“Daily consumption for nuts and seeds was associated with a lower prevalence of NAFLD in non-Mediterranean, US adults, although the benefits seem to be greater in females across all categories of nut and seed consumption groups compared with nonconsumers. Both males and females presented with lower prevalence of NAFLD with intakes of 15–30 g/d.”
Experts are predicting an epidemic of NASH: non-alcoholic steatohepatitis. In other words, fat build-up in the liver with associated inflammation and scarring (fibrosis). Which is related to it’s precursor, NAFLD: non-alcoholic fatty liver disease. These are significant issues particularly for folks with type 2 diabetes. From Diabetes Care:
“The clinical burden of both NAFLD overall and NASH specifically has increased steadily since the 1980s. NAFLD currently affects 25% of the global population and >60% of patients with T2D. Studies evaluating the prevalence of NASH suggest that it may involve an estimated 1.5%–6.5% of the general population and as many as 37% of people with T2D. Prevalence of NASH is expected to increase by 63% between 2015 and 2030. Although these numbers seem substantially lower than those for NAFLD overall, they still translate to 4.9 million to 21 million Americans and more than 100 million individuals worldwide. Modeling data estimate that the number of patients with NASH-related advanced fibrosis will likely double by 2030, resulting in 800,000 liver-related deaths.
NASH is already the number 1 indication for liver transplantation in women, patients older than 54 years, and Medicare recipients. Beyond the significant impairment of quality of life experienced by individuals with NASH and advanced fibrosis, Younossi et al. estimated in 2017 that the overall lifetime direct costs of NASH in the United States would be $222.6 billion, and approximately $95.4 billion over the next 2 decades, suggesting a substantial economic burden.”
Loss of excess weight is one way to combat or avoid non-alcoholic fatty liver disease.
Steve Parker, M.D.
PS: The Paleobetic Diet can help you lose excess weight and keep it off.
Haven’t we know this for years? From New England Journal of Medicine:
Most data regarding the association between the glycemic index and cardiovascular disease come from high-income Western populations, with little information from non-Western countries with low or middle incomes. To fill this gap, data are needed from a large, geographically diverse population.
This analysis includes 137,851 participants between the ages of 35 and 70 years living on five continents, with a median follow-up of 9.5 years. We used country-specific food-frequency questionnaires to determine dietary intake and estimated the glycemic index and glycemic load on the basis of the consumption of seven categories of carbohydrate foods. We calculated hazard ratios using multivariable Cox frailty models. The primary outcome was a composite of a major cardiovascular event (cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure) or death from any cause.
In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease.
In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death.
A recent study looked at the health benefits of type 2 diabetes drugs, comparing drugs that can cause hypoglycemia and those that don’t. The very first sentence of the abstract didn’t give me much hope for what followed. That sentence was: “Different guidelines provide similar, but not identical, therapeutic targets for HbA1c in type 2 diabetes. These targets can also depend from the different pharmacological strategies adopted for intensifying glycemic control.” Did you catch the misprint?
This meta-analysis of 13 clinical trials was looking for differences in various health outcomes over the course of at least two years, comparing successful intensive management to standard care or placebo. Successful intensive management was defined as at least a 0.5% (6 mmol/mol) improvement in hemoglobin A1c (HgbA1c) level. “Intensification” of drug therapy is usually applied to a patient who is not at goal HgbA1c level. Undoubtedly, the benefits of intensification will be greater for those at HgbA1c of 10% than for those at 7.5%. BTW, few large clinical trials include patients over 75 years of age.
For my U.S. readers, note that other countries often specify HgbA1c values as mmol/mol instead of %. And blood sugars are not our usual mg/dl, but instead reported as mmol/l. HbA1c of 7% equals 53 mmol/mol, which would indicate and average blood sugar of 154 mg/dl or 8.6 mmol/l. As another example, HbA1c of 6.5% is 48 mmol/mol, reflecting average blood sugar of 140 mg/dl or 7.8 mmol/l. Are you thoroughly confused yet?
In the general population, lowest levels of mortality are seen at HgbA1c’s around 5 to 5.5% (31 to 36.6 mmol/mol). The average healthy non-diabetic adult hemoglobin A1c is 5% (31 mmol/mol) and translates into an average blood sugar of 100 mg/dl (5.56 mmol/l). This will vary a bit from lab to lab. Most healthy non-diabetics would be under 5.7% (38.8 mmol/mol). In December, 2009, the American Diabetes Association established a hemoglobin A1c criterion for the diagnosis of diabetes: 6.5% (47.5 mmol/mol) or higher. Diagnosis of prediabetes involves hemoglobin A1c in the range of 5.7 to 6.4% (38.8 to 46.5 mmol/mol).
Some expert panels recommend aiming for HgbA1c under 7% (53 mmol/mol), others recommend under 6.5% (48 mmol/mol). A major point of debate between the two guideline goals, is that the lower you set the goal, the greater the risk of drug-induced hypoglycemia, which can be lethal. In the early 1980s, the only drugs we had for diabetes were insulin, sulfonylureas, and metformin. Two of those three can can cause hypoglycemia. Now, a majority of our type 2 diabetes drugs don’t cause hypoglycemia.
The Italian researchers did this meta-analysis as part of their effort to produce diabetes drug treatment guidelines for the Italian population. On to the study at hand…
What Did the Researchers Find?
Improved glycemic (blood sugar) control by intensive attention reduced the major cardiovascular event rate by 10% and reduced renal adverse events by 25% but did not affect overall mortality or eye complications.
Intensified therapy with hypoglycemia-inducing drugs did not reduce overall mortality.
Drugs without potential for causing hypoglycemia were linked to lower risk of major cardiovascular events, kidney adverse events, and overall mortality, for HgbA1c under 7% (53 mmol/mol).
In conclusion, the results of this meta-analysis of RCTs show that in people with T2DM the improvement of glycemic control with drugs not inducing hypoglycemia is associated with a reduction in the risk of long-term chronic vascular complications (major adverse cardiac events and renal adverse events) and all-cause mortality, at least for HbA1c levels above 7%. The reduction of HbA1c below that threshold could have some favorable effects, but there is no available direct evidence in this respect. When the reduction of HbA1c is achieved with drugs inducing hypoglycemia, a progressive reduction of complications and an increase in the risk of severe hypoglycemia is observed. Therefore, the choice of the most adequate HbA1c target for each patient with T2DM should be made considering an appropriate risk/benefit ratio.
I think the researchers were particularly glad to find that intensification of drug therapy can reduce risk of heart attack, stroke, kidney complications, and death; all this without the risk of hypoglycemia that comes with drugs like insulin and sulfonylureas. The lack of a mortality benefit from hypoglycemia-inducing drugs may also be important. The benefits of intensive drug therapy (or lack thereof) depend somewhat on the particular complication you’re trying to avoid, and on baseline HgbA1c. Drug therapy is complicated! I expect these researchers would recommend a treatment HgbA1c goal of <7% rather than <6.5%.
Steve Parker, M.D.
PS: Reduce your need for diabetes drugs by losing excess weight, exercising, and eating low-carb.
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.
“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.
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 decrease 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.
Surely paleolithic humans had greater germ exposure than modern humans who use masks, use hand sanitizer and soap, cook food thoroughly, and drink purified water.
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.
Compared to no coffee-drinking, drinking four cups a day reduced overall death rate by 20%, reduced cardiovascular deaths by 40%, and reduced death rate form coronary artery disease by 30%. The study at hand was a meta-analysis involving over 80,000 folks with type 2 diabetes living in multiple studies and followed clinically for 5-20 years. “Cardiovascular deaths” are usually heart attacks, strokes, cardiac arrest, or heart failure.
I vaguely recall a study several decades ago linking coffee to pancreas cancer, one of the deadliest cancers. The research was subsequently discredited.
From Nutrition, Metabolism & Cardiovascular Diseases:
To evaluate the long-term consequences of coffee drinking in patients with type 2 diabetes.
PubMed, Scopus, and Web of Sciences were searched to November 2020 for prospective cohort studies evaluating the association of coffee drinking with risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. Two reviewers extracted data and rated the certainty of evidence using GRADE approach. Random-effects models were used to estimate the hazard ratios (HRs) and 95% CIs. Dose–response associations were modeled by a one-stage mixed-effects meta-analysis. Ten prospective cohort studies with 82,270 cases were included. Compared to those with no coffee consumption, the HRs for consumption of 4 cups/d were 0.79 (95%CI: 0.72, 0.87; n = 10 studies) for all-cause mortality, 0.60 (95%CI: 0.46, 0.79; n = 4) for CVD mortality, 0.68 (95%CI: 0.51, 0.91; n = 3) for coronary heart disease (CHD) mortality, 0.72 (95%CI: 0.54, 0.98; n = 2) for CHD, and 0.77 (95%CI: 0.61, 0.98; n = 2) for total CVD events. There was no significant association for cancer mortality and stroke. There was an inverse monotonic association between coffee drinking and all-cause and CVD mortality, and inverse linear association for CHD and total CVD events. The certainty of evidence was graded moderate for all-cause mortality, and low or very low for other outcomes.
Drinking coffee may be inversely associated with the risk of mortality in patients with type 2 diabetes. However, more research is needed considering type of coffee, sugar and cream added to coffee, and history of CVD to present more confident results.
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 index and glycemic load low, thereby preventing weight regain.
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. IIRC, 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.
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.