Type 1 Diabetes in children

1. Diabetes Mellitus
in Children
Dr. C.S.N.Vittal

2. Definition
Diabetes a chronic metabolic disorder characterized by
hyperglycemia
as a cardinal biochemical feature, caused by
deficiency of insulin or its inaction,
manifested by
abnormal metabolism of
carbohydrates, protein and fat.

3. Historical
Symptoms of DM were first mentioned in the ‘Ebers’ papyrus (about 1550 BC)
‘Diabetes’ (siphon/diuresis) first used by the Turkish physician Aretaeos of Capadokia
(ad 130–200)
The sweetness of diabetic urine (‘mellitus’ = sweet), first mentioned in 6th century
by Thomas Willis (1674)
Matthew Dobson (1775) showed that the sweet taste was due to sugar and that
serum also tasted sweet
Von Mering & Minkowski showed that total pancreatectomy resulted in DM
The discovery of insulin by Banting and Best in 1922

4. Types of Diabetes mellitus
(β-cell destruction, usually leading to absolute insulin deficiency)
Type 1A :- Immune mediated (with islet cell antibodies)
Type 1B: - Idiopathic. Without autoantibodies
Type 1
Predominantly insulin resistance with relative insulin deficiency OR a
predominantly secretory defect with insulin resistance
Type 2
Type 3
Type 4
Proposed to describe the hypothesis that Alzheimer’s disease, is triggered
by a type of insulin resistance and insulin-like growth factor dysfunction that
occurs specifically in the brain
New proposal - is associated with older ageNot Final

5. Types of Diabetes Mellitus - Other Specific types:
• Genetic defects in b cell function: MODY, Neonatal DM, Mitochondrial disorders
• Genetic defects in insulin: Insulin receptor defects, Type A insulin resistance
• Exocrocrine pancreatic diseases: Pancreatitis, cystic fibrosis, hemochromtosis
• Drug / chemical induced: Steroids, diagoxide, phynetoin, interferon, L-
asparaginase,
• Immune mediated
• Endocrinopathies: Growth hormone excess, Cushing’s syndrome,
hyperthyroidism
• Infections: CMV, Coxsackieviruses
• Gestational diabetes
• Neonatal diabetes

6. Type I DM
• Commonest form in children
• Insulin deficiency due to damage to beta cells
• Needs lifelong insulin replacement
• Characterized by autoimmune destruction of pancreatic
islet β-cells.
• Both genetic susceptibility and environmental factors
contribute to the pathogenesis.

7. Type I DM - Incidence
• Incidence in India - 10.5/100,000/year.
• Peaks of presentation occur in 2 age groups:
• at 5-7 yr of age (infectious) and
• at the time of puberty (gonadal steroids ).
• Risk is higher, if the affected parent is father (7% compared to 4%, if
mother is affected).
• Identical twins, concordance rates of only 30-40%
• Known associations include the HLA DR3/4-DQ2/8 genotype, HLA-B39

8. T1DM - Stages
Preclinical β-cell autoimmunity with progressive defect of insulin secretion1
Onset of clinical diabetes,2
Transient remission “honeymoon period,”3
Established diabetes during which there may occur acute and/or chronic
complications and decreased life expectancy.
4

9. T1DM - The Hygiene Hypothesis
• Lack of exposure to childhood infections
may increase an individual's chances of
developing autoimmune diseases,
including T1DM
• Decreased exposure to certain parasites
and other microbes in early childhood
may lead to an increased risk of
autoimmunity in later life, including
autoimmune diabetes.

10. T1DM - Pathogenesis
Genetic susceptibility (predisposed individuals)

Environmental factors like seasonal infections,
dietary factors cowmilk protein exposure, drugs

Leading to insulitis (autoimmune disease)

B cell damage

Insulin def & Glucose intolerance

Overt diabetes

11. Physiology of Insulin
1. Reduces blood glucose by:
• i Gluconeogenesis
• i Glycogenolysis
• h Uptake of glucose by cells
2. Inhibits fat breakdown (lipolysis)
3. Inhibits protein breakdown (protolysis)

12. T1DM - Pathophysiology
• At even lower insulin levels, the liver produces excessive glucose via glycogenolysis and
gluconeogenesis, and fasting hyperglycemia begins.
• Hyperglycemia produces an osmotic diuresis (glycosuria) when the renal threshold is
exceeded (180 mg/dL; 10 mmol/L).
• The resulting loss of calories and electrolytes, as well as the worsening dehydration,
produces a physiologic stress with hypersecretion of stress hormones
• Insulin deficiency and elevated plasma values of the counter regulatory hormones is also
responsible for accelerated lipolysis and impaired lipid synthesis, with resulting increased
plasma concentrations of total lipids, cholesterol, triglycerides, and free fatty acids.
• Insulin deficiency and glucagon excess shunts the free fatty acids into ketone body
formation

13. T1DM - Presentation
Ketotic onset : DKA ; more common
• - 20- 40% present
 Non Ketotic onset
• Most symptoms are nonspecific >>

14. T1DM - Non Ketotic onset : 3 - Ps
Polyuria Polydypsia Polyphagia

15. T1DM - Non Ketotic onset:
Weight loss Nausea & Vomiting Fatigue

16. T1DM - Non Ketotic onset:
• Recurrent infection: skin or UTI, Vulval moniliasis in female children

17. Diabetes: Diagnostic Criteria
American Diabetes Association’s (ADA) criteria
# polyuria, polydipsia, and unexplained weight loss with glucosuria and ketonuria.
• Standards in Medical Care of Diabetes-2017. Diabetes Care 40 (Suppl 1):S11–S24, 2017
• ≥ 126 mg/dL (7.0 mmol/L)
• ≥ 200 mg/dL (11.1 mmol/L)
• ≥ 200 mg/dL (11.1 mmol/L)
• ≥ 6.5% (48 mmol/mol)

18. Other Labs
•Ketone testing: either urine strips, or blood.
•Urine: glucosuria & Ketonuria if DKA suspected.
•TSH & thyroid antibodies
•Serological markers: GAD, IA-2, IA- 2β, or insulin
autoantibodies, islet cell antibodies
•Gene studies: HLA typing

19. T1DM - Management - Goals
1. Medical management of glycemic control – Insulin Therapy
2. Age adapted structured education
3. Psychosocial care of the family affected
4. Avoidance of acute complications
5. Prevention of chronic complications
Teamwork approach with paediatrician / endocrinologists, diabetic nurse educator, social worker and nutritionist is essential.

20. (NPH)
(glargine, detemir, deglutec)
(lispro, aspart, glulisine)

21. T1DM - Insulin Therapy
• Dose (Subcutaneous):
• For prepubertal children : 0.6 unit/kg/day
• For Pubertal children : 1.0 - 1.2 unit/kg/day
• Post pubertal children : 1.0 unit/kg/day
• In the post-ketoacidosis phase : 2 - 2.5 unit/kg/day

22. T1DM - Insulin Therapy - Regimen
• Intermediate- (NPH) or
long acting insulin
(glarglne or detemir) is
given before dinner or
at bedtime (40-50% of
total daily dose;
• Short-acting Insulin
(aspart or llspro) is given
before each meal (50-
60% of total dally dose;

23. T1DM - Insulin Therapy - Regimen
• Insulin Is given before breakfast
(two-thirds of daily dose) and
dinner (one-third of dally dose).
• Each Injection Is a combination
of Intermediate- or long-acting
(NPH or detemir; two-thirds of
the total dose and short-
(regular) or rapid-acting Insulin
(llspro or aspart. one-third of
the total dose
• Regular meal pattern Is required
to prevent hypoglycemia

24. T1DM - Insulin Therapy –
Modified mixed spilt regimen
• Night-time intermediate-
acting Insulin has been shifted
from before dinner to
bedtime.
• This Is indicated In the
presence of nocturnal
hypoglycemia and high pre-
breakfast blood glucose levels.

25. Insuine administering syringes / pens

26. T1DM - Insulin Therapy –
Contentious subcutaneous insulin infusion
(Infusion pump):
• An external device that infuses insulin at
a predetermined rate with additional
boluses given at mealtime. The basal
dose can be adjusted for different times
of the day and boluses tailored to
different amount and types of meals to
provide good glycemic control with
limited glycemic variability.

27. T1DM - Therapy: Newer Advances
• Islet cell transplantation:
• Edmonton protocol: islets cells isolated from pancreas of cadavers are perfused
percutanoeusly into the portal vein, has the advantage of being a minimally invasive
procedure
• Artificial pancreas:
• Include a CGM that is in constant communication with an infusion pump, with a blood
glucose device (eg, a glucose meter) utilized for CGM calibration. An external processor,
such as a cell phone, runs control algorithm software,
• Adjunctive therapies to insulin
(i) insulin sensitizing agents (e.g. biguanides and thiazolidinediones)
(ii) medications altering GI nutrient delivery (e.g., acarbose and amylin)
(iii) other targets of action [e.g., pirenzepine, insulin-like growth factor-1 (IGF-1), or
glucagon like peptide-1

28. 1
2
3
4
5
6
7
8
Education about
diabetes
Differences between
Type 1 & Type 2 DMs
Role of Insulin as life
saving medicine
Skills of insulin
storage, drawing and
mixing insulins
Healthy eating
Hypoglycaemia –
recognition and
management
Honeymoon phase
Sick day guidelines
T1DM - Diabetes Education

29. T1DM - Nutritional Management
• There is No diabetic diet for children
• Avoid overzealous control
• Children encouraged to have healthy normal diet
• Importance given to consistency of meal timings
• Dietary exchanges and Nutrition Pyramid approaches are
useful
• Occasional treats during special occasions and eating are
allowed

30. Nutrition – Age related glycemic targets
Target < 6 years 6 – 12 years > 12 years
Blood Glucose
Premeal
Bedtime
100-180 mg/dL
110-200 mg/dL
70-180 mg/dL
100-180 mg/dL
70-130 mg/dL
90-140 mg/dL
HbA1c < 8% < 7.5% < 7.5%

31. T1DM - Monitoring
• Blood Glucose monitoring
• Self monitoring of blood glucose (SMBG) is critical: Ideally
before each meal and at bed time
• Post meal and midnight blood sugars are required
• Continuous blood glucose monitoring (CGMS): for children
with significant glycemic variability
• HbA1c: every 6 - 12 weeks - a marker of glycemic control over
previous 3 months and is the best predictor of long term
complications.

32. T1DM - Monitoring

33. T1DM - Monitoring

34. T1DM - Monitoring
 HbA1c: A marker of glycemic control over previous 3 months and is the best
predictor of long term complications: every 6 - 12 weeks -
 Microalbuminuria: Once an year from age 11 or 5 yrs after diagnosis
 Retinal examination: Every 1-2 yrs from age 11 or 5 yrs after diagnosis
 Nerve conduction studies: Once an year from age 11 or 5 yrs after diagnosis
 Blood pressure: every 3 months – at least annually from age 11
 Hyperlipidaemia: during first year after diagnosis; very 5 years before
puberty; then every 2 years
 Thyroid function studies
 Growth monitoring: Every visit
 Dental examinations every 2 years

35. T1DM
Honeymoon Phase
Somogyi Phenomenon
Dawn Phenomenon
Management during Infections
Diabetic Ketoacidosis
Special
Considerations

36. Type 1 DM : Special Considerations
• Insulin requirements can decrease transiently following
initiation of insulin treatment.
• Treatment by reduce the dose of Insulin accordingly.
Honeymoon
Phase

37. Type 1 DM : Special Considerations
• In children with Normal dose of Insulin at
Night & Normal midnight glucose
(Normoglycemia),
• Overnight growth hormone & increased
insulin clearance may normally leads to early
morning modest Hyperglycemia.
Treatment: Increase the dose of Long acting
Insulin at Night .
Dawn
Phenomenon

38. Type 1 DM : Special Considerations
• In children with High dose of Insulin at night (Long
acting) > develop late night (3-4 am) Hypoglycemia
• Exaggerated counter regulatory hormones respons
will increase > Early morning Hyperglycemia.
Treatment: Reduce the dose of Long acting Insulin at
Night .
Somogyi
Phenomenon

39. Type 1 DM : Special Considerations
During Infections: Sick Day Care
• Frequent blood glucose monitoring
• Regular fluid intake
• Treatment of intercurrent illness
• Tailoring insulin dosage (increasing dose by
10-15%) for milder infections
• Monitoring blood ketone levels
• Sever infection necessitate hospitalization
Management during
Infections

40. Type 1 DM : Special Considerations
• When to suspect?
• Acute abdomen
• Encephalopathy
• Severe Dehydration / GE
• Sepsis
• Starvation
D K A

41. T1DM - Complications
 Hypoglycemic episodes – with treatment
 Neuroglycopenic symptoms –
 lethargy, irritability, seizures, coma,
 Adrenergic symptoms –
 Tachycardia, sweating, palpitations
 Treatment with Glucose / glucagon
 Diabetic Keto acidosis
 Lipoatrophy – at injection sites

42. T1DM - Long Term Sequalae
 Microvascular - retinopathy, nephropathy
 Macrovascular - cerebrovascular, peripheral vascular, coronary artery
disease
 Neuropathy - Peripheral and autonomic
 Cataract
 Restriction of joint mobility
 Thyroid disease
 Coeliac disease

43. Type 2 DM
 Increasingly encountered in children
 Look for obesity and acanthosis nigricans
 Normal C-peptide levels
 Lack of glutamic acid decarboxylase (GAD) antibodies
 Needs life style modification
 May need insulin along with biguanides
 Children at risk – should be screened regularly

44. Type 2 DM
An oral glucose tolerance test for early recognition of type 2 diabetes
should be conducted for all overweight children (BMI > percentile 90)
of age 10 or older who have two or more of the following risk factors:
• A close blood relation has type 2 diabetes
• Membership of a group with elevated risk (e.g.EastAsians,Afro-Americans,
Hispanics)
• Extreme obesity (BMI > Percentile 99.5)
• Signs of insulin resistance or of changes associated with it (arterial
hypertension, dyslipidaemia, elevated transaminases, polycystic ovary
syndrome, acanthosis nigricans).

45. Type 2 DM
Obesity - Acanthosis nigricans

46. Maturity Onset Diabetes of Young (MODY)
• A group of inherited conditions characterized by impaired cell
function.
• Relatively mild, non-ketotic diabetes in lean individual with
strong family history of diabetes affecting three generations.
• Responds to life style measures and low doses of sulfonylurea.

47. Differences between Type 1 and Type 2 DMs
Feature Type 1 Type 2 MODY (monogenic)
Onset Sudden Gradual Insidious
Age of onset Mostly children Mostly adults Post-pubertal
Prevalence ~ 10% ~90% < 5%
Body habitat Thin / Normal Often obese Normal
Ketoacidosis Common Rare Rare
Autoantibody Usually present Absent Absent
Endogenous insulin Low or absent Normal, decreased or
increased
C – peptide levels Low High, normal Low, normal
Management Insulin Diet, Metformin Diet, Sulfonylurea
Inheritance Polygenic Polygenic Autosomal dominant

48. Dr CSN Vittal
World Diabetes Day
14th November