My Lab Notebook!

I am a full time biomedical scientist and researcher working in the field of nanomedicine at Oregon Health & Science University in Portland, OR.  Other than that I am a health-fitness enthusiast, public-health advocate, writer, and presenter. My current research involves finding new ways to treat type-1-diabetes and pancreatic cancer. Previosuly, I have worked towards understanding the pathological endochondral bone formation at nonskeletal sites and developed a gene therapy for it's inhibition. Via this platform, I aim to connect with the lay audience and communicate the lessons I have learned over the years while researching various diseases and discovering/developing novel treatment therapies, in easy to understand language with out the use of any scientific jargons. I hope you find it interesting and useful.

[sciencesmart]

“Sequence Me”: Importance of genome sequencing in cancer treatment

By Swati Mishra Ph.D.

10 Minutes Read

“When something is important enough, you do it even if odds are not in your favor” - Elon Musk

My this post tells a story of an unusual cancer survivor who not only fought his battle with cancer differently but used his journey with cancer as an opportunity to learn his disease at the molecular level and to educate other cancer patients with the lessons he learned. On October 1, I got an opportunity to meet with a Intel Corp. executive Bryce Olson, global head of marketing for health and life sciences, in an event Patient Views, Patient Voices and Bio on the Rocks, organized by Oregon Bioscience Association where I served as a member of the programing committee. Bryce’s role at his current position involves bringing technology and science together in the exciting area of genomics and personalized medicine with an overarching goal of saving lives using precision medicine. Bryce did not attend this event as the audience, rather participated as a patient and patient’s advocate. After hearing Bryce’s story, I was sincerely moved by his will of over coming odds, his determination to his goals and the realization that how each and every event in our lives, that otherwise seems chaotic at times, has a truly unique purpose. For me - It was THE first time when precision medicine seemed like a reality than just a promise.

So without further ado, Bryce’s story goes like this - in 2014, Bryce was diagnosed with an advanced stage metastatic prostate cancer at the age of 44. At the time of diagnosis, his cancer was already reached to his bones. According to him, this was one of the most aggressive cases of prostrate cancer doctors have seen at OHSU (Oregon Health & Science University), where he was receiving the treatment. He was given just 21 months to live. And in his words “He did not like that!”.  He simply put it this way. As recommended by his oncologist, Bryce took a route of standard therapy that incorporated first surgical removal of the prostate gland, followed by numerous rounds of cytotoxic chemotherapy, which caused serious side effects like mouth sores and numbness in his feet along with other well known side effects that I am not going to elaborate. His standard cancer treatment inhibited the uncontrolled growth of the cancer cells for sometime until 2015, when the cancer resurfaced again. Anyways, long story short – my this post is inspired by my meeting with Bryce, which means he is still alive and he’s beaten the odds. 

Star panelists @ashanthidesilva @TruEvolutionInc @bryceolson and @Biotronik for #patientviews2018 advocacy event.

Being at the position of global marketing director at Intel’s Health and Life Sciences group, during his initial battle with cancer, Bryce came across two most important words that changed his life forever: “Sequence Me”. And at the event he rocked his black t-shirt printed, “Sequence Me”. He took over the decision-making process from his doctor and strategically planned his battle against cancer, taking the approach of “precision medicine”. For those who are not familiar with the term - According to the national cancer institute “Precision medicine is an approach to patient care that allows doctors to select treatments that are most likely to help patients based on a genetic understanding of their disease. This may also be called personalized medicine.”

Picture Courtesy: Schematic shows the working mechanism of precision medicine

He started to assemble a team of scientists and first requested the genomic/DNA sequencing of his cancer cells so that he could get a clear understanding of what exactly at the molecular level was driving his cancer. In other words, with the help of genomic sequencing of his cancer cells, he wanted to know, which part of his DNA had accumulated the cancer causing mutation. He knew that with this kind of detailed molecular level understanding, he would be able to shortlist best and most effective treatment regime that would exactly match to target his cancer type. He contacted the head of pathology at OHSU and asked them to sequence the genetic material of his DNA. Just for your information, this procedure is state of the art in cancer research, relatively expensive, doesn’t come under standard procedures for cancer care and is not covered by most of the insurance plans. Therefore, most of the cancer patients are not aware of the procedure. And because every cancer is different at the molecular level, in the lack of this sequencing data, it is very difficult to figure out the most effective treatment for a particular type of cancer. Which explains why standard chemo drugs would never be effective for all types of cancers and why our current one-size-fits-all approach could never be an efficience approach in cancer treatment.  

The sequencing data informed Bryce that his cells got mutations in a couple of genes, Pi3K and PTEN, which was causing cells to proliferate uncontrollably. Pi3K (Phosphatidylinositol-4,5-bisphosphate 3-kinase), are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. The PTEN gene provides instructions for making the enzyme Pi3K. Therefore, Pi3K acts as a tumor suppressor, which means that it helps regulate cell division by keeping cells from growing and dividing too rapidly or in an uncontrolled way. Now you can easily understand, why mutations in these genes were causing his cells to behave crazy and divide uncontrollably.  

With this data handy, Bryce looked for all the available treatment options and found out that Cedars-Sinai Medical Center in Los Angeles was conducting a phase 1 clinical trial for an oral Pi3K inhibitor. In his words; “I called the principal investigator and told him that I want to get enrolled myself on the trial”. He received the response; “Sorry, there are no spots available.” Bryce told them that he had his sequencing data. “You have what?” asked the investigator. “No one ever called us with that before; can you come down?” He enrolled in March 2015. His cancer specific biomarkers started to go down and eventually cancer shut-down. He left the center with nothing more than a tiny bone lesion and some minor side effect of the experimental drug. This drug was approved only for his treatment so far by FDA. However, the limited supply of the experimental drug he received lasted only until April 2017 and when his cancer biomarker started to show up again, he had no option other than going back on standard radiation and chemotherapy. But this time, Bryce knows that there is a perfect treatment available, which is tailored just for him. Additionally, he could go for other drug options too that can keep uncontrolled cell proliferation under check. 

Bryce’s story depicts the true power of genomic data and how it could facilitate the development of customized treatment options based on the type of cancer. Bryce speaks about his story and how translating the advances in life sciences into clinical practice saved his life as a keynote speaker in biomedical and life science conferences, aiming to help patients understand these new opportunities. In addition, he uses music to raise money to develop the genomic healthcare technologies and to make — precision medicine — available to everyone with cancer. He also serves as a patient’s advocate/activist with a goal of empowering cancer patients with their own sequencing data.

To know more about precision medicine and Bryce Olson’s efforts to revolutionize precision medicine, please visit the following links:

Precision Medicine in Cancer Treatment

Precision medicine: the foundation of future cancer therapeutics

BRYCE OLSON WORKING TO RAISE $1 MILLION FOR THE KNIGHT CANCER INSTITUTE

Making Genomic Healthcare Available to Everyone

FACTS (Fighting against cancer through songs) Movement 

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[sciencesmart]

Wild: From Lost to Found on the Pacific Crest Trail

By Swati Mishra, Ph.D.

2 Minutes Read

This is my favorite read of 2018 so far. I couldn't put it down. Literally, could not put it (I mean my Kindle e-reader) down! Now can’t wait to start The Dream of a Common Language by Adrienne Rich. Once I learned about the poem “power”, and how it kept on pushing, inspiring and motivating the author Cheryl Strayed during her difficult teenage years, while she was struggling at becoming her true self and of course at the pacific crest trail, I fell in love with the poem. I found every word of the poem corroborating with Rich’s primary concern of promoting solidarity among women,

Power, by Adrienne Rich

“Living in the earth-deposits of our history

Today a backhoe divulged out of a crumbling flank of earth

one bottle amber perfect a hundred-year-old

cure for fever or melancholy a tonic

for living on this earth in the winters of this climate

Today I was reading about Marie Curie:

she must have known she suffered from radiation sickness

her body bombarded for years by the element

she had purified

It seems she denied to the end

the source of the cataracts on her eyes

the cracked and suppurating skin of her finger-ends

till she could no longer hold a test-tube or a pencil

She died a famous woman denying

her wounds

denying

her wounds came from the same source as her power”

[damienhaaas]

FAMOUS AUTHORS

Classic Bookshelf: This site has put classic novels online, from Charles Dickens to Charlotte Bronte.

The Online Books Page: The University of Pennsylvania hosts this book search and database.

Project Gutenberg: This famous site has over 27,000 free books online.

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Online Library of Literature: Find full and unabridged texts of classic literature, including the Bronte sisters, Mark Twain and more.

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eMedicine: This project from WebMD is continuously updated and has articles and references on surgery, pediatrics and more.

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FullBooks.com: This site has “thousands of full-text free books,” including a large amount of scientific essays and books.

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Online Mathematics Texts: Here you can find online textbooks likeElementary Linear Algebra and Complex Variables.

Science and Engineering Books for free download: These books range in topics from nanotechnology to compressible flow.

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byGosh: Find free illustrated children’s books and stories here.

Munseys: Munseys has nearly 2,000 children’s titles, plus books about religion, biographies and more.

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Bored.com: Bored.com has music ebooks, cooking ebooks, and over 150 philosophy titles and over 1,000 religion titles.

Ideology.us: Here you’ll find works by Rene Descartes, Sigmund Freud, Karl Marx, David Hume and others.

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The Sociology of Religion: Read this book by Max Weber, here.

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ReadBookOnline.net: Here you can read plays by Chekhov, Thomas Hardy, Ben Jonson, Shakespeare, Edgar Allan Poe and others.

Plays: Read Pygmalion, Uncle Vanya or The Playboy of the Western World here.

The Complete Works of William Shakespeare: MIT has made available all of Shakespeare’s comedies, tragedies, and histories.

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Public Bookshelf: Find romance novels, mysteries and more.

The Internet Book Database of Fiction: This forum features fantasy and graphic novels, anime, J.K. Rowling and more.

Free Online Novels: Here you can find Christian novels, fantasy and graphic novels, adventure books, horror books and more.

Foxglove: This British site has free novels, satire and short stories.

Baen Free Library: Find books by Scott Gier, Keith Laumer and others.

The Road to Romance: This website has books by Patricia Cornwell and other romance novelists.

Get Free Ebooks: This site’s largest collection includes fiction books.

John T. Cullen: Read short stories from John T. Cullen here.

SF and Fantasy Books Online: Books here include Arabian Nights,Aesop’s Fables and more.

Free Novels Online and Free Online Cyber-Books: This list contains mostly fantasy books.

FOREIGN LANGUAGE

Project Laurens Jz Coster: Find Dutch literature here.

ATHENA Textes Francais: Search by author’s name, French books, or books written by other authors but translated into French.

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Bibliolteca Virtual Miguel de Cervantes: Look up authors to find a catalog of their available works on this Spanish site.

KEIMENA: This page is entirely in Greek, but if you’re looking for modern Greek literature, this is the place to access books online.

Proyecto Cervantes: Texas A&M’s Proyecto Cervantes has cataloged Cervantes’ work online.

Corpus Scriptorum Latinorum: Access many Latin texts here.

Project Runeberg: Find Scandinavian literature online here.

Italian Women Writers: This site provides information about Italian women authors and features full-text titles too.

Biblioteca Valenciana: Register to use this database of Catalan and Valencian books.

Ketab Farsi: Access literature and publications in Farsi from this site.

Afghanistan Digital Library: Powered by NYU, the Afghanistan Digital Library has works published between 1870 and 1930.

CELT: CELT stands for “the Corpus of Electronic Texts” features important historical literature and documents.

Projekt Gutenberg-DE: This easy-to-use database of German language texts lets you search by genres and author.

HISTORY AND CULTURE

LibriVox: LibriVox has a good selection of historical fiction.

The Perseus Project: Tufts’ Perseus Digital Library features titles from Ancient Rome and Greece, published in English and original languages.

Access Genealogy: Find literature about Native American history, the Scotch-Irish immigration in the 19th and 20th centuries, and more.

Free History Books: This collection features U.S. history books, including works by Paul Jennings, Sarah Morgan Dawson, Josiah Quincy and others.

Most Popular History Books: Free titles include Seven Days and Seven Nights by Alexander Szegedy and Autobiography of a Female Slave by Martha G. Browne.

RARE BOOKS

Questia: Questia has 5,000 books available for free, including rare books and classics.

ARTS AND ENTERTAINMENT

Books-On-Line: This large collection includes movie scripts, newer works, cookbooks and more.

Chest of Books: This site has a wide range of free books, including gardening and cooking books, home improvement books, craft and hobby books, art books and more.

Free e-Books: Find titles related to beauty and fashion, games, health, drama and more.

2020ok: Categories here include art, graphic design, performing arts, ethnic and national, careers, business and a lot more.

Free Art Books: Find artist books and art books in PDF format here.

Free Web design books: OnlineComputerBooks.com directs you to free web design books.

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MYSTERY

MysteryNet: Read free short mystery stories on this site.

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Mystery Books: Read books by Sue Grafton and others.

POETRY

The Literature Network: This site features forums, a copy of The King James Bible, and over 3,000 short stories and poems.

Poetry: This list includes “The Raven,” “O Captain! My Captain!” and “The Ballad of Bonnie and Clyde.”

Poem Hunter: Find free poems, lyrics and quotations on this site.

Famous Poetry Online: Read limericks, love poetry, and poems by Robert Browning, Emily Dickinson, John Donne, Lord Byron and others.

Google Poetry: Google Books has a large selection of poetry, fromThe Canterbury Tales to Beowulf to Walt Whitman.

QuotesandPoem.com: Read poems by Maya Angelou, William Blake, Sylvia Plath and more.

CompleteClassics.com: Rudyard Kipling, Allen Ginsberg and Alfred Lord Tennyson are all featured here.

PinkPoem.com: On this site, you can download free poetry ebooks.

MISC

Banned Books: Here you can follow links of banned books to their full text online.

World eBook Library: This monstrous collection includes classics, encyclopedias, children’s books and a lot more.

DailyLit: DailyLit has everything from Moby Dick to the recent phenomenon, Skinny Bitch.

A Celebration of Women Writers: The University of Pennsylvania’s page for women writers includes Newbery winners.

Free Online Novels: These novels are fully online and range from romance to religious fiction to historical fiction.

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Authorama: Books here are pulled from Google Books and more. You’ll find history books, novels and more.

Prize-winning books online: Use this directory to connect to full-text copies of Newbery winners, Nobel Prize winners and Pulitzer winners.

[science-junkie]

… and here is a gift for all of us.

[sciencesmart]

For the love of books, here is the stuff to die for...

[sciencesmart]

Why elephants are resistant to cancer and what they teach us about cancer prevention

By Swati Mishra, Ph.D.

5 minutes read

Last week I have attended the 2018 Nanomedicine and Drug Delivery Symposium (NanoDDS), hosted here in Portland, Oregon. This three days scientific meeting brought together some of the world’s eminent scientists and clinical researchers from diverse array of fields including nanotechnology, materials science, imaging, cell biology, tissue engineering, gene editing, drug and gene delivery, who are trying to solve range of clinical problems with a common goal of improving the quality of life. The aim of this meeting was to highlight new groundbreaking discoveries and developments in nanomedicine and drug delivery. One of the talks that particularly enticed my attention was on developing “Personalized Cancer Nanomedicines”. The talk was delivered by Dr. Avi Schroeder from Technion-Israel Institute of Technology. Dr. Schroeder’s work is inspired by the cancer-resistance mechanism in elephants and is an attempt to apply this knowledge to humans in the hopes of developing new cancer treatments for children and families at high risk for developing cancer.

To summarize it for those who are not familiar with the pathogenesis of cancer, in healthy individuals, on an average a cell will divide for 50-70 times before it grows old and dies. Cancers develop when some of the cells in ours body accumulate mutations in their DNA that cause them to divide and proliferate uncontrollably and eventually start spreading into surrounding tissues.  Mutations in DNA, leading to cancer, can start in any one of the 30 trillion cells that make our body, which means all the cells are equally susceptible to cancer causing mutations. Therefore, the risk of cancer causing DNA mutation in any species theoretically increases with the total number of cells, which is directly proportional to the body-size and species life span, which is correlated to the total number of cell divisions. Though statistically this correlation holds true with in the species for eg, taller and over-sized humans are more likely to develop malignant tumors and bigger dogs are more susceptible to get cancers, this is not necessarily true across species. Which means it is not true that larger and longer-lived animals – like elephants and whales – would have a higher risk of cancer than smaller and shorter-lived animals – like mice and Chihuahuas.

Peto’s Paradox, published some 35 years ago by British epidemiologist Richard Peto of the University of Oxford, suggests that larger and longer-lived mammals develop less cancer than expected.

Though scientists have come up with multiple hypothesis while trying to solve Peto’s paradox over the years, the exact reason behind this mismatch of species size and cancer rate was mostly unknown until 2015, when two independent scientific discoveries by Dr. Joshua Schiffman and his team as well as by an evolutionary biologist at University of Chicago Dr. Vincent Lynch and his team, reported an important cellular mechanism for this phenomenon of cancer resistance. Before diving into the details reported in these papers, I would like to draw your attention to our body’s natural defense mechanism against cancer and to the role of a tumor suppressor gene that provides instructions for making tumor suppressor protein p53 (one of the most important players in cancer biology), which is often referred as “guardian of the genome”. Protein p53 is a crucial tumor protein that helps control cell growth and fight against cancer by either repairing the broken or damaged strands of DNA (repairing mutations), or kills off cells containing defective DNA. With p53 working enthusiastically against cancer, the probability of getting cancer causing mutation is one in billion: which means if exposed to massive DNA damaging carcinogenic environment like high doses of nuclear radiation, toxic chemicals, ultraviolet (UV) rays from sunlight etc. p53 will kill all the damaged cells and only about one in a billion damaged cells will contain a mutation likely to cause cancer. But, what if you get a mutation in the gene that encodes “guardian of the genome”. It has been seen that greater than half of all the tumors exhibit mutation in this gene and normal p53 function is compromised in most of human tumors. It is now known that the “mutant p53 proteins” (produced after mutation in the “guardian of the genome”) surprisingly gain tumor-promoting functions, which means inactivation of normal p53 protein leads to three cancer specific characteristics in the mutated cells - (1) cells with mutant p53 stimulate their own growth (cells will grow forever); (2) they resist inhibitory signals that might otherwise stop their growth (their DNA will be full of mutations); (3) they resist their programmed cell death even after infinite divisions (cells will never die). 

Picture Courtesy 

Each and every cell in our body contains two functional copies of this p53 gene. Here it is important to note that  –  with two functional p53 gene copies, the odds of getting cancer in your lifetime without ever being exposed into carcinogenic environment are; 1 in 2 for men and 1 in 3 for women.  Now let’s discuss the findings of the above two papers, Lynch and Schiffman hypothesized that elephants held some biological insight that could explain their resistance to develop cancer for an animal of their size and wondered whether that insight could help fight against cancer in humans. In two independent studies they subsequently found out that this large long-lived mammal indeed have 40 functional copies of p53 gene. It was later found that the african-elephant’s genome holds 40 copies of p53 where as asian-elephant’s genome holds p53 copies ranging from 30 to 40. These extra copies make elephant cells more sensitive to DNA mutations, and instead of repairing DNA the elephant cells prefer to launch the self-suicide program at levels of damage that human cells would tolerate. So under conditions that trigger DNA damage, elephant cells would just die to kill the tumor in the bud before it becomes malignant and that explains why elephants are so resistant to cancer for an animal of their size. 

This is not the end of the story, just so you know that it's not only elephants - there are some smaller species too that are highly cancer-resistant, for example naked mole rats, microbats and grey squirrels. Extensive molecular level investigation on these cancer resistance animals would allow scientists to explore – genetic differences, underlying mechanisms against cancer and cellular responses to DNA damage. And I am hopeful that the findings would soon help us putting the learnt lessons into a perspective that could strategically be applied in humans to prevent, to diagnose and to develop better treatment modalities for – cancer.

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Science backs - a diet that mimics fasting may reverse diabetes

By Swati Mishra Ph.D.

4 Minutes Read

You all must have heard of the ancient art of fasting and must have known someone in your lives an avid fast-dieter at some point of time. Fasting, that implicates abstinence of all or some types of foods or drinks or even water for certain durations of time, plays an integrative role in many cultural, religious and spiritual lifestyles. It is only recently that scientists and health care practitioner have begun to understand fasting associated potential health benefits for example healthy weight management, efficient blood glucose control, cardiovascular health, brain function and cognitive health and prevention from cancer. 

However, the focus of this post is not on fasting, instead on something slightly different from fasting – a scientific diet that mimics fasting with out skipping food for long periods of time. Fast mimicking diet (FMD™) is a periodic low-calorie (40% of normal calorie in-take) healthy diet protocol that consists of foods that are low-protein, low-carbohydrate and high-fat. This patented diet plan mimics the physiological and therapeutic effects of complete abstinence of food intake or water fasting over the course of five days, without depriving the body from important nutrients. Dr. Valter D. Longo, an Italian-American bio-gerontologist and a professor at the USC Davis School of Gerontology, who has been researching the link between caloric restriction and human health since 1997, last year published the findings of his pioneer study on the effects of FMD on the reversal of diabetes in the journal Cell. The study suggests that a temporary and specifically formulated FMD reverse the symptoms of type-1 and type 2 diabetes in late stage diabetic laboratory mice by promoting the growth of new insulin-producing pancreatic cells that otherwise have very limited capability to regenerate on their own. The study also showed that when the pancreatic cells, obtained from type-1-diabetic patients, were grown in lab under the conditions representing FMD, they interestingly re-started insulin production. 

In type 1 and late-stage type 2 diabetes, the pancreas loses most of it’s insulin-producing beta cells thereby it’s ability to produce insulin in response to fluctuating blood glucose levels. Growth of new insulin producing beta cells, scientifically referred as “regeneration of beta cells” where the damaged cells are replaced by the new healthy and functional cells, is one of the few interventional strategies to compensate for the damaged beta cells or loss of their functionality thus to help regulate blood glucose levels . 

At the molecular level, the diet induced regeneration in insulin producing beta cells occurred as the periodic cycles of FMD switched on genes responsible for the production of a protein, neurogenin-3 (Ngn3), which subsequently initiates the generation of new, healthy insulin-producing beta cells. At this point these results are only limited in mice and more research is needed to confirm these findings in humans, yet it provides a strong indication that along with healthy life style practices and strict exercise regimen, the FMD may help control or even reverse diabetes in humans.

Other than reversal in diabetes, Dr. Longo also found out that periodic fasting stimulates immune protection and regeneration during chemotherapy, and reduces risk factors for various age-related disorders including cardiovascular disease, Alzheimer’s disease and cancer.

Now let’s dive a little deeper and explore the nutritional configuration of a typical FMD plan - under FMD protocol, it is recommended to eat 1,100 calories that consist of 34% carbohydrates, 10% protein and 56% fat on day one, and 47% carbohydrates, 9% protein and 44% fat for the last four days. You might find modified versions elsewhere, specifically designed for weight loss, recommending even higher intake of fat, which allows for up to 80% calories coming from fast and 10% from protein and carbs, respectively. Therefore, it is advisable to consult your doctor, dietician or diabetes coach and customize the diet plan just for you under a professional guidance that takes care of proper micronutrients ratio and calorie counts based on your personal needs and health conditions. 

In Dr. Valter’s words “The Fasting Mimicking Diet allows the natural process of starvation (autophagy, protection, stem cell regeneration) to occur. You don’t interfere with the natural process. That’s a key of the Fasting Mimicking Diet.” 

If you are interested in learning more about FMD from authentic resources and it’s effects on human health, please visit the following links:

Fast Mimicking Diet by Dr. Valter Longo

Dr. Valter Longo on Resetting Autoimmunity and Rejuvenating Systems with Prolonged Fasting & the FMD

Live to 100: Valter Longo, PhD | Rich Roll Podcast

Fasting: Awakening the Rejuvenation from Within | Valter Longo | TEDxEchoPark

What to know about fasting, aging, the ‘longevity diet‘ and when you should eat

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Economic revolution and devolution of physical activity are linked to the unprecedented progression of type 2 diabetes in India and China

By Swati Mishra, Ph.D.

2 minutes read

I recently came across the article “Mysteries of type 2 diabetes: the Indian Elephant meets the Chinese Dragon” published last year in European Journal of Clinical Nutrition. I was intrigued by the title as much as the next guy, but the statistical figures about growing diabetes burden in asian countries especially india and china and the unconventional reason behind this, are what stumped me the most . Alarmingly, in just two decades, the number of individuals living with T2D is nearly doubled for india and tripled for china. Though T2D is highly complex and multifactorial in nature, which means there are several factors like genetic, epigenetic, environment etc; that play crucial role in the disease development; yet the authors present a pretty neat argument on how socioeconomic aspects in these two countries played a pivotal role in the progression of T2D. 

Over the past two decades, India and China have witnessed massive development in their economies, which facilitated spontaneous urbanization/industrialization and low physically active lifestyle due to increase in service sector jobs. Authors explain that - on one hand the rapid urbanization caused a dramatic migration to unplanned cities, lacking infrastructure to support physical activity, on the other hand the rapid westernization and improvement in socioeconomic status directed the increased consumption of processed foods which is easily available and usually high in refined sugars, carbohydrates and fat but deficient in protein and other micronutrients. In addition, improved per capita income encouraged sedentary lifestyle that increase a person’s risk for obesity and other diseases. Nevertheless, improved socioeconomic status was found to cause over nutrition as early as in the uterus. The study suggests that due to maternal obesity and development of diabetes during pregnancy (also known as gestational diabetes) provides excess nutrition in the uterus, which is also associated with an increased risk of diabetes in children. Interestingly, a similar study published in the Nature - Scientific reports earlier this year (April, 2018) confirms the findings by the PERU MIGRANT Study which addressed the impact of urban exposure on the incidence of T2D.

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[sciencesmart]

Type 2 Diabetes and Insulin Resistance

By Swati Mishra, Ph.D.

5 minutes read

Type 2 diabetes (T2D) is the most common form of diabetes and the most common long-term illness around the world. According to various sources, about 95% of all cases of diabetes are type 2. The way, number of T2Diabetics has risen over the past two decades around the world, currently makes it a global epidemic. In 1980 the number of people living with T2D was 108 million, this number has risen to 422 million in 2014. Amusingly at that time, researchers had estimated that there will be 400 million cases of T2D by the year 2015, well we have surpassed that target way ahead of time.  

Unlike type 1 diabetes, in T2D, cells in our body become resistant to the effects of insulin — which means cells don’t open their doors for glucose to enter for its metabolism even if insulin is around — and the beta cells in pancreas fail to meet the demand to overcome this insulin-resistance by producing and secreting more insulin. Though, insulin-resistant is the most prevalent cause of the clinical presentation of hyperglycemia in T2D, yet it is not the only cause. It is also possible to have T2D with out being insulin resistant; in that case which is less common — our beta cells are simply not making required insulin efficiently. Researchers have not yet come up with a cure for type 2 diabetes, but this condition if mild can be easily managed by making modifications in our daily life-style; for example — by carefully choosing our daily diet and planning meals in advance as well as by religiously sticking to a workout routine to maintain healthy weight. In more advance cases of diabetes, standard care medicines or insulin therapy can be recommended along with other life-style changes.

Photo Courtesy: http://diabetes-cure.me/

Therefore, by controlling our blood glucose levels through proper meal planning, exercise, and medical intervention, T2D associated long-term complications can be easily avoided or delayed. Yet, as the insulin resistance is believed to get worse overtime in the individuals diagnosed with type 2 diabetes, the condition eventually leads to the diagnosis of other medical complications in the long-term for example atherosclerosis (plaque builds up overtime leading to a heart attack, stroke or vessel blockage), coronary artery disease (major blood vessels that supply blood, oxygen and nutrients to our heart become damaged or diseased), hypertension (high blood-pressure), retinopathy (progressive damage to the retina leading to serious sight-threatening complication), nephropathy (kidney dysfunction leads to dialysis and/or kidney transplant) and neuropathy (nerve damage in hand and feet leading to lost sensation, pain, weakness, or tingling). Therefore the best practice in type 2 diabetes care is not just controlling the blood glucose levels but also keeping blood pressure, cholesterol and triglyceride levels in check.

There are several factors that place certain individuals at higher risk for T2D. Most important of them are their genetic predisposition, life-style choices and environmental factors. T2D has been strongly linked to our genes. However, exactly what gene or genes are responsible for it is still a topic of research. In addition, unlike other genetic disorders diabetes is not inherited in a simple pattern, which means it is not necessary that if you are a diabetic your children will develop it too. Researchers have put a great deal of effort in identifying the genes associated with diabetes with little success, further progress in this direction will enable it’s earlier detection or diagnosis before clinical presentation of hyperglycemia, implementation of early interventions and preventive measures in individuals at highest risk and development of more effective drug molecules and therapies.

If you are interested in learning ways to reduce your risk or motivation to manage your type 2 diabetes, please see the following links —

Choose More than 50 Ways to Prevent Type 2 Diabetes

Type 2 Diabetes and the Circle of Life

Diabetes Patients Need Guidance, Not Just Warnings

Six Ways to Stay Motivated to Manage Your Diabetes Well

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Glucagon : Risk of Hypoglycemia in Type 1 Diabetes

By Swati Mishra, Ph.D.

4 minutes read

So now we know what is insulin, its role and significance in type 1 diabetes (T1D) –Today’s blog post is about another very important metabolic hormone called “Glucagon” which works in tandem with insulin in regulating blood glucose levels and maintains the concentration in the tight range. 

People with T1D are absolute insulin deficient and are mostly put on insulin replacement therapy, which requirer them to inject exogenous insulin (exogenous insulin is any insulin that is not produced by the body and comes from outside) multiple times a day via syringe, inhalation device, insulin pump, insulin pen or insulin jet injector, in order to keep their blood glucose in check. In normal healthy people, the insulin-producing beta cells maintain a “perfect natural balance” between amount of glucose produced based on our food intake and insulin. Which means, whether we eat Wendy’s 940 calories Beaconator Burger or a 660 calories Taco Salad, pancreas puts out the exact amount of insulin needed to turn the glucose into energy. Since people with T1D cannot produce their own insulin and rely on external insulin, which is injected manually into the blood stream to metabolize glucose, they lose their ability to tightly maintain the perfect glucose-insulin balance. Therefore, sometimes too much insulin or not eating enough carbohydrates, results into blood-glucose levels lower than that required for normal functioning [healthy range is 90–130 milligrams per deciliter (mg/dL)]. This condition is called Hypoglycemia. In non-diabetic individuals, on the event of hypoglycemia (too much exercise, carbohydrate deficient diet, starving, fasting, sickness etc), “glucagon” takes matter into its hands. Unlike insulin, glucagon is produced by alpha cells in the pancreas in response to the below normal glucose levels. Glucagon works against insulin; it directs our liver to produce glucose from stored glycogen to replenish low glucose levels. At the same time it activates the synthesis of glucose from amino acids that are derived from proteins in our diet and accelerates break down of stored fats into fatty acids that can be used by cells as a fuel. 

Picture Courtesy: http://traitement-diabetee.com/ameli-diabete/?traitement-diabetee=858287641454664781

In people with T1D, the beta cells are damaged, but the alpha cells are still there to produce glucagon. However, in most of the type-1-diabetics, due to all time high levels of circulating insulin, the alpha cells are no more signal responsive – which means hypoglycemia does not stimulate glucagon production. This makes the matter worse, and make type-1-diabetics prone to severe hypoglycemia. Common symptoms associated with hypoglycemia are: sweating, fatigue, dizziness, hunger, and weakness. Severe symptoms include: heart rate higher than usual, blurred-vision, confusion, convulsions (a sudden, violent, irregular movement of a limb or of the body, caused by involuntary contraction of muscles), loss of consciousness and coma.

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Basic Science of Type 1 Diabetes

By Swati Mishra, Ph.D.

4 minute read

Type 1 diabetes is an autoimmune disorder, where our body’s immune system - our very own defense against infectious organisms and other invaders, mistakenly turns on us and starts attacking and destroying the insulin-producing beta cells in the pancreas. 

Due to the loss of these important cells, our body is no more able to produce insulin, a very important hormone responsible for the metabolism of glucose. Glucose - a type of sugar produced when the food we eat is digested, once metabolized generates energy that runs each and every cell in our body and sustain life. Upon production, glucose is absorbed by intestine and is delivered into the bloodstream, which transports it to all the cells. Now - insulin comes into play. While glucose circulating in the bloodstream can reach all the cells, it can't enter them by crossing over the cell membrane on it’s own. Insulin is the hormone which tells the cells to open their doors for glucose to enter. This becomes possible only when beta cells that tirelessly keep on sensing blood glucose levels, produce insulin upon sensing high concentration of glucose in blood.

In the absence of enough healthy beta cells or when the beta cells are dysfunctional, our bodies are unable to produce enough insulin to take care of circulating glucose. Therefore, glucose ends up circulating in blood for long period of times, without getting into the cells and the concentration builds up over time - resulting in the condition called hyperglycemia. If hyperglycemia is left untreated, could lead to serious complications requiring emergency care, such as a diabetic coma. Furthermore,  persistently high glucose concentrations in blood for long period of times, makes the blood sugary, sticky and thick, which eventually damages the blood vessel in our body where blood circulates - all the blood vessels ranging from the tiny ones in our toes and eyes to the large ones in hour heart are susceptible for this kind of damage. However, the damage most often occurs the eyes, heart, nerves, feet, and kidney.

Although type1 diabetes is often diagnosed in children and young adults, it can occur at any age. 

**Statistics: **Most reliable and up-to-date estimate of the world-wide burden of type 1 diabetes are available

American Diabetes Association estimates, there are 1.25 million Americans are living with this type of diabetes, which is about 5 percent of all diagnosed cases.

Furthermore, 40,000 people are diagnosed with type-1-diabetes each year in the United States.

Photo courtesy : The Courageous 1′s and Abbott Diabetes Care

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