OBESITY AND DIABETES
From the Cape Cod Conference on Pediatrics 2008, presented by Nemours
Educational Objectives
| The goals of this program are to improve management of obesity in children and lower their risk of developing
diabetes, and to improve management of type 1 diabetes during illness. After hearing and assimilating this program,
the clinician will be better able to:
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 | 1. Recognize when to screen for type 2 diabetes in a child.
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| 2. Recommend lifestyle changes to families with obese or overweight children.
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| 3. Describe the metabolic effects of illness on glucose homeostasis in a child.
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| 4. Manage low blood glucose during illness with carbohydrates and fluids.
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| 5. Instruct parents in the use of mini-dose glucagon for hypoglycemia.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the
planning committee to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in
health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr.
Haymond is a consultant for Novo Nordisk and has received grants from Sanofi-Aventis, Novo Nordisk, and Medtronics.
The planning committee reported nothing to disclose.
Acknowledgements
Dr. Haymond was recorded at the Cape Cod Conference on Pediatrics 2008, held August 1-3, 2008, in Hyannis, MA,
and sponsored by Nemours. The Audio-Digest Foundation thanks Dr. Haymond and Nemours for their cooperation in
the production of this program.
Morey W. Haymond, MD
Professor of Pediatrics, Children’s Nutrition Research Center, Department of Pediatric Endocrinology and Metabolism,
Baylor College of Medicine, and Director, Diabetes Care Center, Section of Endocrinology, Texas Children’s Hospital,
Houston
Obesity and Type 2 Diabetes in Children: A Weighty Problem
| Incidence: United States becoming progressively obese society; incidence of obesity worldwide also increasing,
particularly in evolving (eg, Middle East, India, China) and developed countries; prevalence of obese and
overweight children approaching 16% to 18%; seen predominantly in Latinos and blacks; also dramatic increase
in children 2 to 5 yr of age; consequently, earlier onset of type 1 diabetes seen
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| Insulin resistance: key issue; subnormal biologic response to certain concentration of insulin in plasma;
weight and obesity contributing factors; mechanism in postreceptor activation of insulin signaling; physical
inactivity also contributes; increased by—aging, glucocorticoids and growth hormones, increased free fatty
acids (FFAs; higher circulating concentration of FFAs seen in obese people; FFAs interfere with insulin signaling;
increased FFAs seen not just in plasma but also intracellularly); in obesity, adipokines and cytokines
affect insulin signaling; genetic factors (not just predisposition to obesity but also defects in insulin signaling
and insulin release); classic defects in insulin receptors rare; in obesity, increase in fat and plasma FFAs leads
to insulin signaling defect (takes more insulin to reduce blood glucose [BG] to shut off insulin secretory stimulus);
acanthosis nigricans, prediabetes, type 2 diabetes, dyslipidemia, hepatic steatosis, polycystic ovary syndrome
(PCOS), and hypertension seen with insulin resistance
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| Acanthosis nigricans: predominantly seen in Latinos, blacks, and Asians; at its worst, rugated skin with increased
pigmentation around neck, armpits, groin, and behind folds of legs; seen in 20% of children in public
schools; when present in children in younger age range (eg, early elementary school), as time goes on, incidence
of type 2 diabetes progressively rises (heralds onset of potential β-cell failure and, ultimately, type 2 diabetes);
Pima Indians have highest incidence of type 2 diabetes
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| Diabetes: ideally, fasting BG <100 mg/dL; 100 to 125 mg/dL prediabetes; ≥126 mg/dL meets fasting criterion
for diabetes; utilizing 2-hr postprandial or poststandard oral glucose tolerance test (GTT), results between 140
and 200 mg/dL, prediabetes, and >200 mg/dL, diabetes; children with type 2 diabetes often lost to follow-up;
risk factors—obesity; ethnicity (non-European ancestry); acanthosis nigricans; sex (more common in girls,
possibly related to physical inactivity); birth weight; gestational diabetes in mother; based on body composition
data, at given body mass index (BMI), Latinos have greater intravisceral fat than blacks or whites; increased
risk for type 2 diabetes seen in low birth weight and high birth weight infants; incidence of children
having diabetes greater in those whose mothers diabetic or prediabetic; in patients with type 2 diabetes, majority
have BMI >85th percentile; in speaker’s practice, children with type 2 diabetes have BMIs between 27
and 38; rare that child with type 2 diabetes not obese; screening—any child >10 yr of age, with BMI >85th
percentile, and with 2 of following (family history of diabetes [parent or relative], non-European ancestry,
other evidence of insulin resistance [eg, acanthosis nigricans], hypertension, dyslipidemia, PCOS)
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| Role of primary care physician: key to stemning tide of obesity; must measure height and weight of all children
and plot measurements; no BMI criteria for children <5 yr of age (use height-to-weight ratio); if BMI
crossing isobars, make common-sense changes (eg, avoiding whole milk) and intervene early with entire family
(have discussion about health); overweight child commonly reflects family problem; requires substantial
lifestyle changes (decreasing caloric intake and increasing physical activity)
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New Approaches to the Management of Type 1 Diabetes
| Effect of illness on glucose homeostasis in child: during incubation phase of infectious disease—dramatic
metabolic effects include increased secretion of growth hormone and cortisol (regulatory hormones that induce
insulin resistance), increased hepatic glucose production, and decreased peripheral glucose utilization;
in susceptible patient, this results in hyperglycemia; as child becoming more insulin-resistant and unable to
counterregulate with increased insulin secretion, more FFAs mobilized, resulting in ketone production; diabetic
child—unable to respond to subtle changes in insulin sensitivity, and therefore becomes prone to outcomes
of hormonal changes; insulin resistance or insufficiency leads to increased glucose production and
lipolysis; increased lipolysis—leads to release of glycerol, which drives gluconeogenesis, leading to FFA release;
FFAs—go directly to peripheral tissue for utilization and to liver for partial oxidation (formation of ketones);
ketones utilized by brain; increased FFA and ketone availability—results in decreased glucose
utilization (at time when it should be increased); increased glucose production and decreased glucose utilization
result in hyperglycemia, glycosuria, osmotic diuresis; patient becomes ketotic; ketones passively filtered
in kidney; ketonuria—additional osmotic forces driving osmotic diuresis; with ketosis, increase seen in β-hydroxybutyrate/acetoacetate
(B/A) ratio, as result of change in redox state of body (has implications when using
nitroprusside tablets to measure ketones); these 2 factors lead to osmotic diuresis, which results in
increased fluid and electrolyte losses; increased ketosis leads to acidosis and nausea; acidosis—potassium
loss and compensatory hyperventilation for metabolic acidosis (creating ventilatory alkalosis and hypothermia);
osmotic diuresis—water, potassium, sodium, and phosphate lost (primarily due to buffering of hydrogen
ion); leads to dehydration, volume contraction, thirst, and polydipsia; if patient nauseated, unable to compensate;
ultimate result—additional counterregulatory hormone secretion, preserved circulating blood volume
and perfusion pressure with cortisol, growth hormone, glucagon, and, ultimately, epinephrine; all these drive
gluconeogenesis and mobilization of FFAs (ketosis), moving patient from mild decompensation to ketoacidosis
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| Gastroenteritis in child with type 1 diabetes: difficult to ascertain whether child decompensating to ketoacidosis
or has gastroenteritis independent of diabetes; all potential substrate and hormone changes involved occur
in addition to slowing of gastric emptying (nausea and vomiting, delayed absorption or loss of
carbohydrates, and accelerated water loss); increased transit time leads to decreased absorption time for carbohydrates
and increased water loss from diarrhea; important to remember that severe ketonemia itself causes
nausea and vomiting
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| Risk for illness in diabetic child: includes hypoglycemia, dehydration, and diabetic ketoacidosis
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| Keys to therapeutic success: manage hyperglycemia, hypoglycemia, and ketonemia; maintain hydration by
decreasing urinary losses (by keeping BG in range of 100 to 200 mg/dL) and providing oral fluids; goal to
maintain BG between 100 and 200 mg/dL and ketone bodies at <0.6 mmol
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| Tools in management of ill child with diabetes: home glucose monitoring useful; measuring β-hydroxybutyrate;
nitroprusside tablets or dipsticks to measure ketones (not as accurate); maintain patient with oral carbohydrates
and fluids; insulin; glucagon; antiemetics
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| Self-BG monitoring: standard of care; check BG on regular basis as prescribed; diabetic ketoacidosis (DKA)
should not occur during illness and almost always due to poor antecedent diabetic control
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| Ketone body measurement: dipsticks—previously used; active ingredient nitroprusside, which reacts only
with acetoacetate; actually measuring smaller of 2 concentrations of ketone bodies; urine test; dependent on
state of hydration of patient and filtered load of ketones; unable to provide exact level; Precision Xtra—
measures BG and β-hydroxybutyrate; if β-hydroxybutyrate <0.6 mmol, not problem; if child ill, usual insulin
management; if β-hydroxybutyrate between 0.6 and 1.5 mmol, push fluids, watch child carefully, and provide
extra insulin injections if necessary; if >5 mmol, admit patient to hospital
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| Managing diabetes during illness: check BG more frequently; if BG >300 mg/dL, check periodically; provide
correct fluids and food choices; low BG—treat with 5 to 10 g of carbohydrate in younger child (15 g in
older child) and recheck BG (not effective if child vomiting); important to modulate amount of carbohydrate
given; small repeated doses of carbohydrate better than large bolus; if child vomiting or unsuccessful in increasing
BG, mini-dose glucagon protocol recommended; foods—offer whatever child likes; 2 to 4 oz every 2
to 4 hr, depending on BG level; offer carbohydrate-containing fluids and clear fluids when child nauseated or
vomiting; attempt to keep BG <200 mg/dL and ketones in reasonable range; offer solid food when child ready
(ie, no longer vomiting); begin with bland or soft foods as tolerated and advance to regular diet
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| Mini-dose glucagon: in child with gastroenteritis and diabetes who has postinsulin vomiting, parents have
choice of bringing child to emergency department or force-feeding fluids to child; parents reluctant to give
glucagon (feels like failure); parents intimidated by intramuscular (IM) administration via 3-mL syringe
with 21-gauge needle; however, mini-dose glucagons given subcutaneously with insulin syringe; 1 U/yr of
age; start with 2 U, maximum 15 U; check BG every 15 to 20 min; if BG does not increase, double dose or
repeat dose; does not result in nausea or vomiting; cost-effective (≈$60 for vial of glucagon) and saves time
and effort; in child with severe hypoglycemia—glucagon kit traditionally used; 1 mg fits all, using 18- to 20-
gauge needle; instruction to give IM; dosage increased 10-fold over that used for mild hypoglycemia (1 U/
yr); glucagon kit also for child in danger of ketoacidosis; glucagon, once mixed, should be refrigerated and
kept ≤24 hr; reorder additional glucagon kit immediately as reserve
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| Antiemetic: efficacy unknown; advantage possible decrease in nausea and vomiting; disadvantages include inability
to shorten period of illness and masking of other ongoing problems; ondansetron (Zofran)—used by
speaker (despite mixed feelings); developed to prevent nausea and vomiting in patient on chemotherapy; no
data on efficacy; activation of serotonin receptors associated with nausea; works by blocking 5-hydroxytryptamine
3 (5-HT3) serotonin receptor; if child >12 yr of age, dose 8 mg (if <12 yr of age, 4 mg); side effects
include headache, fatigue, and constipation
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| Summary: promote home glucose and ketone monitoring; when child with diabetes has illness, goal to keep
BG between 100 and 200 mg/dL (requires insulin supplements, oral carbohydrates, and possibly mini-dose
glucagon); maintain ketone bodies at <0.6 mmol via insulin supplementation and oral hydration; maintain hydration
by decreasing osmotic diuresis, encouraging oral fluids, and using antiemetics
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Suggested Reading
Chiolero A et al: Changes in BMI: an important metric for obesity prevention. Pediatrics 122:683; author reply 684, 2008;
Cummings DM et al: Insulin resistance status: predicting weight response in overweight children. Arch Pediatr Adolesc
Med 162:764, 2008; Haas JS et al: The association of race, socioeconomic status, and health insurance status with the prevalence
of overweight among children and adolescents. Am J Public Health 93:2105, 2003; Hasan KS et al: Mini-dose glucagon
is effective at diabetes camp. J Pediatr 144:834, 2004; Haymond MW et al: Mini-dose glucagon rescue for
hypoglycemia in children with type 1 diabetes. Diabetes Care 24:643, 2001; Heptulla RA et al: The role of amylin and glucagon
in the dampening of glycemic excursions in children with type 1 diabetes. Diabetes 54:1100, 2005; Jones KL: Role of
obesity in complicating and confusing the diagnosis and treatment of diabetes in children. Pediatrics 121:361, 2008; Lipton
RB et al: Obesity at the onset of diabetes in an ethnically diverse population of children: what does it mean for epidemiologists
and clinicians? Pediatrics 115:e553, 2005; Maffeis C et al: Waist-to-height ratio, a useful index to identify high metabolic
risk in overweight children. J Pediatr 152:207, 2008; Mayer-Davis EJ: Type 2 diabetes in youth: epidemiology and current
research toward prevention and treatment. J Am Diet Assoc 108:S45, 2008; Rao G: Childhood obesity: highlights of AMA Expert
Committee recommendations. Am Fam Physician 78:56, 2008; Rasouli N et al: Impact of family history of diabetes and
ethnicity on -cell function in obese, glucose-tolerant individuals. J Clin Endocrinol Metab 92:4656, 2007; Rodden AM et
al: Insulin resistance in adolescents. J Pediatr 151:275, 2007; Shaibi GQ et al: Examining metabolic syndrome definitions
in overweight Hispanic youth: a focus on insulin resistance. J Pediatr 152:171, 2008; Spear BA et al: Recommendations for
treatment of child and adolescent overweight and obesity. Pediatrics 120 Suppl 4:S254, 2007.
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