By: Dr. Doaa Khater Yassin, MM and M.D Paed Sr. specialist of Pediatrics SQUH
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1 By: Dr. Doaa Khater Yassin, MM and M.D Paed Sr. specialist of Pediatrics SQUH
2 Born SGA with birth weight of 2.4 kg, had IUGR Hospitalized at the age of 2 month with severe dehydration Diagnosed as DKA ph 7.05, BE -23, - blood glucose 27 mmol/l, glucosuria and ketonuria Started on insulin drip infusion and IV fluid as per DKA protocol
3 C-peptide&insulin Ab (ICA/IA) Lipid level&lft HbA1C Low Negative Normal High US. pancreas was normal
4 After few days started feeding on breast milk with added formula every 3 hours At that time insulin changed to basal bolus SC insulin synchronized with feeds The blood sugar was tested prior to each feed In the following months He had hypoglycemic episodes. So, tapering of insulin gradually.. Finally insulin stopped after 6 months (age of 8 month)
5 What happened... Is it diabetes -Presentation with DKA -Labs; high BS, Low insulin and C peptide & high HbA1c -Response to insulin therapy 6
6 Which type of diabetes Type 1 DM -No markers of autoimmunity -Measurable C-peptide -Cured 7
7 Which type of diabetes Type 1 DM Type 2 DM -No obesity, or F.H -No insulin resistance -Normal lipids 8
8 Which type of diabetes Type 1 DM Type 2 DM Something else Neonatal DM 9
9 Neonatal diabetes mellitus (NDM) Classically defined as diabetes mellitus occurring in the first 6 weeks of life up to 6 months Incidence: 1 in 100, ,000 live births They present with weight loss, volume depletion, hyperglycemia, and glucosuria with or without ketonuria and ketoacidosis. Etiology: Single gene disorders (rather than classical autoimmune type 1 diabetes) so expected to have a higher incidence in regions with high rates of consanguinity
10 Transient Permanent According to the resolution or persistence beyond the first year of life
11 Transient neonatal diabetes mellitus (TNDM)
12 TNDM TNDM contributes 50 % of cases of neonatal DM Diabetes starts in the first few weeks of life requiring insulin but goes into remission in few months Possible relapse to a permanent diabetes with stress such as puberty or pregnancy or as adults (60%)
13 Etiology of TNDM : ZAC =(Zinc finger protein associated with Apoptosis and cell Cycle arrest) A zinc finger protein on ch 6 which induces apoptosis Overexpression of ZAC gene Will inhibit -cell proliferation & insulin secretion ND
14 Etiology of TNDM : Chromosome 6 anomalies: a disease linked to imprinting inherited 2 identical copies of chr 6 from father with no contribution from mother Unbalanced duplication of paternal chromosome 6q24
15 Permanent neonatal diabetes mellitus (PNDM)
16 PNDM Does not go into remission Mechanism: Insulin secretory failure in the late fetal or early postnatal period
17 Normal Insulin secretion Glucose Glucokinase Metabolism +++ ATP K ATP Channel close x K + K ATP Channel Insulin Insulin secretion by exocytosis
18 PNDM Activation mutation of K ATP Channel gene K ATP Channel open Glucose Metabolism +++ ATP K x x Insulin x
19 Same potassium channels play a role in CNS Activation mutation of K ATP Channel gene Diabetes + neurological disease Developmental delay Epilepsy Neonatal DM
20 Other causes of permanent neonatal DM Insulin (INS) gene mutation Homozygous glucokinase gene mutation
21 Inctivation mutation of glucokinase gene Glucose Glucokinase x Metabolism +++ ATP K ATP Channel open K x x Insulin x PNDM
22
23 Sulphonylureas Close K ATP channels by an ATP-independent mechanism shift from SC insulin to oral sulphonylurea
24 Other causes of permanent neonatal DM Pancreatic hypoplasia Wolcott-Rallison syndrome Neonatal diabetes Epiphyseal dysplasia Mental retardation Hepatomegaly Renal failure and early death
25 How To Treat
26 Treatment Options Insulin therapy should be started in both In TNDM insulin is required until remission to prevent dehydration and allow normal growth In PNDM insulin is required for life Patients with mutations in K ATP channels may be shifted from insulin to sulphonylureas
27 Home message: An Infant diagnosed with diabetes under 6 months of age is likely to have NEONATAL DIABETES Unlike other forms of DM, Genetic Mutation should be identified in Neonatal form As 50% of cases can be treated with oral sulfonylurea
28
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