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Diabetes, Obesity & Metabolism

Russell Scott, Jerry Morgan, Zachary Zimmer, Raymond L H Lam, Edward A O'Neill, Keith D Kaufman, Samuel S Engel, Annaswamy Raji
AIMS: To compare the efficacy and safety of the DPP-4 inhibitor sitagliptin with the SGLT-2 inhibitor dapagliflozin in patients with type 2 diabetes and mild renal insufficiency. MATERIALS AND METHODS: Patients with HbA1c 7.0 to 9.5% (53 to ≤80 mmol/mol) and eGFR 60 to <90 mL/min/1.73m2 on metformin (≥1500 mg/day) ± sulfonylurea were randomized to sitagliptin 100 mg (N=307) or dapagliflozin 5 mg titrated to 10 mg (N=306) once-daily for 24 weeks. A longitudinal data analysis model was used to test the primary hypothesis that sitagliptin is non-inferior to dapagliflozin in reducing HbA1c at Week 24, with superiority to be tested if non-inferiority is met...
July 18, 2018: Diabetes, Obesity & Metabolism
Francesca Piccinini, David C Polidori, Barbara A Gower, Jose R Fernandez, Richard N Bergman
AIMS: Adult African American (AA) women have 1/3 the hepatic insulin extraction as European American (EA) women. This lower hepatic (but not extra-hepatic) insulin clearance in AA is associated with higher plasma insulin concentrations. This study aims to understand whether hepatic insulin clearance impairment is seen in AA since childhood, possibly suggesting that genetic/epigenetic factors, rather than lifestyle only, contribute. MATERIALS AND METHODS: The FSIGT was performed at the University of Alabama at Birmingham, General Clinical Research Center and Department of Nutrition Sciences on 203 children: 105 boys and 98 girls [55 AA, 88 EA and 60 Hispanic American (HA), ages 7-13 years, mean BMI = 19 kg/m2 ]...
July 18, 2018: Diabetes, Obesity & Metabolism
David G Bruce, Wendy A Davis, Timothy Me Davis
AIMS: To investigate whether tight glycaemic control achieved with metformin, insulin or sulphonylurea-based pharmacotherapy increases all-cause mortality in older people with type 2 diabetes. MATERIALS AND METHODS: A prospective cohort study of individuals with known diabetes recruited between 2008 and 2011 and followed until 2016. The impact of baseline glycated haemoglobin (HbA1c) on mortality hazards was investigated in participants aged ≥75 years. Proportional hazards models for time to death were constructed from the baseline clinical assessment then the variables of interest (HbA1c, treatment category and their interactions) were entered...
July 13, 2018: Diabetes, Obesity & Metabolism
Emanuel Raschi, Elisabetta Poluzzi, Gian Paolo Fadini, Giulio Marchesini, Fabrizio De Ponti
Sodium glucose cotransporter 2 inhibitors (SGLT2-Is) have attracted the interest of the scientific community following the results from dedicated cardiovascular outcome trials (CVOTs), which demonstrated remarkable reduction in all-cause mortality and other cardiovascular (CV) endpoints with empagliflozin and canagliflozin. These impressive results raised further expectations on real world data from large observational cohort studies. They were designed to address the possible existence of a class effect, and the uncertainty on whether this benefit can be extended from secondary to primary CV prevention of patients with type 2 diabetes...
July 13, 2018: Diabetes, Obesity & Metabolism
F Javier Escalada, Serge Halimi, Peter A Senior, Mireille Bonnemaire, Anna Mg Cali, Lydie Melas-Melt, Janaka Karalliedde, Robert A Ritzel
AIMS: Impaired renal function increases hypoglycemia risk in type 2 diabetes (T2DM). Insulin glargine 300 U/mL (Gla-300) has previously demonstrated reduced hypoglycemia risk versus insulin glargine 100 U/mL (Gla-100). Therefore, we investigated the impact of renal function on the safety and efficacy of Gla-300 and Gla-100. MATERIALS AND METHODS: A meta-analysis was performed using pooled 6-month data from the EDITION 1, 2 and 3 trials (N=2496). Eligible participants, aged ≥18 years with a diagnosis of T2DM, were randomized to receive once-daily evening injections of Gla-300 or Gla-100...
July 13, 2018: Diabetes, Obesity & Metabolism
Domenico Tricò, Andrea Natali, Andrea Mari, Ele Ferrannini, Nicola Santoro, Sonia Caprio
Excess insulin secretion and hyperinsulinemia contribute to the progression of type 2 diabetes. However, the mechanisms leading to insulin hypersecretion remain largely unknown. Based on our preliminary data, we examined whether triglycerides and very low-density lipoprotein (VLDL) are independently associated with insulin secretion, and whether the ethnicity/race modulates these associations. Fasting triglycerides and VLDL were measured in a multiethnic cohort of 630 non-diabetic adolescents. Insulin secretion, β-cell function parameters, insulin sensitivity and insulin clearance were estimated through a 3-h OGTT...
July 12, 2018: Diabetes, Obesity & Metabolism
Nienke M A Idzerda, Frederik Persson, Michelle J Pena, Barry M Brenner, Patrick Brunel, Nish Chaturvedi, John J McMurray, Hans-Henrik Parving, Dick de Zeeuw, Hiddo J L Heerspink
Sodium retention and volume overload are main determinants of poor response to RAAS inhibition in patients with diabetes. As volume excess can exist without symptoms, biomarkers are needed to identify a priori which patients are volume overloaded and may experience less benefit from RAAS inhibition. N-terminal pro-brain natriuretic peptide (NT-proBNP) is released in the setting of increased cardiac wall stress and volume overload. We conducted a post-hoc analysis among 5081 patients with type 2 diabetes mellitus participating in the ALTITUDE trial to investigate whether NTproBNP can predict the effects of additional therapy with aliskiren on cardio-renal endpoints...
July 10, 2018: Diabetes, Obesity & Metabolism
Takashi Kadowaki, Nobuaki Sarai, Takeshi Hirakawa, Kentaro Taki, Kosuke Iwasaki, Hisashi Urushihara
No abstract text is available yet for this article.
July 4, 2018: Diabetes, Obesity & Metabolism
Chioma Izzi-Engbeaya, Alexander N Comninos, Sophie A Clarke, Anne Jomard, Lisa Yang, Sophie Jones, Ali Abbara, Shakunthala Narayanaswamy, Pei Chia Eng, Debbie Papadopoulou, Julia K Prague, Paul Bech, Ian F Godsland, Paul Bassett, Caroline Sands, Stephane Camuzeaux, Maria Gomez Romero, Jake T M Pearce, Matthew R Lewis, Elaine Holmes, Jeremy K Nicholson, Tricia Tan, Risheka Ratnasabapathy, Ming Hu, Gaelle Carrat, Lorenzo Piemonti, Marco Bugliani, Piero Marchetti, Paul R Johnson, Stephen J Hughes, A M James Shapiro, Guy A Rutter, Waljit S Dhillo
BACKGROUND: Reproduction and metabolism are inter-dependent, but our understanding of the hormones which regulate both these systems is currently limited. Kisspeptin has well-established crucial roles in mammalian reproduction, and recent reports in animal models suggest kisspeptin may have additional roles in metabolism. However, the effects of kisspeptin on metabolism in humans are as yet unknown. AIMS: To investigate the effect of kisspeptin on glucose-stimulated insulin secretion and appetite in humans...
July 4, 2018: Diabetes, Obesity & Metabolism
Julio Rosenstock, Yehuda Handelsman, Josep Vidal, F Javier Ampudia Blasco, Francesco Giorgino, Minzhi Liu, Riccardo Perfetti, Juris J Meier
AIM: Simultaneous treatment with insulin glargine 100 U (iGlar) and the glucagon-like peptide-1 receptor agonist (GLP-1 RA) lixisenatide (Lixi) as a single-pen, titratable, fixed-ratio combination (iGlarLixi) is a new option for patients with type 2 diabetes (T2D) initiating or intensifying basal insulin. Two exploratory analyses indirectly compared efficacy and safety of simultaneous administration of iGlarLixi (LixiLan trials) vs sequential administration of iGlar+Lixi (GetGoal Duo trials)...
July 4, 2018: Diabetes, Obesity & Metabolism
Jiun-Ling Wang, Yaa-Hui Dong, Wen-Chien Ko, Chia-Hsuin Chang, Li-Chiu Wu, Lee-Ming Chuang, Pau-Chung Chen
AIM: Previous research has suggested that peroxisome proliferator-activated receptor-gamma (PPAR-γ) may play an important role in immunomodulation. We aimed to examine the association between thiazolidinediones, PPAR-γ agonists, and incidence of bacterial abscess among patients with type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study included 46,986 propensity (PS)-matched patients diagnosed with type 2 diabetes between 2000 and 2010. We compared incidence of bacterial abscess, including liver and non-liver abscesses, between patients treated with metformin plus a thiazolidinedione (M+T, N=7831) or metformin plus a sulfonylurea (M+S, N=39,155)...
July 4, 2018: Diabetes, Obesity & Metabolism
Liyuan Han, Donghui Duan, Shuang Zhang, Weiqin Li, Leishen Wang, Huikun Liu, Junhong Leng, Nan Li, Xiaoyun Shang, Gang Hu, Lu Qi
AIM: We aimed to investigate the interaction between genetic risk score of HbA1c and weight changes during and after pregnancy(postpartum weight reduction and gestational weight gain) on long-term glycemic changes in the largest cohort of women with preceding history of gestational diabetes mellitus (GDM) . METHODS: This is a retrospective cohort using the baseline data from the Tianjin Gestational Diabetes Mellitus Prevention Program. A genetic risk score was established by combining 10 HbA1c related single nucleotide polymorphisms (SNPs), which were identified by genome-wide association studies (GWAS)...
July 4, 2018: Diabetes, Obesity & Metabolism
Sruthi Adimadhyam, Todd A Lee, Gregory S Calip, Daphne E Smith Marsh, Brian T Layden, Glen T Schumock
INTRODUCTION: Based on findings from a large clinical trial program, the U.S. Food and Drug Administration issued a safety alert for increased risk of amputations in patients with diabetes treated with canagliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i). However, other clinical trials and observational studies report conflicting results. OBJECTIVE: To determine the risk of amputations associated with SGLT2i relative to dipeptidyl peptidase-4 inhibitors (DPP4i)...
July 3, 2018: Diabetes, Obesity & Metabolism
Ki Heon Nam, Hae-Ryong Yun, Young Su Joo, Joohwan Kim, Sangmi Lee, Changhyun Lee, Kyoung Sook Park, Jung Tak Park, Tae-Ik Chang, Ea Wha Kang, Tae-Hyun Yoo, Shin-Wook Kang, Seung Hyeok Han
AIM: We aimed to examine an association between metabolically healthy obese (MHO) phenotype and incident chronic kidney disease (CKD) and studied whether changes in metabolic phenotype over time could affect CKD risk. METHODS: A total of 8,589 subjects from the Korean Genome and Epidemiology Study were categorized into four groups based on the presence of obesity and metabolic abnormalities (MA). The primary endpoint was an onset of incident CKD defined as an eGFR of ≤ 60 ml/min/1...
July 3, 2018: Diabetes, Obesity & Metabolism
Lisa Logie, Zoe Lees, J William Allwood, Gordon McDougall, Craig Beall, Graham Rena
AIM: Recently we have observed differences in the ability of metformin and AICAR to repress glucose production from hepatocytes using 8CPT-cAMP. Previous results indicate that besides activating protein kinase A, 8CPT-modified cAMP analogues suppress the Nitrobenzylthioinosine (NBMPR)-sensitive equilibrative nucleoside transporter ENT1. We aimed to exploit 8CPT-cAMP, 8CPT-2-Methyl-O-cAMP and NBMPR, which is highly selective for a high-affinity binding-site on ENT1, to investigate the role of ENT1 in the liver specific glucose lowering properties of AICAR and metformin...
July 2, 2018: Diabetes, Obesity & Metabolism
Valma Harjutsalo, Merlin C Thomas, Carol Forsblom, Per-Henrik Groop
AIMS: In order to be able to distinguish patients with type 1 diabetes (T1D) with different cardiovascular risk profiles the aim of this study was to dissect the effect of different stages of diabetic nephropathy (DN) and sex on the excess and absolute morbidity of coronary artery disease (CAD) and stroke in T1D. MATERIALS AND METHODS: The study included 4,410 patients with T1D from the Finnish Diabetic Nephropathy Study (FinnDiane) divided by DN status and 12,434 non-diabetic control individuals...
July 2, 2018: Diabetes, Obesity & Metabolism
Martin Ridderstråle, Julio Rosenstock, Knut Robert Andersen, Hans J Woerle, Afshin Salsali
OBJECTIVE: In the EMPA-REG H2H-SU trial in patients with type 2 diabetes with inadequate glycemic control on metformin, empagliflozin 25 mg given for 104 weeks provided a sustained reduction in HbA1c , with a small yet statistically significant benefit versus glimepiride, sustained reductions in weight and blood pressure, and low risk of hypoglycemia. We report results at week 208 including a 104-week masked extension. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes and HbA1c 7%-10% were randomized to empagliflozin 25 mg or glimepiride 1-4 mg for 104 weeks as add-on to metformin...
July 2, 2018: Diabetes, Obesity & Metabolism
Lixin Guo, Li Chen, Baocheng Chang, Liyong Yang, Yu Liu, Bo Feng
AIM: To confirm non-inferiority of biphasic insulin aspart 30 (BIAsp 30) + metformin to BIAsp 30 in lowering glycated haemoglobin (HbA1c) in Chinese patients with inadequately controlled type 2 diabetes on oral antidiabetic drugs. MATERIALS AND METHODS: In this 16-week, prospective, randomized, open-label, multicentre, parallel-controlled study, patients aged 18-79 years with HbA1c ≥7% were randomized to BIAsp 30 + metformin (n=130) or BIAsp 30 (n=127). Initially, 500 mg metformin was given twice daily and BIAsp 30 at 0...
July 2, 2018: Diabetes, Obesity & Metabolism
Andrew R Zullo, Michelle Hersey, Yoojin Lee, Sadia Sharmin, Elliott Bosco, Lori A Daiello, Nishant R Shah, Vincent Mor, W John Boscardin, Christine M Berard-Collins, David D Dore, Michael A Steinman
AIMS: Some beta-blockers may worsen glycemic control, which could be important for frail older nursing home (NH) residents with type 2 diabetes mellitus (T2D). There is little evidence that prescribers consider the glycometabolic properties of beta-blockers or that such properties affect clinical outcomes. We assessed whether NH residents with T2D preferentially received "T2D-friendly" (versus "T2D-unfriendly") beta-blockers after acute myocardial infarction (AMI), and evaluated their comparative effects...
June 28, 2018: Diabetes, Obesity & Metabolism
Dirk Müller-Wieland, Monika Kellerer, Katarzyna Cypryk, Dasa Skripova, Katja Rohwedder, Eva Johnsson, Ricardo Garcia-Sanchez, Raisa Kurlyandskaya, C David Sjöström, Stephan Jacob, Jochen Seufert, Nalina Dronamraju, Katalin Csomós
OBJECTIVE: To compare efficacy and safety of dapagliflozin ± saxagliptin with glimepiride as add-on to metformin in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This 52-week, multicenter, double-blind, active-controlled study (NCT02471404) randomized (1:1:1) patients (n=939; HbA1C 7.5-10.5%) on metformin monotherapy (≥1500 mg/day) to add-on dapagliflozin 10 mg, dapagliflozin 10 mg plus saxagliptin 5 mg, or glimepiride 1-6 mg (titrated). The primary efficacy end point was change in HbA1C from baseline to week 52...
June 27, 2018: Diabetes, Obesity & Metabolism
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