Download Management of Type II Diabetes in Children and Adolescents

MANAGEMENT OF TYPE 2
DIABETES IN CHILDREN
AND ADOLESCENTS
Dr. Huen Kwai Fun
Chief of Service & Consultant Paediatrician
Dept. of Paediatrics
Tseung Kwan O Hospital
Outline (I)

Q1: What is the classification of diabetes in
children and adolescents?

Q2: What is the epidemiology of type 2 diabetes in
children and adolescents?

Q3: What is the pathophysiology of type 2 diabetes
in children and adolescents?

Q4: Who should be tested for diabetes?

Testing recommendations


Population selection
Test methods
Outline (II)


Q5: How should children and adolescents with
type 2 diabetes be treated?

Lifestyle changes

Pharmaceutical therapy

Monitoring for complications

Hypertension treatment

Hyperlipidemia treatment
Q6: Can type 2 diabetes in children and
adolescents be prevented?
Criteria for the diagnosis of diabetes

Symptoms of diabetes plus casual plasma glucose
concentration ≧ 200mg/dl (11.1 mmol/l). Casual is
defined as any time of day without regard to time since last meal. The classic
symptoms of diabetes include polyuria, polydipsia, and unexplained weight
loss.

OR,
FPG ≧126mg/dl (7.0 mmol/l).
intake for at least 8 hours.

Fasting is defined as no caloric
OR,
2-h PG ≧ 200mg/dl (11.1 mmol/l) during an OGTT.
The test should be performed as described by the World Health Organization,
using a glucose load containing the equivalent of 75-g anhydrous glucose
dissolved in water.
In the absence of unequivocal hyperglycemia with acute metabolic
decompensation, these criteria should be confirmed by repeat testing on a
different day. The third measure (OGTT) is not recommended for routine
clinical use. Adapted from the Report of the Expert Committee on the Diagnosis and Classification
of Diabetes Mellitus.
Etiologic classification of diabetes

Type 1 diabetes* (β-cell destruction, usually leading to absolute insulin
deficiency)
Immune-mediated
Idiopathic

Type 2 diabetes* (may range from predominantly insulin resistance with
relative insulin deficiency to a predominantly secretory defect with insulin
resistance)

Other specific types
Genetic defects of β-cell function (e.g. MODY)
Genetic defects in insulin action (e.g. lipoatrophic diabetes)
Diseases of the exocrine pancreas (e.g. cystic fibrosis)
Endocrinopathies (e.g. Cushing’s syndrome)
Drug- or chemical- induced (e.g. glucocorticoids)
Infections (e.g. congenital rubella)
Uncommon forms of immune-mediated diabetes
Other genetic syndromes sometimes associated with diabetes (e.g. PraderWilli syndrome)

Gestational diabetes mellitus (GDM)
* Patients with any form of diabetes may require insulin treatment at some stage at their disease. Use of
insulin does not, of itself, classify the patient. Adapted from the Report of the Expert Committee on
Research schema for classification of
diabetes in children and youths
Obese
Yes
No
Autoantibodies
Fasting C-peptide/insulin
No
Yes
Fasting C-peptide/insulin
High
Low
Autoantibodies
Yes
Type 2
1M Type 1
No
Low
Idiopathic Type 1 or MODY
High
Type 2 1M Type 1
Estimates of the magnitude of type 2
diabetes in North American Children (I)
Years
Race / Ethnicity
Age (Years)
Estimates
Study types
Population-based studies
Arizona
Manitoba
1992-96
Prevalence per 1,000
Pima Indians
10-14
22.3
15-19
50.9
1996-97
First Nations
10-19
36.0 in girls
1988-94
Whites, Africans
12-19
4.1*
NHANES IlI
all US
Americans, Mexican
Americans
Clinic-based studies
Indian Health
1996
American Indians 0-14
1.3*
Services (all U.S.)
Manitoba
1998
First Nations
15-19
4.5*
5-14
1.0
15-19
2.3
Estimates of the magnitude of type 2
diabetes in North American Children (II)
Clinic-based studies
Cincinnati, OH
Case series
Years
Race / Ethnicity
1994
Whites, AfricanAmericans
Cincinnati, OH
1994
Charleston, SC
San Diego, CA
1997
1993-94
San Antonio, TX
Ventura, CA
1990-97
1990-94
Whites, AfricanAmericans
Blacks
Whites, AfricanAmericans,
Hispanics, AsianAmericans
Hispanics, Whites
Hispanics
Age (Years)
Estimates
Incidence per 100,000/year
10-19
7.2
Percentage of type 2 diabetes
among new cases of diabetes
0-19
10-19
0-19
0-16
16
33
46+
8
0-17
18
45
* Estimates include type 1 and 2 diabetes
+ Percentage of type 2 among nonincident cases of diabetes
Annual incidence of type 2 diabetes
in Tokyo
1976-80
7.3 per 100,000
1981-85
12.1 per 100,000
1991-95
13.9 per 100,000

Junior high school children

Urine glucose screening

Confirmed by OGTT
Characteristics & Risk
Factors




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

Obesity
Decreased exercise
Increased calorie and fat intake
Family History
Low birth weight
Females
Pubertal age period
Research needs

Magnitude of type 2 diabetes

Confirm any significant rising trend

Characteristics of those affected

Risk factors

Natural history
Pathophysiology

Type 2 diabetes is a complex
metabolic disorder of
heterogeneous etiology with social,
behavioral, and environmental risk
factors unmasking the effects of
genetic susceptibility
Primary Defect

The constellation of clinical
characteristics in type 2 diabetes
suggests that the initial abnormality
is impaired insulin action (insulin
resistance), compounded later with
β-cell failure (insulin insufficiency)
Evolution
Prediabetic
Normoglycaemic
Impaired G
tolerance
Insulin
Resistance
Worsening of
insulin resistance
Compensatory
Hyperinsulinaemia
uncompensated
hyperinsulinaemia
(relative insulin
insufficiency)
Clinical
diabetes
Impaired
insulin action
Insulin
secretory
failure
Glucose toxicity

Hyper G beget more hyper G by
worsening both insulin resistance and
insulin secretory abnormalities

Ameliorated by correction of hyper G
Puberty-related insulin resistance

Insulin-mediated glucose disposal is on
average 30% lower in adolescents between
Tanner stages II and IV compared with
prepubertal children and compared with young
adults

Increased GH secretion is most likely
responsible

Sex steroids – unlikely cause

Peak ages at presentation coincides with usual
age of mid-puberty
Obesity

Obese children are hyperinsulinaemic and have
~40% lower insulin-stimulated glucose
metabolism compared with non obese

BMI increase, insulin resistance increase, fasting
insulin levels increase

Relationship stronger with abdominal visceral fat
than for subcutaneous fat
Hyperandrogenism

PCOS – increased risk of type 2 DM

31% IGT, 7.5-16% type 2 diabetes

Profound insulin resistance (indep of
obesity)

Abnormal β-cell function
Genetic predisposition

Racial differences

Family History

African-Americans adolescents – 30% lower
insulin sensitivity of White

American Indians, Hispanic, Asian/ Pacific
Inlanders increase risk
Testing for type 2 diabetes on children

Criteria*


Overweight (BMI > 85th percentile for age and sex,
weight for height > 85th percentile, or weight >120%of
ideal for height)
PLUS
Any two of the following risk factors:






Family history of type 2 diabetes in first- or second-degree
relatives
Race/ethnicity (American Indian, African-American,
Hispanic, Asian / Pacific Islander)
Signs of insulin resistance or conditions associated with
insulin resistance (acanthosis nigricians, hypertension,
dyslipidemia, PCOS)
Age of initiation: age 10 years or at onset of
puberty if puberty occurs at a younger age
Frequency: every 2 years
Test: FPG preferred
* Clinical judgment should be used to test for diabetes in high-risk patients who do not meet these criteria
Recommendations based on limited data.
School or community-based studies needed.
Other possible influencing factors



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Blood pressure
Fat distribution
Socioeconomic status
Low birth weight
Other tests: 2-h PG
 Random glucose
 HbAlc
Treatment goals

Normalization of blood glucose and HbAlc
[ADA: Standards of Medical Care for Patients with Diabetes Mellitus
(Position Statement). Diabetes Care 22 (Suppl 1): S32-S41, 1999]

Successful control of hypertension and
hyperlipidaemia

Decrease risk of acute and chronic
complications
Treatment

Diabetic ketoacidosis (DKA)

Hyperglycaemic hyperosmolar nonketotic
(HHNK) states

Associated with high morbidity and mortality in
children

Risk of cerebral oedema

Early consultation and referral
Management

Medical nutrition therapy

Exercise

drugs
Lifestyle changes

Comprehensive self-management education
[ADA: Clinical Practice Recommendations 1999. Diabetes Care 22
(Suppl. 1): S1-S114, 1999]



Self-monitoring of blood glucose (SMBG)
(Fasting, postprandial, acute illness, Sxs of hyper
G or hypo G)
Nutritional Mx:



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
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Culturally appropriate
Sensitive to family resources
Given to all caregivers
Healthy eating habits by entire family
Decrease high-caloric high fat food choices
Behavior modification
[Willet WC et al – Guidelines for healthy weight. N Engl J Med
341:427-434, 1999]


Increase daily physical activity
Decrease sedentary activity
Pharmaceutical therapy
[DeFronzo RA: Ann Intern Med 131:281-303, 1999]

5 types of of oral hypoglycaemic agents:


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
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Biguanides: decrease hepatic glucose output and enhance
primarily hepatic and also muscle insulin sensitivity without a
direct effect on β-cell function: metformin
Sulfonylureas: promote insulin secretion: acetohexamide,
chlorpropamide, gliclazide, glimepiride, glipizide, glyburide,
tolazamide, and tolbutamide
Meglitinide: short-term promotion of glucose-stimulated
insulin secretion: repaglinide
Glucosidase inhibitors: slow hydrolysis of complex
carbohydrates and slow carbohydrate absorption: acarbose
and miglitol
Thiazolidenediones: improve peripheral insulin sensitivity:
troglitazone, rosiglitazone, and pioglitazone
No oral agent should be used during pregnancy
Important to counsel adolescents with type 2 diabetes about
sexuality and pregnancy
Metformin – 1st oral agent used

No risk of hypo G

Weight decreased or remains stable

LDL – cholesterol and TG decrease

May normalize ovulatory abnormalities in girls with PCOS
and increase risk unplanned pregnancy – preconception and
pregnancy counseling

CI in impaired renal function (lactic acidosis), hepatic disease,
hypoxemic conditions, severe infections, alcohol abuse

Discontinued with administration of radiocontrast material,
acute illness associated with dehydration/hypoxemia

SE: GI disturbances

Proper dosing in children not been evaluated

Add sulfonylurea if not successful over 3-6 months
Monitoring for complications

Microalbuminuria

Dilated eye examinations

Foot examinations

BP

Lipid abnormalities
Hypertension treatment

ACE inhibitors – 1st line

α- blockers, calcium antagonists
(long-acting), low dose diuretics

β- blockers – hypo G, mask hypo G
Sxs
Hyperlipidaemia treatment

Weight loss

Increase activity

Improve glycaemic control

Change food choices and preparation

Medications
[Pediatrics 89 (Suppl.):525-584, 1992]

HMG CoA reductase inhibitors (“statins”)
absolutely CI in pregnancy – should not be used in
females of childbearing potential unless highly
effective contraception in use and patient
extensively counseled
Prevention (I)




Primary prevention directed to high-risk or to
overall population of children
Primary care providers have an obligation to
encourage lifestyle modifications that might delay
or prevent onset of type 2 diabetes in children at
high risk
To whatever degree hyperinsulinaemia and insulin
resistance contribute to long term cardiovascular
morbidity and mortality, early lifestyle intervention
have long-term beneficial effects
Intervention using oral hypo G agents for
prevention of diabetes in children not
recommended
Prevention (II)

Nutritional interventions guided by health care
provider with knowledge and expertise in growth
and development in children

Drug therapy to reduce weight not recommended
until more safety and efficacy data available

Use of very-low-calorie or high-protein diets or
other fad diets not recommended

Quick-fix weight loss programs unsafe for children
and rarely result in long-term weight control. They
do not promote long-term healthy eating behavior
Prevention (III)

6-year Da Qing IGT and Diabetes Study
(Diabetes Care 20:537-544, 1997)

126 Chinese men with IGT

Randomized to a program with both dietary
and exercise intervention

Developed type 2 diabetes 32% less frequently
than 133 men in control group
Prevention (IV)

Ideally public health approach targets general
population

School- and community-based programs to
promote improved dietary and physical activity
behaviors for all children and their families

Schools, religious organizations, youth and family
organizations, and government agencies should
assume some responsibility for promoting a
healthy life style