Comparison of HIV-Infected and Noninfected Patients Undergoing Bariatric Surgery: The ObeVIH Study.

OBJECTIVE: The aim of this study was to compare clinical characteristics and adipose/liver tissue histology analysis in HIV-infected and HIV-uninfected subjects undergoing bariatric surgery. DESIGN: This was a cross-sectional study of HIV-infected subjects undergoing single-port sleeve gastrectomy with prospective enrolment and frequency age (±5 years), sex, and body mass index (BMI, ± 5 kg/m2) matched on HIV-uninfected subjects. METHODS: This study was conducted at a single clinical site at Pitié-Salpêtrière hospital-Paris-France comprising 19 HIV-uninfected and 21 HIV-infected subjects with plasma VL < 20 copies/mL, all with a BMI > 40 kg/m2 or >35 kg/m2 with comorbidities. Histology of subcutaneous and visceral abdominal adipose tissue (SCAT/VAT) and liver biopsies was collected during single-port sleeve gastrectomy. Outcomes included anthropometric characteristics, comorbidities, cardiovascular parameters, adipose tissue, and liver histology. RESULTS: The age of HIV-infected participants was (median, interquartile range IQR) 48 y (42-51), with 76.2% females, a BMI of 41.4 kg/m2 (37.3-44.4), an antiretroviral duration of 16 y (8-21), current integrase strand transfer inhibitor (INSTI)-based regimen in 15 participants and non-INSTI regimen in 6 participants, and a CD4 count of 864/mm3 (560-1066). The age of controls was 43 y (37-51), with 78.9% females and a BMI of 39.2 kg/m2 (36.3-42.6). Anthropometric characteristics, comorbidities, and cardiovascular parameters did not differ according to HIV status and INSTI treatment. The number of macrophage crown-like structures in SCAT was lower in INSTI-treated participants than in HIV-uninfected participants (P = 0.02) and non-INSTI-treated HIV-infected subjects (P = 0.07). Hepatic steatosis and liver disease severity global score were lower in INSTI-treated participants than in non-INSTI-treated HIV-infected participants (P = 0.05 and P = 0.04, respectively). CONCLUSIONS: HIV-infected and HIV-uninfected subjects undergoing bariatric surgery presented a similar profile regarding anthropometric measures, cardiovascular parameters, and comorbidities. However, INSTI-treated participants presented milder SCAT and liver alterations than non-INSTI-treated participants.

Diabetes and dyslipidaemia are associated with oxidative stress independently of inflammation in long-term antiretroviral-treated HIV-infected patients.

AIM: Ageing HIV-infected patients controlled by antiretroviral therapy (ART) frequently present age-related comorbidities, such as cardiovascular (CV) events, diabetes, dyslipidaemia, hypertension and chronic kidney disease (CKD). The prevalence of these comorbidities was evaluated in a cohort of long-term-monitored ART-controlled HIV-infected patients, then followed by a search into whether oxidative stress, like inflammation, might be associated with metabolic parameters and/or comorbidities. METHODS: Included were 352 long-term ART patients who started with protease inhibitors (PIs) in 1997-1999. They were evaluated at their final visit, 11 years later, for previous CV events, prevalence of diabetes, LDL-related and atherogenic (high TG/HDL) dyslipidaemias, hypertension and CKD. Also measured were circulating biomarkers to explore oxidative stress (Lp-PLA2, oxLDL, oxLDL/LDL ratio, paraoxonase and arylesterase activities), inflammation/immune activation (hsCRP, hsIL-6, D dimer, soluble CD14, ß2 microglobulin, cystatin C), adipokines and insulin resistance. Levels were compared in patients with and without each comorbidity or condition using non-parametric correlation tests and multivariate adjusted analyses. RESULTS: At the final visit, 81.5% of patients were male and were aged (median, IQR) 49 years (45-56); BMI was 23.0 kg/m2 (21.1-25.4), CD4+ lymphocytes were 620 cells/mm3 (453-790) and 91.5% had undetectable HIV-1 viral loads. The prevalence of diabetes was 11%, and LDL-related dyslipidaemia 28%, atherogenic dyslipidaemia 9%, hypertension 28%, CKD 9% and previous CV events 9%. Diabetes and atherogenic dyslipidaemia were associated with increased oxidative stress and independently with inflammation. LDL-related dyslipidaemia and impaired fasting glucose were associated with increased oxidative stress. No association of these biomarkers was detected with hypertension, CKD and previous CV events. CONCLUSION: In long-term-treated HIV-infected patients with frequent comorbid conditions, oxidative stress could be contributing to diabetes and LDL-related and atherogenic dyslipidaemias independently of inflammation.

The negative impact of HBV/HCV coinfection on cirrhosis and its consequences.

BACKGROUND: Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series. AIM: To compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study. PATIENTS AND METHODS: Of the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti-HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis. RESULTS: F3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P < .0001), but similar in HCV-monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) (P < .003). Multivariable analysis confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients (OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42-22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22-7.44). CONCLUSIONS: HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients.

Characterization of diabetic osteoarthritic cartilage and role of high glucose environment on chondrocyte activation: toward pathophysiological delineation of diabetes mellitus-related osteoarthritis.

OBJECTIVE: To examine the relationship between osteoarthritis (OA) and type 2 diabetes mellitus (DM). METHODS: OA cartilage from DM and non-DM patients undergoing knee replacement were stimulated by IL-1ß for 24 h and release of interleukin-6 (IL-6) and prostaglandin E2 (PGE2) was measured. Primary cultured murine chondrocytes were stimulated for 24 and 72 h with or without IL-1ß (5 ng/mL) under normal-glucose (5.5 mM) or high-glucose (25 mM) conditions. The expression and release of pro-inflammatory mediators (IL-6, cyclooxygenase 2 [COX2]/PGE2) were analyzed by quantitative RT-PCR and ELISA/EIA. Glucose uptake was assessed with ((14)C)-2-deoxyglucose. Reactive oxygen species (ROS) and nitric oxide (NO) production were measured. To analyze the mechanism of IL-1ß-induced inflammation, cells were pretreated or treated with inhibitors of glucose transport (cytochalasin B), the polyol pathway (epalrestat), mitochondrial oxidative stress (MitoTEMPO) or nitric oxide synthase (l-NAME). RESULTS: With IL-1ß stimulation, IL-6 and PGE2 release was greater in human DM than non-DM OA cartilage (2.7- and 3-fold, respectively) (P < 0.05). In vitro, with IL-1ß stimulation, IL-6 and COX2 mRNA expression, IL-6 and PGE2 release, and ROS and NO production were greater under high-than normal-glucose conditions in cultured chondrocytes. IL-1ß-increased IL-6 release was reduced with cytochalasin B, epalrestat, L-NAME or MitoTEMPO treatment (-45%, -62%, -38% and -40%, respectively). CONCLUSION: OA cartilages from DM patients showed increased responsiveness to IL-1ß-induced inflammation. Accordingly, high glucose enhanced IL-1ß-induced inflammation in cultured chondrocytes via oxidative stress and the polyol pathway. High glucose and diabetes may thus participate in the increased inflammation in OA.

Association between IL28B polymorphism, TNFα and biomarkers of insulin resistance in chronic hepatitis C-related insulin resistance.

TNFα has been shown to play a role in hepatitis C virus (HCV)-induced insulin resistance (IR). Polymorphism of the IL28B gene that encodes IFN-lambda 3 may be associated with IR through modulation of TNFα. The aim of this study was to investigate the relationship between IL28B rs12979860 genotype, the level of TNFα activation and the degree of IR in patients with chronic hepatitis C. One hundred and thirty-three nondiabetic genotype 1 HCV-infected patients with biopsy proven noncirrhotic hepatitis C were investigated for IR (using HOMA index), IL28B rs12979860 genotype and fasting circulating levels of soluble receptor 1 of TNFα (sTNFR1) and adipokines: leptin, adiponectin and IL-6. The HOMA-IR was positively correlated with serum levels of leptin (r = 0.35, P < 0.0001) and sTNFR1 (r = 0.35, P < 0.0001) but not with IL-6 or adiponectin. IL28B rs12979860 CC genotype was observed in 35% patients. Genotype CC and nongenotype CC patients were similar in terms of HOMA-IR (means 1.6 ± 0.9 vs 1.7 ± 1.4) and had similar circulating levels of sTNFR1 and adipokines. Independent factors associated with IR were ferritin (OR = 1.002, P = 0.02), leptin (OR = 1.06, P = 0.02) and sTNFR1 (OR = 7.9, P = 0.04). This study suggests that in nondiabetic, noncirrhotic, HCV genotype 1-infected patients, there is no relationship between IL28B rs12979860 genotype and HOMA-IR or sTNFR1 level. HCV-related IR may be mediated through TNFα independent of IL28B genotype.

Ten-year improvement of insulin resistance and growth with recombinant human insulin-like growth factor 1 in a patient with insulin receptor mutations resulting in leprechaunism.

AIM: Leprechaunism, a rare genetic disease resulting from mutations in two alleles of the insulin receptor gene, is characterized by severe insulin resistance, retarded growth and, usually, premature death. The ability of treatment with recombinant human insulin-like growth factor 1 (rhIGF1) to improve metabolic and clinical parameters in the long-term is still controversial. METHODS: Mutations were looked for in the insulin receptor gene of a four-month-old female baby with leprechaunism. The patient's skin fibroblasts were analyzed for response to insulin and IGF1. At the clinical level, the very long-term effects of treatment with rhIGF1/rhIGFBP3 were evaluated by clinical and metabolic parameters. RESULTS: The patient's diagnosis was based on compound heterozygous mutations in two alleles of the insulin receptor gene, thus confirming leprechaunism. Cultured fibroblasts showed a decreased number of insulin receptors and were insulin-resistant. However, IGF1 was able to stimulate IGF1 receptor signalling, suggesting possible activation of a salvage pathway. Treatment with IGF1/IGFBP3 for 8.7 years, then IGF1 for 2 years, resulted in normalization of circulating levels of IGF1 and IGFBP3. Large daily variations in glycaemia and insulinaemia persisted, but mean glycaemia decreased. Regarding growth, the patient's BMI Z score normalized and length/height score improved. Our patient presented normal neurological development and academic achievement. The treatment was free of adverse effects. CONCLUSION: Our results provide evidence that rhIGF1 with and without rhIGFBP3 can prevent fatal outcomes, and improve growth and metabolic parameters, for more than 10 years in a patient with leprechaunism. Long-term rhIGF1 for severe insulin resistance syndrome should be considered.

Nuclear envelope-related lipodystrophies.

Several alterations in nuclear envelope proteins building up the lamina meshwork beneath the inner nuclear membrane (mutations in lamins A/C, alterations of prelamin-A maturation, lamin B mutations or deregulation) have been shown to be responsible for or associated to human lipodystrophic syndromes. Lipodystrophic syndromes are rare and heterogeneous diseases, either genetic or acquired, characterized by generalized or partial fat atrophy associated with metabolic complications comprising insulin-resistant diabetes, dyslipidemia, and non-alcoholic fatty liver disease. Recent advances in the molecular genetics of different types of lipodystrophies generally pointed to primary adipocyte alterations leading to impaired adipogenesis and/or deregulation of the adipocyte lipid droplet. However, the precise mechanisms linking nuclear envelope abnormalities to lipodystrophies remain largely unknown. The phenotype of nuclear envelope-linked lipodystrophies ranges from the typical familial partial lipodystrophy of the Dunnigan type (FPLD2), due to heterozygous substitutions of the 482nd arginine of lamins A/C, to complex diseases that can combine lipodystrophy, metabolic complications, muscular or cardiac alterations and/or signs of accelerated aging. In this review we present the clinical, tissular and cellular characteristics of the nuclear envelope-linked lipodystrophies, as well as their hypothetical pathophysiological mechanisms.

Thiazolidinediones partially reverse the metabolic disturbances observed in Bscl2/seipin-deficient mice.

AIMS/HYPOTHESIS: Mutations in BSCL2/seipin cause Berardinelli-Seip congenital lipodystrophy (BSCL), a rare recessive disorder characterised by near absence of adipose tissue and severe insulin resistance. We aimed to determine how seipin deficiency alters glucose and lipid homeostasis and whether thiazolidinediones can rescue the phenotype. METHODS: Bscl2 (-/-) mice were generated and phenotyped. Mouse embryonic fibroblasts (MEFs) were used as a model of adipocyte differentiation. RESULTS: As observed in humans, Bscl2 (-/-) mice displayed an early depletion of adipose tissue, with insulin resistance and severe hepatic steatosis. However, Bscl2 (-/-) mice exhibited an unexpected hypotriglyceridaemia due to increased clearance of triacylglycerol-rich lipoproteins (TRL) and uptake of fatty acids by the liver, with reduced basal energy expenditure. In vitro experiments with MEFs demonstrated that seipin deficiency led to impaired late adipocyte differentiation and increased basal lipolysis. Thiazolidinediones were able to rescue the adipogenesis impairment but not the alteration in lipolysis in Bscl2 (-/-) MEFs. In vivo treatment of Bscl2 (-/-) mice with pioglitazone for 9 weeks increased residual inguinal and mesenteric fat pads as well as plasma leptin and adiponectin concentrations. Pioglitazone treatment increased energy expenditure and improved insulin resistance, hypotriglyceridaemia and liver steatosis in these mice. CONCLUSIONS/INTERPRETATION: Seipin plays a key role in the differentiation and storage capacity of adipocytes, and affects glucose and lipid homeostasis. The hypotriglyceridaemia observed in Bscl2 (-/-) mice is linked to increased uptake of TRL by the liver, offering a new model of liver steatosis. The demonstration that the metabolic complications associated with BSCL can be partially rescued with pioglitazone treatment opens an interesting therapeutic perspective for BSCL patients.

[Lipodystrophies]. / Syndromes lipodystrophiques.

Human lipodystrophies represent a group of diseases characterized by altered body fat amount and/or repartition. Most forms of lipodystrophies are associated with metabolic alterations such as insulin resistance, diabetes and dyslipemia, leading to diabetic complications, increased cardiovascular risk or liver steatosis. Lipodystrophies can be classified as genetic or acquired, generalized or partial. Genetic forms such as Berardinelli-Seip syndrome or partial familial lipodystrophies are uncommon and acquired forms are much more frequent. Beside the rare Lawrence or Barraquer-Simons syndromes, the main forms of acquired lipodystrophies are those observed in HIV-infected people treated with antiretroviral therapies or in people exposed to an endogenous or an exogenous hypercortisolism. The treatment of lipodystrophies is difficult. Lifestyle modifications (e.g., specific diet, physical training) may be helpful but are usually insufficient. Associated metabolic disorders should be treated as soon as possible with insulin sensitizers, insulin and lipid lowering drugs. New therapies such as leptin have been proven to be helpful in some genetic or acquired forms of lipodystrophy.

Visceral and subcutaneous adipose tissue from lean women respond differently to lipopolysaccharide-induced alteration of inflammation and glyceroneogenesis.

OBJECTIVE: Experimental endotoxaemia induces subcutaneous adipose tissue inflammation and systemic insulin resistance in lean subjects. Glyceroneogenesis, by limiting free fatty acids (FFA) release from adipocytes, controls FFA homoeostasis and systemic insulin sensitivity. The roles of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in metabolic deregulation are intrinsically different. We compared the effect of lipopolysaccharide (LPS) on the inflammation profiles of SAT and VAT explants from lean women, as well as on glyceroneogenesis, to test whether these two fat depots have intrinsically different responses to this metabolic endotoxin. DESIGN: Abdominal SAT and VAT explants from eight lean women were treated in vitro with LPS. Their inflammatory status was evaluated by cytokine gene expression and secretion; glyceroneogenesis was evaluated by cytosolic phosphoenolpyruvate carboxykinase activity and FFA vs glycerol release. RESULTS: In the basal state, the cytokine status and expression of macrophage markers were lower in SAT than VAT. In the presence of 100 ng ml(-1) LPS, SAT exhibited a strong inflammatory response (increased interleukin-6 and tumor necrosis factor-α expression) and increased release of FFA due to inhibition of glyceroneogenesis, whereas VAT was only mildly affected. The effects of LPS on both tissues were blocked by the nuclear factor-κB (NF-κB) inhibitor, parthenolide. A significant effect of LPS on VAT occurred only at 1 µg ml(-1) LPS. CONCLUSION: SAT explants from lean women are more sensitive to LPS-induced NF-κB activation than are VAT explants, leading to a depot-specific dysfunction of FFA storage. As SAT is the major player in FFA homoeostasis, this SAT dysfunction could be associated with visceral fat hypertrophy and systemic lipid disorders.

How can we measure insulin sensitivity/resistance?

Insulin resistance represents a major public health problem, as it plays a major role in the pathophysiology of type 2 diabetes mellitus; it is also associated with increased cardiovascular risk and atherogenic dyslipidaemia, and is a central component of the cluster of metabolic abnormalities that comprise the metabolic syndrome. Thus, the development of tools to quantify insulin sensitivity/resistance has been the main objective of a number of studies. Insulin resistance can be estimated with the use of several biological measurements that evaluate different aspects of this complex situation. To that end, it requires various resources, ranging from just a single fasting blood sample for simple indices, such as the HOMA or QUICKI, to a research setting in which to perform the gold-standard hyperinsulinaemic-euglycaemic clamp test. The choice of method for evaluating insulin resistance depends on the nature of the information required (classification of individual subjects, group comparisons, precise measurement of either global, muscle or liver insulin sensitivity/resistance) and on the available resources. The aim of this review is to analyze the most frequently used assay methods in an attempt to evaluate when and why these methods may be useful.

Adiponectin and leptin in Afro-Caribbean men and women with HIV infection: association with insulin resistance and type 2 diabetes.

AIM: Insulin resistance and type 2 diabetes (T2D) are commonly seen in human immunodeficiency virus (HIV) infection and are related to antiretroviral therapy. Adiponectin and leptin secreted by adipocytes are both linked to body-fat distribution and insulin sensitivity. The present study aimed to assess the prevalence of insulin resistance and T2D, and their association with adiponectin and leptin, in Afro-Caribbean men and women with HIV infection. METHODS: This cross-sectional study was conducted in an unselected sample of 237 HIV-1-infected patients. Clinical and metabolic parameters were measured, including fasting and postload plasma insulin, and circulating adiponectin and leptin levels. Insulin resistance was estimated by homoeostasis model assessment (HOMA-IR). Adjusted multiple logistic regressions were used to estimate the association of insulin resistance with adipokine levels and patients' characteristics. RESULTS: A total of 132 men (mean age: 49 years) and 105 women (mean age: 48 years) were included in the study. Prevalences of T2D and insulin resistance were higher in women than in men [16.2% vs 8.3% (P = 0.06) and 24% vs 9.9% (P < 10⁻³), respectively]. Abdominal obesity was found in 47% of women and in 7% of men (P < 10⁻4). Insulin resistance was independently associated with adiponectin in women and with leptin in men. CONCLUSION: Insulin resistance is frequent in Afro-Caribbean women with HIV infection. Overweight and obesity are major risk factors in such a population. Systematic screening for insulin resistance should be carried out in this population, which has a high prevalence of T2D.

Diagnostic value of procalcitonin in acutely hospitalized elderly patients.

The aim of this study was to evaluate procalcitonin as an adjunct to diagnose bacterial infections in older patients. One hundred seventy-two patients admitted to an acute-care geriatric unit during a 6-month period were prospectively included, 39 of them with an invasive bacterial infection. The best cut-off value to rule in a bacterial infection was 0.51 microg/l with sensitivity 64% and specificity 94%. The best cut-off value to rule out a bacterial infection was 0.08 microg/l with sensitivity 97% and specificity 20%. Procalcitonin was inconclusive (between 0.08 and 0.51 microg/l) for 112 admissions. Procalcitonin over 0.51 microg/l was useless 22 times out of 33 (infection already ruled in on clinical grounds) and misleading in eight of the 11 remaining cases (no infection). Procalcitonin below 0.08 microg/l was useless 23 times out of 27 (infection already ruled out on clinical grounds) and misleading in one of the four remaining cases (infection). Despite a good overall diagnostic accuracy, the clinical usefulness of PCT to diagnose invasive bacterial infections in elderly patients hospitalized in an acute geriatric ward appears to be very limited.

Metabolic disorders and chronic viral disease: the case of HIV and HCV.

The importance of metabolic disorders in the pathophysiology of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections is becoming increasingly apparent. Metabolic anomalies, with their potential for multiple-organ involvement, are to be expected, given the chronic nature of these diseases, and the intracellular dysregulation associated with them. Not only have the endocrine and cytokine metabolic anomalies seen in HIV and HCV infections been linked with the metabolic syndrome, but they also appear to have some pathways in common. Studying the differences and similarities between these metabolic anomalies may add to our understanding of HIV and HCV infection, and provide guidance on how to treat these chronic diseases. This review highlights the principal underlying factors for metabolic disorders in these chronic viral diseases-namely insulin resistance and liver damage. Both the chronic viral state itself and the host immune response give rise to glucose and lipid metabolic disorders that, in turn, are risk factors for hepatic damage. The various interactions between HIV and/or HCV with insulin resistance, type 2 diabetes, steatosis and fibrogenesis should be considered when determining the treatment and long-term follow-up of patients. Recent data indicate that HCV clearance improves insulin resistance and hepatic function in HCV-infected patients treated with interferon with or without ribavirin.

Fertility and obstetrical complications in women with LMNA-related familial partial lipodystrophy.

OBJECTIVE: Familial partial lipodystrophy due to LMNA (lamin A/C) mutations is a rare disorder characterized by a selective loss of adipose tissue and insulin resistance. Dyslipidemia and severe diabetes often occur during its evolution. Only isolated and contradictory case reports have been published on the obstetrical prognosis in lipodystrophy. The aim of our study was to compare the fertility and occurrence of obstetrical complications of women with familial partial lipodystrophy due to LMNA (lamin A/C) mutations with those of nonaffected relatives, women from the general population, and women with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: Data were obtained from clinical follow-up of seven families with patients exhibiting mutations in LMNA (five R482W, one R482Q, one R439C) (14 affected among 48 women). RESULTS: The mean number of live children per woman was 1.7 in affected patients vs. 2.8 in nonaffected relatives. Fifty-four percent of LMNA-mutated women exhibited a clinical phenotype of PCOS, 28% suffered from infertility, 50% experienced at least one miscarriage, 36% developed gestational diabetes, and 14% experienced eclampsia and fetal death. Mean blood leptin level was significantly lower in LMNA-mutated patients than in nonaffected relatives (5.0 +/- 3.8 ng/ml vs 14.3 +/- 3.6; P < 0.001) despite similar body mass index (21.0 +/- 4.2 vs 22.4 +/- 2.2; P = 0.49). CONCLUSION: In these LMNA-linked lipodystrophic patients, the prevalence of PCOS, infertility, and gestational diabetes was higher than in the general population. Moreover, the prevalence of gestational diabetes and miscarriages was higher in lipodystrophic LMNA-mutated women than previously reported in PCOS women with similar body mass index. Women with lipodystrophies due to LMNA mutations are at high risk of infertility, gestational diabetes, and obstetrical complications and require reinforced gynecological and obstetrical care.

Insulin resistance and steatosis in humans.

Insulin resistance is commonly found in a large number of adults-in particular, those with android obesity, the metabolic syndrome or type 2 diabetes. Strong adverse relationships between adipose tissue, liver and muscles in these patients result in lipotoxicity, with deposition of triglycerides (TG) within the liver and muscles together with insulin resistance. Such a situation is also seen in lipodystrophic patients with fat loss. Insulin signals in the liver through its tyrosine-kinase receptors to negatively control hepatic glucose production (HGP), replenish glycogen stores and synthesize fatty acids (FA), leading to TG exported as VLDL. In liver insulin resistance, HGP is increased mainly by activation of the gluconeogenic pathway, resulting in increased fasting glycemia. Lipogenesis is also increased possibly due to direct activation of the SREBP-1 transcription factor and together with increased FA availability results in an increased production of VLDL-TG. An imbalance between the pathways of TG synthesis and oxidation or export results in 'metabolic' steatosis. Increased cellular FA derivatives activate stress kinases, leading to phosphorylation of serine in insulin receptor substrate (IRS) proteins and, hence, insulin resistance. A number of studies in normal subjects and patients have revealed a strong association between insulin resistance and metabolic steatosis. Moreover, when insulin resistance is decreased by weight loss in obese subjects or by treatment with insulin sensitizers such as thiazolidinediones, the levels of liver fat and insulin resistance vary accordingly. An important question that remains unanswered concerns the relationship between steatosis and non-alcoholic steatohepatitis (NASH), and the potential roles of insulin resistance together with inflammation and oxidative stress in such a setting.

[Interference of ethylene glycol on lactate assays]. / Interférences des métabolites de l'éthylène glycol avec les dosages du lactate.

Ethylene glycol is broken down to three main organic acids: glycolic acid, glyoxylic acid and oxalic acid which cause severe metabolic acidosis. Effect of these three acids on lactate assays was evaluated in five blood gas analysers and two clinical chemistry analysers. For all systems, no influence of oxalic acid on lactate results could be demonstrated. No interference of glycolic acid could be observed on lactate assay performed with Rapid Lab 1265 (R: 104,9 +/- 12,1%), Vitros 950 (R: 105,7 +/- 5,3 %) and Architect ci8200 (R: 104,9 +/- 4,7%), but on the contrary, CCX 4, OMNI S, ABL 725 and 825 demonstrated a concentration-dependent interference. No interference of glyoxylic acid could be observed with Vitros 950, but a positive interference could be observed with ABL 725 and 825, OMNI S, CCX4 and Architect ci8200 A linear relationship between apparent lactate concentration found with ABL 725 and 825, OMNI S, CCX 4, and glyoxylic acid could be observed (0,94 < r < 0,99), a weaker interference being observed with Rapid Lab 1265 and Architect ci 8200. Our results demonstrated that in case of ethylene glycol poisoning, cautious interpretation of lactate assay should be done, since wrong results of lactacidemia could lead to misdiagnostic and delay patient treatment.