Goals and Guidelines for HbA1c, LDL-C, and Blood Pressure in Patients With Diabetes: Sorting Out the Confusion

ABSTRACT: Diabetes management presents challenges for patients and clinicians alike. A number of expert organizations have developed guidelines and recommendations based on the latest knowledge about effective treatment of diabetes. However, differences in the recommendations among the various groups’ guidelines can lead to confusion for both patients and clinicians. This article reviews the different expert guidelines for controlling hemoglobin A_1c, low-density lipoprotein cholesterol, and blood pressure in patients with diabetes and offers suggestions for sorting out the confusion.

KEYWORDS: Diabetes, hemoglobin A_1c, low-density lipoprotein cholesterol, blood pressure

Diabetes is the most difficult of all chronic diseases for both patients and clinicians. The demands of the disease require a significant investment of time and energy from both. Appropriate care requires that clinicians have the knowledge and ability to collaborate and advise patients about lifestyle changes, medication choices, goal setting, and the physical and psychological impact of the disease. Patients face many barriers as they attempt to implement the recommendations of their clinician. Primary care offices also have barriers that make it difficult to achieve appropriate care.

Several expert organizations have developed guidelines and recommendations to help clinicians use the latest advances in knowledge about diabetes treatment. Unfortunately, some of the organizations’ guidelines differ from those of other organizations. These differing guidelines can lead to confusion for both patients and clinicians. This article discusses the different guidelines for controlling hemoglobin A_1c (HbA_1c), low-density lipoprotein cholesterol (LDL-C), and blood pressure (BP) in patients with diabetes and offers suggestions for sorting out the confusion.

HbA_1c Goals: 7% or 6.5%

What HbA_1c goal should we attempt to achieve in our patients with diabetes, and what parameters should be used to make that decision? The American Diabetes Association (ADA) suggests a general HbA_1c goal of less than 7%,¹ and the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) suggest 6.5% or lower.²

The ADA bases its recommendation for an HbA_1c of less than 7% on the Diabetes Complications and Control Trial (DCCT)³ and its long-term follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) trial⁴ in patients with type 1 diabetes, and the United Kingdom Prospective Diabetes Study⁵ for type 2 diabetes, that demonstrated a reduction in microvascular complications when HbA_1c levels reached to below 7%. The ADA goes on to say in its 2016 position statement that select patients with few comorbidities and a long life expectancy may benefit from an HbA_1c target of less than 6.5%, as long as significant hypoglycemia does not become a barrier.¹

The AACE/ACE guidelines support an HbA_1c goal of 6.5% or lower for most patients, and a goal of greater than 6.5% (up to 8%) if the lower target cannot be achieved without adverse outcomes.² The AACE and ACE based their recommendation on the significant reductions in the risk or progression of nephropathy noted in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) study,⁶ which targeted an HbA_1c of less than 6.5% in patients undergoing intensive glycemic control therapy compared with standard approaches. Moreover, the AACE/ACE guidelines note that in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial,⁷ intensive glycemic control significantly reduced the risk and/or progression of microvascular complications (ie, retinopathy, nephropathy, and neuropathy).² However, the guidelines note that in the ACCORD trial—which enrolled older and middle-aged patients with longstanding type 2 diabetes, with established cardiovascular disease (CVD), and with a baseline HbA_1c of less than 8.5%—the group of patients randomized to achieving an HbA_1c target of less than 6% had an increased death rate. The excess mortality occurred only in patients whose HbA_1c level remained above 7% despite undergoing intensive glycemic control therapy, whereas among patients in the standard therapy group (HbA_1c target of 7%-8%), mortality followed a U-shaped curve, with increasing mortality rates at low HbA_1c levels (<7%) and high HbA_1c levels (>8%).

HbA_1c Goal Decisions in Primary Care

The HbA_1c goals recommended by the ADA and the AACE/ACE are both acceptable as general starting points but not as absolute rules. Many clinicians seem to use the 7% or lower as a general HbA_1c goal for most patients but individualize the goal for each patient based on a set of specific parameters. The criteria include the following⁸:

Psychosocial. More-intensive therapy (an HbA_1c goal closer to 6%) is recommended if the patient has a good support system, has sufficient resources, is motivated, is not depressed, and has minimal diabetes distress.⁹ Less-intensive therapy (a goal closer to 8%) is called for in a patient who is less motivated, has fewer resources, is depressed, and has significant diabetes distress.

Frailness/life expectancy. This is not to be confused with age alone, which is an arbitrary number depending on the clinician. Some 70-year-olds are very active and have a 10- to 15-year life expectancy. More-intensive treatment and an HbA_1c goal close to 6% are more realistic for a patient who has a longer life expectancy. Less-intensive treatment and a goal closer to 8% are reasonable when life expectancy is 1 to 2 years and/or the patient is frail.

Comorbidities and cardiovascular complications. Patients with no or minimal comorbidities or cardiovascular complications should receive more-intensive therapy and attempt to achieve an HbA_1c goal close to 6%. Patients with a history of a significant cardiovascular event (eg, myocardial infarction, stroke), chronic renal disease, retinopathy, and/or severe neuropathy should be guided to a goal closer to 8% and less-intensive therapy.

Risk of hypoglycemia. The best predictor for hypoglycemia is a past history of hypoglycemia. Many of the parameters mentioned above, especially the comorbidities, are associated with a higher incidence of hypoglycemia. Medications such as insulin and sulfonylureas are associated with hypoglycemia. If a patient has a longer life expectancy, is not frail, has no comorbidities, and minimal psychosocial risks, intensive therapy and an HbA_1c goal closer to 6% is reasonable. Higher goals and less-intense therapy are indicated when many or all of the above parameters are present.

Recommendation. An HbA_1c goal of 7% or below is a good starting point, but lower is acceptable. Use the parameters mentioned above to guide goal selection in individual patients.

LDL-C goals

The most common cause of morbidity and mortality in diabetes is CVD, and decreasing the LDL-C level is fundamental to CVD prevention. Patients with type 2 diabetes have insulin resistance and atherogenic dyslipidemia (high triglyceride levels and low high-density lipoprotein cholesterol [HDL-C] levels). LDL-C is not always elevated, but non–HDL-C (ie, total cholesterol minus HDL-C) is usually elevated in diabetes.

From 2001 until 2013, lipid treatment decisions were guided by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).¹⁰ These guidelines recommended LDL-C goals and encouraged clinicians to treat patients with statins alone or in combination with other drugs to decrease LDL-C to these recommended target levels. 

The 2013 cholesterol guidelines from the American Heart Association and the American College of Cardiology (AHA/ACC),¹¹ however, recommend significant changes in the treatment of patients with dyslipidemia. These newer guidelines suggest a reduction in LDL-C of 50% from baseline, abandoning specific targets, and using only high- or moderate-intensity statins for treatment. The AHA/ACC guideline developers felt that the scientific evidence favored using a statin, but no evidence exists to support treating patients to reach a target LDL-C level.

The AHA/ACC guideline also suggests treatment for 4 distinct groups: patients with documented clinical atherosclerotic cardiovascular disease (ASCVD); patients with an LDL-C level of 190 mg/dL or above; patients from 40 to 75 years of age with diabetes and an LDL-C level of 70 to 189 mg/dL; and patients 40 to 75 years of age without diabetes, with an LDL-C level of 70 to 189 mg/dL, and with a 7.5% or higher calculated risk of a ASCVD in the next 10 years.¹¹

The ADA in its 2016 guidelines¹ follows these AHA/ACC guidelines, setting no LDL-C goal but recommending a 50% reduction in the LDL-C level. The AACE/ACE guidelines² and the National Lipid Association (NLA) guidelines¹² recommend LDL-C goals of less than 100 mg/dL for low-, moderate-, and high-risk patients and less than 70 mg/dL for very-high-risk patients. Many patients who reach these goals still have residual risk, so the additional goal of a non–HDL-C level of below 130 mg/dL for low-, moderate-, and high-risk patients and below 100 mg/dL for very-high-risk patients is recommended. These 2 expert groups recommend the use of statins and other lipid-lowering agents if needed to reach goal. All groups recommend obtaining LDL-C levels periodically. In the AHA/ACC and ADA guidelines, measuring LDL-C levels evaluates the ability of patients to reach the 50% reduction goal. In the ACCE and NLA guidelines, measuring LDL-C levels evaluates the ability of low-, moderate-, and high-risk patients to reach a target of less than 100 mg/dL and very-high-risk patients to reach a target of less than 70 mg/dL.

Additional evidence for treating to a LDL-C target can be found in the Cholesterol Treatment Trialists’ meta-analysis.¹³ This study demonstrated that for every 38.7 mg/dL drop in LDL-C, there was a 22% relative risk reduction across the spectrum of LDL-C levels.

Another meta-analysis¹⁴ demonstrated a linear reduction in risk down to an LDL-C level of 50 mg/dL. In this meta-analysis, individuals with LDL-C levels below 50 mg/dL had a significantly lower risk of major cardiovascular events compared with individuals who had higher LDL-C levels, including those with levels of 50 to 74 mg/dL and 75 to 99 mg/dL.

No organization has yet defined how low the LDL-C goal should be, and some experts recognize that even more-intensive therapy, aimed at LDL-C levels lower than 70 mg/dL, or non–HDL-C levels lower than 100 mg/dL, might be warranted for secondary prevention. The Cholesterol Treatment Trialists’ meta-analysis suggests that an LDL-C level less than 50 mg/dL leads to regression in plaque and a lower risk of cardiovascular events.¹³

The recent Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT)¹⁵ provided evidence that lowering LDL-C levels from 70 mg/dL to 54 mg/dL is beneficial for patients after acute coronary syndromes.

The longer the endothelium is exposed to elevated LDL-C levels, especially in combination with other risk factors (eg, hyperglycemia, hypertension, obesity, smoking), the greater the chance of a cardiovascular event. Good evidence exists that lowering LDL-C levels decreases the risk of cardiovascular events. Even lower LDL-C levels of 25 mg/dL may be safe.¹⁶

Obtaining periodic LDL-C levels and treating to a target makes sense for several reasons. Patients want to know whether their treatment is effective, so a target level can increase medication regimen adherence. Not all patients respond the same way to statins, and patients have varying degrees of adherence to medications, and periodic measurement of LDL-C levels informs the clinician of patients’ level of response and level of adherence. Some patients need an increase in statin dosage or an additional medication to increase effectiveness, so setting an LDL-C goal and measuring its levels periodically makes sense.

Recommendation. Attempt to achieve an LDL-C goal of 100 mg/dL or lower for moderate-risk patients and a goal of 70 mg/dL or lower for high-risk patients. Even lower LDL-C levels likely are safe and can further reduce the risk of cardiovascular events. Achieving non–HDL-C goals (usually when triglycerides are elevated) will decrease residual risk. Statins plus ezetimibe are associated with a decreased risk of cardiovascular events and are the preferred treatment choice.

Blood Pressure Goals

A vast majority (70%-80%) of patients with type 2 diabetes have hypertension. BP treatment goals have undergone several changes in the last few years.

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)¹⁷ recommends a target BP of less than 130/80 mm Hg in patients with type 2 diabetes and hypertension (and even lower to 120/75 mm Hg in those with chronic kidney disease). The updated report from the panel members appointed to the Eighth Joint National Committee (JNC 8)¹⁸ recommends a target BP level of less than 140/90 mm Hg for patients younger than 60 years and less than 150/90 mm Hg for patients 60 years and older. Most other organizations recommend a goal of 150/90 mm Hg for patients older than 80 years.

The ADA recommends that patients with diabetes be treated to a systolic BP goal of less than 140 mm Hg.¹ A lower BP target of 130 mm Hg may be appropriate for certain individuals, such as younger patients, those with albuminuria, and those with one or more additional ASCVD risk factors. A lower goal is important if it can be achieved without undue treatment burden. The diastolic BP goal is less than 90 mm Hg. A lower diastolic BP target of 80 mm Hg may be appropriate for younger patients, those with albuminuria, and those with one or more additional ASCVD risk factors. Again, a lower goal is important if it can be achieved without undue treatment burden for the patient.¹

The AACE/ACE guidelines² recommend that BP control be individualized, and a target of less than 130/80 mm Hg is appropriate for most patients. Similar to the parameters for choosing HbA_1c goals, BP goals are less stringent for patients who are frail, have complicated comorbidities, and/or have adverse medication effects. The AACE/ACE guidelines suggest a more intensive goal of less than 120/80 mm Hg for some patients if the target can be reached safely without adverse effects.²

The Systolic Blood Pressure Intervention Trial (SPRINT)¹⁹ adds more evidence that lower is better. It demonstrated that a lower target (120 mm Hg systolic) was beneficial in reducing the trial’s composite endpoint when treating high BP. SPRINT did not enroll patients with diabetes, however.

The American Society for Hypertension (ASH) recommends a treatment goal of less than 140/90 mm Hg.²⁰ Previous ASH guidelines had recommended a goal of less than 130/80 mm Hg for patients with diabetes, chronic kidney disease, and coronary artery disease. Evidence to support this lower target in patients with these conditions is lacking, so the goal of less than 140/90 mm Hg generally should be used, although some experts still recommend a BP goal of less than 130/80 mm Hg if albuminuria is present with chronic kidney disease.

Guidelines from JNC 8,¹⁸ ADA,¹ and ASH²⁰ recommend a treatment goal of less than 140/90 mm Hg. AACE/ACE² recommends a treatment goal of less than 130/80 mm Hg and SPRINT¹⁹ demonstrated that a systolic BP goal of less than 120 mm Hg reduced the occurrence of cardiovascular events. All groups mention the importance of reaching BP targets safely without adverse effects.

Recommendation: Lifestyle treatment should be initiated in patients with diabetes if their BP is greater than 120/80 mm Hg. Pharmacologic treatment (usually 2 drugs) is recommended to keep BP below 140/90 mm Hg. In some patients, pharmacologic treatment may be appropriate to keep the BP below 130/80 mm Hg. Once a patient reaches age 80 years, the target BP may change to below 150/90 mm Hg.

Stay tuned for future recommendations from these different expert organizations.

Edward J. Shahady, MD, ABCL, is a clinical professor of family medicine at the University of Florida and the University of Miami and is president and medical director of the Diabetes Master Clinician Program in Fernandina Beach, Florida.

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