DIABETES RESEARCH RIGHT NOW! #19: After Fasting, Why the @!&%$ Are My Blood Sugars STILL Through the ROOF???

From the first moment I discovered I had been diagnosed with DIABETES, I joined a HUGE “club” that has been rapidly expanding since it stopped being a death sentence in the early 20th Century. Currently, there are about HALF A BILLION PEOPLE who have Type 2 Diabetes. For the past 3500 years – dating back to Ancient Egypt – people have suffered from diabetes. Well, I’m one of them now… Not one to shut up for any known reason, I added a section to this blog…

Every month, I’ll be highlighting Diabetes research that is going on RIGHT NOW! Harvested from different websites, journals and podcasts, I’ll translate them into understandable English and share them with you. Today: “One of the most confusing aspects for patients with type 2 diabetes is that we have high fasting glucose levels.” So – WHAT’S THE ANSWER???

“The World Health Organization (WHO) considers type 2 diabetes, one of the pandemics of the 21st century…it is a condition that results in high levels of circulating glucose -- the cellular energy fuel -- due to a deficient insulin response in the body…When blood glucose, also called blood sugar, levels rise after you eat, your pancreas [is supposed to] releases insulin into the blood. Insulin then lowers blood glucose to keep it in the normal range…In T2 patients, the glucose synthesis pathway in the liver (gluconeogenesis) is hyperactivated, a process that can be controlled by drugs such as metformin. ”

But metformin has never CURED T2. It wasn’t meant to. It’s a way to CONTROL T2. This group of researchers noticed something odd. From the beginning of the COVID 19 pandemic, “…factors involved in the control of gluconeogenesis [which is the liver making blood sugars and injecting them into our bloodstream]… sometimes patients hospitalized with COVID-19 showed high glucose levels…[it] seems to be related to the ability of the virus to spark the activity of proteins involved in starting the liver up making glucose and sending it to the bloodstream…”

So, that response of the bodies of people with COVID sometimes made their body react as if they were also Type 2 diabetic. Now, I take FOUR metformin tablets every day. I was SHOCKED to read this: “The mechanisms of action of metformin, the most commonly prescribed drug for the treatment of type 2 diabetes, which reduces how much glucose is in the blood, are still not fully understood.”

In other words, researchers, doctors, and pharmacists DON’T KNOW HOW METFORMIN WORKS!!!!!!! While I intentionally made that more alarm than I could have, the fact is that as researches dig into the method of metformin function, they’re finding out WAY more than they expected, up to and including the effect of metformin in REDUCING AGING!!! “Early evidence highlighted the liver as the major organ involved in the effect of metformin on reducing blood levels of glucose. However, increasing evidence points towards other sites of action that might also have an important role, including the gastrointestinal tract, the gut microbial communities and the tissue-resident immune cells.”

“At the molecular level, it seems that the mechanisms of action vary depending on the dose of metformin used and duration of treatment. Initial studies have shown that metformin targets hepatic mitochondria; however, the identification of a novel target at low concentrations of metformin at the lysosome surface might reveal a new mechanism of action. Based on the effectiveness and safety records in T2DM, attention has been given to the repurposing of metformin as part of adjunct therapy for the treatment of cancer, age-related diseases, inflammatory diseases, and COVID-19.”

Rest assured, I’ll be poking around this paper more as time goes on!

To briefly recap, it seems that HOW metformin works is even deeper than just at the level of CELLS – but deeper still into the “powerhouse” of every cell in your body: the mitochondria…

So, that’s it for now. Obviously I’ll continue to dig deeper into HOW metformin works. (I commented to my wife with a sigh, “Oh, great, now metformin with become as hard to get as Ozempic because the rich will start to pop the pills to stay young and beautiful!”

*sigh* I vote we should just suppress THAT little bit of information!

Links: https://www.sciencedaily.com/releases/2024/06/240607121434.htm; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214027/; https://fagron.com/news-media/post/exploring-the-multifaceted-benefits-of-metformin-hydrochloride-beyond-diabetes-management/ ; https://www.nature.com/articles/s41574-023-00833-4

Image: https://asploro.com/wp-content/uploads/2019/12/Diabetes-Research_Open-Access.jpg

GUY’S GOTTA TALK ABOUT…TYPE 2 DIABETES #22: Getting Older With Type 2

For the first time since I started this blog eleven years ago, it’s going to be about me. I was diagnosed with Type 2 Diabetes two weeks ago. While people are happy to talk about their experiences with diabetes, I WASN’T comfortable with talking about diabetes. My wife is Type 2, as are several friends of ours. The “other Type” of diabetes was what caused the death of my Best Man a year after my wife and I got married. He was diagnosed with diabetes when he was a kid. It was called Juvenile Diabetes then. Today it’s Type 1. Since then, I haven’t WANTED to talk about diabetes at all. But…for my own education and maybe helping someone else, and not one to shut up for any known reason, I’m reopening my blog rather than starting a new one. I MAY take a pause and write about Breast Cancer or Alzheimer’s as medical headlines dictate; but this time I’m going to drag anyone along who wants to join my HIGHLY RELUCTANT journey toward better understanding of my life with Type 2 Diabetes. You’re Welcome to join me!

I was diagnosed with Type 2 diabetes in 2022, so it’s become a “part of who I am”.

I’m gonna confess it right here – I haven’t changed in most ways. I DO exercise more (I bike, on average of three miles a week, between nine and 21 miles a week – depending on how much time I have, the temperature, windiness, rain, and even if I feel like it or not! Even so, my accumulated miles over the past two years went past 1000 a couple weeks ago! AMAZING!

However, I still do Dairy Queen occasionally; I eat peanut-butter/better roll ups for lunch sometimes; eat cookies, candy, and other stuff that’s not good for me…OTOH, I DO watch my diet better than I ever did before my diagnosis. I’m more aware of how foods and exercise affect me; so overall, I’m more cautious about what I eat and how much I exercise than I EVER was in my entire life!

I’m aware of my blood pressure as well. Research has clear connections between diabetes and high blood pressure: “High blood pressure can lead to many complications of diabetes: eye and kidney disease; heart and circulation problems; damages arteries and makes them targets for hardening, called atherosclerosis. That can cause high blood pressure, which if not treated, can lead to trouble including blood vessel damage, heart attack, and kidney failure; coronary artery disease or heart disease; stroke; peripheral vascular disease; hardening of the arteries in the legs and feet; heart failure. Even elevated blood pressure that's at the higher end of normal (120/80 to 129/80) [!!!! My current 20 day BP average is 115/82 – and the bottom one, “diastolic” is more important than the top one “systolic”] impacts your health. Studies show that you have a two to three times greater chance of getting heart disease over 10 years.”

So – how does my upward creeping age affect my diabetes?

“Many of the things you do for your diabetes will also help with high blood pressure:

1. Control your blood sugar – working on it.
2. Stop smoking – never did.
3. Eat healthy – I try…
4. Exercise most days – yes.
5. Keep your weight in a healthy range – what the heck is THAT??? Ideal weight 177-188…in the name of perfect transparency: I’ve been 250 +/- for a LONG TIME…
6. Don't drink a lot of alcohol – don’t do this AT ALL…never have.
7. Limit how much salt you eat – lately I’ve been experiencing water retention (one of the bits of advice in the article referenced below “Your symptoms may be different”. I’ve never experienced water retention – I suppose that’ll be a great subject for my next “GGTA: Diabetes”…
8. Visit your doctor regularly – done

With that, I bid you adieu…

Source: https://www.healthline.com/health/type-2-diabetes/changes-after-age-50#changing-symptoms , https://www.webmd.com/diabetes/high-blood-pressure
Image: https://www.hcd.com/wp-content/uploads/2021/01/living-well-with-diabetes.jpg

DIABETES RESEARCH RIGHT NOW! #18: Researchers Discover New, Safer Treatment Using An OUTDATED Diabetes Drug!

From the first moment I discovered I had been diagnosed with DIABETES, I joined a HUGE “club” that has been rapidly expanding since it stopped being a death sentence in the early 20th Century. Currently, there are about HALF A BILLION PEOPLE who have Type 2 Diabetes. For the past 3500 years – dating back to Ancient Egypt – people have suffered from diabetes. Well, I’m one of them now… Not one to shut up for any known reason, I added a section to this blog.

Every month, I’ll be highlighting Diabetes research that is going on RIGHT NOW! Harvested from different websites, journals and podcasts, I’ll translate them into understandable English and share them with you. Today: From the “this was useless!” camp – an OLD, BETTER Type 2 treatment!

“For decades, TZDs have been the only drugs we have that can reverse insulin resistance, but we seldom use them anymore because of their side effects profile," said Jerrold Olefsky, M.D., a professor of medicine and assistant vice chancellor for integrative research at UC San Diego Health Sciences. "Impaired insulin sensitivity is the root cause of type 2 diabetes, so any treatment we can develop to safely restore this would be a major step forward for patients.’”

Apparently though, they stopped using them because they weren’t MAGIC. They DIDN’T cause INSTANT, miraculous, fabulous, and undeniable FAT REMOVAL! Moreover they had HORRIBLE, AWFUL, HORRENDOUS side-effects!!! Yes! People’s hair fell out; they broke out in instant cancer! they caused warts! retained water! gained weight! caused blindness! heart disease! the automatic falling-off of random limbs! increased dandruff! flatulence! baldness!

Therefore, in the sight of Americans, TZDs were EVIL! HORRIBLE! USELESS! We want our drugs to do everything – including the laundry and make Big Macs calorie free and make beer non-alcoholic and calorie-free (but not different in ANY other way)

Drugs like TZD and others related to it provide other benefits: “…anti-inflammatory and anti-cancer properties…slow the progression…of coronary hyperplasia ( = “the enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells, often as an initial stage in the development of cancer.”)…beneficial effects on endothelial function, atherogenesis, fibrinolysis, and ovarian steroidogenesis ( = “the processes by which cholesterol is converted to steroid hormones”.)

There are several undesirable side effects to thiazolidinediones, particularly with long-term use. The risks versus benefits require discussion with patients, and alternative first-line agents (metformin, using insulin injections) attempted before using TZDs.

But they are very specific and not common.

Edema and Congestive Heart Failure: (20% of patients; lower doses decrease the risk of edema and weight gain); NOT useful for people who have CHF)

Weight Gain and Fluid Retention: TZDs expand fat tissue mass and can increase weight. Fat gain occurs primarily in tissues just under the skin, sparing the belly area.

Fractures: increased risk and decreased bone density, and are most likely in the forearm, wrist, ankle, foot, tibia, rather than in the hip, pelvis, femur).

Bladder Cancer: One of the TZDs has, in some studies, shown correlations with an increased risk of bladder cancer. However, the most recent analyses do not support an increased risk, and only one of the TZDs increased the risk.

Diabetic Macular Edema: IF an individual takes both the TZDs and regularly use insulin, there may be an increased incidence of diabetic macular edema at 1-year and 10-year follow-up. (Macular edema happens when blood vessels leak into a part of the retina, making it swell, causing blurry vision.)

Increased Ovulation and Teratogenic Effects: This may result in ovulation in some premenopausal women, leading to improved rates of spontaneous pregnancy, but TZDs have some fetal abnormality potential.

So, this research led to a way AROUND using the original TZDs in a totally new way. 

How? When fat is inflamed, macrophages release tiny bits of instructions to the cells called microRNAs, small fragments of genetic material that help control what the DNA does for the surrounding cells. These are called exosomes. Released into the bloodstream, they’re picked up by the liver and muscles. This can then lead to changes in obesity and insulin resistance – REDUCING BOTH.

The researchers treated a group of obese mice with a TZD drug. Those mice became more sensitive to insulin, but they also gained weight and retained excess fluid. 

When the researchers split the exosomes OUT of the fat tissue, they then injected the macrophages into A DIFFERENT group of fat mice and ALL OF THE positive effects of the TZD worked with none of the bad. The researchers were also able to identify the specific microRNA within the exosomes that was responsible for the beneficial metabolic effects of rosiglitazone. This molecule, called miR-690, could eventually be leveraged into new therapies for type 2 diabetes.

One of the researchers noted, “There's plenty of precedent for using microRNAs themselves as drugs, so that's the possibility we're most excited about exploring for miR-690 going forward.”

It’s NOT today, but because of the discontinued use of one drug, researchers have been able to use increasingly sophisticated procedures to turn it into a NEW drug!

Who knows when? But this is certainly “What’s Next!”

Links: https://www.sciencedaily.com/releases/2024/04/240411130116.htm, https://www.ncbi.nlm.nih.gov/books/NBK551656/

Image: https://asploro.com/wp-content/uploads/2019/12/Diabetes-Research_Open-Access.jpg