Pediatric T2DM: A Growing Threat to US Health

Additional treatment options
While metformin and insulin are the only FDA-approved medications for the treatment of T2DM in the pediatric population, additional medications may be used if needed because of deteriorating glycemic control.⁴ If treated with noninsulin agents (including metformin), adolescent female patients should be counseled to avoid pregnancy because long-term data are lacking about the safety to the fetus of noninsulin agents.²²

Metformin-rosiglitazone. In the TODAY trial,²³ 699 participants (ages 10 to 17) with T2DM were randomly assigned one of three treatment options: metformin alone, metformin plus rosiglitazone, and metformin with lifestyle intervention. The study found that monotherapy with metformin was often insufficient to achieve glycemic control, with a rate of treatment failure of 51.8%. Rates of failure for the other groups were 38.6% and 46.6%, respectively.

While the combination of metformin and rosiglitazone was found to be most effective, at the time these results were published, access to rosiglitazone was restricted by the FDA because of concerns about the drug’s cardiovascular safety. The FDA has since determined that rosiglitazone’s cardiovascular risks are comparable to those of other diabetes drugs and directed in November 2013 that the restrictions be removed.²⁴ In this context, the TODAY study researchers concluded that it was unclear if the results were specific to rosiglitazone, to the thiazolidinedione drug class as a whole, or to some attribute of combination therapy; they suggested, however, that combination therapy may be superior for pediatric T2DM treatment.²³

Incretin-based therapies. Another potential therapeutic option is the use of incretin-based therapies, such as the glucagon-like peptide (GLP-1) agonists exenatide or liraglutide. These have been shown to be effective at lowering BG levels in the adult population and have the added benefit of causing weight loss.

Although not approved for pediatric use, GLP-1 agonists would provide a means of therapy intensification without weight gain, which can worsen insulin resistance and propel the disease process forward. Further research is needed, and there is an ongoing multicenter safety and efficacy trial of exenatide use in adolescents with T2DM.¹³

Self-monitoring of blood glucoseInitiation and frequency of self-monitoring of BG (SMBG) in pediatric T2DM patients depends on the treatment regimen and achievement of BG goals.

The American Academy of Pediatrics recommends initiation of SMBG when the patient is 1) taking insulin or medications with risk for hypo­glycemia; 2) initiating or changing a treatment regimen; 3) not meeting treatment goals; or 4) experiencing an intercurrent illness.⁴ In addition, a patient with hyperglycemic or hypoglycemic symptoms should perform SMBG at least for the duration of the symptoms.

For all patients newly diagnosed with T2DM, SMBG is recommended before meals (including morning fasting) and at bedtime until target BG levels are achieved.⁴ For patients whose disease is well controlled with metformin, SMBG can be performed on an infrequent or intermittent basis.

In most cases, the clinician should advise the patient to perform morning and bedtime SMBG to assess fasting and postprandial glucose levels. Postprandial SMBG will allow both caregivers and clinicians to assess for glycemic excursions, especially in cases in which A1C is above goal, despite an FBG level that is at goal.⁴ Premeal SMBG may also be temporarily utilized during acute illness and to monitor for glycemic excursions.

Patients receiving multiple daily injections or insulin pump therapy require BG testing prior to every meal and often postprandial or bedtime SMBG as well.

Therapy intensification
At any point during treatment, if glycemic goals are not being met, the clinician should analyze the patient’s current medication(s), lifestyle interventions, and treatment adherence for opportunities to optimize treatment effectiveness. Therapy intensification may require more frequent office visits and SMBG, augmenting or adding medication, and referral to a nutritionist or diabetes educator. The need for treatment individualization and enhancement is likely to arise frequently, and it is often beneficial to set this expectation early in the T2DM management process with the pediatric patient and his/her family.⁴

SCREENING FOR AND MANAGEMENT OF COMPLICATIONS
Due in part to the prolonged duration of illness, patients diagnosed with T2DM as children or adolescents are at higher risk than adults for microvascular and macrovascular complications. Therefore, regular screening for retinopathy, nephropathy, hypertension, and dyslipidemia is essential, as follows:

• A dilated eye exam for diabetic retinopathy is recommended at diagnosis, annually, and more frequently as needed, depending on findings.¹³
• Annual screening for microalbuminuria will assess for early renal impairment and allow treatment to prevent diabetic nephropathy. As in adults, pediatric cases of microalbuminuria are treated with ACE inhibitors or angiotensin receptor blockers (ARBs). ACE inhibitors are dosed at 0.05-0.15 mg/kg/d in pediatric patients.¹¹ Adolescent female patients should avoid pregnancy if taking an ACE inhibitor or ARB because of risks to the fetus from these Category D medications.¹³
• In children and adolescents, the diagnosis of hypertension is made using age-, height-, and gender-adjusted percentiles. The 2011 National Heart, Lung and Blood Institute’s (NHLBI’s) integrated guidelines for cardiovascular health and risk reduction in children and adolescents include updated blood pressure tables and diagnostic algorithms for this purpose.²⁵ Pediatric hypertension is treated with ACE inhibitors and ARBs, and dosing recommendations are also available in the NHLBI guidelines.²⁵
• Acceptable lipid levels for children and adolescents are as follows: LDL, < 110 mg/dL; HDL, > 45 mg/dL; and triglycerides, < 75 mg/dL (those ages 0 to 9) and < 90 mg/dL (those ages 10 to 19.)²⁵ For dyslipidemia, diagnostic algorithms and treatment recommendations may be found in the NHLBI guidelines.²⁵

Next page: Transitioning to adult care >>