Elevated Hepatic Glucose Production in Children with Cystic Fibrosis

Cl, Kien; Ca, Horswill; Wb, Zipf; Ks, McCoy; O'Dorisio, Thomas M.

doi:10.1203/00006450-199505000-00007

Cited by 27 publications

(13 citation statements)

References 22 publications

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“…Dogs with CP, however, lacked the expected suppression of HGP by insulin, although insulin’s effect on glucose disposal was normal or increased. This isolated hepatic resistance to insulin has subsequently been shown to be uniformly present and characteristic of pancreatogenic diabetes in patients with pancreatic malignancy [28], pancreatic resection [13], CP [29], and cystic fibrosis [30]. …”

Section: Pancreatogenic Diabetesmentioning

confidence: 99%

Pancreatogenic Diabetes: Special Considerations for Management

2011

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Section: Pancreatogenic Diabetesmentioning

confidence: 99%

Pancreatogenic Diabetes: Special Considerations for Management

2011

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“…A resistência insulínica nesse distúrbio tem sido justificada por vários mecanismos: infecções pulmonares recorrentes ou crônicas, fibrose hepática subclínica, elevação de hormônios contra-reguladores (cortisol e catecolaminas), níveis elevados de citocinas (interleucinas e TNFa) e, em pacientes com diabetes manifesto, a glicotoxicidade. O aumento da produção hepática de glicose, secundária à resistência à insulina nesse orgão, foi demonstrada em pacientes, ainda não diabéticos, com mucoviscidose [13][14][15][16] . Estudos anteriores estabeleceram uma correlação direta do aparecimento do DM com a insuficiência exócrina 17,18 .…”

Section: Study Of the Frequency Of Diabetes Mellitus And Glucose Intounclassified

Estudo da freqüência de diabetes mellitus e intolerância à glicose em pacientes com fibrose cística

Castro¹,

Fernandes²,

Júnior³

et al. 2001

J. Pediatr. (Rio J.)

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ResumoObjetivo: avaliar a freqüência de diabetes mellitus (DM) e de intolerância à glicose nos pacientes com fibrose cística seguidos no Serviço de Gastropediatria do HC-FMRP-USP.Métodos: foi realizado estudo analítico transversal de um grupo de 25 pacientes mucoviscidóticos do HC-FMRP-USP. Foram realizados testes orais de tolerância à glicose (OGTT) com determinação concomitante da glicemia e da insulinemia. Foram obtidas áreas sob as curvas da glicemia (G) e da insulinemia (I) e calculada a relação I/G, correlacionando-as com o tempo de doença clinicamente manifesta e função exócrina pancreática.Resultados: cinco pacientes apresentaram alterações: um é diabético e quatro são intolerantes à glicose e/ou hiperinsulinêmicos. Há correlação direta entre a área sob a curva de insulinemia e o tempo de mucoviscidose. Verificou-se também relação inversa estatisticamente significativa entre a área sob a curva de insulinemia e o índice I/G com o número de cápsulas de enzima/kg/dia.Conclusão: a freqüência de alterações na homeostase glicêmica nos mucoviscidóticos estudados é maior que na população em geral (20% da amostra total e 33% do grupo de pacientes com glicemia e insulinemia no OGTT). Assim, é importante a realização sistemática de testes de tolerância à glicose em mucoviscidóticos, visando à detecção precoce de anormalidades metabólicas para adequado tratamento.J Pediatr (Rio J) 2001; 77 (4): 321-6: diabetes mellitus; mucoviscidose; fibrose cística; intolerância à glicose. AbstractObjective: to evaluate the frequency of diabetes mellitus and glucose intolerance in patients with cystic fibrosis treated at the Pediatric Gastroenterology Service of HC-FMRP-USP.Methods: a cross-sectional analytical study was conducted on a group of 25 patients with mucoviscidosis who were followed up at HC-FMRP-USP. Oral glucose tolerance tests (OGTT) were performed, with simultaneous determination of glycemia and insulinemia. Areas under the curve were obtained for glycemia (G) and insulinemia (I) and the I/G ratio was calculated and correlated with the duration of clinical manifestation and pancreatic exocrine function.Results: five patients presented alterations: one was diabetic and four had glucose intolerance and/or hyperinsulinemia. There was a direct correlation between the area under the curve for insulinemia and the duration of mucoviscidosis. A significant inverse correlation was also observed between the area under the curve for insulinemia and I/G ratio, and number of enzyme capsules/kg/ day.Conclusions: the frequency of alterations in glucose homeostasis observed in patients with mucoviscidosis was higher than in the population at large (20% of the total sample and 33% of the group of patients with glycemia and insulinemia on OGTT). Therefore, it is important that glucose tolerance tests be performed systematically in patients with mucoviscidosis so that metabolic abnormalities can be early detected, and proper treatment can be initiated.

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“…1,2 Hepatic glucose production (HGP) is an important regulator of glycemic control, 3 and elevated HGP has been described in children 4 and adults with CF. 5 We have previously described hepatic insulin resistance 6 and close correlation between elevated HGP and postprandial glucose levels.…”

Section: Introductionmentioning

confidence: 99%

Elevated Gluconeogenesis and Lack of Suppression by Insulin Contribute to Cystic Fibrosis-Related Diabetes

Hardin

Ahn

Rice

et al. 2008

Journal of Investigative Medicine

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The incidence of diabetes is high in cystic fibrosis (CF) and is an important cause of morbidity and mortality. Understanding the pathophysiology is imperative. Studies have documented increased endogenous (mostly hepatic) glucose production (HGP) but have not distinguished the relative contribution of gluconeogenesis (GNG). The purpose of this study was to quantitate GNG, to determine its contribution to high HGP, and to measure insulin's suppression of GNG. We recruited 31 adult CF subjects (age, 26.2+/-7.9 years; 12 female subjects) and quantified GNG by measuring the incorporation of H into the second and fifth carbons of glucose. Hepatic glucose production was measured using [6,6-H2]glucose. Protein breakdown was measured using [1-C]leucine. Data were compared with that from 11 healthy volunteers (age, 27.5+/-7.0 years) who underwent both GNG and clamp studies. Thirteen CF subjects and all controls had a hyperinsulinemic euglycemic clamp during measures of GNG. Other measures included glucose tolerance and glucagon and cortisol levels. Rate of GNG was higher in CF subjects than controls and comprised a greater percentage of fasting HGP (GNG as percent of HGP: CF=68%; controls=44%; P=0.034). Suppression of GNG by insulin was significantly lower in CF than in controls and was lower in CF subjects with abnormal glucose tolerance than in those with normal glucose tolerance. Gluconeogenesis correlated with protein breakdown. These studies suggest that high HGP in CF is mostly from elevated rates of GNG and that resistance to insulin's suppression of GNG may contribute to abnormal glucose tolerance in CF.

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Elevated Hepatic Glucose Production in Children with Cystic Fibrosis

Cited by 27 publications

References 22 publications

Pancreatogenic Diabetes: Special Considerations for Management

Pancreatogenic Diabetes: Special Considerations for Management

Estudo da freqüência de diabetes mellitus e intolerância à glicose em pacientes com fibrose cística

Elevated Gluconeogenesis and Lack of Suppression by Insulin Contribute to Cystic Fibrosis-Related Diabetes

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