Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus
Open accessAbstract
Background— Postprandial hyperglycemia may be a risk factor for cardiovascular disease. We compared the effects of two insulin secretagogues, repaglinide and glyburide, known to have different efficacy on postprandial hyperglycemia, on carotid intima-media thickness (CIMT) and markers of systemic vascular inflammation in type 2 diabetic patients. Methods and Results— We performed a randomized, single-blind trial on 175 drug-naive patients with type 2 diabetes mellitus (93 men and 82 women), 35 to 70 years of age, selected from a population of 401 patients who participated in an epidemiological analysis assessing the relation of postprandial hyperglycemia to surrogate measures of atherosclerosis. Eighty-eight patients were randomly assigned to receive repaglinide and 87 patients to glyburide, with a titration period of 6 to 8 weeks for optimization of drug dosage and a subsequent 12-month treatment period. The effects of repaglinide (1.5 to 12 mg/d) and glyburide (5 to 20 mg/d) on CIMT were compared by using blinded, serial assessments of the far wall. After 12 months, postprandial glucose peak was 148±28 mg/dL in the repaglinide group and 180±32 mg/dL in the glyburide group ( P <0.01). HbA 1c showed a similar decrease in both groups (−0.9%). CIMT regression, defined as a decrease of >0.020 mm, was observed in 52% of diabetics receiving repaglinide and in 18% of those receiving glyburide ( P <0.01). Interleukin-6 ( P =0.04) and C-reactive protein ( P =0.02) decreased more in the repaglinide group than in the glyburide group. The reduction in CIMT was associated with changes in postprandial but not fasting hyperglycemia. Conclusions— Reduction of postprandial hyperglycemia in type 2 diabetic patients is associated with CIMT regression.
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Most large outcome trials conducted so far have been mostly based on preprandial glucose and A1C targets, with limited evidence of a long-term benefit of targeting PPG alone.
“Most of the large outcome trials conducted so far have been mostly based on preprandial glucose and A1C targets, with limited evidence of a long-term benefit of targeting PPG alone (49,50).”
From Targets for Glycemic Control (2018) · cites this paper as [49]
The Discussion says earlier intervention studies paid no attention to controlling postprandial hyperglycemia, and that this trial’s limited follow-up prevented evaluation of clinical events. That supports the point about limited long-term outcome evidence, but the paper does not establish that most large trials used preprandial glucose and A1C targets. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA major challenge in using evidence-based observations to determine the value of tighter PPG control has been the lack of well-designed, long-term outcome studies where assessing PPG values is the major objective.
“However, a major challenge in attempting to use evidencebased observations to determine the value of tighter PPG control has been the lack of well-designed, long-term outcome studies where assessing PPG values is the major objective of the study.”
From Targets for Glycemic Control (2018) · cites this paper as [49]
Controlling postprandial hyperglycaemia with repaglinide compared with glyburide produced similar HbA1c improvement but was associated with regression of carotid artery atherosclerosis.
“specifically controlling post-prandial hyperglycaemia using a rapid-acting secretagogue (repaglinide) compared with glyburide resulted in a similar improvement of HbA 1c but was associated with a regression of carotid artery atherosclerosis [28]”
From Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus (2006) · cites this paper as [28]
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- Authors
- Esposito, K., Giugliano, D., Nappo, F., & Marfella, R.
- Affiliations
- University of Campania "Luigi Vanvitelli" (IT)
- Corresponding author
- Giugliano, Dario
- Venue
- Circulation
- Published
- 2004-07-13
- Volume
- 110
- Issue
- 2
- Pages
- 214-219
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2042518766
- Cited by
- 440
- References
- 26
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 10 · 2021: 9 · 2020: 12 · 2019: 7 · 2018: 19 · 2017: 17 · 2016: 13 · 2015: 21 · 2014: 15 · 2013: 26 · 2012: 29
- FWCI
- 25.10
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Funders
- Università degli Studi di Napoli Federico II
- Regione Campania
- Seconda Università degli Studi di Napoli
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- postprandial hyperglycemia, type 2 diabetes, carotid intima-media thickness, atherosclerosis regression, repaglinide, glibenclamide, insulin secretagogues, vascular inflammation, interleukin-6, C-reactive protein, glycemic control
- MeSH terms
- Adult, Aged, Blood Glucose, Carbamates, Carotid Artery Diseases, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Fasting, Female, Glyburide, Glycated Hemoglobin, Humans, Hyperglycemia, Hypoglycemic Agents, Inflammation, Insulin, Lipids, Male, Middle Aged, Piperidines, Ultrasonography, Biomarkers, Single-Blind Method, Tunica Intima, Tunica Media, Postprandial Period
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