Evidence of increased inflammation and microcirculatory abnormalities in patients with type 1 diabetes and their role in microvascular complications

Sridevi Devaraj, Anthony T. Cheung, Ishwarlal Jialal, Steven C. Griffen, Danh Nguyen, Nicole Glaser, Thomas Aoki

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

OBJECTIVE - Type 1 diabetes is associated with increased microvascular complications and inflammation. The monocyte-macrophage is a pivotal cell in atherogenesis. There are scanty data on noninvasive measures of microvascular abnormalities and inflammation in type 1 diabetic subjects with microvascular complications. Thus, we examined systemic and cellular biomarkers of inflammation in type 1 diabetic patients with microvascular complications (T1DM-MV patients) and type 1 diabetic patients without microvascular complications (T1DM patients) compared with matched control subjects and determined the microcirculatory abnormalities in the T1DM and T1DM-MV patients using computer-assisted intravital microscopy (CAIM). RESEARCH DESIGN AND METHODS - Fasting blood, 24-h urine, and CAIM measurements were obtained from the T1DM and T1DM-MV patients and matched control subjects. C-reactive protein, E-selectin, nitrotyrosine, monocyte superoxide, and cytokines were elevated in the T1DM and T1DM-MV patients compared with control subjects (P < 0.01). RESULTS - Severity index, as assessed by CAIM, was significantly increased in the T1DM and T1DM-MV patients compared with the control subjects (P < 0.001). There was a significant increase in C-reactive protein, nitrotyrosine, vascular cell adhesion molecule and monocyte superoxide anion release, and interleukin-1 release in T1DM-MV compared with T1DM patients (P < 0.05). T1DM-MV patients had significantly increased CAIM severity index and microalbumin-to-creatinine ratio compared with T1DM patients (P < 0.05). Furthermore, pp38MAPK, pp65, and pERK activity were significantly increased in monocytes from the T1DM and T1DM-MV patients compared with those from the controls subjects, and pp38MAPK and pp65 activity were significantly increased in the T1DM-MV compared with the T1DM patients (P < 0.01). CONCLUSIONS - T1DM-MV patients have increased inflammation compared with T1DM patients. CAIM provides an effective biomarker of microvascular complications, since it is significantly elevated in T1DM-MV compared with T1DM patients and can be monitored following therapies targeted at improving inflammation and/or microvascular complications of type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)2790-2796
Number of pages7
JournalDiabetes
Volume56
Issue number11
DOIs
StatePublished - Nov 2007

Fingerprint

Type 1 Diabetes Mellitus
Inflammation
Monocytes
Superoxides
C-Reactive Protein
Biomarkers
E-Selectin
Vascular Cell Adhesion Molecule-1
Interleukin-1
Fasting
Creatinine
Atherosclerosis
Research Design

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Evidence of increased inflammation and microcirculatory abnormalities in patients with type 1 diabetes and their role in microvascular complications. / Devaraj, Sridevi; Cheung, Anthony T.; Jialal, Ishwarlal; Griffen, Steven C.; Nguyen, Danh; Glaser, Nicole; Aoki, Thomas.

In: Diabetes, Vol. 56, No. 11, 11.2007, p. 2790-2796.

Research output: Contribution to journalArticle

Devaraj, Sridevi ; Cheung, Anthony T. ; Jialal, Ishwarlal ; Griffen, Steven C. ; Nguyen, Danh ; Glaser, Nicole ; Aoki, Thomas. / Evidence of increased inflammation and microcirculatory abnormalities in patients with type 1 diabetes and their role in microvascular complications. In: Diabetes. 2007 ; Vol. 56, No. 11. pp. 2790-2796.
@article{3ced905f40bf47d396a407e6ceb7ffce,
title = "Evidence of increased inflammation and microcirculatory abnormalities in patients with type 1 diabetes and their role in microvascular complications",
abstract = "OBJECTIVE - Type 1 diabetes is associated with increased microvascular complications and inflammation. The monocyte-macrophage is a pivotal cell in atherogenesis. There are scanty data on noninvasive measures of microvascular abnormalities and inflammation in type 1 diabetic subjects with microvascular complications. Thus, we examined systemic and cellular biomarkers of inflammation in type 1 diabetic patients with microvascular complications (T1DM-MV patients) and type 1 diabetic patients without microvascular complications (T1DM patients) compared with matched control subjects and determined the microcirculatory abnormalities in the T1DM and T1DM-MV patients using computer-assisted intravital microscopy (CAIM). RESEARCH DESIGN AND METHODS - Fasting blood, 24-h urine, and CAIM measurements were obtained from the T1DM and T1DM-MV patients and matched control subjects. C-reactive protein, E-selectin, nitrotyrosine, monocyte superoxide, and cytokines were elevated in the T1DM and T1DM-MV patients compared with control subjects (P < 0.01). RESULTS - Severity index, as assessed by CAIM, was significantly increased in the T1DM and T1DM-MV patients compared with the control subjects (P < 0.001). There was a significant increase in C-reactive protein, nitrotyrosine, vascular cell adhesion molecule and monocyte superoxide anion release, and interleukin-1 release in T1DM-MV compared with T1DM patients (P < 0.05). T1DM-MV patients had significantly increased CAIM severity index and microalbumin-to-creatinine ratio compared with T1DM patients (P < 0.05). Furthermore, pp38MAPK, pp65, and pERK activity were significantly increased in monocytes from the T1DM and T1DM-MV patients compared with those from the controls subjects, and pp38MAPK and pp65 activity were significantly increased in the T1DM-MV compared with the T1DM patients (P < 0.01). CONCLUSIONS - T1DM-MV patients have increased inflammation compared with T1DM patients. CAIM provides an effective biomarker of microvascular complications, since it is significantly elevated in T1DM-MV compared with T1DM patients and can be monitored following therapies targeted at improving inflammation and/or microvascular complications of type 1 diabetes.",
author = "Sridevi Devaraj and Cheung, {Anthony T.} and Ishwarlal Jialal and Griffen, {Steven C.} and Danh Nguyen and Nicole Glaser and Thomas Aoki",
year = "2007",
month = "11",
doi = "10.2337/db07-0784",
language = "English (US)",
volume = "56",
pages = "2790--2796",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "11",

}

TY - JOUR

T1 - Evidence of increased inflammation and microcirculatory abnormalities in patients with type 1 diabetes and their role in microvascular complications

AU - Devaraj, Sridevi

AU - Cheung, Anthony T.

AU - Jialal, Ishwarlal

AU - Griffen, Steven C.

AU - Nguyen, Danh

AU - Glaser, Nicole

AU - Aoki, Thomas

PY - 2007/11

Y1 - 2007/11

N2 - OBJECTIVE - Type 1 diabetes is associated with increased microvascular complications and inflammation. The monocyte-macrophage is a pivotal cell in atherogenesis. There are scanty data on noninvasive measures of microvascular abnormalities and inflammation in type 1 diabetic subjects with microvascular complications. Thus, we examined systemic and cellular biomarkers of inflammation in type 1 diabetic patients with microvascular complications (T1DM-MV patients) and type 1 diabetic patients without microvascular complications (T1DM patients) compared with matched control subjects and determined the microcirculatory abnormalities in the T1DM and T1DM-MV patients using computer-assisted intravital microscopy (CAIM). RESEARCH DESIGN AND METHODS - Fasting blood, 24-h urine, and CAIM measurements were obtained from the T1DM and T1DM-MV patients and matched control subjects. C-reactive protein, E-selectin, nitrotyrosine, monocyte superoxide, and cytokines were elevated in the T1DM and T1DM-MV patients compared with control subjects (P < 0.01). RESULTS - Severity index, as assessed by CAIM, was significantly increased in the T1DM and T1DM-MV patients compared with the control subjects (P < 0.001). There was a significant increase in C-reactive protein, nitrotyrosine, vascular cell adhesion molecule and monocyte superoxide anion release, and interleukin-1 release in T1DM-MV compared with T1DM patients (P < 0.05). T1DM-MV patients had significantly increased CAIM severity index and microalbumin-to-creatinine ratio compared with T1DM patients (P < 0.05). Furthermore, pp38MAPK, pp65, and pERK activity were significantly increased in monocytes from the T1DM and T1DM-MV patients compared with those from the controls subjects, and pp38MAPK and pp65 activity were significantly increased in the T1DM-MV compared with the T1DM patients (P < 0.01). CONCLUSIONS - T1DM-MV patients have increased inflammation compared with T1DM patients. CAIM provides an effective biomarker of microvascular complications, since it is significantly elevated in T1DM-MV compared with T1DM patients and can be monitored following therapies targeted at improving inflammation and/or microvascular complications of type 1 diabetes.

AB - OBJECTIVE - Type 1 diabetes is associated with increased microvascular complications and inflammation. The monocyte-macrophage is a pivotal cell in atherogenesis. There are scanty data on noninvasive measures of microvascular abnormalities and inflammation in type 1 diabetic subjects with microvascular complications. Thus, we examined systemic and cellular biomarkers of inflammation in type 1 diabetic patients with microvascular complications (T1DM-MV patients) and type 1 diabetic patients without microvascular complications (T1DM patients) compared with matched control subjects and determined the microcirculatory abnormalities in the T1DM and T1DM-MV patients using computer-assisted intravital microscopy (CAIM). RESEARCH DESIGN AND METHODS - Fasting blood, 24-h urine, and CAIM measurements were obtained from the T1DM and T1DM-MV patients and matched control subjects. C-reactive protein, E-selectin, nitrotyrosine, monocyte superoxide, and cytokines were elevated in the T1DM and T1DM-MV patients compared with control subjects (P < 0.01). RESULTS - Severity index, as assessed by CAIM, was significantly increased in the T1DM and T1DM-MV patients compared with the control subjects (P < 0.001). There was a significant increase in C-reactive protein, nitrotyrosine, vascular cell adhesion molecule and monocyte superoxide anion release, and interleukin-1 release in T1DM-MV compared with T1DM patients (P < 0.05). T1DM-MV patients had significantly increased CAIM severity index and microalbumin-to-creatinine ratio compared with T1DM patients (P < 0.05). Furthermore, pp38MAPK, pp65, and pERK activity were significantly increased in monocytes from the T1DM and T1DM-MV patients compared with those from the controls subjects, and pp38MAPK and pp65 activity were significantly increased in the T1DM-MV compared with the T1DM patients (P < 0.01). CONCLUSIONS - T1DM-MV patients have increased inflammation compared with T1DM patients. CAIM provides an effective biomarker of microvascular complications, since it is significantly elevated in T1DM-MV compared with T1DM patients and can be monitored following therapies targeted at improving inflammation and/or microvascular complications of type 1 diabetes.

UR - http://www.scopus.com/inward/record.url?scp=35748942911&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35748942911&partnerID=8YFLogxK

U2 - 10.2337/db07-0784

DO - 10.2337/db07-0784

M3 - Article

C2 - 17686944

AN - SCOPUS:35748942911

VL - 56

SP - 2790

EP - 2796

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 11

ER -