Type 2 Diabetes Mellitus and Its Etiology

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Decreased insulin sensitivity in the muscle, tissue, and liver leads to increased insulin production by beta cells of the pancreas. When beta cells can no longer secrete enough insulin to maintain blood sugar levels, hyperglycemia occurs. Left untreated, hyperglycemia may lead to coma and death (Silva et al., 2018).

Epidemiology

As childhood obesity rates rise, so does the rate of type 2 diabetes mellitus (T2DM). T2DM occurs in one out of three new diagnoses of diabetes in children (American Academy of Pediatrics, 2021). Ethnic minorities have higher risks of insulin resistance and beta-cell dysfunction and are, thus, disproportionately affected (American Academy of Pediatrics, 2021).

Pathophysiology

Obesity contributes to insulin resistance, which may result in hyperglycemia. One of the symptoms of hyperglycemia is osmotic diuresis, which causes moderate to severe dehydration. Prolonged hyperglycemia can lead to diabetic ketoacidosis or Hyperglycemic Hyperosmolar State (HHS). Ketoacidosis is the hyper-production of ketones as the body breaks down lipids for energy. HHS is continued osmotic diuresis (American Academy of Pediatrics, 2021). Both complications can result in coma or death.

Clinical Manifestations

Children with T2DM may have symptoms of excess urine, extreme thirstiness and hunger, blurred vision, and unexplained weight loss. When conducting a physical examination, clinicians may find acanthuses nigricans (dark, velvety rash usually in the axillae and neck) or skin tags (benign skin growths on the body or face) (Silva et al., 2018).

Workup

Patients who are overweight and have multiple screen factors should be tested every three years. Venous blood samples are taken, and a hemoglobin a1c test is conducted in conjunction with random blood glucose, fasting blood glucose, or oral glucose tolerance (Silva et al., 2018). T2DM is diagnosed depending on the results.

Nonpharmacological and Pharmacological Management

Clinicians should initiate a lifestyle modification program and metformin as the first-line therapy. The American Academy of Pediatrics (2021) recommends healthy eating, sixty minutes of physical activity, and a maximum of two hours of screen time per day. Patients start metformin at a low dose of 500 mg daily, increasing by 500 mg every 1-2 weeks up to an ideal dose of 2000 mg twice daily (American Academy of Pediatrics, 2021). In cases of ketoacidosis, patients require immediate treatment with insulin and fluid replacement. Once acidosis is resolved, metformin should be initiated and insulin gradually tapered off (Silva et al., 2018).

Education

Since sustaining lifestyle changes is an essential component of diabetes treatment, so is patient education. Establishing a comprehensive family-centered, culturally sensitive management plan is necessary to ensure adherence (American Academy of Pediatrics, 2021).

Follow-Up

Ideally, HbA1c concentration should be less than 7% but ultimately depends on the individual patient. HbA1c concentrations should be monitored every three months (American Academy of Pediatrics, 2021). Blood pressure should be measured at every visit. Urine albumin/creatinine ratio, estimated glomerular filtration rate, neuropathy by foot, retinal photography or dilated fundoscopy, NAFLD and lipid testing should be screened annually (Silva et al., 2018). Clinicians should also review patient adherence to lifestyle changes, and conduct annual assessments of educational and psychosocial needs.

Second-Line and Third-Line Treatment

If metformin is insufficient to attain target blood glucose levels, patients should initiate basal insulin therapy, increase the frequency of clinic visits and testing, meet with a registered dietitian and increase attention to nutrition and physical activity (American Academy of Pediatrics, 2021). If the combination of metformin and basal insulin is ineffective, higher doses of insulin, multiple daily injections or more concentrated doses should be considered (American Academy of Pediatrics, 2021). There is also the option of metabolic surgery for patients with a BMI over 35 kg/m2 (American Diabetes Association, 2017). Various second-line agents such as GLP-1 receptor agonists and SGLT2 inhibitors have been researched in the past years, but none have been approved for pediatric uses so far (Silva et al., 2018).

References

American Academy of Pediatrics. (2021). Pediatric clinical practice guidelines & policies (21st ed.). American Academy of Pediatrics.

American Diabetes Association. (2017). Classification and diagnosis of diabetes. Diabetes Care, 40(Supplement 1), S11-S24.

Silva, A., Bacha, F., Grey, M., Marcus M.D., White, N.H., & Zeitler, P. (2018). Evaluation and management of youth-onset type 2 diabetes: A position statement by the American Diabetes Association. Diabetes Care, 41(12) , 2648-2668. Web.

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