Insulin Resistance in Children

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Insulin Resistance in Children

• Kellie Bryant

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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.

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• 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.

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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 insulin0.5-0.7 units/kg of body weight
  per day.

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Insulins Effects on Body Tissues

• Stimulates entry of amino acids into
  cellsenhances 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

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• 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

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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.

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• Therefore, insulin resistance is most familiarly
  associated with type 2 diabetes and seen in two
  prediabetic statesimpaired fasting glucose and
  impaired glucose tolerance (most recently
  referred to as pre-diabetes.

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• 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.

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• 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.

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Insulin Resistance and Thrifty Phenotype
Hypothesis

• Hypothesispoor 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

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• 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

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Predictors or Insulin Resistance--Adults

• BMI of 25 or higher
• Waist circumference gt40 inches in men and 35
  inches in women
• Triglyceride gt150
• HDL-C lt40
• Blood pressure gt130/85
• Fasting blood glucose gt110
• Although these are adult references many
  practitioners use these values along with other
  predictors as possible clinical signs of insulin
  resistance

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• 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

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• 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.

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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

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• 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

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Insulin Resistance Syndrome

• Characterized by hyperinsulinemia and one or more
  of the following
• HTN
• Hypertriglyceridemia
• Hypercholesterolemia
• Decreased HDL, Increased LDL
• Obesity
• Menstrual disturbances
• Hirsutism

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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

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• 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

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• 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

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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

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Physical activity

• On a steady decline
• Many children live in single parent or dual
  working householdsmore latchkey kids

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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 day2400 hours in one year
• More time spent watching TV, computer and video
  games and less time in physical activity

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Fast Food

• On any given ay 7 of the American population
  eats fast food.
• Todays 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

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Treatment

• Alteration in lifestyle including modifications
  of
• Eating habits
• Increased physical activity
• Preventioncurb the incidence of childhood obesity

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• 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

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• 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

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• Physical activity increases the bodys
  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

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• Children should be encouraged to participate in
  activities they can perform easily and frequently
• Helpful if physical activity is family centered

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Pharmacalogical Agents

• Under exploration in the treatment of insulin
  resistance
• Thiazolidionediones (TZDs) directly address
  insulin resistance
• They enhance glucose transport into target cells
  (especially muscle and adipose tissue)

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• TZDs 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

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• Biguanides (Metformin) inhibit glucose release
  from the liver by blocking gluconeogenesis and
  glycogenolysis
• Biguanides associated with weight loss

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• 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

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Recommendations

• Canadian Pediatric Society position statement for
  all health care professionals to promote healthy
  active living for all family members

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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
  lifestyleslimit exposure to TV, video or
  computer games

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• 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

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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

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• 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

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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

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Conclusion

• Certain genes predispose certain people to
  develop insulin resistance, but other
  factorsinactivity, wt gain trigger insulin
  resistance
• Treatment is change in lifestyle
• Treatment must include the family and a team
  effort with healthcare professionals