Why Isn't Postprandial Insulin Assay Being Used to Predict Diabetes Onset?

While promising, there is no way to know whether introducing lifestyle changes to patients who are diagnosed earlier will positively effect their outcomes.

With James DiNicolantonio, PharmD; Elena Christofides, MD, FACE, and Robert Lustig, MD

The current strategy for screening patients for prediabetes and diabetes—using fasting glucose, oral glucose tolerance testing (OGTT), and hemoglobin A1C—still may be missing millions of individuals with these conditions,1 according findings published in BMJ Open Heart.

Focusing only on glucose levels is too little, too late, said study author, James DiNicolantonio, PharmD, a cardiovascular research scientist at St. Luke's MidAmerica Heart Institute in Kansas City. He and three colleagues made a case for employing the postprandial insulin assay as a more efficient tool to diagnose prediabetes and diabetes sooner than the current standards.1

By the time people are diagnosed using standard glucose testing, ''these individuals likely will have lost up to 50% of their beta cells,'' Dr. DiNicolantonio told EndocrineWeb, ''When a person is diagnosed with prediabetes [using standard glucose testing], the patient will have likely lost 25% of their beta cells."

He added, ''the reason for this outcome is that we have been relying on the wrong surrogate marker: glucose. A patient can be severely ill and still have glucose levels in the normal range; by the time the patient becomes hyperglycemic, the disease had progressed significantly."

Researchers make a case for using postprandial insulin to predict diabetes sooner.

Building a Case for the Insulin Assay

Using the postprandial insulin assay, Dr. DiNicolantonio believes that clinicians may be able to diagnose the onset of decades even up to 24 years earlier.

"Two people may have normal glucose levels, but one of the patients may have severely elevated insulin levels that is keeping their serum glucose within the normal range," he said.

Actually, the concept is not new, but few endocrinologists have used the assay along with glucose testing, DiNicolantonio said, ''and it may be another 10 to 20 years before it is introduced into [practice] guidelines." This is the state of practice despite the fact that most labs have he capability to provide the test now.

The Need to Diagnose Diabetes—the Sooner, the Better

Drawing on decades of research, the researchers pointed out that hyperinsulinemia is linked with hypertension, obesity, atherosclerosis, microvascular disease, neurodegenerative disorders, idiopathic peripheral neuropathy and certain cancers.2 In addition, it is also linked with idiopathic tinnitus, vertigo and hearing loss.3

The researchers also cite studies finding that many with normal glucose tolerance tests had abnormal or borderline insulin response patterns and that insulin concentrations during glucose tolerance testing strongly predict the development of type 2 diabetes.1

The test to measure hyperinsulinemia is called by a variety of names, including the Glucose Tolerance with Insulin Assay or Glucose Tolerance Insulin Response (GTIR) test.  We believe that many patients presenting with a normal OGTT may have diabetes, which would be confirmed when assessed using the GTIR test, the researchers said

The Challenges of Adopting a New Diagnostic Approach

While two protocols are suggested for the test, the principle of both are the same. Preparation includes two weeks or more of a diet with at least 150 g of carbohydrate per day. Following an overnight fast of more than 10 hours, the patient has a 75 g OGTT with plasma glucose and insulin samples at baselines and again at 30, 60, 120 and 180 minutes.

Five patterns categorize the response:1

  • Normal: Sum of 2nd and 3rd hour insulins should be less than 60uU/mL.
  •  Borderline hyperinsulinemia or borderline insulin resistant: Sum of the 2nd and 3rd hour insulins are 60 or higher but less than 100.
  • Hyperinsulinemia: Sum of the 2nd and 3rd hour insulins are 100 or more.
  •  Hyperinsulinemia: Delayed insulin peak (2 hours or 3)
  • ·Hyperinsulinemia: Fasting insulin above 50.

Experts Temper Their Enthusiasm

Two experts were invited to review the paper and came up with similar feedback about the value of the postprandial assay. While the concept is sound, the practicality of employing this level of testing makes widespread use unlikely. As well, there is a need to be clear about what action to take in patients when insulin is found to be high.

The reasoning behind the researchers' argument, ''has been understood for decades," said Elena Christofides, MD, FACE, chief operating officer of Endocrinology Associates in Columbus, Ohio, told EndocrineWeb. However, she indicated that “while someone with elevated insulin levels may be metabolically unhealthy, we can't say why.  While insulin levels typically correlate with levels of metabolic ''unfitness," the patient may or may not be prediabetic, but there’s no way to be certain.”

Use of the Postprandial Assay Likely Premature

As such, it would be premature to suggest that every patient who presented with high insulin levels be treated as if they have diabetes and to treat to reduce the risk of cardiovascular disease and other comorbid conditions, she said.

Endocrinologists would benefit from more training so we are prepared to suggest preventive strategies to our patients once a patient presents with high insulin, said Dr. Christofides, and currently, many clinicians lacking sufficient training to counsel patients on steps that would be suitable to the individual to improve their lifestyle.

For now, she said, the test should remain in the hands of metabolic specialists who understand how to interpret the findings, and are capable of applying the findings to the individual patient.

The effort involved in the employing the test is substantial, said Robert Lustig, MD, emeritus professor of pediatrics at the University of California San Francisco.  And, he said that ''once you have identified someone with insulin resistance, it behooves you to do something about it, not just note it exists.”  The first strategy is to encourage an emphasis on foods with a low glycemic load diet—which is simply a low-sugar, high fiber diet—that may need to support weight loss, and be heart healthy, and to direct the patient to do the right activity given any other health limitations.

While the idea of testing insulin levels is sound, Dr. Lustig said: "whether it has therapeutic import, at present, is not yet clear."

Dr. DiNicolantonio is associate editor of BMJ Open Heart and Dr. Lustig is the author of the Hacking of the American Mind and Fat Chance. None of the authors declared any financial conflict.


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