HPV ctDNA detection of high-risk HPV types during chemoradiotherapy for locally advanced cervical cancer.

BACKGROUND: Chemoradiotherapy (CRT) is the standard of care for patients diagnosed with locally advanced cervical cancer (LACC), a human papillomavirus (HPV)-related cancer that relapses in 30%-60% of patients. This study aimed to (i) design HPV droplet digital PCR (ddPCR) assays for blood detection (including rare genotypes) and (ii) monitor blood HPV circulating tumor DNA (HPV ctDNA) levels during CRT in patients with LACC. METHODS: We analyzed blood and tumor samples from 55 patients with HPV-positive LACC treated by CRT in a retrospective cohort (n = 41) and a prospective cohort (n = 14). HPV-ctDNA detection was carried out by genotype-specific ddPCR. RESULTS: HPV ctDNA was successfully detected in 69% of patients (n = 38/55) before CRT for LACC, including nine patients with a rare genotype. HPV-ctDNA level was correlated with HPV copy number in the tumor (r = 0.41, P < 0.001). HPV-ctDNA positivity for HPV18 (20%, n = 2/10) was significantly lower than for HPV16 (77%, n = 27/35) or other types (90%, n = 9/10, P = 0.002). HPV-ctDNA detection (positive versus negative) before CRT was associated with tumor stage (P = 0.037) and lymph node status (P = 0.02). Taking into account all samples from the end of CRT and during follow-up in the prospective cohort, positive HPV-ctDNA detection was associated with lower disease-free survival (DFS) (P = 0.048) and overall survival (OS) (P = 0.0013). CONCLUSION: This is one of the largest studies to report HPV-ctDNA detection before CRT and showed clearance of HPV ctDNA at the end of treatment in most patients. Residual HPV ctDNA at the end of CRT or during follow-up could help to identify patients more likely to experience subsequent relapse.

[E-consult®, an e-health application to improve breast cancer surgery patient's information]. / E-consult®, application d'e-santé pour mieux informer les patientes en consultation de chirurgie pour cancer du sein.

INTRODUCTION: The use of new information and communication technologies is one way of better informing the patient. E-health includes telemedicine but also patient information and self-monitoring, or continuous remote monitoring with connected objects and mobile apps. It is in this context that we have developed and designed a digital application, e-consult®, which we use at the François Baclesse center, dedicated to improving information for patients. The objective of this study was to assess the performance of the e-consult® application in current practice, in order to know if the information delivered to patients was better retained with the application. METHODS: We conducted a prospective, single-center study at the Cancer Center François Baclesse. One group was received in consultation with the use of e-consult®, the other without. Following the consultation, the patient was given a questionnaire concerning her illness and a satisfaction questionnaire concerning the application. RESULTS: The average score obtained on the questionnaire in the group having benefited from a consultation with e-consult® (7.12/10) was significantly higher than that obtained in the group having benefited from a consultation without e-consult® (6.4/10) (P=0.0276). CONCLUSION: Our study showed that patients understood better the information transmitted in consultation with the use of e-consult®. In our opinion, this is the only study evaluating an application in consultation. However, our study has several weaknesses, including the lack of randomization, a small number of patient, and unvalidated questionaries. Despite these promising results, more studies with better internal validity are needed. Future research may also study the impact of the application on the doctor-patient relationship.

[Robotic surgery in endometrial cancer: Feasibility in obese patients]. / Chirurgie robotique du cancer de l'endomètre chez la patiente obèse.

OBJECTIVE: Minimally invasive surgery is a technique frequently used in gynecologic surgery. The robot-assisted surgery is a recent approach, and the benefits are not yet proven. The objective of this study was to evaluate the feasibility to use robot-assisted surgery for obese patient with endometrial cancer. METHODS: All patients undergoing a robotic surgery for uterus malignant indication between March 2013 and May 2016 in our center were retrospectively included. Patients were divided in two groups, according to their body mass index (BMI). The group with BMI<30kg/m2 was the reference for this comparative study. The main criteria was the robot operative time. The other criteria were total operating time, hospital stay and intraoperative and postoperative complications. RESULTS: Seventy-seven patients met inclusion criteria for analysis. The median robot operative time was 110minutes for all patients [21-341], without difference between the five groups (P=0.60). There was no difference for the total operative time (P=0.50). The median hospital stay was 3 days (P=0.92). There were ten intraoperative complications. One patient had a conversion (1.3%). There was no statistical difference for postoperative complications (P=1). CONCLUSION: Our study found few differences in the surgical management by laparoscopic robot-assisted between obese and non obese women. Robot-assisted surgery seems to be feasible for uterine cancer treatment of obese patients. Prospective and randomized studies are needed to assess the benefit of the robotic surgery.

[Child protection system: Knowledge and role of the general practitioners in Ille-et-Vilaine]. / Protection de l'enfance : connaissance et place des médecins généralistes en Ille-et-Vilaine.

BACKGROUND AND AIMS: On 5 March 2007 the law concerning the child protection system was reformed. Since this date, child protection services are responsible for child abuse and neglect. Child protection services are now attempting to determine the rightful place for parents. Asking for child protection is now easier for the general practitioner (GP), who can submit a "preoccupying information (PI)" form. The aim of this study was to review GPs' knowledge on this issue 6 years after the passage of this new law. METHODS: Prospective postal investigation between 04/01/2013 and 06/01/2013. RESULTS: A total of 298 (113 women) of the 899 GPs of the Ille-et-Vilaine area in Brittany answered a few questions about their activity and their knowledge on child abuse and neglect. The sample's mean age, sex, and practice was representative of the GPs in this area. Only 25.5% of the GPs had any knowledge of this new law. The term "preoccupying information" was unfamiliar to 70.1% of the GPs and what to do with the PI was unknown to 77.2%. The GPs did not know which type of letter to send nor where to send it between legal child protection and social protection services. Only 5% of the GPs had child protection training on PI. The main problem informing the child protection services was the lack of training. Consequently, 91.9% of the GPs would like training. CONCLUSIONS: The GPs in the Ille-et-Vilaine area in Brittany are unfamiliar with the child protection updates and need special training.

[Diagnostic laparoscopy in gynecological cancer, prophylactic oophorectomy: feasibility study on 22 cases]. / Cœlioscopie diagnostique en cancérologie gynécologique, annexectomie bilatérale prophylactique : étude de faisabilité sur 22 cas.

OBJECTIVES: The purpose of our study was to assess the feasibility of outpatient laparoscopy in a cohort of 22 patients admitted for bilateral oophorectomy (n=11) and preoperative diagnostic laparoscopy (n=11). PATIENTS AND METHODS: Between December 2012 and May 2013, we included 22 patients in our study. All selected patients received a questionnaire the day before surgery. The questionnaire consisted of chapters on intraoperatively, and the postoperative assessments of patients regarding a possible return home on the evening of surgery. The ability to output was measured with the score of Chung at the evening of surgery and in the morning before leaving. RESULTS: The mean age of patients was 60 years. The average length of stay was 1.2 days. Postoperative pain tends to be higher in the morning in the bilateral oophorectomy group (P=0.06), nausea and vomiting are the same in both groups. In the bilateral oophorectomy group, six patients were able to go out and five wished it; in the diagnostic laparoscopy group nine patients were able to go out and two wished it, this difference was significant (P=0.041). DISCUSSION: The outpatient hospital is the norm for many surgeries. In our study, 47% of patients able to go out wishing that output. This difference is important when comparing the two groups. There are more patients wishing an output in the oophorectomy group. This reduction in length of stay must be compensated by a medical and paramedical supervision at home. CONCLUSION: A large number of surgical procedure are performed on an outpatient basis. Patients who underwent diagnostic laparoscopy are more fragile, they should receive active postoperative support to enable an outpatient hospital.

[Quality of life after lipomodelling: retrospective study of 42 patients]. / Qualité de vie après lipomodelage: étude rétrospective à propos de 42 patientes.

OBJECTIVES: Study of the quality of life of 42 patients who underwent a lipofilling in our institution between 2009 and 2010. PATIENTS AND METHOD: Analysis of cosmetic outcomes, side effects, emotional life and preoperative information received by a cohort of 42 patients contacted by anonymous questionnaires. Comparisons between patients with a single prothesis, latissimus dorsi flap with prothesis, autologous latissimus dorsi flap and rectus abdominal flap. RESULTS: The response rate was 56% (42 patients). The average volume of fat injected was 80mL. The aspect of the reconstructed breast and the harmony between two breasts were better after lipofilling (P=0.0001, P=0.0005). The evolution of the aesthetic result is satisfying for 64.1% of the patients. In 29% of cases, patients noticed adhesions at the injection site. Apprehension to touch the reconstructed breast and to wear a swimsuit decreases after lipofilling (P=0.0345;P=0.0284). All patients declared to be satisfied with the presurgery information. Half of the patients declare that the final result corresponds to their wishes. DISCUSSION: The side effects of lipofilling were studied from an oncological point of view. Less publications describe the patients quality of life after lipofilling. This surgery improves the breast reconstruction results and helps patients in a social, affective and aesthetic way. Overall, lipofilling improves more consistency in patients reconstructed by single prothesis and improves more appearance in patients reconstructed by single flap. CONCLUSION: Lipofilling improves significantly patients' quality of life. A clinical research protocol (GRATSEC) is currently underway to extend its indications. The lipofilling should not replace a bad indication of breast reconstruction.

Accuracy assessment of online glucose monitoring by a subcutaneous enzymatic glucose sensor during exercise in patients with type 1 diabetes treated by continuous subcutaneous insulin infusion.

AIM: Online continuous glucose monitoring (CGM) during physical exercise would be highly useful in patients with insulin-treated diabetes. For this reason, this study assessed whether such a goal could be reached with a subcutaneous 'needle-type' enzymatic sensor. METHODS: Ten patients (five women/five men), aged 51 ± 12 years, with type 1 diabetes for 24 ± 11 years treated by continuous subcutaneous insulin infusion (CSII) for more than 1 year (HbA1c: 7.5 ± 0.8%) performed a 30-min bout of exercise at a constant high-intensity load (15% above their individual ventilatory threshold) on a cycle ergometer. All patients wore a subcutaneous 'needle-type' enzymatic glucose sensor linked to a portable monitor (Guardian(®) RT, Medtronic-MiniMed, Northridge, CA, USA) that had been inserted the previous evening. Sensor calibration was performed against capillary blood glucose immediately before the exercise. CGM values were recorded every 5 min from T(-10) to T(+30), then every 10 min during the recovery period from T(+30) to T(+90). These recorded values were compared with blood glucose assays performed on simultaneously collected venous samples. RESULTS: Sensor functioning and tolerability raised no problems except for one sensor that could not be adequately calibrated. Data from this patient were excluded from the data analysis. An average blood glucose decrease of 63 ± 63 mg/dL (3.5 ± 3.5 mmol/L) (median decrease: 58 mg/dL [3.22 mmol/L]; range: -3 mg/dL [0.16 mmol/L] to 178 mg/dL [9.8 mmol/L]) occurred during exercise bouts, while CGM values decreased by 38 ± 49 mg/dL (2.11 ± 2.72 mmol/L) (median: 32 mg/dL [1.7 mmmol/L]; range: -15 mg/dL [0.83 mmol/L] to 58 mg/dL [3.22 mmol/L]). Cumulative paired glucose values (n = 135) could be analyzed. The correlation factor between CGM and blood glucose values was 0.957 with an intercept of 0.275. The mean difference between paired values according to Bland-Altman analysis was 10 ± 31 mg/dL (0.56 ± 1.72 mmol/L). Clarke error grid analysis showed 91% of paired points in A and B zones, while 0%, 9% and 0% of paired points were in the C, D and E zones, respectively. CONCLUSION: Blood glucose changes during intensive physical-exercise bouts performed by CSII-treated type 1 diabetes patients can be estimated with acceptable clinical accuracy by online CGM.

Physical activity targeted at maximal lipid oxidation: a meta-analysis.

Exercise is recognized as a part of the management of obesity and diabetes. Various protocols of exercise are proposed for the management of obesity, diabetes, and other metabolic diseases. One of the strategies proposed by several authors is low intensity endurance training targeted at the level of maximal oxidation. Large series using this technique are lacking. Addressing this issue, we performed a meta-analysis of the studies on anthropometric measurements. From a database of 433 articles, 15 were selected, including 279 subjects with 6 different populations. Studies duration ranged from 2 months to 12 months. Concerning weight loss, in the intervention versus control analysis, five studies with 185 participants were included with a significant effect size favors exercise (P = 0.02) without significant heterogeneity (I(2) = 0.0%, P = 0.83). Further randomized controlled trials for comparing it with other exercise protocols and defining its dose effectiveness on large samples are needed.

Maximal lipid oxidation during exercise: a target for individualizing endurance training in obesity and diabetes?

This review summarizes the rationale for personalized exercise training in obesity and diabetes, targeted at the level of maximal lipid oxidation as can be determined by exercise calorimetry. This measurement is reproducible and reflects muscles' ability to oxidize lipids. Targeted training at this level is well tolerated, increases the ability to oxidize lipids during exercise and improves body composition, lipid and inflammatory status, and glycated hemoglobin, thus representing a possible future strategy for exercise prescription in patients suffering from obesity and diabetes.

Decreased fat oxidation during exercise in severe obstructive sleep apnoea syndrome.

AIM: To assess whether the severity of obstructive sleep apnoea syndrome (OSAS) is associated with altered fat oxidation (FO) during physical exercise in men with type 2 diabetes (T2DM) and/or the metabolic syndrome (MetS). METHODS: A total of 105 consecutive overweight or/and T2DM male patients were hospitalized for metabolic check-ups including bioimpedancemetry to measure lean body mass (LBM), standardized exercise calorimetry to assess FO, maximum fat oxidation (MFO) and carbohydrate oxidation (CHO), and OSAS screening using respiratory polygraphy. Twenty patients were classified as having severe OSAS, according to the apnoea/hypopnoea index (AHI), with greater than 30 events/h (mean AHI: 45.2±14.3 events/h). They were group-matched for age, BMI, and the presence of T2DM and/or MetS with two other OSAS groups: mild (AHI<15 events/h [n=20]; mean AHI: 8.8±4.5 events/h); and moderate (AHI>15 events/h and<30 events/h [n=20]; mean AHI: 23.7±4.2 events/h). RESULTS: MFO adjusted for LBM was severely decreased in the severe OSAS group (1.6±1.0 mg.min(-1).kgLM(-1)) compared with the moderate (2.5±0.9 mg.min(-1).kgLM(-1); P=0.008) and mild (2.9±0.8 mg.min(-1).kgLM(-1); P=0.003) groups. All exercise-intensity levels (20%, 30%, 40% and 60% of the theoretical maximum aerobic power) showed reduced FO levels between the severe and mild-to-moderate OSAS groups. However, no differences in CHO were seen at any level of exercise between groups. Pearson's correlation analysis showed that AHI and the oxygen desaturation index were negatively associated with MFO corrected for LBM (r=0.41 and r=0.37, respectively; P<0.005). CONCLUSION: OSAS severity is associated with altered FO during exercise.

Six-minute walking test predicts maximal fat oxidation in obese children.

BACKGROUND: Obesity is associated with reduced exercise maximal fat oxidation rate (FATmax), which is generally assessed by cardiopulmonary cycling test. The six-minute walking test (6MWT) presents an alternative method in patients. OBJECTIVE: The aim of this study was to establish a practical reference equation facilitating the prediction of FATmax from the 6 MWT in obese children of both genders. DESIGN: This study is a cross-sectional study using mixed linear and multiple regression models. RESEARCH METHODS AND PROCEDURES: Anthropometric measurements were recorded and submaximal cycling test and 6 MWT conducted for 131 school-aged obese children, 68 boys and 63 girls. A multiple regression analysis for FATmax, including six-minute walking distance (6 MWD), anthropometric and cardiac parameters as the dependent variables, was performed for the two genders separately. RESULTS: Mean 6 MWD and FATmax were 564.9 ± 53.7 m and 126.5 ± 12.1 mg min(-1) for boys and 506.7 ± 55.0 m and 120.7 ± 10.0 mg min(-1) for girls, respectively. The 6MWD, body mass index, Z-score, fat-free mass, waist and hip circumferences (WC and HC), rest heart rate, and systolic and diastolic blood pressures were highly correlated with FATmax for both genders. There was a significant correlation between 6 MWD and FATmax in both boys and girls (r = 0.88 and r = 0.81, P<0.001, respectively). Stepwise regression analyses revealed that the combinations of 6 MWD with HC for boys and 6MWD with WC for girls improved the predictability of the model (R(2) = 0.81 for boys and R(2) = 0.72 for girls; P<0.001). CONCLUSION: In obese children, the 6MWT can be used to predict FATmax when formal test of exercise capacity and gas exchange analysis are unavailable or impractical. It is therefore possible to prescript targeted exercises at FATmax, without performing indirect calorimetry, just from a field test.

The effects of short term recombinant human growth hormone (rhGH) on blood rheology in healthy young males.

INTRODUCTION: It has been shown that growth hormone (GH) exerts regulatory effects on hemorheology and other metabolic functions. GH stimulates the production of insulin-like growth factor I (IGF-I) and GH-IGF-I system has profound effects on body fluid status. There are speculations that GH has become widely used as a performance enhancing drug among athletes of various sports. The present study evaluated the possible hemorheological effects of short term administration of human recombinant growth hormone (rhGH) in healthy young males. METHODOLOGY: Thirty young healthy males (27 ± 9) participated in a 29 days study where it was administered either 0.9% sodium chloride or 1 mg of human rhGH from day 1 to day 7. The participants were randomly assigned into either placebo (C) n = 15 or rhGH 1 mg/day (rhGH) group n = 15. This study evaluated plasma fibrinogen levels, red blood cell (RBC) aggregation, deformability and serum IGF-I levels between and within the groups along 29 days. RESULTS: There was a significant increase in erythrocytes aggregation index post injection (day 8), in accordance to an increase in serum IGF-I.

Cost-saving effect of supervised exercise associated to COPD self-management education program.

BACKGROUND: Although the benefits of comprehensive pulmonary rehabilitation have been demonstrated in patients with COPD, the effects of exercise sessions within self-management programs remain unclear. We hypothesized that 8 supervised exercise sessions incorporated in a 1-month self-management education program in COPD patients would be effective to improve health outcomes and to reduce direct medical costs after one year, compared to usual care. METHODS: In this randomized controlled trial, 38 moderate-to-severe COPD patients were assigned either to an intervention group or to a usual care group. The hospital-based intervention program provided a combination of 8 sessions of supervised exercise with 8 self-management education sessions over a 1-month period. The primary end-point was the 6-min walking distance (6MWD), with secondary outcomes being health-related quality of life (HRQoL)--using the St. George's Respiratory Questionnaire (SGRQ) and Nottingham Health Profile (NHP), maximal exercise capacity and healthcare utilization. Data were collected before and one year after the program. RESULTS: After 12 months, we found statistically significant between-group differences in favor of the intervention group in 6MWD (+50.5 m (95%CI, 2 to 99), in two domains of NHP (energy, -19.8 (-38 to -1); emotional reaction, -10.4 (-20 to 0)); in SGRQ-symptoms (-14.0 (-23 to -5)), and in cost of COPD medication (-480.7 € (CI, -891 to -70) per patient per year). CONCLUSION: The present hospital-based intervention combining supervised exercise with self-management education provides significant improvements in patient's exercise tolerance and HRQoL, and significant decrease of COPD medication costs, compared to usual care.

Intramyocellular lipid accumulation is associated with permanent relocation ex vivo and in vitro of fatty acid translocase (FAT)/CD36 in obese patients.

AIMS/HYPOTHESIS: Intramyocellular lipids (IMCL) accumulation is a classical feature of metabolic diseases. We hypothesised that IMCL accumulate mainly as a consequence of increased adiposity and independently of type 2 diabetes. To test this, we examined IMCL accumulation in two different models and four different populations of participants: muscle biopsies and primary human muscle cells derived from non-obese and obese participants with or without type 2 diabetes. The mechanism regulating IMCL accumulation was also studied. METHODS: Muscle biopsies were obtained from ten non-obese and seven obese participants without type 2 diabetes, and from eight non-obese and eight obese type 2 diabetic patients. Mitochondrial respiration, citrate synthase activity and both AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation were measured in muscle tissue. Lipid accumulation in muscle and primary myotubes was estimated by Oil Red O staining and fatty acid translocase (FAT)/CD36 localisation by immunofluorescence. RESULTS: Obesity and type 2 diabetes are independently characterised by skeletal muscle IMCL accumulation and permanent FAT/CD36 relocation. Mitochondrial function is not reduced in type 2 diabetes. IMCL accumulation was independent of type 2 diabetes in cultured myotubes and was correlated with obesity markers of the donor. In obese participants, membrane relocation of FAT/CD36 is a determinant of IMCL accumulation. CONCLUSIONS/INTERPRETATION: In skeletal muscle, mitochondrial function is normal in type 2 diabetes, while IMCL accumulation is dependent upon obesity or type 2 diabetes and is related to sarcolemmal FAT/CD36 relocation. In cultured myotubes, IMCL content and FAT/CD36 relocation are independent of type 2 diabetes, suggesting that distinct factors in obesity and type 2 diabetes contribute to permanent FAT/CD36 relocation ex vivo.

Limited predictive value of the IDF definition of metabolic syndrome for the diagnosis of insulin resistance measured with the oral minimal model.

AIM: To assess the agreement of the NCEP ATP-III and the IDF definitions of metabolic syndrome and to determine their predictive values for the diagnosis of insulin resistance. METHODS: For this purpose, we recruited 150 subjects (94 women and 56 men) and determined the presence of metabolic syndrome using the NCEP-ATP III and IDF definitions. We evaluated their insulin sensitivity S(I) using Caumo's oral minimal model after a standardized hyperglucidic breakfast test. Subjects whose S(I) was in the lowest quartile were considered as insulin resistant. We then calculated sensitivity, specificity, positive and negative predictive values of both definitions for the diagnosis of insulin resistance. RESULTS: The prevalence of metabolic syndrome was 37.4% (NCEP-ATP III) and 40% (IDF). Agreement between the two definitions was 96%. Using NCEP-ATP III and IDF criteria for the identification of insulin resistant subjects, sensitivity was 55.3% and 63%, specificity was 68.8% and 67.8%, positive predictive value was 37.5% and 40%, negative predictive value was 81.9% and 84.5%, respectively. Positive predictive value increased with the number of criteria for both definitions. CONCLUSION: Whatever the definition, the scoring of metabolic syndrome is not a reliable tool for the individual diagnosis of insulin resistance, and is more useful for excluding this diagnosis.

Association of the FTO gene with obesity and the metabolic syndrome is independent of the IRS-2 gene in the female population of Southern France.

AIM: The objective of the present study was to investigate the genetic association of the fat-mass-and-obesity-associated (FTO) gene in obese women in the presence of the known influential role of the insulin receptor substrate 2 (IRS-2) gene. METHODS: This case-control study was carried out in the Languedoc-Roussillon region of France, and included lean control women (n=128), and women (n=119) of various degrees of obesity (body mass index [BMI] mean+/-S.D.: 39.3+/-7.4kg/m(2)) and a prevalence of 26.9% of the metabolic syndrome (MetS). For the FTO gene, genotyping was performed by sequence-specific oligonucleotide-polymerase chain reaction (SSO-PCR) on the single nucleotide polymorphism (SNP) rs1421085 (C/T) while, for IRS-2, the rs1805097 (G/A) corresponding to variant Gly1057Asp was genotyped by direct sequencing. RESULTS: The FTO gene (homozygous C/C) was significantly associated to both simple and morbid obesity (P<0.026 and P<0.0034, respectively), with odds-ratios (ORs) of 2.58 (95% CI: 1.1-6.0) and 4.1 (95% CI: 1.6-10.5), respectively, independent of IRS-2. MetS was also associated with FTO (P<0.032, OR: 3.1, 95% CI: 1.1-8.5), but not with IRS-2. Genotypes of FTO were correlated with insulin resistance, and homozygous C/C was positively correlated with an increase in insulin resistance over the value predicted by the increase in BMI. CONCLUSION: These data confirm the influential role of the FTO gene in obesity in the French female population and, in addition, revealed the role of FTO in insulin resistance and MetS. These effects appeared to be independent of IRS-2, which is directly involved in insulin action. This study may offer new insights into the genetic determinants of obesity and MetS in women.

Effects of acute exercise on insulin sensitivity, glucose effectiveness and disposition index in type 2 diabetic patients.

AIM: The aim of this work was to quantify the magnitude of changes in insulin sensitivity (S(I)) and glucose effectiveness (S(G)) in response to acute exercise in type 2 diabetic (T2D) patients, as previously studied in non-diabetic subjects. METHODS: Seven T2D patients and seven non-diabetic controls participated in the study. Two intravenous glucose tolerance tests (0.5 g/kg) with frequent blood sampling over 180 minutes and mathematical modelling were carried out in a randomized fashion, one at rest and the other immediately following 15 minutes of exercise at 50% of the maximum theoretical heart rate (HR(max)) followed by five minutes at 85% of the HR(max). S(I) and S(G) were calculated using Bergman's minimal model. RESULTS: After exercise, S(I) was increased by 773% (from 0.62+/-0.16 to 5.41+/-1.59 min(-1) x 10(-4)/(microU/mL) and even reached the zone of control values at rest (5.52+/-2.28), whereas S(G) remained unchanged. The disposition index acute insulin response (AIR(G)) x S(I) and the product of fasting insulin (I(B)) x S(I) also increased after exercise. CONCLUSION: A single bout of exercise at moderate intensity in type 2 diabetics did not improve S(G), but markedly improved the low S(I) values found in these patients, indicating that the acute effects of exercise on S(I) are quantitatively important in the interpretation of training-related S(I) changes and may even be therapeutically useful on their own. Surrogates such as homoeostasis model assessment (HOMA) and quantitative insulin-sensitivity check index (QUICKI) were not sensitive enough to detect this increase in S(I) and should probably be used with caution in the follow-up of exercise protocols in diabetic patients.

Cost-sparing effect of twice-weekly targeted endurance training in type 2 diabetics: a one-year controlled randomized trial.

OBJECTIVE: We evaluated the effects of targeted, moderate endurance training on healthcare cost, body composition and fitness in type 2 diabetes patients routinely followed within the French healthcare system. DESIGN AND METHODS: A total of 25 type 2 diabetic patients was randomly assigned to one of two groups: 13 underwent a training programme (eight sessions, followed by training twice a week for 30-45 minutes at home at the level of the ventilatory threshold [V(T)]); and 12 received their usual routine treatment. Both groups were followed for one year to evaluate healthcare costs, exercise effectiveness and a six-minute walking test. RESULTS: The training prevented loss of maximum aerobic capacity, which decreased slightly in the untrained group (P=0.014), and resulted in a higher maximum power output (P=0.041) and six-minute walking distance (P=0.020). The Voorrips activity score correlated with both V(O2max) (r=0.422, P<0.05) and six-minute walking distance (r=0.446, P<0.05). Changes in V(O2max) were negatively correlated with changes in body weight (r=0.608, P<0.01). Training decreased the insulin-resistance index (HOMA-IR) by 26% (P<0.05). Changes in percentages of fat were correlated to changes in waist circumference (r=0.436, P<0.05). The total healthcare cost was reduced by 50% in the trained group (euro 1.65+/-1 per day versus euro 3.00+/-1.47 per day in the untrained group; P<0.02) due to fewer hospitalizations (P=0.05) and less use of sulphonylureas (P<0.05). CONCLUSION: Endurance training at V(T) level prevented the decline in aerobic working capacity seen in untrained diabetics over the study period, and resulted in a marked reduction in healthcare costs due to less treatments and fewer hospitalizations.

Training-induced improvement in lipid oxidation in type 2 diabetes mellitus is related to alterations in muscle mitochondrial activity. Effect of endurance training in type 2 diabetes.

AIM: We investigated whether or not, in type 2 diabetic (T2D) patients, an individualized training effect on whole-body lipid oxidation would be associated with changes in muscle oxidative capacity. METHODS: Eleven T2D patients participated in the study. Whole-body lipid oxidation during exercise was assessed by indirect calorimetry during graded exercise. Blood samples for measuring blood glucose and free fatty acids during exercise, and muscle oxidative capacity measured from skeletal muscle biopsy (mitochondrial respiration and citrate synthase activity), were investigated in the patients before and after a 10-week individualized training program targeted at LIPOXmax, corresponding to the power at which the highest rate of lipids is oxidized (lipid oxidation at LIPOXmax). RESULTS: Training induced both a shift to a higher-power intensity of LIPOXmax (+9.1+/-4.2W; P<0.05) and an improvement of lipid oxidation at LIPOXmax (+51.27+/-17.93 mg min(-1); P<0.05). The improvement in lipid oxidation was correlated with training-induced improvement in mitochondrial respiration (r=0.78; P<0.01) and citrate synthase activity (r=0.63; P<0.05). CONCLUSION: This study shows that a moderate training protocol targeted at the LIPOXmax in T2D patients improves their ability to oxidize lipids during exercise, and that this improvement is associated with enhanced muscle oxidative capacity.

Exercise calorimetry in sedentary patients: procedures based on short 3 min steps underestimate carbohydrate oxidation and overestimate lipid oxidation.

OBJECTIVES: Among exercise calorimetry tests designed for calculating the respective part of carbohydrates and lipids oxidized at exercise, some use 6 min steps and others use 3 min steps. Is this last method, which has been validated in healthy subjects, still accurate in very sedentary patients, who need more time to reach a steady state in respiratory gas exchanges? METHODS: We compared data obtained with calorimetry (RER and indicators of substrate oxidation) performed on the 2nd-3rd min and the 5th-6th min of each step of a protocol using four 6-min submaximal steps in 17 sedentary subjects (mean age: 51 years) including seven type 2 diabetics and six obese persons. RESULTS: Respiratory exchange ratio (RER) measured with the 3 min steps procedure are well correlated with the 6 min procedure in sedentary patients (r=0.928). However, a Bland-Altman analysis indicated an average underestimation of RER with 3 min steps (-0.0138). Moreover, we observed an average underestimation of carbohydrate oxidation rates of 70.1 mg/min with the 3 min steps procedure. On the contrary, as to lipid oxidation, we measured an average overestimation of 16.2 mg/min. Furthermore, carbohydrate and lipid oxidation rates measured with the 3 min steps procedure are well correlated with the 6 min steps procedure. Moreover, there was an average overestimation of the point at cross over with 3 min steps (+3.29 Watts). For lipox max point (power at which the increase in lipid oxidation induced by the increasing workload reaches a maximum), we observed an average underestimation with 3 min steps (-1.88 Watt). Although the differences between respectively mean values in cross over point and lipox max point between the two protocols are weak, a Bland-Altman analysis indicated more relevant discrepancies in many subjects between the two protocols. CONCLUSION: In very sedentary patients undergoing such tests for targeting exercise prescription, the 3-min procedure appears to be too short for performing an accurate calorimetry and we rather recommend the protocol using 6-min steps.