Diabetes in Children

1. Childhood Diabetes
Classification, Epidemiology, Etiology
Clinical Features, Complications, Management
Prognosis and Prevention
Prof. Imran Iqbal
Fellowship in Pediatric Neurology (Australia)
Prof of Paediatrics (2003-2018)
Prof of Pediatrics Emeritus, CHICH
Prof of Pediatrics, CIMS
Multan, Pakistan

2. (God speaking to Prophet Muhammad (PBUH)
And He (God Almighty) is the One who has created the night and the day;
and the sun and the moon, each of them is floating in its own orbit
The Holy Quran; surah Al-Anbiya 21:33
In the name of Our Creator Allah, the most Gracious, the most Merciful

3. Types of Diabetes Mellitus
• Type 1 DM - IDDM (Insulin Dependent Diabetes Mellitus)
• Type 2 DM – Non-IDDM (Non Insulin Dependent Diabetes
Mellitus)

4. Types of Diabetes Mellitus – Type 1 DM
• Type 1 Diabetes Mellitus
• IDDM (Insulin Dependant Diabetes Mellitus)
• Seen in children from infancy to adulthood
• Insulin deficiency in body
• Treated essentially with Insulin

5. Types of Diabetes Mellitus – Type 2 DM
• Type 2 Diabetes Mellitus
• Non IDDM (Non Insulin Dependant Diabetes Mellitus)
• Seen in adults
• Can be seen in obese adolescents with acanthosis nigricans
• Resistance to insulin actions
• Serum Insulin / C – peptide levels are high
• Treated initially with Oral Hypo-glycemics

6. IDDM - Epidemiology
• IDDM makes 10% of all cases of Diabetes
• IDDM is seen equally in boys and girls
• Prevalence of IDDM in children is 1 case in 1000 children
• Diabetes amongst children is increasing
• Throughout the world, incidence of diabetes is increasing

7. IDDM - Etiology
• Inherited genetic characteristics are the basis of IDDM
• IDDM is triggered by environmental factors
• Viral infections may affect Beta cells of Pancreas
• Autoimmunity (antibodies and lymphocytes) developed
against Beta cells antigens may destroy these cells

9. IDDM – Other factors in Etiology
• All causes and factors which predispose to IDDM are
incompletely known
• Breast feeding lowers the risk of IDDM
• Psychologic stress may predispose to IDDM

10. IDDM – Pathology
• There is gradual destruction of Beta cells of Pancreas
• This destructive process may take months to years
• Destruction of Beta cells produces hyperglycemia
• Clinical disease is seen when 90% of Beta cells are destroyed
• Some insulin secretion remains in children with IDDM

11. 11
The Natural History of Type 1 Diabetes
Islet
Cell
Mass
Islet Antigens
IAA, GAD65A, IA-
2A, IA-2bA,
Glima-38A Cell Mediated
response to islet
antigens
Genetic Predispositions
HLA-DR/DQ
? A.B.C
VNTR INS.
CTLA-4
Others
Lack of environmental
protection from NK-T
cells / CD25+ T cells
Inductive Event
eg. Coxsackie virus
IL-12 / INF-g
Metabolic
Derangements
FPIR to IVGTT
Impaired OGTT
Elevated fasting
glucose
Diabetes Onset
Honeymoon
Phase
9 months – 3 years months to years months

12. IDDM – Pathophysiology

13. Insulin
• Insulin is the anabolic hormone secreted in response to
feeding
• Insulin stores glycogen (carbohydrate) in the liver and muscles
• Insulin stimulates synthesis and storage and fats in the body
• Insulin helps in synthesis of proteins

14. Insulin secretion in the body
• Insulin is the major hormone to maintain Blood Glucose level
• Insulin is secreted in the body according to body needs - at a
variable level - all the time of day and night
• Insulin secretion increases as a response to food intake
• Insulin secretion decreases in fasting

15. Absence of Insulin
• Absence of Insulin produces a catabolic state
• Glycogen is converted to glucose producing hyperglycemia
• Lipolysis occurs producing Free Fatty Acids and ketosis
• Protein breaks down with formation of Amino acids which are
converted to glucose (gluconeogenesis)

16. IDDM – Clinical Features

17. Case scenario
• A six year child presents with loss of weight for the lost one
month. Mother says child appears much thinner now.
• For the last two weeks, he has started passing urine during
the night. He does not go out to play as before.
• On examination, weight of child is 15 kg. He appears lethargic
and keeps sitting. His pulse is 100/min, respiration 20/min and
temperature 98F. His eyes are a bit sunken but no other signs
of dehydration are present
• What is the most likely diagnosis ?

18. Investigations
• Urine dipstick is performed in clinic and shows glycosuria ++
and ketones +
• Glucometer shows his Random Blood Sugar to be 240 mg / dl.
• Diagnosis is Diabetes Mellitus
• Lab investigations sent include CBC and CRP, HbA1c, ALT, Urea,
Creatinine, Serum electrolytes including bicarbonate,

19. Symptoms of Diabetes

20. IDDM - Deficiency of Insulin
• Symptoms often develop quickly in days or gradually over
weeks
• Fatigue and polyuria are most prominent symptoms
• 20 % of diabetic children present initially with Diabetic
Ketoacidosis (DKA)
• These children may present with abdominal pain, nausea and
vomiting
• Dehydration and acidotic breathing are usually present
• Lethargy and coma may develop rapidly

21. DKA – Case scenario
• A 10 year old child presents to the emergency in a lethargic condition.
Parents tell that he has not been well for the last 15 days. He has been
drinking more water and has started bedwetting. Today he could not get
up in the morning and has become more drowsy in last few hours.
• On examination, weight of child is 25 kg. His pulse is 130/min, respiration
30/min and temperature 98F. His eyes are sunken and tongue is dry. He is
drowsy and His GCS is 12/15.
• His blood sugar is checked and is 400 mg /dl. Management for DKA is
started
• Other investigations sent include urine for ketones, HbA1c, ALT, Urea,
creatinine, serum electrolytes including bicarbonate, CBC and CRP

22. IDDM – Diagnosis

23. Diagnosis of IDDM
• Suggestive Symptoms and any of three biochemical features:
• Random plasma glucose > 200mg/dl
OR
• Fasting plasma glucose > 126mg/dl
OR
• HbA1C > 6.5 %
• Urine glucose and Urine ketones may be positive

24. Diagnostic Criteria for Diabetes Mellitus
American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S5-S10
Fasting PG Random PG / 2-h PPG
126
60
80
100
120
140
160
180
200
Plasma glucose
(mg/dl)
Normal
Diabetes
Mellitus
240
220
Diabetes
Mellitus
Normal
IGT
IGT

25. IDDM – Complications

26. Acute Complications
• Acute infections – bacterial and fungal infections
• Hypoglycemia – caused by poor intake or extra exercise or
overdose of insulin
• DKA - Diabetic ketoacidosis – Low insulin levels
-- catabolism of fats into fatty acids which make ketones
-- ketosis causes metabolic acidosis
-- hyperglycemia, glycosuria and acidosis result in
-- dehydration, hypotension, shock, lethargy, coma,

27. Infections
• Acute and Chronic infections are common in diabetic children
• Infections disturb the glycemic control and result in increased
Insulin requirements
• Diabetic Ketoacidosis – DKA – can develop with infections
• Early and effective treatment of infections is needed to
prevent further complications

28. Hypoglycemia

29. Chronic Complications
• Psychological problems
• Growth retardation
• Nephropathy, retinopathy, neuropathy and hypertension are
seen rarely in older children with pediatric diabetes

30. Psychological / Psychiatric Risks
• Children and adolescents with diabetes have significant risks
for psychological problems:
– Depression
– Anxiety
– Eating disorders
– Externalizing disorders

31. Chronic Complications – how to screen

32. IDDM – Management

33. IDDM – Principles of Management
• Parents are told the briefly told about the diagnosis keeping in
mind the protocol of breaking bad news
• Family needs education about the disease, diet, monitoring,
insulin doses and administration and complications of the
disease
• Insulin administration needs to be started early
• Child may be admitted to hospital or detailed management is
done in the clinic with daily visits

34. IDDM - Patient Education
• Nature of disease and its management
• Nutrition
• Exercise
• Insulin action and administration
• Insulin dosage adjustment
• Blood glucose (BG) measurement and log book
• Sick-day management
• Prevention, detection and treatment of hypoglycemia
• Prevention of DKA

35. IDDM - Diet
• Diet charts are used to guide about food restrictions
• Sugar containing foods are avoided
• Complex carbohydrates are allowed
• Adequate proteins and fats are given

36. Insulin secretion in the body
• Insulin is the major hormone to maintain Blood Glucose level
• Insulin is secreted in the body according to body needs - at a
variable level - all the time of day and night
• Insulin secretion increases as a response to food intake
• Insulin secretion decreases in fasting
• IDDM – exogenous insulin should mimic physiological insulin
secretion

37. Types of Insulin – duration of action

38. Pharmaceutical types of Insulin – onset and duration of action
Insulin Type (trade name) Onset Peak Duration
Bolus (prandial) Insulins
Rapid-acting insulin analogues:
• Insulin aspart (NovoRapid®)
• Insulin glulisine (Apidra™)
• Insulin lispro (Humalog®)
10 - 15 min
10 - 15 min
10 - 15 min
1 - 1.5 h
1 - 1.5 h
1 - 2 h
3 - 5 h
3 - 5 h
3.5 - 4.75 h
Short-acting insulins:
• Insulin regular (Humulin®-R) 30 min 2 - 3 h 6.5 h
Basal Insulins
Intermediate-acting insulins:
• Insulin NPH (Humulin®-N) 1 - 3 h 5 - 8 h Up to 18 h
Long-acting basal insulin analogues
• Insulin detemir (Levemir®)
• Insulin glargine (Lantus®)
90 min Not
applicable
Up to 24 h
(glargine 24 h,
detemir 16 - 24 h)

39. Serum
Insulin
Level
Time
Analogue Bolus: Apidra, Humalog, NovoRapid
Human Basal: Humulin-N, NPH
Analogue Basal: Lantus, Levemir
Human Bolus: Humulin-R,
Insulin doses related to meals

40. Insulin
• A regime containing both
short-acting and long-acting
insulins is used
• Child may need 2 – 4 insulin
injections in a day

41. Insulin Regime - Short and Intermediate acting Insulins
• Dose of Insulin is individualised for each patient
• Total daily Insulin dose is calculated as 0.5 – 1.0 unit / kg /day
• Two doses per day are given
• Two-thirds of calculated dose is given in morning and one-
third in evening
• Two daily injections of short-acting insulin (Regular Insulin)
combined with intermediate acting insulin (NPH) are given
twice a day in a combination of 30:70

42. Insulin Regime – Rapid and Long acting Insulins
• Dose of Insulin is individualised for each patient
• Total daily Insulin dose is calculated as 0.5 – 1.0 unit / kg /day
• Four doses per day are given
• One dose - 50 % of calculated dose is given as Long-acting
Insulin in evening as basal insulin
• Three doses of Rapid-acting insulin (Ultra-short Insulin) are
given along with daily meals to cover the hypoglycemia
related to meals (15 % of total calculated dose each)

43. IDDM – Home Monitoring
• Blood glucose monitoring is essential
• Daily diary of Glucose level checks and insulin doses needs to
be kept in a notebook
• Blood glucose monitoring is essential initially 2-4 times in a
day to adjust the daily insulin dose
• In stable patients, blood glucose may be checked once or
twice a day
• Mobile apps available to keep track of monitoring and doses

44. IDDM – Insulin Sensor and Pump
(closed loop system)
Software automatically increases / decreases insulin
delivery to target blood glucose level of 120 mg/dl

45. Diabetic Child – Management of Acute Illness
 Monitor Blood glucose and Urine ketones more frequently
 Maintain hydration and nutritional intake
 Avoid hyperglycemia and hypoglycemia
 Do not omit insulin – adjust the dose as needed
 Look at the warning signs of DKA
 Treat the underlying illness

46. Diabetic ketoacidosis
DKA - diagnosis

47. Case scenario – known diabetic child
• A 6 year old child presents to the emergency in a lethargic
condition.
• Parents tell that he was diagnosed as Diabetes 3 months ago
• He was taking Mixtard (regular+NPH) insulin doses morning
and evening
• For the last 2 day he was having fever and diarrhea and was
not taking his foods.
• As he was not eating so he was not given his Insulin doses
• Today he could not get up in the morning and has become
more drowsy in last few hours.

48. Case scenario – known diabetic child
• On examination, weight of child is 15 kg.
• His pulse is 130/min, respiration 40/min and temperature 98F.
• His eyes are sunken and tongue is dry.
• He is drowsy and His GCS is 10/15.
• His blood sugar is checked and is 426 mg /dl.
• Urine test shows ketones 3 +
• Management for DKA is started
• Other investigations sent include VBGs, HbA1c, ALT, Urea,
creatinine, serum electrolytes including bicarbonate, CBC and
CRP

49. DKA – Risk Factors
 Delayed diagnosis of diabetes
 Insulin omission in the diabetic child
 Poor control of diabetes
 Peri-pubertal & adolescent girls
 Challenging social & family circumstances
 Limited access to medical services

50. DKA – Clinical Features
 Nausea, vomiting, abdominal pain
 Tachycardia
 Tachypnea
 Deep, sighing (Kussmaul) respiration
 Dehydration
 Confusion, drowsiness, coma

51. DKA – Investigations
1) Serum or plasma glucose
2) Blood ketones
3) Plasma pH and Electrolytes
4) Blood urea nitrogen, creatinine
5) Complete blood count.
6) Calcium, Phosphorus, Magnesium concentrations
7) Urinalysis and urine ketones

52. DKA – Diagnosis
• Hyperglycemia – RBS > 200 mg/dl
• Ketosis and Ketonuria
• Metabolic Acidosis
– Plasma pH < 7.3
-- Plasma Bicarbonate < 15 mmol/L

53. Diabetic ketoacidosis
DKA – Management

54. DKA – Specific management
 Fluid and electrolytes to correct dehydration
 Insulin – continuous administration
 Prevent and manage complications

55. DKA – Fluid Therapy
 Fluid replacement should begin before starting insulin
therapy.
 Resuscitation / Initial phase –
10 - 20ml/kg 0.9 % Normal Saline over 1-hour
 Rehydration / Subsequent phase (0.45 % to 0.9 % saline)
-- Fluid needed to correct dehydration – 85 ml / kg
-- Maintenance fluid requirements – 1500 ml / m2
-- Total calculated fluid is given in 24 hours
The approximate calculated rate of fluid administration is
1.5‐2 times the usual daily maintenance requirement

56. DKA – Insulin Therapy
• Low-dose continuous regular insulin infusion (0.1 U / kg/ hr) is
given IV with start of Rehydration / Subsequent phase
• Blood glucose should not decrease rapidly – RBS should
decline by 100 mg / hour
• When blood glucose is < 250 mg/dl, 5% dextrose is added to
IV fluids to slow the fall in blood glucose
• Start SC insulin when ketosis is resolved, and patient is
conscious and taking orally

57. DKA – Complications
• CNS : Cerebral Edema and Stroke
• Cardiac: Arrhythmias, Long QT interval
• Pulmonary: ARDS
• Kidney: Acute kidney injury,
• Coagulation: Venous Thrombosis

58. Medical Ethics