title: Relationship between insulin resistance and nonmodulating hypertension: linkage of metabolic abnormalities and cardiovascular risk.
abstract: Insulin resistance is a feature common to patients with diabetes and to some with hypertension. It is assumed that this feature confers the increased metabolic risk in hypertension. However, the state of the renin-angiotensin system might contribute to cardiovascular risk, although there is no clear mechanistic explanation. Our recent observation that insulin levels are increased in a specific subset of patients with normal/high-renin hypertension, the nonmodulators, provided the background for the current hypothesis: to ascertain whether abnormalities in lipid and carbohydrate metabolism are observed in the same patients in whom alterations in sodium transport, sodium homeostasis, and the renin-aniotensin system response have been identified. Exploration of a family history of cardiovascular risk was a secondary goal. Insulin sensitivity (assessed by a 75-g oral glucose load), lipid levels, and two defects in the renin-angiotensin system were assessed in 62 hypertensive and 14 normotensive subjects placed on a high (210 mmol/l) and a low (10 mmol/l) sodium intake for 2 weeks, to classify them as low-renin, nonmodulator, or modulating hypertensive subjects. Only in nonmodulators were the following cardiovascular risk factors significantly increased: fasting insulin (P < 0.01); increment in post-glucose load insulin (P < 0.01); total, LDL, and VLDL cholesterol and triglyceride levels (P < 0.05); and erythrocyte Na+/Li+ countertransport activity (P < 0.001). Both nonmodulators and low-renin hypertensive subjects had a significantly (P < 0.01) increased frequency of a family history of hypertension by questionnaire compared with subjects with intact modulation. However, only nonmodulators had a significantly (P < 0.02) higher frequency of a family history of myocardial infarction. Thus, there is a clustering of metabolic abnormalities in a discrete subset of the essential hypertensive population with a specific dysregulation of the renin-angiotensin system--nonmodulation. The absence of this cluster in low-renin hypertensive subjects may explain their relatively diminished cardiovascular risk. Its presence in nonmodulators likely contributes to the increased cardiovascular risk observed in normal/high-renin hypertension.
authors.affiliation: Institute of I Clinica Medica, Andrea Cesalpino Foundation, University La Sapienza, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ferri
authors.forename: C
authors.initials: C
authors.lastname: Bellini
authors.forename: G
authors.initials: G
authors.lastname: Desideri
authors.forename: M
authors.initials: M
authors.lastname: Valenti
authors.forename: G
authors.initials: G
authors.lastname: De Mattia
authors.forename: A
authors.initials: A
authors.lastname: Santucci
authors.forename: N K
authors.initials: NK
authors.lastname: Hollenberg
authors.forename: G H
authors.initials: GH
authors.lastname: Williams
mesh_terms: D000328:Adult; D017920:Antiporters / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology*; D004032:Diet; D004912:Erythrocytes; D005215:Fasting / Q000502:physiology; D005947:Glucose / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D008499:Medical Records; D008875:Middle Aged; D012307:Risk Factors; D012964:Sodium / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D017920:Antiporters; C045885:sodium-lithium countertransporter; D012964:Sodium; D005947:Glucose