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REVIEW
Yehuda Handelsman, Javed Butler, George L Bakris, Ralph A DeFronzo, Gregg C Fonarow, Jennifer B Green, George Grunberger, James L Januzzi, Samuel Klein, Pamela R Kushner, Darren K McGuire, Erin D Michos, Javier Morales, Richard E Pratley, Matthew R Weir, Eugene Wright, Vivian A Fonseca
Increasing rates of obesity and diabetes have driven corresponding increases in related cardiorenal and metabolic diseases. In many patients, these conditions occur together, further increasing morbidity and mortality risks to the individual. Yet all too often, the risk factors for these disorders are not addressed promptly in clinical practice, leading to irreversible pathologic progression. To address this gap, we convened a Task Force of experts in cardiology, nephrology, endocrinology, and primary care to develop recommendations for early identification and intervention in obesity, diabetes, and other cardiorenal and metabolic diseases...
February 2023: Journal of Diabetes and its Complications
#22
JOURNAL ARTICLE
Alexander J Moody, Marjorie Molina-Wilkins, Geoffrey D Clarke, Aurora Merovci, Carolina Solis-Herrera, Eugenio Cersosimo, Robert J Chilton, Patricia Iozzo, Amalia Gastaldelli, Muhammad Abdul-Ghani, Ralph A DeFronzo
AIMS: To examine the effect of pioglitazone on epicardial (EAT) and paracardial adipose tissue (PAT) and measures of diastolic function and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). METHODS: Twelve patients with T2DM without clinically manifest cardiovascular disease and 12 subjects with normal glucose tolerance (NGT) underwent cardiac magnetic resonance imaging to quantitate EAT and PAT and diastolic function before and after pioglitazone treatment for 24 weeks...
February 2023: Diabetes, Obesity & Metabolism
#23
JOURNAL ARTICLE
Eithan Kotkowski, Larry R Price, Ralph A DeFronzo, Crystal G Franklin, Maximino Salazar, Amy S Garrett, Mary Woolsey, John Blangero, Ravindranath Duggirala, David C Glahn, Peter T Fox
Introduction: This project aimed to investigate the association between biometric components of metabolic syndrome (MetS) with gray matter volume (GMV) obtained with magnetic resonance imaging (MRI) from a large cohort of community-based adults ( n = 776) subdivided by age and sex and employing brain regions of interest defined previously as the "Neural Signature of MetS" (NS-MetS). Methods: Lipid profiles, biometrics, and regional brain GMV were obtained from the Genetics of Brain Structure (GOBS) image archive...
2022: Frontiers in Aging Neuroscience
#24
JOURNAL ARTICLE
Anthony H Cincotta, Eugenio Cersosimo, Mariam Alatrach, Michael Ezrokhi, Christina Agyin, John Adams, Robert Chilton, Curtis Triplitt, Bindu Chamarthi, Nicholas Cominos, Ralph A DeFronzo
Bromocriptine-QR is a sympatholytic dopamine D2 agonist for the treatment of type 2 diabetes that has demonstrated rapid (within 1 year) substantial reductions in adverse cardiovascular events in this population by as yet incompletely delineated mechanisms. However, a chronic state of elevated sympathetic nervous system activity and central hypodopaminergic function has been demonstrated to potentiate an immune system pro-oxidative/pro-inflammatory condition and this immune phenotype is known to contribute significantly to the advancement of cardiovascular disease (CVD)...
August 9, 2022: International Journal of Molecular Sciences
#25
Lawrence Blonde, Guillermo E Umpierrez, S Sethu Reddy, Janet B McGill, Sarah L Berga, Michael Bush, Suchitra Chandrasekaran, Ralph A DeFronzo, Daniel Einhorn, Rodolfo J Galindo, Thomas W Gardner, Rajesh Garg, W Timothy Garvey, Irl B Hirsch, Daniel L Hurley, Kenneth Izuora, Mikhail Kosiborod, Darin Olson, Shailendra B Patel, Rodica Pop-Busui, Archana R Sadhu, Susan L Samson, Carla Stec, William V Tamborlane, Katherine R Tuttle, Christine Twining, Adrian Vella, Priyathama Vellanki, Sandra L Weber
OBJECTIVE: The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS: The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022...
October 2022: Endocrine Practice
#26
JOURNAL ARTICLE
Marzieh Salehi, Ralph DeFronzo, Amalia Gastaldelli
Background : The liver has the capacity to regulate glucose metabolism by altering the insulin clearance rate (ICR). The decreased fasting insulin concentrations and enhanced prandial hyperinsulinemia after Roux-en-Y gastric-bypass (GB) surgery and sleeve gastrectomy (SG) are well documented. Here, we investigated the effect of GB or SG on insulin kinetics in the fasting and fed states. Method : ICR was measured (i) during a mixed-meal test (MMT) in obese non-diabetic GB (n = 9) and SG (n = 7) subjects and (ii) during a MMT combined with a hyperinsulinemic hypoglycemic clamp in the same GB and SG subjects...
July 11, 2022: International Journal of Molecular Sciences
#27
RANDOMIZED CONTROLLED TRIAL
Ricardo J Samms, Christine C Cheng, Marcel Fourcaudot, Sami Heikkinen, Ahmed Khattab, John Adams, Eugenio Cersosimo, Curtis Triplitt, Curtis Puckett, Kostas Tsintzas, Andrew C Adams, Muhammad A Abdul-Ghani, Ralph A DeFronzo, Luke Norton
Fibroblast growth factor 21 (FGF21) is increased acutely by carbohydrate ingestion and is elevated in patients with type 2 diabetes (T2D). However, the physiological significance of increased FGF21 in humans remains largely unknown. We examined whether FGF21 contributed to the metabolic improvements observed following treatment of patients with T2D with either triple (metformin/pioglitazone/exenatide) or conventional (metformin/insulin/glipizide) therapy for 3 yr. Forty-six patients with T2D were randomized to receive either triple or conventional therapy to maintain HbA1c < 6...
August 1, 2022: American Journal of Physiology. Endocrinology and Metabolism
#28
JOURNAL ARTICLE
Christopher E Shannon, Aurora Merovci, Marcel Fourcaudot, Devjit Tripathy, Muhammad Abdul-Ghani, Hu Wang, Xianlin Han, Luke Norton, Ralph A DeFronzo
CONTEXT: Sustained increases in plasma glucose promote skeletal muscle insulin resistance independent from obesity and dyslipidemia (ie, glucotoxicity). Skeletal muscle lipids are key molecular determinants of insulin action, yet their involvement in the development of glucotoxicity is unclear. OBJECTIVE: To explore the impact of mild physiologic hyperglycemia on skeletal muscle lipids. DESIGN: Single group pretest-posttest. PARTICIPANTS: Healthy males and females with normal glucose tolerance...
July 14, 2022: Journal of Clinical Endocrinology and Metabolism
#29
JOURNAL ARTICLE
Marzieh Salehi, Amalia Gastaldelli, Ralph DeFronzo
AIMS/HYPOTHESIS: Roux-en Y gastric bypass surgery (GB) and sleeve gastrectomy (SG) alter prandial glucose metabolism, producing lower nadir glucose values and predisposing susceptible individuals to prandial hypoglycemia. The glycemic phenotype of GB or SG is associated with prandial hyperinsulinemia and hyperglucagonemia along with an increased influx of ingested glucose. Following insulin-induced hypoglycemia, glucagon is the most important stimulus for hepatic glucose production (HGP)...
June 2022: Metabolism: Clinical and Experimental
#30
REVIEW
Luke Norton, Chris Shannon, Amalia Gastaldelli, Ralph A DeFronzo
Insulin is the master regulator of glucose, lipid, and protein metabolism. Following ingestion of an oral glucose load or mixed meal, the plasma glucose concentration rises, insulin secretion by the beta cells is stimulated and the hyperinsulinemia, working in concert with hyperglycemia, causes: (i) suppression of endogenous (primarily reflects hepatic) glucose production, (ii) stimulation of glucose uptake by muscle, liver, and adipocytes, (iii) inhibition of lipolysis leading to a decline in plasma FFA concentration which contributes to the suppression of hepatic glucose production and augmentation of muscle glucose uptake, and (iv) vasodilation in muscle, which contributes to enhanced muscle glucose disposal...
April 2022: Metabolism: Clinical and Experimental
#31
JOURNAL ARTICLE
Olga Lavynenko, Muhammad Abdul-Ghani, Mariam Alatrach, Curtiss Puckett, John Adams, Siham Abdelgani, Naim Alkhouri, Curtis Triplitt, Geoffrey D Clarke, Juan A Vasquez, Jinqi Li, Eugenio Cersosimo, Amalia Gastaldelli, Ralph A DeFronzo
AIM: To compare the efficacy of triple therapy (metformin/exenatide/pioglitazone) versus stepwise conventional therapy (metformin → glipizide → glargine insulin) on liver fat content and hepatic fibrosis in newly diagnosed, drug-naïve patients with type 2 diabetes. METHODS: Sixty-eight patients completed the 6-year follow-up and had an end-of-study (EOS) FibroScan to provide measures of steatosis (controlled attenuation parameter [CAP] in dB/m) and fibrosis (liver stiffness measurement [LSM] in kPa); 59 had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to measure liver fat...
May 2022: Diabetes, Obesity & Metabolism
#32
JOURNAL ARTICLE
George Hindy, Peter Dornbos, Mark D Chaffin, Dajiang J Liu, Minxian Wang, Margaret Sunitha Selvaraj, David Zhang, Joseph Park, Carlos A Aguilar-Salinas, Lucinda Antonacci-Fulton, Diego Ardissino, Donna K Arnett, Stella Aslibekyan, Gil Atzmon, Christie M Ballantyne, Francisco Barajas-Olmos, Nir Barzilai, Lewis C Becker, Lawrence F Bielak, Joshua C Bis, John Blangero, Eric Boerwinkle, Lori L Bonnycastle, Erwin Bottinger, Donald W Bowden, Matthew J Bown, Jennifer A Brody, Jai G Broome, Noël P Burtt, Brian E Cade, Federico Centeno-Cruz, Edmund Chan, Yi-Cheng Chang, Yii-Der I Chen, Ching-Yu Cheng, Won Jung Choi, Rajiv Chowdhury, Cecilia Contreras-Cubas, Emilio J Córdova, Adolfo Correa, L Adrienne Cupples, Joanne E Curran, John Danesh, Paul S de Vries, Ralph A DeFronzo, Harsha Doddapaneni, Ravindranath Duggirala, Susan K Dutcher, Patrick T Ellinor, Leslie S Emery, Jose C Florez, Myriam Fornage, Barry I Freedman, Valentin Fuster, Ma Eugenia Garay-Sevilla, Humberto García-Ortiz, Soren Germer, Richard A Gibbs, Christian Gieger, Benjamin Glaser, Clicerio Gonzalez, Maria Elena Gonzalez-Villalpando, Mariaelisa Graff, Sarah E Graham, Niels Grarup, Leif C Groop, Xiuqing Guo, Namrata Gupta, Sohee Han, Craig L Hanis, Torben Hansen, Jiang He, Nancy L Heard-Costa, Yi-Jen Hung, Mi Yeong Hwang, Marguerite R Irvin, Sergio Islas-Andrade, Gail P Jarvik, Hyun Min Kang, Sharon L R Kardia, Tanika Kelly, Eimear E Kenny, Alyna T Khan, Bong-Jo Kim, Ryan W Kim, Young Jin Kim, Heikki A Koistinen, Charles Kooperberg, Johanna Kuusisto, Soo Heon Kwak, Markku Laakso, Leslie A Lange, Jiwon Lee, Juyoung Lee, Seonwook Lee, Donna M Lehman, Rozenn N Lemaitre, Allan Linneberg, Jianjun Liu, Ruth J F Loos, Steven A Lubitz, Valeriya Lyssenko, Ronald C W Ma, Lisa Warsinger Martin, Angélica Martínez-Hernández, Rasika A Mathias, Stephen T McGarvey, Ruth McPherson, James B Meigs, Thomas Meitinger, Olle Melander, Elvia Mendoza-Caamal, Ginger A Metcalf, Xuenan Mi, Karen L Mohlke, May E Montasser, Jee-Young Moon, Hortensia Moreno-Macías, Alanna C Morrison, Donna M Muzny, Sarah C Nelson, Peter M Nilsson, Jeffrey R O'Connell, Marju Orho-Melander, Lorena Orozco, Colin N A Palmer, Nicholette D Palmer, Cheol Joo Park, Kyong Soo Park, Oluf Pedersen, Juan M Peralta, Patricia A Peyser, Wendy S Post, Michael Preuss, Bruce M Psaty, Qibin Qi, D C Rao, Susan Redline, Alexander P Reiner, Cristina Revilla-Monsalve, Stephen S Rich, Nilesh Samani, Heribert Schunkert, Claudia Schurmann, Daekwan Seo, Jeong-Sun Seo, Xueling Sim, Rob Sladek, Kerrin S Small, Wing Yee So, Adrienne M Stilp, E Shyong Tai, Claudia H T Tam, Kent D Taylor, Yik Ying Teo, Farook Thameem, Brian Tomlinson, Michael Y Tsai, Tiinamaija Tuomi, Jaakko Tuomilehto, Teresa Tusié-Luna, Miriam S Udler, Rob M van Dam, Ramachandran S Vasan, Karine A Viaud Martinez, Fei Fei Wang, Xuzhi Wang, Hugh Watkins, Daniel E Weeks, James G Wilson, Daniel R Witte, Tien-Yin Wong, Lisa R Yanek, Sekar Kathiresan, Daniel J Rader, Jerome I Rotter, Michael Boehnke, Mark I McCarthy, Cristen J Willer, Pradeep Natarajan, Jason A Flannick, Amit V Khera, Gina M Peloso
Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples...
January 6, 2022: American Journal of Human Genetics
#33
JOURNAL ARTICLE
Juan P Palavicini, Alberto Chavez-Velazquez, Marcel Fourcaudot, Devjit Tripathy, Meixia Pan, Luke Norton, Ralph A DeFronzo, Christopher E Shannon
The insulin-sensitizer pioglitazone exerts its cardiometabolic benefits in type 2 diabetes (T2D) through a redistribution of body fat, from ectopic and visceral areas to subcutaneous adipose depots. Whereas excessive weight gain and lipid storage in obesity promotes insulin resistance and chronic inflammation, the expansion of subcutaneous adipose by pioglitazone is associated with a reversal of these immunometabolic deficits. The precise events driving this beneficial remodeling of adipose tissue with pioglitazone remain unclear, and whether insulin-sensitizers alter the lipidomic composition of human adipose has not previously been investigated...
2021: Frontiers in Physiology
#34
REVIEW
Yehuda Handelsman, John E Anderson, George L Bakris, Christie M Ballantyne, Joshua A Beckman, Deepak L Bhatt, Zachary T Bloomgarden, Biykem Bozkurt, Matthew J Budoff, Javed Butler, Samuel Dagogo-Jack, Ian H de Boer, Ralph A DeFronzo, Robert H Eckel, Daniel Einhorn, Vivian A Fonseca, Jennifer B Green, George Grunberger, Chris Guerin, Silvio E Inzucchi, Paul S Jellinger, Mikhail N Kosiborod, Pamela Kushner, Norman Lepor, Christian W Mende, Erin D Michos, Jorge Plutzky, Pam R Taub, Guillermo E Umpierrez, Muthiah Vaduganathan, Matthew R Weir
Type 2 diabetes (T2D), chronic kidney disease (CKD), atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF)-along with their associated risk factors-have overlapping etiologies, and two or more of these conditions frequently occur in the same patient. Many recent cardiovascular outcome trials (CVOTs) have demonstrated the benefits of agents originally developed to control T2D, ASCVD, or CKD risk factors, and these agents have transcended their primary indications to confer benefits across a range of conditions...
February 2022: Journal of Diabetes and its Complications
#35
JOURNAL ARTICLE
Ralph A DeFronzo, Muhammad Abdul-Ghani
Diabetic kidney disease (DKD) accounts for about half of individuals entering end-stage renal disease programs. Patients with DKD frequently have associated microvascular complications and are at very high risk for developing macrovascular complications. Comprehensive treatment involves slowing or preventing the decline in glomerular filtration rate (GFR) and preventing macrovascular and further microvascular complications. Maintaining an A1C <6.5% represents primary prevention; in established DKD, tight blood pressure control is essential...
August 2021: Diabetes Spectrum: a Publication of the American Diabetes Association
#36
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
August 2021: Diabetes Spectrum: a Publication of the American Diabetes Association
#37
JOURNAL ARTICLE
Ralph A DeFronzo, Guest Editor
No abstract text is available yet for this article.
August 2021: Diabetes Spectrum: a Publication of the American Diabetes Association
#38
JOURNAL ARTICLE
Muhammad Abdul-Ghani, Ralph A DeFronzo
INTRODUCTION: Cluster analysis has identified distinct groups of type 2 diabetes (T2D) subjects with distinct metabolic characteristics. Thus, personalizing pharmacologic therapy to individual phenotypic and pathophysiologic characteristics has potential to improve metabolic control and reduce risk of microvascular and macrovascular complications. AREAS COVERED: The authors review the classification of T2D, genetic markers, pathophysiology and natural history of T2D, the ABCDE approach to therapy, the ADA/EASD stepwise approach to therapy, available antidiabetic agents, and provide a more rational therapeutic approach based upon pathophysiology and cardiovascular and renal outcome trials...
November 2021: Expert Opinion on Pharmacotherapy
#39
JOURNAL ARTICLE
Chao Zhang, Shuyuan Chen, Qunying Li, Jiao Wu, Fuqiang Qiu, Zhiyi Chen, Yang Sun, Jieli Luo, Raul A Bastarrachea, Paul A Grayburn, Ralph A DeFronzo, Yajing Liu, Kun Qian, Pintong Huang
Ultrasound-targeted microbubble destruction (UTMD) mediates gene transfection with high biosafety and thus has been promising toward treatment of type 1 diabetes. However, the potential application of UTMD in type 2 diabetes (T2D) is still limited, due to the lack of systematic design and dynamic monitoring. Herein, an efficient gene delivery system is constructed by plasmid deoxyribonucleic acid (DNA) encoding glucagon-like peptide 1 (GLP-1) in ultrasound-induced microbubbles, toward treatment of T2D in macaque...
August 2021: Small
#40
JOURNAL ARTICLE
Jiyoon Ryu, Jason T Hadley, Zhi Li, Feng Dong, Huan Xu, Xiaoban Xin, Ye Zhang, Cang Chen, Senlin Li, Xiaoning Guo, Jared L Zhao, Robin J Leach, Muhammad A Abdul-Ghani, Ralph A DeFronzo, Amrita Kamat, Feng Liu, Lily Q Dong
Adiponectin is an adipokine that exerts insulin-sensitizing and anti-inflammatory roles in insulin target tissues including liver. While the insulin-sensitizing function of adiponectin has been extensively investigated, the precise mechanism by which adiponectin alleviates diet-induced hepatic inflammation remains elusive. Here, we report that hepatocyte-specific knockout (KO) of the adaptor protein APPL2 enhanced adiponectin sensitivity and prevented mice from developing high-fat diet-induced inflammation, insulin resistance, and glucose intolerance, although it caused fatty liver...
June 2021: Diabetes
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