1. Diabetes mellitus in childrenBy
Henry Cummings
MBBS, FMCPaed
Delsuth, Oghara

2. Pre-test Dm is the commonest endocrine disorder in children
Only type 1 dm occurs in children
TIDm is a non progressive low-insulin catabolic state
Exogenous insulin replacement remains the only form of replacement therapy
In managing DKA, always add kcl to the initial rehydrating fluid.

3. Childhood Diabetes mellitus
Definition
Types
Patho physiology
Clinical features
Modalities of management
Complications, short term, long term
Recent advancements
Conclusion

4. DEFINITION BY WHO:
DM is a metabolic disorder of multiple aetiologies characterised by chronic disturbances of carbohydrate, fat & protein metabolism, resulting from defects in insulin secretion, insulin action or both.
DM is the commonest endocrine disease in childhood & adolescence.

5. MAGNITUDE OF THE PROBLEM
Overall incidence 1 to 2 per 1000 school age children.
Estimated prevalence of childhood DM in were:
430,000 globally
250,000 live developing countries.
63,000 live in 58 poorest countries(least developed countries).

6. TYPES OF DM Type 1 DM(IDDM) Beta cell autoimmune destruction
Absolute insulin deficiency
Requires insulin for survival
Accounts for over 90% of childhood DM
Peak age incidence years
Slight male predominance
Prone to ketosis

7. Type 2 DM (NIDDM) Insulin resistance with relative deficiency OR
Secretory defect with or without resistance
Does not require insulin for survival
Strong genetic component
Not prone to ketosis
Acanthosis nigrans may be present
No islet cell antibodies
Associated with overweight teenagers

8. Maturity onset diabetes of the youth (MODY)
Early onset of dominantly inherited type 2 DM
Non- obese children
No islet cell antibodies
Family history in several generation
Identified genetic mutations e.g mutations of glucokinase or hepatic nuclear factor 1 & 2 genes
Non- ketotic
Two (or at least one)family member diagnosed before age of 25 years

9. Neonatal Diabetes
hyperglycemia requiring insulin in the first 3months of life
Rare condition 1:400,000
Associated with IUGR
50% of cases are transient
Associated with paternal isodomy & other imprinting defects of Chr 6
In transient NND permanent DM may appear later in life

10. Secondary diabetes mellitus
May be associated with cystic fibrosis, hemochromatosis, drugs such as L- Asparaginase

11. Criteria for diagnosis
Symptoms of DM and casual plasma glucose conc > 11.1mmol/L(200mg/dl) (10 for venous)
FPG > 7.0mmol/L(126mg/dl) (6.3 for venous and cap)
2hr post load of glucose >11.1mmol/L during an OGTT

12. blood sugars Normal RPG: 70 – 140mg/dl Normal FBS: 70 – 100mg/dl
Hypoglycemia:
Mild 40 – 70mg/dl
Severe 40mg/dl
Neonatal <50mg/dl

13. Autoimmunity & Insulitis
Etiology of T1Diabetes
Environmental
Factors
Cow’s milk?
Viruses ?
Nitrates?
Genetic
Susceptibility
DM1: HLADR3,DR4↑
Protective DRB1,DQB1↓
DM2
Autoimmunity & Insulitis
Destruction of pancreatic β cells
JBEE 13

14. Pathophysiology Insulin essential to process CHO, fat, protein
It  blood glucose levels by glucose uptake into muscle cells and fat cells
stimulates glycogenesis
inhibits glycogenolysis
 the breakdown of fat to triglycerides, free fatty acids, and ketones. (lipolysis)

15. Pathophysiology Lack of Insulin
 glucose oxidation in muscle & fat cells
Proteolysis & amino acid release
Glycogenolysis & gluconeogenesis
all result in Hyperglycaemia
Glucose intake still continues

16. Pathophysiology
The kidneys cannot reabsorb the excess glucose load, causing glycosuria, osmotic diuresis(polyuria), thirst, and dehydration.
Untreated pt excrete high glucose load causing polyphagia
Increased fat and protein breakdown leads to ketone production and weight loss.

17. Pathophysiology contd
Acidosis result from ketosis
Acidosis leads to  renal excretion of K+ and Po4
Na+ loss is due to osmotic diuresis & vomiting
Hypokalemia is due to vomiting, osmotic diuresis & hyperaldosteronism
Coma likely due to ketosis, acidosis, dehydration & hyperosmolality

18. Lipolysis Absolute insulin deficiency OR
Stress, infection or insufficient insulin intake
Counter-regulatory hormones:  Glucagon, Cortisol,
Catecholamines, GH
Lipolysis
Glucose
utilization
 Proteolysis
 Protein synthesis
 Glycogenolysis
Gluconeogenic substrates
 FFA to liver
 Gluconeogenesis
 Ketogenesis
Hyperglycemia
 Alkali reserve
Glucosuria (osmotic diuresis)
Acidosis
Loss of water and electrolytes
 Lactate
Dehydration
Hyperosmolarity
Impaired renal function

19. Phases of T1DM Preclinical diabetes Presentation of DM
Partial remission or honeymoon phase
Chronic phase of lifelong dependency on administered insulin

20. Preclinical DM
Occurs months to years preceding the clinical presentation of T1DM
Antibodies can be detected as markers of beta cell auto immunity:- GAD, IA,ICA, IA2 etc
IVGTT

21. T1DM: a slowly progressive T-cell mediated autoimmune illness
Genetic
susceptibility
Diabetes
Onset
Time (years)
“Silent” 
Cell Loss
Inciting
Event(s)
Diabetes
100%
Islet
Cell
Mass I
50% II
III
cell
Mass?? 0%
Is  cell loss
exclusively
immune mediated?
JBEE 21

22. Clinical presentation
Vary from non-emergency px( polydipsia, polyuria, weight loss, enuresis) to severe dehydration, shock and DKA
Onset may be acute, precipitated by an acute illness, or more chronic and insidious over weeks or even months.

23. Lab Investigations Glucose levels E & U Ketones C peptides
Islets cell antibodies

24. Other Lab Investigations
Lipids
Microalbumin
Thyroid fxn test
Hb A1c
fructosamine

25. Modalities of management
requires Multidisciplinary team
Insulin therapy
Diabetic education
Exercise
Diet
Psychological care
Monitoring
Others:- sick day mx, adjusting to school

26. Insulin therapy
Exogenous insulin replacement remains the only form of replacement therapy

27. The Basal/bolus Insulin Concept
Basal Insulin
- Suppresses glucose production btw meals and overnight
40% to 50% of daily needs
Bolus Insulin (meal time)
Limits hyperglycaemia after meals
Immediate rise and sharp peak at 1 hour
50% -60% total daily insulin requirement for meals

28. Basal/bolus therapy regimens
Intensive management:
MDI – Multiple Dose Insulin
Once-daily IA or LA insulin usually given at night and 3-ce daily SA or VA before each meal
Mixed preps e.g. Mixtard, humulin 70/30
CSII – Continuous Subcutaneous Insulin Infusion (Insulin pump therapy)

29. INSULIN THERAPY contd. Twice daily regimen:
Split dose regimen (2/3 morning, 1/3 evening; 2/3 intermediate acting, 1/3 soluble).
Aim at maintaining blood glucose within mg/dl, with the occurrence of as few hypoglycaemic episodes as possible.

30. Twice a day insulin Insulin Endogenous insulin Soluble insulin60 20 40
Endogenous insulin
Soluble insulin
Intermediate-acting insulin
This regimen usually uses a soluble or rapid-acting insulin combined with an intermediate-acting insulin. This is often given using pre-mixed insulin, 30/70, 20/80, 40/60 or 50/50.
As can be seen here, the intermediate-acting insulin given at breakfast and supper (dinner) time peaks in the early hours of the afternoon and night, putting the person at risk of hypoglycaemia at these times. This type of regimen requires the person to be consistent with meal times, to eat mid meal snacks and to be consistent with the amount of carbohydrate eaten. This is often inconvenient for the patient. This type of regimen is also associated with weight gain.
Breakfast
Lunch
Supper

31. DIET
Complex carbohydrates (CBHs) are preferred to simple refined CBHs.
Dietary regimen should be adjusted according to convenience of the family and school timings to ensure better compliance.
Total CBH content of the meal &snacks should be kept constant.

32. EXERCISE Encourage regular exercise.
Insulin requirement may be lower, metabolic control improved and self- esteem & body image better in physically fit child.

33. SELF- CARE EDUCATION
Should include nature of illness, acute & chronic complications, insulin action, duration and timing, injection techniques, nutrition information, self blood glucose monitoring and urine ketone checks.
Education must be appropriate to child’s age & family educational background.

34. Monitoring
Monitoring of growth & development: the use of percentile charts is a crucial element in the care of children & adolescents with DM
Poor gain of height & weight, hepatomegaly and delayed puberty might be seen in children with persistently poorly controlled DM

35. Monitoring HbA1c at least twice a year
Screening for long term complications

36. Partial remission (honeymoon) phase
Defined as when the patient requires < 0.5units of insulin/kg/day and has an HbA1c <7%
Due to partial recovery of the damaged beta cells
Commences within days or weeks of start of insulin therapy and may last for weeks to months
Ketoacidosis at presentation & young age reduces the likelihood of a remission phase

37. Complications comprised of 3 major categories:
1. acute complications - reflect the difficulties of maintaining a balance between insulin therapy, dietary intake, and exercise.
2. long-term complications
3. complications caused by associated autoimmune diseases

38. ACUTE COMPLICATIONS
Hypoglycaemia
Diabetic ketoacdosis
Infections

39. HYPOGLYCAEMIA
Defined as blood glucose level < 60mg/dl (3.3mmol/L). For preschool children, values below 70mg/dl (3.9mmol/L) should be a cause for concern.
Severe episodes occur 10-25% of pts per year
Commonest acute complication of Type 1 DM

40. WHY WORRY ABOUT HYPOGLYCAEMIA?
Recurrent severe hypoglycaemia can lead to:
Hypoglycaemia unawareness(25% of DM pts)
Epilepsy
Learning difficulty
Death (accounts for 4% of deaths in DM as a result of unintentional trauma).

41. Diabetic ketoacidosis
creates a life-threatening medical emergency.
is the most important cause of mortality and severe morbidity in children with diabetes, particularly at the time of first diagnosis.
Early recognition and careful management are essential if death and disability are to be avoided.

42. Diagnosis 3 cardinal features: Clinical features
Hyperglycemia - >200mg/dl(11.1mmol/l)
Ketonuria >5mmol/l, ketonemia
Venous ph<7.3 or metabolic acidosis < 15mmol/l
Clinical features
Severe dehydration, shock
Frequent vomitng
Polyuria despite dehydration
Weight loss in spite of good intake
Acetone breath – (Kussmaul respiration) deep and rapid
Altered sensorium
Signs of raised intracranial pressure – bradycardia, HT, anisocoria

43. RISK FACTORS AS INITIAL PRESENTATION: Young age: < 5 years
Low socioeconomic background
IN ESTABLISHED TYPE 1 DM:
Higher HbA1c
Adolescents, particularly females
Psychiatric disorders
Longer duration of diabetes

44. severity mild = pH < 7.30 or bicarb < 15 mmol/L
moderate = pH < 7.20 or bicarb < 10 mmol/L
severe = pH < 7.10 or bicarb < 5 mmol/L

45. 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

46. Emergency assessment Brief history to find cause Weigh the child
Assess degree of dehydration
Assess level of consciousness(glasgow coma scale)
Biochemical assessment

47. Biochemical assessment
Blood samples:
Plasma glucose
E&U, Cr, Ca, PO4, Mg
HbA1c
Venous pH
pCO2 Hb
FBC( Leucocytosis could exist without infection due to stress)
Beta hydroxybutyrate

48. Biochemical assessment
Urine sample
Urinalysis for ketones (acetoacetate)
Others include culture samples:- (blood , urine, throat)
ECG:- k status

49. Supportive therapy Secure airway
A peripheral IV catheter should be placed in for convenient and repetitive sampling
Cardiac monitor
Give oxygen to pts with severe circulatory impairment or shock
Give anitbiotics to febrile patients after cultures have been taken

50. FLUID THERAPY
1st hr: 10 – 20ml/kg 0.9% Nacl with insulin infusion at 0.05 – 0.1 U/kg/hr
2nd hr & subsequent hrs: 0.45% Nacl plus continuous insulin drip + 20mEq/L K+
5% dextrose if blood glucose <250mg/dl (14mmol/L)
IV Rate= 85ml/kg +(maintenance minus bolus) divided by 23

51. TREATMENT contd Maintain IV insulin until DKA resolves:
pH > 7.3, bicarbonate > 15mmol/L, stable serum Na+ 135 – 145mmol/L, No emesis;
then switch to SC insulin (maintain IV insulin 30min after SC)
Ketones may take longer to clear

52. POTASSIUM HYPOKALEMIC = give with initial resuscitation 20mmol/l
EUKALEMIC = at the time of insulin intro
HYPERKALEMIC = when patient makes urine

53. Potassium Max dose 0.5mmol/kg/hr
If hypokalemia persist then reduce insulin infusion rate!
ECG monitoring helps!

54. Acidosis Is given cautiously only if pH < 6.9 HCO3 < 5mmol/l
1 – 2mmol/kg over one hour!

55. Monitoring/charting Hourly monitoring and charting of Blood pressure
Respiratory rate
Heart rate
Level of consciousness
Blood sugar
Blood ketones
Electrolyte and urea(Ca,PO4,Mg)
Input /output
Insulin given

56. Complications of therapy
Inadequate rehydration
Hypoglycemia
Hypokalemia
hypophosphatemia
Cerebral edema

57. Management of DKA
Follow up

58. HHS (Hyperglycemic hyperosmolar state)
PG >33.3 mmol/L (600 mg/dL)
Arterial pH >7.30
Serum bicarbonate >15 mmol/L
Small ketonuria, absent to low ketonemia
Effective serum osmolality >320 mOsm/kg Stupor or coma

59. Long-term complications
Retinopathy
Cataracts
Hypertension
Progressive renal failure
Early coronary artery disease
Peripheral vascular disease
Neuropathy, both peripheral and autonomic
Increased risk of infection
Injection-site hypertrophy
Growth failure. Delayed puberty

60. Recent advancements Whole pancreas transplantation
Islet cell transplantation
Engineered stem cells manipulated genetically to produce insulin
Techniques to protect b cells from autoimmune attack – Immunotherapy
Alternate non invasive routes for insulin administration
Chemical alteration of insulin molecule
Artificial pancreas
Adding c peptide to insulin
Implantable insulin pumps
New blood glucose meters

61. Conclusion
DM (particularly T1DM), a common and potentially life threatening endocrine disorder in children is often misdiagnosed or poorly managed
Having a regularly updated management protocol in our Paediatric units will greatly improve the level and quality of care these children receive.
Thank you for listening.

62. Post test Dm is the commonest endocrine disorder in children
Only type 1 dm occurs in children
TIDm is a non progressive low-insulin catabolic state
Exogenous insulin replacement remains the only form of replacement therapy
In managing DKA, always add kcl to the initial rehydrating fluid.