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Dhieb D, Mustafa D, Hassiba M, Alasmar M, Elsayed MH, Musa A, Zirie M, Bastaki K. Harnessing Pharmacomultiomics for Precision Medicine in Diabetes: A Comprehensive Review. Biomedicines 2025; 13:447. [PMID: 40002860 PMCID: PMC11853021 DOI: 10.3390/biomedicines13020447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Revised: 12/08/2024] [Accepted: 12/11/2024] [Indexed: 02/27/2025] Open
Abstract
Type 2 diabetes (T2D) is the fastest-growing non-communicable disease worldwide, accounting for around 90% of all diabetes cases and imposing a significant health burden globally. Due to its phenotypic heterogeneity and composite genetic underpinnings, T2D requires a precision medicine approach personalized to individual molecular profiles, thereby shifting away from the traditional "one-size-fits-all" medical methods. This review advocates for a thorough pharmacomultiomics approach to enhance precision medicine for T2D. It emphasizes personalized treatment strategies that enhance treatment efficacy while minimizing adverse effects by integrating data from genomics, proteomics, metabolomics, transcriptomics, microbiomics, and epigenomics. We summarize key findings on candidate genes impacting diabetic medication responses and explore the potential of pharmacometabolomics in predicting drug efficacy. The role of pharmacoproteomics in prognosis and discovering new therapeutic targets is discussed, along with transcriptomics' contribution to understanding T2D pathophysiology. Additionally, pharmacomicrobiomics is explored to understand gut microbiota interactions with antidiabetic drugs. Emerging evidence on utilizing epigenomic profiles in improving drug efficacy and personalized treatment is also reviewed, illustrating their implications in personalized medicine. In this paper, we discuss the integration of these layers of omics data, examining recently developed paradigms that leverage complex data to deepen our understanding of diabetes. Such integrative approaches advance precision medicine strategies to tackle the disease by better understanding its complex biology.
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Affiliation(s)
- Dhoha Dhieb
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (D.D.); (D.M.); (M.H.); (M.H.E.)
| | - Dana Mustafa
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (D.D.); (D.M.); (M.H.); (M.H.E.)
| | - Maryam Hassiba
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (D.D.); (D.M.); (M.H.); (M.H.E.)
| | - May Alasmar
- Hamad Medical Corporation, Doha P.O. Box 3050, Qatar; (M.A.); (M.Z.)
| | - Mohamed Haitham Elsayed
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (D.D.); (D.M.); (M.H.); (M.H.E.)
| | - Ameer Musa
- College of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, Qatar;
| | - Mahmoud Zirie
- Hamad Medical Corporation, Doha P.O. Box 3050, Qatar; (M.A.); (M.Z.)
| | - Kholoud Bastaki
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (D.D.); (D.M.); (M.H.); (M.H.E.)
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An X, Zhang Y, Sun W, Kang X, Ji H, Sun Y, Jiang L, Zhao X, Gao Q, Lian F, Tong X. Early effective intervention can significantly reduce all-cause mortality in prediabetic patients: a systematic review and meta-analysis based on high-quality clinical studies. Front Endocrinol (Lausanne) 2024; 15:1294819. [PMID: 38495794 PMCID: PMC10941028 DOI: 10.3389/fendo.2024.1294819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 02/19/2024] [Indexed: 03/19/2024] Open
Abstract
Background Reducing the occurrence of diabetes is considered a primary criterion for evaluating the effectiveness of interventions for prediabetes. There is existing evidence that early lifestyle-based interventions can significantly decrease the incidence of diabetes. However, whether effective interventions can reduce long-term outcomes in patients, including all-cause mortality, cardiovascular risks, and the occurrence of microvascular complications, which are the most concerning issues for both patients and clinicians, remains a subject of inconsistent research findings. And there is no direct evidence to answer whether effective intervention has long-term benefits for prediabetic patients. Therefore, we conducted a systematic review and meta-analysis to assess the relationship between early effective intervention and macrovascular and microvascular complications in prediabetic patients. Methods PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for the randomized controlled trials of lifestyle or/and drugs intervention in prediabetes from inception to 2023.9.15. Two investigators independently reviewed the included studies and extracted relevant data. Random or fixed effects model meta-analysis to derive overall relative risk (RR) with 95% CI for all-cause mortality, cardiovascular events, and microvascular complications. Results As of September 15, 2023, a total of 7 effective intervention studies were included, comprising 26 articles out of 25,671 articles. These studies involved 26,389 patients with a total follow-up duration of 178,038.6 person-years. The results indicate that effective intervention can significantly reduce all-cause mortality in prediabetic patients without a history of cardiovascular disease by 17% (RR 0.83, 95% CI 0.70-0.98). Additionally, effective intervention reduced the incidence of retinopathy by 38% (RR 0.62, 95% CI 0.70-0.98). Furthermore, the study results suggest that women and younger individuals have lower all-cause mortality and cardiovascular mortality. Subsequently, we conducted an in-depth analysis of patients without a history of cardiovascular disease. The results revealed that prediabetic patients with a 10-year cardiovascular risk >10% experienced more significant benefits in terms of all-cause mortality (P=0.01). When comparing the results of all-cause mortality and cardiovascular mortality from the Da Qing Diabetes Prevention Outcome Study longitudinally, it was evident that the duration of follow-up is a key factor influencing long-term benefits. In other words, the beneficial effects become more pronounced as the intervention duration reaches a certain threshold. Conclusion Early effective intervention, which significantly reduces the incidence of diabetes, can effectively lower all-cause mortality in prediabetic patients without a history of cardiovascular disease (especially those with a 10-year cardiovascular risk >10%), with women and younger individuals benefiting more significantly. Additionally, the duration of follow-up is a key factor influencing outcomes. The conclusions of this study can provide evidence-based guidance for the clinical treatment of prediabetic patients to prevent cardiovascular and microvascular complications. Systematic review registration https://www.crd.york.ac.uk/prospero, identifier CRD42020160985.
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Affiliation(s)
- Xuedong An
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuehong Zhang
- Fangshan Hospital of Beijing University of Chinese Medicine, Beijing, China
| | - Wenjie Sun
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaomin Kang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hangyu Ji
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuting Sun
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Linlin Jiang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xuefei Zhao
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qing Gao
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Fengmei Lian
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaolin Tong
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Oikonomou E, Xenou M, Zakynthinos GE, Tsaplaris P, Lampsas S, Bletsa E, Gialamas I, Kalogeras K, Goliopoulou A, Gounaridi MI, Pesiridis T, Tsatsaragkou A, Vavouranakis M, Siasos G, Tousoulis D. Novel Approaches to the Management of Diabetes Mellitus in Patients with Coronary Artery Disease. Curr Pharm Des 2023; 29:1844-1862. [PMID: 37403390 DOI: 10.2174/1381612829666230703161058] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Revised: 05/20/2023] [Accepted: 05/29/2023] [Indexed: 07/06/2023]
Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with diabetes mellitus (DM). Although benefit has been attributed to the strict control of hyperglycemia with traditional antidiabetic treatments, novel antidiabetic medications have demonstrated cardiovascular (CV) safety and benefits by reducing major adverse cardiac events, improving heart failure (HF), and decreasing CVD-related mortality. Emerging data underline the interrelation between diabetes, as a metabolic disorder, and inflammation, endothelial dysfunction, and oxidative stress in the pathogenesis of microvascular and macrovascular complications. Conventional glucose-lowering medications demonstrate controversial CV effects. Dipeptidyl peptidase- 4 inhibitors have not only failed to prove to be beneficial in patients with coronary artery disease, but also their safety is questionable for the treatment of patients with CVD. However, metformin, as the first-line option for type 2 DM (T2DM), shows CVD protective properties for DM-induced atherosclerotic and macrovascular complications. Thiazolidinedione and sulfonylureas have questionable effects, as evidence from large studies shows a reduction in the risk of CV events and deaths, but with an increased rate of hospitalization for HF. Moreover, several studies have revealed that insulin monotherapy for T2DM treatment increases the risk of major CV events and deaths from HF, when compared to metformin, although it may reduce the risk of myocardial infarction. Finally, this review aimed to summarize the mechanisms of action of novel antidiabetic drugs acting as glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors that show favorable effects on blood pressure, lipid levels, and inflammation, leading to reduced CVD risk in T2DM patients.
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Affiliation(s)
- Evangelos Oikonomou
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Xenou
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - George E Zakynthinos
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Paraskevas Tsaplaris
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Stamatios Lampsas
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Evanthia Bletsa
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Gialamas
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Konstantinos Kalogeras
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Athina Goliopoulou
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria I Gounaridi
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Theodoros Pesiridis
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Aikaterini Tsatsaragkou
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Manolis Vavouranakis
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Gerasimos Siasos
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
- Cardiovascular Division, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA
| | - Dimitris Tousoulis
- 3rd Department of Cardiology, Medical School, "Sotiria" Chest Diseases Hospital, National and Kapodistrian University of Athens, Athens, Greece
- 1st Department of Cardiology, Medical School, Hippokration General Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Xiao PJ, Zeng JC, Lin P, Tang DB, Yuan E, Tu YG, Zhang QF, Chen JG, Peng DY, Yin ZP. Chalcone-1-Deoxynojirimycin Heterozygote Reduced the Blood Glucose Concentration and Alleviated the Adverse Symptoms and Intestinal Flora Disorder of Diabetes Mellitus Rats. Molecules 2022; 27:7583. [PMID: 36364410 PMCID: PMC9658082 DOI: 10.3390/molecules27217583] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 10/30/2022] [Accepted: 11/02/2022] [Indexed: 02/04/2024] Open
Abstract
Chalcone-1-deoxynojirimycin heterozygote (DC-5), a novel compound which was designed and synthesized in our laboratory for diabetes treatment, showed an extremely strong in vitro inhibitory activity on α-glucosidase in our previous studies. In the current research, its potential in vivo anti-diabetic effects were further investigated by integration detection and the analysis of blood glucose concentration, blood biochemical parameters, tissue section and gut microbiota of the diabetic rats. The results indicated that oral administration of DC-5 significantly reduced the fasting blood glucose and postprandial blood glucose, both in diabetic and normal rats; meanwhile, it alleviated the adverse symptoms of elevated blood lipid level and lipid metabolism disorder in diabetic rats. Furthermore, DC-5 effectively decreased the organ coefficient and alleviated the pathological changes of the liver, kidney and small intestine of the diabetic rats at the same time. Moreover, the results of 16S rDNA gene sequencing analysis suggested that DC-5 significantly increased the ratio of Firmicutes to Bacteroidetes and improved the disorder of gut microbiota in diabetic rats. In conclusion, DC-5 displayed a good therapeutic effect on the diabetic rats, and therefore had a good application prospect in hypoglycemic drugs and foods.
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Affiliation(s)
- Pin-Jian Xiao
- Jiangxi Key Laboratory of Natural Products and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China
| | - Jia-Cheng Zeng
- Jiangxi Key Laboratory of Natural Products and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China
| | - Ping Lin
- Jiangxi Key Laboratory of Natural Products and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China
| | - Dao-Bang Tang
- Sericultural & Agri-Food Research Institute, Guangdong Academy of Agricultural Sciences/Key Laboratory of Functional Foods, Guangdong Key Laboratory of Agricultural Products Processing, Guangzhou 510610, China
| | - En Yuan
- College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Yong-Gang Tu
- Jiangxi Key Laboratory of Natural Products and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China
| | - Qing-Feng Zhang
- Jiangxi Key Laboratory of Natural Products and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China
| | - Ji-Guang Chen
- Jiangxi Key Laboratory of Natural Products and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China
| | - Da-Yong Peng
- Jiangxi Key Laboratory of Natural Products and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China
| | - Zhong-Ping Yin
- Jiangxi Key Laboratory of Natural Products and Functional Food, College of Food Science and Engineering, Jiangxi Agricultural University, Nanchang 330045, China
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Buysschaert M, Bergman M, Valensi P. 1-h post-load plasma glucose for detecting early stages of prediabetes. DIABETES & METABOLISM 2022; 48:101395. [PMID: 36184047 DOI: 10.1016/j.diabet.2022.101395] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 09/28/2022] [Accepted: 09/28/2022] [Indexed: 06/16/2023]
Abstract
Prediabetes is a very prevalent condition associated with an increased risk of developing diabetes and/or other chronic complications, in particular cardiovascular disorders. Early detection is therefore mandatory since therapeutic interventions may limit the development of these complications. Diagnosis of prediabetes is currently based on glycemic criteria (fasting plasma glucose (PG), and/or glycemia at 120 min during a 75 g oral glucose tolerance test (OGTT) and/or glycated hemoglobin (HbA1c). Accumulating longitudinal evidence suggests that a 1-hour PG ≥155 mg/dl (8.6 mmol/l) during the OGTT is an earlier marker of prediabetes than fasting PG, 2-h post-load PG, or HbA1c. There is substantial evidence demonstrating that the 1-h post-load PG is a more sensitive predictor of type 2 diabetes, cardiovascular disease, microangiopathy and mortality compared with conventional glucose criteria. The aim of this review is to highlight the paramount importance of detecting prediabetes early in its pathophysiological course. Accordingly, as recommended by an international panel in a recent petition, 1-h post-load PG could replace current criteria for diagnosing early stages of "prediabetes" before prediabetes evolves as conventionally defined.
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Affiliation(s)
- M Buysschaert
- Service d'Endocrinologie et Nutrition, Cliniques universitaires UCLouvain Saint-Luc, B-1200 Brussels, Belgium.
| | - M Bergman
- NYU Grossman School of Medicine, Division of Endocrinology, Diabetes and Metabolism, New York, NY, USA
| | - P Valensi
- Unit of Endocrinology-Diabetology-Nutrition. Jean Verdier Hospital, APHP, Paris 13 University, Sorbonne Paris Cité, CINFO, CRNH-IdF. Bondy, France
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Koniari I, Velissaris D, Kounis NG, Koufou E, Artopoulou E, de Gregorio C, Mplani V, Paraskevas T, Tsigkas G, Hung MY, Plotas P, Lambadiari V, Ikonomidis I. Anti-Diabetic Therapy, Heart Failure and Oxidative Stress: An Update. J Clin Med 2022; 11:4660. [PMID: 36012897 PMCID: PMC9409680 DOI: 10.3390/jcm11164660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 07/31/2022] [Accepted: 08/01/2022] [Indexed: 11/17/2022] Open
Abstract
Diabetes mellitus (DM) and heart failure (HF) are two chronic disorders that affect millions worldwide. Hyperglycemia can induce excessive generation of highly reactive free radicals that promote oxidative stress and further exacerbate diabetes progression and its complications. Vascular dysfunction and damage to cellular proteins, membrane lipids and nucleic acids can stem from overproduction and/or insufficient removal of free radicals. The aim of this article is to review the literature regarding the use of antidiabetic drugs and their role in glycemic control in patients with heart failure and oxidative stress. Metformin exerts a minor benefit to these patients. Thiazolidinediones are not recommended in diabetic patients, as they increase the risk of HF. There is a lack of robust evidence on the use of meglinitides and acarbose. Insulin and dipeptidyl peptidase-4 (DPP-4) inhibitors may have a neutral cardiovascular effect on diabetic patients. The majority of current research focuses on sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. SGLT2 inhibitors induce positive cardiovascular effects in diabetic patients, leading to a reduction in cardiovascular mortality and HF hospitalization. GLP-1 receptor agonists may also be used in HF patients, but in the case of chronic kidney disease, SLGT2 inhibitors should be preferred.
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Affiliation(s)
- Ioanna Koniari
- Department of Cardiology, University Hospital of South Manchester NHS Foundation Trust, Manchester M23 9LT, UK
| | - Dimitrios Velissaris
- Department of Internal Medicine, University Hospital of Patras, 26500 Patras, Greece
| | - Nicholas G. Kounis
- Department of Cardiology, University Hospital of Patras, 26500 Patras, Greece
| | - Eleni Koufou
- Department of Cardiology, University Hospital of Patras, 26500 Patras, Greece
| | - Eleni Artopoulou
- Department of Internal Medicine, University Hospital of Patras, 26500 Patras, Greece
| | - Cesare de Gregorio
- Department of Clinical and Experimental Medicine, University of Messina Medical School, 98122 Messina, Italy
| | - Virginia Mplani
- Intensive Care Unit, Patras University Hospital, 26500 Patras, Greece
| | | | - Grigorios Tsigkas
- Department of Cardiology, University Hospital of Patras, 26500 Patras, Greece
| | - Ming-Yow Hung
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
- Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
- Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan
| | - Panagiotis Plotas
- Laboratory Primary Health Care, School of Health Rehabilitation Sciences, University of Patras, 26504 Patras, Greece
| | - Vaia Lambadiari
- Second Department of Internal Medicine, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
| | - Ignatios Ikonomidis
- Second Cardiology Department, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece
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Venkatachalapathy P, Padhilahouse S, Sellappan M, Subramanian T, Kurian SJ, Miraj SS, Rao M, Raut AA, Kanwar RK, Singh J, Khadanga S, Mondithoka S, Munisamy M. Pharmacogenomics and Personalized Medicine in Type 2 Diabetes Mellitus: Potential Implications for Clinical Practice. Pharmgenomics Pers Med 2021; 14:1441-1455. [PMID: 34803393 PMCID: PMC8598203 DOI: 10.2147/pgpm.s329787] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 10/04/2021] [Indexed: 12/20/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, and is rising in incidence with widespread prevalence. Multiple gene variants are associated with glucose homeostasis, complex T2DM pathogenesis, and its complications. Exploring more effective therapeutic strategies for patients with diabetes is crucial. Pharmacogenomics has made precision medicine possible by allowing for individualized drug therapy based on a patient's genetic and genomic information. T2DM is treated with various classes of oral hypoglycemic agents, such as biguanides, sulfonylureas, thiazolidinediones, meglitinides, DPP4 inhibitors, SGLT2 inhibitors, α-glucosidase inhibitors, and GLP1 analogues, which exhibit various pharmacogenetic variants. Although genomic interventions in monogenic diabetes have been implemented in clinical practice, they are still in the early stages for complex polygenic disorders, such as T2DM. Precision DM medicine has the potential to be effective in personalized therapy for those suffering from various forms of DM, such as T2DM. With recent developments in genetic techniques, the application of candidate-gene studies, large-scale genotyping investigations, genome-wide association studies, and "multiomics" studies has begun to produce results that may lead to changes in clinical practice. Enhanced knowledge of the genetic architecture of T2DM presents a bigger translational potential. This review summarizes the genetics and pathophysiology of T2DM, candidate-gene approaches, genome-wide association studies, personalized medicine, clinical relevance of pharmacogenetic variants associated with oral hypoglycemic agents, and paths toward personalized diabetology.
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Affiliation(s)
| | - Sruthi Padhilahouse
- Department of Pharmacy Practice, Karpagam College of Pharmacy, Coimbatore, Tamilnadu, India
| | - Mohan Sellappan
- Department of Pharmacy Practice, Karpagam College of Pharmacy, Coimbatore, Tamilnadu, India
| | | | - Shilia Jacob Kurian
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Sonal Sekhar Miraj
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Mahadev Rao
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Ashwin Ashok Raut
- Translational Medicine Centre, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Rupinder Kaur Kanwar
- Translational Medicine Centre, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Jitendra Singh
- Translational Medicine Centre, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Sagar Khadanga
- Department of General Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Sukumar Mondithoka
- Department of General Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
| | - Murali Munisamy
- Translational Medicine Centre, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India
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Madsen KS, Chi Y, Metzendorf M, Richter B, Hemmingsen B, Cochrane Metabolic and Endocrine Disorders Group. Metformin for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev 2019; 12:CD008558. [PMID: 31794067 PMCID: PMC6889926 DOI: 10.1002/14651858.cd008558.pub2] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether metformin can prevent or delay T2DM and its complications in people with increased risk of developing T2DM is unknown. OBJECTIVES To assess the effects of metformin for the prevention or delay of T2DM and its associated complications in persons at increased risk for the T2DM. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform and the reference lists of systematic reviews, articles and health technology assessment reports. We asked investigators of the included trials for information about additional trials. The date of the last search of all databases was March 2019. SELECTION CRITERIA We included randomised controlled trials (RCTs) with a duration of one year or more comparing metformin with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or standard care in people with impaired glucose tolerance, impaired fasting glucose, moderately elevated glycosylated haemoglobin A1c (HbA1c) or combinations of these. DATA COLLECTION AND ANALYSIS Two review authors read all abstracts and full-text articles and records, assessed risk of bias and extracted outcome data independently. We used a random-effects model to perform meta-analysis and calculated risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the certainty of the evidence using GRADE. MAIN RESULTS We included 20 RCTs randomising 6774 participants. One trial contributed 48% of all participants. The duration of intervention in the trials varied from one to five years. We judged none of the trials to be at low risk of bias in all 'Risk of bias' domains. Our main outcome measures were all-cause mortality, incidence of T2DM, serious adverse events (SAEs), cardiovascular mortality, non-fatal myocardial infarction or stroke, health-related quality of life and socioeconomic effects.The following comparisons mostly reported only a fraction of our main outcome set. Fifteen RCTs compared metformin with diet and exercise with or without placebo: all-cause mortality was 7/1353 versus 7/1480 (RR 1.11, 95% CI 0.41 to 3.01; P = 0.83; 2833 participants, 5 trials; very low-quality evidence); incidence of T2DM was 324/1751 versus 529/1881 participants (RR 0.50, 95% CI 0.38 to 0.65; P < 0.001; 3632 participants, 12 trials; moderate-quality evidence); the reporting of SAEs was insufficient and diverse and meta-analysis could not be performed (reported numbers were 4/118 versus 2/191; 309 participants; 4 trials; very low-quality evidence); cardiovascular mortality was 1/1073 versus 4/1082 (2416 participants; 2 trials; very low-quality evidence). One trial reported no clear difference in health-related quality of life after 3.2 years of follow-up (very low-quality evidence). Two trials estimated the direct medical costs (DMC) per participant for metformin varying from $220 to $1177 versus $61 to $184 in the comparator group (2416 participants; 2 trials; low-quality evidence). Eight RCTs compared metformin with intensive diet and exercise: all-cause mortality was 7/1278 versus 4/1272 (RR 1.61, 95% CI 0.50 to 5.23; P = 0.43; 2550 participants, 4 trials; very low-quality evidence); incidence of T2DM was 304/1455 versus 251/1505 (RR 0.80, 95% CI 0.47 to 1.37; P = 0.42; 2960 participants, 7 trials; moderate-quality evidence); the reporting of SAEs was sparse and meta-analysis could not be performed (one trial reported 1/44 in the metformin group versus 0/36 in the intensive exercise and diet group with SAEs). One trial reported that 1/1073 participants in the metformin group compared with 2/1079 participants in the comparator group died from cardiovascular causes. One trial reported that no participant died due to cardiovascular causes (very low-quality evidence). Two trials estimated the DMC per participant for metformin varying from $220 to $1177 versus $225 to $3628 in the comparator group (2400 participants; 2 trials; very low-quality evidence). Three RCTs compared metformin with acarbose: all-cause mortality was 1/44 versus 0/45 (89 participants; 1 trial; very low-quality evidence); incidence of T2DM was 12/147 versus 7/148 (RR 1.72, 95% CI 0.72 to 4.14; P = 0.22; 295 participants; 3 trials; low-quality evidence); SAEs were 1/51 versus 2/50 (101 participants; 1 trial; very low-quality evidence). Three RCTs compared metformin with thiazolidinediones: incidence of T2DM was 9/161 versus 9/159 (RR 0.99, 95% CI 0.41 to 2.40; P = 0.98; 320 participants; 3 trials; low-quality evidence). SAEs were 3/45 versus 0/41 (86 participants; 1 trial; very low-quality evidence). Three RCTs compared metformin plus intensive diet and exercise with identical intensive diet and exercise: all-cause mortality was 1/121 versus 1/120 participants (450 participants; 2 trials; very low-quality evidence); incidence of T2DM was 48/166 versus 53/166 (RR 0.55, 95% CI 0.10 to 2.92; P = 0.49; 332 participants; 2 trials; very low-quality evidence). One trial estimated the DMC of metformin plus intensive diet and exercise to be $270 per participant compared with $225 in the comparator group (94 participants; 1 trial; very-low quality evidence). One trial in 45 participants compared metformin with a sulphonylurea. The trial reported no patient-important outcomes. For all comparisons there were no data on non-fatal myocardial infarction, non-fatal stroke or microvascular complications. We identified 11 ongoing trials which potentially could provide data of interest for this review. These trials will add a total of 17,853 participants in future updates of this review. AUTHORS' CONCLUSIONS Metformin compared with placebo or diet and exercise reduced or delayed the risk of T2DM in people at increased risk for the development of T2DM (moderate-quality evidence). However, metformin compared to intensive diet and exercise did not reduce or delay the risk of T2DM (moderate-quality evidence). Likewise, the combination of metformin and intensive diet and exercise compared to intensive diet and exercise only neither showed an advantage or disadvantage regarding the development of T2DM (very low-quality evidence). Data on patient-important outcomes such as mortality, macrovascular and microvascular diabetic complications and health-related quality of life were sparse or missing.
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Affiliation(s)
- Kasper S Madsen
- University of CopenhagenFaculty of Health and Medical SciencesBlegdamsvej 3BCopenhagen NDenmark2200
| | - Yuan Chi
- University Hospital Zurich and University of ZurichInstitute for Complementary and Integrative MedicineSonneggstrasse 6ZurichBeijingSwitzerland8006
| | - Maria‐Inti Metzendorf
- Institute of General Practice, Medical Faculty of the Heinrich‐Heine‐University DüsseldorfCochrane Metabolic and Endocrine Disorders GroupMoorenstr. 5DüsseldorfGermany40225
| | - Bernd Richter
- Institute of General Practice, Medical Faculty of the Heinrich‐Heine‐University DüsseldorfCochrane Metabolic and Endocrine Disorders GroupMoorenstr. 5DüsseldorfGermany40225
| | - Bianca Hemmingsen
- Institute of General Practice, Medical Faculty of the Heinrich‐Heine‐University DüsseldorfCochrane Metabolic and Endocrine Disorders GroupMoorenstr. 5DüsseldorfGermany40225
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Impact of PPAR-Alpha Polymorphisms-The Case of Metabolic Disorders and Atherosclerosis. Int J Mol Sci 2019; 20:ijms20184378. [PMID: 31489930 PMCID: PMC6770475 DOI: 10.3390/ijms20184378] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Revised: 09/01/2019] [Accepted: 09/04/2019] [Indexed: 02/07/2023] Open
Abstract
Peroxisome proliferator activated receptor α (PPARα) has the most relevant biological functions among PPARs. Activation by drugs and dietary components lead to major metabolic changes, from reduced triglyceridemia to improvement in the metabolic syndrome. Polymorphisms of PPARα are of interest in order to improve our understanding of metabolic disorders associated with a raised or reduced risk of diseases. PPARα polymorphisms are mainly characterized by two sequence changes, L162V and V227A, with the latter occurring only in Eastern nations, and by numerous SNPs (Single nucleotide polymorphisms) with a less clear biological role. The minor allele of L162V associates with raised total cholesterol, LDL-C (low-density lipoprotein cholesterol), and triglycerides, reduced HDL-C (high-density lipoprotein metabolism), and elevated lipoprotein (a). An increased cardiovascular risk is not clear, whereas a raised risk of diabetes or of liver steatosis are not well supported. The minor allele of the V227A polymorphism is instead linked to a reduction of steatosis and raised γ-glutamyltranspeptidase levels in non-drinking Orientals, the latter being reduced in drinkers. Lastly, the minor allele of rs4353747 is associated with a raised high-altitude appetite loss. These and other associations indicate the predictive potential of PPARα polymorphisms for an improved understanding of human disease, which also explain variability in the clinical response to specific drug treatments or dietary approaches.
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Tamarai K, Bhatti JS, Reddy PH. Molecular and cellular bases of diabetes: Focus on type 2 diabetes mouse model-TallyHo. Biochim Biophys Acta Mol Basis Dis 2019; 1865:2276-2284. [PMID: 31082469 DOI: 10.1016/j.bbadis.2019.05.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 05/08/2019] [Accepted: 05/09/2019] [Indexed: 12/17/2022]
Abstract
Diabetes is a chronic lifestyle disorder that affects millions of people worldwide. Diabetes is a condition where the body does not produce sufficient insulin or does not use it efficiently. Insulin resistance in diabetes or obesity causes the pancreatic β-cells to increase the insulin output. Diabetes occurs in multiple forms, including type 1, type 2, type 3 and gestational. Type 2 diabetes accounts for ∼90-95% of total affected population and is associated with both impaired insulin production by the β-cells of the pancreas and impaired insulin release in response to high blood glucose levels. Diabetes is tightly linked with genetic mutations and genetic and lifestyle activities, including diet and exercise. Recent epidemiological studies established a close link between the diabetes and progression to Alzheimer's disease. This article summarizes various molecular mechanisms involved in the developments of diabetes, including biochemical characteristics, genetic and molecular links with Alzheimer's disease, β-cell function, and factors associated with diabetes. This will help us in the development of novel therapeutic strategies targeting AD in future.
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Affiliation(s)
- Kavya Tamarai
- Internal Medicine Department, Texas Tech University Health Sciences Center, 3601 4(th) Street, Lubbock, TX 79430, United States
| | - Jasvinder Singh Bhatti
- Internal Medicine Department, Texas Tech University Health Sciences Center, 3601 4(th) Street, Lubbock, TX 79430, United States; Department of Biotechnology, Sri Guru Gobind Singh College, Chandigarh, India
| | - P Hemachandra Reddy
- Internal Medicine Department, Texas Tech University Health Sciences Center, 3601 4(th) Street, Lubbock, TX 79430, United States; Garrison Institute on Aging, Texas Tech University Health Sciences Center, 3601 4(th) Street, MS 9424, Lubbock, TX 79430, United States; Cell Biology & Biochemistry Department, Texas Tech University Health Sciences Center, 3601 4(th) Street, Lubbock, TX 79430, United States; Pharmacology & Neuroscience Department, Texas Tech University Health Sciences Center, 3601 4(th) Street, MS 9424, Lubbock, TX 79430, United States; Neurology Department, Texas Tech University Health Sciences Center, 3601 4(th) Street, MS 9424, Lubbock, TX 79430, United States; Speech, Language and Hearing Sciences Department, Texas Tech University Health Sciences Center, 3601 4(th) Street, MS 9424, Lubbock, TX 79430, United States; Department of Public Health, Graduate School of Biomedical Sciences, 3601 4(th) Street, MS 9424, Lubbock, TX 79430, United States.
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11
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Dastbarhagh H, Kargarfard M, Abedi H, Bambaeichi E, Nazarali P. Effects of food restriction and/or aerobic exercise on the GLUT4 in type 2 diabetic male rats. Int J Prev Med 2019; 10:139. [PMID: 31516680 PMCID: PMC6710916 DOI: 10.4103/ijpvm.ijpvm_383_17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2017] [Accepted: 10/05/2017] [Indexed: 12/25/2022] Open
Abstract
Background The aim of present study was to compare the effects of negative energy balance with food restriction and/or aerobic exercise on the glucose, insulin, and GLUT4 levels in diabetic male rats. Methods Fifty-six 10-week old male Wistar rats were randomly assigned to seven groups: a non-diabetic (ND) group and six diabetic groups. After an infusion of type 2 diabetes, the diabetic groups were given labels as well, namely diabetic control (DC) group, exercise (Ex) group, food restriction with standard diet (FRSD) group, food restriction with low-carbohydrate diet (FRLCD) group, food restriction with standard diet combination in exercise (FRSDE) group, and food restriction with low-carbohydrate diet combination in exercise (FRLCDE) group. Further, to induce caloric restriction (CR), food intake was reduced by 20% and given to food restriction consists of both of (FRSD and FRLCD). Hundred percent food consumption for the Ex group was fixed, but instead, 20% of their energy intake in exercise was calculated, and time of daily exercise was determined. Finally, a combination of reduced food intake (10%) and exercise (10%) was applied in each group FRSDE and FRLCDE for 8 weeks. Results The results showed that type 2 diabetes inductions had reduced glucose, insulin, and GLUT4 gene expression compared to the ND group (P = 0.001). However, there were significant differences in GLUT4 gene expression between groups after 8 weeks of intervention (P = 0.001). A post hoc least significant difference test show that compared to DC group, GLUT4 gene expression level of Ex, FRSDE, and FRLCDE groups was significantly increased 47% (P = 0.004), 60% (P = 0.001), and 65% (P = 0.001), respectively after 8 week of intervention, but it was not significant or with any other diabetic groups (P > 0.05). Moreover, glucose levels were significantly higher in the FRLCDE, FRLCD, FRSD, FRSDE, Ex groups compared with the DC group in the same period (P = 0.0.01). Conclusions It was concluded that FRSD and FRLCD combination in regular exercise was elevated of GLUT4 gene expression in type 2 diabetes. These results may help to develop new methods for the treatment of obesity and type 2 diabetes mellitus.
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Affiliation(s)
- Hossien Dastbarhagh
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran
| | - Mehdi Kargarfard
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran
| | - Hassanali Abedi
- Research Center for Noncommunicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran
| | - Effat Bambaeichi
- Department of Exercise Physiology, Faculty of Sport Sciences, University of Isfahan, Isfahan, Iran
| | - Parvaneh Nazarali
- Faculty of Physical Education and Sport Sciences, Alzahra University, Tehran, Iran
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12
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Guo F, Zhang S, Yan X, Dan Y, Wang J, Zhao Y, Yu Z. Bioassay-guided isolation of antioxidant and α-glucosidase inhibitory constituents from stem of Vigna angularis. Bioorg Chem 2019; 87:312-320. [DOI: 10.1016/j.bioorg.2019.03.041] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 02/27/2019] [Accepted: 03/15/2019] [Indexed: 10/27/2022]
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13
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Kar P, Plummer MP, Ali Abdelhamid Y, Giersch EJ, Summers MJ, Weinel LM, Finnis ME, Phillips LK, Jones KL, Horowitz M, Deane AM. Incident Diabetes in Survivors of Critical Illness and Mechanisms Underlying Persistent Glucose Intolerance: A Prospective Cohort Study. Crit Care Med 2019; 47:e103-e111. [PMID: 30398977 DOI: 10.1097/ccm.0000000000003524] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Stress hyperglycemia occurs in critically ill patients and may be a risk factor for subsequent diabetes. The aims of this study were to determine incident diabetes and prevalent prediabetes in survivors of critical illness experiencing stress hyperglycemia and to explore underlying mechanisms. DESIGN This was a prospective, single center, cohort study. At admission to ICU, hemoglobin A1c was measured in eligible patients. Participants returned at 3 and 12 months after ICU admission and underwent hemoglobin A1c testing and an oral glucose tolerance test. Blood was also collected for hormone concentrations, whereas gastric emptying was measured via an isotope breath test. β-cell function was modeled using standard techniques. SETTING Tertiary-referral, mixed medical-surgical ICU. PATIENTS Consecutively admitted patients who developed stress hyperglycemia and survived to hospital discharge were eligible. MEASUREMENTS AND MAIN RESULTS Consent was obtained from 40 patients (mean age, 58 yr [SD, 10], hemoglobin A1c 36.8 mmol/mol [4.9 mmol/mol]) with 35 attending the 3-month and 26 the 12-month visits. At 3 months, 13 (37%) had diabetes and 15 (43%) had prediabetes. At 12 months, seven (27%) participants had diabetes, whereas 11 (42%) had prediabetes. Mean hemoglobin A1c increased from baseline during the study: +0.7 mmol/mol (-1.2 to 2.5 mmol/mol) at 3 months and +3.3 mmol/mol (0.98-5.59 mmol/mol) at 12 months (p = 0.02). Gastric emptying was not significantly different across groups at either 3 or 12 months. CONCLUSIONS Diabetes and prediabetes occur frequently in survivors of ICU experiencing stress hyperglycemia. Based on the occurrence rate observed in this cohort, structured screening and intervention programs appear warranted.
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Affiliation(s)
- Palash Kar
- Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Mark P Plummer
- Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA, Australia
- Intensive Care Unit, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia
| | - Yasmine Ali Abdelhamid
- Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA, Australia
- Intensive Care Unit, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia
| | - Emma J Giersch
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Matthew J Summers
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Luke M Weinel
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA, Australia
| | - Mark E Finnis
- Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA, Australia
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, SA, Australia
| | | | - Karen L Jones
- National Health and Medical Research Council Centre of Research Excellence (CRE) in the Translation of Nutritional Science into Good Health, University of Adelaide, Adelaide, SA, Australia
- Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia
| | | | - Adam M Deane
- Discipline of Acute Care Medicine, University of Adelaide, Adelaide, SA, Australia
- Intensive Care Unit, Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia
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Moelands SVL, Lucassen PLBJ, Akkermans RP, De Grauw WJC, Van de Laar FA, Cochrane Metabolic and Endocrine Disorders Group. Alpha-glucosidase inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus. Cochrane Database Syst Rev 2018; 12:CD005061. [PMID: 30592787 PMCID: PMC6517235 DOI: 10.1002/14651858.cd005061.pub3] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Alpha-glucosidase inhibitors (AGI) reduce blood glucose levels and may thus prevent or delay type 2 diabetes mellitus (T2DM) and its associated complications in people at risk of developing of T2DM. OBJECTIVES To assess the effects of AGI in people with impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was December 2017. SELECTION CRITERIA We included randomised controlled trials (RCTs), with a duration of one year or more, comparing AGI with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with IFG, IGT, moderately elevated HbA1c or combinations of these. DATA COLLECTION AND ANALYSIS Two review authors read all abstracts and full-text articles or records, assessed quality and extracted outcome data independently. One review author extracted data, which were checked by a second review author. We resolved discrepancies by consensus or involvement of a third review author. For meta-analyses we used a random-effects model with assessment of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall quality of the evidence by using the GRADE instrument. MAIN RESULTS For this update of the Cochrane Review (first published 2006, Issue 4) we included 10 RCTs (11,814 participants), eight investigating acarbose and two investigating voglibose, that included people with IGT or people "at increased risk for diabetes". The trial duration ranged from one to six years. Most trials compared AGI with placebo (N = 4) or no intervention (N = 4).Acarbose reduced the incidence of T2DM compared to placebo: 670 out of 4014 people (16.7%) in the acarbose groups developed T2DM, compared to 812 out of 3994 people (20.3%) in the placebo groups (RR 0.82, 95% CI 0.75 to 0.89; P < 0.0001; 3 trials; 8008 participants; moderate-certainty evidence). One trial including participants with coronary heart disease and IGT contributed 64% of cases for this outcome. Acarbose reduced the risk of T2DM compared to no intervention: 7 out 75 people (9.3%) in the acarbose groups developed T2DM, compared to 18 out of 65 people (27.7%) in the no-intervention groups (RR 0.31, 95% CI 0.14 to 0.69; P = 0.004; 2 trials; 140 participants; very low-certainty evidence).Acarbose compared to placebo did not reduce or increase the risk of all-cause mortality (RR 0.98, 95% CI 0.82 to 1.18; P = 0.86; 3 trials; 8069 participants; very low-certainty evidence), cardiovascular mortality (RR 0.88; 95% CI 0.71 to 1.10; P = 0.26; 3 trials; 8069 participants; very low-certainty evidence), serious adverse events (RR 1.12, 95% CI 0.97 to 1.29; P = 0.13; 2 trials; 6625 participants; low-certainty evidence), non-fatal stroke (RR 0.50, 95% CI 0.09 to 2.74; P = 0.43; 1 trial; 1368 participants; very low-certainty evidence) or congestive heart failure (RR of 0.87; 95% CI 0.63 to 1.12; P = 0.40; 2 trials; 7890 participants; low-certainty evidence). Acarbose compared to placebo reduced non-fatal myocardial infarction: one out of 742 participants (0.1%) in the acarbose groups had a non-fatal myocardial infarction compared to 15 out of 744 participants (2%) in the placebo groups (RR 0.10, 95% CI 0.02 to 0.53; P = 0.007; 2 trials; 1486 participants; very low-certainty evidence). Acarbose treatment showed an increased risk of non-serious adverse events (mainly gastro-intestinal events), compared to placebo: 751 of 775 people (96.9%) in the acarbose groups experienced an event, compared to 723 of 775 people (93.3%) in the placebo groups (RR 1.04; 95% CI 1.01 to 1.06; P = 0.0008; 2 trials; 1550 participants). Acarbose compared to no intervention showed no advantage or disadvantage for any of these outcome measures (very low-certainty evidence).One trial each compared voglibose with placebo (1780 participants) or diet and exercise (870 participants). Voglibose compared to placebo reduced the incidence of T2DM: 50 out of 897 participants (5.6%) developed T2DM, compared to 106 out of 881 participants (12%) in the placebo group (RR 0.46, 95% CI 0.34 to 0.64; P < 0.0001; 1 trial; 1778 participants; low-certainty evidence). For all other reported outcome measures there were no clear differences between voglibose and comparator groups. One trial with 90 participants compared acarbose with diet and exercise and another trial with 98 participants reported data on acarbose versus metformin. There were no clear differences for any outcome measure between these two acarbose interventions and the associated comparator groups.None of the trials reported amputation of lower extremity, blindness or severe vision loss, end-stage renal disease, health-related quality of life, time to progression to T2DM, or socioeconomic effects. AUTHORS' CONCLUSIONS AGI may prevent or delay the development of T2DM in people with IGT. There is no firm evidence that AGI have a beneficial effect on cardiovascular mortality or cardiovascular events.
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Affiliation(s)
- Suzanne VL Moelands
- Radboud University Nijmegen Medical CenterDepartment of Primary and Community CarePO Box 9101NijmegenNetherlands6500 HB
| | - Peter LBJ Lucassen
- Radboud University Nijmegen Medical CenterDepartment of Primary and Community CarePO Box 9101NijmegenNetherlands6500 HB
| | - Reinier P Akkermans
- Radboud University Nijmegen Medical CenterDepartment of Primary and Community CarePO Box 9101NijmegenNetherlands6500 HB
| | - Wim JC De Grauw
- Radboud University Nijmegen Medical CenterDepartment of Primary and Community CarePO Box 9101NijmegenNetherlands6500 HB
| | - Floris A Van de Laar
- Radboud University Nijmegen Medical CenterDepartment of Primary and Community CarePO Box 9101NijmegenNetherlands6500 HB
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Blaslov K, Naranđa FS, Kruljac I, Renar IP. Treatment approach to type 2 diabetes: Past, present and future. World J Diabetes 2018; 9:209-219. [PMID: 30588282 PMCID: PMC6304295 DOI: 10.4239/wjd.v9.i12.209] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2018] [Revised: 11/20/2018] [Accepted: 11/26/2018] [Indexed: 02/05/2023] Open
Abstract
Type 2 diabetes mellitus (DM) is a lifelong metabolic disease, characterized by hyperglycaemia which gradually leads to the development and progression of vascular complications. It is recognized as a global burden disease, with substantial consequences on human health (fatality) as well as on health-care system costs. This review focuses on the topic of historical discovery and understanding the complexity of the disease in the field of pathophysiology, as well as development of the pharmacotherapy beyond insulin. The complex interplay of insulin secretion and insulin resistance developed from previously known "ominous triumvirate" to "ominous octet" indicate the implication of multiple organs in glucose metabolism. The pharmacological approach has progressed from biguanides to a wide spectrum of medications that seem to provide a beneficial effect on the cardiovascular system. Despite this, we are still not achieving the target treatment goals. Thus, the future should bring novel antidiabetic drug classes capable of acting on several levels simultaneously. In conclusion, given the raising burden of type 2 DM, the best present strategy that could contribute the most to the reduction of morbidity and mortality should be focused on primary prevention.
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Affiliation(s)
- Kristina Blaslov
- Department of Endocrinology, Diabetes and Metabolic Diseases Mladen Sekso, University Hospital Center Sestre Milosrdnice, Zagreb 10000, Croatia
| | | | - Ivan Kruljac
- Department of Endocrinology, Diabetes and Metabolic Diseases Mladen Sekso, University Hospital Center Sestre Milosrdnice, Zagreb 10000, Croatia
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A Synergistic Formulation of Plant Extracts Decreases Postprandial Glucose and Insulin Peaks: Results from Two Randomized, Controlled, Cross-Over Studies Using Real-World Meals. Nutrients 2018; 10:nu10080956. [PMID: 30044398 PMCID: PMC6115802 DOI: 10.3390/nu10080956] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Revised: 07/19/2018] [Accepted: 07/23/2018] [Indexed: 01/21/2023] Open
Abstract
This study investigated the efficacy of a plant-derived dietary supplement with respect to decreasing postprandial glucose and insulin peaks after the intake of real-world meals. Two randomized, double-blind, placebo-controlled, cross-over experiments were conducted on healthy subjects who received a supplement containing extracts of white mulberry, white bean, and green coffee or one containing the three extracts with added fibre before consuming high-GI/GL (glycaemic index/glycaemic load) meals. In study one, 32 subjects received an investigational product/placebo before a standardized meal at two visits. In study two, 150 subjects received an investigational product/placebo before five different standardized meals. Postprandial glucose and insulin concentrations were lower 20–35 min after meal intake among subjects taking the investigational product, and fewer episodes of postprandial reactive hypoglycaemia were noted. For example, after consuming breakfast cereal with milk, lower glucose peaks were observed for the investigational product (vs. placebo) after 20 min (100.2 ± 1.97 vs. 112.5 ± 3.12 mg/dL, respectively; p < 0.01); lower insulin peaks were noted at the same time point (45.9 ± 4.02 IU/mL vs. 68.2 ± 5.53 IU/mL, respectively, p < 0.01). The combined formulation decreases the adverse consequences of high-GI/GL meal consumption. It can be an effective dietary supplement for the management of metabolic syndrome and type 2 diabetes mellitus.
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Alloubani A, Saleh A, Abdelhafiz I. Hypertension and diabetes mellitus as a predictive risk factors for stroke. Diabetes Metab Syndr 2018; 12:577-584. [PMID: 29571978 DOI: 10.1016/j.dsx.2018.03.009] [Citation(s) in RCA: 104] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 03/15/2018] [Indexed: 12/26/2022]
Abstract
BACKGROUND Stroke is becoming a major challenge in healthcare systems, and this has necessitated the study of the various risk factors. As the number of people with hypertension, diabetes mellitus and obesity increases, the problem is expected to worsen. This review paper evaluates what can be done to eliminate or reduce the risk of stroke. OBJECTIVE The aim of the research is to evaluate the risk factors for stroke. The paper also aims to understand how these risks can be handled to avoid incidences of stroke. METHOD Published clinical trials of stroke risk factors studies were recognised by a search of EMBASE and MEDLINE databases with keywords hypertension, blood pressure, diabetes mellitus, stroke or cardiovascular disease, or prospective study, and meta-analysis. RESULTS The findings of this review are that the prevention of stroke starts with identifying risk factors for stroke, most of the patients diagnosed with stroke have various risk factors. Consequently, it is a very significant to identify all the risk factors for stroke as well as to teach the patient how to dominate them. CONCLUSION after summarising all the studies mentioned in the paper, it can be established that hypertension and diabetes mellitus are a stroke risk factors and correlated in patients with atherosclerosis.
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Affiliation(s)
- Aladeen Alloubani
- King Hussein Cancer Center, Nursing Supervisor for Research & Evidence Based Practice, Amman, Jordan.
| | - Abdulmoneam Saleh
- University of Tabuk, Family Medicine, Faculty of Medicine, Tabuk, Saudi Arabia
| | - Ibrahim Abdelhafiz
- Al-Ghad International Health Sciences Colleges, Health Management, Najran, Saudi Arabia
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Kishibuchi R, Nishibori N, Sagara T, Morita K. Putative Effect of Spirulina Extract on Enzyme Activities Participating in Lipid and Carbohydrate Digestion Processes. J Diet Suppl 2018; 16:521-529. [PMID: 29958046 DOI: 10.1080/19390211.2018.1472166] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Excessive calorie intake is generally accepted as a primary cause of metabolic syndrome, and therefore a well-balanced diet and moderate exercise can be expected to be the most effective measures to avoid the disorder of energy utilization and storage. Furthermore, as any other way to improve the disorder of energy balance, it may be effective to delay and lower the digestion and/or absorption of energy sources, lipids, and carbohydrates. As a primary screening of effective substances to delay and lower the digestion and absorption processes among natural materials, the protein-deprived extract was prepared from blue-green algae Spirulina platensis, and the effect of this extract on lipase and α-glucosidase activities was examined. The extract was shown to inhibit lipase activity but not α-glucosidase activity, thus proposing the possibility that the extract prevented the postprandial elevation of blood triglyceride (TG) levels as a result of reducing the digestion and absorption of lipids in the intestinal tract. Therefore, it seems possible to speculate that nonprotein components of Spirulina may be able to effectively improve the disorder of energy balance as a consequence of suppressing the excessive intake of calories by reducing the absorption of lipids in patients with metabolic syndrome.
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Affiliation(s)
- Reina Kishibuchi
- Life Science Research Group, Shikoku University School of Health Sciences , Tokushima , Japan
| | - Naoyoshi Nishibori
- Life Science Research Group, Shikoku University School of Health Sciences , Tokushima , Japan.,Department of Food Science and Nutrition, Shikoku Junior College , Tokushima , Japan
| | - Takefumi Sagara
- Department of Food and Nutrition, Shokei Junior College , Kumamoto , Japan
| | - Kyoji Morita
- Life Science Research Group, Shikoku University School of Health Sciences , Tokushima , Japan
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Nishibori N, Kishibuchi R, Morita K. Suppressive effect of Okara on intestinal lipid digestion and absorption in mice ingesting high-fat diet. Int J Food Sci Nutr 2017; 69:690-695. [DOI: 10.1080/09637486.2017.1404969] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Naoyoshi Nishibori
- Life Science Research Group, Shikoku University School of Health Sciences, Tokushima, Japan
- Laboratory of Cell Biology and Toxicology, Department of Food Science and Nutrition, Shikoku Junior College, Tokushima, Japan
| | - Reina Kishibuchi
- Life Science Research Group, Shikoku University School of Health Sciences, Tokushima, Japan
| | - Kyoji Morita
- Life Science Research Group, Shikoku University School of Health Sciences, Tokushima, Japan
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Diabetes Medications and Cardiovascular Outcomes in Type 2 Diabetes. Heart Lung Circ 2017; 26:1133-1141. [PMID: 28473214 DOI: 10.1016/j.hlc.2017.02.030] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Revised: 02/19/2017] [Accepted: 02/23/2017] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Patients with type 2 diabetes have an increased risk of developing adverse cardiovascular (CV) outcomes. The evidence relating to the effects of glucose-lowering medications on CV outcomes is of variable quality and there are numerous trials ongoing. RESULTS In this review, we summarise the available literature on CV outcomes of the following diabetes treatments: metformin, the sulfonylureas, acarbose, glucagon-like peptide 1 (GLP1) receptor agonists, dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i), thiazolidinediones (TZDs) and insulin. CONCLUSIONS Insulin is required if glucose levels are very high. Otherwise, metformin, acarbose, some GLP1 receptor agonists and one SGLT2i appear beneficial for CV outcomes.
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Suzuki K, Takano H, Kubota Y, Inui K, Nakamura S, Tokita Y, Kato K, Asai K, Shimizu W. Plaque Characteristics in Coronary Artery Disease Patients with Impaired Glucose Tolerance. PLoS One 2016; 11:e0167645. [PMID: 27936195 PMCID: PMC5147949 DOI: 10.1371/journal.pone.0167645] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2016] [Accepted: 11/17/2016] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Impaired glucose tolerance (IGT) patients are known to have a high risk of cardiovascular events and their prognosis has been reported to be poor. The present study aimed to compare coronary plaque characteristics among coronary artery disease (CAD) patients with normal glucose tolerance (NGT), those with IGT, and those with diabetes mellitus (DM) by using optical coherence tomography (OCT). METHODS The present study included 101 coronary artery disease patients (mean age, 67.9 ± 10.4 years; 82.4% male). OCT was performed for target and non-target vessels during percutaneous coronary intervention. The patients were divided into the following 3 groups: the NGT, IGT, and DM groups. RESULTS A total of 136 non-target residual plaques were found in 101 patients (27, 30, and 44 in the NGT, IGT, and DM groups, respectively). The size of the lipid core expressed as the mean angle of the lipid arc was significantly greater in the IGT and DM groups than in the NGT group (163.0 ± 58.7°, 170.1 ± 59.3°, and 130.9 ± 37.7°, respectively, P < 0.05). The fibrous cap covering the lipid core was significantly thinner in the IGT group than in the NGT group (77.0 ± 23.4 μm vs. 105.6 ± 47.0 μm, P = 0.040). CONCLUSION The coronary plaques in CAD patients are more vulnerable when having IGT compared to those with NGT, and similar to those with DM. This finding may explain the high risk of cardiovascular events in CAD patients with IGT.
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Affiliation(s)
- Keishi Suzuki
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
| | - Hitoshi Takano
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
- * E-mail:
| | - Yoshiaki Kubota
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
| | - Keisuke Inui
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
| | - Shunichi Nakamura
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
| | - Yukichi Tokita
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
| | - Koji Kato
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
| | - Kuniya Asai
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
| | - Wataru Shimizu
- Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan
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Lovre D, Htun W, Carrion C, Fonseca VA. What Are We Learning from the FDA-Mandated Cardiovascular Outcome Studies for New Pharmacological Antidiabetic Agents? Curr Diab Rep 2016; 16:94. [PMID: 27541296 DOI: 10.1007/s11892-016-0788-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Cardiovascular disease (CVD) is common in patients with diabetes. For these patients, clinicians should seek diabetes treatment that is beneficial rather than harmful in relation to CVD. Until recently, there have been many treatments for hyperglycemia, whose impact on CVD has been controversial. The aims of this review are to evaluate the effectiveness of antihyperglycemic medications on risk factors for CVD and to examine the impact of these drugs on CVD in cardiovascular (CV) outcome trials. In this article, we summarize current knowledge about the impacts of these drugs on various risk factors as well as CV outcomes. We identify the recent emergence of trials with antihyperglycemic agents showing newly discovered CV benefits as well as past trials with antihyperglycemic agents not showing much benefit on CV events. Rather than focusing on treatment strategies, we review the effects of individual drug classes on CV outcomes. We also briefly review goal-driven glycemia reduction and its impact on CVD. We conclude that antihyperglycemic agents are associated with improvement in CV risk factors in patients with diabetes and insulin resistance; in fact, a few drugs reduced CV events in randomized CV outcome trials. Therefore, the use of these drugs is appropriate for reducing glucose and decreasing CV event risk in a select subpopulation.
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Affiliation(s)
- Dragana Lovre
- Tulane University Health Sciences Center, 1430 Tulane Ave., SL-53, New Orleans, LA, 70112, USA.
| | - Wynn Htun
- Tulane University Health Sciences Center, 1430 Tulane Ave., SL-53, New Orleans, LA, 70112, USA
| | - Carly Carrion
- Tulane University Health Sciences Center, 1430 Tulane Ave., SL-53, New Orleans, LA, 70112, USA
| | - Vivian A Fonseca
- Tulane University Health Sciences Center, 1430 Tulane Ave., SL-53, New Orleans, LA, 70112, USA
- Southeast Louisiana Veterans Health Care Systems, New Orleans, USA
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Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C, del Cañizo-Gómez FJ. Update on the treatment of type 2 diabetes mellitus. World J Diabetes 2016; 7:354-95. [PMID: 27660695 PMCID: PMC5027002 DOI: 10.4239/wjd.v7.i17.354] [Citation(s) in RCA: 366] [Impact Index Per Article: 40.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 07/02/2016] [Accepted: 07/20/2016] [Indexed: 02/05/2023] Open
Abstract
To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus (T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2DM, with an emphasis on agents introduced within the last decade.
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Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 2015; 58:429-42. [PMID: 25583541 DOI: 10.1007/s00125-014-3460-0] [Citation(s) in RCA: 509] [Impact Index Per Article: 50.9] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Accepted: 10/20/2014] [Indexed: 12/15/2022]
Affiliation(s)
- Silvio E Inzucchi
- Section of Endocrinology, Yale University School of Medicine, Yale-New Haven Hospital, New Haven, CT, USA
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Ezeji GC, Inoue T, Bahtiyar G, Sacerdote A. Hallucinations associated with miglitol use in a patient with chronic kidney disease and hypothyroidism. BMJ Case Rep 2015; 2015:bcr-2014-207345. [PMID: 25666246 DOI: 10.1136/bcr-2014-207345] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
A 71-year-old woman with type 2 diabetes mellitus, chronic kidney disease stage IV, primary hypothyroidism and osteoarthritis, whose prescribed treatment included miglitol 50 mg thrice daily with the first bite of meals, reported that she suffered visual hallucinations while taking miglitol, which resolved within a few days of stopping the drug. When she resumed miglitol, hallucinations recurred within a few days and again resolved within a few days of stopping the drug. To our knowledge, this is the first reported case of hallucinations associated with the use of an α-glucosidase inhibitor and highlights a previously unappreciated risk associated with the use of this generally quite benign drug class.
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Affiliation(s)
- George Chinedu Ezeji
- Department of Internal Medicine, Woodhull Medical Center, New York, New York, USA
| | - Taiga Inoue
- Department of Internal Medicine, Woodhull Medical Center, Brooklyn, New York, USA
| | - Gul Bahtiyar
- Department of Internal Medicine, Woodhull Medical Center, Brooklyn, New York, USA
| | - Alan Sacerdote
- Department of Internal Medicine, Woodhull Medical Center, Brooklyn, New York, USA
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Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015; 38:140-9. [PMID: 25538310 DOI: 10.2337/dc14-2441] [Citation(s) in RCA: 1887] [Impact Index Per Article: 188.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Silvio E Inzucchi
- Section of Endocrinology, Yale University School of Medicine, Yale-New Haven Hospital, New Haven, CT
| | | | - John B Buse
- Division of Endocrinology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Michaela Diamant
- Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Ele Ferrannini
- Department of Medicine, University of Pisa School of Medicine, Pisa, Italy
| | - Michael Nauck
- Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany
| | - Anne L Peters
- Division of Endocrinology, Keck School of Medicine of the University of Southern California, Los Angeles, CA
| | - Apostolos Tsapas
- Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece
| | - Richard Wender
- American Cancer Society, Atlanta, GA Department of Family and Community Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA
| | - David R Matthews
- Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, U.K. National Institute for Health Research (NIHR), Oxford Biomedical Research Centre, Oxford, U.K. Harris Manchester College, University of Oxford, Oxford, U.K
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Martín-Timón I, Sevillano-Collantes C, Segura-Galindo A, Cañizo-Gómez FJD. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength? World J Diabetes 2014; 5:444-470. [PMID: 25126392 PMCID: PMC4127581 DOI: 10.4239/wjd.v5.i4.444] [Citation(s) in RCA: 547] [Impact Index Per Article: 49.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Revised: 03/11/2014] [Accepted: 06/20/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin. Compared with individuals without diabetes, patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality, and are disproportionately affected by cardiovascular disease. Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension, dyslipidaemia and obesity in these patients. However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors. Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus. Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events. Many of these risk factors could be common history for both diabetes mellitus and cardiovascular disease, reinforcing the postulate that both disorders come independently from “common soil”. The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.
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Holman RR, Bethel MA, Chan JC, Chiasson JL, Doran Z, Ge J, Gerstein H, Huo Y, McMurray JJ, Ryden L, Liyanage W, Schröder S, Tendera M, Theodorakis MJ, Tuomilehto J, Yang W, Hu D, Pan C. Rationale for and design of the Acarbose Cardiovascular Evaluation (ACE) trial. Am Heart J 2014; 168:23-9.e2. [PMID: 24952856 DOI: 10.1016/j.ahj.2014.03.021] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Accepted: 03/17/2014] [Indexed: 01/26/2023]
Abstract
Patients with cardiovascular disease and impaired glucose tolerance are at increased risk of cardiovascular events and type 2 diabetes mellitus (T2DM). Lifestyle modification or pharmacological intervention can delay progression to T2DM, but there is no clear evidence that they reduce cardiovascular risk in this population. Acarbose, an α-glucosidase inhibitor that lowers postprandial blood glucose, has been shown to reduce T2DM risk by 25%, and possibly cardiovascular risk in impaired glucose tolerance subjects without cardiovascular disease.
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Sawada T, Shiotani H, Terashita D, Nagasawa Y, Kim SS, Koide M, Yokoyama M. Comparison of effects of α-Glucosidase inhibitors and glinide drugs on endothelial dysfunction in diabetic patients with coronary artery disease. Circ J 2013; 78:248-55. [PMID: 24225338 DOI: 10.1253/circj.cj-13-0918] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Studies have shown that repeated post-prandial hyperglycemia may play an important role in the development of atherosclerosis by suppressing endothelial function. α-Glucosidase inhibitors (α-GIs), which reduce post-prandial hyperglycemia without stimulating insulin secretion, significantly reduce the risk of coronary artery disease (CAD), whereas glinides, which improve post-prandial hyperglycemia through post-prandial insulin secretion, do not appear to affect CAD. METHODS AND RESULTS A total of 104 diabetic patients with CAD were randomly divided into 2 groups: those treated with miglitol (M-group; n=52) and those treated with nateglinide (N-group; n=52). After 4 months' treatment, although hemoglobin A1c and 1,5-anhydroglucitol were significantly improved in both groups, only the M-group had significant reductions in insulin resistance index and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C; a beneficial index for assessing the presence of small dense low-density lipoprotein, and a marker of atherogenic dyslipidemia). Furthermore, only the M-group had improvement in percentage flow-mediated dilatation (%FMD) and reactive oxygen metabolites. In the M-group, multiple regression analysis showed that improvement in TG/HDL-C, in addition to 1,5-anhydroglucitol, was an independent predictor of improvement in %FMD. CONCLUSIONS The ameliorating effect of α-GI on post-prandial hyperglycemia without stimulating insulin secretion may improve atherogenic dyslipidemia by reducing insulin resistance. These effects are associated with its beneficial impact on oxidative stress, consequently leading to an improvement in endothelial dysfunction.
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Affiliation(s)
- Takahiro Sawada
- Division of Cardiovascular Medicine, Himeji Brain and Heart Center
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Kojima Y, Kaga H, Hayashi S, Kitazawa T, Iimura Y, Ohno M, Yoshitsugu M, Fujiwara M, Hiyoshi T. Comparison between sitagliptin and nateglinide on postprandial lipid levels: The STANDARD study. World J Diabetes 2013; 4:8-13. [PMID: 23493856 PMCID: PMC3596777 DOI: 10.4239/wjd.v4.i1.8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2012] [Accepted: 01/06/2013] [Indexed: 02/05/2023] Open
Abstract
AIM: To assess the effects of sitagliptin and nateglinide on lipid metabolism.
METHODS: In a parallel group comparative open trial, patients with type 2 diabetes mellitus under treatment at the Japanese Red Cross Medical Center were randomly assigned to receive either sitagliptin (50 mg once daily) or nateglinide (90 mg three times daily before meals). Eligible patients met the following criteria: age ≥ 20 years; hemoglobin A1c (HbA1c) > 6.5% despite diet and exercise; HbA1c between 6.5% and 8.0%; fasting glucose < 7.77 mmol/L; diet and exercise therapy for more than 3 mo; and ability to read and understand the information for written informed consent. Exclusion criteria were contraindications to sitagliptin, contraindications to nateglinide, pregnancy or possible pregnancy, and severe liver/renal failure. Patients who were considered to be unsuitable by the attending physician for other reasons were also excluded. Blood samples were collected at one and three hours after intake of a test meal. The primary outcome measure was the area under the curve (AUC) of apolipoprotein (Apo) B48 at three hours postprandially.
RESULTS: Twenty patients were randomly assigned to the sitagliptin group and sixteen patients were randomized to the nateglinide group. All 36 patients took the medication as directed by the physician in both groups, and they all were analyzed. Apart from antidiabetic drugs, there was no difference between the two groups with respect to the frequency of combined use of lipid-lowering, antihypertensive, and/or antiplatelet drugs. The doses of these medications were maintained during 12 wk of treatment. Detailed dietary advice, together with adequate exercise therapy, was given to the patients so that other factors apart from the two test drugs were similar in the two groups. There were no significant differences of the baseline characteristics between the two groups, except for body mass index (the sitagliptin group: 25.14 ± 3.05 kg/m2; the nateglinide group: 21.39 ± 2.24 kg/m2). Fasting levels of HbA1c, glycated albumin, 1.5-anhydroglucitol, and blood glucose, as well as the blood glucose levels at one and three hours postprandially, improved in both groups after 12 wk of treatment, and there were no significant differences between the two groups. However, the glucagon level at one hour postprandially (P = 0.040) and the diastolic blood pressure (P < 0.01) only showed a significant decrease in the sitagliptin group. In the nateglinide group, there was no significant change in the AUC of Apo B48, the glucagon level at one hour postprandially, the fasting triglyceride level, or the diastolic blood pressure. Body weight was unchanged in both groups. However, the AUC of Apo B48 at three hours postprandially showed a significant decrease in the sitagliptin group from 2.48 ± 0.11 at baseline to 1.94 ± 0.78 g/L per hour after 12 wk (P = 0.019). The fasting triglyceride level also decreased significantly in the sitagliptin group (P = 0.035). With regard to lipid-related markers other than Apo B48 and fasting triglycerides, no significant changes were observed with respect to Apo A1, Apo B, or Apo C3 in either group. No adverse events occurred in either group.
CONCLUSION: Sitagliptin significantly improves some lipid parameters while having a comparable effect on blood glucose to nateglinide. A large-scale prospective study of sitagliptin therapy is warranted.
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Zacharova J, Chiasson JL, Laakso M. Leptin Receptor Gene Variation Predicts Weight Change in Subjects with Impaired Glucose Tolerance. ACTA ACUST UNITED AC 2012; 13:501-6. [PMID: 15833934 DOI: 10.1038/oby.2005.52] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The leptin receptor (OB-R) gene is a promising candidate gene for type 2 diabetes, because leptin and its receptor play an important role in insulin secretion and the development of obesity. Therefore, we studied whether the pentanucleotide insertion polymorphism of the 3'-untranslated region (3'UTR) of the OB-R gene has an influence on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the STOP-Noninsulin-Dependent Diabetes Mellitus trial. The STOP trial was a longitudinal, double-blind, placebo-controlled randomized trial that included 1429 subjects with IGT from high-risk populations. Using the restriction fragment length polymorphism method, we genotyped 770 subjects whose DNA was available for the insertion/deletion polymorphism of the 3'UTR of the OB-R gene. We did not find a relationship between the OB-R polymorphism and the conversion from IGT to type 2 diabetes (p = 0.747). However, the insertion allele was associated with a significant reduction in weight (p = 0.016), BMI (p = 0.009), and waist circumference (p = 0.006) in all subjects. Women carrying the I allele had a larger waist circumference change (p = 0.036), whereas men lost more weight and had a greater decrease in BMI. The pentanucleotide insertion/deletion polymorphism in the 3'UTR of the OB-R gene did not influence the conversion to type 2 diabetes in obese patients with IGT. However, this polymorphism was associated with a significant weight change, suggesting that it may potentially modulate the risk for type 2 diabetes.
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Abstract
The huge increase in type 2 diabetes is a burden worldwide. Many marketed compounds do not address relevant aspects of the disease; they may already compensate for defects in insulin secretion and insulin action, but loss of secreting cells (β-cell destruction), hyperglucagonemia, gastric emptying, enzyme activation/inhibition in insulin-sensitive cells, substitution or antagonizing of physiological hormones and pathways, finally leading to secondary complications of diabetes, are not sufficiently addressed. In addition, side effects for established therapies such as hypoglycemias and weight gain have to be diminished. At present, nearly 1000 compounds have been described, and approximately 180 of these are going to be developed (already in clinical studies), some of them directly influencing enzyme activity, influencing pathophysiological pathways, and some using G-protein-coupled receptors. In addition, immunological approaches and antisense strategies are going to be developed. Many compounds are derived from physiological compounds (hormones) aiming at improving their kinetics and selectivity, and others are chemical compounds that were obtained by screening for a newly identified target in the physiological or pathophysiological machinery. In some areas, great progress is observed (e.g., incretin area); in others, no great progress is obvious (e.g., glucokinase activators), and other areas are not recommended for further research. For all scientific areas, conclusions with respect to their impact on diabetes are given. Potential targets for which no chemical compound has yet been identified as a ligand (agonist or antagonist) are also described.
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Affiliation(s)
- E J Verspohl
- Department of Pharmacology, Institute of Medicinal Chemistry, University of Muenster, Hittorfstr. 58-62, 48149 Muenster, Germany.
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HE LH. Comparative Study for α-Glucosidase Inhibitory Effects of Total Iridoid Glycosides in the Crude Products and the Wine-processed Products from Cornus officinalis. YAKUGAKU ZASSHI 2011; 131:1801-5. [DOI: 10.1248/yakushi.131.1801] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Li-Hua HE
- The Medical School, Hunan Normal University
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Ngatena IJ, Kapustin JF. Preventing Type 2 Diabetes: What Really Works? J Nurse Pract 2011. [DOI: 10.1016/j.nurpra.2011.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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Kim SH, Jo SH, Kwon YI, Hwang JK. Effects of onion (Allium cepa L.) extract administration on intestinal α-glucosidases activities and spikes in postprandial blood glucose levels in SD rats model. Int J Mol Sci 2011; 12:3757-69. [PMID: 21747704 PMCID: PMC3131588 DOI: 10.3390/ijms12063757] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2011] [Revised: 05/19/2011] [Accepted: 05/31/2011] [Indexed: 12/21/2022] Open
Abstract
Diets high in calories and sweetened foods with disaccharides frequently lead to exaggerated postprandial spikes in blood glucose. This state induces immediate oxidant stress and free radicals which trigger oxidative stress-linked diabetic complications. One of the therapeutic approaches for decreasing postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate hydrolyzing enzymes, α-amylase and α-glucosidases, in the digestive organs. Therefore, the inhibitory activity of Korean onion (Allium cepa L.) extract against rat intestinal α-glucosidases, such as sucrase, maltase, and porcine pancreatic α-amylase were investigated in vitro and in vivo. The content of quercetin in ethyl alcohol extract of onion skin (EOS) was 6.04 g/100 g dried weight of onion skin. The in vitro half-maximal inhibitory concentrations (IC50) of EOS and quercetin, a major phenolic in onion, on rat intestinal sucrase were 0.40 and 0.11 mg/mL, respectively. The postprandial blood glucose lowering effects of EOS and quercetin were compared to a known type 2 diabetes drug (Acarbose), a strong α-glucosidase inhibitor in the Sprague-Dawley (SD) rat model. In rats fed on sucrose, EOS significantly reduced the blood glucose spike after sucrose loading. The area under the blood glucose-time curve (AUClast) in EOS-treated SD rats (0.5 g-EOS/kg) was significantly lower than in untreated SD rats (259.6 ± 5.1 vs. 283.1 ± 19.2 h·mg/dL). The AUClast in quercetin-treated SD rats (0.5 g-quercetin/kg) was similar to in EOS-treated group (256.1 ± 3.2 vs. 259.6 ± 5.1 h·mg/dL). Results from this study indicates that although quercetin does have blood glucose lowering potential via α-glucosidase inhibition, there are other bioactive compounds present in onion skin. Furthermore, the effects of two weeks administration of EOS in a high carbohydrate-dietary mixture (Pico 5053) on sucrase and maltase activities in intestine were evaluated in SD rat model. Compared to the upper and middle parts of intestine, the activities of sucrase in the lower parts of intestine remained significantly higher after two weeks of EOS treatment. These results indicate that EOS may improve exaggerated postprandial spikes in blood glucose and glucose homeostasis since it inhibits intestinal sucrase and thus delays carbohydrate absorption, although clinical trials are needed.
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Affiliation(s)
- Sun-Ho Kim
- Department of Biomaterials Science and Technology, Yonsei University, Seoul 120-749, Korea; E-Mail:
| | - Sung-Hoon Jo
- Department of Food and Nutrition, Hannam University, Daejeon 305-811, Korea; E-Mail:
| | - Young-In Kwon
- Department of Food and Nutrition, Hannam University, Daejeon 305-811, Korea; E-Mail:
- Authors to whom correspondence should be addressed; E-Mails: (Y.-I.K.); (J.-K.H.); Tel.:+82-42-629-8790 (Y.-I.K.); +82-2-456-7657 (J.-K.H.); Fax: +82-42-629-8789 (Y.-I.K.); +82-2-456-7567 (J.-K.H.)
| | - Jae-Kwan Hwang
- Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea
- Authors to whom correspondence should be addressed; E-Mails: (Y.-I.K.); (J.-K.H.); Tel.:+82-42-629-8790 (Y.-I.K.); +82-2-456-7657 (J.-K.H.); Fax: +82-42-629-8789 (Y.-I.K.); +82-2-456-7567 (J.-K.H.)
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Whittemore R, Melkus GD, Alexander N, Zibel S, Visone E, Muench U, Magenheimer E, Wilborne S. Implementation of a lifestyle program in primary care by nurse practitioners. JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS 2010; 22:684-93. [PMID: 21129077 PMCID: PMC3058230 DOI: 10.1111/j.1745-7599.2010.00562.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
PURPOSE The purpose of this study is to describe the implementation process and participant satisfaction with a lifestyle program provided by nurse practitioners (NPs) in primary care to adults at risk for type 2 diabetes (T2D) compared to enhanced standard care. DATA SOURCES A mixed-method clinical trial design was used (n= 58). NPs were interviewed prior to beginning the program, at 3 months, and at completion of the program. NPs also completed a questionnaire on lifestyle counseling at baseline. Process data were collected on attendance, attrition, and intervention fidelity. Participants completed a satisfaction survey at completion of the program and a sub-sample were interviewed at the end of the program. CONCLUSIONS NPs reported that they felt well-prepared and moderately effective in providing lifestyle change counseling. Participant attendance was high and in-person sessions were implemented with good success. Participants in the lifestyle program were more satisfied with the program, reporting that the program was a good experience. IMPLICATIONS FOR PRACTICE Implementation of a lifestyle program to prevent T2D in primary care is feasible and acceptable to NPs and participants. Developing a structured program may improve health outcomes.
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Phillippe HM, Wargo KA. Mitiglinide: a novel agent for the treatment of type 2 diabetes mellitus. Ann Pharmacother 2010; 44:1615-23. [PMID: 20841518 DOI: 10.1345/aph.1p136] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE To review the pharmacology, pharmacokinetics, efficacy, and safety of mitiglinide, a rapid-acting insulin secretion-stimulating agent to determine its potential role in therapy for the treatment of type 2 diabetes mellitus. DATA SOURCES A MEDLINE search (1966-May 2010) was conducted for English-language, human studies using the terms mitiglinide, KAD 1229, S 21403, and meglitinide analogs. Abstracts presented at the American Association and European Association for the Study of Diabetes annual meetings from 2005 to 2009 were also evaluated for relevant data. STUDY SELECTION AND DATA EXTRACTION Articles pertinent to the pharmacology, pharmacokinetics, efficacy, and safety of mitiglinide were reviewed. DATA SYNTHESIS Mitiglinide has been shown through small clinical studies (N <400) to modestly decrease hemoglobin A(1c), postprandial hyperglycemia, and oxidative stress and inflammatory markers associated with postprandial hyperglycemia. Mitiglinide exerts its hypoglycemic activity by closing adenosine triphosphate (ATP)-sensitive potassium channels in the β-islet cells of the pancreas. This agent has a rapid onset and short duration of action, mimicking a physiologic pattern of insulin release in nondiabetic people. Studies suggest a starting dose of 5 mg 3 times daily with meals and a maximum dose of 20 mg 3 times daily. Overall, mitiglinide is well tolerated, with the most common adverse effect being hypoglycemia. CONCLUSIONS Mitiglinide is the third agent in the class of meglitinides that targets postprandial hyperglycemia. Because of a more intensive dosing regimen, potential cost, and lack of studies assessing the clinical impact of mitiglinide therapy on oxidative stress and inflammatory markers secondary to postprandial hyperglycemia, we cannot recommend this therapy over currently approved therapies.
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Prevención de diabetes mellitus 2. REVISTA MÉDICA CLÍNICA LAS CONDES 2010. [DOI: 10.1016/s0716-8640(10)70595-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Yuen A, Sugeng Y, Weiland TJ, Jelinek GA. Lifestyle and medication interventions for the prevention or delay of type 2 diabetes mellitus in prediabetes: a systematic review of randomised controlled trials. Aust N Z J Public Health 2010; 34:172-8. [DOI: 10.1111/j.1753-6405.2010.00503.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Have Clinical Studies Demonstrated Diabetes Prevention or Delay of Diabetes Through Early Treatment? Am J Ther 2010; 17:201-9. [DOI: 10.1097/mjt.0b013e3181b64aa1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Tuomilehto J, Lindström J, Hellmich M, Lehmacher W, Westermeier T, Evers T, Brückner A, Peltonen M, Qiao Q, Chiasson JL. Development and validation of a risk-score model for subjects with impaired glucose tolerance for the assessment of the risk of type 2 diabetes mellitus-The STOP-NIDDM risk-score. Diabetes Res Clin Pract 2010; 87:267-74. [PMID: 20022651 DOI: 10.1016/j.diabres.2009.11.011] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2009] [Revised: 11/12/2009] [Accepted: 11/16/2009] [Indexed: 10/20/2022]
Abstract
AIMS To develop a risk-score model, based on available clinical data to assess absolute risk of type 2 diabetes among people with impaired glucose tolerance (IGT). METHODS Data from the study to prevent non-insulin dependent diabetes mellitus (STOP-NIDDM) investigating acarbose treatment in individuals with IGT were used to develop multivariable Cox proportional hazards model for the time to onset of diabetes. The final model equation was externally validated using data from the Finnish Cardiovascular Risk Factor (FINRISK) population. RESULTS The risk-score model included the variables acarbose treatment, gender, serum triglyceride level, waist circumference, fasting plasma glucose, height, history of cardiovascular disease (CVD) and hypertension. The final model yielded an area under the receiver-operating-characteristic curve (AUC(ROC)) of 0.64 when applied to people with IGT in the STOP-NIDDM, and 0.84 and 0.90 when applied to FINRISK population with IGT alone and IGT and normal glucose tolerance combined, respectively; AUC(ROC) is a measure of the discriminatory power of the model (1, perfect discrimination). CONCLUSIONS The STOP-NIDDM risk-score is a simple and validated tool that can identify high-risk individuals with IGT who would benefit most from type 2 diabetes or CVD prevention strategies, such as lifestyle management or early acarbose treatment.
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Magalhães MEC, Cavalcanti BA, Cavalcanti S. Could pre-diabetes be considered a clinical condition? opinions from an endocrinologist and a cardiologist. Diabetol Metab Syndr 2010; 2:2. [PMID: 20205782 PMCID: PMC2823595 DOI: 10.1186/1758-5996-2-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2009] [Accepted: 01/15/2010] [Indexed: 12/20/2022] Open
Abstract
The prevalence of pre-diabetes is increasing worldwide and may start 7 to 10 years before the clinical diagnosis of diabetes. In this stage the presence and accumulation of risk factors is common and already implies an increase in cardiovascular risk. Likewise, the onset of cardiovascular diseases (CVD), mainly coronary artery disease (CAD), peripheral vascular disease and cerebrovascular disease can also take place, all of which account for high rates of morbidity and mortality worldwide. Considering pre-diabetes as a clinical entity, non-pharmacological and pharmacological treatments are indicated with drugs which have shown clinical benefits related to reduction in morbidity and mortality. However, there is still need for new long-term studies to assess the real benefits of several new therapeutical approaches, as well as its cost-effectiveness.
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Affiliation(s)
| | | | - Saulo Cavalcanti
- Division of Endocrinology, School of Medical Sciences of Minas Gerais, Belo Horizonte, Brazil
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Alpha-glucosidase inhibitory effect of anti-diabetic metal ions and their complexes. Biochimie 2009; 91:1339-41. [DOI: 10.1016/j.biochi.2009.06.005] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2009] [Accepted: 06/05/2009] [Indexed: 11/22/2022]
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Abstract
The goal of pharmacogenetics is to define the genetic determinants of individual drug responsiveness, and thereby provide personalized treatment to each individual. The peroxisome proliferator-activated receptors (PPARs) are polypeptide products of a set of related genes functioning to regulate several cellular processes that are central to cardiovascular health and disease. Given their pleiotropic roles in lipid and glucose homeostasis, cardiac energy balance and regulation of adipocyte release of circulating inflammatory factors, it is not surprising that PPARs represent an attractive target for clinical investigation and intervention in disease states, such as diabetes, obesity, atherosclerosis, cardiomyopathy, cardiac hypertrophy and heart failure. Research into the manipulation of PPAR function by pharmacologic agents has already resulted in important advances in the treatment of diabetes mellitus and cardiovascular disease. It follows that PPAR pharmacogenetics promises important advances in the personalized treatment of cardiovascular disease.
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Affiliation(s)
- Sharon Cresci
- Washington University School of Medicine, Department of Medicine, Saint Louis, Missouri, 660 South Euclid Avenue, Campus Box 8086 Saint Louis, MO 63110-1093, USA
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Hanefeld M. Cardiovascular benefits and safety profile of acarbose therapy in prediabetes and established type 2 diabetes. Cardiovasc Diabetol 2007; 6:20. [PMID: 17697384 PMCID: PMC2040135 DOI: 10.1186/1475-2840-6-20] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2007] [Accepted: 08/15/2007] [Indexed: 12/13/2022] Open
Abstract
Dysglycaemic disease is one of the most important health issues facing the world in the 21st century. Patients with type 2 diabetes and individuals with prediabetes are at risk of developing macrovascular and microvascular complications. Long-term management strategies are therefore required that are effective at controlling dysglycaemia, well tolerated and, ideally, offer additional cardiovascular disease (CVD) risk-reduction benefits. The efficacy, safety and tolerability of the α-glucosidase inhibitor acarbose have been well-established in a wide range of patient populations in both clinical and community trials. In addition, acarbose has been shown to reduce cardiovascular complications in type 2 diabetes and prevent hypertension and CVD in individuals with impaired glucose tolerance (IGT). Acarbose has a very good safety profile and, owing to its straightforward, non-systemic mode of action, avoids most adverse events. The most common side-effects of acarbose are mild-to-moderate gastrointestinal complaints that subside as treatment continues. They can be minimised through the use of an appropriate stepwise dosing regimen and careful choice of diet. Acarbose is therefore a valuable option for the management of type 2 diabetes and, as the only oral antidiabetes agent approved for the treatment of prediabetes, can help to improve clinical management across the dysglycaemic disease continuum.
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Affiliation(s)
- Markolf Hanefeld
- Zentrum für Klinische Studien, GWT, Technische Universität Dresden, Dresden, Germany.
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Mayer C, Holstein A, Stumvoll M. Oral antidiabetic agents: how much kidney disease can we tolerate? Expert Rev Endocrinol Metab 2007; 2:469-475. [PMID: 30290417 DOI: 10.1586/17446651.2.4.469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Type 2 diabetes mellitus and chronic kidney disease in mild and moderate stages is a common and underestimated comorbidity with relevant therapeutic consequences. Available oral antidiabetic agents are effectively used in keeping blood glucose levels within the guideline range but long lists of contraindications often limit their use. Chronic kidney disease is a very common reason to withhold or discontinue an oral antidiabetic therapy, precluding many patients from drugs with proven benefit, such as metformin. Often contraindications are not based on data but on theoretical grounds or expert opinion. In this review, we critically review threshold levels of kidney function for common oral antidiabetic agents, the evidence from which they were derived and offer advice on how to monitor kidney function as an important procedure in clinical practice.
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Affiliation(s)
- Christof Mayer
- a University of Leipzig, Third Medical Department, Philipp-Rosenthalstr. 27, D-04103, Germany.
| | - Andreas Holstein
- b Clinic Lippe, First Department of Medicine, Roentgenstr. 18, D-32756 Detmold, Germany.
| | - Michael Stumvoll
- c University of Leipzig, Third Medical Department, Philipp-Rosenthal-Str. 27, D-04103 Leipzig, Germany.
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Hussain A, Claussen B, Ramachandran A, Williams R. Prevention of type 2 diabetes: a review. Diabetes Res Clin Pract 2007; 76:317-26. [PMID: 17069920 DOI: 10.1016/j.diabres.2006.09.020] [Citation(s) in RCA: 130] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2006] [Accepted: 09/19/2006] [Indexed: 11/30/2022]
Abstract
One of the major public health challenges of the 21st century is type 2 diabetes. WHO estimates that by 2025 as many as 200-300 million people worldwide will have developed the disease. A distressing increase in children is perhaps the most alarming sign of something going wrong. Roughly half of the risk of type 2 diabetes can be attributed to environmental exposure and the other half to genetics. Central themes for prevention are the risk factors overweight, sedentary lifestyle, certain dietary components and perinatal factors. Overweight is the most critical risk factor, and should be targeted for prevention of type 2 diabetes especially among children and youths. Ethnicity and perinatal factors are also worth considering. Today we know that prevention helps. In the US Diabetes Prevention Programme for high risk individuals, there was a 58% relative reduction in the progression to diabetes in the lifestyle group compared with the controls. Within the lifestyle group, 50% achieved the goal of more than 7% weight reduction, and 74% maintained at least 150 min of moderately intense activity each week. This review discusses different forms of prevention, and proposes first of all to target people with Impaired Glucose Tolerance with increasing activity and altering dietary factors. And secondly, population-based measures to encourage increased physical activity and decreased consumption of energy-dense foods are important, and may target school children and young people, certain ethnic groups and women with gestational diabetes.
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Affiliation(s)
- A Hussain
- Department of General Practice and Community Medicine, University of Oslo, Post Box 1130 Blindern, Oslo, Norway.
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Mudra M, Ercan-Fang N, Zhong L, Furne J, Levitt M. Influence of mulberry leaf extract on the blood glucose and breath hydrogen response to ingestion of 75 g sucrose by type 2 diabetic and control subjects. Diabetes Care 2007; 30:1272-4. [PMID: 17303787 DOI: 10.2337/dc06-2120] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Mitchell Mudra
- Minneapolis VA Medical Center Research Service, Minneapolis, Minnesota 55414, USA
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