Treatment: Diabetes Mellitus

Optimal treatment of DM requires more than plasma glucose management. Comprehensive diabetes care should also detect and manage DM-specific complications and modify risk factors for DM-associated diseases. The pt with type 1 or type 2 DM should receive education about nutrition, exercise, care of diabetes during illness, and medications to lower the plasma glucose. In general, the target HbA_1c level should be <7.0%, although individual considerations (age, ability to implement a complex treatment regimen, and presence of other medical conditions) should also be taken into account. Intensive therapy reduces long-term complications but is associated with more frequent and more severe hypoglycemic episodes. Goal preprandial capillary plasma glucose levels should be 3.9-7.2 mmol/L (70-130 mg/dL) and postprandial levels should be <10.0 mmol/L (<180 mg/dL) 1-2 h after a meal.

In general, pts with type 1 DM require 0.5-1.0 U/kg per day of insulin divided into multiple doses. Combinations of insulin preparations with different times of onset and duration of action should be used (Table 173-2). Preferred regimens include injection of glargine at bedtime with preprandial lispro, glulisine, or insulin aspart or continuous SC insulin using an infusion device. Pramlintide, an injectable amylin analogue, can be used as adjunct therapy to control postprandial glucose excursions.

Pts with type 2 DM may be managed with diet and exercise alone or in conjunction with oral glucose-lowering agents, insulin, or a combination of oral agents and insulin. The classes of oral glucose-lowering agents and dosing regimens are listed in Table 173-3. In addition, exenatide and liraglutide are injectable glucagon-like peptide 1 (GLP-1, an incretin) analogues that may be used in combination with metformin or sulfonylureas. A reasonable treatment algorithm for initial therapy proposes metformin as initial therapy because of its efficacy (1-2% decrease in HbA_1c), known side-effect profile, and relatively low cost (Fig. 173-1). Metformin has the advantage that it promotes mild weight loss, lowers insulin levels, improves the lipid profile slightly, lowers cancer risk, and does not cause hypoglycemia when used as monotherapy, although it is contraindicated in renal insufficiency, congestive heart failure, any form of acidosis, liver disease, or severe hypoxia, and should be temporarily discontinued in pts who are seriously ill or receiving radiographic contrast material. Metformin therapy can be followed by addition of a second oral agent (insulin secretagogue, DPP-IV inhibitor, thiazolidinedione, α-glucosidase inhibitor, or SLGT2 inhibitor). Combinations of two oral agents may be used with additive effects, with stepwise addition of bedtime insulin or a third oral agent if adequate control is not achieved. As endogenous insulin production falls, multiple injections of long-acting and short-acting insulin may be required, as in type 1 DM. Individuals who require >1 U/kg per day of long-acting insulin should be considered for combination therapy with an insulin-sensitizing agent such as metformin or a thiazolidinedione. Insulin-requiring type 2 DM pts may also benefit from addition of pramlintide.

Bariatric surgery should be considered in selected pts (Chap. 172. Obesity).

The morbidity and mortality of DM-related complications can be greatly reduced by timely and consistent surveillance procedures (Table 173-4). A routine urinalysis may be performed as an initial screen for diabetic nephropathy. If it is positive for protein, quantification of protein on a 24-h urine collection should be performed. If the urinalysis is negative for protein, a spot collection for microalbuminuria should be performed (present if 30-300 µg/mg creatinine on two of three tests within a 3- to 6-month period). A resting ECG should be performed in adults, with more extensive cardiac testing for high-risk pts. Therapeutic goals to prevent complications of DM include management of proteinuria with ACE inhibitor or angiotensin receptor blocker therapy, bp control (<130/80 mmHg if no proteinuria, <125/75 if proteinuria), and dyslipidemia management (LDL <2.6 mmol/L [<100 mg/dL], HDL >1.1 mmol/L [>40 mg/dL] in men and >1.38 mmol/L [50 mg/dL] in women, triglycerides <1.7 mmol/L [<150 mg/dL]). In addition, any diabetic pt >40 years should take a statin, regardless of the LDL cholesterol, and in those with existing cardiovascular disease, the LDL target should be <1.8 mmol/L (70 mg/dL).

For a more detailed discussion, see Powers AC: Diabetes Mellitus: Diagnosis, Classification, and Pathophysiology Chap. 417, p. 2399; Powers AC: Diabetes Mellitus: Management and Therapies, Chap. 418, p. 2407; and Powers AC: Diabetes Mellitus: Complications Chap. 419, p. 2422, in HPIM-19.