Congenital Hyperinsulinism International

Research

With the help of Parent Research Coordinator Sarah Bates, CHI has developed a list of helpful research reference materials.  Sarah has provided commentary on most of the listed articles.  Check back often as we will continue to update this list.


Stanley, CA, De León, DD, (Philadelphia, Pa.) Volume Editors: Monogenic Hyperinsulinemic Hypoglycemia Disorders,Vol 21 in Frontiers in Diabetes. Series Editors: Porta and Matschinsky.Krager, 2012

This book covers a wide range of topics related to congenital hyperinsulinism (HI) including a brief history of the disorder, known genetic mutations, diagnostic technologies, current research, and the details of the biochemical processes that cause the different forms of HI.  The chapters are written by a diverse group of expert scientists and physicians.  The chapters are quite technical.  Another hidden benefit of this text is the bibliography for each chapter which contains a wealth of information for those wishing to learn even more!


Porterfield SP, White BA. (2007) Endocrine physiology. Philadelphia, PA:Mosby

This is one of many books that details how the normal endocrine system works and is therefore an excellent foundation for future study of HI.  Chapter 3 details the functions of the pancreas with a long section on diabetes.  The text is aimed at medical students and does not cover congenital hyperinsulinism.


Stanley CA.  Hyperinsulinism in infants and children. Ped Clin of North Am. 1997; April;44(2):363-374.

This was written many years ago and much more is now  known about the genetics of congenital hyperinsulinism,focal lesion location and removal.  We have included the article because the general overview of hypoglycemia in infants, including basic treatments and prognoses, is excellent.


Mikhailov MV, Campbell JD, et al. 3- D structural and functional characterization of the purified KATP channel complex Kir6.2- SUR1. EMBO J 2005 24: 4166-4175.

This article begins by fully explaining the importance of KATP channels in the functioning of the human body. The focus is on the structural components for the KATP channel complex to help diagram the functions it retains. This article is a good place to start for  those who want more information on KATP channels.


Sharma N, Crane A, et al.  Familial hyperinsulinism and pancreatic beta- cell ATP- sensitive potassium channels.  Kidney Int  2005 57: 803-808.

This paper is very accessible for people who do not have a background in medicine.  It covers current trends in understanding HI, which is called familial hyperinsulinism in the article.


Li C, Allen A, et al. Green tea polyphenols modulate insulin secretion by inhibiting glutamate dehydrogenase.  J Biol Chem 2006 281: 10214-10221.

This article explores the potential of green tea to modulate insulin secretion.

 

GENETIC TYPES OF CHI:

KATP Dysfunction:

Diffuse


Loechner, KJ, et al. Congenital hyperinsulinism and glucose hypersensitivity in homozygous and heterozygous carriers of Kir6.2 (KCNJ11) mutation V290M mutation: K(ATP) channel inactivation mechanism and clinical management. Diabetes, 2011;60(1):209-17

This is a relatively easy-to-follow article on a study of two families that have the Kir6.2 [V290M] mutation. The discussion is paired with clear charts.


Henquin JC, et al. In vitro insulin secretion deviates from model predictions in infants with diazoxide- resistant congenital hyperinsulinism. J Clin Invest 2011;121:3932-3942.

A very readable article on the effects of various agents on glucose secretion. Nicely stated and easy to follow. This article is accompanied by photos, tables, and charts for visual aid in the understanding of FoCHI and DiCHI glucose secretion issues.


Flanagan SE, et al:    Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat 2009 30(2):170-80.

This article on the mutations that cause HI is fairly easy to follow. In addition to HI, it focuses on neonatal diabetes mellitus.


Shimomura K, et al:  Adjacent mutations in the gating loop of Kir6.2 produce neonatal diabetes and hyperinsulinism. EMBO Mol Med 2009 1(3) 166-77.

Each section of this article is clearly explained. Moderate understanding of mutations that affect KATP and ATP sensitivity is helpful but not completely necessary to follow the discussion. There is a very good side box with clear explanations of the discoveries laid out in the course of the paper.


Marthinet E,  et al. Severe congenital hyperinsulinism caused by a mutation in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium channel impairing trafficking and function.  J Clin Endocrinol Metab 2005 90(9) 5401-6.

This article focuses on the combined use of immunohistochemistry, advanced life fluorescence imaging, and electrophysiology to help identify a new homozygous mutation in the Kir6.2 subunit in a patient with severe CHI. The discussion is about how Kir6.2 protein is exported for ER under certain conditions and how this can create a scenario of the severity and early onset of hypoglycemia. This information is helpful in understanding identification processes and observations in CHI patients.


Henwood MJ, Kelly A, et al.  Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate- sensitive potassium channel genes. J Clin Endocrinol Metab 2005 90: 789-794.

This article is also relatively easy for the lay reader to follow.

 

Focal:


Hussain K et al. The diagnosis of ectopic focal hyperinsulinism of infancy with [18F]‑dopa positron emission tomography. J Clin Endocrinol Metab 2006;91:2839-2842.

This is an excellent article covering the genetic basis of focal lesions, focal lesions must be properly identified, and the shortcomings more invasive alternatives to L-DOPA PETscans.


Suchi M, MacMullen CM, Thornton PS, Adzick NS, Ganguly A, Ruchelli ED, Stanley CA: Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism. Mod Pathol. 2006; Jan;19(1): 122-9

This article presents the genetic combinations that give rise to focal lesions and an immunohistochemical analysis of the lesions themselves.


Suchi M,  MacMullen CM, et al.   Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism.  Mod Pathol 2006       19:  122-129.

This article does an excellent job of explaining the difference between focal and diffuse HI in scientific terms.


Giurgea I, Sempoux C, et al.  The Knudson’s two- hit model and timing of somatic mutation may account for the phenotypic diversity of focal congenital hyperinsulinism. J Clin Endocrinol Metab 2006 91: 4118-4123.

This paper will be accessible to most readers. It looks at focal hyperinsulinism patients who have multiple pancreatic lesions.

 

Other:

PET Scans:


Ribeiro MJ, et al: The added value of [18F]fluoro-L-DOPA PET in the diagnosis of hyperinsulinism of infancy: a retrospective study involving 49 children. Eur J Nucl Med Mol Imaging 2007;34:2120-21128.

This article shows that the PETscan correctly identifies diffuse disease and focal lesions. Some of the patients in the study also had pancreatic venous catheterization (PVS) studies done, a highly invasive procedure.  After surgery the pathology reports confirmed the results of the PETscan in 21 of 24 cases with focal lesions.


Hardy OT, et al: Accuracy of [18F]fluoro-L-DOPA positron emission tomography for diagnosing and localizing focal congenital hyperinsulinism. J Clin endocrinol Metab 2007;92:4706-4711.

In this study of 50 patients, the PETscans identified 75% of all focal lesions and did not falsely identify any lesions.


de Lonlay P, et al: Congenital hyperinsulinism: pancreatic [18F] fluoro-L-dihydroxyphenylalanine (DOPA) positron emission tomography and immunohistochemistry study of DOPA decarboxylase and insulin secretion. J Clin Endocrinol Metab 2006;91:933-940

This article explains the basics of the PETscan.  It describes how the scan is believed to work for focal lesion identification and gives the outcome of the ten patients in the study.


Mohnike K, et al: [18F]-DOPA positron tomography for preoperative localization in congenital hyperinsulinism. Horm Res. 2008;70(2):65-72. Epub 2008 June 12. Review.

This is an excellent article that explains the basics of diagnosing HI, how the F‑DOPA PET scan works, and the advantages of PET compared to PVS.


Otonkoski T, et al: Noninvasive diagnosis of focal hyperinsulinism of infancy with [18F]- DOPA positron emission tomography. Diabetes 2006;55;13-18

In this article, 14 patients were evaluated with L-DOPA PETscans preoperatively.  Nine of the patients were found to have diffuse HI and 5 were found to have focal lesions.

 

Outcome Studies (These articles focus on developmental outcomes for patients with HI):


Ludwig A, et al: Glucose metabolism and neurological outcome in congenital hyperinsulinism. Semin Pediatr Surg 2011;20:45-49.


Meissner T, et al: Long- term follow- up of 114 patients with congenital hyperinsulinism. Eur J Endocrinol 2003;149:43-51.


Menni F, et al: Neurologic outcomes of 90 neonates and infants with persistent hyperinsulinemic hypoglycemia. Pediatrics 2001;107:476-479.


Mazor- Aronovitch K, et al: Long- term neurodevelopmental outcome in conservatively treated congenital hyperinsulinism. Eur J Endocrinol 2007;157:491-497.


Steinkrauss L, et al: Effects of hypoglycemia on developmental outcome in children with congenital hyperinsulinism. J Pediatr Nurs 2005;20:109-118.


Ludwig A, Ziegenhorn K, et al.  Glucose metabolism and neurological outcome in congenital hyperinsulinism. Semin Pediatr Surg 2011; 20 :45-49.

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