Page 779 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 41 Pancreatic Hormones & Antidiabetic Drugs 765

the action profile of the insulins. He or she should know how to and macrovascular disease. For the elderly frail patient an HbA
1c
determine if the basal insulin dose is correct and how to adjust greater than 8% may be appropriate.
the rapidly acting insulin dose for carbohydrate content of meals.
Insulin adjustments for exercise and infections should be dis- Treatment
cussed. The patient and family members also should be informed
about the signs and symptoms of hypoglycemia. Treatment must be individualized on the basis of the type of dia-
betes and specific needs of each patient.
Glycemic Targets A. Type 1 Diabetes

The American Diabetes Association criteria for acceptable control For most type 1 patients, at least 3 or 4 insulin injections a day are
include an HbA of less than 7% (53 mmol/mol) and pre-meal necessary for safe and effective control of glucose levels. A com-
1c
glucose levels of 90–130 mg/dL (5–7.2 mmol/L) and less than bination of rapidly acting insulin analogs and long-acting insulin
180 mg/dL (10 mmol/L) one hour and 150 mg/dL (8.3 mmol/L) analogs allow for more physiologic insulin replacement. Generally,
two hours after meals. While the HbA target is appropriate for for an adult with type 1 diabetes, the total daily insulin require-
1c
individuals treated with lifestyle interventions and euglycemic ment in units is equal to the weight in pounds divided by four, or
therapy, it may need to be modified for individuals treated with 0.55 times the person’s weight in kilograms. Approximately 40%
insulin or insulin secretagogues due to their increased risk of of the total daily insulin dosage covers the background or basal
hypoglycemia. Less stringent blood glucose control also is appro- insulin requirements, and the remainder covers meal and snack
priate for children as well as patients with a history of severe hypo- requirement and high blood sugar corrections. This is an approxi-
glycemia, limited life expectancy, and significant microvascular mate calculation and should be individualized. Examples of

Benefits of Tight Glycemic Control in Diabetes

A long-term randomized prospective study involving 1441 type for patients with inadequate response to other therapies. Tight
1 patients in 29 medical centers reported in 1993 that “near control of blood pressure was added as a variable, with an angio-
normalization” of blood glucose resulted in a delay in onset tensin-converting enzyme inhibitor, a β blocker, or in some cases,
and a major slowing of progression of microvascular and neu- a calcium channel blocker available for this purpose.
ropathic complications of diabetes during follow-up periods of Tight control of diabetes, with reduction of HbA 1c from 9.1%
up to 10 years (Diabetes Control and Complications Trial [DCCT] to 7%, was shown to reduce the risk of microvascular complica-
Research Group, 1993). In the intensively treated group, mean tions overall compared with that achieved with conventional
glycated hemoglobin (HbA 1c ) of 7.2% (normal <6%) and mean therapy (mostly diet alone, which decreased HbA 1c to 7.9%).
blood glucose of 155 mg/dL were achieved, whereas in the Cardiovascular complications were not noted for any particular
conventionally treated group, HbA 1c averaged 8.9% with mean therapy; metformin treatment alone reduced the risk of macro-
blood glucose of 225 mg/dL. Over the study period, which aver- vascular disease (myocardial infarction, stroke). Epidemiologic
aged 7 years, a reduction of approximately 60% in risk of diabetic analysis of the study suggested that every 1% decrease in the
retinopathy, nephropathy, and neuropathy was noted in the HbA 1c achieved an estimated risk reduction of 37% for micro-
tight control group compared with the standard control group. vascular complications, 21% for any diabetes-related end point
The DCCT study, in addition, introduced the concept of and death related to diabetes, and 14% for myocardial infarction.
glycemic memory, which comprises the long-term benefits of any Tight control of hypertension also had a surprisingly sig-
significant period of glycemic control. During a 6-year follow-up nificant effect on microvascular disease (as well as more conven-
period, both the intensively and conventionally treated groups tional hypertension-related sequelae) in these diabetic patients.
had similar levels of glycemic control, and both had progression of Epidemiologic analysis of the results suggested that every
carotid intimal-medial thickness. However, the intensively treated 10-mmHg decrease in the systolic pressure achieved an esti-
cohort had significantly less progression of intimal thickness. mated risk reduction of 13% for diabetic microvascular complica-
The United Kingdom Prospective Diabetes Study (UKPDS) tions, 12% for any diabetes-related complication, 15% for death
was a very large randomized prospective study carried out related to diabetes, and 11% for myocardial infarction.
to study the effects of intensive glycemic control with several Post-study monitoring showed that 5 years after the closure
types of therapies and the effects of blood pressure control in of the UKPDS, the benefits of intensive management on diabetic
type 2 diabetic patients. A total of 3867 newly diagnosed type 2 end points were maintained and the risk reduction for a myo-
diabetic patients were studied over 10 years. A significant frac- cardial infarction became significant. The benefits of metformin
tion of these were overweight and hypertensive. Patients were therapy were maintained.
given dietary treatment alone or intensive therapy with insulin, These studies show that tight glycemic control benefits both
chlorpropamide, glyburide, or glipizide. Metformin was an option type 1 and type 2 patients.