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Diabetes, Obesity & Metabolism

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https://www.readbyqxmd.com/read/28523737/comment-on-strengths-and-limitations-of-healthcare-databases-in-the-evaluation-of-hypoglycaemia
#1
LETTER
Francesco Zaccardi, Nafeesa N Dhalwani, Melanie J Davies, Kamlesh Khunti
We thank Loke and Mattishent for their commentary on our paper investigating risk factors for hospitalisation for hypoglycaemia in England.(1, 2) In their editorial, they further underlined the challenges we recognised in the manuscript over the use of administrative databases for epidemiological research and, in particular, for identifying potential risk factors for hypoglycaemia.
May 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28517913/sodium-glucose-co-transporter-2-inhibitors-and-diabetic-ketoacidosis-an-updated-review-of-the-literature
#2
REVIEW
Benedetta Maria Bonora, Angelo Avogaro, Gian Paolo Fadini
AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are increasingly used for the treatment of type 2 diabetes (T2D) and can improve glucose control also in type 1 diabetes (T1D). In May 2015, regulatory agencies issued a warning that SGLT2i may cause diabetic ketoacidosis (DKA). We report details on two new cases of SGLT2i-associated DKA and review the literature for similar cases within randomised controlled trials (RCTs), cohort studies, and single reports. METHODS: We searched the medical literature for reports of SGLT2i-associated DKA cases...
May 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28509408/insulin-associated-weight-gain-in-obese-type-2-diabetes-mellitus-patients-what-can-be-done
#3
REVIEW
Adrian Brown, Nicola Guess, Anne Dornhorst, Shahrad Taheri, Gary Frost
Insulin therapy (IT) is initiated for patients with type 2 diabetes mellitus when glycaemic targets are not met with diet and other hypoglycaemic agents. The initiation of IT improves glycaemic control and reduces the risk of microvascular complications. There is, however, an associated weight gain following IT, which may adversely affect diabetic and cardiovascular morbidity and mortality. A 3 to 9 kg insulin associated weight gain (IAWG) is reported to occur in the first year of initiating IT, consisting predominantly of adipose tissue...
May 16, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28503750/comparative-effects-of-liraglutide-3%C3%A2-mg-versus-structured-lifestyle-modification-on-body-weight-liver-fat-and-liver-function-in-obese-patients-with-non-alcoholic-fatty-liver-disease-a-pilot-randomized-trial
#4
Joan Khoo, John Hsiang, Ranu Taneja, Ngai-Moh Law, Tiing-Leong Ang
We compared effects of weight loss induced by the glucagon-like peptide 1-agonist liraglutide with a structured lifestyle intervention in obese adults with non-alcoholic fatty liver disease (NAFLD). Obese (BMI ≥ 30 kg/m(2) , mean weight 96.0 ± 16.3 kg) non-diabetic Asian adults, with NAFLD diagnosed by liver fat fraction (LFF) ≥ 5.5% on MRI without other causes of hepatic steatosis, were randomized to a supervised program of dieting (restriction by 400 kilocalories/day) plus moderate-intensity aerobic exercise (~200 minutes/week) (DE group, n = 12), or liraglutide at the 3 mg daily dose approved for weight loss (LI group, n = 12), for 26 weeks...
May 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28497592/hypoglycaemia-seriousness-and-weight-gain-as-determinants-of-cardiovascular-disease-outcomes-among-sulfonylurea-users
#5
Anthony P Nunes, Kristy Iglay, Larry Radican, Samuel S Engel, Jing Yang, Michael C Doherty, David D Dore
AIMS: Certain treatments for type 2 diabetes mellitus cause hypoglycaemia and weight gain, and thus might counteract the benefits of intensive glucose control. We quantify the association of cardiovascular disease (CVD) outcomes with hypoglycaemia and weight gain among patients with type 2 diabetes treated with sulfonylureas. MATERIALS AND METHODS: This cohort study included patients from January 2009 through December 2014 identified within a deidentified nationwide electronic health records repository, including multiple provider networks and electronic medical records systems...
May 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28497570/-laps-insulin115-a-novel-ultra-long-acting-basal-insulin-with-a-unique-action-profile
#6
Nina Wronkowitz, Thorsten Hartmann, Sven Görgens, Daniela Dietze-Schroeder, Ira Indrakusuma, In Young Choi, Sung Hee Park, Young-Mi Lee, Se Chang Kwon, Yeonjoo Kang, Marcus Hompesch, Juergen Eckel
AIMS: Developing a safe, while more convenient long-acting basal insulin for diabetic patients is still an unmet medical need. Thus, we conducted a comprehensive pre-clinical study of the novel ultra-long acting insulin analogue (LAPS) Insulin115. METHODS: Pharmacokinetic/pharmacodynamic studies comparing (LAPS) Insulin115 with other basal insulins were conducted in (db/db) mice. Insulin signaling in the major target organs was analysed by Western blot after single subcutaneous injection in wildtype male Wistar rats...
May 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28493515/a-review-of-methods-for-measuring-%C3%AE-cell-function-design-considerations-from-the-restoring-insulin-secretion-rise-consortium
#7
REVIEW
T S Hannon, S E Kahn, K M Utschneider, T A Bucahan, K J Nadeau, P Zeitler, D A Ehrmann, S A Arslanian, S Caprio, S L Edelstein, P J Savage, K J Mather
The Restoring Insulin Secretion (RISE) study was initiated to evaluate interventions to slow or reverse the progression of β-cell failure in type 2 diabetes (T2D). To design RISE, we undertook an evaluation of methods for measurement of β-cell function and changes in β-cell function in response to interventions. Here we present a review of approaches for measurement of β-cell function, focusing on methodologic and feasibility considerations. Methodologic considerations included 1) the utility of each technique for evaluating key aspects of ß-cell function (first- and second-phase insulin secretion, maximal insulin secretion, glucose sensitivity, incretin effects); and 2) tactics for incorporating a measurement of insulin sensitivity in order to appropriately adjust insulin secretion measures for insulin sensitivity...
May 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28493502/fasiglifam-for-glycemic-control-in-patients-with-type-2-diabetes-a-phase-3-placebo-controlled-study
#8
John Marcinak, Charles Cao, Douglas Lee, Zhan Ye
AIM: To investigate the effect of fasiglifam on glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: In total, 421 patients with T2DM and glycosylated hemoglobin (HbA1c) ≥7.0% but ≤10.5% who had been treated with diet and exercise only for ≥12 weeks prior to screening were randomized to receive fasiglifam 25 mg or 50 mg or placebo. The primary efficacy endpoint was change from baseline in HbA1c at week 24. RESULTS: Patient mean age was 53...
May 11, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28477418/sodium-glucose-sglt-and-glucose-glut-transporter-expression-in-the-kidney-of-type-2-diabetic-subjects
#9
Luke Norton, Christopher Shannon, Marcel Fourcaudot, Cheng Hu, Niansong Wang, Wei Ren, Jun Song, Muhammad Abdul-Ghani, Ralph A DeFronzo, Jimmy Ren, Weiping Jia
The sodium-glucose cotransporters (SGLTs) are responsible for the tubular reabsorption of filtered glucose from the kidney into the bloodstream. The inhibition of SGLT2-mediated glucose reabsorption is a novel and highly effective strategy to alleviate hyperglycemia in patients with type 2 diabetes mellitus (T2DM). However, the effectiveness of SGLT2 inhibitor therapy is diminished due, in part, to a compensatory increase in the maximum reabsorptive capacity (Tm) for glucose in patients with T2DM. We hypothesized that this increase in Tm could be explained by an increase in the tubular expression of SGLT and GLUT transporters in these patients...
May 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28474817/relationship-between-diabetes-and-ischemic-injury-among-patients-with-revascularized-st-elevation-myocardial-infarction-diabetes-and-myocardial-damage
#10
Sebastian J Reinstadler, Thomas Stiermaier, Charlotte Eitel, Bernhard Metzler, Suzanne de Waha, Georg Fuernau, Steffen Desch, Holger Thiele, Ingo Eitel
AIMS: Studies comparing reperfusion efficacy and myocardial damage between diabetic and non-diabetic patients with ST-elevation myocardial infarction (STEMI) are scarce and have reported conflicting results. Aim was to investigate the impact of preadmission diabetic status on myocardial salvage and damage as determined by cardiac magnetic resonance (CMR) and to evaluate its prognostic relevance. MATERIALS AND METHODS: We enrolled 792 patients with STEMI at eight sites...
May 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28474383/intraperitoneal-insulin-delivery-provides-superior-glycemic-regulation-to-subcutaneous-insulin-delivery-in-model-predictive-control-based-fully-automated-artificial-pancreas-in-patients-with-type-1-diabetes-a-pilot-study
#11
Eyal Dassau, Eric Renard, Jérôme Place, Anne Farret, Marie-José Pelletier, Justin Lee, Lauren M Huyett, Ankush Chakrabarty, Francis J Doyle, Howard C Zisser
AIMS: To compare intraperitoneal (IP) to subcutaneous (SC) insulin delivery in an artificial pancreas (AP). MATERIALS AND METHODS: Ten adults with type 1 diabetes participated in a non-randomized, non-blinded sequential AP study using the same SC glucose sensing and Zone Model Predictive Control (ZMPC) algorithm adjusted for insulin clearance. On first admission, subjects underwent closed-loop control with SC delivery of a fast-acting insulin analogue for 24 hr...
May 5, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28474496/an-arduous-journey-from-human-pluripotent-stem-cells-to-functional-pancreatic-%C3%AE-cells
#12
REVIEW
Larry Sai Weng Loo, Hwee Hui Lau, Joanita Binte Jasmen, Chang Siang Lim, Adrian Kee Keong Teo
Type 1 and type 2 diabetes are caused by either a destruction or decrease in the number of functional insulin-producing β-cells, respectively. Therefore, the generation of functional β-cells from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), collectively known as human pluripotent stem cells (hPSCs), for potential cell replacement therapy and disease modeling is an intensely investigated area. Recent scientific breakthroughs enabled derivation of large quantities of human pancreatic β-like cells in vitro although with varied glucose-stimulated insulin secretion kinetics...
May 4, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28474401/a-review-of-glucagon-like-peptide-1-receptor-agonists-and-their-effects-on-lowering-postprandial-plasma-glucose-and-cardiovascular-outcomes-in-the-treatment-of-type-2-diabetes-mellitus
#13
REVIEW
D R Owens, L Monnier, M Hanefeld
Type 2 diabetes mellitus (T2DM) is an independent risk factor for cardiovascular (CV) comorbidities, with CV disease being the most common cause of death in adults with T2DM. Although glucocentric therapies may improve glycaemic control (as determined by glycated haemoglobin levels), evidence suggests that this approach alone has limited beneficial effects on CV outcomes relative to improvements in lipid and blood pressure control. This may be explained in part by the fact that current antidiabetic treatment regimens primarily address overall glycaemia and/or fasting plasma glucose, but not the postprandial plasma glucose (PPG) excursions that have a fundamental causative role in increasing CV risk...
May 4, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28474371/metformin-associated-lactic-acidosis-mala-moving-towards-a-new-paradigm
#14
EDITORIAL
Thomas A Bicsak, Brandon Walsh, Mark Fineman
The history of Metformin-Associated Lactic Acidosis (MALA) is rooted in the earlier experience with phenformin, another biguanide treatment for type 2 diabetes that was removed from the market owing to a clear causal association with cases of lactic acidosis (LA). Although metformin is less problematic in this regard, metformin can and does induce lactic acidosis, and under the right circumstances it continues to present a potential risk to patients. Recent liberalization of the prescribing guidelines in the US and EU specifically regarding use in more advanced stages of Chronic Kidney Disease (CKD) have led to renewed interest in the topic of MALA, and this issue of the Journal presents two timely articles on the topic by Lalau et al...
May 4, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28474364/pancreatic-%C3%AE-cell-mass-in-obesity
#15
Johanne H Ellenbroek, Hendrica A M Töns, Maaike A J Hanegraaf, Ton J Rabelink, Marten A Engelse, Françoise Carlotti, Eelco J P de Koning
While it is well recognized that obesity is associated with an increased β-cell mass, it is less clear with respect to α-cell mass. Type 2 diabetes associated with obesity is a bihormonal disease characterized by inadequate insulin secretion and hyperglucagonemia. We examined β- and α-cell mass of obese and lean human subjects throughout the pancreas. Pancreatic tissue of the head-, body- and tail-region of the pancreas was examined from 15 obese subjects (Body Mass Index (BMI) ≥ 27 kg/m2) and 15 age-matched lean subjects (BMI ≤ 25 kg/m2) without diabetes...
May 4, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28466587/camp-signalling-in-insulin-and-glucagon-secretion
#16
REVIEW
A Tengholm, E Gylfe
The "second messenger" archetype cAMP is one of the most important cellular signalling molecules with central functions including the regulation of insulin and glucagon secretion from the pancreatic β- and α-cells, respectively. cAMP is generally considered as an amplifier of insulin secretion triggered by Ca(2+) elevation in the β-cells. Both messengers are also positive modulators of glucagon release from α-cells, but in this case cAMP may be the important regulator and Ca(2+) have a more permissive role...
May 3, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28466490/local-and-regional-control-of-calcium-dynamics-in-the-pancreatic-islet
#17
REVIEW
Guy A Rutter, David J Hodson, Pauline Chabosseau, Elizabeth Haythorne, Timothy J Pullen, Isabelle Leclerc
Ca(2+) is the key intracellular regulator of insulin secretion, acting in the beta cell as the ultimate trigger for exocytosis. In response to high glucose, ATP-sensitive K(+) channel closure and plasma membrane depolarisation engage a sophisticated machinery to drive pulsatile cytosolic Ca(2+) changes. Voltage-gated Ca(2+) channels, Ca(2+) -activated K(+) channels and Na(+) /Ca(2+) exchange all play important roles. The use of targeted Ca(2+) probes has revealed that during each cytosolic Ca(2+) pulse, uptake of Ca(2+) by mitochondria, endoplasmic reticulum (ER), secretory granules and lysosomes fine-tune cytosolic Ca(2+) dynamics and control organellar function...
May 3, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28452101/combined-low-dose-spironolactone-plus-vitamin-e-vs-vitamin-e-monotherapy-on-insulin-resistance-noninvasive-indices-of-steatosis-and-fibrosis-and-adipokine-levels-in-nonalcoholic-fatty-liver-disease-a-randomized-controlled-trial
#18
Stergios A Polyzos, Jannis Kountouras, Christos S Mantzoros, Vaia Polymerou, Panagiotis Katsinelos
The beneficial effects of mineralocorticoid receptor blockade by spironolactone have been shown in animal models of nonalcoholic fatty liver disease (NAFLD). The aim of this 52-week randomized controlled trial was to compare the efficacy of low-dose spironolactone and vitamin E combination vs. vitamin E monotherapy on insulin resistance, noninvasive indices of hepatic steatosis and fibrosis, liver tests, circulating adipokines and hormones in patients with histologically confirmed NAFLD. Homeostasis model of assessment-insulin resistance (HOMA-IR) and noninvasive indices of steatosis and fibrosis were calculated...
April 28, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28452095/cost-effectiveness-of-exenatide-twice-daily-versus-insulin-glargine-as-add-on-therapy-to-oral-anti-diabetic-agents-in-type-2-diabetes-in-china
#19
Shuyan Gu, Xiaoyong Wang, Qing Qiao, Weiguo Gao, Jian Wang, Hengjin Dong
AIMS: This study aimed to estimate long-term cost-effectiveness of exenatide twice daily (EBID) versus insulin glargine once daily (IGQD) as add-on therapy to oral anti-diabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM). MATERIALS AND METHODS: Cardiff Diabetes Model was used to simulate disease progression and estimate long-term effects of EBID versus IGQD. Model-required patient profiles and treatment effects were obtained from literature reviews (English and Chinese databases) and meta-analysis of eight randomized clinical trials comparing EBID versus IGQD add-on to OADs for T2DM in China...
April 28, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28449416/strengths-and-limitations-of-healthcare-databases-in-the-evaluation-of-hypoglycaemia
#20
Yoon Kong Loke, Katharina Mattishent
In this issue of DOM, Zaccardi et al. present an analysis of hypoglycaemia-related hospitalizations in the Hospital Episodes Statistics (HES) administrative database of the English National Health Service. [1] Notable strengths of the work include a large sample size involving more than 100 000 cases of hypoglycaemia, and nationwide capture spanning a duration of ten years. Key conclusions include the possibility of a U-shaped relationship between risk of hypoglycaemia and age, as well as possible associations between social deprivation and ethnicity with greater risk of hypoglycaemia...
April 27, 2017: Diabetes, Obesity & Metabolism
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