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). ≧ Fasting is defined as no caloric

intake for at least 8 hours. 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-mediatedIdiopathic

Type 2 diabetes* (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance)

Other specific typesGenetic 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 diabetesOther genetic syndromes sometimes associated with diabetes (e.g. Prader-Willi 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 the Diagnosis and Classification of Diabetes Mellitus.

Research schema for classification of diabetes in children and youths

Obese

Yes No Autoantibodies

Fasting C-peptide/insulin No Yes

Fasting C-peptide/insulinHigh Low

Autoantibodies

Yes No Low High

Type 2 1M Type 1 Idiopathic Type 1 or MODY 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 Prevalence per 1,000

Arizona 1992-96 Pima Indians 10-14 22.3

15-19 50.9

Manitoba 1996-97 First Nations 10-19 36.0 in girls

NHANES IlI

all US 1988-94 Whites, Africans 12-19 4.1*

Americans, Mexican

Americans

Clinic-based studies

Indian Health 1996 American Indians 0-14 1.3*

Services (all U.S.)

15-19 4.5*

Manitoba 1998 First Nations 5-14 1.0

15-19 2.3

Estimates of the magnitude of type 2 diabetes in North American Children (II)

Years Race / Ethnicity Age (Years) EstimatesClinic-based studies Incidence per

100,000/yearCincinnati, OH 1994 Whites, African- 10-19 7.2

Case series Americans Percentage of type 2 diabetes among new cases of diabetes

Cincinnati, OH 1994 Whites, African- 0-19 16Americans 10-19 33

Charleston, SC 1997 Blacks 0-19 46+San Diego, CA 1993-94 Whites, African- 0-16 8

Americans, Hispanics, Asian-Americans

San Antonio, TX 1990-97 Hispanics, Whites 18Ventura, CA 1990-94 Hispanics 0-17 45

* Estimates include type 1 and 2 diabetes+ Percentage of type 2 among nonincident cases of diabetes

Annual incidence of type 2 diabetesin 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 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 Impaired G Clinical

Normoglycaemic tolerance diabetes

Insulin Worsening of Impaired

Resistance insulin resistance insulin action

Compensatory uncompensated Insulin

Hyperinsulinaemia hyperinsulinaemia secretory

(relative insulin failure

insufficiency)

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 criteriaRecommendations based on limited data.School or community-based studies needed.

Other possible influencing factors

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:

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:-

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