The goals of therapy are to alleviate symptoms; to achieve glycemic, blood pressure, and lipid targets; and to prevent acute and chronic complications of DM. The recommended targets for control of type 1 and type 2 DM are similar:
This degree of glycemic control has been associated with the lowest risk of microvascular complications in both type 1 and type 2 DM.
Type 1 diabetes mellitus
Treatment of type 1 DM requires lifelong insulin replacement and careful coordination of insulin doses with food intake and activity. Insulin can be administered by subcutaneous injection, continuous subcutaneous infusion, or inhalation. A regimen of multiple daily insulin injections that includes basal, premeal, and correction doses is preferred to obtain optimal control in patients. Capillary glucose monitoring 4 times daily, 10–30 minutes before meals and at bedtime, is required for such a regimen.
Continuous subcutaneous insulin infusion by means of an insulin pump is widely used in patients with type 1 and, increasingly, with type 2 DM. However, it does not automatically improve glycemic control without patient self-management. A typical regimen provides 50% of total daily insulin as basal insulin and the remainder as multiple preprandial boluses of insulin using a programmable insulin pump. Patients must check their blood glucose regularly because diabetic ketoacidosis can occur rapidly if the insulin infusion is disrupted.
Regular human insulin is now available in inhaled form as Technosphere insulin (Afrezza). The onset of effect occurs about 15 minutes after administration, with a peak effect in the first hour and a duration of action of 3 hours. It is contraindicated in patients with asthma or COPD because of the risk of bronchospasm. Pulmonary function tests are required prior to initiation of therapy and at regular intervals during therapy.
Pancreas transplantation For patients with type 1 DM, pancreas transplantation can be performed alone or in conjunction with kidney transplantation. With modern techniques and immunosuppression, the transplant survival rate is high, and most patients become euglycemic without the need for insulin. Although quality of life is usually improved, the patient faces risks both from the surgery and from long-term immunosuppression. Thus, pancreas transplantation alone is limited to specific situations, such as in patients with frequent metabolic complications or in whom standard insulin therapy consistently fails to control disease. However, when pancreas transplantation and kidney transplantation are combined in patients with end-stage renal disease, the benefits far outweigh the risks.
Transplantation of pancreatic islet cells has been shown to improve the quality of life for patients with type 1 DM that is difficult to control, which includes patients with DM with frequent episodes of severe and potentially fatal hypoglycemia. These cells can be injected directly into the liver without the need for formal transplantation. After injection, patients remain on lifelong immunosuppression therapy to prevent transplant rejection. A recent phase 3 clinical trial funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), both part of the National Institutes of Health, released results from a study of pancreatic islet cell transplantation. At 1-year follow-up after transplant, 88% of transplant recipients had no episodes of severe hypoglycemia and approximately 50% of recipients no longer needed insulin use to achieve glycemic control.
Foster ED, Bridges ND, Feurer ID, et al; Clinical Islet Transplantation Consortium. Improved health-related quality of life in a phase 3 islet transplantation trial in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care. 2018;41(5):1001–1008.
Type 2 diabetes mellitus
The achievement of glycemic control requires individualized therapy in a comprehensive approach that incorporates lifestyle and pharmacologic interventions. Following are considerations for noninsulin therapy in patients with type 2 DM:
Noninsulin therapy should be considered early in the course of the disease, in conjunction with diet and exercise. Metformin is the recommended first-line therapy if tolerated.
When used as monotherapy at the maximum dose, insulin secretagogues, metformin, and thiazolidinediones (TZDs) have comparable glucose-lowering effects. The glucose-lowering effects of these medications and analogues are observed within days to weeks, except for the maximum effect of TZDs, which may not be apparent for several weeks to months.
Combination therapy with 2 or more oral or injectable agents may be needed to achieve targets for HbA1C and blood glucose in patients presenting with significant hyperglycemia and will likely become necessary as β-cell function deteriorates over time. Dual therapy may be considered when the initial HbA1C is ≥7.5%, and triple therapy or insulin when the initial HbA1C is >9%.
Because all noninsulin therapies require some pancreatic β-cell function to achieve glucose-lowering effects, many patients will eventually need insulin replacement therapy.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.