Decreased non-esterified fatty acid suppression and features of the insulin resistance syndrome occur in a sub-group of individuals with normal glucose tolerance

Byrne, Christopher D.; Wareham, Nicholas J.; Day, Nicholas E.; McLeish, R.; Williams, D. R. R.; Hales, C. N.

doi:10.1007/bf00401770

Cited by 31 publications

(11 citation statements)

References 24 publications

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“…This affect was not apparent in men who, in this cohort, are more insulin resistant. 35 Female carriers of the t-55 allele then seem better able to switch from fatty acid to glucose metabolism following an insulin surge. The increased NEFA suppression associated with the t-55 genotype may be exposed by the greater insulin sensitivity in women.…”

Section: Discussionmentioning

confidence: 99%

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Uncoupling protein 3 genetic variants in human obesity: the c-55t promoter polymorphism is negatively correlated with body mass index in a UK Caucasian population

et al. 2001

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OBJECTIVE: To investigate whether genetic variation at the UCP3 locus contributes to human obesity. SUBJECTS: Ninety-one obese children (BMI b 4 standard deviations from age related mean) and 419 Caucasian adults from the Isle of Ely Study. DESIGN: Single strand conformation polymorphism (SSCP) analysis was used to scan the coding region of the UCP3 gene in 91 severely obese children. A common polymorphism identi®ed in this gene (c-55t) has been shown to associate with lower UCP3 mRNA expression. Polymerase chain reaction-based forced restriction digestion was used to detect this allele in Caucasian adults. Multiple regression analysis was used to determine associations between the c-55t genotype and anthropometric, energetic and biochemical indices relevant to obesity. MEASUREMENTS: For the obese children, SSCP analysis and sequencing of variants were carried out. For the Isle of Ely Study, c-55t genotype and anthropometric (body mass index, waist ± hip ratio, percentage body fat), energetic (dietary fat intake, physical activity index, adjusted metabolic rate, maximum oxygen consumption) and biochemical indices (pre-and postglucose challenge plasma triglycerides, non-esteri®ed fatty acids, insulin and glucose) were determined. RESULTS: A previously reported missense mutation (V102I) was detected in a single obese Afro-Carribean child. Twenty-one percent of the genes examined in the Isle of Ely study carried the c-55t promoter variant. Age-adjusted body mass index (BMI) was signi®cantly (P 0.0037) lower in carriers of this variant. CONCLUSION: Mutations in the coding sequence of UCP3 are unlikely to be a common monogenic cause of severe human obesity. In a Caucasian population the UCP3 c-55t polymorphism is negatively associated with BMI.

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Section: Discussionmentioning

confidence: 99%

“…18 The area under the curve (AUC) for plasma NEFA was used as a composite measure of NEFA suppression following the OGTT. 19 Methods DNA extraction protocol. Whole blood was collected into EDTA tubes (Sarstedt, Leicester UK).…”

Section: Physical Measurementsmentioning

confidence: 99%

Uncoupling protein 3 genetic variants in human obesity: the c-55t promoter polymorphism is negatively correlated with body mass index in a UK Caucasian population

et al. 2001

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“…NEFA were measured in the fasting state and during the OGTT to allow measurement of insulin-mediated suppression of NEFA concentration [25,27,28]. NEFA concentrations were measured in heparinised plasma samples with an autoanalyser (Konelab 20; Thermo Electon, Waltham, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

Differential effects of fatness, fitness and physical activity energy expenditure on whole-body, liver and fat insulin sensitivity

et al. 2007

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Aims/hypothesis The relative contributions of fitness (maximal oxygen uptake), physical activity energy expenditure (PAEE) and fatness to whole-body, liver and fat insulin sensitivity is uncertain. The aim of this study was to determine whether fitness and PAEE are associated with whole-body, liver and fat insulin sensitivity independently of body fat. Materials and methods We recruited 25 men (mean [SD] age 53 [6] years). Whole-body (M value) and liver (percentage suppression of endogenous glucose output) insulin sensitivity were estimated using a hyperinsulinaemic-euglycaemic clamp. Insulin sensitivity in fat (insulin sensitivity index for NEFA) was estimated during an OGTT. Total and truncal fat were measured by dual-energy X-ray absorptiometry, fitness by treadmill, and PAEE (n=21) by 3 day heart rate monitoring and Baecke questionnaire. Results In univariate analyses, fatness was strongly associated with insulin sensitivity (whole-body, liver and fat). Fitness was associated with whole-body (r=0.53, p<0.007) and liver (0.42, p=0.04) insulin sensitivity, while PAEE was associated with liver insulin sensitivity (r=0.55, p=0.01). Regression models were established to describe associations between fatness, fitness and physical activity and measures of insulin sensitivity (whole-body, fat and liver) as outcomes. Only fatness was independently associated with whole-body insulin sensitivity (B coefficient −0.01, p=0.001). Fitness was not associated with any outcome. Only PAEE was independently associated with liver insulin sensitivity (B coefficient 13.5, p=0.02). Conclusions/interpretation Fatness explains most of the variance in whole-body insulin sensitivity. In contrast, PAEE explains most of the variance in liver insulin sensitivity.Keywords Fitness . Hyperinsulinaemic-euglycaemic clamp . Insulin resistance . Insulin sensitivity (whole-body, liver and fat) . Obesity (visceral, truncal and subcutaneous

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“…Adiponectin, IL-1β, IL-6 and TNF-α were analysed using an ELISA kit (R and D Systems, Abingdon, UK). Suppression of NEFA was measured during the OGTT [17][18][19]. To assess insulin sensitivity in skeletal muscle and liver, we used a hyperinsulinaemic-euglycaemic clamp technique [20] with a labelled glucose tracer to determine insulin-mediated suppression of hepatic glucose output during the early phase of the clamp [7,8,21].…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

“…NEFA were measured fasting at 0, 10, 20, 30, 40, 60, 90 and 120 min during the OGTT to allow measurement of insulin-mediated suppression of NEFA concentration [17][18][19].…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

Non-esterified fatty acid concentrations are independently associated with hepatic steatosis in obese subjects

Holt

Wild

Wood³

et al. 2005

Diabetologia

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Aims/hypothesis: We tested the hypothesis that NEFA concentrations are higher in obese subjects with fatty liver than in obese subjects without fatty liver. Materials and methods: We recruited 22 obese (BMI>30 kg/m 2 ) men aged 42-64 years, in whom liver fat was assessed by ultrasound and classified into categories of no, mild to moderate and severe fatty liver by two independent radiologists. Regional and visceral abdominal fat were assessed by dualenergy X-ray absorptiometry and magnetic resonance imaging, and endogenous glucose production, whole-body glucose disposal during an insulin clamp, and NEFA concentrations were measured, along with NEFA suppression (percent (%) suppression and insulin sensitivity index for NEFA during an OGTT). Results: Seven subjects had no evidence of fatty liver, nine had mild or moderate fatty liver and six had severe fatty liver. The amount of visceral fat was not associated with the degree of fatty liver. Whole-body glucose disposal was inversely associated with fatty liver (38.4, 26.5 and 23.9 μmol kg −1 min −1 for the groups with no fatty liver, mild to moderate fatty liver and severe fatty liver, respectively, p=0.004). NEFA suppression during the OGTT was decreased (62.5, 50.8 and 41%, p=0.03, for no, mild to moderate, and severe fatty liver, respectively) and the insulin sensitivity index for NEFA was decreased (0.80, 0.40 and 0.34, p<0.0001). Regression modelling suggested that NEFA concentrations were associated with fatty liver independently of whole-body glucose production and disposal measurements. Conclusions/interpretation: In obese men, NEFA concentrations during an OGTT are associated with fatty liver independently of classic measures of insulin sensitivity determined by the hyperinsulinaemic clamp. The contribution to this association by factors regulating NEFA concentrations requires further study.

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Decreased non-esterified fatty acid suppression and features of the insulin resistance syndrome occur in a sub-group of individuals with normal glucose tolerance

Cited by 31 publications

References 24 publications

Uncoupling protein 3 genetic variants in human obesity: the c-55t promoter polymorphism is negatively correlated with body mass index in a UK Caucasian population

Uncoupling protein 3 genetic variants in human obesity: the c-55t promoter polymorphism is negatively correlated with body mass index in a UK Caucasian population

Differential effects of fatness, fitness and physical activity energy expenditure on whole-body, liver and fat insulin sensitivity

Non-esterified fatty acid concentrations are independently associated with hepatic steatosis in obese subjects

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