Obesity and Diabetes: Genetic Markers and Pharmacological Interventions

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Pharmacogenetics".

Deadline for manuscript submissions: closed (25 February 2023) | Viewed by 18757

Special Issue Editors


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Guest Editor
School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
Interests: type 1 and type 2 diabetes mellitus; vitamin D; incretin-based therapies; pharmacogenetics in diabetes

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Guest Editor
Division of Endocrinology and Metabolism, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, 55535 Thessaloniki, Greece
Interests: intermittent fasting; periodic fasting; religious fasting: fasting glucose; obesity; impaired fasting glucose; non-fasting triglycerides; fasting blood glucose; caloric restriction; meal frequency; calorie restriction
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Guest Editor
Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
Interests: diabetes

Special Issue Information

Dear Colleagues,

Obesity and diabetes mellitus prevalence has been rising rapidly over the last few decades. Novel pharmacological agents targeting both diabetes mellitus and its complications have redirected medical interventions towards a patient-centered method of treatment. However, in an extremely heterogenous group of diabetic patients, patient-tailored treatment protocols still remain challenging.

Precision medicine refers to the opportunity to provide the right therapy for the right patient at the right time. Recently, advances in medical science, biology, genetics, basic research and technology have made the implementation of precision medicine more attractive and affordable at the same time.

In this Special Issue, we will try to present existing evidence about genetic markers that have been associated with obesity, diabetes mellitus and diabetes complication predisposition, diagnosis, and treatment. We will also try to collect and analyze primary research data on the efficacy of newer antidiabetic agents based on genetic markers to shed light on the future of precision medicine in diabetes and obesity.

Dr. Kalliopi Kotsa
Dr. Theocharis Koufakis
Dr. Maria Grammatiki
Guest Editors

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Keywords

  • type 1 diabetes mellitus
  • type 2 diabetes mellitus
  • obesity
  • precision medicine in diabetes
  • pharmacogenetics
  • diabetes genetic biomarkers

Published Papers (6 papers)

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Research

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14 pages, 288 KiB  
Article
Immune Response and Lipid Metabolism Gene Polymorphisms Are Associated with the Risk of Obesity in Middle-Aged and Elderly Patients
by Anastasia Ponasenko, Maxim Sinitsky, Varvara Minina, Anna Vesnina, Maria Khutornaya, Alexander Prosekov and Olga Barbarash
J. Pers. Med. 2022, 12(2), 238; https://doi.org/10.3390/jpm12020238 - 08 Feb 2022
Cited by 6 | Viewed by 1601
Abstract
More than two billion people around the world are overweight or obese. Even in apparently healthy people, obesity has a potent effect on their quality of life. Experimental data indicate the role of infectious agents in systemic inflammation, revealing a correlation between the [...] Read more.
More than two billion people around the world are overweight or obese. Even in apparently healthy people, obesity has a potent effect on their quality of life. Experimental data indicate the role of infectious agents in systemic inflammation, revealing a correlation between the dietary habits of people with obesity and the level of systemic inflammation mediators, serum lipid concentration, and hormonal and immune status. This study aimed to determine the association of immune response and lipid metabolism gene polymorphisms with the risk of obesity. This study included 560 Caucasian participants living in Western Siberia (Russian Federation). A total of 52 polymorphic sites in 20 genes were analyzed using the 5′ TaqMan nuclease assay. Four risk-associated polymorphic variants were discovered—two variants in immune response genes (IL6R rs2229238, OR = 1.92, 95% CI = 1.36–2.7, p = 0.0002 in the dominant model; IL18 rs1946518, OR = 1.45, 95% CI = 1.03–2.04, p = 0.033 in the over-dominant model) and two variants in lipid metabolism genes (LPA rs10455872, OR = 1.86, 95% CI = 1.07–3.21, p = 0.026 in the log-additive model; LEPR rs1137100, OR = 2.88, 95% CI = 1.52–5.46, p = 0.001 in the recessive model). Thus, polymorphisms in immune response and lipid metabolism genes are potentially associated with the modification of obesity risk in the Caucasian population. Full article
11 pages, 705 KiB  
Article
A Clinical-Genetic Score for Predicting Weight Loss after Bariatric Surgery: The OBEGEN Study
by Andreea Ciudin, Enzamaría Fidilio, Liliana Gutiérrez-Carrasquilla, Assumpta Caixàs, Núria Vilarrasa, Silvia Pellitero, Andreu Simó-Servat, Ramon Vilallonga, Amador Ruiz, Maricruz de la Fuente, Alexis Luna, Enric Sánchez, Mercedes Rigla, Cristina Hernández, Eduardo Salas, Rafael Simó and Albert Lecube
J. Pers. Med. 2021, 11(10), 1040; https://doi.org/10.3390/jpm11101040 - 17 Oct 2021
Cited by 14 | Viewed by 2524
Abstract
Around 30% of the patients that undergo bariatric surgery (BS) do not reach an appropriate weight loss. The OBEGEN study aimed to assess the added value of genetic testing to clinical variables in predicting weight loss after BS. A multicenter, retrospective, longitudinal, and [...] Read more.
Around 30% of the patients that undergo bariatric surgery (BS) do not reach an appropriate weight loss. The OBEGEN study aimed to assess the added value of genetic testing to clinical variables in predicting weight loss after BS. A multicenter, retrospective, longitudinal, and observational study including 416 patients who underwent BS was conducted (Clinical.Trials.gov- NCT02405949). 50 single nucleotide polymorphisms (SNPs) from 39 genes were examined. Receiver Operating Characteristic (ROC) curve analysis were used to calculate sensitivity and specificity. Satisfactory response to BS was defined as at nadir excess weight loss >50%. A good predictive model of response [area under ROC of 0.845 (95% CI 0.805–0.880), p < 0.001; sensitivity 90.1%, specificity 65.5%] was obtained by combining three clinical variables (age, type of surgery, presence diabetes) and nine SNPs located in ADIPOQ, MC4R, IL6, PPARG, INSIG2, CNR1, ELOVL6, PLIN1 and BDNF genes. This predictive model showed a significant higher area under ROC than the clinical score (p = 0.0186). The OBEGEN study shows the key role of combining clinical variables with genetic testing to increase the predictability of the weight loss response after BS. This finding will permit us to implement a personalized medicine which will be associated with a more cost-effective clinical practice. Full article
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11 pages, 1023 KiB  
Article
Effect of Resistance Exercise on the Lipolysis Pathway in Obese Pre- and Postmenopausal Women
by Sunghwun Kang, Kyu-Min Park, Kun-Young Sung, Yuning Yuan and Seung-Taek Lim
J. Pers. Med. 2021, 11(9), 874; https://doi.org/10.3390/jpm11090874 - 31 Aug 2021
Cited by 7 | Viewed by 2323
Abstract
Physical exercise may stimulate lipolytic activity within adipose tissue. Furthermore, resistance exercise may contribute to the more efficient reduction in adipose tissue mass and prevent the accumulation thereof in obese women. The purpose of this study was to examine the effects of regular [...] Read more.
Physical exercise may stimulate lipolytic activity within adipose tissue. Furthermore, resistance exercise may contribute to the more efficient reduction in adipose tissue mass and prevent the accumulation thereof in obese women. The purpose of this study was to examine the effects of regular resistance exercise for 12 weeks on the lipolysis pathway in women with obesity. Twenty-three pre- and postmenopausal women with body fat percentages of 30% or more were divided into the premenopausal group (n = 9) and the postmenopausal group (n = 14). All subjects participated in resistance exercise training for 12 weeks. Anthropometric and physical fitness tests were performed on all participants. Protein analyses were performed on extracted subcutaneous fatty tissue, and changes in the relevant protein levels in the samples were analyzed by Western blotting. All serum samples were submitted for enzyme-linked immunosorbent assay measurements of adipocyte factors. After 12 weeks, the adipose triglyceride lipase, monoacylglycerol lipase, and perilipin1 protein levels were significantly lower in the postmenopausal group than in the premenopausal group. The hormone-sensitive lipase protein levels were significantly higher in the postmenopausal group than in the premenopausal group. In addition, leptin concentrations were significantly decreased after resistance exercise in the postmenopausal group. Adiponectin concentrations were significantly increased after resistance exercise in both groups. These findings indicate that regular resistance exercise is effective in reducing the weight and body fat of obese premenopausal women, and in the secretion of adiponectin. On the other hand, postmenopausal women were found to have redeced weight and body fat, and were found to be positive for the secretion of adipokine factors. In addition, positive changes in lipolysis pathway factors in adipose tissue promote lipid degradation and reduce fat mass. Thus, regular resistance exercise shows positive changes in the lipolysis pathway more effectively in weight and body fat reduction in postmenopausal women than in premenopausal women. Full article
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Review

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15 pages, 618 KiB  
Review
Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care
by Elpiniki Rentzeperi, Stavroula Pegiou, Theocharis Koufakis, Maria Grammatiki and Kalliopi Kotsa
J. Pers. Med. 2022, 12(3), 454; https://doi.org/10.3390/jpm12030454 - 13 Mar 2022
Cited by 26 | Viewed by 6221
Abstract
The available data suggest differences in the course of type 2 diabetes mellitus (T2DM) between men and women, influenced by the distinguishing features of the sex. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a relatively new class of antidiabetic drugs that act [...] Read more.
The available data suggest differences in the course of type 2 diabetes mellitus (T2DM) between men and women, influenced by the distinguishing features of the sex. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a relatively new class of antidiabetic drugs that act by mimicking the function of endogenous glucagon-like peptide 1. They constitute valuable agents for the management of T2DM as, in addition to exerting a strong hypoglycemic action, they present cardiorenal protective properties, promote weight loss, and have a good safety profile, particularly with respect to the risk of hypoglycemia. Due to the precedent of studies having identified sexual dimorphic elements regarding the action of other antidiabetic agents, ongoing research has attempted to examine whether this is also the case for GLP-1 RAs. Until now, sex differences have been observed in the impact of GLP1-RAs on glycemic control, weight reduction, and frequency of adverse events. On the contrary, the question of whether these drugs differentially affect the two sexes with respect to cardiovascular risk and incidence of major adverse cardiovascular events remains under investigation. Knowledge of the potential sex-specific effects of these medications is extremely useful for the implementation of individualized therapeutic plans in the treatment of T2DM. This narrative review aims to present the available data regarding the sex-specific action of GLP-1 RAs as well as to discuss the potential pathophysiologic mechanisms explaining these dissimilarities. Full article
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11 pages, 569 KiB  
Review
Evidence for Cardiorenal Protection with SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Patients with Diabetic Kidney Disease
by Panagiotis I. Georgianos, Vasilios Vaios, Stefanos Roumeliotis, Konstantinos Leivaditis, Theodoros Eleftheriadis and Vassilios Liakopoulos
J. Pers. Med. 2022, 12(2), 223; https://doi.org/10.3390/jpm12020223 - 06 Feb 2022
Cited by 6 | Viewed by 2282
Abstract
For almost two decades, the management of patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) was based on the optimal glycemic and blood pressure control as well as on the adequate blockade of the renin-angiotensin-system. Over the past few [...] Read more.
For almost two decades, the management of patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) was based on the optimal glycemic and blood pressure control as well as on the adequate blockade of the renin-angiotensin-system. Over the past few years, sodium-glucose co-transporter 2 (SGLT-2) inhibitors and glucagone-like peptide 1 receptor agonists (GLP1-RAs) were added to our therapeutic armarhatum, offering promise for more effective mitigation of the substantial residual cardiorenal risk of these patients. Large randomized controlled trials (RCTs) designed to demonstrate the cardiovascular safety of SGLT-2 inhibitors and GLP1-RAs showed that these novel anti-diabetic medications improve cardiovascular outcomes in patients with T2DM. RCTs conducted specifically in CKD patients with or without T2DM demonstrated that SGLT-2 inhibitors were also effective in retarding the progression of kidney injury to end-stage kidney disease. The kidney protective effects of GLP1-RA are not yet proven, but RCTs are currently ongoing to investigate this crucial research question. In this article, we review the available clinical-trial evidence supporting the use of SGLT-2 inhibitors and GLP1-RAs for cardiorenal protection in patients with T2DM and CKD. We provide clinical practice recommendations for a personalized approach in the use of these novel therapies, according to the severity of CKD and the presence of other cardiometabolic risk factors. Full article
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30 pages, 502 KiB  
Review
Innate-Immunity Genes in Obesity
by Svetlana V. Mikhailova and Dinara E. Ivanoshchuk
J. Pers. Med. 2021, 11(11), 1201; https://doi.org/10.3390/jpm11111201 - 14 Nov 2021
Cited by 10 | Viewed by 2658
Abstract
The main functions of adipose tissue are thought to be storage and mobilization of the body’s energy reserves, active and passive thermoregulation, participation in the spatial organization of internal organs, protection of the body from lipotoxicity, and ectopic lipid deposition. After the discovery [...] Read more.
The main functions of adipose tissue are thought to be storage and mobilization of the body’s energy reserves, active and passive thermoregulation, participation in the spatial organization of internal organs, protection of the body from lipotoxicity, and ectopic lipid deposition. After the discovery of adipokines, the endocrine function was added to the above list, and after the identification of crosstalk between adipocytes and immune cells, an immune function was suggested. Nonetheless, it turned out that the mechanisms underlying mutual regulatory relations of adipocytes, preadipocytes, immune cells, and their microenvironment are complex and redundant at many levels. One possible way to elucidate the picture of adipose-tissue regulation is to determine genetic variants correlating with obesity. In this review, we examine various aspects of adipose-tissue involvement in innate immune responses as well as variants of immune-response genes associated with obesity. Full article
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