Why Following the ADA Standards of Care for Laboratory Testing Makes a Difference

Fonseca, Vivian, MD
Professor of Medicine and Pharmacology
Tullis Tulane Alumni Chair in Diabetes
Chief, Section of Endocrinology
Tulane University Health Sciences Center
New Orleans, LA Also by this Author 

The growing prevalence of diabetes in the United States is a significant public health concern. Over the last thirty years the number of U.S. adults aged 18 years or older diagnosed with diabetes has more than tripled - from 5.5 million to 19.6 million – with prevalence increasing from 2.5% to 6.9%.1

Achieving glycemic control is a critical component of diabetes care and an important factor in reducing the microvascular complications in diabetic patients.2 Dr. Vivian Fonseca, Chief, Section of Endocrinology, Tulane University Health Sciences Center, discusses the current American Diabetic Association (ADA) recommendations for monitoring glycemic control, in particular testing for Hemoglobin A1C (A1C).

The Rationale for Monitoring A1C

“A1C is recognized as the single most important measure of glycemic control,” says Dr. Fonseca. “The reason for this is that there is a very close relationship between A1C and long-term microvascular complications, as demonstrated by many epidemiological studies and clinical trials. If you lower A1C you can more or less predict the reduction in the risk of long-term microvascular complications.”2-6

ADA Recommendations - Frequency of Monitoring

The ‘ADA Standards of Medical Care in Diabetes – 2014’ recommends measuring A1C at least twice a year in patients who are meeting their treatment goals and have stable glycemic control. Since A1C reflects glycemic control over the previous two to three months there is also a recommendation to test quarterly in patients whose therapy has changed or who are not meeting glycemic goals to help determine whether a patient’s glycemic targets are being reached and maintained.2, 3

Glycemic Goals

Lowering A1C to below or around 7% has been shown to reduce microvascular complications of diabetes and, if implemented soon after the diagnosis of diabetes, is associated with long-term reduction in macrovascular disease. The ADA therefore recommends an A1C level of <7% as a reasonable goal for many nonpregnant adults.  More stringent A1C goals (such as <6.5%) may be appropriate for selected individual patients, if this can be achieved without significant hypoglycemia or other adverse effects of treatment.  Patients in this category might include those with short duration of diabetes, long life expectancy, and no significant cardiovascular disease (CVD). Less stringent A1C goals (such as <8%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions, and those with longstanding diabetes in whom the general goal is difficult to attain despite diabetes self-management education, appropriate glucose monitoring, and effective doses of multiple glucose lowering agents including insulin.2

Limitations of the A1C Test

“It is also important to be aware of the situations when A1C measurement has limitations,” notes Dr Fonseca. “A1C is problematic in people who have anemia, kidney disease, certain hemoglobinopathies, or have received recent blood transfusions. Also, in certain people there are sometimes discrepancies between A1C and their mean blood glucose. We don't fully understand the reason for that or its impact but believe it may partly be genetically determined. In African-Americans, for example, the A1C tends to read a little bit higher than the average glucose. The ADA and others have not recommended against using A1C in these patient groups, but advise extreme caution when doing so.”

The ADA recommends that for patients prone to glycemic variability, glycemic control is best judged by the combination of self-monitoring of blood glucose (SMBG) testing and A1C. For patients in whom A1C and measured blood glucose appear discrepant, physicians are advised to consider more frequent and/or different timing of SMBG or the use of continuous glucose monitoring.

“In people where you cannot use A1C, there are alternative methods, like measuring fructosamine,” continues Dr. Fonseca, “but their relationship to average glucose and their significance are not as clear as with A1C. In some countries glycated albumin is used, but that is not widely available as a test in the U.S.  You can also use frequent blood glucose monitoring, or continuous glucose monitoring, and there are other tests that are available which are not very widely used, like 1,5-AG.”

Other Laboratory Testing

There is other testing to monitor patients and risk for complications. Cardiovascular disease (CVD) is the major cause of morbidity and mortality for individuals with diabetes, and the largest contributor to the direct and indirect costs of diabetes.2

“For this reason it’s particularly important to measure the lipid profile at least once a year in most patients,” says Dr. Fonseca. “Following changes in therapy, testing may be more frequent and then will revert to once a year once the patient is stable. In adults with low-risk lipid values the ADA indicates lipid assessments may be repeated every two years.”

Another laboratory test to perform is for urine microalbumin. The ADA recommends performing an annual test to quantitate urine albumin excretion in type 1 diabetic patients with diabetes duration of 5 years or more, and in all type 2 diabetic patients starting at diagnosis. Continued monitoring of urine albumin excretion to assess both response to therapy and progression of disease is considered “reasonable” though Dr. Fonseca points out that there is debate about the role of microalbumin testing in people who are already on renin-angiotensin system (RAS) blockers. “Since there is no additional therapy other than good blood pressure control to lower proteinuria there is a case to be made that once somebody is on treatment, you don't need to be testing it regularly.”

The ADA also recommends that serum creatinine should be measured at least annually for the estimated glomerular filtration rate (eGFR) in all adults with diabetes regardless of the degree of urine albumin excretion. “In a patient who is stable and has a good eGFR, monitoring eGFR once a year is adequate, but in others you may need to test more often,” notes Dr. Fonseca. “This is certainly the case in people who have impaired renal function. You need to check these patients at almost every visit, because they may deteriorate quite rapidly. There are also recommendations against using metformin, SGLT2 inhibitors, and other drug therapies, as well as for changing the dose of DPP-4 inhibitors, as eGFR falls.”

Increased Adherence, Reduced Complications

Dr. Fonseca notes that the inclusion of A1C as a quality measure by Centers for Medicare & Medicaid Services(CMS) has had an impact on physician practice, leading to greater compliance in performing the test. “This has really been prompted by the recognition that regular monitoring of A1C improves outcomes. This is demonstrated by the reduction in complications due to diabetes as levels of A1C have declined. A recent paper in the New England Journal of Medicine shows that there was a reduction in lower-extremity amputation, end-stage renal disease, acute myocardial infarction, stroke, and death from hyperglycemic crisis between 1990 and 2010.7 Additionally we’ve seen the average level of A1C decline in the US: from 1988-1994 to 2003-2006 the mean A1C in adults declined from 7.7 to 7.2 and the 75th percentile dropped from 9.0 to 7.8.8 So we’re seeing a significant drop and you can’t achieve that without effective monitoring.”

 

References

  1. Centers for Disease Control and Prevention. Diabetes Public Health Resource.  http://www.cdc.gov/diabetes/statistics/prevalence_national.htm Accessed November 20, 2014
  2. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care 2014;37(suppl 1)S14-S80
  3. Sacks DB, Arnold M, Bakris GL, et al. National Academy of Clinical Biochemistry. Position statement executive summary: guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Diabetes Care 2011;34:1419–1423
  4. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–986
  5. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Engl JMed 2000;342:381–389
  6. Martin CL, Albers J, Herman WH, et al for the DCCT/EDIC Research Group. Neuropathy among the diabetes control and complications trial cohort 8 years after trial completion. Diabetes Care 2006;29:340–344
  7. Edward WG, Li Y, Wang J, at al. Changes in Diabetes-Related Complications in the United States, 1990–2010. N Engl J Med 2014; 370:1514-1523
  8. Centers for Disease Control and Prevention. Mean/Median A1c Among Adults with Diagnosed Diabetes, United States, 1988–1994 to 1999–2006 http://www.cdc.gov/diabetes/statistics/a1c/a1c_mean_median.htm  Accessed November 20, 2014