Tag Archives: cardiovascular disease

No Clear Survival Differences Seen Between Diabetes Drugs

"How about this one?"

“How about this one?”

A multinational group of researchers tried to determine which drugs for type 2 diabetes were better at prolonging life and preventing cardiovascular deaths. They reviewed the existing literature (i.e., they did a meta-analysis of prior clinical studies.

There are no clear winners. Placebo worked as well as the eight drug classes examined!

Unfortunately, the abstract doesn’t say how long the clinical studies lasted, only mentioning that they were at least 24 weeks long. It’s quite possible it would take at least three to five years to see an effect on death rates.

Click the source link at the bottom of the page for details at MPT.

Selected quotes:

“Eight different diabetes drug classes examined in a meta-analysis failed to demonstrate improved cardiovascular or all-cause mortality compared with placebo.Researchers analyzed 301 randomized clinical trials of patients with type 2 diabetes, and found that, metformin outperformed some other drug classes for its effect on hemoglobin A1c levels, there were no significant differences in mortality — including when placebo was included as a drug class.”

***

“A central finding in this meta-analysis was that despite more than 300 available clinical trials involving nearly 120,000 adults and 1.4 million patient-months of treatment, there was limited evidence that any glucose-lowering drug stratified by coexisting treatment prolonged life expectancy or prevented cardiovascular disease,” the authors wrote.”

***

“The authors wrote that their findings are consistent with guidelines from the American Diabetes Association, which — like the algorithm from the American Association of Clinical Endocrinologists — recommend that metformin monotherapy be used for the initial treatment of patients with type 2 diabetes. “Based on this review, clinicians and patients may prefer to avoid sulfonylureas or basal insulin for patients who wish to minimize hypoglycemia, choose GLP-1 receptor agonists when weight management is a priority, or consider SGLT-2 inhibitors based on their favorable combined safety and efficacy profile,” the authors wrote.”

Source: No Clear Survival Benefit Seen Among Diabetes Drugs | Medpage Today

Open wide!

Open wide!

1 Comment

Filed under Drugs for Diabetes

Sitting Is the New Smoking: Too Much Is Bad for Your Heart

“How much sitting can a body take without hurting the heart? A meta-analysis of prospective cohort studies found a nonlinear association with cardiovascular disease (CVD), suggesting that 10 hours a day might be a critical threshold.”

Source: Long Periods of Sitting Take Toll on the Heart | Medpage Today

Comments Off on Sitting Is the New Smoking: Too Much Is Bad for Your Heart

Filed under Uncategorized

Are These Two Diabetes Drugs Better Than the Others?

Better living through chemistry

Empagliflozin is a pill. Liraglutide is a once-daily subQ injection.

The two drugs in question are empagliflozin (aka Jardiance) and liraglutide (aka Victoza). Both are used to treat type 2 diabetes, not type 1.

A major problem we have with most diabetes drugs is that while they do lower blood sugars, we don’t have much evidence on whether they actually prolong life and prevent bad outcomes like heart attacks, strokes, cancer, blindness, kidney failure, amputations, and serious infections. It gets even more complicated. For instance, a given drug may eventually be proven to prolong life by a year via prevention of death from heart disease, while at the same time increasing the risk of spending that last year bedridden from a stroke.

It’s extremely difficult and costly to suss out these issues. It requires large clinical trials wherein half of the PWDs (people with diabetes) are treated with a particular drug, and the other half are treated with “standard therapy.” Five or 10 years later you compare clinical endpoints between the two groups. A couple studies have done this recently.

A blogger I follow, Larry Husten, wrote the following:

But it was the secondary goal of these trials that led to the transformation of the field. Baked into the trial design was the provision that if they were able to establish noninferiority then the trial investigators were permitted to test for superiority. The second phase began when Empa-Reg became the first trial to convincingly show a clear benefit, including a reduction in cardiovascular death and a reduction in hospitalization for heart failure. with empagliflozin (Jardiance, Merck). Then, more recently, the LEADER trial showed a significant reduction in cardiovascular events with liraglutide (Victoza, Novo Nordisk). In both trials nearly all the patients had significant established cardiovascular disease—precisely the population that cardiologists are likely to see.

Click the embedded links above for more details. Even better, read the original research reports if you have the time and knowledge. I support my family with a full-time job taking care of patients, so it will be a while (if ever) before I can dig into this further. (When my book sales make me independently wealthy, I’ll have more time for this!)

diabetic diet, low-carb Mediterranean Diet, low-carb, Conquer Diabetes and Prediabetes

Analyzing clinical reports requires a good grasp of logic, statistics, and basic science

Are the LEADER and Empa-Reg trials valid? Yeah, maybe. In an ideal world, other investigators would try to replicate the results with additional clinical trials. Are the published results free of fraud and bias? I don’t know.

Because we don’t know the long-term effects of many of our diabetes drugs, I favor doing as much as possible to control blood sugars with diet, exercise, and weight management.

Stay tuned for future developments.

Steve Parker, M.D.

PS: Just because one drug in a class of drugs reduces bad clinical outcomes, it doesn’t mean all drugs in the class do.

PPS: If it’s hard for you to pronounce empagliflozin and liraglutide, some of my books don’t even have them.

Comments Off on Are These Two Diabetes Drugs Better Than the Others?

Filed under Drugs for Diabetes

Low-Fat Diet Loses to Mediterranean Diet in Heart Disease Prevention

The American Journal of Medicine has an article entitled “Diets to Prevent Coronary Heart Disease 1957- 2013: What Have We Learned?” The authors conclude:

The Mediterranean-style diet, with a focus on vegetables, fruit, fish, whole grains and olive oil, has proven to reduce cardiovascular events to a degree greater than low fat diets, and equal to or greater than the benefit observed in statin trials.

The only bone I’ll pick with that quote today is that folks with diabetes and prediabetes often have unacceptable blood sugar spikes when they eat whole grains. That’s one reason I designed the Low-Carb Mediterranean Diet.

Steve Parker, M.D.

Comments Off on Low-Fat Diet Loses to Mediterranean Diet in Heart Disease Prevention

Filed under Diabetes Complications, Grains, Health Benefits, Heart Disease, Mediterranean Diet

Which Tree Nut Provides the Most Omega-3 Fatty Acid?

David Mendosa says the answer is the macadamia nut.

Paleobetic diet

Macadamia nuts

A great thing about the macadamia nut is that it’s one of the few nuts with a good omega-6/omega-3 fatty acid ratio. In other words, it’s high in omega-3 and low in 6. This may have important cardiovascular health implications. Macadamias are one of the nuts I recommend in the Low-Carb Mediterranean Diet and  Paleobetic Diet.

David writes:

The first Australian macadamia plantation didn’t begin until the 1880s. And not until 1954 with the introduction of mechanised processing did commercial production became viable. Nowadays about 90 percent of the the world’s macadamia nut production comes from Hawaii, where it has become its third most important crop, according to The Wellness Encyclopedia of Food and Nutrition, University of California at Berkeley (1992).

Read the rest, where you’ll learn that macadamia nuts are the highest of all nuts in calories, gram for gram.

Steve Parker, M.D.

Paleobetic diet

Macadamia nuts on the tree

3 Comments

Filed under Heart Disease, Mediterranean Diet, nuts, Paleo diet

Do Low-Carb Diets Cause Premature Death?

Adult life is a battle against gravity. Eventually we all lose.

Adult life is a battle against gravity. Eventually we all lose.

Japanese researchers say low-carb diets are causing premature death. I’m skeptical.

The potentially healthful side effects linked to low-carb eating include reduced weight, higher HDL cholesterol, and lower triglycerides and blood pressure. The Japanese investigators wondered if the improved cardiovascular risk factors seen with low-carb diets actually translate into less heart disease and death.

How Was the Study At Hand Done?

The best way to test long-term health effects of a low-carb diet (or any diet) is to do a randomized controlled trial. You take 20,000 healthy and very similar people—not rodents—and randomize half of them to follow a specific low-carb diet while the other half all eat a standard or control diet. Teach them how to eat, make damn sure they do it, and monitor their health for five, 10, or 20 years. This has never been, and never will be, done in humans. The Nazis may have done it, but it’s not published. In the old days, we could do this study on inmates of insane asylums or prisons.

What we have instead are observational studies in which people voluntarily choose what they’re eating, and we assume they keep eating that way for five or 10+ years. You also assume that folks who choose low-carb diets are very similar to other people at the outset. You depend on regular people to accurately report what and how much they’re eating. You can then estimate how much of their diet is derived from carbohydrate and other macronutrients (protein and fat), then compare health outcomes of those who were in the top 10% of carb eaters with those in the bottom 10%. (We’ve made a lot of assumptions, perhaps too many.)

Of the observational studies the authors reviewed, the majority of the study participants were from the U.S. or Sweden. So any true conclusions may not apply to you if you’re not in those countries. In looking for articles, they found no randomized controlled trials.

The observational studies estimated carb consumption at the outset, but few ever re-checked to see if participants changed their diets. That alone is a problem. I don’t know about you, but I’ve had significant changes in my diet depending on when I was in college and med school, when I was a bachelor versus married, when my income was higher or lower, and when I had young children versus teenagers. But maybe that’s just me.

The researchers looked at all-cause mortality, deaths from cardiovascular disease, and incidence of cardiovascular disease. They don’t bother to define cardiovascular disease. I assume heart attack, strokes, and peripheral vascular disease. (But aren’t aneurysms, deep vein thrombosis, and pulmonary embolism vascular diseases, too?) Wouldn’t you think they’d carefully define their end-points? I would. Since they were going to all this trouble, why not look at cancer deaths, too?

What Did the Investigators Conclude?

Very low-carbohydrate dieters had a 30% higher risk of death from any cause (aka all-cause mortality) compared to very high-carb eaters. The risk of cardiovascular disease incidence or death were not linked with low-carb diets. Nor did they find protection against cardiovascular disease.

Finally, “Given the facts that low-carbohydrate diets are likely unsafe and that calorie restriction has been demonstrated to be effective in weight loss regardless of nutritional composition, it would be prudent not to recommend low-carbohydrate diets for the time being.”

If Low-Carb Dieters Die Prematurely, What Are They Dying From?

The top four causes of death in the U.S. in 2011, in order, are:

  1. heart attacks
  2. cancer
  3. chronic lower respiratory tract disease
  4. stroke

You’ll note that two of those are cardiovascular disease (heart attacks and stroke). So if low-carb diets promote premature death, it’s from cancer, chronic lung disease, or myriad other possibilities. Seventy-five percent of Americans die from one of the top 10 causes. Causes five through 10 are:

  • accidents
  • Alzheimer disease
  • diabetes
  • flu and pneumonia
  • kidney disease
  • suicide

Problem is, no one has ever linked low-carb diets to higher risk of death from any specific disease, whether or not in the top ten. Our researchers don’t mention that. That’s one reason I’m very skeptical about their conclusion. If you’re telling me low-carb diets cause premature death, tell me the cause of death.

Another frustration of mine with this report is that they never specify how many carbohydrates are in this lethal low-carb diet. Is it 20 grams, 100, 150? The typical American eats 250-300 grams of carb a day. If you’re going to sound the alarm against low-carb diets, you need to specify the lowest safe daily carb intake.

For most of my career—like most physicians—I’ve been wary of low-carb diets causing cardiovascular disease. That’s because they can be relatively high in total fat and saturated fat. In 2009, however, I did my own review of the scientific literature and found little evidence of fats causing cardiovascular disease.

If you’re looking for a reason to avoid low-carb diets, you can cite this study and its finding of premature death. I’m not convinced. I’ll turn it around on you and note this study found no evidence that low-carb diets cause cardiovascular disease. The risk of cardiovascular disease had been the traditional reason for physicians to recommend against low-carb diets.

Steve Parker, M.D.

Reference: Noto, Hiroshi et al. Low-Carbohydrate diets and all-cause mortality: A systematic review and meta-analysis of observational studies. PLoS One, 2013; 8(1): e55050

4 Comments

Filed under Carbohydrate, coronary heart disease, Longevity, Weight Loss

Supplemental Omega-3 Fats’ Effect on Heart Disease, Stroke, Cancer, and Death: No Relationship In a General Population

Salmon is one the the cold-water fatty fish loaded with omega-3 fatty acids

Salmon is one the the cold-water fatty fish loaded with omega-3 fatty acids

I’ve been sitting on this research report a few years, waiting until I had time to dig into it. That time never came. The full report is free online (thanks, British Medical Journal!). I scanned the full paper to learn that nearly all the studies in this meta-analysis used fish oil supplements, not the cold-water fatty fish the I recommend my patients eat twice a week.

Here’s the abstract:

Objective: To review systematically the evidence for an effect of long chain and shorter chain omega 3 fatty acids on total mortality, cardiovascular events, and cancer.

Data sources: Electronic databases searched to February 2002; authors contacted and bibliographies of randomised controlled trials (RCTs) checked to locate studies.

Review methods Review of RCTs of omega 3 intake for 3 6 months in adults (with or without risk factors for cardiovascular disease) with data on a relevant outcome. Cohort studies that estimated omega 3 intake and related this to clinical outcome during at least 6 months were also included. Application of inclusion criteria, data extraction, and quality assessments were performed independently in duplicate.

Results: Of 15 159 titles and abstracts assessed, 48 RCTs (36 913 participants) and 41 cohort studies were analysed. The trial results were inconsistent. The pooled estimate showed no strong evidence of reduced risk of total mortality (relative risk 0.87, 95% confidence interval 0.73 to 1.03) or combined cardiovascular events (0.95, 0.82 to 1.12) in participants taking additional omega 3 fats. The few studies at low risk of bias were more consistent, but they showed no effect of omega 3 on total mortality (0.98, 0.70 to 1.36) or cardiovascular events (1.09, 0.87 to 1.37). When data from the subgroup of studies of long chain omega 3 fats were analysed separately, total mortality (0.86, 0.70 to 1.04; 138 events) and cardiovascular events (0.93, 0.79 to 1.11) were not clearly reduced. Neither RCTs nor cohort studies suggested increased risk of cancer with a higher intake of omega 3 (trials: 1.07, 0.88 to 1.30; cohort studies: 1.02, 0.87 to 1.19), but clinically important harm could not be excluded.

Conclusion: Long chain and shorter chain omega 3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.

Reference: Hooper, Lee et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ  2006;332:752-760 (1 April), doi:10.1136/bmj.38755.366331.2F (published 24 March 2006).

3 Comments

Filed under coronary heart disease, Diabetes Complications, Fat in Diet, Fish, Heart Disease, Longevity, Stroke