Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany.
Diabetes. 2023 Oct 1;72(10):1483-1492. doi: 10.2337/db23-0353.
Intramyocellular lipid content (IMCL) is elevated in insulin-resistant humans, but it changes over time, and relationships with comorbidities remain unclear. We examined IMCL during the initial course of diabetes and its associations with complications. Participants of the German Diabetes Study (GDS) with recent-onset type 1 (n = 132) or type 2 diabetes (n = 139) and glucose-tolerant control subjects (n = 128) underwent 1H-MRS to measure IMCL and muscle volume, whole-body insulin sensitivity (hyperinsulinemic-euglycemic clamps; M-value), and cycling spiroergometry (VO2max). Subgroups underwent the same measurements after 5 years. At baseline, IMCL was ∼30% higher in type 2 diabetes than in other groups independently of age, sex, BMI, and muscle volume. In type 2 diabetes, the M-value was ∼36% and ∼62% lower compared with type 1 diabetes and control subjects, respectively. After 5 years, the M-value decreased by ∼29% in type 1 and ∼13% in type 2 diabetes, whereas IMCL remained unchanged. The correlation between IMCL and M-value in type 2 diabetes at baseline was modulated by VO2max. IMCL also associated with microalbuminuria, the Framingham risk score for cardiovascular disease, and cardiac autonomic neuropathy. Changes in IMCL within 5 years after diagnosis do not mirror the progression of insulin resistance in type 2 diabetes but associate with early diabetes-related complications.
Intramyocellular lipid content (IMCL) can be elevated in insulin-resistant humans, but its dynamics and association with comorbidities remain unclear. Independently of age, sex, body mass, and skeletal muscle volume, IMCL is higher in recent-onset type 2, but not type 1 diabetes, and remains unchanged within 5 years, despite worsening insulin resistance. A degree of physical fitness modulates the association between IMCL and insulin sensitivity in type 2 diabetes. Whereas higher IMCL associates with lower insulin sensitivity in people with lower physical fitness, there is no association between IMCL and insulin sensitivity in those with higher degree of physical fitness. IMCL associates with progression of microalbuminuria, cardiovascular disease risk, and cardiac autonomic neuropathy.
在胰岛素抵抗的人群中，肌细胞内脂质含量（IMCL）升高，但它会随时间变化，与合并症的关系仍不清楚。我们在糖尿病的初始病程中检查了 IMCL，并研究了其与并发症的关系。德国糖尿病研究（GDS）的参与者包括近期诊断的 1 型（n = 132）或 2 型糖尿病（n = 139）患者和葡萄糖耐量正常的对照受试者（n = 128），他们接受了 1H-MRS 测量 IMCL 和肌肉量、全身胰岛素敏感性（高胰岛素-正常血糖钳夹；M 值）和循环测功计（VO2max）。部分受试者在 5 年后进行了相同的测量。基线时，2 型糖尿病患者的 IMCL 比其他组高约 30%，且独立于年龄、性别、BMI 和肌肉量。与 1 型糖尿病和对照组相比，2 型糖尿病患者的 M 值分别低约 36%和 62%。5 年后，1 型糖尿病患者的 M 值降低了约 29%，2 型糖尿病患者降低了约 13%，而 IMCL 保持不变。基线时 2 型糖尿病患者中 IMCL 与 M 值之间的相关性受 VO2max 的调节。IMCL 还与微量白蛋白尿、心血管疾病的弗雷明汉风险评分和心脏自主神经病变相关。在诊断后 5 年内，IMCL 的变化并不能反映 2 型糖尿病患者胰岛素抵抗的进展，而是与早期糖尿病相关并发症相关。
肌细胞内脂质含量（IMCL）在胰岛素抵抗的人群中可能升高，但它的动态变化及其与合并症的关系尚不清楚。独立于年龄、性别、体重和骨骼肌体积，近期诊断的 2 型糖尿病患者的 IMCL 高于 1 型糖尿病患者，但在 5 年内保持不变，尽管胰岛素抵抗恶化。一定程度的身体适应性调节了 2 型糖尿病患者中 IMCL 与胰岛素敏感性之间的关联。在体力活动程度较低的人群中，较高的 IMCL 与较低的胰岛素敏感性相关，而在体力活动程度较高的人群中，IMCL 与胰岛素敏感性之间没有关联。IMCL 与微量白蛋白尿、心血管疾病风险和心脏自主神经病变的进展相关。
