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Vascular resistance and insulin

Vascular resistance, insulin clearance and weight loss

Clamp derived glucose utilisation post weight loss were positively associated with both measures of insulin clearance

There is a bidirectional inter-relationship between changes in insulin clearance and vascular endothelial function during the course of a weight loss programme, according to a study by researchers from Australia. They claim that improvements in risk factors associated with metabolic syndrome such as insulin resistance, hyperglycaemia, proinflammatory state, blood pressure and HDL-cholesterol could underlie the vascular benefit and enhancement in insulin clearance.

The paper, ‘Reduction in peripheral vascular resistance predicts improvement in insulin clearance following weight loss.’ published in Cardiovascular Diabetology by authors from the Baker IDI Heart and Diabetes Institute and Monash University, Melbourne, Australia, designed the study to examine the effects of weight loss induced by hypocaloric diet (HCD) on insulin clearance, SNS activity and vascular function, and to delineate the pathophysiological drivers of improvement in insulin clearance following lifestyle intervention.


Seventeen overweight and obese subjects were included in a weight loss trial (HCD group) and compared with age- and BMI-matched controls (n=17). Subjects were non-smokers, aged 45–65 years, with a stable body weight (±1kg) in the previous six months and were not taking medications that could affect study parameters

Dietary intake was assessed by four-day prospective diet records using Australian food composition tables and subjects were prescribed HCD at 25% energy deficit using a modified Dietary Approach to Stop Hypertension (DASH) eating plan, including 14-day menu plans and recipes and prepared food in their home environment. They attended fortnightly for body weight measurement and dietary counselling with the study dietician. With regards to exercise they were instructed to walk briskly for 30 min, at least five days per week.

The control subjects were told to maintain their usual eating and exercise habits. Dietary intake was monitored by prospective four-days diet records and 24 hour urinalysis (collected on the day prior to SNS tests) to quantify sodium, potassium, urea and creatinine excretion. Clinical testing was performed on two separate mornings a week apart. Subjects attended at 8am after an overnight fast and having abstained from alcohol and heavy exercise for 36 hour and caffeine for 18 hour. Participants also underwent a standard 75g oral glucose tolerance test (OGTT) with 30min blood sampling. Endothelial function was evaluated non-invasively in the index finger of the non-dominant hand by the EndoPAT 2000 device.


The results showed that weight loss averaged −8.3±0.6 % of body weight in the HCD group and was accompanied by increased clamp-derived glucose utilisation (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.

“There are three main findings from our study,” the authors write. “First, that weight loss of −8.3% of baseline body weight elicited significant improvement in whole-body insulin clearance (by 12%) and a non-significant increase in fasting hepatic insulin extraction (by 17%) within our cohort. Second, that although vascular responses to weight loss were heterogeneous, reduction in calf vascular resistance was the strongest independent predictor of improvement in exogenous insulin clearance, whilst improvements in endothelial function (quantified as the finger reactive hyperaemic response) and glucose tolerance predicted improvement in endogenous insulin clearance. Third, that the sympathoinhibition attained following HCD was modulated by baseline insulin status and did not correlate directly with changes in insulin clearance.”

“The salient finding of our study is that improvement in vascular parameters (reduction in calf vascular resistance and increase in finger reactive hyperaemic index), independent of weight changes, delineated those subjects who gained a benefit in insulin clearance following HCD from those who did not,” they report. “Moreover, this relationship was bidirectional as enhanced insulin clearance post weight loss independently predicted reduction in calf vascular resistance…Our findings support the notion that insulin clearance and sensitivity are closely aligned as improvement in Matsuda ISI and clamp derived glucose utilisation post weight loss were positively associated with both measures of insulin clearance, and suggest that vascular function may be a common pathophysiological mediator of this association.”

To access this paper, please click here

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