Biomedical subjects

E Renard

Publications and source records attributed to E Renard.

At least 19 recordsLinked to original sources

PubMed2006

Non-arteritic anterior ischaemic optic neuropathy is nearly systematically associated with obstructive sleep apnoea.

AIM: To evaluate newly diagnosed non-arteritic anterior ischaemic optic neuropathy (NAION) patients for the existence of an associated sleep apnoea syndrome. METHODS: Newly identified NAION patient underwent polysomnography. The prevalence of sleep apnoea in NAION patients was compared to the prevalence previously found in the general population. Hypertension, diabetes, hyperlipidaemia, and atheromatous lesions of carotid vessels as classic risk factors associated with NAION were also identified. RESULTS: 27 consecutive newly diagnosed NAION patients (18 men and nine women, mean age 65 (SD 8) years, body mass index 27.2 (3.8) kg/m2) were included in the study. 24 of these 27 NAION patients (89%) exhibited a sleep apnoea syndrome (respiratory disturbance index: 37.2/h (SD 18.3/h). Risk ratio for a NAION patient to have sleep apnoea was 4.9 compared to the general population (p < 0.001). Sleep apnoea was 1.5-2-fold more frequent than the rate of the other identified risk factors typically associated with NAION (hypertension, diabetes). CONCLUSIONS: Sleep apnoea is the most frequent disorder associated with NAION and should be screened in this population. At least a questionnaire related to obstructive sleep apnoea symptoms and assessment of sleepiness should be systematically proposed to patients with NAION.

Adult↗

PubMed2006

Resting energy expenditure and fuel metabolism following laparoscopic adjustable gastric banding in severely obese women: relationships with excess weight lost.

BACKGROUND: Although adjustable gastric banding is increasingly proposed for massively obese patients, little is known about the modifications of resting metabolic rate and substrate oxidation or about metabolic determinants of weight loss following this type of bariatric surgery. OBJECTIVES: To evaluate the relationships between excess weight loss, resting metabolic rate (RMR) and substrate oxidation, and to identify metabolic predictive factors of weight loss after adjustable gastric banding. SUBJECTS: Seventy-three obese nondiabetic women aged 39.1+/-10.4 years (18.4-64.8). DESIGN: Resting metabolic rate and substrate oxidation (indirect calorimetry), body composition (bio-impedance), lipid profile and insulin sensitivity indexes were assessed before and after (13.3+/-6.0 months, range 6.0-31.1) adjustable gastric banding. Patients were classified according to postsurgery time: group A (6-12 months, n=39); group B (12-18 months, n=21); group C (>18 months, n=13). Metabolic parameters associated with the percentage of excess weight lost (EWL) 1 year after surgery were analyzed in univariate and multivariate regressions. RESULTS: Mean weight loss was 26.2+/-11.4 kg. Mean fat mass loss was 17.3+/-8.1 kg. All biological parameters associated with excess weight improved after surgery. Excess weight lost at 1 year was 45.9+/-17.1% in group A, 47.4+/-17.1% in group B and 51.4+/-18.5% in group C (P=NS). Resting metabolic rate/fat-free mass (FFM) slightly decreased (28.9+/-3.26 vs 30.3+/-2.8, P<0.00001) and RMR/body weight slightly increased (18.5+/-2.8 vs 17.3+/-1.9, P<0.00001) after surgery. Respiratory quotient (0.81+/-0.06 vs 0.82+/-0.05) and FFM-adjusted lipid oxidation (1.10+/-0.41 vs 1.05+/-0.33 mg/min/kg FFM) were not significantly modified after surgery. In multiple linear regression analysis, difference in RMR/body weight, difference in energy sparing, baseline BMI and postsurgery time, were significantly and independently correlated with EWL (total R2=72.5%). CONCLUSIONS: Adjustable gastric banding promotes gradual but sustained weight loss and is associated with long-term conservation of lipid oxidation and energy expenditure. The individual variability in energy sparing mechanisms predicts weight loss during the first year after surgery.

Adolescent↗

PubMed2006

Artificial beta-cell: clinical experience toward an implantable closed-loop insulin delivery system.

AIM: Restoration of long-term normal blood glucose control in diabetic patients supports the elaboration of an artificial beta cell. The possibility of implantation of the three crucial components of such a system (insulin delivery device, glucose sensor and controller) is analyzed. METHODS: The Long-Term Sensor System project, aiming at a fully implantable artificial beta cell, assessed the feasibility of glucose control by the combined implantation of a pump for peritoneal insulin delivery and a central intravenous glucose sensor close to the right atrium, connected via a subcutaneous lead. It was initiated in 10 Type 1 diabetic patients in our clinic from 2000. Data obtained during this experience are reviewed and confronted to reported closed-loop trials using other approaches. RESULTS: No significant complication related to prolonged implantation of intravenous sensors occurred and the combined implants were well tolerated. Glucose measurement by the intravenous sensors correlated well with meter values (r=0.83-0.93, with a mean absolute deviation of 16.5%) and accuracy has been sustained for an average duration of 9 months. Uploading of pump electronics by algorithms designed for closed-loop insulin delivery allowed in-patient 48 hour-trials aiming at automated glucose control. Glucose control was similar to that reported by investigations combining subcutaneous sensors to wearable pumps for subcutaneous insulin infusion. The benefits of more physiological insulin kinetics due to intra-peritoneal delivery have been hampered by the slow response time of intravenous sensors. CONCLUSION: Although the concept of a fully implantable artificial beta cell has been validated as feasible, the limited performance in achieving glucose control requests improvements in the sensor structure to increase its longevity and decrease sensor delay.

Clinical Trials as Topic↗

PubMed2006

Accuracy of continuous subcutaneous glucose monitoring with the GlucoDay in type 1 diabetic patients treated by subcutaneous insulin infusion during exercise of low versus high intensity.

AIM: The GlucoDay allows continuous glucose monitoring by subcutaneous microdialysis in sedentary conditions. To validate it when glycaemia may undergo rapid and dramatic changes, we investigated its accuracy during two exercise sessions with markedly different glucose disposal rates. METHODS: Nine male diabetic patients, aged 32-61, treated by insulin pumps, first underwent a standard maximal exercise-test designed for determining the maximal oxygen consumption and the first ventilatory threshold (Vt1). Then two 30 min steady-state workloads at 15% below and 15% above the Vt1 were performed in random order with the GlucoDay, and measurement of CHO oxidation rates was made by indirect calorimetry. RESULTS: CHO oxidation during exercise at +15% Vt1 was higher (+943.5 mg/min, ie +45.5%, P<0.01) than during exercise at -15% Vt1 No hypoglycaemia occurred. Due to breakages of 39% of subcutaneous probes, eleven steady-state sessions in 7 subjects allowed to compare 141 paired glucose (sensor vs. venous) determinations. The Clarke error grid situates 92.9% of glucose values within the A zone and 6.4% within the B zone, while only one pair of values (0.7%) falls in the D zone. Venous glucose tended to decrease more rapidly than sensor glucose during exercise. Bland-Altman plots evidence for a few cases of underestimation of venous glucose at high intensity. CONCLUSIONS: This study showed satisfactory accuracy of the GlucoDay during exercise. A slight lag time in sensor values likely explains a few discrepancies that do not appear as clinically meaningful. Reduction of probe fragility and confirmed sensor accuracy in hypoglycaemia would further support applicability of GlucoDay at exercise.

Adult↗

PubMed2006

Continuous intraperitoneal insulin infusion does not increase the risk of organ-specific autoimmune disease in type 1 diabetic patients: results of a multicentric, comparative study.

AIM: The purpose of this national multicenter prospective study by the French EVADIAC group was to investigate the possibility that continuous intraperitoneal insulin infusion using an implanted pump (CIpii) increases the risk of autoimmune disease in type 1 diabetic patients as it increased anti-insulin immunogenicity. METHODS: Prevalence of clinical (Hashimoto's disease, hyperthyroidism, gastric atrophic disease and vitiligo) and subclinical (presence of anti-thyroperoxidase antibodies, anti-intrinsic factor antibodies, abnormal TSH levels) autoimmune diseases was estimated by comparing two groups of patients already treated by either CIpii (n=154) or external pump (CSII) (n=121) for an average of 6 years. Incidence of autoimmune disease was determined by comparing the same measurements one year after inclusion. RESULTS: No significant difference was observed for the total prevalence of clinical and subclinical auto-immune thyroid and gastric di-seases (35.6% and 3.2% respectively in the CIpii group versus 40.4% and 2.6% in the CSII group). No significant difference for the incidence of clinical and subclinical auto-immune diseases was observed: 7.2% and 0% in CIpii and 7.3% and 1.7% in CSII. CONCLUSION: As previously shown AIA (anti-insulin antibodies) levels were higher in CIpii than in CSII (32.9% vs 20.2%, P<0.0001) but no correlation was observed with either clinical or subclinical autoimmune disease. This large-scale study eliminates the possibility that CIpii increases the risk of autoimmune disease.

Adult↗

PubMed2006

Myocardial perfusion imaging and cardiac events in a cohort of asymptomatic patients with diabetes living in southern France.

AIMS: To assess the association between abnormal stress myocardial perfusion imaging (MPI) and cardiac events (CE) in asymptomatic patients with diabetes and with > or = 1 additional risk factor. Predictors of abnormal stress MPI were also evaluated. METHODS: Four hundred and forty-seven consecutive patients who underwent stress MPI were prospectively followed for 2.1 [0.5-4.1] years for the subsequent occurrence of hard CE (myocardial infarction and sudden or coronary death) and soft CE (unstable angina and ischaemic heart failure requiring hospitalization). Re-vascularization procedures performed as a result of the screening protocol were not included in the analysis. RESULTS: Follow-up was successful in 419 of 447 patients (94%), of whom 71 had abnormal MPI at baseline. Medical therapy was intensified in all subjects and especially in those with abnormal MPI. Twenty-three patients with abnormal MPI underwent a re-vascularization procedure. CEs occurred in 14 patients, including six of 71 patients (8.5%) with abnormal MPI and eight of 348 patients (2.3%) with normal MPI (P < 0.005). Only two patients developed a hard CE and 12 a soft CE. In multivariate analysis, abnormal MPI was the strongest predictor for CEs [odds ratio (OR) (95% CI) = 5.6 (1.7-18.5)]. Low-density lipoprotein cholesterol > or = 3.35 mmol/l [OR (95% CI) = 7.3; 1.5-34.7] and age > median [OR (95% CI) = 6.0 (1.2-28.6)] were additional independent predictors for CE. The independent predictors for abnormal MPI were male gender, plasma triglycerides > or = 1.70 mmol/l, creatinine clearance < 60 ml/min and HbA1c > 8%, with male gender the strongest [OR (95% CI) = 4.0 (1.8-8.8)]. CONCLUSIONS: Asymptomatic patients with diabetes in this study had a very low hard cardiac event rate over an intermediate period. This could be explained by the effects of intervention or by the low event rate in the background population. Randomized studies of cardiac heart disease screening are required in asymptomatic subjects with diabetes to determine the effectiveness of this intervention.

Aged↗

PubMed2005

Intensive insulin therapy today: 'basal-bolus' using multiple daily injections or CSII?

Intensive insulin therapy aiming at normoglycemia in order to prevent long-term complications is not questionable for the management of type 1 diabetes mellitus nowadays. The gold standard mode of insulin therapy in this view is CSII using fast-acting analogues. Whether this reference method can be challenged by MDI using recently available long- and fast-acting analogues remains an open question. Use of fast-acting analogues provides similar benefits on post-meal glucose control either by MDI or by CSII. Long-acting analogues glargine and detemir have shown better effectiveness on basal blood glucose control, including improved stability and reduced occurrence of hypoglycemic episodes, than NPH and ultralente. Reported comparisons between CSII and MDI using glargine have been limited until now. While some of them have shown that CSII allowed both lower HbA1(c) and incidence of hypoglycemia, similar effects have been obtained in other experiences. From present data, it appears that CSII remains the most effective mode of intensive insulin therapy although it may be challenged in patients with stable basal insulin needs. Nevertheless, individual factors seem to be decisional in the choice between CSII and MDI using long-acting analogues, among which patient ability and will to use an insulin pump are critical.

Blood Glucose↗

PubMed2005

Subcutaneous insulin resistance successfully circumvented on long term by peritoneal insulin delivery from an implantable pump in four diabetic patients.

UNLABELLED: Extreme subcutaneous insulin resistance is a rare syndrome characterized by a severe resistance to subcutaneous (S/C) insulin together with persistence of normal or near normal intravenous (IV) insulin sensitivity. Its pathophysiology is unknown, although increased insulin degrading activity has been reported in the S/C adipose tissue fraction in some cases. Until now, proposed treatments have been disappointing. We report 4 cases who were successfully treated by intraperitoneal (IP) route. METHODS: The diagnosis of subcutaneous insulin resistance was based upon following combined conditions: resistance to hypoglycaemic action of subcutaneous insulin but normal or near normal sensitivity to IV or IP insulin. RESULTS: 4 patients among those followed by EVADIAC group met these criteria: 3 with type 1 diabetes (C peptide=0), the last one with unexplained non insulin-deficient diabetes (no anti-GAD antibodies, C peptide=5 ng/ml). All of them had been treated with subcutaneous insulin therapy without success despite huge doses (up to 4000 IU/day in two patients). The 3 type 1 diabetic patients presented with a history of repeated ketoacidosis episodes. A treatment of insulin mixed with aprotinin had been proposed to 2 patients without success. The IV insulin sensitivity was proved to be normal in two patients by euglycaemic clamp data. A skin biopsy was performed in 1 patient. An accumulation of insulin in the derma was revealed with no increase of degradation products of insulin. In these 4 patients, a dramatic improvement of diabetes control was obtained by IP insulin delivery from an implantable pump (HbA1c decrease by at least 3%). CONCLUSION: Although pathophysiology of the subcutaneous insulin resistance syndrome remains unexplained, our data show that intra-peritoneal insulin therapy from an implantable pump allows diabetes control in patients affected by this uncommon but severely disabling condition.

Adult↗

PubMed2004

[Long-term risks of polycystic ovaries syndrome].

The prevalence of the polycystic ovaries syndrome (PCOS) is high but it is a heterogeneous disorder with implications in numerous medical domains. Abdominal obesity and insulin resistance, which are the main metabolic disorders, are strong links between hormonal abnormalities and long-term medical consequences. The latter begin to be better understood. Some studies suggest that PCOS may increase the risk for several conditions, including type 2 diabetes, dyslipidemia, hypertension, cardiovascular disease and some cancers.

Cardiovascular Diseases↗

PubMed2003

Combined improvements in implantable pump technology and insulin stability allow safe and effective long term intraperitoneal insulin delivery in type 1 diabetic patients: the EVADIAC experience.

OBJECTIVE: To report a long-term multicentre experience with implantable insulin pumps in type 1 diabetic patients, and to test safety and accuracy of the systems following improvements in infused insulin solutions and peritoneal catheter. RESEARCH DESIGN AND METHODS: Forty MiniMed Implantable Pumps model 2001 were consecutively implanted over a two-month period in type 1 diabetic volunteers. The systems were equipped by a new compliant sideport catheter and were refilled at 45-day intervals with HOE 21 PH ETP insulin batches showing enhanced physical stability in vitro. Safety was assessed from the incidence of acute adverse events and effectiveness from quarterly HbA(1c) assays. Accuracy of delivery was measured at each pump refill by comparing residual insulin in the pump reservoir with expected amount according to programmed infusion. The study lasted until pump battery depletion or premature pump explantation. RESULTS: Cumulated experience was 106 patient-years. Premature explantations occurred in 3 cases, due to one electronic pump failure and two "pump-pocket" infections. Near-normal insulin delivery was sustained until expected battery depletion in 13 cases. Forty underdelivery events occurred in 24 pumps, but 36 among them were related to pump slowdowns due to insulin aggregation in pumps that were promptly solved by an outpatient NaOH rinse procedure. Only 4 underdeliveries were caused by catheter obstructions that required laparoscopy to remove peritoneal tissue overgrowth around the catheter. Over pump lifetime, HbA(1c) was 7.2 +/- 0.2% in the 13 patients with no underdelivery and 7.7 +/- 0.5% in the other ones. Only one severe hypoglycemia and one ketoacidosis occurred during the whole study. CONCLUSION: Our current experience with improved implantable pumps and insulin solutions shows both long-term safety and effectiveness of this treatment in type 1 diabetic patients following improvement in infused insulin solutions and catheter. This therapy may be a good alternative for patients that experience frequent severe hypoglycemia with intensive subcutaneous insulin therapy.

Adult↗

PubMed2003

[Insulin therapy by insulin pump: continuous or conventional self-blood glucose monitoring? ].

Use of portable pumps is increasing to achieve intensive insulin treatment. Beside unpredictable insulin absorption and insufficient reactivity to changes of insulin flow rate due to the subcutaneous route, this therapy is however limited by the lack of information on blood glucose level provided by self-blood glucose monitoring. Thus, patient interpretation only leads to speculative adaptation of pump flow rate. The lack of alert toward the risk of hypoglycemia or hyperglycemic ketogenic deviations can lead to the occurrence of deleterious metabolic distorsions, among which severe hypoglycemia stands in first rank. Starting experiences of continuous recording of interstitial glucose level by portable systems using glucose-oxidase allow on short time durations the identification of daily periods of poor metabolic control. Retrospective availability of information gives the possibility of more adequate treatment adaptations than conventional capillary blood glucose monitoring, but does not allow immediate prevention of metabolic events. Only devices providing real time or near-real time information to the patient can fulfill this function. However, the absence of tight parallelism between variations of interstitial and blood glucose levels may lead to erroneous decisions. A true continuous real time information on blood glucose level on long-term seems only expectable from implantable glucose sensors. Still under investigation, these systems should be able to insure vigilance toward the risk of hypo- and hyperglycemia on weekly or monthly periods. Initially used as complementary to capillary self-monitoring, their reliability should allow their use as substitutes for conventional monitoring, except for measurements aimed at signal calibration. Pump control by the sensor signal is conceivable if it corresponds to a direct, continuous, real time measurement of blood glucose, and subject to a simultaneous improvement of insulin infusion modes.

Blood Glucose↗

PubMed2003

[Menopause: towards treatment "à la carte" ].

In spite of questioning and doubt arising from WHT study hormone substitution therapy (HST) has proven efficacy on climacteric symptoms and certain short-term and long-term consequences of menopause. Among 1000 women taking HST for ten years, eight supplementary cases of breast cancer and 6 fewer cases of colonic cancer are observed. No cardiovascular protection has been demonstrated. A history of coronary artery disease, vascular disease, stroke or thromboembolism are contraindications for HST. The vascular impact of estradiol administered via an extra-digestive route in women with a low vascular risk cannot be extrapolated from the HERS and WHI trials because these trials were conducted is high-risk women, using specific types of steroids given orally. Tibolone has demonstrated efficacy and in an alternative to HST after more than one year of menopause. The usefulness of phytoestrogens remains to be determined, particularly due to the wide individual variability of their effects on climacteric symptoms and the low level of proof provided by epidemiological or clinical studies conducted to study the prevention of osteoporosis and the risk of breast cancer. Most of the analyses present methodological biases. Currently, the most widely accepted notion is that there is a beneficial effect on cardiovascular risk. To date, SERMs have selective indications and cannot be prescribed for all women: raloxifen is used for the prevention and treatment of menopause-related osteoporosis. The relative risk of venous thromboembolism with SERMs (raloxifen and tamoxifen) is comparable to that observed with HST. HST or any other treatment given for menopause must be an individual decision balancing the benefits against the risks and taking into account the desires of the patient perfectly informed of the currently available evidence. Prescriptions should be part of an overall scheme including nutritional advise and physical exercise aimed at preserving quality of life and preventing age-related effects which largely depend on genetic predisposition and the psycho-affective environment.

Cardiovascular Diseases↗

PubMed2002

Comparison of blood glucose stability and HbA1C between implantable insulin pumps using U400 HOE 21PH insulin and external pumps using lispro in type 1 diabetic patients: a pilot study.

BACKGROUND: To assess the efficacy on blood glucose control of continuous peritoneal insulin infusion from implantable pump (CPII) compared with continuous subcutaneous infusion using insulin lispro (CSII-IL) in type 1 diabetic patients. METHODS: Fourteen type 1 diabetic patients (5 males and 9 women, age 50.6 +/- 12.8, diabetes duration 28.0 +/- 13.4 years) were treated with CSII-IL and CPII. Capillary blood glucose (BG) was monitored and recorded at least 4 times per day during 2 study periods of 45 days: using CSII-IL (period A), and from 45th to 90th day after implantation (period B). HbA1C was measured at the end of each period. RESULTS: Both daily BG levels (145 +/- 18 vs 153 +/- 17 mg/dl, p<0.01) and preprandial BG levels (139 +/- 20 vs 147 +/- 22 mg/dl, p<0.05) were lower in period B. Although postprandial BG values tended to be lower in period B, this reduction did not reach statistical significance (149 +/- 20 vs 157 +/- 16 mg/dl, p=0.07). Meanwhile, SD of all BG values was lower with CPII (69 +/- 11 vs 79 +/- 17 mg/dl, p<0.01) and HbA1c levels were lower at the end of period B (7.3 +/- 0.9 vs 7.8 +/- 0.9%, p=0.04). Low blood glucose index was comparable during both periods (2.8 +/- 1.6 vs 3.1 +/- 1.5, p=0.4). CONCLUSION: CPII may provide a better BG control and stability than CSII-IL. However, a long-term randomized prospective study is needed to confirm these improvements.

Age of Onset↗

PubMed2002

[From external to implantable insulin pump, can we close the loop?].

The project to finalize a 'closed loop' insulin delivery according to blood glucose level, i.e. an implanted artificial beta cell, is born from the development of the first miniaturized portable insulin pumps during the 1970s. Continuous improvements in micro-electronics, as well as in the development of biomaterials and stable insulin solutions, have led to the availability of implantable pumps able to infuse insulin by the peritoneal route, in a continuous and programmable way, for several years. These systems represent the most efficient and physiological mode of insulin therapy at the present time. More recently, we have demonstrated during clinical trials that intravascular, implantable, glucose sensors using glucose-oxidase were able to measure with good accuracy real-time blood glucose for several months. The combination of these two devices to form a prototype of implantable artificial beta cell, designated as Long Term Sensor System, allowed us to perform the first trials of closed-loop insulin delivery according to sensor signal for periods of 48 hours in type 1 diabetic patients. This mode of functioning appeared to be feasible and able to establish glucose control closer to physiology than the use of implantable pumps in open-loop, i.e. by adapting insulin delivery according to capillary blood glucose. Although algorithms tuning automated insulin delivery are improvable, the success of these initial trials materializes the perspective of a possible restoration of physiological insulin function by the mean of an implanted artificial beta cell in diabetic patients.

Blood Glucose↗

PubMed2002

Reduction of fat accumulation and lipid disorders by individualized light aerobic training in human immunodeficiency virus infected patients with lipodystrophy and/or dyslipidemia.

BACKGROUND: The management of abdominal fat accumulation and metabolic disorders in HIV1-infected patients, by an aerobic training program, is considered. METHODS: Seventeen lipodystrophic and 2 dyslipidemic (without body modification) adults were studied before and after 4 months of training. The training load was individualized on a ventilatory threshold basis, determined during a maximal exercise test on cycle ergometer. Total (TAT), Visceral (VAT) and Subcutaneous Adipose Tissue (SAT) were assessed by CT-scan. Total (TC) and High Density Lipoprotein (HDL-C) Cholesterol, Triglycerides (TG), lactate (La), insulin and glucose were measured after a 12-hour-overnight fast. LDL, TC/HDL, TG/HDL, HOMA-insulin resistance index and coronary heart disease (CHD) relative risk (RR(CHD)) were calculated. RESULTS: Besides a significant improvement of aerobic fitness, trained patients exhibited a reduction in TAT (-12.8%, p < 0.001), specially at the visceral level (- 12%, p < 0.01) and in TC, TG and La (- 23%, - 43% and - 19% respectively, p < 0.01). HDL-C was increased (+ 6%, p < 0.01). All these effects were above changes that could be expected by a possible regression to the mean artefact. Both TC/HDL and TG/HDL were reduced (p < 0.01) and the estimated RR(CHD) decreased by approximately 13% (p < 0.01). No significant training effect was observed on the 9 available HOMAs. Significant correlations were found between changes in blood lipid values and baseline measures (r range - 0.55 to - 0.79, p < 0.05), indicating a larger improvement when baseline lipid parameters were higher. CONCLUSION: Aerobic training reduced visceral fat, lipid disorders, basal blood lactate and CHD markers in HIV patients. Training effects were particularly important for patients with marked dyslipidemia.

Adipose Tissue↗

PubMed2001

Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome.

To assess the role of insulin receptor, insulin receptor substrate (IRS)-1, and IRS-2 genes in insulin resistance, we explored the genomic DNA in women with polycystic ovary syndrome (PCOS) and a variable degree (mean +/- SE) of insulin resistance (homeostasis model assessment index for insulin resistance [HOMA(IR)] 3.2 +/- 0.6, n = 53; control subjects 1.56 +/- 0.34, n = 102) using direct sequencing. Whereas no novel mutations were found in these genes, gene-dosage effects were found on fasting insulin for the Gly972Arg IRS-1 variant and on 2-h plasma glucose for the Gly1057Asp IRS-2 variant. The Gly972Arg IRS-1 variant was more prevalent in insulin-resistant patients compared with non-insulin-resistant individuals or control subjects (39.3 vs. 4.0 and 16.6%, P < 0.0031, respectively). A multivariate model that included BMI as a variable revealed significant effects of the Gly1057Asp IRS-2 variant on insulin resistance (P < 0.016, odds ratio [OR] 7.2, 95% CI 1.29-43.3). HOMA(IR) was higher in carriers of both IRS variants than in those with IRS-2 mutations only or those with wild-type variants (6.2 +/- 2.3, 2.8 +/- 0.5, and 1.8 +/- 0.2, respectively; P < 0.01), and it was significantly associated with this genotype (P < 0.0085, OR 1.7, 95% CI 1.09-2.99). We conclude that polymorphic alleles of both IRS-1 and IRS-2, alone or in combination, may have a functional impact on the insulin-resistant component of PCOS.

Adult↗

PubMed2001

Implantable insulin pumps: infections most likely due to seeding from skin flora determine severe outcomes of pump-pocket seromas.

Complications at implantation site of implantable insulin pumps may lead to premature removal. To elucidate the origins and the outcomes of these local adverse events. We investigated seromas of the 'pump-pocket' that have been detected for an eight month-period during the follow-up of such-treated forty type 1 diabetic patients. At the start of study period, skin bacterial flora was sampled at umbilicus and groin, and isolated strains of Staphylococcus epidermidis were preserved in specific vials at -20 degrees C. Each time a seroma was detected at transcutaneous 45 days-refill of pump reservoir, it was sampled for bacterial cultures. Isolated strains of S. epidermidis from seroma were genetically compared to preserved strains of corresponding patients using Pulsed-Field Gel Electrophoresis (PFGE) after genomic restriction by SmaI. Among the ten seromas that occurred after a mean time of 9.9 months since implantation, S. epidermidis were isolated in five cases. Genetic comparison of isolated strains could be performed in three cases. Compared strains showed identical (in 2 cases) or closely related (in one case) PFGE profiles. While the five aseptic seromas resolved with rest, four infected cases required explantations after one to nineteen months in spite of antibiotic therapy and the fifth one persisted without impairment under long-term antibiotics. Our results suggest that seeding from the skin flora is a key-factor determining the severity of pump-pocket complications. We recommend that bacterial investigations of pump-pocket seromas should be systematically performed, while prophylactic measures might include antibiotic cover for each puncture of the pump-pocket.

Adult↗

PubMed2001

[Insulin sensitivity and polycystic ovarian syndrome].

Insulinresistance, commonly associated with polycystic ovarian syndrome (PCOS), raises many unresolved debates about its prevalence, mechanism and true pathological role. Low insulin sensibility may have multiple origins among them genetic molecular defects in pathways of cellular insulin effects. A weight gain and android distribution of fat mass may reveal or increase insulin resistance and hyperinsulinemia. The preexisting unbalanced ovarian steroidogenesis secondary to abnormalities in gene coding for enzymes of P450C17 alpha might be the necessary support facilitating the stimulatory effect of hyperinsulinemia or other factors (LH, IGF1) on ovarian androgens. In practice, the phycisian has to know how to evaluate and to treat insulin resistance in view of its implication in dysovulation and, later on, metabolic and cardiovascular risks. Nutritional education and regular physical exercice are the necessary approaches. The efficacy and indications of metformin and thiazolidinediones have to be further evaluated.

Adipose Tissue↗