Is NASH the Next Epidemic?

Stages of liver damage. Healthy, fatty, liver fibrosis, and cirrhosis.

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. Let me help.

Steve Parker, M.D.

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Is There Anything It DOESN’T Do?: Mediterranean Diet Improves Erectile Dysfunction

From EdenMagnet.com:

A Mediterranean diet is associated with improvements in erectile dysfunction, according to research presented at the European Society of Cardiology Congress 2021.

Erectile dysfunction primarily occurs when small arteries lose the ability to dilate and allow proper blood flow. It is more common in men with hypertension or declining testosterone levels.


“In our study, consuming a Mediterranean diet was linked with better exercise capacity, healthier arteries, and blood flow, higher testosterone levels, and better erectile performance,” says Angelis.

This is news to me.

Steve Parker, M.D.

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Seed and Nut Consumption May Prevent Liver Disease

What kind of liver disease? NAFLD: non-alcoholic fatty liver disease.

mixed nuts
Remember…peanuts aren’t nuts, they’re legumes

See the Journal of Nutrition for details:

Conclusions

“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.”

Steve Parker, M.D.

PS: The Low-Carb Mediterranean Diet includes nuts and seeds.

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Researchers Looking for Volunteers With Type 2 Diabetes Who Want to Try a Mediterranean Diet

Steve Parker MD, low-carb diet, diabetic diet
Olives, olive oil, and vinegar: classic Mediterranean foods

Researchers at RMIT University in Australia, are seeking volunteer research participants to be involved in a study about the management of type 2 diabetes through an alternative dietary plan based on the Mediterranean diet.

Through the clinical trial scientists hope to learn whether a Mediterranean dietary pattern with or without intermittent fasting may better control diabetes, as compared with a conventional diet based on the current recommendations for patients with type 2 diabetes.

Click for brief details. I saw nothing that restricts participation to Australia residents. “Attend online appointments (via Zoom, phone or FaceTime) with the research nutritionist (PhD student) at the start of the study and again at 6 weeks, 12 weeks and 24 weeks.” This type of research is usually very safe and approved by university institutional review boards.

Steve Parker, M.D.

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Premature Death and Cardiovascular Disease Linked to High Glycemic Index Eating

Naan, a type of flat bread with a high glycemic index

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death.

Source: Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality | NEJM

The Advanced Mediterranean Diet (2nd edition) is low glycemic index.

Steve Parker, M.D.

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Avoid Age-Related Frailty With the Mediterranean Diet

Winning against gravity, for now…

The opposite of vigor is frailty. Aging is a life-long fight with gravity. If you’re frail, you’ll lose the battle sooner. In the study at hand, frailty was measured by exhaustion, weakness, physical activity, walking speed, and weight loss. The Mediterranean diet is linked to decreased frailty. From the Journal of the American Medical Medical Directors Association way back in 2014:

Abstract

Background and objective: Low intake of certain micronutrients and protein has been associated with higher risk of frailty. However, very few studies have assessed the effect of global dietary patterns on frailty. This study examined the association between adherence to the Mediterranean diet (MD) and the risk of frailty in older adults.

Design, setting, and participants: Prospective cohort study with 1815 community-dwelling individuals aged ≥60 years recruited in 2008-2010 in Spain.

Measurements: At baseline, the degree of MD [Mediterranean Diet] adherence was measured with the Mediterranean Diet Adherence Screener (MEDAS) score and the Mediterranean Diet Score, also known as the Trichopoulou index. In 2012, individuals were reassessed to detect incident frailty, defined as having at least 3 of the following criteria: exhaustion, muscle weakness, low physical activity, slow walking speed, and weight loss. The study associations were summarized with odds ratios (OR) and their 95% confidence interval (CI) obtained from logistic regression, with adjustment for the main confounders.

Results: Over a mean follow-up of 3.5 years, 137 persons with incident frailty were identified. Compared with individuals in the lowest tertile of the MEDAS score (lowest MD adherence), the OR (95% CI) of frailty was 0.85 (0.54-1.36) in those in the second tertile, and 0.65 (0.40-1.04; P for trend = .07) in the third tertile. Corresponding figures for the Mediterranean Diet Score were 0.59 (0.37-0.95) and 0.48 (0.30-0.77; P for trend = .002). Being in the highest tertile of MEDAS was associated with reduced risk of slow walking (OR 0.53; 95% CI 0.35-0.79) and of weight loss (OR 0.53; 95% CI 0.36-0.80). Lastly, the risk of frailty was inversely associated with consumption of fish (OR 0.66; 95% CI 0.45-0.97) and fruit (OR 0.59; 95% CI 0.39-0.91).

Conclusions: Among community-dwelling older adults, an increasing adherence to the MD was associated with decreasing risk of frailty.

Did you notice another good reason to eat fish?

I wonder why the research was published in the Journal of the American Medical Medical Directors Association?

Steve Parker, M.D.

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Type 2 Diabetes: Significant Health Benefits From Drugs Without Hypoglycemia

Insulin isn’t yellow

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.

“Try this for your vertigo”

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.

Full text in Nutrition, Metabolism & Cardiovascular Diseases.

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.

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Prevent Second Heart Attack With the Mediterranean Diet

Heart attacks and chest pains are linked to blocked arteries in the heart

Most patients with a heart attack have underlying atherosclerosis (“hardening of the arteries”) in the heart, called coronary artery disease. Around the time of a heart attack (if not before), doctors and patients should focus on mitigating risk factors for future heart attacks and other cardiac events. This is called “secondary prevention.” Risk factor modification might include smoking cessation, regular exercise, stress reduction, and diet modification. For years, I’ve been recommending the Mediterranean diet. Many others recommend a low-fat diet instead. A recent study supports my diet recommendation.

One way to assess risk of progressive atherosclerosis is to measure the thickness of the the carotid artery wall by ultrasound. Increasing thickness of the artery wall is linked to higher risk of atherosclerotic complications like heart attack and stroke. To drill down deeper, it’s the thickness of the innermost two layers of the artery wall, called the intima-media, that matters. The study at hand showed a reduction in carotid artery intima-media thickness over five years on a Mediterranean diet compared to a low-fat diet. Here’s the abstract:

Background and Purpose:

Lifestyle and diet affect cardiovascular risk, although there is currently no consensus about the best dietary model for the secondary prevention of cardiovascular disease. The CORDIOPREV study (Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention) is an ongoing prospective, randomized, single-blind, controlled trial in 1002 coronary heart disease patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat rich in complex carbohydrates versus Mediterranean diet rich in extra virgin olive oil) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study. Thus, to evaluate the efficacy of these diets in reducing cardiovascular disease risk. Intima-media thickness of both common carotid arteries (IMT-CC) was ultrasonically assessed bilaterally. IMT-CC is a validated surrogate for the status and future cardiovascular disease risk.

Methods:

From the total participants, 939 completed IMT-CC evaluation at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids, <50% carbohydrates) or a low-fat diet (28% fat, 12% monounsaturated fatty acids, >55% carbohydrates) with IMT-CC measurements at 5 and 7 years. We also analyzed the carotid plaque number and height.

Results:

The Mediterranean diet decreased IMT-CC at 5 years (−0.027±0.008 mm; P<0.001), maintained at 7 years (−0.031±0.008 mm; P<0.001), compared to baseline. The low-fat diet did not modify IMT-CC. IMT-CC and carotid plaquemax height were higher decreased after the Mediterranean diet, compared to the low-fat diet, throughout follow-up. Baseline IMT-CC had the strongest association with the changes in IMT-CC after the dietary intervention.

Conclusions:

Long-term consumption of a Mediterranean diet rich in extra virgin olive oil, if compared to a low-fat diet, was associated with decreased atherosclerosis progression, as shown by reduced IMT-CC and carotid plaque height. These findings reinforce the clinical benefits of the Mediterranean diet in the context of secondary cardiovascular prevention.

Reference

Parker here again. Undoubtedly, it would be more helpful if the investigators reported the actual rates of heart attack, stroke, and death in the two diet groups over five years. I suspect that will be in a future report.

An article in Clinical Cardiology states the serious nature of coronary artery disease (CAD) in those with diabetes (DM): “CAD is the main cause of death in both type 1 and type 2 DM, and DM is associated with a 2 to 4-fold increased mortality risk from heart disease. Over 70% of people >65 years of age with DM will die from some form of heart disease or stroke. Furthermore, in patients with DM there is an increased mortality after MI [myocardial infarction], and worse overall long-term prognosis with CAD.”

Steve Parker, M.D.

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Type 2 Diabetes? Drink Coffee and You May Live Longer

“Is the world shaking, or is it just me?”

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:

Aims

To evaluate the long-term consequences of coffee drinking in patients with type 2 diabetes.

Data synthesis

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.

Conclusions

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.

Citation

Steve Parker, M.D.

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Sad News

Photo by Pixabay on Pexels.com

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.

Photo by Pixabay on Pexels.com

“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.”

Photo by Min An on Pexels.com

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