Approach Considerations
Ideally, management of diabetes should involve a pediatric endocrinologist, a diabetes nurse educator, a nutritionist, and a behavioral specialist.
In January 2013, the American Academy of Pediatrics (AAP) issued clinical practice guidelines on the management of type 2 diabetes in children and adolescents. The guidelines recommend insulin treatment in all patients who present with ketosis or extremely high blood glucose levels because it may not be clear initially whether these patients have type 2 or type 1 diabetes. Once a diagnosis of type 2 diabetes is confirmed, lifestyle modification and metformin treatment should be initiated. [45]
The goal of therapy is to achieve and maintain euglycemia, as well as near-normal hemoglobin A1c (HbA1c) levels (≤7%). Patients who are not ill at diagnosis can be treated initially with lifestyle changes (eg, diet, exercise, weight control). However, because few patients can maintain euglycemia with lifestyle changes alone, most children and adolescents require medication. [2]
Hemoglobin A1c (HbA1c) levels should be measured every 3 months and treatment adjusted if goals for both HbA1c and blood glucose are not met. Fingerstick self-glucose monitoring is recommended for all patients receiving insulin or sulfonylureas, those starting or changing therapy, and those who have not met treatment goals or who have intercurrent illness. [45]
Insulin therapy is indicated in symptomatic patients with persistent hyperglycemia, the presence of an HbA1c of more than 9%, or ketoacidosis. After blood glucose levels are normalized, efforts to taper insulin with progressive substitution of an oral agent are undertaken.
Glycemic and nonglycemic goals should be clearly stated and may include the following [4] :
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Fasting glycemia of less than 126 mg/dL
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Resolution of polyuria, nocturia, and polydipsia
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Healthy body weight
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Maintenance of cardioprotective levels of lipids and blood pressure—ie, LDL level of less than 100 mg/dL, triglyceride level of less than 150 mg/dL, HDL level of greater than 35 mg/dL, blood pressure of less than the 95th percentile for age, sex, and height
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Participation of the whole family as a unit
Unless an acute complication (eg, recurrent hypoglycemia, persistent ketosis, hyperglycemic hyperosmolar state) occurs or there is poor patient compliance with treatment, type 2 diabetes is usually managed in an outpatient setting.
Recognize that, in patients with PCOS who are receiving metformin, possible resumption of normal ovulation and menstrual cycles increases the risk of pregnancy. Transfer care to an obstetrician when pregnancy is established.
Diet
Referral to a nutritionist with experience in pediatric diabetes is necessary. Dietary recommendations should be culturally appropriate, sensitive to family resources, and provided to all caregivers, especially those in charge of cooking the family's meals.
The entire family should be encouraged to adopt healthier lifestyle habits such as participation in daily exercise and decreasing the intake of high-calorie, high-fat foods. [2]
Activity
A study by Loimaala et al study showed that long-term endurance and strength training resulted in improved metabolic control of type 2 diabetes compared with standard treatment. However, significant cardiovascular risk reduction and conduit arterial elasticity did not improve. [46]
Prevention
Because type 2 diabetes in children and adolescents is strongly associated with obesity and sedentary lifestyle, any intervention designed to increase physical activity and improve dietary habits should be encouraged. [47]
Pharmacologic Therapy
Pharmacologic therapy is indicated when the disease is not well controlled with diet and exercise. Metformin should be the first oral agent used in children and teenagers with an HbA1c level of less than 9%. If metformin is unsuccessful as monotherapy, the addition of insulin, a sulfonylurea, or another hypoglycemic agent may be appropriate. [2]
In June 2019, the US Food and Drug Administration (FDA) approved liraglutide for children aged 10 years or older with type 2 diabetes mellitus. Liraglutide, a glucagonlike peptide-1 (GLP-1) agonist, is the first noninsulin drug approved to treat type 2 diabetes in pediatric patients since metformin was approved for pediatric use in 2000. Liraglutide activates the GLP-1 receptor, a membrane bound cell-surface receptor coupled to adenylyl cyclase by the stimulatory G-protein, Gs, in pancreatic beta cells. Increases intracellular cyclic AMP (cAMP) leads to insulin release in the presence of elevated glucose concentrations.
Approval was based on the ELLIPSE clinical trial (n=134). Patients aged 10 years to younger than 17 years were randomized in a 1:1 ratio to receive liraglutide SC (up to 1.8 mg/day) or placebo for a 26-week double-blind period, followed by a 26-week open-label extension period. At week 26, mean HbA1c decreased by 0.64% with liraglutide and increased by 0.42% with placebo, for an estimated treatment difference of -1.06% (P< 0.001). The difference increased to -1.3% by 52 weeks. [48]
Another GLP-1 agonist, exenatide injectable suspension (Bydureon, Bydureon BCise), gained FDA approval for T2DM in children aged 10 years and older in July 2021. Approval was based on a 24-week, randomized, double-blind, placebo-controlled phase III trial (BCB114), with a 28-week open-label extension in pediatric patients aged 10-17 years (N=82) with T2DM. Patients who were treated with diet and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or insulin were randomized to receive exenatide extended-release 2 mg SC once weekly or placebo. Results demonstrated that patients administered exenatide extended-release achieved a significantly greater mean change in HbA1c from baseline compared with placebo (-0.25%, n=58, baseline A1c 8.13% vs +0.45%, n=24, baseline A1c 8.28%, respectively; P< 0.05). [49]
Lipid-lowering agents, such as 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), and blood pressure medications (ideally, angiotensin-converting enzyme [ACE] inhibitors) should be used if lifestyle modifications are insufficient in achieving cardioprotective levels of lipids and blood pressure. For example, statins may be needed to treat hyperlipidemia patients with type 2 diabetes if their fasting LDL ̶ level goals are not met after 3-6 months of lifestyle modification. [50, 3] ACE inhibitors are the agents of choice to treat hypertension and microalbuminuria. [51]
Proposed Management Algorithm
Diabetes education is indicated, including lifestyle changes to achieve healthy weight goals. First-line therapy is metformin at 1000-2000 mg/d. Goals include a fasting glucose level goal of less than 126 mg/dL and/or an HbA1c level of less than 7%. [4] If goals in step 1 are achieved, continue therapy.
If goals in step 1 not achieved after 3 months (fasting glucose level >126 mg/dL or HbA1c level >7%), add 0.4-0.6 U/kg of 24-hour insulin at bedtime (Glargine or Levemir). If combination therapy is adequate, continue therapy. If combination therapy is inadequate after 3 months, intensify insulin therapy until the fasting plasma glucose level is less than 126 mg/dL and the HbA1c level is less than 7%.
Stroke Prevention
In 2010, the American Heart Association-American Stroke Association released updated guidelines for the primary prevention of stroke. Specific recommendations for patients with diabetes are incorporated in these. [52]
Hypertension
Regular blood pressure screening, lifestyle modification, and drug therapy are recommended. A lower risk of stroke and cardiovascular events are seen when systolic blood pressure levels are less than 140 mm Hg and diastolic blood pressure is less than 90 mm Hg. In patients who have hypertension with diabetes or renal disease, the blood pressure goal is less than 130/80 mm Hg.
Diabetes
Blood pressure control is recommended in type 1 and 2 diabetes. Hypertensives agents that are useful in the diabetic population include ACE inhibitors and angiotensin receptor blockers (ARBs). Treating adults with diabetes with statin therapy, especially patients with other risk factors, is recommended, and monotherapy with fibrates may also be considered to lower stroke risk. Taking aspirin is reasonable in patients who are at high cardiovascular disease risk; however, the benefit of taking aspirin in diabetic patients for the reduction of stroke risk has not been fully demonstrated.
Dyslipidemia
Treating patients with statins is recommended in patients with coronary heart disease or certain high-risk conditions, for the primary prevention of ischemic stroke. In addition to statin therapy, therapeutic lifestyle changes and LDL-cholesterol goals are recommended. Niacin may be used in patients with low HDL cholesterol or elevated lipoprotein (a), but its efficacy in preventing ischemic stroke is not established.
Fibric-acid derivatives, niacin, bile acid sequestrants, and ezetimibe may be useful in patients who have not achieved target LDL levels with statin therapy or who cannot tolerate statins. However, their effectiveness in reducing the risk of stroke has not been established.
Diet
A diet that is low in sodium and high in potassium is recommended to reduce blood pressure. Diets that promote the consumption of fruits, vegetables, and low-fat dairy products, such as the DASH (Dietary Approaches to Stop Hypertension)-style diet, help to lower blood pressure and may lower risk of stroke.
Physical activity
Increasing physical activity is associated with a reduction in the risk of stroke. The goal is to engage in at least 30 minutes of moderate intensity activity on a daily basis.
Long-Term Monitoring
Prevention and treatment of hyperlipidemia and hypertension in individuals with type 2 diabetes are necessary in order to protect these patients from future cardiovascular disease. (The risk for vascular complications and cardiovascular mortality in patients with diabetes mellitus is increased by poor glucose control.) Treatment of type 2 diabetes should target the improvement of glycemia, dyslipidemia, and hypertension, as well as weight management and the prevention of short- and long-term complications. [4] Blood sugar monitoring should be performed 2-3 times daily, and more often than this when insulin treatment is being adjusted.
The patient should be seen every 3 months at the diabetes clinic, and more often, as necessary, when treatment is being adjusted.
Hemoglobin monitoring
HbA1c values should be monitored at each quarterly visit. An international expert committee composed of appointed representatives of the American Diabetes Association, the European Association for the Study of Diabetes, and others, recommended HbA1c assay for the diagnosis of diabetes mellitus in nonpregnant adults. [53] The committee’s recommendation to diagnose diabetes is an HbA1c level of 6.5% or higher, with confirmation from repeat testing (unless clinical symptoms are present and the glucose level is >200 mg/dL). Glucose measurement should remain the choice for diagnosing pregnant women or should be used if HbA1c assay is unavailable. The committee listed the following advantages of HbA1c testing over glucose measurement:
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Captures long-term glucose exposure
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Has less biologic variability
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Does not require fasting or timed samples
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Is currently used to guide management decisions
Additional concerns
Additional monitoring should be performed as follows:
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Microalbuminuria and fasting lipid profile - Should be checked yearly
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Dilated eye examination - Should be done annually
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Blood pressure evaluation and careful neurologic - Should be performed at each clinic visit
Weight loss, increased physical activity, and better food choices should be encouraged because they improve fasting lipid profile. Growth assessment is important.
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Simplified scheme for the pathophysiology of type 2 diabetes mellitus.
