Insulin resistance, lipid and fatty acid concentrations in 867 healthy Europeans

Baldeweg, Stephanie E; Golay, Alain; Natali, Andrea; Balkau, Beverley; Prato, Stefano Del; Coppack, Simon W.

doi:10.1046/j.1365-2362.2000.00597.x

Cited by 112 publications

(67 citation statements)

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“…We expected to show increased subcutaneous adipose tissue NEFA release, leading to elevated NEFA concentrations in insulin resistance, in line with previous observations in the literature [9][10][11]. Instead, we found that systemic NEFA concentrations were not elevated in insulin-resistant men compared with controls and that NEFA release (expressed per unit weight of adipose tissue) was somewhat lower in the insulin-resistant men.…”

Section: Discussionsupporting

confidence: 91%

“…This process is suppressed by insulin in the period following a meal. Both fasting NEFA concentrations and the failure to suppress NEFA under euglycaemic-hyperinsulinaemic clamp conditions have been correlated with measures of insulin resistance in healthy individuals [9]. Defects in insulin-mediated suppression of NEFA concentrations have been shown in obesity [10], in impaired glucose tolerance [11] and in patients with type 2 diabetes [12].…”

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confidence: 99%

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Adipose tissue fatty acid metabolism in insulin-resistant men

et al. 2008

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Aims/hypothesis Increased NEFA production and concentrations may underlie insulin resistance. We examined systemic and adipose tissue NEFA metabolism in insulinresistant overweight men (BMI 25-35 kg/m 2 ). Methods In a cohort study we examined NEFA concentrations in men in the upper quartile of fasting insulin (n=124) and in men with fasting insulin below the median (n = 159). In a metabolic study we examined NEFA metabolism in the fasting and postprandial states, in ten insulin-resistant men and ten controls. Results In the cohort study, fasting NEFA concentrations were not significantly different between the two groups (median values: insulin-resistant men, 410 µmol/l; controls, 445 µmol/l). However, triacylglycerol concentrations differed markedly (1.84 vs 1.18 mmol/l respectively, p<0.001). In the metabolic study, arterial NEFA concentrations again did not differ between groups, whereas triacylglycerol concentrations were significantly higher in insulin-resistant men. Systemic NEFA production and the release of NEFA from subcutaneous adipose tissue, expressed per unit of fat mass, were both reduced in insulin-resistant men compared with controls (fasting values by 32%, p=0.02, and 44%, p=0.04 respectively). 3-Hydroxybutyrate concentrations, an index of hepatic fat oxidation and ketogenesis, were lower (p=0.03). Conclusions/interpretation Adipose tissue NEFA output is not increased (per unit weight of tissue) in insulin resistance. On the contrary, it appears to be suppressed by high fasting insulin concentrations. Alterations in triacylglycerol metabolism are more marked than those in NEFA metabolism and are indicative of altered metabolic partitioning of fatty acids (decreased oxidation, increased esterification) in the liver.

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Section: Discussionsupporting

confidence: 91%

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confidence: 99%

Adipose tissue fatty acid metabolism in insulin-resistant men

et al. 2008

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“…The question arises as to whether these findings represent only coincidental changes or are causally related. Obesity, particularly abdominal obesity as reflected by increased WHR, is associated with elevated NEFA concentrations [28,29,30]. NEFA in plasma is mainly derived from intravascular lipolysis of triglyceride-rich lipoproteins by lipoprotein lipase and from lipolysis of adipose tissue triglyceride by hormone-sensitive lipase.…”

Section: Discussionmentioning

confidence: 99%

Parallel manifestation of insulin resistance and beta cell decompensation is compatible with a common defect in Type 2 diabetes

et al. 2004

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Aims/hypothesis. The aim of the study was to evaluate the relationship between insulin sensitivity, beta cell function and glucose tolerance, and its dependence on variants in the newly identified Type 2 diabetes susceptibility gene, calpain-10 (CAPN10). Methods. We studied 203 men of the same age but with varying degrees of glucose tolerance. These men participated in (i) an oral glucose tolerance test, (ii) a euglycaemic clamp combined with indirect calorimetry and infusion of [3-3 H]-glucose and (iii) a stepwise assessment of acute insulin response to arginine (AIR) at three different glucose concentrations (fasting, 14 and 28 mmol/l).Results. There was a linear increase in NEFA levels (p<0.0005) and WHR (p<0.0005) and decrease in glucose uptake due to a reduction in glucose storage over the entire range of glucose tolerance (r=−0.404; p<0.005). No increase in endogenous glucose production (EGP) was seen until patients had manifest diabetes. However, when EGP was expressed relative to fasting insulin concentrations, there was a linear deterioration of basal hepatic insulin sensitivity (r= −0.514; p<0.005). The AIR followed a bell-shaped curve with an initial rise and subsequent decrease. However, AIR adjusted for insulin sensitivity (disposition index) showed a linear decrease with increasing glucose concentrations (r=−0.563; p<0.001) starting already in subjects with normal glucose tolerance. There was an inverse correlation between increase in WHR and NEFA and peripheral as well as hepatic insulin sensitivity. Subjects with the genotype combination of CAPN10 consisting of SNP44 TT and SNP43 GG genotypes had significantly lower insulin-stimulated glucose uptake than carriers of the other genotype combinations (5.3±0.4 vs 7.2±0.4 mg·ffm kg −1 min −1 ·mU·l −1 ; p<0.005). Conclusions/interpretation. We conclude that the prediabetic state is characterised by a similar linear deterioration of peripheral and hepatic insulin sensitivity as beta cell function and that variants in the CAPN10 gene modify this relationship. These findings are compatible with a common defect in muscle, liver and beta cells in the pathogenesis of Type 2 diabetes.

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“…Type 2 diabetes mellitus is associated with increased plasma concentrations of circulating NEFA [1], which are thought to contribute to the pathogenesis of insulin resistance [2]. Plasma NEFA concentration reflects the balance between adipose tissue lipolysis and uptake (oxidation and esterification) by peripheral tissues.…”

Section: Introductionmentioning

confidence: 99%

Hormone-sensitive lipase is reduced in the adipose tissue of patients with type 2 diabetes mellitus: influence of IL-6 infusion

et al. 2004

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Aims/hypothesis: Type 2 diabetes mellitus is characterised by increased plasma NEFA and IL-6 concentrations, and IL-6 increases lipolysis in healthy men. We assessed the adipose tissue hormone-sensitive lipase (HSL) mRNA expression, protein expression and HSL activity in patients with type 2 diabetes mellitus, and determined the effect of IL-6 administration on these measures. Methods: Seven patients with type 2 diabetes mellitus (age 67±4 years, weight 87±7 kg) and six age-and weight-matched individuals visited the laboratory on two occasions. Subcutaneous adipose tissue biopsies and blood samples were obtained prior to and during 3 h of either saline or recombinant human IL-6 infusion. Results: HSL mRNA was reduced (p<0.05) by ∼40% in type 2 diabetes mellitus relative to control subjects, while HSL protein expression showed a tendency to be decreased (35%, p=0.09). HSL activity averaged 8.87±1.25 and 6.91±1.20 nmol min −1 mg −1 protein for control and type 2 diabetic subjects respectively (p<0.05). IL-6 administration increased (p<0.05) HSL mRNA 2-fold at 60 min in both groups, whereas HSL protein and activity were unaffected by IL-6. Plasma insulin was elevated (p<0.05) in patients with type 2 diabetes mellitus at rest and was blunted (p<0.05) during IL-6 infusion in both groups. Plasma glucagon and cortisol were elevated (p<0.05) by IL-6 in both groups. Conclusions/interpretation: Our data demonstrate that basal HSL is decreased in patients with type 2 diabetes mellitus, and this may be a consequence of elevated plasma insulin levels. We have also shown that IL-6 administration increases HSL gene expression, although it exerted no effect on HSL protein and activity. This disparity between mRNA, protein and enzyme activity may be a function either of the marked alterations in the hormonal milieu induced by IL-6 administration and/or of post-transcriptional events.

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Insulin resistance, lipid and fatty acid concentrations in 867 healthy Europeans

Abstract: The results in this large cohort of healthy European subjects suggest that triglyceride concentrations depend upon both insulin's gluco-regulation (estimated by glucose uptake) and antilipolytic insulin action (measured by NEFA levels) during an euglycaemic clamp.

Cited by 112 publications

References 50 publications

Adipose tissue fatty acid metabolism in insulin-resistant men

Adipose tissue fatty acid metabolism in insulin-resistant men

Parallel manifestation of insulin resistance and beta cell decompensation is compatible with a common defect in Type 2 diabetes

Hormone-sensitive lipase is reduced in the adipose tissue of patients with type 2 diabetes mellitus: influence of IL-6 infusion

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