Diabetes: Switching to Sulfonylureas from Metformin Linked to Increased Side Effects

MedicalResearch.com Interview with:

Samy Suissa, PhD Director, Centre for Clinical Epidemiology, Lady Davis Institute Professor, Departments of Epidemiology and Biostatistics and of Medicine McGill University

Dr. Suissa

Samy Suissa, PhD
Director, Centre for Clinical Epidemiology, Lady Davis Institute
Professor, Departments of Epidemiology and Biostatistics and of Medicine
McGill University 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Sulfonylureas are widely used oral antidiabetic drugs that are recommended as second-line treatments after first-line metformin to treat patients with type 2 diabetes. While their safety has been studied extensively, studies in patients with poorly controlled diabetes in need of pharmacotherapy escalation have been sparse and limited. Our study evaluated whether adding or switching to sulfonylureas after initiating metformin treatment is associated with increased cardiovascular or hypoglycaemic risks, compared with remaining on metformin monotherapy.

Using a large cohort of over 77,000 patients initiating treatment with metformin monotherapy, we found that adding or switching to sulfonylureas is associated with modest increases of 26% in the risk of myocardial infarction and 28% in the risk of death, as well as an over 7-fold major increase in the risk of severe hypoglycaemia leading to hospitalisation.

In particular, we found that switching from metformin to sulfonylureas was associated with higher risks of myocardial infarction and death, compared with adding sulfonylureas to metformin.  Continue reading

Greater Risk of Diabetes in Women With Longer Work Week

MedicalResearch.com Interview with:

Mahée Gilbert-Ouimet, PhD Postdoctoral fellow/Chercheure postdoctorale Institute for Work & Health Hôpital du St-Sacrement,  Québec 

Dr. Gilbert-Ouimet

Mahée Gilbert-Ouimet, PhD
Postdoctoral fellow/Chercheure postdoctorale
Institute for Work & Health
Hôpital du St-Sacrement,  Québec 

MedicalResearch.com: What is the background for this study? 

Response: Diabetes is one of the primary causes of death worldwide, in addition to being a major risk factor for several other chronic diseases including cardiovascular diseases. Considering the rapid and substantial increase of diabetes prevalence, identifying modifiable risk factors is of major importance. In this regard, long work hours have recently been linked with diabetes, but more high-quality prospective studies are needed. Our study evaluated the relationship between long work hours and the incidence of diabetes among 7065 workers over a 12-year period in Ontario, Canada.

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More Evidence Ancient Retrovirus Linked to Type 1 Diabetes

MedicalResearch.com Interview with:

Sandrine Levet PhD Student Preclinical Study Manager GeNeuro

Sandrine Levet

Sandrine Levet PhD
Preclinical Study Manager
GeNeuro

MedicalResearch.com: What is the background for this study?

Response: Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies. In particular, the envelope protein of HERV-W family (HERV-W Env) has been involved in multiple sclerosis pathogenesis.

A previous study published in JCI Insight revealed that HERV-W Env is also involved in Type 1 diabetes (T1D) pathogenesis. In this study, we observed that HERV-W-Env protein and RNA are detected respectively in sera and peripheral blood mononuclear cell (PBMC) of T1D patients.

We also demonstrated that this pathogenic protein is expressed by acinar cells in human T1D pancreas and is associated with the recruitment of macrophages within the pancreas of these patients. HERV-W Env also displays direct pathogenic properties as it inhibits insulin secretion by human islets of Langerhans.

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Closed-Loop Diabetes Systems (Artificial Pancreas) Can Be Used For Inpatient Care

MedicalResearch.com Interview with:

Roman Hovorka PhD FMedSci Director of Research University of Cambridge Metabolic Research Laboratories  Wellcome Trust-MRC Institute of Metabolic Science Addenbrooke’s Hospital Cambridge

Dr. Hovorka

Roman Hovorka PhD FMedSci
Director of Research
University of Cambridge Metabolic Research Laboratories
Wellcome Trust-MRC Institute of Metabolic Science
Addenbrooke’s Hospital
Cambridge

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Inpatient diabetes is generally not managed well when patients are admitted for a range of health issues on the general ward.

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OPTIFAST Program Resulted in Weight Loss and Greater Improvement in Diabetes Control

MedicalResearch.com Interview with:

Dr. Rothberg . 7/3/07 Headshots of Internal Medicine fellows for Metabolism, Endocrinology and Diabetes.

Dr. Rothberg

Dr. Amy Rothberg MD PhD
Associate Professor, Endocrinology and Medicine
Michigan Medicine Metabolism, Endocrinology and Diabetes Clinic
University of Michigan 

MedicalResearch.com: What is the background for this study? Would you briefly outline the essentials of the Optifast plan?

Response: OPTIWIN is a year-long, multi-center, open-label, randomized, head-to-head study. It was designed to evaluate the effectiveness of the medically-monitored, meal replacement OPTIFAST Program on weight loss and maintenance, in comparison with a standard-of-care, food-based diet among adults with a BMI higher than 30 kg/m2.

Nestlé Health Science’s OPTIFAST Program combines proven essential features of weight loss success ‒ medical monitoring, nutrition education, exercise guidance, in-person support, full meal replacement and behavior modification. With OPTIFAST meal replacement products, the program gives patients the prescribed amount of calories and micronutrients each day. It is a non-surgical option designed for people with a Body Mass Index (BMI) greater than 30, and is available in more than 400 weight loss clinics nationwide.

The Program is comprised of three core phases ‒ active weight loss (during which total diet replacement is used), transition to self-prepared ‘everyday’ meals and maintenance. Clinical supervision is a key component of the program as it helps assess progress towards better health and emotional well-being.

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Artificial Pancreas Reduces Hypoglycemia in Type 1 Diabetes

MedicalResearch.com Interview with:

Dr-Apostolos Tsapas

Dr. Tsapas

Apostolos Tsapas, MD PhD MSc(Oxon)
Associate Professor of Medicine
Director of the Second Medical Department | Aristotle University Thessalonik
Cruddas Link Fellow
Harris Manchester College
University of Oxford  

MedicalResearch.com: What is the background for this study?

Response: Artificial pancreas treatment, also referred to as closed loop glucose control, is an emerging treatment option combining a pump and continuous glucose monitoring with a control algorithm to deliver insulin (and potentially glucagon) in a glucose responsive manner. Compared with insulin pumps or sensor augmented pumps, artificial pancreas use can reduce the burden for patients by automatically adjusting the amount of insulin entering the body on the basis of sensor glucose levels. The US Food and Drug Administration has recently approved the first artificial pancreas system for use by people with type 1 diabetes over 14 years of age, based on a safety outpatient study.

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Which Diabetes Meds Reduce Heart Failure and Death?

MedicalResearch.com Interview with:

Sean Lee Zheng BM BCh MA MRCP Cardiovascular Division King's College Hospital London British Heart Foundation Centre of Research Excellence London, UK

Dr. Zheng

Sean Lee Zheng BM BCh MA MRCP
Cardiovascular Division
King’s College Hospital London
British Heart Foundation Centre of Research Excellence
London, UK

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The growing prevalence of type 2 diabetes and its associated burden on cardiovascular disease is a global problem. A number of drug treatments effective in lowering blood glucose are now available, with the three latest drug classes developed being the DPP-4 inhibitors, GLP-1 agonists and SGLT-2 inhibitors. While the use of medications from these three classes are increasing, it remains unknown how they compare in lowering the risk of death or cardiovascular disease. This leads to clinical uncertainty when it comes to introducing new medicines for our patients. Our study aimed to use data from randomized clinical trials in a network meta-analysis, allowing these three drug classes to be compared with one another.

Our study, which included 236 studies enrolling 176310 participants, showed that the use of SGLT-2 inhibitors or GLP-1 agonists were associated with a lower risk of death than with DPP-4 inhibitors. SGLT-2 inhibitors had additional beneficial effects on heart failure events compared with the other two drug classes.

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Screening Criteria Can Miss Over Half of Adults with Prediabetes

MedicalResearch.com Interview with:
“Diabetes Mellitus” by Steve Davis is licensed under CC BY 2.0Matthew James O’Brien MD

Assistant Professor, Medicine
General Medicine Division
Assistant Professor, Preventive Medicine
Northwestern University 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The USPSTF is an expert group that makes recommendations for screening and other preventive services. In December 2015, they recommend that providers screen for diabetes in patients who are 40-70 years old and also overweight/obese. The same recommendation stated that clinicians “should consider screening earlier” in patients who have any of the following risk factors: non-white race/ethnicity, family history of diabetes, or personal history of gestational diabetes or polycystic ovarian syndrome. Using nationally representative data, we studied the performance of the “limited” criteria based on age and weight alone vs. the “expanded criteria” mentioned above.

The main findings were that following the “limited” screening criteria of age and weight would result in missing over 50% of adults with prediabetes and diabetes. In other words, if providers followed the “limited” criteria, over 50% of adults with prediabetes and diabetes would not get screened. The “expanded” criteria exhibited much better performance, resulting in 76.8% of adults with prediabetes and diabetes who would be screened.  Continue reading

Obese Children Who Lose Weight Before Adulthood Can Reduce Risk of Diabetes

MedicalResearch.com Interview with:

Lise Geisler Bjerregaard PhD

Dr. Geisler Bjerregaard

Lise Geisler Bjerregaard PhD
Postdoc, PhD, M.Sc. Public Health
Center for Klinisk Forskning og Sygdomsforebyggelse/ Center for Clinical Research and Disease Prevention
Sektion for Klinisk Epidemiologi
Frederiksberg Hospital, Frederiksberg

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Being overweight in childhood and early adulthood is associated with an increased risk of developing type 2 diabetes in adulthood. We wanted to know whether or not remission of overweight before early adulthood can reduce the risks of type 2 diabetes later in life.

We studied the associations between different combinations of weight status in childhood, adolescence and early adulthood, and later development of type 2 diabetes.

We found that men who had been overweight at 7 years of age but normalised weight by age 13 years and were normal weight as young men had similar risks of type 2 diabetes as men who were never overweight. Men who normalised weight between age 13 years and early adulthood had increased risks of type 2 diabetes, but lower risks than men who were overweight at all ages.  Continue reading

DPP-4 inhibitor Class of Diabetes Medications Linked To Increase Risk of Inflammatory Bowel Disease

MedicalResearch.com Interview with:
Devin Abrahami,
graduate student
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal
Department of Epidemiology, Biostatistics, and Occupational Health
McGill University, Montreal, QC, Canada

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: The goal of our study was to assess whether a class of antidiabetic drugs, the dipeptidyl peptidase-4 (DPP-4) inhibitors, is associated with the risk of inflammatory bowel disease (IBD). While these drugs control blood sugar levels in patients with type 2 diabetes, there is some evidence that they may also be involved in immune function, and possibly in conditions such as IBD.

In our study, we found that the use of DPP-4 inhibitors was associated with a 75% increased risk of IBD, with the highest risk observed after three to four years of use. Continue reading

Cardiovascular Trials Need Better Characterization of Heart Failure in Diabetics

MedicalResearch.com Interview with:

Stephen J. Greene, MD Division of Cardiology Duke University Medical Center Durham, NC

Dr. Greene

Stephen J. Greene, MD
Division of Cardiology
Duke University Medical Center
Durham, NC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In 2008, the United States FDA issued an industry guidance specifying that diabetes drugs should routinely be tested in large cardiovascular outcome trials to confirm cardiovascular safety. The guidance specifically mentioned cardiovascular safety in terms of MACE, or major adverse cardiac events, including cardiovascular death, myocardial infarction, and stroke.  Largely because of this, these trials have traditionally had a focus on cardiovascular disease in terms of atherosclerotic events. Heart failure was not mentioned in the FDA document and these trials have had a lesser focus on it.

As the years have gone by, we have learned more and more about the connection between diabetes and heart failure. There is tremendous overlap between the two patient populations. Also, as more and more of the large cardiovascular outcome trials have been completed, we have seen multiple examples of various glucose lowering therapies either increasing or decreasing risk of heart failure events. Given all these data on heart failure/ diabetes interactions, the goal of our research was to carefully examine all of the completed large cardiovascular outcome trials of diabetes therapies to systematically describe the type of heart failure-related data they capture. As an initial step in improving heart failure characterization in these trials, we wanted to first describe what trials have already been doing and where the gaps in understanding heart failure in these trials exist.

Overall, we found major gaps in the amount and quality of the heart failure data capture in these trials. We looked at 21 large trials, including over 150,000 patients. Rates of patients with baseline heart failure were inconsistently provided, and among those trials that did provide it, heart failure patients tended to be underrepresented compared to the general population. Patients with baseline heart failure were also poorly characterized, with minimal data on functional status, ejection fraction, or heart failure medications. Only 6 trials reported rates of new-onset heart failure and the definitions used were non-specific. Most trials tended to report rates of heart failure hospitalization, but did not include data on fatal or other types of heart failure events. Only 2 trials included heart failure events within the primary study endpoint. More details are included in our full manuscript, which was published in the Journal of the American College of Cardiology to coincide with our presentation at the ACC conference.

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Dietary Fiber Promotes Beneficial Bacteria, Improving Glucose Control in Diabetes

MedicalResearch.com Interview with:

Liping Zhao PhD, Professor Department of Biochemistry and Microbiology School of Environmental and Biological Sciences Rutgers University-New Brunswick NJ

Dr. Zhao

Liping Zhao PhD, Professor
Department of Biochemistry and Microbiology
School of Environmental and Biological Sciences
Rutgers University-New Brunswick NJ

MedicalResearch.com: What is the background for this study?

Response: Microbes in the human gut (collectively known as the gut microbiota) provide many functions that are important for human health. A notable example is that some gut bacteria are able to ferment non-digestible carbohydrates in our diet, e.g. dietary fibers, to produce short-chain fatty acids (SCFAs). These SCFAs nourish our gut epithelial cells, reduce inflammation, and play a role in appetite control. Deficiency of SCFAs has been associated with many diseases including type 2 diabetes. Many gut bacteria have the genes (and therefore the capacity) to produce SCFAs from carbohydrate fermentation. However, we know little about how these bacteria, as individual strains and as a group, actually respond to an increased supply of carbohydrates. This is key to improve clinical efficacy of dietary fiber interventions to improve human health. Continue reading

Risk Factors For Sudden Death in Heart Failure with Preserved Ejection Fraction

MedicalResearch.com Interview with:

Muthiah Vaduganathan, MD MPH Heart and Vascular Center Brigham and Women's Hospital 

Dr. Vaduganathan

Muthiah Vaduganathan, MD MPH
Heart and Vascular Center
Brigham and Women’s Hospital 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The prevalence of heart failure with preserved ejection fraction (HFpEF) is rising globally, yet no medical therapies are currently available to alter its natural history and its progression remains incompletely understood.

Sudden death may represent a target for therapy in this disease entity. In 1,767 patients with HFpEF enrolled in the Americas region of the TOPCAT trial, we found that sudden death accounts for ~20% of all deaths. Male sex and insulin-treated diabetes mellitus identify patients at higher risk for sudden death. Sudden death was numerically lower but not statistically reduced in those randomized to spironolactone.

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Bariatric Surgery Associated With Reduced Need For Diabetes Medications at Six Years

MedicalResearch.com Interview with:
Dr Jérémie Thereauz
Praticien Hospitalier
Chirurgie viscérale et digestive 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Bariatric surgery has been proved to reduce type 2 diabetes in morbid obese patients. However, results of bariatric surgery at a nationwide level are lacking.

The aim of our study was to assess the 6-year antidiabetic treatment continuation, discontinuation or initiation rates after BS compared with matched control obese patients.

This large-scale nationwide study confirms that bariatric surgery is responsible for a significant 6-year postoperative antidiabetic treatment discontinuation rate compared to baseline and compared to an obese control group without surgery, and a low treatment initiation rate, with gastric bypass being the most effective procedure. 

MedicalResearch.com: What should readers take away from your report?

Response: This long term study confirms at a nationwide level, previous mid term randomized studies finding effiicency of bariatric surgery in type 2 diabetes for patients with morbid obesity associated.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Patients and physicians must be aware that morbid obesity still remains a chronic disease even after bariatric surgery, as 50% of patients with pre-existing antidiabetic treatment remained on treatment 6 years after surgery. Our study highlights the message that these patients require careful lifelong follow-up to monitor obesity complications. Complementary medico-economic study would be helpful to determine the relevance of such treatment in a national health care system.

No disclosures

Citations:

Thereaux J, Lesuffleur T, Czernichow S, Basdevant A, Msika S, Nocca D, Millat B, Fagot-Campagna A. Association Between Bariatric Surgery and Rates of Continuation, Discontinuation, or Initiation of Antidiabetes Treatment 6 Years Later. JAMA Surg. Published online February 14, 2018. doi:10.1001/jamasurg.2017.6163

https://jamanetwork.com/journals/jamasurgery/fullarticle/2672216?resultClick=1

 

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Irregular or Rotating Night Shifts Linked To Increased Risk of Diabetes

MedicalResearch.com Interview with:
“Night Shift - Hard@Work (5of8)” by cell105 is licensed under CC BY 2.0Dr. Céline Vetter

Assistant Professor
Department of Integrative Physiology
University of Colorado at Boulder
Boulder, CO

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Shift work, particularly night shifts, can change our social rhythms, as well as the internal biological rhythms including our sleep, and these effects could explain why shift work is linked to conditions such as obesity and type 2 diabetes. However, we don’t know which type of shift pattern is most strongly linked to type 2 diabetes. In addition, we know that some lifestyle factors can modify the link between a genetic predisposition to a disease and the disease itself, but we don’t know if this applies to shift work and type 2 diabetes.

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Pregnancy in Type 1 Diabetes: Glucose Control Can Reduce Fetal Overgrowth

MedicalResearch.com Interview with:

Rachel McGrath BSc (Hons), PhD Senior Research Fellow - Department of Endocrinology, RNSH Clinical Senior Lecturer - Northern Clinical School University of Sydney

Dr. Rachel McGrath

Rachel McGrath BSc (Hons), PhD
Senior Research Fellow – Department of Endocrinology, RNSH
Clinical Senior Lecturer – Northern Clinical School
University of Sydney 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Women with type 1 diabetes are significantly more likely to experience complications during pregnancy and to have infants with high birth weights. This can result in adverse outcomes at the time of delivery for both mother and baby, and can also predispose infants to obesity and chronic disease in later life.

The relationship between maternal blood glucose levels and foetal growth in type 1 diabetes in pregnancy has not been completely elucidated. Thus, we examined the association between maternal glycaemic control and foetal growth by examining serial ultrasound measurements and also by determining the relationship between HbA1c (a measure of circulating glucose exposure over a three month time period) and infant birth weight.

We found that maternal glucose levels were directly related to foetal abdominal circumference in the late second and third trimesters and also to birth weight. We also confirmed the results of previous studies to show that the optimal HbA1c during pregnancy to reduce the likelihood of large-for-gestational-age neonates is < 6%.  Continue reading

Experimental Bioelectronic Modulation of the Carotid Sinus Improves Glucose Tolerance

MedicalResearch.com Interview with:

Silvia Conde, PhD CEDOC, NOVA Medical School Faculdade de Ciências Médicas Universidade Nova de Lisboa Lisboa

Dr. Conde

Silvia Conde, PhD
CEDOC, NOVA Medical School
Faculdade de Ciências Médicas
Universidade Nova de Lisboa
Lisboa

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In 2013, Silvia Vilares Conde and her research group described that the carotid body, a paired organ that is located in the bifurcation of the common carotid artery and that is classically defined as an oxygen sensor, regulates peripheral insulin sensitivity and that its dysfunction is involved in the development of metabolic diseases.

This first study (Ribeiro et al. 2013, Diabetes, 62:2905-16) and others afterwards performed by her group in diabetic rats (Sacramento et al. 2017, Diabetologia 60(1):158-168) showed that the bilateral resection of the carotid sinus nerve, and therefore the abolishment of the connection between the carotid body and the brain, restore insulin sensitivity and glucose tolerance. Although efficient this surgical irreversible approach has disadvantages, since the carotid body possesses other physiological functions as the response to the lack of oxygen (hypoxia) or the adaptation to exercise. Silvia Conde’s team also described that the carotid body is over-activated in animal models of type 2 diabetes, suggesting that decreasing the activity of the organ could be a good therapeutic strategy.

In this new work (Sacramento et al. 2018, doi: 10.1007/s00125-017-4533-7), her group in collaboration with Galvani Bioelectronics (former Glaxo Smith Kline Bioelectronics) demonstrated that is possible to electrically modulate the carotid sinus nerve to maintain glucose homeostasis in diabetic animals without significant adverse effects.  Continue reading

Benefits of Gastric Bypass in Diabetes Control Significant But Diminish Over Time

MedicalResearch.com Interview with:

Charles Billington MD Chief, Section of Endocrinology and Metabolism Minneapolis VA Health Care System Professor of Medicine, University of Minnesota 

Dr. Billington

Charles Billington MD
Chief, Section of Endocrinology and Metabolism
Minneapolis VA Health Care System
Professor of Medicine, University of Minnesota 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: We wanted to know if adding gastric bypass to intense lifestyle and medical therapy would improve overall diabetes treatment as represented by the triple endpoint of blood sugar, blood pressure and cholesterol control. We found that adding gastric bypass did provide significant benefit at five years after surgery, but that the size of the benefit declined substantially from the first to the fifth year. We also found that gastric bypass did provide significantly better blood sugar control throughout the five years, but the rate of diabetes remission at five years was low. There were many more adverse events in the gastric bypass group. 

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Viral Vector Delivered Gene Therapy That Reversed Diabetes in Mice

MedicalResearch.com Interview with:
Xiangwei Xiao, M.D., Ph.D.
Assistant Professor of Department of Surgery,
Children’s Hospital of Pittsburgh
University of Pittsburgh School of Medicine,
Pittsburgh, PA

MedicalResearch.com: What is the background for this study?

Response: Diabetes is a prevalent chronic disease characterized by persistently high blood glucose. Diabetes has two main subtypes, type 1 diabetes and type 2 diabetes. In type 1 diabetes, the immune system attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood levels of glucose. In type 2 diabetes, the beta cells do not produce enough insulin or the body is not able to use insulin effectively.

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Increased Diabetes Risk in African Americans Explained by Greater Obesity Rates

MedicalResearch.com Interview with:

Michael P. Bancks, PhD Northwestern University Chicago, Illinois 

Dr. Bancks

Michael P. Bancks, PhD
Northwestern University
Chicago, Illinois 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We know that the disparity in diabetes between black and white youth and young adults is growing, but the reasons why are unclear. We also know that traditional risk factors for diabetes, such as obesity and low socioeconomic status, are more common among blacks as compared with whites.

Our study describes how the unequal rates of these traditional diabetes risk factors explain or account for the higher rates of diabetes among blacks.

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