Sasaki Nobuo, Ueno Yoshitaka, Ozono Ryoji, Nakano Yukiko, Higashi Yukihito
Health Management and Promotion Center, Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan.
Department of Regenerative Medicine, Division of Radiation Medical Science, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Diabetes Obes Metab. 2025 Jun;27(6):3025-3035. doi: 10.1111/dom.16307. Epub 2025 Mar 5.
Insulin resistance in adipose tissue causes dysregulation of various adipokine levels and ectopic fat accumulation in other organs, such as the liver. This study investigated the effects of insulin resistance in adipose tissue and concomitant fatty liver on each stage of impaired glucose metabolism compared with visceral fat mass.
This observational study included 3644 individuals who underwent two 75-g oral glucose tolerance tests at baseline and follow-up. Adipose insulin resistance index (Adipo-IR), lipid accumulation product (LAP) and fatty liver index (FLI) were used as indicators of insulin resistance in the adipose tissue, visceral fat mass and fatty liver, respectively.
Over a mean 2.9-year follow-up period, 463 (32.4%) individuals progressed from normoglycaemia to prediabetes, and 198 (10.6%) developed type 2 diabetes from prediabetes. Comparing the highest-to-lowest quartiles, baseline levels and changes in Adipo-IR were associated with an increased odds of progression from normoglycaemia to prediabetes (odds ratio [OR], 2.22; 95% CI, 1.36-3.65, OR, 2.70; 95% CI, 1.83-3.98, respectively) and from prediabetes to the onset of type 2 diabetes (OR, 2.02; 95% CI, 1.04-3.92, OR, 3.09; 95% CI, 1.84-4.19, respectively), after adjusting for possible confounders. Changes in FLI were associated with progression from prediabetes to type 2 diabetes. LAP did not affect the progression of impaired glucose metabolism.
Adipose tissue insulin resistance, rather than fat mass, is crucial in all stages of deterioration of glycaemic status. Fatty liver plays a decisive role in the eventual development of type 2 diabetes.
脂肪组织中的胰岛素抵抗会导致各种脂肪因子水平失调以及其他器官（如肝脏）的异位脂肪堆积。本研究调查了脂肪组织中的胰岛素抵抗和伴随的脂肪肝与内脏脂肪量相比，对葡萄糖代谢受损各阶段的影响。
这项观察性研究纳入了3644名在基线和随访时接受两次75克口服葡萄糖耐量试验的个体。脂肪胰岛素抵抗指数（Adipo-IR）、脂质积聚产物（LAP）和脂肪肝指数（FLI）分别用作脂肪组织、内脏脂肪量和脂肪肝中胰岛素抵抗的指标。
在平均2.9年的随访期内，463名（32.4%）个体从血糖正常进展为糖尿病前期，198名（10.6%）个体从糖尿病前期发展为2型糖尿病。比较最高四分位数与最低四分位数，调整可能的混杂因素后，Adipo-IR的基线水平和变化与从血糖正常进展为糖尿病前期的几率增加相关（优势比[OR]分别为2.22；95%置信区间[CI]，1.36 - 3.65；OR为2.70；95% CI，1.83 - 3.98），以及从糖尿病前期到2型糖尿病发病的几率增加相关（OR分别为2.02；95% CI，1.04 - 3.92；OR为3.09；95% CI，1.84 - （此处原文有误，应为4.19））。FLI的变化与从糖尿病前期进展为2型糖尿病相关。LAP不影响葡萄糖代谢受损的进展。
脂肪组织胰岛素抵抗而非脂肪量，在血糖状态恶化的所有阶段都至关重要。脂肪肝在2型糖尿病的最终发展中起决定性作用。
