Endothelial inflammation in insulin resistance

doi:10.1016/S0140-6736(05)17912-4

The Lancet

Volume 365, Issue 9459, 12–18 February 2005, Pages 610-612

https://doi.org/10.1016/S0140-6736(05)17912-4 Get rights and content

Summary

Context

Type 2 diabetes and attendant cardiovascular morbidity are becoming major health concerns globally. Obesity-related type 2 diabetes is rapidly rising in prevalence, probably largely because of increased longevity and sedentary lifestyles. Insulin resistance and type 2 diabetes are associated with increased coronary heart disease, but the severity of glycaemia during the diabetic phase can only to a minor extent explain the increased risk. Increased levels of the acute-phase inflammatory marker, C-reactive protein (CRP), are related to insulin resistance and the metabolic syndrome, suggesting a role for chronic low-grade inflammation. CRP levels might predict the development of type 2 diabetes.

Starting point

Subodh Verma and associates (Circulation 2004; 109: 2058–67) recently showed that CRP attenuates the survival, differentiation, and function of endothelial progenitor cells, partly by CRP reducing expression of endothelial nitric-oxide synthase. Rosiglitazone, a peroxisome-proliferator-activator receptor γ agonist, inhibits the negative effects of CRP on endothelial progenitor cells. The results are consistent with the suggestion that CRP directly promotes atherosclerotic processes and endothelial cell inflammation. CRP might thus directly trigger the development of a proinflammatory and proatherosclerotic state, leading to atherothrombosis.

Where next

Cell-surface CRP receptors and signalling pathways need to be characterised. From such study might come novel drugs that will defer proinflammatory reactions leading to insulin resistance and atherothrombosis.

Section snippets

Epidemiological studies

Population studies show strong correlation between proinflammatory biomarkers (such as CRP, interleukin 6, and tumour necrosis factor α) and perturbations in glucose homoeostasis, obesity, and atherosclerosis.10, 11, 12, 13 CRP levels might be independently related to the degree of insulin resistance, independently of obesity.14, 15 Plasma levels of high-sensitive CRP predict future cardiovascular risk, even in apparently healthy individuals.¹² In a post-hoc analysis of the predictive value of

Interventions and mechanisms

CAPPP was the first controlled study to show that captopril, an angiotensin-converting-enzyme inhibitor, decreased the risk of developing type 2 diabetes in hypertensive patients.¹⁹ The study was designed to compare the effect of captopril with conventional antihypertensive treatment on cardiovascular morbidity and mortality. There were 11% fewer patients with new-onset type 2 diabetes in the captopril group than in those on conventional treatment.

These results were confirmed in HOPE, in which

Clinical perspectives

That subclinical chronic inflammation might be an important pathogenetic factor in the development of insulin resistance and type 2 diabetes opens new perspectives for diagnosis and treatment of early insulin resistance and incipient glucose intolerance. More specific and sensitive biomarkers should be identified, to predict early disturbances in insulin sensitivity and cardiovascular risk. Inflammatory signalling pathways need to be explored in greater detail, as possible drug targets.

We have

References (36)

P Dandona et al.
Inflammation: the link between insulin resistance, obesity and diabetes
Trends Immunol
(2004)
L Hansson et al.
Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension
Lancet
(1999)
MA Pfeffer et al.
Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme
Lancet
(2003)
S Yusuf et al.
Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial
Lancet
(2003)
P Zimmet et al.
Global and societal implications of the diabetes epidemic
Nature
(2001)
P Dandona et al.
The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complications in type 2 diabetes
J Clin Endocrinol Metab
(2003)
V Fonseca et al.
Nontraditional risk factors for cardiovascular disease in diabetes
Endocr Rev
(2004)
P Libby
Inflammation in atherosclerosis
Nature
(2002)
JM Fernandez-Real et al.
Insulin resistance and chronic cardiovascular inflammatory syndrome
Endocr Rev
(2003)
S Verma et al.
C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function
Circulation
(2004)

S Verma et al.

Endothelial function testing as a biomarker of vascular disease

Circulation

(2003)

S Verma et al.

C-reactive protein and atherothrombosis

Am J Physiol Regul Integr Comp Physiol

(2003)

TS Han et al.

Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study

Diabetes Care

(2002)

BB Duncan et al.

Low-grade systemic inflammation and the development of type 2 diabetes

Diabetes

(2003)

CJ Lyon et al.

Minireview: adiposity, inflammation, and atherogenesis

Endocrinology

(2003)

AD Pradhan et al.

C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus

JAMA

(2001)

A Festa et al.

Chronic subclinical inflammation as part of the insulin resistance syndrome

Circulation

(2000)

T McLaughlin et al.

Differentiation between obesity and insulin resistance in the association with C-reactive protein

Circulation

(2002)

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Neither erupted nor impacted third molars were associated with high-sensitivity C-reactive protein, white blood cell count, or fibrinogen as markers for systemic inflammation. Participants with erupted third molars had markedly lower serum levels of leptin (β coefficient, −2.47; 95% confidence interval [CI], −4.47 to −0.48), angiopoietin-2 (β coefficient, −135.1; 95% CI, 248.6 to −21.5), and ratio of angiopoietin-2 to tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2 (β coefficient, −6.57; 95% CI, −13.06 to −00.7) than participants without third molars. No such associations were observed for impacted third molars.
The present results did not substantiate a relation between third molars and an increase in systemic inflammatory markers. Therefore, dental practitioners should be careful when considering this as the only indication for removal of third molars, especially in medically compromised patients. The results of this study showed that participants with erupted third molars had lower levels of messenger peptide hormones, such as leptin and angiopoetin-2.
Combined Influence of Insulin Resistance and Inflammatory Biomarkers on Type 2 Diabetes: A Population-based Prospective Cohort Study of Inner Mongolians in China
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This prospective study was designed to examine the combined influence of insulin resistance (IR) and inflammatory biomarker levels on type 2 diabetes mellitus (T2DM) among 1,903 Inner Mongolians. During follow-up, 205 (10.77%) participants developed T2DM, and the incidence of T2DM was higher among subjects with IR, elevated C-reactive protein (CRP), elevated sICAM-1, elevated sE-selectin, or the coexistences of IR with elevated CRP, elevated sICAM-1, elevated sE-selectin, and elevated angiotensin II (all P < 0.05) compared with patients without IR or any elevated biomarkers. In multivariate analysis, the odd ratios [OR, (95% confidence intervals)] for these conditions were 1.944 (1.405–2.691), 2.003 (1.449–2.767), 1.706 (1.232–2.362), 1.560 (1.123–2.165), 2.708 (1.809–4.054), 1.885 (1.155–3.078), 2.101 (1.340–3.295), and 2.260 (1.426–3.582), respectively. Our findings demonstrated that IR and elevated inflammatory biomarkers were associated with T2DM, and that the coexistence of IR and elevated inflammatory biomarkers increased the risk of T2DM.
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Advanced oxidation protein products (AOPPs) are used as a marker to estimate oxidative stress in plasma proteins. Oxidative stress is considered a factor of cardiovascular risk (CVRF) related to increased blood pressure, and dyslipidaemia. The aim of this study was to evaluate the association between plasma AOPPs and CVRF in apparently healthy young adults.
A prospective cross-sectional study was conducted on 120 students of the Faculty of Chemical-Pharmacobiology of the UMSNH. Body mass index (BMI) and blood pressure were determined. A blood specimen was also collected to quantify AOPPs, glucose, total cholesterol, lipoproteins (high, low, and very low density), and triglycerides.
Differences were observed in the groups with and without CVRF, with significant differences in BMI, waist, body fat (P < .05), and lipid profile (P < .0001). AOPPs were higher in the group of young people with three and four CVRF (F: 4.651; P = .002). A negatively correlation was found between AOPPs and LDL cholesterol (r = –0.364; P = .0001).
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Rapid ReviewEndothelial inflammation in insulin resistance

Summary

Context

Starting point

Where next

Section snippets

Epidemiological studies

Interventions and mechanisms

Clinical perspectives

Trends Immunol

Lancet

Lancet

Lancet

Global and societal implications of the diabetes epidemic

Nature

The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complications in type 2 diabetes

J Clin Endocrinol Metab

Nontraditional risk factors for cardiovascular disease in diabetes

Endocr Rev

Inflammation in atherosclerosis

Nature

Insulin resistance and chronic cardiovascular inflammatory syndrome

Endocr Rev

C-reactive protein attenuates endothelial progenitor cell survival, differentiation, and function

Circulation

Endothelial function testing as a biomarker of vascular disease

Circulation

C-reactive protein and atherothrombosis

Am J Physiol Regul Integr Comp Physiol

Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study

Diabetes Care

Low-grade systemic inflammation and the development of type 2 diabetes

Diabetes

Minireview: adiposity, inflammation, and atherogenesis

Endocrinology

C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus

JAMA

Chronic subclinical inflammation as part of the insulin resistance syndrome

Circulation

Differentiation between obesity and insulin resistance in the association with C-reactive protein

Circulation

Rapid Review
Endothelial inflammation in insulin resistance