bluuebunny/crossref_metadata_2025 huggingface dataset:
Balancing Efficacy and Tolerability Issues with Statin Therapy— Considerations for the Use of Pitavastatin in Special Patient Populations
Authors: Falko James M ,   Professor of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado Denver
Published: October 2015

One of the main objectives of cardiovascular care is to control elevated low-density lipoprotein cholesterol (LDL-C). Statins are the mainstay for managing LDL-C with proven high efficacy and satisfactory safety profiles. However, the most known side effects are muscle symptoms, which are particularly common in individuals who often have co-existing conditions and are taking multiple medications. The latest statin that has become available, pitavastatin, is not known to cause cytochrome P450-mediated drug–drug interactions, making it an ideal statin for individuals at a high risk for side effects. Pitavastatin will be particularly beneficial in treating patients with mixed dyslipidemia, as it is effective in reducing triglycerides and increasing high-density lipoprotein cholesterol (HDL-C). Pitavastatin has an established history of use, and has a safety and adverse event profile similar to that of other existing statins. Individuals at high risk from side effects with statins include older people (>65 years), individuals with diabetes, kidney disease, or metabolic syndrome and individuals taking multiple medications. South Asian populations that have migrated to Western countries are at particularly high risk for cardiovascular disease, and this population also has an increased risk for statin-related side effects. This article will summarize the factors that place individuals at high risk for dyslipidemia, treatment of high risk populations with statins, and the issues associated with treating high risk populations with statins. The benefits of treating these individuals with pitavastatin will be reviewed, as well as alternative forms of therapy.
Diagnosis and Management of Acromegaly in 2012
Authors: Katznelson Laurence ,   Professor of Medicine and Neurosurgery, Stanford University
Published: October 2015

Acromegaly is an insidious disease that, in most cases, is a result of a pituitary adenoma that hypersecretes growth hormone (GH). The goals of therapy are to control excess GH secretion and tumor growth, and to limit, if not reverse, the long-term medical consequences and risk of premature mortality associated with acromegaly. Surgery is the preferred primary therapeutic option because it can lead to rapid reductions in GH levels and prevent mass effects from local tumor growth. Medical therapy, including somatostatin analogs, dopamine agonists, and the GH receptor antagonist pegvisomant, is used most often in an adjuvant, secondary role for patients in whom surgery has been unsuccessful. Radiation therapy is most commonly recommended in the setting of failed surgery and lack of adequate control with medical therapy. A role of primary medical therapy for de novo patients has been proposed, particularly with somatostatin analogs. Using a multimodality approach, successful management of the disease and associated consequences should be achieved in the majority of subjects.
Congenital Hypothyroidism—Monitoring Thyroid Function in Infants
Authors: Straussman Sharon , Levitsky Lynne L ,   Fellow in Pediatric Endocrinology,   Chief, Pediatric Endocrine Unit and Associate Professor of Pediatrics, Massachusetts General Hospital, Harvard Medical School
Published: October 2015

Guidelines for monitoring thyroid function in congenital hypothyroidism (CH) are published by the American Academy of Pediatrics, the European Society for Paediatric Endocrinology, and the UK Newborn Screening Programme Centre. The fact that the recommendations are not uniform reflects management uncertainty. In addition, clinical care may not always be informed by these guidelines. Recent studies suggest that more frequent monitoring is indicated in some infants. Monitoring to identify delayed thyroid stimulating hormone (TSH) rise is indicated in pre-term, low birth weight, and sick full-term newborns. Monitoring thyroid function in infants with CH monthly after normalization of TSH until six months of age, and every one to two months between six and 12 months of age, will decrease exposure to suboptimal thyroid hormone levels. Assessment for permanency of hypothyroidism should be done only in children in which there is likelihood of resolution and not earlier than three years of age. In some instances when TSH elevations persist after normalization of the free thyroxine, it may be reasonable to try combined therapy with triiodothyronine.
The Role of Steroids in Endothelial Function in the Aging Male
Authors: Aversa Antonio , Bruzziches Roberto , Francomano Davide , Greco Emanuela A , Migliaccio Silvia , Lenzi Andrea ,   Senior Lecturer, Department of Experimental Medicine, Medical Pathophysiology Section, ‘La Sapienza’ University of Rome,   Research Fellow, Department of Experimental Medicine, Medical Pathophysiology Section, ‘La Sapienza’ University of Rome,   Research Fellow, Department of Experimental Medicine, Medical Pathophysiology Section, ‘La Sapienza’ University of Rome,   Research Fellow, Department of Experimental Medicine, Medical Pathophysiology Section, ‘La Sapienza’ University of Rome,   Researcher, Department of Health Sciences, Endocrinology Unit, Foro Italico University of Rome,   Full Professor, Department of Experimental Medicine, Medical Pathophysiology Section, ‘La Sapienza’ University of Rome
Published: October 2015

Normal vascular endothelium is essential for the synthesis and release of substances affecting vascular tone, cell adhesion, and the homoeostasis of clotting and fibrinolysis. The degeneration of endothelial integrity promotes adverse events leading to atherogenesis. Circulating levels of endogenous hormones decline during aging and this may contribute to the occurrence of major adverse cardiovascular events, independently of gender differences. During the last decade, more attention has been drawn to the importance of testosterone, estradiol and adrenal androgens in the pathophysiology, prevention, and treatment of male aging-associated diseases. A considerable body of literature is available indicating that steroid hormones, particularly the sex steroids, are known to modulate endothelial function in all vascular beds and that their deficiency may promote endothelial dysfunction. Testosterone decrease and increased mineralocorticoid activity in the aging male are frequent and may yield endothelial dysfunction and increased cardiovascular burden. We recommend careful hormonal investigations in men who present comorbidities such as diabetes, hypertension and dyslipidemia.
Hypoglycemia in Type 2 Diabetes—Consequences and Risk Assessment
Authors: Lingvay Ildiko ,   Assistant Professor, Internal Medicine, University of Texas Southwestern Medical Center
Published: October 2015

Although hypoglycemia has traditionally been considered a significant complication of the treatment of type 1 diabetes, the greater incidence of type 2 diabetes compared with type 1, the intensive treatment strategies currently employed, and the longer life expectancy of patients with diabetes, give rise to a large number of type 2 patients at risk for hypoglycemia. This number is likely to rise in an aging population with the increasing use of insulin to treat diabetes. The highest incidence of hypoglycemia is seen in older patients with poor glycemic control and is associated with the use of antidiabetic agents that increase blood insulin concentrations independently of blood glucose concentration (oral antidiabetic drugs or exogenous insulin). Hypoglycemia has a substantial clinical impact in terms of mortality, morbidity, and quality of life. The economic impact of severe hypoglycemic events owing to direct hospital costs and the indirect costs of the inability to work are considerable. Furthermore, both patients’ and physicians’ fear of hypoglycemia reduces adherence to therapeutic regimens and limits the ability of current diabetes medications to achieve the level of glycemic control required to prevent disease progression. Newer therapies and improvements in patient education may help patients achieve improved glucose control by safely reducing glycosylated hemoglobin (HbA1c) with a lower risk of hypoglycemia.
When Will We Agree on the Origin and Meaning of Wellbeing?
Authors: Blevins Lewis S , Knutzen Robert ,   Clinical Professor of Neurological Surgery and Medicine and Medical Director, California Center for Pituitary Disorders, University of California San Francisco,   President and CEO, Pituitary Network Association, Thousand Oaks, California, US
Published: October 2015

Quality of life is a nebulous term that is applied in medicine to assess the impact of disease states on the overall health of affected patients. It is difficult to measure, subject to interpretation based on the relative experiences of those assessing and reporting it, and there are no assessments or tools available to describe or determine the relative contributions of particular disease states and the affected persons constitution and pre-morbid state or personality to their quality of life.
Using Diabetes Therapy Management Software to Support Behavior ChangeA Case-based Approach
Authors: Grunberger George ,   Clinical Professor of Internal Medicine and of Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit and Founder and Chairman, Grunberger Diabetes Institute, Bloomfield Hills, Michigan, US
Published: October 2015

The management of diabetes is complex and requires a team approach for optimal outcomes. This team is comprised of the patient, numerous healthcare providers, and various technologies to elicit the behavioral changes needed in the ongoing care of the disease. This paper uses a case-based approach to demonstrate the patienthealthcare provider relationship and the use of various technologies when managing diabetes. The use of diabetes therapy management software demonstrates enhanced patienthealthcare provider communication, provides data showing that behavioral changes can improve outcomes, and allows the patient to enact positive self-management practices.
Early Glomerular Filtration Rate Loss as a Marker of Diabetic Nephropathy
Authors: Jerums George , Ekinci Elif , Panagiotopoulos Sianna , MacIsaac Richard J ,   Professor, Endocrine Centre, Austin Health and University of Melbourne, Heidelberg Repatriation Hospital, Heidelberg,   Endocrinologist, Endocrine Centre, Austin Health and University of Melbourne, Heidelberg Repatriation Hospital, Heidelberg,   Manager, Office for Research, Endocrine Centre, Austin Health and University of Melbourne, Heidelberg Repatriation Hospital, Heidelberg,   Professor, St Vincents Hospital and University of Melbourne, Victoria, Australia
Published: October 2015

In the early 1980s, studies in type 1 diabetes suggested that glomerular filtration rate (GFR) loss begins with the onset of macroalbuminuria. However, recent evidence indicates that up to one-quarter of subjects with diabetes reach a GFR of less than 60 ml/min/1.73 m2(chronic kidney disease [CKD] stage 3) before developing micro- or macroalbuminuria. Furthermore, the prospective loss of GFR can be detected in early diabetic nephropathy (DN) well before CKD stage 3. Early GFR loss usually reflects DN in type 1 diabetes but, in older patients with type 2 diabetes, the assessment of early GFR loss needs to take into account the effects of aging. The assessment of GFR is now feasible at clinical level, using formulas based on serum creatinine, age, gender, and ethnicity. Overall, the estimation of early GFR loss is more accurate with the Chronic Kidney Disease Epidemiology (CKD–EPI) formula than with the Modification of Diet in Renal Disease (MDRD) study formula, but there is some evidence that the CKD-EPI formula does not exhibit better performance than the MDRD formula for estimating GFR in diabetes. Both formulas underestimate GFR in the hyperfiltration range. Formulas based on the reciprocal of cystatin C can also be used to estimate GFR, but their cost and lack of assay standardization have delayed their use at clinical level. In summary, early GFR loss is an important marker of DN as well as a potentially reversible target for interventions in DN.
Cell Therapy for Diabetic RetinopathyA Work in Progress
Authors: Kent David ,   Consultant Ophthalmic Surgeon, The Vision Clinic, Kilkenny, Ireland
Published: October 2015

As the incidence of diabetes continues to rise worldwide, the challenge in preventing vision loss secondary to diabetic retinopathy (DR) remains a formidable one. Current treatments are only indicated in advanced disease when vision loss is imminent or has already occurred. In recent years, due to the discovery that post-natal vasculogenesis plays a role in vascular repair, there has been increasing optimism that cell therapy using endothelial progenitor cells (EPCs) can be harnessed therapeutically for conditions such as DR. Although autologous EPC therapy offers promise for DR, EPCs from patients with diabetes are themselves dysfunctional, while the diabetic milieu itself contributes further to this dysfunctionality. Additional research is required to unravel the complete science of vasculogenesis and the role of EPCs in repair, so that treatment can be optimized in terms of actual cell choice, pre-conditioning prior to transplantation, maximizing cell survival in the recipient, and preparation of the recipient tissue to ensure an adequate therapeutic response.
Treatment of Aggressive Pituitary Adenomas and CarcinomasAn Overview
Authors: Syro Luis V , Ortiz Leon D , Rotondo Fabio , Uribe Humberto , Penagos Luis C , Horvath Eva , Kovacs Kalman ,   Neurosurgeon, Department of Neurosurgery, Pablo Tobón Uribe Hospital and Medellin Clinic, Medellin, Colombia,   Neuro-oncologist, Division of Neuro-oncology, Cancerology Institute, Las Americas Clinic, Medellin, Colombia,   Research Associate, Department of Laboratory Medicine, Division of Pathology, St Michaels Hospital, University of Toronto, Ontario, Canada,   Professor, Department of Neurosurgery, SOMA Clinic, Medellin, Colombia,   Professor, Division of Otolaryngology, Medellin Clinic, Medellin, Colombia,   Senior Scientist, Department of Laboratory Medicine, Division of Pathology, St. Michaels Hospital, University of Toronto, Ontario, Canada,   Emeritus Professor, Department of Laboratory Medicine, Division of Pathology, St. Michaels Hospital, University of Toronto, Ontario, Canada
Published: October 2015

Most pituitary tumors are non-invasive, benign adenomas that remain confined to the sella turcica. Some of them recur, have a rapid growth rate, and invade surrounding tissues. These adenomas, considered aggressive pituitary tumors, are difficult to manage and present problems due to incomplete resection. A pituitary carcinoma is diagnosed when craniospinal and/or systemic metastases are documented. Treatment options for pituitary adenomas are surgery, radiation, and drugs. Recent publications report the efficacy of temozolomide in the treatment of aggressive pituitary adenomas and carcinomas. Indications for, results with, and side effects of temozolomide therapy in aggressive pituitary tumors and pituitary carcinomas are reviewed here. Alternative treatment options for resistant or recurrent pituitary tumors are also discussed.
Statin Drug Interactions in Patients with Comorbidities and on Multiple Medications
Authors: Ito Matthew K ,   Professor of Pharmacy Practice, College of Pharmacy, Oregon State University/Oregon Health & Science University, Portland, Oregon, US
Published: October 2015

Extensive clinical evidence has demonstrated the efficacy of statin treatment in the prevention of cardiovascular disease (CVD). However, nearly half of patients taking statins discontinue their use, largely as a result of side effects. Many patients receiving statins are elderly, and/or have comorbid conditions, increasing the potential for drug-drug interactions (DDIs). Statin DDIs are largely the result of altered drug metabolism via cytochrome P450s (CYPs), glucuronidation or altered drug transport via organic anion-transporting polypeptides (OATPs) and P-glycoprotein (P-gp). There is a need for discussion and education about DDIs within the clinical consultation. Statins that are not significantly metabolized via the CYP system have a reduced risk of DDIs. To date, pitavastatin has shown a low rate of DDIs compared to other available statins metabolized by CYP3A4 isozymes. Its potential for CYP-mediated DDIs has been studied in combination with a wide range of drug classes known to be CYP inhibitors and has been clinically evaluated in patients populations where multiple medications are used, including the elderly, those high risk of CVD, and those taking protease inhibitors. It may also have beneficial effects on parameters of glucose metabolism, and has shown improved outcomes in patients with chronic kidney disease. Knowledge of statin pharmacokinetics, their dose limitations and contraindications, and their mechanisms of DDI allows improved therapeutic choices, avoiding adverse interactions without compromising patient care.
Witnessing a New Era?—The Emerging Role of Targeted Drugs in the Medical Treatment of Advanced Medullary and Anaplastic Thyroid Cancer
Authors: Lorch Jochen , Voigt Wieland ,   Assistant Professor, Dana Farber Cancer Institute, Boston, Massachusetts, US,   Associate Professor, Department of Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Halle, Germany
Published: October 2015

The treatment of advanced thyroid cancer is currently entering a new era due to the introduction of targeted therapy into modern cancer treatment. The growing insight into the molecular biology of thyroid cancer and on the development of numerous mainly multitargeted agents provide the basis for new treatment strategies. In particular, activation of mitogenic and angiogenic signaling pathways are suitable targets as preclinical and clinical data suggest. Several Phase II and a few Phase III studies were launched in thyroid cancer which included medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) but only a few focused specifically on theses subtypes. A number of smaller Phase II trials reported promising response rates and progression-free survival. Results from a randomized Phase III trial in MTC with vandetanib, a combined vascular endothelial growth factor receptor 2 + 3 (VEGF-R2+3) and RET multi tyrosine kinase inhibitor demonstrated significant clinical activity and resulted in the first approval of a kinase inhibitor for the treatment of MTC in 2011. Unlike in MTC, in ATC the prognosis is dismal due to the aggressive nature of the disease. Some mainly vascular targeting agents alone or in combination with chemotherapy have shown interesting activity in this disease and have raised new hope. Particularly the combination of fosbretabulin with a chemotherapy backbone of paclitaxel and carboplatin tripled the one-year survival rate in a recent Phase II trial which included 80 patients with ATC. In this review, we provide a brief overview of the general treatment concept of MTC and ATC and summarize the compiled evidence published on targeted agents in these rare thyroid cancer subtypes.
AGE, RAGE, and Diabetic Nephropathy
Authors: Daroux Maïté , Grossin Nicolas , Boulanger Eric ,   Physician, Biology of Aging Laboratory, University Hospital of Lille, Lille and Department of Nephrology, Duchenne Hospital, Boulogne-sur-Mer Cedex, France,   Postdoctoral Researcher, Biology of Aging Laboratory, University Hospital of Lille, Lille, France,   Professor of Aging Biology and Geriatrics, Head of the Aging Biology Team, Lille 2 University School of Medicine, Lille, France
Published: October 2015

Diabetes is a disease that is present worldwide and which is associated with a large number of potential complications including chronic kidney disease (CKD). Several factors have been implicated in the development of the latter, including advanced glycation end-products (AGEs), which are formed from the interaction between sugar and proteins. AGE toxicity may be triggered via different mechanisms, especially by receptor binding. Immunohistochemical studies have demonstrated the presence of AGEs in all renal structures (vessels, glomeruli, tubules, and the interstitium). They appear to be involved in the exacerbation of renal injury observed during diabetic nephropathy. At present, no specific treatment is yet available, although several therapeutic approaches are under development.
Obesity and Vitamin D Deficiency—Current Concepts on their Impact on Pregnancy
Authors: McAree Trixie ,   Consultant Midwife, North West London Hospitals NHS Trust, Harrow, UK
Published: October 2015

Both obesity and vitamin D deficiency are linked to morbidity and ultimately mortality. Vitamin D sufficiency is believed to confer many health benefits; however, with the exception of the classic functions related to bone health these are not yet well understood, especially in relationship to pregnancy and infant health outcomes.1Conversely, insufficiency is associated with adverse health outcomes, which are consequently related to public health concerns that arise from these and these need addressing.2,3While the links between health and vitamin D are being considered and researched, there are an increasing number of reports that demonstrate vitamin D deficiency is prevalent particularly among people who are darker skinned, those who live at latitudes above 52°, and are therefore exposed to reduced sunlight especially in the autumn and winter months, those who through lifestyle choices cover their bodies, preventing sunlight exposure, and in obese people.3–6Obesity is also of growing concern. Health journalists and academics sometimes dramatically refer to ‘obesity epidemics,’ which is not surprising as over one-third of Americans are obese.7–9This problem, if not addressed, will lead to adverse health outcomes for individuals as well as being a long-term burden both to families and society.10–11It is interesting to note that both vitamin D deficiency and obesity have shared risks for mortality and morbidity including cardiovascular disease, diabetes, respiratory problems, cancer, and musculoskeletal disease. This paper considers current concepts and the links between obesity and vitamin D deficiency in pregnancy seeking to determine whether being vitamin D deficient and obese is simply double trouble, where both are present, or whether there are there other factors that need further exploration, reviewing the associated implications for practice.12–15
Vitamin D and Cancer—A Review
Authors: Friedman Claire F , Bachow Spencer H ,   Internal Medicine Residents, Department of Medicine, Hospital of the University of Pennsylvania, PA, US,   Internal Medicine Residents, Department of Medicine, Hospital of the University of Pennsylvania, PA, US
Published: October 2015

Vitamin D is a steroid hormone that has traditionally been recognized for its role in calcium metabolism and skeletal homeostasis. However, there is growing recognition of its immunomodulatory and anti-tumorigenic effects both in vivo and in vitro. Vitamin D and its receptor form a nuclear receptor-ligand complex that exerts anti-proliferative effects via downstream intracellular signaling. While basic science data for the role of vitamin D in both treating and preventing malignancy have been promising, clinical and epidemiologic data in cancer patients have been mixed. In this paper, we will briefly review the basic science and clinical data for the role of vitamin D in cancer prevention and treatment for the four most common malignancies: breast, prostate, colorectal, and lung cancer.
Ezetimibe in the Treatment of Patients with Metabolic Diseases
Authors: Nehme Mayssam A , Upadhyay Ashish ,   Resident in Internal Medicine,   Assistant Professor of Medicine, Renal Section, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Massachusetts, US
Published: October 2015

Dyslipidemia is an established risk factor for cardiovascular disease. While statin therapy remains the most important component of dyslipidemia management, a substantial proportion of patients on statin monotherapy fails to achieve guideline-recommended lipid levels. Ezetimibe is a secondline lipid-lowering agent that reduces sterol absorption, and has a favorable effect on lipid profile. This article reviews studies examining the role of ezetimibe on lipid profile, metabolic biomarkers, and cardiovascular outcomes in individuals with metabolic diseases. Special focus is given to studies in patients with dyslipidemia, Type 2 diabetes, and the metabolic syndrome. The controversy surrounding the role of ezetimibe in mitigating atherosclerosis is also highlighted. The article concludes that the ezetimibe–statin combination improves lipid parameters and helps attain guidelinerecommended lipid goals in patients with metabolic diseases. However, further research is needed to better understand the role of ezetimibe monotherapy, and the impact of ezetimibe on clinical cardiovascular outcomes.
Extra-hepatic Acromegaly
Authors: Franck Sanne E , Lely Aart Jan van der , Neggers Sebastian ,   Department of Internal Medicine, Erasmus University MC, Rotterdam, the Netherlands,   Department of Internal Medicine, Erasmus University MC, Rotterdam, the Netherlands,   Department of Internal Medicine, Erasmus University MC, Rotterdam, the Netherlands
Published: October 2015

After the introduction of somatostatin analogs (LA-SMSA) and the growth hormone (GH) receptor antagonist, pegvisomant (Peg-v) normal serum insulin-like growth factor-1 (IGF-1) concentrations in virtually every patients with acromegaly is possible. The impact of these products on the GH–IGF1 axis is completely different. We advocate that LA-SMSA may normalize serum IGF1 levels in the presence of elevated GH actions in extrahepatic tissues. This results in persistent peripheral disease activity that we call ‘extra-hepatic acromegaly’. Peg-v competitively blocks systemic GH action and results in a GH serum level increase. Therefore high doses of Peg-v are necessary to control IGF-1. Since the mode of action differs between these products, it is questionable if identical IGF-1 levels, during Peg-v or LA-SMSA are really identical representations of the biochemical situation. With the traditional biomarkers medical treatment is therefore difficult to monitor with the traditional biomarkers. Additionally, Peg-v and LA-SMSA could be ideal combination since they have different mode of actions. We believe that the time has come to challenge the existing concepts of treatment and monitoring of patients with acromegaly.
Can Bariatric Surgery be Considered Standard Therapy to Treat Type 2 Diabetes?
Authors: Meyvis Karen , Block Christophe De , Gaal Luc F Van ,   Endocrinologist,   Associate Professor of Medicine,   Professor of Medicine and Head, Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Belgium
Published: October 2015

With the rapid increase in obesity there has been a pronounced increase in obesity-related metabolic disorders including type 2 diabetes, cardiovascular disease, dyslipidemia, and hypertension. Bariatric surgery is a highly effective treatment for achieving long-term weight loss and is increasingly recognized to have benefits in diabetes treatment and cause improvement in other metabolic factors. Recent small randomized trials reported better glycemic control after surgical intervention compared with pharmacologic therapy. Physiologic studies suggest a surgeryspecific, weight-independent effect on glucose homeostasis. Long-term efficacy is to be proven. Consensus on definition of diabetes and diabetes remission must be achieved. Larger multicentre, randomized trials need to be performed to clarify the place of metabolic surgery in diabetes treatment algorithms.
Advances in Insulin Injection Research Influences Patient Adherence
Authors: Aronson Ronnie , Bailey Timothy , Hirsch Laurence , Saltiel-Berzin Rita ,   Executive Director, LMC Endocrinology Centres, Toronto, Ontario, Canada,   Director, AMCR Institute, Inc., Escondido, California, US,   BD (Becton Dickinson and Company), Franklin Lakes, New Jersey, US,   BD (Becton Dickinson and Company), Franklin Lakes, New Jersey, US
Published: October 2015

Insulin formulations and injection devices have improved dramatically since the first insulin injection was given in 1922. Adherence to insulin therapy, however, is estimated at 62–64 % despite research indicating that good glycemic control improves patient outcomes. The challenge is to improve the rates of adherence and to intensify or progress insulin therapy as needed. Changes in insulin delivery devices, especially innovations in needle technology in combination with education and support, have the potential to improve the comfort of insulin injections and encourage patients to adhere to their insulin regimens.
The Role of Fructose, Sucrose, and High-fructose Corn Syrup in Diabetes
Authors: Cozma Adrian I , Sievenpiper John L ,   Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael’s Hospital, Toronto, Ontario, Canada,   Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada,   Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael’s Hospital, Toronto, Ontario, Canada,   Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada,   Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
Published: October 2015

Concerns are growing regarding the role of dietary sugars in the development of obesity and cardiometabolic diseases, including diabetes. High-fructose corn syrup (HFCS) and sucrose are the most important dietary sweeteners. Both HFCS and sucrose have overlapping metabolic actions with adverse effects attributed to their fructose moiety. Ecologic studies have linked the rise in fructose availability with the increases in obesity and diabetes worldwide. This link has been largely underpinned by animal models and select human trials of fructose overfeeding at high levels of exposure. Although prospective cohort studies have shown significant associations comparing the highest with the lowest levels of intake sugar-sweetened beverages, these associations are small, do not hold at moderate levels of intake, and are subject to collinearity effects from related dietary and lifestyle factors. Most systematic reviews and meta-analyses from controlled feeding trials have shown that fructosecontaining sugars in isocaloric exchange for other carbohydrates do not show evidence of harm and, in the case of fructose, may even have advantages for glycemic control, especially at small doses. Nevertheless, trials in which fructose-containing sugars supplement diets with excess energy have shown adverse effects, effects that appear more attributable to the excess energy than the sugar. There is no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects, although there is potentially cause for concern where fructose is provided at high doses or contributes excess energy to diets. Further investigation is warranted due to the significant knowledge gaps and weaknesses in existing research.
Challenges of Statins in HIV Hyperlipidemia
Authors: Malvestutto Carlos D , Aberg Judith A ,   Assistant Professor, Division of Infectious Diseases and Immunology, Department of Medicine, New York University School of Medicine, New York, US,   Chief, Division of Infectious Diseases and Professor of Medicine, ICAHN School of Medicine at Mount Sinai, New York, and Professor of Medicine, Division of Infectious Diseases and Immunology, Department of Medicine, New York University School of Medicine, New York, New York, US
Published: October 2015

As a result of access to potent antiretroviral therapy (ART), HIV-infected adults with virologic suppression are living longer, but unfortunately are at increased risk for developing comorbid conditions. It is postulated that this increased risk seen at all ages is partly due to the effects of viral-mediated chronic inflammation in addition to the traditional risk factors. One of the more common traditional risk factors, hyperlipidemia, may be worsened by ART. However, the benefits of ART greatly outweigh the possible negative effects of ART agents on lipid parameters. As the HIV-infected patient population ages, it is critical to control hyperlipidemia in ART-treated patients in order to reduce the risk for long-term cardiovascular complications. If hyperlipidemia cannot be managed through lifestyle modifications, clinical guidelines recommend the use of lipid-lowering medication, particularly HMG Co-A reductase inhibitors (statins), to reduce low-density lipoproteins-cholesterol. However, many ART agents inhibit or induce major metabolic pathways of statins, creating potentially serious drug–drug interactions. In this article, we present a review of the various challenges in managing hyperlipidemia with a focus on drug–drug interactions.
Congenital Growth Hormone Deficiency—A Review with a Focus on Neuroimaging
Authors: Tsai Sarah L , Laffan Eoghan ,   Pediatric Endocrinologist and Assistant Professor of Pediatrics, Section of Endocrinology and Diabetes, Children’s Mercy Hospital and Clinics, University of Missouri Kansas City School of Medicine, Kansas City, Missouri, US,   Consultant Pediatric Radiologist, Children’s University Hospital, Dublin, Ireland
Published: October 2015

Growth hormone deficiency is an important cause of short stature in childhood. It is characterized by low growth velocity in childhood and is diagnosed by stimulation testing. Individuals with growth hormone deficiency may have other pituitary hormone deficits in addition to growth hormone deficiency. When multiple pituitary hormone deficiencies are present, abnormal pituitary anatomy, as visualized on magnetic resonance imaging (MRI), is a frequent finding. The classic triad (ectopic posterior pituitary, hypoplastic or aplastic anterior pituitary, and absent/thin pituitary stalk) or variants of the classic triad are commonly seen in these patients. Volumetric sequencing allows all three planes of visualization to be reconstructed in postprocessing, allowing the radiologist to more fully evaluate pituitary anatomy. The normal dimensions of the pituitary gland vary by age and precise definitions of what constitutes a hypoplastic gland are not clearly defined in the medical literature. Having an experienced neuroradiologist interpret the MRI in patients with pituitary dysfunction is very important.
Dual-release Hydrocortisone in Addison’s Disease—A Review of the Literature
Authors: Giordano Roberta , Guaraldi Federica , Berardelli Rita , Karamouzis Ioannis , Angelo Valentina D , Zichi Clizia , Grottoli Silvia , Ghigo Ezio , Arvat Emanuela ,   Department of Clinical and Biological Sciences,   Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences,   Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences,   Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences,   Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences,   Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences,   Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences,   Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences,   Division of Oncological Endocrinology, Department of Medical Sciences, University of Turin, Turin, Italy
Published: October 2015

In patients with adrenal insufficiency, glucocorticoids (GCs) are insufficiently secreted and GC replacement is essential for health and, indeed, life. Despite GC-replacement therapy, patients with adrenal insufficiency have a greater cardiovascular risk than the general population, and suffer from impaired health-related quality of life. Although the aim of the replacement GC therapy is to reproduce as much as possible the physiologic pattern of cortisol secretion by the normal adrenal gland, the pharmacokinetics of available oral immediate-release hydrocortisone or cortisone make it impossible to fully mimic the cortisol rhythm. Therefore, there is an unmet clinical need for the development of novel pharmaceutical preparations of hydrocortisone, in order to guarantee a more physiologic serum cortisol concentration time-profile, and to improve the long-term outcome in patients under GC substitution therapy.
Bone Involvement in Primary Hyperparathyroidism and Changes After Parathyroidectomy
Authors: Rolighed Lars , Rejnmark Lars , Christiansen Peer ,   Senior Resident, Department of Surgery P,   Consultant, Department of Endocrinology and Internal Medicine,   Professor and Consultant, Department of Surgery P, Aarhus University Hospital, Aarhus, Denmark
Published: October 2015

Parathyroid hormone (PTH) is produced and secreted by the parathyroid glands and has primary effects on kidney and bone. During the pathologic growth of one or more parathyroid glands, the plasma level of PTH increases and causes primary hyperparathyroidism (PHPT). This disease is normally characterized by hyperparathyroid hypercalcemia. In PHPT a continuously elevated PTH stimulates the kidney and bone causing a condition with high bone turnover, elevated plasma calcium, and increased fracture risk. If bone resorption is not followed by a balanced formation of new bone, irreversible bone loss may occur in these patients. Medical treatment can help to minimize the loss of bone but the cure of PHPT is by parathyroidectomy. After operation, bone mineral density increases during the return to normal bone metabolism. Supplementation with calcium and vitamin D after operation may improve the normalization to normal bone metabolism with a secondary reduction in fracture risk.
Psychophysical Exams as Early Indicators of Diabetic Retinopathy
Authors: Pescosolido Nicola , Buomprisco Giuseppe ,   Professor, Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences,   Resident Physician (Intern), University Sapienza of Rome, Faculty of Medicine and Dentistry, Department of Sense Organs, Rome, Italy
Published: October 2015

Retinopathy is a serious and common complication of diabetes that represents the leading cause of blindness, among people of working age, in developed countries. It is estimated that the number of people with diabetic retinopathy (DR) will increase from 126.6 million in 2011 to 191 million by 2030. The visual function that seems to be affected first in the course of DR is probably the contrast sensitivity; in addition, being mainly a macular function, the perception of color is also compromised. Moreover, the duration of the disease, the levels of glycated hemoglobin (HbA1c) and the presence of cystoid macular edema are strongly associated with the impairment of fixation stability in patients with diabetes with clinically significant macular edema, suggesting the possible diagnostic role of microperimetry. The test of contrast sensitivity and the microperimetry and the chromatic sensitivity tests have proved to be useful, safe, reproducible, and inexpensive tools to diagnose the
What is Causing the Worldwide Rise in Body Weight?
Authors: Shook Robin P , Blair Steven N , Duperly John , Hand Gregory A , Matsudo Sandra M , Slavin Joanne L ,   Postdoctoral Researcher, Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, US,   Professor, Departments of Exercise Science, Epidemiology, and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, US,   Associate Professor, Department of Internal Medicine, Universidad de los Andes Medical School, Bogotá, Colombia,   Professor, Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, US,   Professor and Director General, Agita São Paulo Program-Studies Center, Physical Fitness Research Center for São Caetano do Sul, São Caetano do Sul, São Paulo, Brazil,   Professor, Department of Food Science and Nutrition, University of Minnesota, St Paul, Minnesota, US
Published: October 2015

The worldwide rise in body weight has reached epidemic proportions and this has serious public health consequences. Despite the universal recognition of this problem, its causes are still debated: some attribute it to excess caloric intake; others blame a lack of physical activity (PA); some implicate specific changes to micro- and macro-nutrients. During the past century, government health agencies have developed guidance on healthy eating. These, along with advances in agriculture and food manufacturing, have largely eliminated nutrient deficiencies and helped reduce the consumption of fat. Over the past 60 years, however, technological advances and shifts in the types of occupations prominent in industrialized as well as developing countries have resulted in well-documented decreases in energy expenditure. Energy intake must be balanced with energy expenditure in order to prevent weight gain, and there is increasing evidence that this balance must be at a relatively high level of energy flux. A program that was started in São Paulo in 1996 known as ‘Agita’ has sought to motivate populations to engage in small amounts of physical exercise daily to tackle growing obesity levels. This multi-agency initiative is one example of how to successfully increase exercise within a community and scale both within (e.g. all states in Brazil) and across many nations. Reducing caloric intake in whole populations is challenging especially at relatively low levels of energy expenditure, and evidence suggests that there is a critical energy flux threshold for regulating intake to achieve energy balance. Increasing PA, however, may be more achievable than reducing intake. Activity raises caloric expenditure and can offset excess intake. The implementation of programs to achieve greater PA is therefore vital if the worldwide rise in body weight is to be halted, while we also need to implement programs to help people eat smarter.
Sustained-release Naltrexone/Bupropion A Novel Pharmacologic Approach to Obesity and Food Craving
Authors: Fujioka Ken ,   Director, Nutrition and Metabolic Research and Director, Weight Management, Scripps Clinic, San Diego, California, US
Published: October 2015

Long-term pharmacologic strategies that may be used in conjunction with lifestyle changes to address the obesity epidemic have, until recently, been an unmet clinical need. Interestingly, pharmacologic interventions to date have not specifically focused on modifying the behavioral aspects of eating. Food intake is influenced by multiple pathways, including the homeostatic regulation of energy balance controlled by the hypothalamus and the mesolimbic reward system, dysregulation of which can lead to reward eating, food craving, and overconsumption of food. A growing body of evidence suggests that targeting the reward system can be a successful intervention for obesity management. Sustained-release naltrexone/bupropion is a novel combination therapy that targets both the hypothalamic melanocortin system and the reward system. In clinical trials, naltrexone/bupropion has been associated with sustained and clinically meaningful weight loss together with beneficial effects on eating behavior and improvements in cardiometabolic factors. Craving and control of food intake were also measured and correlated with improved outcome.
The Influence of Statins on Glucose Tolerance and Incipient Diabetes
Authors: O’Keefe James H , DiNicolantonio James J , Lavie Carl J , Bell David SH ,   Cardiologist, Saint Lukes Hospital, Mid America Heart Institute, Kansas City, Missouri, US,   Cardiovascular Research Scientist, Saint Lukes Hospital, Mid America Heart Institute, Kansas City, Missouri, US,   Professor of Medicine, Medical Director, and Cardiac Rehabilitation and Prevention Director, Stress Testing Laboratory, Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, and Department of Preventive Medicine, Pennington Biomedical Research Center, Baton Rouge, Louisiana, US,   Professor of Medicine (Retired), University of Alabama Medical School and Southside Endocrinology, Birmingham, Alabama, US
Published: October 2015

The US Food and Drink Administration (FDA) recently published a warning that statin usage may increase the risk for type 2 diabetes. However, the incidence of new-onset diabetes varies substantially among clinical trials investigating the efficacy and safety of statins. Meta-analyses indicate that statin therapy is associated with an increased risk for diabetes of approximately 9 %. The risk for incident diabetes may be associated with higher doses and potencies of statins. Mechanisms explaining the potentially higher incidence of type 2 diabetes with statin therapy have not been fully elucidated, and statins differ considerably in terms of their effect on glucose metabolism and ultimately incident diabetes. It is widely accepted that the cardiovascular benefits associated with statin use greatly outweigh the risks for diabetes. However, the effect of different statins on glycemic parameters may influence the choice of statin in those with risk factors for diabetes. Unlike the other stains, pitavastatin raises adiponectin levels, which in turn lowers insulin resistance and improves insulin secretion. Furthermore, numerous studies have concluded that pitavastatin and pravastatin do not affect glycemic control and may be favorable treatment options in patients with, or at risk for, type 2 diabetes.
Glucose Control and Cardiovascular Outcomes in Clinical Trials of Sodium Glucose Co-transporter 2 Inhibitor Treatments in Type 2 Diabetes
Authors: Oliveros Rene A , Pham Son V , Bailey Steven R , Chilton Robert J ,   Assistant Professor and Director, Cardiac Care Unit, Audie L Murphy VA Hospital, University of Texas Health Science Center at San Antonio,   Assistant Professor and Chief of Cardiology, Audie L Murphy VA Hospital, University of Texas Health Science Center at San Antonio,   Professor and Chief, Division of Cardiology, University of Texas Health Science Center at San Antonio,   Professor and Director, Catherization Lab, Audie L Murphy VA Hospital, University of Texas Health Science Center at San Antonio, San Antonio, Texas, US
Published: October 2015

Currently available medications for the treatment of type 2 diabetes have limitations, and many patients do not achieve glycemic control. Recently, a new approach has emerged using sodium glucose co-transporter 2 (SGLT2) inhibitors that decrease glucose reabsorption in the kidneys, increasing urinary glucose excretion. These agents offer the potential to improve glycemic control independently of insulin pathways while avoiding hypoglycemia. Two drugs of this class, canagliflozin and dapagliflozin, have been approved by the US Food and Drug Administration (FDA); another, empagliflozin, has been filed for regulatory approval and several others are in advanced development. These drugs have been shown to effectively reduce blood glucose, fasting plasma glucose, and glycated hemoglobin (HbA1C) levels in phase III clinical trials when used as monotherapy and as add-on therapy to other diabetes medications, including insulin. Another advantage of the SGLT2 inhibitors over existing treatments is the improvement in cardiovascular risk factors, particularly in terms of reductions in blood pressure and body weight. SGLT2 inhibitors have been generally well tolerated. While more long-term safety data are required to elucidate the benefit–risk profile of SGLT2 inhibitors, the rationale for their use in type 2 diabetes therapy is strong.