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M Sénéchal1,2, H Arguin6, DR Bouchard4,5, AC Carpentier3, JL Ardilouze3, IJ Dionne1,2, M Brochu1,21Research Centre on Aging, Health and Social Services Centre, University Institute of Geriatrics of Sherbrooke, 2Faculty of Physical Education and Sports, University of Sherbrooke, 3Clinical Research Centre, Sherbrooke University Hospital Centre, Sherbrooke, QC; 4Faculty of Kinesiology and Recreation Management, University of Manitoba, Winnipeg, MB; 5Health, Leisure & Human Performance Research Institute, Winnipeg, MB; 6Division of Kinesiology, Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, QC, CanadaObjective: To examine the association between weight gain since menopause and weight regain after a weight loss program.Methods: Participants were 19 obese women who participated in a 15-week weight loss program and a 12-month follow-up. Main outcomes were: body composition, resting metabolic rate, energy intake, energy expenditure, and weight regain at follow-up.Results: All body composition measures significantly decreased after intervention (all P ≤ 0.01) while all measures of fatness increased significantly after the 12-month follow-up (P ≤ 0.01). Body weight gain since menopause was associated with body weight regain (r = 0.65; P = 0.003) after follow-up even after adjustment for confounders.Conclusion: Weight gain since menopause is associated with body weight regain following the weight loss program. Therefore, weight gain since menopause should be considered as a factor influencing weight loss maintenance in older women.Keywords: obesity, body weight, weight regain, postmenopausal women, aging

Objective: Injected volume and subcutaneous adipose tissue blood flow (ATBF) affect insulin absorption. Pharmacokinetics of short-acting insulin analogs were established by assessing injection of small doses in lean subjects, healthy or with type 1 diabetes. In obese patients, however, daily dosages are larger and ATBF is decreased. This study assessed the kinetics of a short-acting insulin analog in obese subjects with type 2 diabetes.Research Design and Methods: Euglycemic clamps after subcutaneous lispro injections were performed. Six healthy control subjects received 10 units. Seven obese (BMI 38.3 ± 7.0 kg/m(2)) subjects with type 2 diabetes received 10, 30, and 50 units. Plasma lispro was measured by specific radioimmunoassay and ATBF by the (133)Xe-washout technique.Results: ATBF was 64% lower in subjects with type 2 diabetes than in control subjects. After 10 units injection, time to lispro plasma peak (T(max)) was similar (48.3 vs. 55.7 min; control subjects versus type 2 diabetic subjects), although maximal concentration (C(max))/dose was 41% lower in subjects with type 2 diabetes, with lower and delayed maximal glucose infusion rate (GIR(max): 9.0 vs. 0.6 mg/kg/min, P < 0.0001, 69 vs. 130 min, P < 0.0001, respectively). After 30- and 50-unit injections, T(max) (88.6 and 130.0 min, respectively) and time to GIR(max) (175 and 245 min) were further delayed and dose related (r(2) = 0.51, P = 0.0004 and r(2) = 0.76, P < 0.0001, respectively).Conclusions: Absorption and hypoglycemic action of increasing dosages of lispro are critically delayed in obese subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. In non-pregnant populations, low leptin levels stimulate positive energy balance. In pregnancy, both the placenta and adipose tissue contribute to circulating leptin levels. We tested whether maternal leptin levels are associated with subsequent GWG and whether this association varies depending on stage of pregnancy and on maternal body mass index (BMI)., Methods: This prospective cohort study included 675 pregnant women followed from 1(st) trimester until delivery. We collected anthropometric measurements, blood samples at 1(st) and 2(nd) trimester, and clinical data until delivery. Maternal leptin was measured by ELISA (Luminex technology). We classified women by BMI measured at 1(st) trimester: BMI < 25 kg/m(2) = normal weight; 25 ≤ BMI < 30 kg/m(2) = overweight; and BMI ≥ 30 kg/m(2) = obese., Results: Women gained a mean of 6.7 ± 3.0 kg between 1(st) and 2(nd) trimester (mid pregnancy GWG) and 5.6 ± 2.5 kg between 2(nd) and the end of 3(rd) trimester (late pregnancy GWG). Higher 1(st) trimester leptin levels were associated with lower mid pregnancy GWG, but the association was no longer significant after adjusting for % body fat (%BF; β = 0.38 kg per log-leptin; SE = 0.52; P = 0.46). Higher 2(nd) trimester leptin levels were associated with greater late pregnancy GWG and this association remained significant after adjustment for BMI (β = 2.35; SE = 0.41; P < 0.0001) or %BF (β = 2.01; SE = 0.42; P < 0.0001). In BMI stratified analyses, higher 2(nd) trimester leptin levels were associated with greater late pregnancy GWG in normal weight women (β = 1.33; SE = 0.42; P =0.002), and this association was stronger in overweight women (β = 2.85; SE = 0.94; P = 0.003--P for interaction = 0.05)., Conclusions: Our results suggest that leptin may regulate weight gain differentially at 1(st) versus 2(nd) trimester of pregnancy: at 2(nd) trimester, higher leptin levels were associated with greater subsequent weight gain--the opposite of its physiologic regulation in non-pregnancy--and this association was stronger in overweight women. We suspect the existence of a feed-forward signal from leptin in second half of pregnancy, stimulating a positive energy balance and leading to greater weight gain.

Purpose: We initiated the Genetics of Glucose regulation in Gestation and Growth (Gen3G) prospective cohort to increase our understanding of biological, environmental and genetic determinants of glucose regulation during pregnancy and their impact on fetal development., Participants: Between January 2010 and June 2013, we invited pregnant women aged ≥ 18 years old who visited the blood sampling in pregnancy clinic in Sherbrooke for their first trimester clinical blood samples: 1034 women accepted to participate in our cohort study., Findings to Date: At first and second trimester, we collected demographics and lifestyle questionnaires, anthropometry measures (including fat and lean mass estimated using bioimpedance), blood pressure, and blood samples. At second trimester, women completed a full 75 g oral glucose tolerance test and we collected additional blood samples. At delivery, we collected cord blood and placenta samples; obstetrical and neonatal clinical data were abstracted from electronic medical records. We also collected buffy coats and extracted DNA from maternal and/or offspring samples (placenta and blood cells) to pursue genetic and epigenetic hypotheses. So far, we have found that low adiponectin and low vitamin D maternal levels in first trimester predict higher risk of developing gestational diabetes., Future Plans: We are now in the phase of prospective follow-up of mothers and offspring 3 and 5 years postdelivery to investigate the consequences of maternal dysglycaemia during pregnancy on offspring adiposity and metabolic profile., Trial Registration Number: NCT01623934., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Acetylcholine (Ach) has vasodilatory actions. However, data are conflicting about the role of Ach in regulating blood flow in subcutaneous adipose tissue (ATBF). This may be related to inaccurate ATBF recording or to the responder/nonresponder (R/NR) phenomenon. We showed previously that healthy individuals are R (ATBF increases postprandially by >50% of baseline BF) or NR (ATBF increases ≤50% postprandially). Our objective was to assess the role of the cholinergic system on ATBF in R and NR subjects. ATBF was manipulated by in situ microinfusion of vasoactive agents (VA) in AT and monitored by the (133)Xenon washout technique (both recognized methods) at the VA site and at the control site. We tested incrementally increasing doses of Ach (10(-5), 10(-3), and 10(-1) mol/l; n = 15) and Ach receptor antagonists (Ra) before and after oral administration of 75-g glucose using atropine (muscarinic Ra; 10(-4) mol/l, n = 13; 10(-5) mol/l, n = 22) and mecamylamine (nicotinic Ra; 10(-3) mol/l, n = 15; 10(-4) mol/l, n = 10). Compared with baseline [2.41 (1.36-2.83) ml·100 g(-1)·min(-1)], Ach increased ATBF dose dependently [3.32 (2.80-5.09), 6.46 (4.36-9.51), and 10.31 (7.98-11.52), P < 0.0001], with no difference between R and NR. Compared with control side, atropine (both concentrations) had no effect on fasting ATBF; only atropine 10(-4) mol/l decreased post-glucose ATBF [iAUC: 1.25 (0.32-2.91) vs. 1.98 (0.64-2.94); P = 0.04]. This effect was further apparent in R. Mecamylamine had no impact on fasting and postglucose ATBF in R and NR. Our results suggest that the cholinergic system is implicated in ATBF regulation, although it has no role in the blunting of ATBF response in NR., (Copyright © 2015 the American Physiological Society.)

Objective: The lifetime risk of metabolic diseases in offspring of women with gestational diabetes mellitus (GDM) depends, at least in part, on the impact of glycemic fetal programming. To quantify this impact, we have developed and validated a unique mass spectrometry method to measure the percentage of glycated hemoglobin in cord blood., Research Design and Methods: This case-control study includes 37 GDM women and 30 pregnant women with normal glucose tolerance (NGT)., Results: Glycation of the α-chain (Glα) was higher in neonates from GDM (2.32 vs. 2.20%, P < 0.01). Glα strongly correlated with maternal A1C measured at delivery in the overall cohort (r = 0.67, P < 0.0001) as well as in each group (GDM: r = 0.66, P < 0.0001; NGT: r = 0.50, P = 0.01)., Conclusions: Thus, Glα may reflect hyperglycemic exposure during the last weeks of fetal development. Future studies will confirm Glα is a predictive biomarker of prenatally programmed lifetime metabolic health and disease., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: The use of a weight-based nomogram is considered as standard care for prescribing appropriate doses of unfractionated heparin (UFH). Because of the need for multiple other medications that may affect bleeding and that clinical data have relied on similar dosing algorithms, maximum initial bolus and infusion rates have been suggested (capped initial dose). Whether these weight-based heparin nomograms properly address therapeutic dosing in obese patients remains questionable., Design and Methods: Thirty patients treated for acute coronary syndrome and weighing ≥110 kg were retrospectively compared with 90 controls (three groups of 30 patients, weighting 50-69.9, 70-89.9, or 90-109.9 kg), all treated with UFH, July 2008 to April 2009. The primary end point was the time required to obtain a threshold activated partial thromboplastin time (aPTT)., Results: Mean time to achieve threshold aPTT was longer for obese patients weighing ≥110 kg than for controls (31.47 vs. 12.89 hours; P < 0.0001). At 24 hours, 63% of obese patients weighing ≥110 kg had not reached threshold aPTT vs. 7% of controls (P < 0.0001). However, threshold infusion rate did not differ between weight categories (13.0 vs. 13.1 U/kg/h; P = NS) and approximated the initial infusion rate recommended by nomograms without applying the dose cap (12 U/kg/h)., Conclusions: Adequate anticoagulation time doubled in patients weighing ≥110 kg, suggesting that these patients were not receiving appropriate heparin doses initially to achieve threshold aPTT rapidly. Using initial infusion rate recommended by a nomogram without capping for total body weight is suggested as acceptable in this study. This approach should be further evaluated in a prospective study., (Copyright © 2012 The Obesity Society.)

Objective: To evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, β-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women., Research Design and Methods: We performed anthropometric measurements and collected blood samples at 1st (6-13 weeks) and 2nd (24-28 weeks) trimesters. Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test (International Association of the Diabetes and Pregnancy Study Groups criteria). Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUC(insulin/glucose)), and β-cell compensation (insulin secretion sensitivity index-2). Adiponectin was measured by radioimmunoassay., Results: Among the 445 participants included in this study, 38 women developed GDM. Women who developed GDM had lower 1st-trimester adiponectin levels (9.67 ± 3.84 vs. 11.92 ± 4.59 µg/mL in women with normal glucose tolerance). Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1.12 per 1 µg/mL decrease of adiponectin levels; P = 0.02, adjusted for BMI and HbA1c at 1st trimester). Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r = -0.22, P < 0.0001) and Matsuda index (r = 0.28, P < 0.0001, and r = 0.29, P < 0.0001). After adjustment for confounding factors, we found no significant association with HOMA-B and AUC(insulin/glucose)., Conclusions: Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements.

According to Fick's principle, any metabolic or hormonal exchange through a given tissue depends on the product of the blood flow to that tissue and the arteriovenous difference. The proper function of adipose tissue relies on adequate adipose tissue blood flow (ATBF), which determines the influx and efflux of metabolites as well as regulatory endocrine signals. Adequate functioning of adipose tissue in intermediary metabolism requires finely tuned perfusion. Because metabolic and vascular processes are so tightly interconnected, any disruption in one will necessarily impact the other. Although altered ATBF is one consequence of expanding fat tissue, it may also aggravate the negative impacts of obesity on the body's metabolic milieu. This review attempts to summarize the current state of knowledge on adipose tissue vascular bed behavior under physiological conditions and the various factors that contribute to its regulation as well as the possible participation of altered ATBF in the pathophysiology of metabolic syndrome.

Objective: To evaluate (1) the effect on gestational diabetes mellitus (GDM) screening rates of having a specialized clinic for pregnant women offering blood sampling and screening for GDM, and (2) the impact on perinatal outcomes of having early GDM screening and follow-up provided by the specialized clinic., Methods: We performed a retrospective cohort study, based on electronic health records. We compared data from women who delivered during a period when the Blood Sampling in Pregnancy (BSP) clinic was operating (2008-2009; n = 2780) to a time period before the clinic was established (2006-2007; n = 2591). During the 2008-2009 period, we compared data from women who had GDM screening in the first trimester with women who had screening during the second trimester and with women who were not screened., Results: Following the creation of the BSP clinic, overall GDM screening rates reached 72.4% in 2008-2009, compared with 48.9% in 2006-2007 (P < 0.001) and GDM screening was more likely to be performed in the first trimester (36.7% vs. 0.4%; P < 0.001). During the period when the BSP clinic was operating (2008-2009), women who had GDM screening in the first trimester had lower rates of Caesarean section (15.7% vs. 22.1%; P < 0.001) and neonatal complications (bradycardia: 3.6% vs. 6.8%; P = 0.003; respiratory distress: 9.6% vs. 13.2%; P = 0.02; and admission to NICU: 15.4% vs. 26.8%; P < 0.001) than women who did not perform GDM screening., Conclusion: In our population, creation of a clinic offering specialized care to pregnant women improved GDM screening rates. With the support of the BSP clinic, women who had early GDM screening were less likely to undergo Caesarean section and their offspring had fewer perinatal complications.

The aim of this review is to explore the dysregulation of adrenocortical secretions as a major contributor in the development of obesity and insulin resistance. Disturbance of adipose tissue physiology is one of the primary events in the development of pathologies associated with the metabolic syndrome, such as obesity and type 2 diabetes. Several studies indicate that alterations in metabolism of glucocorticoids (GC) and androgens, as well as aldosterone in excess, are involved in the emergence of metabolic syndrome. Cross talk among adipose tissue, the hypothalamo-pituitary complex, and adrenal gland activity plays a major role in the control of food intake, glucose metabolism, lipid storage, and energy balance. Perturbation of this cross talk induces alterations in the regulatory mechanisms of adrenocortical steroid synthesis, secretion, degradation, and/or recycling, at the level of the zonae glomerulosa (aldosterone), fasciculata (GC and GC metabolites), and reticularis (androgens and androgen precursors DHEA and DHEAS). As a whole, these adrenocortical perturbations contribute to the development of metabolic syndrome at both the paracrine and systemic level by favoring the physiological dysregulation of organs responsive to aldosterone, GC, and/or androgens, including adipose tissue.

Background: National guidelines for managing diabetes set standards for care. We sought to determine whether a 1-year intensive multitherapy program resulted in greater goal attainment than usual care among patients with poorly controlled type 2 diabetes mellitus., Methods: We identified patients with poorly controlled type 2 diabetes receiving outpatient care in the community or at our hospital. Patients 30-70 years of age with a hemoglobin A1c concentration of 8% or greater were randomly assigned to receive intensive multitherapy (n = 36) or usual care (n = 36)., Results: The average hemoglobin A1c concentration at entry was 9.1% (standard deviation [SD] 1%) in the intensive therapy group and 9.3% (SD 1%) in the usual therapy group. By 12 months, a higher proportion of patients in the intensive therapy group than in the control group had achieved Canadian Diabetes Association (CDA) goals for hemoglobin A(1c) concentrations (goal < or = 7.0%: 35% v. 8%), diastolic blood pressure (goal < 80 mm Hg: 64% v. 37%), low-density lipoprotein cholesterol (LDL-C) levels (goal < 2.5 mmol/L: 53% v. 20%) and triglyceride levels (goal < 1.5 mmol/L: 44% v. 14%). There were no significant differences between the 2 groups in attaining the targets for fasting plasma glucose levels, systolic blood pressure or total cholesterol:high-density lipoprotein cholesterol ratio. None of the patients reached all CDA treatment goals. By 18 months, differences in goal attainment were no longer evident between the 2 groups, except for LDL-C levels. Quality of life, as measured by a specific questionnaire, increased in both groups, with a greater increase in the intensive therapy group (13% [SD 10%] v. 6% [SD 13%], p < 0.003)., Interpretation: Intensive multitherapy for patients with poorly controlled type 2 diabetes is successful in helping patients meet most of the goals set by a national diabetes association. However, 6 months after intensive therapy stopped and patients returned to usual care, the benefits had vanished.

Background: Blood flow mediates the metabolic and endocrine roles of adipose tissue. We have previously shown that the postprandial adipose tissue blood flow (ATBF) increase is dependent on insulin sensitivity. However, subcutaneous local insulin delivery had no demonstrable effect on either preprandial or postprandial ATBF. We hypothesized that insulin may act indirectly via sympathetic activation, mainly in the postprandial period, and that nitric oxide may be an overall major regulator of subcutaneous ATBF., Methods and Results: We investigated the endogenous preprandial and postprandial regulation of ATBF by applying local tissue blockade of beta-adrenergic (propranolol), alpha-adrenergic (phentolamine and yohimbine), and nitric oxide (NG-monomethyl-L-arginine, L-NMMA) regulation of blood flow. Healthy subjects (body mass index, 18 to 31 kg/m2) were challenged with 75 g glucose for endogenous stimulation of ATBF. We used the novel "microinfusion" technique, which allows for simultaneous local delivery of pharmacological agents (or contralateral saline) and measurement of ATBF with the 133Xe washout method. Compared with control, the preprandial ATBF was not affected by propranolol but was increased by 21% (P<0.013) and 15% (P=0.004) with phentolamine and yohimbine, respectively. A decrease of 42% (2.97+/-0.33 versus 4.75+/-0.47 mL x min(-1) x 100 g tissue(-1), P<0.01) was seen with L-NMMA. The postprandial response was blunted by 58% (0.81+/-0.42 versus 1.90+/-0.44 mL x min(-1) x 100 g tissue(-1), P<0.004) with propranolol, but neither phentolamine, yohimbine, or L-NMMA altered this response., Conclusions: Nitric oxide seems to determine the absolute level of ATBF, whereas a major proportion of the postprandial enhancement of ATBF is under beta-adrenergic regulation in vivo in humans.

Adipose tissue blood flow (ATBF) rises after nutrient ingestion. It is not clear whether this is due to insulin. The aim of this study was to investigate the role of insulin in the regulation of subcutaneous ATBF. We have investigated the role of insulin in the regulation of ATBF in normal, healthy subjects in a three-step procedure to determine the functional level at which insulin may potentially exert its effect. Fifteen subjects were studied on two occasions. On the first visit, 75 g oral glucose was given. In the second, similar plasma concentrations of insulin and glucose were achieved by dynamic intravenous infusions of insulin and glucose. The increase in ATBF after oral glucose (4.2 +/- 1.4 ml min(-1) (100 g tissue)(-1), P = 0.01) was significantly greater (P < 0.05) than that after intravenous infusions (1.5 +/- 0.6 ml min(-1) (100 g tissue)(-1) P < 0.05). For the local delivery of potentially vasoactive substances and simultaneous measurement of ATBF, we describe a novel combination of methods, which we have called 'microinfusion'. We have used this technique to show that locally infused insulin, even at pharmacological concentrations, had no demonstrable effect on ATBF in nine subjects. We conclude that whilst insulin does not have a direct effect on ATBF, it is likely to be an important mediator, possibly acting via sympathetic activation. In the postprandial state, other candidate peptides and hormones are also likely to play important roles.

Objective: The objective of this study was to compare clinical and biomechanical characteristics of balance in diabetic polyneuropathic elderly patients and normal age-matched subjects., Research Design and Methods: Fifteen elderly with distal neuropathy (DNP) and 15 healthy age-matched subjects were evaluated with the biomechanical variable COP-COM, which represents the distance between the center of pressure (COP) and the center of mass (COM). Measurements were taken in the quiet position with a double-leg stance, in eyes-open (EO) and eyes-closed (EC) conditions. Subjects were also assessed with clinical balance evaluations., Results: The COP-COM variable was statistically significantly larger in the DNP group than in the healthy group in anterior-posterior (A/P) and medial-lateral (M/L) directions. Furthermore, the DNP group showed statistically significantly larger amplitudes of the COP-COM variable without vision. The severity of the neuropathy, as quantified using the Valk scoring system, was correlated with COP-COM amplitude in both directions., Conclusions: Evaluation of the postural stability of an elderly diabetic population using the COP-COM variable can detect a very small change in postural stability and could be helpful in identifying elderly with DNP at risk of falling.