Department of Pathophysiology, Third Faculty of Medicine, Charles University, Ruska 87, 100 00, Prague 10, Czech Republic.
Department of Cardiology, University Hospital Královské Vinohrady, Prague, Czech Republic.
Sci Rep. 2021 Feb 11;11(1):3567. doi: 10.1038/s41598-021-83018-1.
Obstructive sleep apnoea (OSA) is associated with type 2 diabetes mellitus (T2DM). However, mechanisms mediating association between these two conditions remain unclear. This study investigated, whether the OSA-associated changes in adipose tissue lipolysis might contribute to impaired glucose homeostasis in patient with T2DM. Thirty-five matched subjects were recruited into three groups: T2DM + severe OSA (T2DM + OSA, n = 11), T2DM with mild/no OSA (T2DM, n = 10) and healthy controls (n = 14). Subcutaneous abdominal adipose tissue microdialysis assessed spontaneous, epinephrine- and isoprenaline-stimulated lipolysis. Glucose metabolism was assessed by intravenous glucose tolerance test. Spontaneous lipolysis was higher in the T2DM + OSA compared with the T2DM (60.34 ± 23.40 vs. 42.53 ± 10.16 μmol/L, p = 0.013), as well as epinephrine-stimulated lipolysis (236.84 ± 103.90 vs. 167.39 ± 52.17 µmol/L, p < 0.001). Isoprenaline-stimulated lipolysis was unaffected by the presence of OSA (p = 0.750). The α anti-lipolytic effect was decreased in T2DM + OSA by 59% and 315% compared with T2DM and controls (p = 0.045 and p = 0.007, respectively). The severity of OSA (AHI) was positively associated with spontaneous (p = 0.037) and epinephrine-stimulated (p = 0.026) lipolysis. The α-adrenergic anti-lipolytic effect (p = 0.043) decreased with increasing AHI. Spontaneous lipolysis was positively associated with Insulin resistance (r = 0.50, p = 0.002). Epinephrine-stimulated lipolysis was negatively associated with the Disposition index (r = - 0.34, p = 0.048). AHI was positively associated with Insulin resistance (p = 0.017) and negatively with the Disposition index (p = 0.038). Severe OSA in patients with T2DM increased adipose tissue lipolysis, probably due to inhibition of the α-adrenergic anti-lipolytic effect. We suggest that dysregulated lipolysis might contribute to OSA-associated impairments in insulin secretion and sensitivity.
阻塞性睡眠呼吸暂停（OSA）与 2 型糖尿病（T2DM）有关。然而，介导这两种情况之间关联的机制仍不清楚。本研究旨在探讨 OSA 相关的脂肪组织脂解变化是否会导致 T2DM 患者葡萄糖稳态受损。将 35 名匹配的受试者分为三组：T2DM+重度 OSA（T2DM+OSA，n=11）、T2DM 伴轻度/无 OSA（T2DM，n=10）和健康对照组（n=14）。通过皮下腹部脂肪组织微透析评估自发性、肾上腺素和异丙肾上腺素刺激的脂解作用。通过静脉葡萄糖耐量试验评估葡萄糖代谢。与 T2DM 相比，T2DM+OSA 患者的自发性脂解作用更高（60.34±23.40 与 42.53±10.16 μmol/L，p=0.013），以及肾上腺素刺激的脂解作用（236.84±103.90 与 167.39±52.17 μmol/L，p<0.001）。OSA 的存在对异丙肾上腺素刺激的脂解作用没有影响（p=0.750）。与 T2DM 和对照组相比，T2DM+OSA 患者的α抗脂解作用降低了 59%和 315%（p=0.045 和 p=0.007）。OSA 的严重程度（AHI）与自发性（p=0.037）和肾上腺素刺激的脂解作用呈正相关（p=0.026）。α-肾上腺素能抗脂解作用（p=0.043）随着 AHI 的增加而降低。自发性脂解作用与胰岛素抵抗呈正相关（r=0.50，p=0.002）。肾上腺素刺激的脂解作用与处置指数呈负相关（r=-0.34，p=0.048）。AHI 与胰岛素抵抗呈正相关（p=0.017），与处置指数呈负相关（p=0.038）。T2DM 患者重度 OSA 增加了脂肪组织脂解作用，可能是由于α-肾上腺素能抗脂解作用的抑制。我们认为，脂解作用失调可能导致 OSA 相关的胰岛素分泌和敏感性受损。
