RESEARCH ARTICLE SA JOURNAL OF DIABETES & VASCULAR DISEASE 14 VOLUME 20 NUMBER 1 • JUNE 2023 On the contrary, in the IR state, this metabolic flexibility is lost.27 The synthesis of glycogen and the catabolism of proteins in skeletal muscles is impaired, and the activity of lipoprotein lipases in adipocytes is inhibited, resulting in an increased release of free fatty acids and inflammatory cytokines such as interleukin-6, tumour necrosis factor alpha and leptin.28,29 The heart is therefore integrated in an environment rich in fatty acids and glucose.30-33 This stimulates the absorption of free fatty acids into the myocardium33,34 due to upregulation of CD36,31 which is a powerful transporter of free fatty acids, thus increasing the levels of intracellular fatty acids and the expression of PPAR-α. The excess lipids in the cardiomyocytes are transferred into non-oxidative pathways, leading to the accumulation of toxic lipid species such as ceramides, diacylglycerols, long chain acyl-CoA and acylcarnitines,35 which contribute to alteration of mitochondrial function, apoptosis and cardiac hypertrophy.36,37 Insulin regulates a wide range of functions in the heart, including heart growth.38 The responsibility for hyperinsulinaemia, which may be a cause or a consequence of IR39 in the development of LVH,8,9 and the deterioration of diastolic function8,40,41 is generally accepted and could be accounted for by the trophic and profibrotic properties of insulin.8,9,42,43 The dilator effect of IR on the LVED could be explained by volume overload. The latter is the consequence of insulininduced sodium retention.44-47 Our results indicate that 29.4% of variation in RWT could be explained by insulinaemia, suggesting concentric remodelling. We also found that IR and hyperinsulinaemia increased the DT, which is a parameter of grade I diastolic dysfunction,19,21 in 31% of patients (R2 = 0.309). These findings are in accordance with the results of a population-based prospective study by Cauwenberghs et al.48 showing that basal IR and its increase during follow up was positively associated with development of concentric LVH. Similarly, Velagaleti et al. assessed the influence of IR on LVM, measured by magnetic resonance imaging, and also concluded that IR caused concentric LVH.49 Participants in the study by Cauwenberghs et al., who remained or became IR during follow up, experienced worse changes in E/e′, which is a parameter of diastolic dysfunction.19,21 Such diastolic dysfunction is probably imputable to IR,50 with underlying LVH and myocardial fibrosis.21,51-54 But this is still a subject of debate, as a certain degree of diastolic dysfunction exists in hypertensive patients long before they develop LVH,55 and regression of LVH after antihypertensive treatment does not necessarily lead to normalisation of diastolic function.56 Nonetheless, some studies have shown that normalisation of LVM leads to normalisation of diastolic function.57 Therefore, IR/hyperinsulinaemia appears to increase cardiovascular risk in patients with hypertension, at least in part, by promoting concentric LVH and diastolic dysfunction. Indeed, concentric LVH is the independent cardiovascular risk factor most strongly associated with a poor prognosis,12 and diastolic dysfunction is a strong predictor of cardiovascular outcomes in essential hypertension.58,59 Strengths and limitations Our study has to be interpreted within the context of its potential strengths and limitations. To the best of our knowledge, this is the first study to address the question of the collective or individual influence of IR/hyperinsulinaemia on the components of Devereux’s formula and on the parameters of diastolic function in Africans. However echocardiographic measurements are prone to errors as a result of signal noise, acoustic artefacts and angle dependency, although in our study, echocardiography was performed by an experienced cardiologist with post-graduate training in cardiac imaging. Moreover, the cross-sectional design of this study is a limitation, which means that causal relationships cannot be firmly established. Also, measurement of waist circumference at the level of the umbilicus is a possible cause of error as it will vary with the habitus of the individual, obese individuals with protuberant abdominal walls or those with a large umbilical hernia, giving false measurements. Finally, the in-hospital and single-centre design precludes extrapolation of the results to all essential hypertensive patients. Conclusions Our study suggests that IR appears to act on LVED, while hyperinsulinaemia affects the PWT. Both conditions act on the IVS and contribute to diastolic dysfunction via E-wave deceleration time. Insulin sensitivity of hypertensive patients should therefore be of concern to the physician managing hypertension, in order to take appropriate measures to improve the prognosis. A prospective, population-based study with serial imaging remains essential to better understand subclinical LV deterioration over time and to confirm the role of IR in essential hypertensives. Even better would be the Mendelian randomisation approach, which would however be costly, time consuming and more difficult to apply. Table 4. Multiple linear regression analysis between HOMAIR, insulin and LV echocardiographic parameters Equation parameters Overall Parameters β SE p-value R2 p-value LVED (mm) 0.301 0.001 (constant) 41.375 0.729 0.000 HOMAIR 1.599 0.823 0.013 Insulin 0.001 0.017 0.954 IVS (mm) 0.468 < 0.001 (constant) 9.723 0.254 0.000 HOMAIR 0.860 0.287 0.016 Insulin 0.021 0.006 0.000 PWT (mm) 0.463 < 0.001 (constant) 9.787 0.230 0.000 HOMAIR 0.063 0.260 0.810 Insulin 0.016 0.005 0.002 RWT 0.294 0.011 (constant) 0.467 0.014 0.000 HOMAIR 0.014 0.016 0.377 Insulin 0.001 0.000 0.007 DT ms 0.309 0.003 (constant) 175.610 6.374 0.000 HOMAIR 6.453 7.203 0.017 Insulin 0.409 0.145 0.005 LVED: left ventricular end-diastolic diameter; IVS: interventricular septum; PWT: posterior wall thickness; RWT: relative wall thickness; DT: deceleration time.
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