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Diabetes, Obesity & Metabolism

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https://www.readbyqxmd.com/read/29460474/specific-synbiotics-in-early-life-protect-against-diet-induced-obesity-in-adult-mice
#1
Mona Mischke, Tulika Arora, Sebastian Tims, Eefje Engels, Nina Sommer, Kees van Limpt, Annemarie Baars, Raish Oozeer, Annemarie Oosting, Fredrik Bäckhed, Jan Knol
AIMS: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health long-lastingly. Here, we determined how beneficial microbiome interventions in early life affect metabolic health in adulthood. METHODS: Postnatal diets were supplemented with either prebiotics (scGOS/lcFOS) or synbiotics (scGOS/lcFOS with Bifidobacterium breve M-16V) until post-natal (PN) day 42 in a well-established rodent model for nutritional programming...
February 20, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29460379/5-years-long-term-clinical-outcome-after-bariatric-surgery-a-multi-ethnic-asian-population-in-singapore
#2
B C Toh, W H Chan, Akh Eng, Ekw Lim, C H Lim, K W Tham, S Fook-Chong, Jth Tan
Bariatric surgery is an effective treatment for morbid obesity and its metabolic related comorbidities - Type II Diabetes, Hypertension and Hyperlipidaemia.1 However, the literature is scarce regarding the long-term outcome after bariatric surgery especially among multi-ethnic Asian populations. Considering the growing number of bariatric metabolic operations in Asia, we have attempted to provide a regional perspective on 5-year long-term clinical outcomes post bariatric surgery in Singapore. Between years 2010 to 2016, all bariatric operative cases consisted of 393 Laparoscopic Sleeve Gastrectomy (LSG), 125 Laparoscopic Roux-En-Y Gastric Bypass (RYGB) and 43 Laparoscopic Mini-gastric Bypass (MGB) were included...
February 20, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29457876/pharmacokinetics-of-metformin-in-patients-with-gastrointestinal-intolerance
#3
L McCreight, T B Stage, P Connelly, M Lonergan, F Nielsen, C Prehn, J Adamski, K Brosen, E R Pearson
AIMS: Metformin intolerance symptoms are gastrointestinal in nature, but the underlying mechanism is poorly understood. The aim of this study was to assess potential causes of metformin intolerance including: altered metformin uptake from the intestine; increased anaerobic glucose utilisation and subsequent lactate production; altered serotonin uptake; and altered bile acid pool. METHODS: This pharmacokinetic study recruited ten severely intolerant and ten tolerant individuals matched for age, sex and BMI...
February 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29457866/epigenetic-effects-of-metformin-from-molecular-mechanisms-to-clinical-implications
#4
REVIEW
S C Bridgeman, G C Ellison, P E Melton, P Newsholme, Cds Mamotte
There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly via modulating the activation of AMP-activated protein kinase (AMPK)...
February 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29451721/sodium-glucose-co-transporter-2-sglt2-inhibitors-as-add-on-therapy-to-insulin-for-type-1-diabetes-mellitus-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#5
Tomohide Yamada, Nobuhiro Shojima, Hisashi Noma, Toshimasa Yamauchi, Takashi Kadowaki
New treatments for type 1 diabetes are an unmet need. We investigated the efficacy and safety of adding SGLT-2is to insulin for type 1 diabetes by meta-analysis of prospective randomized, placebo-controlled trials. Searching electronic databases up to October 2017 identified 1361 studies, among which 14 were investigated (N=4,591). Meta-analysis revealed that SGLT-2i therapy significantly reduced HbA1c by 0.4% (95% confidence interval [CI]: 0.35, 0.46; P<0.001; I2=0%), fasting plasma glucose by 1.14 mmol/l (0...
February 16, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29451706/insulin-degludec-insulin-aspart-lowers-fasting-plasma-glucose-and-rates-of-confirmed-and-nocturnal-hypoglycaemia-independent-of-baseline-hba-1c-levels-disease-duration-or-bmi-a-pooled-meta-analysis-of-phase-3-studies-in-patients-with-type-2-diabetes
#6
Martin Haluzík, Greg Fulcher, Thomas R Pieber, Lars Bardtrum, Deniz Tutkunkardas, Helena W Rodbard
AIMS: Previous studies demonstrated the co-formulation of insulin degludec (IDeg)/insulin aspart (IAsp) 'IDegAsp' offers lower rates of hypoglycaemia with smaller changes in weight compared with basal-bolus (IDeg once daily [OD] + IAsp [2-4 injections]) and premix insulin (BIAsp 30 twice daily [BID]) comparators. This study aimed to investigate whether the benefits of IDegAsp, given twice daily, extend across a wide spectrum of patients with diabetes. MATERIALS AND METHODS: This was a post hoc pooled analysis of five phase 3 randomised, 26-week, open-label, BID, treat-to-target trials comparing IDegAsp BID (n = 1111) with one of two 'comparators' - BIAsp 30 BID (n = 561) or IDeg OD + IAsp (n = 136)...
February 16, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29446554/impact-of-cigarette-smoking-on-the-relationship-between-bmi-and-insulin-longitudinal-observation-from-the-bogalusa-heart-study
#7
Ying Li, Tao Zhang, Tianshu Han, Shengxu Li, Lydia Bazzano, Jiang He, Wei Chen
BACKGROUND: Despite the inverse association between cigarette smoking and body mass index (BMI), it is unknown about whether the effect of smoking on insulin is mediated through decreased BMI. This study aims to examine the temporal relationship between BMI and insulin, the impact of smoking on this relationship and mediation effect of BMI on the association between smoking and insulin levels. METHODS: The longitudinal cohort consisted of 1,121 adults (807 whites and 314 blacks, mean age=42...
February 15, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29446523/safety-and-tolerability-of-dapagliflozin-saxagliptin-and-metformin-in-combination-post-hoc-analysis-of-concomitant-add-on-versus-sequential-add-on-to-metformin-and-of-triple-versus-dual-therapy-with-metformin
#8
Stefano Del Prato, Julio Rosenstock, Ricardo Garcia-Sanchez, Nayyar Iqbal, Lars Hansen, Eva Johnsson, Hungta Chen, Chantal Mathieu
The safety of triple oral therapy with dapagliflozin plus saxagliptin plus metformin, versus dual therapy with dapagliflozin or saxagliptin plus metformin, was compared in a post hoc analysis of three randomized trials of sequential or concomitant add-on of dapagliflozin and saxagliptin to metformin. In the concomitant add-on trial, patients with type 2 diabetes on stable metformin received dapagliflozin 10 mg/day plus saxagliptin 5 mg/day. In sequential add-on trials, patients on metformin plus either saxagliptin 5 mg/day or dapagliflozin 10 mg/day received add-on dapagliflozin 10 mg/day or saxagliptin 5 mg/day, respectively...
February 15, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29436761/a-52-week-extension-study-of-switching-from-gemigliptin-vs-sitagliptin-to-gemigliptin-only-as-an-add-on-to-patients-with-type-2-diabetes-inadequately-controlled-on-metformin-alone
#9
Chan-Hee Jung, Eun-Jung Rhee, Won-Young Lee, Kyung Wan Min, Vyankatesh K Shivane, Aravind R Sosale, Hak Chul Jang, Choon Hee Chung, Il Seong Nam-Goong
We investigated the long-term efficacy and safety of gemigliptin and the efficacy and safety of gemigliptin treatment after once daily treatment with sitagliptin 100 mg, in patient with type 2 diabetes. This study was a 28-week, extension of a 24-week, randomized, double-blind, parallel study of gemigliptin or sitagliptin, added to ongoing metformin therapy. After randomized to sitagliptin 100 mg qd(S), gemigliptin 25 mg bid (G1), or gemigliptin 50 mg qd(G2) groups and completing treatment of 24 weeks, 118 patients switched from gemigliptin 25 mg bid to 50 mg qd(G1/G2), 111 patients continued gemigliptin 50 mg qd(G2/G2), and 106 patients switched from sitagliptin 100 mg qd to gemigliptin 50 mg qd(S/G2)...
February 13, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29436756/alirocumab-versus-usual-lipid-lowering-care-as-add-on-to-statin-therapy-in-individuals-with-type-2-diabetes-and-mixed-dyslipidaemia-the-odyssey-dm-dyslipidemia-randomized-trial
#10
Kausik K Ray, Lawrence A Leiter, Dirk Müller-Wieland, Bertrand Cariou, Helen M Colhoun, Robert R Henry, Francisco J Tinahones, Maja Bujas-Bobanovic, Catherine Domenger, Alexia Letierce, Rita Samuel, Stefano Del Prato
AIMS: Individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia represent a high-risk and difficult-to-treat population. ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) compared alirocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor, with usual care (UC) in individuals with T2DM and mixed dyslipidaemia not optimally managed by maximally-tolerated statins. MATERIALS AND METHODS: UC options (no additional lipid-lowering therapy; fenofibrate; ezetimibe; omega-3 fatty acid; nicotinic acid) were selected prior to stratified randomization to open-label alirocumab 75 mg every 2 weeks (Q2W; with increase to 150 mg Q2W at Week [W]12 if W8 non-high-density lipoprotein cholesterol [non-HDL-C] was ≥2...
February 13, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29431272/prolonged-uninterrupted-sitting-elevates-postprandial-hyperglycaemia-proportional-to-degree-of-insulin-resistance
#11
Paddy C Dempsey, Robyn N Larsen, Elisabeth A H Winkler, Neville Owen, Bronwyn A Kingwell, David W Dunstan
Prolonged uninterrupted sitting is related adversely to cardiometabolic risk markers and postprandial hyperglycaemia, relative to sitting interrupted by regular brief activity breaks. However, whether the magnitude of hyperglycaemic responses to prolonged sitting is dependent upon the underlying degree of insulin resistance remains unclear. Data were pooled from three randomised cross-over laboratory-based trials (n=62) that examined the postprandial blood glucose- and insulin-lowering effects of prolonged sitting versus sitting interrupted by regular brief activity breaks in overweight/obese adults who had normal or impaired glucose metabolism (two trials), or type 2 diabetes not treated by insulin (one trial)...
February 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29430814/sglt-2-inhibitors-and-the-risk-of-lower-limb-amputation-is-this-a-class-effect
#12
Charles Khouri, Jean-Luc Cracowski, Matthieu Roustit
OBJECTIVE: Inhibitors of the sodium-glucose co-transporter-2 (SGLT-2) are a novel class of glucose lowering agents showing promising results. However, the use of canagliflozin has been associated with an increased risk of lower-limb amputation. Whether this risk concerns other SGLT-2 inhibitors is unclear. METHODS: We performed a disproportionality analysis using the WHO global database of individual case safety reports (VigiBase®) to address this issue. RESULTS: Among the 8,293,886 reports available between January 2013 and December 2017, we identified 79 reports of lower-limb amputations associated with SGLT-2 inhibitors...
February 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29430801/dulaglutide-1-5-mg-as-an-add-on-option-for-patients-uncontrolled-on-insulin-subgroup-analysis-by-age-duration-of-diabetes-and-baseline-hba1c
#13
Kevin M Pantalone, Hiren Patel, Maria Yu, Laura Fernández Landó
AIMS: To assess efficacy and safety of dulaglutide 1.5 mg combined with insulin, categorised by subgroups of baseline HbA1c (≤9% and >9%), age (<65 and ≥65 years), and duration of diabetes (<10 and ≥10 years) at 6 months in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: This pooled analysis was conducted in a similar T2D population from the AWARD-4 and AWARD-9 clinical trials randomised to dulaglutide 1.5 mg (pooled mean baseline age: 59 years, duration of diabetes: 13 years, HbA1c: 8...
February 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29430799/direct-medical-costs-of-diabetes-mellitus-in-the-year-of-mortality-and-year-before-mortality
#14
Carlos King Ho Wong, Fangfang Jiao, Eric Ho Man Tang, Thaison Tong, Praveen Thokala, Cindy Lo Kuen Lam
AIMS: Studies have shown that health service utilization often increases in few years immediately before death. Estimates of direct medical cost of diabetes mellitus (DM) in mortality year and the previous year is not well understood. This study aimed to report the health resource use and estimate the direct medical costs among DM patients in the year of mortality and the year before mortality. MATERIALS AND METHODS: We analysed a population-based, retrospective cohort study including all adults with DM diagnosis in Hong Kong between 2009 and 2013, and death between January 1, 2010 and December 31, 2013...
February 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29424957/hnf1a-variant-energy-reduced-diets-and-insulin-resistance-improvement-during-weight-loss-the-pounds-lost-and-direct-trials
#15
Tao Huang, Tiange Wang, Yoriko Heianza, Dianjianyi Sun, Kerry Ivey, Ronen Durst, Dan Schwarzfuchs, Meir J Stampfer, George A Bray, Frank M Sacks, Iris Shai, Lu Qi
BACKGROUND: The majority of patients with maturity-onset diabetes of the young (MODY) has mutations in the hepatocyte nuclear factor 1α (HNF1A) gene. A common variant rs7957197 at HNF1A locus for type 2 diabetes was identified. Dietary macronutrients regulate the HNF1A gene expression. OBJECTIVE: We aimed to determine whether weight loss diets varying in macronutrients modulate the genetic effect of HNF1A rs7957197 on weight loss and improvement of insulin resistance...
February 9, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29424470/results-of-accordian-in-accord-with-lower-blood-pressure-begetting-lower-mortality-in-patients-with-diabetes
#16
EDITORIAL
Luke J Laffin, George L Bakris
The ACCORD trial used 2x2 factorial design and enrolled 10,251 participants. The trial recruited patients with Type 2 diabetes and randomized them to two different glucose levels and office systolic blood pressure (SBP) goal of < 140mmHg versus an intensive goal of < 120mmHg.
February 9, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29424469/effect-of-intensive-blood-pressure-control-in-patients-with-type-2-diabetes-mellitus-over-9-years-of-follow-up-a-subgroup-analysis-of-high-risk-accordion-trial-participants
#17
Leo F Buckley, Dave L Dixon, George F Wohlford, Dayanjan S Wijesinghe, William L Baker, Benjamin W Van Tassell
Although guidelines recommend strict blood pressure (BP) control in patients with type 2 diabetes mellitus (T2DM) and elevated cardiovascular risk, the long-term effects of this approach are unknown. We investigated the effect of intensive BP control on clinical outcomes in patients with T2DM over 9 years of follow-up. We included ACCORD BP participants in the standard glucose control arm who had established cardiovascular disease, chronic kidney disease, age ≥75 years or 10-year coronary heart risk ≥15%...
February 9, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29419917/long-term-efficacy-and-safety-of-ertugliflozin-monotherapy-in-patients-with-inadequately-controlled-t2dm-despite-diet-and-exercise-vertis-mono-extension-study
#18
Ronnie Aronson, Juan Frias, Allison Goldman, Amanda Darekar, Brett Lauring, Steven G Terra
AIM: This phase III, multicenter, randomised study evaluated the efficacy and safety of ertugliflozin monotherapy in adults with inadequately controlled type 2 diabetes (glycated haemoglobin [HbA1c] 7.0% to 10.5% [53-91 mmol/mol]) despite diet and exercise. MATERIALS AND METHODS: The 52-week study comprised a 26-week, double-blind, placebo-controlled period (phase A) where 461 participants received placebo, ertugliflozin 5-mg/day, or ertugliflozin 15-mg/day. This was followed by a 26-week active-controlled period (phase B) where participants in the placebo group who had not received glycaemic rescue therapy had blinded metformin added...
February 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29419909/cardiovascular-biomarkers-in-clinical-studies-of-type-2-diabetes
#19
REVIEW
M P A Baldassarre, A Andersen, A Consoli, F K Knop, T Vilsbøll
When planning cardiovascular studies in type 2 diabetes, selection of cardiovascular biomarkers is a complex issue. Since the pathophysiology of cardiovascular disease in type 2 diabetes is multifactorial, ideally, the selected cardiovascular biomarkers should cover all aspects of the known pathophysiology of the disease. This will allow the researcher to distinguish between effects on different aspects of the pathophysiology. To this end, we will discuss a host of biomarkers grouped according to their role in the pathogenesis of CV disease, namely: 1) cardiac damage biomarkers 2) inflammatory biomarkers and 3) novel biomarkers (oxidative stress and endothelial dysfunction biomarkers)...
February 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29405635/metformin-does-not-affect-postabsorptive-hepatic-free-fatty-acid-uptake-oxidation-or-resecretion-in-humans-a-3-months-placebo-controlled-clinical-trial-in-patients-with-type-2-diabetes-and-healthy-controls
#20
Lars C Gormsen, Esben Søndergaard, Nana L Christensen, Steen Jakobsen, Erik H T Nielsen, Ole L Munk, Lars P Tolbod, Niels Jessen, Søren Nielsen
AIMS: Metformin is due to its well-documented glucose lowering effect the most commonly used drug in patients with T2D. However, metformin have also in pre-clinical studies been shown to improve lipid metabolism, possibly through modulation of intrahepatic partitioning of fatty acids towards oxidation and away from reesterification and resecretion as triglycerides. MATERIALS AND METHODS: To explore whether these pre-clinical findings can be translated to a human setting, we performed a 3-month randomized, placebo controlled, parallel-group clinical trial in patients with T2D (24 patients) and healthy controls (12 subjects)...
February 6, 2018: Diabetes, Obesity & Metabolism
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