1. In The Name Of God

2. Dr. Zahra Alian Pediatric Endocrinologist
Approach to diabetes mellitus in children and Adolescents
Dr. Zahra Alian
Pediatric Endocrinologist

3. INTRODUCTION
Diabetes mellitus (DM) is a common, chronic, metabolic syndrome characterized by hyperglycemia as a cardinal biochemical feature.

4. INTRODUCTION The major forms of diabetes are classified:
deficiency of insulin secretion due to pancreatic β-cell damage (T1DM)
insulin resistance occurring at the level of skeletal muscle, liver, and adipose tissue, with various degrees of β-cell impairment (T2DM).

5. Diabetes type 1

6. EPIDEMIOLOGY T1DM accounts for about 10% of all diabetes.
It is not limited to childhood.
Approximately 50% of individuals with T1DM present as adults.
Two-thirds of new diagnoses of diabetes in patients ≤ 19 years of age.
Nelson Textbook Of Pediatrics 20th edition 2016

7. CLINICAL PRESENTATION
 Childhood type 1 diabetes can present in several different ways :
Classic new onset
Diabetic ketoacidosis
Silent (asymptomatic) incidental discovery
Nelson Textbook Of Pediatrics 20th edition 2016

8. Classic new onset most common presentation
Symptoms include polyuria, polydipsia, weight loss despite increased appetite initially (polyphagia), and lethargy.
Nelson Textbook Of Pediatrics 20th edition 2016

9. Diabetic ketoacidosis
frequency of DKA as the initial presentation for childhood type 1 diabetes varies from 15 to 67 percent.
Young children (<6 years of age) or from a low socioeconomic background are more likely to have DKA as their initial presentation of type 1 diabetes.
Nelson Textbook Of Pediatrics 20th edition 2016

10. Silent presentation less common
Typically occurs in children who have another close family member with type 1 diabetes
The diagnosis is made based upon an elevated blood glucose concentration.
Nelson Textbook Of Pediatrics 20th edition 2016

11. Criteria for diagnosis DM
Symptom of diabetes + Random plasma Glucose ≥200 mg/dl or
Fasting plasma Glucose ≥126 mg/dl fasting:no caloric intake for at least 8h
2 hr plasma Glucose ≥200mg/dl during an OGTT
OGTT:1.75 g/kg (max 75g)glucose load
HbA1c>6.5
Nelson Textbook Of Pediatrics 20th edition 2016

12. Diabetes Mellitus type 2

13. Introduction
Type 2 diabetes is a progressive syndrome that gradually leads to complete insulin deficiency during the patient’s life.
Lifestyle modification (diet and exercise) is an essential part of the treatment regimen, and consultation with a dietitian is usually necessary.
Nelson Textbook Of Pediatrics 20th edition 2016

14. There is no particular dietary or exercise regimen ,but most centers recommend a lowcalorie, low-fat diet and min of physical activity at least 5 times/ wk.
Nelson Textbook Of Pediatrics 20th edition 2016

15. Commonly observed behaviors
skipping meals
heavy snacking
excessive daily television viewing, video game playing, and computer use.
non–eating (emotional eating, television-cued eating, boredom) and cyclic dieting (“yo-yo” dieting).
Nelson Textbook Of Pediatrics 20th edition 2016

16. Treatment
is frequently challenging and may not be successful unless the entire family buys into the need to change their unhealthy lifestyle.
It is recommended that oral hypoglycemic agents be introduced at the time of diagnosis.
Nelson Textbook Of Pediatrics 20th edition 2016

17. Principles of Diabetic Therapy
Controlled diabetes
Prevention of DKA
Avoidance of hypoglycemia
Providing normal growth by recording height and weight on pediatric growth charts
Prevention of obesity

18. Principles of Diabetic Therapy
Detection of associated diseases
Prevention and treatment of hyperlipidemia
Treatment of hypertension
Prevention of emotional disorders
Prevention of chronic vascular disease

19. Principles of Diabetic Therapy
Prevention of Retinopathy
Treatment of Hypothyroidism
Prevention of Limited joint mobility

20. Insulin Therapy In Diabetes

21. Insulin Types Duration Peak Onset Type 3-4 1 0.25 Lispro Aspart 6-8
2-4
0.5-1
Regular
12-16
1-3
NPH
11-26 NA
Glargine

23. To obtain near-normal glucose control,
Insulin is administered in 2-4 injections daily

24. postprandial hyperglycemia is more strongly associated with cardiovascular risk and mortality than FPG

25. Starting Doses of Insulin (units/kg/day)
NO DIABETIC KETOACIDOSIS
Prepubertal
Pubertal
Postpubertal
Nelson Textbook Of Pediatrics 20th edition 2016

26. Starting Doses of Insulin (units/kg/day)
DIABETIC KETOACIDOSIS
Prepubertal
Pubertal
Postpubertal
Nelson Textbook Of Pediatrics 20th edition 2016

27. Follow-up visits are individualize

28. Insuline syringe
100 unit
50 unit
30 unit

29. Insulin Pen

30. Sites of injection

33. Insulin therapy in type 1 diabetes mellitus

34. Regimen choices Conventional insulin therapy(regular and NPH insulins)
Intensive insulin therapy (three or more injections , insulin pump)
Nelson Textbook Of Pediatrics 20th edition 2016

35. Conventional regimen
NPH at least twice a day (at breakfast and a second dose either at dinner or bedtime)
with a rapid-acting or short-acting insulin two or three times a day
The rapid- or short-acting insulin would be given at breakfast and dinner, lunch
Nelson Textbook Of Pediatrics 20th edition 2016

36. ½-2/3 total daily dose :before breakfast (2/3 NPH & 1/3 rapid- or short-acting insulin)
¼ lunch
1/3-1/4 before dinner or at bedtime (1/3 to 1/2 as rapid- or short-acting insulin and 2/3 to 1/2 as NPH)

37. control of BS is important
This is not a rule
control of BS is important
With twice a day insulin injection we can’t control BG

38. Intensive regimens Multiple daily injections
The basal insulin glargine should be , 25-30% of the total dose in toddlers and 40-50% in older children. , with premeal/snack boluses of rapid- or short-acting insulin
Nelson Textbook Of Pediatrics 20th edition 2016

39. Glargine may be given every 12 hr in young children if a single daily dose of glargine does not produce complete 24 hr basal coverage.
Nelson Textbook Of Pediatrics 20th edition 2016

40. Intensive insulin therapy is recommended for the majority of patients with type 1 diabetes.
Nelson Textbook Of Pediatrics 20th edition 2016

41. Drawbacks to intensive insulin
hypoglycemia (increased up to threefold)
Weight gain
cost (three times )

42. When to start intensive therapy
 Intensive therapy should be started as early as possible following the diagnosis of type 1 diabetes.

43. Insulin pump Should be considered in: Recurrent severe hypoglycemia
Wide fluctuations in BG levels
Suboptimal diabetes control
Microvascular complications and/or risk factors for macrovascular complications.

44. Advantages of continuous subcutaneous insulin :
better glycemic control .
lower A1C and premeal glucose levels
insulin absorption is less variable from day to day
fewer episodes of hypoglycemia
Nelson Textbook Of Pediatrics 20th edition 2016

45. Disadvantages The costs of the pump and supplies are higher
infection at the site of needle insertion
infusion-system failure
diabetic ketoacidosis(more common)

47. Age-specific blood glucose ranges
Target Premeal
<5 years : 100 to 200 mg/dL
5 to 11 years : 80 to 150 mg/dL
12 to 15 years : 80 to 130 mg/dL
16-18years:70-120mg/dl
Nelson Textbook Of Pediatrics 20th edition 2016

48. Ideally, the blood glucose concentration should range from approximately 80 mg/dL in the fasting state to 140 mg/dL after meals.
Nelson Textbook Of Pediatrics 20th edition 2016

49. Target Hemoglobin A1c for Each Age Group
>5 yr yr yr yr
Nelson Textbook Of Pediatrics 20th edition 2016

50. BLOOD GLUCOSE MONITORING
ADA recommends testing of blood glucose at least four times a day.
(fasting & 2 hr after meals)
At 3 AM 3-4×mo

51. PHARMACOLOGIC THERAPY In Diabetes Type 2

52. Introduction weight reduction increased physical activity
adherence to lifestyle modifications
These nonpharmacologic modalities may not be able to successfully meet the targeted glycemic control goal
Nelson Textbook Of Pediatrics 20th edition 2016

53. Indications  
1-In asymptomatic patients who fail to achieve glycemic control three months after the initiation of lifestyle modifications.
2-In patients who are symptomatic at presentation (eg, polyuria and polydipsia), including those with ketosis.
2015 UpToDate

54. Pharmacologic therapy
In these patients, it is important to distinguish type 2 from type 1 diabetes based upon clinical features, presentation, and laboratory studies.
2015 UpToDate

55. Type 1 versus type 2 diabetes
Body habitus — Patients with type 2 diabetes are generally overweight with body mass index >85th percentile for age and gender.
In contrast, children with type 1 diabetes are usually not overweight and often have a recent history of weight loss.
Nelson Textbook Of Pediatrics 20th edition 2016

56. Type 1 versus type 2 diabetes
Age —type 2 diabetes present after the onset of puberty
type 1 disease is bimodal, with a peak between 4 and 6 years and a second at prepuberty or early puberty, between 10 and 14 years of age.
Nelson Textbook Of Pediatrics 20th edition 2016

57. Type 1 versus type 2 diabetes
Insulin resistance :type 2 diabetes frequently have acanthosis nigricans (a sign of insulin resistance), hypertension, dyslipidemia, and polycystic ovary syndrome, which are less likely in children with type 1 disease.
Nelson Textbook Of Pediatrics 20th edition 2016

58. Type 1 versus type 2 diabetes
Family history — Patients with either type 1 or type 2 diabetes can have an affected close relative.
Nelson Textbook Of Pediatrics 20th edition 2016

59. Type 1 versus type 2 diabetes
there is no diagnostic test, type 1 diabetes is suggested by the presence of serum islet-specific pancreatic autoantibodies, glutamic acid decarboxylase (GAD), the 40K fragment of tyrosine phosphatase (IA2), and/or insulin.
Nelson Textbook Of Pediatrics 20th edition 2016

60. Type 1 versus type 2 diabetes
absence of pancreatic autoantibodies does not rule out the type 1 diabetes.
up to 30 percent of individuals with the type 2 diabetes have positive autoantibodies.
Nelson Textbook Of Pediatrics 20th edition 2016

61. Medications Exogenous insulin
Biguanides (metformin) increase insulin responsiveness by improving insulin sensitivity and decreasing hepatic glucose production
2015 UpToDate

62. Medications
Thiazolidinediones, such as rosiglitazone and pioglitazone, also increase insulin responsiveness and may also improve insulin secretion by preserving pancreatic beta cell function
2015 UpToDate

63. Medications
The use of thiazolidinediones are not approved by FDA for pediatric patients with type 2 diabetes.
2015 UpToDate

64. Medications
Sulfonylureas or meglitinides, both of which increase insulin secretion
sulfonylureas can be considered as an alternative to insulin therapy, but it is not currently FDA approved for use in pediatric patients.
2015 UpToDate

65. Medications
Alpha-glucosidase inhibitors (eg, acarbose) that delay the absorption of carbohydrates or lipase inhibitors that reduce the absorption of fat .
2015UpToDate

66. Medications
DPP-IV inhibitors (, sitagliptin) that increase insulin production and decrease the liver's production of glucose
2015UpToDate

67. Medications
Incretin mimetics ( exenatide) that act to increase glucose-dependent insulin secretion from beta cells and help to ensure an appropriate insulin response following ingestion of a meal
2015 UpToDate

68. Medications
Amylin analogs (, pramlintide acetate) that are used to slow gastric emptying and suppress glucagon secretion, which leads to suppression of endogenous glucose output from the liver
2015 UpToDate

69. Medications
Insulin and metformin are the only agents approved by (FDA) for the treatment of type 2 diabetes in children.
2015 UpToDate

70. Insulin therapy & type 2 diabets
 Patients who present with ketosis
severe hyperglycemia (plasma glucose ≥200 mg/dL (and/or A1C >8.5 percent)
Insulin dose may be as high as 2 U/kg per day(insulin resistant).
2015 UpToDate

71. Follow up
Insulin continue until ketosis resolves and plasma glucose returned to normal.
differentiate patients with type 2 diabetes from type 1 diabetes for example:
Absent of islet cell autoimmunity
Fasting C-peptide >0.6 ng/mL
2015 UpToDate

72. Follow up
patients who are euglycemic, can be weaned from insulin and switched to metformin.
If metformin and lifestyle modifications fail to maintain glycemic control , require additional therapy:
Insulin therapy(glargine+metformin)
Metformin plus sulfonylureas
2015 UpToDate

73. Metformin & Diabetes type 2

74. Benefit
In children with type 2 diabetes, metformin is safe and effective
Improving glycemic control
Modest weight loss or, weight stabilization
Reductions in A1C, and fasting plasma glucose
2015 UpToDate

75. Indication
1-Fail to attain glycemic control after three months of lifestyle modifications (weight reduction and increased physical activity).
2-Patients with mild symptoms and mild to moderate hyperglycemia (Metformin concurrently with lifestyle modifications).
2015 UpToDate

76. Indication
3-After plasma glucose approaches normal in patients who present with severe hyperglycemia and/or ketosis and were initially treated with insulin.
2015 UpToDate

77. Side effects Abdominal pain (25 percent)
Nausea and vomiting (17 percent)
Diarrhea
Headaches
2015 UpToDate

78. Side effects It can be minimized by: administering metformin with food
and/or by lowering the dose and increasing it slowly as needed.
2015 UpToDate

79. Contrindication
1- Baseline liver enzymes are greater than 2.5 times the upper limit of normal.
Plane:
insulin therapy should be continued or initiated
liver enzyme measured after three to six months.
2015 UpToDate

80. contraindication 2- Impaired renal function
3- cardiopulmonary insufficiency because it can cause lactic acidosis in these settings.
2015 UpToDate

81. Dose metformin is started of 500 mg, once a day.
Increased by 500 mg twice a day, to a maximum daily dose of 2000 mg given as 1000 mg twice a day.
daily multivitamin, ( compromised absorption of vitamin B12 and/or folic acid )
2015 UpToDate

82. surgery In elective surgery:
stop the metformin 24 hours prior to the surgery and to resume the metformin 48 hours after the procedure.
2015 UpToDate

83. metformin therapy may regain normal menstrual cycles in PCOs, thereby increasing their risk of unplanned pregnancy.
2015 UpToDate

84. Thanks for your Attention