Type 1 Diabetes Goals • Glycated hemoglobin • General goal is <7% • A1C goals may be higher in patients in whom the risks of tighter control outweigh benefits. • A1C goals are generally set higher for older adults and those with a history of severe hypoglycemia, hypoglycemia unawareness, comorbidities, or a limited life expectancy. • Glucose • healthy, young and middle-aged adults, the target glucose range is 70 to 180 mg/dL • minimizing time in hypoglycemia <70 mg/dL and hyperglycemia >180 mg/dL and avoiding glucose readings of <54 mg/dL and >250 mg/dL Delivery • Choice of insulin delivery — • multiple daily injections (MDI) • continuous subcutaneous delivery of a rapid-acting insulin preparation via a pump (CSII) • Glycemic control is generally similar • The impact on hypoglycemia is less certain • Newer insulin pumps, which are integrated with continuous glucose monitoring (CGM) systems, have features that can reduce hypoglycemia by temporarily suspending insulin infusion Pharmacology • Insulin acts via specific membrane-bound receptors on target tissues to regulate metabolism of carbohydrate, protein, and fats. • Target organs for insulin include the liver, skeletal muscle, and adipose tissue. • Liver, • insulin stimulates hepatic glycogen synthesis • hepatic synthesis of fatty acids, which are released into the circulation as lipoproteins. • Skeletal muscle • effects of insulin include increased protein synthesis and increased glycogen synthesis. • Adipose tissue • • • • insulin stimulates the processing of circulating lipoproteins to provide free fatty acids, facilitating triglyceride synthesis and storage by adipocytes inhibits the hydrolysis of triglycerides stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. • By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium. ADE • Frequency not defined: • Cardiovascular: Peripheral edema • Dermatologic: Injection site pruritus • Endocrine & metabolic: Amyloidosis (localized at injection site), hypoglycemia, hypokalemia, weight gain • Hypersensitivity: Anaphylaxis, hypersensitivity reaction • Immunologic: Immunogenicity • Local: Erythema at injection site, hypertrophy at injection site, lipoatrophy at injection site, swelling at injection sites Insulin Preparations • Human insulin • Regular insulin (short-acting) • soluble insulin complexed with zinc that has the same amino acid sequence as endogenous human insulin. • It can be used to control the postprandial rise in glucose • NPH (intermediate-acting insulin) • is a crystallized suspension of human insulin, protamine, and zinc in a neutral buffer that delays the release of the insulin into the bloodstream. • To provide 24-hour basal coverage, NPH needs to be administered at least twice daily. • When given in the morning, there is an increased risk of hypoglycemia if food is not consumed during the time of its peak action. • When given in the evening or at bedtime, a bedtime snack may be needed to avoid nocturnal hypoglycemia. Human Insulin • U-500 regular • insulin contains 500 units per mL of regular insulin. • Treatment of severely insulin-resistant patients (eg, requiring more than 200 total units of insulin daily). • High concentration of insulin delays absorption, the pharmacologic profile of U-500 regular insulin is most similar to that of NPH. • However, the pharmacokinetics can be highly variable and hypoglycemia remains a potential risk. • Higher doses can result in significantly longer duration of insulin action. • dispense with the U-500 insulin syringe. Analog insulins • Insulin analogs • manufactured using recombinant DNA technology, were designed to produce more physiologic insulin profiles, especially for type 1 diabetes, and reduce the risk of hypoglycemia. • The rapid-acting insulin analogs (insulin lispro, aspart, faster aspart, and glulisine) • faster onset • shorter duration of action than regular insulin for pre-meal coverage Basal insulin analogs • Lispro (Humalog) • Aspart (Novolog) • Glulisine (Apidra) • Rapid acting insulin • short-term outcomes minor advantage over regular in type 1 • A1C • risk of hypoglycemia Basal insulin analogs • Glargine (Lantus) • usually 24 hours enabling once-daily dosing, but some patients have better basal coverage with twice-daily dosing • Detemir (Levemir) • Higher doses are associated with longer durations of action. • Compared with glargine, it does have a noticeable peak and rarely lasts 24 hours. • (Degludec) Tresiba • almost identical to human insulin • reduces variability in plasma concentration • once-daily dosing https://www-uptodate-com.libproxy.umflint.edu/contents/general-principles-of-insulin-therapy-in-diabetesmellitus?search=insulin&sectionRank=1&usage_type=default&anchor=H3&source=machineLearning&selectedTitle=2~116&display_rank=1#H2426537056 Multiple Daily Injections (MDI) • basal/prandial insulin (basal/bolus) • basal • NPH, glargine, detemir, or degludec • prandial • lispro, aspart, glulisine, regular insulin Designing an MDI insulin regimen • Initial total daily dose (TDD) – • Most newly diagnosed patients with type 1 diabetes can be started on a TDD of 0.2 to 0.4 units of insulin/kg/day • most will ultimately require 0.6 to 0.7 units/kg/day. • Adolescents, especially during puberty, often need more. • The starting dose can be adjusted upward every few days based upon symptoms and blood glucose measurements. • Basal bolus composition and timing • about 40 to 50% TDD should be given as a basal insulin • either as once-daily degludec, once- or twice-daily glargine or detemir, or as twice-daily intermediate-acting insulin (NPH). • can be given either at bedtime or in the morning • NPH is usually given as approximately two-thirds of the dose in the morning and one-third at bedtime Designing an MDI insulin regimen • The rest of the TDD • short-acting or rapid-acting insulin, divided before meals. • The pre-meal dosing is determined by the pre-meal glucose level, meal size, and content, glucose trends • activity and exercise pattern • Regimens that use NPH in the morning may not require a pre-lunch dose of short-acting (regular) or rapid-acting insulin because the peak of NPH action is occurring at that time. • Injection sites • The abdomen is the preferred site for pre-meal injections of regular insulin because absorption is quicker from this site • the thigh or buttock is a good site for the evening intermediate-acting insulin (NPH) dose • the slower rate of absorption • last through the night. • The site of injection is less important for rapid-acting or long-acting insulin analogs, and therefore, they may be administered in the abdomen, thighs, buttock, or upper arms Continuous subcutaneous insulin infusion (CSII) • CSII • basal insulin is supplied in the form of a continuous infusion • 40 and 60 percent of the TDD • pre-meal bolus doses given to minimize postprandial glucose excursions. • A variety of insulin pumps are available, and the choice among pumps is largely a matter of patient preference, cost, and lifestyle. • Choice of insulin • Rapid-acting insulin analogs (lispro, aspart, and glulisine) are typically preferred over regular insulin • In a meta-analysis of trials comparing rapid-acting insulin analogs with regular insulin for use in CSII, there was a small but significant reduction in A1C with use of insulin analogs
