Among 100 patients evaluated by OGTT 54 showed NGT, 28 IGT and 18 have T2DM. Considering the cut-off point of 155 mg/dl for one-hour post load plasma glucose, NGT subjects were stratified into two groups: 30 with NGT<155 (55.6%), and 24 NGT≥155 (44.4%).
In table 1, the demographic, clinical and biochemical characteristics of the study population are reported according to different metabolic states. There were no significant differences among groups regarding gender distribution and age. Anthropometric parameters, DBP, PP, heart rate (HR), total, HDL and LDL cholesterol, and haemoglobin (Hb), were also not significantly different. From the first to the fourth group, there was a significant increase of SBP, triglyceride and hs-CRP values as well as a reduction in e-GFR.
Of interest, one-hour post load plasma glucose levels (p< 0.0001) and two-hours post load plasma glucose levels (p<0.0001), as well as fasting (p<0.0001), one-hour (p = 0.001) and two-hours (p<0.0001) insulin values during OGTT significantly increased from the first to the fourth group. As expected, there was a worsening of insulin sensitivity accounting for the reduction of MATSUDA/ISI (p<0.0001).
Post-hoc analysis by Bonferroni test confirmed that NGT ≥155 subjects have significantly worse insulin sensitivity as represented by a lower Matsuda index (p<0.0001) and higher values of hs-CRP (p =0.006), in comparison with NGT<155, showing a metabolic and inflammatory profile similar to IGT individuals.
Oxidative stress serum parameters
Figure 1A and 1B show serum levels of oxidative stress biomarkers (8-isorpostane, Nox-2), according to glucose tolerance status. There was a significant increase, from the first to the fourth group, of 8-isoprostane (p<0.0001), and Nox-2 (p<0.0001) serum levels, indicating a worsening in oxidative stress with the deterioration of metabolic status. In particular, 8-isoprostane (p<0.0001) and Nox-2 (p<0.0001) levels were significantly higher in the NGT≥155 subjects compared to NGT<155 group, without significant differences with IGT and diabetic patients.
Echocardiographic parameters according to glucose tolerance
In Table 2, morphological and functional echocardiographic parameters of the study population according to different glycometabolic status are reported. From the first to the fourth group there was a significant increase in LVMI; diabetic subjects exhibited a worsening in both LVM (p<0.0001) and LVMI (p<0.0001) in comparison with NGT<155, NGT≥155 and IGT. In particular, NGT≥155 patients showed significantly higher values of diastolic interventricular septum (dIVS) (p=0.009), diastolic posterior wall (dPW) (p=0.01) and LVMI (p=0.026) in comparison with NGT<155, but similar to IGT. By contrast, NGT≥155 group compared with T2DM group, exhibited significantly lower LVMI (p=0.009), while no significant differences were detected between the two groups as regards dIVS and dPW. Regarding the left ventricular end-diastolic diameter (LVEDD), there were no statistically significant differences between the four groups.
Regarding left global systolic function values evaluated as EF and stroke volume, significantly differences were not detected among the four groups.
From the first to the fourth group, there was a progressive worsening of left global systolic function evaluated as myocardial deformation and GLS (p<0.0001) (Fig 1C). Furthermore NGT ≥ 155 subjects in comparison with NGT<155 patients, showed a more compromised GLS (p<0.0001), but similar to IGT. In addition, there was a progressive impairment in GLS endo values (p<0.0001) and GLS endo/epi (p<0.0001) proceeding from the NGT<155 group to T2DM group. No differences were highlighted in GLS epi values among the four groups.
Moreover, from the first to the fourth group there was a progressive reduction of GWE (Fig 1D) (p<0.0001) and a progressive increment of GWW (p<0.0001). In detail, NGT≥155 exhibited a worsening of GWE in comparison with NGT≥155 (p=0.027), but similar to IGT and diabetic patients.
In addition, a significant reduction of right systolic function was observed as demonstrated by lower values of TAPSE (p=0.006) in NGT≥155 group compared to NGT<155; this parameter was also decreased in diabetic patients compared to the remaining groups (p<0.0001). Values of left pulmonary systolic pressure (s-PAP) were similar in NGT≥155, IGT and T2DM groups, with significant lower values in NGT<155 (p<0.0001). Moreover, TAPSE/s-PAP ratio significantly decreased in T2DM group compared to NGT<155 (p<0.0001) and NGT≥155 (p=0.025), remaining similar to IGT.
Finally, NGT≥155 had a significantly lower E/A ratio in comparison with NGT<155 (p<0.0001), but similar to IGT and T2DM patients.
Correlation analysis was performed to test the correlation between echocardiographic parameters (GLS endo/epi ratio, GLS and GWE) and different covariates (Table 3).
GLS endo/epi ratio was significantly correlated with e-GFR (r=0.280, p=0.002), Matsuda/ISI (r=0.541, p<0.0001), and inversely correlated with one-hour glucose (r= -0.559, p<0.0001), 8-isoprostane (r= -0.537, p<0.0001), hs-CRP (r= -0.276, p=0.003), Nox-2 (r= -0.551, p<0.0001), E/e’ (r= -0.494, p<0.0001), LVMI (r= -0.401, p<0.0001). When GLS was considered as a dependent variable, in the whole study population it was significantly correlated with e-GFR (r= -0.184, p=0.034), Matsuda/ISI (r= -0.538, p<0.0001), Hb (r= -0195, p=0.026), one-hour glucose (r= -0.564, p<0.0001), 8-isoprostane (r=0.445, p<0.0001), hs-CRP (r=0.370, p=0.005), Nox-2 (r=0.468, p<0.0001), E/e’ (r=0.473, p<0.0001), LVMI (r=0.408, p<0.0001).
Subsequently, GWE was considered as a dependent variable and was significantly correlated with e-GFR (r=0.199, p=0.023), Matsuda/ISI (r=0.496, p<0.0001), Hb (r=0.347, p<0.0001), one-hour glucose (r= -0.420, p<0.0001), PP (r=-0.237, p=0.009), 8-isoprostane (r= -0.279, p=0.002), hs-CRP (r= -0.465, p<0.0001), Nox-2 (r= -0.336, p<0.0001), E/e’ (r= -0.359, p<0.0001), LVMI (r= -0.302, p=0.001).
Finally, variables achieving statistical significance were inserted in a stepwise multivariate linear regression model to determine the independent predictors of GLS endo/epi ratio, GLS and GWE respectively. In the whole study population, one-hour glucose was the major predictor of GLS endo/epi ratio explaining 31.3% of its variation (p<0.0001) and Nox-2 added another 4.1%. Moreover, one-hour glucose was the major predictor of GLS explaining a 31.8% of its variation (p<0.0001) and Matsuda/ISI added another 4.7% (p<0.0001). Considering GWE as dependent variable, Matsuda/ISI was the main predictor justifying 24.6% (p<0.0001) of its variation; Hb added another 7.8% and hs-CRP another 3.4%. When Matsuda/ISI was excluded from the model, hs-CRP resulted the major predictor of GWE variation justifying a 21.6% of its variation (p<0.0001), one-hour glucose added a 7.3% (p<0.0001) and Hb another 3.8% (p<0.0001). The respective models justified a 35.4% for GLS endo/epi ratio, a 36.5% for GLS and 35.8% for GWE variation, respectively.