American Diabetes Association 60th Scientific Sessions, 2000: glucose tolerance, diabetes and cancer, glycemic control, monitoring, and related topics.

Postload Glycemia in the Diagnosis of Diabetes At a symposium on diagnostic criteria for diabetes James Gavin, Chevy Chase, MD, discussed the dilemma that fasting and post–glucose load glucose levels are differently regulated and that diagnosis based on the two criteria therefore define somewhat different populations. The use of fasting glucose has several advantages. It is more convenient to perform and limits a missed diagnosis of diabetes. Gavin noted that microvascular complications begin to occur above a fasting glucose of 126 mg/dl. A concern, however, is that more than half of patients with diabetes diagnosed by a glucose tolerance test have a fasting glucose below 126 mg/dl. Given new data showing that the fasting glucose level is less predictive of cardiovascular disease (CVD) risk than postchallenge glucose level, Gavin concluded that “fundamentally, we are back at ‘square one’ in asking ‘What is diabetes?’” Daniel Porte, San Diego, CA, noted that “cause and effect is not necessary when we see associations,” an important caveat in the new emphasis on glucose tolerance testing and postchallenge glycemia for diabetes diagnosis. Jaakko Tuomilehto, Helsinki, Finland, reviewed data from the Diabetes Epidemiology Collaborative Analysis of Diagnostic Criteria in Europe (DECODE) Study of 18,048 men and 7,316 women aged 30 years or older followed for an average of 7 years after glucose tolerance testing, addressing the question of whether fasting glucose or 2-h postload glucose better predicts mortality (1) There were a total of 1,836 deaths. The World Health Organization (WHO) criteria for diabetes, based mainly on 2-h glucose .200 mg/dl, and the ADA criteria, based on fasting glucose .126 mg/dl, were shown to convey a similar (1.85-fold and 1.75-fold) increase in risk among men; but among women, the WHO criteria for diabetes conveyed a 2.43-fold increase, compared with the 1.77-fold increase with the ADA criteria. Adjusting the fasting for the 2-h glucose greatly decreased the significance of the increase in mortality risk, whereas adjusting the 2-h for the fasting glucose had little such influence. In all fasting glucose categories (normal, impaired fasting glucose [IFG], and diabetes), mortality increased with increasing 2-h glucose, but in the 2-h categories (normal, impaired glucose tolerance [IGT], and diabetes), there was little increase in risk as the fasting glucose level increased. No threshold was seen for increasing mortality with increasing 2-h glucose, whereas for fasting glucose the threshold was ;126 mg/dl. Finally, Tuomilehto pointed out that the greatest number of excess deaths occurred in the large group of individuals with normal fasting glucose and IGT determined on the basis of postload glucose. David Nathan, Boston, MA, stressed the need to clarify the association between hyperglycemia and risk of complications, listing three questions: What is the correct glycemic threshold for diagnosis of diabetes? Do glucose levels in the subdiabetic range impart risk for diabetes? And is there therapeutic value in identifying patients in this glucose range? Most diabetes occurs in the setting of aging. HbA1c levels increase with age, even in patients with neither diabetes nor IGT. For diabetesspecific complications, risk increases with glucose above a threshold defined by HbA1c ;6.0%. The DECODE data shows, however, that subdiabetic degrees of glycemia increase the risk of CVD. Similarly, in the Framingham Offspring Study, individuals without diabetes showed an increase in CVD risk with increasing levels of HbA1c (2). The important question Nathan raised is whether it is glucose per se that increases the risk of CVD in this population. In the Framingham study, there is a direct and continuous relationship between blood glucose and blood pressure, triglyceride, low HDL, and a variety of other risk factors in patients without diabetes. Thus, it may be overly simplistic to conceptualize individuals as either having normal glucose tolerance or IGT. Similarly, glycemic treatment may or may not be relevant to CVD risk reduction in this population. The Diabetes Prevention Program (DPP) is studying patients in the “upper half” of IGT, allowing the potential to identify patients before the onset of disease and to prevent CVD complications. Nathan acknowledged that CVD risk factor treatment is being recommended for all patients in the DPP, including those in the control group. Thus, it may not be possible to learn from this study what are the essential characteristics of the increase in CVD risk in patients ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●