Endothelial Dysfunction in Impaired Fasting Glycemia, Impaired Glucose Tolerance, and Type 2 Diabetes Mellitus

doi:10.1016/j.amjcard.2008.03.087

The American Journal of Cardiology

Volume 102, Issue 4, 15 August 2008, Pages 497-498

https://doi.org/10.1016/j.amjcard.2008.03.087 Get rights and content

The aim of this study was to evaluate whether abnormal endothelial function is present in early stages of diabetes, such as impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Endothelial function was assessed by measuring flow-mediated dilatation and nitrate-induced dilatation of the brachial artery using high-resolution ultrasound. Fasting serum lipid levels were determined, and glucose and insulin values in response to a 75-g oral glucose load were also measured. The results showed the following new findings: (1) compared with subjects with normal glucose tolerance, those with IFG and IGT had impaired flow-mediated dilatation, more remarkable in subjects with type 2 diabetes mellitus than those with IFG and IGT, and (2) flow-mediated dilatation was inversely and strongly related to the extent of hyperglycemia. In conclusion, endothelial dysfunction is present in subjects with IGT and IFG, indicating endothelial damage in these stages.

Section snippets

Methods and Results

Subjects were divided into different categories (46 with normal glucose tolerance, 30 with IFG, 38 with IGT, and 44 with T2DM) on the basis of fasting plasma glucose concentrations and 2-hour plasma glucose concentrations during the standard 75-g oral glucose tolerance test (OGTT; 2-hour plasma glucose). IFG was defined as fasting plasma glucose of 5.6 to <7.0 mmol/L and OGTT 2-h plasma glucose <7.8 mmol/L. IGT was defined as OGTT 2-hour plasma glucose of 7.8 to <11.1 mmol/L and fasting plasma

Discussion

The results of this study show the following new findings: (1) compared with control subjects, subjects with IFG and IGT had impaired FMD, more remarkable in those with T2DM than those with IFG and IGT, and (2) FMD was inversely and strongly related to the extent of hyperglycemia.

The endothelium is the common target of all cardiovascular risk factors, and functional impairment of the vascular endothelium in response to injury occurs long before the development of visible atherosclerosis.⁶ The

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Poor glycemic control has been linked to psychiatric symptoms. However, studies investigating the relationship between glycemic variability (GV) and depression and anxiety disorders are limited. We investigated the association of GV with depression and anxiety disorders. In addition, the relationship between trends in fasting plasma glucose (FPG) levels and these disorders were explored.
We analyzed the National Health Insurance Service-National Sample Cohort database (2002−2013) with 151,814 participants who had at least three health screenings between 2002 and 2010. Visit-to-visit FPG variability was measured as variability independent of the mean (VIM). Depression and anxiety disorders were diagnosed using ICD-10 codes (F41 for anxiety and F32 or F33 for depression) after index date. We analyzed the association between GV and incidences of these disorders using Kaplan-Meier and Cox proportional hazards methods. Trajectory analysis was conducted to explore the relationship between FPG trends and these disorders.
During follow-up, 7166 and 14,149 patients were newly diagnosed with depression and anxiety disorders, respectively. The highest quartile group of FPG-VIM had a greater incidence of depression and anxiety than the lowest quartile group, with adjusted hazard ratios of 1.09 (95 % confidence interval [CI]: 1.02–1.17) and 1.08 (95 % CI: 1.03–1.14). Group with persistent hyperglycemia, identified through trajectory clustering of FPG levels, had a 1.43-fold increased risk of depression compared to those with consistently low FPG levels.
Potential selection bias by including participants with at least three health screenings.
High GV and persistent hyperglycemia are associated with increased incidence of depression and anxiety disorders.
Prediabetes versus type 2 diabetes in patients with acute myocardial infarction and current smoking
2022, American Journal of the Medical Sciences
Smoking is linked with increased risk of cardiovascular events among diabetic patients. Prediabetes is associated with increased risk for microvascular and macrovascular complications. We compared the 2-year clinical outcomes of current smoking between prediabetic and type 2 diabetes mellitus (T2DM) patients with acute myocardial infarction (AMI) after newer-generation drug-eluting stent (DES) implantation.
A total of 5161 AMI patients who were currently smoking were classified into normoglycemia (group A: 1,416), prediabetes (group B: 1,740), and T2DM (group C: 2,005) groups. The primary endpoint was major adverse cardiac events (MACEs), defined as all-cause death, recurrent myocardial infarction and any repeat revascularization. The secondary endpoint was the occurrence of stent thrombosis (ST) and stroke.
The cumulative incidences of all primary and secondary endpoints including MACEs (adjusted hazard ratio [aHR]: 1.150; 95% confidence interval [CI]: 0.891–1.484; P = 0.284), ST, and stroke were similar between group B and group C. The cumulative incidences of MACEs (aHR: 1.385; 95% CI: 1.007–1.904; P = 0.045) and all-cause death or MI were significantly higher in group B than in group A. The cumulative incidences of MACEs (aHR: 1.572; 95% CI: 1.157–2.137; P = 0.004), all-cause death, Re-MI, and all-cause death or MI were significantly higher in group C than in group A.
Current smoking leads to worse clinical outcomes in patients with AMI and prediabetes, and thus, similarly to T2DM patients, more attention and more intensive treatment strategy including quitting smoking would be advantageous.
Coronary artery calcification, carotid intima-media thickness and cardiac dysfunction in young adults with type 2 diabetes mellitus
2020, Journal of Diabetes and its Complications
Citation Excerpt :
Thus CIMT, rather than CAC score, may be a more appropriate surrogate marker of subclinical atherosclerosis in young patients with T2DM. Endothelial dysfunction can occur early in the process of atherosclerosis; even present in patients with impaired glucose tolerance.31 Our study supports the findings of previous studies where a lower FMD was found in patients with T2DM.32,33
Cardiovascular diseases (CVD) are the major causes of mortality in patients with type 2 diabetes mellitus (T2DM). There is paucity of information on prevalence of subclinical atherosclerosis and cardiac dysfunction in young adults with T2DM. This study aimed to assess the prevalence of subclinical atherosclerosis and cardiac dysfunction in young adults with T2DM, asymptomatic for CVD.
Sixty-two patients with T2DM, age between 30 and 50 years were evaluated for coronary artery calcium (CAC) score, carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD) at the brachial artery. All were subjected to 2D-color Doppler echocardiography, electrocardiography and testing for serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP). The results were compared with those in 60 age, sex and BMI-matched healthy controls.
Prevalence of a positive CAC score was comparable among subjects with and without T2DM (14.5% vs 11.7%). Patients with T2DM had a significantly higher CIMT (0.54 ± 0.15 vs 0.49 ± 0.10 mm, p = 0.01), left ventricular (LV) mass (170 ± 36 vs 147 ± 23 g, p < 0.001), heart rate (83 ± 13 vs 74 ± 11, p < 0.001) and QTc interval (402 ± 20 vs 382 ± 21 ms, p < 0.001) compared to controls. FMD was lower in patients with T2DM compared to controls (9.1 ± 4.4% vs 10.7 ± 3.9%, p = 0.04). There was a higher prevalence of LV hypertrophy (37% vs 7%, p < 0.001) and diastolic dysfunction (7% vs 0) in patients with T2DM compared to controls. None of the participants had systolic dysfunction. Hypertension (42 vs 7%, p < 0.001) and metabolic syndrome (76 vs 35%, p < 0.001) were more prevalent in the patient group. In the multivariate analysis, age was the lone predictor of CIMT and FMD; while T2DM and male gender were the independent predictors of LV mass.
Young adults with T2DM, asymptomatic for CVD had a higher prevalence of CVD risk factors, LV hypertrophy and diastolic dysfunction. A higher CIMT and LV mass, and a lower FMD were noted in patients with T2DM. CAC score was comparable between the groups and thus may not be a useful tool for assessment of subclinical atherosclerosis in this cohort, where CIMT and FMD may be more appropriate.
Association between glycemic load and cognitive function in community-dwelling older adults: Results from the Brain in Motion study
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Impaired glucose tolerance is a risk factor for non-age-related cognitive decline and is also associated with measures of physical activity (PA) and cardiorespiratory fitness (CRF). A low glycemic load (GL) diet can aid in the management of blood glucose levels, but little is known about its effect on cognition with poor glucoregulation.
We assessed the relation between GL and cognitive function by glucoregulation and possible mediatory effects by CRF and PA in older adults from the Brain in Motion Study.
A cross-sectional analysis of 194 cognitively healthy adults aged ≥55 years (mean = 65.7, SD = 6.1) was conducted. GL was assessed using a quantitative food frequency questionnaire, and glucoregulation was characterized on the HOMA-IR index. Subjects also completed a cognitive assessment, CRF testing, a validated self-reported PA questionnaire, and a blood draw. Multiple linear regression models adjusted for significant covariates were used to evaluate the relation between GL and cognition, and mediation by CRF and PA was also assessed.
GL was inversely associated with global cognition (β = −0.014; 95% CI −0.024, −0.004) and figural memory (β = −0.035; 95% CI −0.052, −0.018) in subjects with poor glucoregulation. Neither CRF nor PA mediated these relations. In subjects with good glucoregulation, no association was found between GL and cognitive function (p > 0.05).
A low GL diet is associated with better cognitive function in older adults with poor glucoregulation. This study provides supportive evidence for the role of GL in maintaining better cognitive function during the aging process.
Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms
2018, Canadian Journal of Cardiology
Citation Excerpt :
This profile is associated with increased production of leptin, decreased production of adiponectin, higher circulating levels of nonesterified fatty acids (NEFAs), and activation of mitochondrial oxidative stress pathways in vascular endothelial cells.7 These proinflammatory and metabolic consequences of obesity and insulin resistance result in endothelial dysfunction, a key antecedent and modulator of atherosclerosis that has been demonstrated not only in hypertension but also in prediabetes,21 first-degree relatives of individuals with T2D,22 and even insulin-resistant healthy individuals.22,23 It is characterized by disruption of the intricate physiological balance between vasoconstrictors (endothelin, angiotensin II) and vasodilators (nitric oxide, prostacyclin), growth promoting and inhibitory factors, proatherogenic and antiatherogenic factors, and procoagulant and anticoagulant factors.24,25
Hypertension and type 2 diabetes are common comorbidities. Hypertension is twice as frequent in patients with diabetes compared with those who do not have diabetes. Moreover, patients with hypertension often exhibit insulin resistance and are at greater risk of diabetes developing than are normotensive individuals. The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by hypertension. Accordingly, diabetes and hypertension are closely interlinked because of similar risk factors, such as endothelial dysfunction, vascular inflammation, arterial remodelling, atherosclerosis, dyslipidemia, and obesity. There is also substantial overlap in the cardiovascular complications of diabetes and hypertension related primarily to microvascular and macrovascular disease. Common mechanisms, such as upregulation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, and activation of the immune system likely contribute to the close relationship between diabetes and hypertension. In this article we discuss diabetes and hypertension as comorbidities and discuss the pathophysiological features of vascular complications associated with these conditions. We also highlight some vascular mechanisms that predispose to both conditions, focusing on advanced glycation end products, oxidative stress, inflammation, the immune system, and microRNAs. Finally, we provide some insights into current therapies targeting diabetes and cardiovascular complications and introduce some new agents that may have vasoprotective therapeutic potential in diabetes.
L’hypertension et le diabète de type 2 sont des affections concomitantes fréquentes. L’hypertension est deux fois plus fréquente chez les patients atteints de diabète que chez ceux qui n’en sont pas atteints. De plus, les patients atteints d’hypertension sont souvent résistants à l’insuline et sont plus susceptibles de souffrir de diabète que les personnes normotendues. Chez les diabétiques, la principale cause de morbidité et de mortalité est la maladie cardiovasculaire, qui est exacerbée par l’hypertension. En conséquence, le diabète et l’hypertension sont étroitement interreliés en raison de facteurs de risques similaires, comme la dysfonction endothéliale, l’inflammation vasculaire, le remodelage artériel, l’athérosclérose, la dyslipidémie et l’obésité. On observe un chevauchement important entre les complications cardiovasculaires du diabète et celles de l’hypertension liées principalement à des maladies microvasculaires et macrovasculaires. Des mécanismes communs, comme une stimulation du système rénine-angiotensine-aldostérone, un stress oxydatif, une inflammation et une activation du système immunitaire, sont susceptibles de contribuer à la relation étroite entre le diabète et l’hypertension. Dans cet article, nous abordons le diabète et l’hypertension comme des affections concomitantes et nous parlons des caractéristiques physiopathologiques des complications vasculaires associées à ces affections. Nous soulignons également certains mécanismes vasculaires qui prédisposent à ces deux affections, en mettant l’accent sur les produits finaux de glycation avancée, le stress oxydatif, l’inflammation, le système immunitaire et les micro-ARN. Finalement, nous présentons certaines connaissances sur les traitements actuels ciblant le diabète et les complications cardiovasculaires et nous présentons de nouveaux agents qui pourraient avoir un pouvoir vasoprotecteur chez les patients diabétiques.
Subclinical vascular disease in patients with diabetes is associated with insulin resistance
2019, Diabetes and Metabolic Syndrome: Clinical Research and Reviews
Citation Excerpt :
Likewise, patients with T2D show impaired forearm flow-mediated vasodilation compared to healthy individuals. Further, flow-mediated vasodilation is impaired in normotensive and normoglycemic first-degree relatives of patients with T2D compared to control subjects [21–24]. In a cross-sectional study including 800 asymptomatic adults with no clinical evidence of vascular disease (102 patients with T2D), multivariate analyses show that diabetes is an independent predictor of reduced vasodilatation in response to nitroglycerin [25].
Patients with diabetes experience increased cardiovascular risk that is not fully explained by deficient glycemic control or traditional cardiovascular risk factors such as smoking and hypercholesterolemia. Asymptomatic patients with diabetes show structural and functional vascular damage that includes impaired vasodilation, arterial stiffness, increased intima-media thickness and calcification of the arterial wall. Subclinical vascular injury associated with diabetes predicts subsequent manifestations of cardiovascular disease, such as ischemic heart disease, peripheral artery disease and stroke. Noninvasive detection of subclinical vascular disease is commonly used to estimate cardiovascular risk associated to diabetes. Longitudinal studies in normotensive subjects show that arterial stiffness at baseline is associated with a greater risk for future hypertension independently of established risk factors. In patients with type 2 diabetes, vascular disease begins to develop during the latent phase of insulin resistance, long before the clinical diagnosis of diabetes. In contrast, patients with type 1 diabetes do not manifest vascular injury when they are first diagnosed due to insulin deficiency, as they lack the preceding period of insulin resistance. These findings suggest that insulin resistance plays an important role in the development of early vascular disease associated with diabetes. Cross-sectional and prospective studies confirm that insulin resistance is associated with subclinical vascular injury in patients with diabetes, independently of standard cardiovascular risk factors. Asymptomatic vascular disease associated with diabetes begins to occur early in life having been documented in children and adolescents. Insulin resistance should be considered a therapeutic target in order to prevent the vascular complications associated with diabetes.

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MiscellaneousEndothelial Dysfunction in Impaired Fasting Glycemia, Impaired Glucose Tolerance, and Type 2 Diabetes Mellitus

Section snippets

Methods and Results

Discussion

Diabetes Res Clin Pract

Endothelial dysfunction in type 2 diabetes: effect of antioxidants

Rev Port Cardiol

Approaches to prevention of cardiovascular complications and events in diabetes mellitus

Drugs

Current concepts in diabetic microvascular dysfunction

J Am Podiatr Med Assoc

Folic acid does not improve endothelial function in obese children and adolescents

Diabetes Care

Miscellaneous
Endothelial Dysfunction in Impaired Fasting Glycemia, Impaired Glucose Tolerance, and Type 2 Diabetes Mellitus