1. Treatment of Type 1 diabetes
Dr. Amir Babiker
MBBS, FRCPCH (UK), CCT (UK)
Consultant Paediatric Endocrinologist, KKUH
and Assistant Professor, King Saud University

2. DM A metabolic disorder of multiple aetiologies characterized by:
Chronic hyperglycemia
Disturbances of CHO, fat and protein metabolism
Defects of insulin secretion, insulin action or both.

3. Diagnostic Criteria DM ≥11.1 (≥200) ≥7.0 (≥126) ≥ 6.5
Diabetes mellitus is characterized by recurrent or persistent hyperglycaemia, and is diagnosed by demonstrating any one of the following:[
Condition
2 hour glucose
Fasting glucose
HbA1c
mmol/l(mg/dl) %
Normal
<7.8 (<140)
<6.1 (<110)
<6.0
Impaired fasting glycaemia
≥ 6.1(≥110) & <7.0(<126)
6.0–6.4
Impaired glucose tolerance
≥7.8 (≥140)
<7.0 (<126) DM
≥11.1 (≥200)
≥7.0 (≥126)
≥ 6.5
OR Symptoms of hyperglycaemia and casual plasma glucose ≥ 11.1 mmol/l (200 mg/dl)
A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above methods on a different day.

4. Types of DM T1DM (IDDM, Juvenile DM): Autoimmune, idiopathic
T2DM (NIDDM, Adult onset):Obesity, Acanthosis nigricans, FH.
Gestational DM
Other: Monogenic, congenital, neonatal, 2ry..etc

7. Map of published incidence rates (per ) of type 1 diabetes in children. Source: Solte´sz et al. (2). Childhood type 1 diabetes Pediatric Diabetes 2007: 8 (Suppl. 6): 6–14

11. Management Goals Prevent death & alleviate symptoms
Achieve biochemical control
Maintain growth & development
Prevent acute complications
Prevent or delay late-onset complications

12. Management Components
Insulin:
Regular and NPH (1/3 and 2/3)
Analogues (Mixed, ultra short, Detemir & Glargine)
Insulin pumps (CSII): Open and closed loops.
Support:
Education: CHO counting, I:CHO, Self care & injections, hypos management, Sick day rules
Psychological
Annual review: Examination, Invx: Blood and urine, Eye
Life style:
Diet (CHO = %, Fats: < 30%, Proteins 10 – 20%)
Sensible exercise

13. Concepts Honeymoon phase or partial remission:
weeks to 2 years, due to B cell hyperplasia.
Early morning hyperglycaemia: with NPH & Regular (Somogyi & Dawn phenomena)
Sick day rules:
Check Blood sugar every 2-4 hrs
Check ketones
Drink plenty of fluids
Need extra insulin to clear ketones
Never omit insulin
Hypoglycaemia may be a problem especially in young children

14. DKA Children with T1DM who have: Hyperglycaemia (BG >11 mmol/l)
pH < 7.3
Bicarbonate < 15 mmol/l
With ketonaemia and/ or ketonuria.
and who has:
Acidotic respiration, dehydration, drowsiness and/or
abdominal pain/vomiting

15. DKA
They can die from :
Cerebral oedema: This is unpredictable, occurs more frequently in younger children and newly diagnosed diabetes and has a mortality of around 25%.
Hypokalaemia: This is preventable with careful monitoring and management
Aspiration pneumonia: NGT.

16. Hypoglycaemia Target blood glucose: 4 – 8 mmol/l.
Treat all blood glucose below 4 mmol/l to avoid hypo unawareness.
Symptoms:
Sympathetic: pallor, tachycardia, sweating, tremors
Neuroglycopoenic: irritability, headache, nausea, seizure, stupor, coma

17. Hypoglycaemia Causes: Treatment:
Missed or delayed meal
Exercise
Alcohol
Overdose of insulin
Impaired food absorption (CD)
Addison’s disease
Treatment:
Oral CHO: glucose tabs, gel and fluids
I/M glucagon
10% Dx 2 ml/kg bolus

18. Modern Management “Optimized” or “Intensive” therapy.
Physiological insulin replacement
Assessment of glycaemic control (SMBG)
Hospital tests (HbA1c, …etc)
Insulin dosage adjustment
Healthy diet
Diabetes education

19. T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.
Intensive Therapy for Diabetes: Reduction in Incidence of Complications
T1DM
DCCT
T2DM
Kumamoto
UKPDS
A1C
9% → 7%
8% → 7%
Retinopathy
63%
69%
17%–21%
Nephropathy
54%
70%
24%–33%
Neuropathy
60%
58% –
Cardiovascular disease
41%*
52*
16%*✝
Review Data
T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.
*Not statistically significant due to small number of events.
†Showed statistical significance in subsequent epidemiologic analysis.
DCCT Research Group. N Engl J Med. 1993;329: ; Ohkubo Y, et al. Diabetes Res Clin Pract. 1995;28: ; UKPDS 33: Lancet. 1998;352: ; Stratton IM, et al. Brit Med J. 2000;321:

20. Elements of Intensive therapy
Multiple-component insulin regimen
Careful balance of food intake, activity, and insulin dosage
Daily self-monitoring of blood glucose (SMBG)
Patient adjustments of food intake and insulin dosage and use of insulin supplements according to predetermined plan
Defined target blood glucose levels (individualized)
Frequent contact between patient and staff
Patient education and motivation
Psychological support
Assessment (HbA1c and annual review)

21. Representative target blood glucose levels suitable for young otherwise healthy patient
Ideal
mg/dl (mM)
Acceptable
mg/dl (mM)
Preprandial
( )
( )
1-h postprandial
( )
( )
2-h postprandial
( )
( )
2-4 h postprandial
( )
( )

22. Insulin
Since the discovery of insulin less than 100 years ago, diabetes treatment and technology have come a long way in helping people with diabetes manage their disease.

25. Type Product Brand Rapid-Acting Lispro Aspart Glulisine Humalog
Types of Insulin JAMA 2003;289: Clin Pharmacology Online, 2009
Type
Product
Brand
Rapid-Acting
Lispro
Aspart
Glulisine
Humalog
Novolog
Apidra
Short-Acting
Regular “R”
Humulin, Novolin, ReliOn
Intermediate-Acting
NPH “N”
Basal
Glargine
Detemir
Lantus
Levemir
Premixed
70/30 regular
75/25 lispro
70/30 aspart
50/50
Humalog 75/25
Novolog Mix 70/30
Humulin, Humalog

26. Comparison of Human Insulin and Analogues JAMA 2003;289:2254-64
Comparison of Human Insulin and Analogues JAMA 2003;289: Clin Pharmacology Online, 2009
Insulin
Preparations
Onset of
Action
Peak
Duration
of Action
Lispro, Aspart,
Glulisine*
5-15 min
30-90 min
4-6 h
(*6-8 h)
Regular
30-60 min
2-4 h
6-10 h
NPH
1-2 h
4-8 h
10-20 h
Glargine
None
24 h
Detemir
6-8 h
12-24 h

30. Principles of Management
Relationship with the patients/families:
Communication: Education – Motivation –Support
Dose or treatment changes
Basic concepts:
Insulin analogues - basal bolus regimen
CHO Counting
I:CHO ratio
IS (CF)

31. Insulin regimens Once daily insulin (NPH or basal)- partial remission
Twice daily
Three times a day
4 times a day
Continuous subcutaneous insulin infusion (CSII)
Closing the loop (Artificial pancreas)

32. Twice daily regimens

33. 3 times/day regimen

34. 4 times/day regimen

36. Basal bolus regimen
This is the most intensive regime with three pre-prandial doses of short /rapid acting insulin and a bedtime dose of intermediate or long acting insulin. While this regime offers no improvement in metabolic control compared to any other insulin regime, this may be the most suitable regimen for people who do not have a stable daily routine as the time and dose of insulin can be varied according to when the meal is taken and its carbohydrate content.
Generally % of the total daily insulin requirements should be given as intermediate or long acting insulin at bedtime with the remaining insulin being given as short / rapid acting before breakfast, lunch and evening meal depending on the needs of the individual.

37. Dose adjustment Premixed/Biphasic insulin (2/day)
Blood Testing
Times
Blood Glucose
<4mmol/l
Or Hypo
Blood
Glucose
4-7 mmol/l
8 – 14 mmol/l
>15mmol/l
Before Bed
and Before
Breakfast
Reduce
Evening meal
insulin
by 4 units
Optimal
Increase
by 2 units
Before Lunch
Evening Meal
morning insulin

38. Dose adjustment - MDI Blood Testing Times Blood Glucose <4mmol/l
Or Hypo
Blood
Glucose
4-7 mmol/l
8 – 14 mmol/l
>15mmol/l
Before
Breakfast
Reduce bedtime intermediate insulin by 4 units
OPTIMAL
Increase bedtime intermediate /long insulin by 2 units
Increase bedtime intermediate /long insulin by 4 units
Lunch
Reduce morning short acting insulin by 2-4 units
Increase morning short acting insulin by 2 units
Increase
morning short acting insulin by 4 units
Evening
Meal
Reduce lunchtime short acting insulin by 2-4 units
Increase lunchtime short acting insulin by 2 units
Increase lunchtime short acting insulin by 4 units
Supper/
Bedtime
Reduce Evening meal short acting insulin by 2-4 units
Increase evening meal short acting insulin by 2 units

39. General Advice on Insulin Dose Adjustment
Insulin may need adjusting for exercise, meal composition, patterns in blood sugar levels, during illness and weight loss or gain episodes.
Do not adjust dose on a “single” raised blood glucose.
Adjust according to the chart above and monitor for at least 48 hours to judge the effect before further adjustment
Blood glucose target range should be set Individually for each patient.
Dose adjustment is individualized and needs to be monitored closely.
Patients should be educated to adjust their own insulin
Document change of insulin dose in the nursing notes.
If problems persist in controlling the blood glucose level seek advice from the Diabetologist.

40. Insulin Pumps (CSII)

43. Type 1 diabetes – children/adolescents
Current technologies
Insulin analogues
Fast acting: lispro, aspart, glulisuline
long acting (basal): glargine, detemir, Degludec
Insulin pump therapy (CSII)
Continuous Glucose Monitoring systems (CGMS)
Insulin dose delivery & adjustment strategies
Patient education/empowerment tools
SMBG + basal/bolus therapy
CHO counting techniques (DAFNE: Dose Adjustment for Normal Eating)
Insulin sensitivity

44. New approaches to the management of Type 1 diabetes
• Limitations of current treatment approaches
• Future therapy options:
Immune manipulation/modulation
Optimizing Sc insulin delivery
Optimizing Sc insulin action

45. Challenges Non-availability of insulin in poor countries
injection sites & technique
Insulin storage & transfer
Mixing insulin preparations
Insulin & school hours
Adjusting insulin dose at home
Sick-day management
Recognition & Rx of hypo at home

47. Thank You