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A history of previous gestational diabetes mellitus is associated with adverse changes in insulin secretion and VLDL metabolism independently of increased intrahepatocellular lipid

Forbes, S. ; Godsland, I. F. ; Taylor-Robinson, S. D. ; Bell, J. D. ; Thomas, E. L. ; Patel, N. ; Hamilton, G. ; Parker, K. H. ; Marshall, I. ; Gray, C. D. ; Bedford, D. ; Caslake, M. ; Walker, B. R. ; Johnston, D. G.

Diabetologia, 2013-09, Vol.56 (9), p.2021-2033 [Periódico revisado por pares]

Berlin/Heidelberg: Springer Berlin Heidelberg

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Título:
A history of previous gestational diabetes mellitus is associated with adverse changes in insulin secretion and VLDL metabolism independently of increased intrahepatocellular lipid
Autor: Forbes, S. ; Godsland, I. F. ; Taylor-Robinson, S. D. ; Bell, J. D. ; Thomas, E. L. ; Patel, N. ; Hamilton, G. ; Parker, K. H. ; Marshall, I. ; Gray, C. D. ; Bedford, D. ; Caslake, M. ; Walker, B. R. ; Johnston, D. G.
Assuntos: Adult ; Biological and medical sciences ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes, Gestational - metabolism ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Fatty Liver - metabolism ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Human Physiology ; Humans ; Insulin - metabolism ; Insulin Resistance - physiology ; Internal Medicine ; Lipoproteins, VLDL - metabolism ; Liver - metabolism ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Medicine ; Medicine & Public Health ; Metabolic Diseases ; Non-alcoholic Fatty Liver Disease ; Other diseases. Semiology ; Pregnancy
É parte de: Diabetologia, 2013-09, Vol.56 (9), p.2021-2033
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Descrição: Aims/hypothesis We have previously reported a high prevalence of non-alcoholic fatty liver disease (NAFLD) among women with previous gestational diabetes mellitus (pGDM). We wanted to confirm that intrahepatocellular lipid (IHCL) is associated with pGDM independently of adiposity and determine: (1) if VLDL metabolism is dysregulated; and (2) the extent to which NAFLD and IHCL account for the dysmetabolic phenotype in pGDM. Methods We analysed data from a cohort of 234 women (114 with pGDM) and identified effects of pGDM on lipid and glucoregulation that were independent of ultrasound-diagnosed NAFLD. We then measured IHCL by MR spectroscopy in a representative subgroup ( n = 36) and conducted detailed metabolic studies (IVGTT, VLDL apolipoprotein B [apoB] kinetics and palmitate turnover) and measurement of regional body fat by MRI to demonstrate effects of IHCL that were independent of a history of pGDM. Results pGDM was associated with increased IHCL ( p = 0.04) after adjustment for adiposity. Independently of IHCL, pGDM was associated with a lower IVGTT disposition index ( p = 0.02) and acute insulin response to glucose (pGDM+/NAFLD−, 50% lower; pGDM+/NAFLD+, 36% lower; effect of pGDM, p = 0.03), increased VLDL apoB pool size (pGDM+/NAFLD−, 3.1-fold higher; pGDM+/NAFLD+, 1.2-fold higher; effect of pGDM, p = 0.02) and, at borderline significance ( p = 0.05), increased rate of VLDL apoB synthesis. Conclusions/interpretation pGDM is associated with increased IHCL independently of adiposity. The increased liver fat contributes to the phenotype, but pGDM status is independently associated with diminished insulin secretion and (shown for the first time) augmented VLDL metabolism. IHCL with pGDM may compound a dysmetabolic phenotype.
Editor: Berlin/Heidelberg: Springer Berlin Heidelberg
Idioma: Inglês

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A history of previous gestational diabetes mellitus is associated with adverse changes in insulin secretion and VLDL metabolism independently of increased intrahepatocellular lipid

Forbes, S. ; Godsland, I. F. ; Taylor-Robinson, S. D. ; Bell, J. D. ; Thomas, E. L. ; Patel, N. ; Hamilton, G. ; Parker, K. H. ; Marshall, I. ; Gray, C. D. ; Bedford, D. ; Caslake, M. ; Walker, B. R. ; Johnston, D. G.

Berlin/Heidelberg: Springer Berlin Heidelberg

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