It is well known that Type 2 diabetes mellitus is associated with a marked increase in CVD. Increased risk factors for CVD before the onset of Type 2 diabetes have been shown in several populations.[1
] It is not known whether the increased atherogenicity of the prediabetic state is primarily due to increased insulin resistance or impaired blood glucose.[15
It has been recognized that prediabetic hyperglycemia confers an increased risk for cardiovascular disease (CVD).[16
] In 1997, the American Diabetes Association (ADA) introduced the concept of impaired fasting glucose (IFG), a prediabetic state initially defined by fasting plasma glucose (FPG) of 110–125mg/dL, in which those afflicted were significantly more likely to develop diabetes.[18
] The risk of developing CVD was not considered in establishing criteria for IFG. Since the introduction of the concept of IFG, there has been considerable debate regarding where the lower limit should be set to achieve a reasonable balance between sensitivity and specificity for diabetes prediction. In 2003, the ADA lowered its threshold for diagnosis of IFG from 110 mg/dL to 100 mg/dL on the basis of evidence in selected samples that suggested diabetes prediction may be optimized at a lower threshold.[21
] The effect of this lowered cut point is that a much larger proportion of the population is now considered to have IFG. Using data from the Third National Health and Nutrition Examination Survey, Benjamin et al
] found that the prevalence of IFG among adults was estimated to increase from 8.3% to 30.2%.
In the context of current literature, conflicting data exist regarding the effect of nondiabetic fasting hyperglycemia on cardiovascular risk. Although some studies have found that the 1997 IFG definition is associated with significantly increased risk for CVD,[23
] others have shown no significantly increased risk for CVD with the 1997 IFG definition.[25
The progression from prediabetes to Type 2 diabetes occurs over many years before the development of overt hyperglycemia seen in diabetes.[28
] However, the state of perfusion in prediabetes has received little attention. We, therefore, studied prediabetic normotensive adults in whom the prevalence of insulin resistance and impaired glucose tolerance is high to test the hypotheses that insulin resistance is associated with myocardial perfusion defects and that this relationship is dependent or independent of glucose tolerance status.
The main finding of this study is that insulin resistance is associated with myocardial perfusion defects and that the association appears to be independent of glucose tolerance status and obesity. Results from this study did not identify an increase in myocardial perfusion defects among individuals with insulin-sensitive prediabetes. Furthermore, no correlation was found between them and fasting glucose measurements. Our data suggest that insulin resistance may be more important in the development of myocardial perfusion defects. The mechanism underlying the relationship between insulin resistance and myocardial perfusion defects is not clear enough. Prediabetes is not only a significant risk factor for progression to Type 2 diabetes, but is also considered a risk factor for macrovascular disease and for retinopathy. Some of this risk may be associated with progression to overt diabetes, but there is still increased risk in individuals who have not yet progressed to diabetes. A meta-analysis of 38 prospective studies, for example, suggests that postchallenge blood glucose levels in the nondiabetic range appear to have a linear relationship with cardiovascular disease risk and a possible threshold risk with FPG of about 100 mg/dL.[30
The risk of progressing to diabetes depends on the degree of insulin resistance and deficiency of insulin secretion as well as other diabetes risk factors, such as age, family history, overweight/obesity, or history of gestational diabetes.[31
] Previous studies have shown that visceral fat in young healthy individuals and older adults is associated with increased cardiovascular risk factors.[33
] This study confirms this association. Although it is observed that abdominal adiposity as measured by waist circumference was strongly and adversely associated with myocardial perfusion defects, body mass index as a measure of general adiposity was not. In addition, this study found that insulin resistance appears to be more strongly associated with perfusion defects than with measures of obesity. These results suggest that the obesity–perfusion defects relationship may be mediated in part through increasing insulin resistance. In general, adipocytes, in particular from visceral abdominal regions, produce several bioactive peptides which in turn impact on microcirculation.[34
] However, impact of hypertension upon microcirculation was ameliorated as all subjects were normotensives, such the association was not held. On the other hand, total lipids had insignificant correlation with myocardial perfusion defects. When the components of the lipids were considered separately, perfusion defect showed direct associations only with triglycerides in this study, age was an independent predictor of having perfusion defects. It is known that different arterial segments respond differently to aging.[36
In conclusion, we have shown that prediabetics have myocardial perfusion defects which represent a pattern of cardiovascular risk, and these changes are predominantly observed in prediabetics with increased HOMA IR and visceral obesity. As the silent ischemic changes in the prediabetic state are limited to subjects with insulin resistance, the use of insulin-sensitizing agents to prevent diabetes could have a beneficial effect on CVD. None of the studied prediabetic adult had symptomatic cardiac disease. The findings of this study revealed that changes can be detected before the appearance of clinically apparent coronary myocardial perfusion defects and may act as a marker for the development of future CVD. It is likely that over the next few years screening for ischemic in asymptomatic prediabetics for perfusion defects will become an increasingly important part of the process of risk assessment, and may possibly also improve the monitoring of therapy.[30
] However, these studies are beyond doubt have limitations regarding radiation exposure, cost, and feasibility. Additional studies will be needed to assess the effect of an improvement in insulin sensitivity to improve the myocardial perfusion as well to investigate cost effectiveness of using SPECT in prediabetics.
It is important to note several limitations in this study design, first, the relatively small sample size. Second, this study enrolled a relatively population of older individuals carefully screened to exclude diabetes and hypertension. Further research will be needed to confirm whether these results generalize to middle-aged, more insulin-sensitive individuals and those with hypertension through a large community-based study. Further studies are needed for prevention of Type 2 diabetes and the prediabetic state as well.