insulin resistance in children kellie bryant. introduction type 2 diabetes once considered a disease...
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Introduction Type 2 diabetes once considered a
disease of adults has increased dramatically since 1980 in children.
One third of all children less than 18 years of age diagnosed with diabetes have type 2.
The incidence of type 2 diabetes have paralleled the prevalence of obesity.
Type 2 diabetes in children is most commonly diagnosed at puberty.
One of the major characteristics of type 2 diabetes is insulin resistance which is considered the hallmark of type 2 dm.
Physiologic Effects of Insulin Insulin is a hormone produced in the beta
cells of the pancreas. Insulin is formed from proinsulin When the pancreas is stimulated by
elevated blood glucose proinsulin is broken a part leaving insulin and C-peptide.
Both are secreted and enter the blood stream in equimolar amounts.
Normal insulin—0.5-0.7 units/kg of body weight per day.
Insulin’s Effects on Body Tissues Stimulates entry of amino acids into cells—
enhances protein synthesis Enhances fat storage and prevents the
mobilization of fat for energy Stimulates the entry of glucose into cells to use
as an energy source Promotes the storage of glucose as glycogen in
muscle and liver cells Inhibits production of glucose from liver or
muscle glycogen Inhibits the formation of glucose from non-
carbohydrates
Since insulin and C-peptide are jointly secreted, either can be used to monitor endogenous insulin production.
Normal values for fasting serum insulin and C-peptide are 0-30 µIU/ml
Characteristics of Insulin Resistance Metabolic state characterized by fasting
and or postprandial hyperinsulinemia Reduced hepatic and skeletal muscle
insulin sensitivity is compensated for by increased pancreatic insulin secretion to maintain normal blood glucose, which overtime contributes to the development of postprandial hypergycemia.
Therefore, insulin resistance is most familiarly associated with type 2 diabetes and seen in two prediabetic states—impaired fasting glucose and impaired glucose tolerance (most recently referred to as pre-diabetes.
Insulin resistance is also associated with hypertension, dyslipidemia and coronary heart disease.
It is speculated that hyperinsulinemia contributes to large vessel atheroschlerosis whether or not glucose intolerance exists.
Researchers believe that insulin resistance is caused by abnormalities within cells called post-binding abnormalities.
Many individuals with insulin resistance are deficient in a glucose transporter called a GLUT-4.
GLUT-4 is regulated by the amount of insulin present in the body.
Insulin Resistance and Thrifty Phenotype Hypothesis Hypothesis—poor nutrition in fetal
and infant life is believed to impair the normal development and function of beta cells as well as insulin-responsive tissues primarily in the skeletal muscle causing the development of insulin resistance
Maternal diabetes, high and low birth weights and the later development of diabetes has been reported in Pima Indians.
This suggests that high birth weight influences the development of insulin resistance as much as fetal underdevelopment
Predictors or Insulin Resistance--Adults BMI of 25 or higher Waist circumference >40 inches in men and
35 inches in women Triglyceride >150 HDL-C <40 Blood pressure >130/85 Fasting blood glucose >110 Although these are adult references many
practitioners use these values along with other predictors as possible clinical signs of insulin resistance
According to Hansen, Fulop and Hunter studies for children should include Fasting blood glucose Fasting insulin Lipoproteins Cortisol Free T4 TSH (thyroid stimulating hormone Serum acetone HbA1c Urinalysis of glycosuria and ketonuria
Karotype and specialized genetic studies may be necessary if unusual phenotypic features are present to suggest chromosomal syndrome that may be associated with insulin resistance
Radiograph of the left hand and wrist may be indicated to assess bone age since insulin resistance in children is associated with advanced skeletal maturation.
Acanthosis nigricans Result of hyperinsulinemia
(consequence of insulin resistance Caused from the binding of insulin
to insulin-like growth factor receptors on keratinocytes and fibroblasts which results in hyperplasia of the skin
Causes light brown to black velvety rough areas typically at the base of the neck and skin folds
May be seen over joints including elbow, knees and knuckles or on the face and palms
60-90% of children who develop diabetes have acanthosis nigricans
It is helpful clinical sign because it is truly a manifestation of insulin resistance
Insulin Resistance Syndrome Characterized by hyperinsulinemia and
one or more of the following HTN Hypertriglyceridemia Hypercholesterolemia Decreased HDL, Increased LDL Obesity Menstrual disturbances Hirsutism
Insulin Resistance Seen as early as 2 years of age in
children with with appropriate genes, and environmental influences (ethnicity, obesity, decreased activity
Most common in puberty secondary to increased growth hormone secretion
Higher rate among African Americans, Hispanics and American Indians
Seen across all racial boundaries with increased obesity
Both parents obese the child has 66% chance of developing obesity
50% chance if one parent is obese Hyperinsulinemia contributes to
development of obesity and obesity exacerbates insulin resistance Insulin stimulates the appetite due to
its anabolic mechanisms
Obesity and high body fat mass decrease insulin sensitivity in skeletal muscle and liver
Children usually begin to develop body fat mass in preschool years
Obesity is the most significant risk factor for developing insulin resistance
Obesity In the last 30 years the % of young
people who are overweight has doubled
10-15% of children 6-17 years are overweight
40% of obese 7 year olds and 70% of obese adolescents become obese adults
Physical activity On a steady decline Many children live in single parent
or dual working households—more latchkey kids
Television Many children begin watching TV as
early as 6 months and are regular viewers by age 2.
American children watch TV for an average of 4 hours a day—2400 hours in one year
More time spent watching TV, computer and video games and less time in physical activity
Fast Food On any given ay 7% of the American
population eats fast food. Today’s children have grown up in the era
of “enhanced portion size” Typical fast food mal is high in calories, fat
and sugar Even though families may choose to eat
from home many rely on pre-processed “fast food” equivalents purchased at the grocery store because of lack of time to prepare a meal from scratch
Treatment Alteration in lifestyle including
modifications of Eating habits Increased physical activity Prevention—curb the incidence of
childhood obesity
Educational efforts targeted at the eating habits of both parents and children
Requires significant family involvement
May benefit from multidisciplinary approach from: primary care physician, RD or CDE, school personnel, psychologist
MNT remains the mainstay in treatment Regimen used most often by pediatric
diabetes dietitians is a variation of CHO counting
Reductions in calories and recommendations of 50% CHO, 20% protein and 30% fat
Fixed amount of CHO at each meal and snack
Physical activity increases the body’s sensitivity to insulin during activity and up to one day after activity
Studies show that regular aerobic exercise can reduce the risk of developing diabetes by 1/3 to ½
Encourage daily with a sustained heart rate of 80% of maximum for 20-30 minutes
Children should be encouraged to participate in activities they can perform easily and frequently
Helpful if physical activity is “family centered”
Pharmacalogical Agents Under exploration in the treatment
of insulin resistance Thiazolidionediones (TZD’s)
directly address insulin resistance They enhance glucose transport
into target cells (especially muscle and adipose tissue)
TZD’s activate the peroxisome-proliferator receptor-gamma which stimulates a genetic transcription factor that enhances production of GLUT-4
Many individuals with insulin resistance are deficient in GLUT-4
Biguanides (Metformin) inhibit glucose release from the liver by blocking gluconeogenesis and glycogenolysis
Biguanides associated with weight loss
There are no specific guidelines for using pharmacological agents in the treatment of insulin resistance
Specifically none of these medications have been sanctioned by the FDA to use in children
Given the prominence of insulin resistance and pathophysiology it is logical to theorize that reduction of insulin resistance before the development of diabetes may at least delay its occurrence
Recommendations Canadian Pediatric Society position
statement for all health care professionals to promote healthy active living for all family members
Highlights of recommendations Inquire about eating habits and physical
activity at all health care visits Promote consumption of fiber rich foods
instead of high fat high sugar foods Encourage to spend 30 minutes every
day in physical activity Counsel families to reduce sedentary
lifestyles—limit exposure to TV, video or computer games
Encourage parents to be positive role models and incorporate physical activities all family members can do together
Advise parents to enroll their children in age and developmentally appropriate recreational activities
Advocate Initiatives to serve healthy foods and
eliminate the sale of high CHO soft drinks and high fat/sugar snacks in schools
Policies to reduce the sale of over-sized fast foods
Initiatives that provide children with quality daily physical education classes and use of school facilities after school
Community sport and recreation programs
Construction of safe recreation facilities, parks and playgrounds
Physical education throughout all age groups in all schools
Allocation of funding for research in the prevention of childhood obesity
Oklahoma State Department of Health-Chronic Disease Service-Recommendations All overweight children with 2 other risk
factors tested for diabetes at the onset of puberty (random bs or 8h fasting bs)
If tests negative but remains high risk, test annually thereafter with aggressive lifestyle modifications
Treat HTN, dyslipidemia, etc aggressively and evaluate yearly
Families should be counseled on eating habits that maintain normal body wt and 30 minutes of daily physical activity as a family lifestyle