Understanding How Diabetes Affects Patient Response To Medications

Robert G. Smith DPM, MSc, RPh, CPed

Diabetes mellitus is associated with a progression of microvascular and macrovascular complications.1,2 It is understandable that with the progression of these diabetes-related complications, the consumption of medications to prevent and treat them would be greater in comparison to those age-matched individuals without diabetes mellitus.3,4 Often, the use of medication by patients with diabetes is frequent and in many cases involves highly potent drugs or pharmaceuticals with narrow therapeutic ranges.5

   Although drugs develop to treat patients who have diseases, relatively little attention has focused on the fact that the diseases themselves exert important effects that influence patient response to drug therapy. Variability in drug action and, consequently, drug response may be of a pharmacokinetic or a pharmacodynamic origin. The effects of diabetes mellitus on the pharmacokinetics and pharmacodynamics of drugs have been well described in experimental animal models. However, only minimal data exists for humans and the current knowledge regarding the effects of diabetes on these properties remains unclear.5,6

   Diabetes mellitus affects protein, lipid and carbohydrate metabolism as well as the biochemical pathways that are involved in drug biotransformation.6 The principles of pharmacokinetics that may be influenced by diabetes mellitus include: absorption, distribution, biotransformation and excretion.5,6 Diabetic changes in subcutaneous and muscle blood flow, and delayed gastric emptying may influence how a drug is absorbed.5,6 Non-enzymatic glycation of albumin secondary to diabetes mellitus may affect a medication’s distribution within the body.5,6

   The biotransportation of a drug may change in the presence of diabetes mellitus due to regulation of enzymes involved in drug biotransformation and drug transporters.5,6 Finally, a medication’s elimination, mainly its excretion, may be influenced by diabetic nephropathy.5,6 Once a clinician appreciates diabetes mediated changes as a source of drug-patient variability, it should lead to an improvement of medical management and clinical outcomes in patients with diabetes mellitus.

Considering The Impact Of Diabetes On Drug Absorption And Distribution

Absorption is the rate and extent to which a drug leaves its site of administration. Drug absorption occurs at different sites along the gastrointestinal tract, including the stomach and the small and large intestines. After a drug is absorbed or injected into the bloodstream, it enters circulation and distributes throughout the body. Gastric emptying is frequently abnormal in patients with long-standing type 1 and type 2 diabetes mellitus.7 Symptoms commonly associated with delayed gastric emptying include nausea, vomiting, bloating and epigastric pain. These patients are also at risk of malnutrition, weight loss, impaired drug absorption, disordered glycemic control and having a poor quality of life.7 Despite the fact that many studies have reported diabetes-mediated changes in gastric emptying time, the magnitude of the delay is modest and at this time, some authors may not consider it clinically important.5,6

   Drug distribution is the process by which a drug reversibly leaves the bloodstream and enters the extracellular fluid or the cells of the tissues. Drugs can be distributed into different compartments of the body (i.e., blood, plasma, fat or bone). Clinicians commonly use the term “volume of distribution” to describe the extent of drug distribution to tissues relative to the plasma volume. The volume of distribution of a drug correlates with the degree of obesity and obesity is a factor in the development of insulin resistance and diabetes.5,6,8 Various authors have observed that the volume of distribution of lipophilic drugs is affected by diabetes mellitus.5,6,8

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