Type 2 diabetes mellitus

DeFronzo, Ralph A.; Ferrannini, Ele; Groop, Leif; Henry, Robert R.; Herman, William H.; Holst, Jens Juul; Hu, Frank B.; Kahn, C. Ronald; Raz, Itamar; Shulman, Gerald I.; Simonson, Donald C.; Testa, Marcia A.; Weiss, Ram

doi:10.1038/nrdp.2015.19

Cited by 2,611Diabetes Treatment and ManagementDiabetes, Cardiovascular Risks, and LipoproteinsDiabetes Management and Research

Type 2 diabetes mellitus

DeFronzo, Ralph A., Ferrannini, Ele, Groop, Leif, Henry, Robert R., Herman, William H., Holst, Jens Juul, Hu, Frank B., Kahn, C. Ronald +5 more·2015·Nature Reviews Disease Primers

DOI 10.1038/nrdp.2015.19

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Abstract

Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN.

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The systemic low-grade proinflammatory state that accompanies obesity contributes in part to insulin resistance in skeletal muscle and liver.
“the hallmark systemic low-grade proinflammatory state that accompanies obesity has been described to contribute in part to insulin resistance in skeletal muscle (SkM) and in the liver”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [20]
Proinflammatory cytokines such as TNF-α and IL-1β exacerbate insulin resistance, while anti-inflammatory cytokines such as IL-4 and IL-10 promote insulin sensitivity.
“Proinflammatory cytokines such as TNF-α and IL-1β exacerbate insulin resistance [20], while anti-inflammatory cytokines such as IL-4 and IL-10 promote insulin sensitivity [248].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [20]
M1 macrophages secrete TNF-α, IL-1β, IL-6, and chemokines that promote the influx of activated CD4+ Th1 cells.
“M1 macrophages secrete TNF-α, IL-1β, IL-6, and chemokines that promote the influx of activated CD4+ Th1 cells [14,20,239,248].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [20]
Type 2 diabetes mellitus is a complex chronic disorder highly prominent in older people, characterized by chronic increase in blood glucose levels, impaired insulin secretion by pancreatic β-cells, and insulin resistance.
“T2DM is a complex chronic disorder highly prominent in older people, characterized by the chronic increase in blood glucose levels, impaired insulin secretion by pancreatic β-cells, and insulin resistance (DeFronzo et al., 2015).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as DeFronzo et al., 2015

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Effects of an Engineered Human Anti–TNF-α Antibody (CDP571) on Insulin Sensitivity and Glycemic Control in Patients With NIDDM
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Insulin in the Brain: Its Pathophysiological Implications for States Related with Central Insulin Resistance, Type 2 Diabetes and Alzheimer’s Disease
Blázquez, E., Velázquez, E., Hurtado-Carneiro, V., & Ruiz-Albusac, J. M. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00161 · Cited by 502 · see citing works
Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies.
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Pancreatic safety of incretin-based drugs–FDA and EMA assessment
Egan, A. G., Blind, E., Dunder, K., de Graeff, P. A., Hummer, B. T., Bourcier, T., & Rosebraugh, C. (2014) · New England Journal of Medicine · doi:10.1056/nejmp1314078 · Cited by 498 · see citing works
Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease
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Preventive Foot Care in People With Diabetes
Mayfield, J. A., Reiber, G. E., Sanders, L. J., Janisse, D. J., & POGACH, L. M. (1998) · Diabetes Care · doi:10.2337/diacare.21.12.2161 · Cited by 495 · see citing works
Loss-of-function mutations in SLC30A8 protect against type 2 diabetes
Go-T2D Consortium, Flannick, J., T2D-GENES Consortium, Thorleifsson, G., Beer, N. L., Jacobs, S. B. R., Grarup, N., Burtt, N. P., Mahajan, A., Fuchsberger, C., et al. (2014) · Nature Genetics · doi:10.1038/ng.2915 · Cited by 492 · see citing works
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Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss
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Prevention of Type 2 Diabetes With Troglitazone in the Diabetes Prevention Program
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Development and Progression of Renal Disease in Pima Indians with Non-Insulin-Dependent Diabetes Mellitus
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Long-Term Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Receiving High Doses of Insulin
Wilding, J. P. H., Woo, V., Soler, N. G., Pahor, A., Sugg, J., Rohwedder, K., Parikh, S., & for the Dapagliflozin 006 Study Group* (2012) · Annals of Internal Medicine · doi:10.7326/0003-4819-156-6-201203200-00003 · Cited by 469 · see citing works
Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals
Boden, G., Duan, X., Homko, C., Molina, E. J., Song, W., Perez, O., Cheung, P., & Merali, S. (2008) · Diabetes · doi:10.2337/db08-0604 · Cited by 468 · see citing works
Meta-analysis: The Effect of Dietary Counseling for Weight Loss
Dansinger, M. L., Tatsioni, A., Wong, J. B., Chung, M., & Balk, E. M. (2007) · Annals of Internal Medicine · doi:10.7326/0003-4819-147-1-200707030-00007 · Cited by 467 · see citing works
Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?
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Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus
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Main Risk Factors for Nephropathy in Type 2 Diabetes Mellitus Are Plasma Cholesterol Levels, Mean Blood Pressure, and Hyperglycemia
Ravid, M., Brosh, D., Ravid-Safran, D., Levy, Z., & Rachmani, R. (1998) · Archives of Internal Medicine · doi:10.1001/archinte.158.9.998 · Cited by 449 · see citing works
Role of Sodium-Glucose Cotransporter 2 (SGLT 2) Inhibitors in the Treatment of Type 2 Diabetes
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The PROMIS Physical Function item bank was calibrated to a standardized metric and shown to improve measurement efficiency
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New insights into the pathophysiology of dyslipidemia in type 2 diabetes
Taskinen, M.-R., & Borén, J. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.01.039 · Cited by 440 · see citing works
The Bedford Survey: Ten year mortality rates in newly diagnosed diabetics, borderline diabetics and normoglycaemic controls and risk indices for coronary heart disease in borderline diabetics
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Loss of the Tuberous Sclerosis Complex Tumor Suppressors Triggers the Unfolded Protein Response to Regulate Insulin Signaling and Apoptosis
Özcan, U., Özcan, L., Yılmaz, E., Düvel, K., Şahin, M., Manning, B. D., & Hotamışlıgil, G. S. (2008) · Molecular Cell · doi:10.1016/j.molcel.2007.12.023 · Cited by 434 · see citing works
Tumor Necrosis Factor α Produces Insulin Resistance in Skeletal Muscle by Activation of Inhibitor κB Kinase in a p38 MAPK-dependent Manner
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Health Economic Benefits and Quality of Life During Improved Glycemic Control in Patients With Type 2 Diabetes Mellitus
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Role of diacylglycerol activation of PKCθ in lipid-induced muscle insulin resistance in humans
Szendroedi, J., Yoshimura, T., Phielix, E., Koliaki, C., Marcucci, M., Zhang, D., Jelenik, T., Müller, J., Herder, C., Nowotny, P., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409229111 · Cited by 415 · see citing works
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Use of Dermagraft, a Cultured Human Dermis, to Treat Diabetic Foot Ulcers
Gentzkow, G. D., Iwasaki, S. D., Hershon, K. S., Mengel, M. C., Prendergast, J. J., Ricotta, J. J., Steed, D. P., & Lipkin, S. (1996) · Diabetes Care · doi:10.2337/diacare.19.4.350 · Cited by 414 · see citing works
The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients
Marchetti, P., Bugliani, M., Lupi, R., Marselli, L., Masini, M., Boggi, U., Filipponi, F., Weir, G. C., Eizirik, D. L., & Cnop, M. (2007) · Diabetologia · doi:10.1007/s00125-007-0816-8 · Cited by 413 · see citing works
Association of Hypoglycemia and Cardiac Ischemia
Desouza, C., Salazar, H., Cheong, B., Murgo, J., & Fonseca, V. (2003) · Diabetes Care · doi:10.2337/diacare.26.5.1485 · Cited by 406 · see citing works
Antioxidant status in patients with uncomplicated insulin‐dependent and non‐insulin‐dependent diabetes mellitus
Maxwell, S. R. J., Thomason, H., Sandler, D., Leguen, C., Baxter, M. A., Thorpe, G. H. G., Jones, A. F., & Barnett, A. H. (1997) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1997.1390687.x · Cited by 404 · see citing works
Identification of Adipose Tissue Dendritic Cells Correlated With Obesity-Associated Insulin-Resistance and Inducing Th17 Responses in Mice and Patients
Bertola, A., Ciucci, T., Rousseau, D., Bourlier, V., Duffaut, C., Bonnafous, S., Blin‐Wakkach, C., Anty, R., Iannelli, A., Gugenheim, J., et al. (2012) · Diabetes · doi:10.2337/db11-1274 · Cited by 403 · see citing works
Effect of Pioglitazone on Pancreatic β-Cell Function and Diabetes Risk in Hispanic Women With Prior Gestational Diabetes
Xiang, A. H., Peters, R. K., Kjos, S. L., Marroquin, A., Goico, J., Ochoa, C., Kawakubo, M., & Buchanan, T. A. (2006) · Diabetes · doi:10.2337/diabetes.55.02.06.db05-1066 · Cited by 402 · see citing works
Metabolic Consequences of a Family History of NIDDM (The Botnia Study): Evidence for Sex-Specific Parental Effects
Groop, L., Forsblom, C. M., Lehtovirta, M., Tuomi, T., Karanko, S., Nissén, M., Ehrnstrom, B. O., Forsén, B., Isomaa, B., Snickars, B., et al. (1996) · Diabetes · doi:10.2337/diab.45.11.1585 · Cited by 384 · see citing works
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Metabolic Syndrome, Insulin Resistance, and Roles of Inflammation – Mechanisms and Therapeutic Targets
Romeo, G. R., Lee, J., & Shoelson, S. E. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.241869 · Cited by 384 · see citing works
Suppression of Diacylglycerol Acyltransferase-2 (DGAT2), but Not DGAT1, with Antisense Oligonucleotides Reverses Diet-induced Hepatic Steatosis and Insulin Resistance
Choi, C. S., Savage, D. B., Kulkarni, A., Yu, X. X., Liu, Z.-X., Morino, K., Kim, S., Distefano, A., Samuel, V. T., Neschen, S., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704213200 · Cited by 383 · see citing works
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Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis
Eng, C., Kramer, C. K., Zinman, B., & Retnakaran, R. R. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61335-0 · Cited by 381 · see citing works
Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients
Krook, A., Björnholm, M., Galuska, D., Jiang, X. J., Fahlman, R., Myers, M. G., Wallberg-Henriksson, H., & Zierath, J. R. (2000) · Diabetes · doi:10.2337/diabetes.49.2.284 · Cited by 375 · see citing works
Pancreatic Safety of Incretin-Based Drugs — FDA and EMA Assessment
(2014) · New England Journal of Medicine · doi:10.1056/nejmx140026 · Cited by 372 · see citing works
Attenuation of leptin and insulin signaling by SOCS proteins
Howard, J. K., & Flier, J. S. (2006) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2006.09.007 · Cited by 371 · see citing works
Predictors of and Longitudinal Changes in Insulin Sensitivity and Secretion Preceding Onset of Type 2 Diabetes
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Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes
Gough, S. C. L., Bode, B. W., Woo, V. C., Rodbard, H. W., Linjawi, S., Poulsen, P., Damgaard, L. H., & Buse, J. B. (2014) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(14)70174-3 · Cited by 367 · see citing works
Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance
Liu, L., Zhang, Y., Chen, N., Shi, X., Tsang, B., & Yu, Y.-H. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30565 · Cited by 356 · see citing works
Structural and Functional Abnormalities in the Islets Isolated From Type 2 Diabetic Subjects
Deng, S., Vatamaniuk, M. Z., Huang, X., Doliba, N. M., Lian, M.-M., Frank, A. M., Velidedeoğlu, E., Desai, N. M., Koeberlein, B., Wolf, B. A., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.3.624 · Cited by 346 · see citing works

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2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension: Endorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA)
Mancia, G., Kreutz, R., Brunström, M., Burnier, M., Grassi, G., Januszewicz, A., Muiesan, M. L., Tsioufis, K., Agabiti-Rosei, E., Algharably, E. A. E., et al. (2023) · Journal of Hypertension · doi:10.1097/hjh.0000000000003480 · Cited by 3,473 · see citing works
Gestational diabetes mellitus
McIntyre, H. D., Catalano, P., Zhang, C., Desoye, G., Mathiesen, E. R., & Damm, P. (2019) · Nature Reviews Disease Primers · doi:10.1038/s41572-019-0098-8 · Cited by 1,850 · see citing works
The PI3K/AKT Pathway in Obesity and Type 2 Diabetes
Huang, X., Liu, G., Guo, J., & Su, Z. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.27173 · Cited by 1,673 · see citing works
“Unfortunately, these treatments currently cannot ensure long-term glycaemic control or reverse the progress [4].”
Background
Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation
Bray, G. A., Kim, K. K., Wilding, J. P. H., & on behalf of the World Obesity Federation (2017) · Obesity Reviews · doi:10.1111/obr.12551 · Cited by 1,612 · see citing works
Pathogenesis of type 2 diabetes mellitus
DeFronzo, R. A. (2004) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.04.013 · Cited by 1,342 · see citing works
Self-citation
Lipotoxicity and the gut-liver axis in NASH pathogenesis
Marra, F., & Svegliati-Baroni, G. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.014 · Cited by 847 · see citing works
The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus
Westman, E. C., Yancy, W. S., Mavropoulos, J. C., Marquart, M., & McDuffie, J. R. (2008) · Nutrition & Metabolism · doi:10.1186/1743-7075-5-36 · Cited by 475 · see citing works
The cell biology of systemic insulin function
Tokarz, V. L., MacDonald, P. E., & Klip, A. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201802095 · Cited by 471 · see citing works
“…2018) and CEA CAM1 expression (Lee, 2011) in obesity • Impaired vasoactive effects of insulin during insulin resistance, including capillary recruitment (de Jongh et al., 2004; Clerk et al., 2006; Keske et al., 2009); reduced insulin delivery to muscle in obesity and diabetes (Broussard et al.,…”
Background
Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data
Goldenberg, J. Z., Day, A., Brinkworth, G. D., Sato, J., Yamada, S., Jönsson, T., Beardsley, J., Johnson, J. A., Thabane, L., & Johnston, B. C. (2021) · BMJ · doi:10.1136/bmj.m4743 · Cited by 428 · see citing works
Wearable Electrochemical Glucose Sensors in Diabetes Management: A Comprehensive Review
Saha, T., Del Caño, R., Mahato, K., De la Paz, E., Chen, C., Ding, S., Yin, L., & Wang, J. (2023) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00078 · Cited by 442 · see citing works
Mediterranean Diet Effects on Type 2 Diabetes Prevention, Disease Progression, and Related Mechanisms. A Review
Martín-Peláez, S., Fito, M., & Castaner, O. (2020) · Nutrients · doi:10.3390/nu12082236 · Cited by 330 · see citing works
The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review
Gonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278 · see citing works
“Furthermore, the hallmark systemic low-grade proinflammatory state that accompanies obesity has been described to contribute in part to insulin resistance in skeletal muscle (SkM) and in the liver, which compromises their normal metabolic functions [20].”
BackgroundInfluential
Cardiometabolic-Based Chronic Disease, Adiposity and Dysglycemia Drivers
Mechanick, J. I., Farkouh, M. E., Newman, J. D., & Garvey, W. T. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.044 · Cited by 243 · see citing works
Pioglitazone: the forgotten, cost-effective cardioprotective drug for type 2 diabetes
DeFronzo, R. A., Inzucchi, S., Abdul-Ghani, M., & Nissen, S. E. (2019) · Diabetes and Vascular Disease Research · doi:10.1177/1479164118825376 · Cited by 223 · see citing works
Self-citation
Mechanisms underlying the pathophysiology of type 2 diabetes: From risk factors to oxidative stress, metabolic dysfunction, and hyperglycemia
Lima, J. E. B. F., Moreira, N. C. S., & Sakamoto-Hojo, E. T. (2022) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2021.503437 · Cited by 203 · see citing works
Healthy lifestyle behaviors, mediating biomarkers, and risk of microvascular complications among individuals with type 2 diabetes: A cohort study
Geng, T., Zhu, K., Lu, Q., Wan, Z., Chen, X., Liu, L., Pan, A., & Liu, G. (2023) · PLOS Medicine · doi:10.1371/journal.pmed.1004135 · Cited by 205 · see citing works
Incidence of new-onset diabetes and impaired fasting glucose in patients with recent myocardial infarction and the effect of clinical and lifestyle risk factors
Mozaffarian, D., Marfisi, R., Levantesi, G., Silletta, M. G., Tavazzi, L., Tognoni, G., Valagussa, F., & Marchioli, R. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61343-9 · Cited by 179 · see citing works
Targeting p21Cip1 highly expressing cells in adipose tissue alleviates insulin resistance in obesity
Wang, L., Wang, B., Gasek, N. S., Zhou, Y., Cohn, R. L., Martin, D. E., Zuo, W., Flynn, W. F., Guo, C., Jellison, E. R., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.11.002 · Cited by 163 · see citing works
Beyond HbA1c and glucose: the role of nontraditional glycemic markers in diabetes diagnosis, prognosis, and management
Parrinello, C. M., & Selvin, E. (2014) · Current Diabetes Reports · doi:10.1007/s11892-014-0548-3 · Cited by 154 · see citing works
Accelerated osteocyte senescence and skeletal fragility in mice with type 2 diabetes
Eckhardt, B. A., Rowsey, J. L., Thicke, B. S., Fraser, D. G., O’Grady, K. L., Bondar, O. P., Hines, J. M., Singh, R. J., Thoreson, A. R., Rakshit, K., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.135236 · Cited by 130 · see citing works
Insulin Resistance Promotes Parkinson’s Disease through Aberrant Expression of α-Synuclein, Mitochondrial Dysfunction, and Deregulation of the Polo-Like Kinase 2 Signaling
Hong, C.-T., Chen, K.-Y., Wang, W., Chiu, J.-Y., Wu, D., Chao, T.-Y., Hu, C.-J., Chau, K.-Y., & Bamodu, O. (2020) · Cells · doi:10.3390/cells9030740 · Cited by 133 · see citing works
Direct and indirect effects of liraglutide on hypothalamic POMC and NPY/AgRP neurons – Implications for energy balance and glucose control
He, Z., Gao, Y., Lieu, L., Afrin, S., Cao, J., Michael, N. J., Dong, Y., Sun, J., Guo, H., & Williams, K. W. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.07.008 · Cited by 128 · see citing works
Tirzepatide for the treatment of adults with type 2 diabetes: An endocrine perspective
De Block, C., Bailey, C., Wysham, C., Hemmingway, A., Allen, S. E., & Peleshok, J. (2023) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14831 · Cited by 121 · see citing works
Obesity and breast cancer: A case of inflamed adipose tissue
Kolb, R., & Zhang, W. (2020) · Cancers · doi:10.3390/cancers12061686 · Cited by 119 · see citing works
Chia seeds (Salvia hispanica L.): A therapeutic weapon in metabolic disorders
Khalid, W., Arshad, M. S., Aziz, A., Rahim, M. A., Qaisrani, T. B., Afzal, F., Ali, A., Ranjha, M. M. A. N., Khalid, M. Z., & Anjum, F. M. (2023) · Food Science & Nutrition · doi:10.1002/fsn3.3035 · Cited by 108 · see citing works
Glucagon-like peptide-1 receptor action in the vasculature
Almutairi, M., Al Batran, R., & Ussher, J. R. (2019) · Peptides · doi:10.1016/j.peptides.2018.09.002 · Cited by 99 · see citing works
Flavonoids intake and risk of type 2 diabetes mellitus: A meta-analysis of prospective cohort studies
Xu, H., Luo, J., Huang, J., & Wen, Q. (2018) · Medicine · doi:10.1097/md.0000000000010686 · Cited by 95 · see citing works
Sleep, circadian rhythms, and type 2 diabetes mellitus
Parameswaran, G., & Ray, D. W. (2022) · Clinical Endocrinology · doi:10.1111/cen.14607 · Cited by 85 · see citing works
Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes
Piccialli, I., Tedeschi, V., Caputo, L., D’Errico, S., Ciccone, R., De Feo, V., Secondo, A., & Pannaccione, A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.876614 · Cited by 73 · see citing works
Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose
Burmeister, M. A., Ayala, J., Drucker, D. J., & Ayala, J. E. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00446.2012 · Cited by 64 · see citing works
Gliclazide modified release: a critical review of pharmacodynamic, metabolic, and vasoprotective effects
Schernthaner, G. (2003) · Metabolism · doi:10.1016/s0026-0495(03)00215-4 · Cited by 66 · see citing works
Targeting aging and age-related diseases with vaccines
Wu, R., Sun, F., Zhang, W., Ren, J., & Liu, G.-H. (2024) · Nature Aging · doi:10.1038/s43587-024-00597-0 · Cited by 66 · see citing works
In silico network pharmacology and in vivo analysis of berberine-related mechanisms against type 2 diabetes mellitus and its complications
Di, S., Han, L., An, X., Kong, R., Gao, Z., Yang, Y., Wang, X., Zhang, P., Ding, Q., Wu, H., et al. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114180 · Cited by 57 · see citing works
The effects of dietary education interventions on individuals with type 2 diabetes: a systematic review and meta-analysis
Kim, J., & Hur, M.-H. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18168439 · Cited by 51 · see citing works
Magnoflorine Prevent the Skeletal Muscle Atrophy Via Akt/mTOR/FoxO Signal Pathway and Increase Slow-MyHC Production in Streptozotocin-Induced Diabetic Rats
Yadav, A., Singh, A., Phogat, J., Dahuja, A., & Dabur, R. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.113510 · Cited by 49 · see citing works
Effect of Tai Chi on Quality of Life, Body Mass Index, and Waist-Hip Ratio in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Qin, J., Chen, Y., Guo, S., You, Y., Xu, Y., Wu, J., Liu, Z., Huang, J., Chen, L., & Tao, J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.543627 · Cited by 47 · see citing works
Concentrated insulins: Clinical update of therapeutic options
Umpierrez, G. E., Holt, E. H., Einhorn, D., & McGill, J. B. (2020) · Endocrine Practice · doi:10.4158/ep-2019-0607 · Cited by 44 · see citing works
Creatine supplementation and glycemic control: A systematic review
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An estrogen receptor α-derived peptide improves glucose homeostasis during obesity
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Authors: DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., Hu, F. B., Kahn, C. R., Raz, I., Shulman, G. I., Simonson, D. C., Testa, M. A., & Weiss, R.
Affiliations: The University of Texas at San Antonio Health Science Center (US)
Istituto di Fisiologia Clinica (IT)
Lund University (SE)
University of California San Diego (US)
University of Michigan (US)
University of Copenhagen (DK)
Brigham and Women's Hospital (US)
Joslin Diabetes Center (US)
Hadassah Medical Center (IL)
Howard Hughes Medical Institute (US)
Harvard University (US)
Hebrew University of Jerusalem (IL)
Corresponding author: DeFronzo, Ralph A.
ORCID: DeFronzo, Ralph A.
Ferrannini, Ele
Groop, Leif
Henry, Robert R.
Herman, William H.
Holst, Jens Juul
Hu, Frank B.
Kahn, C. Ronald
Raz, Itamar
Shulman, Gerald I.
Simonson, Donald C.
Testa, Marcia A.
Weiss, Ram
Venue: Nature Reviews Disease Primers
Publisher: Springer Science and Business Media LLC
Published: 2015-07-23
Volume: 1
Issue: 1
Pages: 15019-15019
ISSN: 2056-676X (ISSN-L)
DOI: 10.1038/nrdp.2015.19
OpenAlex: W44929223
Semantic Scholar: 9826997ad233ac10f32ccd21e5d4b612f16005e7
Cited by: 2,611
References: 414
Citations by year: 2026: 301 · 2025: 372 · 2024: 375 · 2023: 337 · 2022: 305 · 2021: 263 · 2020: 176 · 2019: 156 · 2018: 75 · 2017: 34 · 2016: 19 · 2015: 26 · 2014: 35 · 2013: 26 · 2012: 20
FWCI: 7.76
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Reviews Disease Primers (publishedVersion)
PubMed (publishedVersion)
Lund University Publications (Lund University) (submittedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (R24DK085610, R01DK049230, R01DK031036, R01DK058845, P30DK046200, R01DK040936, R01DK033201, P30DK092926, P30DK036836, R01DK082659, R01DK024092)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords: type 2 diabetes, obesity, insulin resistance, impaired glucose homeostasis, impaired insulin secretion, pancreatic beta-cell failure, microvascular complications, macrovascular complications, cardiovascular comorbidity, antidiabetic drugs, insulin sensitizers, pathophysiology
MeSH terms: Blood Glucose, Diabetes Mellitus, Type 2, Humans, Hyperglycemia, Hypoglycemic Agents, Insulin, Insulin Resistance, Metabolic Syndrome, Insulin-Secreting Cells

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