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Title: Increased gluconeogenesis in youth with newly diagnosed type 2 diabetes

item CHUNG, STEPHANIE - National Institute Of Diabetes And Digestive And Kidney Diseases
item HSIA, DANIEL - Texas Children'S Hospital
item CHACKO, SHAJI - Children'S Nutrition Research Center (CNRC)
item RODRIGUEZ, LUISA - Texas Children'S Hospital
item HAYMOND, MOREY - Children'S Nutrition Research Center (CNRC)

Submitted to: Diabetologia
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2014
Publication Date: 3/1/2015
Citation: Chung, S.T., Hsia, D.S., Chacko, S.K., Rodriguez, L.M., Haymond, M.W. 2015. Increased gluconeogenesis in youth with newly diagnosed type 2 diabetes. Diabetologia. 58(3):596-603.

Interpretive Summary: The objective of this research was to determine whether increased glucose production from liver is an important contributor to higher blood sugar concentration during the onset of diabetes. This study demonstrated that Type 2 diabetes was associated with higher glucose production and contributes to higher blood sugar concentration during fasting condition. The findings from this research indicate that elevated glucose production from liver in newly diagnosed untreated adolescents is an early pathological feature of type 2 diabetes.

Technical Abstract: 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 (umol 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 umol 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 umol kg(FFM)**(-1)'min**(-1), p=0.06; and 6.2+/-0.8 vs 5.3+/-0.7 umol 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