Author Interviews, Diabetes, Immunotherapy, Kidney Disease, University of Michigan / 13.06.2015

MedicalResearch.com Interview with: Frank C. Brosius, MD Professor, Internal Medicine and Physiology Chief, Division of Nephrology University of Michigan Ann Arbor, MI Dr. Matthias Kretzler MD Professor, Internal Medicine Research Professor, Computational Medicine and Biology University of Michigan Ann Arbor, MI Katherine R. Tuttle MD Clinical Professor of Medicine, Division of Nephrology Medical & Scientific Director, Providence Medical Research Center/Sacred Heart Center Professor of Basic Medical Sciences, WWAMI Program Washington State University Medical Research: What is the background for this study? Response: Our University of Michigan team had found that JAK-STAT gene expression was increased in kidneys in patients with diabetic kidney disease and that these changes correlated with progression of kidney disease.  We subsequently substantiated these changes in other studies and have found that by increasing expression of just one of these genes, JAK2, in a single kidney cell type (podocytes) in mice that we can make their diabetic kidney disease much worse. At around the same time, investigators at Eli Lilly and Co. had FDA approval to test a JAK1-2 inhibitor, baricitinib, in patients with rheumatoid arthritis.  The Lilly scientists saw our human results and thought about using baricitinib in patients with diabetic kidney disease.  After initial discussions with Dr. Kretzler and myself they concluded that there was good reason to move ahead with this study and just 14 months after the initial meeting the phase 2 clinical trial of baricitinib in the treatment of patients with diabetic kidney disease was initiated. (more…)
Author Interviews, Diabetes, Lancet, McGill / 13.06.2015

MedicalResearch.com Interview with: Dr Ahmad Haidar Ph.D. Division of Experimental Medicine Department of Medicine, McGill University Montreal, QC, CanadaDr. Ahmad Haidar Ph.D Division of Experimental Medicine, Department of Medicine McGill University, Montreal, QC, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Haidar: This is the first head-to-head-to-head comparison in outpatient setting of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional pump therapy in children and adolescents with type 1 diabetes. The main finding is that the dual-hormone artificial pancreas seems to outperform the other two systems in reducing nocturnal hypoglycemia in camp settings when the patients are very physically active during the day. Medical Research: What should clinicians and patients take away from your report? Dr. Haidar: Glucagon has the potential to reduce nocturnal hypoglycemia if added to the artificial pancreas. However, this needs to be confirmed in larger and longer studies as the single-hormone artificial pancreas might be sufficient in home settings (this study was conducted at a camp, which is an environment different that home). (more…)
Author Interviews, Depression, Diabetes, Heart Disease, Pharmacology, Women's Heart Health / 08.06.2015

Dr. Karin Rådholm MD Ph.D. Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University, Department of Local Care West, County Council of Östergötland, Linköping, SwedenMedicalResearch.com Interview with Dr. Karin Rådholm MD Ph.D. student Division of Community Medicine, Primary Care, Department of Medicine and Health Sciences, Faculty of Health Sciences, Linköping University Department of Local Care West, County Council of Östergötland, Linköping, Sweden MedicalResearch: What is the background for this study? Dr. Rådholm: Psychosocial risk factors and depressive disorders often co-occur with general medical comorbidities, such as myocardial infarction. Depression is more common in patients with diabetes than in patients without diabetes. About 10-30% of patients with diabetes have a comorbid depressive disorder, which is double the estimated prevalence of depression in individuals without diabetes. There is an association between comorbid depressive symptoms and diabetes complications. This is believed to be mainly due to poor adherence to treatment recommendations and diabetes self-management activities, but could also possibly be due to biological and behavioural causes that could predispose for both metabolic and affective disorders. The general risk of myocardial infarction is strongly dependent on age and sex, where men have an earlier disease onset compared to women. In the general population women are at much lower risk for ischemic heart disease mortality than men are. However, women with diabetes are at especially high risk for coronary heart disease, relatively more so than men with type 2 diabetes, meaning that the impact of diabetes on the risk of coronary death is significantly greater for women than men. The age- and gender-specific risk for myocardial infarction due to diabetes with coexistent depression has not previously been described. Data on all dispensed drug prescriptions in Sweden are available in the Swedish Prescribed Drug Register and all myocardial infarctions are registered in the Myocardial Infarction Statistics. These registers are population-based and have a total national coverage and high validity, which has been previously shown. Prescribed and dispensed antidiabetics and antidepressants were used as markers of disease. Our objective was to prospectively explore the gender- and age-specific risk of first myocardial infarction in people treated with antidiabetic and/or antidepressant drugs compared to participants with no pharmaceutical treatment for diabetes or depression in a nationwide register study. (more…)
Author Interviews, Diabetes, JAMA, Ophthalmology, University of Michigan / 06.06.2015

Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of MichiganMedicalResearch.com Interview with: Julia E. Richards, Ph.D. Harold F. Falls Professor of Ophthalmology and Visual Sciences Professor of Epidemiology Director, Glaucoma Research Center The University of Michigan Medical Research: What is the background for this study? Response: We have a special interest in how the developmental processes of aging increase the risk of late onset diseases. We wondered whether drugs that target known aging pathways might be able to reduce risk of late onset disease. In the aging field, an emerging area of interest has been the category of drugs called caloric restriction mimetic (CRM) drugs, which have been found to extend life span and to reduce risk or delay onset of some late-onset diseases. These caloric restriction mimetic drugs target a set of pathways that have come to be seen as playing roles in longevity. One of these caloric restriction mimetic drugs, metformin, happens to also be one of the most common drugs used in the treatment of type 2 diabetes. Glaucoma is a leading cause of blindness worldwide and classical open-angle glaucoma shows onset in late middle age or late age, so we hypothesized that a caloric restriction mimetic drug might be able to reduce the risk of open-angle glaucoma. We used data from a large health services database to compare the rate at which open-angle glaucoma developed in individuals with diabetes mellitus who used metformin versus those who did not use metformin. We predicted that metformin would be associated with reduced risk of open-angle glaucoma. Medical Research: What are the main findings? Response: We found that use of metformin was associated with reduced risk of open-angle glaucoma. A 2 gram per day dose of the CRM drug metformin for two years was associated with a 20.8% reduction in risk of developing open-angle glaucoma. When we looked at the highest quartile of drug prescribed (>1,100 grams over a two year period) we found a 25% reduction in risk relative to those taking no metformin. This risk reduction is seen even when we account for glycemic control in the form of glycated hemoglobin, and use of other diabetes drugs was not associated with reduced risk of open-angle glaucoma. A possible explanation for our findings might be that the mechanism of risk reduction is taking place by CRM drug mechanisms that target aging pathways rather than through glycemic control of diabetes. In the long run, the approaches to late onset diseases in general will become much more powerful if we can use parallel approaches that simultaneously target both the aging processes going on and the disease-specific pathways going on. In the literature we see caloric restriction mimetic drugs metformin, rapamycin and resveratrol all being explored for their ability to target points in aging pathways in ways that can impact the risk of a variety of late-onset diseases, so it will be important for those interested in the risk factors affecting late onset diseases to pay attention to how caloric restriction mimetic drugs might be altering risk for those late onset diseases. (more…)
Author Interviews, Diabetes, mBio, Microbiome / 04.06.2015

Patrick M. Schlievert Ph.D Professor and Chair Department of Microbiology Carver College of Medicine Iowa City Iowa 52242MedicalResearch.com Interview with: Patrick M. Schlievert Ph.D Professor and Chair Department of Microbiology Carver College of Medicine Iowa City Iowa 52242 Medical Research: What is the background for this study? Dr. Schlievert:
  1. As people become obese and enter pre-diabetes type II, there is a gut microbiome shift in bacteria from Bacteroidetes to Firmicutes. A dominant pathogenic Firmicute in humans is Staphylococcus aureus.
  2. As people become obese, their skin becomes wetter due to enhanced sweating upon exertion and the presence of more skin folds. These, plus mucous membranes have enhanced Staphylococcus aureus numbers, such that 100% of people become colonized and numbers of the bacterium rise to 1013 per person. This number of bacteria is like a cubic inch of margarine spread across the skin and mucous membranes.
  3. All pathogenic Staphylococcus aureus bacteria make and secrete a family of toxins called superantigens, including toxic shock syndrome toxin and staphylococcal enterotoxins. In high amounts (0.1 μg/human), these toxins can be lethal, causing toxic shock syndrome. At lower concentrations, the same superantigen toxins cause total body inflammation without lethality.
  4. In order to show that a microbes causes human disease, it is necessary to fulfill Koch’s postulates:
    1. Must associate human symptoms with a particular disease,
    2. Must isolate a potentially causative bacterium that is always present when the disease is present.
    3. Must produce the disease in an experimental animal.
    4. Must re-isolate the microbe from the experimental animal and re-cause the disease in another animal.
Medical Research: What are the main findings? Dr. Schlievert: We have fulfilled Koch’s postulates, showing that Staphylococcus aureus and its superantigen toxins cause type II diabetes. (more…)
Author Interviews, Diabetes, Surgical Research / 03.06.2015

MedicalResearch.com Interview with: Tom E. Robinson School of Population Health University of Auckland, New Zealand Medical Research: What is the background for this study? What are the main findings? Response: Diabetic foot disease affects up to 50% of people with diabetes and lower limb amputation is a serious complication that has a great impact both on patient quality of life and healthcare costs.  Foot complications are however potentially preventable with good diabetes and foot care and early intervention. There is international evidence of unexplained ethnic variations in the incidence of lower limb amputation.  This study found that ethnicity was strongly associated with risk of lower limb amputation. For example, New Zealand Maori people with diabetes have 63% higher rates of lower limb amputations and this increased risk is not altered by controlling for a range of demographic and clinical risk factors.  Asian New Zealander's have much lower risks of amputation but this may, at least in part, be explained by the 'healthy migrant effect'. (more…)
Author Interviews, Diabetes, Diabetologia, Imperial College, Nutrition / 02.06.2015

Dagfinn Aune, PhD student Norwegian University of Science and Technology and Imperial College LondonMedicalResearch.com Interview with: Dagfinn Aune, PhD student Norwegian University of Science and Technology and Imperial College London Medical Research: What is the background for this study? What are the main findings? Response: There are more than 360 million people worldwide that are affected by diabetes, and this number is projected to increase to more than 550 million by 2030, with serious consequences for the health and economy of both developed and developing countries. While previous research has found an association between increased dietary fibre intake and a reduced risk of developing type 2 diabetes, most of these data come from the United States, and amounts and sources of fiber intake differ substantially between countries. In this article the we evaluated the associations between total fiber as well as fiber from cereal, fruit, and vegetable sources, and new-onset type 2 diabetes in a large European cohort across eight countries, in the EPIC-InterAct Study (and included 12403 type 2 diabetes cases and 16835 sub-cohort members). We also conducted a meta-analysis where we combined the data from this study with those from 18 other independent studies from across the globe. We found that participants with the highest total fiber intake (more than 26 g/day) had an 18% lower risk of developing diabetes compared to those with the lowest total fiber intake (less than 19g/day), after adjusting for the effect of other lifestyle and dietary factors. When the results were adjusted for body mass index (BMI) as a marker of obesity, higher total fiber intake was found to be no longer associated with a lower risk of developing diabetes, suggesting that the beneficial association with fiber intake may be mediated at least in part by BMI. In other words, dietary fiber may help people maintain a healthy weight, which in turn reduces the chances of developing type 2 diabetes. In a meta-analysis of the EPIC-InterAct study and 18 other independent studies (>41000 type 2 diabetes cases) we found that the risk was reduced by 9% for each 10 g/day increase in total fiber intake and 25% for each 10 g/day increase in cereal fiber intake. There was no statistically significant association between fruit or vegetable fiber intake and diabetes. (more…)
Author Interviews, Diabetes, Genetic Research, Lipids, PLoS / 31.05.2015

Dr. Yann C Klimentidis, PhD Assistant professor of Epidemiology and Biostatistics Mel and Enid Zuckerman College of Public Health University of Arizona Medical CenterMedicalResearch.com Interview with: Yann Klimentidis Ph.D. Assistant Professor Mel and Enid Zuckerman College of Public Health University of Arizona Medical Research: What is the background for this study? What are the main findings? Dr. Klimentidis: Previous studies have hinted at the possibility that genes which are associated with higher triglyceride levels may also be associated with lower type-2 diabetes. We set out  to test this hypothesis in multiple prospective cohort studies, in European-Americans and in African-Americans. We found that on a collective basis, the alleles which are associated with higher triglycerides are also associated with reduced type-2 diabetes risk. We also identified some individual genetic variants which are driving this trend. (more…)
Author Interviews, Diabetes, Johns Hopkins, Macular Degeneration, Ophthalmology, PNAS / 29.05.2015

MedicalResearch.com Interview with: Akrit Sodhi, M.D., Ph.D. Assistant Professor of Ophthalmology Retina Division Wilmer Eye Institute Johns Hopkins Medical Institutions Medical Research: What is the background for this study? What are the main findings? Dr. Sodhi: Diabetic eye disease is the most common cause of severe vision loss in the working age population in the developed world, and proliferative diabetic retinopathy (PDR) is its most vision-threatening sequela. In proliferative diabetic retinopathy, retinal ischemia leads to the upregulation of angiogenic factors that promote neovascularization. Therapies targeting vascular endothelial growth factor (VEGF) delay the development of neovascularization, in some, but not all diabetic patients, implicating additional factor(s) in proliferative diabetic retinopathy pathogenesis. In our study, we demonstrate that the angiogenic potential of aqueous fluid from PDR patients is independent of VEGF concentration, providing an opportunity to evaluate the contribution of other angiogenic factor(s) to PDR development. We identified angiopoietin-like 4 (ANGPTL4) as a potent angiogenic factor whose expression is upregulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. Expression of ANGPTL4 was increased in the aqueous and vitreous of PDR patients, independent of VEGF levels, correlated with the presence of diabetic eye disease, and localized to areas of retinal neovascularization. Inhibition of ANGPTL4 expression reduced the angiogenic potential of hypoxic Müller cells; this effect was additive with inhibition of VEGF expression. An ANGPTL4 neutralizing antibody inhibited the angiogenic effect of aqueous fluid from proliferative diabetic retinopathy patients, including samples from patients with low VEGF levels or receiving anti-VEGF therapy. Collectively, our results suggest that targeting both ANGPTL4 and VEGF may be necessary for effective treatment or prevention of proliferative diabetic retinopathy and provide the foundation for studies evaluating aqueous ANGPTL4 as a biomarker to help guide individualized therapy for diabetic eye disease. (more…)
Author Interviews, Diabetes, Nature, Neurological Disorders, Vegetarians / 26.05.2015

Ulka Agarwal, M.D. California State University, East Bay Student Health and Counseling Services, Hayward, MedicalResearch.com Interview with: Ulka Agarwal, M.D. California State University, East Bay Student Health and Counseling Services Hayward, CA MedicalResearch: What is the background for this study? What are the main findings? Dr. Agarwal: Diabetic peripheral neuropathy affects 60 percent of patients with type 2 diabetes and can come with painful symptoms but limited treatment options. We thought a dietary intervention may help alleviate these symptoms since glycemic control plays a role in diabetes complications. To get started with the pilot, we put 17 adults on a low-fat vegan diet for 20 weeks and prescribed weekly nutrition classes. We found significant improvements in pain, measured by the Short Form McGill Pain questionnaire, the Michigan Neuropathy Screening Instrument physical assessment, and through electrochemical skin conductance in the foot. The participants also lost an average of 14 pounds. (more…)
Author Interviews, Diabetes, Genetic Research, Weight Research / 22.05.2015

MedicalResearch.com interview Dorota Kaminska, MSc Department of Clinical Nutrition University of Eastern Finland MedicalResearch: What is the background for this study? What are the main findings? Response: The prevalence of obesity is increasing worldwide, making it one of the biggest health problems currently facing both developed and developing countries. Obesity is considered a primary risk factor for developing type 2 diabetes. While the majority of people with type 2 diabetes are obese, most of obese people do not develop diabetes, indicating that obesity is not the only risk factor for type 2 diabetes. Both obesity and type 2 diabetes are multifactorial complex diseases that are caused by a combination of genetic, environmental, and lifestyle factors. Results from twin studies suggest that genetic factors explain 50% to 90% of the variance in body mass index (BMI) and from 45% to 85% of the diabetes risk. However genetic variations identified by genome wide association studies (GWAS) explain only 2-4% of the obesity risk and 5-10% of the type 2 diabetes risk. Several options have been debated to be a source of so called “missing heritability”, including, among others, structural DNA variations, gene-gene and gene-environment interactions, epigenetic modifications and RNA splicing. We used adipose tissue samples from Kuopio Obesity Surgery (KOBS), very low calorie diet (VLCD), Metabolic Syndrome in Men (METSIM) and European Network on Functional Genomics of Type 2 Diabetes (EUGENE2) studies to determine alternative splicing pattern of selected genes. The study focused on determining the effects of obesity and weight loss on alternative splicing of metabolically active genes (TCF7L2 and INSR). We showed that alternative splicing of both genes is dysregulated in obesity and type 2 diabetes, resulting in impaired insulin action in adipose tissue. Additionally we demonstrated, that obesity induced changes in splicing can be reversed by weight loss induced by gastric bypass surgery or very low calorie diet. Furthermore, the study identified alternatively spliced genes in the genomic regions associated with obesity risk, demonstrating that splicing of the MSH5 gene in subcutaneous fat is regulated by weight loss. The study also found that body mass index is a main determinant of TRA2B, BAG6 and MSH5 splicing in subcutaneous fat; however, the functional consequences of this finding require further investigation. These findings imply that the obesity-associated gene variants might act through regulation of splicing which in turn might underlie the pathogenesis of obesity in individuals carrying the risk variants. (more…)
Author Interviews, Diabetes, Endocrinology, HIV, Infections, JCEM / 18.05.2015

Kevin Yarasheski, PhD Assistant Director, Biomedical Mass Spectrometry Research Facility Professor of Medicine, Cell Biology & Physiology, Physical Therapy Washington University School of MedicineMedicalResearch.com Interview with: Kevin Yarasheski, PhD Assistant Director, Biomedical Mass Spectrometry Research Facility Professor of Medicine, Cell Biology & Physiology, Physical Therapy Washington University School of Medicine Medical Research: What is the background for this study? Dr. Yarasheski:   People living with HIV and taking combination antiretroviral therapy (cART) have successfully reduced the amount of HIV virus in their blood and have partially reconstituted their immune system (CD4+ T-cell count >250 cells/µL).  Despite this, many still experience residual immune cell activation and inflammation that is believed to increase HIV morbidity (non-AIDS conditions e.g., CVD, T2DM, obesity, liver fat, bone loss, dementia) and mortality.  Scientists are seeking safe and effective interventions for residual immune cell activation and inflammation, that have the potential to reduce non-AIDS complications that threaten quality and quantity of life among HIV infected adults. We have been testing the safety and efficacy of sitagliptin in people living with HIV; a dipeptidyl peptidase 4 inhibitor that is FDA approved for treating T2DM, and appears to have favorable anti-inflammatory and immune modulatory properties that might specifically benefit people living with HIV and experiencing cardiometabolic complications associated with residual immune cell activation and inflammation. Medical Research: What are the main findings? Dr. Yarasheski:   In a randomized, double-blinded, placebo controlled 8-wk trial, we found that sitagliptin had beneficial anti-inflammatory, immune regulatory, hematopoietic progenitor cell mobilizing, and glucose lowering effects in cART-treated virally suppressed HIV adults with impaired glucose tolerance.  Sitagliptin improved glucose tolerance (a risk factor for CVD), reduced circulating and adipose-specific inflammatory markers (risk factors for obesity, T2DM, liver fat accumulation, and CVD), and increased the number of blood stem cells that can repair damage and inflammation in the vascular walls. (more…)
Anemia, Author Interviews, Diabetes, Diabetologia / 18.05.2015

MedicalResearch.com Interview with: Emma English PhD Lecturer in Healthcare Science and Academic Lead for Clinical Biochemistry University of Nottingham, School of Medicine Royal Derby Hospital, UK MedicalResearch: What is the background for this study? What are the main findings? Dr. English: HbA1c is widely used for monitoring glycaemic control in people with diabetes as there is clear evidence that lowering HbA1c values leads to reductions in the rates of diabetes complications. Recently the World Health Organization and the American Diabetes Association have both advocated the use of HbA1c for the diagnosis of Type 2 diabetes at a value of ≥48 mmol/mol (6.5%). Whilst there are many advantages to the use of HbA1c as a diagnostic tool there are equally some significant limitations to its use. A widely cited confounder is anaemia, however to what extent and which types of anaemia affect HbA1c results was not clearly understood. When HbA1c was introduced as a diagnostic test in England we received many queries from healthcare professionals asking questions such as ‘at what level of anaemia should I not use HbA1c?’ and ‘should I routinely screen patients for anaemia when using HbA1c? And if so, what test should I use?’. In order to answer these questions we conducted a systematic review of the literature to determine what was known on this subject. Our findings, presented in Diabetologia, suggest that iron deficiency and iron deficiency anaemia may lead to a spuriously elevated HbA1c level, thus may lead a false positive diagnosis of diabetes. However, non-iron deficiency anaemias can lead to an artificially lower HbA1c and may lead to a false negative result where a diagnosis of diabetes would be missed. There is no clear evidence to suggest at what levels anaemia can give rise to these effects on HbA1c value and also there does not appear to be a single ideal test for identifying patients where this could be an issue. (more…)
Author Interviews, Diabetes, Weight Research / 13.05.2015

MedicalResearch.com Interview with: Martin Reinhardt, MD Postdoctoral Fellow PECRB, NIDDK, NIH Phoenix, AZ 85016 Medical Research: What is the background for this study? What are the main findings? Dr. Reinhardt:  It can be very difficult for some people with obesity to lose weight despite great efforts. There is an immense deal of individual variability in weight loss success. Beyond differences in diet adherence, it is not clear what causes this variability in weight loss. Through a study conducted at our facilities at the National Institutes of Health in Phoenix, Arizona, we have now shown that individual differences in biology – more precisely, differences in the amount of energy bodies use during fasting – make it difficult for certain obese people to lose weight. (more…)
Author Interviews, Diabetes, Diabetes Care, Exercise - Fitness, Weight Research / 13.05.2015

MedicalResearch.com Interview with: Edward "Ted" Weiss, Ph.D. Associate Professor Department of Nutrition and Dietetics Saint Louis University Saint Louis MO Medical Research: What is the background for this study? What are the main findings? Dr. Weiss:  Results from one of our previous study yielded a surprising result that diet-induced weight loss improved insulin sensitivity (major diabetes risk factor) by the same amount as exercise induced weight loss. We thought that the exercise-induced weight loss would have yielded benefits from the weight loss itself but also from a weight loss-independent benefit that has been reported in other studies. One explanation for dietary restriction providing the same benefit of exercise was that it also provides benefits besides those that are attributable to weight loss. Our recently completed/published study was designed to evaluate this possibility and the finding do suggest what we hypothesized... i.e. that dietary restriction provides benefits above and beyond that which are attributable to weight loss. (more…)
Author Interviews, Diabetes / 11.05.2015

Meir Stampfer, MD, DrPH Professor of Medicine, Harvard Medical School Professor of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health Assoc Director, Channing Division of Network Medicine Department of Medicine, Brigham and Women's Hospital Boston, MAMedicalResearch.com Interview with: Meir Stampfer, MD, DrPH Professor of Medicine, Harvard Medical School Professor of Epidemiology and Nutrition Harvard T.H. Chan School of Public Health Assoc Director, Channing Division of Network Medicine Department of Medicine, Brigham and Women's Hospital Boston, MA Medical Research: What is the background for this study? What are the main findings? Response: Moderate alcohol has repeatedly been linked to lower risk of developing diabetes, and among diabetics, those who drink moderately at at substantially lower risk for cardiovascular outcomes. However, there have been no long term trial of alcohol among diabetics. In this two-year randomized trial, we found that wine caused modest improvements in glucose metabolism and in blood lipid levels, with a somewhat greater benefit observed for red wine, for changes in lipids. (more…)
Author Interviews, Diabetes, General Medicine, Statins, UT Southwestern / 08.05.2015

Ishak Mansi, MD Staff Internist, VA North Texas Health System. Professor in Department of Medicine & Department of Clinical Sciences, Division of Outcomes and Health services Research, University of Texas Southwestern, Dallas, TXMedicalResearch.com Interview with: Ishak Mansi, MD Staff Internist, VA North Texas Health System. Professor in Department of Medicine & Department of Clinical Sciences, Division of Outcomes and Health services Research, University of Texas Southwestern, Dallas, TX MedicalResearch: What is the background for this study? What are the main findings? Dr. Mansi:  Statin use is associated with increased incidence of diabetes, and possibly increased body weight, and less exercise capacity. Data on the long-term effects of these associations in healthy adults are very limited. Additionally, the effects of these associations on diabetic complications have not been adequately studied. Dr. Mansi at VA North Texas Health System, Dallas and Professor of Medicine and Clinical Sciences at the University of Texas Southwestern, Dallas, TX and his colleagues found that among generally healthy individuals, statin-users in comparison to non-users had a higher odds of being diagnosed with new onset diabetes, diabetes with complications, and overweight/obesity. The researchers examined the records of tens of thousands of Tricare beneficiaries, during the period from 10/1/2003 to 3/1/2012. After excluding patients who had at baseline a preexisting cardiovascular diseases or severe chronic diseases that may be life-limiting (including diabetes mellitus), they identified a cohort of 25,970 patients as “healthy cohort”. They, further, matched 3,351 statins-users and 3,351 nonusers on several baseline characteristics to ensure comparability. There are 3 main important findings for our study:
  1. Statin use was associated with significantly higher risk of new onset diabetes even in a very healthy population. Whereas the risk of diabetes with statins is known, it was thought that this may be due to the overall multiple risks of statin-users (that caused them to receive statins as a therapy).
  2. Statin use was associated with very high risk of diabetes complications in this healthy population: this was never shown before.
  3. Statin use is associated with higher risk of obesity: this also is widely unknown. However, few studies have noted this (one study using patient survey noted this, another study using Mendelian randomization showed it, and post-hoc analysis of a clinical trial showed that statin user gained more weight). Our study, which used a different methodology (retrospective cohort study) add another piece of evidence. Obesity is at endemic level in the US and treatment options are limited.
High-intensity statins was associated with greater risks of all outcomes. This article is published in the Journal of General Internal Medicine (JGIM). JGIM is the official journal of the Society of General Internal Medicine. (more…)
AHA Journals, Author Interviews, Diabetes, Heart Disease / 06.05.2015

Michelle Schmiegelow MD, PhD Student Gentofte Hospital Copenhagen Area, Capital Region, DenmarkMedicalResearch.com Interview with: Michelle Schmiegelow MD, PhD Student Gentofte Hospital Copenhagen Area, Capital Region, Denmark

Medical Research: What is the background for this study? Dr. Schmiegelow: Use of cardiovascular risk stratification models is highly encouraged by U.S. and European guidelines in order to prevent cardiovascular disease (CVD). Individuals with insulin resistance are likely to progress to type 2 diabetes, but measures of insulin resistance are not included in current risk stratification models, although this might improve prediction of CVD in patients without diabetes. The aim of this study was to evaluate whether measures of insulin resistance would improve CVD risk predictions based solely on traditional CVD risk factors in postmenopausal women without existing CVD or diabetes. The main outcome was risk of developing CVD, defined as non-fatal and fatal coronary heart disease and ischemic stroke, within ten years, and the measures of insulin resistance considered were fasting serum glucose, fasting serum insulin, “homeostasis model assessment-insulin resistance“ (HOMA-IR) and the ratio of triglycerides and high-density lipoprotein-cholesterol (TG/HDL-C). From the Women’s Health Initiative Biomarkers studies we identified 15,288 postmenopausal women with no history of CVD, atrial fibrillation, or diabetes at baseline (included 1993–1998), who over a mean follow-up of 9.2 years (standard deviation 1.9 years) had 894 first CVD events (5.8%). (more…)
Author Interviews, Diabetes, Lifestyle & Health / 03.05.2015

MedicalResearch.com Interview with: Marianna Virtanen PhD Finnish Institute of Occupational Health, Helsinki, Turku and Tampere, FinlandMedicalResearch.com Interview with: Marianna Virtanen PhD Finnish Institute of Occupational Health, Helsinki, Turku and Tampere, Finland Medical Research: What is the background for this study? What are the main findings? Dr. Virtanen: Diabetes is a common chronic condition among working-aged populations but few studies have investigated work disability associated with diabetes. In this study, we examined trajectories of register-based work disability days over a 5-year period and lifestyle-related factors predicting these trajectories. Five trajectories described work disability: ‘no/very low disability’ (41.1% among diabetes cases, 48.0% among controls); ‘low–steady’ (35.4%, 34.7%); ‘high–steady’ (13.6%, 12.1%); and two ‘high–increasing’ trajectories (10.0%, 5.2%). Diabetes was associated with ending up to the ’high-increasing disability trajectory’, however, this affected only 10% of the population with diabetes. Obesity and physical inactivity predicted an adverse trajectory similarly among people with diabetes and those without diabetes while smoking was a stronger risk factor for an adverse trajectory in diabetes. (more…)
Artificial Sweeteners, Author Interviews, Diabetes, Diabetologia, Nutrition, Sugar / 02.05.2015

Dr Nita Forouhi, MRCP, PhD, FFPHM MRC Programme Leader and Consultant Public Health Physician MRC Epidemiology Unit University of Cambridge School of Clinical Medicine Cambridge Biomedical Campus Cambridge UKMedicalResearch.com Interview with: Dr Nita Forouhi, MRCP, PhD, FFPHM MRC Programme Leader and Consultant Public Health Physician MRC Epidemiology Unit University of Cambridge School of Clinical Medicine Cambridge Biomedical Campus Cambridge UK Medical Research: What is the background for this study? What are the main findings? Dr. Forouhi: Consumption of soft drinks is known to cause obesity and may contribute to the development of type 2 diabetes. We had previously published findings from the EPIC-InterAct study in 8 European countries that habitual consumption of sugar sweetened beverages increases the risk of developing type 2 diabetes, and we now wanted to probe deeper to understand more about this relationship between sweet beverages and diabetes. We conducted research in the large EPIC-Norfolk study which included more than 25,000 men and women aged 40–79 years living in Norfolk, UK. Study participants recorded everything that they ate and drank for 7 consecutive days covering weekdays and weekend days, with particular attention to type, amount and frequency of consumption, and whether sugar was added by the participants. During approximately 11 years of follow-up, 847 study participants were diagnosed with new-onset type 2 diabetes. By using this detailed information on diet, we were able to study several different types of sugary beverages, including sugar-sweetened soft drinks, sweetened tea or coffee and sweetened milk drinks as well as artificially sweetened beverages (ASB) - such as diet soft drinks - and fruit juice, and to examine what would happen if plain water, unsweetened tea or coffee or artificially sweetened beverages were substituted for sugary drinks. Our study provided three main findings: First, there was an approximately 22% increased relative risk of developing type 2 diabetes per extra serving per day habitually of each of soft drinks, sweetened milk beverages and ASB consumed, even after accounting for a range of important factors including other lifestyle and social factors and for total energy intake. However, after further accounting for body mass index and waist girth as markers of obesity, there remained a higher risk of diabetes associated with consumption of both soft drinks and sweetened milk drinks, but the link with ASB consumption no longer remained, possibly because artificially sweetened beverages was likely to be consumed by those who were already overweight or obese. Second, when we estimated the likely effects of replacing a habitual serving of soft drinks with a serving of water or unsweetened tea or coffee, we found that the risk of diabetes could have been cut by 14%; and by replacing a habitual serving of sweetened milk beverage with water or unsweetened tea or coffee, that reduction could have been 20%–25%.  However, consuming ASB instead of any sugar-sweetened drink was not likely to reduce the risk of diabetes, when accounting for baseline obesity and total energy intake. Third, we found that each 5% of higher intake of energy (as a proportion of total daily energy intake) from total sweet beverages (soft drinks, sweetened tea or coffee, sweetened milk beverages, fruit juice) was associated with a 18% higher risk of diabetes. We estimated that if study participants had reduced the energy they obtained from sweet beverages to below 10%, 5% or 2% of total daily energy, 3%, 7% or 15% respectively of new-onset type 2 diabetes cases could have been potentially avoided. (more…)
Alzheimer's - Dementia, Author Interviews, Diabetes, JAMA / 28.04.2015

MedicalResearch.com Interview with: Dimitry S. Davydow, MD, MPH Associate Professor Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine Seattle, WA 98195 Dr, Davydow wishes to acknowledge Dr. Wayne Katon, the lead investigator of the study, who passed away on March 1, 2015. Medical Research: What is the background for this study? Dr. Davydow: The medical and public health communities have known for quite a while that diabetes and depression are both potential risk factors for developing dementia later in life. Dr. Wayne Katon previously published two articles detailing the results of two studies of relatively large groups of patients (one with nearly 4,000 patients and the other with 29,000 patients) with diabetes showing that those with diabetes and co-existing depression had a greater risk of developing dementia later in life than those patients with just diabetes. These initial studies were important since patients with diabetes are 3 to 4-times more likely to suffer from depression compared to the general population. However, it remained unclear when comparing to a population without either diabetes or depression, to what extent each independently raised the risk of developing dementia, and then to what extent having both conditions increased an individual’s subsequent risk of dementia. We sought to answer these questions with this study. In addition, with the growing obesity epidemic, which carries with it higher burdens of both diabetes and depression, there is reason to be concerned that the risk of dementia could be higher at even younger ages. To address this issue, we also wanted to see if there was a differential impact of the combination of diabetes and co-existing depression on dementia risk among those younger than 65 compared to individuals 65 or older. We were fortunate to be able to examine health data from all Danish citizens 50 or older over a 6 year period, a population numbering nearly 2.5 million people to be able to answer these questions. Medical Research: What are the main findings? Dr. Davydow: We found that compared to individuals without diabetes or depression, those with diabetes alone had about a 15% greater risk of developing dementia, those with depression alone had about an 83% greater risk of developing dementia, and those with both diabetes and co-existing depression had a 107% greater risk of developing dementia compared to those without either condition. We also found that of all of the cases of dementia diagnosed in Denmark among individuals 50 or older between 2007 through 2013, 6% were potentially due to combination of having both diabetes and depression. This was also true for those 65 or older, where 6% of all diagnosed dementia was potentially attributable to the combination of both diabetes and depression. However, among individuals under age 65, we found that 25% of all cases of dementia may have been directly attributable to the combination of diabetes and co-existing depression. (more…)
Author Interviews, Diabetes, Diabetologia, Pediatrics, Social Issues / 10.04.2015

MedicalResearch.com Interview with: Maria Nygren Division of Pediatrics Linköping University, Sweden MedicalResearch: What is the background for this study? What are the main findings? Response: What factors that cause type 1 diabetes is still unknown, but we know that environmental factors are involved besides the genetics. Since the incidence of type 1 diabetes among children have increased worldwide in recent decades, it is important to find out the reasons behind the disease to hopefully be able to prevent new cases. We have in a prospective study of over 10000 children and their parents in Sweden investigated if psychological stress can be a risk-factor, and found that childhood experience of serious life events (such as death/illness in family, divorce, new adult/child in the family) was associated with increased risk for diagnosis of type 1 diabetes up to 14 years of age. (more…)
Author Interviews, Diabetes, Diabetologia, Lifestyle & Health, University of Pittsburgh / 02.04.2015

MedicalResearch.com Interview with: Bonny Rockette-Wagner, Ph.D. Director of physical activity assessment, University of Pittsburgh Graduate School of Public Health and Andrea Kriska, Ph.D. Professor of epidemiology, University of Pittsburgh Graduate School of Public Health Researchers’ Note: Drs. Kriska and Rockette-Wagner: It should be noted that this study looked at adults at high risk for diabetes. Not everyone in the general population would be at high risk. We would hypothesis that the risk increase from TV watching may be lower in those not at high risk for diabetes, but obviously could not test that in our study population. MedicalResearch: What is the background for this study? Response: In this research effort focused on participants in the Diabetes Prevention Program (DPP) study (published in 2002 and funded by the National Institute of Digestive and Diabetes and Kidney Diseases [NIDDK] section of the US National Institutes of Health [NIH]). That study enrolled 3,234 overweight US adults (1996–1999) of at least 25 years of age with the goal of delaying or preventing type 2 diabetes in high risk individuals with either a metformin drug or lifestyle intervention. The DPP demonstrated that the lifestyle intervention was successful at reducing the incidence of diabetes and achieving its goals of 150 minutes per week of moderate intensity activity (such as brisk walking) and a 7% weight loss (New England Journal of Medicine, 2002). There was no goal to reduce sitting in the Diabetes Prevention Program. Results from other studies suggest that it is unclear if interventions focusing on increasing physical activity also reduce time spent sitting. This current investigation examined whether the Diabetes Prevention Program lifestyle intervention, which was shown to be effective at increasing physical activity, also decreased self-reported sitting time. The effect of sedentary behavior on diabetes development was also examined. MedicalResearch: What are the main findings? Response: For the lifestyle participants, a reduction in reported TV watching alone and the combination of TV watching and work sitting was observed. This reduction was significantly greater than any changes seen in the other two randomized groups, who did not receive the intervention. Because these reductions were accomplished without an explicit program goal to reduce sitting we feel optimistic that with better awareness of sitting behaviors and goal setting to reduce sitting it may be possible to have an even greater impact than what was achieved in this cohort. Additionally, our results showed that for every hour spent watching TV there was a 3.4% increased risk of developing diabetes during the 3 year follow-up period in individuals at high risk for diabetes. This finding means that reductions in sitting can translate into a positive health effect separate from improvements in moderate-vigorous activity. (more…)
Antioxidants, Author Interviews, Diabetes, Nutrition / 01.04.2015

MedicalResearch.com Interview with: Isao Saito, MD, PhD Department of Basic Nursing and Health Science, Ehime University Graduate School of Medicine Toon, Ehime Medical Research: What is the background for this study? What are the main findings? Response: Type 2 diabetes is a major lifestyle-related disease with a rapid increasing prevalence in Japan. One meta-analysis of six cohort studies showed that an increase in daily food intake of 1.15 servings of green leafy vegetables was associated with a 14% reduction in the incidence of type 2 diabetes. Therefore, it is evident to think that green and yellow vegetables have beneficial effects against type 2 diabetes. Nonetheless, the relationship of their nutritive content with insulin resistance is poorly understood. We conducted the Toon Health Study initiated in 2009, which was a prospective cohort study of the Japanese general population. The cohort study was intended to characterize environmental risk factors related to incident diabetes and cardiovascular disease. Participants were recruited from the general population aged 30–79 years who were living in Toon City, Ehime Prefecture, Japan. Of them, we investigated 951 Japanese men and women aged 30–79 years who were not undergoing treatment for diabetes and measured their serum β-carotene and retinol concentrations. A 75-g oral glucose tolerance test was performed and the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and the Matsuda Index were calculated as measures of insulin resistance. Multivariable-adjusted odds ratios of the highest quartile of serum β-carotene compared with the lowest quartile for HOMA-IR >1.6 and Matsuda Index <4.9 were 0.56 (95% confidence interval, 0.34–0.94) and 0.62 (0.37–1.02), respectively. When stratified by sex and overweight status, these associations were observed for women and non-overweight individuals. Serum retinol concentration was not associated with either index. Furthermore, according to the nutritional survey, serum β-carotene concentration was associated with green and yellow vegetable intake (p = 0.01). (more…)
Author Interviews, Diabetes, JAMA, Pediatrics / 01.04.2015

MedicalResearch.com Interview with: Dr. Michele Jonsson Funk, PhD Research Associate Professor, Dept of Epidemiology Director, Methods Core, Center for Women’s Health Research University of North Carolina at Chapel Hill and Dr. Wendy Camelo Castillo, MD, PhD Post-doctoral fellow at the University of Maryland Medical Research: What is the background for this study? Response: Gestational diabetes is a condition that affects between 8-11% of pregnant women worldwide. In the United States, the prevalence of gestational diabetes has more than doubled since the 1990’s. Most women can control their blood glucose levels with changes in diet and exercise, but approximately 10% need to take medication during pregnancy. Over the last decade, the use of glyburide (a pill) to manage gestational diabetes has increased and it is now used more often than insulin (an injectable). Medical Research: What are the main findings? Response: Treatment with glyburide (compared with insulin) was associated with higher risks of admission to the neonatal intensive care unit (NICU) (by 41%), respiratory distress (by 63%), hypoglycemia in the newborn (40% ), birth injury (35% ) and being large for gestational age (43% ).  The risk of NICU admission, large for gestational age and respiratory distress between glyburide and insulin treated women was increased by 3.0%, 1.4% and 1.1% respectively. (more…)
Author Interviews, Diabetes, Stem Cells, Weight Research / 25.03.2015

Timothy J. Kieffer Ph.D. | Professor Laboratory of Molecular & Cellular Medicine Department of Cellular & Physiological Sciences Department of Surgery | Life Sciences Institute The University of British Columbia Vancouver BC Canada MedicalResearch.com Interview with: Timothy J. Kieffer Ph.D. | Professor Laboratory of Molecular & Cellular Medicine Department of Cellular & Physiological Sciences Department of Surgery | Life Sciences Institute The University of British Columbia Vancouver BC Canada Medical Research: What is the background for this study? What are the main findings? Dr. Kieffer: Previously we have examined the therapeutic potential of pancreatic precursor cells derived from human stem cells for insulin replacement in models of type 1 diabetes (PMID: 22740171 & PMID: 23771205). Here we sought to test the efficacy of cell-based insulin replacement in a model of type 2 diabetes, which is by far the most common form of diabetes. Key aspects of type 2 diabetes could be mimicked in immunodeficient mice, namely hyperglycemia and insulin resistance accompanied by excess body weight, by placing the mice on high fat diets. These diabetic mice were transplanted with human stem cell derived pancreatic precursor cells contained within macroencapsulation devices. The diabetic setting did not negatively impact the ability of the transplanted cells to mature into insulin-producing cells. Moreover, the cell transplants were able to significantly improve glucose homeostasis, particularly when combined with low doses of traditional anti-diabetic drugs. Intriguingly, the combined therapy also induced weight loss, such that treated mice were similar in weight to control mice reared on a low fat diet. (more…)
Author Interviews, Compliance, Diabetes, Heart Disease / 17.03.2015

Sameer Bansilal, MD, MS Asst. Prof.- Medicine and Cardiology Clinical Trials & Global Health Studies Icahn School of Medicine at Mount SinaiMedicalResearch.com Interview with: Sameer Bansilal, MD, MS Asst. Prof.- Medicine and Cardiology Clinical Trials & Global Health Studies Icahn School of Medicine at Mount Sinai Medical Research: What is the background for this study? What are the main findings? Dr. Bansilal: Our group has previously published data from FREEDOM, COURAGE and BARI showing that adherence to recommended therapies are low in diabetic (DM) patients. We have spent the last decade developing a potential solution to this- the Fuster-Ferrer polypill. This study was done to better inform the association between levels of medication adherence and long term major adverse cardiovascular events (MACE) in high risk diabetic patients. We analyzed a U.S. health insurers’ claims data for 19,962 high risk diabetic subjects. Using proportion of days covered (PDC) for 1 year after first refill, we stratified patients as fully adherent (FA≥80%), partially adherent (PA ≥40- ≤79%) or non-adherent (NA <40%) and examined the associations with a primary cardiovascualr outcome measure of death, myocardial infarction, stroke and coronary revascularization. We found that only 34% participants were fully adherent to therapy. When compared to being non-adherent at 2 yrs follow up,, being fully adherent was associated with a 28% lower rate of MACE; being partially adherent was associated with a 21% lower rate of MACE. Efforts towards improving adherence in diabetic subjects may lead to substantial reductions in MACE. (more…)
Author Interviews, Diabetes, Heart Disease, JAMA, Lipids, Statins / 11.03.2015

Joost Besseling PhD-student Academic Medical Center Dept. of Vascular Medicine AmsterdamMedicalResearch.com Interview with: Joost Besseling PhD-student Academic Medical Center Dept. of Vascular Medicine Amsterdam Medical Research: What is the background for this study? What are the main findings? Response: Statins are associated with an increased risk for type 2 diabetes mellitus (DM). The exact mechanism for this adverse event is largely unknown, although the upregulation of the low-density lipoprotein receptor (LDLR) has been suggested to play a role. In familial hypercholesterolemia (FH) the uptake of LDL-cholesterol via the LDLR is decreased due to a genetic defect. We found that the prevalence of type 2 DM is 50% lower in relative terms in patients with familial hypercholesterolemia. Moreover, there was a dose-response relationship: the more severe the genetic defect that causes familial hypercholesterolemia, the lower the prevalence of type 2 DM. (more…)
Author Interviews, Diabetes, Neurological Disorders / 06.03.2015

Dr. John A Kessler MD The Ken and Ruth Davee Professor of Stem Cell Biology Department of Neurology Professor, Department of Pharmacology Northwestern University Feinberg School of MedicineMedicalResearch.com Interview with: Dr. John A Kessler MD The Ken and Ruth Davee Professor of Stem Cell Biology Department of Neurology Professor, Department of Pharmacology Northwestern University Feinberg School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Kessler: Painful diabetic neuropathy afflicts millions of patients. It interferes with sleep and many daily activities of living, and predisposes to depression. There is a loss of sensation in the legs which predisposes to foot/leg ulcers which may lead to amputation. The only currently available treatments, other than controlling glucose levels, are drugs including gabapentin, pregabalin, or antidepressants which have major side effects and which help only some patients. These are medications which must be taken daily or several times daily and are often poorly tolerated by patients. This study examined the effects of a nonviral gene therapy approach for using hepatocyte growth factor (HGF) to treat patients with painful diabetic neuropathy. HGF helps to support the health of neurons and it also helps to grow new blood vessels to support nerve function. Patients received two sets of treatments (injections) and were then followed for 9 months.  The treatment was exceptionally well tolerated -  literally without significant side effects. The patients had highly significant reductions in pain and improvement in the quality of life, and their ability to sense gentle pressure (touch) was improved. The benefits lasted months without additional treatment. (more…)
Author Interviews, Compliance, Diabetes, Pediatrics / 03.03.2015

Dr. Yang Lu Ph.D Los Angeles Biomedical Research Institute Dr. Lu’s research interests include utilization, cost and treatment regimen adherence of chronic conditions, such as obesity and diabetes; behavioral economic interventions, and cost effectiveness studiesMedicalResearch.com Interview with: Dr. Yang Lu Ph.D Los Angeles Biomedical Research Institute Dr. Lu’s research interests include utilization, cost and treatment regimen adherence of chronic conditions, such as obesity and diabetes; behavioral economic interventions, and cost effectiveness studies MedicalResearch: What is the background for this study? Response: Non-adherence is a serious issue in type 1 diabetes management. It leads to poor glycemic control and peaks in adolescence and young adulthood. Peer support is critical for young patients yet few studies examined whether pairing youth with slightly older and more experienced peers with diabetes improves their diabetes self-management and glycemic control. This study had two aims: (1) assess whether adolescents (as prospective mentees) and young adults (as prospective mentors) with diabetes would be interested in peer mentoring as a way to improve adherence, and (2) identify contents and delivery modes for a peer mentoring topic from the perspective of patients and their parents. Fifty-four adolescents and 46 young adults with type 1 diabetes were surveyed. (more…)