Posted on Diabetes

Obesity is more prevalent in people with type 1 diabetes than previously thought


People with type 1 diabetes should be screened regularly for obesity and chronic kidney disease, according to a study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Almost half of the adults in the United States have obesity, a chronic progressive disease characterized by an individual having an excess of body fat. Obesity is one of the leading causes of death in the United States, and people with obesity are at an increased risk for many serious diseases and health conditions such as diabetes, heart and liver disease. Obesity is a main risk factor for developing type 2 diabetes, but it has not been previously seen as a major complication in type 1 diabetes.

In type 1 diabetes, the body completely stops making insulin. In type 2 diabetes, the body produces insulin, but the cells do not respond to insulin as well as they should and later in the disease often do not make enough insulin. Type 2 diabetes is more likely to occur in people who are over the age of 40, overweight, and have a family history of diabetes, although more and more younger people, are developing type 2 diabetes.

“Our study shows that obesity rates in adults with type 1 diabetes are increasing and mirror the rates in the general adult population,” said Elizabeth Selvin, Ph.D., M.P.H., of Johns Hopkins Bloomberg School of Public Health and John Hopkins University in Baltimore, Md. “Our research also highlights the high risk of kidney disease in people with type 1 diabetes. Kidney disease is often considered more common in people with type 2 diabetes, but our data shows adults with type 1 diabetes actually had a higher risk of kidney disease than those with type 2.”

The researchers studied data from 4,060 people with type 1 diabetes and 135,458 people with type 2 diabetes from the Pennsylvania based Geisinger Health System between 2004-2018. They found 37% of people with type 1 diabetes had obesity, and the prevalence of kidney disease was higher in people with type 1 diabetes than those with type 2 after adjusting for age differences (16% vs. 9% in 2018).

“Our results highlight the need for interventions to prevent weight gain and end-stage kidney disease in people with type 1 diabetes,” Selvin said.

Posted on Multiple Sclerosis

Unique weapon in immune system arsenal could unlock Multiple Sclerosis treatment

Generic drugs image


Generic drugs image CREDIT Unsplash

Researchers from The Australian National University (ANU) have identified why certain cells in the body, known as Th17 cells, go rogue and promote the onset of autoimmune diseases such as multiple sclerosis (MS). 

In a new study published in Nature Communications, scientists have discovered a previously unknown and nasty side effect of a bacteria-fighting weapon in the immune system’s arsenal called neutrophil extracellular traps (NETs). 

NETs are responsible for directly enhancing the production of harmful Th17 cells. 

“This discovery is significant as it provides a novel therapeutic target to disrupt these harmful inflammatory responses,” lead author Dr Alicia Wilson, from the Johannes Gutenberg-University Mainz in Germany, said.  

“It opens the doors to the development of new therapies targeting this harmful NET-Th17 interaction, hopefully improving treatments for MS and other autoimmune conditions in the future.” 

NETs, which are similar in appearance and function to spider webs, are produced by a subset of white blood cells called neutrophils. They capture and kill nasty bacteria and are designed to protect the body from infection. But as ANU researchers demonstrate, NETs also have a “dark side” causing them to manipulate Th17 cells, making them stronger and more dangerous.  

Th17 cells are normally beneficial because they defend the body against bacterial and fungal infections, but when over-activated, they can cause serious inflammation. In their aggressive form, Th17 cells are responsible for promoting autoimmune diseases such as MS.  

“We found that the NETs cause Th17 cells to become more powerful, which enhances their detrimental effects,” senior author Associate Professor Anne Bruestle, from the ANU Department of Immunology and Infectious Disease, said.  

By understanding how NETs turn Th17 cells from friend to foe, scientists believe they can use targeted therapies to inhibit the bad effects of NETs. 

Associate Professor Bruestle and a team of international researchers believe a drug originally designed to treat sepsis could be used to target the bad Th17 cells and in turn help patients with MS better manage their condition by providing some reprieve.  

The drug was developed by Professor Christopher Parish and his team, also from ANU, and has been more than 10 years in the making.  

“Because we see in both mice and humans that a group of proteins in NETs called histones can activate Th17 cells and cause them to become harmful, it makes sense that our histone-neutralising drug, mCBS, which was developed to treat sepsis, may also be able to inhibit the undesirable effects of NETs which are linked to driving MS,” Professor Parish said.  

Associate Professor Bruestle said: “While we cannot prevent autoimmune diseases such as MS, thanks to these types of therapies we hope to treat the condition and make it more manageable for people living with MS.” 

You can read more about the drug here. 

Posted on Diabetes, Obesity

Diabetes and Obesity – Harnessing intestinal cells to treat endocrine disorders?

Enteroendocrine cells growing in intestinal organoids


Using a newly developed protocol, Daniel Zeve, MD, and David Breault, MD, have been able to derive human enteroendocrine cells from human intestinal stem cells. They are shown here growing in a 3-D intestinal organoid . CREDIT Daniel Zeve, Boston Children’s Hospital

Enteroendocrine cells punch above their weight. Comprising just about 1 percent of intestinal cells, they produce, as a group, around 15 different hormones. These not only regulate intestinal function and digestion, but also influence metabolic functions like insulin secretion and appetite regulation.

A new technology platform developed at Boston Children’s could set the stage for tapping enteroendocrine (EE) cells to reverse diabetes, obesity, and gastrointestinal conditions like inflammatory bowel disease and irritable bowel syndrome. The platform, described in the journal Nature Communications, is designed to identify drugs that could expand EE numbers, get them to produce more of the needed hormones, or both.

“There’s been interest in exploiting human intestinal stem cells and EE cells to treat disease,” says David Breault, MD, PhD, associate chief of the Division of Endocrinology at Boston Children’s. “But the field is still in a nascent stage. This will open new avenues of discovery.”

Expanding enteroendocrine cells

Breault is founder and director of the Gastrointestinal Organoid Core, based jointly in the Divisions of Endocrinology and Gastroenterology at Boston Children’s. He and the study’s lead investigator, Daniel Zeve, MD, PhD, obtained tissue from intestinal biopsies of patients at Boston Children’s, housed in a biorepository, and from adult GI patients at Massachusetts General Hospital.

From the patient samples, the researchers isolated the intestinal crypts, the “valleys” between intestinal villi where many intestinal stem cells reside. From the intestinal stem cells, they created organoids, three-dimensional mini-organs that replicate the biology of the duodenum and rectum. These locations house relatively large numbers of hormone-producing cells. These organoids then became their platform for systematic testing of libraries of drugs.

“We tried a variety of small molecules with the goal of making more EE cells and/or more hormones,” says Zeve, an attending physician in endocrinology and a member of Breault’s lab.

The system identified three chemicals that, used in different combinations, drove the formation of EE cells and the production of six different hormones: somatostatin, serotonin, glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin, peptide YY, and glucagon-like peptide-1 (GLP-1).

Focus on diabetes

While others have tried to expand populations of EE cells, the new protocols are more efficient and avoid the need to use genetic techniques. Breault and Zeve have filed a U.S. patent application and now hope to scale up their platform for high-throughput drug testing. Their goal is to find FDA-approved compounds that have the same effect as their small molecules.

They are particularly interested in finding an oral drug that would enable people with type 1 diabetes to make insulin, or enable people with obesity to lose weight by getting them to produce GLP-1 to help regulate appetite and food intake. Drugs that mimic GLP-1 activity have been approved for weight loss and are frequently prescribed for type 2 diabetes. However, they have side effects, including nausea, vomiting, diarrhea, constipation, increased risk of respiratory infections, headaches, and possibly pancreatitis.

Breault and Zeve may also investigate medications to induce production of GIP, cholecystokinin, and peptide YY for diabetes and weight management.