A dysregulation of glucose metabolism control is associated with carotid atherosclerosis in patients with coronary heart disease (CORDIOPREV-DIAB study)

Authors: YUBERO-SERRANO, ELENA - Universidad De Cordoba; DELGADO-LISTA, JAVIER - Universidad De Cordoba; ALCALA-DIAZ, JUAN - Universidad De Cordoba; GARCIA-RIOS, ANTONIO - Universidad De Cordoba; PEREZ-CABALLERO, ANA - Universidad De Cordoba; BLANCO-ROJO, RUTH - Universidad De Cordoba; GOMEZ-DELGADO, FRANCISCO - Universidad De Cordoba; MARIN, CARMEN - Universidad De Cordoba; TINAHONES, FRANCISCO - Hospital Universitario Virgen De La Victoria; CABALLERO, JAVIER - University Hospital Reina Sofia; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; VAN OMMEN, BEN - The Netherlands Organisation For Applied Scientific Research (TNO); PEREZ-JIMENEZ, FRANCISCO - Universidad De Cordoba; PEREZ-MARTINEZ, PABLO - Universidad De Cordoba; LOPEZ-MIRANDA, JOSE - Universidad De Cordoba

Submitted to: Atherosclerosis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/14/2016
Publication Date: 10/1/2016
Citation: Yubero-Serrano, E.M., Delgado-Lista, J., Alcala-Diaz, J.F., Garcia-Rios, A., Perez-Caballero, A.I., Blanco-Rojo, R., Gomez-Delgado, F., Marin, C., Tinahones, F., Caballero, J., Ordovas, J.M., Van Ommen, B., Perez-Jimenez, F., Perez-Martinez, P., Lopez-Miranda, J. 2016. A dysregulation of glucose metabolism control is associated with carotid atherosclerosis in patients with coronary heart disease (CORDIOPREV-DIAB study). Atherosclerosis. doi: 10.1016/j.atherosclerosis.2016.07.903.

Interpretive Summary: Patients with type-2 diabetes mellitus (T2DM) who also have coronary heart disease (CHD) are at a very high risk of having a recurrent cardiovascular event. However, it is unclear whether they have increased common carotid intima-media thickness (CCIMT,) which is a measurement of the thickness of the innermost two layers of the wall of an artery and is a marker of atherosclerosis progression. Moreover, it is not known whether this relation is dependent on the glycemic control of the T2DM in an individual. Therefore, our aim was to shed some light on the association between markers of glucose metabolism and CCIMT in CHD patients. We investigated this in 1,002 patients aged 20-75 years and categorized into normal glucose tolerance (NGT,) impaired fasting glucose (IFG,) impaired glucose tolerance (IGT,) or T2DM. These patients underwent an oral glucose tolerance test (OGTT,) CCIMT measurement, and determination of plasma levels of glycosylated hemoglobin (HbA1c,) a marker of habitual levels of glucose in the blood. Our results show that CCIMT was higher in T2DM subjects with higher Hb1Ac, and this effect was preferentially observed in subjects <61 years. Moreover, we found that the levels of glucose at 120 min in the OGTT was the measure that was more closely associated with CCIMT. In conclusion, our results highlight the importance of properly controlling glucose metabolism in CHD patients. This is especially relevant in subjects <61 years of age. Moreover, glucose concentration at 120 min could contribute to CVD risk, and its determination could be used as a predictive tool to identify those CHD patients at the highest risk.

Technical Abstract: Background and aims: Patients with coexisting coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM) are at high risk of cardiovascular recurrence, however, it is not well established whether they exhibit an increased intima-media thickness of both common carotid arteries (IMT-CC). Furthermore, whether this relationship is inherent to T2DM or depends on glycemic control has not been tested in large cohorts. Our aim was to determine whether clinical categories and/or analytical markers of glucose metabolism control were associated with IMT-CC in CHD patients. Methods: 1002 patients aged 20-75 years, categorized into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or T2DM, underwent an oral glucose tolerance test (OGTT) and an IMT-CC measurement. Results: IMT-CC was higher in T2DM patients with HbA1c > 6.5% compared to T2DM patients with HbA1c < 6.5% (p = 0.001), patients with IFG or IGT (p < 0.001) and NGT (p < 0.001). When age was considered, IMT-CC was influenced by glucose metabolism control only in those patients with age <61 years (p < 0.01). In a multiple linear regression analysis, glucose concentration at 120 min, but not other OGTT time-points appeared as a significant independent contributor of IMT-CC (p < 0.001). Moreover, a multiple logistic regression and the area under curve (AUC) of the ROC curve analysis showed a predictive power of glucose at 120 min to detect those CHD patients at the highest risk, defined as IMT-CC >/= 0.7 mm (R2 = 0.221; AUC = 0.761). Conclusions: Our results highlight the importance of properly controlling glucose metabolism in CHD patients, in younger populations in particular, providing an easy way of categorizing patients with an increased IMT-CC. Moreover, glucose concentration at 120 min could contribute to CVD risk and its determination could be used as a predictive tool to identify those CHD patients at the highest risk.