Euglycemic Clamp Insulin Sensitivity and Longitudinal Systolic Blood Pressure

Abstract

Abstract-Insulin resistance may be an independent risk factor for the development of hypertension, but change in blood pressure (BP) over time has not been adequately studied in healthy individuals fully characterized for insulin sensitivity.In the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study, we measured insulin sensitivity (M/I) using the euglycemic clamp technique in 1073 healthy European adults (587 women, 486 men) aged 30 to 60 years followed up 3 years later. Systolic BP (SBP) at baseline was higher in insulin-resistant women (ie, those in the low sex-specific M/I tertile) compared with those in the intermediate (P<0.001) or high tertiles (P=0.06; mean±SD: 117±13, 111±12, 114±12 mm Hg, respectively). It did not differ across M/I tertiles in men. After adjustment for age, body mass index, baseline SBP, and other covariates, low insulin sensitivity (M/I) predicted a longitudinal rise in SBP in women but not in men; M/I was not associated with change in diastolic BP. SBP rose over time in both sexes and within all M/I tertiles (P<0.05), except in women with high insulin sensitivity. Therefore, in women (but not in men), low insulin sensitivity was associated with higher SBP at 3 years, and high insulin sensitivity was associated with a lower rise in SBP BP and Physical ExaminationBP was measured sitting after 5-minute rest by trained study nurses (OMRON 705CP, Hamburg, Germany) in triplicate, according to a standard protocol: the median of these readings was used in this analysis. Median systolic BP (SBP) ≥140 mm Hg and median diastolic BP (DBP) ≥90 mm Hg at follow-up were taken to indicate hypertension. 34,35 Participants who had been identified and commenced on treatment in routine care (n=46) were classified as hypertensive. Height was measured by stadiometer. Body weight, percentage of body fat, and lean body mass (lbm) were evaluated by bioimpedance (TBF-300, Tanita International Division, United Kingdom). Insulin SensitivityInsulin sensitivity was measured by a standard hyperinsulinemic euglycemic clamp technique as previously described, after central training of site staff.33 Target plasma glucose concentration was between 4.5 and 5.5 mmol/L; insulin was infused at a rate of 240 pmol·min. Plasma glucose was measured at 5-to 10-minute intervals to ensure it remained within 0.8 mmol/L (±15%) of target glucose concentration. The steady-state period (for calculation of insulin sensitivity) was between 80 and 120 minutes. The glucose infusion rate (M value) was expressed in mg·min Biological SamplesTotal cholesterol, high-density lipoprotein cholesterol, and triglycerides were assayed by enzymatic colorimetric assay (Roche), and low-density lipoprotein cholesterol was calculated by the Friedewald formula. A 75-g oral glucose tolerance test was used to exclude participants with diabetes mellitus at inclusion (or developing diabetes mellitus during follow-up), with glucose assayed centrally by the glucose oxidase method (Cobas Integra, Roche). Other MeasuresPhysical acti...

Female Sex and Angiotensin-Converting Enzyme (ACE) Insertion/Deletion Polymorphism Amplify the Effects of Adiposity on Blood Pressure

“…Interestingly, our data show that the II ACE genotype increases the risk of central adiposity-mediated hypertension, despite the favorable metabolic characteristics observed in these patients, which are described both in previous reports 45 and our data. We hypothesize that the possible explanation may lie in the increased salt sensitivity found in the II genotype, with mechanisms that are still unclear and that, based on our findings, are likely to overcome the independent effect of a small difference in insulin sensitivity.…”

Sex specific impact of different obesity phenotypes on the risk of incident hypertension: Tehran lipid and glucose study

“…This higher impact of IR on hypertension risk among women compared to men, was recently addressed in a meta-analysis conducted by Feng Wangs et al [27], showing an independent association between fasting insulin as well as IR with a more pronounced risk of hypertension, in women (relative risk (RR) 2.07; 95% CI 1.19–3.60) than in men (RR 1.48; 95% CI 1.17–1.88). Likewise, the study conducted by Petrie et al [28] showed that in women (but not men) low insulin sensitivity, measured by the euglycemic clamp technique, was associated with higher levels of SBP over time, independent of key covariates including age, baseline blood pressure, BMI and change in BMI. The higher impact of IR in the development of hypertension among women, might be attributable to the effect of lower lean body mass in women; hence, fasting insulin or HOMA-IR values in women reflect a higher level of tissue IR [28].…”

“…Likewise, the study conducted by Petrie et al [28] showed that in women (but not men) low insulin sensitivity, measured by the euglycemic clamp technique, was associated with higher levels of SBP over time, independent of key covariates including age, baseline blood pressure, BMI and change in BMI. The higher impact of IR in the development of hypertension among women, might be attributable to the effect of lower lean body mass in women; hence, fasting insulin or HOMA-IR values in women reflect a higher level of tissue IR [28]. On the other hand, other studies showed similar or higher impact of IR among men rather than women [29, 30].…”

Gender‐specific considerations in physical activity, thermogenesis and fat oxidation: implications for obesity management

“…Furthermore, the presence of any of the components of metabolic syndrome appears to pose a much greater risk to health in women than in men. Indeed, (i) obesity increases inflammatory markers and is a more prominent risk factor for type 2 diabetes in women than in men ; (ii) type 2 diabetes confers a much higher risk of cardiovascular‐related mortality and is more frequently characterized by postprandial hyperglycaemia in women than in men and (iii) low insulin sensitivity independently predicts longitudinal change in blood pressure in women but not in men .…”