The present investigation was designed to test the association between carotid atherosclerosis and two simple markers of insulin resistance, i.e. HOMA-Index and TyG-Index. The study was performed in two different cohorts. In the first cohort, 330 individuals were enrolled. Blood pressure, lipids, glucose, waist and cigarette smoking were evaluated. HOMA-IR and TyG-Index were calculated as markers of prevalent hepatic and muscular insulin resistance respectively. Carotid atherosclerosis was assessed by Doppler ultrasonography. The association between cardiovascular risk factors, markers of insulin resistance and carotid atherosclerosis was assessed by multiple logistic regression analyses. In the second cohort, limited to the evaluation of TyG-Index, 1432 subjects were studied. In the first cohort, TyG-Index was significantly associated with carotid atherosclerosis in a model including age, sex, diabetes, cigarette smoking and LDL cholesterol, while HOMA-IR was not. When components of metabolic syndrome were added to the model as dichotomous variables (absent/present), TyG-Index retained its predictive power. The same result was obtained when the metabolic syndrome was added to the model (absence/presence). The association between TyG-Index and carotid atherosclerosis was confirmed in the second cohort. The present findings suggest that TyG-Index is better associated with carotid atherosclerosis than HOMA-IR.

OBJECTIVE: Blood viscosity (BV) is higher in diabetic patients and might represent a risk factor for the development of insulin resistance and type 2 diabetes. However, data in subjects with normal glucose or prediabetes are missing. In the current study, we evaluated the relationship between BV and blood glucose in subjects with normal glucose or prediabetes. RESEARCH DESIGN AND METHODS: Enrolled subjects were divided into three groups according to blood glucose: group A (n = 74), blood glucose <90 mg/dL; group B (n = 96), blood glucose ranging from 90 to 99 mg/dL; and group C (n = 94), blood glucose ranging from 100 to 125 mg/dL. BV was measured at 37°C with a cone-plate viscometer at shear rates ranging from 225 to 22.5 s−1. RESULTS: Blood pressure, blood lipids, fibrinogen, and plasma viscosity were similar in the three groups. BMI and waist circumference were significantly increased in group C. Hematocrit (P < 0.05) and BV (P between 0.01 and 0.001) were significantly higher in groups B and C compared with group A. Blood glucose was significantly and inversely correlated with HDL cholesterol and directly with BMI, waist, hematocrit (r = 0.134), and BV (from 225 s−1 to 22.5 s−1; r ranging from 0.162 to 0.131). BV at shear rate 225 s−1 was independently associated with blood glucose. CONCLUSIONS: The current study shows a direct relationship between BV and blood glucose in nondiabetic subjects. It also suggests that, even within glucose values ​​considered completely normal, individuals with higher blood glucose levels have increased BV comparable with that observed in subjects with prediabetes.

The GLP-1 receptor agonist exenatide has been approved for adjunctive treatment of type 2 diabetes. Continuous GLP-1 infusion improves endothelial function in vivo; no evidence about a beneficial effect of exenatide on vascular function has been published. The aim of our observational study was to evaluate whether exenatide would improve brachial artery function evaluated by the flow mediated dilation (FMD) technique, compared with glimepiride, in subjects with type 2 diabetes. FMD time course was assessed by ultrasound, after 5 min forearm ischaemia, at baseline and after 16-week treatment. At the end of the study FMD was significantly higher in subjects who assumed exenatide compared with glimepiride (9.1 ± 3.6 vs. 5.6 ± 1.0, p = 0.01). Even if limited by the small number of studied subjects, who were not matched in the two treatment groups, this research study represents the first FMD evidence suggesting that chronic administration of exenatide improves arterial dilation.

Cardiovascular protection following empagliflozin therapy is not entirely attributable to the glucose lowering effect. Increased hematocrit might influence the shear stress that is the main force acting on the endothelium, regulating its anti-atherogenic function. We designed the study with the aim of investigating the effect of empagliflozin on blood viscosity and shear stress in the carotid arteries. A secondary endpoint was the effect of empagliflozin on carotid artery wall thickness. The study was a non-randomized, open, prospective cohort study including 35 type 2 diabetic outpatients who were offered empagliflozin or incretin-based therapy (7 liraglutide, 8 sitagliptin) in combination with insulin and metformin. Blood viscosity, shear stress and carotid wall thickness were measured at baseline and at 1 and 3 months of treatment. Blood viscosity was measured with a viscometer, and shear stress was calculated using a validated formula. Intima-media thickness (IMT) of the carotid artery was detected by ultrasound and was measured with dedicated software. Blood viscosity (4.87 ± 0.57 vs 5.32 ± 0.66 cP, p < 0.02) and shear stress significantly increased in the Empagliflozin group while no change was detected in the Control group (4.66 ± 0.56 vs 4.98 ± 0.73 cP, p = NS). IMT significantly decreased in the Empagliflozin group after 1 and 3 months (baseline: 831 ± 156, 1-month 793 ± 150, 3-month 766 ± 127 μm; p < 0.0001), while in the liraglutide group, IMT significantly decreased only after 3 months (baseline 879 ± 120; 1-month 861 ± 163; 3-month 802 ± 114 μm; p < 0.001). In the sitagliptin group, IMT remained almost unchanged (baseline 901 ± 135; 1-month 902 ± 129; 3-month 880 ± 140 μm; p = NS). This study is the first to describe a direct effect of empagliflozin on blood viscosity and wall shear stress. Furthermore, IMT was markedly reduced early on in the Empagliflozin group.