Type 2 Diabetes in Children

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Type 2 Diabetes in Children
Dr. Abdulmoein Al-Agha, MBBS,DCH,CABP, MRCP(UK)
Consultant, Pediatric Endocrinologist, King
AbdulAziz University Hospital, Jeddah.
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• Diabetes mellitus type 2
• Is a metabolic disorder that is primarily
  characterized by insulin resistance, relative
  insulin deficiency hyperglycemia
• It is rapidly increasing in the developed world
• Has characterized the increase as an epidemic
• Unlike type 1 diabetes, there is little tendency
  toward ketoacidosis in Type 2 diabetes, though it
  is not unknown
• Complex and multi-factorial metabolic changes
  lead to damage function impairment of many
  organs, most importantly the cardiovascular system

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Criteria for the Diagnosis of Diabetes

• Symptoms of diabetes plus random plasma glucose
  concentration ? 200 mg/dl (11.1 mmol/l).
• The classic symptoms of diabetes include
• polyuria, polydepsia, and unexplained weight
  loss.
• OR
• FPG ? 126 mg/dl (7.0 mmol/l).
• Fasting is defined as no caloric intake for at
  least 8 h.
• OR
• 2-h PG ? 200 mg/dl (11.1 mmol/l) during OGTT
• The test should be performed as described by W HO
  using a glucose load containing equivalent of
  75-g anhydrous glucose dissolved in water.

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• Pathophysiology
• Insulin resistance means that body cells do not
  respond appropriately when insulin is present
• Other important contributing factors
• increased hepatic glucose production (e.g., from
  glycogen degradation), especially at
  inappropriate times
• decreased insulin-mediated glucose transport in
  (primarily) muscles adipose tissues (receptor
  and post-receptor defects)
• impaired beta-cell functionloss of early phase
  of insulin release in response to hyperglycemic
  stimuli

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Underlying causes of type 2 diabetes
Insulin resistance
Hyperinsulinaemia
?-cell defect
Impaired glucose tolerance
Decreased insulin secretion
Obesity
Early diabetes
?-cell failure
Late diabetes
Adapted from Saltiel AR. J Clin Invest
2000106163164.
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Obesity Type 2 Diabetes
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Too large meals ! Too high Calories !
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Sedentary life style!!
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The progressive nature of type 2 diabetes
Normal
Impaired glucose tolerance
Type 2 diabetes
Late type 2 diabetes complications
Insulin sensitive
Hyperglycaemia
Normal insulin secretion
Insulin resistance
Normoglycaemia
ß-cell exhaustion
Fasting plasma glucoseInsulin sensitivityInsulin
secretion
Adapted from Bailey CJ et al. Int J Clin Pract
200458867876. Groop LC. Diabetes Obes Metab
19991 (Suppl. 1)S1S7.
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Type 2
Genetic susceptibility
Obesity Insulin resistance
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Type 2 Diabetes in Children

• Clinical presentation
• Children with type 2 diabetes are usually
  diagnosed over age of 10 years
• Middle to late puberty
• Milder symptoms than type 1 with mild polydepsia,
  polyuria, little or no weight loss
• Glucosuria with / without ketonuria
• Up to 33 have ketonuria at diagnosis
• 525 of patients with type 2 diabetes have
  ketoacidosis at presentation

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Associated problems with type 2 DM

• Obesity
• Insulin resistance
• Hyperinsulinism
• Arterial hypertension
• Hyperlipidemia
• Acanthosis Nigerians
• Macro microangiopathy
• PCOS

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Acanthosis Nigricans

• Acanthosis nigricans is a cutaneous finding
  frequently in darker-skinned obese individuals
• Characterized by velvety hyperpigmented patches
  most prominent in intertriginous areas and is
  present in as many as 90 of children with type
  II diabetes

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Screening for type 2 DM in Children
Adolescents
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Why to screen for type 2 DM?

• As in adults, a substantantial number of children
  with type 2 can be detected in A
  symptomatic state
• In type 2, there is a prolonged latency period
  without symptoms during which abnormality can be
  detected
• Only children at risk for the presence or
  development of type 2 should be screened

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Criteria of screening for Type 2 DM in Children
Adolescents

• overweight which is defined as (WHO)
• body mass index (BMI) gt 85th percentile for age
  and sex
• weight for height gt 85th ile
• weight gt120th ile of ideal (50) for height
• Plus two of the following risk factors
• Family history of type 2 DM in first or
  second-degree relative

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Criteria of screening for Type 2 DM in Children
Adolescents

• Race/ethnicity (Pima Indian, African-American,
  Hispanic, Asian / Pacific Islander)
• Signs of insulin resistance or conditions
  associated with insulin resistance
• acanthosis nigricans
• polycystic ovary syndrome
• hypertension
• dyslipidemia

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Type 2 diabetes is NOT a mild disease
Stroke
Diabeticretinopathy
1.2- to 1.8-fold increase in stroke3
Leading cause of blindness in working-age adults1
Cardiovasculardisease
75 diabetic patients die from CV events4
Diabetic nephropathy
Diabeticneuropathy
Leading cause of end-stage renal disease2
Leading cause of non-traumatic lower extremity
amputations5
1Fong DS, et al. Diabetes Care 200326 (Suppl.
1)S99S102. 2Molitch ME, et al. Diabetes Care
200326 (Suppl. 1)S94S98. 3Kannel WB, et al.
Am Heart J 1990120672676. 4Gray RP Yudkin
JS. In Textbook of Diabetes 1997. 5Mayfield JA,
et al. Diabetes Care 200326 (Suppl. 1)S78S79.
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Prevention of type 2 DM
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Prevention of obesity
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Prevention of type 2 DM

• Public health measures
• 1. Media
• 2. School
• 3. Community
• 4. Family
• Increase physical activity
• Reduce caloric intake/obesity
• Decrease sedentary life style
• I. Computer
• 2. Video games
• 3. Television

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Treatment of type 2 diabetes

• There are limited data available regarding
  management of type 2 diabetes in children
• As a result, the goals of treatment in type 2
  diabetes in adults have been applied to children
  and adolescents
• These goals include
• achieving psychological physical well-being
• long term glycemic control
• defined as a fasting plasma glucose lt 130mg/dL
• HbA1c lt 7
• preventing microvascular macrovascular
  complications

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• Initial treatment of type 2 DM, will vary
  depending on clinical presentation
• Wide range from A symptomatic hyperglycemia to
  DKA
• Children who are not ill at diagnosis can be
  managed with diet ,exercise oral agents
• Children who are ill, dehydrated, presence of
  ketosis and acidosis need insulin therapy
• When stabilized, tapering of insulin gradually
  and introduction oral agents
• In all patients, identification treatment of
  co-morbid conditions are important

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How can insulin resistance be managed?

• Improve insulin resistance through
• Diet
• Exercise
• Pharmacological intervention with agents that
  target insulin resistance

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Oral hypoglycemic agents

• Biguanides Metformin
• The first oral agent used should be metformin.
• decrease hepatic glucose output
• enhance hepatic muscle insulin sensitivity
  without a direct effect on b-cell function
• Sulfonylureas chlorpropamide, gliclazide,
  glimepiride, glipizide, tolazamide, tolbutamide
• promote insulin secretion from islet cells
• Thiazolidenediones troglitazone, rosiglitazone
• improve peripheral insulin sensitivity
• Troglitazone has been associated with fatal
  hepatic
• failure its use in children is not
  recommended

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Metformin

• The first oral agent should be used in type 2
• Metformin has advantage over sulfonylureas of a
  similar reduction in HbA1c without the risk of
  hypoglycemia
• Metformin normalizes ovulatory abnormalities in
  girls with PCOS
• Because of concerns about lactic acidosis,
  Metformin is contraindicated in patients with
• impaired renal function
• should be discontinued with the administration
  of radiocontrast material.
• should not be used in patients with known hepatic
  disease, hypoxemic conditions, severe infections,
  or alcohol abuse

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Metformin

• The most common side effects of Metformin
• Gastrointestinal disturbances
• Because proper dosing in children has not been
  evaluated because most patients are near or at
  adult weight, it is reasonable to use the doses
  recommended for adults
• If monotherapy with Metformin is not successful
  over a period of time (36 months), Some
  clinicians would add a sulfonylurea, whereas
  others might add insulin

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• Sulfonylureas stimulate insulin secretion and
  reduce HbA1c levels by 12
• Sulfonylureas may cause weight gain and are
  associated with the highest incidence of
  hypoglycemia among the oral antidiabetic agents.
• Glucosidase inhibitors slow the hydrolysis of
  complex carbohydrates and carbohydrate absorption
  (acarbose and miglitol)
• The glucosidase inhibitors reduce HbA1c by
  0.50.9

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• The thiazolidinediones improve peripheral insulin
  sensitivity reduce HbA1c by 0.51.5
• The thiazolidinediones do not cause hypoglycemia
  when used as monotherapy, but may cause edema
  weight gain
• The sulfonylureas, nonsulfonylureas, glucosidase
  inhibitors thiazolidinediones have not received
  approval by FDA for use in the pediatric
  population

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