WHO CLASSIFICATION 2000
- Is based on etiology not on type of treatment or age of the patient.
- Type 1 Diabetes (idiopathic or autoimmune b-cell destruction)
- Type 2 Diabetes (defects in insulin secretion or action)
- Other specific types
Both type 1 & type 2 can be further subdivided into:
* Not insulin requiring
* Insulin requiring for control
* Insulin requiring for survival
- Gestational diabetes is a separate entity
- Impaired Glucose Tolerance (IGT) indicates blood glucose levels between normal & diabetic cut off points during glucose tolerance test.

Is the Presentation the Same as in Adults?
- Does not appear to be preceded by long asymptomatic period.
- Do not find undiagnosed cases on screening.

Is the Pathophysiology the Same as in Adults?
- Associated with significant b-cell failure as well as insulin resistance.
- Occurs at the time of intense insulin resistance due to puberty.

Factors involved in development of insulin resistance
- Obesity is significantly associated with insulin resistance.
- Increased body fat mass, especially abdominal obesity, is linked with:
(Low physical activity Genetic factors Dietary factors)

Measuring insulin resistance
- The clamp technique, considered the ‘gold standard’, measures insulin resistance under hyperinsulinaemic conditions.
- HOMA estimates insulin resistance in the fasted state from a single sample and correlates well with other insulin resistance tests

b-cell dysfunction
(Insulin resistance + b-cell dysfunction = Type 2 diabetes)
- Genetic and environmental pathophysiology
- One of the two core defects in type 2 diabetes
- Impaired ability of b-cells to compensate for insulin resistance
- Reduced ability of b-cells to secrete insulin

Treating the underlying causes of type 2 diabetes "insulin resistance"
How can insulin resistance be managed? Improve insulin resistance through:
- Diet
- Exercise
- Pharmacological intervention with agents that target insulin resistance

Treating the underlying causes of type 2 diabetes "b-cell function"
DIAGNOSIS
- In symptomatic children a random plasma glucose >11 mmol (200 mg) is diagnostic.
- A modified OGTT (fasting & 2h) may be needed in asymptomatic children with hyperglycemia if the cause is not obvious.
- Remember: acute infections in young non-diabetic children can cause hyperglycemia without ketoacidosis.

COMPLICATIONS OF DIABETES
- Acute (DKA, Hypoglycemia)
- Late-onset (Retinopathy, Neuropathy, Nephropathy, Ischemic heart disease & stroke)

Type 1 versus type 2 Diabetes in youth?
T1DM
Weight: 20% may be overweight / obese
Course: Rapid from DPT-1 can be indolent
DKA: 35%-40%
Relative with DM: 5% with T1DM, Up to 30% may have with T2DM
FH of T2 2-3Xs in person with T1
Comorbid: Thyroid, adrenal, vitiligo, celiac
C-peptide: C-peptide can be preserved at DX
Antibody: 85%

T2DM
Weight: Virtually all BMI > 85%Th percentile
Course: Indolent, Virtually none found on screening
DKA: Ketonuria (33%), Mild DKA (5%-25%)
Relative with DM: 74%-100% - 1st –2nd degree with T2DM
Comorbid: Increase in polycystic ovary syndrome Acanthosis nigricans
C-peptide: Normal or increased
Antibody: 15% (reported as high as 30%)

Treatment Type I Diabetes Elements
- Education
- Insulin therapy
- Diet and meal planning

- Monitoring
* HbA1c every 2-months
* Home regular BG monitoring
* Home urine ketones tests when indicated

Insulin Regimens
- Twice daily: NPH alone or NPH+SI.
- Thrice daily: SI before each meal and NPH only before dinner.
- Intensive: 4 times/day SI before meals + NPH or Glargine at bed time.
- Continuous: s/c infusion using pumps loaded with SI.

Options in Insulin Therapy for Type 1 Diabetes
- Current (Multiple injections, Insulin pump (CSII))
- Future (Implant, Transplant)

Insulin Management
- Fixed dose regimens:
(Requires scheduled meals and snacks and is not flexible enough for most young children)
-Basal: bolus regimens:
* MDI useful only if child is willing to take frequent injections.
* Insulin pumps, child must be willing to wear the pump.

The Basal/Bolus Insulin Concept
- Basal insulin
* Suppresses glucose production between meals and overnight
* 40% to 50% of daily needs
- Bolus insulin (mealtime)
* Limits hyperglycemia after meals
* Immediate rise and sharp peak at 1 hour
* 10% to 20% of total daily insulin requirement at each meal

Starting MDI
-Starting insulin dose is based on weight (0.2 x wt in lb or 0.45 x wt in kg).
- Bolus dose (aspart/lispro); 20% of starting dose at each meal.
- Basal dose (glargine/NPH); 40% of starting dose at bedtime.

Basal Bolus Advantages
- Much more flexibility
- Can alter doses according to size of meal
- Less need to have between meal snacks
- If child unwell & not eating can omit doses of fast insulin

Basal Bolus Disadvantages
- 4 injections a day
- Need injection at school
- Easier to manipulate insulin
- Need to have clear understanding of diabetes
Advantages of CSII
- More flexible lifestyle & eating pattern.
- Delivers insulin in more physiological way.
- Can improve diabetes control.
- Lessens the risk of hypoglycaemia.
- Multiple injections a day replaced by insertion of cannula every 2 to 4 days.
- Positive effects on quality of life.

Syrian Experience for Treatment of Diabetes with Insulin pumps
2004-2006
Study Design
1- Patient number; 43 patients participated in this study aged 4 – 70 yrs, (23 males and 20 females)
2- Study Duration; 3 yrs (from January 2004 to December 2006)
3- Pumps used; Medtronic insulin pumps using both basal and bolus infusions
4- Insulin used; Regular insulin, and insulin analogues.

Study Results
- The rate of HbA1c decrease;
- Most patients had HbA1c of 10 -12% before starting the treatment, with HbA1c of 7.5 – 7% after few months of treatment.
- The hypoglycemia rate was significantly improved after pump treatment.
- Improvement of children height after pump TX; Children height, Wt, and height curves were measured and assessed with the change in their standard deviation (SD)
- Improvement in Psychosocial condition.
- Improvement in school performance.

Glucose Monitors
- Minimally invasive continuous glucose monitors
- Implanted glucose sensors
- Implanted insulin pumps
- “Closed-loop” systems

Design elements for “artificial” b-cell
- Insulin pump to accurately and precisely deliver variable amounts of insulin.
- Continuous glucose sensor to accurately determine ambient glucose levels.
- Effective algorithms to vary insulin delivery rates based on real-time glucose sensor outputs.

Future Promisis
- The cure for IDDM is successful islet cell transplantation, which will be available in the near futur.
- Primary prevention by a vaccine or drug will be offered to at risk subjects identified by genetic studies.
- Gene modulation therapy for susceptible subjects is a promising preventive measure.
Pancreas & Islet Cell Transplantation
- Pancreas transplants are usually given to diabetics with end stage renal disease.
- Islet cell transplants, the ultimate treatment of type 1 diabetes is under trial in many centers in the US & Europe with encouraging results but graft rejection & recurrence of autoimmunity are serious limitations.

Immune Modulation
- Immunosuppressive therapy for
* Newly diagnosed
* Prolonged the honey moon
For high risk children
- Immune modulating drugs
* Nicotinamide
* Mycophenolate

Gene Therapy
- Blocks the immunologic attack against islet-cells by DNA-plasmids encoding self antigen.
- Gene encodes cytokine inhibitors.
- Modifying gene expressed islet-cell antigens like GAD.

Prediction of Diabetes
- Sensitive & specific immunologic markers
* GAD Antibodies
* GLIMA antibodies
* IA-2 antibodies
- Sensitive genetic markers
* HLA haplotypes
* DQ molecular markers

Prevention of Diabetes
- Primary prevention
* Identification of diabetes gene
* Tampering with the immune system
* Elimination of environmental factor
- Secondary prevention
* Immunosuppressive therapy
- Tertiary prevention
* Tight metabolic control & good monitoring

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