37 research outputs found

    Is skeletal muscle mitochondrial dysfunction a cause or an indirect consequence of insulin resistance in humans?

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    The precise cause of insulin resistance and type 2 diabetes is unknown. However, there is a strong association between insulin resistance and lipid accumulation — and, in particular, lipotoxic fatty acid metabolites — in insulin-target tissues. Such accumulation is known to cause insulin resistance, particularly in skeletal muscle, by reducing insulin-stimulated glucose uptake. Reduced fat-oxidation capacity appears to cause such lipid accumulation and, over the past few years, many studies have concluded that decreased mitochondrial oxidative phosphorylation could be the initiating cause of lipid deposition and the development of insulin resistance. The aim of this review is to summarize the latest findings regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance in humans. At present, there are too few studies to definitively conclude that, in this context, mitochondria are functionally impaired (dysfunction in the respiratory chain). Indeed, insulin resistance could also be related to a decrease in the number of mitochondria or to a combination of this and mitochondrial dysfunction. Finally, we also consider whether or not these aberrations could be the cause of the development of the disease or whether mitochondrial dysfunction may simply be the consequence of an insulin-resistant state

    A truncated ultrasound screening procedure for atheroma of the cervical arteries in asymptomatic diabetic patients: Evidence from a retrospective study

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    AimTo demonstrate that ultrasound screening of diabetic patients presenting with no cerebrovascular symptoms for evaluation of atheroma of the cervical arteries can be limited to the carotid arteries. Methods We retrospectively analyzed the results of cervical artery ultrasound imaging of diabetic patients with no cerebrovascular symptoms. This diabetic population was divided into two subpopulations according to whether or not the vertebral and subclavian artery findings were normal or abnormal. Results Of the 760 patients who fulfilled the criteria for study inclusion, the ultrasound imaging findings of the vertebral and subclavian arteries were normal in 712 cases. Review of the files of the 48 remaining patients showed that findings for either the vertebral or subclavian arteries did not lead to any changes in patient management because of associated risk factors, carotid atheroma or peripheral arterial disease. Conclusion A vascular risk evaluation in diabetic patients could include ultrasound imaging assessment for cervical artery atheroma and our data suggest that such an evaluation could be focused solely on the carotid arteries

    Severe episodes of extra cellular dehydration : an atypical adult presentation of cystic fibrosis

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    Cystic fibrosis (CF) is usually diagnosed during childhood by respiratory or gastro-intestinal symptoms. Hyponatremic hypochloremic dehydration with metabolic alkalosis is a rare but typical presentation of CF in infants. In contrast, only 3 cases have been described in adults. We report a case of CF in a 33-year-old Caucasian female presenting with a severe sodium and chloride depletion caused by inappropriate sweating. She experienced three episodes of severe dehydration before the diagnosis was suspected. Sweat chloride test was pathological and mild pulmonary involvement was found on CT scan. AF508 mutation and a rare mutation (3849+40 A/G) on the intron 19 of CFTR gene were found. Interestingly, our patient has a heterozygote twin sister, carrier of the same mutations of CFTR gene who also developed CF but with a different phenotype. We suspect modifier genes to be implicated in the differences observed between the two phenotypes. We discuss the physiopathology of electrolyte disturbance and review the other similar adults cases

    Is a Failure to Recognize an Increase in Food Intake a Key to Understanding Insulin-Induced Weight Gain?

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    The present study aimed to assess the contribution of energy intake to positive energy balance and weight gain with insulin therapy. Changes in energy intake (self-report and weighed food intake), dietary behavior (auto-questionnaires), resting energy expenditure (REE) (indirect calorimetry), physical activity (accelerometry), and glucosuria were monitored over the first 6 months of insulin therapy in 46 diabetic adults. No change in REE, activity, or glucosuria could explain weight gain in the type 1 (4.1 ± 0.6 kg, P < 0.0001) or type 2 (1.8 ± 0.8 kg, P = 0.02) diabetic groups. An increase in energy intake provides the most likely explanation for weight gain with insulin. However, it is not being recognized because of significant underestimation of self-reported food intake, which appears to be associated with increased dietary restraint

    Axon-reflex cutaneous vasodilatation is impaired in type 2 diabetic patients receiving chronic low-dose aspirin

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    Low-dose aspirin is largely but non-homogeneously used in primary prevention of cardiovascular complication in type-2 diabetic patients. We hypothesised that low-dose aspirin could interfere with the cutaneous neurovascular responses in type-2 diabetic patients. Galvanic current-induced vasodilatation (CIV) is an original non-noxious integrative model of neurovascular interaction and is impaired under low-dose aspirin in healthy subjects. Twenty type-2 diabetic patients (ten not receiving aspirin: D-NA and ten regularly receiving ≤ 150 mg/day aspirin: D-A), and ten age-, BMI-, and gender-matched non-diabetic control volunteers (MC), underwent macro- and microvascular investigations, including: CIV, acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis, post-occlusive hyperemia (POH), neuropathy symptom (NSS) and disability (NDS) scores, and thermal and vibration sensory thresholds. Results are presented as median [25–75 centile] and microvascular results are expressed in multiple from baseline conductance (%Cb). CIV was 554 [349–769] %Cb in MC, 251 [190–355] %Cb in D-NA and 159 [136–202] %Cb in D-A (p < 0.05). No differences were observed between the three groups except for CIV, which is impaired in diabetic patients and further impaired in those regularly receiving low-dose aspirin, while other macrovascular, microvascular and clinical-sensitivity investigations show no significant difference. Potential clinical markers for the impairment of the neurovascular interaction are still required in diabetes. Correlation of the CIV response with the risk of cutaneous complications in diabetic patients remains to be tested

    Fatty liver and insulin resistance in obese Zucker rats: No role for mitochondrial dysfunction

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    The relationship between insulin resistance and mitochondrial function is of increasing interest. Studies looking for such interactions are usually made in muscle and only a few studies have been done in liver, which is known to be a crucial partner in whole body insulin action. Recent studies have revealed a similar mechanism to that of muscle for fat-induced insulin resistance in liver. However, the exact mechanism of lipid metabolites accumulation in liver leading to insulin resistance is far from being elucidated. One of the hypothetical mechanisms for liver steatosis development is an impairment of mitochondrial function. We examined mitochondrial function in fatty liver and insulin resistance state using isolated mitochondria from obese Zucker rats. We determined the relationship between ATP synthesis and oxygen consumption as well as the relationship between mitochondrial membrane potential and oxygen consumption. In order to evaluate the quantity of mitochondria and the oxidative capacity we measured citrate synthase and cytochrome c oxidase activities. Results showed that despite significant fatty liver and hyperinsulinemia, isolated liver mitochondria from obese Zucker rats display no difference in oxygen consumption, ATP synthesis, and membrane potential compared with lean Zucker rats. There was no difference in citrate synthase and cytochrome c oxidase activities between obese and lean Zucker rats in isolated mitochondria as well as in liver homogenate, indicating a similar relative amount of hepatic mitochondria and a similar oxidative capacity. Adiponectin, which is involved in bioenergetic homeostasis, was increased two-fold in obese Zucker rats despite insulin resistance. In conclusion, isolated liver mitochondria from lean and obese insulin-resistant Zucker rats showed strictly the same mitochondrial function. It remains to be elucidated whether adiponectin increase is involved in these results

    Osteoprotegerin levels are associated with liver fat and liver markers in dysmetabolic adults

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    AIM: This study aimed to determine the association between visceral adipose tissue (VAT), liver fat (LF) content, and other markers of the metabolic syndrome (MetS) and osteoprotegerin (OPG) in dysmetabolic adults. METHODS: Subjects from the NUMEVOX cohort were included if they fulfilled at least one MetS criterion. They then underwent a thorough metabolic and cardiovascular evaluation, including arterial stiffness, atherosclerotic plaques, homoeostasis model assessment for insulin resistance (HOMA-IR) indices and OPG. VAT and LF content were measured by magnetic resonance imaging (MRI). Ultrasound examination of arteries and arterial stiffness were recorded, and age- and gender-adjusted paired correlations calculated. RESULTS: Body mass index, waist circumference and MRI-derived VAT correlated with OPG, whereas abdominal subcutaneous fat did not. OPG levels were strongly correlated with LF content (r=0.25, P=0.003), liver markers such as alanine aminotransferase (r=0.39, P<0.001) and HOMA-IR index (r=0.39, P<0.0001). Plasma OPG also correlated with arterial stiffness and the number of atherosclerotic sites. CONCLUSION: Plasma OPG levels are positively associated with both liver markers and increased LF content, but not with subcutaneous fat in dysmetabolic men. These findings suggest that elevated OPG levels may play a role in the link between fatty liver disease and enhanced cardiovascular risk

    Rigidité artérielle mesurée par pOpmètre® chez les patients à risque cardiovasculaire, lien aux plaques d’athérome carotidien

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    PURPOSE: Aortic stiffness is a functional and structural consequence of ageing and arteriosclerosis. Regional arterial stiffness can be easily evaluated using pOpmetre(®) (Axelife SAS, France). This new technique assesses the pulse wave transit time (TT) between the finger (TTf) and the toe (TTt). Based on height chart, regional pulse wave velocity (PWV) between the toe and the finger can be estimated (PWVtf). pOpscore(®) index is also calculated as the ratio between PWVtoe and PWVfinger and can be considered as a peripheral vascular stiffness index. The aim of the study was to evaluate the relationship between pOpmetre(®) indices and the presence of carotid plaques in a population with cardiovascular risk factors. METHODS: In 77 consecutive patients recruited for a vascular screening for atherosclerosis (46 men aged 54 ± 2 years; 31 women aged 49 ± 3 years; ns), the difference between TTt and TTf (called Dt-f), the regional pulse wave velocity between the toe and the finger (PWVtf = constant × height/Dt-fm/s) and pOpscore(®) were measured by pOpmetre(®). Presence of carotid plaques was assessed using ultrasound imaging. The local aortic stiffness (AoStiff) was evaluated by the Physioflow(®) system. RESULTS: No difference was found between patients with or without carotid plaques (n=25 versus 52) for Ankle-Brachial Pressure Index (ABPI: 1.15 ± 0.04 versus 1.12 ± 0.03), nor for diastolic or systolic blood pressure (87 ± 3 versus 82 ± 2; 137 ± 3 versus 132 ± 2 mmHg). The first group was older than the second (59 ± 2 versus 49 ± 2 years, P<0.002) with a larger intimae media thickness (0.69 ± 0.02 versus 0.63 ± 0.01 mm, P<0.004), a higher AoStiff (10.4 ± 0.7 versus 8.2 ± 0.5m/s, P<0.02), and PWVtf (14.3 ± 1.0 versus 10.7 ± 0.7 m/s, P<0.004) and a shorter Dt-f (57.9 ± 5.1 versus 73.5 ± 3.5 ms, P<0.01). PWVtf (r(2)=0.49, P<0.0001) and Dt-f (r(2)=0.54, P<0.0001) correlated with age. A significant difference in pOpscore(®) index was observed between both groups (1.51 ± 0.3 versus 1.41 ± 0.2, P<0.006). CONCLUSION: Our results show a significant arterial stiffness indices measured by pOpmetre(®) in patients with and without carotid plaques

    Noninvasive assessment of endothelial function in the skin microcirculation

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    BACKGROUND: The structure and function of blood vessels varies along the vascular tree. Endothelial dysfunction is a hallmark of increased cardiovascular (CV) risk that can be assessed by several methods, some of which are invasive and of restricted application. The aim of this study was to determine whether the laser Doppler response of skin microcirculation to acetylcholine, reflects that of conduit artery assessed by brachial artery flow-mediated dilation (FMD). METHODS: Noninvasive measurement of endothelium-dependent vasodilation in the skin microcirculation by laser Doppler flowmetry (LDF) in response to a local transdermal iontophoretic application of acetylcholine (Ach-SkBF) is an operator-independent method. Ach-SkBF and FMD were measured in the nondominant upper limb of 55 unselected consecutive patients admitted in our department for evaluation of CV risk factors. RESULTS: Ach-SkBF was (mean +/- s.d. (min-max)) 490 +/- 414%, (10-1667%) and FMD was 3.77 +/- 3.01% (0.91-10.91). A strong linear relationship was found between Ach-SkBF and FMD: Ach-SkBF = 122.7 FMD + 25.8 (r = 0.92, P < 0.0001). CONCLUSIONS: Endothelial dilatory response to increased blood flow and to acetylcholine are similar in large arteries and in the skin microvasculature. Thus, measurement of blood flow changes in the skin microcirculation using LDF coupled with acetylcholine iontophoresis represents a technically challenging and reliable noninvasive method for the assessment of endothelial function within a large range of normal and altered endothelium responses
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