Diabetes Mellitus

April 2014
 Definition

DM is a chronic metabolic disorder of childhood

and adolescence resulting from lack of
insulin or its action
• Characterized by hyperglycemia as a cardinal
biochemical feature
Classification
1. Type I-DM
2. Type II-DM
 TYPE I-DM

Epidemiology
• The most common endocrine metabolic disorder in
children & adolescents
• Bimodal peak age of presentation
– 5-7 years – Time for exposure to infections
– Puberty – ↑ in growth hormone secretion + ↑ gonadal
steroids
• ↑ed incidence in individuals with
HLA – DR3 or HLA – DR4 gene
• Polygenic ( multifactorial) inheritance
 Natural history includes
1. Initiation of autoimmunity
2. Preclinical β-cell autoimmunity with
progressive defect of insulin secretion
3. Onset of clinical diabetes
4. Transient remission “honeymoon period”
5. Established DM
6. Development of complications
 Etiology
 Immunologic damage to the insulin-producing B-cells of the pancreas
 Genetic predisposition – polygenic
 The most important genes are located within the MHC HLA class II
 Genes -HLA- DR3 and HLA-DR4 account for about 60% genetic
susceptibility
 Environmental factors – Trigger autoimmunity
 Viral infections
– Coxsackie B virus
– Mumps
– CMV
– Rubella virus
 Environmental factors
• Pathogens can precipitate the self-reactive
process by 3 mechanisms.
1. Molecular mimicry b/n viral proteins & self-
proteins
2. Antigen presenting cells present the self-
peptides to T cells
3. Cytokines secreted during viral infection up-
regulate the expression of co-stimulatory
molecules
 Cont,
• Prenatal infection with rubella is associated
with β-cell autoimmunity in up to 70%, with
development of T1DM in up to 40% of
infected children
• Pubertal changes may contribute to
accelerated onset of type 1 DM in genetically
susceptible individuals
 Pathogenesis
Autoimmune Injury
• T cell–mediated autoimmune destruction of the
pancreatic islets
• Genetic predisposition & environmental factors lead to
initiation of the autoimmune process
• Anti–islet cell antibodies (GADA, ICA,IA, and IAA)
before the onset of diabetes
• Gradual and progressive destruction of β cells ,and at
the onset of clinical diabetes 80–90% of the pancreatic
islets are destroyed
The autoimmune response against pancreatic
β cells consist of 4 phases:
Proposed model of the pathogenesis & natural
history of T1DM
IAA- insulin auto ab
GADA- glutamic acid decarboxylase ab
ICA- islet cell ab
IVGTT- IV glucose tolerance test
 Pathophysiology
• Hyperglycemia – Osmotic diuresis (glycosuria)
→ polyuria & Polydipsia
• Lack of glucose utilization by the body
→ Polyphagia
• Mobilization of fat from adipose tissues and excess
free fatty acid production that are converted to
ketone bodies
– Ketonemia
– Ketonuria
 Cont,
• Impaired Protein synthesis resulting in
Weight loss
Muscle wasting
Growth retardation
• Loss of calories, electrolyte & persistent DHN due to polyuria
 physiologic stress
 hyper secretion of counter– regulatory hormones
 impair insulin secretion (Epinephrine)
antagonizing its action (epinephrine, cortisol, GH)
 Cont,
Insulin deficiency + Counter- regulatory hormones result in

• Excess free fatty acid accumulation due to

– Accelerated lipolysis and
– Impaired lipid synthesis

• Insulin deficiency and glucagon excess shunts FFA in to

ketone bodies(Acetoacetate, ß– hydroxybutyrate)

• Accumulation of these ketone bodies results in metabolic

acidosis ( DKA)
 Cont,
• Acetone formed from Acetoacetate →Fruity odor of
breath

• Compensatory rapid, deep breathing to excrete excess CO2

/ kussmaul respiration

• Hyperglycemia causes
• Movement of water out of cells
→ Intracellular DHN
→ Extracellular fluid expansion and hyponatremia
Effect of changes
 Clinical Manifestation
Symptoms of hyperglycemia
– Polyuria/nocturia , polydipsia, polyphagia
– Weight loss
– Recurrent infections /Candidiasis/
– May present initially with DKA up to 20% of the
cases
 Laboratory
• RBS ≥ 200mg/dl
• FBS ≥126 mg/dl or

• U/A
– Glucosuria
– Ketonuria
 Cont,
CBC (Hgb A1C)
Serum electrolyte
– Hypokalemia
– Hypophosphatemia
– Serum Bicarbonate – low
– PH – low in DKA
– Antithyroid peroxidase and antithyroglobulin
antibodies
Criteria for Impaired Glucose Tolerance &
DM
 Complications

Acute

– DKA
– Hypoglycemia
– Infection
– Cerebral edema
 Chronic complications
1. Microvascular complications
-Due to glycation of tissue proteins resulting in vessel wall
thickening
-Retinopathy
-Nephropathy
2. Macrovascular complications
– Coronary artery disease
– Cerebrovascular disease
– Peripheral vascular disease
 Diabetic Ketoacidosis(DKA)
• End result of metabolic abnormalities from severe
deficiency or effectiveness of insulin
• Leading cause of morbidity & mortality in Type I-DM
• Occurs in 20–40% of children with new-onset DM
Risk factors
• Initial presentation
• Infection & other medical illnesses
• Insulin omission/poor control
• Previous DKA
 Clinical

• Poly Symptoms
• Profound dehydration
 Hypotension
 Sunken eyes
 Dry mucosa
 Lethargy – coma
• Kusmaul respiration
 Diagnosis
Biochemical data
• Hyperglycemia
• Venus PH < 7.3 and / or
• Venous bicarbonate < 15 mmol/L
• Urinary ketone ≥ 3+
• Glycosuria
• Ketonemia
• Hyponatremia
• Hypophosphatemia
 DKA Classification
Parameter Normal Mild Moderate Severe

Bicarbonat 20-28 16-20 10-15 <10

e
(mEq/L)
(Venous)
PH 7.35-7.45 7.25-7.35 7.15-7.25 <7.15

Clinical No •Oriented •Kusmaul •Kusmaul

Change •Alert breathing breathing
•Fatigued •Lethargic •Depressed
Sensorium
to coma
 Management
Goals
 To maintain balance b/n tight glucose control & avoiding
hypoglycemia
 To prevent ketoacidosis
 To permit normal growth & development with minimal
effect on lifestyle
Principles of Rx
 Initiation & adjustment of insulin
 Health education
 Reestablishment of the life routines
 New onset DM without DKA

Initial daily insulin dose

 usually higher in pubertal children, & in those who
have to restore greater deficits of body glycogen,
protein, & fat stores
 In the “honeymoon” period reduces exogenous
insulin
 0.7 U/kg/d if prepubertal
 1.0 U/kg/d at midpuberty, and
 1.2 U/kg/d by the end of puberty
 Insulin Schedule
 2/3 of insulin in morning subcutaneous (SC)
 1/3 of insulin evening subcutaneous
 For better glycemic control
Regular insulin 1/3 of dose
Lente insulin 2/3 of the dose

Monitoring
 Frequent blood glucose monitoring
 Insulin dose adjustment
 How insulin works

• Insulin opens the door for glucose to enter the

cells
• It stimulates the storing of glucose in the liver
• It stimulates the development of fat from
excess carbohydrates
• And it stimulates the development of protein
compounds in the body
 Diabetic Ketoacidosis
Management
1. Correction of shock
2. Correction of dehydration
3. Correction of hyperglycaemia
4. Correction of deficits in electrolytes
5. Correction of acidosis
6. Treatment of infection
7. Treatment of complications
 Cont,
Fluid replacement
– Severe DKA - Deficit ~10% of body wt(100ml/kg)

– Total 24 hr fluid =deficit plus maintenance

– IV Rate (85ml/kg +Maintenance) - Bolus
23 hours
- Bolus= 20ml/kg of RL/NS 1st hour
- The remaining over the next 23 hrs
- Change IV fluid to 0.45 NS in 5% glucose
solution; when RBS <300mg/dl
 Insulin therapy for DKA

 Intermittent regular insulin administration based on

blood glucose values, determined every 2-4 hrs
 Insulin infusion of any short acting insulin at
0.1U/kg/hour (0.05 U/kg/hr if younger than 5 years)
 Do not correct glucose too rapidly. Aim for decrease
of 5 mmol/l per hour
 Example:-A 24 kg child will need 2.4 U/hour, Put 24
U short acting insulin into 100 ml saline and run at
10 ml/hour
 Transition to oral intake and subcutaneous insulin:

 When DKA has essentially resolved (HCO3 >15 mEq/L;

pH >7.30; sodium stable between 135 and 145 mEq/L;
no emesis) and blood glucose level is below 250-
300mg/dl
 Regular insulin 0.2 – 0.4 u/kg/dose q 6 -8 hrs for 24 – 48
hrs
 Monitoring
-RBS at least 6 hourly
-Urinary ketone
- Clinical response
 Cont,
• DKA usually corrected in 36 – 48 hrs
• Then combine therapy with Lente + Regular insulin
Dosage
• 2/3 of the past 24 hrs regular insulin dose
– 2/3rd of total dose morning
_1/3 of total dose evening
• Regular insulin 1/3rd
• Lente insulin 2/3rd -Given subcutaneously
 Complications during treatment

Hypoglycemia – RBS < 60mg/dl

Characterized by
Palpitation, sweating, tremor
Dizziness, weakness
Pallor, vomiting
Anxiety, confusion ,convulsion, coma
 RX
– Sweet drinks
– Glucose solution
– Glucagons – in severe cases
 Other complication during treatment

• Electrolyte imbalance
• Brain edema
• Fluid over load
• Hyponatremia
 Other related events
Somogyi phenomenon
Hypoglycemia induced morning hyperglycemia
Due to larger doses of evening insulin and an
exaggerated counter-regulatory response

Dawn phenomenon
 Morning hyperglycemia with out preceding
hypoglycemia
 Is due to overnight growth hormone secretion and
increased insulin clearance
 Cont,
Brittle diabetes
- Marked fluctuation of blood glucose often with
recurrent DKA despite frequent insulin dose
adjustment
Hypoglycemia
Hyperglycemia and ketosis
 Diet Managment

• Nutritionally balanced diet with adequate

calories and nutrients for normal growth
• Diabetic diet should contain
– Carbohydrate ……………. 50%
– Fat ……………………………..30%
– Protein ……………………….20 %
– Avoid readily absorbable refined carbohydrates
 Cont,
Exercise : -To improve metabolic control
-To lower insulin requirement
Patient and parent education
Diabetic diet
Insulin injection, dose, storage and
complications of insulin
Home blood sugar monitoring
Understanding symptoms and signs of
hyperglycemia and hypoglycemia
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