PP007-SUN: Determining Changes in Insulin Sensitivity Following Major Abdominal Surgery: Homa-IR VS The Hyperinsulinaemic-Euglycaemic Clamp – Data from a Randomised Study (NCT01470534)

2014 ◽  
Vol 33 ◽  
pp. S21
Author(s):  
N. Tewari ◽  
S. Awad ◽  
F. Duška ◽  
I.A. Macdonald ◽  
D.N. Lobo
Keyword(s):  
Insulin Sensitivity ◽  
Abdominal Surgery ◽  
Major Abdominal Surgery ◽  
Euglycaemic Clamp ◽  
Randomised Study ◽  
Hyperinsulinaemic Euglycaemic Clamp

scholarly journals Plasma cathepsin D activity is negatively associated with hepatic insulin sensitivity in overweight and obese humans

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 374-384 ◽  
Author(s):  
Lingling Ding ◽  
Gijs H. Goossens ◽  
Yvonne Oligschlaeger ◽  
Tom Houben ◽  
Ellen E. Blaak ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Cathepsin D ◽  
Insulin Infusion ◽  
Hepatic Insulin Sensitivity ◽  
Euglycaemic Clamp ◽  
Negatively Associated ◽  
Peripheral Insulin Sensitivity ◽  
Hyperinsulinaemic Euglycaemic Clamp ◽  
Tnf Α ◽  
Glucose Output

Abstract Aims/hypothesis Insulin resistance in skeletal muscle and liver plays a major role in the pathophysiology of type 2 diabetes. The hyperinsulinaemic–euglycaemic clamp is considered the gold standard for assessing peripheral and hepatic insulin sensitivity, yet it is a costly and labour-intensive procedure. Therefore, easy-to-measure, cost-effective approaches to determine insulin sensitivity are needed to enable organ-specific interventions. Recently, evidence emerged that plasma cathepsin D (CTSD) is associated with insulin sensitivity and hepatic inflammation. Here, we aimed to investigate whether plasma CTSD is associated with hepatic and/or peripheral insulin sensitivity in humans. Methods As part of two large clinical trials (one designed to investigate the effects of antibiotics, and the other to investigate polyphenol supplementation, on insulin sensitivity), 94 overweight and obese adults (BMI 25–35 kg/m2) previously underwent a two-step hyperinsulinaemic–euglycaemic clamp (using [6,6-2H2]glucose) to assess hepatic and peripheral insulin sensitivity (per cent suppression of endogenous glucose output during the low-insulin-infusion step, and the rate of glucose disappearance during high-insulin infusion [40 mU/(m2 × min)], respectively). In this secondary analysis, plasma CTSD levels, CTSD activity and plasma inflammatory cytokines were measured. Results Plasma CTSD levels were positively associated with the proinflammatory cytokines IL-8 and TNF-α (IL-8: standardised β = 0.495, p < 0.001; TNF-α: standardised β = 0.264, p = 0.012). Plasma CTSD activity was negatively associated with hepatic insulin sensitivity (standardised β = −0.206, p = 0.043), independent of age, sex, BMI and waist circumference, but it was not associated with peripheral insulin sensitivity. However, plasma IL-8 and TNF-α were not significantly correlated with hepatic insulin sensitivity. Conclusions/interpretation We demonstrate that plasma CTSD activity, but not systemic inflammation, is inversely related to hepatic insulin sensitivity, suggesting that plasma CTSD activity may be used as a non-invasive marker for hepatic insulin sensitivity in humans.

scholarly journals Longitudinal Changes in Insulin Resistance in Normal Weight, Overweight and Obese Individuals

2019 ◽  
Vol 8 (5) ◽  
pp. 623 ◽  
Author(s):  
Alice Tang ◽  
Adelle C. F. Coster ◽  
Katherine T. Tonks ◽  
Leonie K. Heilbronn ◽  
Nicholas Pocock ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Normal Weight ◽  
Liver Fat ◽  
Resonance Spectroscopy ◽  
Change Over Time ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp ◽  
Over Time

Background: Large cohort longitudinal studies have almost unanimously concluded that metabolic health in obesity is a transient phenomenon, diminishing in older age. We aimed to assess the fate of insulin sensitivity per se over time in overweight and obese individuals. Methods: Individuals studied using the hyperinsulinaemic-euglycaemic clamp at the Garvan Institute of Medical Research from 2008 to 2010 (n = 99) were retrospectively grouped into Lean (body mass index (BMI) < 25 kg/m2) or overweight/obese (BMI ≥ 25 kg/m2), with the latter further divided into insulin-sensitive (ObSen) or insulin-resistant (ObRes), based on median clamp M-value (M/I, separate cut-offs for men and women). Fifty-seven individuals participated in a follow-up study after 5.4 ± 0.1 years. Hyperinsulinaemic-euglycaemic clamp, dual-energy X-ray absorptiometry and circulating cardiovascular markers were measured again at follow-up, using the same protocols used at baseline. Liver fat was measured using computed tomography at baseline and proton magnetic resonance spectroscopy at follow-up with established cut-offs applied for defining fatty liver. Results: In the whole cohort, M/I did not change over time (p = 0.40); it remained significantly higher at follow-up in ObSen compared with ObRes (p = 0.02), and was not different between ObSen and Lean (p = 0.41). While BMI did not change over time (p = 0.24), android and visceral fat increased significantly in this cohort (ptime ≤ 0.0013), driven by ObRes (p = 0.0087 and p = 0.0001, respectively). Similarly, systolic blood pressure increased significantly over time (ptime = 0.0003) driven by ObRes (p = 0.0039). The best correlate of follow-up M/I was baseline M/I (Spearman’s r = 0.76, p = 1.1 × 10−7). Conclusions: The similarity in insulin sensitivity between the ObSen and the Lean groups at baseline persisted over time. Insulin resistance in overweight and obese individuals predisposed to further metabolic deterioration over time.

Apelin administration improves insulin sensitivity in overweight men during hyperinsulinaemic‐euglycaemic clamp

2017 ◽  
Vol 20 (1) ◽  
pp. 157-164 ◽  
Author(s):  
Pierre Gourdy ◽  
Laurent Cazals ◽  
Claire Thalamas ◽  
Agnès Sommet ◽  
Fabienne Calvas ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp

Intramyocellular lipid levels are associated with peripheral, but not hepatic, insulin sensitivity in normal healthy subjects

2009 ◽  
Vol 117 (3) ◽  
pp. 111-118 ◽  
Author(s):  
Burak Salgin ◽  
Alison J. Sleigh ◽  
Rachel M. Williams ◽  
Sarah J. Jackson ◽  
Les J. Bluck ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Fat Mass ◽  
Fat Free Mass ◽  
Whole Body ◽  
Glucose Disposal ◽  
Resonance Spectroscopy ◽  
Intramyocellular Lipid ◽  
1H Mrs ◽  
Euglycaemic Clamp ◽  
Hyperinsulinaemic Euglycaemic Clamp

Increased levels of IMCL (intramyocellular lipid) have been shown to be associated with reduced steady-state glucose infusion rates during a hyperinsulinaemic–euglycaemic clamp (M-value). The aim of the present study was to explore how IMCL levels relate to the insulin-mediated suppression of endogenous glucose production [hepatic SI (insulin sensitivity)] and increase in glucose disposal (peripheral SI). In the present study, 11 healthy young adults (7 male, 4 female; aged 21–31 years) undertook, in random order, an hyperinsulinaemic–euglycaemic clamp combined with stable glucose isotope enrichment to measure peripheral and hepatic SI, a 1H-MRS (proton-magnetic resonance spectroscopy) scan to determine IMCL levels and a DXA (dual-energy X-ray absorptiometry) scan to assess body composition. IMCL levels (range, 3.2–10.7) were associated with whole-body fat mass (r=0.787, P=0.004), fat mass corrected for height (r=0.822, P=0.002) and percentage of central fat mass (r=0.694, P=0.02), but were not related to whole-body FFM (fat-free mass; r=−0.472, P=0.1). IMCL levels correlated closely with the M-value (r=−0.727, P=0.01) and FFM-corrected peripheral SI (r=−0.675, P=0.02), but were not related to hepatic SI adjusted for body weight (r=0.08, P=0.8). The results of the present study suggest that IMCL accumulation may be a sensitive marker for attenuations in peripheral, but not hepatic, SI in normal populations. Given the close relationship of IMCL levels to whole-body and central abdominal fat mass, relative increases in the flux of lipids from adipose tissue to the intramyocellular compartment may be an integral part of the mechanisms underlying reductions in SI.

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