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Blood glucose concentrations <= 125 mg/dl and coronary heart disease risk
Abstract
T his study sought to determine the relation between fasting glucose levels, coronary heart disease (CHD) risk factors, and the prevalence of CHD in a high-risk group of patients attending a cardiology prevention clinic. The study was designed to address 2 questions. (1) Are increasing fasting glucose concentrations in the nondiabetic range (less than or equal to125 mg/dl) associated with an increased burden of traditional (smoking, central obesity, systemic hypertension, dyslipidemia) and nontraditional (e.g., fibrinogen, homocysteine, lipoprotein(a) [Lp(a)]) CHD risk factors? (2) Are increasing blood glucose concentrations in this range associated with a continuous and graded risk for CHD independent of these risk factors?.
... Our findings are in general agreement with previous studies in other populations (18,19,25,26), which showed that IFG is associated with CVD risk independent of other CVD risk factors. Although there have been a number of studies on this issue, most studies were performed in Europe and North America, and adjustments for confounding factors were heterogeneous among studies. ...
... However, the study included only postmenopausal women with established CHD, and the sample size was small; therefore, it is difficult to generalize their results. In contrast, studies in China (14) and the U.S. (25) showed that IFG defined as FSG 100-125 mg/dL was associated with increased risk of CHD. In the Asia Pacific Cohort Studies (18), a positive log-linear association was reported between FSG and the risk of total stroke and IHD. ...
... Second, we could not exclude participants who developed incident diabetes before CVD events from IFG groups, because we used only baseline FSG levels. However, most other studies (13,14,18,25) also used only baseline glucose values, except one study (17) that excluded incident diabetes. Third, our cohort was not based on a general population sample that could represent the Korean population. ...
OBJECTIVE
The relationship between impaired fasting glucose (IFG) and risk of cardiovascular disease (CVD) or ischemic heart disease (IHD) varies widely according to sex and ethnicity. We evaluated the relationship between IFG and CVD or IHD among Korean men and women.
RESEARCH DESIGN AND METHODS
A total of 408,022 individuals who underwent voluntary private health examinations in 17 centers in South Korea were followed for 10 years. Data regarding CVD or IHD events were obtained from the Korean National Health Insurance database. IFG was categorized as grade 1 (fasting glucose 100–109 mg/dL) or grade 2 (110–125 mg/dL).
RESULTS
Incidence rates of CVD (per 100,000 person-years) were 2,203 for diabetes. Age-adjusted hazard ratios (HRs) for CVD were 1.17 (95% CI 1.13–1.20) for grade 1 IFG, 1.30 (1.24–1.35) for grade 2 IFG, and 1.81 (1.75–1.86) for diabetes. The increased risk for women was similar to that of men. Age-adjusted HRs for IHD and ischemic stroke were also significantly increased for men and women with IFG and diabetes. After multivariate adjustment of conventional risk factors (hypertension, dyslipidemia, smoking, obesity, and family history of CVD), the overall risk of CVD was greatly attenuated in all categories. However, the HRs for IHD and ischemic stroke remained significantly increased in men for grade 2 IFG but not in women.
CONCLUSIONS
In Korea, grade 2 IFG is associated with increased risk of IHD and ischemic stroke, independent of other conventional risk factors, in men but not in women.
... of cardiovascular disease in patients with CHD and T2DM. [6,7] However, more and more studies have shown that the existence of sustained high BG is not the single risk factor, the existence of blood glucose fluctuation (BGF) in patients with T2DM also correlated tightly with the occurrence and development of chronic ...
... Studies used to consider the pathophysiological alterations in cardiac neurons or nerve fibers induced by hyperglycemia were the key pathologic mechanism of cardiovascular autonomic neuropathy. High blood concentration of glucose [7] or HbA1c [24] level was the main pathogenic risk factor. However, recent studies have pointed out that diabetes-induced oxidative stress is the key factor in the initiation of diabetic complications, including diabetes-induced cardiovascular autonomic neuropathy. ...
Aim:
This retrospective analysis aims to evaluate the correlation between blood glucose fluctuation (BGF) and heart rate variability (HRV) in patients with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM).
Subjects and methods:
In total, 210 patients with CHD and T2DM from January 2014 to January 2019 admitted to Wenling Hospital of Traditional Chinese Medicine were enrolled in this study. Based on whether BGF existed, patients were allocated to BG control group and BG fluctuation group. The HRV parameters, frequency of adverse events, and Gensini score between groups were recorded and Pearson analysis was performed.
Results:
Results displayed that no significant differences in age, gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), alcohol consumption history, drinking history, or serum lipid were found between groups (P > 0.05 for all items). However, the BGF parameters were significantly higher while the HRV parameters were significantly lower in BG fluctuation group, compared with BG control group (P < 0.05 for all items). Pearson analysis showed that despite mean blood glucose (MBG) and mean amplitude of glycemic excursions (MAGE) both correlated with a standard deviation of NN intervals (SDNN) level, the correlation coefficient of MAGE-SDNN was much higher (-0.705 vs -0.185). Additionally, the frequencies of adverse events and Gensini scores were also significantly higher in the BG fluctuation group than the BG control group.
Conclusions:
It suggests that BGF strongly correlated with HRV in patients with CHD and T2DM. It also provides experimental instructions for clinical practice.
... In 2002, Hoogwerf et al. reported that fasting glucose quintiles throughout the nondiabetic range were graded and continuously associated with cardiovascular RF [15]. They also assessed the prevalence of coronary heart disease (CHD) through glucose quintiles and found a direct and significant association, even when adjusting for traditional and nontraditional RF. ...
... Neither was glucose tolerance measured. Postload glucose levels have shown a better association with CV risk than IFG [9,15]. However, this study sought to demonstrate whether FBG would be a good marker of CV RF clustering, mainly because it has a low cost and is commonly measured in the clinical setting. ...
. Impaired fasting glucose (IFG) through the nondiabetic range (100–125 mg/dL) is not considered in the cardiovascular (CV) risk profile.
Aim
. To compare the clustering of CV risk factors (RFs) in nondiabetic subjects with normal fasting glucose (NFG) and IFG.
Material and Methods
. Cross-sectional study in 3739 nondiabetic subjects. Demographics, medical history, and CV risk factors were collected and lipid profile, fasting glucose levels (FBG), C-reactive protein (hsCRP), blood pressure (BP), anthropometric measurements, and aerobic capacity were determined.
Results
. 559 (15%) subjects had IFG: they had a higher mean age, BMI, waist circumference, non-HDL cholesterol, BP, and hsCRP (
p
<
0.0001
) and lower HDL (
p
<
0.001
) and aerobic capacity (
p
<
0.001
). They also had a higher prevalence of hypertension (34% versus 25%;
p
<
0.001
), dyslipidemia (79% versus 74%;
p
<
0.001
), and obesity (29% versus 16%;
p
<
0.001
) and a higher Framingham risk score (8% versus 6%;
p
<
0.001
). The probability of presenting 3 or more CV RFs adjusted by age and gender was significantly higher in the top quintile of fasting glucose (≥98 mg/dL; OR = 2.02; 1.62–2.51).
Conclusions
. IFG in the nondiabetic range is associated with increased cardiovascular RF clustering.
... Glycaemic thresholds for diabetes are based on elevated microvascular disease risk [10] and may be less relevant to macrovascular disease [2]. One cross-sectional US study of 2500 individuals without known diabetes but with hypertension or hyperlipidaemia, found a significantly elevated independent risk of self-reported ischaemic heart disease (n = 1274) at all fasting blood glucose levels > 4.8 mmol/l compared with < 4.4 mmol/l [16]. To our knowledge, no studies in mainland China have published data on the association of blood glucose with ischaemic heart disease or stroke risk amongst individuals without diabetes. ...
To examine the relationship of self-reported diabetes, and of random blood glucose levels among individuals without known diabetes, with the prevalence of cardiovascular disease in Chinese adults.
We examined cross-sectional data from the China Kadoorie Biobank of 0.5 million people aged 30-79 years recruited from 10 diverse regions of China in the period 2004-2008. Logistic regression was used to estimate the odds ratios of prevalent cardiovascular disease associated with self-reported diabetes, and with measured random blood glucose levels among participants with no history of diabetes, adjusting simultaneously for age, sex, area, education, smoking, alcohol, blood pressure and physical activity.
A total of 3.2% of participants had self-reported diabetes (men 2.9%; women 3.3%) and 2.8% had screen-detected diabetes (men 2.6%; women 2.8%), i.e. they had no self-reported history of diabetes but a blood glucose level suggestive of a diagnosis of diabetes. Compared with individuals without a history of diabetes, the odds ratios associated with self-reported diabetes were 2.18 (95% CI 2.06-2.30) and 1.88 (95% CI 1.75-2.01) for prevalent ischaemic heart disease and stroke/transient ischaemic attack, respectively. Among participants without self-reported diabetes there was a positive association between random blood glucose and ischaemic heart disease and stroke/transient ischaemic attack prevalence (P for trend <0.0001). Below the diabetic threshold (<11.1 mmol/l) each additional 1 mmol/l of random blood glucose was associated with 4% (95% CI 2-5%) and 5% (95% CI 3-7%) higher odds of prevalent ischaemic heart disease and stroke/transient ischaemic attack, respectively.
In this adult Chinese population, self-reported diabetes was associated with a doubling of the odds of prevalent cardiovascular disease. Below the threshold for diabetes there was still a modest, positive association between random blood glucose and prevalent cardiovascular disease.
... 1,2 In addition, associations of prediabetes and T2DM with subclinical atherosclerosis and renal function risk have also been assessed, with T2DM robustly associated with these risk factors but with less consistent associations among those with prediabetes as defined by impaired fasting glucose (IFG = 100-125 mg/dL). [3][4][5][6][7][8][9][10] In this context, the degree to which IFG and the more recently established HbA1c diagnostic thresholds for prediabetes individually and jointly associate with subclinical atherosclerosis and abnormal renal measures as antecedents to clinical complications of T2DM remains poorly defined. ...
Background:
Prediabetes defined by fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1c) predicts incident diabetes, but their individual and joint associations with micro- and macro-vascular risk remain poorly defined.
Methods:
FPG, HbA1c, coronary artery calcium (CAC), carotid wall thickness, estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) were measured in adults free from prior diabetes or cardiovascular disease (CVD) in the Dallas Heart Study 2 (DHS-2), a population-based cohort study. Prediabetes was defined by FPG 100-125 mg/dL and/or HbA1c 5.7%-6.4%. Multivariable logistic regression was used to analyse associations of HbA1c and/or FPG in the prediabetes range with subclinical atherosclerosis and renal measures.
Results:
The study comprised 2340 participants, median age = 49 years; 60% women and 50% black. Those with prediabetes were older (52 vs 48 years), more often men (63% vs 53%), black (53% vs 47%) and obese (58% vs 40%; p < 0.001 for each). Prediabetes was captured by FPG alone (43%), HbA1c alone (30%) or both (27%). Those with prediabetes by HbA1c or FPG versus normal HbA1c/FPG had more CAC [odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.5-2.2], higher carotid wall thickness (1.32 vs 1.29 mm, p < 0.001), eGFR < 60 mL/min [OR = 1.6 (95% CI = 1.1-2.4)], UACR > 30 mg/dL [OR = 1.8 (95% CI = 1.2-2.7)] and a higher odds for the composite eGFR + UACR [chronic kidney disease (CKD) ≥ 2] [OR = 1.9 (95% CI = 1.5-2.6)]. After multivariable adjustment, none of these associations remained significant.
Conclusion:
Prediabetes defined by HbA1c and/or FPG criteria is crudely associated with markers of diabetic macro- and micro-vascular disease, but not after statistical adjustment, suggesting the relationships are attributable to other characteristics of the prediabetes population.
... It may also indicate that the course of events leading to amputation, most notably peripheral macrovascular disease, begins prior to the onset of diabetes. This would be consistent with observations that there is an association between cardiovascular disease and higher glucose levels even below those diagnostic of diabetes (10)(11)(12). These observations may imply that diabetes programs should address the needs for risk factor reduction among those who have prediabetes (impaired fasting glucose and impaired glucose tolerance). ...
The prevalence of diabetes is increasing rapidly among Alaska's Indian, Eskimo and Aleut populations. Approximately half the Native people with diabetes have no road access to hospitals or physicians, presenting a challenge in the attempt to prevent lower extremity amputation as a complication. In late 1998 funding became available for diabetes prevention and treatment among Native Americans. The tribal health corporations in Alaska decided to use a portion of this funding to implement a high-risk foot program to decrease the amputation rate. PROGRAM DESIGN: The program initially involved a surgical podiatrist who provided training to local staff and performed preventive and reconstructive surgery on several patients with impending amputations. The program then provided training for a physical therapist to become a certified pedorthist. This individual established the long-term maintenance phase of the program by conducting diabetic foot clinics routinely at the Alaska Native Medical Center, a referral center in Anchorage. He also travels to other regions of the state to provide training for village and hospital-based health care providers and to conduct field clinics. A system was established in a common database management program to track the patients' foot conditions. Patient education is emphasized.
The overall amputation incidence among all Alaska Native patients with diabetes decreased from 7.6/1,000 in the pre-program period (1996 to 1998) to 2.7/1,000 in the post-program period (1999-2001) (p<.001). The rate among Aleuts, who previously had the highest amputation incidence, decreased from 17.4/1,000 to 3.1/1,000 over the same time periods (p<.001). Among people who had had diabetes at least 10 years, the overall amputation incidence decreased from 16.4/1,000 to 6.8/1,000 (p=.021); among Aleuts the rate fell from 24.5/1,000 to 2.6/1,000 (p=.01).
Though longer follow-up is needed, these data suggest that even in populations living in isolated regions, diabetic amputations can be prevented by a coordinated system to identify high-risk feet and provide preventive treatment and education in the context of a comprehensive diabetes management program in an integrated health system.
... 22 Most outcomes in these patients are due to insulin insufficiency, but hyperglycaemia itself, as an independent variable, has deleterious effects, such as glycosylation of tissue proteins and hyperosmolality. 23,24 ...
The vascular endothelium is injured by blood flow abnormalities exacerbated by different risk factors, including markers of haemoconcentration. The aim of the present study was to assess the association between markers of haemoconcentration and dehydration and the prevalence and severity of coronary artery disease (CAD).
Subjects in the present study (189 men and 126 women) were classified as either CAD cases or controls according to the results of coronary angiography. The severity of CAD was scored on the basis of the number and the extent of lesions on coronary arteries. Serum electrolytes, osmolality and haematological parameters were measured.
Compared with control subjects, patient with CAD had increased levels of serum osmolality, calculated osmolality, tonicity, sodium, glucose and blood urea nitrogen (BUN). Significant differences were also observed in the haematocrit and haemoglobin concentration, but not in erythrocyte counts and total serum protein. On multiple logistic regression analysis adjusting for major risk factors, serum osmolality, glucose and BUN exhibited significant associations with CAD, but the correlations were lessened by diabetes. Analysis using anova showed a significant correlation between serum osmolality, sodium, glucose and BUN and the severity of CAD. The area under the receiver operating characteristic curves, as a relative measure of the test's efficiency, was the highest and significant for serum osmolality, BUN and glucose.
The results indicate that some of the markers of dehydration and haemoconcentration are associated significantly with the prevalence and severity of CAD, but the independence of these correlations is questioned. These markers may play a role in the pathogenesis of atherosclerosis.
Although mass spectrometry (MS) of metabolites has the potential to provide real‐time monitoring of patient status for diagnostic purposes, the diagnostic application of MS is limited due to sample treatment and data quality/reproducibility. Here, the generation of a deep stabilizer for ultra‐fast, label‐free MS detection and the application of this method for serum metabolic diagnosis of coronary heart disease (CHD) are reported. Nanoparticle‐assisted laser desorption/ionization‐MS is used to achieve direct metabolic analysis of trace unprocessed serum in seconds. Furthermore, a deep stabilizer is constructed to map native MS results to high‐quality results obtained by established methods. Finally, using the newly developed protocol and diagnosis variation characteristic surface to characterize sensitivity/specificity and variation, CHD is diagnosed with advanced accuracy in a high‐throughput/speed manner. This work advances design of metabolic analysis tools for disease detection as it provides a direct label‐free, ultra‐fast, and stabilized platform for future protocol development in clinics.
Aims
Previous studies have proposed potential benefit of glycated hemoglobin (HbA1c) supplementary to fasting glucose in detecting metabolic syndrome (MetS). This study was to investigate an association of incident MetS with levels of HbA1c and fasting glucose.
Methods
In a cohort of Korean Genome and Epidemiology Study, 5515 non-diabetic adults were grouped by the levels of baseline fasting glucose and HbA1c, and followed-up for 10 years. Using multivariate Cox proportional hazards assumption, hazards ratios (HRs) and 95% confidence interval (CI) for incident MetS (adjusted HRs [95% CI]) were calculated according to baseline fasting glucose and HbA1c. In individuals with normal fasting glucose, subgroup analysis was conducted to evaluate an association of HbA1c levels with MetS.
Results
The risk for MetS significantly increased proportionally to fasting glucose ≥ 80 mg/dL and HbA1c ≥ 5.5%, compared with fating glucose < 80 mg/dL and HbA1c < 5.3%, respectively. In subgroups of normal fasting glucose, HbA1c ≥ 5.7% had the increased risk of MetS in fasting glucose < 80 mg/dL (5.7–5.9%: 1.41 [1.07–1.86] and 6.0–6.4%: 2.20 [1.40–2.92]), and HbA1c ≥ 5.5% had the increased risk of MetS in fasting glucose of 80–99 mg/dL (5.5–5.6%: 1.33 [1.08–1.64], 5.7–5.9%: 1.57 (1.27–1.93), and 6.0–6.4%: 2.37 [1.87–3.00]).
Conclusions
Both elevated fasting glucose and HbA1c were significantly associated with the increased risk of MetS even within normal range. HbA1c is effective in identifying high-risk group for MetS in individuals with normal fasting glucose.
Before the onset or diagnosis of overt type 2 diabetes, individuals may have significant “dysglycemia” for years, characterized by plasma glucose levels that do not meet the criteria for diabetes but are higher than those considered normal. Diagnosis of the “prediabetic state” is mandatory because numerous clinical studies have indicated that a substantial number of individuals with this disorder will later develop diabetes and that the condition is associated with an increased risk of chronic complications, in particular cardiovascular events. This chapter provides an overview of the historical definitions of the prediabetic state and the status of current diagnostic criteria of prediabetes on the basis of long-standing glucose criteria; namely, the fasting plasma glucose and/or oral glucose tolerance test and more recently, the HbA1c (glycated hemoglobin) level.
Prediabetes represents an elevation of plasma glucose above the normal range but below that of clinical diabetes. Prediabetes includes individuals with IFG, IGT, IFG with IGT and elevated HbA1c levels. Insulin resistance and β-cell dysfunction are characteristic of this disorder. The diagnosis of prediabetesis is vital as both IFG and IGT are indeed well-known risk factors for type 2 diabetes with a greater risk in the presence of combined IFG and IGT. Furthermore, as will be illustrated in this review, prediabetes is associated with associated disorders typically only considered in with established diabetes. These include cardiovascular disease, periodontal disease, cognitive dysfunction, microvascular disease, blood pressure abnormalities, obstructive sleep apnea, low testosterone, metabolic syndrome, various biomarkers, fatty liver disease, and cancer. As the vast majority of individuals with prediabetes are unaware of their diagnosis, it is therefore vital that the associated conditions are identified, particularly in the presence of mild hyperglycemia, so they may benefit from early intervention.
The costs of diabetes in the United States are enormous and growing. Although environmental and social interventions for addressing the underlying causative risk factors for diabetes including obesity and physical inactivity are promising, their effectiveness and cost-effectiveness are not presently established (72). Although more expensive than usual care, screening and intensive lifestyle interventions and interventions with metformin and acarbose targeting individuals at high risk for diabetes are effective and safe. Lifestyle interventions directly improve quality-of-life and delay or prevent the decrement in quality-of-life and the costs associated with diabetes and its complications (72). Metformin and acarbose interventions are effective in delaying or preventing the decrement of quality-of-life and the costs associated with diabetes and its complications. As a result, intensive lifestyle, metformin, and acarbose interventions are very cost-effective.
Purpose of review: The prevalence of cardiovascular disease is markedly increased in patients with type 2 diabetes and to a somewhat lesser extent impaired glucose tolerance (IGT). This has generally been attributed to the concurrent presence of cardiovascular disease risk factors, including dyslipidemia, hypertension, coagulation abnormalities, and insulin resistance (i.e., the metabolic syndrome). This article reviews the current literature on cardiovascular disease in patients with diabetes, and in particular, the notion that treatment should be initiated as early as possible, indeed even prior to the onset of diabetes, to prevent this complication.
Recent findings: The recently reported Steno-2 Trial on multifactorial intervention and cardiovascular disease in type 2 diabetic patients with microalbuminuria demonstrated a 50% decrease in the incidence of cardiovascular events. However, morbidity and mortality rates were still high, suggesting the need either for additional therapies or for earlier treatment, or both. The potential of earlier treatment was evaluated in the Diabetes Prevention Program Trial (DPP) in which the effects of lifestyle modification with diet and exercise and pharmacologic therapy were assessed in patients with IGT. Cardiovascular endpoints have not yet been reported; however, it was clearly shown that progression to type 2 diabetes was diminished by nearly 60% when patients were treated with diet and exercise and by 31% when metformin was used. Similar results with lifestyle modification were also obtained in the Finnish Diabetes Prevention Study.
The metabolic syndrome antedates and may be causal for type 2 diabetes, IGT, and cardiovascular disease in many patients, and hypothetically it could be an even more effective target for prevention. Recent studies suggest that the metabolic syndrome may be related to dysregulation of a malonyl CoA-AMP-activated protein kinase (AMPK) fuel sensing mechanism that allows lipid to accumulate in muscle, liver, and other sites. Therapeutically, this is an attractive notion, since AMPK is activated by exercise, metformin, thiazolidinediones, and the fat cell-derived hormone adiponectin, all of which appear to diminish tissue lipid accumulation, increase insulin sensitivity, and decrease coronary heart disease.
Summary: Numerous studies suggest that treatment directed at the metabolic syndrome, which often antedates type 2 diabetes and IGT should be considered as a means of preventing both these disorders and the cardiovascular disease with which they are often associated. Available evidence suggests that diet, exercise, and other treatments that activate AMPK could be useful in diminishing cardiovascular disease risk in these individuals, as well as retarding the development of diabetes.
Diabetes mellitus (DM) is associated with an increased risk for coronary heart disease (CHD), less favorable outcomes from
intervention procedures, and CHD-related mortality (1–56) (Table 1). Hyperglycemia by itself likely contributes to this risk, however, DM–especially type 2 DM–and impaired glucose
tolerance are associated with a number of other CHD risk factors. These risk factors include dyslipidemia, hypertension, central
obesity, albuminuria, a procoagulant state, and markers of inflammation (10,26–28,45,57–88). These risk factors are associated with insulin resistance and have also been described as the “metabolic syndrome” for
coronary artery disease (CAD). There accumulating data to suggest that these abnormalities may be associated with endothelial
cell dysfunction. In addition to these risk factors, the concepts of protein glycation, as well as oxidized lipoproteins as
possible mechanisms for CHD have been proposed (89–92).
Although diabetes mellitus is well known to result in systolic and diastolic left ventricular (LV) dysfunction at the subclinical level, even when it is not accompanied by hypertension and coronary artery disease, this situation has not been sufficiently investigated in prediabetes, which is the precursor of diabetes. The aims of the present study were to investigate LV systolic and diastolic function in normotensive and low-risk prediabetic and diabetic subjects for coronary disease using sensitive tissue Doppler echocardiographic parameters, to investigate early possible negative effects of glucose metabolism impairment on LV longitudinal function.
Two hundred subjects (92 with prediabetes, 48 with type 2 diabetes, and 60 age-matched healthy volunteers) were studied by conventional, tissue Doppler, and strain and strain rate echocardiography. All study subjects were normotensive, and coronary artery disease was excluded. Forty-eight patients had isolated fasting glucose impairment, and 44 patients had combined fasting glucose and glucose tolerance impairment. Longitudinal peak systolic strain and the peak systolic and diastolic strain rates of six walls in the apical four-chamber, long-axis, and two-chamber views were evaluated.
Clinical and standard echocardiographic characteristics were comparable among all groups. Mean systolic (P = .01) and diastolic (P = .02) tissue velocities, mean strain (P = .004), and mean systolic (P = .002) and diastolic (P = .001) strain rates were significantly lower in the diabetic groups than in control subjects. There were no difference between patients with isolated fasting glucose impairment and controls for tissue Doppler parameters, but mean early diastolic tissue velocity and mean strain and strain rates were statistically lower in patients with combined fasting glucose and glucose tolerance impairment compared with controls (P < .05).
LV longitudinal systolic and diastolic function was impaired in both normotensive diabetic and prediabetic patients.
Diabetes evolves through prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Subjects with IFG/IGT have an increased risk of developing diabetes and a higher prevalence of cardiovascular disease than normoglycemic individuals. However, there is considerable evidence that glucose levels lower than those meeting the current definition of prediabetes may also be associated with similar concerns, particularly in high-risk individuals in accordance with a continuous glycemic risk perspective. Therefore, an absolute definition of prediabetes may underestimate the implications and vastness of this disorder. Research should focus on these aspects to minimize the risk of developing a preventable condition.
Prediabetes comprising Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT) represents an intermediate stage of altered glucose metabolism between normal glucose levels and type 2 diabetes mellitus and is associated with an increased risk for the development of diabetes and cardiovascular disease. There is considerable evidence that glucose levels lower than those meeting the current definition of prediabetes may also be associated with similar risks particularly in high-risk individuals. Prediabetes is often unrecognized and therefore constitutes a major public health concern suggesting the need for earlier intervention than is currently recommended.
With the increased attention being given to cardiovascular risk factor reduction, the opportunity exists to substantially decrease the largest cause of mortality in diabetic patients. The concept that type 2 diabetes and CVD are linked via a common etiologic pathway (metabolic syndrome) has substantial ramifications for the care of individual patients. Many of the metabolic abnormalities that contribute to both glycemic disorders and CVD are interrelated. For example, hyperinsulinemia and insulin resistance coupled with abdominal obesity further worsens HTN and hyperlipidemia. Likewise, the procoagulant state and endothelial dysfunction increase with worsening glycemic control. Specific interventions include tobacco cessation, a food management and physical activity plan, choice of antidiabetic agent (such as metformin), and use of ACE inhibitors for hypertension and microalbuminuria (Table 5). Programs to enhance cardiovascular risk factor reduction as part of the comprehensive evaluation and management of diabetic patients have been described [95,99]. One community-based program provided free screening to diabetic patients with randomization to either annotated result reports provided to the patient and their physician or results provided by a project nurse (either face-to-face or over the phone). Greater improvements in mean glycohemoglobin, cholesterol, and blood pressure were noted with verbal presentation of results [99]. Recent data from the Centers for Disease Control and Prevention Diabetes Cost-effectiveness Group support the idea that interventions to decrease CVD in diabetics are economically beneficial. Intensive management of hypertension, glycemic control, and hyperlipidemia each improved health outcomes. Hypertension control reduced costs. Although intensive treatment of glucose and hyperlipidemia increased costs, the increase was comparable to that of other frequently used health care interventions [100]. Further directions include further exploration of the implications and management of metabolic syndrome as it relates to CVD prevention. Interventions such as exercise, which can impact on all outcomes, require special attention. Efforts by physicians, health systems, and society are necessary to increase physical activity for individuals of all ages. It makes clinical sense that the recommendations for prevention of CVD in diabetics described in this article may also benefit patients with prediabetes (fasting glucose 110-125 mg/dl), but this remains to be definitively shown.
This study examined the relation of depressive symptomatology, hostility, and anger expression to indices of glucose metabolism and tested whether gender moderates these associations in a sample of 135 healthy, nondiabetic adults (75 men, 60 women). The severity of depressive symptoms, hostility, and anger expression was positively associated with estimated insulin resistance (IR) and insulin in women but not in men. Anger expression was positively associated with glucose in women only. A summary score of depressive symptoms, hostility, and anger expression was positively associated with estimated IR, insulin, and glucose in women but not in men. Hence, in women, IR and elevated levels of fasting insulin and glucose may be one pathophysiological mechanism mediating the increased risk of cardiovascular disease and Type 2 diabetes associated with these psychological attributes.
It is unclear if metabolic syndrome (MS) is equal to type 2 diabetes mellitus (DM) in predicting cardiovascular disease (CVD) risk and mortality, and its prognostic value compared to Framingham risk model is controversial. We assessed mortality, CVD risk and prevalence in patients with DM and those without DM who met National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) MS criteria compared to patients without DM or MS. We analysed which component(s) of NCEP MS criteria had greatest predictive value for mortality.
Retrospective cohort analysis of 1189 DM, 1241 MS (fasting glucose < 126 mg/dl and > or =3 components NCEP-ATP III criteria) and 3023 non-DM/non-MS patients presented for baseline visit to Preventive Cardiology clinic between 1995 and 2006, whose subsequent vital status was determined for a median of 5.2 years. The association with mortality was determined by Cox proportional hazards models. The incremental predictive value of MS components was performed by concordance indexes.
DM group had highest mortality and CVD prevalence vs. MS and non-DM/non-MS groups respectively (all p < or = 0.001). Patients with MS criteria had increased CVD prevalence and 1.5-fold increased mortality vs. non-DM/non-MS group (all p < 0.02). In NCEP MS criteria, only fasting glucose significantly predicted mortality in MS group (p = 0.05). MS criteria predicted CVD prevalence in a parallel manner to Framingham risk score assessment. In a cohort of patients at high risk for CVD whose risk factors are being treated, presence of diabetes in addition to plasma glucose within NCEP MS criteria strongly predicts all-cause mortality.
The time may have come—or at least will soon arrive—when the diagnostic categories related to diabetes and its close relatives, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), should be reconsidered. IGT, IFG, and the combination of the two are now considered pre-diabetes because, compared with normal glucose tolerance, they signal an increased risk of developing diabetes (1). Before 1979, when the National Diabetes Data Group defined IGT (2) and declared it to be an official diagnostic category, one either did or did not have diabetes and nondiagnostic glucose levels were de facto “normal.” A middle ground was recognized by some physicians, but it was not enshrined in all epidemiological studies or in clinical practice.
The addition of IFG in 1997 for the purpose of creating a state equivalent to IGT both added to the middle ground and raised awareness and appreciation of intermediate levels of glucose intolerance (3). There was now a distinctive group of individuals whose fasting plasma glucose (FPG) lay between normal (<110 mg/dl) and the new 1997 lower diabetes cut point of 126 mg/dl and who may not meet the IGT criterion of 140–199 mg/dl 2 h after a standard oral glucose load of 75 g (3). A further refinement of IFG in 2003 altered the lower IFG cut point from 110 to 100 mg/dl, a change recommended to make both intermediate states equivalent and to define a more realistic upper limit of normal (4).
Recently, however, more and more studies have demonstrated that at glycemic levels above normal but within the range of either IFG or IGT, there is an increasing risk of crossing the diabetes line (FPG 126 mg/dl and/or a 2-h post–glucose load level of 200 mg/dl) within a few years (1). These latter numbers are based on the association of …
THE PURPOSE of the "Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" (JNC VI) is to provide guidance for primary care clinicians. The committee recognizes that the responsible clinician's judgment of the individual patient's needs remains paramount. Therefore, this national guideline should serve as a tool to be adapted and implemented in local and individual situations. Using evidence-based medicine and consensus, the report updates contemporary approaches to hypertension control. Among the issues covered are the important need for prevention of high blood pressure by improving lifestyles, the cost of health care, the use of self-measurement of blood pressure, the role of managed care in the treatment of high blood pressure, the introduction of new combination antihypertensive medications and angiotensin II receptor blockers, and strategies for improving adherence to treatment. The JNC VI report places more emphasis than earlier reports on absolute
To determine whether there are thresholds for fasting and for 2-h glucose above which the risk of death from all causes and from coronary heart disease (CHD) increases.
We studied 23-year mortality data from the Paris Prospective Study of the 7,018 men, aged 44-55 years, who were not known as diabetic at the baseline examination. The effect of glucose concentrations on mortality was studied using the observed relative risks and an age-adjusted Cox proportional hazards model.
For all causes of death, there were J-shaped relationships with both fasting and 2-h glucose concentrations, and the lowest observed death rates were in the intervals centered on 5.5 mmol/l for fasting glucose and 5.0 mmol/l for 2-h glucose. The death rates for CHD were low in this population: for fasting glucose, the hazards ratio was best modeled by a positive linear relationship; for 2-h glucose, it was modeled by a J-shaped curve and the lowest observed death rate was in the interval centered on 6.0 mmol/l.
In the Paris Prospective Study, there were no clear thresholds for fasting or 2-h glucose concentrations above which mortality sharply increased; in the upper levels of the glucose distributions, the risk of death progressively increased with increasing fasting and 2-h glucose concentrations.
To assess the relationship between nondiabetic glucose levels and cardio vascular risk.
Three independent searches using MEDLINE (1966-1996), followed by a manual search of the references from each retrieved article, were conducted by two physicians and one medical librarian. Data had to be reported in at least three quantiles or intervals so that the nature of the relationship between glucose and cardiovascular events (i.e., linear or nonlinear) could be explored, and to ensure that any incremental cardiovascular risk was consistent across quantiles or intervals.
Analyzed studies comprised 95,783 people (94% male) who had 3,707 cardiovascular events over 12.4 years (1,193,231 person-years). Studies reporting fasting glucose levels (n = 6), 2-h glucose levels (n = 7), 1-h glucose levels (n = 5), and casual glucose levels (n = 4) were included. The glucose load used varied from 50 to 100 g. The highest glucose interval for most studies included glucose values in the diabetic range. The relationship between glucose levels and the risk of a cardiovascular event was modeled for each study and the beta-coefficients were combined. Compared with a glucose level of 4.2 mmol/l (75 mg/dl), a fasting and 2-h glucose level of 6.1 mmol/dl (110 mg/dl) and 7.8 mmol/l (140 mg/dl) was associated with a relative cardiovascular event risk of 1.33 (95% CI 1.06-1.67) and 1.58 (95% CI 1.19-2.10), respectively.
The progressive relationship between glucose levels and cardiovascular risk extends below the diabetic threshold.
Because of the available conflicting epidemiological data, we investigated the possible impact of fasting blood glucose as a risk factor for cardiovascular death in nondiabetic men. This study reports the results from a 22-year prospective study on fasting blood glucose as a predictor of cardiovascular death.
Of the 1,998 apparently healthy nondiabetic men (aged 40-59 years), a total of 1,973 with fasting blood glucose < 110 mg/dl were included in the study in which also a number of conventional risk factors were measured at baseline.
After 22 years of follow-up, 483 men had died, 53% from cardiovascular diseases. After dividing men into quartiles of fasting blood glucose level, it was found that men in the highest glucose quartile (fasting blood glucose > 85 mg/dl) had a significantly higher mortality rate from cardiovascular diseases compared with those in the three lowest quartiles. Even after adjusting for age, smoking habits, serum lipids, blood pressure, forced expiratory volume in 1 s, and physical fitness (Cox model), the relative risk of cardiovascular death for men with fasting blood glucose > 85 mg/dl remained 1.4 (95% CI 1.04-1.8). Noncardiovascular deaths were unrelated to fasting blood glucose level.
Fasting blood glucose values in the upper normal range appears to be an important independent predictor of cardiovascular death in nondiabetic apparently healthy middle-aged men.
Background: Categorical definitions for glucose intolerance imply that risk thresholds exist, but metabolic risk for type 2 diabetes mellitus or cardiovascular disease may increase continuously as glucose intolerance increases. Objective: To examine the distributions of the following metabolic risk factors across the spectrum of glucose tolerance : overall and central obesity, hypertension, low levels of high-density lipoprotein cholesterol, and increased triglyceride and insulin levels. Design: Cross-sectional analysis. Setting: The community-based Framingham Offspring Study. Participants: 2583 adults without previously diagnosed diabetes. Measurements: Clinical data; fasting glucose, insulin, and lipid levels; and glucose and insulin levels taken 2 hours after oral challenge were collected from 1991 to 1993. Glucose tolerance was determined by 1980 World Health Organization criteria. Patients with normal glucose tolerance were categorized into quintiles of fasting glucose. The distributions of each metabolic risk factor and the metabolic sum of the six risk factors were assessed across seven categories from the lowest quintile of normal fasting glucose level through impaired glucose tolerance and previously undiagnosed diabetes. Results: The mean age of patients was 54 years (range, 26 to 82 years); 52.7% of patients were women. Glucose tolerance testing found that 12.7% of patients had impaired glucose tolerance and 4.8% had previously undiagnosed diabetes. Multivariable-adjusted mean measures of risk factors and odds ratios for obesity, elevated waist-tohip ratio, hypertension, low levels of high-density lipoprotein cholesterol, elevated triglyceride levels, and hyperinsulinemia showed continuous increases across the spectrum of nondiabetic glucose tolerance. Although a threshold effect near the upper range of nondiabetic glucose tolerance could not be ruled out for triglyceride levels in men and for insulin levels 2 hours after oral challenge in men and women, no other metabolic risk factors showed clear evidence of thresholds for increased risk. Conclusions: Metabolic risk factors for type 2 diabetes mellitus and for cardiovascular disease worsen continuously across the spectrum of glucose tolerance categories, beginning in the lowest quintiles of normal fasting glucose level.
The Caerphilly and Speedwell studies have previously reported the predictive power of heat-precipitation, nephelometric, fibrinogen for 10-year incidence of ischaemic heart disease. A Clauss, clotting time, fibrinogen was also measured at baseline, but has not previously been reported. The predictive power of the two assays is compared. Both methods were employed on fasting blood samples from a total of 4391 men aged 45–63 years. Over the following 10 years 533 (12%) developed major ischaemic heart disease. Nephelometric fibrinogen was higher by 0.33 g/l among the men who developed disease; clottable fibrinogen was higher by 0.20 g/l. This difference is statistically significant (P = 0.01). Relative odds of developing heart disease increased steadily to 3.53 (P < 0.0001) in the 20% of men with the highest nephelometric fibrinogen; for clottable fibrinogen the corresponding relative odds increased to 2.24 (P < 0.0001). When both measures of fibrinogen were included in logistic regression models together with age and smoking habit, the trend for incidence to increase with increasing nephelometric fibrinogen remained highly significant (P < 0.0001), whereas for the Clauss fibrinogen the trend almost entirely disappeared (P = 0.37).
We conclude that functional assays of clottable fibrinogen may not reflect all of the mechanisms which mediate the association between fibrinogen and cardiovascular disease and that assays of both ‘heat precipitable’ and ‘clottable’ fibrinogen should be included in all future prospective studies.
High-performance liquid chromatography with fluorescence detection has been utilized for the rapid determination of total homocysteine, cysteine, and cysteinylglycine in human serum and plasma. Our earlier procedure (Anal Biochem 1989;178:208), which used monobromobimane to specifically derivatize thiols, has been extensively modified to allow for rapid processing of samples. As a result, > 80 samples a day can be assayed for total homocysteine, cysteine, and cysteinylglycine. The method is sensitive (lower limit of detection < or = 4 pmol in the assay) and precise (intra- and interassay CV for homocysteine, 3.31% and 4.85%, respectively). Mean total homocysteine concentrations in plasma and serum were significantly different, both from healthy male donors (9.26 and 12.30 mumol/L, respectively; P < 0.001) and healthy female donors (7.85 and 10.34 mumol/L, respectively; P < 0.001). The differences in total homocysteine between sexes were also significant (P = 0.002 for both plasma and serum). Similar differences were found for cysteine and cysteinylglycine. We found a significant inverse correlation between serum cobalamin and total homocysteine in men (P = 0.0102) and women (P = 0.0174). Serum folate also inversely correlated with total homocysteine in both sexes.
Categorical definitions for glucose intolerance imply that risk thresholds exist, but metabolic risk for type 2 diabetes mellitus or cardiovascular disease may increase continuously as glucose intolerance increases.
To examine the distributions of the following metabolic risk factors across the spectrum of glucose tolerance: overall and central obesity, hypertension, low levels of high-density lipoprotein cholesterol, and increased triglyceride and insulin levels.
Cross-sectional analysis.
The community-based Framingham Offspring Study.
2583 adults without previously diagnosed diabetes.
Clinical data; fasting glucose, insulin, and lipid levels; and glucose and insulin levels taken 2 hours after oral challenge were collected from 1991 to 1993. Glucose tolerance was determined by 1980 World Health Organization criteria. Patients with normal glucose tolerance were categorized into quintiles of fasting glucose. The distributions of each metabolic risk factor and the metabolic sum of the six risk factors were assessed across seven categories from the lowest quintile of normal fasting glucose level through impaired glucose tolerance and previously undiagnosed diabetes.
The mean age of patients was 54 years (range, 26 to 82 years); 52.7% of patients were women. Glucose tolerance testing found that 12.7% of patients had impaired glucose tolerance and 4.8% had previously undiagnosed diabetes. Multivariable-adjusted mean measures of risk factors and odds ratios for obesity, elevated waist-to-hip ratio, hypertension, low levels of high-density lipoprotein cholesterol, elevated triglyceride levels, and hyperinsulinemia showed continuous increases across the spectrum of nondiabetic glucose tolerance. Although a threshold effect near the upper range of nondiabetic glucose tolerance could not be ruled out for triglyceride levels in men and for insulin levels 2 hours after oral challenge in men and women, no other metabolic risk factors showed clear evidence of thresholds for increased risk.
Metabolic risk factors for type 2 diabetes mellitus and for cardiovascular disease worsen continuously across the spectrum of glucose tolerance categories, beginning in the lowest quintiles of normal fasting glucose level.
To assess the relationship between dysglycemia and myocardial infarction in nondiabetic individuals.
Nondiabetic hyperglycemia may be an important cardiac risk factor. The relationship between myocardial infarction and glucose, insulin, abdominal obesity, lipids and hypertension was therefore studied in South Asians-a group at high risk for coronary heart disease and diabetes.
Demographics, waist/hip ratio, fasting blood glucose (FBG), insulin, lipids and glucose tolerance were measured in 300 consecutive patients with a first myocardial infarction and 300 matched controls.
Cases were more likely to have diabetes (OR 5.49; 95% CI 3.34, 9.01), impaired glucose tolerance (OR 4.08; 95% CI 2.31, 7.20) or impaired fasting glucose (OR 3.22; 95% CI 1.51, 6.85) than controls. Cases were 3.4 (95% CI 1.9, 5.8) and 6.0 (95% CI 3.3, 10.9) times more likely to have an FBG in the third and fourth quartile (5.2-6.3 and >6.3 mmol/1); after removing subjects with diabetes, impaired glucose tolerance and impaired fasting glucose, cases were 2.7 times (95% CI 1.5-4.8) more likely to have an FBG >5.2 mmol/l. A fasting glucose of 4.9 mmol/l best distinguished cases from controls (OR 3.42; 95% CI 2.42, 4.83). Glucose, abdominal obesity, lipids, hypertension and smoking were independent multivariate risk factors for myocardial infarction. In subjects without glucose intolerance, a 1.2 mmol/l (21 mg/dl) increase in postprandial glucose was independently associated with an increase in the odds of a myocardial infarction of 1.58 (95% CI 1.18, 2.12).
A moderately elevated glucose level is a continuous risk factor for MI in nondiabetic South Asians with either normal or impaired glucose tolerance.
This study was designed to examine the association of heart rate variability (HRV) with blood glucose levels in a large community-based population. Previous reports have shown HRV to be reduced in diabetics, suggesting the presence of abnormalities in neural regulatory mechanisms. There is scant information about HRV across the spectrum of blood glucose levels in a population-based cohort. One thousand nine hundred nineteen men and women from the Framingham Offspring Study, who underwent ambulatory electrocardiographic recordings at a routine examination, were eligible. HRV variables included the SD of normal RR intervals (SDNN), high-frequency (HF, 0.15 to 0.40 Hz) and low-frequency (LF, 0.04 to 0.15 Hz) power, and LF/HF ratio. Fasting plasma glucose levels were used to classify subjects as normal (<110 mg/dl; n = 1, 779), as having impaired fasting glucose levels (110 to 125 mg/dl; n = 56), and as having diabetes mellitus (DM >/=126 mg/dl or receiving therapy; n = 84). SDNN, LF and HF power, and LF/HF ratio were inversely related to plasma glucose levels (p <0.0001). SDNN and LF and HF powers were reduced in DM subjects (4.28 +/- 0.03, 6.03 +/- 0. 08, and 4.95 +/- 0.09) and in subjects with impaired fasting glucose levels (4.37 +/- 0.04, 6.26 +/- 0.10, and 5.06 +/- 0.11) compared with those with normal fasting glucose (4.51 +/- 0.01, 6.77 +/- 0.02, and 5.55 +/- 0.02, all p <0.005), respectively. After adjusting for covariates (age, sex, heart rate, body mass index, antihypertensive and cardiac medications, systolic and diastolic blood pressures, smoking, and alcohol and coffee consumption), LF power and LF/HF ratio were lower in DM subjects than in those with normal fasting glucose (p <0.005). HRV is inversely associated with plasma glucose levels and is reduced in diabetics as well as in subjects with impaired fasting glucose levels. Additional research is needed to determine if low HRV contributes to the increased cardiovascular morbidity and mortality described in subjects with hyperglycemia.
The relationship between glucose and incident cardiovascular events ©2002 by Excerpta Medica, Inc. All rights reserved
- Coutinho M H Gerstein
- Wang Y Yusuf
Coutinho M, Gerstein H, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. Diabetes Care 1999;22:233–240. ©2002 by Excerpta Medica, Inc. All rights reserved. 0002-9149/02/$–see front matter The American Journal of Cardiology Vol. 89 March 1, 2002 PII S0002-9149(01)02303-7
The relationship between glucose and incident cardiovascular events
- Coutinho
Manual of Laboratory Operations, Lipid and Lipoprotein Analysis
- Programs
Rapid HPLC determination of total homocysteine and other thiols in serum and plasma
- Jacobsen
Fasting blood glucose
- Bjornholt
Glucose tolerance and cardiovascular mortality