Clinical and molecular characterisation of hyperinsulinaemic hypoglycaemia in infants born small-for-gestational age.
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ABSTRACT:
SUBMITTER: Arya VB
PROVIDER: S-EPMC3686249 | biostudies-literature | 2013 Jul
REPOSITORIES: biostudies-literature
Publications
Clinical and molecular characterisation of hyperinsulinaemic hypoglycaemia in infants born small-for-gestational age.
Arya Ved Bhushan VB Flanagan Sarah E SE Kumaran Anitha A Shield Julian P JP Ellard Sian S Hussain Khalid K Kapoor Ritika R RR
Archives of disease in childhood. Fetal and neonatal edition 20130129 4
<h4>Objective</h4>To characterise the phenotype and genotype of neonates born small-for-gestational age (SGA; birth weight <10th centile) who developed hyperinsulinaemic hypoglycaemia (HH).<h4>Methods</h4>Clinical information was prospectively collected on 27 SGA neonates with HH, followed by sequencing of KCNJ11 and ABCC8.<h4>Results</h4>There was no correlation between the maximum glucose requirement and serum insulin levels. Serum insulin level was undetectable in five infants (19%) during hy ...[more]
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Project description:ObjectiveIn adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary centre over a thirteen-year period.DesignClinical, biochemical, radiological and histological data were reviewed from all confirmed cases of adult-onset hyperinsulinaemic hypoglycaemia at our centre between 2003 and 2016. In a subset of patients with stage I insulinoma, whole-exome sequencing of tumour DNA was performed.ResultsTwenty-nine patients were identified (27 insulinoma, including 6 subjects with metastatic disease; 1 pro-insulin/GLP-1 co-secreting tumour; 1 activating glucokinase mutation). In all cases, hypoglycaemia (glucose ≤2.2 mmol/L) was achieved within 48 h of a supervised fast. At fast termination, subjects with stage IV insulinoma had significantly higher insulin, C-peptide and pro-insulin compared to those with insulinoma staged I-IIIB. Preoperative localisation of insulinoma was most successfully achieved with EUS. In two patients with inoperable, metastatic insulinoma, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE rapidly restored euglycaemia and lowered fasting insulin. Finally, in a subset of stage I insulinoma, whole-exome sequencing of tumour DNA identified the pathogenic Ying Yang-1 (YY1) somatic mutation (c.C1115G/p.T372R) in one tumour, with all tumours exhibiting a low somatic mutation burden.ConclusionOur study highlights, in particular, the utility of the 48-h fast in the diagnosis of insulinoma, EUS for tumour localisation and the value of PRRT therapy in the treatment of metastatic disease.
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Project description:AimAdverse (poor or excessive) fetal growth "programs" an elevated risk of type 2 diabetes. Fatty acid binding protein 4 (FABP4) has been implicated in regulating insulin sensitivity and lipid metabolism relevant to fetal growth. We sought to determine whether FABP4 is associated with poor or excessive fetal growth and fetal lipids.MethodsIn a nested case-control study in the Shanghai Birth Cohort including 60 trios of small-for-gestational-age (SGA, an indicator of poor fetal growth), large-for-gestational-age (LGA, an indicator of excessive fetal growth) and optimal-for-gestational-age (OGA, control) infants, we measured cord blood concentrations of FABP4 and lipids [high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterols, triglycerides (TG)].ResultsAdjusting for maternal and neonatal characteristics, higher cord blood FABP4 concentrations were associated with a lower odds of SGA [OR = 0.29 (0.11-0.77) per log unit increment in FABP4, P = 0.01], but were not associated with LGA (P = 0.46). Cord blood FABP4 was positively correlated with both LDL (r = 0.29, P = 0.025) and HDL (r = 0.33, P = 0.01) in LGA infants only.ConclusionFABP4 was inversely associated with the risk of SGA. The study is the first to demonstrate LGA-specific positive correlations of cord blood FABP4 with HDL and LDL cholesterols, suggesting a role of FABP4 in fetal lipid metabolism in subjects with excessive fetal growth.
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