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.
MedicalResearch.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.
MedicalResearch.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:
MedicalResearch.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.
MedicalResearch.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.
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.
MedicalResearch.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.
MedicalResearch.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.
MedicalResearch.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.
MedicalResearch.com Interview with:
Professor Daniela Jakubowicz MD
Diabetes Unit. E. Wolfson Medical Center
Sackler Faculty of Medicine,
Tel Aviv University and Tel Aviv Medical Center
Israel
MedicalResearch: What is the background for this study? What are the main findings?
Professor Jakubowicz: Obesity epidemic have lead to alarming rise of type 2 diabetes. It is estimated that more than 382 million worldwide have diabetes, predominately type 2 diabetes.
In these persons the cardiovascular disease is the leading complication, carrying 10 to 20-fold increase in the risk compared with persons without diabetes.
It has been shown that large glucose peaks after meals along the day, are strongly associated with increased a risk for cardiovascular complications.
Therefore the mitigation of glucose excursions after meals becomes a major target in the treatment of type 2 diabetes in order to improve glucose balance and prevent complications.
Accordingly, dietary modification focused on reduction post meal glucose peaks is needed. Even though still there is no consensus on which of the dietary strategies (i.e. low-fat diet, Mediterranean and low-carbohydrate, higher fiber, low GI glycemic index meals, etc.) is more suitable in improving post-meal glycemic responses along the day.
However in none of these interventions has been considered that modifying the meal timing pattern or daily caloric distribution, may lead to improved post-meal glycemic responses in type 2 diabetic patients.
The circadian clock genes existing in the pancreatic β-cells, gut, liver and in skeletal muscle, regulate the diurnal (circadian) oscillation of post-meal glucose responses. In fact, post-meal glycemia displays a clear diurnal variation: it is higher and more prolonged in the evening than in the morning. Meal timing schedule, on the other hand, exerts strong controlling influence on circadian clock regulation, thereby influencing the variation and degree of the post meal glycemic elevations. Indeed meal timing non-aligned with the clock gene circadian rhythms, such as breakfast skipping or high-energy intake at dinner, is associated with obesity, higher HbA1C and poor glycaemic control in type 2 diabetes.
To clarify the impact of meal timing and composition on overall post-meal glucose responses, we tested the effect of 2 isocaloric diets with different meal timing one with high energy breakfast (704 kcal), mid-sized lunch (600 kcal) and reduced dinner (200 kcal) and other with similar lunch but reduced breakfast (704 kcal) and high energy dinner(704 kcal).
The study clearly demonstrated that in type 2 diabetic patients, a diet consisting on high energy breakfast, and reduced dinner, resulted in significantly reduced glucose response after meals and lower overall plasma glucose levels along the entire day, when compared to a diet with the same caloric content but inverse distribution: breakfast (200 kcal) , lunch (600 kcal) and high energy dinner(704 kcal).
Moreover, when we compared the glucose response after high energy meal consumed at breakfast (700 kcal) versus in the dinner (700 kcal), it comes out that the glucose response was significantly higher after dinner than after breakfast. It shows that just by changing the time of the high energy meal we may achieve significant reduction in the glucose response.
MedicalResearch.com Interview with:
Kari Johansson, PhD
Department of Medicine Solna, Karolinska Institutet
Clinical Epidemiology
Karolinska University Hospital
Stockholm, Sweden
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Johannson: The number of women who are obese in early pregnancy has increased dramatically over the last decades. Consequently, there has been a dramatic rise in the number of women becoming pregnant after bariatric surgery. In Sweden the number of births of women with a history of bariatric surgery has increased from 150 (≈0.15%) to more than 500 (0.5%) per year between 2006 and 2011. The positive effects of bariatric surgery on health outcomes, such as diabetes and cardiovascular disease, are reasonably well-studied, but less is known about the effects on pregnancy and perinatal outcomes. We therefore conducted a population-based study, using data from nationwide Swedish registers.
The main findings are that women who had a history of bariatric surgery were much less likely to develop gestational diabetes (2% compared to 7%; P<0.001) and give birth to large-for-gestational age babies (9% vs 22%; P<0.001). On the other hand, the operated women were twice as likely to give birth to babies who were small for gestational age (16% vs 8%), and have pregnancies of shorter duration (273 vs 277.5; P<0.001).
MedicalResearch.com Interview with:
Rohit Varma, MD, MPH
Professor and Chair, Department of Ophthalmology
USC Eye Institute, Keck School of Medicine
University of Southern California, Los Angeles, California
Medical Research: What is the background for this study? What are the main findings?
Dr. Varma: The Centers for Disease Control and Prevention estimates that 4.4% of adults with diabetes aged 40 and older have advanced diabetic retinopathy that may result in severe vision loss. Clinical trials have shown that intravitreal injections of anti-VEGFs, such as ranibizumab, can reduce visual impairment and even in some cases improve visual acuity outcomes in patients with diabetic macular edema. We developed a model, based on data from the RIDE and RISE clinical trials, to estimate the impact of ranibizumab treatment on the number of cases of vision loss and blindness avoided in non-Hispanic white and Hispanic persons with diabetic macular edema in the United States.Results from the model suggest that, compared with no treatment, every-4-week ranibizumab 0.3 mg reduces legal blindness between 58%-88% and reduces vision impairment between 36%-53% over 2 years in this population.
MedicalResearch.com Interview with:
Katherine A James, PhD, MSPH, MSCE
Colorado School of Public Health
University of Colorado Denver,
Aurora, Colorado
Medical Research: What is the background for this study? What are the main findings?
Dr. James: Exposure to inorganic arsenic in drinking water has been associated with several chronic diseases including cardiovascular disease and diabetes mellitus in areas with high levels of exposure. Our study is one of the first to show association with cardiovascular disease and diabetes mellitus in a low-moderately exposed population. Our results show that for every 15 micrograms per liter of inorganic arsenic in drinking water the risk for CHD disease increased 38% and for diabetes it increases 27%.
MedicalResearch.com Interview with: Adam Glassman, M.S. Director, DRCRnet Coordinating Center Jaeb Center for Health Research Tampa, FL 33647 Medical Research: What is the background for this study? What are the main findings? Response: Diabetic macular edema (DME) is the most common cause of vision loss in patients with diabetes, impairing the vision of approximately 750,000 people...
MedicalResearch.com Interview with: Sheena M. Patel, MPH, ORISE, Fellow Division for Heart Disease and Stroke Prevention CDC MedicalResearch: What is the background for this study? What are the main findings? Dr. Patel: Although significant evidence reveals reduced sodium intake lowers blood pressure, some studies report that sodium reduction could have a negative impact on insulin...
MedicalResearch.com Interview with:
Dr. Therese Tillin
Research Fellow, Cardiometabolic Phenotyping Group
Institute of Cardiovascular Science
Faculty of Pop Health Sciences
Medical Research: What is the background for this study? What are the main findings?
Dr. Tillin: The global burden of type 2 diabetes is rising rapidly and people of South Asian origins (from the Indian subcontinent) remain at much higher risk of developing diabetes than people of European origin. Why is this? Although it is thought that increased levels of obesity around the waist level, diet, physical activity levels and genetic factors contribute, no study to date has been able to tease out fully the underlying causes for the added risk in South Asian people. However, it is likely that complex metabolic disturbances may play an important role.
We have been studying a British cohort of people of European and South Asian origin for nearly 20 years and have used nuclear magnetic resonance spectroscopy to build a profile of amino acids in blood samples that were collected at the start of the study between 1988 and 1991. We found that higher levels of some amino acids, in particular tyrosine, were already present in non-diabetic South Asian individuals back then. Some of these amino acids, again especially tyrosine, more strongly predicted later development of type 2 diabetes in the South Asian people than in the Europeans in our study, even after adjustment for other risk factors such as obesity and insulin resistance. A given increase (one standard deviation) in tyrosine increased risk of developing diabetes by just 10% in Europeans, while in South Asians the increase in risk was 47%.
MedicalResearch.com Interview with:
Prof. Kazem Rahimi DM MSc FESC
Associate Professor of Cardiovascular Medicine, University of Oxford ;Deputy Director, The George Institute for Global Health; James Martin Fellow in Healthcare Innovation, Oxford Martin School; Honorary Consultant Cardiologist, Oxford University Hospitals NHS Trust The George Institute for Global Health Oxford Martin School United Kingdom
Medical Research: What is the background for this study? What are the main findings?
Dr. Rahimi: Lowering blood pressure (BP) in individuals with diabetes is an area of current controversy. Although it is widely accepted that lowering blood pressure in people with diabetes and elevated blood pressure will reduce the risk of heart and circulatory problems, it is less certain whether diabetics whose blood pressure is not very high should be treated with blood pressure lowering drugs, and how far their blood pressure should be reduced. It is also less well known how blood pressure lowering affects a range of other potential health complications for diabetes patients, such as diabetic eye disease.
We found that each 10-mm Hg lower systolic blood pressure led to a lower risk of mortality, cardiovascular disease events, coronary heart disease events, stroke, albuminuria (the presence of excessive protein in the urine), and retinopathy (loss of vision related to diabetes). Although proportional effects of blood pressure lowering treatment for most outcomes studied were diminished below a systolic BP level of 140 mm Hg, data indicated that further reduction below 140 mm Hg led to a lower risk of stroke, retinopathy, and albuminuria, potentially leading to net benefits for many individuals at high risk for those outcomes.
MedicalResearch.com Interview with:
Dr Sandra L Jackson PhD
Atlanta VA Medical Center, Decatur, GA, Nutrition and Health Sciences, Graduate Division of Biological and Biomedical Sciences Emory University, Atlanta, GA, USA
Medical Research: What is the background for this study? What are the main findings?
Dr. Jackson: Lifestyle change programs are aimed to improve health, yet little is known about their impact once translated into clinical settings. The Veterans Health Administration (VA) MOVE! program is the largest lifestyle change program in the U.S. Participation is a key challenge of the program, as only 13% of the eligible population participated. However, among patients who did not have diabetes at baseline, we found that MOVE! participation was associated with lower diabetes incidence.
James J. DiNicolantonio, PharmD
Associate Editor BMJ Open Heart
Cardiovascular Research Scientist
Saint Luke's Mid America Heart Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. DiNicolantonio: We performed a comprehensive literature review comparing the isocaloric exchange of added sugars (sucrose, also known as table sugar, or high fructose corn syrup) versus other types of carbohydrates (such as lactose found in milk, glucose, starch, or dextrose). Our main findings were that "a calorie isn't a calorie," i.e., that added sugars are more harmful than other carbohydrates even when matched for calories for promoting pre-diabetes and diabetes and the related morbidity and mortality associated with these diseases
MedicalResearch.com Interview with:
Dr. Holger Rehmann
Department of Molecular Cancer Research
UMC Utrecht The Netherlands
Medical Research: What is the background for this study? What are the main findings?
Dr. Rehmann: We have developed a chemical modified version of the second messenger cAMP, Sp-8-BnT-cAMPS that allows selective activation of Epac2, a protein that augments glucose induced insulin secretion.
The second messenger cAMP activates a couple of receptor proteins, which controls such divergent physiological effects as gene transcription, pacemaker activity, olfaction, and cell adhesion. Almost any cell responses in one or the other way to cAMP and thus selective action on only one cAMP receptor would be a requirement for a drug to induce specific effects.
The study confirms that it is possible to pharmacologically discriminate between structurally highly related cAMP receptors. And indeed, Sp-8-BnT-cAMPS augments glucose induced insulin secretion in primary human islets. Epac2 is thus a putative target for the development of an antidiabetic drug.
MedicalResearch.com Interview with:
Jinnie J. Rhee MSc, ScD
Department of Medicine, Stanford University School of Medicine Palo Alto, CA
Medical Research: What is the background for this study? What are the main findings?
Response: The goal of this study was to see if the dietary determinants of type 2 diabetes observed in predominantly white populations were similar to those in other racial and ethnic groups. We created a dietary diabetes risk reduction score using eight different dietary factors found to be associated with risk of type 2 diabetes, where a higher score indicates a healthier overall diet (A higher score included low intakes trans fat, sugar-sweetened beverages, and red and processed meats; lower glycemic index; and higher intakes of cereal fiber, nuts, and coffee; and higher polyunsaturated to saturated fat ratio). We found a protective association of similar magnitude between a healthy overall diet and type 2 diabetes risk in all racial and ethnic groups. However, in terms of the actual number of preventable cases, a healthier diet conferred even greater benefit for minority women because they were initially at higher risk than white women.
This study is significant because diabetes is a rapidly growing epidemic in most parts of the world, but most previous studies of diet and diabetes have been conducted in populations of European origin. This analysis was very powerful because it combined two large populations with a total of 156,030 women who were followed for up to 28 years with many repeated assessments of diet. This allowed us to conduct detailed analyses within specific racial and ethnic groups.