Standardized Treatment Goals
Key Points:
- The following standardized treatment goals are recommended: A1c individualized to patient and blood sugars at goal, use of statins and titrating LDL cholesterol to goal of less than 100 mg/dL without coronary artery disease and less than 70 mg/dL with coronary artery disease, blood pressure less than 130/80 mmHg, daily aspirin for patients 40 years of age and over, and avoidance of tobacco use.
- Individual patients with special circumstances must have treatment goals based on the risks and benefits for that patient. The American Geriatric Society recommends A1c less than 8% for many patients, and the benefits of tight glucose control diminish for many patients with life expectancy less than five years.
The physician and patient must discuss and document the treatment goals and the plan to achieve the desired goals. Less strict goals may be established for the very elderly or for the patient with severe health problems (e.g., severe coronary artery disease, metastatic cancer, dementia, limited life expectancy from other causes).
Control of hyperglycemia is important; however, in older persons with diabetes, a greater reduction in morbidity and mortality may result from control of cardiovascular risk factors than from tight glycemic control [R].
Factors to consider for individualized treatment goals:
- Advanced age or estimated survival of less than five years
- Cognitive impairment or advanced neurological disease such as stroke or dementia
- Polypharmacy concerns
- Multiple comorbidities
- Hypoglycemia unawareness, history of severe hypoglycemia requiring assistance
- Inability to recognize and treat hypoglycemia or the inability to comply with standard goals
- Duration of diabetes
- Cardiovascular risk
Goals for Glycemic Control -- A1c Individualized to Patient
Early evidence on the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Steno 2 Study have further reinforced the need for individualization of glycemic management goals of patients with type 2 diabetes.
The Data Safety and Monitoring Board (DSMB) and the director of the National Heart, Lung, and Blood Institute (NHLBI) recommended that ACCORD intensive glycemia intervention participants (A1c goal <6.0%) be transitioned to standard glycemia treatment (A1c goal of 7%-7.9%) due to safety concerns. The ACCORD study found a 20% higher risk of all-cause mortality in the intensive treatment group (with an achieved median of 6.4%) than in the standard treatment group (with an achieved median of 7.5%). The rate of death for intensive glycemia participants was about 14 people per 1,000 participants treated in the intensive group for one year, compared to about 11 in the standard group. No link was identified by the Data Safety and Monitoring Board between the increased risk of death and any particular medication (including Avandia) or to severe hypoglycemia.
The Steno 2 Study of 160 patients with type 2 diabetes and microalbuminuria showed a 50% reduction in mortality and significant reduction in microvascular complications five years after ending a 7.8-year multifactorial intervention that achieved A1c of 7.8%, LDL 83 mg/dL, blood pressure (BP) 131/73, compared to a conventional group that achieved A1c 9%, LDL 126 mg/dL and BP 146/78 [A]. Results of this study are consistent with the need for reasonable blood sugar control with emphasis on blood pressure and lipid management.
The work group believes that additional sources of data may be available in the near future to provide more evidence for determining optimal glycemic targets.
Until more data is available from ACCORD and other emerging studies, the work group recommends following the suggestion of the director of NHLBI, who states, "Our message to individuals with type 2 diabetes who are at especially high risk for heart disease is to target your A1c level to about 7 percent and not to more intensive levels. No one with diabetes should change their treatment without consulting with their healthcare professional first and we concur with the ADA recommendations that treatment must be individualized." "Especially high risk for heart disease" includes those patients with known heart disease and microalbuminuria, as well as those with two or more risk factors such as obesity, hypertension, hyperlipidemia and smoking.
For patients with long-standing diabetes and cardiovascular risk on insulin or multiple glycemic medications and an A1c under 6.5%, it would be appropriate to make slight medication reductions. For instance, reduce total insulin dose by 10% to 20%, or reduce sulfonylurea dose, particularly if patients have hypoglycemia, or reduce or stop thiazolidinediones (TZDs) if patient has experienced weight gain or edema.
The goal for an individual may be higher or lower depending on the predicted life expectancy, expected clinical benefits and risk of treatment [R]. Based on current available evidence, the following factors should be considered when individualizing therapy:
Support for more intensive treatment goals:
- Younger age
- Early disease
- Management with medical nutrition therapy and/or single oral agents
Support for less intensive treatment goals
- Advanced age
- Cardiovascular risk
- Longer duration of diabetes
- Limited life expectancy
- History of severe hypoglycemia
- Hypoglycemia unawareness
- Advanced neurological disease (stroke, dementia)
- Multiple comorbidities
- Polypharmacy concerns
[D]
Glycosylated hemoglobin assays provide an accurate indication of long-term glycemic control. A1c is formed by the continuous non-enzymatic glycosylation of hemoglobin throughout the lifespan of an erythrocyte. This assay yields an accurate measure of time-averaged blood glucose during the previous six to eight weeks.
There are various methodologies (e.g., HbA, A1c, glycated hemoglobin) for this assay. At present, there are no established criteria for use as a diagnostic test. Clinically it can assist in determining duration and severity of hyperglycemia and can help guide treatment.
A1c is not influenced by food intake, physical activity or acute metabolic stress. The test can be done at any time of day and does not require fasting.
Blood sugars should also be used to assess level of glycemic control, in addition to A1c. It is appropriate to determine need for medication changes based on blood sugars whenever this information is available.
Medical centers need to know what the standard is for A1c and glycosylated hemoglobin in their labs and make the appropriate conversions.
Self-Monitoring Blood Glucose (SMBG)
The frequency and timing of self-monitoring blood glucose should be dictated by the particular needs and goals of the individual patient. Patients with type 2 diabetes on insulin typically need to perform self-monitoring blood glucose more frequently than those not using insulin, particularly if using glucose readings to guide mealtime insulin dosing. It is recommended that patients should perform self-monitoring blood glucose three or more times daily for patients using multiple insulin injections [R].
The optimal frequency and timing of self-monitoring blood glucose for patients with type 2 diabetes on oral agent therapy are not known but should be sufficient to facilitate reaching glucose goals. Self-monitoring blood glucose should be performed more frequently when adding or modifying therapy, two-hour postprandial glucose testing is useful in some patients. The role of self-monitoring blood glucose in stable diet-treated patients with type 2 diabetes is not known.
Because the accuracy of self-monitoring blood glucose is instrument and user dependent, it is important for health care providers to evaluate each patient's monitoring technique. In addition, optimal use of self-monitoring blood glucose requires proper interpretation of the data. Patients should be taught how to use the data to adjust food intake, exercise or pharmacological therapy to achieve specific glycemic goals.
Examples of self-monitoring glucose goals, frequency and timing are [R]:
- Target preprandial plasma glucose values to a goal of 90 to 130 mg/dL for an A1c goal less than 7%. Target blood sugar readings could be higher or lower depending on individualized A1c goal.
- Average two-hour postprandial plasma glucose values less than 180 mg/dL
- Two-hour postmeal plasma blood glucoses can be helpful for adjusting mealtime medications. The target range for postmeal glucoses is controversial at this time, but a reasonable two-hour postprandial target is within 40 mg/dL higher than the preprandial reading.
- Average bedtime plasma glucose values are less than 120 mg/dL with a goal of 110 to 150 mg/dL
- Bedtime glucose goals vary dependent on the patient's treatment program, risks for hypoglycemia, and time after last meal.
- More than half of the plasma blood glucose readings should fall in the desired goal range.
Start or Intensify Statin Dose
The LDL cholesterol goal for people with diabetes mellitus without coronary artery disease (CAD) is less than 100 mg/dL. The goal with CAD is less than 70 mg/dL.
Intensify statin or lipid-lowering medications to meet LDL cholesterol goals [A].
Recent evidence [A] and Adult Treatment Panel III (ATPIII) consensus guidelines [R] suggest that statins are beneficial for high-risk patients with a 10-year risk of cardiovascular (CV) event of more than 20% (e.g., coronary heart disease [CHD] equivalency), even with baseline LDL of less than 100 mg/dL.
For patients with type 2 diabetes mellitus, consider use of a statin. [Conclusion Grade I: See Conclusion Grading Worksheet A -- Annotation #11(Statin Use) [A] in the original guideline document].
Use of moderate- to high-dose statins or other LDL cholesterol-lowering medications as needed to achieve an LDL cholesterol value less than 70 mg/dL is recommended for patients with CHD [A].
Three pathways to improve lipids are:
- Medical nutrition therapy
- Increased physical exercise
- Pharmacotherapy
Beneficial effects of statins on cardiovascular risk reduction may, in part, be independent of their effects on lipids. Diabetes is considered a coronary artery disease equivalent. There is an online and a Palm format-downloadable CV risk calculator that is used in assessing 10-year risk of CV disease used in the Adult Treatment Panel III (ATP III) guideline report and this guideline on lipid management [R]. The links are:
Online calculator: http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof, and
Palm format (downloadable): http://hin.nhlbi.nih.gov/atpiii/riskcalc.htm.
There currently is not evidence for safety and efficacy of combination therapy with statins and other lipid drugs. National Institutes of Health-sponsored randomized controlled studies are currently underway to determine whether adding fibrates or niacin to statin therapy will lower the risk of cardiovascular events for patients with diabetes.
Seventy to seventy-five percent of adult patients with diabetes die of macrovascular disease, specifically coronary, carotid, and/or peripheral vascular disease. Dyslipidemia is a known risk factor for macrovascular disease.
Small density LDL-cholesterol (more atherogenic) particles are increased in type 2 diabetes, and LDL-cholesterol itself may differ in people with diabetes compared with people without diabetes [R]. Patients with diabetes develop more atherosclerosis than patients without diabetes with the same quantitative lipoprotein profiles. In individuals with elevated triglycerides, a statin can reduce major vascular events [C].
High triglycerides and low HDL-cholesterol are independent risk factors for cardiovascular disease in the patient with diabetes [R]. Individuals with elevated triglycerides have significant cardiovascular risk reduction with the use of fibrates [A] or statins [A]. While a number of studies support favorable changes in lipid profiles with niacin alone, randomized controlled trials considering hard cardiovascular outcomes are lacking.
Goals for Blood Pressure Control: BP Less Than 130/80 mm Hg, Emphasis on Systolic BP Control
[R]
In type 2 diabetes, insulin resistance may cause hypertension by increasing sympathetic activity, renal reabsorption of sodium, or vascular tone.
Uncontrolled hypertension is a major cardiovascular risk factor that also accelerates the progression of diabetic nephropathy [B]. When hypertension is identified, it should be aggressively treated to achieve a target blood pressure of less than 130/80 mm Hg. See the Blood Pressure Control algorithm below.
For patients with type 2 diabetes mellitus, the systolic blood pressure goal is less than 130 mm Hg and the diastolic blood pressure goal is less than 80 mm Hg. [Conclusion Grade II: See Conclusion Grading Worksheet B -- Annotations #11,24, 26 (Goals for BP) in the original guideline document] [A].
Aspirin/Antiplatelet Medication Use Unless Contraindicated [A]
Patients with type 2 diabetes are at a significantly high risk for development of heart disease [R]. For patients with type 2 diabetes mellitus, initiate low-dose aspirin therapy (81 to 325 mg daily) in patients 40 and older unless there is a contraindication to aspirin therapy. [Conclusion Grade I: See Conclusion Grading Worksheet C -- Annotation #11 (Aspirin Use) in the original guideline document] [A], [B].
Higher doses of aspirin thought in the past to be required for clinical effects have been shown to be unnecessary, and are undesirable because of dose-related gastric and hemorrhagic side effects.
If aspirin is contraindicated, consider use of clopidogrel or ticlopidine. For more information, please refer to the NGC summary of the ICSI guideline Stable Coronary Artery Disease and the Antithrombotic Therapy Supplement.
On September 8, 2006, the Food and Drug Administration issued a Safety Information and Adverse Event Report regarding the concomitant use of aspirin and ibuprofen.
Health care professionals should counsel patients about the appropriate timing of ibuprofen dosing if they are taking aspirin for cardioprotective effects.
With occasional use of ibuprofen, there is likely to be minimal risk from any attenuation of the antiplatelet effect of low-dose aspirin, because of the long-lasting effect of aspirin on platelets.
Recommendations include taking immediate-release aspirin (not enteric-coated) 30 minutes or longer prior to taking ibuprofen (400 mg). If ibuprofen is taken first, aspirin should not be taken for at least eight hours after ingestion of ibuprofen.
Enteric-coated aspirin and concomitant use of ibuprofen is unclear. One study showed that 400 mg ibuprofen interfered with the antiplatelet effect of enteric-coated low-dose aspirin at 2, 7 and 12 hours after ingestion [C].
Other non-selective over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) should be viewed as having the potential to interfere with the antiplatelet effect of low-dose aspirin unless proven otherwise.
For more information, please refer to the information listed on the Food and Drug Administration's Web site for a complete copy of the alert and cited references: http://www.fda.gov/medwatch/safety/2006/safety06.htm#aspirin.
Goals for Tobacco Use - Smoking Cessation, if Indicated
At a minimum, identify all individuals who use or are exposed to tobacco and provide a brief intervention to help eliminate or at least decrease their use or exposure.
Because effective tobacco dependence treatments are available, every patient who uses tobacco should be offered at least one of these treatments:
- Patients willing to try to quit tobacco use should be provided with treatments identified as effective in this guideline.
- Patients unwilling to try to quit tobacco use should be provided with a brief intervention designed to increase their motivation to quit.
There is a strong dose-response relation between the intensity of tobacco dependence counseling and its effectiveness. Treatments involving person-to-person contact (via individual, group or proactive telephone counseling) are consistently effective, and their effectiveness increases with treatment intensity, (e.g., minutes of contact) [R].
Brief interventions consist of feedback of screening data designed to increase motivation to change tobacco use behavior, simple advice, health education, goal-setting, practical suggestions, and follow-up, with referral when appropriate. Brief tobacco dependence treatment is effective, and every patient who uses tobacco should be offered at least brief treatment [R].
Tobacco telephone quit lines and proactive telephone counseling increase the odds of abstinence by about 20%. Three types of counseling and behavioral therapies were found to be especially effective and should be used with all patients attempting tobacco cessation:
- Provision of practical counseling (problem-solving/skills training)
- Provision of social support as part of treatment (intratreatment social support)
- Help in securing social support outside of treatment (extratreatment social support)
Numerous effective pharmacotherapies for smoking cessation now exist. Except in the presence of contraindications, these should be used with all patients attempting to quit smoking.