Low-Grade Systemic Inflammation and the Development of Type 2 Diabetes
Open accessAbstract
To examine the association of low-grade systemic inflammation with diabetes, as well as its heterogeneity across subgroups, we designed a case-cohort study representing the ∼9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants. Analytes were measured on stored plasma of 581 incident cases of diabetes and 572 noncases. Statistically significant hazard ratios of developing diabetes for those in the fourth (versus first) quartile of inflammation markers, adjusted for age, sex, ethnicity, study center, parental history of diabetes, and hypertension, ranged from 1.9 to 2.8 for sialic acid, orosomucoid, interleukin-6, and C-reactive protein. After additional adjustment for BMI, waist-to-hip ratio, and fasting glucose and insulin, only the interleukin-6 association remained statistically significant (HR = 1.6, 1.01–2.7). Exclusion of GAD antibody-positive individuals changed associations minimally. An overall inflammation score based on these four markers plus white cell count and fibrinogen predicted diabetes in whites but not African Americans (interaction P = 0.005) and in nonsmokers but not smokers (interaction P = 0.13). The fully adjusted hazard ratio comparing white nonsmokers with score extremes was 3.7 (P for linear trend = 0.008). In conclusion, a low-grade inflammation predicts incident type 2 diabetes. The association is absent in smokers and African-Americans.
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T2DM is associated with low-grade inflammation, cardiovascular disease, nephropathy and alterations in secretion of various hormones including IL-6, IL-18, TNF-α, adiponectin, leptin, neuropeptides, ghrelin, and incretins GLP-1 and GIP.
“Furthermore, T2DM is associated with low-grade inflammation,382, 383 cardiovascular disease,384, 385 nephropathy386, 387 and alterations in the secretion of various hormones, including IL-6, IL-18, tumor necrosis factor-α,388 adiponectin and leptin,389 neuropeptides,390 ghrelin391, 392 and the incretins GLP-1 and GIP.219, 220, 221, 222, 223”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [382]
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References 42 · Cited by 1,036
- Authors
- Duncan, B. B., Schmidt, M. I., Pankow, J. S., Ballantyne, C. M., Couper, D., Vigo, A., Hoogeveen, R., Folsom, A. R., & Heiss, G.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Graduate Studies Program in Epidemiology, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
- University of Minnesota (US)
- Baylor College of Medicine (US)
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2003-07-01
- Volume
- 52
- Issue
- 7
- Pages
- 1799-1805
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2117121624
- Cited by
- 1,036
- References
- 42
- Citations by year
- 2026: 13 · 2025: 28 · 2024: 40 · 2023: 58 · 2022: 58 · 2021: 56 · 2020: 52 · 2019: 64 · 2018: 49 · 2017: 48 · 2016: 47 · 2015: 44 · 2014: 58 · 2013: 44 · 2012: 58
- FWCI
- 23.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- National Institutes of Health (5r01dk056918-08, n01hc55021-47-0-1, n01hc55020-39-0-0, n01hc55016-37-0-0, n01hc055022-024, n01hc55019-35-0-1, n01hc55018-38-0-1, n01hc55015-48-0-1)
- National Heart, Lung, and Blood Institute (N01-HC55022, N01-HC-55018, N01 HC 55020, N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022, N01 HC 55019, N01-HC55016, N01‐HC‐55015, N01-HC55021)
- National Institute of Diabetes and Digestive and Kidney Diseases (5R01 DK 56918-03)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Keywords
- low-grade inflammation, type 2 diabetes, interleukin-6, C-reactive protein, sialic acid, alpha-1-acid glycoprotein, fibrinogen, white blood cell count, inflammation score, incident diabetes risk, racial differences, smoking, African Americans, Atherosclerosis Risk in Communities Study
- MeSH terms
- Black or African American, Blood Glucose, Diabetes Mellitus, Type 2, Female, Humans, Inflammation, Male, Middle Aged, Reference Values, Risk Factors, Smoking, United States, Cohort Studies, Incidence, Case-Control Studies, Black People, White People
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