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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]

Objectives: To compare: 1) 75 g oral glucose tolerance test (OGTT) and self-monitoring of blood glucose (SMBG) in identifying gestational diabetes mellitus (GDM) and other hyperglycemic statuses in pregnant women; 2) pregnancy outcomes according to glycemic status; and 3) participants' opinions regarding both methods., Methods: A prospective study in women with a 50 g glucose load test ≥7.2 mmol/L at 24 to 28 weeks' gestation and singleton pregnancy. Women underwent OGTT (blinded) at day 1, followed by 7 days of SMBG (4 daily measurements: fasting and 2 h postprandially) without modifying diet or lifestyle. GDM (OGTT+) was diagnosed using the criteria of the International Association of the Diabetes and Pregnancy Study Groups, while pregnancy hyperglycemia (SMBG+) was defined as ≥4/7 glucose values ≥5.3 after fasting or ≥6.7 mmol/L 2 h postprandially for any meal of the day. Equivalent management was provided to women with GDM and/or pregnancy-related hyperglycemia., Results: We divided 103 participants (age: 29.5±5.0 years; prepregnancy body mass index: 25.3±5.4 kg/m 2 ) into 4 groups according to test results: OGTT+/SMBG+ (n=12, 11.7%); OGTT+/SMBG- (n=14, 13.6%); OGTT-/SMBG+ (n=9, 8.7%); and OGTT-/SMBG- (n=68, 66.0%). Clinical characteristics and maternal outcomes were statistically similar between groups. Neonatal complication rates were greater in groups with hyperglycemia than in the OGTT-/SMBG- group, notably neonatal hypoglycemia (9/12, 7/14, 5/9 vs. 6/68; p<0.001). Participants reported no convenience difference between methods but would prefer OGTT for a future pregnancy., Conclusions: More than half of the women with OGTT+ were normoglycemic in daily life. Conversely, 11.7% of women with OGTT- had pregnancy hyperglycemia. OGTT+ and/or SMBG+ were equally associated with greater neonatal complications. This study suggests that alongside OGTT, SMBG could improve the care of pregnant women., (Copyright © 2019 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Aims: To assess perceptions of patients using subcutaneous insulin infusion (CSII) about metabolic control, pump malfunctions, technical and insertion site adverse events (AEs) related to infusion sets/catheters as well as patients' practices., Methods: Online survey (from June 2016 to January 2017) using an actualized 39-item questionnaire directed to adults with type 1 diabetes (T1D) using CSII therapy and living in the province of Quebec, Canada., Results: Participants with T1D (n = 115, 72% females, 39.7 ± 14.0 years, diabetes duration: 20.9 ± 12.2 years, CSII use: 6.2 ± 4.1 years) adequately completed the survey. Infusion sets were changed every 3.3 ± 0.9 day. Improved glucose control and decreased number/severity of hypoglycemic episodes were reported by 80% and 68%/50% of subjects, respectively. Over the past year of CSII use, participants perceived no increase in anxiety/worry (84%), no negative impact on life (89%) or on time off from work/school (82%). Conversely, many experienced at least one clinical AEs at insertion site [pain (84%), adhesion (76%), irritation (69%), lipodystrophy (45%)] and technical issues [blockage (52%), cannula kinking (50%), pump stop (55%), air bubbles (46%)]. No significant association was observed between catheter wear-time and AEs. All participants had one or more problems related to CSII use, although only 37% reported addressing these issues with health professionals., Conclusion: Our study suggests that patients positively perceived CSII use although they experienced a high frequency of clinical and technical AEs. This warrants further attention by health professionals, investigators and manufacturers to optimize CSII therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Increasing proportions of patients with diabetes use continuous subcutaneous insulin infusion (CSII) therapy mostly due to its clinical efficacy and flexibility for insulin dosing and adjustments. Some challenges are nevertheless associated with this technology. A key and underlooked component of CSII technical difficulties is the subcutaneous catheter used to infuse insulin. Several adverse events (AEs) have been experienced by patients in relation to catheters, such as blockage, kinking, and insertion site reactions, including irritation, infections, lipohypertrophies etc., all of which could compromise the metabolic control. With the objective of minimizing these AEs, recommendations for changing catheters every 2-3 days have historically been provided by manufacturers based on reports derived from small studies and anecdotal data. The aim of this review was to provide an updated analysis of current recommendations and patients' practices in relation to frequency of catheter change. Our main findings are: (1) adequately designed and powered studies investigating optimal catheter wearing time are still lacking; (2) increasing catheter wearing time is generally associated with increased frequency of catheter AEs; (3) however, interpatient variability is large, with some individuals needing to change their catheters every 2-3 days, whereas others probably being able to keep them in place for longer periods without problems. Further research is thus warranted to provide more solid and evidence-based recommendations while exploring personalized approaches at the same time. Increasing catheter wear life without significant side effects is an important goal to simplify CSII therapy and reduce its associated costs and burdens.

Background: The goal was to evaluate whether there was neurodevelopmental deficits in newborns born to mothers with gestational diabetes mellitus (GDM) compared to control newborns born to healthy mothers., Methods: Forty-six pregnant women (21 controls and 25 GDM) were recruited. Electroencephalogram (EEG) was recorded in the newborns within 48 h after birth. The EEG signal was quantitatively analyzed using power spectral density (PSD); coherence between hemispheres was calculated in paired channels of frontal, temporal, central and occipital regions., Results: The left centro-occipital PSD in control newborns was 12% higher than in GDM newborns (p = 0.036) but was not significant after adjustment for gestational age. While coherence was higher in the frontal regions compared to the occipital regions (p < 0.001), there was no difference between the groups for the fronto-temporal, frontal-central, centro-occipital and tempo-occipital regions., Conclusion: Our results support that EEG differences between groups were mainly modified by gestational age and less by GDM status of the mothers. However, there is a need to confirm this result with a higher number of mother-newborns. Quantitative EEG in GDM newborns within 48 h after birth is feasible. This study emphasizes the importance of controlling blood glucose during GDM to protect infant brain development., (Copyright © 2018 ISDN. Published by Elsevier Ltd. All rights reserved.)

Background: During pregnancy, maternal circulating leptin is released by maternal adipose tissue and the placenta, and may have a role in fetal development., Objectives: We investigated maternal leptinemia and glycemia associations with neonatal adiposity, taking into account pregravid weight status., Methods: We included 235 pregnant women from the Genetics of Glucose Regulation in Gestation and Growth prospective cohort with data: blood samples collected during the 2nd trimester, an oral glucose tolerance test (OGTT), and the measured leptin and glucose levels. As an integrated measure of maternal leptin exposure, we calculated the area under the curve for maternal leptin at the OGTT (AUCleptin). Within 72 h of delivery, we measured the triceps, biceps, subscapular, and suprailiac skinfold thicknesses (SFTs); the sum of these SFTs represented neonatal adiposity. We conducted a regression analysis to assess the maternal metabolic determinants of neonatal adiposity, adjusting for parity, smoking status, maternal triglyceride levels, gestational weight gain, placental weight, delivery mode, neonate sex, and gestational age at delivery., Results: The pregravid BMI of the participating women was 23.3 (21.2-27.0). In the 2nd trimester, maternal AUCleptin was 1,292.0 (767.0-2,222.5) (ng × min)/mL, and fasting glucose levels were 4.2 ± 0.4 mmol/L. At delivery, the neonatal sum of 4 SFTs was 17.9 ± 3.3 mm. Higher maternal leptinemia was associated with higher neonatal adiposity (β = 4.23 mm [SE = 1.77] per log-AUCleptin; p = 0.02) in mothers with a BMI ≥25, independently of confounders and maternal glycemia, but not in mothers with a BMI <25. Higher maternal fasting glucose was associated with higher neonatal adiposity (β = 0.88 mm [SE = 0.30] per SD glucose; p = 0.005) in mothers with a BMI <25, independently of confounders and maternal leptinemia., Conclusion: Maternal leptinemia may be associated with neonatal adiposity in offspring from overweight/obese mothers, independently of maternal glycemia., (© 2017 S. Karger AG, Basel.)

Objective: To evaluate the fatty acid profile of cord blood phospholipids (PL), cholesteryl esters (CE), triglycerides (TG) and non-esterified fatty acids (NEFA) in neonates born to mothers with gestational diabetes mellitus (GDM) compared to non-diabetic mothers., Methods: The offspring of 30 pregnant women (15 non-diabetic controls, 15 with diet- or insulin-controlled GDM) were recruited before delivery. Cord blood was collected. After lipid extraction, PL, CE, TG and NEFA were separated by thin layer chromatography and analysed by gas chromatography., Results: In GDM vs. control mothers, maternal glycated haemoglobin (A 1C , mean±SD) was not different between groups: 5.3±0.5% vs. 5.3±0.3% (p=0.757), respectively. Cord plasma fatty acids were not different in TG, CE and NEFA between GDM and non-diabetic mothers. However, in PL, levels of palmitate, palmitoleate, oleate, vaccinate and di-homo-gamma-linolenate were significantly lower, with a trend for lower arachidonate (p=0.078), in neonates born to GDM mothers compared to controls., Conclusion: In contrast to other studies on cord blood docosahexaenoic acid (DHA) levels in GDM mothers, we did not found lower levels of DHA in cord PL, CE, TG or NEFA in neonates born to GDM compared to non-diabetic mothers., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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/)

Objective: Excessive gestational weight gain (GWG) is associated with increased birth weight and neonatal adiposity. However, timing of excessive GWG may have a differential impact on birth outcomes. The objective of this study was to compare the effect of early and mid/late excessive GWG on newborn anthropometry in the context of the Canadian clinical recommendations that are specific for first trimester and for second/third trimesters based on maternal pre-pregnancy BMI., Methods: We included 607 glucose-tolerant women in our main analyses, after excluding women who had less than the recommended total GWG. Maternal body weight was measured in early pregnancy, mid-pregnancy, and late pregnancy. Maternal and fetal clinical outcomes were collected, including newborn anthropometry. Women were divided into four groups according to the Canadian guidelines for GWG in the first and in the second/third trimesters: (1) "overall non-excessive" (reference group); (2) "early excessive GWG"; (3) "mid/late excessive GWG"; and (4) "overall excessive GWG." Differences in newborn anthropometry were tested across GWG categories., Results: Women had a mean (±SD) pre-pregnancy BMI of 24.7 ± 5.2 kg/m(2) and total GWG of 15.3 ± 4.4 kg. Women with mid/late excessive GWG gave birth to heavier babies (gestational age-adjusted birth weight z-score 0.33 ± 0.91) compared with women in the reference group (0.00 ± 0.77, P = 0.007), whereas women with early excessive GWG gave birth to babies of similar weight (gestational age-adjusted z-score 0.01 ± 0.86) to the reference group (0.00 ± 0.77, P = 0.84). When we stratified our analyses and investigated women who gained within the recommendations for total GWG, mid/late excessive GWG specifically was associated with greater newborn size, similar to our main analyses., Conclusion: Excessive GWG in mid/late pregnancy in women who did not gain weight excessively in early pregnancy is associated with increased birth size, even in those who gained within the Canadian recommendations for total GWG., (Copyright © 2016. Published by Elsevier Inc.)

Hypertensive disorders of pregnancy (HDP) lead to high rates of maternal and fetal morbidity. Existing studies on inflammatory marker TNFα in HDP offspring are inconsistent. We performed a population-based cohort study of 636 pregnancies, including normotensive (NT) women and women with preeclampsia (PE) or gestational hypertension (GH). TNFα was measured in maternal blood in the first and second trimesters and in cord blood at the time of delivery. Cord blood TNFα was higher in offspring delivered of women with PE (6.53 [4.94-8.38]pg/mL) versus those delivered of NT women (5.13 [4.11-6.72]pg/mL; p=0.01), independent of confounders. Maternal TNFα levels were not different among groups (p>0.1) in either the first or second trimester., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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.)

In Sherbrooke, the gestational diabetes mellitus (GDM) Regional Committee proposed GDM screening during the first trimester for all pregnant women based on a 50 g glucose challenge test (50 g GCT) followed directly by capillary self-monitoring blood glucose (SMBG) at home. We evaluated implementation of committee's recommendations on the clinical trajectory of women receiving prenatal care at our institution. We analyzed data collected systematically by the Blood Sampling in Pregnancy clinic from 2008 to 2011. We evaluated the clinical trajectory of 7710 pregnant women to assess GDM screening/diagnoses and referral rates to the diabetes care centre (DCC) for education and treatment during both the first and second trimesters. The Canadian Diabetes Association glycemic treatment targets in women with GDM were used as diagnosis thresholds and DCC referral decisions: Fasting glucose of 5.3 mmol/L and postprandial 2 h glucose of 6.7 mmol/L. We found that pregnant women were 28.0±4.8 years old, and their body mass indexes were 24.5±5.5 kg/m(2). During the first trimester, 47% of women were screened for GDM, mostly (84%) using the 50 g GCT. Following SMBG, 5.7% were referred to the DCC. Only 32% of women with early GDM had >1 GDM risk factor. Thereafter, 67% of normoglycemic women screened during the first trimester were screened again during the second trimester. Among women screened during the second trimester, most screening was done using 50 g GCT, and 8.8% were referred to the DCC following SMBG. Implementation of 50 g GCT testing followed by direct home SMBG was well implemented in our area. The importance of early GDM screening and rescreening during the second trimester still needs to be emphasized., (Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

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.)

The progressive increase of insulin resistance observed in pregnancy contributes to the pathophysiology of gestational diabetes mellitus (GDM). There is controversy whether vitamin D deficiency contributes to abnormal glycemic regulation in pregnancy. We tested the associations between first trimester 25-hydroxyvitamin D (25OHD) levels and: 1) the risk of developing GDM; 2) insulin resistance/sensitivity, beta cell function and compensation indices in a large population-based prospective cohort of pregnant women. Participants (n = 655) were seen at first (6-13 weeks) and second (24-28 weeks) trimesters for blood samples. At first trimester, 25OHD levels were measured. At second trimester, glucose and insulin were measured 3 times during the oral glucose tolerance test to estimate insulin resistance (HOMA-IR), beta cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUCins/gluc) and beta cell compensation (ISSI-2). Based on IADPSG criteria, 54 participants (8.2 %) developed GDM. Lower first trimester 25OHD levels were associated with higher risk of developing GDM even after adjustment for vitamin D confounding factors and GDM risk factors (OR = 1.48 per decrease of one SD in 25OHD levels; P = 0.04). Lower first trimester 25OHD levels were associated with higher HOMA-IR (r = - 0.08; P = 0.03), lower Matsuda index (r = 0.13; P = 0.001) and lower ISSI-2 (r = 0.08; P = 0.04). After adjustment for confounders, we found no significant association with HOMA-B and AUCins/gluc. Our results suggest that low levels of 25OHD at first trimester are (1) an independent risk factor for developing GDM and (2) associated with insulin resistance at second trimester.

Introduction: TNFα is suspected to play a role in inflammation and insulin resistance leading to higher risk of metabolic impairment. Controversies exist concerning the role of TNFα in gestational insulin resistance. We investigated the interrelations between TNFα and insulin resistance in a large population-based cohort of pregnant women., Methods: Women (n = 756) were followed prospectively at 5-16 weeks and 24-28 weeks of pregnancy. Anthropometric measures and blood samples were collected at both visits. A 75-g oral glucose tolerance test (OGTT) was conducted at the second trimester to assess insulin sensitivity status (homeostasis model of assessment of insulin resistance and Matsuda index). TNFα was measured at the first trimester (nonfasting) and at each time point of the OGTT., Results: Participants were 28.4 ± 4.4 years old and had a mean body mass index of 25.5 ± 5.5 kg/m(2) at first trimester. Median TNFα levels were 1.56 (interquartile range, 1.18-2.06) pg/mL at first trimester and 1.61 (interquartile range, 1.12-2.13) pg/mL at second trimester (1 h after glucose load). At second trimester, higher TNFα levels were associated with higher insulin resistance index levels (r = 0.37 and -0.30 for homeostasis model of assessment of insulin resistance and Matsuda index, respectively; P < .0001), even after adjustment for age, body mass index, triglycerides, and adiponectin. Women with higher insulin resistance showed a continuing decrease in TNFα levels during the OGTT, whereas women who were more insulin sensitive showed an increase in TNFα at hour 1 and a decrease at hour 2 of the test., Conclusion: Higher insulin resistance is associated with higher levels of circulating TNFα at first and second trimesters of pregnancy. TNFα level dynamics during an OGTT at second trimester vary according to insulin-resistance state.

Adipose tissue (AT) is a very active organ, both metabolically and hormonally. These important functions depend on adequate blood flow (BF). Metabolic, hormonal, and vascular processes within AT are highly interconnected and any disruption will invariably impact the others. Therefore, any alteration of ATBF with obesity and/or insulin resistance will impact metabolic and hormonal AT functions. Similarly, metabolic or hormonal changes in AT will lead to ATBF disturbance. Thus, it is plausible that insufficient ATBF alters AT metabolic processes and response to regulatory signals, and may even aggravate the negative impacts of dysfunction in AT. The role of BF in AT metabolism can be evaluated by several techniques, but the xenon washout method is considered the "gold" standard. This technique can be combined with local microinfusion protocols, and the combination allows for precise assessment of mechanisms implicated in ATBF regulation., (© 2014 Elsevier Inc. All rights reserved.)

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.

This 24 month study evaluated the effect of dietitian coaching combined with minimal endocrinologist follow up on the glycemic control and cardiovascular risks of diabetic participants, compared with conventional endocrinologist follow up. Participants with type 1 or type 2 diabetes were assigned to either the control group with conventional endocrinologist follow up (C; n = 50) or the dietitian-coached group (DC; n = 51) with on-site diabetes self-management education every 3 months combined with annual endocrinologist followup. Over the 24 month intervention, weight (-0.7 vs. +2.1 kg; p = 0.04), BMI (+0.3 vs. +0.7 kg/m(2); p = 0.009), and waist circumference (-1.3 vs. +2.4 cm; p = 0.01) significantly differed between the DC and control groups. HbA(1C) dropped significantly in participants of the DC versus the control group (-0.6% vs.-0.3%; p = 0.04). This was accompanied by improved overall energy intake (-548 vs. -74 kcal/day; p = 0.04). However, no link associated glycemic control to nutrient intake or intensiveness of pharmacotherapy. Coaching by a dietitian improves glycemic control and reduces certain cardiovascular risk factors in diabetic subjects, demonstrating that a joint dietitian-endocrinologist model of care provides a convenient strategy for cardiovascular risk management in the diabetic population.

To compare the effect of rapid or slow weight loss (WL) on body composition and metabolic risk factors following a caloric restriction. Ten obese, postmenopausal women were matched for total body WL. Dependent variables were: body composition, lipid profile and blood pressure. Both groups decreased obesity measures (all P≤0.05) while lean body mass decreased in the rapid WL group (P≤0.05). Significant improvements in fasting triglyceride level and diastolic blood pressure were observed only in the slow WL group. A slower WL seems to be more beneficial to improve body composition as well as metabolic risk factors in postmenopausal women., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

Aims: Adequate adipose tissue blood flow (ATBF) is essential for its metabolic and endocrine functions. From a metabolic point of view, sufficient increases in ATBF after meals permits full storage of excess energy into fat, thus protecting other tissues against the toxic effects of fatty acids and glucose spillover. It was previously shown that postprandial increases in ATBF are blunted in obese and insulin-resistant subjects, and that much of the postprandial ATBF response is the result of β-adrenergic activation. Examination of previously recorded data on postprandial ATBF responses revealed an underlying heterogeneity, with postprandial ATBF being largely unresponsive to food stimuli in a substantial proportion of normal weight healthy people (low responders). Our study tests the hypothesis that this unresponsive pattern is due to resistance to β-adrenergic stimulation in adipose tissue., Methods: Five responders and five low responders were selected from a previously studied cohort and matched for BMI (20.5±0.7 vs 22±1 kg/m(2), respectively), gender (male/female: 2/3) and age (30±3 vs 37±6 years). Subcutaneous adipose tissue microinfusions of stepwise increasing doses of isoproterenol were performed with concomitant monitoring of blood flow, using the (133)Xenon washout technique., Results: Although BMI was similar between responders and low responders, there were significant differences in fat mass (9.9±1.6 vs 14.4±1.6 kg; P<0.05) and four-point skinfold thickness (33±4 vs 52±16 mm; P<0.05). Lack of ATBF response to oral glucose was confirmed in the low responder group. In responders, ATBF was higher at baseline (5.4±1 vs 3.4±1 mL/min/100 g of tissue) and responded more distinctly to increasing isoproterenol doses (10(-8) M: 7.6±1.4 vs 4.9±1; 10(-6) M: 12.5±1.7 vs 7.5±1.6; and 10(-4) M: 20 ±1.7 vs 9±0.9 mL/min/100 g of tissue)., Conclusion: These data suggest that the lack of glucose-stimulated ATBF is associated with resistance to sympathetic activation in adipose tissue., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

The characterization of cord blood hemoglobin at the molecular level is a daunting challenge because hemoglobin F (HbF) and hemoglobin A (HbA) coexist in neonatal blood. We developed and validated a method using electrospray time-of-flight mass spectrometry (ES-TOF-MS) that measures, in a single analysis, relative levels of glycated and acetylated hemoglobin and allows the calculation of relative proportions of HbA, HbF(0), and HbF(1) in cord blood. Specific sections of acquired spectra were deconvoluted using a maximum entropy-based approach to true mass scale spectra. Mass precisions were less than 3 ppm with similar accuracies. Intra-interday precisions for α- and γ-chain glycation levels were 2.10%/3.72% and 2.75%/6.79%, respectively. The linearity of the α-chain glycation response was excellent (r(2) = 0.9990). We performed sample analysis on 39 cord blood specimens and found that the glycated α- and γ-chain levels were 2.27 ± 0.21% and 2.38 ± 0.29%, respectively, while the acetylated (G)γ and (A)γ-chain levels were 8.48 ± 0.53% and 7.14 ± 0.74%, respectively. We observed three types of HbF distinguishable by the intensities of γ-chain variants. Two-thirds of cord blood specimens were classified as HbF(I) with an intensity ratio (G)γ/(A)γ of 1.90 ± 0.12. For HbF(II) type (10/39 neonates), the intensity ratio of (G)γ/(A)γ was 3.71 ± 0.28. For three neonates with HbF(III), no (A)γ-chain was detected.

According to the Fick principle, any metabolic or hormonal exchange through a given tissue depends on the product of blood flow by arteriovenous difference. Because adipose tissue plays dual storage and endocrine roles, regulation of adipose tissue blood flow (ATBF) is of pivotal importance. Monitoring ATBF in humans can be achieved through different methodologies, such as the (133)Xe washout technique, considered to be the "gold standard", as well as microdialysis and other methods that are not well validated as of yet. This report describes a new method, called "adipose tissue microinfusion" or "ATM", which simultaneously quantifies ATBF by combining the (133)Xe washout technique together with variations of ATBF induced by local infusion of vasoactive agents. The most appropriate site for ATM investigation is the subcutaneous adipose tissue of the anterior abdominal wall. This innovative method conveniently enables the direct comparison of the effects on ATBF of any vasoactive compound, drug, or hormone against a contralateral saline control. The ATM method improves the accuracy and feasibility of physiological and pharmacological studies on the regulation of ATBF in vivo in humans.

Introduction: Gestational diabetes mellitus (GDM), the most frequent medical complication of pregnancy, is associated with several adverse outcomes over the short- and long-term for both mother and offspring. Standard treatment for GDM consists of insulin injections. Oral hypoglycemic agents (OHAs), on the other hand, are still the subject of controversy. Although OHAs are seemingly as efficient as insulin and may provide better quality of life, congenital malformations and unknown long-term effects are still feared., Areas Covered: Recent data on the pharmacokinetics of two OHAs (glyburide and metformin) and their clinical use for GDM are reviewed, with a focus on clinical trials and observational studies comparing insulin with glyburide or metformin (1960 - 2010). The review will provide a comprehensive overview of the pros and cons of OHA usage, an appreciation of OHAs' efficiency for the purpose of controlling glycemia and embryogenetic basics relating to congenital malformations., Expert Opinion: While insulin treatment is an effective therapy for controlling maternal glycemia, it nevertheless requires sufficient education and skills on the part of the patient to manage properly and may cause hypoglycemia, fear and anxiety. Oral treatment as a more user-friendly alternative may thus facilitate the control of GDM in some patients.

Background: Several techniques are currently used for measurement of body composition. Bioelectrical impedance assessment (BIA) is a simple, noninvasive method of assessing body composition. We aimed to compare multifrequency hand-to-foot (HF-BIA) and foot-to-foot (FF-BIA) bioelectrical impedance analysis techniques to assess fat-free mass (FFM) in a population with a wide range of body mass indices (BMI)., Methods: This was a cross-sectional study of 198 adult subjects. Anthropometric and BIA measures (HF-BIA with Hydra ICF/ECF, Xitron Technologies and FF-BIA with Tanita, model TBF-300A) were recorded after a 12-h fast., Results: Participants had a mean age of 42 years and BMI of 33.50.7 (range, 17.7-65.6) kg/m2. Mean FFM with HF-BIA (FFM BIA/HF) and FF-BIA (FFM BIA/FF) were 61.31.3 kg and 58.10.9 kg, respectively (P < 0.001). In subjects with BMI <25 kg/m2, FFM BIA/FF was not significantly different compared to FFMBIA/HF (-0.2 kg; P=0.8). However, FFM BIA/FF was significantly lower in subjects with BMI 25-30 kg/m2 (-2.0 kg; P=0.009), 30-34 kg/m2 (-1.8 kg; P¼0.04), 34-42 kg/m2 (-4.7 kg; P<0.001) and >42 kg/m2 (-8.0 kg; P=0.001). Pearson correlations between both methods were very high for FFM (r=0.92), fat mass (r=0.91), and % fat mass (r=0.85), all P<0.001. Correlation coefficients for FFM were high in each quintile of BMI. FFM BIA/FF was the only significant independent predictor of FFM BIA/HF (P<0.001) in linear regression analyses using clinical and FF-BIA variables, but introducing BMI in the model added precision., Conclusion: FFM BIA/FF correlates closely with FFM BIA/HF across all quintiles of BMI, but FF-BIA gives lower FFM in overweight and obese subjects.

Evaluation of: Balani J, Hyer SL, Rodin DA, Shehata H. Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. Diabet. Med. 26(8), 798-802 (2009). This paper reviews a case-control study, reported by Balani et al., comparing maternal and neonatal outcomes of women treated for gestational diabetes mellitus with either metformin or insulin. A cohort of 100 women treated with metformin alone, without insulin rescue, was compared with a retrospective cohort of 100 women treated with insulin. Results favored metformin. This paper discusses issues related to the safety and efficiency of metformin treatment during pregnancy, the attitudes of pregnant women toward treatment options, public health policy and the worldwide gestational diabetes mellitus epidemic, as well as the financial burden of therapy, particularly for developing countries. It also looks at the pathophysiology of gestational diabetes mellitus and the need for clinical trial assessment of combination oral-hypoglycemic therapy.

The objective of the study was to examine if decreases in resting metabolic rate (RMR) take place early in the weight loss process and if they remain throughout the duration of the weight loss intervention. Twenty obese postmenopausal women (61.8 +/- 5.9 years) participated in a 15-week weight loss program. After the fifth week, subjects were characterized as having an increased (>5%) or a decreased (<5%) RMR based on baseline values. Afterward, they were followed for an additional 10 weeks. Outcome measures were as follows: fat mass ([FM] total, trunk), lean body mass (total, trunk), RMR, resting heart rate (RHR), and physical activity level. After 5 weeks, significant decreases were observed for lean body mass, FM, and RHR (P < .05), whereas no overall changes in physical activity level and RMR were observed. However, on an individual basis, large variations in RMR were observed (ranging from -320 to +330 kcal/d). Analyses showed that subjects characterized as either having an increased or a decreased RMR after the fifth week maintained these adaptations at the end of intervention. Finally, subjects displaying a decreased RMR during weight loss had a significantly higher RMR and lower FM accumulations at baseline (total and trunk) compared with those with an increased RMR. Interindividual variations in RMR took place early in the weight loss process and were maintained over the duration of the weight loss program in our cohort of obese postmenopausal women. Baseline RMR, changes in RHR, and FM accumulations (total and trunk) seem to be important factors to consider when studying the effects of weight loss on RMR., (Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.)

The six-minute walk test (6MWT) is an inexpensive, quick and safe tool to evaluate the functional capacity of patients with heart failure and chronic obstructive pulmonary disease. The aim of this study was to determine the reproducibility of the 6MWT in overweight and obese individuals. We thus undertook a prospective repeated-measure validity study taking place in our academic weight management outpatient clinic. The 6MWT was conducted twice the same day in 21 overweight or obese adult subjects (15 females and 6 males). Repeatability of walking distance was the primary outcome. Anthropometric measures, blood pressure and heart rate were also recorded. Participant's mean BMI was 37.2+/-9.8 kg/m(2) (range: 27.0-62.3 kg/m(2)). Walking distance in the morning (mean=452+/-90 m) and in the afternoon (mean=458+/-97 m) were highly correlated (r=0.948; 95% Confidence Interval 0.877-0.978; p<0.001). Walking distance was negatively correlated with BMI (r=-0.47, p=0.03), waist circumference (r=-0.43, p=0.05) and pre-test heart rate (r=-0.54, p=0.01). Our findings indicate that the 6MWT is highly reproducible in obese subjects and could thus be used as a fitness indicator in clinical studies and clinical care in this population., (Georg Thieme Verlag KG Stuttgart New York.)

Background: Obesity is a worldwide health problem assuming epidemic proportions. Development of effective clinical interventions is needed to lower the impact of associated morbidity and mortality, without forgetting related costs. We have established an interdisciplinary clinic for obesity management, Unité d'Enseignement, de Traitement et de Recherche sur l'Obésité (UETRO), which consists of individual consultations combined with group sessions. We report here the effectiveness of this program for weight reduction over the first year of follow up., Methods: We performed retrospective analysis of standardized patient records of the first 115 consecutive subjects referred to UETRO with available follow up for 1 year., Results: Mean age, body mass index (BMI), and waist circumference (WC) of our cohort were 46 +/- 13 years, 44.7 +/- 0.9 kg/m(2), and 120.5 +/- 1.9 cm, respectively. Hypertension and diabetes were present in 46% and 23% of our patients. Weight and WC loss were gradual over 1 year and were significantly reduced by 6.6 +/- 0.8 kg and 6.7 +/- 0.7 cm, respectively (P < 0.001), without attainment of a plateau. Blood pressure and lipid profile significantly improved after 1 year of follow up. However, the proportion of patients taking metformin, lipid-lowering, antihypertensive, or antiobesity drugs increased significantly over follow up, reflecting intensification of treatment of co-morbidities and weight management. Significant weight and WC loss occurred independently of diabetes status and use of antiobesity medications., Conclusions: This program appears to be as effective for treating obesity as more intensive treatment programs. Future prospective studies are needed to evaluate the benefits and costs of this therapeutic approach.

Approximately 25% of weight lost during restrictive diets (without exercise) is lean body mass (LBM). No study has yet investigated the impact of the rate of weight loss (RWL) on LBM and fat mass (FM). The purpose of this study was to investigate the relationships between the RWL and body composition in older obese women. Twenty obese postmenopausal women aged between 51 and 74 years enrolled in a 5 week dietary weight loss intervention. Subjects were characterized according to their RWL (low RWL < 0.74 kg.week(-1) (n = 9) vs. high RWL > or = 0.74 kg.week(-1) (n = 11)). Total and trunk FM and LBM (by dual-energy X-ray absorptiometry) were measured before and after weight loss. A significant correlation was observed between the RWL (kg.week(-1)) and changes in LBM (kg.week(-1)) (r = 0.75; p = 0.0002). However, no association was observed with changes in FM (kg.week(-1)) (r = 0.40; p = 0.08). Both groups showed a similar decrease in FM (low RWL, -2.7 +/- 0.9 kg,; high RWL, -3.2 +/- 0.8 kg; p = 0.38), whereas losses in LBM were significantly higher in the high RWL than in the low RWL group (-1.6 +/- 1.2 kg vs. -0.4 +/- 1.1 kg; p = 0.05). An RWL > 0.74 kg.week(-1) was associated with a greater loss of LBM, but had no extra benefits on FM after a 5 week weight loss program. Current guidelines, which recommend RWL up to 0.91 kg.week(-1), might not be optimal to prevent decreases in LBM in postmenopausal women when no exercise is added.

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.

Aim: To assess the impact of an intensive multitherapy (IMT) on perceived quality of life (QOL), attitudes, knowledge and diabetes self-management in patients with poorly controlled type 2 diabetes., Methods: A 12-month randomized trial was conducted in 72 patients with type 2 diabetes, HbA1c>or=8%, blood pressure (BP)>130/80 mmHg and dyslipidemia. Subjects were assigned to the IMT or control group, each n=36. IMT consisted in monthly visits including clinical and biochemical assessment, education sessions on diet, physical exercise, medical management of diabetes and associated diseases and adjustments in medication. Control patients were under the care of their physicians. We developed and validated a diabetes-specific questionnaire assessing QOL, attitudes, knowledge, diabetes self-management and socio-demographic data for this study. Outcomes were measured at 0, 6 and 12 months., Results: Subjects were 54.8+/-8.1 years old (duration of diabetes: 10.3+/-7.2 years). At baseline, questionnaires showed no difference in QOL between groups. At 12 months, QOL improved significantly in the IMT group when compared to controls (+13.2+/-10.3/+5.6+/-13.2%, P=0.003), particularly with respect to the satisfaction scale (+25.3+/-13.9/+5.4+/-21.7%, P<0.001). QOL was not affected by complications or hypoglycaemic episodes. QOL scores improved in IMT subjects who began insulin therapy during the trial. Attitude scores, in the high normal range at baseline, did not change. Knowledge (+18.2+/-26.3/+8.9+/-30.4%, P=0.047) and diabetes self-management (+22.6+/-35.3/+6.8+/-20.1%, P<0.001) improved., Conclusions: In poorly controlled subjects, QOL improved statistically despite the inherent constraints imposed by IMT.

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.

Objective: Blood flow regulation is thought to mediate the metabolic functions of adipose tissue. Different depots, and even different layers within the subcutaneous adipose tissue, may vary in metabolic activity and blood flow. Therefore, we investigated if any differences in subcutaneous adipose tissue blood flow (ATBF) exist at different locations of the anterior abdominal wall., Methods: ATBF was measured 8-10 cm above or below the umbilicus, at 8-10 cm (both sides) from the midline, in 18 healthy subjects (BMI range 18-33 kg/m(2)). Measurements of ATBF were performed using (133)xenon washout, during a stable baseline period and after ingestion of 75 g of glucose., Results: At baseline, ATBF was greater at the upper level compared to the lower level (4.4+/-0.3 vs 3.8+/-0.2 ml min(-1) 100 g tissue(-1), P=0.005), but was not different between the right and the left sides at either level. ATBF increased in response to oral glucose at all sites. The mean increase at the superior level was also greater than the inferior level (3.5+/-0.7 vs 2.2+/-0.6 ml min(-1) 100 g tissue(-1), P=0.001)., Conclusions: Even at a constant depth and with only 16-20 cm difference between sites, there are significant differences in function of the same adipose depot. These findings have physiological and methodological implications for in vivo metabolic studies of human adipose tissue.

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.