MPV is modified by various biosocial and lifestyle factors such as race, gender, age, blood pressure, smoking habits, and alcohol consumption [17, 18]. In a previous study, MPV could be positively correlated with fasting glucose levels in diabetic and prediabetic groups; however, the sample size was modest (50 diabetic subjects and 50 prediabetic subjects) and some confounding factors were not investigated sufficiently . Muscari et al.  showed that MPV values were associated with FPG in Italian subjects. However, these subjects were not entirely representative of the general population because most of the subjects were elderly (mean age, 72.9 years), hypertensive (86%), hypercholesterolemic (47%), and overweight or obese (46%).
In the present study, we investigated the relation of MPV and FPG levels in general population using an adequate sample size, and observed that MPV in prediabetic subjects was higher than that in normoglycemic subjects. Furthermore, MPV of the high-normal glucose subjects was higher than that of the low-normal glucose subjects. Moreover, we observed a positive correlation between MPV and FPG levels, not only in the prediabetic but also in the normoglycemic subjects, independent from variable factors. We excluded subjects with extremely low FPG levels (< 70 mg/dL); therefore, there is a possibility that MPV follows a J-shaped curve at the low glucose levels. However, at least in the physiological glycemic range, the correlation between MPV and FPG levels was confirmed. Unlike our results, Kim et al.  reported a negative correlation between MPV and FPG in Korean subjects with normal glucose tolerance and intermittent hyperglycemia, although intermediate hyperglycemia is associated with an increased risk of cardiovascular diseases. In contrast, we evaluated triglyceride and uric acid levels and alcohol consumption as confounding factors and reported that MPV can differ based on individual characteristics, including lipid profiles, alcohol intake, genetics, race/ethnicity, and different populations.
The definition of IFG is not consistent worldwide. According to the American Diabetes Association (ADA) criterion, IFG is defined as FPG levels of 100–125 mg/dL; this threshold was lowered in 2003 for better prediction of future diabete incidence . Other organizations, including the European Diabetes Epidemiology Group (EDEG) and the Japan Diabetes Society (JDS), have retained the original diagnostic range for IFG at FPG levels of 110–125 mg/dL [21, 22]. In the present study, we adopted ADA criterion, more strictly than EDEG and JDS criteria, in order to distinguish prediabetic subjects from normoglycemic subjects more efficiently. These stringent criteria ensured increased sample confidence in our study.
The term “prediabetes” has replaced the clinical definitions known as borderline or chemical diabetes, traditionally used to identify the individuals at high risk of progression to overt diabetes. Prediabetes has been linked to a modest increase in overall cardiovascular events and has been associated with a higher risk of stroke [4, 23]. Moreover, it has been reported that in prediabetic individuals, the von Willebrand factor levels, essential for platelet aggregation and adhesion, is significantly higher than in the controls, and Willebrand factor levels were positively correlated with MPV in the prediabetic group (r = 0.452, P = 0.001) . In our study, MPV in the prediabetic subjects (Q4) was significantly higher than those in low-normal glucose group (Q1), middle-normal glucose group (Q2), and high-normal glucose group (Q3). Our results suggest that the subjects with prediabetes tend to have increased MPV that could have contributed to an increased risk of cardiovascular disease.
A study using a large multiethnic cohort has demonstrated that the risk of cardiovascular events or death in normoglycemic and prediabetic subjects increases progressively with increasing FPG levels. A 1 mmol/l (18 mg/dl) increase in FPG has been associated with a 17% increase in the risk of future cardiovascular events or death . Even within the normoglycemic range, elevated cardiovascular risk is strongly and independently associated with glucose levels. Subjects with fasting glucose levels in the high-normal range (95–99 mg/dL) have an increased cardiovascular risk when compared with subjects in low-normal range (< 80 mg/dL) . In the present study, MPV in the high-normal glucose group (Q3) was higher than that in the low-normal glucose group (Q1). Although the underlying mechanism of higher MPV in Q3 subjects remains unclear, it has been suggested that increased MPV may be due to osmotic swelling as a result of hyperglycemia . Another postulated mechanism from a study in mice demonstrated that insulin induces megakaryocytes to produce larger platelets .
Obesity is a risk factor of cardiovascular disorders, partly due to increased oxidative stress and inflammation, which are associated with increased reactive oxygen species (ROS) production and decreased NO bioavailability. Recently, Monteiro et al.  showed that metabolic abnormalities, as a consequence of high-fat diets, cause platelet hyperaggregability involving enhanced intraplatelet ROS production and decreased NO bioavailability. In mildly hypertriglyceridemic subjects, n-3 polyunsaturated fatty acids increased MPV values slightly . Although we did not measure dietary fat intake in our subjects, there is a possibility that a high-fat diet increases MPV. In obese subjects, MPV was positively correlated with BMI and a positive correlation was also shown between weight loss and reduction in MPV . A higher BMI value was strongly associated with higher insulin levels and insulin resistance. In subjects with cardiovascular disease, MPV was significantly elevated in those with insulin resistance when compared to insulin-sensitive subjects . However, there are few reports regarding the correlation between MPV and insulin level in the general population. Nonetheless, MPV was positively associated with insulin level in polycystic ovary syndrome, which is related to increased insulin levels and the incidence of obesity . Therefore, hyperinsulinemia that accompanies obesity may influence platelet reactivity in obese patients.
There are several limitations to our study. It has been shown that up to five percent of subjects with IFG appear to have diabetes as per the results of the 2-hour glucose tolerance tests [34, 35]. True diabetic and prediabetic groups are demarcated by glucose tolerance tests. Therefore, some of the people in the prediabetic group might have had diabetes. Second, Our study was retrospective and we did not determine the relationship between MPV and the clinical events. Lastly, our present study only included Japanese subjects, in which the prevalence of obesity (BMI > 30) was < 3%, in contrast to > 30% in Europeans and Americans . Therefore, a duplicate study with other populations is indispensable to confirm our results.
Using a representative sample of Japanese adults, we found that the prediabetic subjects had higher MPV than the control individuals. Furthermore, MPV could be positively and independently correlated with the FPG levels, not only in the prediabetic subjects but also in normoglycemic subjects, after correcting for confounding variables.