didiasis, which can occur in girls secondary to increased urinary excretion of glucose. Commonly, children with T1DM present in diabetic ketoacidosis (DKA), a life-threatening complication of diabetes (ADA et al., 2022g). In the absence of insulin and the ability to utilize glucose, the body uses fat for energy, which produces ketones and creates an acidotic state (Glaser et al., 2022). In response to the inability to utilize glucose, counterregulatory hormones, such as glucagon, catecholamines, and cortisol, are released, which increases glu- cose production. Diabetic ketoacidosis is considered a medical emergency and typically requires hospitalization for monitoring and treatment. This is a rarer occurrence in children with T2DM unless triggered by a concomitant illness or hyperglycemia-induc- ing medication (ADA et al., 2022a). Only about 6% of youth pres- ent with DKA at the onset of T2DM (ADA et al., 2022g). Patients with T2DM who present with severe hyperglycemia (defined as a blood glucose ≥ 600 mg/dL) may experience hy - perglycemic hyperosmolar state (HHS; ADA et al., 2022g). Hy- perglycemic hyperosmolar state is similar to DKA but without the significant accumulation of ketone bodies. Hyperglycemic hyperosmolar state results in decreased uptake of glucose into peripheral tissues, but since insulin is still being produced, keto- genesis is generally inhibited (Glaser et al., 2022). Similar to DKA,
this “starvation” process causes counterregulatory hormones to be released, which further increases glucose levels in the blood- stream. Hyperglycemia increases serum osmolarity, which causes free water to be drawn out of the extracellular space and excreted in the urine. This process can cause moderate to severe dehy- dration and electrolytes losses. While HHS is more common than DKA in T2DM, it is still relatively rare in children. When HHS does occur, it is usually precipitated by an infectious process. Hypergly- cemic hyperosmolar state has a high mortality rate and typically requires hospitalization for aggressive fluid resuscitation. Self-Assessment Quiz Question #1 Which of the following is FALSE regarding the pathophysiology of type 2 diabetes mellitus? a. Insulin resistance leads to increased insulin secretion. b. Antibody-mediated ß-cell destruction contributes to insulin dysfunction. c. Pancreatic ß-cell dysfunction progresses more rapidly in youth-onset type 2 diabetes compared to adult-onset type 2 diabetes. d. Surplus body fat contributes to insulin resistance.
DIAGNOSIS
According to the American Diabetes Association (ADA) 2022 cri- teria, diabetes is defined by one of the following criteria (ADA et al., 2022a): ● Hemoglobin A1C (HbA1C) ≥ 6.5%. ● Fasting (no caloric intake for ≥ 8 hours) plasma glucose ≥ 126 mg/dL. ● Oral glucose tolerance test (75-gram glucose load) with 2-hour plasma glucose ≥ 200 mg/dL. ● Random plasma glucose ≥ 200 mg/dL with classic hypergly - cemic symptoms. In the absence of symptomatic hyperglycemia, diagnosis of dia- betes should be confirmed with a second abnormal result during a subsequent screening (ADA et al., 2022a). Patient-specific fac - tors that alter hemoglobin, including sickle cell disease, pregnan- cy, and recent blood loss, can affect the accuracy of the HbA1C result. If there exists a discordance between the HbA1C value and plasma glucose levels, the latter is more reliable and accurate, especially in patients with hemoglobinopathies. Billy presents to his annual visit with concerns about risk factors for prediabetes and type 2 diabetes mellitus. Which of his risk factors meet screening criteria? Discussion Screening for prediabetes and diabetes should begin at ≥10 years of age or puberty for pediatric patients who are overweight with additional risk factors or symptoms of diabetes. Billy’s body mass index is over the 95th percentile, which meets criteria for obesity, and he has poor eating habits and a sedentary lifestyle. These unhealthy habits are not criteria for screening but may contribute to Billy’s obesity and put him at risk for prediabetes and diabetes. He has a first-degree relative with diabetes and darkening of skin folds, which could be indicative of acanthosis nigricans, a condi- tion strongly associated with type 2 diabetes and a sign of insulin resistance. These two criteria are listed by the American Diabetes Association as risk factors for screening. Although he is not oth- erwise symptomatic, Billy may be found to have elevated blood glucose levels and insulin resistance, and he should be screened for prediabetes and type 2 diabetes. Children who present with hyperglycemia and symptoms of di- abetes require further testing to differentiate a T1DM diagnosis from a T2DM diagnosis (ADA et al., 2022a). In T1DM, detection Case study: Billy Question
Children and adolescents who are overweight (defined as BMI ≥ 85th percentile for age) or obese (defined as BMI ≥ 95th percen - tile for age) are at risk for T2DM, especially if they have additional risk factors (ADA et al., 2022g). Obese or overweight children with one or more additional risk factors should be screened for predi- abetes and T2DM after the onset of puberty or ≥ 10 years of age, whichever occurs earlier. Additional risk factors for screening, as outlined by the ADA, are maternal history of diabetes or gestation- al diabetes during the child’s gestation, family history of T2DM in a first- or second- degree relative, high-risk race or ethnicity, and signs of insulin resistance or associated conditions. Signs of insu- lin resistance include acanthosis nigricans, hypertension, dyslip- idemia, polycystic ovary syndrome, and small-for-gestational-age birth weight (ADA et al., 2022a). In children with these risk factors whose tests are normal, repeat testing is recommended at 3-year intervals or sooner if their BMI continues to increase. Identification of prediabetes is critical for early intervention and prevention of progression to diabetes. Prevention may help lower rates of de- veloping retinopathy and nephropathy, which are complications of diabetes. of islet autoantibodies is a clear indication of ß-cell destruction. Islet autoantibody testing should always be performed to exclude the diagnosis of T1DM, even in patients with classic findings of T2DM. Healthcare Consideration: Although obesity is a risk factor for and is associated with type 2 diabetes, overweight and obese pediatric patients who meet criteria for a diabetes diagno- sis may have type 1 diabetes (ADA et al., 2022g). One study demonstrated that nearly 10% of youth clinically diagnosed with type 2 diabetes were positive for circulating antibodies (Klingensmith et al., 2010). Although a patient’s presentation may align with one type of diabetes, the initial diagnosis must often be reconsidered. A diagnosis of “prediabetes” may be made in individuals who do not yet meet the ADA criteria for diagnosis of diabetes but who are displaying signs and symptoms of abnormal carbohydrate me- tabolism (ADA et al., 2022a). An impaired fasting plasma glucose, defined as 100 to 125 mg/dL, or poor glucose tolerance, defined as a 2-hour plasma glucose of 140 to 199 mg/dL during a 75-gram oral glucose tolerance test, may be attributed to prediabetes. An- other potential marker is HbA1C between 5.7% and 6.4%. The most common finding in adolescents is impaired fasting glucose
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