Chung Stephanie T, Hsia Daniel S, Chacko Shaji K, Rodriguez Luisa M, Haymond Morey W
National Institute of Diabetes and Digestive and Kidney Diseases, NIH 10 Center Dr. Bld 10-CRC, RM 5-5740, MSC 1612, Bethesda, MD, 20892-1612, USA,
Diabetologia. 2015 Mar;58(3):596-603. doi: 10.1007/s00125-014-3455-x. Epub 2014 Dec 3.
AIMS/HYPOTHESIS: The role of increased gluconeogenesis as an important contributor to fasting hyperglycaemia at diabetes onset is not known. We evaluated the contribution of gluconeogenesis and glycogenolysis to fasting hyperglycaemia in newly diagnosed youths with type 2 diabetes following an overnight fast.
Basal rates (μmol kg(FFM) (-1) min(-1)) of gluconeogenesis ((2)H2O), glycogenolysis and glycerol production ([(2)H5] glycerol) were measured in 18 adolescents (nine treatment naive diabetic and nine normal-glucose-tolerant obese adolescents).
Type 2 diabetes was associated with higher gluconeogenesis (9.2 ± 0.6 vs 7.0 ± 0.3 μmol kg(FFM) (-1) min(-1), p < 0.01), plasma fasting glucose (7.0 ± 0.6 vs 5.0 ± 0.2 mmol/l, p = 0.004) and insulin (300 ± 30 vs 126 ± 31 pmol/l, p = 0.001). Glucose production and glycogenolysis were similar between the groups (15.4 ± 0.3 vs 12.4 ± 1.4 μmol kg(FFM) (-1) min(-1), p = 0.06; and 6.2 ± 0.8 vs 5.3 ± 0.7 μmol kg(FFM) (-1) min(-1), p = 0.5, respectively). After controlling for differences in adiposity, gluconeogenesis, glycogenolysis and glucose production were higher in diabetic youth (p ≤ 0.02). Glycerol concentration (84 ± 6 vs 57 ± 6 μmol/l, p = 0.01) and glycerol production (5.0 ± 0.3 vs 3.6 ± 0.5 μmol kg(FFM) (-1) min(-1), p = 0.03) were 40% higher in youth with diabetes. The increased glycerol production could account for only ~1/3 of substrate needed for the increased gluconeogenesis in diabetic youth.
CONCLUSION/INTERPRETATIONS: Increased gluconeogenesis was a major contributor to fasting hyperglycaemia and hepatic insulin resistance in newly diagnosed untreated adolescents and was an early pathological feature of type 2 diabetes. Increased glycerol availability may represent a significant source of new carbon substrates for increased gluconeogenesis but would not account for all the carbons required to sustain the increased rates.
目的/假设：糖尿病发病时糖异生增加作为空腹高血糖的一个重要促成因素，其作用尚不清楚。我们评估了糖异生和糖原分解对新诊断的2型糖尿病青少年空腹禁食后高血糖的影响。
对18名青少年（9名未经治疗的糖尿病青少年和9名糖耐量正常的肥胖青少年）测量糖异生（（2）H2O）、糖原分解和甘油生成（[（2）H5]甘油）的基础速率（μmol kg（FFM）（-1）min（-1））。
2型糖尿病与更高的糖异生（9.2±0.6 vs 7.0±0.3 μmol kg（FFM）（-1）min（-1），p<0.01）、空腹血糖（7.0±0.6 vs 5.0±0.2 mmol/l，p = 0.004）和胰岛素（300±30 vs 126±31 pmol/l，p = 0.001）相关。两组之间的葡萄糖生成和糖原分解相似（15.4±0.3 vs 12.4±1.4 μmol kg（FFM）（-1）min（-1），p = 0.06；以及6.2±0.8 vs 5.3±0.7 μmol kg（FFM）（-1）min（-1），p = 0.5）。在控制了肥胖差异后，糖尿病青少年的糖异生、糖原分解和葡萄糖生成更高（p≤0.02）。糖尿病青少年的甘油浓度（84±6 vs 57±6 μmol/l，p = 0.01）和甘油生成（5.0±0.3 vs 3.6±0.5 μmol kg（FFM）（-1）min（-1），p = 0.03）高出40%。甘油生成增加仅能解释糖尿病青少年糖异生增加所需底物的约1/3。
结论/解读：糖异生增加是新诊断的未经治疗的青少年空腹高血糖和肝脏胰岛素抵抗的主要促成因素，是2型糖尿病的早期病理特征。甘油可用性增加可能是糖异生增加的新碳底物的重要来源，但不能解释维持增加速率所需的所有碳。
