Gene Study for Infantile Onset Diabetes

Study Genetic Basis of Infantile Onset Diabetes Mellitus Clinical Trial

Official title:

Human Leucocytic Antigen Typing and Mutation of Adenosine Triphosphate Sensitive Potassium Channel Gene in Diabetic Patients Diagnosed Under the Age of One Year.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03169413
• Other study ID #: IDM
• Status: Not yet recruiting
• Phase: N/A
• First received: May 25, 2017
• Last updated: May 28, 2017
• Start date: January 2018
• Est. completion date: August 2020

Study information

• Verified date: May 2017
• Source: Assiut University
• Contact: Prof Hanaa Abdellatif Mohamed, MD
• Phone: 01120096055
• Email: Hae50[@]hotmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both.

According to American Diabetes Association diabetes can be classified into the following general categories: Type one diabetes (due to beta cell destruction, usually leading to absolute insulin deficiency), Type two diabetes (due to a progressive insulin secretory defect on the background of insulin resistance), Gestational diabetes mellitus and specific types of diabetes due to other causes, example monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young, diseases of the exocrine pancreas, and drug induced diabetes.

Description:

Type one diabetes mellitus is one of the most common endocrine and metabolic conditions in childhood, it accounts for 5-10 percent of all diabetes cases.

Three-quarters of all cases of type one diabetes are diagnosed in individuals under eighteen years of age.

Data on incidence of childhood onset type one diabetes mellitus are very limited. Data from large epidemiological studies worldwide indicate that on an annual basis, the overall increase in the incidence of type one diabetes mellitus is around three percent.

The incidence rate increases from birth and peaks between the ages of ten to fourteen years. There is increase in incidence of type one diabetes mellitus throughout the world is especially, marked in young children, Registries in Europe suggest that incidence of type one diabetes mellitus were highest in the youngest age-group less than four years There is a seasonal pattern in the onset of type one diabetes mellitus with increased cases during late autumn, winter, and early spring.

Although most common autoimmune diseases usually affect females, but girls and boys are equally affected with type one diabetes mellitus in young populations.

The underlying pathophysiological mechanism of the disease is cellular-mediated autoimmune destruction of the pancreatic beta cells, the rate of beta cell destruction is quite variable, being rapid in some individuals (mainly infants and children) and slow in others (mainly adult).

The triggers for the autoimmune attack are not fully understood, but it is now widely accepted that both environmental and genetic factors contribute to it.

The genetic basic of the disease can be explained as the disease involves many genes, the risk of a child developing type one diabetes is about five percent if the father has it, about eight percent if a sibling has it, about three percent if the mother has type one diabetes.

If one identical twin is affected there is about a fifty percent chance the other will also be affected.

Some studies of heritability has estimated it at eighty to eighty sex percent. Depending on locus or combination of loci, they can be dominant, recessive, or somewhere in between. The strongest gene is located in the major histocompatability class two region on chromosome sex, at staining region 6p21. It has been reported that only ten percent of those who are genetically predisposed to type one diabetes mellitus actually develop the disease; however, that percentage appears to be changing and environmental factors may play an increasingly important role in determining risk.

Finally, migration studies show an increased type one diabetes mellitus incidence in population groups who move from an area of low incidence to one of high incidence.

The Possible maternal risk factors for type one diabetes mellitus include maternal age older than twenty five years, cesarean section, high level of education, infants of mothers with body mass index of thirty or higher. or higher, infants of white mothers, and maternal diabetes.

Some studies have reported associations between birth weight and risk of type one diabetes mellitus, being born large for gestational age, and rapid postnatal growth associated with an increased risk for type one diabetes.

Other risk factors include: lack of breast feeding, early introduction of cow milk, and early introduction of gluten containing food before age of four month or late introduction after the age of seven months, lack of vitamin D supplementation during first year of life consumption of sugary foods, exposure to certain viruses as cytomegalovirus, measles, or mumps, childhood vaccination, and maternal-childhood blood group incompatibility.

Neonatal diabetes is a rare cause of hyperglycemia, with an estimated incidence of 1 in 500,000 births.

Two main subgroups are recognized in about equal proportions: permanent neonatal diabetes and transient neonatal diabetes.The latter remits in infancy or early childhood but may recur later in life.

Patients with permanent neonatal diabetes typically have reduced birth weight, a reflection of reduced insulin production in utero, and whilst most are diagnosed with diabetes before sex months a few rare cases have been reported with diabetes diagnosed between sex and twelve months of life. In contrast to Type one diabetes permanent diabetes mellitus is not associated with high risk human leucocytic antigen haplotypes or the presence of pancreatic autoantibodies, and is most commonly due to activating mutations in either of the genes encoding the two subunits of the adenosine triphosphate sensitive potassium channel (potassium channel, inwardly rectifying subfamily J member 11) these mutations also occur in transient neonatal diabetes. In most of these patients, switching from insulin to oral sulfonylurea therapy leads to improved metabolic control.

The diabetes presenting within the first sex months of life is unlikely to represent type one diabetes and usually due to gene mutation, so molecular genetic analysis of this group of patients should be done. Additionally, individuals with a diagnosis of diabetes after sex months-of-age should also receive genetic analysis if their diabetes presentation is atypical for type one diabetes, has features consistent with a known monogenic cause, or if there are additional affected family members with a history of neonatal diabetes.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: August 2020
• Est. primary completion date: January 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year to 3 Years

Eligibility

Inclusion Criteria:

• Diabetic patients with disease onset under the age of one year according to American Diabetes Association criteria 2016 which include:

• Fasting plasma glucose level at or above 7 millimol/Litre.

• Plasma glucose at or above 11.1 millimol/Litre two hours after a 1.75 gram/kilogram oral glucose load as in a glucose tolerance test.

• Symptoms of hyperglycemia and random plasma glucose at or above 11.1 millimol/Litre.

• Glycated hemoglobin at or above 48 millimol/mol.

Exclusion Criteria:

-Diabetic children with the disease onset above the age of one year.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Study Genetic Basis of Infantile Onset Diabetes Mellitus

Intervention

Genetic:
• Human Leucocytic antigen typing and mutation of adenosine triphosphate sensitive K channel gene in diabetic patients diagnosed under the age of one year.
Gene study

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (11)

Aguilar-Bryan L, Bryan J. Neonatal diabetes mellitus. Endocr Rev. 2008 May;29(3):265-91. doi: 10.1210/er.2007-0029. Epub 2008 Apr 24. Review. — View Citation

Babenko AP, Polak M, Cavé H, Busiah K, Czernichow P, Scharfmann R, Bryan J, Aguilar-Bryan L, Vaxillaire M, Froguel P. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N Engl J Med. 2006 Aug 3;355(5):456-66. — View Citation

Bluestone JA, Herold K, Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature. 2010 Apr 29;464(7293):1293-300. Review. — View Citation

D'Angeli MA, Merzon E, Valbuena LF, Tirschwell D, Paris CA, Mueller BA. Environmental factors associated with childhood-onset type 1 diabetes mellitus: an exploration of the hygiene and overload hypotheses. Arch Pediatr Adolesc Med. 2010 Aug;164(8):732-8. doi: 10.1001/archpediatrics.2010.115. — View Citation

Knip M, Simell O. Environmental triggers of type 1 diabetes. Cold Spring Harb Perspect Med. 2012 Jul;2(7):a007690. doi: 10.1101/cshperspect.a007690. Review. — View Citation

Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK. Environmental triggers and determinants of type 1 diabetes. Diabetes. 2005 Dec;54 Suppl 2:S125-36. Review. — View Citation

Noble JA, Valdes AM. Genetics of the HLA region in the prediction of type 1 diabetes. Curr Diab Rep. 2011 Dec;11(6):533-42. doi: 10.1007/s11892-011-0223-x. Review. — View Citation

Pociot F, Lernmark Å. Genetic risk factors for type 1 diabetes. Lancet. 2016 Jun 4;387(10035):2331-9. doi: 10.1016/S0140-6736(16)30582-7. Review. — View Citation

Rewers M, Ludvigsson J. Environmental risk factors for type 1 diabetes. Lancet. 2016 Jun 4;387(10035):2340-8. doi: 10.1016/S0140-6736(16)30507-4. Review. — View Citation

Rubio-Cabezas O, Ellard S. Diabetes mellitus in neonates and infants: genetic heterogeneity, clinical approach to diagnosis, and therapeutic options. Horm Res Paediatr. 2013;80(3):137-46. doi: 10.1159/000354219. Epub 2013 Sep 18. Review. — View Citation

Soltesz G, Patterson CC, Dahlquist G; EURODIAB Study Group.. Worldwide childhood type 1 diabetes incidence--what can we learn from epidemiology? Pediatr Diabetes. 2007 Oct;8 Suppl 6:6-14. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Human Leucocytic antigen typing and mutation of adenosine triphosphate sensitive potassium channel gene in diabetic patients diagnosed under the age of one year.	Polymerase chain reaction / Deoxyribonucleic acid sequencing	At time of diagnosis with diabetes under the age of one year
Secondary	Rate of diabetes mellitus in patients under age of one year attending pediatric endocrinology unit in Pediatric assiut University Hospital	Total coverage of all diabetic cases diagnosed under the age of one year	Within two years
Secondary	dentification of possible demographic and environmental risk factors associated with increased risk of diabetes in diabetic patient under the age of one year.	Identification of prenatal, perinatal, natal history,nutritional history, vaccination history and hygiene measures	Within two years