Diabetes mellitus in children

BASIM AL-ZOUBI

BA

SIM

A-Z

OU

BI

Types of DM in Children

Type 1 DMType 2 DMMODY TypeNeonatal DM

BA

SIM

A-Z

OU

BI

TYPE 1 DM

BA

SIM

A-Z

OU

BI

Maturity-onset diabetes in youth (MODY) autosomal dominant noninsulin-dependent diabetes onset in the second or third decade of life

Neonatal DMDue to mutations in the genes encoding potassium channel of the beta-cell (KCNJ11, encoding the Kir6.2 subunit, and ABCC8, encoding the SUR1 subunit) or a mutation in the insulin gene. In ABCC8 mutation treatment is possible with oral hypoglycemic agents that stimulate endogenous insulin secretion through binding to the sulfonylurea receptor (SUR1).

BA

SIM

A-Z

OU

BI

Epidemiology

The prevalence of diabetes among school-aged children is about 2/1,000 in USA and UK.

The incidence is variable according to the different countries and it varies from 0.6/100,000 in China to42.9/100,000 in Finland.

There are small peaks in incidence at 4 to 6 years of age and a larger peak at 10 to 14 years of age.

BA

SIM

A-Z

OU

BI

Pathogenesis

Type 1 diabetes is caused by T cell–mediated autoimmune destruction of the beta cells of the pancreas believed to be triggered by an environmental factor in a genetically susceptible individual and lead to absolute insulin deficiency.

The largest genetic component of the risk of diabetes is the major histocompatibility complex on chromosome 6, including the DR3-DQ2 and DR4- DQ8 alleles that increase risk and the DR2-DQ6 allele, which is protective.

BA

SIM

A-Z

OU

BI

Inheritance of HLA-DR3 or -DR4 antigens increase the risk for the development of T1DM by 2- to 3-folds

When both DR3 and DR4 are inherited, the relative risk for the development of diabetes is increased by 7- to 10-fold.

BA

SIM

A-Z

OU

BI

However, only 10% to 20% of individuals who have type 1 diabetes have a similar family history.

BA

SIM

A-Z

OU

BI

Risk of developing type 1 diabetes for individuals who have an affected relative

For siblingsOverall 6%HLA identical 15%HLA nonidentical 1%OffspringFrom father 6%From mother 2%Both parents 30%

BA

SIM

A-Z

OU

BI

T1DM may be associated with other autoimmune diseases such as thyroiditis, celiac disease, multiple sclerosis, and Addison disease.

BA

SIM

A-Z

OU

BI

DM1 ANTIBODIES

• The islet cell antibodies (ICA)• Insulin autoantibodies (IAA)• Glutamic Acid Decarboxylase antibodies (GAD/GAD

65)• Transmembrane Tyrosine Phosphatase IA-2 or

ICA512

BA

SIM

A-Z

OU

BI

In the nonobese child, testing for autoimmunity to β cells is not necessary.

BA

SIM

A-Z

OU

BI

Environmental risk Factors

viral infectionsAlthough the etiologic role of viral infections in human T1DM is controversial, coxsackie, cytomegalovirus, rubella, and mumps can infect human β cells.

Seasons New cases are seen more commonly in Autumn and winter.

Vit. DIt has been found that Diabetes risk may be increased by low vitmain D level in young infants.

BA

SIM

A-Z

OU

BI

Cow's milk Breastfeeding seems to provide protection against the riskof developing type 1 diabetes.The reaction of an infant's immature immune system to a protein found in cow's milk infant formula called beta-lactoglobulin may explain the suspected link between early consumption of cow's milk and an increased risk of developing type 1 diabetes later.

Chemical toxinsIngestion of the rodenticide vacor is associated with thedevelopment of type 1 diabetes.

Stress

BA

SIM

A-Z

OU

BI

Diagnosis

symptoms of diabetes arepolydipsia,polyuria, polyphagia, and weight loss. Bedwetting diabetic ketoacidosis (DKA) presention with nausea, vomiting, abdominal pain, dehydration, lethargy and coma .

BA

SIM

A-Z

OU

BI

Diagnostic criteria for DMFasting plasma glucose at or above 126 mg/dL (7.0 mmol/L). Random plasma glucose at or more than 200 mg/dl associated with DM symptoms. 2-hour post challenge plasma glucose value at or above 200 mg/dL (11.1 mmol/L) on an oral glucose tolerance test.

One third of new diabetes cases in children 10 to 19 years of age were due to type 2 diabetes.

BA

SIM

A-Z

OU

BI

MANAEGEMENT OF TYPE 1 DM

BA

SIM

A-Z

OU

BI

BA

SIM

A-Z

OU

BI

NUTRITIONNo special nutrition.No particular food shouldbe considered forbidden.

It is recommended that approximately 30-35% of dietary energy intake should be derived from fat (mainly mono- and polyunsaturated fats), 15% from protein and 50-55% from carbohydrate.

Approximately 70% of the carbohydrate content should be derived from complex carbohydrates such as starch.

BA

SIM

A-Z

OU

BI

The total daily caloric intake 20% at breakfast, 20% at lunch, and 30% at dinner, 10% for each of the midmorning, midafternoon, and evening snacks

Intake of sucrose and highly refined sugars should be limited.Alternative sweeteners:Use of a variety of sweeteners can be used.

Carbohydrate Counting:Each carbohydrate exchange unit is 15 g.

BA

SIM

A-Z

OU

BI

Meals and snacks should be taken at about the same time of the day every day.

meal times and contents correlates with daily activities, e.g. taking physical exercise or sitting at a desk?

Extra insulin when necessary, e.g. at parties, or when eating lots of sweet things.

fresh fruit as a snack better than drinking fruit juice.

A high fibre content in TH food.

BA

SIM

A-Z

OU

BI

BA

SIM

A-Z

OU

BI

Glucose Monitoring

Continuous Glucose Monitoring System (CGMS)

The interstitial glucose levels lag 13 min behind the blood glucose values at any given level.

The CGMS values tend to have a high correlation coefficient for blood glucose values ranging between 40 and 400 mg/dL.

BA

SIM

A-Z

OU

BI

Elevated fasting blood sugar at the morning may be due:Dawn Phenomenon : Which due overnight growth hormone secretion and increased insulin clearance.Somogyi Phenomenon: Which is due to rebound from late night or early morning hypoglycemia, thought to be due to an exaggerated counter-regulatory response.

BA

SIM

A-Z

OU

BI

HbA1C

Glucose is bound to haemoglobin in the red blood cells.

The level of HbA1c depends on the blood glucose levels during the life span of the red blood cells.

A red blood cell lives for about 120 days. HbA1c reflects the average blood glucose during

the previous 2-3 months.

BA

SIM

A-Z

OU

BI

Transplantation

Transplantation of segment of the pancreas is done usually in those patients who need kidney transplantation at the same time in which the immunosuppressive regimen is indicated for the renal transplantation.

Transplantation of isolated islet cells have been tried but only half of the cases remained insulin free for 2 years.

Stem cell transplantation

BA

SIM

A-Z

OU

BI

Complications

Acute Comlications

DKAHypoglycemia

BA

SIM

A-Z

OU

BI

DKA

DKA is the most common cause of death in children who have type 1 diabetes and isassociated with a significant risk of morbidity.

BA

SIM

A-Z

OU

BI

Clinical manifestations of diabetic ketoacidosis

• Dehydration• Rapid, deep (Kussmaul respiration)• Nausea, vomiting, and abdominal pain • Progressive loss of consciousness• Fever only when infection is present

BA

SIM

A-Z

OU

BI

Definition of DKA

¤ Hyperglycemia (blood glucose > 11 mmol/L ≈ 200 mg/dL])¤ Venous pH < 7.3 or bicarbonate < 15 mmol/L¤ Ketonemia and ketonuria

BA

SIM

A-Z

OU

BI

Supportive measures

¤ Secure the airway¤ Insert peripheral intravenous catheter¤ A cardiac monitor should be used to assess T waves for evidence of hyper- or hypokalemia¤ Give oxygen to patients with severe circulatory impairment or shock.

BA

SIM

A-Z

OU

BI

Monitoring¤ Hourly:vital signs, neurological evaluation, fluid input and output.¤ Capillary blood glucose should be measured hourly ¤ Laboratory tests: Na, K, glucose, blood urea nitrogen and blood gases every 2 then 4 hours.

BA

SIM

A-Z

OU

BI

Goals of therapy

¤ Correct dehydration¤ Correct acidosis and reverse ketosis¤ Restore blood glucose to near normal¤ Avoid complications of therapy¤ Identify and treat any precipitating event

BA

SIM

A-Z

OU

BI

Fluids and salt.In moderate DKA use 5-7% and in sever DKA use 7-10% dehydration.

¤ If needed to restore peripheral circulation, give 0.9% saline 10–20 mL/kg over 1–2 h, and repeat it, if necessary ( not more than 30 ml/kg).¤ Add calculated maintenance (for 24-48 hrs) and estimated deficit, subtract the amount already given as resuscitation fluid, and give the total volume over the next 24 - 48 hours. i.e. ¤ Subsequent fluid management should be with a solution with a tonicity equal to or greater than 0.45% saline

•.

BA

SIM

A-Z

OU

BI

Insulin therapy Begin with 0.1 U/kg/h. insulin infusion. .The dose of insulin should usually remain at 0.1 unit/kg/h at least until resolution of DKA (pH > 7.30, bicarbonate > 15 mmol/L and/or closure of the anion gap).To prevent a rapid decrease in plasma glucose concentration and hypoglycemia, 5% glucose should be added to the 0.45% saline (5% glucose in 0.45% saline ) when the plasma glucose falls to approximately 14–17 mmol/L (250–300 mg/dL.

BA

SIM

A-Z

OU

BI

Potassium replacement

Start replacing potassium after initial volume expansion (1-2 hours) and concurrent with starting insulin therapy.

BA

SIM

A-Z

OU

BI

AcidosisAlkali therapy may be given only to patients with severe acidemia (arterial pH, 6.9), and patients with life-threatening hyperkalemia.¤ Bicarbonate then may be given cautiously at a dose of 1–2 mmol/kg over 60 min.

BA

SIM

A-Z

OU

BI

Introduction of oral fluids and transition to SC insulin injections

Oral fluid should be given only when there is substantial clinical improvement.

BA

SIM

A-Z

OU

BI

Treatment of cerebral edema¤ Give mannitol¤ Reduce the rate of fluid administration by one-third.¤ Hypertonic saline (3%), 5–10 mL/kg over 30 min, may be an alternative to mannitol, especially if there is no initial response to mannitol.¤ Elevate the head of the bed.

BA

SIM

A-Z

OU

BI

LONG-TERM COMPLICATIONS: RELATION TO GLYCEMIC CONTROL. 1-microvascular complications, specifically, retinopathy and nephropathy; 2- macrovascular complications, particularly accelerated coronary artery disease, cerebrovascular disease, and peripheral vascular disease; and 3- neuropathies, both peripheral and autonomic, affecting a variety of organs and systems . In addition, cataract may occur more frequently.

BA

SIM

A-Z

OU

BI

Hypoglycemia

Hypoglycemia, a blood glucose concentration less than 60 mg/dL (3.3 mmol/L.

Symptoms of hypoglycemia includesweating, hunger, and palpitations, headache, dizziness, diplopia, and confusion. coma and seizures.

Mild-to-moderate hypoglycemia is treated by ingesting 10 to 15 g of glucose Sever cases may need Glucagone injection or Dextrose 10% iv bolus.

BA

SIM

A-Z

OU

BI

Insulin Therapy

The initial total amount of insulin varies from 0.5 to 2 U/kg per day.

BA

SIM

A-Z

OU

BI

N Engl J Med 2005;352:174-83.

Glulisine

BA

SIM

A-Z

OU

BI

*Clin Pharmacokinet 2008; 47 (9): 595-610*Drugs 2008

BA

SIM

A-Z

OU

BI

Pediatric Diabetes 2007: 8 (Suppl. 6): 49–56

BA

SIM

A-Z

OU

BI

BA

SIM

A-Z

OU

BI

Basal InsulinThe new basal insulin analogues are Glargine approved April 20, 2000Detemir. Approved in 2005

They show a more predictable insulin effect withless day-to-day variation compared with NPHinsulin.

Glargine is not approved in children younger than 6 while Detemir is approved in children over 2 years.

*Pediatr Diabetes 2005: 6: 150–154.

BA

SIM

A-Z

OU

BI

The effect of glargine lasts for 20 to 24 h while that for detemir is between 6 and 23 h according to the dose given.* B

ASIM

A-Z

OU

BI

Idealized insulin curves for prandial insulin with a rapid-acting analogue (insulin aspart, insulin lispro, or insulin glulisine) with basal insulin given as insulin glargine or insulin detemir

Chapter 20. The Management of Type 1 Diabetes Irl B. Hirsch, M.D., and Jay S. Skyler, M.D. Updated: August 27, 2006

BA

SIM

A-Z

OU

BI

BA

SIM

A-Z

OU

BI

BA

SIM

A-Z

OU

BI

HONEYMOONWithin 1 month of diagnosis, most pediatric patientswho have type 1 diabetes enter a remission or “honeymoon”phase, although this may not occur in very youngchildren. Patients require little exogenous insulin duringthis phase, often less than 1/3 U/kg per day, but theyshould not be weaned off insulin injections.

BA

SIM

A-Z

OU

BI

BA

SIM

A-Z

OU

BI

BA

SIM

A-Z

OU

BI

BA

SIM

A-Z

OU

BI

THANK YOU

BA

SIM

A-Z

OU

BI