Novel pharmacological therapy in type 2 diabetes mellitus with established cardiovascular disease: Current evidence

Cardiovascular diseases(CVDs) remain the leading cause of death in the world and in most developed countries. Patients with type 2 diabetes mellitus(T2DM)suffer from both microvascular and macrovascular diseases and therefore have higher rates of morbidity and mortality compared to those without T2DM. If current trends continue, the Center for Disease Control and Prevention estimates that 1 in 3 Americans will have T2DM by year 2050. As a consequence of the controversy surrounding rosiglitazone and the increasing prevalence of diabetes and CVDs, in 2008 the Food and Drug Administration(FDA) established new expectations for the evaluation of new antidiabetic agents, advising for pre and,in some cases, post-marketing data on major cardiovascular events. As a direct consequence, there has been a paradigm shift in new antidiabetic agents that has given birth to the recently published American Diabetes Association/European Association for the Study of Diabetes consensus statement recommending sodium-glucose cotransporter-2 inhibitors(SGLT2i) and glucagon like peptide-1 receptor agonists(GLP-1RA) in patients with T2DM and established CVD. As a result of over a decade of randomized placebo controlled cardiovascular outcome trials, the aforementioned drugs have received FDA approval for risk reduction of cardiovascular(CV) events in patients with T2DM and established CV disease.SGLT2i have been shown to have a stronger benefit in patients with congestiveheart failure and diabetic kidney disease when compared to their GLP-1RA counterparts. These benefits are not withstanding additional considerations such as cost and the multiple FDA Black Box warnings. This topic is currently an emerging research area and this mini-review paper examines the role of these two novel classes of drugs in patients with T2DM with both confirmed, and at risk for, CVD.     

Predictors of hypoglycemia in insulin-treated patients with type 2 diabetes mellitus in Basrah

AIM To measure the incidence and determinants(predictors) of hypoglycemia among patients with type 2 diabetes mellitus(T2DM) who were on insulin treatment for at least one year. METHODS The present study is an out-patients based inquiry about the risk and predictors of hypoglycemia among patients with T2DM seeking care at the Al-Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah over a period of 7 mo(from 15~(th) of April, 2013 to 15~(th) of October, 2013). The data used in the study were based on all detailed interview and selected laboratory investigations. A total of 336 patients could be included in the study.RESULTS The incidence of overall hypoglycemia among the studied patients was 75.3% within the last 3 mo preceding the interview. The incidence of hypoglycemia subtypes were 10.2% for severe hypoglycemia requiring medical assistance in the hospital, 44.36% for severe hypoglycemia treated at home by family; this includes both confirmed severe hypoglycemia with an incidence rate of 14.6% and unconfirmed severe hypoglycemia for which incidence rate was 29.76%. Regarding mild self-treated hypoglycemia, the incidence of confirmed mild hypoglycemia was 21.42%, for unconfirmed mildhypoglycemia the incidence rate was 50.0% and for total mild hypoglycemia, the incidence rate was 71.42%. The most important predictors of hypoglycemia were a peripheral residence, increasing knowledge of hypoglycemia symptoms, in availability and increasing frequency of self-monitoring blood glucose, the presence of peripheral neuropathy, higher diastolic blood pressure, and lower Hemoglobin A1c.CONCLUSION Hypoglycemia is very common among insulin-treated patients with T2DM in Basrah. It was possible to identify some important predictors of hypoglycemia.     

Prevention of macrovascular complications in patients with type 2 diabetes mellitus: Review of cardiovascular safety and efficacy of newer diabetes medications

Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus(DM). Highly publicized controversy surrounding cardiovascular(CV) safety of rosiglitazone resulted in major changes in United States Food and Drug Administration policy in 2008 regarding approval process of new antidiabetic medications, which has resulted in revolutionary data from several large CV outcome trials over the last few years. All drugs in glucagon-like peptide-1 receptor agonist(GLP-1 RA) and sodium-glucose cotransporter-2(SGLT-2) inhibitor classes have shown to be CV safe with heterogeneous results on CV efficacy. Given twofold higher CV disease mortality in patients with DM than without DM, GLP-1 RAs and SGLT-2-inhibitors are important additions to clinician's armamentarium and should be second line-therapy particularly in patients with T2 DM and established atherosclerotic CV disease or high risks for CV disease. Abundance of data and heterogeneity in CV outcome trials results can make it difficult for clinicians, particularly primary care physicians, to stay updated with all the recent evidence. The scope of this comprehensive review will focus on all major CV outcome studies evaluating CV safety and efficacy of GLP-1 RAs and SGLT-2 inhibitors.     

SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: A systematic review

BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is a common comorbidity with type 2 diabetes. The existing therapeutic options for NAFLD are not adequate.Hypocaloric diet and exercise is the cornerstone of therapy in NAFLD.Pioglitazone is the only drug recommended in diabetes patients with biopsy proven non-alcoholic steatohepatitis. The frequent coexistence of NAFLD and type 2 diabetes with their combined adverse health consequences and inadequate therapeutic options makes it necessary to search for newer alternatives.AIM To assess the effect of sodium glucose cotransporter-2(SGLT-2) inhibitors on liver enzymes in type 2 diabetes patients with NAFLD.METHODS We searched Pub Med/MEDLINE, Cochrane library, Google scholar, and Clinicaltrials.gov for the relevant articles to be included in this systematic review.Human studies done in type 2 diabetes patients with NAFLD treated with SGLT-2 inhibitors for at least 12 wk were included. Data from eight studies(four randomised controlled trials and four observational studies) were extracted and a narrative synthesis was done. A total of 214 patients were treated with SGLT-2 inhibitors in these studies(94 in randomised controlled trials and 120 in observational studies).RESULTS The primary outcome measure was change in serum alanine aminotransferase level. Out of eight studies, seven studies showed a significant decrease in serum alanine aminotransferase level. Most of the studies revealed reduction in serum level of other liver enzymes like aspartate aminotransferase and gamma glutamyl transferase. Five studies that reported a change in hepatic fat exhibited a significant reduction in hepatic fat content in those treated with SGLT-2 inhibitors. Likewise, among the three studies that evaluated a change in indices of hepatic fibrosis, two studies revealed a significant improvement in liver fibrosis. Moreover, there was an improvement in obesity, insulin resistance,glycaemia, and lipid parameters in those subjects taking SGLT-2 inhibitors. The studies disclosed that about 17%(30/176) of the subjects taking SGLT-2 inhibitors developed adverse events and more than 40%(10/23) of them had genitourinary tract infections.CONCLUSION Based on low to moderate quality of evidence, SGLT-2 inhibitors improve the serum level of liver enzymes, decrease liver fat, and fibrosis with additional beneficial effects on various metabolic parameters in type 2 diabetes patients with NAFLD.     

老年患者术前主要心血管不良事件风险评估与医疗费用的相关性

目的 分析老年患者术前主要心血管不良事件(MACEs)风险评估与围术期麻醉费用及住院总费用的相关性,探讨优化医疗保险支付制度的新路径.方法 前瞻性选择2020年1—12月本院行全身麻醉下手术的老年患者5642例,男3152例,女2490例,年龄≥65岁,BMI 16～36 kg/m2,ASAⅠ—Ⅳ级.所有患者术前进行术...     

Efficacy of anagliptin as compared to linagliptin on metabolic parameters over 2 years of drug consumption: A retrospective cohort study

AIM To evaluate the comparative effectiveness of anagliptin and linagliptin on the clinical parameters in patients with type 2 diabetes mellitus(T2 DM). METHODS A 2-year retrospective cohort study was conducted in patients with T2 DM who received anagliptin and linagliptin. We enrolled 234 patients(anagliptin group, 117 patients; linagliptin group, 117 patients). RESULTS The glycemic control considerably improved 3, 6, 12, and 24 mo after the administration of both dipeptidyl peptidase-4(DPP-4) inhibitors. Following the administration of anagliptin, the diastolic blood pressure and serum total cholesterol levels decreased. However, serum high-density lipoprotein cholesterol levels increased and urinary albumin-creatinine ratio decreased following linagliptin administration. Furthermore, the liver function improved after the administration of linagliptin.CONCLUSION These findings suggest that that the efficacy of DPP-4 inhibitors on the blood pressure, lipid profile, and liver function differs between anagliptin and linagliptin.     

Fear of hypoglycemia,a game changer during physical activity in type 1 diabetes mellitus patients

Hypoglycemia limits optimal glycemic management of patients with type 1 diabetes mellitus (T1DM). Fear of hypoglycemia (FoH) is a significant psychosocial consequence that negatively impacts the willingness of T1DM patients to engage in and profit from the health benefits of regular physical activity (e.g., cardiometabolic health, improved body composition, cardiovascular fitness, quality of life). Technological advances, improved insulin regimens, and a better understanding of the physiology of various types of exercise could help ameliorate FoH. This narrative review summarizes the available literature on FoH in children and adults and tools to avoid it.     

Sleeve gastrectomy and type 2 diabetes mellitus: a systematic review

BackgroundExisting evidence has suggested that bariatric surgery produces sustainable weight loss and remission or cure of type 2 diabetes mellitus (DM). Laparoscopic sleeve gastrectomy (LSG) has garnered considerable interest as a low morbidity bariatric surgical procedure that leads to effective weight loss and control of co-morbid disease. The objective of the present study was to systematically review the effect of LSG on type 2 DM.MethodsAn electronic data search of MEDLINE, PubMed, Embase, Scopus, Dare, Clinical Evidence, TRIP, Health Technology Database, Conference abstracts, clinical trials, and the Cochrane Library database was completed. The search terms used included LSG, vertical gastrectomy, bariatric surgery, metabolic surgery, and diabetes (DM), type 2 DM, or co-morbidities. All human studies, not limited to those in the English language, that had been reported from 2000 to April 2010 were included.ResultsAfter an initial screen of 3621 titles, 289 abstracts were reviewed, and 28 studies met the inclusion criteria and the full report was assessed. One study was excluded after a careful assessment because the investigators had combined LSG with ileal interposition. A total of 27 studies and 673 patients were analyzed. The baseline mean body mass index for the 673 patients was 47.4 kg/m² (range 31.0–53.5). The mean percentage of excess weight loss was 47.3% (range 6.3–74.6%), with a mean follow-up of 13.1 months (range 3–36). DM had resolved in 66.2% of the patients, improved in 26.9%, and remained stable in 13.1%. The mean decrease in blood glucose and hemoglobin A1c after sleeve gastrectomy was ?88.2 mg/dL and ?1.7%, respectively.ConclusionMost patients with type 2 DM experienced resolution or improvement in DM markers after LSG. LSG might play an important role as a metabolic therapy for patients with type 2 DM.     

Daily physical activity and type 2 diabetes: A review

Physical activity improves glycemic control and reduces the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes (T2D). Moderate to vigorous physical activity is recommended to manage T2D; however, patients with T2D can be physically weak, making it difficult to engage in the recommended levels of physical activity. Daily physical activity includes various activities performed during both occupational and leisure time such as walking, gardening, and housework that type 2 diabetic patients should be able to perform without considerable physical burden. This review focuses on the association between daily physical activity and T2D. Walking was the most common form of daily physical activity, with numerous studies demonstrating its beneficial effects on reducing the risk of T2D, CVD, and mortality. Walking for at least 30 min per day was shown to reduce the risk of T2D by approximately 50%. Additionally, walking was associated with a reduction in mortality. In contrast, evidence was extremely limited regarding other daily physical activities such as gardening and housework in patients with T2D. Recent studies have suggested daily physical activity, including non-exercise activity thermogenesis, to be favorably associated with metabolic risks and mortality. However, well-designed longitudinal studies are warranted to elucidate its effects on overall health.     

Psychosocial factors affecting the etiology and management of type 1 diabetes mellitus: A narrative review

Type 1 diabetes (T1D) is one of the most common chronic diseases in children and adolescents worldwide. Its etiopathogenesis results from the interplay of genetic and environmental variables. Among the latter, psychological stress has been implicated in disease onset as well as disease management. Various studies, including large population-based studies, have highlighted the role of stressful life events in the etiopathogenesis of T1D. In this article, we also emphasize the importance of attachment in the early child-caregiver relationship, which can be seen as a measure of the quality of the relationship and is crucial for stress and emotional regulation. It serves as a model for all subsequent relationships in one’s life. We summarize some of the few studies performed in the field of attachment and T1D etiopathogenesis or management. T1D management demands a lifelong therapeutic regimen to prevent acute and chronic complications. In addition to psychological stress, psychological factors such as family functioning, developmental adjustment, autonomy, mental health problems and other factors have been found to relate to metabolic control. Psychological factors need to be understood not as a single directional causality-based principle but as a dynamic bi- or multidirectional system that is affected by the normal developmental transitions of childhood and adolescence.     

Association between sarcopenic obesity and higher risk of type 2 diabetes in adults: A systematic review and meta-analysis

BACKGROUND The coexistence of sarcopenia and obesity is referred to as sarcopenic obesity(SO)and it has been hypothesized that the two components of SO may synergistically increase their negative effects. However, many uncertainties still surround this condition especially with regard to its potential negative effects on health outcomes.AIM To conduct a systematic review to determine the prevalence of sarcopenia among adults with overweight and obesity and to investigate whether SO was associated with a higher risk of type 2 diabetes(T2 D).METHODS This study was conducted in adherence with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Literature searches, study selection, methodology development and quality appraisal were performed independently by two authors and the data were collated by means of metaanalysis and narrative synthesis.RESULTS Of the 606 articles retrieved, 11 studies that comprised a total of 60118 adults with overweight and obesity of both genders met the inclusion criteria and were reviewed, revealing two main findings. First, the overall prevalence of sarcopenia is 43% in females and 42% in males who are with overweight and obesity.Secondly, the presence of SO increases the risk of T2D by 38% with respect to those without SO(OR = 1.38, 95%CI: 1.27-1.50).CONCLUSION A high prevalence of sarcopenia has been found among adults with overweight and obesity regardless of their gender and this condition seems to be associatedwith a higher risk of T2D. Clinician should be aware of this scenario in their clinical practice for the better management of both obesity and T2D.     

A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus

BackgroundPancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus (DM). It is widely accepted as an optimal procedure for type 1 DM (T1DM), but its application in type 2 DM (T2DM) is not unanimously acknowledged.MethodsIn total, 146 diabetes patients undergoing pancreas transplantation were included in this study. Clinical data and outcomes were compared between the T1DM and T2DM groups.ResultsMajority (93%) of the pancreas transplantations in T2DM were for uremic recipients. Complications occurred in 106 (73%) patients, including 70 (48%) with early complications before discharge and 79 (54%) with late complications during follow-up period. Overall, rejection of pancreas graft occurred in 37 (25%) patients. Total rejection rate in T2DM recipients was significantly lower than that in T1DM. The short- and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups.ConclusionsT2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks, immunological and endocrine outcomes, and graft survival rates. Therefore, pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.     

Literature review of type 2 diabetes mellitus among minority Muslim populations in Israel

This review surveys the literature published on the characteristics and implications of pre-diabetes and type 2 diabetes mellitus(T2DM) for the Arab andBedouin populations of Israel. T2 DM is a global health problem. The rapid rise in its prevalence in the Arab and Bedouin populations in Israel is responsible for their lower life expectancy compared to Israeli Jews. The increased prevalence of T2 DM corresponds to increased rates of obesity in these populations. A major risk group is adult Arab women aged 55-64 years. In this group obesity reaches 70%. There are several genetic and nutritional explanations for this increase. We found high hospitalization rates for micro and macrovascular complications among diabetic patients of Arab and Bedouin origin. Despite the high prevalence of diabetes and its negative health implications, there is evidence that care and counseling relating to nutrition, physical activity and self-examination of the feet are unsatisfactory. Economic difficulties are frequently cited as the reason for inadequate medical care. Other proposed reasons include faith in traditional therapy and misconceptions about drugs and their side effects. In Israel, the quality indicators program is based on one of the world’s leading information systems and deals with the management of chronic diseases such as diabetes. The program’s baseline data pointed to health inequality between minority populations and the general population in several areas, including monitoring and control of diabetes. Based on these data, a pilot intervention program was planned, aimed at minority populations. This program led to a decrease in inequality and served as the basis for a broader, more comprehensive intervention that has entered the implementation stage. Interventions that were shown to be effective in other Arabic countries may serve as models for diabetes management in the Arab and Bedouin populations in Israel.     

Management of type 2 diabetes mellitus in youth

The rising rates of obesity in youth have concurrently led to an increase in the rates of type 2 diabetes mellitus(T2DM) in this age group.However,there are limited data on the efficacy of different antidiabetic agents in youth.In this context,the Treatment Options for Type 2 Diabetes in Adolescents and Youth trial recently reported that the majority of obese children and adolescents 10-17-years old with newly diagnosed T2DM(T2DM duration less than 2 years) could not achieve HbA1c levels < 8% for more than 1 year with metformin monotherapy,metformin plus rosiglitazone combination,or metformin and lifestyle changes.These findings suggest that,in the majority of youth with T2DM,tight long-term glycemic control with oral agents is an elusive goal and that most patients will require treatment with insulin within a few years of diagnosis to achieve HbA1c targets and reduce the risk of macroand microvascular complications.Therefore,reducing the incidence of T2DM by preventing pediatric obesity through the implementation of lifestyle changes in the community should be the primary objective of healthcare systems.     

Bone fragility in type 2 diabetes mellitus

The number of patients with osteoporosis or type 2 diabetes mellitus (T2DM) is increasing in aging and westernized societies. Both disorders predispose elderly people to disabling conditions by causing fractures and vascular complications, respectively. Recent animal studies have shown that administration of osteocalcin, which is specifically secreted from osteoblasts, can increase insulin secretion and ameliorate hyperglycemia, obesity, and high triglyceride levels in mice fed a high-fat diet. Moreover, several studies have shown that antagonism of Wnt signaling by oxidative stress contributes to the development of osteoporosis, as well as insulin resistance and hyperlipidemia. Thus, bone metabolism and glucose/fat metabolism seem to be etiologically related to each other. Meta-analyses of multiple clinical studies in humans have shown that hip fracture risk of T2DM patients is increased by 1.4-1.7-fold, although bone mineral density (BMD) is not diminished. Vertebral fracture risk of T2DM patients is also increased, and BMD is not sensitive enough to assess the risk. These findings suggest that bone fragility in T2DM, which is not reflected by BMD, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. Pentosidine, the endogenous secretory receptor for advanced glycation endproducts, and insulin-like growth factor-I seem to be such candidates, although further studies are required to clarify whether or not these markers could predict the occurrence of new fractures of T2DM patients in a prospective fashion.     

Effect of glycemic control on markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus: A review

Cardiovascular disease is the predominant cause of death in type 2 diabetes mellitus (T2DM). Evidence suggests a strong association between duration and degree of hyperglycemia and vascular disease. However, large trials failed to show cardiovascular benefit after intensive glycemic control, especially in patients with longer diabetes duration. Atherosclerosis is a chronic and progressive disease, with a long asymptomatic phase. Subclinical atherosclerosis, which is impaired in T2DM, includes impaired vasodilation, increased coronary artery calcification (CAC), carotid intima media thickness, arterial stiffness, and reduced arterial elasticity. Each of these alterations is represented by a marker of subclinical atherosclerosis, offering a cost-effective alternative compared to classic cardiac imaging. Their additional use on top of traditional risk assessment strengthens the predictive risk for developing coronary artery disease (CAD). We, herein, review the existing literature on the effect of glycemic control on each of these markers separately. Effective glycemic control, especially in earlier stages of the disease, attenuates progression of structural markers like intima-media thickness and CAC. Functional markers are improved after use of newer anti-diabetic agents, such as incretin-based treatments or sodium-glucose co-transporter-2 inhibitors, especially in T2DM patients with shorter disease duration. Larger prospective trials are needed to enhance causal inferences of glycemic control on clinical endpoints of CAD.     

胃肠外科手术治疗肥胖症及2型糖尿病

肥胖症是现今社会所面临的最严重的公共健康问题之一,手术治疗是使肥胖症患者获得长期而稳定的减重效果的唯一方法。自从1954年报道第1例减肥手术以来,外科手术治疗肥胖症在全球范围内获得了很大的发展,逐渐成为治疗病态性肥胖的＂金标准＂。随着研究的不断深入,越来越多的证据表明,胃肠外科手术不仅能减重,同时可以改善甚至治愈肥胖症相关的多种代谢性疾病,尤其是2型糖尿病。目前国内外的胃肠外科医师们正致力于将手术推广到2型糖尿病的治疗中去。外科手术治疗肥胖症及2型糖尿病将有巨大的发展空间。     

胃旁路术治疗2型糖尿病的研究进展

随着国内外相关减重手术治疗2型糖尿病（T2DM）病例报道的增多,并显现出了良好的短期及长期的临床效果,该方法更加引人关注。然而手术治疗2型糖尿病的机制如何尚无明确结论,认为可能的治疗机制是十二指肠和近端空肠被旷置,从而引发胃肠道激素分泌的变化,使T2DM得到控制。本文分别对手术的类别、治疗效果及治疗机制进行综述。