Qualitative detection of ketone bodies can be accomplished by nitroprusside tests (Acetest or Ketostix). Although these tests do not detect beta-hydroxybutyric acid, which lacks a ketone group, the semiquantitative estimation of ketonuria thus obtained is nonetheless usually adequate for clinical purposes. Many laboratories now measure beta-hydroxybutyric acid, and meters are available (Precision Xtra; Nova Max Plus) for patient use that measure beta-hydroxybutyric acid levels in capillary glucose samples. Betahydroxybutyrate levels >0.6 mmol/L require evaluation. A level >3.0 mmol/L, which is equivalent to very large urinary ketones, will require hospitalization.
D. Self-Monitoring of Blood Glucose
Capillary blood glucose measurements performed by patients themselves, as outpatients, are extremely useful. In type 1 patients in whom “tight” metabolic control is attempted, they are indispensable. Several paper strip methods and a large number of blood glucose meters are now available for measuring glucose on capillary blood samples. All are accurate, but they vary with regard to speed, convenience, size of blood samples required, reporting capability, and cost. Some meters are designed to communicate with an insulin pump. A number of continuous glucose monitoring (CGM) systems are also available for clinical use. The systems utilize a subcutaneous sensor that measures glucose concentrations in the interstitial fluid for 3–7 days. Studies show that adult type 1 patients who use continuous systems have improved glucose control without an increased incidence of hypoglycemia. There is great interest in using continuous glucose monitoring systems to automatically deliver insulin by continuous subcutaneous insulin infusion pump. The first artificial pancreas system has been approved by the U.S. Food and Drug Administration (FDA) and will become available in 2017. With this system, the continuous glucose monitor readings are used to automatically adjust the basal insulin dosing by the insulin pump.
Human insulin is dispensed as regular (R) and neutral protamine hagedorn (NPH) formulations. There are also six analogs of human insulin. Three of the analogs are rapidly acting: insulin lispro, insulin aspart, and insulin glulisine; and three are long acting: insulin glargine, insulin detemir, and insulin degludec. Animal insulins are not available in the United States. Pork and beef preparations (isophane, neutral, 30/70, and lente) are still available in other parts of the world. All the insulins in the United States are available in a concentration of 100 units/ML (U100) and dispensed as 10-mL vials or 0.3-mL cartridges or prefilled disposable pens. Several insulins are also available at higher concentrations in the prefilled disposable pen form: insulin glargine 300 units/mL (U300); insulin degludec (U200); insulin lispro 200 units/mL (U200); and regular insulin 500 units/mL (U500) (Tables 41–5, 41–6).
A. Short-Acting Insulin Preparations (Tables 41–5, 41–6)
The short-acting preparations include regular human insulin and the three rapidly acting insulin analogs. All are clear solutions at neutral pH. The insulin molecules exist as dimers that assemble into hexamers in the presence of two zinc ions. The hexamers are further stabilized by phenolic compounds such as phenol and meta-Cresol. The mutations engineered into the rapidly acting insulin analogs are designed to disrupt the stabilizing intermolecular interactions of the dimers and hexamers, leading to more rapid absorption into the circulation after subcutaneous injection.