DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1248 Therapy of Diabetes
SECTION V
HORMONES AND HORMONE ANTAGONISTS
Goals of Therapy. The goals of therapy for diabetes are to
alleviate the symptoms related to hyperglycemia (fatigue,
polyuria, etc.) and to prevent or reduce the acute and
chronic complications of diabetes. Accomplishment of
these goals requires a multidisciplinary team (physicians,
nurse educators, pharmacists) with expertise in pharmacology,
nutrition, and patient education. Central to the
treatment plan is the patient who must actively participate
in the care of his or her diabetes.
Glycemic control is assessed using both shortterm
(blood glucose self-monitoring) and long-term
metrics (A1C, fructosamine). Using capillary blood
glucose measurements, the patient assesses capillary
blood glucose on a regular basis (fasting, before meals,
or postprandially) and reports these values to the diabetes
management team. A1C reflects glycemic control
over the prior 3 months; glycosylated albumin
(fructosamine) is a measure of glycemic control over
the preceding 2 weeks.
Approaches to diabetes care are sometimes termed intensive
insulin therapy, intensive glycemic control, and tight control. This
chapter use the term comprehensive diabetes care to describe optimal
therapy, which involves more than glucose management and
includes aggressive treatment of abnormalities in blood pressure and
lipids and detection and management of diabetes-related complications
(Figure 43–6). Table 43–4 shows the ADA-recommended
treatment goals for comprehensive diabetes care, for glucose, blood
pressure, and lipids (Brunzell et al., 2008). Improved glycemic control
reduces the complications when started relatively early in the
course of both type 1 and type 2 diabetes, but very intensive glucose
lowering (with A 1c
near 6.0) has not shown benefit in individuals
with type 2 diabetes and atherosclerotic disease (Duckworth et al.,
2009; Holman et al., 2008; Skyler et al., 2009). A summary of available
pharmacologic agents for the treatment of diabetes is at the end
of this chapter (Table 43–9).
Nonpharmacologic Aspects of Diabetes Therapy. The patient with
diabetes should be educated about nutrition, exercise, and medications
aimed at lowering the plasma glucose. The role of the certified
diabetes educator, a healthcare professional (nurse, dietician, or
pharmacist) with specialized patient education skills, is critical. In
terms of diet, the ADA uses the term medical nutrition therapy to
describe the diet that coordinates calorie intake and other aspects of
diabetes therapy such as pharmacological agents and exercise. In
type 1 diabetes, matching caloric intake and insulin dosing is very
important. In type 2 diabetes, the diet is directed at weight loss and
reducing blood pressure and atherosclerotic risk. Exercise provides
multiple benefits for patients with diabetes, but dosing of the glucose-lowering
therapy may require adjustment to avoid exerciserelated
hypoglycemia.
In addition to lifestyle modification, the other major nonpharmacological
means to reduce the progression of abnormal glucose
metabolism is bariatric surgery (Sjostrom et al., 2004). A number of
procedures, including gastric banding, gastric bypass, and biliopancreatic
diversion, improve glucose tolerance and prevent or reverse
type 2 diabetes.
Insulin Therapy
Insulin is the mainstay for treatment of virtually all type 1
and many type 2 diabetes patients. Insulin may be
administered intravenously, intramuscularly, or subcutaneously.
Long-term treatment relies predominantly on
subcutaneous injection. Subcutaneous administration
of insulin differs from physiological secretion of insulin
in two major ways:
• The absorption kinetics do not reproduce the rapid
rise and decline of endogenous insulin in response to
glucose following intravenous or oral administration.
• Injected insulin is delivered into the peripheral circulation
instead of being released into the portal circulation.
Thus the portal/peripheral insulin concentration
is not physiological, and this may alter the influence
of insulin on hepatic metabolic processes.
Nonetheless, insulin delivered into the peripheral
circulation can lead to normal or near-normal glycemia.
Glycemic control
• Diet/lifestyle
• Exercise
• Medication
Management of
diabetes
Treat associated
conditions
• Dyslipidemia
• Hypertension
• Obesity
• CV disease
Screen for/manage
complications
of diabetes
• Retinopathy
• Cardiovascular
disease
• Neuropathy
• Nephropathy
• Other complications
Figure 43–6. Components of comprehensive diabetes care.
History. The discovery of insulin is a dramatic story. The discovery
is attributed to Frederick Banting, Charles Best, J.J.R. Macleod, and
J.B. Collip at the University of Toronto, but others provided important
observations and techniques that made it possible (Bliss, 2005).
In 1869, a German medical student, Paul Langerhans, noted that the
pancreas contains two distinct groups of cells—the acinar cells,
which secrete digestive enzymes, and cells that are clustered in
islands, or islets, which he suggested served a second function.
Direct evidence for this function came in 1889, when Minkowski
and von Mering showed that pancreatectomized dogs exhibit a syndrome
similar to human diabetes mellitus. Thereafter, there were
numerous attempts to extract the pancreatic substance responsible
for regulating blood glucose. Between 1903 and 1909, the Romanian