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https://www.readbyqxmd.com/read/28637886/cardiovascular-disease-and-type-2-diabetes-has-the-dawn-of-a-new-era-arrived
#1
Muhammad Abdul-Ghani, Ralph A DeFronzo, Stefano Del Prato, Robert Chilton, Rajvir Singh, Robert E J Ryder
Hyperglycemia is the major risk factor for microvascular complications in patients with type 2 diabetes (T2D). However, cardiovascular disease (CVD) is the principal cause of death, and lowering HbA1c has only a modest effect on reducing CVD risk and mortality. The recently published LEADER and SUSTAIN-6 trials demonstrate that, in T2D patients with high CVD risk, the glucagon-like peptide 1 receptor agonists liraglutide and semaglutide reduce the primary major adverse cardiac events (MACE) end point (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) by 13% and 24%, respectively...
July 2017: Diabetes Care
https://www.readbyqxmd.com/read/28615237/erratum-combination-therapy-with-exenatide-plus-pioglitazone-versus-basal-bolus-insulin-in-patients-with-poorly-controlled-type-2-diabetes-on-sulfonylurea-plus-metformin-the-qatar-study-diabetes-care-2017-40-325-331
#2
Muhammad Abdul-Ghani, Osama Migahid, Ayman Megahed, John Adams, Curtis Triplitt, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi
No abstract text is available yet for this article.
June 14, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28611037/inhibition-of-renal-sodium-glucose-co-transport-with-empagliflozin-lowers-fasting-plasma-glucose-and-improves-beta-cell-function-in-subjects-with-impaired-fasting-glucose
#3
Muhammad Abdul-Ghani, Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Curtis Triplitt, Ralph A DeFronzo
To examine the effect of renal sodium glucose co-transporter inhibition with empagliflozin on the fasting plasma glucose concentration and beta cell function in subjects with impaired fasting glucose (IFG).8 subjects with normal fasting glucose and 8 subjects with IFG received empagliflozin (25 mg/day) for 2 weeks. Fasting plasma glucose concentration and beta cell function was measured with a 9-step hyperglycemic clamp before and 48 hours and 14 days after the start of empagliflozin.Empagliflozin caused 50±4 and 45±4 grams glucosuria on day 2 in IFG and NFG subjects, respectively, and the glucosuria was maintained for 2 weeks in both groups...
June 13, 2017: Diabetes
https://www.readbyqxmd.com/read/28516253/comparison-of-the-effects-of-three-different-baccaurea-angulata-whole-fruit-juice-doses-on-plasma-aorta-and-liver-mda-levels-antioxidant-enzymes-and-total-antioxidant-capacity
#4
Muhammad Ibrahim, Maryam Abimbola Mikail, Idris Adewale Ahmed, Norazlanshah Hazali, Mohammad Syaiful Bahari Abdul Rasad, Radiah Abdul Ghani, Ridzwan Hashim, Solachuddin Jahuari Arief, Muhammad Lokman Md Isa, Samsul Draman
PURPOSE: Baccaurea angulata (common names: belimbing dayak or belimbing hutan) is a Malaysian underutilized fruit. The preliminary work on B. angulata fruit juice showed that it possesses antioxidant properties. Therefore, further work is needed to confirm the efficacy and proper dosage of B. angulata as a potential natural antioxidant. The present study was thus carried out to compare the effects of three different B. angulata whole fruit (WF) juice doses administered at nutritional doses of 0...
May 17, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28477418/sodium-glucose-sglt-and-glucose-glut-transporter-expression-in-the-kidney-of-type-2-diabetic-subjects
#5
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/28428225/empagliflozin-and-kinetics-of-renal-glucose-transport-in-healthy-and-type-2-diabetic-individuals
#6
Hussein Al-Jobori, Giuseppe Daniele, Eugenio Cersosimo, Curtis Triplitt, Luke Norton, Ralph A DeFronzo, Muhammad Abdul-Ghani
Renal glucose reabsorption was measured with the stepped-hyperglycemic clamp in 15 T2DM and 15 non-diabetic subjects after 2 days and after more chronic (14 days) treatment with empagliflozin. T2DM patients had significantly greater maximal renal glucose transport (TmG) compared to nondiabetic subjects at baseline (459±53 vs 337±25 mg/min, p<0.05). Empagliflozin treatment for 48 hours reduced the TmG in both diabetic and non-diabetic individuals by 44±7% and 53±6%, respectively (both p<0.001). TmG was further reduced by empagliflozin in both groups on day 14 (by 65±5% and 75±3%, respectively)...
April 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28367184/identification-of-metabolic-risk-phenotypes-predisposing-to-non-alcoholic-fatty-liver-disease-in-a-pakistani-cohort
#7
Rizwana Abdul Ghani, Muhammad Saqlain, Muhammad Mobeen Zafar, Shagufta Jabeen, Syed Muhammad Saqlan Naqvi, Ghazala Kaukab Raja
OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) has emerged in the last two decades with worldwide prevalence of 25.24%. Due to its increasing frequency in Pakistan, it was aimed to identify disease predisposing metabolic risks and their association with NAFLD. METHODS: Anthropometric and biochemical investigations were collected from 1366 subjects with minor metabolic disturbances. Comparative analyses were performed to compute frequencies of common metabolic risk phenotypes while their associations with NAFLD were explored using regression analyses...
January 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28331967/decreased-basal-hepatic-glucose-uptake-in-impaired-fasting-glucose
#8
Mariam Alatrach, Christina Agyin, John Adams, Ralph A DeFronzo, Muhammad A Abdul-Ghani
AIMS/HYPOTHESIS: This research aimed to define the pathophysiological defects responsible for the elevated fasting plasma glucose (FPG) concentration and excessive rise in post-load plasma glucose observed in individuals with impaired fasting glucose (IFG). METHODS: We used tracer techniques to quantify basal splanchnic (primarily hepatic) glucose uptake and glucose fluxes following glucose ingestion in individuals with normal glucose tolerance (NGT; n = 10) and IFG (n = 10)...
March 22, 2017: Diabetologia
https://www.readbyqxmd.com/read/28324038/efficacy-of-exenatide-plus-pioglitazone-versus-basal-bolus-insulin-in-t2dm-patients-with-very-high-hba1c
#9
Muhammad Abdul-Ghani, Osama Mujahid, Ayman Mujahid, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi
Aim: To examine the efficacy and safety of combination therapy with exenatide plus pioglitazone versus basal-bolus insulin in poorly controlled type 2 diabetic patients with very high HbA1c (HbA1c>10%) on metformin plus sulfonylurea and long duration of disease. Research Design and Methods: 101 participants in Qatar Study with very poor glycemic control (HbA1c > 10%) and long duration of diabetes (10.9 years) on maximum/near-maximum doses of sulfonylurea plus metformin were randomized to receive: (i) pioglitazone plus weekly exenatide (Combination Therapy), or (ii) basal plus prandial insulin (Insulin Therapy) to maintain HbA1c <7...
February 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28128510/determinants-of-the-increase-in-ketone-concentration-during-sglt2-inhibition-in-ngt-ifg-and-t2dm-patients
#10
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
https://www.readbyqxmd.com/read/28096223/combination-therapy-with-exenatide-plus-pioglitazone-versus-basal-bolus-insulin-in-patients-with-poorly-controlled-type-2-diabetes-on-sulfonylurea-plus-metformin-the-qatar-study
#11
Muhammad Abdul-Ghani, Osama Migahid, Ayman Megahed, John Adams, Curtis Triplitt, Ralph A DeFronzo, Mahmoud Zirie, Amin Jayyousi
OBJECTIVE: The Qatar Study was designed to examine the efficacy of combination therapy with exenatide plus pioglitazone versus basal/bolus insulin in patients with long-standing poorly controlled type 2 diabetes mellitus (T2DM) on metformin plus a sulfonylurea. RESEARCH DESIGN AND METHODS: The study randomized 231 patients with poorly controlled (HbA1c >7.5%, 58 mmol/mol) T2DM on a sulfonylurea plus metformin to receive 1) pioglitazone plus weekly exenatide (combination therapy) or 2) basal plus prandial insulin (insulin therapy) to maintain HbA1c <7...
March 2017: Diabetes Care
https://www.readbyqxmd.com/read/27987376/pioglitazone-inhibits-mitochondrial-pyruvate-metabolism-and-glucose-production-in-hepatocytes
#12
Christopher E Shannon, Giuseppe Daniele, Cynthia Galindo, Muhammad A Abdul-Ghani, Ralph A DeFronzo, Luke Norton
Pioglitazone is used globally for the treatment of type 2 diabetes mellitus (T2DM) and is one of the most effective therapies for improving glucose homeostasis and insulin resistance in T2DM patients. However, its mechanism of action in the tissues and pathways that regulate glucose metabolism are incompletely defined. Here we investigated the direct effects of pioglitazone on hepatocellular pyruvate metabolism and the dependency of these observations on the purported regulators of mitochondrial pyruvate transport, MPC1 and MPC2...
February 2017: FEBS Journal
https://www.readbyqxmd.com/read/27941935/renal-metabolic-and-cardiovascular-considerations-of-sglt2-inhibition
#13
REVIEW
Ralph A DeFronzo, Luke Norton, Muhammad Abdul-Ghani
The kidney has a pivotal role in maintaining glucose homeostasis by using glucose as a metabolic fuel, by producing glucose through gluconeogenesis, and by reabsorbing all filtered glucose through the sodium-glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule. In patients with diabetes, the maximum glucose reabsorptive capacity (TmG) of the kidney, as well as the threshold for glucose spillage into the urine, are elevated, contributing to the pathogenesis of hyperglycaemia. By reducing the TmG and, more importantly, the threshold of glucosuria, SGLT2 inhibitors enhance glucose excretion, leading to a reduction in fasting and postprandial plasma glucose levels and improvements in both insulin secretion and insulin sensitivity...
January 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27561923/dapagliflozin-enhances-fat-oxidation-and-ketone-production-in-patients-with-type-2-diabetes
#14
Giuseppe Daniele, Juan Xiong, Carolina Solis-Herrera, Aurora Merovci, Roy Eldor, Devjit Tripathy, Ralph A DeFronzo, Luke Norton, Muhammad Abdul-Ghani
OBJECTIVE: Insulin resistance is associated with mitochondrial dysfunction and decreased ATP synthesis. Treatment of individuals with type 2 diabetes mellitus (T2DM) with sodium-glucose transporter 2 inhibitors (SGLT2i) improves insulin sensitivity. However, recent reports have demonstrated development of ketoacidosis in subjects with T2DM treated with SGLT2i. The current study examined the effect of improved insulin sensitivity with dapagliflozin on 1) mitochondrial ATP synthesis and 2) substrate oxidation rates and ketone production...
November 2016: Diabetes Care
https://www.readbyqxmd.com/read/27489336/discordance-between-central-brain-and-pancreatic-action-of-exenatide-in-lean-and-obese-subjects
#15
Roy Eldor, Giuseppe Daniele, Claudia Huerta, Mariam Al-Atrash, John Adams, Ralph DeFronzo, Timothy Duong, John Lancaster, Mahmoud Zirie, Amin Jayyousi, Muhammad Abdul-Ghani
OBJECTIVE: This study examined the effect of exenatide on brain activity measured by functional (f)MRI and on insulin secretion in lean and obese normal-glucose-tolerant individuals. RESEARCH DESIGN AND METHODS: The brain fMRI signal in response to high-calorie-content food pictures was measured with and without intravenous exenatide infusion in 10 lean and 10 obese healthy volunteers. Insulin secretion was measured with a two-step (+100 and +200 mg/dL) hyperglycemic clamp with exenatide and with saline infusion...
October 2016: Diabetes Care
https://www.readbyqxmd.com/read/27389083/prediabetes-and-risk-of-diabetes-and-associated-complications-impaired-fasting-glucose-versus-impaired-glucose-tolerance-does-it-matter
#16
Muhammad Abdul-Ghani, Ralph A DeFronzo, Amin Jayyousi
PURPOSE OF REVIEW: The purpose of this review is to summarize the distinct metabolic and pathophysiologic phenotype of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and the subsequent clinical implications with regard to future type 2 diabetes mellitus (T2DM) and cardiovascular risk. RECENT FINDINGS: Both IFG and IGT manifest the two core defects of T2DM, that is, insulin resistance and β-cell dysfunction. However, the site of insulin resistance and shape of β-cell dysfunction differ...
July 6, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/27208375/sglt2-inhibitors-and-cardiovascular-risk-lessons-learned-from-the-empa-reg-outcome-study
#17
Muhammad Abdul-Ghani, Stefano Del Prato, Robert Chilton, Ralph A DeFronzo
Although cardiovascular (CV) mortality is the principal cause of death in individuals with type 2 diabetes (T2DM), reduction of plasma glucose concentration has little effect on CV disease (CVD) risk. Thus, novel strategies to reduce CVD risk in T2DM patients are needed. The recently published BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) study demonstrated that in T2DM patients with high CVD risk empagliflozin reduced the primary major adverse cardiac event end point (CV death, nonfatal myocardial infarction, nonfatal stroke) by 14%...
May 2016: Diabetes Care
https://www.readbyqxmd.com/read/26919068/revitalization-of-pioglitazone-the-optimum-agent-to-be-combined-with-a-sodium-glucose-co-transporter-2-inhibitor
#18
REVIEW
R A DeFronzo, R Chilton, L Norton, G Clarke, R E J Ryder, M Abdul-Ghani
The recently completed EMPA-REG study showed that empagliflozin significantly decreased the major adverse cardiac events (MACE) endpoint, which comprised cardiovascular death, non-fatal myocardial infarction (MI) and stroke, in patients with high-risk type 2 diabetes (T2DM), primarily through a reduction in cardiovascular death, without a significant decrease in either MI or stroke. In the PROactive study, pioglitazone decreased the MACE endpoint by a similar degree to that observed in the EMPA-REG study, through a marked reduction in both recurrent MI and stroke and a modest reduction in cardiovascular death...
May 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/26826924/diverted-sleeve-gastrectomy-with-ileal-transposition-in-overweight-obese-and-morbidly-obese-patients-with-type-2-diabetes-results-of-1-year-follow-up
#19
Alper Celik, Eylem Cagiltay, Surendra Ugale, Muharrem Asci, Bahri Onur Celik, Can Karaca, Muhammad Abdul-Ghani
BACKGROUND: Bariatric surgery is an effective intervention for morbidly obese individuals, and it normalizes the level of glycemia in the majority of patients with type 2 diabetes mellitus (T2DM). OBJECTIVES: The primary aim of the study was to examine the efficacy of diverted sleeve gastrectomy with ileal transposition on weight loss and glycemic control in overweight, obese, and morbidly obese T2DM patients. The secondary aim was to examine the relationship between the effect of surgery and body mass index (BMI)...
March 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/26765576/effect-of-dapagliflozin-with-and-without-acipimox-on-insulin-sensitivity-and-insulin-secretion-in-t2dm-males
#20
Aurora Merovci, Muhammad Abdul-Ghani, Andrea Mari, Carolina Solis-Herrera, Juan Xiong, Giuseppe Daniele, Devjit Tripathy, Ralph A DeFronzo
AIM: To investigate the effect of lowering the plasma glucose and free fatty acid (FFA) concentrations with dapagliflozin and acipimox, respectively, on insulin sensitivity and insulin secretion in T2DM individuals. METHODS: Fourteen male T2DM patients received an oral glucose tolerance test and euglycemic hyperinsulinemic clamp at baseline and were treated for 3 weeks with dapagliflozin (10 mg per day). During week 3, acipimox (250 mg four times per day) treatment was added to dapagliflozin...
March 2016: Journal of Clinical Endocrinology and Metabolism
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