1. Diabetes Mellitus in Children
Dr Nadeem Zubairi

2. D.M.
Diabetes mellitus is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced.
This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).

3. Before Insulin
JL on 12/15/22 and 2 mos later
Before insulin was discovered in 1921, everyone with type 1 diabetes died within weeks to years of its onset
© 2004, John Walsh, P.A., C.D.E.

4. 1923
Banting and Best Awarded
Nobel Prize for Discovery
And Use of Insulin in the
Treatment of IDDM

5. OLD CLASSIFICATION (1985) Type 1, Insulin-dependent (IDDM)
Type 2, Non Insulin-dependent (NIDDM)
obese
non-obese
MODY
IGT
Gestational Diabetes

6. © 2004, John Walsh, P.A., C.D.E.

7. WHO CLASSIFICATION 2000
Is based on etiology not on type of treatment or age of the patient.
Type 1 Diabetes
( autoimmune b-cell destruction)
Type 2 Diabetes
(defects in insulin secretion or action)
Other specific types

8. Types of Diabetes in Children
Type 1 diabetes mellitus accounts for >90% of cases.
Type 2 diabetes is increasingly recognized in children with presentation like in adults.
Permanent neonatal diabetes
Transient neonatal diabetes
Secondary diabetes e.g. in cystic fibrosis or Cushing syndrome.

9. EPIDEMIOLOGY Type 1 DM Most common metabolic disease in childhood
Annual incidence 15 new cases per 100,000 in children < 18 yrs
Frequency increases with increasing age.
1: 1400 at age 5 yrs
1: 400 at age 16 yrs
Males and females equally affected
No correlation with socioeconomic status

10. Etiology
Type 1 DM usually results from both an inherited risk and external triggers,
Infection,
diet .
Type 1 diabetes is an autoimmune disorder in which the body attacks its pancreatic beta cells.

11. Genetic issues
Clear evidence suggests a genetic component in type 1 diabetes mellitus.
Monozygotic twins have a 60% lifetime concordance for developing type 1 diabetes mellitus, although only 30% do so within 10 years after the first twin is diagnosed. In contrast, dizygotic twins have only an 8% risk of concordance, which is similar to the risk among other siblings.
The frequency of diabetes developing in children with a diabetic mother is 2-3% and 5-6% if the father has type 1 diabetes mellitus. The risk to children rises to almost 30% if both parents are diabetic.

12. Type I – IDDM Two shared HLA haplotypes (DR3 + DR4) 12-20% risk
One shared HLA haplotype
(DR3 or DR4)
5-7% risk
No shared HLA haplotypes
1-2% risk
HLA DQ(beta) Asp57
virtual protection
HLA DQ(beta) non-Asp57
100 X increased risk

13. Environmental factors
Viral infections (most important) probably by initiating or modifying an autoimmune process.( Mumps, coxsackie virus, CMV, congenital rubella)
Dietary factors are also relevant
Breastfed infants have a lower risk for Type 1 DM. Some cow's milk proteins (e.g., bovine serum albumin) have antigenic similarities to an islet cell antigen.

14. Diagnosis
Symptoms of diabetes + casual plasma glucose concentration ≽ 11.1 mmol/L (≽200mg/dl).¹
Casual is defined as at any time of the day without regard to time since the last meal. Or
Fasting plasma glucose ≽ 7.0 mmol/L (≽126mg/dl).²
Fasting is defined as no caloric intake for at least 8h.
2h post load glucose ≽ 11.mmol/L (≽200mg/dl) during
an OGTT.

15. Progression to Type 1 DM Autoimmune markers (ICA, IAA, GAD
Autoimmune destruction
Honeymoon
100% Islet loss
“Diabetes threshold”

16. Honeymoon Period
In patients with new onset of DM1 who do not have DKA, the beta cell mass has not been completely destroyed.
The remaining functional beta cells seem to recover with insulin treatment, and they are again able to produce insulin.
When this occurs, insulin requirements decrease, and there is a period of stable blood glucose control, often with nearly normal glucose concentrations.
This phase of the disease, known as the honeymoon period, usually starts in the first weeks of therapy and usually continues for a few months at most, but can last 2 years

17. CLINICAL PRESENTATIONS
Classical symptom triad:
polyuria, polydipsia and weight loss
DKA
Accidental diagnosis

18. COMPLICATIONS OF DIABETES
Acute:
DKA
Hypoglycemia
Late-onset:
Retinopathy
Neuropathy
Nephropathy
Ischemic heart disease & stroke
Others:
Arthropathy & limited joint mobility
Muco-cutaneous lesions
Impotence
Associated autoimmune diseases

19. DCCT And Other Studies
Research studies between 1970 and 2000 showed that complications could be prevented by lowering high glucose levels
Studies
DCCT
EDIC 1996
UKPDS
Kumamoto
Results
Better health
Fewer complications
Improved sense of well-being
More flexible lifestyle
Although research in the 1960’s through 1980’s strongly suggested that it was high glucose levels that were causing eye, kidney, nerve, and cardiovascular problems in diabetes, it was not until these large scale studies were done that a causal connection was confirmed.
© 2004, John Walsh, P.A., C.D.E.

20. TREATMENT ELEMENTS Education Insulin therapy Diet and meal planning
Exercise
Monitoring
HbA1c every 2-months
Home regular BG monitoring
Home urine ketones tests when indicated

21. EDUCATION Educate child & care givers about: Diabetes Insulin
Life-saving skills
Recognition of Hypo & DKA
Meal plan
Sick-day management

22. Management Principles of insulin therapy
Varies between individuals and changes over time
The correct dose of insulin is the dose that achieves the best glycemic control without causing obvious hypoglycemia problems and achieving normal growth(height and weight)
Dosage depends on,
Age, weight, stage of puberty, duration and phase of diabetes, state of injection sites, nutritional intake and distribution, exercise pattern, daily routine

23. Hyperglycemia:
Microangiopathic
complications
Hypoglycemia:
Neuronal loss
Poor school performance
seizures

24. TYPES OF INSULIN Short acting (neutral, soluble, regular)
Peak 2-3 hours & duration up to 8 hours
Intermediate acting
Isophane (peak 6-8 h & duration h)
Biphasic (peak 4-6 h & duration h)
Semilente (peak 5-7 h & duration h)
Long acting (lente, ultralente & PZI)
Peak 8-14 h & duration h

25. INSULIN ANALOGS Ultra short acting
Insulin Lispro
Insulin Aspart
Long acting without peak action to simulate normal basal insulin
Glargine

26. FREQUENTLY USED REGIMES
Twice daily regimes
2 daily injections of a mixture of a short or rapid insulin with an intermediate acting insulin (before meal and before main evening meal).
Approximately 1/3 of the total insulin dose is short acting and 2/3 is intermediate.
2/3 of the total daily insulin is given in the morning and 1/3 in the evening.
Three injections daily
Before breakfast – mixture of rapid or short with intermediate
Before afternoon snack or evening meal – rapid or short
Before bed – intermediate acting

27. Insulin Dosage Prepubertal children usually require 0.7-1.0 IU/kg/day
During puberty, requirements may rise above 1 and even up to 2 IU/kg/day

28. INSULIN CONCENTRATIONS
Insulin is available in different concentrations 40, 80 & 100 Unit/ml.
WHO now recommends U 100 to be the only used insulin to prevent confusion.
Special preparation for infusion pumps is soluble insulin 500 U/ml.

29. ADVERSE EFFECTS OF INSULIN
Hypoglycemia
Lipoatrophy
Lipohypertrophy
Obesity
Insulin allergy
Insulin antibodies
Insulin induced edema

30. PRACTICAL PROBLEMS injection sites & technique
Insulin storage & transfer
Mixing insulin preparations
Insulin & school hours
Adjusting insulin dose at home
Sick-day management
Recognition & Rx of hypo at home

31. TREATMENT MADE EASY Insulin pens & new delivery products
Handy insulin pumps
fine micro needles
Simple accurate glucometers
Free educational material
computer programs for comprehensive management & monitoring

32. Diet
On the standard twice daily regime, food intake is divided into 3 main meals with snacks between meals and before going to bed.
Diet should be high in fibre which will provide a sustained release of carbs.

33. Type of Food
The following are among the most recent consensus recommendations:
Carbohydrates should provide 50-55% of daily energy intake. (No more than 10% of carbohydrates should be from sucrose or other refined carbohydrates.)
Fat should provide 30-35% of daily energy intake.
Protein should provide 10-15% of daily energy intake.

34. Activity
Type 1 diabetes mellitus requires no restrictions on activity; exercise has real benefits for a child with diabetes.
Most children can adjust their insulin dosage and diet to cope with all forms of exercise.
The current guidelines are increasingly sophisticated and allow children to compete at the highest levels in sport.

35. Dreams are the seedlings of realities

36. FUTURE PROMISES
The cure for IDDM is successful islet cell transplantation, which will be available in the near future.
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.

37. DIABETES MELLITUS - TYPE 1 MONITORING STRATEGIES
Self Blood Glucose Monitoring – 2 to 4 / day
Urine Testing – Ketones
Glycosylated Hemoglobin - HbA1 C - quarterly
Blood lipids - annually
Thyroid function – annually
Urine micro albumin – quarterly after 5 yr
Dilated fundoscopy – age 10 yr yr

38. Diabetic ketoacidosis
Ketoacidosis is a state of uncontrolled catabolism associated with insulin deficiency
Diabetic ketoacidosis tends to occur in individuals younger than 19 years, but it may occur in patients with diabetes at any age.
Criteria
Hyperglycemia: blood glucose >11mmol/L(200mg/dL)
Venous pH<7.3 or bicarbonate <15 mmol/L
Ketonemia and ketonuria

39. Diabetic ketoacidosis
In the absence of insulin, hepatic glucose production accelerates, and peripheral uptake by tissues such as muscle is reduced.
Rising glucose levels lead to an osmotic diuresis, loss
of fluid and electrolytes, and dehydration.
Plasma osmolality rises and renal perfusion falls.
In parallel, rapid lipolysis occurs, leading to elevated circulating free fatty-acid levels.
The free fatty acids are broken down to fatty acyl-CoA within the liver cells, and this in turn is converted to
ketonebodies within the mitochondria

40. Diabetic ketoacidosis
Accumulation of ketone bodies produces a metabolic acidosis. Vomiting leads to further loss of fluid and electrolytes.
The excess ketones are excreted in the urine but also appear in the breath, producing a distinctive smell
similar to that of acetone.
Respiratory compensation for the acidosis leads to hyperventilation, graphically described as 'air hunger'.
Progressive dehydration impairs renal excretion of hydrogen ions and ketones, aggravating the acidosis

41. Diabetic ketoacidosis
Mostly the causes are
Previous undiagnosed diabetes
Interruption of insulin therapy
The stress of intercurrent illness
Goals of therapy
Correct dehydration
Correct acidosis and reverse ketosis
Restore blood glucose to near normal
Avoid complications of therapy
Identify and treat precipitating event

42. History Classic symptoms of hyperglycemia Thirst Polyuria, polydipsia
Nocturia
Other symptoms
Generalized weakness
Malaise/lethargy
Nausea/vomiting
Decreased perspiration
Fatigue
Anorexia or increased appetite
Confusion
Symptoms of associated infections and conditions
Fever
Dysuria
Chills
Chest pain
Abdominal pain
Shortness of breath

43. Physical General signs Ill appearance Dry skin Labored respirations
Dry mucous membranes
Decreased skin turgor
Decreased reflexes
Vital signs
Tachycardia
Hypotension
Tachypnea
Hypothermia
Fever, if infection
Specific signs
Ketotic breath (fruity, with acetone smell)
Confusion
Coma
Abdominal tenderness

44. Management Fluids Fluid input and output
If in shock, initial resuscitation with normal saline. Dehydration should then be corrected gradually over 48 to 72 hour
using 0.45% Saline
Monitor :
Fluid input and output
Electrolytes, creatinine and acid-base status regularly
Neurological states
2. Insulin
- insulin infusion is started, titrating the dose according to the blood glucose. Monitor blood glucose regularly.
- aim for gradual reduction of blood glucose .

45. 4. Sodobicarb(used only in selected patients)
3. Potassium
Although the initial plasma concentration may be high, it will fall following treatment with insulin and rehydration
High doses (20 to 40 mEq/L) to be added to drips
4. Sodobicarb(used only in selected patients)
-severe acidemia(arterial pH<6.9)in whom decreased cardiac contractility and peripheral vasodilation can further impair tissue function
- life threatening hyperkalemia
- cautiously give 1-2 mmol/kg over 60 min

46. COMPLICATIONS OF THERAPY
Main complication is BRAIN EDEMA
© 2004, John Walsh, P.A., C.D.E.

47. TYPE 2 DM IN CHILDREN Among 10 – 19 yr olds
T2 DM accounts for 33% of all new cases
African Americans – 42%
Caucasians – 10%

48. Obesity
Adolescence
Acanthosis Nigricans

49. Natural History of Type 2 Diabetes
Genetic susceptibility
Environmental factors
Complications
Disability
Onset of diabetes
PRE
Obesity Insulin resistance
Ongoing hyperglycemia
Death
Risk for
Disease
Metabolic
Syndrome
Retinopathy Nephropathy Neuropathy
Blindness Renal failure CHD Amputation
Atherosclerosis Hyperglycemia Hypertension

50. Therapy of T2 DM in Children
Reduce calories – weight loss
NOT T1 DM diet with high complex CHO
No Between meal snacks
NOT T1 DM where hypoglycemia is frequent
Reduce CHO intake
Reduce fat intake
Exercise – increase healthy
life style
Drug treatment early x

51. Start with insulin and diet, exercise
Diagnosis
BG 250 mg/dL or 12 mmol/L
Asymptomatic
Start with insulin and diet, exercise
Diet and exercise
<7%
<7%
Monthly review, A1C q3mo
Add metformin
Attempt to
wean insulin
>7%
Add metformin
>7%
Add insulin, TZD, sulfonylurea
>7%
Add 3rd agent
TZD = thiazolidinedione
Silverstein JH, Rosenbloom AL.
J Pediatr Endcrinol Metab. 2000;13 Suppl 6:

52. T2 DM vs T1 DM T2 DM T1 DM Obesity 95% > 85%tile Not Common
+ Family Hx T2
72 – 85%
Acanthosis Nigricans
60 – 86%
7% all school aged children
Maternal Gestational DM +
IUGR
Not common

53. T2 DM vs. T1 DM T2 - DM T1 – DM Polyuria/dypsia + Ketonuria + / - DKA
Autoimmunity
Initial insulin
Often required
Required
Honeymoon
illness

54. Uncontrolled diabetes
Amputations
Loss of Sensations
Heart disease
and strokes
Blindness
Uncontrolled diabetes
can lead to…
Death
Kidney failure

55. By learning you will teach; By teaching you will learn.
Latin Proverb
© 2004, John Walsh, P.A., C.D.E.

56. Research tells us 14 out of any 10 individuals likes Candy 
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