Diabetes Mellitus Treatment & Goals

• DM (Diabetes Mellitus) treatment goals involve managing long-term microvascular, macrovascular, and neuropathic complications.
• Treatment aims to preserve β-cell function.
• Preventing acute complications from high blood glucose levels, minimizing hypoglycemic episodes, and maintaining the patient's overall quality of life are important
• Glycemic therapy goals include A1C less than 7.0%.
• A1C should be checked every 6 months for patients at goal and every 3 months for those not at goal.
• FPG (Fasting Plasma Glucose) or premeal glucose target is 70–130 mg/dL.
• Frequency of monitoring glucose depends on diabetes regimen, type, and current glycemic control.
• Peak postprandial glucose (measured 1–2 hours after a meal) should be less than 180 mg/dL.

Type 1 Diabetes Mellitus (T1DM)

• T1DM treatment requires providing exogenous insulin to replace the endogenous loss from the nonfunctional pancreas.
• Insulin therapy should ideally mimic normal insulin physiology.
• The basal-bolus approach attempts to reproduce basal insulin response with intermediate- or long-acting insulin.
• Short- or rapid-acting insulin replicates bolus release, like what is physiologically seen around a meal in non-diabetics.
• Basal insulin makes up approximately 50% of the total daily dose, with the remaining 50% provided as bolus doses with three daily meals.
• Exact insulin doses are individualized based on the patient and the amount they eat

T1DM Insulin Dosing

• T1DM patients are often started on about 0.6 unit/kg/day and then titrated until glycemic goals are met.
• Most people with T1DM use between 0.6 and 1 unit/kg/day of insulin.

Type 2 Diabetes Mellitus (T2DM)

• T2DM treatment has evolved with new drugs and recommendations for tighter glycemic control.
• Lifestyle modifications, like education, nutrition, and exercise, are critical for managing T2DM.

Gestational Diabetes

• An individualized meal plan consisting of three meals and three snacks per day is commonly recommended.
• Goals for patients with gestational diabetes include preventing ketosis, promoting adequate fetal growth, and maintaining satisfactory blood glucose levels.
• Goals of gestational diabetes management include preventing nausea and other undesired GI side effects.
• Insulin should be used when blood glucose is not maintained adequately by diet and physical activity alone.
• Insulin detemir, insulin aspart, lispro, and regular insulin are considered Category B for safety during pregnancy.

Nonpharmacologic Therapy

• Medical Nutrition Therapy (MNT) is an integral component of diabetes management and self-management education.
• People with diabetes should receive individualized MNT, ideally from a registered dietitian.
• The primary focus of MNT for patients with T1DM is matching optimal insulin dosing to carbohydrate consumption.
• In T2DM, the primary focus of MNT is individualizing limits of carbohydrates, saturated fats, sodium, and calories.
• Carbohydrates are the primary contributor to post-meal glucose levels.
• The percentages of fat, protein, and carbohydrates should be individualized based on patient goals.
• Moderate weight loss in patients with T2DM reduces cardiovascular risk and can delay or prevent the onset of diabetes in those with prediabetes.

Weight Management

• Therapeutic lifestyle change (TLC), integrating a 7% reduction in body weight and increased physical activity, is the recommended approach.
• A slow, progressive weight loss of 0.45 to 0.91 kg (1–2 lb) per week is preferred.

Physical Activity

• Regular physical activity improves blood glucose control and reduces cardiovascular risk factors like hypertension and elevated serum lipid levels.
• Physical activity aids long-term weight loss and overall weight control.
• Regular physical activity can prevent the onset of T2DM in high-risk individuals.
• Before starting a physical activity program, patients should have a detailed physical exam to screen for microvascular or macrovascular complications.
• Low-impact exercises like walking, swimming, and cycling are encouraged.
• Physical activity goals for patients with T2DM include 150 minutes per week.

Pharmacological Treatment of Type 1 DM: Insulin

• Insulin can be used in all types of diabetes and has no specific maximum dose, allowing titration to suit individual needs.
• Insulin is the primary treatment for T1DM, and injected amylin can be added to decrease fluctuations in blood glucose levels.
• Insulin is divided into basal and bolus classes, based on their length of action. Most insulin formulations are U-100 (100 units/mL).
• Insulin is typically refrigerated, but most vials are stable for 28 days at room temperature.
• Subcutaneous injection is the most common route of administration for insulin, using a syringe or pen device.
• Rotate injection sites to minimize lipohypertrophy, which is a build-up of fat that decreases or prevents proper insulin absorption.
• Absorption rates vary by injection site; the abdomen is the fastest, and the buttocks are the slowest.

Bolus Insulins : Regular Insulin

• Regular insulin is unmodified crystalline insulin and a clear solution with a relatively short onset and duration of action.
• Regular insulin covers insulin response to meals.It should be injected subcutaneously 30 minutes before a meal or can be administered intravenously (IV).

Bolus Insulins: Rapid-Acting Insulin

• Three rapid-acting injectable insulins are aspart, glulisine, and lispro.
• Injectable forms have an onset of 15 to 30 minutes, peak effects in 1-2 hours, and are dosed before or with meals.
• Inhaled rapid-acting insulin has a peak effect in 15 to 20 minutes and a duration of action of only two to three hours.

Basal Insulin: Intermediate-Duration Insulin

• Neutral Protamine Hagedorn (NPH) insulin is prepared by conjugating protamine with regular insulin.
• This gives it a delayed onset and extended duration of action, covering insulin requirements between meals and/ or overnight.
• NPH insulin use has declined due to unpredictable peak effects and a <24-hour duration.
• Protamine can increase the possibility of an allergic reaction
• NPH insulin can be mixed with regular insulin for immediate or future use or mixed with aspart or lispro insulins for immediate injection.
• Mixtures including regular-acting and intermediate-acting insulin are stable for 14 days refrigerated or 7 days at room temperature.

Basal Insulin: Long-Duration Insulin

• Glargine and detemir insulins are designed for once-daily dosing, providing a relatively constant insulin concentration over 24 hours.
• Detemir binds to albumin in plasma, giving sustained action.
• Glargine and detemir cannot be administered IV or mixed with other insulin products.
• Detemir can be administered in the evening if used as a once-daily dose, but both could be administered irrespective of meals or time of day.
• Insulin degludec, another long-duration insulin, offers a more consistent insulin concentration throughout the day and is under FDA review.

Combination Insulin Products

• A number of combination insulin products are available commercially.
• NPH is available in combinations of 70/30 (70% NPH and 30% regular insulin) and 50/50 (50% NPH and 50% regular insulin).
• Humalog mix 75/25 contains 75% insulin lispro protamine suspension and 25% insulin lispro
• Novolog mix 70/30 contains 70% insulin aspart protamine suspension and 30% insulin aspart.
• Lispro and aspart insulin protamine suspensions were developed specifically for these mixture products and are not commercially available separately

Insulin Pump Therapy

• Insulin pump therapy uses a programmable infusion device for basal insulin infusion 24 hours daily and bolus administration at meals and snacks.
• Regular or rapid-acting insulin is delivered from a reservoir via infusion set tubing or a small canula.
• Pump infusion sets are often inserted in the abdomen, arm, or other site, with the abdomen preferred for optimal absorption.
• Infusion sets should be changed every 2 to 3 days to reduce infection risk.
• Patients use a carbohydrate-to-insulin ratio to determine how many units of insulin are required.
• Insulin pump therapy can lower blood glucose in any type of diabetes; however, patients with T1DM are the most likely candidates.
• Using an insulin pump may improve blood glucose control, reduce fluctuations, and allow for more flexible meal and exercise schedules.

Initial Dosage of Insulin for T1DM

• a) T1DM, without concomitant infection or physiologic stress
• Insulin should be dosed based on weight and requires the total daily dose (TDD).
• The total daily dose for an adult with T1DM is estimated as 0.6 units/kg/day.
  • 50% of TDD is the basal dose e.g., NPH, glargine, detemir
  • Remaining 50% is the bolus e.g., regular lispro, aspart, glulisine, divided between meals.
• A 53 kg person that has just started insulin, TDD would be approx. 32 units

The Half DTD Bolus Example:

• Half of the TDD (16 units) would be initiated as the basal insulin and the remaining 16 units would be divided into an approximate bolus dose as follows
• Glargine/Detemir as a basal w/ short/rapid: 16 Units once daily of basil insulin; 5 units t.i.d of bolus insulin w/ meals
• NPH as a basal requires twice daily dosing in persons w/ T1DM
• Bolus dose needs to be decreased by 20% and given twice a day (8 units of NPH w 6 units of bolus)

Premixed Insulin Example Using TDD

• Should be initiated as two-thirds of the TDD in the morning and the remaining one-third in the evening prior to meals.
• Example: With a TDD of 32 units, use 21 units in the morning and 11 units in the evening
• This form of dosage adjustment is not preferrable because it cannot be adjusted for changes in diet, exercise, or health.
• It also does not allow the titration of one insulin type to target the specific insulin release.

Insulin for Type 2 Diabetes

• Basal insulin may be initiated at 10 units/daily in the average-sized individual or 0.1 to 0.2 units/kg/day in the overweight/obese.
• If administered in the evenings, the dose of insulin should be titrated as necessary to achieve fasting blood glucose levels in the target range.
• Bolus insulin can be added as needed based on pre- and post-meal blood glucose monitoring.
• Premixed insulin should be initiated based on TDD of 0.2 units/kg/day, with two-thirds of the TDD given in the morning prior to breakfast and one-third of the TDD given in the evening prior to the last meal.