Wellness

[cherry]

Study finds gene variant predisposes people to both Type 2 diabetes and low body weight

The counterintuitive finding underscores the importance of genetic data and the need for individualized diabetes risk assessment

University of North Carolina at Chapel Hill

A research team at the University of North Carolina at Chapel Hill's Gillings School of Global Public Health found that a well-known gene variant linked to Type 2 diabetes, called transcription Factor-7 like 2 gene, may also predispose someone to being leaner, or having a lower body weight.

These findings are striking because many individuals with Type 2 diabetes are obese. But individuals with this gene variant may be at risk for Type 2 diabetes even while maintaining a low body weight. As researchers uncover genes, they are finding distinct pathways through which individuals develop Type 2 diabetes. This information may be used in the future to tailor treatments to populations and individuals to help prevent diabetes or better control blood glucose levels once they develop diabetes.

Kari North, senior author of the study, is a professor of epidemiology in the UNC Gillings School of Global Public Health. This study is one of the first studies of the TCF7L2 gene in a very large, representative sample of diverse Hispanic Latinos and was published today in the journal BMC Obesity.

"The counterintuitive discovery that some people are predisposed to both being thin and developing Type 2 diabetes refocuses our attention on the need to collect data in diverse populations and across time," said North. "Hispanic Latinos are a diverse and understudied population, so this study is an important step forward for understanding their health risks."

The team used population-based study data from more than 9,000 Hispanic Latino adults, ages 21 to 76 years old, with complete weight history and genetic data from the Hispanic Community Health Study/Study of Latinos. Using complex modeling, researchers looked at the impact of a specific complex gene variant on changes in body mass index and then estimated the odds of Type 2 diabetes across time.

In the United States, Hispanic Latinos face a striking disparity in Type 2 diabetes, with one in two developing Type 2 diabetes. This population is also 50 percent more likely than whites to die of Type 2 diabetes.

"The other important takeaway from this study, which is especially timely now during National Hispanic Heritage Month, is that diverse populations, like Hispanics, who have ancestry from the Americas, Europe and Africa, are heterogeneous with distinct genetics," says North. "As we continue to develop initiatives around personalized medicine, we need to make sure that we are addressing the needs of all populations."

The research paper notes that the transcription Factor-7 like 2 gene is not routinely screened for in clinical practice. In the future, this research will help scientists use genetic information to understand the causes of diabetes and obesity and understand their relationship to each other. This can lead to personalization in medication and help clinicians offer better treatment and advice on adopting healthy lifestyles.

The study used cohort data with detailed medical histories, allowing the research team to demonstrate that leanness and Type 2 diabetes co-occur at a high rate in this diverse Hispanic Latino population.

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Lindsay Fernández-Rhodes, now of Pennsylvania State University, is lead author of the study and conducted research while at UNC-Chapel Hill. North and Fernández-Rhodes' research collaborators were Annie Green Howard, Mariaelisa Graff, Heather Highland and Kristin Young of UNC-Chapel Hill; Carmen Isasi, Qibin Qi and Robert Kaplan of Albert Einstein College of Medicine; Esteban Parra of University of Toronto at Mississauga; Jennifer Below of Vanderbilt University Medical Center; Anne Justice of Geisinger Health System; George Papanicolauo of National Heart Lung and Blood Institute; Cathy Laurie of University of Washington; Struan Grant of Children's Hospital of Philadelphia Research Institute; Christopher Haiman of University of Southern California; and Ruth Loos of Icahn School of Medicine at Mount Sinai.

About the University of North Carolina at Chapel Hill

The University of North Carolina at Chapel Hill, the nation's first public university, is a global higher education leader known for innovative teaching, research and public service. A member of the prestigious Association of American Universities, Carolina regularly ranks as the best value for academic quality in U.S. public higher education. Now in its third century, the University offers 77 bachelor's, 111 master's, 65 doctorate and seven professional degree programs through 14 schools and the College of Arts and Sciences. Every day, faculty, staff and students shape their teaching, research and public service to meet North Carolina's most pressing needs in every region and all 100 counties. Carolina's more than 323,000 alumni live in all 50 states, the District of Columbia and 149 countries. More than 169,000 live in North Carolina.

[cherry]

A clinical trial has shown that letting an algorithm decide the amount of insulin a person with type 1 diabetes needs can help keep blood sugar levels under control.

The algorithm, being developed at the University of Cambridge, is able to predict how much insulin is needed at each point in time based on the evolution of blood sugar levels of the patient, measured with a continuous glucose monitor. Although the goal is to fully automate the process to create an ‘artificial pancreas’, the version used in the trial still requires input from the patient during meals.

The study, funded by the JDRF, recruited 86 people with type 1 diabetes that were being treated with insulin pumps with non-optimal levels of blood sugar. Over 12 weeks, the patients that used the automated system had their blood glucose levels under control 65% of the time, as compared to 54% for those patients that decided the insulin they needed completely on their own.

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The automated system seemed to help particularly with high blood sugar, decreasing the median time spent with high sugar levels by almost 2.5 hours. Detailed results have been published on The Lancet.

These improvements are particularly relevant given that, sustained over time, high sugar levels cause severe long-term complications, including damage to the heart, nerves, kidney, eyes and skin.

“If sustained over longer period, the improvements will lead to significant reductions in diabetes complications and reduced burden of diabetes,” says Roman Hovorka, Professor at the University of Cambridge, who led the study.

As Hovorka told me, his group is now working on building a smartphone app to facilitate the use of this algorithm. “Our aim is to commercialize in 2019 or 2020.”

The algorithm sends the instructions to an insulin pump to release the amount of insulin needed at any moment

Some efforts to find a cure for type 1 diabetes, using stem cells or targeting the immune system, are underway, but they are still far from the market. In the meantime, automated insulin delivery could help improve the control of blood sugar levels and reduce the long-term complications of type 1 diabetes.

“The first devices that can change insulin dosing automatically based on sensor data are on the market now,” Rachel Connor, Director of Research Partnerships at JDRF, told me. “Technologies to push further and help people with type 1 manage their diabetes more closely, with fewer actions to take day to day are proving their worth in clinical trials.” 

Besides Hovorka’s group, the French company CellNovo is also developing systems for automatic insulin delivery along with a big consortium of research institutions.  

The ultimate goal is to build an artificial pancreas — a fully automated system that doesn’t need any input from humans to determine the insulin needed, even after a meal. But, as Hovorka pointed out, we’re not there yet. Faster insulins that shorten the reaction time to big, sudden changes in blood sugar are needed for that to happen.  

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[cherry]

Most patients diagnosed with type 2 diabetes are treated with a "one-size-fits-all" protocol that is not tailored to each person's physiology and may leave many cases inadequately managed. A new study by scientists at the Broad Institute of MIT and Harvard and Massachusetts General Hospital (MGH) indicates that inherited genetic changes may underlie the variability observed among patients in the clinic, with several pathophysiological processes potentially leading to high blood sugar and its resulting consequences.

By analyzing genomic data with a computational tool that incorporates genetic complexity, the researchers identified five distinct groups of DNA sites that appear to drive distinct forms of the illness in unique ways.

The work represents a first step toward using genetics to identify subtypes of type 2 diabetes, which could help physicians prescribe interventions aimed at the cause of the disease, rather than just the symptoms.

The study appears in PLOS Medicine.

"When treating type 2 diabetes, we have a dozen or so medications we can use, but after you start someone on the standard algorithm, it's primarily trial and error," said senior author Jose Florez, an endocrinologist at MGH, co-director of the Broad's Metabolism Program, and professor at Harvard Medical School. "We need a more granular approach that addresses the many different molecular processes leading to high blood sugar."

It's known that type 2 diabetes can be broadly grouped into cases driven either by the inability of pancreatic beta cells to make enough insulin, known as insulin deficiency, or by the inability of liver, muscle or fat tissues to use insulin properly, known as insulin resistance.

Previous research attempted to define more subtypes of type 2 diabetes based on indicators such as beta-cell function, insulin resistance, or body-mass index, but those traits can vary greatly through life and during the course of disease. Inherited genetic differences are present at birth, and so a more reliable method would be to create subtypes based on DNA variations that have been associated with diabetes risk in large-scale genetic studies. These variations can be grouped into clusters based on how they impact diabetes-related traits; for example, genetic changes linked to high triglyceride levels are likely to work through the same biological processes.

Early efforts to do so used a "hard-clustering" approach, in which each genetic variation was assigned to only one cluster. However, this failed to produce patterns that made biological sense.

Miriam Udler, an endocrinologist at MGH and postdoctoral researcher in the Florez lab, took another approach. She teamed up with Gaddy Getz and Jaegil Kim of the Broad's Cancer Genomics team to apply a "soft-clustering" approach known as Bayesian non-negative matrix factorization, which allows each variant to fall into more than one cluster.

"The soft-clustering method is better for studying complex diseases, in which disease-related genetic sites may regulate not just one gene or process, but several," said Udler.

The new work revealed five clusters of genetic variants distinguished by distinct underlying cellular processes, within the existing major divisions of insulin-resistant and insulin-deficient disease. Two of these clusters contain variants that suggest beta cells aren't working properly, but that differ in their impacts on levels of the insulin precursor, proinsulin. The other three clusters contain DNA variants related to insulin resistance, including one cluster mediated by obesity, one defined by disrupted metabolism of fats in the liver, and one driven by defects in the distribution of fat within the body, known as lipodystrophy.

To confirm these observations, the team analyzed data from the National Institutes of Health's Roadmap Epigenomics Project, a public resource of epigenomic data for biology and disease research. They found that the genes contained in the clusters were more active in the tissue types one would expect.

To further test whether each cluster had been assigned the correct biological mechanism, the researchers gathered data from four independent cohorts of patients with type 2 diabetes and first calculated the patients' individual genetic risk scores for each cluster. They found nearly a third of patients scored highly for only one predominant cluster, suggesting that their diabetes may be driven predominantly by a single biological mechanism.

When they next analyzed measurements of diabetes-related traits from high-scoring subjects, they saw patterns that strongly reflected the suspected biological mechanism and distinguished them from all other patients with type 2 diabetes -- for example, patients who fell into the obesity-mediated cluster were indeed found to have increased body-mass index and body fat percentage.

The results appear to reflect some of the diversity observed by endocrinologists in the clinic. For example, people who scored high on the lipodystrophy-like cluster were likely to be thinner than average but have insulin-resistant diabetes, similar to a rare type of diabetes in which fat accumulates in the liver, which is a fundamentally different process from insulin resistance that results from obesity.

"The clusters from our study seem to recapitulate what we observe in clinical practice," said Florez. "Now we need to determine whether these clusters translate to differences in disease progression, complications, and response to treatment."

In addition to paving the way to clinically useful subtypes, the work sheds light on the diverse pathophysiology underlying type 2 diabetes and offers a model for unraveling the heterogeneity of other complex diseases.

"This study has given us the most comprehensive view to date of the genetic pathways underlying a common illness, which if not adequately treated can lead to devastating complications," said Udler. "We're excited to see how our approach can help researchers make steps towards precision medicine for other illnesses as well."

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Story Source:

Materials provided by Broad Institute of MIT and Harvard. Original written by Leah Eisenstadt. Note: Content may be edited for style and length.

[cherry]

Researcher Shares How He Manages His Type 1 Diabetes

By Sysy Morales

October 2nd, 2018

Scientists who also live with diabetes are a great resource. They really “get” diabetes and they can help us with our diabetes questions.

Andrew Koutnik has lived with type 1 diabetes for 12 years and is a Ph.D. candidate in his last year at the University of Florida State, and he holds a Master’s in Biomedical Sciences.

He gave a TEDx UFS talk recently titled, Rethinking Nutrition for Type-1 Diabetics where he shares his type 1 diagnosis story and explains how he manages his diabetes and why he chooses to do it that way.

Koutnik shares that he found himself in the position to give this talk because of his type 1 diabetes and work as a metabolic researcher on low carb diets; his background in exercise physiology and awareness of other dietary lifestyle options, and his experience working with “some outstanding coaches who were professional athletes with and without Type-1,” he writes.

Koutnik stresses that as a researcher who approaches things with an open mind, he is “an advocate for what works.”

Watch the video to find out what worked to help him achieve incredible type 1 diabetes blood sugar management.

Soon we’ll be covering an urgent and fascinating 3-part series he’s written on the topic of type 1 diabetes so look out for that!

https://www.diabetesdaily.com/blog/do-we-have-to-accept-current-type-1-diabetes-protocol-594532/

[cherry]

http://typeonegrit.blogspot.com/

This will tell all diabetics how to achieve a low carb diet

[Trinity11]

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@cherry wrote:

Researcher Shares How He Manages His Type 1 Diabetes

By Sysy Morales

October 2nd, 2018

Scientists who also live with diabetes are a great resource. They really “get” diabetes and they can help us with our diabetes questions.

Andrew Koutnik has lived with type 1 diabetes for 12 years and is a Ph.D. candidate in his last year at the University of Florida State, and he holds a Master’s in Biomedical Sciences.

He gave a TEDx UFS talk recently titled, Rethinking Nutrition for Type-1 Diabetics where he shares his type 1 diagnosis story and explains how he manages his diabetes and why he chooses to do it that way.

Koutnik shares that he found himself in the position to give this talk because of his type 1 diabetes and work as a metabolic researcher on low carb diets; his background in exercise physiology and awareness of other dietary lifestyle options, and his experience working with “some outstanding coaches who were professional athletes with and without Type-1,” he writes.

Koutnik stresses that as a researcher who approaches things with an open mind, he is “an advocate for what works.”

Watch the video to find out what worked to help him achieve incredible type 1 diabetes blood sugar management.

Soon we’ll be covering an urgent and fascinating 3-part series he’s written on the topic of type 1 diabetes so look out for that!

https://www.diabetesdaily.com/blog/do-we-have-to-accept-current-type-1-diabetes-protocol-594532/

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Thanks for posting @cherry. Unfortunately, he is eating a lot of very high fat meals which will still probably affect his cardiovascular health. I followed his diet for almost 50 years and it still wasn't enough. Hopefully, some day we will have a cure.

[cherry]

Maybe it works for him @Trinity11..

[Trinity11]

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@cherry wrote:

Maybe it works for him @Trinity11..

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@cherry... wait, he is very young and has only had diabetes for 12 years. If he makes a habit of eating steak like he said in the video, he may regret it down the line.

Just because his A1C is normal if he is eating a very high fat diet, he will pay down the road.

[cherry]

I don't know about type 1 ,but I have had borderline  high cholesterol most of my life, and my heart is fine..I can't take statins, and I don't trust or like vegetarins  diets.  So many people in India are diabetic ,and its a big vegetarian society @Trinity11

Our bodies are so complex t,hings don't always affect us all the same

My neighbor has to have his eyes examined every 6 months. I don't .( We go to the same ophthalmologist. He  is very slim ,and has a lot of trouble with his bs crashing. He is very active...Last year when I went to the eye Dr, my vision hasn't changed. I have been wearing the same glasses for 4 years. I decided this year I will get new glasses even if my old ones are OK..WE are all different, but  we all still have something to deal with

[Trinity11]

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@cherry wrote:

I don't know about type 1 ,but I have had borderline  high cholesterol most of my life, and my heart is fine..I can't take statins, and I don't trust or like vegetarins  diets.  So many people in India are diabetic ,and its a big vegetarian society @Trinity11

Our bodies are so complex t,hings don't always affect us all the same

My neighbor has to have his eyes examined every 6 months. I don't .( We go to the same ophthalmologist. He  is very slim ,and has a lot of trouble with his bs crashing. He is very active...Last year when I went to the eye Dr, my vision hasn't changed. I have been wearing the same glasses for 4 years. I decided this year I will get new glasses even if my old ones are OK..WE are all different, but  we all still have something to deal with

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@cherry..Type 1 diabetes is very different than Type 2 diabetes. The majority develop it in early life and have many years ahead of them to develop complications. It often takes years for complications to show up, so the later in life you develop diabetes it has less impact. Maybe you can sustain higher cholesterol numbers but a Type 1 diabetic has triple the risk of dying from high cholesterol. Without treatment, it can be risky.

I agree totally with you about vegetarian diets. Mary Tyler Moore followed one for years and she still succumbed to the ravages of diabetes. One being her eyesight.