1型糖尿病超重患者的肝脏脂肪含量与肝脏胰岛素敏感性
Liver fat content and hepatic insulin sensitivity in overweight patients with type 1 diabetes.
作者信息
Llauradó Gemma, Sevastianova Ksenia, Sädevirta Sanja, Hakkarainen Antti, Lundbom Nina, Orho-Melander Marju, Groop Per-Henrik, Forsblom Carol, Yki-Järvinen Hannele
机构信息
Minerva Foundation Institute for Medical Research (G.L., K.S., H.Y.-J.), FI-00290 Helsinki, Finland; Department of Medicine (K.S., S.S., H.Y.-J.), University of Helsinki, and Helsinki University Central Hospital, FI-00290 Helsinki, Finland; Helsinki Medical Imaging Center (A.H., N.L.), Helsinki University Central Hospital, FI-00290 Helsinki, Finland; Department of Clinical Sciences (M.O.-M.), Diabetes and Endocrinology, University Hospital Malmö, Lund University, SE-205 02 Malmö, Sweden; Folkhälsan Research Centre (P.-H.G., C.F.), Folkhälsan Institute of Genetics, Biomedicum Helsinki, FI-00290 Helsinki, Finland; and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (G.L.), Endocrinology Unit, Joan XXIII University Hospital, IISPV Pere Virgili Health Research Institute, Rovira i Virgili University, 43005 Tarragona, Spain.
出版信息
J Clin Endocrinol Metab. 2015 Feb;100(2):607-16. doi: 10.1210/jc.2014-3050. Epub 2014 Nov 18.
OBJECTIVES
Patients with type 1 diabetes mellitus (T1DM) lack the portal/peripheral insulin gradient, which might diminish insulin stimulation of hepatic lipogenesis and protect against development of nonalcoholic fatty liver disease (NAFLD). We compared liver fat content and insulin sensitivity of hepatic glucose production and lipolysis between overweight T1DM patients and nondiabetic subjects.
MATERIALS AND METHODS
We compared 32 overweight adult T1DM patients and 32 nondiabetic subjects matched for age, body mass index (BMI), and gender. Liver fat content was measured using proton magnetic resonance spectroscopy ((1)H-MRS), body composition by magnetic resonance imaging, and insulin sensitivity using the euglycemic-hyperinsulinemic clamp technique (insulin 0.4 mU/kg · min combined with infusion of D-[3-(3)H]glucose). We also hypothesized that low liver fat might protect from obesity-associated increases in insulin requirements and, therefore, determined insulin requirements across BMI categories in 3164 T1DM patients.
RESULTS
Liver fat content was significantly lower in T1DM patients than in nondiabetic subjects (0.6% [25th-75th quartiles, 0.3%-1.1%] vs 9.0% [3.0%-18.0%]; P < .001). The endogenous rate of glucose production (R(a)) during euglycemic hyperinsulinemia was significantly lower (0.4 [-0.7 to 0.8] mg/kg fat-free mass · min vs 0.9 [0.2-1.6] fat-free mass · min; P = .012) and the percent suppression of endogenous Ra by insulin was significantly greater (89% [78%-112%] vs 77% [50%-94%]; p = .009) in T1DM patients than in nondiabetic subjects. Serum nonesterified fatty acid concentrations during euglycemic hyperinsulinemia were significantly lower (78.5 [33.0-155.0] vs 306 [200.0-438.0] μmol/L; P < .001) and the percent suppression of nonesterified fatty acids significantly higher (89.1% [78.6%-93.3%] vs 51.4% [36.5%-71.1%]; P < .001) in T1DM patients than in nondiabetic subjects. Insulin doses were similar across BMI categories.
CONCLUSIONS
T1DM patients might be protected from steatosis and hepatic insulin resistance. Obesity may not increase insulin requirements in T1DM.
目的
1型糖尿病（T1DM）患者缺乏门静脉/外周胰岛素梯度，这可能会减少胰岛素对肝脏脂肪生成的刺激，并预防非酒精性脂肪性肝病（NAFLD）的发生。我们比较了超重T1DM患者和非糖尿病受试者的肝脏脂肪含量以及肝脏葡萄糖生成和脂肪分解的胰岛素敏感性。
材料与方法
我们比较了32名超重成年T1DM患者和32名年龄、体重指数（BMI）和性别相匹配的非糖尿病受试者。使用质子磁共振波谱（（1）H-MRS）测量肝脏脂肪含量，通过磁共振成像测量身体成分，并使用正常血糖-高胰岛素钳夹技术（胰岛素0.4 mU/kg·min联合输注D-[3-(3)H]葡萄糖）测量胰岛素敏感性。我们还假设低肝脏脂肪可能会预防肥胖相关的胰岛素需求增加，因此，我们确定了3164名T1DM患者不同BMI类别下的胰岛素需求。
结果
T1DM患者的肝脏脂肪含量显著低于非糖尿病受试者（0.6%[第25-75四分位数，0.3%-1.1%]对9.0%[3.0%-18.0%]；P<.001）。正常血糖高胰岛素血症期间内源性葡萄糖生成率（R(a)）显著更低（0.4[-0.7至0.8]mg/kg去脂体重·min对0.9[0.2-1.6]去脂体重·min；P=.012），且T1DM患者中胰岛素对内源性R(a)的抑制百分比显著更高（89%[78%-112%]对77%[从50%-94%]；P=.009）。正常血糖高胰岛素血症期间血清非酯化脂肪酸浓度显著更低（78.5[33.0-155.0]对306[200.0-438.0]μmol/L；P<.至001），且T1DM患者中非酯化脂肪酸的抑制百分比显著更高（89.1%[78.6%-93.3%]对51.4%[36.5%-71.1%]；P<.001）。不同BMI类别间胰岛素剂量相似。
结论
T1DM患者可能对脂肪变性和肝脏胰岛素抵抗具有保护作用。肥胖可能不会增加T1DM患者的胰岛素需求。
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