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Dipeptidyl peptidase-4 inhibitors commonly used to control blood sugar levels in people with type 2 diabetes may also reduce the risk of autoimmune diseases in these patients, according to research presented this week at the American College of Rheumatology Annual Meeting in San Diego.
Dipeptidyl peptidase-4 inhibitors (commonly called DPP-4 inhibitors) such as linagliptin (Tradjenta), saxagliptin (Onglza), and sitagliptin (Januvia) are approved by the United States Food and Drug Administration for the treatment of type 2 diabetes.
Patients taking insulin, or with pre-existing systemic autoimmune diseases, HIV or cancer were excluded.
Rheumatoid arthritis and other autoimmune diseases were defined with two or more diagnosis codes that were seven or more days apart and one or more prescriptions for disease-specific immunosuppressive drugs or steroids. Scientists at an Academy of Finland Centre of Excellence have discovered a new mechanism regulating the immune response that can leave a person susceptible to autoimmune diseases. Females can mount more powerful immune responses than males, but the flip side of this enhanced protection against infections is a greater risk for autoimmune disorders.
UCLA researchers have designed a portable imaging system that can diagnose gout, a condition that affects more than 8 million adults in the U.S. The very first bony fish on Earth was susceptible to arthritis, according to a USC-led discovery that may fast-track therapeutic research in preventing or easing the nation's most common cause of disability.
What began as a chat between husband and wife has evolved into an intriguing scientific discovery. University of Queensland researchers have developed a world-first vaccine-style therapeutic approach to treat rheumatoid arthritis, a debilitating disease affecting more than 450,000 people in Australia.
Influence of IRF5 on the nature of adipose tissue in obese patients and its metabolic consequences. Metabolic complications of obesity and overweight, such as type 2 diabetes, are an important challenge to public health.
Following excessive weight gain, the adipose tissue develops in an abnormal manner in the intra-abdominal region (android obesity), and becomes an important source of pro-inflammatory mediators, the "chemical messengers" that activate inflammation, with harmful metabolic consequences.
In order to demonstrate the importance of IRF5 in obesity and type 2 diabetes, the authors generated mice lacking this factor, and then subjected them to a high-fat diet that usually induces obesity and type 2 diabetes.
Data obtained with mice were confirmed in overweight, obese or massively obese patients, by showing significant correlation between IRF5 expression in the visceral adipose tissue and metabolic dysfunctions associated with obesity.
This pioneering study suggests that the immune system (in this case the macrophages of the adipose tissue) directly influences the accumulation of fatty matter in the visceral region, a likely target in the prevention of type 2 diabetes. The approach implemented in this study encapsulates translational research, which is aimed at developing effective therapies for patients by establishing a fruitful dialogue between clinicians and researchers, in order to produce robust results that are supported by mouse models while being relevant to humans.
New research in mice suggests that an unusual type of immune cell called "I?I? T cells" may be a new drug and research target for treating or preventing type 2 diabetes caused by obesity.
A study by researchers in Duke-NUS Graduate Medical School Singapore (Duke-NUS) has shown a new way that brown fat, a potential obesity-fighting target, is regulated in the body.
Visceral fat deposits around internal organs in the stomach are particularly harmful: they are associated with insulin resistance, type-2 diabetes and heart disease. A handful of large studies of cancer risk factors have found that working the night shift, as nearly 15 percent of Americans do, boosts the chances of developing cancer. In their mission to design new biomaterials that promote tissue regeneration, Drexel University researchers have identified how inflammation, when precisely controlled, is crucial to bone repair. New research by University of Iowa scientists helps explain how a hormone system often targeted to treat cardiovascular disease can also lower metabolism and promote obesity. A low-intensity type of laser treatment may offer a non-invasive, drug-free treatment for thrombocytopenia - a potentially life-threatening shortage of the blood cells called platelets that are essential to blood clotting. Researchers at Johns Hopkins Medicine report they have identified a biochemical pathway linking oxidative stress and the amino acid cysteine in Huntington's disease. New evidence shores up findings that whey protein, which is found in milk and cheese, could have health benefits for people who are obese and do not yet have diabetes.
They gave volunteers who were obese and non-diabetic the same meal of soup and bread plus one kind of protein, either from whey, gluten, casein (another milk protein) or cod. Whey Protein Delays Gastric Emptying and Suppresses Plasma Fatty Acids and Their Metabolites Compared to Casein, Gluten, and Fish Protein, J. Abstract Whey protein has been demonstrated to improve fasting lipid and insulin response in overweight and obese individuals.
A new study published online in the Journal of Applied Physiology shows additional benefits of consuming a blend of soy and dairy proteins after resistance exercise for building muscle mass. In healthy individuals, the amount of glucose, or sugar, in the blood increases after eating. A study of 4,046 genetically identical twin pairs with different amounts of body fat shows that twin siblings with a higher Body Mass Index, as a measure of obesity, do not have an increased risk of heart attack or mortality.
The use of cannabis as a health treatment is highly controversial but now a new study has suggested that smoking the drug may help protect against type 2 diabetes. The team at the Cardiovascular Epidemiology Research Unit at the Beth Israel Deaconess Medical Centre in Boston, analysed data on almost 5,000 patients who were quizzed about their use of recreational drugs as part of the National Health and Nutrition Survey between 2005 and 2010.
Tests showed that current users had 16% lower fasting insulin levels and reduced insulin resistance than those who had never used cannabis. Team leader Murray Mittleman said that the same benefits were seen among participants who had used the drug in the past but the associations were not as strong, indicating that the effects of cannabis use on insulin levels and insulin sensitivity wear off over time.
Smoking cannabis is illegal in many countries although there have been moves to make it permissible for medical conditions and rules are more lax in some countries, such as the Netherlands. About Speaking of DiabetesSpeaking of Diabetes is produced by Joslin Diabetes Center for people with diabetes and those who care for them..
Joslin Diabetes Center, a teaching and research affiliate of Harvard Medical School, is a one-of-a-kind institution on the front lines of the world epidemic of diabetes - leading the battle to conquer diabetes in all forms through cutting-edge research and innovative approaches to clinical care and education.

This entry was posted in Complications Research, Inside Joslin, Research, Research and tagged diabetes and brain, hypoglycemia, hypoglycemia and brain. When you attend diabetes education classes you learn about all the complications you can avoid by keeping your blood glucose and weight in control. But few diabetes classes ever address the toil that diabetes takes on another of our organs: our brains.
Gail Musen, PhD, Assistant Investigator at the Joslin Diabetes Center is a cognitive psychologist with interests in the areas of memory and cognition. Using a technique called magnetic resonance imaging (MRI) Musen and her team were able to identify brain areas that may be associated with alterations caused by diabetes. Musen’s research showed that people with type 1 diabetes have less gray matter in some brain regions than people of the same age who don’t have diabetes. In addition to looking at how diabetes can change brain anatomy, she also compared brain activity during episodes of experimentally induced hypoglycemia in people with and without diabetes.
Luckily, these changes don’t necessarily translate into poor cognitive function for people with type 1 diabetes. When people with type 1 are acutely hypoglycemic they draw on more areas of the brain to help them maintain cognitive capacity than people without diabetes who have had hypoglycemia induced. For example, Musen and colleagues showed that during a memory task conducted while hypoglycemic, people with type 1 diabetes needed to engage more brain regions than non-diabetic control subjects to maintain good performance.
What this means is that even though people with type 1 have less gray matter in certain regions, they may be able to compensate by recruiting more brain tissue than non-diabetic individuals to complete the same task.
Researchers have been attempting to determine the affects of glycemic control on real-world cognitive performance for some time now.
EDIC, however, discerned no long-term effects of frequent hypoglycemia on cognitive performance. Does this mean that because you have diabetes you will automatically lose cognitive function?
Like other diseases that cause structural brain changes, the effects of glycemic variation appear to take a long time to produce detrimental effects on long-term cognition.
Advances in medicine and knowledge about proper lifestyle have far extended the years people with diabetes can expected to live healthy lives. Researchers recently studied how often people with type 2 diabetes taking a DPP-4 inhibitor developed autoimmune diseases—such as rheumatoid arthritis, lupus, inflammatory bowel disease, psoriasis and multiple sclerosis—when compared to those not taking one. Kim's team compared two mutually exclusive groups: 58,275 patients with type 2 diabetes starting DPP4i combination therapy with patients with type 2 diabetes starting non-DPP4i combination therapy.
Potential confounders such as age, sex, co-existing conditions, diabetes-related factors, medications, and health care utilization were controlled for in the analysis. Kim's team found that patients with type 2 diabetes who were starting a DPP-4 inhibitor appear to be at a lower risk of developing RA or other autoimmune diseases compared to those starting non-DPP4i drugs. Thyroid diseases, type 1 diabetes, rheumatoid arthritis, psoriasis and inflammatory bowel disease are some examples. We have known for about a decade that a chronic state of inflammation is present in obese patients. This phenomenon is particularly provoked by the accumulation of pro-inflammatory macrophages in this tissue. Surprisingly, mice deficient in IRF5 did develop obesity, but without metabolic complications, in contrast to wild-type mice expressing IRF5. The study, which appears in ACS' Journal of Proteome Research, examined how different protein sources affect metabolism.
Dragsted, Kjeld Hermansen and colleagues point out that obesity continues to be a major public health problem worldwide.
The scientists found that the meal supplemented with whey caused the subjects' stomachs to empty slower than the others'. To establish new hypotheses for this effect and to investigate the impact of stomach emptying, we compared plasma profiles after intake of whey isolate (WI), casein, gluten (GLU), and cod (COD). When glucose increases, levels of insulin increase to carry the glucose to the rest of the body. Pay attention to how thirsty you are, suggests a new study that found a link between poor hydration and obesity.
Researchers in the United States have found that regular users of the drug have better blood sugar control but the effects wear off over time. They found that 2,103 had never used cannabis, 975 had used the drug in the past but were not current users, and 579 had inhaled or ingested it in the past month. Non-users also had larger waistlines and lower levels of high density lipoprotein (HDL or good) cholesterol, both of which are risk factors for type 2 diabetes.
Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar.
In the United States, 19 states have legalised cannabis for medicinal purposes by patients with one of several conditions including multiple sclerosis and cancer, while recreational use of the drug is now legal in two states, Colorado and Washington.
A1Cs under seven lower the risk of nerve and kidney damage, heart attacks, oral problems, eye disease and sexual dysfunction. Unfortunately, the brain isn’t magically spared from the ravages of high or low blood glucose. She has collaborated with biophysicists, psychiatrists and endocrinologists at Joslin and Beth Israel Deaconess Hospital to design studies looking at what areas of the brain are affected by diabetes and how glycemic variations can modify usual brain processes.
Most of us have heard of gray matter which is involved in muscle control, seeing and hearing, memory, emotions, and speech.

Specifically, there was less gray matter density in areas that are responsible for learning and memory. A special kind of MRI called a functional MRI (fMRI) can detect blood flow and oxygen consumption in the brain. This may help to explain why people who are frequently hypoglycemic can often appear to be in control even though they have blood glucose values in the 40s. The Epidemiology of Diabetes Interventions and Complications (EDIC) study, which continued where the Diabetes Control and Complications Trial (DCCT) left off, compared the brain function of those who received intensive control (lower A1C) to those who received conventional therapy (higher A1C). Will people with type 1 in the 70s and 80s start to show cognitive dysfunction directly attributable to diabetes, even if they have been in excellent control? Although the overall incidence rate of RA or other autoimmune diseases was low (approximately one in 1,000), patients taking DPP4i combination therapy appeared to be 34 percent less likely to develop RA and 27 percent less likely to develop the other autoimmune diseases. This state might play a fundamental role in the development of associated metabolic diseases.
By characterising these macrophages, they were able to identify transcription factor IRF5 (Interferon Regulatory Factor 5) as the orchestral conductor of macrophage activation in adipose tissue in obesity. This beneficial adaptation by IRF5-deficient mice can be explained by preferential storage of fat in the subcutaneous (protective) and not the intra-abdominal (harmful) region. These subjects also had lower levels of fatty acids in their blood after meals but higher amounts of the specific types of amino acids that boost insulin levels. Obese, nondiabetic subjects were included in the randomized, blinded, crossover meal study. This technique allows scientists to see which brain regions are most active as we perform particular tasks. One concerning finding of the DCCT was that intensive control equaled a greater risk of hypoglycemia. We don’t know at present but the brain is a very resilient organ with a large reserve capacity.
Keeping blood glucose in good control especially in middle age is the best preventive medicine we have to ensure long-term brain health. All materials contained on this site are protected by United States copyright law and may be used for personal, noncommercial use only. Subgroup analysis comparing DPP4i to sulfonylurea showed similarly protective effect of DPP4i on autoimmune diseases, but not comparing DPP4i versus thiazolidinediones. This inflammation results from abnormal activity of the immune system observed both systemically (bloodstream) and locally (in metabolic organs such as the liver, muscles, pancreas and especially the adipose tissue). Indeed, when adipose tissue expansion occurs in the more superficial deposits, such as the subcutaneous adipose tissue (gynoid obesity), the risk of developing metabolic complications is reduced. Decoding of molecular and cellular mechanisms made it possible to show a substantial reprogramming of inflammation in the visceral adipose tissue when IRF5 is absent, which helps to limit its expansion.
The gray matter we have is divided into different regions and the white matter helps these regions talk to each other. And like so many other risks associated with diabetes, new research is investigating the benefits of diet and exercise as a preventative measure.
Indeed, in the absence of IRF5, obesity induces an immune response characterised by the presence of anti-inflammatory macrophages and reduced immune response activation. One risk factor for cardiovascular disease in people who are obese is high levels of fat in their blood after meals. Plasma samples were collected at five time points and metabolites analyzed using LC-Q-TOF-MS.
You can think of the white matter as the network cabling connecting a series of computers together. In the general population, groups at risk for dementia show less brain activity in some regions than people without that risk– Musen and her team showed that this was also true in those with type 2 diabetes. You may not alter or remove any trademark, copyright or other notice from copies of the content. This modification induces tissue remodelling that limits the expansion of intra-abdominal adipose tissue. But recent research has found that these levels partly depend on the kind of protein included in the meal.
In contrast to previous studies, the WI meal caused a decreased rate of gastric emptying compared to the other test meals.
This allows the redistribution of lipids in the intra-abdominal cavity to the subcutaneous deposits, a less harmful form of storage for the body. Studies have suggested that whey protein can lower the amount of fat and increase insulin, which clears glucose in the blood, keeping sugar levels where they're supposed to be.
The WI meal also caused elevated levels of a number of amino acids, possibly stimulating insulin release leading to reduced plasma glucose. The WI meal also caused decreased levels of a number of fatty acids, while the GLU meal caused elevated levels of a number of unidentified hydroxy fatty acids and dicarboxylic fatty acids.

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