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Summary: Phaeochromocytoma, a rare neuroendocrine tumour of chromaffin cell origin, is characterised by catecholamine excess. Clinical presentation ranges from asymptomatic disease to life-threatening multiorgan dysfunction. Catecholamine-induced cardiomyopathy is a dreaded complication with high lethality. While there is lack of evidence-based guidelines for use of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) in the management of this condition, limited to case reports and small case series, V-A ECMO has been reported as 'bridge to recovery' therapy, providing circulatory support in the initial period of stabilisation prior to surgery. We report on two patients presenting with catecholamine-induced cardiomyopathy and circulatory collapse who were successfully treated with V-A ECMO for 5 and 6 days, respectively, providing initial haemodynamic support. After stabilisation and introduction of alpha-blockade, both cases had favourable outcomes, with successful laparoscopic adrenalectomies on days 62 and 83 of admission, respectively. Our case reports provide further support for the use of V-A ECMO in the treatment of such gravely ill patients. Learning points: Phaeochromocytoma should be considered in the diagnosis of patients presenting with acute cardiomyopathy. Management of catecholamine-induced cardiomyopathy is complex and requires multidisciplinary specialist input. Pre-operative management of phaeochromocytoma involves alpha-blockade; however, haemodynamic instability in the setting of cardiogenic shock can preclude alpha-blockade use. Veno-arterial extracorporeal membrane oxygenation is a life-saving intervention which may be considered in cases of acute catecholamine-induced cardiomyopathy and cardiogenic shock in order to provide the required haemodynamic support in the initial phase of treatment, enabling the administration of traditional pharmacological agents, including alpha-blockade.
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PURPOSE: The trace element iodine is a vital constituent of thyroid hormones. Iodine requirements increase during pregnancy, when even mild deficiency may affect the neurocognitive development of the offspring. Urinary iodine concentration (UIC) is the means of assessing iodine status in population surveys; a median UIC of 100-199 µg/L is deemed sufficient in a non-pregnant population. Milk is the main dietary source of iodine in the UK and Ireland. METHODS: We surveyed the iodine status of 903 girls aged 14-15 years in seven sites across the island of Ireland. Urine iodine concentration was measured in spot-urine samples collected between March 2014 and October 2015. Food group intake was estimated from iodine-specific food-frequency questionnaire. Milk-iodine concentration was measured at each site in summer and winter. RESULTS: The median UIC overall was 111 µg/L. Galway was the only site in the deficient range (median UIC 98 µg/L). All five of the Republic of Ireland sites had UIC ≤ 105 µg/L. In the two sites surveyed twice, UIC was lower in summer vs winter months [117 µg/L (IQR 76-165) vs 130 µg/L (IQR 91-194) (p < 0.01)]. Milk samples collected from Galway and Roscommon had a lower mean iodine concentration than those from Derry/Londonderry (p < 0.05). Milk intake was positively associated with UIC (p < 0.001). CONCLUSIONS: This is the largest survey of its kind on the island of Ireland, which currently has no iodine-fortification programme. Overall, the results suggest that this young female population sits at the low end of sufficiency, which has implications if, in future, they enter pregnancy with borderline status.
Assuntos
Iodo , Adolescente , Animais , Estudos Transversais , Dieta , Feminino , Humanos , Iodetos , Irlanda/epidemiologia , Leite , Estado Nutricional , GravidezRESUMO
BACKGROUND: Klinefelter syndrome (KS) is the most common sex-chromosomal disorder in males. Frequently under-recognized, it occurs in 1 in 500-600 male births. It is caused by the inheritance of at least one additional X chromosome from either parent. Patients often have uncommon or atypical malignancies. PATIENT: We describe the case of a 35-year-old man with 47XXY KS and previous cryptorchidism, presenting with a painful testicular mass. Histology confirmed Leydig cell hyperplasia. DISCUSSION: Cryptorchidism is an established risk factor for testicular tumours and occurs six times more commonly in KS than in the general population. Despite this, large epidemiological studies have shown a reduced burden of testicular cancer in these patients. The presentation of a hypoechoic lesion on ultrasound will prompt consideration of testicular tumours, however orchalgia represents an atypical presentation. In patients with KS, Leydig cell hyperplasia is a much more common entity and should be considered early in the differential diagnosis. LEARNING POINTS: The differential diagnosis of a testicular mass in Klinefelter syndrome includes malignancy and nodular Leydig cell hyperplasia.Diagnosis can be challenging, both radiologically and histologically.Orchalgia is atypical in Leydig cell hyperplasia.
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BACKGROUND AND AIMS: The provision of medical care to young adults with type 1 diabetes mellitus is challenging. The aim of this study was to determine the rates of microvascular complications and their progression among patients with type 1 diabetes mellitus attending a specialist young adult diabetes service in Ireland. METHODS: A retrospective review of 62 (male 56.5%) patients with type 1 diabetes mellitus attending the young adult diabetes service at our institution was undertaken. Data was recorded across two time points, clinic registration and at 5 years following initial contact. RESULTS: The mean ± SD age at first attendance was 17.4 ± 2.0 years. Mean ± SD duration of diabetes was 6.3 ± 3.9 years with most patients treated using multiple daily insulin injections (75.8%). diabetic retinopathy rate at first attendance was 17.7% and after 5 years was 37.1% (p = 0.003). The majority of cases were background retinopathy. The prevalence of diabetic kidney disease was 6.4% and this remained unchanged at follow-up. Mean ± SD HbA1c improved from 76.1 ± 22.4 mmol/mol (9.1 ± 4.2%) to 69.1 ± 14.9 mmol/mol (8.5 ± 3.5%), p = 0.044. Duration of diabetes was the only clinical variable associated with retinopathy risk at 5 years on multiple regression analysis (p = 0.037). CONCLUSIONS: Diabetic retinopathy is prevalent in young adults with type 1 diabetes attending specialist secondary care diabetes services. Duration of diabetes was the strongest determinant of retinopathy risk.
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Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/epidemiologia , Retinopatia Diabética/epidemiologia , Adolescente , Diabetes Mellitus Tipo 1/sangue , Nefropatias Diabéticas/etiologia , Retinopatia Diabética/etiologia , Progressão da Doença , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Irlanda/epidemiologia , Masculino , Microvasos , Prevalência , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
The accumulation of abdominal adipose tissue has long been associated with adverse cardiovascular outcomes. Paradoxically, increased gluteofemoral adipose tissue, which is predominantly subcutaneous fat, seems to play a protective role. There has been significant scientific interest in understanding how abdominal and gluteofemoral depots confer opposing metabolic risks. However, the study of regional adipose physiology in vivo remains challenging. We discuss some of the methodologies used. We focus specifically on the arteriovenous difference technique and present some insights into gluteofemoral adipose physiology.
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Upper- and lower-body fat depots exhibit opposing associations with obesity-related metabolic disease. We defined the relationship between DEXA-quantified fat depots and diabetes/cardiovascular risk factors in a healthy population-based cohort (n = 3,399). Gynoid fat mass correlated negatively with insulin resistance after total fat mass adjustment, whereas the opposite was seen for abdominal fat. Paired transcriptomic analysis of gluteal subcutaneous adipose tissue (GSAT) and abdominal subcutaneous adipose tissue (ASAT) was performed across the BMI spectrum (n = 49; 21.4-45.5 kg/m(2)). In both depots, energy-generating metabolic genes were negatively associated and inflammatory genes were positively associated with obesity. However, associations were significantly weaker in GSAT. At the systemic level, arteriovenous release of the proinflammatory cytokine interleukin-6 (n = 34) was lower from GSAT than ASAT. Isolated preadipocytes retained a depot-specific transcriptional "memory" of embryonic developmental genes and exhibited differential promoter DNA methylation of selected genes (HOTAIR, TBX5) between GSAT and ASAT. Short hairpin RNA-mediated silencing identified TBX5 as a regulator of preadipocyte proliferation and adipogenic differentiation in ASAT. In conclusion, intrinsic differences in the expression of developmental genes in regional adipocytes provide a mechanistic basis for diversity in adipose tissue (AT) function. The less inflammatory nature of lower-body AT offers insight into the opposing metabolic disease risk associations between upper- and lower-body obesity.
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Tecido Adiposo/metabolismo , Doenças Cardiovasculares/metabolismo , Obesidade/metabolismo , Gordura Abdominal/metabolismo , Adulto , Metilação de DNA , Feminino , Humanos , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Gordura Subcutânea Abdominal/metabolismo , Proteínas com Domínio T/metabolismoRESUMO
OBJECTIVE: Lipotoxicity and ectopic fat deposition reduce insulin signaling. It is not clear whether excess fat deposition in nonadipose tissue arises from excessive fatty acid delivery from adipose tissue or from impaired adipose tissue storage of ingested fat. RESEARCH DESIGN AND METHODS: To investigate this we used a whole-body integrative physiological approach with multiple and simultaneous stable-isotope fatty acid tracers to assess delivery and transport of endogenous and exogenous fatty acid in adipose tissue over a diurnal cycle in lean (n = 9) and abdominally obese men (n = 10). RESULTS: Abdominally obese men had substantially (2.5-fold) greater adipose tissue mass than lean control subjects, but the rates of delivery of nonesterified fatty acids (NEFA) were downregulated, resulting in normal systemic NEFA concentrations over a 24-h period. However, adipose tissue fat storage after meals was substantially depressed in the obese men. This was especially so for chylomicron-derived fatty acids, representing the direct storage pathway for dietary fat. Adipose tissue from the obese men showed a transcriptional signature consistent with this impaired fat storage function. CONCLUSIONS: Enlargement of adipose tissue mass leads to an appropriate downregulation of systemic NEFA delivery with maintained plasma NEFA concentrations. However the implicit reduction in adipose tissue fatty acid uptake goes beyond this and shows a maladaptive response with a severely impaired pathway for direct dietary fat storage. This adipose tissue response to obesity may provide the pathophysiological basis for ectopic fat deposition and lipotoxicity.
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Tecido Adiposo/metabolismo , Obesidade/metabolismo , Tecido Adiposo/anatomia & histologia , Adulto , Metabolismo Basal , Glicemia/metabolismo , Índice de Massa Corporal , HDL-Colesterol/sangue , Regulação para Baixo , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos não Esterificados/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/metabolismo , RNA Mensageiro/genética , Valores de Referência , Magreza/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismoRESUMO
OBJECTIVE: Gluteo-femoral, in contrast to abdominal, fat accumulation appears protective against diabetes and cardiovascular disease. Our objective was to test the hypothesis that this reflects differences in the ability of the two depots to sequester fatty acids, with gluteo-femoral fat acting as a longer-term "sink." RESEARCH DESIGN AND METHODS: A total of 12 healthy volunteers were studied after an overnight fast and after ingestion of a mixed meal. Blood samples were taken from veins draining subcutaneous femoral and abdominal fat and compared with arterialized blood samples. Stable isotope-labeled fatty acids were used to trace specific lipid fractions. In 36 subjects, adipose tissue blood flow in the two depots was monitored with (133)Xe. RESULTS: Blood flow increased in response to the meal in both depots, and these responses were correlated (r(s) = 0.44, P < 0.01). Nonesterified fatty acid (NEFA) release was suppressed after the meal in both depots; it was lower in femoral fat than in abdominal fat (P < 0.01). Plasma triacylglycerol (TG) extraction by femoral fat was also lower than that by abdominal fat (P = 0.05). Isotopic tracers showed that the difference was in chylomicron-TG extraction. VLDL-TG extraction and direct NEFA uptake were similar in the two depots. CONCLUSIONS: Femoral fat shows lower metabolic fluxes than subcutaneous abdominal fat, but differs in its relative preference for extracting fatty acids directly from the plasma NEFA and VLDL-TG pools compared with chylomicron-TG.
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Tecido Adiposo/metabolismo , Gorduras na Dieta/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Lipoproteínas VLDL/metabolismo , Gordura Abdominal/metabolismo , Adulto , Transporte Biológico , Velocidade do Fluxo Sanguíneo/fisiologia , Capilares/metabolismo , Quilomícrons/metabolismo , Creatinina/sangue , Gorduras na Dieta/sangue , Ingestão de Alimentos , Jejum , Ácidos Graxos/metabolismo , Ácidos Graxos não Esterificados/sangue , Feminino , Fêmur , Glucose/metabolismo , Humanos , Lipoproteínas VLDL/sangue , Masculino , Valores de Referência , Relação Cintura-QuadrilRESUMO
Liver fat represents a balance between input, secretion, and oxidation of fatty acids. As humans spend the majority of a 24-h period in a postprandial state, dietary fatty acids make an important contribution to liver fat metabolism. We compared hepatic fatty acid partitioning in healthy lean (n = 9) and abdominally obese (n = 10) males over 24 h. Volunteers received three mixed meals adjusted for basal metabolic rate. U-13C-labeled fatty acids were incorporated into the meals, and [2H2]palmitate was infused intravenously to distinguish between sources of fatty acids incorporated into VLDL-TG. Immunoaffinity chromatography was used to isolate VLDL-TG of hepatic origin. Liver and whole body fatty acid oxidation was assessed by isotopic enrichment of 3-hydoxybutyrate and breath CO2. We found a similar contribution of dietary fatty acids to VLDL-TG in the two groups over 24 h. The contribution of fatty acids from splanchnic sources was higher (P < 0.05) in the abdominally obese group. Ketogenesis occurred to a significantly greater extent in abdominally obese compared with lean males, largely due to lessened downregulation of postprandial ketogenesis (P < 0.001). The appearance of 13C in breath CO2 was also greater (P < 0.001) in abdominally obese compared with lean men. Hepatic elongation and desaturation of palmitic acid were higher (P < 0.05) in abdominally obese than in lean males. Oxidation of dietary fatty acids and hepatic desaturation and elongation of palmitic acid occurred to a greater extent in abdominally obese men. These alterations may represent further pathways for redirection of fatty acids into export from the liver or oxidation to prevent liver fat accumulation.
Assuntos
Gorduras na Dieta/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Fígado Gorduroso/metabolismo , Lipoproteínas VLDL/metabolismo , Obesidade/metabolismo , Triglicerídeos/metabolismo , Ácido 3-Hidroxibutírico/sangue , Ácido 3-Hidroxibutírico/metabolismo , Adulto , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Apolipoproteínas B/sangue , Apolipoproteínas B/metabolismo , Área Sob a Curva , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Ácidos Graxos não Esterificados/sangue , Humanos , Insulina/sangue , Insulina/metabolismo , Lipoproteínas/sangue , Lipoproteínas/metabolismo , Lipoproteínas VLDL/sangue , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Triglicerídeos/sangue , Adulto Jovem , gama-Glutamiltransferase/sangue , gama-Glutamiltransferase/metabolismoRESUMO
Gluteofemoral adipose tissue (AT) has interesting positive associations with metabolic health, yet little is known of its metabolic physiology. Here, we describe a technique for cannulation of a vein draining the femoral fat depot. Using ultrasound guidance, a cannula was introduced into a superficial branch of the great saphenous vein. We also obtained arterialized blood and, for comparison, blood representing drainage from forearm muscle and from subcutaneous abdominal AT. We measured appropriate biomarkers of skeletal muscle (creatinine) and AT (nonesterified fatty acids (NEFAs), glycerol, leptin) drainage. Blood obtained in this way from the saphenous vein did not show creatinine release (creatinine concentration 100.5 +/- 0.4%, mean +/- s.e.m., of that in arterialized blood), whereas creatinine concentrations in blood draining forearm muscle averaged 121 +/- 1% of those in arterialized blood. Fatty acid release from the tissue drained was suppressed after feeding and increased during beta-adrenergic stimulation. We also demonstrated leptin secretion. These findings suggest that blood so obtained is representative of AT drainage with little apparent contribution of skeletal muscle. We believe this technique will facilitate physiological studies of a lower-body fat depot in humans.
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Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/metabolismo , Veia Safena/fisiologia , Coxa da Perna , Biomarcadores/sangue , Cateteres de Demora , Ácidos Graxos/sangue , Feminino , Humanos , Leptina/sangue , MasculinoRESUMO
OBJECTIVE: Osteopontin (OPN) plays an important role in the development of insulin resistance and liver complications in dietary murine models. We aimed to determine the expression pattern of OPN and its receptor CD44 in obese patients and mice according to insulin resistance and liver steatosis. RESEARCH DESIGN AND METHODS: OPN and CD44 expressions were studied in 52 morbidly obese patients and in mice. Cellular studies were performed in HepG2 cells. RESULTS: Hepatic OPN and CD44 expressions were strongly correlated with liver steatosis and insulin resistance in obese patients and mice. This increased OPN expression could be due to the accumulation of triglycerides, since fat loading in HepG2 promotes OPN expression. In contrast, OPN expression in adipose tissue (AT) was enhanced independently of insulin resistance and hepatic steatosis in obese patients. The elevated OPN expression in AT was paralleled with the AT macrophage infiltration, and both phenomena were reversed after weight loss. The circulating OPN level was slightly elevated in obese patients and was not related to liver steatosis. Further, AT did not appear to secrete OPN. In contrast, bariatric surgery-induced weight loss induced a strong increase in circulating OPN. CONCLUSIONS: The modestly elevated circulating OPN levels in morbidly obese patients were not related to liver steatosis and did not appear to result from adipose tissue secretion. In subcutaneous AT, expression of OPN was directly related to macrophage accumulation independently from liver complications. In contrast, hepatic OPN and CD44 expressions were related to insulin resistance and steatosis, suggesting their local implication in the progression of liver injury.
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Tecido Adiposo/metabolismo , Fígado Gorduroso/metabolismo , Macrófagos/metabolismo , Obesidade Mórbida/metabolismo , Osteopontina/metabolismo , Tecido Adiposo/efeitos dos fármacos , Adulto , Animais , Linhagem Celular Tumoral , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Receptores de Hialuronatos/metabolismo , Immunoblotting , Fígado/metabolismo , Fígado/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Obesidade Mórbida/genética , Obesidade Mórbida/patologia , Ácido Oleico/farmacologia , Osteopontina/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/metabolismo , Redução de Peso/efeitos dos fármacosRESUMO
There has been much interest in the health effects of dietary fat, but few studies have comprehensively compared the acute metabolic fate of specific fatty acids in vivo. We hypothesized that different classes of fatty acids would be variably partitioned in metabolic pathways and that this would become evident over 24 h. We traced the fate of fatty acids using equal amounts of [U-(13)C]linoleate, [U-(13)C]oleate, and [U-(13)C]palmitate given in a test breakfast meal in 12 healthy subjects. There was a tendency for differences in the concentrations of the tracers in plasma chylomicron-triacylglycerol (TG) (oleate > palmitate > linoleate). This pattern remained in plasma nonesterified fatty acid (NEFA) and very low-density lipoprotein (VLDL)-TG (P Assuntos
Gorduras na Dieta/metabolismo
, Ácidos Graxos/metabolismo
, Adulto
, Cromatografia de Afinidade
, Quilomícrons/sangue
, Quilomícrons/metabolismo
, Eritrócitos/metabolismo
, Ácidos Graxos/sangue
, Feminino
, Humanos
, Ácido Linoleico/sangue
, Ácido Linoleico/metabolismo
, Lipoproteínas VLDL/sangue
, Lipoproteínas VLDL/metabolismo
, Masculino
, Ácido Oleico/sangue
, Ácido Oleico/metabolismo
, Palmitatos/sangue
, Palmitatos/metabolismo
, Período Pós-Prandial
, Triglicerídeos/sangue
, Triglicerídeos/metabolismo
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The purpose of this study was to determine if immune mechanisms in GAD positive patients' contribute to the pathogenesis of a specific sub-type of Type 2 diabetes. GAD positive (n=8) and GAD negative (n=8) subjects diagnosed with Type 2 diabetes were matched for age, gender, body mass index, duration of diabetes and glycaemic control. All subjects underwent an insulin-modified frequently sampled intravenous glucose tolerance test to measure insulin sensitivity and insulin secretory function with minimal model analysis. In addition, BRIN-BD11 clonal beta-cells were supplemented with patients' sera to determine basal and alanine-stimulated insulin secretion and terminal complement complex (TCC) formation. Both groups were severely insulin resistant (0.56+/-0.17 vs. 0.99+/-0.3310(-4)min(-1)/(microUml(-1)) for GADneg and GADpos, respectively) but the GAD negative subjects had a higher basal (87+/-11 vs. 58+/-14pmoll(-1), p<0.05) and glucose-stimulated insulin secretion (DeltaAUCins 0.96+/-0.12 vs. 0.60+/-0.12pmol/(l(-1)min), p<0.05). In vivo measures of insulin secretion were negatively correlated with TCC formation, independent of antibody status. In conclusion, GAD positive subjects initially diagnosed with Type 2 diabetes are unable to compensate for insulin resistance due to more pronounced beta-cell impairment. TCC formation may be partly responsible for the insulin secretory dysfunction associated with this specific sub-type of Type 2 diabetes.
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Anticorpos/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Glutamato Descarboxilase/imunologia , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Sobrevivência Celular , Diabetes Mellitus Tipo 2/enzimologia , Feminino , Glutamato Descarboxilase/genética , Humanos , Insulina/metabolismo , Anticorpos Anti-Insulina/sangue , Secreção de Insulina , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , RatosRESUMO
OBJECTIVE: We aimed to determine differences in the postprandial contributions of different fatty acid sources to VLDL triglycerides (TGs) in healthy men and women with varying degrees of insulin resistance. RESEARCH DESIGN AND METHODS: Insulin-resistant (n = 11) and insulin-sensitive (n = 11) men and women (n = 6) were given an intravenous infusion of [(2)H(2)]palmitic acid to investigate systemic nonesterified fatty acid (NEFA) incorporation into VLDL TGs. Participants were also fed a mixed meal containing [U-(13)C]palmitic acid to investigate the contribution of dietary fatty acids to VLDL TG production. Blood samples were taken over the following 6 h. Separation of VLDL was performed by density gradient ultracentrifugation and immunoaffinity techniques specific to apolipoprotein B-100. RESULTS: Insulin-resistant and insulin-sensitive men had similar postprandial chylomicron and chylomicron remnant TG concentrations, but insulin-resistant men had higher postprandial VLDL TG concentrations (median [range]; area under the curve 485 micromol/l [123-992] vs. 287 micromol/l [162-510]; P < 0.05). At 360 min, most of the difference in VLDL TGs was accounted for by an additional contribution from splanchnic fat (means +/- SE; 331 +/- 76 micromol/l vs. 89 +/- 25 micromol/l; P < 0.01). The contribution of fatty acids from endogenous systemic NEFAs was similar across the groups, as were dietary fatty acids. There was no difference in the VLDL TG concentration or the contribution of different fatty acid sources between insulin-sensitive men and women. CONCLUSIONS: In the postprandial period, the only sources of fatty acids for VLDL TG production to differ in the insulin-resistant compared with the insulin-sensitive men are those derived from splanchnic sources.