Insulin and Diastolic Dysfunction in Lean and Obese Hypertensives

Abstract

Abstract-We investigated the influence of genetic predisposition to hypertension by studying the relation between insulin sensitivity and left ventricular (LV) mass and function in untreated lean and obese hypertensives. We selected 50 lean hypertensives with normotensive parents (negative family history of hypertension [FϪ]), 64 lean hypertensives with 1 or both parents hypertensive (positive family history of hypertension [Fϩ]), 40 obese FϪ hypertensives, and 43 obese Fϩ hypertensives. The 4 groups were comparable regarding age, gender, 24-hour blood pressure profile, and known duration of hypertension. We measured glucose, insulin, and C-peptide during fasting and during an oral glucose tolerance test; LV morphology and function were assessed by digitized M-mode echocardiography. Glucose (fasting and test) levels were normal in all and similar among the 4 groups. Insulin and C-peptide (fasting and stimulated) levels were higher in obese hypertensives than in lean hypertensives; at similar body mass index, insulin and C-peptide levels were higher in Fϩ than in FϪ groups. Compared with lean hypertensives, obese hypertensives had greater LV mass index; LV systolic function was normal in all and similar among the groups. The indices of LV diastolic function were significantly lower in Fϩ than in FϪ groups. LV mass index did not correlate with metabolic parameters; the indices of LV diastolic function were inversely correlated with insulin area during test in only the 2 Fϩ groups. In conclusion, genetic predisposition to hypertension is associated with a reduced insulin sensitivity and affects the response of the myocardium to increased insulin levels, inducing a greater impairment of diastolic function. Insulin sensitivity and genetic predisposition to hypertension seem to have no influence on LV mass. (Hypertension. 1999;34:1208-1214.)Key Words: insulin Ⅲ diastole Ⅲ hypertension, essential Ⅲ obesity Ⅲ hypertrophy E ssential hypertension and obesity are often associated, and each one, per se, can induce myocardial hypertrophy and left ventricular (LV) diastolic dysfunction. 1-5 Insulin resistance and hyperinsulinemia have been described in both hypertension and obesity. 6,7 In experimental studies, insulin has been demonstrated to exert a growth-stimulating effect on cardiomyocytes and to increase collagen production in fibroblasts 8 -12 ; therefore, clinical studies have evaluated the possible contribution of insulin resistance and hyperinsulinemia to the development of myocardial hypertrophy and diastolic dysfunction in hypertension and in obesity and have obtained conflicting results. [13][14][15][16][17][18][19][20] Recently, it has been suggested that genetic factors play an important role in the link between insulin resistance, hypertension, and obesity. In fact, a reduced insulin sensitivity has been demonstrated in lean and obese normotensives and hypertensives with hypertensive parents (positive family history of hypertension [Fϩ]) compared with offspring of normotensive parents (negative family history...

Fasting Plasma Glucose Is an Independent Determinant of Left Ventricular Diastolic Dysfunction in Nondiabetic Patients with Treated Essential Hypertension.

“…In addition, some of these studies reported that the relation between the two was independent of LVMI (31)(32)(33). Studies on the association between insulin and LV mass in humans have yielded conflicting results (23,27,31,(33)(34)(35)(36)(37)(38)(39)(40), but recent studies have demonstrated that neither plasma insulin concentration nor insulin sensitivity is an independent determinant of LVMI in nondiabetic subjects (38,39). Therefore, the findings in our study might have been at least partly caused by hyperinsulinemia linked to glucose intolerance and hypertension.…”

“…Many studies have reported that the existence of hyperinsulinemia or insulin resistance is related to LV diastolic dysfunction in nondiabetic hypertensives (27,(30)(31)(32)(33)(34)(35). In addition, some of these studies reported that the relation between the two was independent of LVMI (31)(32)(33).…”

“…Many studies have reported that the existence of hyperinsulinemia or insulin resistance is related to LV diastolic dysfunction in nondiabetic hypertensives (27,(30)(31)(32)(33)(34)(35). In addition, some of these studies reported that the relation between the two was independent of LVMI (31)(32)(33). Studies on the association between insulin and LV mass in humans have yielded conflicting results (23,27,31,(33)(34)(35)(36)(37)(38)(39)(40), but recent studies have demonstrated that neither plasma insulin concentration nor insulin sensitivity is an independent determinant of LVMI in nondiabetic subjects (38,39).…”

Left ventricular filling abnormalities and obesity-associated hypertension: relationship with overproduction of circulating transforming growth factor β1

“…A significant increase in TGFb1 values and LVM/h 2.7 and a higher prevalence of subjects with left ventricular hypertrophy were found in the subset of hypertensives with diastolic dysfunction in comparison with patients with normal diastolic function. According to literature data [37][38][39][40] and to higher prevalence of LVH found in our hypertensives with altered diastolic function, TGFb1 overproduction might be able to affect diastolic function through an altered left ventricular geometry. Surprisingly, in our study, multivariate analysis indicated an independent role of TGFb1 in the occurence of alteration in left ventricular filling.…”

“…39 Obviously, the present study does not explore the pathophysiology of the possible link between TGFb1 overproduction, hyperinsulinaemia or insulin resistance, RAS hyperactivity and diastolic dysfunction, but we could hypothesize that TGFb1 overproduction may be able to affect left ventricular filling early in obese hypertensives, independent of the effects related to increased LVM. This hypothesis might be supported by the statement that, with the fibrotic remodelling process, an increase in the stiffness of left ventricular myocardium can lead to an early impairment of the diastolic function.…”