Diabetes%20mellitus%20(pediatric) Treatment

Goals of Therapy

• Maintain a balance between tight glucose control and avoiding hypoglycemia
• To eliminate polyuria and nocturia
• To prevent ketoacidosis
• To permit normal growth and development

Insulin Preparations

• Goal of therapy is to duplicate normal physiologic secretion of insulin
• May be used in both type 1 and type 2 DM
  • Patient with severe hyperglycemia (random plasma/venous blood glucose ≥250 mg/dL), HbA1c >9%, and/or ketosis should be treated initially with insulin to achieve metabolic control
• Insulin requirements are based on body weight, age and pubertal status
  • Newly diagnosed type 1 DM usually requires approximately 0.5-1 U/kg/day
  • Insulin treatment must be started after diagnosis, usually within 6 hours if ketonuria is present, to prevent DKA and metabolic compensation
  • Both multiple-dose insulin (MDI) and continuous subcutaneous insulin infusion (CSII) should be offered at the time of diagnosis or if control of blood glucose is not achieved
  • Younger children require lower doses
  • Patients at puberty may require up to 1.5 U/kg/day due to hormonal changes
  • Prandial insulin should be matched according to carbohydrate intake, premeal glucose, and physical activity
  • Presence of diabetic ketoacidosis (DKA) and use of steroids also require higher doses
  • Insulin is primarily used if unsure whether it is a type 1 or type 2 DM and in patients who have a random blood glucose level of ≥250 mg/dL (13.9 mmol/L) and/or HbA1c ≥8.5% (69 mmol/mol)
• Type 2 DM
  • Initiate treatment in type 2 DM patients with severe hyperglycemia (>11.1 mmol/L), glycosylated hemoglobin (HbA1c) >8.5%, or signs/symptoms of severe insulin deficiency (eg DKA, ketoacidosis) despite lifestyle modifications (balanced diet and regular exercise)
  • Use when patients are unable to maintain adequate control with diet, exercise and oral antidiabetic agents
  • Initiate treatment with basal insulin in markedly hyperglycemic type 2 DM symptomatic patients [blood glucose ≥250 mg/dL (13.9 mmol/L), HbA1c ≥8.5% (69 mmol/mol)] but without ketoacidosis 
    • Type 2 DM adolescents with obesity or overweight and presenting with acidosis or DKA or hyperosmolar hyperglycemic nonketotic (HHNK) syndrome should be managed with IV insulin until resolution of acidosis followed by SC insulin administration
  • Start basal insulin when the goal to achieve a certain HbA1c level can no longer be attained with Metformin alone or if there are contraindications or adverse reactions with Metformin use
    • MDI with basal insulin and premeal bolus insulins or insulin pump therapy is recommended in patients on Metformin, GLP-1 receptor agonist and basal insulin, and not achieving glycemic targets
  • May taper basal insulin in patients on combination therapy once glucose targets are met, gradually reduce dose by 10-30% every few days within 2-6 weeks
  • Use during times of illness or stress to maintain glycemic control
• Patients, parents/caregivers need to be instructed on monitoring of blood glucose and educated to adjust insulin dose based on blood glucose levels
  • Especially during times of illness, changes in food intake and physical activity
• Signs and management of hypoglycemia must be explained
• Exact time course of each insulin will depend on each particular preparation and site of injection
  • Should be encouraged to administer consistently within the same area (eg abdomen, arm, buttocks, thigh) at a particular time of day and avoid injecting repeatedly on the same spot to prevent lipohypertrophy

Short- and Rapid-Acting Insulins

• Short-acting insulin: Regular insulin
• Rapid-acting insulins: Insulin aspart, Insulin glulisine and Insulin lispro
• Act as mealtime insulin
• Regular insulin
  • As a mealtime insulin, its use may be limited because the onset is not rapid enough to meet the quick, unpredictable increase in postprandial blood glucose
  • Also considered a basal insulin as its duration of action may extend beyond the time required for food absorption
  • Administer 30-60 minutes before meals to mimic normal physiologic increases of insulin
• Newer rapid-acting insulin analogues (eg Insulin aspart, Insulin glulisine and Insulin lispro) seem to have better postprandial blood glucose control
  • They have more rapid onset of action and shorter duration of action than regular insulin
  • Premeal control before the next meal may be difficult due to the short duration of action if used alone without a long- or intermediate-acting insulin
  • Administer immediately (within 15 minutes) before meals
  • Faster-acting Insulin aspart showed better post-meal control and caused less hypoglycemia

Intermediate- and Long-Acting Insulins

• Intermediate-acting insulin: Human NPH (neutral protamine Hagedorn)
• Long-acting insulin: Insulin glargine, Insulin detemir and Insulin degludec
• Mimics normal physiologic basal insulin secretion
• Neutral protamine Hagedorn (NPH) and Lente insulins produce significant hypoglycemic effect during the midrange of their duration 
• Long-acting insulins create more controlled postprandial glucose elevation and hypoglycemia between meals and are reduced at nighttime
• Usually given 1-2x/day

Insulin Combinations

• Patients often require MDI using combinations of short-, rapid-, intermediate- or long-acting insulin before meals and at bedtime for optimal control of blood glucose
• Premixed insulins: NPH/Regular 70/30, 70/30 Aspart mix, 75/25 Lispro mix, 50/50 Lispro mix, Deglutec/Aspart 70/30
• Clinical studies show that combination of 2-3 doses of short- or rapid-acting insulin with intermediate-acting insulin do not sufficiently achieve optimal glycemic control
• Combination of rapid-acting insulin and long-acting insulin may result in stable glycemic control and less hypoglycemia especially at night
  • It allows coverage for snacks, however, requires intensive blood glucose monitoring, improved medical nutrition therapy (MNT) and careful insulin adjustment with exercise

Insulin Pump Therapy

• CSII consists of regular- and rapid-acting insulins administered subcutaneous (SC) in an external infusion pump
• Can be programmed to deliver constant amount of basal insulin and boluses of insulin for meals
  • Increased physical activity can be managed by reducing amount of basal insulin
• May be used instead of multiple daily injections to provide intensive diabetes management
  • Provides closer approximation of normal plasma insulin profiles and increased flexibility regarding timing of meals and snacks compared
  • Associated with improved metabolic control and reduced risk of severe hypoglycemia without affecting psychosocial outcomes in adolescents with type 1 DM
  • May improve metabolic control in children 7-10 years
• Consider a sensor-augmented low glucose threshold suspend pump in patients with frequent nocturnal hypoglycemia and/or hypoglycemia unawareness

Metformin

• A biguanide approved for nonketotic pediatric patients with type 2 DM
• May be used as monotherapy (in metabolically stable patients) or in combination with insulin
• 1st-line therapy for newly diagnosed type 2 DM pediatric patients
  • 1st-line treatment of choice in patients who are in a stable metabolic state (HbA1c <8.5%), without symptoms and with renal function of >30 mL/min/1.73 m²
• May also be used to prevent type 2 DM in patients with impaired glucose tolerance, increased fasting glucose, or HbA1c 5.7-6.4%
• Actions: Improve insulin action at the liver which decreases hepatic glucose production
  • Increase peripheral glucose uptake and utilization
• Effects: Significantly reduces HbA1c and improves fasting plasma glucose (FPG) and postprandial blood glucose
  • Maintains or decreases weight, decreases low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG)
  • May also normalize ovulatory abnormalities in patients with polycystic ovarian syndrome (PCOS)
• Contraindicated in patients with moderate to severe renal insufficiency
• Should not be given to patient with ketosis because it may precipitate lactic acidosis
  • May be started once the child recovers from ketosis after treatment by rehydration and with insulin
• Insulin should be added whenever glucose control cannot be achieved after 3-6 months of Metformin therapy

Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists

• Eg Exenatide, Liraglutide
• 2nd-line agents approved for use in ≥10-year-old type 2 DM patients without family history or previous history of medullary thyroid carcinoma or type 2 multiple endocrine neoplasia if glycemic targets are not reached with Metformin with or without insulin and as adjunct to diet and exercise
• Increase glucose-dependent insulin secretion from beta cells and help ensure an appropriate response following meal ingestion

Medical Nutrition Therapy (MNT)

• Integral component of DM prevention and management
• MNT should be provided at diagnosis and annually thereafter, by an individual experienced with the nutritional needs of the growing child and the behavioral issues that have an impact on adolescent diets
• Consult with a dietitian experienced in pediatrics and DM to discuss MNT
• Base MNT on recommended dietary intakes appropriate for age, gender, physical activity and growth rate
  • Please see Growth Charts clinical reference table for further information 
  • Conduct a complete medical exam prior to prescribing any low-calorie diet
  • Evaluate height, weight, body mass index (BMI) and MNT plan annually
• Individualize MNT according to food preferences, cultural influences, physical activity patterns, family eating patterns, etc
• Calorie intake of overweight/obese patients should be based on patient’s energy requirements by direct measurement thought indirect calorimetry
• MNT alone or in combination with appropriate insulin therapy averts or relieves symptoms of hyperglycemia in patients with diabetes
• Nutritional practices may influence the development of long-term complications of diabetes
• General goals of MNT
  • Attain optimal metabolic outcomes
    • Blood glucose levels in normal range, lipid profile, HbA1c <7% and blood pressure (BP) which reduces risk of vascular disease
    • Prevent and treat diabetic comorbidities (eg obesity, CVD, hypertension, dyslipidemia, etc)
  • Improve overall health
• MNT goals in type 1 DM
  • Provide enough energy for growth and development in young DM patients
  • Insulin needs to be integrated into the meal routine and to be based on food choices
  • Patient should be taught flexibility of insulin dosing and timing
  • Patients with abnormal lipid profile should avoid trans fats, restrict amount of fat calories to 25-30% and saturated fat to <7%, limit cholesterol to <200 mg/day, and aim for approximately 10% calories from monosaturated fats
• MNT goals in type 2 DM
  • Decrease energy intake and increase expenditure of energy as most type 2 DM patients are overweight/obese
    • A macronutrient diet of ≥900-≤1,200 kcal/day is recommended for children 6-12 years of age
    • ≥1,200 kcal/day for patients ages 13-18 may help improve weight and body composition
  • Patients with abnormal lipid profile should avoid trans fats, restrict amount of fat calories to 25-30% and saturated fat to <7%, limit cholesterol to <200 mg/day, and aim for approximately 10% calories from monosaturated fats
  • Reduce insulin resistance and improve metabolic status especially in young DM patients
  • For overweight/obese youth with type 2 DM, assist with appropriate changes of physical activity and eating habits
    • Increased fruits and vegetable in a child’s diet may help decrease risk for obesity; dairy and calcium-rich should is essential and should be included in their diet
    • High-calorie containing beverages and fatty foods should be monitored and restricted in overweight pediatric patients
    • Short-term restriction of high-carbohydrate diet (up to 20-60 g) may help with weight management

Metabolic Surgery

• May be an option for the management of type 2 DM in adolescents who are severely obese (BMI >35 kg/m²) and with uncontrolled glycemia and/or serious comorbidities even with lifestyle modification and pharmacological therapy
• Must be performed by an experienced surgeon together with a multidisciplinary team including an endocrinologist, nutritionist, behavioral specialist and nurse