Management and Evaluation of Diabetes Mellitus

Treatment and evaluation of diabetes (see Chapter 27 ) includes diet, oral hypoglycemic drugs, exercise, exogenous insulin, and weight reduction if warranted. Insulin preparations include those from pork, beef, and human

TABLE 46-18 -- Classification of insulin preparations

Preparation	Type	Onset	Peak	Duration
Fast acting	Insulin lispro injection (Humalog)	15 min	30–90 min	3.5–4 hr
	Regular	30–60 min	2–4 hr	6–8 hr
	Semilente	1–3 hr	5–10 hr	16 hr
Intermediate acting	Isophane (NPH)	2–4 hr	6–12 hr	18–26 hr
	Lente (Humulin)	2–4 hr	6–12 hr	18–26 hr
Long acting	Protamine zinc	4–8 hr	14–24 hr	28–36 hr
	Ultralente	4–8 hr	14–24 hr	28–36 hr
Adapted from Stoelting RK, Dierdorf SF: Endocrine disease. In Anesthesia and Co-Existing Disease, 3rd ed. New York, Churchill Livingstone, 1993, p 340.

or recombinant sources. Most diabetics are prescribed a combination of rapid-acting and intermediate-acting insulin before breakfast and before bedtime. Rebound hyperglycemia may follow a hypoglycemic reaction (i.e., Somogyi effect). In the past decade, newer therapies for new-onset insulin-dependent diabetes mellitus (type 1 diabetes) have been introduced, including transplantation of pancreatic tissue and immunosuppression. It is important to realize that 15% of patients with type 1 diabetes have other autoimmune processes and that the elevated glucose levels are probably caused by destruction of pancreatic beta cells in these instances ( Table 46-18 ).

Insulin therapy can result in anaphylactic and anaphylactoid reactions, especially when using protamine-containing insulin preparations. Protamine-derived insulin is made from fish sperm and can cause immunologic sensitization when protamine reversal is administered after cardiopulmonary bypass or heparin reversal.^[73] The protamine reaction can be devastating and includes profound hypotension, pulmonary vasoconstriction, and noncardiogenic pulmonary edema. Insulin analogs have been developed with improved time-action profiles.

The first insulin analog was introduced in the mid-1990s. Subsequently, several other insulin analogs have been formulated ( Table 46-19 ). Insulin lispro (Humalog) is a genetically engineered protein identical to human insulin except for a reversal of the amino acids, proline and lysine, at positions 28 and 29 of the β chain.^[74]

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This reversal in the amino acid sequence allows for a more rapid absorption and faster onset of action compared with regular insulin.^{[75] [76] [77] [78]} Reversal of the proline-lysine sequence eliminates two critical hydrophobic interactions responsible for the β-sheet conformational changes and dimerization. Decreased propensity for dimerization is the key to understanding the absorptive characteristics of insulin lispro.

Another insulin analog has been released. Insulin glargine (Lantus) resembles the human insulin protein with addition of two arginine amino acids to the β chain and replaces asparagine with glycine at the α-21 position. The addition of the two arginine units causes a shift in the isoelectric point to 6.7 ± 0.2, which allows for precipitation of the insulin glargine in the neutral pH of human tissue. The substitution of glycine in the α chain and the addition of 30 µg/mL of zinc increase the hexamer stability of the precipitate.^{[79] [80]} This precipitate slowly dissolves and results in a relatively constant time-action profile with no pronounced peak. This time-action profile allows for once-daily dosing and a duration of action of 18 to 24 hours. These new preparations will be encountered more often in patients being assessed for surgery, and understanding their time-action profiles will be essential in clinical management.