Author Interviews, Diabetes, JAMA, Kidney Disease / 01.09.2015

George L. Bakris MD Professor of Medicine Director, Comprehensive Hypertension Center University of Chicago MedicineMedicalResearch.com Interview with: George L. Bakris MD Professor of Medicine Director, Comprehensive Hypertension Center University of Chicago Medicine Medical Research: What is the background for this study? What are the main findings? Dr. BakrisAldosterone receptor antagonists such as spironolactone are known to reduce mortality from heart failure and reduce albuminuria, a well-known marker of diabetic kidney disease progression. Finerenone is a novel nonsteroidal aldosterone receptor antagonist and is associated with less hyperkalemia (high blood potassium levels) compared to traditional aldosterone receptor blockers like spironolactone. The current study was a dose finding study to ascertain the optimal dose of finerenone for reducing urine albumin (a key risk marker in people with diabetic kidney disease) that is also associated with the smallest rise in serum potassium. The main findings are that in a dose dependent manner finerenone reduced albuminuria and at the highest dose a modest rise in serum potassium. Finerenone was also very well tolerated.  (more…)
Author Interviews, Diabetes, JAMA, Weight Research / 19.08.2015

Melanie J Davies MB ChB MD FRCP FRCGP Professor of Diabetes Medicine 
NIHR Senior Investigator Leicester Diabetes Unit
Leicester Diabetes Centre Bloom
University of Leicester MedicalResearch.com Interview Invitation Melanie J Davies MB ChB MD FRCP FRCGP Professor of Diabetes Medicine 
NIHR Senior Investigator Leicester Diabetes Unit
Leicester Diabetes Centre Bloom
 University of Leicester   MedicalResearch: What is the background for this study? What are the main findings?
 Dr. Davies: This study was designed to test the efficacy and safety of Liraglutide using a dose of 3mg for weight loss among patients with type 2 diabetes.  It was a large international study in which we compared once daily subcutaneous Liraglutide at a dose of 3mg to Liraglutide 1.8mg which is the current maximum dose licenced in patients with diabetes and placebo.  In all patients we offered a calorie deficit diet and lifestyle advice to increase physical activity.  Our main findings were that the dose of 3mg of Liraglutide resulted in greater weight loss than both other arms of the study indeed 54% of patients at 56 weeks achieved more than 5% weight loss and a further 25% were able to achieve more than 10% weight loss.  The 3mg of Liraglutide compared to the placebo, there were also significant impacts on HbA1c and other cardiovascular risk factors such as systolic blood pressure and lipids as well as improving patient quality of life particularly physical functioning and patient treatment satisfaction.  (more…)
Author Interviews, Diabetes, Diabetes Care, Lifestyle & Health / 14.08.2015

Dr. Kaberi Dasgupta MD, MSc, FRCPC Associate Professor, Department of Medicine Divisions of Internal Medicine, Clinical Epidemiology, and Endocrinology and Metabolism Royal Victoria Hospital Quebec, Canada MedicalResearch.com Interview with: Dr. Kaberi Dasgupta MD, MSc, FRCPC Associate Professor, Department of Medicine Divisions of Internal Medicine, Clinical Epidemiology, and Endocrinology and Metabolism Royal Victoria Hospital Quebec, Canada   Medical Research: What is the background for this study? What are the main findings? Dr. Dasgupta: We know that health behaviours can contribute to developing gestational diabetes and type 2 diabetes (e.g., eating out frequently, lack of fruits and vegetables, not walking enough, spending most of the day sitting). We also know that genetic factors are important. Sometimes we focus more on the genetic factors than on health behaviours. By showing that spouses share diabetes risk, we highlight the importance that behaviour and environment play as spouses are not generally related biologically. In a previous meta-analysis, we showed that spouses were concordant for diabetes (if one had it, there was a 24% relative risk increase that the other did too.) In the study Gestational Diabetes Mellitus in Mothers as a Diabetes Predictor in Fathers: A Retrospective Cohort Analysis, we took it further and compared men whose partners had gestational diabetes and men whose partners did not. Over a 13 year period of follow-up, the men whose partners had gestational diabetes were 33% more likely to develop diabetes.  (more…)
Author Interviews, Case Western, Diabetes, Infections, PLoS / 14.08.2015

Wesley M. Williams, PhD Cell molecular biologist Department of Biological Sciences Case Western Reserve University School of Dental MedicineMedicalResearch.com Interview with: Wesley M. Williams, PhD Cell molecular biologist Department of Biological Sciences Case Western Reserve University School of Dental Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Williams: Individuals with uncontrolled blood sugar levels frequently present with higher than normal rates of infection and protracted wound healing. The beta-defensin family of antimicrobial peptides responds to bacterial, fungal and viral invasion. As part of the innate immune system, these cationic peptides normally expressed by epithelial cells are important early responders that, together with other components of the innate immune response, act to inhibit microbial infection. Our initial observations led us to question whether glucose or a metabolite of glucose could contribute to antimicrobial peptide dysfunction, and thus compromise control of infection. Elevated levels of glucose result in increased production of dicarbonyls, a class of molecule that can selectively react with proteins having an unusually high content of cationic amino acids, such as arginine and lysine. We first investigated the effects of two well-characterized dicarbonyls, methylglyoxal (MGO) and glyoxal (GO) on recombinant beta-defensin 2 (rHBD-2) structure using MALDI TOF and LC/MS/MS mass spectral analysis of the recombinant peptide. We found MGO to be particularly reactive with the rHBD-2 peptide as it readily and irreversibly adducted to two arginine residues and the N-terminal glycine. Next we tested in vitro for the effects of adducted rHBD-2 on antimicrobial and chemotactic functions, both essential to an effective innate and adaptive immune response in vivo. Through radial diffusion testing on gram-negative E. coli and P. aeruginosa, and gram-positive S. aureus, and a chemotaxis assay for CEM-SS cells, we found that both antimicrobial and chemotactic functions of rHBD-2 were significantly compromised by MGO. (more…)
Alzheimer's - Dementia, Author Interviews, Diabetes, Diabetologia / 14.08.2015

Laura Ekblad, MD, researcher Turku PET CentreMedicalResearch.com Interview with: Laura Ekblad, MD, researcher Turku PET Centre Medical Research: What is the background for this study? What are the main findings? Dr. Ekblad: The background for our study is that the metabolic syndrome and diabetes have been shown to increase the risk for cognitive decline and dementia. Also, insulin resistance is thought to play a pivotal role in the pathophysiology of Alzheimer´s disease. In addition, intranasal insulin administration is being studied as a promising treatment for Alzheimer´s disease. Previous studies indicate that both gender and APOE epsilon 4 genotype modulate the effects of insulin on cognition. Our main findings are that insulin resistance is associated with poorer verbal fluency, but only in women. Our population-based study consisted of adults from 30-97 years of age and we had nearly 6000 participants. Age did not modulate the association of insulin resistance and cognition, which means that our results apply even to young adults. We also found that insulin resistance associated with poorer verbal fluency only in non-carriers of the APOE epsilon 4 genotype. (more…)
Author Interviews, Diabetes, Kidney Disease, Lancet / 12.08.2015

MedicalResearch.com Interview with: Prof. Der-Cherng Tarng, MD, PhD Division of Nephrology Taipei Veterans General Hospital, and National Yang-Ming University, Taiwan MedicalResearch: What is the background for this study? What are the main findings? Prof. Tarng: Metformin is generally recommended as a first-line therapy for type 2 diabetes mellitus, but the use of metformin has been limited in patients with impaired kidney function because of the perceived risk of lactic acidosis. More recently, available evidence supports the cautious expansion of metformin use in patients with mild to moderate chronic kidney disease (CKD). However, no studies have yet examined whether metformin can be prescribed more widely to patients with advanced CKD. We conducted a propensity score-matched cohort study using Taiwan’s National Health Insurance Research Database to assess the safety of metformin in patients with type 2 diabetes and serum creatinine levels >6 mg/dL, enrolled between January 1, 2000 and June 30, 2009 and followed-up until December 31, 2009, before Taiwan’s prescribing guidelines for metformin contraindicated its use in patients with CKD. From a consecutive sample of 12350 patients, 1005 (8.1%) were metformin users. Of these, 813 were successfully matched 1:3 to 2439 metformin nonusers. After multivariate adjustment, metformin use remained was an independent risk factor for mortality (hazard ratio 1.35, 95% confidence interval 1.20–1.45; p<0.0001). The increased risk was dose-dependent and was consistent across all subgroup analyses. However, metformin users compared with non-users were associated with a higher but insignificant risk of metabolic acidosis (hazard ratio 1.30, 95% confidence interval 0.88–1.93; p=0.188). (more…)
Alzheimer's - Dementia, Author Interviews, Diabetes, JAMA, Nutrition / 31.07.2015

Auriel A. Willette, M.S., Ph.D. Food Science and Human Nutrition Neuroscience Interdepartmental Graduate Program Gerontology Interdepartmental Graduate Program Iowa State University, AmesMedicalResearch.com Interview with: Auriel A. Willette, M.S., Ph.D. Food Science and Human Nutrition Neuroscience Interdepartmental Graduate Program Gerontology Interdepartmental Graduate Program Iowa State University, Ames Medical Research: What is the background for this study? What are the main findings? Response: Obesity is a major health concern around the world. Obesity causes insulin resistance, defined in this case as the inability of insulin to bind to its receptor and mediate glucose metabolism. Other researchers and I have recently found that higher insulin resistance is associated with less glucose metabolism in the brains of patients with Alzheimer's disease. This relationship is found primarily in medial temporal lobe, an area necessary for generating new memories of facts and events. This is important because Alzheimer's disease is characterized by progressive decreases in glucose metabolism over time, and partly drives worse memory performance. Insulin resistance in midlife also increases the risk of developing Alzheimer's disease. We wanted to determine if insulin resistance is linked to similar effects in cognitively normal, late middle-aged participants decades before Alzheimer's disease typically occurs. If so, insulin resistance might be an important biological marker to track from middle-age onwards. Thus, we examined the association between insulin resistance, regional glucose metabolism using FDG-PET, and memory function in 150 middle-aged participants, many of whom had a mother or father with Alzheimer's disease. We found that higher insulin resistance was strongly associated with less glucose metabolism throughout many brain regions, predominantly in areas that are affected by Alzheimer's disease. The strongest statistical effects were found in left medial temporal lobe, which again is important for generating new memories. This relationship, in turn, predicted worse memory performance, both immediately after learning a list of words and a 20-minute delay thereafter. The take-home message is that insulin resistance has an Alzheimer's-like association with glucose metabolism in middle-aged, cognitively normal people at risk for Alzheimer's, an association which is related to worse memory. (more…)
Author Interviews, Diabetes, PLoS / 23.07.2015

Dr. Stephanie K. Venn-Watson Doctor of Veterinary Medicine, MS Director, Translational Medicine and Research Program National Marine Mammal FoundationMedicalResearch.com Interview with: Dr. Stephanie K. Venn-Watson Doctor of Veterinary Medicine, MS Director, Translational Medicine and Research Program National Marine Mammal Foundation
    Medical Research: What is the background for this study? What are the main findings? Dr. Venn-Watson: Bottlenose dolphins, just like people, can develop a condition called metabolic syndrome. In humans, metabolic syndrome is also called prediabetes, which affects 1 in every 3 adults in the U.S. Some human studies have suggested that eating a diet high in fish may lower the risk of developing metabolic syndrome. Other similar studies, however, have had inconsistent findings. To better understand how fish diets may be associated with dolphin metabolic health, we compared 55 fatty acids among 49 dolphins and their dietary fish. We were surprised to find that the strongest predictor of lower, healthier insulin levels in dolphins was a saturated fat called, heptadecanoic acid (or C17:0). When we provided a diet higher in C17:0 to six dolphins over six months, their insulin, glucose, and triglycerides normalized. We also saw an immediate decrease in ferritin, a protein which - at high levels - may be a risk factor for metabolic syndrome. In addition to some fish, C17:0 is present in dairy fat, including whole fat milk and butter. C17:0 was not present in nonfat dairy products. We hypothesize that movement towards nonfat dairy foods may be lowering human C17:0 blood levels, which may be contributing to the global rise in metabolic syndrome and type 2 diabetes. (more…)
Author Interviews, Brigham & Women's - Harvard, Diabetes, Nutrition, Pediatrics / 22.07.2015

Prof. Lu Qi, Assistant Professor, Department of Nutrition Harvard School of Public Health and Channing Division of Network Medicine Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MAMedicalResearch.com Interview with: Lu Qi, MD, PhD, FAHA Associate Professor of Medicine Harvard Medical School Assistant Professor of Nutrition HarvardSchool of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Lu QiMost previous studies focus on the effects of either lifestyle or prenatal malnutrition on diabetes risk; no study has assess these two types of risk factors in combination. (more…)
Author Interviews, Diabetes, Lipids / 22.07.2015

Petter Bjornstad, MDFellow in Pediatric Diabetes & Endocrinology Children's Hospital Colorado & Barbara Davis Center for Childhood Diabetes Aurora, CO 80045MedicalResearch.com Interview with: Petter Bjornstad, MD Fellow in Pediatric Diabetes & Endocrinology Children's Hospital Colorado & Barbara Davis Center for Childhood Diabetes Aurora, CO 80045 MedicalResearch: What is the background for this study? Dr. Bjornstad: Apolipoprotein B (apoB) and non-high density lipoprotein-cholesterol (nonHDL-C) have been proposed to be superior indicators of cardiovascular (CV) risk than total cholesterol and/or low density lipoprotein-cholesterol (LDL-C). Some authors argue that while nonHDL-C and apoB correlate, they are not necessarily interchangeable, and may in fact provide unique information about cardiovascular risk. However, there are insufficient data on the concordance between apoB and nonHDL-C in adults with type 1 diabetes mellitus (DM) across a wide range of risk factors for cardiovascular disease. MedicalResearch: What are the main findings? Dr. Bjornstad: Adults with type 1 diabetes and elevated apoB (≥90mg/dL) and nonHDL-C (≥130mg/dL) had greater odds of coronary artery calcification progression compared to adults with type 1 diabetes and normal apoB and nonHDL-C (OR: 1.90, 95% CI 1.15-3.15), and compared to adults with type 1 diabetes with elevated apoB alone (OR: 2.86, 95% CI 1.43-5.74) adjusting for age, sex, duration, HbA1c and statins. We also obtained similar results with elevated apoB and nonHDL-C defined as ≥ the cohort means. Accordingly, we concluded that elevated apoB and nonHDL-C carry a greater risk of atherosclerosis than elevated apoB in the absence of elevated nonHDL-C in adults with type 1 diabetes.  (more…)
Author Interviews, Beth Israel Deaconess, Diabetes, Heart Disease, University of Michigan / 18.07.2015

MedicalResearch.com Interview with: Venkatesh L. Murthy, MD, PhD, FACC, FASNC University of MichiganVenkatesh L. Murthy, MD, PhD, FACC, FASNC University of Michigan Dr. Ravi Shah MD Beth Israel Deaconess Medical Centerand Dr. Ravi Shah MD Beth Israel Deaconess Medical Center   MedicalResearch: What is the background for this study? Response: Recent changes recommend statin therapy for cardiovascular risk reduction in an increasingly large number of Americans. Conversely, a number of studies have identified an increased risk of diabetes with statin treatment. Thus, there is increasing need for tools to target statin therapy to those with a favorable risk-benefit profile. MedicalResearch: What are the main findings? Response: In our study, we analyzed data from 3,153 individuals from the Multi-Ethnic Study of Atherosclerosis who underwent CT scanning at baseline for assessment of calcium score. The CT scans were analyzed to assess liver attenuation as a measure of the amount of liver fat. We demonstrated that high liver fat doubled the risk of diabetes over a median of 9 years of follow-up. Importantly, statin therapy also doubled the risk of diabetes. The two together had an additive effect, even after adjusting for BMI, age, gender, family history of diabetes, waist circumference, lipids, hsCRP and exercise habits. As in prior studies, the risk of cardiovascular disease (CVD) events increased with increasing calcium score, as has previously been shown in MESA and in other studies. We then divided the cohort into six groups based on calcium score (0, 1-100 and >100) and liver fat (low/high). Using published data from meta-analyses of statin trials, we computed the number needed to treat to prevent one hard CVD event for statin therapy. Using data from our study, we computed the number needed to harm to cause one additional case of diabetes from statin therapy. The numbers needed to treat with ranged from 29-40 for calcium score of >100 to 218-252 for calcium score of 0. Conversely, the numbers needed to harm were approximately 63-68 for those with low liver fat versus 22-24 for those with high liver fat. Thus the combination of calcium score and liver fat assessment, from a single standard calcium score scan, allows for physicians to provide better assessment of risk and benefit of statins in discussion with their patients. (more…)
Author Interviews, Cognitive Issues, Diabetes, JCEM / 11.07.2015

MedicalResearch.com Interview with: Wei-Che Chiu, MD, PhD National Taiwan University College of Public Health, Cathay General Hospital and Fu Jen Catholic University Taipei, Taiwan Medical Research: What is the background for this study? Response: Diabetes mellitus is a common risk factor for dementia and accounts for 6–8% of all cases of dementia in older populations. Cognitive impairment is associated with the presence of diabetic complications and diabetic severity, but the effects of diabetic severity on dementia are unclear. Our study was to investigate the association between the severity and progress of diabetes and the risk of dementia. Medical Research: What are the main findings? Response: The diabetic severity and progression reflected the risk of dementia, and the early progress in diabetic severity could predict the risk of dementia in new-onset diabetic patients. (more…)
Author Interviews, Beth Israel Deaconess, Cognitive Issues, Diabetes, Neurology / 11.07.2015

Vera Novak, MD PhD Associate Professor of Neurology Dept. of Neurology, Stroke Division Director Syncope and Falls in the Elderly Laboratory Beth Israel Deaconess Medical Center Boston, MAMedicalResearch.com Interview with: Vera Novak, MD PhD Associate Professor of Neurology Dept. of Neurology, Stroke Division Director Syncope and Falls in the Elderly Laboratory Beth Israel Deaconess Medical Center Boston, MA MedicalResearch: What is the background for this study? Dr. Novak: Diabetes mellitus (DM) is a major contributor to morbidity and mortality. Type 2 diabetes mellitus affects more than 44 million people in the U.S., and its numbers are growing rapidly, affecting up to 27% of older adults. Diabetes mellitus accelerates brain aging by about 5 years1, manifests as a widespread generalized atrophy2, and promotes earlier onset of vascular dementia and Alzheimer’s disease (AD).3,4 Diabetes mellitus -related atrophy manifests as worse cognitive function, memory, and gait, especially during a dual task, 5,6 and even a tight glycemic control did not improve cognitive function in participants of the large clinical trials 7. MedicalResearch: What are the main findings? Dr. Novak: Sixty-five participants (aged 66± 9.2 years) 35 with T2DM and 30 non-diabetic controls participated in this study. After 2 years of follow-up, participants with T2 Diabetes mellitus had diminished vascular reactivity in the brain (an ability to increase blood flow in responses to a task or metabolic demands) and performed worse on multiple cognitive tasks (in particular verbal learning and memory). In T2DM group, lower cerebral vasoreactivity correlated with worse performance on daily living activities. Specifically, the lower vasodilatation (ability to increase blood flow) was associated with worse mental functions. In addition, those with higher markers of inflammation had greater decline in vascular function in the brain. (more…)
Author Interviews, Diabetes, Weight Research / 08.07.2015

Subhadra Gunawardana DVM, Ph.D Research Associate Professor Department of Molecular Physiology & Biophysics Vanderbilt University Medical Center Nashville, TN 37232MedicalResearch.com Interview with: Subhadra Gunawardana DVM, Ph.D Research Associate Professor Department of Molecular Physiology & Biophysics Vanderbilt University Medical Center Nashville, TN 37232 Medical Research: What is the background for this study? What are the main findings? Response: For many years the general consensus has been that insulin replacement is essential for treating type 1 diabetes. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Our work on mouse models show that type 1 diabetes can be effectively reversed without insulin, through subcutaneous transplantation of embryonic brown adipose tissue (BAT). BAT transplantation leads to replenishment of recipients' white adipose tissue; dramatic decrease of inflammation; secretion of a number of beneficial adipokines; and fast and long-lasting euglycemia. Insulin-independent glucose homeostasis is established physiologically, through a combination of endogenously generated hormones arising from the transplant and/or newly-replenished white adipose tissue. Medical Research: What should clinicians and patients take away from your report? Response: If translated to human patients, this approach could provide a cure for type 1 diabetes that does not require regular exogenous administration of insulin or any other compound, and would thus avoid the many inherent difficulties with such therapies. (more…)
Author Interviews, Diabetes, Lipids, Ophthalmology / 06.07.2015

Dr Ruth Hogg, Lecturer Centre for Experimental Medicine (formerly Centre for Vision and Vascular Science) Institute of Clinical Science Block Belfast Northern IrelandMedicalResearch.com Interview with: Dr Ruth Hogg, Lecturer Centre for Experimental Medicine (formerly Centre for Vision and Vascular Science) Institute of Clinical Science Block Belfast Northern Ireland Medical Research: What is the background for this study? What are the main findings? Dr. Hogg: The development of Diabetic macular edema (DME) in patients with diabetes can result in severe visual loss.  Understanding the factors driving the development of these conditions is important for developing effective treatments.  The role of lipids has been suggested by previous studies however as the evidence overall appeared to have significant uncertainty we decided to undertake a systematic review and where possible perform a meta-analysis or results. The study revealed that the evidence of a relationship between blood lipid levels and Diabetic macular edema from cohort and case control studies was strong but evidence from the randomised control trials (RCTs) was weak.  The RCTS evaluated however were often not designed to look at Diabetic macular edema as an primary outcome, and this was often part of a secondary analysis leaving uncertainty over the power to detect the association.  (more…)
Author Interviews, Columbia, Diabetes, NEJM, Weight Research / 03.07.2015

Dr. F. Xavier Pi-Sunyer MD Division of Endocrinology and Obesity Research Center Columbia University, New YorkMedicalResearch.com Interview with: Dr. F. Xavier Pi-Sunyer MD Division of Endocrinology and Obesity Research Center Columbia University, New York Medical Research: What is the background for this study? What are the main findings? Dr. Pi-Sunye: In a large randomized trial, the drug Liraglutide was compared to placebo in overweight and obese non-diabetic volunteers. Over 52 weeks, in combination with diet and increased physical activity, Liraglutide lowered body weight by 8.4 kg as compared to 2.8 kg in placebo. 63% vs 27% lost at least 5% of baseline weight, 33% vs 10% lost more than 10% of baseline weight. (more…)
Author Interviews, Diabetes, Endocrinology, JAMA / 21.06.2015

MedicalResearch.com Interview with: Francis de Zegher, MD, PhD Department of Development and Regeneration, University of Leuven Leuven, Belgium & Lourdes Ibáñez, MD, PhD Hospital Sant Joan de Déu, University of Barcelona Barcelona, Spain Medical Research: What is the background for this study? Response: Hyperinsulinemic androgen excess is the most frequent hormonal disorder of adolescent girls. It seems to be mainly driven by an excessive and/or inappropriate storage of fat due to a chronically positive energy balance. The traditional approach (not approved by FDA or EMA) is to silence the ovaries by giving an oral contraceptive. An alternative approach is to change the storage of fat by giving an insulin-sensitizing combination of generics in low dose. (more…)
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…)