Page 766 - Basic _ Clinical Pharmacology ( PDFDrive )

752 SECTION VII Endocrine Drugs

They can be treated at first with oral hypoglycemic agents Laboratory Findings
but then need insulin as their beta cell function declines.
Antibody studies in northern Europeans indicate that up to A. Plasma or Serum Glucose
10–15% of “type 2” patients may actually have this milder A plasma glucose level of 126 mg/dL (7 mmol/L) or higher
form of type 1 diabetes (latent autoimmune diabetes of adult- on more than one occasion after at least 8 hours of fasting is
hood; LADA). diagnostic of diabetes mellitus (Table 41–4). Fasting plasma
glucose levels of 100–125 mg/dL (5.6–6.9 mmol/L) are associ-
Type 2 Diabetes Mellitus ated with increased risk of diabetes (impaired fasting glucose
tolerance).
Type 2 diabetes is a heterogenous group of conditions charac- If the fasting plasma glucose level is less than 126 mg/dL
terized by tissue resistance to the action of insulin combined (7 mMol/L) but diabetes is nonetheless suspected, then a stan-
with a relative deficiency in insulin secretion. A given indi- dardized oral glucose tolerance test may be done (Table 41–4).
vidual may have more resistance or more beta-cell deficiency, The patient should eat nothing after midnight prior to the test
and the abnormalities may be mild or severe. Although the day. On the morning of the test, adults are then given 75 g of
circulating endogenous insulin is sufficient to prevent ketoaci- glucose in 300 mL of water; children are given 1.75 g of glucose
dosis, it is inadequate to prevent hyperglycemia. Patients with per kilogram of ideal body weight. The glucose load is consumed
type 2 diabetes can initially be controlled with diet, exercise within 5 minutes. Blood samples for plasma glucose are obtained
and oral glucose lowering agents or non-insulin injectables. at 0 and 120 minutes after ingestion of glucose. An oral glucose
Some patients have progressive beta cell failure and eventually tolerance test is normal if the fasting venous plasma glucose value
may also need insulin therapy. is less than 100 mg/dL (5.6 mmol/L) and the 2-hour value falls
below 140 mg/dL (7.8 mmol/L). A fasting value of 126 mg/dL
Other Specific Types of Diabetes Mellitus (7 mmol/L) or higher or a 2-hour value of greater than 200 mg/dL
(11.1 mmol/L) is diagnostic of diabetes mellitus. Patients with
The “other” designation refers to multiple other specific causes 2-hour value of 140–199 mg/dL (7.8–11.1 mmol/L) have
of an elevated blood glucose: pancreatectomy, pancreatitis, non- impaired glucose tolerance.
pancreatic diseases, drug therapy, etc. For a detailed list the reader
is referred to the reference Expert Committee, 2003.
B. Hemoglobin A1c Measurements
Gestational Diabetes Mellitus When plasma glucose levels are in the normal range, about 4–6%
of hemoglobin A has one or both of the N terminal valines of their
Gestational diabetes (GDM) is defined as any abnormality in glu- beta chains irreversibly glycated by glucose—referred to as hemo-
cose levels noted for the first time during pregnancy. Gestational globin A1c (HbA1 ). The HbA1 fraction is abnormally elevated
c
c
diabetes is diagnosed in approximately 7% of all pregnancies in in people with diabetes with chronic hyperglycemia. Since red
the United States. During pregnancy, the placenta and placental cells have a lifespan of up to 120 days, the HbA1 value reflects
c
hormones create an insulin resistance that is most pronounced in plasma glucose levels over the preceding 8–12 weeks. In patients
the last trimester. Risk assessment for diabetes is suggested start- who monitor their glucose levels, the HbA1 value provides a
c
ing at the first prenatal visit. High-risk women should be screened valuable check on the accuracy of their monitoring. In patients
immediately. Screening may be deferred in lower-risk women who do not monitor their glucose levels, HbA1c measurements
until the 24th to 28th week of gestation. are essential for adjusting treatment. HbA1 can be used to
c

TABLE 41–4 Diagnostic criteria for diabetes.

Normal Glucose
Tolerance, mg/dL
(mMol/L) Prediabetes Diabetes Mellitus 2

Fasting plasma glucose mg/dL (mmol/L) <100 (5.6) 100–125 (5.6–6.9) ≥126
(impaired fasting glucose) (7.0)
1
Two hours after glucose load mg/dL <140 (7.8) ≥140–199 ≥200
(mmol/L)
(7.8–11.0) (11.1)
(impaired glucose tolerance)
HbA 1c (%) (ADA criteria) <5.7 5.7–6.4 ≥6.5
1 Give 75 g of glucose dissolved in 300 mL of water after an overnight fast in persons who have been receiving at least 150–200 g of carbohydrate daily for 3 days
before the test.
2 A fasting plasma glucose ≥126 mg/dL (7.0 mmol) or HbA 1c ≥ 6.5% is diagnostic of diabetes if confirmed by repeat testing.
Symptoms and random glucose level >200 mg/dL (11.1 mmol/L) are diagnostic, and there is no need to do additional testing.