Antibiotic use linked to type 2 diabetes diagnosis

 

Antibiotics may contribute to or serve as early signal of developing condition   People who developed Type 2 diabetes tended to take more antibiotics in the years leading up to the diagnosis than people who did not have the condition, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism. A person develops diabetes, which is characterized by high blood sugar levels, when the individual cannot produce enough of the hormone insulin or insulin does not work properly to clear sugar from the bloodstream. More than 29 million people in the USA have diabetes, according to the Society's Endocrine Facts and Figures report. Type 2 diabetes, the most common form of the condition, accounts for 90 to 95 percent of all cases. "In our research, we found people who have Type 2 diabetes used significantly more antibiotics up to 15 years prior to diagnosis compared to healthy controls," said one of the study's authors, Kristian Hallundbæk Mikkelsen, MD, of Gentofte Hospital in Hellerup, Denmark. "Although we cannot infer causality from this study, the findings raise the possibility that antibiotics could raise the risk of Type 2 diabetes. Another equally compelling explanation may be that people develop Type 2 diabetes over the course of years and face a greater risk of infection during that time." As part of the population-based case-control study, researchers tracked antibiotic prescriptions for 170,504 people who had Type 2 diabetes and for 1.3 million people who did not have diabetes. The researchers identified the subjects using records from three national health registries in Denmark. People who had Type 2 diabetes filled 0.8 prescriptions a year, on average. The rate was only 0.5 prescriptions a year among the study's control subjects. Individuals who filled more prescriptions were more likely to be diagnosed with Type 2 diabetes. Many types of antibiotics were associated with a higher risk of diabetes, but there was a stronger link with the use of narrow-spectrum antibiotics such as penicillin V. Past research has shown that antibiotic treatments can alter the bacteria in an individual's gut. Studies suggest certain gut bacteria may contribute to the impaired ability to metabolize sugar seen in people with diabetes. This may explain why higher rates of antibiotic use are associated with the development of Type 2 diabetes, but more research is needed to explain the findings, Mikkelsen said. "Diabetes is one of the greatest challenges facing modern health care, with a globally increasing incidence" he said. "Further investigation into long-term effect of antibiotic use on sugar metabolism and gut bacteria composition could reveal valuable answers about how to address this public health crisis. Patterns in antibiotic use may offer an opportunity to prevent the development of the disease or to diagnose it early."   http://www.sciencedaily.com/releases/2015/08/150827141859.htm

Attacking type 2 diabetes from a new direction with encouraging results

 

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Victor Shengkan Jin says it is important to find a drug for type 2 diabetes that attacks the root cause of the disease and not just symptoms.

Type 2 diabetes affects an estimated 28 million people in the USA  according to the American Diabetes Association, but medications now available only treat symptoms, not the root cause of the disease. New research from Rutgers shows promising evidence that a modified form of a different drug, niclosamide -- now used to eliminate intestinal parasites -- may hold the key to battling the disease at its source.

The study, led by Victor Shengkan Jin, an associate professor of pharmacology at Rutgers Robert Wood Johnson Medical School, has been published online by the journal Nature Medicine.

Jin says it is important to find a suitable medication to correct the cause of the disease as quickly as possible because the only way now known to "cure" the disease involves major gastric bypass surgery. "The surgery can only be performed on highly obese people," Jin explains, "and carries significant risks that include death, so it is not a realistic solution for most patients."

And the number of patients continues to rise. The Centers for Disease Control and Prevention projects that 40 percent of all Americans now alive will develop type 2 diabetes.

Type 2 is the form of diabetes once known as "adult onset," in which the body produces insulin that ordinarily would keep blood sugar under control, but either it does not produce enough insulin or the body's ability to use that insulin is degraded.

According to Jin, a major cause of insulin resistance is the accumulation of excess fat in the cells of the liver, as well as in muscle tissue. The fat disrupts the process where, ordinarily, insulin would cause body tissues to correctly absorb glucose -- blood sugar -- and use it as a fuel.

With nowhere else to go, much of the excess glucose remains in the bloodstream, where in high concentrations it can damage tissues throughout the body -- potentially leading to blindness, kidney damage, cardiovascular diseases and other severe health problems.

"Our goal in this study was to find a safe and practical way of diminishing fat content in the liver. We used mice to perform proof-of-principle experiments in our laboratory," says Jin. "We succeeded in removing fat, and that in turn improved the animals' ability to use insulin correctly and reduce blood sugar."

The modified medication -- whose full name is niclosamide ethanolamine salt (NEN) -- burned the excess fat in liver cells, through a process known as mitochondrial uncoupling. Mitochondria are the microscopic energy source for each cell in the body, and ordinarily -- like a well-tuned car engine -- they burn fuels including fats and sugars in modest quantities to keep the cells functioning.

Revving up cells' internal engines to burn away harmful fat

"The cell is like a car and the mitochondria are the engine," Jin explains. "What we're doing inside cells is like putting the car's transmission into neutral by uncoupling it from the transmission. Then you step on the gas so the engine runs full throttle but the car doesn't move. If too much of the fuel in the cell is fat, you keep burning it until the fuel gauge reaches empty. Without the interference of fat, you hope that sugar will then enter the cell normally."

Getting rid of the interference of fat in liver and muscle tissue is the key to restoring the cells' ability to respond to insulin properly, which would allow the right amount of sugar to be taken up by cells and ultimately reverse the diabetes entirely. That outcome is far from certain, but Jin says the positive changes he saw in the mice are encouraging.

Jin says it also is significant that the drug he used is a modified form of a medication that the FDA already approved for human use. That was a deliberate choice. "We wanted a safe and practical compound to deplete fat inside cells," says Jin. "We went to the literature and found an approved drug that does in parasitic worms what we wanted to do in liver cells. The modified form of the medication, although itself is not a drug used in humans, has an excellent safety profile in other mammals -- so very likely it would have a good safety profile in humans too."

Also, excess fat in the liver is not just a condition of the obese; people of normal weight can develop fatty livers and type 2 diabetes. Jin says this kind of medication, if shown to be effective, could safely treat patients of all weights.

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Story Source:

The above story is based on materials provided by Rutgers University. The original article was written by Rob Forman. Note: Materials may be edited for content and length.

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Journal Reference:

1. Hanlin Tao, Yong Zhang, Xiangang Zeng, Gerald I Shulman, Shengkan Jin. Niclosamide ethanolamine–induced mild mitochondrial uncoupling improves diabetic symptoms in mice. Nature Medicine, 2014; DOI: 10.1038/nm.3699

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Scientists discover a natural molecule to treat type 2 diabetes: Molecule mimics some effect of physical exercise

 

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A natural molecule has been found with the potential to treat insulin resistance and type 2 diabetes. The molecule, a derivative of omega-3 fatty acids, mimics some of the effects of physical exercise on blood glucose regulation.

Researchers at the Université Laval Faculty of Medicine, the Quebec Heart and Lung Institute Research Center, and the Institute of Nutrition and Functional Foods have discovered a natural molecule that could be used to treat insulin resistance and type 2 diabetes. The molecule, a derivative of omega-3 fatty acids, mimics some of the effects of physical exercise on blood glucose regulation.

The details of the discovery made by Professor André Marette and his team are published today in Nature Medicine.

It has been known for some time that omega-3 fatty acids can help reduce insulin resistance caused by a diet high in saturated fat. In their earlier work, André Marette and his colleagues had linked these effects to a bioactive lipid called protectin D1. In investigating further, they discovered that another member of the same family named protectin DX (PDX) triggers the production and release of interleukin 6 (IL-6) in muscle cells, a response that also occurs during physical exercise. "Once in the bloodstream, IL-6 controls glucose levels in two ways: it signals to the liver to reduce glucose production and acts directly on the muscles to increase glucose uptake," explains the researcher who is also Scientific Director of Université Laval's Institute of Nutrition and Functional Foods.

The researchers used transgenic mice lacking the IL-6 gene to demonstrate the link between PDX and IL-6. PDX had very little effect on the control of blood glucose in these animals. In similar tests conducted on obese diabetic rats, PDX was shown to dramatically improve responsiveness to insulin, the hormone which regulates blood glucose. "The mechanism of action described for PDX represents a new therapeutic strategy for improving glucose control," proposes the researcher. "Its efficacy may be comparable with that of certain drugs currently prescribed to control glycemia."

Even though PDX appears to mimic the effect of physical exercise by triggering IL-6 secretion in the muscles, André Marette warns that it is not a substitute for physical activity. "Exercise has cardiovascular and other hormonal benefits that go well beyond its metabolic effects on the muscles," adds the researcher whose work is supported by the Canadian Institutes of Health Research (CIHR) and the Canadian Diabetes Association.

Professor Marette and Université Laval have filed a patent application for PDX and its therapeutic applications. "For us, the next step is to demonstrate the antidiabetic effects in humans and determine the receptor through which PDX acts."

In addition to André Marette, the study is authored by Phillip White, Philippe St-Pierre, Alexandre Charbonneau, Patricia Mitchell, Emmanuelle St-Amand, and Bruno Marcotte.

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Story Source:

The above story is based on materials provided by Université Laval. Note: Materials may be edited for content and length.

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Journal Reference:

1. Phillip J White, Philippe St-Pierre, Alexandre Charbonneau, Patricia L Mitchell, Emmanuelle St-Amand, Bruno Marcotte, André Marette. Protectin DX alleviates insulin resistance by activating a myokine-liver glucoregulatory axis. Nature Medicine, 2014; DOI: 10.1038/nm.3549

Intensive insulin provides survival benefit in patients with type 2 diabetes after heart attack

 

May 12, 2014

The Lancet

Intensive insulin treatment prolonged life by more than 2 years in patients with diabetes after a heart attack, compared with standard treatment for diabetes, a long term follow-up trial has shown. The trial, involving 620 patients with type 2 diabetes, began in 1990. Patients who were admitted to hospital with a suspected heart attack received either intensive insulin treatment, or standard glucose-lowering treatment for one year. The purpose of the study was to determine whether the difference in treatment affected all-cause mortality in the long-term.

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Long-term follow-up of the DIGAMI 1 trial -- a landmark study of type 2 diabetes in Sweden -- shows that intensive insulin treatment prolonged life by more than 2 years in patients with diabetes after a heart attack, compared with standard treatment for diabetes, reports Dr Viveca Ritsinger from the Unit of Cardiology of the Department of Medicine, Karolinska Institute, Stockholm, Sweden and colleagues in The Lancet Diabetes & Endocrinology.

The trial, involving 620 patients with type 2 diabetes, began in 1990. Patients who were admitted to hospital with a suspected heart attack received either intensive insulin treatment (an insulin-glucose infusion for at least 24 h, followed by insulin injection four times a day for at least 3 months) or standard glucose-lowering treatment (involving insulin only rarely) for one year. The purpose of the study was to determine whether the difference in treatment affected all-cause mortality in the long-term.

In the new study, patients were followed for up to 20 years, during which time most of them died. Those who received intensified insulin treatment during the trial survived an average (median) of 2·3 years longer compared with those who received standard treatment. The effect was apparent for at least 8 years after randomisation and thereafter leveled off. Patients who were at low cardiovascular risk (less than 70 years old, no history of heart attack or congestive heart failure) and had not previously had insulin therapy when the trial started seemed to benefit the most from intensive insulin treatment.

Although the results clearly show a benefit of intensive insulin treatment after a heart attack in patients with type 2 diabetes, the effect on survival seen is probably larger than would be seen if the trial was started today. Compared with 1990, when DIGAMI 1 began, there have been many advances in conventional treatment of patients with type 2 diabetes and cardiovascular complications, such as more frequent use of medication to lower cholesterol (statins) and blood pressure (angiotensin-converting-enzyme inhibitors).

According to Denise Bonds, of the National Institutes of Health, Bethesda, MD, USA, in an accompanying Comment, the new study "points to the benefit of good glucose control even when other risk factors such as lipids or blood pressure cannot be or are not modified…it provides an important reminder of how quickly medicine is advancing, something that is often forgotten in the busy day-to-day practice of medicine. In 20 years, we have gone from few glucose-lowering therapies to over half a dozen oral therapy drugs, plus insulin, plus effective treatments to reduce the risk of elevated lipids and blood pressure. Now, the challenge is choosing the best treatment option for our patients."

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Story Source:

The above story is based on materials provided by The Lancet. Note: Materials may be edited for content and length.

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Journal Reference:

1. Viveca Ritsinger, Klas Malmberg, Anton Mårtensson, Lars Rydén, Hans Wedel, Anna Norhammar. Intensified insulin-based glycaemic control after myocardial infarction: mortality during 20 year follow-up of the randomised Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI 1) trial. Lancet Diabetes Endocrinol, May 2014 DOI: 10.1016/ S2213-8587(14)70088-9