OBJECTIVE Obesity is associated with an increased risk of type 2 diabetes and cardiovascular complications. The risk depends significantly on adipose tissue distribution. Liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We determined whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in obese subjects with prediabetes or early type 2 diabetes.

RESEARCH DESIGN AND METHODS Sixty-two metformin-treated obese subjects with prediabetes or newly diagnosed type 2 diabetes, were randomized to liraglutide (1.8 mg/day) or lifestyle counseling. Changes in SAT and VAT levels (determined by abdominal MRI), insulin sensitivity (according to the Matsuda index), and β-cell function (β-index) were assessed during a multiple-sampling oral glucose tolerance test; and circulating levels of IGF-I and IGF-II were assessed before and after a comparable weight loss (7% of initial body weight).

RESULTS After comparable weight loss, achieved by 20 patients per arm, and superimposable glycemic control, as reflected by HbA_1c level (P = 0.60), reduction in VAT was significantly higher in the liraglutide arm than in the lifestyle arm (P = 0.028), in parallel with a greater improvement in β-index (P = 0.021). No differences were observed in SAT reduction (P = 0.64). IGF-II serum levels were significantly increased (P = 0.024) only with liraglutide administration, and the increase in IGF-II levels correlated with both a decrease in VAT (ρ = −0.435, P = 0.056) and an increase in the β-index (ρ = 0.55, P = 0.012).

CONCLUSIONS Liraglutide effects on visceral obesity and β-cell function might provide a rationale for using this molecule in obese subjects in an early phase of glucose metabolism dysregulation natural history.

目的肥胖与2型糖尿病和心血管并发症的风险增加有关。风险很大程度上取决于脂肪组织的分布。利拉鲁肽（一种胰高血糖素样肽1类似物）与体重减轻，改善的血糖控制和降低的心血管风险有关。我们确定了由利拉鲁肽或生活方式改变引起的同等程度的体重减轻是否对患有前驱糖尿病或早期2型糖尿病的肥胖受试者的皮下脂肪组织（SAT）和内脏脂肪组织（VAT）有不同的影响。

研究设计和方法将62名接受二甲双胍治疗的患有糖尿病前期或新诊断为2型糖尿病的肥胖患者随机分为利拉鲁肽（1.8 mg /天）或生活方式咨询。在多次采样口服葡萄糖耐量试验中评估了SAT和VAT水平（由腹部MRI确定），胰岛素敏感性（根据Matsuda指数）和β细胞功能（β指数）的变化；在可比的减肥前后（初始体重的7％）评估了IGF-I和IGF-II的循环水平。

结果HbA _1c水平可反映出每组20例患者达到了可观的体重减轻，并实现了可叠加的血糖控制（P = 0.60），利拉鲁肽组的VAT降低明显高于生活方式组（P = 0.028） ，与此同时，β指数也有了更大的提高（P = 0.021）。SAT降低没有观察到差异（P = 0.64）。仅使用利拉鲁肽，IGF-II血清水平显着升高（P = 0.024），而IGF-II水平的升高与增值税的下降（ρ= -0.435，P = 0.056）和β-指数（ρ= 0.55，P = 0.012）。

结论利拉鲁肽对内脏肥胖和β细胞功能的影响可能为在葡萄糖代谢异常自然病史早期的肥胖受试者中使用该分子提供了理论依据。