Fasting glucose levels within the high normal range predict cardiovascular outcome

Department of Medicine C, Sheba Medical Center, Tel Hashomer, Israel.
American heart journal (Impact Factor: 4.46). 07/2012; 164(1):111-6. DOI: 10.1016/j.ahj.2012.03.023
Source: PubMed


Diabetes mellitus and impaired glucose metabolism are associated with increased risk for cardiovascular disease (CVD). However, it is still not clear whether glucose levels can predict CVD risk among patients without diabetes. The primary aim of this study is to assess whether normoglycemic fasting plasma glucose (FPG) is associated with increased risk of CVD outcomes in healthy patients.
We obtained blood measurements, data from physical examination, and medical and lifestyle information from 10,913 men and women who were evaluated in the Institute for Preventive Medicine of Sheba Medical Center. Enrolled were participants with FPG <100 mg/dL as well as 100 to 125 mg/dL, who were free of diagnosis of CVD. The participants were actively screened for coronary disease using a stress test. Primary end points were coronary heart disease or self-reported cerebral vascular disease.
A total of 1,119 incident cases of CVD occurred during a mean follow-up of 4.3 years. Subjects with fasting glucose levels in the high normal range (95-99 mg/dL) had an increased CVD risk when compared with levels <80 mg/dL, (HR 1.53;CI 95% [1.22-1.91], P < .001). A multivariate model, adjusted for age, sex, family history of CVD, blood pressure, body mass index, smoking status, pharmacologic treatment, serum triglycerides, and high-density lipoprotein and low-density lipoprotein cholesterol levels, revealed an independent increased risk of CVD with rising FPG levels in the normal range.
Elevated CVD risk is strongly and independently associated with glucose levels within the normoglycemic range. Fasting plasma glucose may help in identifying apparently healthy persons with early metabolic abnormalities who are at increased risk for CVD before progression to prediabetes and overt diabetes mellitus.

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    • "Although the risk of CVD already exists before the onset of diabetes mellitus since other cardiovascular risk factors are still prevalent in prediabetic subjects, a gradual increment of independent risk of CVD has been reported as blood glucose levels up even under prediabetic glucose thresholds [17]. However, whether IFG or IGT differs in the magnitude of the risk of CVD is still not well established yet [18]. "
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    ABSTRACT: Background. Inflammation has been associated with insulin resistance, type 2 diabetes mellitus (T2DM), and atherothrombosis. Aim. To determine differences in levels of proinflammatory and prothrombotic markers such as high sensitivity C-reactive protein (hs-CRP) and fibrinogen in subjects with normal glucose tolerance (NGT), prediabetes, and T2DM and to establish their relationship with other cardiovascular risk factors before clinical manifestations of cardiovascular disease. Methods. We conducted a nonrandomized, cross-sectional assay in a hospital at México City. The levels of hs-CRP and fibrinogen were measured and compared according to glucose tolerance status. Results. We enrolled 1047 individuals and they were distributed into NGT n = 473, pre-DM n = 250, and T2DM n = 216. There was a statistical difference between NGT and T2DM groups for fibrinogen (P = 0.01) and hs-CRP (P = 0.05). Fibrinogen and hs-CRP showed a significant positive correlation coefficient (r = 0.53, P<0.0001). In a multiple stepwise regression analysis, the variability in fibrinogen levels was explained by age, HbA1c, and hs-CRP (adjusted R (2) = 0.31, P<0.0001), and for hs-CRP it was explained by BMI and fibrinogen (adjusted R (2) = 0.33, P<0.0001). Conclusion. Inflammation and prothrombotic state are present in people with T2DM lacking cardiovascular disease. Fibrinogen and Hs-CRP are positively correlated. Fibrinogen and hs-CRP concentrations are predominantly determined by BMI rather than glucose levels.
    Full-text · Article · Mar 2014 · Journal of Diabetes Research
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    • "However, there are reports from the past 3 years that affirm the evidence of the risk of future CVD in prediabetes and the implications of management. For instance, one of the reports indicated that fasting plasma glucose level may help in identifying apparently healthy persons with early metabolic abnormalities who are at increased risk for CVD.[5] Others reported that upto 12% of prediabetes individuals develop DM per year.[67] "
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    ABSTRACT: The study aims to develop a screening protocol for the risk of future cardiovascular disease and diabetes mellitus in people with prediabetes and undiagnosed diabetes; and to establish a framework for early identification and intervention of prediabetes including strategies for holistic management and monitoring of progression. The first phase is to identify prediabetes and undiagnosed diabetes in volunteers who are ≥18-years-old for 5 years. Point-of-care testing and questionnaire will be used to screen for prediabetes and cardiovascular disease. We anticipate screening more than 2000 individuals of both genders by the end of first phase. The second and third phases which shall run for 5-10 years will be longitudinal study involving participants identified in the first phase as having prediabetes without dyslipidaemia, or clinically established cardiovascular disease. The second phase shall focus on preventive management of risk of progress to diabetes with explicit diagnosis of cardiovascular disease. Oxidative stress measurements will be performed cum evaluation of the use of antioxidants, exercise, and nutrition. The third phase will include probing the development of diabetes and cardiovascular disease. Binomial logistic regression would be performed to generate and propose a model chart for the assessment of cardiovascular disease risk in prediabetes.
    Full-text · Article · Nov 2013 · North American Journal of Medical Sciences
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    • "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) [26]. In the present study, MPV in the high-normal glucose group (Q3) was higher than that in the low-normal glucose group (Q1). "
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    ABSTRACT: Background Prediabetes is an independent risk factor for cardiovascular diseases. Mean platelet volume (MPV) can reflect platelet activity, and high MPV is associated with thrombogenic activation and an increased risk of cardiovascular disease. In diabetic patients, MPV is higher when compared with normal subjects. However, the relationship between MPV and prediabetes is poorly understood. The purpose of the present study was to compare MPV in prediabetic and normoglycemic subjects, and to evaluate the relationship between MPV and fasting plasma glucose (FPG) levels in these two groups. Methods We retrospectively studied 1876 Japanese subjects who had undergone health checks at Iida Municipal Hospital. Age, sex, body mass index (BMI), blood pressure, medical history, smoking habits, alcohol intake, lipid profiles, FPG levels, and MPV were evaluated. Subjects were categorized into four groups according to FPG: Q1 (70 mg/dL ≤ FPG < 90 mg/dL, n = 467), Q2 (90 mg/dL ≤ FPG < 95 mg/dl, n = 457), Q3 (95 mg/dL ≤ FPG < 100 mg/dL, n = 442), and Q4 (100 mg/dL ≤ FPG < 126 mg/dL, n = 512). Q1, Q2, and Q3 were defined as normal FPG groups and Q4 was defined as prediabetic group. Results The MPV increased with the increasing FPG levels, in the following order: Q1 (9.89 ± 0.68 fl), Q2 (9.97 ± 0.69 fl), Q3 (10.02 ± 0.72 fl), and Q4 (10.12 ± 0.69 fl). After adjusting for the confounding parameters, MPV of the prediabetic group was higher than that in other groups (P < 0.001 for Q4 vs. Q1 and Q2, and P < 0.05 for Q4 vs. Q3). MPV in the high-normal glucose group (Q3) was significantly higher than in the low-normal glucose group (Q1). MPV was independently and positively associated with FPG, not only in prediabetic subjects but also in normal FPG subjects (β = 0.020 and β = 0.006, respectively). Conclusions MPV in patients with prediabetes was higher than that in normal subjects, and was positively associated with FPG levels in prediabetic and normal subjects.
    Full-text · Article · Jan 2013 · Cardiovascular Diabetology
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