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Cersosimo eugenio

Robert Martinez, Hussein Al-Jobori, Ali M Ali, John Adams, Muhammad Abdul-Ghani, Curtis Triplitt, Ralph DeFronzo, Eugenio Cersosimo
The decrement in plasma glucose concentration with SGLT2i is blunted by a rise in endogenous glucose production (EGP). We investigated the ability of incretin treatment to offset the EGP increase. T2DM (n=36) subjects were randomized to: (i) CANAgliflozin (ii) LIRAglutide (iii) CANA/LIRA. EGP was measured with 3-3 H-glucose with/without drug for 360 minutes. In the pre-treatment studies EGP (mg/kg•min) was comparable and decreased (2.2±0.1 to 1.7±0.2) during 300-360 minute period (p<0.01). The decrement in EGP was attenuated with CANA (2...
March 30, 2018: Diabetes
Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Carolina Solis-Herrera, Curtis Triplitt, Ralph A DeFronzo, Muhammad Abdul-Ghani
Objective: To examine whether lowering the plasma glucose concentration with empagliflozin (SGLT2 inhibitor) improves beta cell function in T2DM. Research Design and Methods: 15 T2DM patients received empagliflozin (25 mg/day) for 2 weeks, and beta cell function was measured with 9-step hyperglycemic clamp (each step = +40 mg/dl) before and 48 hours and 14 days after empagliflozin. Results: Empagliflozin caused 101±10 and 117±11 grams glucosuria on days 1 and 14 and produced 25±6 and 38±8 mg/dl reduction (p<0...
January 12, 2018: Journal of Clinical Endocrinology and Metabolism
Eugenio Cersosimo, Eric L Johnson, Christina Chovanes, Neil Skolnik
There is clear evidence that achieving glycaemic targets reduces the risk of developing complications as a result of type 2 diabetes (T2D). Many patients, however, continue to have suboptimal glycaemic control because of issues that include unclear advice on how to achieve these targets as well as clinical inertia. The two management approaches recommended for patients newly diagnosed with T2D are stepwise and combination therapy, each of which has advantages and disadvantages. Stepwise therapy may result in good patient adherence and allow greater individualization of therapy, and minimization of side effects and cost, and so may be appropriate for patients who are closer to goal...
March 2018: Diabetes, Obesity & Metabolism
Richard E Pratley, Eugenio Cersosimo
In Brief Sodium-glucose cotransporter 2 (SGLT2) inhibitors and incretin-based therapies (dipeptidyl peptidase-4 [DPP-4] inhibitors and glucagon-like peptide-1 [GLP-1] receptor agonists) are widely used to treat patients with type 2 diabetes. In clinical and real-world studies, canagliflozin, an SGLT2 inhibitor, has demonstrated superior A1C lowering compared to the DPP-4 inhibitor sitagliptin. Canagliflozin can also promote modest weight/fat loss and blood pressure reduction. The addition of canagliflozin to treatment regimens that include a DPP-4 inhibitor or a GLP-1 receptor agonist has been shown to further improve glycemic control, while still maintaining beneficial effects on cardiometabolic parameters such as body weight and blood pressure...
July 2017: Clinical Diabetes: a Publication of the American Diabetes Association
Muhammad Abdul-Ghani, Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Curtis Triplitt, Ralph A DeFronzo
The objective of this study was to examine the effect of renal sodium-glucose cotransporter inhibition with empagliflozin on the fasting plasma glucose (FPG) concentration and β-cell function in subjects with impaired fasting glucose (IFG). Eight subjects with normal fasting glucose (NFG) and eight subjects with IFG received empagliflozin (25 mg/day) for 2 weeks. FPG concentration and β-cell function was measured with a nine-step hyperglycemic clamp before and 48 h and 14 days after the start of empagliflozin...
September 2017: Diabetes
Hussein Al-Jobori, Giuseppe Daniele, Eugenio Cersosimo, Curtis Triplitt, Rucha Mehta, Luke Norton, Ralph A DeFronzo, Muhammad Abdul-Ghani
Renal glucose reabsorption was measured with the stepped hyperglycemic clamp in 15 subjects with type 2 diabetes mellitus (T2DM) and 15 without diabetes after 2 days and after more chronic (14 days) treatment with empagliflozin. Patients with T2DM had significantly greater maximal renal glucose transport (TmG ) compared with subjects without diabetes at baseline (459 ± 53 vs. 337 ± 25 mg/min; P < 0.05). Empagliflozin treatment for 48 h reduced the TmG in both individuals with and without diabetes by 44 ± 7 and 53 ± 6%, respectively (both P < 0...
July 2017: Diabetes
Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Curtis Triplitt, Ralph A DeFronzo, Muhammad Abdul-Ghani
AIM: To examine metabolic factors that influence ketone production after sodium-glucose cotransport inhibitor (SGLT2) administration. RESEARCH DESIGN AND METHODS: Fasting plasma glucose (FPG), insulin, glucagon, free fatty acid and ketone concentrations were measured in 15 type 2 diabetes mellitus (T2DM) and 16 non-diabetic subjects before and at day 1 and day 14 after treatment with empagliflozin. RESULTS: Empagliflozin caused a 38 mg/dL reduction in FPG concentration in T2DM patients...
June 2017: Diabetes, Obesity & Metabolism
Amalia Gastaldelli, Melania Gaggini, Giuseppe Daniele, Demetrio Ciociaro, Eugenio Cersosimo, Devjit Tripathy, Curtis Triplitt, Peter Fox, Nicolas Musi, Ralph DeFronzo, Patricia Iozzo
Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1-RAs) act on multiple tissues, in addition to the pancreas. Recent studies suggest that GLP-1-RAs act on liver and adipose tissue to reduce insulin resistance (IR). Thus, we evaluated the acute effects of exenatide (EX) on hepatic (Hep-IR) and adipose (Adipo-IR) insulin resistance and glucose uptake. Fifteen male subjects (age = 56 ± 8 years; body mass index = 29 ± 1 kg/m2 ; A1c = 5.7 ± 0.1%) were studied on two occasions, with a double-blind subcutaneous injection of EX (5 μg) or placebo (PLC) 30 minutes before a 75-g oral glucose tolerance test (OGTT)...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Giuseppe Daniele, Patricia Iozzo, Marjorie Molina-Carrion, Jack Lancaster, Demetrio Ciociaro, Eugenio Cersosimo, Devjit Tripathy, Curtis Triplitt, Peter Fox, Nicolas Musi, Ralph DeFronzo, Amalia Gastaldelli
Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT)...
October 2015: Diabetes
M A Abdul-Ghani, C Puckett, C Triplitt, D Maggs, J Adams, E Cersosimo, R A DeFronzo
AIM: To test our hypothesis that initiating therapy with a combination of agents known to improve insulin secretion and insulin sensitivity in subjects with new-onset diabetes would produce greater, more durable reduction in glycated haemoglobin (HbA1c) levels, while avoiding hypoglycaemia and weight gain, compared with sequential addition of agents that lower plasma glucose but do not correct established pathophysiological abnormalities. METHODS: Drug-naïve, recently diagnosed subjects with type 2 diabetes mellitus (T2DM) were randomized in an open-fashion design in a single-centre study to metformin/pioglitazone/exenatide (triple therapy; n = 106) or an escalating dose of metformin followed by sequential addition of sulfonylurea and glargine insulin (conventional therapy; n = 115) to maintain HbA1c levels at <6...
March 2015: Diabetes, Obesity & Metabolism
Eugenio Cersosimo, Xiaojing Xu, Sikarin Upala, Curtis Triplitt, Nicolas Musi
UNLABELLED: Differential activation/deactivation of insulin signaling, PI-3K and MAP-K pathways by high glucose and palmitate, with/out the insulin sensitizer pioglitazone (PIO), have been previously shown in vascular smooth muscle cells (VSMCs). To determine the biological impact of these molecular changes, we examined VSMC migration and proliferation ("M"&"P") patterns in similar conditions. VSMCs from healthy human coronary arteries were incubated in growth medium and "M"&"P" were analyzed after exposure to high glucose (25 mmol/L) ± palmitate (200 μmol/L) and ± PIO (8 μmol/L) for 5 h...
August 1, 2014: Physiological Reports
Eugenio Cersosimo, Carolina Solis-Herrera, Curtis Triplitt
UNLABELLED: The importance of the kidney in glucose homeostasis has been recognized for many years. Recent observations indicating a greater role of renal glucose metabolism in various physiologic and pathologic conditions have rekindled the interest in renal glucose handling as a potential target for the treatment of diabetes. The enormous capacity of the proximal tubular cells to reabsorb the filtered glucose load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT-2), became the focus of attention...
January 2014: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
Eugenio Cersosimo, Carolina Solis-Herrera, Michael E Trautmann, Jaret Malloy, Curtis L Triplitt
Type 2 diabetes mellitus (T2DM) is characterized by a progressive failure of pancreatic β-cell function (BCF) with insulin resistance. Once insulin over-secretion can no longer compensate for the degree of insulin resistance, hyperglycemia becomes clinically significant and deterioration of residual β-cell reserve accelerates. This pathophysiology has important therapeutic implications. Ideally, therapy should address the underlying pathology and should be started early along the spectrum of decreasing glucose tolerance in order to prevent or slow β-cell failure and reverse insulin resistance...
January 2014: Current Diabetes Reviews
Sharon P Fowler, Sobha Puppala, Rector Arya, Geetha Chittoor, Vidya S Farook, Jennifer Schneider, Roy G Resendez, Ram Prasad Upadhayay, Jane Vandeberg, Kelly J Hunt, Benjamin Bradshaw, Eugenio Cersosimo, John L Vandeberg, Laura Almasy, Joanne E Curran, Anthony G Comuzzie, Donna M Lehman, Christopher P Jenkinson, Jane L Lynch, Ralph A Defronzo, John Blangero, Daniel E Hale, Ravindranath Duggirala
Pediatric metabolic syndrome (MS) and its cardiometabolic components (MSCs) have become increasingly prevalent, yet little is known about the genetics underlying MS risk in children. We examined the prevalence and genetics of MS-related traits among 670 non-diabetic Mexican American (MA) children and adolescents, aged 6-17 years (49 % female), who were participants in the San Antonio Family Assessment of Metabolic Risk Indicators in Youth study. These children are offspring or biological relatives of adult participants from three well-established Mexican American family studies in San Antonio, TX, at increased risk of type 2 diabetes...
September 2013: Human Genetics
Sara M Reyna, Puntip Tantiwong, Eugenio Cersosimo, Ralph A Defronzo, Apiradee Sriwijitkamol, Nicolas Musi
Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD). Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise...
2013: Journal of Diabetes Research
Carolina Solis-Herrera, Curtis Triplitt, Jose de Jesús Garduno-Garcia, John Adams, Ralph A DeFronzo, Eugenio Cersosimo
OBJECTIVE: To assess glucose-lowering mechanisms of sitagliptin (S), metformin (M), and the two combined (M+S). RESEARCH DESIGN AND METHODS: We randomized 16 patients with type 2 diabetes mellitus (T2DM) to four 6-week treatments with placebo (P), M, S, and M+S. After each period, subjects received a 6-h meal tolerance test (MTT) with [(14)C]glucose to calculate glucose kinetics. Fasting plasma glucose (FPG), fasting plasma insulin, C-peptide (insulin secretory rate [ISR]), fasting plasma glucagon, and bioactive glucagon-like peptide (GLP-1) and gastrointestinal insulinotropic peptide (GIP) were measured...
September 2013: Diabetes Care
Eugenio Cersosimo, Xiaojing Xu, Nicolas Musi
To investigate the role of insulin signaling pathways in migration, proliferation, and inflammation of vascular smooth muscle cells (VSMCs), we examined the expression of active components of the phosphatidyl inositol 3 (PI-3) kinase (p-Akt) and mitogen-activated protein kinase (MAPK) (p-Erk) in primary cultures of VSMCs from human coronary arteries. VSMCs were treated in a dose-response manner with insulin (0, 1, 10, and 100 nM) for 20 min, and Akt and Erk phosphorylation were measured by Western blot analysis...
February 15, 2012: American Journal of Physiology. Cell Physiology
Eugenio Cersosimo, Nicolas Musi
The prevalence of type 2 diabetes mellitus is higher in Hispanic/Latino individuals living in the United States compared with their non-Hispanic white counterparts. Many factors contribute to the increased prevalence of type 2 diabetes, including biological characteristics, socioeconomic conditions, and cultural aspects. The contribution of genetics to the risk of type 2 diabetes in Hispanic/Latino patients is becoming increasingly clear, but this inherent risk factor cannot be modified. However, certain socioeconomic and cultural factors, such as reduced access to healthcare, language barriers, cultural beliefs, and lack of cultural competence by the healthcare provider, are modifiable and should be overcome in order to improve the management of type 2 diabetes in Hispanic/Latino patients...
October 2011: American Journal of Medicine
Curtis Triplitt, Eugenio Cersosimo, Ralph A DeFronzo
Insulin resistance and islet (beta and alpha) cell dysfunction are major pathophysiologic abnormalities in type 2 diabetes mellitus (T2DM). Pioglitazone is a potent insulin sensitizer, improves pancreatic beta cell function and has been shown in several outcome trials to lower the risk of atherosclerotic and cardiovascular events. Glucagon-like peptide-1 deficiency/resistance contributes to islet cell dysfunction by impairing insulin secretion and increasing glucagon secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors improve pancreatic islet function by augmenting glucose-dependent insulin secretion and decreasing elevated plasma glucagon levels...
2010: Vascular Health and Risk Management
Puntip Tantiwong, Karthigayan Shanmugasundaram, Adriana Monroy, Sangeeta Ghosh, Mengyao Li, Ralph A DeFronzo, Eugenio Cersosimo, Apiradee Sriwijitkamol, Sumathy Mohan, Nicolas Musi
NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise...
November 2010: American Journal of Physiology. Endocrinology and Metabolism
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