Perspective

Experts push for change in fasting guidelines for lipid testing

Routine lipid testing conducted in a nonfasting state offers a number of advantages for patients and providers and may offer a better prediction for cardiometabolic risk vs. tests conducted in a fasted state, experts argue.

In the United States, blood samples obtained for lipid testing after fasting 8 to 12 hours is a standard of care for the measurement of triglycerides and cholesterol, with published recommendations on the practice dating back to the 1970s. However, experts are challenging accepted guidelines, arguing that lipid tests conducted in a nonfasted state could potentially be safer and more cost-effective.

“Fasting samples have been the standard for measurement of triglycerides and cholesterol because measuring lipids in the fasting state is believed to reduce variability and allow for a more accurate derivation of the commonly used Friedewald-calculated LDL cholesterol,” Samia Mora, MD, MHS, associate professor at Harvard Medical School and cardiologist and director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital, Boston, wrote in a commentary published in JAMA Internal Medicine.

“However, if postprandial effects do not substantially alter lipid levels or their association with cardiovascular risk, then a nonfasting blood draw has many practical advantages.”

Recent studies, Mora said, suggest that the postprandial effects that result from testing in a nonfasting state may even strengthen the risk association between lipids and CVD, providing a more complete picture for health care providers.

“There were really small studies that reported that the Friedewald equation estimate for LDL cholesterol may potentially be different if the triglycerides were measured fasting vs. nonfasting,” Mora told Endocrine Today. “But when we looked at all the literature and the totality of the evidence, that difference is quite small and, in fact, the LDL cholesterol or even non-HDL cholesterol, when it is measured nonfasting, is an even better predictor for risk than fasting because we’re identifying individuals with metabolic syndrome, prediabetes or diabetes.

Samia Mora

“Even if you had an abnormality metabolizing the triglycerides, if you fast for 12 hours, by that time you catch up with the metabolism and process the triglyceride-rich particles fine,” Mora said. “But if [the test] is done nonfasting, you’re not giving the body an extended period to recover. It’s like getting a stress test. This is the active evaluation of someone’s ability to metabolize triglycerides.”

Fasting risks

For a patient with a metabolic condition, such as diabetes, the requirement of an 8- to 12-hour fast is not just inconvenient. For these patients, skipping meals while on insulin therapy or other antidiabetes medications, such as sulfonylureas, without proper guidance can put the patient at risk for serious adverse events, such as hypoglycemia, according to Saleh Aldasouqi, MD, FACE, ECNU, associate professor of medicine and chief of endocrinology at Michigan State University College of Human Medicine.

“There is a large body of evidence now that shows there is no need for fasting, for the most part,” Aldasouqi told Endocrine Today. “It’s not only unnecessary, but in patients with diabetes, it is potentially dangerous.”

Aldasouqi said he observed the risks for fasting-induced hypoglycemia firsthand at his rural endocrinology practice in Cape Girardeau, Missouri, in 2009, where some patients with diabetes drove as far as 100 miles for appointments. Patients who fasted overnight and missed breakfast but did not alter their medication schedule sometimes experienced hypoglycemia, discovered by the lab only after the patient had left.

Aldasouqi and colleagues undertook a retrospective study, published in Diabetes Care. During a 21-month period, researchers identified 55 of patients with hypoglycemia at his laboratory between 8 a.m. and noon. The laboratory did not record fasting-status patients, but chart review and telephone interviews revealed 39 of the 55 patients were taking antidiabetes medications; 15 recalled fasting for their blood test; 20 were uncertain of fasting status; four recalled not fasting. Among patients who recalled fasting or possible fasting, 23 had a blood glucose level of less than 60 mg/dL; 11 less than 50 mg/dL; six less than 40 mg/dL. No patients recalled making adjustments to their antidiabetes medications before the test, Aldasouqi said.

A preventive program implemented at the practice, dubbed the Cape Girardeau Hypoglycemia Prevention Program, resulted in a reduction of critical hypoglycemia by 88%, Aldasouqi said. He is now working to implement the program at other institutions. Aldasouqi and colleagues coined the term Fasting-Evoked Enroute Hypoglycemia in Diabetes (FEEHD) to refer to this iatrogenic form of hypoglycemia.

Saleh Aldasouqi

“In addition to eliminating fasting for lab tests, the preventive program consisted of proper education of patients to adjust antidiabetic medications and to monitor glucose more closely while fasting,” Aldasouqi and colleagues, wrote in Postgraduate Medicine.

A gradual shift

Internationally, recommendations for lipid testing requirements have evolved. In April, the European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine published a joint consensus statement that called for nonfasting lipid profiles to be used for most patients, in part to improve patient compliance.

“Fasting can be a barrier to population screening, is unpopular with children, is often unsuitable for patients with diabetes, and counters the use of point-of-care testing; and fasting requirements can add to the overall costs of lipid testing,” the researchers wrote. “Nonfasting tests are also used to assess other metabolic disorders, such as [HbA1c] in diabetes. The collective sources of evidence reviewed ... led to the notion that fasting samples are not essential for evaluation of [CV] risk.”

Other groups have also called for changes. In a revision to previous recommendations, Hypertension Canada’s 2016 Canadian hypertension education program guideline for blood pressure measurement, diagnosis, assessment of risk, prevention and treatment of hypertension noted that fasting and nonfasting collections are now considered acceptable for a serum lipid profile. In 2014, the National Clinical Guideline Centre and Joint British Societies’ guideline stated that a fasting sample was not needed. The Danish Society of Clinical Biochemistry has recommended since 2009 that routine lipid profiles be measured in a nonfasting state.

However, the 2013 American College of Cardiology/American Heart Association guideline still prefers, but does not mandate, a fasting sample for lipid testing.

There are limitations to the available evidence in favor of nonfasting, Mora said. Although prospective studies point to nonfasting lipid measurements as similar or better for predicting CVD risk in populations, there are no published studies comparing fasting and nonfasting measurements in the same patients for predicting CVD risk, and no randomized controlled trials or cost-effectiveness analyses have been conducted.

“The major advantage is for the patient, especially since nonfasting is better for predicting risk,” Mora said. “We spend most of our day nonfasting, so when the patient comes to their health care provider, [with a fasting requirement] they have to come back a second time, and that requires the physician to follow-up on those tests. That is really cumbersome when you have a busy practice. Patients with diabetes or a problem fasting, like children or the elderly, [with nonfasting] they can come in once and get their blood test. For the labs, they can avoid an influx of people [who fasted overnight] at 8 a.m.”

Aldasouqi and Mora are working together to convene a multidisciplinary expert panel from the United States to form a consensus statement on the topic within 1 year.

“We’re trying to change 40 or 50 years of tradition that is deeply rooted, and you know how that goes in medicine,” Aldasouqi said. “When people see two statements — one from the U.S. and one from Europe — hopefully the change can begin.” – by Regina Schaffer

Disclosure: Aldasouqi reports receiving honoraria from Janssen and Sanofi. Mora reports serving as a consultant to Amgen, Cerenis Therapeutics, Lilly, Pfizer and Quest.

Routine lipid testing conducted in a nonfasting state offers a number of advantages for patients and providers and may offer a better prediction for cardiometabolic risk vs. tests conducted in a fasted state, experts argue.

In the United States, blood samples obtained for lipid testing after fasting 8 to 12 hours is a standard of care for the measurement of triglycerides and cholesterol, with published recommendations on the practice dating back to the 1970s. However, experts are challenging accepted guidelines, arguing that lipid tests conducted in a nonfasted state could potentially be safer and more cost-effective.

“Fasting samples have been the standard for measurement of triglycerides and cholesterol because measuring lipids in the fasting state is believed to reduce variability and allow for a more accurate derivation of the commonly used Friedewald-calculated LDL cholesterol,” Samia Mora, MD, MHS, associate professor at Harvard Medical School and cardiologist and director of the Center for Lipid Metabolomics at Brigham and Women’s Hospital, Boston, wrote in a commentary published in JAMA Internal Medicine.

“However, if postprandial effects do not substantially alter lipid levels or their association with cardiovascular risk, then a nonfasting blood draw has many practical advantages.”

Recent studies, Mora said, suggest that the postprandial effects that result from testing in a nonfasting state may even strengthen the risk association between lipids and CVD, providing a more complete picture for health care providers.

“There were really small studies that reported that the Friedewald equation estimate for LDL cholesterol may potentially be different if the triglycerides were measured fasting vs. nonfasting,” Mora told Endocrine Today. “But when we looked at all the literature and the totality of the evidence, that difference is quite small and, in fact, the LDL cholesterol or even non-HDL cholesterol, when it is measured nonfasting, is an even better predictor for risk than fasting because we’re identifying individuals with metabolic syndrome, prediabetes or diabetes.

Samia Mora

“Even if you had an abnormality metabolizing the triglycerides, if you fast for 12 hours, by that time you catch up with the metabolism and process the triglyceride-rich particles fine,” Mora said. “But if [the test] is done nonfasting, you’re not giving the body an extended period to recover. It’s like getting a stress test. This is the active evaluation of someone’s ability to metabolize triglycerides.”

Fasting risks

For a patient with a metabolic condition, such as diabetes, the requirement of an 8- to 12-hour fast is not just inconvenient. For these patients, skipping meals while on insulin therapy or other antidiabetes medications, such as sulfonylureas, without proper guidance can put the patient at risk for serious adverse events, such as hypoglycemia, according to Saleh Aldasouqi, MD, FACE, ECNU, associate professor of medicine and chief of endocrinology at Michigan State University College of Human Medicine.

“There is a large body of evidence now that shows there is no need for fasting, for the most part,” Aldasouqi told Endocrine Today. “It’s not only unnecessary, but in patients with diabetes, it is potentially dangerous.”

Aldasouqi said he observed the risks for fasting-induced hypoglycemia firsthand at his rural endocrinology practice in Cape Girardeau, Missouri, in 2009, where some patients with diabetes drove as far as 100 miles for appointments. Patients who fasted overnight and missed breakfast but did not alter their medication schedule sometimes experienced hypoglycemia, discovered by the lab only after the patient had left.

Aldasouqi and colleagues undertook a retrospective study, published in Diabetes Care. During a 21-month period, researchers identified 55 of patients with hypoglycemia at his laboratory between 8 a.m. and noon. The laboratory did not record fasting-status patients, but chart review and telephone interviews revealed 39 of the 55 patients were taking antidiabetes medications; 15 recalled fasting for their blood test; 20 were uncertain of fasting status; four recalled not fasting. Among patients who recalled fasting or possible fasting, 23 had a blood glucose level of less than 60 mg/dL; 11 less than 50 mg/dL; six less than 40 mg/dL. No patients recalled making adjustments to their antidiabetes medications before the test, Aldasouqi said.

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A preventive program implemented at the practice, dubbed the Cape Girardeau Hypoglycemia Prevention Program, resulted in a reduction of critical hypoglycemia by 88%, Aldasouqi said. He is now working to implement the program at other institutions. Aldasouqi and colleagues coined the term Fasting-Evoked Enroute Hypoglycemia in Diabetes (FEEHD) to refer to this iatrogenic form of hypoglycemia.

Saleh Aldasouqi

“In addition to eliminating fasting for lab tests, the preventive program consisted of proper education of patients to adjust antidiabetic medications and to monitor glucose more closely while fasting,” Aldasouqi and colleagues, wrote in Postgraduate Medicine.

A gradual shift

Internationally, recommendations for lipid testing requirements have evolved. In April, the European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine published a joint consensus statement that called for nonfasting lipid profiles to be used for most patients, in part to improve patient compliance.

“Fasting can be a barrier to population screening, is unpopular with children, is often unsuitable for patients with diabetes, and counters the use of point-of-care testing; and fasting requirements can add to the overall costs of lipid testing,” the researchers wrote. “Nonfasting tests are also used to assess other metabolic disorders, such as [HbA1c] in diabetes. The collective sources of evidence reviewed ... led to the notion that fasting samples are not essential for evaluation of [CV] risk.”

Other groups have also called for changes. In a revision to previous recommendations, Hypertension Canada’s 2016 Canadian hypertension education program guideline for blood pressure measurement, diagnosis, assessment of risk, prevention and treatment of hypertension noted that fasting and nonfasting collections are now considered acceptable for a serum lipid profile. In 2014, the National Clinical Guideline Centre and Joint British Societies’ guideline stated that a fasting sample was not needed. The Danish Society of Clinical Biochemistry has recommended since 2009 that routine lipid profiles be measured in a nonfasting state.

However, the 2013 American College of Cardiology/American Heart Association guideline still prefers, but does not mandate, a fasting sample for lipid testing.

There are limitations to the available evidence in favor of nonfasting, Mora said. Although prospective studies point to nonfasting lipid measurements as similar or better for predicting CVD risk in populations, there are no published studies comparing fasting and nonfasting measurements in the same patients for predicting CVD risk, and no randomized controlled trials or cost-effectiveness analyses have been conducted.

“The major advantage is for the patient, especially since nonfasting is better for predicting risk,” Mora said. “We spend most of our day nonfasting, so when the patient comes to their health care provider, [with a fasting requirement] they have to come back a second time, and that requires the physician to follow-up on those tests. That is really cumbersome when you have a busy practice. Patients with diabetes or a problem fasting, like children or the elderly, [with nonfasting] they can come in once and get their blood test. For the labs, they can avoid an influx of people [who fasted overnight] at 8 a.m.”

Aldasouqi and Mora are working together to convene a multidisciplinary expert panel from the United States to form a consensus statement on the topic within 1 year.

“We’re trying to change 40 or 50 years of tradition that is deeply rooted, and you know how that goes in medicine,” Aldasouqi said. “When people see two statements — one from the U.S. and one from Europe — hopefully the change can begin.” – by Regina Schaffer

Disclosure: Aldasouqi reports receiving honoraria from Janssen and Sanofi. Mora reports serving as a consultant to Amgen, Cerenis Therapeutics, Lilly, Pfizer and Quest.

    Perspective
    Robert Eckel

    Robert Eckel

    Recent analyses have provided convincing evidence that, in men and women, fasting vs. non-fasting LDL cholesterol values provide equal predictability for all-cause mortality and CVD mortality, and support has grown for lipid testing conducted in a fed state in recent years. This change could offer practical advantages for patients, especially those with diabetes prescribed insulin, sulfonylureas and/or glinides, which can cause hypoglycemia.

    Questions remain, however, regarding how to interpret fasting vs. non-fasting triglyceride levels and their relationship to atherosclerotic CVD risk, and this opens the door to other important considerations. Would fasting vs. non-fasting values for non-HDL cholesterol or even apolipoprotein B be equally predictive of either all-cause or CVD mortality? Would fasting vs. non-fasting LDL cholesterol affect other CVD events differently?

    Currently, the 2013 ACC/AHA Cholesterol Guideline states that a fasting lipid panel is preferred and should be implemented in a manner consistent with previous lipid recommendations (after a 12-hour fast).

    The bottom line is that current U.S. guidelines are based on fasting values, not randomly obtained samples, and in patients with triglyceride levels of at least 400 mg/dL, the LDL cholesterol cannot be accurately calculated. Unless and until that changes, the 12-hour fast recommendation should remain.

    • Robert Eckel, MD
    • Professor of Medicine

    Disclosures: Eckel reports no relevant financial disclosures.