Part 44: Arbitrarily Lowering Blood Glucose Cutoff Points: Was That the Right Thing to Do?

The management of type 2 diabetes (T2D) has markedly improved over the past three decades. Nevertheless, none of the currently available methodologies, including the use of multiple insulin regimens, continuous glucose monitoring, insulin pumps, or the artificial pancreas, etc., are capable of addressing the underlying root causes of T2D or favorably modify the natural course of the disease. Currently marketed anti-diabetic medications are designed primarily to control blood sugar and the severity of the disease.  They are not designed to cure the disease.

Reduction of the cutoff limit for diagnosing diabetes:

In 2003, the American Diabetes Association (ADA) recommended the lowering of the diagnostic threshold for impaired fasting glucose (IFG) to 100 mg/dL (5.6 mmol/L), from, 120 mg/dL. The World Health Organization (WHO) and the ADA used different cutoff values for IFG (WHO: 6.1–6.9 mmol/L; ADA: 5.6–6.9 mmol/L).  This was not based on clinical outcomes, prevalence or complications associated with diabetes but hypothetically.  It assumed that new lower threshold would be able to identify a proportion of people with IFG and impaired glucose tolerance (IGT) more effectively, for which aggressive therapy might prevent progression of prediabetes to diabetes.

The ADA defined IFG as the metabolic stage that is intermediate between the upper limit of normal fasting plasma glucose (FPG) and the lower limit of having diabetic FPG (129). Data from the Pima Indians reported that the risk of diabetes increased with FPG concentrations greater than 5.6 mmol/L.  Despite not having advantage nor the cost–benefit ratio of this drastic reduction of the blood glucose cutoff point, because it was introduced and mandated by leading scientific bodies, it was universally accepted as the standard of care .

Changing diagnostic criteria created millions of people with diabetes, overnight:

Globally, the lowering of the upper limits of fasting blood sugar from 120 to 100 mg/dL, immediately added otherwise healthy, millions of persons (healthy people were labelled ) having diabetes. This forced physicians to follow the new guidelines and start prescribing anti-diabetic medications to this vast number of people and also creating an apparent epidemic of type 2 diabetes (T2D).  These people had to spend extra billions of dollars (or in their local currencies) and had to start taking new medications and undergo otherwise unnecessary investigations.  

Ironically, before the new cutoff limit was imposed, these people were considered healthy. Moreover, with a label of diabetes, they are now subjected to health insurance restrictions and prejudiced in job interviews.  Implemented properly in people with disorders, new technologies are very useful.  However, not for those who do not need such treatment. For them, it is a wastage of resources and subjecting them to unnecessary risks, including adverse drug reactions.

In 1996, the IFG category [levels between ≥ 110 and < 126 mg/dL (6.1 and 6.9 mmol/L)] was introduced and adopted by WHO in 1998.  The rationale for this change/reduction was that the IFG simulates the plasma glucose results following 75 g oral glucose-load, the IGT test.  However, no convincing socioeconomic or cost–benefit analyses have reported to-date, on positive results from this drastic change.  Thus, in the absence of valid and reproducible scientific data, the change—the reduction of plasma glucose cut-off limits—can be considered hypothetical.

Little or no scientific evidence supporting the alleged benefits from lowering plasma glucose cut-off points: 

Supporting the above viewpoint, in 2003 the editor of Diabetes Care—the journal in which most of the key papers related to lowering FPG concentration were published—issued the following critical statement:

"Because of the controversial nature of the new lowered criterion for IFG, I offered the Chairman of the Expert Committee an opportunity to respond to my commentary on the subject.  I would only point out that Dr. Genuth’s reference #8 shows an association between glycemia and cardiovascular disease, as have many other reports, but to date, five prospective studies, analyzed either singly or as a metanalysis, have been unable to demonstrate a beneficial effect of lowering glycemia on cardiovascular disease outcomes."

The Paris Prospective Study by Charles et al. was the first to use the terminology of IFG and the new cutoff point.  At that time the threshold for fasting blood sugar was of 140 mg/dL (7.8 mmol/L) and the non-diabetic fasting glucose levels were comparable to IGT in predicting the incidence of diabetes. To equalize the comparison with IGT, Charles et al. chose a fasting glucose cutoff point that would include an equal number of individuals in the new fasting category as was included in the IGT category.

It is noteworthy that reducing the diagnostic threshold standards by lowering IFG from 6.1 mmol/L to 5.6 mmol/L markedly increased the prevalence of IFG (those people now categorized as having prediabetes or diabetes) by two- to five-fold increase, globally. Millions of otherwise healthy people are now included in this category and are subjected to testing and treatments with antidiabetic medications.  This has had a major impact on individuals and families and the cost of the healthcare systems, worldwide.

Is impaired fasting glucose a disease?

Impaired fasting glucose is not a clinical disease but simply created as an entity to indicate that he or a she might have a higher risk for developing diabetes in the future.  However, the identification and use of this definition is useful only if its predictive value is accurate, and have minimal false-negative and false-positive diagnoses (i.e., the cost of failure to predict and those of not predicting a diagnosis of diabetes are very low).  But this is not always the case.  In addition, there are other caveats, such as ethnic and racial differences, genetic and environmental predisposition, etc., in the rate of progression or non-progression of the disease.

Considering these, creating non-existing ‘disorders,’ such as “borderline diabetes—like  IFG, are in fact, is misleading and thus, are not applicable universally, especially for non-Caucasians.  For example, most persons of south Asia origin with type 2 diabetes do not fit into the western 'classification' of classic, obese T2D, neither they uniformly have higher Body Mass Index (BMI).  In fact, the majority of Asian with T2D have normal BMI—they are not obese or have insulin deficiency but are predominantly insulin resistant.

Summary: The current trend in anti-diabetes treatment is to continually intensify therapies, with the goal of lowering hemoglobin-A1c (HbA1c) to arbitrary lower levels together with keeping blood glucose levels close to harmfully low levels.  Contrary to this, what is beneficial for persons with diabetes is to de-intensifying the treatment schedules and minimize medication-associated complications particularly, hypoglycemic episodes, while improving adherence to therapy and beneficial lifestyle changes, and preventing longer-term complications.  The best attitude is to take the “middle” approach to the therapy for the benefit of patients.  This is “patient-centered” medicine.

The next article discusses the effects of lowering blood glucose cut-off levels and explore the question, should the anti-diabetes treatment should be escalate or de-escalate.

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Professor Sunil J. Wimalawansa, MD, PhD, MBA, DSc, is a physician-scientist, educator, social entrepreneur, and process consultant. He is a philanthropist with experience in long-term strategic planning, and cost-effective investment and interventions globally for preventing non-communicable diseases [recent charitable work]. The author has no conflicts of interest and received no funding for this work.