Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss

Nora E. Straznicky, Mariee T. Grima, Carolina I. Sari, Elisabeth A. Lambert, Sarah E. Phillips, Nina Eikelis, Daisuke Kobayashi, Dagmara Hering, Justin A. Mariani, John B. Dixon, Paul J. Nestel, Sofie Karapanagiotidis, Markus P. Schlaich, Gavin W. Lambert

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Abstract

Background: The hyperinsulinemia of obesity is a function of both increased pancreatic insulin secretion and decreased insulin clearance, and contributes to cardiovascular risk. Whilst weight loss is known to enhance insulin clearance, there is a paucity of data concerning the underlying mechanisms. This study was conducted to examine the inter-relationships between changes in sympathetic nervous system (SNS) activity, vascular function and insulin clearance during a weight loss program. Methods: Seventeen non-smoking, un-medicated individuals aged 55 ± 1 years (mean ± SEM), body mass index (BMI) 33.9 ± 1.7 kg/m2, underwent a 4-month hypocaloric diet (HCD), using a modified Dietary Approaches to Stop Hypertension diet, whilst seventeen age- and BMI-matched subjects acted as controls. Insulin sensitivity and insulin clearance were assessed via euglycemic hyperinsulinemic clamp (exogenous insulin clearance); hepatic insulin extraction was calculated as fasting C-peptide to insulin ratio (endogenous insulin clearance); SNS activity was quantified by microneurographic nerve recordings of muscle sympathetic nerve activity (MSNA) and whole-body norepinephrine kinetics; and vascular function by calf venous occlusion plethysmography and finger arterial tonometry. Results: Weight loss averaged -8.3 ± 0.6 % of body weight in the HCD group and was accompanied by increased clamp-derived glucose utilization (by 20 ± 9 %, P = 0.04) and exogenous insulin clearance (by 12 ± 5 %, P = 0.02). Hepatic insulin extraction increased from 6.3 ± 0.8 to 7.1 ± 0.9 (P = 0.09). Arterial norepinephrine concentration decreased by -12 ± 5 %, whole-body norepinephrine spillover rate by -14 ± 8 %, and MSNA by -9 ± 5 bursts per 100 heartbeats in the HCD group (P all >0.05 versus control group). Step-wise regression analysis revealed a bidirectional relationship between enhanced exogenous insulin clearance post weight loss and reduction in calf vascular resistance (r = -0.63, P = 0.01) which explained 40 % of the variance. Increase in hepatic insulin extraction was predicted by enhanced finger reactive hyperaemic response (P = 0.006) and improvement in oral glucose tolerance (P = 0.002) which together explained 64 % of the variance. Conclusions: Insulin clearance is independently and reciprocally associated with changes in vascular function during weight loss intervention. Trial registration ClinicalTrials.gov: NCT01771042 and NCT00408850.

Original languageEnglish
Article number113
JournalCardiovascular Diabetology
Volume14
Issue number1
DOIs
Publication statusPublished - 22 Aug 2015

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Straznicky, N. E., Grima, M. T., Sari, C. I., Lambert, E. A., Phillips, S. E., Eikelis, N., ... Lambert, G. W. (2015). Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss. Cardiovascular Diabetology, 14(1), [113]. https://doi.org/10.1186/s12933-015-0276-2