Part IV Section 6-C

The Nutritional Implications of Type 2 Diabetes Mellitus in Childhood

Nicole Prudent, MD

Suleiman Mustafa-Kutana, MD

Boston Medical Center

Pre-Test:

Answer True or False?

Q1. Children are miniature adults, and all adult measures of morbidity can be reliably applied to all children too.

Q2. Body Mass Index (BMI) can be expressed as a percentile, but this has to be BOTH age and sex specific to be meaningful.

Q3. To the extent that birth weight contributes to disease or illness in adulthood, having a birth weight of less than 2.5kg is the healthiest.

Q4. Events occurring in-utero can have no permanent or long-term effects on a child who is born healthy.

Q5. White non-Hispanic Americans are at an increased risk for development of Type 2 Diabetes Mellitus.

Q6. African Americans have been noted to develop less diabetes compared to native Africans living in Africa.

Q7. The prevalence of obesity, overweight and Type 2 DM can be related to a person's socio-economic status.

Q8. People who spend more of their money (higher percentage) on housing have greater food insecurity.

Q9. National and State government policies can relieve people of food insecurity and this will eventually translate into reduced obesity in the society.

Q10. Which of the following children is LEAST at risk for T2DM:

A. The Adiposity Rebound (AR) occurs at age 6 - 7 years

B. Has central obesity.

C. Lives in a family with an income just above the poverty level.

D. Has a darkening and thickening of skin on neck and in axillae.

Learning Objectives

On completion of this module, residents will be able to:

1. Define the terms "Overweight" and "Obesity"

2. Recognize the signs and symptoms of T2DM in children

3. Appreciate the relationship between overweight, obesity and T2DM

4. Understand how Intra Uterine Growth Retardation and development might lead to obesity and T2DM

5. Appreciate the pathogenesis (natural history) of T2DM

and diagnostic tests to identify T2DM in children

6. Use preventive measures for overweight and obese children to

Reduce risk for T2DM

Facilitator's Prep:

The issue of obesity is raised in several modules in the Teacher's Guide. [Hyperlink] These should be reviewed. We have not sought to prevent replication; rather, you can use this material intact or augment from other sections. Review micronutrient needs in Pediatric Nutrition Notes [Hyperlink]. There are 8 separate modules in Part II related to obesity, alone. The reading list at the end of this module is a summary that includes the most relevant articles and reviews for the material presented here. The two listed below provide well referenced overviews.

Rocchini AP. Childhood obesity and a diabetes epidemic. New England Journal of Medicine. 2002;346(11): 854-5. provides a fine overview of the "diabesity" epidemic among children in the United States.

Bhargava KS, Sachdev HS, Fall HDC, Osmond C, Lakshmy R, Barker JPD, Biswas SKD, Ramji S, Prabakaran D, Reddy K. Relation of Serial Changes in Childhood Body-Mass Index to Impaired Glucose Tolerance in Young Adulthood. N Engl J Med 2004;350:865-75 provides guidance from several of the most noted researchers in this field, Bhargava, Sachdev, and Barker.

Introduction:

Childhood obesity has reached epidemic proportions with concomitant effects on the prevalence of Type 2 Diabetes Mellitus (T2DM). Worldwide, approximately 22 million children under five years of age are overweight. During the past three decades, the number of overweight children in the Unites States has more than doubled. In 1983, 18.6 percent of preschool children in the United States were defined as overweight, and 8.5 percent were defined as obese; by 2000, 22.0 percent of preschool children were overweight and 10.0 percent were obese.

Data from the National Longitudinal Survey of Youth indicate that the prevalence of overweight has increased by 21.5 percent among non-Hispanic black children, 21.8 percent among Hispanic children, and 12.3 percent among non-Hispanic white children. Similar increases in the prevalence of obesity have been observed worldwide. Childhood obesity is the most serious and prevalent nutritional disorder in the United States.

Type 2 DM is strongly associated with obesity in all ethic groups. More than 80% of patients with T2DM are also obese. The risk of T2DM increases with the degree and duration of obesity, diet and the central distribution of body fat (2). The likely cause for this association is that truncal obesity is associated with hormonal changes increasing insulin resistance. Leptin, a hormone secreted by the "fat body," is increased, but its appetite suppressing qualities seemed diminished. A second hormone, adiponectin, secretions are diminished along with its insulin activity augmentation. Lower body obesity seems to have a lesser effect on insulin activity.

This module addresses the causation, prevention, diagnosis and treatment of T2DM.

A Case study:

Mirlanda Gonzales, a10-year-old girl, comes accompanied by her mother to your clinic for a first time routine health care maintenance visit. The family recently moved from Miami and their new health insurance plan assigned you as the family's pediatrician. Mirlanda and her mother have no special concerns at this point. She brings a packet of old records from her previous health care center in Florida.

Reviewing the old record, you learn that Mirlanda was born after 39 weeks of gestation. Her mother, then 26-year-old woman was apparently in good health at the start of this pregnancy. She had very poor weight gain, and subsequently developed pre-eclampsia starting from the 24th week of gestation. She denied any other illnesses, including febrile ones. She has never smoked, did not drink alcohol, or use any drugs other than prenatal prescriptions. Her husband did not smoke either. She thought that her nutrition was adequate. At birth, Mirlanda weighed 2412 grams, with a length of 45.1 cm (<10th percentile for both) and a head circumference of 32.5 cm (<25th percentile), as noted on her newborn chart (Figure 1).

** FIGURE 1 goes here

With these measurements, she was classified as asymmetric "Small for Gestational Age" (SGA/IUGR). [see PII SII Assessing Nutritional Status.] As an infant, she initially experienced unexplained feeding difficulties, which slowly resolved by her first birthday. Unfortunately, you do not have growth records from birth to 36 months of age.

Mrs. Gonzales reports that around age 4 ½ to 5 years, Mirlanda's previous pediatrician had expressed concern about her accelerating weight gain. Her growth and development were otherwise within normal limits and her good health interrupted only by minor viral illnesses. See Figure - 2.

** Figure 2 goes here.

Family and Social histories:

Mrs. Gonzales is obese (she is 162 cm tall, and weighs 89.5kg). Her mother, Mirlanda's maternal grandmother, has T2DM also. There is a strong paternal family history of hypertension; one paternal cousin died of myocardial infarction (MI) at the age of 42. Mirlanda has twin male siblings, 7 years of age; both are in good health.

Mirlanda lives with her parents and twin siblings. Both parents work outside the home. She is doing well academically in school, as a 5th grader. She shyly confesses to a dislike for athletic activities and some social functions at school because she is bigger and taller than her classmates, and gets teased (usually about her weight) sometimes, when no teachers are within hearing range.

Diet and Activity:

Resident activity: Part II Section 1 has a standard history questionnaire. Let the residents break into triplets with one as a physician, another as Mirlanda, and the third as her mother. Create an imaginary history for her. Compare notes at the end.

Mirlanda has a huge appetite. Her mother had worried about her being "too skinny" since infancy, and she was always encouraged to "clean up her plate", and offered frequent snacks. She has no history of chronic or frequent headaches, or visual disturbances, and had no significant allergies, or reactive airways. Her bowel motions were regular, once or twice daily. She did not pass urine excessively during the day, nor did she wake up at night to pass urine.

Physical Exam:

Height: -137 cm, weight: -46 kg, BP: -110/65, pulse: -84, regular. She is a husky, shy-looking, cooperative girl who seems interested in her environment. Positive findings in her physical exam include: a strong body odor, partially masked by deodorant, a prominent abdomen, a wide chest and large arms, and relatively "skinny" lower body. Her facial skin appears rough and oily and she had micro-comedonal acne. Also, the skin around her neck and axillae was dark, thickened and shiny (velvety).

She also has dark curly hair, over her arms, legs, and her back, and a low hair line. Her sexual maturity rating (SMR) was staged at Tanner III, both for breast development and pubic hair distribution. Her mother indicated that by age five she already had coarse pubic and axillary hair. She has not yet started to menstruate.

Q1. Is Mirlanda overweight or obese?

The terms overweight and obesity are often used interchangeably. However, there is a distinction between them. Obesity refers to a clinical syndrome characterized by excess body fat (adiposity). During the pre-pubertal years, normal children have 15-18% body fat. The measurement of body fat is not routinely made in primary care settings, because it involves specialized instrumentation.

Q2. What Is BMI And How Is It Calculated?

Body Mass Index (BMI) is weight in kilograms, divided by height (in meters) squared (kg/m2) and is used as a measure of overweight and obesity. In adults, "overweight" (or "at risk for obesity") is defined as BMI between 25 and 29.9 kg/m2 and obesity is defined by a BMI of >30 kg/m2. This measure, while performing well as a screening test for excess adiposity, is not perfectly specific: for example, a trained athlete or body builder may have a very low percentage of body fat, but a high BMI. However, actuarial data show that, in adults, BMI is a good predictor of mortality, which rises sharply at the points defining "overweight" and "obese." In children, mortality data cannot be used to describe a biologically meaningful definition based on BMI. Furthermore, adiposity and BMI in normal children change continuously with age, such that there are no absolute norms independent of gender or age.

Residents: With the anthropometric measurements, calculate Mirlanda's BMI and BMI z-score. Her weight = 46 kg; height = 1.37 meters; BMI 24.5 m/kg2]. What are Mirlanda's BMI and BMI Z- score? [BMI = 24.5. It is well above the 95th %ile for age and gender rendering the term "above 95th %ile" meaningless. The 95th %ile is 2 SD above mean. The 24.5 kg/m2 is about 3 times the SD, a "Z-score" of about +3.

Q3. How Is BMI Interpreted In Children?

In children BMI is calculated for both age and sex, since there are important differences. However, the cut-offs for "action" are the same for all children. Children with a BMI-for age and sex <5th percentile are classified as underweight; those with a BMI-for-age and sex at the 85th to < 95th percentile are classified as at risk for overweight; while a BMI-for age and sex > 95th percentile are classified as overweight. When a child is less than two years of age, with a BMI >85 % ile, it is important only to draw the parent's attention to the potential risk, but if the BMI is >95th %ile, then action should be more vigorous, with a view to getting the BMI under acceptable levels. This may be achieved by slowing the rate of weight gain, since children will usually grow taller, with age.

The same may be true for a child between ages two and seven years, with a BMI over the 85th %ile. For a child over age seven years, a BMI >85th %ile is a call for active intervention, especially if there are other risk factors for future morbidity, e.g., ethnicity, family history, etc. Given your calculations of Mirlanda's current BMI, would you say she is underweight, normal weight, at risk for overweight, or overweight (Figure - 3)? [See section on "Defining Overweight and Obesity" below.] Part II Section 2 in the Teacher's Guide gives a full discussion of BMI.

How does fat composition change in the body during the life time?

There are three phases of fat accumulation: immediately after birth, during the "Adiposity Rebound" period, and after adolescence. Body fat percentage rises from ~12% at birth to a peak of ~25% by age 6 months, and then declines to 15-18% in the pre-pubertal years. During puberty, the percentage of body fat further increases in females while often decreasing in males. By 18 years, males have ~15-18 % of body fat, while females have ~ 20-25%.

After puberty, the percentage of body fat continues to increase with age, reaching ~ 30-40% in adults, while total body weight increases only by ~10-15 %. This indicates a reduction in the percentage of lean body mass. This is shown as an "Adiposity Rebound" (AR). Of note, AR occurs earlier in children likely to be obese later on in life. This will be discussed below.

Defining Overweight and Obesity.

Overweight "refers to a weight above normal range," while obesity refers to "the presence of excess body fat." The term "obesity" is not useful in children. The physical development of children involves rapid changes and redistribution of body fat as they grow. Additionally, fat mass is age-related and is different for boys and girls. In general however, BMI decreases during the pre-school years, only to increase in later childhood. Further, obesity is associated with a pattern of chronic health problems and morbidities in adults; a pattern which is not established for all overweight children. In the year 2000, the United States Center for Disease Control (CDC) changed the terminology for children and reclassified children as described above.

Most of the medical literature still refers to "obesity" instead of "overweight" in relation to children. The clinical definition of childhood overweight is based on age and sex specific BMI indices expressed as percentiles of a National Reference Population aged 2-20 years. "At-risk for overweight" and "overweight" are much preferred in discussions with parents and children alike even when we have evidence by BMI or other measures of "obesity."

Q4. Is Mirlanda at risk for type 2 diabetes?

Mirlanda's family history indicates that her maternal grandmother has T2DM. Type 2 diabetes has a strong genetic predisposition. The lifetime risk for the development of T2DM in first degree relatives of a patient is 5-10 times higher than that of age and weight matched subjects without a family history. The genetics of T2DM are complicated. Associated with the genetic predisposition are also, environmental factors, which allow clusters of different ethnic groups to develop diabetes. For example, T2DM is 2 to 6 times more prevalent among African-Americans, Pima Indians and Hispanic Americans than among non-Hispanic Whites. Mirlanda is an African American early pubertal female with a strong family history for diabetes, and can be considered at significant risk for development of diabetes.

Q5. What is the relationship between environment and obesity?

Endemic poverty among children of all backgrounds may be as an important to their development of obesity as are their heredity, race/ethnicity, or culture. Low birth weight sets a trigger for developing obesity later in life. Exposure to intermittent abundance of food, lack of exercise, and a compelling sense of deprivation later in life fire the gun. Food insecurity in itself, an almost universal condition for poor families trying to survive without support for food or rent, leads to metabolic and cultural responses to deprivation and obesity

Common phenomena in families with a high risk for obesity:

Eat whenever there is food - you never know when the next meal will come. Finish your plate, whether you are hungry or not. Being "fat" is considered "healthy", and being "skinny" is considered "unhealthy".

Public support for the poor, including supplemental food programs, have substantial impact on nutrition in pregnancy and limit weight gain for older children and adults. Unfortunately, these resources are being limited in a society promoting self sufficiency as a cure all for the ills of the poor.

In the recent past, among Native Americans and Mexicans the Genetic "Hour Glass Phenomena" [which summarizes the observation that those with an ability to store body fat and keep blood glucose normal in pregnancy survived in times of nutritional adversity] should not be considered independently from an environment that permits inactivity. The Pima, a Native American group, living in the United States suffer one of the highest rates of obesity and T2DM in the world. The cause is thought to be their history of cyclical starvation followed by abundant food and, in modern times, their adoption of a sedentary life style. By contrast, their cousins in Mexico maintain a traditional life style and are neither excessively obese nor diabetic. [This picture may now be changing, with altered non-traditional diets, affecting people all over the world.] Please see Figure - 3. (Hour-Glass from Deck).

** FIGURE 3 from Part II S 6 - Hour glass with caption

Q6. What is the relationship between overweight and type 2 diabetes?

Mirlanda is 10 years old and overweight. Being overweight is a strong predictor and risk factor of T2DM among children in America. More than 80% of all patients with T2DM are also obese or overweight, a twin epidemic of obesity and T2DM has become evident in several studies where the exponential increase in the prevalence of T2DM in relation to childhood overweight were documented. Until recently the link between obesity and diabetes was not clear.

TABLE 1: - Some Endocrine Properties of Adipose tissue

TEACHING CAPTION: The end result of obesity is insulin resistance; the end result of insulin resistance is obesity. Can anyone really say which came first?

Q7. What Is Adiposity Rebound (AR) And How Is It Related To Overweight?

Let us look carefully at Mirlanda's growth curve, and especially her BMI chart (Figure - 3). By age 5, Mirlanda's BMI was greater than 85th percentile for age and sex, already "At-Risk for Overweight." Looking back at her history of poor initial weight gain, her BMI chart is indicative of what is now described as an early "Adiposity Rebound" (AR). [See Part II Section 2 for more information on the AR]

AR of BMI is the period when the initially decreasing BMI flattens out at the nadir, and then begins to rise. This usually occurs between 4 to 6 years of age, on the average, but may occur as late as 7 or 8 years, or as early as 3 years (Figure - 5). For children likely to be lean as adults, AR occurs at 7 years of age for both boys and girls at the fifth percentile. The spread between the 5th and 50th percentile for BMI is substantially less than the spread between the 50th and 95th percentiles. Comparison between data from the current epidemic of obesity and from a prior era is not available. It is likely that AR is now occurring earlier among children "at-risk" for obesity. How early did Mirlanda's AR occur?

AR from section on AR

TEACHING CAPTION: For boys there is a 2.0 kg/m2 difference between the 5th and 50th percentiles (2.2 kg/m2 for girls) and a 4.2kg/m2 difference between the 50th and 95th percentiles (4.8 kg/ m2 for girls). Allison, et al, interpret these data to suggest that "...genetically susceptible individuals are being pushed to ever greater degrees of obesity by an "obesogenic" environment" that promotes obesity for susceptible individuals leaving the less susceptible unaffected.

Mirlanda's AR occurred before she was 3 years old. Several studies have shown a strong association between an early or premature AR in childhood and high BMI as an adult. At age 10+ years, Mirlanda is close to adolescence and that has two implications. First is that being overweight as an adolescent makes it most likely that she will become an obese adult who carries increased risk for chronic condition such as cardiovascular morbidity and mortality. The second point is that she is in early puberty, a period in the life cycle that is associated with rapid hormonal changes. Pubertal hormones have the capacity of decreasing tissue sensitivity to insulin, making the female adolescent particularly vulnerable to T2DM.

Q8. Is there a relation between intra uterine growth retardation and the later development of obesity and diabetes?

Mirlanda's anthropometric parameters at birth classified her as SGA/IUGR. Except for poor maternal weight gain, and the development of pre-eclampsia, there were no other factors known to be associated with IUGR, such as maternal infections like TORCHS syndrome and others. Her mother's pre-eclampsia developed around the 24th week of gestation. Pre-eclampsia is a known cause of utero-placental insufficiency, and leads to poor blood flow (and nutrient delivery) to the placenta, resulting in poor fetal weight gain and thus, IUGR.

Q9. What is Thrifty Genotype?

Intra Uterine Growth Retardation is thought to lead to obesity and diabetes because of a "Thrifty Genotype." As defined by Neel, The Thrifty Gene derives from "inherited metabolic changes likely to increase storage of body fat" and enhance ones chances for survival during periods of starvation or debilitating disease. There are two hypotheses for the origins of thrifty genes and their activation. One possible explanation for IUGR infants' increased risk for developing diabetes is that inadequate pancreatic tissue development occurs due to nutritional deprivation in-utero. The inadequate pancreatic tissue development and the ensuing decrease in ß cell mass will prove insufficient to compensate for the additional demands of the obese individual to maintain normal blood glucose. The traditional theory is that "insulin resistance might improve survival during states of caloric deprivation but would lead to diabetes during states of caloric excess or adequacy."

An alternative hypothesis is that "the malnutrition during fetal life or early life may induce the thrifty genotype; i.e. IUGR, leading to low birth weight, and is associated with increased risk of insulin resistance and type 2 diabetes." Low birth weight children have an increased tendency to develop T2DM in later life. (This is one possible explanation for a programming response described by Barker and colleagues). Krishnaswamy et al. explain the adult response to fetal depravation as follows,

"…the fetus in a malnourished womb has to adapt to a limited supply of nutrients thereby changing its physiology, function, and metabolism. Such 'programmed' changes may trigger a number of diseases in later life when dietary intakes and lifestyles differ greatly from the deprivation experienced in utero."

Curiously, programmed changes in utero also account for Large for Gestational Age (LGA) infants having a similar risk. The mechanism may be different. The link between birth weight and the risk for the later development of diabetes is a U-shaped curve, where normal weight children are at the nadir of the curve and SGA and LGA infants form the two arms of the "U".

In a recent publication, S. Bhargava and colleagues demonstrated a prevalence of 10.8% for impaired glucose tolerance, and a prevalence of 4.4 % for T2DM, in a cohort of 1492 men and women aged 26-32 years all of whom were born SGA and followed from birth.

Q10. What are the clinical signs of type 2 diabetes?

The clinical signs of diabetes are: polyuria, polydipsia, and polyphagia. Diabetes mellitus, regardless of its pathogenesis is characterized primarily by an elevation of plasma glucose, or hyperglycemia. The normal level of glucose in the blood is between 80-120 mg /dl. Renal glucose reabsorption is saturated at a blood sugar concentration of 140mg/dL, beyond which glucosuria occurs. Glucosuria leads to polyuria with a compensatory increase in thirst and drinking (polydipsia).

Excessive food ingestion (polyphagia) in diabetes is usually due to tissue hypoglycemia because glucose is unable to enter the tissues. Therefore the cells suffer from "hunger" and that sends a signal to the brain for increased food intake.

Q11. What are the signs/symptoms that are non specific, but we need to look for?

There are also some non-specific signs to pay attention to in a child with risk factors for diabetes. Younger children may present with unexplained weight loss and abdominal pain, but these signs are seen more often in insulinopenic diabetes or Type 1 Diabetes Mellitus (T1DM). Genital yeast infection, especially in pre-pubertal girls is often an indicator of hyperglycemia, and a reason for a diabetes work up in the absence of another explanation. Finally, adults and children with T2DM may complaint of being chronically tired, and this may be blamed only on their excessive weights. Mirlanda did not have any of these non-specific symptoms either. The velvety hyper-pigmentation noted on her neck and axillae is called Acanthosis Nigricans (AN).

While AN is not pathognomonic of the condition, it is one of the external signs of insulin resistance. Insulin resistance, unmitigated by weight loss or other treatment causes hyperinsulinism and eventually results in pancreatic failure, glucose intolerance, and diabetes. Family history usually underlines the genetic predisposition to this sequence of outcomes.

Q12. What is Polycystic Ovary Syndrome and what is its significance?

At 10+ years of age, she has coarse pubic hair, significant breast development and facial acne. The early appearance of coarse pubic hair is premature pubarche or adrenarche, and indicates excessive androgen production. Mirlanda has a combination of signs (overweight, acanthosis nigricans, precocious puberty and hirsutism) that are all predictors of Polycystic Ovary Syndrome (PCOS) and are associated with the development of T2DM in later life. Even though Mirlanda does not yet have the classical signs of diabetes (polyuria, polydipsia, polyphagia) the family needs to be aware of her risk of developing the condition, in order to muster appropriate interventions to avoid predictable complications.

Q13. What is the pathogenesis of type 2 diabetes and what kind of test. Would help us document the diagnosis?

Type 2 diabetes is characterized by hyperglycemia due to two factors: tissue insulin resistance, and impaired pancreatic insulin release. These two factors work synergistically but can work independently to contribute to T2DM. The hyperglycemia indicates a failure of the insulin to metabolize the blood glucose. Tests used for diagnosis or detection of abnormal glucose metabolism include performance of an Oral Glucose Tolerance Test (OGTT). This involves giving a standard load of glucose to an individual after an overnight fast, and measuring blood sugar levels at predetermined intervals. After two hours a normal individual (able to metabolize glucose well) will have a blood sugar below 140mg/dL. An individual with an impaired glucose tolerance or one with diabetes will have much higher levels of blood sugar. However this test is cumbersome and is used mostly for research purposes. A much simpler test called the Impaired Fasting Glucose (IFG) is presently the gold standard for diagnosis of diabetes. In July 1997, an International Expert Committee on diabetes recommended that diabetes could be diagnosed on the basis of two fasting blood glucose values above 125mg/dL or two random values above 200 mg/dL. The rate of progression from IFG to overt diabetes varies among different populations. Being African American, Mirlanda is from a population known to have a greater risk for progression from IFG to overt diabetes.

INSERT FIG FROM T1DM

Q14. What other tests could be conducted?

Another simple test is the measurement of Glycosylated hemoglobin. An irreversible binding of glucose to hemoglobin occurs, the rate of which depends on the height of blood sugar elevation. The lifespan of the red cells will affect the percentage of hemoglobin that is glycosylated. Hemoglobin A1c (HbA1c) is the more stable and consistent fraction of the hemoglobin-glycated compounds that can be measured. The measurement of HbA1c gives a fairly accurate idea of the mean blood glucose concentration over the previous six to eight weeks. This test is used as an adjunct to adjust medication for the control of glycemia in diabetes care.

Q15. What is the natural history Type 2 Diabetes Mellitus in relation to overweight in children?

Unlike T1DM, which is a well studied condition among youth, T2DM in children and adolescents is a fairly new phenomenon and long-term follow up studies of morbidity and mortality in children are not yet available. Likewise much progress has been made in the management of the former, while new research is now being established in order to find new ways to control the T2DM epidemic in the youth.

Q16. What is MODY and how is it different from T2DM?

Maturity Onset Diabetes of the Youth (MODY) is a form of T2DM characterized by abnormal insulin secretion. MODY is a monogenic disorder, characterized by an autosomal dominant inheritance, early onset (<25yrs) and abnormal pancreatic b-cell function. Non-genetic factors have little influence on the development of this disorder. MODY does not represent a good model for understanding the natural history of T2DM because of the clear differences in genetic and environmental factors that are associated with them (See Table 2 Below).

Table 2: Distinguishing Clinical Characteristics Of MODY And Type 2 Diabetes *

* Replicated from Fajians et al 2001. NICOLE: Need this reference

TEACHING CAPTION: Contrary to common belief, Type 2 DM in childhood is not simply an early occurrence of maturity onset DM.

Left untreated, each one of these conditions: obesity and T2DM in children has the potential for independently causing significant morbidity and mortality, and because of its association with obesity, T2DM may present a more significant risk to young people, than MODY. Both conditions are associated with increased risk for cardiovascular diseases and early development of atherosclerotic lesions. Hypertension, stroke, and end-stage renal disease, as well as proliferative ocular lesions all represent the final stages of underlying micro-vascular and macro-vascular complications that often started during childhood.

Q17. What other complications are associated with childhood overweight?

** Insert Figure here

[See Figure - 6]

Childhood overweight has the following complications:

Sleep Apnea and gallbladder diseases. The cost of hospitalizations for these 2 conditions alone has tripled among children aged 6-17 years between 1979 and 1999.

Bone deformity such as Slipped Capital Femoral Epiphysis (SCFE) occurs during rapid growth in adolescence. Two-thirds of all cases of SCFE occur in overweight children. Blount disease is an abnormality of the medial tibial epiphysis during growth, and is frequently associated with excess weight. Both conditions cause pain and deformity, and can lead to surgery.

Pickwickian Syndrome is associated with extreme obesity. It is characterized by "an intolerably high increase in the work of breathing" due to additional effort needed to move the muscles of ventilation. This leads to retention of carbon dioxide that over a long period of time decreases the drive to breathe. These children can present with hyper somnolence, dyspnea, hypoxemia, and eventually develop pulmonary hypertension.

Polycystic Ovarian Syndrome (PCOS) and the similar Stein-Leventhal Syndrome, is another complication of obesity and insulin resistance. The hyperinsulinemia leads to ovarian hyperandrogenism, which causes amenorrhea. Elevated levels of the gonadotropin Luteinizing Hormone (LH) characterize ovarian hyperandrogenism. This usually leads to an increase in the ratio of LH to Follicle Stimulating Hormone (FSH). The elevated LH levels are thought to be due to hyperinsulinism affecting ovarian response to LH, and thereby driving the levels of LH upwards.

With respect to Mirlanda, she is obese and has apparent signs of hyperandrogenism: premature pubarche, hirsutism, apocrine odor, microcomedone acne, and abdominal obesity. While it is unclear where the androgens originate - since as a pre menarche child it cannot be assumed that the androgen necessarily derive from her supposedly still dormant ovaries - it has been noted that children who present with premature adrenarche are usually hyperinsulinemic. These characteristics make Mirlanda a prime candidate for the development of PCOS or Stein-Levanthal Syndrome after menarche. In fact, she could even present with primary amenorrhea from the complications of ovarian hyperandrogenism.

Q18. Does parenting style affect likelihood of obesity?

Simply stated, teaching effective parenting is essential in obesity prevention. Kyung Rhee and colleagues published a fascinating paper recently. (Rhee KY, et al. 2006). These authors showed similar results to Karp et al (2005) except that they used parenting styles as an independent variable with weight status in first grade (about 6 years of age) as the outcome. Rather than multiples of poverty level as the discriminating factor as to which child was obese, these authors used parenting style.

Children raised in families with an "Authoritarian" style were almost five times as likely to be obese as children raised with "Authoritative" parents and twice as likely as when the parents were either "Permissive" or "Neglectful."

These distinctive parenting styles are defined with 2 by 2 parenting scale developed by Baumrind (2000). High or low expectations for self-control are rated on one axis in Baumrind's model. The other axis is parental sensitivity to child needs.

Their results: in a sample of 872 children, 97 (11.1%) had a BMI score >95th%ile for age and gender. Of note, the relative odds of overweight in the model adjusted for income to needs ratio were significant (OR = 0.89; 0.98; p<0.05). This suggests a correlation between parenting style and levels of poverty. No directionality can be assumed from these data or those provided by Karp, et al. (2005) Race/ethnicity, per se, did not affect outcome.

Authoritarian refers to parents who set firm limits and have high expectations for behavior but who are not sensitive to child needs. [17.1% of these children were obese]

Permissive refers to parents who do not sets firm limits or high expectations for behavior but who are sensitive to child needs. . [9.8% of children were obese]

Neglectful refers to parents who set firm limits and high expectations for behavior and who are not sensitive to child needs. . [8.9% of children were obese]

Authoritative refers to parents who set firm limits and have high expectations for behavior who are also sensitive to child needs. [3.9% of children were obese]

Q19. What measures can be taken to prevent overweight?

Resident exercise:

Consider the need to affect the following interacting variables using the Gonzales family, Mirlanda and the society in which they live as a focus of discussion

1. Public Policy,

2. Family and individual behavior

Public policy changes are arguably the most important factor that will impact on attempts to prevent childhood overweight. As noted earlier, poverty has a profound impact on the prevalence of obesity and T2DM. Measures to improve food security and discretionary income will, in the long run decrease the desire of parents to over feed their children. Moreover, public policy affects the safety of the streets and the availability of play areas for all children. These are discussed more full in the third section of the teacher's guide.

School based interventions can also prove useful. One such intervention, called "Planet Health" is an interdisciplinary curriculum that aims to decrease dietary fat consumption, increase intake of fruits and vegetables, and promote physical activity and limit television time. Similar programs are also being increasingly promoted by Health Insurance plans.

Family Prevention of childhood overweight involves the establishment of good eating habits that take into consideration the principle of energy balance - caloric intake must match caloric output.. There are two important considerations for food intake: the quantity and the quality of the food consumed. Children who eat small amounts of calorie dense, but high glycemic index foods, or get additional calories in sugary beverages can still become overweight. For children, intervention to prevent overweight should always be "Family Based". Measures should be initiated early in a child's life, and take into account the parents feeding practices.

For example "5 - 2 - 1 - 0 Jump Up and Go" is promoted by Blue Cross Blue Shield and encourages the daily consumption of 5 serving of vegetables and fruit combined, limiting of TV watching to a maximum of 2 hours a day (The average for American children watches 5 hours of TV/day), and emphasizing physical exercise for at least 1 hour every day. This turns out to be a simple formula that could be used in a public health campaign. The "0" is for sugar beverages including juice.

Researchers from the Institute of Human Nutrition of Columbia University divide prevention strategies into 3 categories (see Williams, et al):

1- Primordial prevention: aiming to prevent children from becoming "At-Risk of Overweight" or keeping BMI below the 85th percentile.

2- Primary prevention: aiming to prevent "At-Risk of Overweight" children from

becoming "Overweight", or keeping BMI below the 94th percentile.

3. Secondary prevention: aiming to prevent increasing severity of overweight, (keep the BMI as close to 95th percentile as possible) and reduce co-morbidity among "Overweight" children.

The following table presents a summary of principles of pediatric overweight prevention in community, school and home:

Table 3: A Summary of principles of pediatric overweight prevention in community, school and home.

TEACHING CAPTION: No family or individual will be able to accomplish all of the goals listed in this table, but the change to the next rung in some or many variables may have a substantial effect. See Williams, et al.

SUMMARY

Childhood overweight is one of the most difficult problems facing the world and the US public health system in particular. The epidemic of obesity is spreading rapidly among populations who are already at high risk for multiple other problems: higher infant mortality, cardiovascular diseases, cancer, substance abuse, and HIV/AIDS. Disparities in health service access and education must be addressed with programs that go to the root-causes of these problems. Prevention must take place in the context of global efforts to improve public health education on proper nutrition. This will go a long way to keep the families away from the fast food chains. Prevention within families should be part of every medical encounter. These issues are discussed more fully in the sections on obesity (Part III of the Teacher's Guide).

References

Baumrind D. (2000) Rearing competent children (in) Damon W (ed) Child Development Today and Tomorrow. San Francisco Ca. Jossy-Bass pp 349-378.

Ebbeling B Cara, Pawlak B Doroto, Ludwig S David. Childhood Obesity: public health crisis, common sense cure. Lancet 2002, 360:473-82.

Fajians -- Nicole - need reference

Goran Michael I. Geoff D. C. Ball and Martha L. Cruz

Obesity and Risk of Type 2 Diabetes and Cardiovascular Disease in Children and Adolescents. J Clin Endocrinol Metab, 2003;88 (4): 1417-1427.

Ibanez L; Potau N; Zampolli M; Rique S; Saenger P; Carrascosa A. Hyperinsulinemia and decreased insulin-like growth factor-binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche. J Clin Endocrinol Metab 1997 Jul;82(7):2283-8.

Karp RJ, Cheng C, Meyers AF. (2005) The appearance of discretionary income: Influence on the prevalence of under- and overnutrition. International Journal of Health Inequities <http://www.equityhealthj.com/content/4/1/10>

Krishnaswamy K, Naidu AN, Prasad, Reddy GA. Fetal malnutrition and adult chronic disease. Nutrition Reviews; 60(5): 35s.

Rhee KE, Lumeng JC, Appugliese DP, Kaciroti N, Bradley RH. Parenting styles and overweight status in first grade. Pediatrics. 2006 Jun;117(6):2047-54.

Rocchini AP. Childhood obesity and a diabetes epidemic. New England Journal of Medicine. 2002;346(11): 854-5.

Williams L Christine, Gulli T Maria Deckelbaum J Richard. Prevention and Treatment of childhood obesity. Current Atherosclerosis reports 2001; 3:486-97.

Annotated Answers

A1. False. It may have seemed to be an impossibly obvious question, but pediatrics as a specialty did not exist in the mid 19th century. Even today, physicians often ignore important differences associated with infancy, childhood, adolescence and different ages of adults.

A2. True. The BMI is age and sex dependent. The age dependency makes it a problematic tool in that overweight pre-pubescent children are seem to be older.

A3. False. That's the opposite of the reality suggested by the "Barker" hypotheses. Prenatal experience of deprivation my program the fetus to hold body weight later in life with consequences of overweight to follow.

A4. False. As Krishnaswamy et al explains,

" [T]he fetus in a malnourished womb has to adapt to a limited supply of nutrients thereby changing its physiology, function, and metabolism. Such "programmed" changes may trigger a number of diseases in later life when dietary intakes and lifestyles differ greatly from the deprivation experienced in utero.".

A5. False. White non-Hispanic Americans have the lowest rates for obesity and Type 2 DM. As noted below, this is only partly related to a true genetic difference. Income levels and stress impact on the outcome.

A6. False. African peoples living in Africa are generally healthier when living in stable societies than African Americans. The life style and stress of life in the United States have been associated with this discrepancy.

A7. True. Poverty, in itself, increases the risk for all these disorders in that poverty incomes require highly concentrated calories to meet daily requirements. Often poverty is associated with lack of resources or safety for outdoor activities

A8. True. All costs for essential items reduce the amount of income available for food and contribute to Food Insecurity

A9. True. Food Insecurity (FI) is an intermediate variable between poverty and an outcome. For families living at the poverty level and just above, food insecurity is associated with overweight. Food programs help reduce FI by providing a sure continual supply of nutritious food through a one month cycle..

A10. The answer is A. Delayed Adiposity Rebound is an indicator of low risk for obesity and related problems. Central obesity, borderline poverty and early acanthosis nigricans are all high-risk circumstances.