Pediatrics Diabetes mellitus powerpoint.ppt 93.ppt

UG lecture

1. Diabetes mellitus
Dr.p.natarajan

2. Definition
•Diabetes mellitus (DM) is a chronic metabolic
disorder caused by an absolute or relative
deficiency of insulin with hyperglycaemia as a
cardinal biochemical feature

3. Etiologic Classifications of Diabetes Mellitus
1.Type I diabetes (β-cell destruction)
2.Type 2 diabetes (predominantly insulin resistance
with relative insulin deficiency)
3.Other specific types
a.Genetic defects of β-cell secretion
b.Genetic defects in insulin action
4.Diseases of the exocrine pancreas
a.Pancreatitis
b.Cystic fibrosis
c.Hemochromatosis

4. 5.Endocrinopathies
5.Acromegaly
6.Cushing disease
7.Pheochromocytoma
6.Drug-or chemical-induced
1.Glucocorticoids
2.Thyroid hormone
7.Infections
1.Congenital rubella
2.Cytomegalovirus
3.Others—hemolytic uremic syndrome

5. 8.Other genetic syndromes sometimes associated
with diabetes
1.Down syndrome
2.Klinefelter syndrome
3.Turner syndrome
4.Wolfram syndrome
5.Friedreich ataxia
6.Huntington chorea
7.Laurence-Moon-Biedl syndrome
8.Porphyria
9.Prader-Willi syndrome
9.Gestational diabetes mellitus
10.Neonatal diabetes mellitus

6. Type I DM
1.Juvenile-onset ; Insulin-dependent diabetes
2.chronic progressive T-cell-mediated autoimmune
destruction of the β-cells of the pancreas, leading to
severe insulin deficiency
3.About 10% of all diabetes cases
4.1 in 10 000 / year in India
5.Most people develop the disease before age 30;
median age of 7 to 15 yr

7. Type 2 DM
1.Non-insulin-dependent
2.Adult-onset
3.The pancreas continues to produce insulin,
4.Resistance to the effects of insulin,
5.It usually begins in people older than 30 and becomes
progressively more common with age.
6.It also tends to run in families.
7.Obesity is the chief risk factor
8. It also occurs in:
1.Cushing's disease
2.gestational diabetes
3.excess growth hormone (acromegaly)
4.Severe or recurring pancreatitis .

8. Type I: Genetics
•Multifactorial
1.Viral infection or a nutritional factor (cow milk) in
childhood
2.A genetic predisposition
3.Immune mediated damage to the insulin
producing B cells
•Association with HLA-DR3 and DR4
•Association with HLA DQ β gene (absence of aspartic
acid in HLA DQ β chain)
•Genes are responsible for activating autoimmune
cascade

9. Environment
• Absence of protective factors:
1.Breastfeeding
2.Herd immunity to virus transferred to fetus
3.Lack of frequent childhood infections (hygiene
theory)
• Presence of provocative factors:
1.An unknown adverse factor
2.Toxins from vegetables and early infant cereal
diet
3.Entero virus infection

10. Environmental
•Viral infections of β cells:
•Coxackie B3 and B4
•Cytomegalo virus
•Rubella (10-12% congenital rubella develop DM)
•Mumps
•Vaccination: role not established

11. •Seasonal association:
•New cases in adolescent population are
recognized in autumn and winter probably
coinciding with some viral infections like Mumps
etc
•Puberty:
•Pubertal peek incidence occurs earlier in girls due
to estrogen regulated IL6 gene

12. • Body mass index:
•Higher BMI is an independent risk factor for both
Types of DM
•Insulin resistance is a function of fat mass
•Drugs like alloxan, strptozotocin, pentamidine,
and vacor are cytotoxic to β cells

13. Pathogenesis:
1.Molecular mimicry between viral proteins and β
cells
2.Cytokines secreted during viral infections
upregulate autoimmune reactions
3.T cell mediated autoimmune disease leading to
destruction of β cells over a period of time
4.Develop multiple antibodies for β cells
5.Some cells regenerate providing honeymoon phase

14. 6. Psycho social stress in infants may increase
hormonal levels and neuronal signals which
increase insulin resistance, insulin
requirement and immune destruction
7. Overall steps: T cell primingT cell
proliferation β cells destruction

15. Pathophysiology
1.Insulin:
1.Performs storage and retrieval of cellular fuel
2.Secretion is modulated by neural, hormonal and substrate
mediated mechanisms
2.Moderate insulinopenia:
Glucose utilization by tissues is reduced  hyperglycemia
develops after food;
3.Severe insulinopenia :
Glycogenolysis and gluconeogenesis by liver  fasting
hyperglycemia

16. 4.Hyperglycaemia  osmotic dieresis + loss of calories
and electrolytes  persistent dehydration  hyper
secretion of stress hormones: epinephrine, cortisol,
growth hormone and glucagon  further
glycogenolysis, guconeogenesis, lipolysis, ketogenesis
and increase in lipids
5.Glucagon shunts free fatty acids into ketone body
formation
6.Acidosis, hyperosmolality, diminished cerebral O2
utilization  coma

17. Clinical manifestations
1.Symptoms steadily increases with decreasing β cell mass
2.Worsening insulinopenia progressive
hyperglycaemiaeventual ketoacidosis
3.Polyuria, nocturia, plydipsia, glycosuria (caloriuria) and
hyperphagia but with weight loss
4.Monilial vaginitis in female child
5.Ketoacidososis: DKA

18. Diagnosis
1.Non fasting blood glucose: 200 gm/dl with polyuria,
glycosuria with or without ketonuria
2.Fasting plasma glucose level over 126 mg/dL (7 mmol/L) or
3.A plasma glucose level above 200 mg/dL (11.1 mmol/L) 2
hours after an oral glucose load (1.75 g glucose/kg up to a
maximum of 75 g)
•HbA1c: normal is below 6.2% (for future evaluation)
•Tests for other autoimmune disorders:
•IgA: celiac disease
•Antithyroid peroxidase, antithyroglobulin antibodies:
Thyroiditis

19. Treatment
•Patient and family education:
•Regarding symptoms, drug dosing and diet and
glucose monitoring
•Insulin:
•Facilitates cellular entry of glucose; decreases
neoglucogenesis; turns off ketone production
•Dose:
•Prepubertal: 0.7 U/kg/day
•Midpuberty: 1 U/kg/day
•Postpuberty: 1.2 U/kg/day

20. Newly diagnosed cases
•Children receive mixtures of:
– A rapid-acting insulin (to cover food intake or high blood
glucose) plus
–A longer-acting insulin (to suppress endogenous hepatic
glucose production).
•About two-thirds of the total dosage is given before
breakfast
•The remainder before dinner.

21. Other Dosing Methods
•Twice-daily combinations:
•short-acting and intermediate-acting insulin.
•Multiple injection regimens:
•using once-daily or twice-daily injections of long-
acting or intermediate-acting insulin and
•short-acting insulin given at each meal
•Dosage adjusted over a trial period to cover
before meal and after the meal

22. •Insulin pump:
•Continuous subcutaneous insulin infusion (CSII) using
an insulin pump
•Useful for adolescents
•Can be programmed with blood glucose levels and
insulin needs are adjusted by pump computer
•Inhaled insulin therapy:
•Preprandial inhaled insulin and bed time long acting
insulins are being tried with promising results
•Oral insulin: oralin; promising trials are
underway

24. •Inhaled insulin therapy:
–Preprandial inhaled insulin and bed time long
acting insulins are being tried with promising
results
•Oral insulin: oralin; promising trial are
underway

25. Nutrition in DM
•Food :
•20% breakfast; 20% lunch; 30% dinner; 10% in
between snacks
•Carbohydrate: 55% (70% complex
Carbohydrate more fibres
•Fat: 30%polyunsaturated:
saturated 1.2:2; vegetable fat
•Protein: 15%
•Wight in normal range to be maintained

26. Self monitoring
•Blood glucose-
• 4 times daily to monitor glycemic control and insulin dose
•HbA1c :
•Fraction of haemoglobin to which glucose has been attached
•Expressed as a percentage of total Hb;
•Reflects the average blood glucose concentration from the preceding 2-3
months.
•Index of long term glycemic control.
•Elevated in thalassemia (HbF)
•Lowered in sickle cell disease;
•Values 6 to 7.9% represent good metabolic control

27. •Exercise:
• Helps utilization of glucose by muscles and
glucoregulation;
• Planned exercise decreases insulin requirement by 10-
15% and prolonged exercise by 50%;
•Exercise induced hypoglycaemia is avoided by
carbohydrate exchange
•Benefits of good glycemic control:
• Reduces complications such as retinopathy, nephropathy,
and neuropathy

28. Hypoglycemia
•Blood glucose <60mg/dL
•Symptom according to blood levels
•Mild: pallor, sweating, apprehension, tremor and
tachycardia
•Moderate: drowsiness, confusion
•Severe: seizure and coma
•Treatment:
–Beverage or candy
–Glucagon .5 mg IM
–IV glucose

29. Non ketotic hyperosmolarn coma:
•Rare in children
•Blood sugar >800 mg/dL
•No ketosis
•Severe dehydration
•Altered sensorium
•Treatment:
–Insulin infusion
–½ NS in 1
st
12 hour to replace 50% of volume deficit; remainder in next 24
hour
–When blood glucose is < 300 mg/dL .2% NS with 5 % GDW with 20 mEq/L
of Potassium

30. •Somogyi phenomenon:
–Early morning hypoglycaemia due to exaggerated
counter regulatory response
•Brittle diabetes:
–refers to fluctuating blood glucose levels due to
environmental factors such family stress in young
girls

31. Complications
•Microvascular complications:
–Retinopathy
–Nephropathy
•Macrovascular complications:
–Coronary artery disease
–Cerebrovascular disease
–Peripheral vascular disease
•Autonomic:
–Hypotension, or fainting when standing up.
–impotence, diarrhoea, constipation, urinary incontinence
•Cataract

32. Mauriac syndrome
•Moon face
•Protuberant abdomen
•Proximal muscle wasting
•Dwarfism
•Enlarged liver due to glycogen
•Waxy skin
•Restricted joint movements
•IGF 1 deficiency

33. Type 1 DM
•Prognosis:
–Life span 10 years shorter
•Research:
–Islet cell transplantation
–Stem cell therapy
–Β cell regeneration therapy

34. Type II DM
•Polygenic disease plus environmental factors:
–Low physical activity
–Hyperclaoric and lipid rich diet
–Obesity causing:
•Insulin resistance
•Increased hepatic glucose production
•Decreased insulin secretion
•Incidence: 7/ 100 000 among children;
increase due to obesity epidemic

35. Genetic basis
•Polygenic
•Acanthosis nigircans is a marker
•Hisutism with polycystic ovary is associated
with Type II DM
•Gigantism

36. Acanthosis nigircans

37. •Prveniton:
•Avoid:
•heavy snacking
•Emotional eating
•TV, computer – cued eating
•Life style interventions
•Treatment:
•Initial insulin therapy
•Metformin 500 mg bid with meals

38. Diabetic Ketoacidosis
•Commonest cause of death due to DM
•Induced by stress, infection, omitting insulin
dose
•20% of present with symptom before
diagnosis
•Very low insulin levels

39. Clinical
•Ketoacids produce abdominal discomfort, nausea,
vomiting and further dehydration
•Signs of dehydration are masked as intravasular volume
is maintained at the expense of intracellular volume
•Deep heavy rapid breathing: Kussmaul’s respiration
•Fruity odour due to acetone
•Increased ion gap, decreased sodium bicarbonate and
pH
•Confusion leading to coma

40. Complications:
•Cerebral oedema
•Hypokalemia
•Septic shock
•Hypoglycaemia
•Cerebral haemorrhage
•Pancreatitis

41. Problems to be managed
•Dehydration/shock
•Acidosis
•Hypokalemia
•Hypoglycaemia
•Cerebral edema
•infecftion

42. Diagnosis:
•Hyperglycaemia:
– (BG > 200mg/dL or 11 mmol/l)
•pH < 7.3
•Bicarbonate < 15 mmol/l
•More than 3% dehydration
•Clinical:
–Vomiting
–Drowsiness
–Clinical acidosis

43. Management
•Insulin therapy
•Fluid replacement
•Treatment of underlying cause
•Insulin:
•Insulin to drive glucose into cells;
•it is given as infusion .1U/kg/hour

44. Intravenous fluids to correct dehydration
1.Shock treatment:
0-1 hour: 0.9 % NaCl 10-20 ml /kg or RL as bolus
Insulin drip at 0.05 to 0.10 µ/kg/hr
2.Treatment for dehydration:
2nd hour onward : 0.45% Na Cl
plus continue insulin drip
20 mEq/L KPhos and 20 mEq/L KAc
5% glucose if blood sugar < 250 mg/dL (14 mmol/L)
Bicarbonate is not necessary as fluid and insulin
correct acidosis

45. Total Requirement for 48 hours:
Maintenance + Deficit – fluid already given
1.Maintenance: 100 ml/kg first 10 kg wt; plus 50
ml/kg for next 10 kg; plus 25ml/kg for remaining
body weight
2.Deficit: 85 ml/kg for 8.5% dehydration

46. •1st hr
•10-20 mL/kg IV bolus 0.9% NaCl or LR
Insulin drip at 0.05 to 0.10 µ/kg/hr
•2nd hr until DKA resolution
•0.45% NaCl: plus continue insulin drip
20 mEq/L KPhos and 20 mEq/L KAc
5% glucose if blood sugar >250 mg/dL (14
mmol/L)

47. Nonketotic hyperosmolar coma
•Rare in children
•Blood sugar >800 mg/dL
•No ketosis; Severe dehydration; Altered sensorium
•Treatment:
–Insulin infusion
–½ NS in 1
st
12 hour to replace 50% of volume deficit;
remainder in next 24 hour
–When blood glucose is < 300 mg/dL .2% NS with 5 % GDW
with 20 mEq/L of Potassium

48. Nutrition in DM
•Food :
1.20% breakfast; 20% lunch; 30% dinner; 10% in between
snacks
2.Carbohydrate: 55% :70% complex
Carbohydrate more fibres
3.Fat: 30%polyunsaturated:
saturated 1.2:2; vegetable fat
4.Protein: 15%
•Wight in normal range to be maintained

49. Self monitoring & HbA1c
•Blood glucose: 4 times daily to monitor glycemic control and insulin dose
•HbA1c:
1.Fraction of haemoglobin to which glucose has been non enzymatically
attached in the blood
2.Expressed as a percentage of total Hb;
3.It reflects the average blood glucose concentration from the preceding 2-3
months.
4.It is an index of long term glycemic control.
5.It is elevated in Thalassemia (HbF) and lowered in Sickle cell disease;
6. values 6 to 7.9% represent good metabolic control

50. Exercise
•Helps utilization of glucose by muscles and
glucoregulation;
•Planned exercise decreases insulin requirement by 10-
15% and prolonged exercise by 50%;
•Exercise induced hypoglycaemia is avoided by
carbohydrate exchange
Benefits of good glycemic control:
•Reduces complications such as retinopathy,
nephropathy, and neuropathy

51. Hypoglycemia
•Symptom according to blood levels
•Mild: pallor, sweating, apprehension, tremor and
tachycardia
•Moderate: drowsiness, confusion
•Severe: seizure and coma
•Treatment:
1.Beverage or candy
2.Glucagon .5 mg IM
3.IV glucose

52. •Somogyi phenomenon:
•Early morning hypoglycaemia due to exaggerated
counter regulatory response
•Brittle diabetes:
•refers to fluctuating blood glucose levels due to
environmental factors such family stress in young girls

53. Type II DM
•Polygenic disease plus environmental factors:
•Low physical activity
•Hyper caloric and lipid rich diet
•Obesity causing:
•Insulin resistance
•Increased hepatic glucose production
•Decreased insulin secretion

54. •Incidence: 7/ 100 000 among children; increase due to
obesity epidemic
•Genetic basis:
•Polygenic
•Acanthosis nigircans is a marker
•Hirsutism with polycystic ovary is associated with Type II
DM
•Gigantism

55. Prevention:
•Avoid:
•heavy snacking
•Emotional eating
•TV, computer – cued eating
•Life style interventions
Treatment:
•Initial insulin therapy
•Metformin 500 mg bd with meals