Volume 1 number 1 Summer 2003
Special issue for the abstracts of the 7th Pan Arab Conference on Diabetes
PACD7 , 25 – 28 March 2003 Cairo

Abstract Number : 39
POST-CHALLENGE BLOOD GLUCOSE AS AN INDEPENDENT INDICATOR IN CARDIOVASCULAR DISEASE

Jaakko Tuomilehto, MD, MPolSc, PhD; Academy Professor
Department of Public Health, University of Helsinki and
Diabetes and Genetic Epidemiology Unit, National Public Health Institute,
Helsinki Finland

One of the biggest obstacles in implementing efficient control of hyperglycaemia is that the diagnosis of diabetes is usually done at a late stage, only after symptoms occur. However, it is known that at the beginning of the symptomatic stage hyperglycaemia has already existed for more than 10 years. Epidemiological studies have repeatedly shown that for every 10 known Type 2 diabetic patients there are another 8-10 other undiagnosed diabetic subjects in the population. Some of them can be identified by screening for fasting glucose, but most of them would remain undiagnosed if people are not tested for with an oral glucose tolerance test (OGTT) or postprandially. While the prevalence of symptomatic diabetes and elevated 2-hour glucose after the OGTT steeply increase with age, fasting glucose level does not. Therefore, especially in elderly people age 2-hour glucose is much more sensitive test than fasting glucose to detect hyperglycaemia. Actually, in the DECODE study in people aged 70 years or more the prevalence of undiagnosed diabetes was 11.1%, of whom 2.3% has isolated fasting hyperglycaemia, 4.6% isolated post-challenge hyperglycaemia and 4.2% both.

Whether 2-hour or fasting glucose is a continuous risk factor for mortality from all-cause and from cardiovascular diseases (CVD) was investigated in the DECODE study data from 11 studies in Europe. 22,476 subjects aged 30-89 years and not known as diabetic were followed up on average 12 years, a total 262,811-person year and 3,792 deaths accumulated. Cox’s proportional hazards regression analyses show that the relative risk (RR) adjusted for age, sex, centres and other CVD risk factors, corresponding to a one standard deviation increase in fasting glucose concentration, was 1.10 (95%CI 1.07-1.13), 1.08 (1.03-1.13) and 1.10 (1.06-1.14), respectively, for deaths from all-causes, CVD and non-CVD causes. For one standard deviation increase in 2-hour glucose, the RRs were 1.17 (1.14-1.21), 1.15 (1.10-1.20) and 1.16 (1.12-1.20), respectively. When further adjusting for 2-hour glucose, the RRs for fasting glucose reduced and became statistically non-significantly, 1.00 (0.96-1.03) for all-cause, 0.99 (0.93-1.05) for CVD and 1.00 (0.96-1.05) for non-CVD mortality. In contrast, the RRs for 2-hour glucose did not change at all after simultaneous adjusting for fasting glucose, being 1.16 (1.12-1.20), 1.16 (1.09-1.23) and 1.16 (1.10-1.21), respectively. 

Thus, the association between fasting glucose and mortality largely depended on the 2-hour glucose levels, 2-hour glucose concentration was an independent and continuous risk predictor for mortality. The data underscore the significance of mealtime glucose excursions that result from the body’s inability to produce an early insulin response after a meal. The acute toxicity of glucose spikes, as measured by 2h-BG levels, is an independent risk factor for cardiovascular disease and mortality and a better predictor than FPG as seen in the previously published research from the European DECODE study group. Cardiovascular disease is a serious complication, causing a large proportion of deaths in people with type 2 diabetes. The new data from the DECODE study also demonstrate that two-hour blood glucose is a better predictor of mortality than HbA1c, both for all cause and cardiovascular mortality.

Postprandial hyperglycaemia is implicated in the increased production of free radicals through the glycation of amino acids. This is a labile and non-enzymatic process that leads to the exacerbation of oxidative stress -- a known pathogenic factor in diabetic complications. Evidence from recent studies shows that damage to the endothelium of blood vessels resulting from Postprandial hyperglycaemia may be caused through a number of mechanisms, including protein kinase C activation, increased expression of adhesion molecules, increased production of endothelin, and the increased secretion of collagen and fibronectin. These cellular events are all implicated in the atherogenic process. It is however not known whether the reduction of high Postprandial glucose will lead to a decrease in mortality. Non-pharmacologic lifestyle interventions and new pharmacologic agents available today can effectively correct post-prandial hyperglycaemia. This opens a new era of management of diabetes and will hopefully improve the prognosis of many patients who suffer from postprandial hyperglycaemia. 

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