Intensive Lifestyle Intervention or Metformin on Inflammation and Coagulation in Participants With Impaired Glucose Tolerance
Open accessAbstract
Increases in subclinical inflammation (C-reactive protein [CRP]) and impaired coagulation have been associated with increased obesity and insulin resistance. Only a few small studies have examined the effect of lifestyle changes, such as weight loss, increased physical activity, and insulin-sensitizing intervention on inflammation and coagulation. The Diabetes Prevention Program (DPP) clinical trial studied the effect of an intensive lifestyle intervention or metformin on progression to diabetes relative to placebo in 3,234 adults with impaired glucose tolerance. The effects of these interventions on CRP and fibrinogen at 12 months are examined in this report. Metformin reduced CRP in women compared with the placebo group. In men, the median changes in CRP from baseline to 1 year were −33% in the lifestyle group, −7% in the metformin group, and +5% in the placebo group. In women, the changes in CRP from baseline to follow-up were −29% in the lifestyle group, −14% in the metformin group, and 0% in the placebo group. In the lifestyle group weight loss rather than increased physical activity seems to account for most of the changes in CRP. Only modest reductions (although significant) were seen in fibrinogen levels in the lifestyle group relative to the metformin and placebo group. Lifestyle intervention reduced levels of nontraditional cardiovascular risk factors relative to both placebo and to a lesser degree to metformin.
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Rosiglitazone was tested for secondary prevention of cognitive decline in mild AD among persons without T2D and was found to be non-efficacious in a phase III trial after promising results in a pilot study.
“The thiazolidinedione rosiglitazone was tested for secondary prevention of cognitive decline in mild AD among persons without T2D and was found to be non-efficacious in a phase III trial[71] after promising results in a pilot study [72].”
From Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial (2016) · cites this paper as [72]
The decrease in plasma Aβ-42 observed in the placebo group was similar to that in a pilot study of rosiglitazone in mild AD.
“The decrease in plasma Aβ-42 observed in the placebo group was similar to that in a pilot study of rosiglitazone in mild AD [72]”
From Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial (2016) · cites this paper as [72]
Metformin reduces insulin levels, inflammation and thrombosis, and the risk of metabolic syndrome, and improves insulin sensitivity, suggesting its potential to exert protective effects on cognitive function.
“Studies showing that metformin (MET) not only reduces insulin levels (11), inflammation and thrombosis (12), and the risk of the metabolic syndrome (13), but also improves insulin sensitivity (11) suggests its potential to exert protective effects on cognitive function.”
From Type 2 Diabetes and Antidiabetic Medications in Relation to Dementia Diagnosis (2014) · cites this paper as [12]
Many different mechanisms beyond glycemic control have been implicated in vascular protection induced by metformin, including improvements in the inflammatory pathway, coagulation, oxidative stress and glycation, endothelial dysfunction, haemostasis, insulin resistance, lipid profiles, and fat redistribution.
“Many different mechanisms, beyond glycemic control, have been implicated in vascular protection induced by metformin such as improvements in the inflammatory pathway [86], coagulation [87], oxidative stress and glycation [88-92], endothelial dysfunction [88-90], haemostasis [88,91-93], insulin resistance improvement [94], lipid profiles [95,96], and fat redistribution [97,98].”
From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [87]
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- Authors
- The Diabetes Prevention Program Research Group
- Affiliations
- George Washington University (US)
- Corresponding author
- The Diabetes Prevention Program Research Group
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-05-01
- Volume
- 54
- Issue
- 5
- Pages
- 1566-1572
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC1314967
- OpenAlex
- W55232514
- Semantic Scholar
- 343575c164171f37ecc54009da3652a70841bcda
- Cited by
- 333
- References
- 37
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 7 · 2023: 11 · 2022: 9 · 2021: 20 · 2020: 19 · 2019: 8 · 2018: 10 · 2017: 27 · 2016: 22 · 2015: 11 · 2014: 17 · 2013: 13 · 2012: 16
- FWCI
- 14.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- Bristol-Myers Squibb
- Henry M. Jackson Foundation
- National Institutes of Health
- Centers for Disease Control and Prevention
- National Institute on Aging
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK048406, U01DK048489)
- National Institute of Child Health and Human Development
- National Center for Research Resources
- Office of Women's Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- impaired glucose tolerance, intensive lifestyle intervention, metformin, C-reactive protein, fibrinogen, subclinical inflammation, coagulation, weight loss, physical activity, insulin resistance, sex differences, cardiovascular risk factors, type 2 diabetes prevention
- MeSH terms
- Blood Coagulation, Blood Glucose, Diabetes Mellitus, Female, Humans, Inflammation, Life Style, Male, Metformin, Middle Aged, Obesity, Body Mass Index, Glucose Intolerance
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