Diabetes is the ninth leading cause of death, directly accounting for 1.5 million deaths annually worldwide. Despite several breakthrough discoveries, little progress has been made in type 2 diabetes outcomes over the past 100 years. Younger age (below 60 years), a diet high in calories and processed food, and severe obesity (body mass index >35 kg/m2) may identify reversible beta cell dysfunction. Much of the clinical presentation pertains to flooding the body's adaptive limits with overnutrition. Recognizing this as a global societal trend brought about by lifestyle changes, sedentary work, mental stress and unlimited access to calorie-dense foods is crucial. Insulin resistance and genetic abnormalities cannot account for the dramatic increase in diabetes, from only 1% five decades ago to nearly 10% today. Obesity - and not insulin resistance - is at the core of the problem. As well as hyperglycaemia, end-organ damage can also be reversed with diet and weight loss in many affected individuals. We present the evolution of our understanding and compelling reasons to reframe diabetes in the severely obese to what it really is - overweight hyperglycaemia. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles. The objective of this review is to better understand global trends and the potential to improve outcomes by reframing the diabetes narrative towards remission. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles.
{"title":"Early Recognition of Overweight Hyperglycaemia May Improve Clinical Outcomes in Type 2 Diabetes.","authors":"Anand Chockalingam, Pandiyan Natarajan, Smrita Dorairajan, Uzma Khan","doi":"10.17925/EE.2023.19.1.33","DOIUrl":"https://doi.org/10.17925/EE.2023.19.1.33","url":null,"abstract":"<p><p>Diabetes is the ninth leading cause of death, directly accounting for 1.5 million deaths annually worldwide. Despite several breakthrough discoveries, little progress has been made in type 2 diabetes outcomes over the past 100 years. Younger age (below 60 years), a diet high in calories and processed food, and severe obesity (body mass index >35 kg/m<sup>2</sup>) may identify reversible beta cell dysfunction. Much of the clinical presentation pertains to flooding the body's adaptive limits with overnutrition. Recognizing this as a global societal trend brought about by lifestyle changes, sedentary work, mental stress and unlimited access to calorie-dense foods is crucial. Insulin resistance and genetic abnormalities cannot account for the dramatic increase in diabetes, from only 1% five decades ago to nearly 10% today. Obesity - and not insulin resistance - is at the core of the problem. As well as hyperglycaemia, end-organ damage can also be reversed with diet and weight loss in many affected individuals. We present the evolution of our understanding and compelling reasons to reframe diabetes in the severely obese to what it really is - overweight hyperglycaemia. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles. The objective of this review is to better understand global trends and the potential to improve outcomes by reframing the diabetes narrative towards remission. This may shift societal perception, governmental funding, workplace reformations and individual engagement with healthy lifestyles.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9636099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthias Li, Mohammad Sadiq Jeeyavudeen, Ganesan Arunagirinathan, Joseph Pappachan
The prevalence of type 2 diabetes mellitus (T2DM) is steadily rising worldwide due to an increasingly sedentary lifestyle combined with unhealthy food habits. Currently, the burden of diabetes on healthcare systems is unprecedented and rising daily. Several observational studies and randomized controlled trials provide clinical evidence that T2DM remission is possible by adopting dietary interventions and a strict exercise training protocol. Notably, these studies provide ample evidence for remission in patients with T2DM or for prevention in those with risk factors for the disease through various non-pharmacological behavioural interventions. In this article, we present two clinical cases of individuals who showed remission from T2DM/prediabetes via behavioural changes, especially through the adoption of a low-energy diet and exercise. We also discuss the recent advances in T2DM and obesity research, focusing on nutritional interventions and exercise and their benefits for weight loss, improved metabolic profile, enhanced glycaemic control and remission of diabetes.
{"title":"Is Type 2 Diabetes Mellitus a Behavioural Disorder? An Evidence Review for Type 2 Diabetes Mellitus Prevention and Remission through Lifestyle Modification.","authors":"Matthias Li, Mohammad Sadiq Jeeyavudeen, Ganesan Arunagirinathan, Joseph Pappachan","doi":"10.17925/EE.2023.19.1.7","DOIUrl":"https://doi.org/10.17925/EE.2023.19.1.7","url":null,"abstract":"<p><p>The prevalence of type 2 diabetes mellitus (T2DM) is steadily rising worldwide due to an increasingly sedentary lifestyle combined with unhealthy food habits. Currently, the burden of diabetes on healthcare systems is unprecedented and rising daily. Several observational studies and randomized controlled trials provide clinical evidence that T2DM remission is possible by adopting dietary interventions and a strict exercise training protocol. Notably, these studies provide ample evidence for remission in patients with T2DM or for prevention in those with risk factors for the disease through various non-pharmacological behavioural interventions. In this article, we present two clinical cases of individuals who showed remission from T2DM/prediabetes via behavioural changes, especially through the adoption of a low-energy diet and exercise. We also discuss the recent advances in T2DM and obesity research, focusing on nutritional interventions and exercise and their benefits for weight loss, improved metabolic profile, enhanced glycaemic control and remission of diabetes.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9686228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01Epub Date: 2023-05-17DOI: 10.17925/EE.2023.19.1.54
I Gusti Putu Suka Aryana, Ivana Beatrice Paulus, Sanjay Kalra, Dian Daniella, Raden Ayu Tuty Kuswardhani, Ketut Suastika, Sony Wibisono
As age increases, adipose tissue infiltrates muscle tissue and leads to sarcopenia. When excessive accumulation of adipose tissue accompanied progressive decrease in lean body mass especially visceral fat, termed as sarcopenic obesity (SO) and related metabolic intermuscular adipose tissue (IMAT) is an ectopic tissue found between muscle groups, and is distinct from subcutaneous adipose tissue. Until now, the association between IMAT and metabolic health was not understood. This study is the first systematic review assessing the association between IMAT and metabolic health. The PubMed, Science Direct and Cochrane databases were searched for studies reporting IMAT and metabolic risk. The descriptions of the extracted data are guided by the Preferred Reporting Items for Systematic Reviews (PRISMA) statement with a Grading of Recommendations Assessment, Development and Evaluation approach. This study is registered at PROSPERO (identifier: CRD42022337518). Six studies were pooled and reviewed using critical appraisal by the Newcastle Ottawa Scale and Centre for Evidence-Based Medicine checklist. Two clinical trials and four observational trials were included. Our results reveal that IMAT is associated with metabolic risk, especially in older adults and patients with obesity. However, in a person with abdominal obesity, VAT has a more significant role in metabolic risk than IMAT. The largest decrease in IMAT was achieved by combining aerobic with resistance training.
{"title":"The Important Role of Intermuscular Adipose Tissue on Metabolic Changes Interconnecting Obesity, Ageing and Exercise: A Systematic Review.","authors":"I Gusti Putu Suka Aryana, Ivana Beatrice Paulus, Sanjay Kalra, Dian Daniella, Raden Ayu Tuty Kuswardhani, Ketut Suastika, Sony Wibisono","doi":"10.17925/EE.2023.19.1.54","DOIUrl":"10.17925/EE.2023.19.1.54","url":null,"abstract":"<p><p>As age increases, adipose tissue infiltrates muscle tissue and leads to sarcopenia. When excessive accumulation of adipose tissue accompanied progressive decrease in lean body mass especially visceral fat, termed as sarcopenic obesity (SO) and related metabolic intermuscular adipose tissue (IMAT) is an ectopic tissue found between muscle groups, and is distinct from subcutaneous adipose tissue. Until now, the association between IMAT and metabolic health was not understood. This study is the first systematic review assessing the association between IMAT and metabolic health. The PubMed, Science Direct and Cochrane databases were searched for studies reporting IMAT and metabolic risk. The descriptions of the extracted data are guided by the Preferred Reporting Items for Systematic Reviews (PRISMA) statement with a Grading of Recommendations Assessment, Development and Evaluation approach. This study is registered at PROSPERO (identifier: CRD42022337518). Six studies were pooled and reviewed using critical appraisal by the Newcastle Ottawa Scale and Centre for Evidence-Based Medicine checklist. Two clinical trials and four observational trials were included. Our results reveal that IMAT is associated with metabolic risk, especially in older adults and patients with obesity. However, in a person with abdominal obesity, VAT has a more significant role in metabolic risk than IMAT. The largest decrease in IMAT was achieved by combining aerobic with resistance training.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9686223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.17925/EE.2023.19.1.25
Suresh K Sharma, Shiv Kumar Mudgal, Sanjay Kalra, Rakhi Gaur, Kalpana Thakur, Rajat Agarwal
Background: Type 2 diabetes mellitus (T2DM) is a severe public health issue notably impacting human life and health expenditure. It has been observed in literature that intermittent fasting (IF) addresses diabetes and its underlying cause, which benefits people with diabetes. Therefore, this study aimed to evaluate the effectiveness of IF treatment on glycaemic control in people with T2DM compared with control group. Methods: Systematic review and meta-analysis of interventional studies among patients with T2DM with glycated haemoglobin (HbA1c) as an outcome was performed. A comprehensive search of electronic databases, including PubMed, Embase and Google Scholar, for articles published before 24 April 2022, was done. Studies reporting 24 hours of complete fasting or intermittent restricted energy intake (feeding permitted for only 4-8 hours daily, with 16-20 hours of fasting) and reporting changes in HbA1c and fasting glucose levels were eligible. Meta-analysis was performed using Cochrane's Q statistic and the I2 statistical approach. Results: Eleven studies (13 arms) measuring the effect of IF on patients' HbA1c level were analysed. There was no statistically significant difference between IF and control groups (Standardized mean difference [SMD] -0.08, 95% confidence interval [CI] -0.20 to 0.04;p=0.19, I2=22%). Overall, seven studies on patients' fasting blood glucose were analysed, and the meta-analysis revealed no significant difference between the two groups i.e. IF and control groups (SMD 0.06, 95% CI -0.25 to 0.38;p=0.69, I2=76%). Conclusion: IF and usual diet pattern have no difference in terms of glycaemic control. Although, IF may be used as a preventative diet pattern in the pre-diabetic population, as it works well in the long-term to achieve controlled sugar levels. Study registration: The protocol of this study was registered in The International Prospective Register of Systematic Reviews (PROSPERO) with a registration number CRD42022328528.
{"title":"Effect of Intermittent Fasting on Glycaemic Control in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials.","authors":"Suresh K Sharma, Shiv Kumar Mudgal, Sanjay Kalra, Rakhi Gaur, Kalpana Thakur, Rajat Agarwal","doi":"10.17925/EE.2023.19.1.25","DOIUrl":"https://doi.org/10.17925/EE.2023.19.1.25","url":null,"abstract":"<p><p><b>Background:</b> Type 2 diabetes mellitus (T2DM) is a severe public health issue notably impacting human life and health expenditure. It has been observed in literature that intermittent fasting (IF) addresses diabetes and its underlying cause, which benefits people with diabetes. Therefore, this study aimed to evaluate the effectiveness of IF treatment on glycaemic control in people with T2DM compared with control group. <b>Methods:</b> Systematic review and meta-analysis of interventional studies among patients with T2DM with glycated haemoglobin (HbA1c) as an outcome was performed. A comprehensive search of electronic databases, including PubMed, Embase and Google Scholar, for articles published before 24 April 2022, was done. Studies reporting 24 hours of complete fasting or intermittent restricted energy intake (feeding permitted for only 4-8 hours daily, with 16-20 hours of fasting) and reporting changes in HbA1c and fasting glucose levels were eligible. Meta-analysis was performed using Cochrane's Q statistic and the I<sup>2</sup> statistical approach. <b>Results:</b> Eleven studies (13 arms) measuring the effect of IF on patients' HbA1c level were analysed. There was no statistically significant difference between IF and control groups (Standardized mean difference [SMD] -0.08, 95% confidence interval [CI] -0.20 to 0.04;p=0.19, I<sup>2</sup>=22%). Overall, seven studies on patients' fasting blood glucose were analysed, and the meta-analysis revealed no significant difference between the two groups i.e. IF and control groups (SMD 0.06, 95% CI -0.25 to 0.38;p=0.69, I<sup>2</sup>=76%). <b>Conclusion:</b> IF and usual diet pattern have no difference in terms of glycaemic control. Although, IF may be used as a preventative diet pattern in the pre-diabetic population, as it works well in the long-term to achieve controlled sugar levels. Study registration: The protocol of this study was registered in The International Prospective Register of Systematic Reviews (PROSPERO) with a registration number CRD42022328528.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Not only are early detection and treatment of diabetic foot ulcers important, but also acknowledging potential risk factors for amputation gives clinicians a considerable advantage in preventing amputations. Amputations impact both healthcare services and the physical and mental health of patients. This study aimed to investigate the risk factors for amputation in patients with diabetic foot ulcers.
Methods: The sample for this study was patients with diabetic foot ulcers who were treated by the diabetic foot council at our hospital between 2005 and 2020. A total of 32 risk factors for amputation were identified and investigated among 518 patients.
Results: Our univariate analysis showed that 24 of 32 defined risk factors were statistically significant. In the multivariate analysis using the Cox regression model, seven risk factors remained statistically significant. The risk factors most significantly associated with amputation were Wagner grading, abnormal peripheral arteries, hypertension, high thrombocyte levels, low haematocrit levels, hypercholesterolaemia and male sex, respectively. The most common cause of death in patients with diabetes who have undergone amputation is cardiovascular disease, followed by sepsis.
Conclusion: To enable optimum treatment of patients with diabetic foot ulcers it is important for physicians to be aware of the amputation risk factors, and thus avoid amputations. Correcting risk factors, using suitable footwear and routinely inspecting feet are crucial factors for preventing amputations in patients with diabetic foot ulcers.
{"title":"An Overview of Risk Factors for Diabetic Foot Amputation: An Observational, Single-centre, Retrospective Cohort Study.","authors":"Burak Yuzuguldu, Bugra Zengin, Ilgin Yildirim Simsir, Sevki Cetinkalp","doi":"10.17925/EE.2023.19.1.85","DOIUrl":"https://doi.org/10.17925/EE.2023.19.1.85","url":null,"abstract":"<p><strong>Introduction: </strong>Not only are early detection and treatment of diabetic foot ulcers important, but also acknowledging potential risk factors for amputation gives clinicians a considerable advantage in preventing amputations. Amputations impact both healthcare services and the physical and mental health of patients. This study aimed to investigate the risk factors for amputation in patients with diabetic foot ulcers.</p><p><strong>Methods: </strong>The sample for this study was patients with diabetic foot ulcers who were treated by the diabetic foot council at our hospital between 2005 and 2020. A total of 32 risk factors for amputation were identified and investigated among 518 patients.</p><p><strong>Results: </strong>Our univariate analysis showed that 24 of 32 defined risk factors were statistically significant. In the multivariate analysis using the Cox regression model, seven risk factors remained statistically significant. The risk factors most significantly associated with amputation were Wagner grading, abnormal peripheral arteries, hypertension, high thrombocyte levels, low haematocrit levels, hypercholesterolaemia and male sex, respectively. The most common cause of death in patients with diabetes who have undergone amputation is cardiovascular disease, followed by sepsis.</p><p><strong>Conclusion: </strong>To enable optimum treatment of patients with diabetic foot ulcers it is important for physicians to be aware of the amputation risk factors, and thus avoid amputations. Correcting risk factors, using suitable footwear and routinely inspecting feet are crucial factors for preventing amputations in patients with diabetic foot ulcers.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.17925/EE.2023.19.1.60
Gres Karim, Meena B Bansal
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty liver disease, including non-alcoholic fatty liver (NAFL) and its more progressive form, non-alcoholic steatohepatitis (NASH). The prevalence of NAFLD/NASH along with type 2 diabetes and obesity is rising worldwide. In those who develop NASH, unlike those with bland steatosis (NAFL), lipotoxic lipids drive hepatocyte injury, inflammation and stellate cell activation leading to progressive accumulation of collagen or fibrosis, ultimately leading to cirrhosis and increased risk of hepatocellular carcinoma. Hypothyroidism is associated with NAFLD/NASH; specifically, intrahepatic hypothyroidism drives lipotoxicty in preclinical models. Agonists of thyroid hormone receptor (THR)-β, which is primarily found in the liver, can promote lipophagy, mitochondrial biogenesis and mitophagy, stimulating increased hepatic fatty acid β-oxidation, and thereby decreasing the burden of lipotoxic lipids, while promoting low-density lipoprotein (LDL) uptake and favourable effects on lipid profiles. A number of THR-β agonists are currently being investigated for NASH. This review focuses on resmetirom, an orally administered, once-daily, small-molecule, liver-directed, ß-selective THR agonist, as it is furthest along in development. Data from completed clincal studies outlined in this review demonstrate that resmetirom is effective in reducing hepatic fat content as measured by magnetic resonance imaging-derived proton density fat fraction, reduces liver enzymes, improves non-i nvasive markers of liver fibrogenesis and decreases liver stiffness, while eliciting a favourable cardiovascular profile with a reduction in serum lipids, including LDL cholesterol. Topline phase III biopsy data showed resolution of NASH and/or fibrosis improvement after 52 weeks of treatment, with more detailed peer-reviewed findings anticipated in order to certify these findings. Longer term clinical outcomes from both MAESTRO-NASH and MAESTRO-NASH OUTCOMES will be a pivotal juncture in the drug's road towards being approved as a NASH therapeutic.
{"title":"Resmetirom: An Orally Administered, Smallmolecule, Liver-directed, β-selective THR Agonist for the Treatment of Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohepatitis.","authors":"Gres Karim, Meena B Bansal","doi":"10.17925/EE.2023.19.1.60","DOIUrl":"https://doi.org/10.17925/EE.2023.19.1.60","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty liver disease, including non-alcoholic fatty liver (NAFL) and its more progressive form, non-alcoholic steatohepatitis (NASH). The prevalence of NAFLD/NASH along with type 2 diabetes and obesity is rising worldwide. In those who develop NASH, unlike those with bland steatosis (NAFL), lipotoxic lipids drive hepatocyte injury, inflammation and stellate cell activation leading to progressive accumulation of collagen or fibrosis, ultimately leading to cirrhosis and increased risk of hepatocellular carcinoma. Hypothyroidism is associated with NAFLD/NASH; specifically, intrahepatic hypothyroidism drives lipotoxicty in preclinical models. Agonists of thyroid hormone receptor (THR)-β, which is primarily found in the liver, can promote lipophagy, mitochondrial biogenesis and mitophagy, stimulating increased hepatic fatty acid β-oxidation, and thereby decreasing the burden of lipotoxic lipids, while promoting low-density lipoprotein (LDL) uptake and favourable effects on lipid profiles. A number of THR-β agonists are currently being investigated for NASH. This review focuses on resmetirom, an orally administered, once-daily, small-molecule, liver-directed, ß-selective THR agonist, as it is furthest along in development. Data from completed clincal studies outlined in this review demonstrate that resmetirom is effective in reducing hepatic fat content as measured by magnetic resonance imaging-derived proton density fat fraction, reduces liver enzymes, improves non-i nvasive markers of liver fibrogenesis and decreases liver stiffness, while eliciting a favourable cardiovascular profile with a reduction in serum lipids, including LDL cholesterol. Topline phase III biopsy data showed resolution of NASH and/or fibrosis improvement after 52 weeks of treatment, with more detailed peer-reviewed findings anticipated in order to certify these findings. Longer term clinical outcomes from both MAESTRO-NASH and MAESTRO-NASH OUTCOMES will be a pivotal juncture in the drug's road towards being approved as a NASH therapeutic.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9686224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.17925/EE.2023.19.1.38
Casey Berman, Alaina P Vidmar, Lily C Chao
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained traction for the management of type 2 diabetes and obesity. Unlike several classes of antidiabetic medications that contribute to weight gain, GLP-1RAs not only reduce haemoglobin A1c, but also promote weight loss. While there is a large body of evidence supporting its safety and efficacy in adults, paediatric clinical trial data have only emerged in recent years. This review will discuss the limited treatment options for paediatric type 2 diabetes and the mechanism of action of GLP-1RAs as it pertains to physiological pathways relevant for type 2 diabetes, obesity and their related comorbidities. The outcomes of paediatric trials evaluating liraglutide, exenatide, semaglutide and dulaglutide in paediatric type 2 diabetes and obesity will be closely examined, including differences compared with adult studies. Finally, potential barriers and strategies to expanding GLP-1RA access in adolescents will be discussed. Future studies are needed to determine if the cardio-and renal-protective benefits of GLP-1RAs apply to youth-onset type 2 diabetes.
{"title":"Glucagon-like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes in Youth.","authors":"Casey Berman, Alaina P Vidmar, Lily C Chao","doi":"10.17925/EE.2023.19.1.38","DOIUrl":"https://doi.org/10.17925/EE.2023.19.1.38","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained traction for the management of type 2 diabetes and obesity. Unlike several classes of antidiabetic medications that contribute to weight gain, GLP-1RAs not only reduce haemoglobin A1c, but also promote weight loss. While there is a large body of evidence supporting its safety and efficacy in adults, paediatric clinical trial data have only emerged in recent years. This review will discuss the limited treatment options for paediatric type 2 diabetes and the mechanism of action of GLP-1RAs as it pertains to physiological pathways relevant for type 2 diabetes, obesity and their related comorbidities. The outcomes of paediatric trials evaluating liraglutide, exenatide, semaglutide and dulaglutide in paediatric type 2 diabetes and obesity will be closely examined, including differences compared with adult studies. Finally, potential barriers and strategies to expanding GLP-1RA access in adolescents will be discussed. Future studies are needed to determine if the cardio-and renal-protective benefits of GLP-1RAs apply to youth-onset type 2 diabetes.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9988229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.17925/EE.2023.19.1.71
Alessandro D Genazzani, Andrea R Genazzani
Polycystic ovary syndrome (PCOS) is a very frequent disease that affects reproductive ability and menstrual regularity. Other than the criteria established at the Rotterdam consensus, in these last few years a new issue, insulin resistance, has been found frequently, and at a very high grade, in patients with PCOS. Insulin resistance occurs for several factors, such as overweight and obesity, but it is now clear that it occurs in patients with PCOS with normal weight, thus supporting the hypothesis that insulin resistance is independent of body weight. Evidence shows that a complex pathophysiological situation occurs that impairs post-receptor insulin signalling, especially in patients with PCOS and familial diabetes. In addition, patients with PCOS have a high incidence of non-alcoholic fatty liver disease related to the hyperinsulinaemia. This narrative review focuses on the recent new insights about insulin resistance in patients with PCOS, to better understand the metabolic impairment accounting for most of the clinical signs/symptoms of PCOS.
{"title":"Polycystic Ovary Syndrome as Metabolic Disease: New Insights on Insulin Resistance.","authors":"Alessandro D Genazzani, Andrea R Genazzani","doi":"10.17925/EE.2023.19.1.71","DOIUrl":"https://doi.org/10.17925/EE.2023.19.1.71","url":null,"abstract":"<p><p>Polycystic ovary syndrome (PCOS) is a very frequent disease that affects reproductive ability and menstrual regularity. Other than the criteria established at the Rotterdam consensus, in these last few years a new issue, insulin resistance, has been found frequently, and at a very high grade, in patients with PCOS. Insulin resistance occurs for several factors, such as overweight and obesity, but it is now clear that it occurs in patients with PCOS with normal weight, thus supporting the hypothesis that insulin resistance is independent of body weight. Evidence shows that a complex pathophysiological situation occurs that impairs post-receptor insulin signalling, especially in patients with PCOS and familial diabetes. In addition, patients with PCOS have a high incidence of non-alcoholic fatty liver disease related to the hyperinsulinaemia. This narrative review focuses on the recent new insights about insulin resistance in patients with PCOS, to better understand the metabolic impairment accounting for most of the clinical signs/symptoms of PCOS.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10004894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epigenetics of type 2 diabetes mellitus (T2DM) has widened our knowledge of various aspects of the disease. The aim of this review is to summarize the important epigenetic changes implicated in the disease risks, pathogenesis, complications and the evolution of therapeutics in our current understanding of T2DM. Studies published in the past 15 years, from 2007 to 2022, from three primary platforms namely PubMed, Google Scholar and Science Direct were included. Studies were searched using the primary term 'type 2 diabetes and epigenetics' with additional terms such as 'risks', 'pathogenesis', 'complications of diabetes' and 'therapeutics'. Epigenetics plays an important role in the transmission of T2DM from one generation to another. Epigenetic changes are also implicated in the two basic pathogenic components of T2DM, namely insulin resistance and impaired insulin secretion. Hyperglycaemia-i nduced permanent epigenetic modifications of the expression of DNA are responsible for the phenomenon of metabolic memory. Epigenetics influences the development of micro-and macrovascular complications of T2DM. They can also be used as biomarkers in the prediction of these complications. Epigenetics has expanded our understanding of the action of existing drugs such as metformin, and has led to the development of newer targets to prevent vascular complications. Epigenetic changes are involved in almost all aspects of T2DM, from risks, pathogenesis and complications, to the development of newer therapeutic targets.
{"title":"Epigenetics of the Pathogenesis and Complications of Type 2 Diabetes Mellitus.","authors":"Velmurugan Mannar, Hiya Boro, Deepika Patel, Sourabh Agstam, Mazhar Dalvi, Vikash Bundela","doi":"10.17925/EE.2023.19.1.46","DOIUrl":"https://doi.org/10.17925/EE.2023.19.1.46","url":null,"abstract":"<p><p>Epigenetics of type 2 diabetes mellitus (T2DM) has widened our knowledge of various aspects of the disease. The aim of this review is to summarize the important epigenetic changes implicated in the disease risks, pathogenesis, complications and the evolution of therapeutics in our current understanding of T2DM. Studies published in the past 15 years, from 2007 to 2022, from three primary platforms namely PubMed, Google Scholar and Science Direct were included. Studies were searched using the primary term 'type 2 diabetes and epigenetics' with additional terms such as 'risks', 'pathogenesis', 'complications of diabetes' and 'therapeutics'. Epigenetics plays an important role in the transmission of T2DM from one generation to another. Epigenetic changes are also implicated in the two basic pathogenic components of T2DM, namely insulin resistance and impaired insulin secretion. Hyperglycaemia-i nduced permanent epigenetic modifications of the expression of DNA are responsible for the phenomenon of metabolic memory. Epigenetics influences the development of micro-and macrovascular complications of T2DM. They can also be used as biomarkers in the prediction of these complications. Epigenetics has expanded our understanding of the action of existing drugs such as metformin, and has led to the development of newer targets to prevent vascular complications. Epigenetic changes are involved in almost all aspects of T2DM, from risks, pathogenesis and complications, to the development of newer therapeutic targets.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9988227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.17925/EE.2023.19.1.16
Ides M Colin, Lidia W Szczepanski, Anne-Catherine Gérard, Jose-Antonio Elosegi
From an epidemiological and pathophysiological point of view, Alzheimer's disease (AD) and type 2 diabetes (T2DM) should be considered 'sister' diseases. T2DM significantly increases the risk of developing AD, and the mechanisms of neuronal degeneration themselves worsen peripheral glucose metabolism in multiple ways. The pathophysiological links between the two diseases, particularly cerebral insulin resistance, which causes neuronal degeneration, are so close that AD is sometimes referred to as 'type 3 diabetes'. Although the latest news on the therapeutic front for AD is encouraging, no treatment has been shown to halt disease progression permanently. At best, the treatments slow down the progression; at worst, they are inactive, or cause worrying side effects, preventing their use on a larger scale. Therefore, it appears logical that optimizing the metabolic milieu through preventive or curative measures can also slow down the cerebral degeneration that characterizes AD. Among the different classes of hypoglycaemic drugs, glucagon-like peptide 1 receptor agonists, which are widely used in the treatment of T2DM, were shown to slow down, or even prevent, neuronal degeneration. Data from animal, preclinical, clinical phase II, cohort and large cardiovascular outcomes studies are encouraging. Of course, randomized clinical phase III studies, which are on-going, will be essential to verify this hypothesis. Thus, for once, there is hope for slowing down the neurodegenerative processes associated with diabetes, and that hope is the focus of this review.
{"title":"Emerging Evidence for the Use of Antidiabetic Drugs, Glucagon-like Peptide 1 Receptor Agonists, for the Treatment of Alzheimer's Disease.","authors":"Ides M Colin, Lidia W Szczepanski, Anne-Catherine Gérard, Jose-Antonio Elosegi","doi":"10.17925/EE.2023.19.1.16","DOIUrl":"https://doi.org/10.17925/EE.2023.19.1.16","url":null,"abstract":"<p><p>From an epidemiological and pathophysiological point of view, Alzheimer's disease (AD) and type 2 diabetes (T2DM) should be considered 'sister' diseases. T2DM significantly increases the risk of developing AD, and the mechanisms of neuronal degeneration themselves worsen peripheral glucose metabolism in multiple ways. The pathophysiological links between the two diseases, particularly cerebral insulin resistance, which causes neuronal degeneration, are so close that AD is sometimes referred to as 'type 3 diabetes'. Although the latest news on the therapeutic front for AD is encouraging, no treatment has been shown to halt disease progression permanently. At best, the treatments slow down the progression; at worst, they are inactive, or cause worrying side effects, preventing their use on a larger scale. Therefore, it appears logical that optimizing the metabolic milieu through preventive or curative measures can also slow down the cerebral degeneration that characterizes AD. Among the different classes of hypoglycaemic drugs, glucagon-like peptide 1 receptor agonists, which are widely used in the treatment of T2DM, were shown to slow down, or even prevent, neuronal degeneration. Data from animal, preclinical, clinical phase II, cohort and large cardiovascular outcomes studies are encouraging. Of course, randomized clinical phase III studies, which are on-going, will be essential to verify this hypothesis. Thus, for once, there is hope for slowing down the neurodegenerative processes associated with diabetes, and that hope is the focus of this review.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10258618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9988684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}