Current Diabetes Reviews - Volume 12, Issue 4, 2016

Over the last decades, the prevalence of diabetes mellitus (DM) has been increasing globally such that nowadays the disease constitutes an important outcome related to early mortality among adults. In parallel with the high prevalence, healthcare costs related to DM treatment have increased significantly, exacerbating its burden on modern society. The scientific literature points out that obesity and physical inactivity have a central role in the development of most DM cases. In fact, either physical exercise practice or an increase in the level of physical activity, constitute relevant tools in the guidelines for treatment of the disease. On the other hand, the effect of physical activity on the economic consequences of DM is not completely clear. The identification of the actual burden of lifestyle changes on the reduction of healthcare costs related to DM is relevant, primarily for developing nations, where it could represent a cheaper strategy for treating the disease and its complications than paying for drug treatment, which is commonly related to collateral effects. That being said, the prevention of DM and other diseases and consequently the mitigation of the costs related to these outcomes seem to depend essentially on the promotion of healthy habits. The aim of the present review was therefore to discuss recent evidence on the effects of physical activity/exercise on mitigation of health care cost related to DM.

Background: Alternative insulin therapy with continuous subcutaneous insulin infusion (CSII) is offered with an objective of achieving better glycemic control, minimising glucose variability and thereby, preventing or reducing the risk of microvascular and macrovascular complications in people with type 1 or type 2 diabetes. Trials conducted across the world have demonstrated that CSII is more beneficial in terms of achieving better metabolic control in type 2 diabetes. Unawareness about the multiple benefits of CSII is a major hurdle to its widespread use. In India, insulin pumps are more popular in type 2 diabetes and we have been deploying pumps since 2004. Previously, we have reported reduction in HbA1c, body weight and total daily dose of insulin in patients on insulin pump therapy (IPT). Objective: The objective of this study was to assess the attitude and behavior of type 2 diabetes patients on IPT. Methods: A cross sectional survey was conducted among selected type 2 diabetes patients who have been on IPT for more than 3 years. We administered questionnaires to assess level of satisfaction with pump, improvement in quality of life (QoL), use of the advanced functions and average cost incurred by being on pump. Difference in scores between males and females were assessed using chiquare test for proportions and t-test for differences in means. Results: Improvement in QoL after being on pump was appreciated by 92%. The level of satisfaction was rated as ‘fully satisfied’ by 52% of respondents while 26% found being on pump, ‘satisfactory’. Ninety percent thought that the pump met their expectations. Conclusion: The attitude and behavior of type 2 diabetes patients on IPT is positive and promising.

Type 2 diabetes is characterized by decreased functional beta-cell mass, as a consequence of metabolic stress associated with obesity, aging, insulin resistance and pregnancy. The metabolic stress is caused by increased insulin demand, pro-inflammatory cytokines, and free fatty acids. Fortunately, islets have remarkable property to adapt to increased metabolic demand. This review focuses on the mechanisms of islet adaptation to metabolic stress in obesity and insulin resistance

Type 2 diabetes mellitus (T2DM) is a highly prevalent condition and is associated with a number of metabolic risk factors such as excess of weight, impaired lipid profile and higher levels of blood pressure. As other complex diseases, it is strongly related to an environmental component such as sedentarism and unhealthy diet, and also to a genetic component. A cluster of variants (polymorphisms) in a large number of genes seem to interact with nutrients/dietary factors in modulating cardiometabolic parameters in healthy individuals. The role of total calories intake and also different kind of carbohydrates and dietary fats in worsening the excess of weight and/or metabolic profile in patients with diabetes is well known, but the extent to which genetic factors can modify these associations is not yet fully understood. Therefore, the aim of this mini-review is to discuss the interaction of genetics and diet in the T2DM setting, since both are strongly involved in the genesis and development of the disease.

Glucagon-like peptide-1 (GLP-1) has shown to influence the oxidative stress status in a number of in vitro, in vivo and clinical studies. Well-known effects of GLP-1 including better glycemic control, decreased food intake, increased insulin release and increased insulin sensitivity may indirectly contribute to this phenomenon, but glucose-independent effects on ROS level, production and antioxidant capacity have been suggested to also play a role. The potential ‘antioxidant’ activity of GLP-1 along with other proposed glucose-independent modes of action related to ameliorating redox imbalance remains a controversial topic but could hold a therapeutic potential against micro- and macrovascular diabetic complications. This review discusses the presently available knowledge from experimental and clinical studies on the effects of GLP-1 on oxidative stress in diabetes and diabetes-related complications.

The World Health Organization (WHO) has reported that Saudi Arabia ranks the second highest in the Middle East, and is seventh in the world for the rate of diabetes. It is estimated that around 7 million of the population are diabetic and almost around 3 million have pre-diabetes. Even more worrying perhaps, is the increasing pattern of diabetes noted in Saudi Arabia in the recent past. In fact, diabetes has approximately registered a ten-fold increase in the past three eras in Saudi Arabia. Diabetes mellitus (DM) has been found to be related to high mortality, morbidity and vascular complications, accompanied by poor general health and lower quality of life. In Saudi Arabia, DM is quickly reaching disturbing proportions and becoming a significant cause of medical complications and even death. However, when compared with the developed countries, the research work conducted, focusing particularly on the incidence, prevalence and socio-demographic properties of DM is woefully inadequate. The health burden due to DM in Saudi Arabia is predicted to rise to catastrophic levels, unless a wide-ranging epidemic control program is incorporated, with great emphasis laid on advocating a healthy diet, including exercise and active lifestyles, and weight control. To properly manage the DM in Saudi Arabia, a multidisciplinary approach is required. In this review we discuss all the aspects of DM in Saudi Arabia drawing from the published literature currently available.

Deterioration of the structure and function of the vascular system is the underlying feature in cardiovascular disease (CVD), which is the highest cause of mortality in type 2 diabetes (T2D). Studies assessing the effect of exercise on vascular function and stiffness have used different measurement techniques and small cohorts, making it difficult to conclude on the overall efficacy of exercise on these outcomes. The aim of this study was to assess the effect of exercise on vascular function and stiffness in T2D. Electronic database searches were performed in AMED, MEDLINE, MEDLINE Daily Update, PREMEDLINE, SPORTDiscus, CINAHL, EMBASE and Web of Science. The effect size (ES), and 95% confidence intervals (CIs) of eligible studies were calculated. Pooled estimates of the effect of aerobic exercise (AEx) on vascular function and stiffness, using ES, were obtained. Results show that AEx led to a near-significant reduction in PWV (ES = -0.472; 95% CI: -0.949 to 0.005; P = 0.052), a significant reduction in EID (ES = 0.416, 95% CI: 0.062 to 0.769; P= 0.021), and a non-significant benefit in FMD measures. There were limited studies using resistance training or in combination with aerobic exercise, to assess a pooled effect on vascular function or stiffness. These data suggest that aerobic exercise training should be used as a primary treatment strategy for improving vascular smooth muscle function as measured by EID in individuals with T2D. There is currently insufficient evidence concerning the efficacy of regular exercise for improving vascular function and stiffness as measured by FMD and PWV.

The pathogenesis of diabetic cardiomyopathy (DCM) is partially understood and is likely to be multifactorial, involving metabolic disturbances, hypertension and cardiovascular autonomic neuropathy (CAN). Therefore, an important need remains to further delineate the basic mechanisms of diabetic cardiomyopathy and to apply them to daily clinical practice. We attempt to detail some of these underlying mechanisms, focusing in the clinical features and management. The novelty of this review is the role of CAN and reduction of blood pressure descent during sleep in the development of DCM. Evidence has suggested that CAN might precede left ventricular hypertrophy and diastolic dysfunction in normotensive patients with type 2 diabetes, serving as an early marker for the evaluation of preclinical cardiac abnormalities. Additionally, a prospective study demonstrated that an elevation of nocturnal systolic blood pressure and a loss of nocturnal blood pressure fall might precede the onset of abnormal albuminuria and cardiovascular events in hypertensive normoalbuminuric patients with type 2 diabetes. Therefore, existing microalbuminuria could imply the presence of myocardium abnormalities. Considering that DCM could be asymptomatic for a long period and progress to irreversible cardiac damage, early recognition and treatment of the preclinical cardiac abnormalities are essential to avoid severe cardiovascular outcomes. In this sense, we recommend that all type 2 diabetic patients, especially those with microalbuminuria, should be regularly submitted to CAN tests, Ambulatory Blood Pressure Monitoring and echocardiography, and treated for any abnormalities in these tests in the attempt of reducing cardiovascular morbidity and mortality.

Purpose: To systematically review the value of serum inflammatory markers to diagnose diabetic foot osteomyelitis (DFO). Study selection: Studies to diagnose DFO using biomarkers erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-2, IL-6, IL-8) and tumor necrosis factor alfa (TNFα) were retrieved from EMBASE and PubMed with no language restrictions through July 2014. Data extraction: We summarized clinical characteristics of the studies and used bivariate random effects models and summary receiver operating characteristic curves to estimate sensitivity and specificity for each marker. Data synthesis: A total of 8 qualifying studies were included in our meta-analysis. Bivariate pooled sensitivity and specificity of the 6 studies examining ESR were 0.81 (95% CI 0.71-0.88) and 0.90 (95% CI 0.75-0.96) respectively. Due to the paucity of data, models did not converge for the other biomarkers. Conclusions: From the inflammatory markers, ESR appears to be the best laboratory test to identify patients with DFO.

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly being used for the treatment of type 2 diabetes mellitus, but consideration of benefits and potential adverse events is required. This review examines the state of glycemic control, weight loss, blood pressure, and tolerability, as well as the current debate about the safety of GLP-1 RAs, including risk of pancreatitis, pancreatic cancer, and thyroid cancer. Methods: A MEDLINE search (2010-2015) identified publications that discussed longer-acting GLP-1 RAs. Search terms included GLP-1 receptor agonists, liraglutide, exenatide, lixisenatide, semaglutide, dulaglutide, albiglutide, efficacy, safety, pancreatitis, pancreatic cancer, and thyroid cancer. Abstracts from the American Diabetes Association, European Association for the Study of Diabetes, and American Association of Clinical Endocrinologists from 2010 to 2015 were also searched. Efficacy and safety studies, pooled analyses, and meta-analyses were prioritized. Results: Research has confirmed that GLP-1 RAs provide robust glycemic control, weight loss, and blood pressure re-duction. Current studies do not prove increased risk of pancreatitis, pancreatic cancer, or thyroid cancer but more trials are needed since publications that indicate safety or suggest increased risk have methodological flaws that prevent firm conclusions to be drawn about these rare, long-term events. Conclusion: GLP-1 RA therapy in the context of individualized, patient-centered care continues to be supported by current literature. GLP-1 RA therapy provides robust glycemic control, blood pressure reduction, and weight loss, but studies are still needed to address concerns about tolerability and safety, including pancreatitis and cancer.

Objective: Increasing efforts are being made towards pharmacologic activation of brown adipose tissue (BAT) in animals and humans for potential use in the treatment of obesity and diabetes. We and others have reported a number of animal studies using either experimental or therapeutic drugs. There are now efforts to translate these findings to human studies. The goal of this review is to evaluate the various drugs currently being used that have the potential for BAT activation. Methods: Drugs were classified into 4 classes based on their mechanism of action. Class 1 drugs include the use of β3 adrenoceptor agonists for BAT activation. Class 2 drugs include drugs that affect norepinephrine levels and activate BAT with the potential of reducing obesity. Class 3 includes activators of peroxisome proliferator-activated receptor-γ in pursuit of lowering blood sugar, weight loss and diabetes and finally Class 4 includes natural products and other emerging drugs with limited information on BAT activation and their effects on diabetes and weight loss. Results: Class 1 drugs are high BAT activators followed by Class 2 and 3. Some of these drugs have now been extended to diabetes and obesity animal models and human BAT studies. Drugs in Class 3 are used clinically for Type 2 diabetes, but the extent of BAT involvement is unclear. Conclusion: Further studies on the efficacy of these drugs in diabetes and measuring their effects on BAT activation using noninvasive imaging will help in establishing a clinical role of BAT.

Introduction: In recent years, numerous pharmacological approaches for the treatment of type 2 diabetes mellitus (T2DM) have become available. While all of them have proven blood glucose-lowering effects, identifying the most beneficial drug or drug combination for the treatment of an individual patient has become an increasing challenge. Several guidelines attempt to provide decision criteria based on clinical characteristics and comorbidities in patients with T2DM, however, these guidelines still leave a broad range of capabilities for pharmacological treatment escalation. Pathophysiological Approach: Addressing the pathophysiology of T2DM might be a valuable approach for the selection and combination of different drugs that can provide the most comprehensive effects in the treatment of T2DM. Besides decreasing insulin sensitivity, a progressing imbalance in alpha and beta cell function of the Langerhans islet is a fundamental component in the complex pathophysiology of the disease. Conclusion: Considering the effect of different pharmacological interventions on the pathophysiological components in T2DM might be an effective tool guiding to most beneficial treatments, and may lead to a more tailored pharmacological intervention in patients with T2DM. .

Background: With diabetes rates escalating globally, there is the need for a better integration of all aspects of diabetes care for improved population outcomes. An understanding, not only of regional but global literature on physical activity barriers and its facilitators is important if healthcare providers and policy makers are to create programs tailored to their populations. Objectives: Herein, we report the results of a narrative review of the global barriers and facilitators of physical activity for patients with diabetes mellitus. Methodology: An in-depth literature search was conducted to identify English-language studies that examined physical activity barriers and associated facilitators among patients with diabetes mellitus. Major electronic literature databases that were searched included Google Scholar, PubMed, Hub-Med, and Highwire. Results: Studies were available from Africa, Asia, Australia, Europe, and, predominantly North America. A total of 34 predominantly internal barriers emerged globally. The most commonly reported were time constrains, fear of provoking additional disorders, exercise venue and weather related barriers. Facilitators of physical activity were reported for most of the internal barriers (e.g. time constraints, lack of knowledge etc) while the external barriers (e.g. weather, environmental pollution etc) received only a minimal attention. Conclusions: Globally, patients with diabetes are confronted with an enormous number of physical activity barriers. Unlike the robust solutions proffered for the internal barriers, the literature is largely silent about solutions to the external barriers, which though fewer, may be highly influential. Additional data is needed to better understand physical activity behaviors in populations outside of North America.

The exact mechanism by which nutritional deficiency and lysosomal enzyme change, modify periodontal destruction has not yet been precisely defined. The study aimed to determine the serum zinc and β D glucuronidase enzyme level in the selected groups and how its increase or decrease levels are related to type 2 diabetes mellitus (T2DM) with periodontitis when compared to other groups. Six hundred subjects were selected and are categorized into four groups as Group I (control healthy subjects, n=150), Group II (T2DM with periodontitis, n=150), Group III (T2DM without periodontitis, n=150) and Group IV (Non-DM with periodontitis, n=150). The lab investigations included measuring fasting blood glucose, serum zinc and β D- glucuronidase levels. In the results, the level of serum zinc was found to be lesser in group III subjects and the activity of serum β D glucuronidase was found to be elevated nine times in group III (T2DM with periodontitis) and two times elevated in group II (T2DM without periodontitis) and group IV (Non-DM with periodontitis), when compared to control. Zinc has been reported to reduce the stabilization of lysosomal membranes. Periodontitis has been taken as the prime condition in this study and categorized as experimental groups. Perturbations in mineral metabolism are more pronounced in diabetic populations. When the level of zinc is decreased, the structural integrity of lysosomal membrane has been lost and it would have caused for the increased release of β D glucuronidase in T2DM with periodontitis.

Background: Diabetes has been shown to be associated with increased mortality and morbidity worldwide. This study explored whether diabetes significantly impacts on outcomes among elderly adults with cardiovascular disease (CVD) admitted to a specialist hospital in Southern Brazil. Design: A prospective cohort study of 411 patients admitted to hospital after a cardiac event between 2008 and 2010. Methods: The primary end point was death by all causes during the follow up period of 6 months from admission. All hospital death reports matched those reported by the Brazilian Public Health Death Records. Cumulative probability of survival by Kaplan-Meier plot and log rank tests compared hospital admissions with or without diabetes. Adjusted and unadjusted hazard ratios (HR) for overall mortality were calculated. Results and Conclusions: The mean ± SD age of the subjects was 69.8 years ± 14 and 50% were men. Overall study mortality was 8.7%. Half of the deaths occurred in patients ≥80 years (p=0.001). Diabetes was associated with 53% of the overall mortality (p<0.01) and 79% of the CVD-related deaths (p<0.03). The adjusted HR was 2.88 (95% CI 1.42–5.84) for diabetic patients aged ≥80 years. In conclusion, the results suggest that elderly patients of European origin with diabetes residing in Southern Brazil admitted to hospital for specialist CVD treatment have poorer survival and higher risk of further CVD events 6 months after hospital discharge compared with those without. We recommend that better strategies for managing CVD risk factors among elderly diabetic patients from similar patient cohorts in Brazil are necessary.

Background: to assess costs and safety of insulin pen devices and safety needles as compared to vial/syringes in hospitalized patients requiring insulin therapy in a General Hospital in Northern Italy. Materials and Methods: in a prospective 9-month study, consecutive patients admitted to three Hospital Units received insulin therapy through either a traditional disposable syringe method, or pen/safety needles with dual-ended protection, or disposable safety syringes. We compared the median direct (insulin and devices) and indirect (insulin supply at discharge, insulin wastage) costs of a 10-day in-hospital insulin treatment in the 3 study groups, additionally accounting for the costs related to the observed needlestick injury rate. Patients’ safety during in-hospital stay (hypo- and hyperglycemia episodes) and satisfaction were also assessed. Results: N=360 patients (55% men, mean age 75.6 years, 57% with DM since ≥10 years) were recruited in the study. Insulin pens had higher median direct cost than both traditional syringes (43 vs. 18 /patient, p<.0001) and safety syringes (21.5 /patient, p<.0001). However, when also indirect and injuries costs were taken into account, the estimated savings for using pens over traditional syringes were as high as 32 /patient (45.8 vs. 77.6 ε/patient, p-value <.0001). No differences in patients’ safety were observed. 74% and 12% of patients using pens and syringes would like to continue the method at home, respectively (p<0.0001). Discussion: A selective use of individual pre-filled pens/safety needles for patients who are likely to continue insulin therapy at home may strongly reduce hospital diabetes treatment related costs.