Your Brain and Diabetes

This content originally appeared on diaTribe. Republished with permission.

By Brett Goerl and Matthew Garza

Recent studies have shown a link between brain diseases like Alzheimer’s and Parkinson’s and diabetes.  Unfortunately, these conditions are becoming more common as our population grows older. Find out more and ways to improve brain health.

What are neurodegenerative diseases?

The term “neurodegenerative diseases” refers to a range of diseases in which the cells in our brains break down and can no longer perform their designated functions associated with movement or mental ability, according to the EU Joint Programme – Neurodegenerative Disease Research. The most common neurodegenerative diseases that affect people with diabetes are mild cognitive impairment (MCI) and dementia, which includes Alzheimer’s disease.

As we age, it is completely normal for our memory, thinking, and judgment to slightly decline. However, MCI occurs when our mental abilities decline faster than expected and begin to interfere with our daily lives. Age is by far the biggest risk factor for MCI, but diabetes, smoking, high blood pressure and cholesterol, obesity, and depression can further increase a person’s risk of developing MCI.

In around 10-15% of cases each year, the mental decline seen in MCI may progress further, making it difficult for us to carry out a healthy and happy life. When this happens, it is called dementia. The two most common types of dementia that affect people with diabetes are Alzheimer’s disease (AD) and vascular dementia.

While the symptoms of AD and vascular dementia are similar, they are caused by two different processes that occur in our brains. AD is thought to be caused by the abnormal build-up of proteins in the brain. One protein is “amyloid,” which clumps together in spaces around brain cells. The other protein is “tau,” which get tangled up inside brain cells. Vascular dementia, on the other hand, occurs when the blood vessels in our brain become narrow or start to bleed. This reduces the brain’s ability to get the oxygen it needs to keep brain cells healthy and for the brain to function properly. In both cases, brain cells become damaged, leading to a wide range of problems such as memory loss, worsened judgment, and personality changes.

AD is the most common form of dementia in the US, making up 60-70% of dementia cases. In the US, an estimated 5.4 million people of all ages are affected by AD, and one in eight people 65 years and older suffer from it. Considering the 14.3 million adults aged 65 and older in the U.S. who have diabetes, and it is easy to see why Alzheimer’s disease and diabetes are two of the most common diseases of aging. And recent research has suggested that they may be linked in various ways.

How do neurodegenerative diseases like Alzheimer’s and vascular dementia relate to diabetes? 

We often think of diabetes as a problem with our metabolism since the lack of insulin (in type 1 diabetes) or insulin resistance (in type 2 diabetes) affects our body’s ability to maintain normal blood glucose levels. However, our brain consumes the most glucose compared to any other organ in our body. While the brain accounts for roughly 2% of our body weight, it uses almost 20% of the sugars we eat or release from our body’s stores.

An increasing amount of research shows that people with AD and other forms of dementia experience insulin resistance in the CNS (central nervous system, which includes the brain and the spinal cord), similar to what people with type 2 diabetes experience in other areas of the body, such as the muscles, the liver, and the fat. Scientists have yet to determine exactly what the relationship between diabetes and AD or other forms of dementia may be caused by, but there are a few theories that have been proposed.

  • One of these theories focuses on brain insulin resistance, which is when brain cells stop responding normally to insulin, leading to problems related to the ways our brain cells communicate, use energy, and fight infection.
    • Insulin receptors can be found in many areas of the brain, where they are involved with brain cell growth, communication, and survival. While insulin levels are lower in the brain than in the bloodstream, all the insulin that makes its way to the brain comes from the same insulin produced in the pancreas – it crosses over what is known as the blood-brain barrier (or BBB). This barrier prevents unwanted things from the bloodstream from entering the brain. However, injected insulin does not cross the BBB. The reduced transport of insulin across the BBB may be why brain insulin levels are lower when the body experiences insulin resistance (such as in pre-diabetes and type 2 diabetes) and in diseases such as AD.
    • Insulin in the brain is known to help control our metabolism in certain other organs of the body, like the liver and fat tissue. The hypothalamus, the part of our brain that controls hunger, thirst, and emotions, is highly sensitive to levels of insulin in the brain. The association between type 2 diabetes and brain health may be due to problems with insulin’s actions in the hypothalamus, increasing a person’s likelihood of developing whole-body insulin resistance.
  • Diabetes also increases the risk for damaged blood vessels, leading to heart disease and stroke. Damaged blood vessels can starve the brain of oxygen, leading to cognitive decline and vascular dementia.
  • Diabetes disrupts how our bodies produce amylin, a hormone related to insulin that helps our bodies digest food. People with obesity and pre-diabetes often have high amounts of amylin, some of which can circulate and cross into the brain. Studies have shown that amylin can interact with the same protein deposits in the brain known to cause AD.
  • Experiencing hyperglycemia for long periods of time can degrade the myelin sheath (a protective layer that surrounds your neurons). This leads to issues in how your nerves send and receive signals to your body. It can also lead to your brain cells dying.

Type 1 diabetes could be a risk factor for dementia for many of the same reasons as type 2 diabetes. In particular, the cardiovascular complications such as heart disease and stroke that are associated with type 1 diabetes could provide an explanation for its relationship with vascular dementia. Additionally, higher rates of cognitive dysfunction for those with type 1 diabetes could be related to frequent cases of hyperglycemia and hypoglycemia. Indeed, severe hypoglycemic and hypoglycemic events are associated with increased dementia risk for older adults with type 1 diabetes.

Is diabetes a risk factor for developing neurodegenerative disease? 

On average, people with diabetes experience slightly more cognitive difficulties associated with MCI across their lifespan, but experiencing cognitive difficulty does not mean you will eventually get diagnosed with dementia or AD. The prevalence of type 2 diabetes and neurodegenerative diseases, however, both increase with age, meaning it is more common for older people (65+ years) with type 2 diabetes to get diagnosed with vascular dementia or AD.

Data suggests that people with diabetes have a 73% increase in the risk of developing any type of dementia and 56% increase in the risk of developing AD compared to people who do not have diabetes. This makes diabetes one of the strongest risk factors for getting dementia aside from aging. Health measures like A1C, cholesterolhigh blood pressure(or hypertension), and eGFR are negatively impacted by diabetes and may also be associated with cognitive performance and neurodegenerative diseases.

  • In the ACCORD-MIND trial, the largest and most rigorous study on diabetes and the brain to date, higher A1C levels were associated with lower cognitive function in people with diabetes. Similarly, another study found that the risk for dementia increased as a person’s A1C level increased, regardless of whether or not the person had type 2 diabetes.
  • A recent analysis of over 100 studies found that higher levels of LDL cholesterol (known as “bad cholesterol”) was an independent risk factor for the development of AD.
  • High blood pressure in middle-aged people has been linked to future cognitive decline and dementia, and in particular, vascular dementia. This may be due to high blood pressure in the brain causing damage to blood vessels, such as small blockages and bleeding.
  • In a study on kidney health and dementia recently published recently, researchers found that lower rates of kidney filtration (as measured by eGFR) were associated with higher risk of onset of both vascular dementia and AD.

What about Parkinson’s Disease?

Parkinson’s Disease (PD) is another neurodegenerative disease associated with aging. In PD, the cells in your brain deteriorate and begins to affect a person’s ability to perform daily activities associated with movement. Symptoms can include tremors (rhythmic shaking), muscle stiffness and rigidity, and PD can even slow your movement in a process called bradykinesia. It can also lead to other symptoms not associated with movement such as disrupting sleep, constipation, anxiety, depression, and fatigue.

As with other neurodegenerative diseases, research has been conducted to identify if there is a link between diabetes and PD. In particular, one study from 2018 showed an association between the two conditions. The researchers looked at the English National Hospital Episode Statistics and Mortality Data from 1999-2011 and divided the data into two cohorts, those with type 2 diabetes (2,017,115 people) at the time of hospital admission and those without (6,173,208 people). It was found that those with diabetes had a 30% higher chance of developing PD than those without, and the younger a person was with diagnosed type 2 diabetes, the more likely their chance of developing PD.

Though researchers do not yet understand the exact way that diabetes and PD are related, they do have a few hypotheses. Namely, there is the chance that certain genetic abnormalities that lead to diabetes may also lead to PD; even if one of these conditions does not directly cause the other, people who have one may be more likely to also have the other. In addition, when diabetes and PD coexist in a person, they may create a more hostile environment in the brain, leading the neurodegenerative processes underway in PD to speed up and be more severe.

What are strategies to reduce the risk of developing a neurodegenerative disease?

There is evidence that leading a healthy lifestyle can reduce your risk of developing diabetes-related complications like dementia or PD. For example, heart attacks and stroke can increase the risk of developing vascular dementia; therefore, lifestyle modifications that help you maintain an ideal blood pressure and levels of cholesterol for your age and health status are important. This can be accomplished by exercising regularly and consuming a diet low in saturated fat, salt, and sugar.

Below are some other tips for improving brain health, which can go a long way in reducing the risk of neurodegenerative diseases like AD. The good news is that many of these strategies are also recommended for managing diabetes.

  • Take control of your blood glucose levels by aiming for a greater time-in-range (TIR). To learn more about time-in-range goals, click here.
  • Smoking is associated with higher rates of dementia. In a recent review, smokers were 40% more likely to develop AD than non-smokers. Given that people with diabetes are at an increased risk of developing dementia, smoking is likely to increase this risk further. If you smoke or experience nicotine addiction, talk to your healthcare professional about a plan to quit or cut back.
  • Keep blood pressure at the target discussed with your health care provider (which might be 130/80 mmHg or less, if you are at high risk of cardiovascular disease) by exercising regularly and eating a diet low in salt (aim for less than 2,300 mg of sodium each day)
  • Take your diabetes medications consistently and as directed by your healthcare team. Some early evidence shows that certain diabetes drugs, like GLP-1 receptor agonists, may be beneficial for brain health. In fact, exenatide, a GLP-1 receptor agonist, is currently in clinical trials for treating PD.
  • A very active area of research focuses on the dementia-preventing effects of having an active and stimulating mental life and rich social networks. Working to maintain an active and socially rich lifestyle could help prevent some of the effects of diabetes on dementia risk.

If you are 65 years of age or older and have memory concerns or other cognitive complaints (i.e., brain fog, depression, personality change), talk to your healthcare provider about getting a cognitive assessment. Learn more here.

Source: diabetesdaily.com

Michelle L. Litchman Focuses on Diabetes Program Accessibility for People Who Are Deaf

This content originally appeared on Beyond Type 1. Republished with permission.

By Kayla Hui, MPH

Michelle L. Litchman, PhD, FNP-BC, FAANP, FADCES, assistant professor at the college of nursing at the University of Utah and medical director for Diabetes One-Day Education and Care Program at the Utah Diabetes of Endocrinology Center, was selected as a Betty Irene Moore Nurse Fellow. The fellowship is designed to develop nurse leaders and innovators who are making an impact in health care. Each fellow receives $450,000 over their fellowship tenure, including an extra $50,000 for their home institution. For Dr. Litchman, her project will focus on diabetes program accessibility for people who are deaf.

“This is really important to me because I have six family members who are deaf, including my mom. And so I’ve actually witnessed how some deaf people don’t receive the health care that they need,” Litchman tells Beyond Type 1.

Having type 2 diabetes is associated with a higher risk for hearing loss, according to a 2019 research study. For folks with pre-diabetes with blood glucose levels higher than normal, there was an associated 30 percent rate of hearing loss compared to individuals with normal blood sugar.

Barriers to Diabetes Program Accessibility

Litchman says that one of the challenges of current programs is that sign language interpreters are not always offered or available. She adds that when interpreters are available or offered, they are not always certified in communicating health information. “You need a medical interpreter, having someone that’s certified and also really knowledgeable about the medical terminology and space,” Litchman says.

Coupled with not having sign language interpreters available in the healthcare setting, Litchman stresses that health information is not always communicated in the language spoken by the patient who is deaf. “In a situation where there’s somebody who is deaf, you have to be providing that information directly to that person in their primary language,” Litchman explains. “There’s an assumption that people who are deaf also know English. For many, their primary language is actually sign language.”

Over the next three years, Litchman will design diabetes programs with language in mind and a focus on language deprivation–when children are not exposed to sufficient linguistic stimuli during the critical periods of language acquisition. According to Litchman, some parents do not teach their children sign language. “If they’re not taught sign language, they’re relying on reading lips. It actually deprives them of a lot of language, reading lips [has] only about 30 to 40 percent accuracy.”

Research shows that patients who are deaf or hard of hearing experienced poorer direct child-caregiver communication. Continuous exclusion from family communication was associated with a higher risk for chronic health outcomes.

“People may have home sign language, American sign language, reading lips, relying on captions,” Litchman says. Because the language used varies for each person, Litchman will leverage language deprivation research to inform her diabetes programming. “My work has some peer support threads. So I am hoping when we do these sessions, there’ll be group sessions where they can lean on one another for tips and tricks on how to make things work in their life,” Litchman explains. “I think a lot of us hope to improve outcomes related to diabetes, helping people feel like they can self manage, have the information, feel like they also have a group of people that they can lean on,” Litchman shares.

Source: diabetesdaily.com

Insulin at 100, Part 3: Insulin’s Uncertain Future

This content originally appeared on diaTribe. Republished with permission.

This is Part 3 of James S. Hirsch’s exploration of the riveting history of insulin, on the occasion of its 100th birthday.

Part 1: The Discovery

Part 2: Failed Promises, Bold Breakthroughs

Insulin’s Uncertain Future

Insulin

Image source: Emily Ye, Diabetes Daily

As further refinements in insulin occurred, the insulin narrative should have become even more powerful – that insulin not only saves people, but in reaching new pharmacological heights, it is allowing patients to live healthier, better, and more productive lives. These should be insulin’s glory days – as well as days of unprecedented commercial opportunity. According to the International Diabetes Federation, in 2019, the global population of people with diabetes had increased a staggering 63 percent in just nine years – to 463 million patients.

Insulin sales should be booming, with a new generation of Elizabeth Evans Hughes and Eva Saxls to tell the story. In fact, insulin sales are declining, and insulin has no spokespeople. Reasons vary for these developments, but one fact is undeniable: insulin has lost its halo.

Insulin is still essential for any person with type 1 diabetes, though even with type 1 patients, insulin is sometimes under-prescribed as doctors fear getting sued over a severe hypoglycemic incident. The belief is that patients are responsible for high blood sugars, doctors for low blood sugars.

Where insulin has lost its appeal is with type 2 patients, which has driven the diabetes epidemic in the U.S and abroad. According to the CDC, from 2000 to 2018, America’s diabetes population surged 185 percent, from 12 million to 34.2 million, and an estimated 90 percent to 95 percent of that cohort has type 2. (The global percentage is similar.) These patients have long had options other than insulin – metformin, introduced in 1995, remains the ADA’s recommended first-line agent. But as a progressive disease, type 2 diabetes, in most cases, will eventually require a more intensive glucose-lowering therapy. Nothing achieves that objective better than insulin, but insulin is delayed or spurned entirely by many type 2 patients.

Some concerns are longstanding; namely, that insulin can lead to weight gain because patients now retain their nutrients. Some type 2 patients wrongly associate insulin with personal failure surrounding diet or exercise, so they want to avoid the perceived stigma of insulin. Some people just don’t like injections. Meanwhile, other patients associate insulin with the medication that an ailing patient takes shortly before they die: insulin as a precursor to death. Some clinicians who care for Hispanic patients refer to insulin pens as las plumas to avoid using a word that carries so much baggage.

What’s striking is how dramatically the cultural narrative has changed, from insulin the miracle drug to insulin the medical curse. And where are the commercials, the movies, the documentaries, and the splashy publicity campaigns about the wonders of insulin? They don’t exist.

The greatest impact on insulin use in type 2 diabetes has been the emergence of a dozen new classes of diabetic drugs. These include incretin-based therapies known as GLP-1 agonists and DPP-4 inhibitors (introduced in the 2000s) as well as SGLT-2 inhibitors (introduced in 2014). diaTribe has covered these therapies extensively, and their brands are all over TV: Trulicity, Jardiance, Invokana, and more. They all seem to have funky names, and like insulin, they can all lower blood sugars but – depending on which one is used – some have other potential advantages, such as weight loss. (Some have possible disadvantages as well, including nausea.)

The expectations for these drugs were always high, but what no one predicted was that GLP-1 agonists and SGLT-2 inhibitors have been shown to reduce the risk of both heart and kidney disease – findings that are a boon to type 2 patients, who are at higher risk of these diseases. These findings, however, were completely accidental to the original mission of these therapies.

Insulin, the miracle drug, has been eclipsed by drugs that are even more miraculous!

Consider Eli Lilly, whose Humalog is the market-leading insulin in the United States. In 2020, Humalog sales fell 7 percent, to $2.6 billion, while Trulicity, its GLP-1 agonist, saw its sales increase by 23 percent, to $5 billion.

That’s consistent with the global insulin market. Worldwide insulin sales in 2020 declined by 4 percent, to $19.4 billion, marking the first time since 2012 that global insulin sales fell below $20 billion.

It’s quite stunning. Amid a global diabetes epidemic, and with the purity, stability, and quality of insulin better than ever, insulin sales are falling. (Pricing pressures from insurers and government payers have also taken a revenue toll.) In 2019, Sanofi announced that it was going to discontinue its research into diabetes, even though its Lantus insulin had been a blockbuster for years. More lucrative opportunities now lay elsewhere.

Falling sales may not be the insulin companies’ biggest problem. Public scorn is. Though the insulins kept getting better, the prices kept rising, forcing many patients to ration their supplies, seek cheaper alternatives in Canada or Mexico, or settle for inferior insulins. Some patients have died for lack of insulin. According to a 2019 study from the nonprofit Health Care Cost Institute, the cost of insulin nearly doubled for type 1 patients in the United States between 2012 and 2016 – they paid, on average, $5,705 a year for insulin in 2016, compared to $2,864 in 2012.

Many patients are outraged and have used social media to rally support – one trending hashtag was #makeinsulinaffordable. Patient advocates have traveled to Eli Lilly’s headquarters to protest. In March of this year, nine Congressional Democrats demanded that the Federal Trade Commission investigate insulin price collusion among Eli Lilly, Novo Nordisk, and Sanofi, asserting they “are using their stranglehold on the market to drive up costs.” The letter notes that as many as one in four Americans who need insulin cannot afford it, and at least 13 Americans have died in recent years because of insulin rationing.

The criticism has been unsparing. In April 2019, in a hearing for the U.S. House of Representatives on insulin affordability, Democrats and Republicans alike pilloried the insulin executives. At one point, Rep. Jan Schakowsky (D-Illinois) said to them, “I don’t know how you people sleep at night.”

Insulin is hardly the only drug whose price has soared, but as the Washington Post noted last year, insulin is “a natural poster child of pharmaceutical greed.”

In response, the insulin companies have adopted payment assistance programs to help financially strapped consumers. They also blame the middlemen in the system – the PBMs, or the Pharmaceutical Benefit Managers – for high insulin prices, who in turn blame the insulin companies, and everyone blames the insurers, who point the finger at the companies and the PBMs.

Drug pricing in America is so convoluted it’s impossible for any patient to accurately apportion blame, but the history of insulin explains in part why the companies have come under such attack. When Banting made his discovery, he sold the patent to the University of Toronto for $1. He said that insulin was a gift to humankind and should be made available to anyone who needs it. Insulin was always profitable for Eli Lilly and the few other companies who made it, and critics have complained that the companies found ways to protect their patents by making incremental improvements in the drug.

But for years, those complaints were easily dismissed. The companies were revered for their ability to mass produce – and improve – a lifesaving drug that symbolized the pinnacle of scientific discovery while doing so at prices that were affordable.

When prices became unaffordable – and regardless of blame – the companies were seen as betraying the very spirit in which insulin was discovered and produced, and their fall from grace has few equivalents in corporate history.

Is the criticism fair?

Hard to say, but even the companies would acknowledge that they’ve squandered much good will. Personally, I’m the last person to bash the insulin companies – they’ve kept me and members of family alive for quite some time. Collectively, my brother, my son, and I have been taking insulin for 117 years, so I feel more regret than anger: regret that at least one insulin executive didn’t stand up and say loudly and clearly:

“Insulin is a public good. No one who needs it will be without it. And we will make it easy for you.”

Insulin

Image source: Emily Ye, Diabetes Daily

Whatever that would cost in dollars would be made up for in good will – and such a public commitment would honor the many anonymous men, women, and children, before 1921 and after, who gave their lives to this disease.

The next chapter for insulin? It will almost certainly include continued improvements. Both Eli Lilly and Novo Nordisk are trying to develop a once-a-week basal insulin to replace the current once-a-day options – that would be a major advance is reducing the hassle factor in care. Research also continues on a glucose-sensitive insulin, in which the insulin would only take effect when your blood sugar rises. That would be a breakthrough, but investigators have spent decades trying to make it work.

Since its discovery, the ultimate goal of insulin has been to make it disappear, as that would mean diabetes has been cured. It turns out that insulin therapy may indeed disappear someday, even if no cure is found. Since its discovery, the ultimate goal of insulin has been to make it disappear, as that would mean diabetes has been cured. It turns out that insulin therapy may indeed disappear someday, even if no cure is found.

Stem-cell therapy has long held promise in diabetes – specifically, making insulin-producing beta cells from stem cells, which the body would either tolerate on its own (perhaps by encapsulating the cells) or through immunosuppressant drugs. Progress has been halting but is now evident. Douglas Melton began his research in this area in 1991, and in 2014, he reported that his lab was able to turn human stem cells into functional pancreatic beta cells. The company that Melton created for the effort was acquired by Vertex Pharmaceuticals, and earlier this year, Vertex announced that it had received approval to begin a clinical trial on a “stem-cell derived, fully differentiated pancreatic islet cell therapy” to treat type 1 diabetes. Another company, ViaCyte, also announced this year that it will begin phase 2 of a clinical trial using encapsulated cells in hopes that they will mature into insulin-secreting beta cells.

It may take 10 to 15 years, but leaders in the field are cautiously optimistic that a cell-based therapy will someday provide a better option than insulin.

Diabetes would survive, but the therapy once touted as its cure would be dead.

Because I have a soft spot for happy endings – and because so much of own life has been intertwined with insulin – I have my own vision for insulin’s last hurrah.

A group of researchers in Europe are conducting a clinical trial to prevent type 1 diabetes. Called the Global Platform for the Prevention of Autoimmune Diabetes, the initiative began in 2015, and researchers are testing newborns who are at risk of developing type 1 to see if prevention is possible.

And what treatment are they using?

Oral insulin.

Like the discovery of insulin itself, this effort is a longshot, but if it works, insulin will have eradicated diabetes – a fitting coda for a medical miracle.

I want to acknowledge the following people who helped me with this article: Dr. Mark Atkinson, Dr. David Harlan, Dr. Irl Hirsch, Dr. David Nathan, Dr. Jay Skyler, and Dr. Bernard Zinman. Some material in this article came from my book, “Cheating Destiny: Living with Diabetes.”

About James

James S. Hirsch, a former reporter for The New York Times and The Wall Street Journal, is a best-selling author who has written 10 nonfiction books. They include biographies of Willie Mays and Rubin “Hurricane” Carter; an investigation into the Tulsa race riot of 1921; and an examination of our diabetes epidemic. Hirsch has an undergraduate degree from the University of Missouri School of Journalism and a graduate degree from the LBJ School of Public Policy at the University of Texas. He lives in the Boston area with his wife, Sheryl, and they have two children, Amanda and Garrett. Jim has worked as a senior editor and columnist for diaTribe since 2006.

Source: diabetesdaily.com

Insulin at 100: An Inspirational but Complicated History

This content originally appeared on diaTribe. Republished with permission.

By James S. Hirsch

The discovery of insulin promised a new age for an ancient condition but introduced unexpected challenges. James S. Hirsch explores the riveting history of this miracle drug on its 100th anniversary.

PART 1: The Discovery

It was hailed as a miracle cure, a boon to the human race, an elixir that turned death into life and whose discovery was freighted with Biblical allusions. This year marks the one-hundredth anniversary of insulin, and the drug, first coaxed from the pancreas of dogs by unheralded scientists in a crude Canadian laboratory, remains one of the most remarkable feats in medical history.

But the history of insulin is not one of unalloyed celebration. It has moments of triumph as well as grievance. Like diabetes itself, it’s complicated.

***

It’s easy to lose sight of what insulin’s discovery represented in 1921. As the historian John Barry notes, the previous 2,500 years had seen virtually no progress in the treatment of patients, and the world had just emerged from the Spanish flu, which killed more than 50 million people and was ultimately subdued not by medical science but by the immune system’s adapting to the virus.

In other words, doctors in 1921 were all but impotent against any serious disease, including diabetes.

Then came insulin.

Anyone today who uses insulin does not need to be told of its life-saving power, and I am hardly an impartial observer, as it has kept me alive for the past 44 years.

Insulin today, however, bears little resemblance to what it was when I was diagnosed, let alone to what it was in its early decades. Patients then relied on imposing glass syringes whose thick needles had to be sharpened on whet stones and boiled for reuse. Nowadays, the ultrafine needles are disposable; smart insulin pens communicate with the cloud; and sleek insulin pumps are connected to continuous glucose meters. The insulin itself has been transformed – from impure concoctions derived from the smashed, blood-soaked pancreases of pigs or cows to laboratory-created, gene-splitting analogs with an array of pharmacokinetic properties. Inhalable insulin, long promised and finally delivered, represents a vaporous new-age alternative.

Research on insulin has attracted some of the world’s most brilliant scientists, as Nobel prizes have been given for insulin-related research in four separate decades. The work conducted on human insulin in the 1970s and ’80s, involving recombinant DNA, helped give birth to the modern biotechnology industry, including such pillars as Genentech and Biogen.

But there is more to this history than scientific breakthroughs and professional laurels.

Insulin has been misrepresented and misunderstood, even by some of its most important standard bearers, to the detriment of patients. For many years, the miraculous power of insulin, promoted in marketing efforts and publicity stunts, misled the public about the real-life experiences of those actually living with diabetes. In more recent years, insulin has been shunned by type 2 patients who could be using it or has been underused by type 1 patients. We are in the midst of a global diabetes epidemic, but insulin use has actually been declining because better therapies for type 2 diabetes have usurped insulin’s preeminence. And as insulin prices have soared, the insulin companies themselves, in a stunning reversal, have been transformed in some eyes from saviors to villains.

Meanwhile, the future of insulin itself is not certain, as better therapies could someday make obsolete the miracle drug of 1921.

***

Insulin was not technically “discovered” in 1921. Its role in the body was already known, its connection to diabetes already established.

The disease was first identified in 1500 BC, and in 250 BC, the disorder was named “diabetes” from the Greek word syphon, as its victims suffered from excessive urination. (One researcher later described diabetes as “the pissing evil.”) Researchers’ understanding of the disease advanced in 1869, when a German medical student named Paul Langerhans discovered “islands of cells” in the pancreas; and over the next three decades, investigators identified these cells as regulating glucose metabolism and directly associating them with diabetes. By 1916, the word “insulin” had been coined to describe that pancreatic substance.

But after more than 3,000 years, there was still no effective treatment for the disease. Researchers, however, did recognize that carbohydrates accelerated a patient’s decline, so the best treatment, developed in the early 1900s, was to withhold food – also known as the starvation diet, which allowed patients to extend their lives in sinister emaciation. Most of these patients were children, so grieving parents had to watch their children waste away – sometimes clustered together in hospital wards – and die either from starvation or diabetic ketoacidosis.

That made the search for insulin even more desperate, as investigators around the world sought to discover a “pancreatic extract” to save these dying children against the ravages of an ancient disease.

Research

Image source: iStock Photo

The breakthrough happened in Toronto in 1921, led by a prickly researcher who was a mere five years out of medical school. Frederick Banting had tried his hand as a surgeon but couldn’t earn a living, so he turned to teaching. He had no research experience and knew little about diabetes; but he had read a paper on it, and he later said that he had a dream about discovering insulin. In a longshot bid, Banting began his work in May at the University of Toronto, and he was assisted by a young medical student named Charles Best. They removed the pancreases from dogs to make them diabetic and then developed pancreatic extracts to try to lower the blood sugars. It was bloody, messy, difficult work – seven dogs died the first two weeks – but by August, one of the extracts, delivered by intravenous injections, proved successful. A biochemist, James Collip, was summoned to try to purify it for human use – he later called it “bathroom chemistry” – and on January 11, 1922, a 14-year-old boy, Leonard Thompson, received the first injection of insulin.

It was described as a “murky, light brown liquid containing much sediment,” it was given to him over several weeks, and it worked: the sugar and ketones in the boy’s urine disappeared.

“Diabetes, Dread Disease, Yields to New Gland Cure,” the New York Times announced.Tweet this“Diabetes, Dread Disease, Yields to New Gland Cure,” the New York Times announced.

The Toronto researchers couldn’t mass produce insulin, but Eli Lilly could, at least in the United States. (Other companies did in Europe.) Eli Lilly is headquartered in Indianapolis and, at the time, was in convenient proximity to many stockyards. The company stored a million pounds of frozen pancreases from pigs and cows to keep up with demand – there were an estimated one million Americans who needed insulin – and the company’s scientists, managers, and laborers were every bit the heroes as the Toronto researchers.

This new miracle drug did not disappoint.

Frederick Allen, one of America’s leading diabetologists, said his patients, upon receiving insulin, “looked like an old Flemish painter’s depiction of a resurrection after famine. It was a resurrection, a crawling stirring, as of some vague springtime.”

Elliott Joslin, America’s preeminent diabetes clinician, described his patients who took insulin as the “erstwhile dead” and invoked Ezekiel’s vision of the valley of the dry bones, in which God says, “Come from the four winds, O breath, and breathe upon these slain, that they may live.”

The photographs told an even more dramatic story: In one famous picture, a naked 3-year-old boy who weighs 15 pounds clings to his mother, his face grimacing, his ribs exposed. After taking insulin for only three months, a head shot shows the boy with full cheeks, alert brown eyes, and dark locks of hair. He looks normal – and cured.

If there were any doubt about insulin’s curative powers, Elizabeth Evans Hughes removed them. Her father, Charles Evans Hughes, had been the governor of New York, a justice on the U.S. Supreme Court, a candidate for president, and in 1922, was the U.S. Secretary of State. Elizabeth had been diagnosed with diabetes in 1919, so when she took her first dose of insulin in 1922, she became the poster child for this new drug.

After more than three millennia, it appeared that medical science had defeated diabetes.Tweet this“Hughes’ Daughter ‘Cured’ of Diabetes” declared one unidentified newspaper. After more than three millennia, it appeared that medical science had defeated diabetes.

Stay tuned for parts two and three of this riveting story over the next two weeks!

I want to acknowledge the following people who helped me with this article: Dr. Mark Atkinson, Dr. David Harlan, Dr. Irl Hirsch, Dr. David Nathan, Dr. Jay Skyler, and Dr. Bernard Zinman. Some material in this article came from my book, “Cheating Destiny: Living with Diabetes.”

About James

James S. Hirsch, a former reporter for The New York Times and The Wall Street Journal, is a best-selling author who has written 10 nonfiction books. They include biographies of Willie Mays and Rubin “Hurricane” Carter; an investigation into the Tulsa race riot of 1921; and an examination of our diabetes epidemic. Hirsch has an undergraduate degree from the University of Missouri School of Journalism and a graduate degree from the LBJ School of Public Policy at the University of Texas. He lives in the Boston area with his wife, Sheryl, and they have two children, Amanda and Garrett. Jim has worked as a senior editor and columnist for diaTribe since 2006.

Source: diabetesdaily.com

Asian Isn’t a Monolith: Why More Specific Data Matters in Diabetes Research

This content originally appeared on Beyond Type 1. Republished with permission.

By Kayla Hui, MPH

In the United States, diabetes affects 20 percent of the Asian American population, but that broad statistic doesn’t paint the whole picture. Despite being the fastest-growing racial group in the United States, health outcomes are often categorized by broad racial and ethnic categories, which limits our understanding of how diabetes truly impacts individual ethnic groups within the Asian diaspora. Disaggregated data—showing how diabetes impacts people from more specific origins—could help us better understand how to support and treat individual groups within the Asian American Pacific Islander communities.

“Asian Americans have 50 different ethnicities. Putting 50 ethnicities into one Asian American and Pacific Islander (AAPI) group—that is a fallacy,” H. Chris Hahm, PhD, MSSW, professor at the Boston University School of Social Work and lead researcher for the Epi Asian American Women’s Action In Resilience Empowerment (AWARE) study tells Beyond Type 1. According to the Pew Research Center, the majority of the 20 million Asians that live in the U.S. have roots that trace back to at least 19 countries in East Asia, Southeast Asia, or the Indian subcontinent.

Hahm says that because each ethnic group differs significantly across a variety of factors such as educational attainment, culture, and income level, having disaggregated data is imperative when trying to study diabetes among ethnic groups across the Asian diaspora.

For example, a research study, published in Diabetes Care, looked to understand the prevalence of type 2 diabetes among the U.S. South Asian communities when compared with four racial and ethnic groups: African Americans, white, Latinos, and Chinese Americans. In the study, South Asians include individuals originating from India, Pakistan, Nepal, Sri Lanka, and Bangladesh. While the study did not disaggregate based on ethnicity, after factoring in educational attainment, family income, and tobacco use, it was able to find that South Asians had a statistically significant higher age-adjusted prevalence of diabetes when compared to the aforementioned four groups.

The study also found that South Asians were significantly more likely to be insulin resistant and less likely to have responsive beta cell function, meaning the body could not compensate for the insulin resistance on its own. Data such as this helps us further understand that diabetes may develop differently among different groups and a one-size-fits-all approach to treatment is likely inadequate.

Poverty, a social determinant of health and diabetes, also differs by ethnic group. Hahm adds that grouping Asians together despite their varying levels of difference can be harmful when trying to understand the health disparities of different ethnic communities. “When you’re in poverty, you’re more likely to develop [type 2] diabetes or heart disease,” Hahm says. “That’s why it is really important to have disaggregated data.” As an example, 39.4 percent of Burmese Americans and 20 percent of Native Hawaiians and Pacific Islanders live in poverty; both fall within groups that experience higher rates of type 2 diabetes than other Asian subgroups. These correlations could point toward clues that could help better treat individual communities with a whole-person approach.

“Creating that visibility is the power of disaggregated data when it is meant to advance health equity. It is the basis for systemic change and empowerment of groups that have often not been heard,” Angela Glover Blackwell, JD, founder in residence at PolicyLink says in a report.

Unfortunately, having research studies solely focused on one ethnic group becomes challenging given the small amount of research funding allocated to studying the health of Asian Americans. Funding by the National Institutes of Health (NIH) only allocated 0.17 percent of the total NIH budget toward Asian Americans and Pacific Islanders (AAPI) from 1992 to 2018.

“AAPI researchers have a difficult time getting funded,” Hahm states. She adds that funding is so integral to a researcher’s career that without it, researchers wouldn’t get to continue studying their passions. “If you don’t get tenure, that means you are much more likely to go to other teaching universities,” Hahm explains. “This means your research is almost over.”

A report by PolicyLink titled Counting a Diverse Nation: Disaggregating Data on Race and Ethnicity to Advance a Culture of Health found that racial and ethnic health disparities and inequities can only be eliminated if quality data is available. By having disaggregated data by ethnicity, it can help track problems and underlying social determinants which can be used to create culturally-tailored approaches to medicine and public health.

Hahm hopes that more disaggregated research focused on ethnic Asian American groups can bring Asian American issues to the forefront, changing them from invisible to visible, and catalyzing a change in health outcomes for all Asian ethnic groups.

Source: diabetesdaily.com

Research Trends with Dr. Maria: Cholesterol Benefits & More

Dr. Maria Muccioli holds degrees in Biochemistry and Molecular and Cell Biology and has over 10 years of research experience in the immunology field. She is currently a professor of biology at Stratford University and a science writer at Diabetes Daily. Dr. Maria has been living well with type 1 diabetes since 2008 and is passionate about diabetes research and outreach.

In this recurring article series, Dr. Maria will present some snapshots of recent diabetes research, and especially interesting studies than may fly under the mainstream media radar. Check out our first-ever installment of “Research Trends with Dr. Maria”!

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Allergen in Diabetes Tech Adhesives

Diabetes technologies, like insulin pumps and continuous glucose monitors, are steadily gaining popularity, especially among patients with type 1 diabetes. While the technological advances have shown considerable benefit in improving patient outcomes and quality of life, one common issue is the unfavorable reactions to adhesives. A recent study published in Diabetes Technology & Therapeutics identified that a common culprit of these allergic reactions to adhesives may be a chemical called colophonium, a commonly-used adhesive, which was shown to be an allergen in over 40% of patients in the small study. Read more about the study and the use of this adhesive in medical products here.

Bariatric Surgery May Worsen Retinopathy

Retinopathy (eye disease) is a common complication of diabetes, and can be serious, leading to severe visual impairment and even blindness, especially when left untreated. A recent study published in Acta Ophthalmologica has uncovered a potential link between patients who undergo weight loss surgery and worsening retinopathy. Researchers adjusted for confounding variables, including glycemic control (A1c) and found that those who underwent bariatric surgery experienced worse retinopathy outcomes. Although the sample size was small, the data showed a significant worsening of eye disease in those who underwent surgery as compared to controls. Learn more about the study and outcomes here.

Super Healthy Probiotic Fermented Food Sources

Photo credit: Adobe Stock

Benefits of Probiotics for Type 2 Diabetes

The relevance of the gut microbiome in various health conditions, including diabetes, is gaining more and more attention. A recently published meta-analysis in The Journal of Translational Medicine discusses what we currently know about the effects of probiotic supplementation in patients with type 2 diabetes. Excitingly, probiotics can improve insulin resistance and even lower A1c! Learn more about exactly what the clinical trials have shown here.

Herbal Therapies Gaining Attention

With most modern medicines derived from plant compounds, it is not surprising that more research is being geared toward examining the effects of various herbal remedies on blood glucose levels and insulin sensitivity. A recent review published in The World Journal of Current Medical and Pharmaceutical Research summarizes the effects of some medicinal plants with potential anti-diabetic properties. Learn more about what is known about commons herbs and how they may be beneficial for glycemic control here.

Low HDL Cholesterol Linked to Beta Cell Decline

Research has previously suggested that higher HDL cholesterol levels may be protective of beta-cell function. A longitudinal study recently published in Diabetes Metabolism Research and Reviews indicated that patients with lower levels of HDL cholesterol were more likely to experience beta cell deterioration and develop type 2 diabetes than those with higher HDL cholesterol levels. Learn more about this study here.

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Please share your thoughts with us and stay tuned for more recent research updates!

Source: diabetesdaily.com

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