Treatment of Type 1 Diabetes

Treatment of Type 1 Diabetes

Goals

The treatment goals for patients with type 1 diabetes (T1D) are the same as those for patients with type 2 diabetes (T2D), as outlined in Table 1 (1).

Table 1. Glucose goals for patients with diabetes (1).

A1C

Individualize on the basis of age, comorbidities, duration of disease*

  • In general, ≤6.5% for most
  • Closer to normal for healthy
  • Less stringent for “less healthy”

FPG

<100 mg/dL

2-h PPG

<140 mg/dL

Abbreviations: FPG = fasting plasma glucose; PPG = postprandial glucose.
*Considerations include residual life expectancy; duration of diabetes; presence or absence of microvascular and macrovascular complications; CVD risk factors; comorbid conditions; risk for severe hypoglycemia; and psychological, social, and economic status.

Pharmacologic Therapy
Insulin therapy is necessary for survival in all patients with T1D. Physiologic insulin regimens, which provide both basal and prandial insulin, should be used for most patients with T1D. These regimens may comprise either of the following:

  • Multiple daily injections (MDI), which usually involve 1-2 subcutaneous injections per day of basal insulin to control glycemia between meals and overnight, and subcutaneous injections of prandial insulin or inhaled insulin before each meal to control meal-related glycemia
  • Continuous subcutaneous insulin infusion (CSII) to provide a more physiologic way to deliver insulin, which may improve glucose control while reducing risks of hypoglycemia

Insulin analogs are preferred over NPH and regular human insulin for MDI regimens. Although glycemic control as measured with A1C are similar between these regimens, the use of analogs is associated with a consistent reduction of moderate and severe hypoglycemia (2). Comparisons of MDI and CSII for T1D have shown small but consistent improvements in A1C, as well as substantial reductions in severe hypoglycemia (3,4).

Basic Principles of Insulin Therapy for T1D
The starting dose of insulin is usually based on weight, with doses ranging from 0.4-0.5 units/kg per day of total insulin; higher amounts may be required for patients with obesity (increasingly common in T1D) or a sedentary lifestyle, as well as during puberty (1).
In general, basal insulin requirements are usually 40% to 50% of the total daily insulin doses. No data support the superiority of 2 injections of a basal insulin analog over 1 injection of basal insulin analog in patients with T1D (1).
The dose of prandial insulin is usually determined by estimating the carbohydrate content of the meal. Insulin-to-carbohydrate (I:C) ratios usually range from 1:20 for the very insulin sensitive to 1:5 for the insulin-resistant patient. Similarly, correction dose insulin for premeal or between meal hyperglycemia is based on the insulin sensitivity factor (ISF), which is based on the overall insulin sensitivity of the patient, loosely estimated by the individual’s total daily insulin dose. Although various formulas have been used to estimate the appropriate ISF, this parameter should only be viewed as an estimation due to numerous factors that can alter blood glucose. The most commonly used formula is:

1,800/total daily dose of insulin = Number of mg/dL of glucose that will be reduced by 1 unit of insulin

Insulin action time ranges from 4 to 6 hours for most subcutaneous injections, although no available data quantify individual patients’ insulin action times, which may vary from day to day.
With the knowledge of the I:C ratio, ISF, and insulin action time, patients on MDI or CSII can calculate the appropriate correction dose insulin. This is significantly simpler with CSII, which include bolus calculators to perform the calculations. For patients using MDI, smart phone apps are available, and several blood glucose meters can assist patients with these calculations. Most patients using MDI, however, will need to estimate the “insulin on board” from the last injection of prandial insulin based on standard curves that can be provided to them (2).

Adjunctive Medications for T1D
The amylin analog pramlintide, the only noninsulin medication approved for the treatment of T1D, is administered with prandial insulin. A1C reductions are consistently modest and mild weight loss is common. Nausea is a common adverse effect. There is a potential risk of severe hypoglycemia if patients do not appropriately reduce the prandial insulin dosage (5-8). Tachyphylaxis is often seen after several years of therapy.
While there is growing interest and anecdotal reports of successful use of both GLP-1 receptor agonists and SGLT2 inhibitors in T1D, to date appropriate trials have not been published and formal recommendations cannot be provided. SGLT2 inhibitors have been associated with reports of normoglycemic diabetic ketoacidosis when used with insulin in patients with T1D (9). In addition, recommendations for the use of metformin in T1D cannot be made due to lack of indication and concerns of lactic acidosis in a population predisposed to ketoacidosis. Nevertheless, use of metformin in T1D has been of great interest and new data should be available in the future (10).

References

  1. Handelsman Y, Bloomgarden ZT, Grunberger G, Umpierrez G, Zimmerman RS, Bailey TS, et al. American Association of Clinical Endocrinologists and American College of Endocrinology: clinical practice guidelines for developing a diabetes mellitus comprehensive care plan—2015. Endocr Pract. 2015;21:1-87.
  2. Hirsch IB. Insulin analogues. N Engl J Med. 2005;352:174-83.
  3. Misso ML, Egberts KJ, Page M, O'Connor D, Shaw J. Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus. Cochrane Database Syst Rev. 2010:CD005103.
  4. Monami M, Lamanna C, Marchionni N, Mannucci E. Continuous subcutaneous insulin infusion versus multiple daily insulin injections in type 2 diabetes: a meta-analysis. Exp Clin Endocrinol Diabetes. 2009;117:220-2.
  5. Edelman S, Garg S, Frias J, Maggs D, Wang Y, Zhang B, et al. A double-blind, placebo-controlled trial assessing pramlintide treatment in the setting of intensive insulin therapy in type 1 diabetes. Diabetes Care. 2006;29:2189-95.
  6. Ratner RE, Dickey R, Fineman M, Maggs DG, Shen L, Strobel SA, et al. Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in type 1 diabetes mellitus: a 1-year, randomized controlled trial. Diabet Med. 2004;21:1204-12.
  7. Whitehouse F, Kruger DF, Fineman M, Shen L, Ruggles JA, Maggs DG, et al. A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes. Diabetes Care. 2002;25:724-30.