/s12933-024-02349-1.
Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers?
We examined 162 South Asian and 107 Nordic women in Norway 1-3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP.
The mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26 (15-38) vs. 42 (22-66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1-4.4) vs. 1.2 (0.3-4.2) mg/L), IL-6 (2.3 (1.5-3.2) vs. 1.5 (1.5-2.5) pg/mL), leptin (1647 (1176-2480) vs. 1223 (876-2313) pmol/L), and lower adiponectin levels (7.2 (5.3-9.3) vs. 10.0 (7.2-13.5) mg/L) and Matsuda ISI (2.4 (1.7-3.7) vs. 4.2 (2.9-6.1), p<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP.
NT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.
南亚裔个体在患有妊娠糖尿病（GDM）后患心血管疾病的风险高于欧洲个体。B 型利钠肽（BNP）及其前体激素的氨基末端片段（NT-proBNP）常用于心力衰竭的筛查和诊断，但生物体内 BNP 通过拮抗肾素-血管紧张素-醛固酮系统发挥多种有益的心血管作用。我们想知道循环 NT-proBNP 水平的种族差异是否可以用心脏代谢和炎症风险标志物的差异来解释？
我们对挪威的 162 名南亚裔和 107 名北欧裔女性进行了检查，这些女性在 GDM 后 1-3 年进行了临床检查、空腹血样和口服葡萄糖耐量试验。我们测量了 NT-proBNP、高敏心肌肌钙蛋白 T、高敏 C 反应蛋白（hsCRP）、白细胞介素 6（IL-6）、瘦素、脂联素以及胰岛素敏感性标志物，如 Matsuda 胰岛素敏感性指数（ISI）。最后，我们试图确定哪种独立协变量最能介导 NT-proBNP 的种族差异。
平均（SD）年龄为 35.3（4.5）岁，BMI 为 29.1（6.0）kg/m2，腰高比为 0.60（0.08），164 名女性（61%）患有糖尿病前期/糖尿病。值得注意的是，南亚裔女性的 NT-proBNP 水平在血糖正常和糖尿病前期/糖尿病两组中均低于北欧裔女性（中位数（IQR）分别为 26（15-38）和 42（22-66）ng/L，p<0.001）。在南亚裔和北欧裔女性中，更高的 NT-proBNP 水平与更高的胰岛素敏感性相关（p=0.005 和 p<0.001）。南亚裔女性的 hsCRP（中位数（IQR）分别为 2.2（1.1-4.4）和 1.2（0.3-4.2）mg/L）、IL-6（2.3（1.5-3.2）和 1.5（1.5-2.5）pg/mL）、瘦素（1647（1176-2480）和 1223（876-2313）pmol/L）水平更高，脂联素水平更低（7.2（5.3-9.3）和 10.0（7.2-13.5）mg/L）和 Matsuda ISI（2.4（1.7-3.7）和 4.2（2.9-6.1），p<0.01）低于北欧裔女性。即使在调整了这些差异后，更高的 NT-proBNP 水平仍然与胰岛素敏感性相关（每标准差 Matsuda ISI 增加 22%的 NT-proBNP，p=0.015）。胰岛素敏感性和脂联素分别解释了 NT-proBNP 种族差异的 53%和 41%。
GDM 后南亚裔女性的 NT-proBNP 水平低于北欧裔女性。较低的 NT-proBNP 水平与胰岛素敏感性受损相关。南亚裔女性较低的 NT-proBNP 水平可能归因于胰岛素敏感性受损，而不是全身脂肪量。
