Transcript 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). 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-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. 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/insulin High 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)
Race / Ethnicity Age (Years) Estimates Years Study types Population-based studies Arizona 1992-96 Manitoba NHANES IlI all US 1996-97 1988-94 Pima Indians First Nations 10-14 15-19 10-19 Whites, Africans 12-19 Americans, Mexican Americans Prevalence per 1,000 22.3
50.9
36.0 in girls 4.1* Clinic-based studies Indian Health Services (all U.S.) 1996 American Indians 0-14 1.3* Manitoba 1998 First Nations 15-19 5-14 15-19 4.5* 1.0
2.3
Estimates of the magnitude of type 2 diabetes in North American Children (II)
Years Clinic-based studies Cincinnati, OH Case series Cincinnati, OH Charleston, SC San Diego, CA San Antonio, TX Ventura, CA 1994 1994 1997 1993-94 1990-97 1990-94 Race / Ethnicity Whites, African Age (Years) Estimates Incidence per 100,000/year 10-19 7.2
Americans Percentage of type 2 diabetes among new cases of diabetes Whites, African 0-19 16 Americans Blacks Whites, African Americans, 10-19 0-19 0-16 33 46+ 8 Hispanics, Asian Americans Hispanics, Whites Hispanics 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 1981-85 1991-95 7.3 per 100,000 12.1 per 100,000 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 > 85 th weight for height > 85 th ideal for height) percentile for age and sex, percentile, or weight >120%of 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
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 – 1
st
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 – 1 st 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