Sad News

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Jack Thomas is an 82-year-old newspaperman who unexpectedly learned he would die soon. He wrote about it at The Boston Globe. RTWT. If you’re old, you may need a tissue handy, in case you get something in your eye. He’s a talented writer. A few out-of-order excerpts:

“After a week of injections, blood tests, X-rays, and a CAT scan, I have been diagnosed with cancer. It’s inoperable. Doctors say it will kill me within a time they measure not in years, but months.

“As the saying goes, fate has dealt me one from the bottom of the deck, and I am now condemned to confront the question that has plagued me for years: How does a person spend what he knows are his final months of life?

“Atop the list of things I’ll miss are the smiles and hugs every morning from my beautiful wife, Geraldine, the greatest blessing of my life. I hate the notion of an eternity without hearing laughter from my three children. And what about my 40 rose bushes? Who will nurture them? I cannot imagine an afterlife without the red of my America roses or the aroma of my yellow Julia Childs.

“We told each of the three children individually. John Patrick put his face in his hands, racked with sobs. After hanging up the telephone, Jennifer doubled over and wept until her dog, Rosie, approached to lick away the tears but not the melancholy. Faith explained over the telephone that, if I could see her, she was weeping and wondering how she could get along without her dad. Now, she is on the Internet every day, snorkeling for new research, new strategies, new medications. My wife cries every morning, then rolls up her sleeves and handles all doctor appointments and medication. Without her . . . I cannot imagine.

“Editing the final details of one’s life is like editing a story for the final time. It’s the last shot an editor has at making corrections, the last rewrite before the roll of the presses. It’s more painful than I anticipated to throw away files and paperwork that seemed critical to my survival just two weeks ago, and today, are all trash. Like the manual for the TV that broke down four years ago, and notebooks for stories that will never be written, and from former girlfriends, letters whose value will plummet the day I die. Filling wastebasket after wastebasket is a regrettable reminder that I have squandered much of my life on trivia.

“Unlike Roman Catholics, Jews, and atheists, we Episcopalians are very good at fence-sitting. We embrace all viewpoints, and as a result, we are as confused as the Unitarians.

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“Does the intensity of a fatal illness clarify anything? Every day, I look at my wife’s beautiful face more admiringly, and in the garden, I do stare at the long row of blue hydrangeas with more appreciation than before. And the hundreds and hundreds of roses that bloomed this year were a greater joy than usual, not merely in their massive sprays of color, but also in their deep green foliage, the soft petals, the deep colors and the aromas that remind me of boyhood. As for the crises in Cuba and Haiti, however, and voting rights and the inexplicable stubbornness of Republicans who refuse to submit to an inoculation that might save their lives — on all those matters, no insights, no thunderbolts of discovery. I remai­­n as ignorant as ever.

“I’ll miss my homes in Cambridge and Falmouth. I’ll never again see the sun rise over the marsh off Vineyard Sound, never again see that little, yellow goldfinch that perched atop a hemlock outside my window from time to time so that both of us could watch the tide rise to cover the wetland.

“As death draws near, I feel the same uncomfortable transition I experienced when I was a teenager at Brantwood Camp in Peterborough, New Hampshire, packing up to go home after a grand summer. I’m not sure what awaits me when I get home, but this has certainly been an exciting experience. I had a loving family. I had a great job at the newspaper. I met fascinating people, and I saw myriad worldwide wonders. It’s been full of fun and laughter, too, a really good time.

“I just wish I could stay a little longer.”

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The Hygiene Hypothesis and Type 1 Diabetes Mellitus

An agroforestry area

D.P. Strachan in 1958 proposed an idea called the “hygiene hypothesis.” The theory is that infections and exposure to microbes (germs) in early life decreases the incidence of allergic and autoimmune diseases such as type 1 diabetes, asthma, and atopic dermatitis. Autoimmune and allergic diseases seem to be on the rise for more than a half-century, perhaps related to our urbanized lifestyles that have taken us away from the germ-rich environment of farms and forests. And we do our best to sterilize our homes with antimicrobial soaps, countertop cleaners, and hand sanitizers that we didn’t use even 20 years ago.

Exactly how early-life exposure to infections and germs could lead to autoimmune and allergic diseases is beyond the scope of today’s post. I’ll just say that germ exposure may help teach our immune system to better regulate itself. In case you don’t know, the immune system plays a large role in allergic diseases and symptoms.

A recent study out of Finland supports the hygiene hypothesis and was published in Diabetes Care:

OBJECTIVE Environmental microbial exposures have been implicated to protect against immune-mediated diseases such as type 1 diabetes. Our objective was to study the association of land cover around the early-life dwelling with the development of islet autoimmunity and type 1 diabetes to evaluate the role of environmental microbial biodiversity in the pathogenesis.

RESEARCH DESIGN AND METHODS Association between land cover types and the future risk of type 1 diabetes was studied by analyzing land cover types classified according to Coordination of Information on the Environment (CORINE) 2012 and 2000 data around the dwelling during the first year of life for 10,681 children genotyped for disease-associated HLA-DQ alleles and monitored from birth in the Type 1 Diabetes Prediction and Prevention (DIPP) study. Land cover was compared between children who developed type 1 diabetes (n = 271) or multiple diabetes-associated islet autoantibodies (n = 384) and children without diabetes who are negative for diabetes autoantibodies.

RESULTS Agricultural land cover around the home was inversely associated with diabetes risk (odds ratio 0.37, 95% CI 0.16–0.87, P = 0.02 within a distance of 1,500 m). The association was observed among children with the high-risk HLA genotype and among those living in the southernmost study region. Snow cover on the ground seemed to block the transfer of the microbial community indoors, leading to reduced bacterial richness and diversity indoors, which might explain the regional difference in the association. In survival models, an agricultural environment was associated with a decreased risk of multiple islet autoantibodies (hazard ratio [HR] 1.60, P = 0.008) and a decreased risk of progression from single to multiple autoantibody positivity (HR 2.07, P = 0.001) compared with an urban environment known to have lower environmental microbial diversity.

CONCLUSIONS The study suggests that exposure to an agricultural environment (comprising nonirrigated arable land, fruit trees and berry plantations, pastures, natural pastures, land principally occupied by agriculture with significant areas of natural vegetation, and agroforestry areas) early in life is inversely associated with the risk of type 1 diabetes. This association may be mediated by early exposure to environmental microbial diversity.


From the introduction:

“The incidence of type 1 diabetes has increased during the past 70 years in the developed countries paralleling similar increase in other immune-mediated diseases such as allergies and asthma. The rapid increase, together with the conspicuous variation in incidence rates between countries, supports the role of environmental factors in the pathogenesis. Overall, the incidence rate tends to be high in countries located in the north, although exceptions to this trend exist.

“Living in an agricultural environment and contacts with farm animals and pets at home has been associated with a higher microbial diversity indoors and a decreased risk of allergic diseases. Although the mechanisms of this phenomenon are not fully understood, several lines of evidence suggest that exposure to environmental microbial diversity and direct soil contacts may play a role. This, in turn, could lead to the activation of immunoregulatory pathways suppressing overreactive immune responses, as presented by the biodiversity hypothesis. A wide exposure of the skin and mucosal surfaces to all kinds of microbes, including bacteria, viruses, and eukaryotes, regardless of whether they are infecting or colonizing humans, could provide constant immunological stimulation to the immune system, which is needed for the development of healthy immune regulation.

“As with allergic diseases, type 1 diabetes is also associated with failure to control hyperreactive immune responses. In type 1 diabetes, these immune responses target β-cell autoantigens instead of allergens.” 


Steve Parker, M.D.

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High Glycemic Load and Glycemic Index Linked to Weight Regain and Higher Blood Glucose

“Would you like a load?”

My headline says it all. Click for my definitions and discussion of glycemic load and glycemic index.

From Diabetes Care:

OBJECTIVE To examine longitudinal and dose-dependent associations of dietary glycemic index (GI), glycemic load (GL), and fiber with body weight and glycemic status during 3-year weight loss maintenance (WLM) in adults at high risk of type 2 diabetes.

RESEARCH DESIGN AND METHODS In this secondary analysis we used pooled data from the PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World (PREVIEW) randomized controlled trial, which was designed to test the effects of four diet and physical activity interventions. A total of 1,279 participants with overweight or obesity (age 25–70 years and BMI ≥25 kg ⋅ m−2) and prediabetes at baseline were included. We used multiadjusted linear mixed models with repeated measurements to assess longitudinal and dose-dependent associations by merging the participants into one group and dividing them into GI, GL, and fiber tertiles, respectively.

RESULTS In the available-case analysis, each 10-unit increment in GI was associated with a greater regain of weight (0.46 kg ⋅ year−1; 95% CI 0.23, 0.68; P < 0.001) and increase in HbA1c. Each 20-unit increment in GL was associated with a greater regain of weight (0.49 kg ⋅ year−1; 0.24, 0.75; P < 0.001) and increase in HbA1c. The associations of GI and GL with HbA1c were independent of weight change. Compared with those in the lowest tertiles, participants in the highest GI and GL tertiles had significantly greater weight regain and increases in HbA1c. Fiber was inversely associated with increases in waist circumference, but the associations with weight regain and glycemic status did not remain robust in different analyses.

CONCLUSIONS Dietary GI and GL were positively associated with weight regain and deteriorating glycemic status. Stronger evidence on the role of fiber is needed.

Steve Parker, M.D.

PS: The book below will help you keep your glycemic load and glycemic index low, thereby preventing weight regain.

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Pfizer COVID-19 Vaccine: No Deaths Prevented Over Six Months

Alea iacta est

I ran across a pre-print placebo-controlled scientific study looking at results of Pfizer-BionTec vaccination over the course six months. The primary take-home point for me is that the vaccine did not prevent death. Mysteriously, the study authors didn’t discuss the lack of death prevention by the vaccine; I found the data in Figure 1. The vaccine did prevent severe COVID-19 disease.

The scientific name for this particular vaccine is BNT162b2.

Remember that Big Pharma and the CDC have been telling us since November 2020 that the COVID-19 vaccines are highly effective (~90% or better) in preventing severe disease and death.

The study at hand looked at 22,000 folks who got two doses of the vaccine and another 22,000 who got a saline placebo. There were 16 deaths in the vaccine group, 15 in placebo.

Thirty-one participants met the CDC’s definition of severe COVID-19; 30 of these were in the placebo group. So the odds of developing severe COVID-19 over six months if not vaccinated were 0.136%. Or one in 735. (Tell me if my math is wrong.) I fully expect the odds are higher if elderly, lower if young.

Among the vaccinated, 77 developed COVID-19. The placebo group had 850 cases. The report doesn’t state a definition of a “COVID-19 case.” I presume a positive PCR nasal swab and one or more of the usual symptoms. Maddeningly, when the mainstream media mentions a case count, the number may include folks with a positive PCR swab but no symptoms.

Most participants were enrolled between August and October 2020. The U.S. had a major spike in cases in January 2021. The data cut-off date for this study was March 31, 2021, so many of the participants had significant exposure. Median age for both groups was 51. 76% of participants were in the U.S.

The authors note that the risk of developing COVID-19 in the vaccinated tended to rise over time. Vaccine effectiveness declined about 6% every two months. A booster vaccination might be recommended at some point. Pfizer’s CEO revealed this a couple months ago.

For all I know, the linked-to pre-print article above is a hoax. These data are not going to help Pfizer sell more vaccine! If the pre-print is legit, I assume Pfizer was somehow compelled to publish the results.

This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Steve Parker, M.D.

h/t The Last Refuge or theconservativetreehouse.com

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Dr Edelman on Hypoglycemia Unawareness & Glucagon

Diabetes Daily has in important interview with Dr Steven Edelman on hypoglycemia (particularly in type 1 diabetes) and the need for injectable glucacon to treat it. This could easily apply also to type 2 diabetes that’s treated with insulin or other drugs that can cause hypoglycemia. Folks with type 1 diabetes seem to be more prone to hypoglycemia unawareness. That is, the blood sugar is dangerously low, but not recognized or treated promptly, potentially resulting death. Dr Edelman notes that dangerous hypoglycemia has been significantly reduced by the use of continuous glucose monitoring (CGM).

Note that CGM measure glucose levels in the the fluid in between the cells of subcutaneous tissue (AKA interstitial fluid). Your familiar fingerstick glucose is measuring capillary fluid levels. Capillaries are tiny blood vessels at the end of arteries. After going through the capillaries, blood enters veins for the return trip to the lung and heart. Glucose levels in the interstitial fluid and capillaries may not be the same as in the large arteries delivering glucose to the brain. Most CGM devices will provide the user with an alert when the glucose level drops too low, so that remedial action can be taken.

An excerpt from Diabetes Daily:

What are some ways that the CGM can most effectively help avoid hypos?

Well, one of the things I do in clinic is to really check where people set their upper and lower alerts. I had a patient yesterday in clinic who has had type 1 for 60 years. Her A1C is unbelievable, but she does have hypo unawareness and her lower alert was 65. You have to convince people that the extra alerts are worth it to you.

A lot of people said they put their lower alert at 65 and they don’t realize this situation called the “lag time.” So, when your blood sugar is dropping, even if you have a diagonal arrow down compared to, even worse, one arrow down or two arrows down, looking at the Dexcom arrows, they don’t realize that the glucose in your circulation is probably much lower than it appears on the Dexcom monitor or your phone. Because the Dexcom sensor and other sensors too, they measure the glucose in the subcutaneous tissue, and there’s a lag between the subcutaneous tissue and the circulation.

When your Dexcom goes off or when your CGM goes off at 65, and if your trend arrow’s going down, you could be 45 or 40. So that’s really an important issue, especially for people that their symptoms aren’t as obvious anymore. You could be caught off guard. And I had multiple patients that has occurred with. And then unfortunately, as you know, the majority of T1Ds in this country do not wear a CGM and that’s the topic of a whole other story.

Does this lag time issue apply to a regular glucometer as well?

Yes. If your blood sugar is dropping, your meter or CGM may be perfectly accurate of the subcutaneous tissue at 65. If you checked your blood sugar with a meter, it’s still going to say 65, but your circulation that’s going to your brain might be 45. So, the lag time is key. You could have the most accurate meter or CGM in the world, it doesn’t affect the lag time.


Click for my five-year-old article on drugs that can cause diabetes.

Click for my brief article on hypoglycemia unawareness.

Click for my general article on recognition and treatment of hypoglycemia.

Steve Parker, M.D.

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Finerenon: New Hope for Prevention of Kidney Disease and Cardiac Death in Type 2 Diabetes

Your friendly neighborhood drug supplier

Verbatim from the FDA press release:

FDA has approved Kerendia (finerenone) tablets to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes.

Diabetes is the leading cause of chronic kidney disease and kidney failure in the United States. Chronic kidney disease occurs when the kidneys are damaged and cannot filter blood normally. Because of defective filtering, patients can have complications related to fluid, electrolytes (minerals required for many bodily processes), and waste build-up in the body. Chronic kidney disease sometimes can progress to kidney failure. Patients also are at high risk of heart disease.

The ultimate role of finerenone in our armamentarium against disease and suffering will probably depend on cost and the number needed to treat.

The efficacy of Kerendia to improve kidney and heart outcomes was evaluated in a randomized, multicenter, double-blind, placebo-controlled study in adults with chronic kidney disease associated with type 2 diabetes. In this study, 5,674 patients were randomly assigned to receive either Kerendia or a placebo.

The study compared the two groups for the number of patients whose disease progressed to a composite (or combined) endpoint that included at least a 40% reduction in kidney function, progression to kidney failure, or kidney death. Results showed that 504 of the 2,833 patients who received Kerendia had at least one of the events in the composite endpoint compared to 600 of the 2,841 patients who received a placebo.

The study also compared the two groups for the number of patients who experienced cardiovascular death, a non-fatal heart attack, non-fatal stroke, or hospitalization for heart failure. Results showed that 367 of the 2,833 patients receiving Kerendia had at least one of the events in the composite endpoint compared to 420 of the 2,841 patients who received a placebo, with the treatment showing a reduction in the risk of cardiovascular death, non-fatal heart attack, and hospitalization for heart failure.

Side effects of Kerendia include hyperkalemia (high levels of potassium), hypotension (low blood pressure), and hyponatremia (low levels of sodium). Patients with adrenal insufficiency (when the body does not produce enough of certain hormones) and those receiving simultaneous treatment with strong CYP3A4 inhibitors should not take Kerendia.

Kerendia received priority review and fast track designations for this application.

FDA granted the approval of Kerendia to Bayer Healthcare.


Click for prescribing information.


Parker here.

Just offhand, finerenone doesn’t look like a great drug. Helpful, maybe. Chronic kidney disease can end up at ESRD (end stage renal disease), which requires thrice weekly hemodialysis if the patient wants to stay alive. (Yes, peritoneal dialysis is an alternative.) Preventing ESRD is an incredible benefit for an individual.

Finerenone seems to be a well-tolerated daily pill. The main adverse effect is elevated blood potassium level, which can cause palpitations, and death infrequently. Less commonly, the drug can cause low blood pressure.

Steve Parker, M.D.

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My Recent Posts About COVID-19

Artist’s rendition of coronavirus

I write about COVID-19 at one of my other super-secret blogs. If you’re interested:

Steve Parker, M.D.

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QOTD: Men and Women…Together

dementia, memory loss, Mediterranean diet, low-carb diet, glycemic index, dementia memory loss
“Yes, the kids are long gone, but we’re still together.”

Men offer women what other women can’t, and when they do it right, everyone is better off. Women at their best bring out the best in men. They — men, that is — are more inclined to behave themselves, to work harder, scrape off their rougher edges, and be more dependable. This extends into other arenas of social life, like being a good father, a reliable worker, and a helpful neighbor. Women get to have men around to be “the fathers” to the children that they cannot be, to share the burdens and joys of child-rearing, and, together, ease the chastening of old age.

-Stephen Paul Foster, July 1, 2021 (I’d link to the source but the website owner has blocked my IP address)

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Does Salt Restriction Lower Blood Pressure in Type 2 Diabetes?

Yes, according to an article in Nutrition, Metabolism & Cardiovascular Disease. The systolic pressure lowering is 5-6 points, but only 1-2 points on average for diastolic pressure. This degree of BP lowering is not dramatic, but might prevent an escalation of antihypertensive drug dosing or initiation of an additional drug.

Blood pressure control is also extremely important for protection of heart, kidneys, and brain.

Steve Parker, M.D.

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Should You Reduce Your Aspirin Dose from 325 to 81 mg/day?

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For patients with established cardiovascular disease, a recent study found that aspirin 81 mg/day was just as effective as 325 mg/day in preventing combined risk of death and hospitalization for heart attack or stroke. Rates of major bleeding were the same regardless of dose.

Click for details at NEJM.

Don’t make changes in your medication regimen without consulting your personal physician.

Steve Parker, M.D.

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