Is the Hemoglobin A1c Test Always Accurate?

From 97 to 90 mg/dl

Not the only way to assess glucose control

Can you believe I’ve had patients show me a week’s worth of home glucose tests showing great numbers, tell me they’ve been that good for the last three months, and then I find a sky high Hemoglobin A1c test? How can that be?

Hemglobin A1c (or HgbA1c) is a standard measure of glucose control, or lack thereof, over the three months preceding the blood test.

It’s also used for diagnosis of diabetes and prediabetes. Levels between 5.7 and 6.4% suggest prediabetes. Levels of 6.5% of higher indicate diabetes.

Hemoglobin is the oxygen-carrying protein in red blood cells. HgbA1c tells us if many sugar molecules are stuck to the hemoglobin, a process called glycosylation. HgbA1c is sometimes referred to as glycated hemoglobin. About half of the HgbA1c value is determined by blood sugar levels in the month before the blood draw.

But the HgbA1c test is not always an accurate reflection of blood sugar levels.

Many factors unrelated to serum glucose (sugar) levels can alter the HgbA1c value. Here they are:


Pregnant women tend to have lower than average HgbA1c.


Certain Types of Anemia

Iron-deficiency anemia may yield falsely low or high HgbA1c, depending on whether it’s being treated or not.

Acute bleeding and hemolytic anemia give falsely low HbA1c values.

The unifying feature here is that young red blood cells, called reticulocytes, take some time to get glycosylated.

Lack of a Spleen 

HgbA1c will be falsely high. Your spleen removes old red blood cells. Not having a spleen increases the life span of red blood cells, so they can accumulate more glucose molecules.

Various Hemoglobin Types or Congenital Abnormalities

Hemoglobin S and hemoglobin C may lead to deceptively low HgbA1c. Hemoglobin F tends to overestimate.

Blood Transfusions

Recent red blood cell transfusions will lower the HgbA1c if it was elevated to begin with, especially if lots of blood is transfused.

Renal Failure

It’s complicated; talk to your kidney specialist.

Chronic Disease

HgbA1c values can be unreliable in chronic alcoholism, chronic narcotic users, severely high triglyceride or bilirubin levels, kidney failure, vitamin and mineral deficiencies (particularly the vitamins and minerals needed to make red blood cells).


Hispanics, Asians, and Blacks tend to have higher HgbA1c’s than Whites who have the same blood sugar levels. The difference is about 0.3% (absolute, not relative.

Wild Glycemic Excursions

What’s this? You might call it labile diabetes: dramatic swings between sugars too low and way too high. For example, this patient may have daily glucose swings between 40 and 210 mg/dl (2.2  and 11.7 mmol/l). His HgbA1c may turn out near normal or acceptable, but many experts worry that the wild oscillations may contribute to diabetic microvascular complications like eye and kidney disease.

Are There Alternatives to HgbA1c?

Yes. If you think the HgbA1c test is inaccurate, consider other tests such as continuous glucose monitoring, fructosamine, glycated albumin, 1,5-anhydroglucitol, and more frequent home glucose monitoring.

Steve Parker, M.D.

Reference: Bazerbachi, F., et al. Is hemoglobin A1c an accurate measure of glycemic control in all diabetic patients? Cleveland Clinic Journal of Medicine, vol. 81, #3, March 2014: 146-149

Does Diabetes Drug Empagliflozin Reduce Heart Disease Risk?

diabetic mediterranean diet, Steve Parker MD

Pharmacist using her advanced degree to count pills

Larry Husten writing at CardioBrief mentions a recent press release alleging that empagliflozin reduces cardiovascular disease risk.

Larry points out a problem with diabetes drugs that I’ve been harping on for years: we don’t know the long-term outcomes and side effects of most of our drugs. As long as a diabetes drug reduces blood sugar and seems to be relatively safe in the short term, it will be approved for use by the U.S. Food and Drug Administration. Larry writes:

Until now the best thing anyone could say for sure about all the new diabetes drugs was that at least they didn’t kill people. That’s because although these drugs have been shown to be highly effective in reducing glucose levels, a series of large cardiovascular outcomes trials failed to provide any evidence of significant clinical benefit.

Cardiovascular disease is a major stalker of diabetics. I’m talking about heart attacks, strokes, heart failure, sudden cardiac death.

The aforementioned press release touts reduced cardiovascular disease risk in patients taking empagliflozin. What’s missing is any mention of overall death reduction. Even if the drug really prevents heart attacks and strokes, which I doubt, don’t you want to know about overall death rates? I do. For all we know, the drug could promote illness and death from infections and cancer while reducing heart attacks and strokes. The drug’s net effect could be premature death. 

I’m 99% certain the researchers doing the work have the mortality data. Unless they don’t want to know.

By no means am I against drug use. But if I had type 2 diabetes, I’d do all I can with exercise, weight control, and low-carb eating before resorting to new or higher doses of drugs.

Steve Parker, M.D.

Long-Term T2 Diabetes Diet Trial: Low-Carb Edges Out High-Carb Eating

Paleo-compliant low-carb meal. I almost used this for my Paleobetic Diet book cover.

Paleo-compliant low-carb meal. I almost used this for my Paleobetic Diet book cover.

This is an important report because most diet studies last much less than one year. Details are in the American Journal of Clinical Nutrition.

Study participants were 115 obese (BMI 35) type 2 diabetics with hemoglobin A1c averaging 7.3%. Average age was 58. So pretty typical patients, although perhaps better controlled than average.

They were randomized to follow for 52 weeks either a very low-carbohydrate or a high-carbohydrate “low-fat” diet. Both diets were designed to by hypocaloric, meaning that they provided fewer calories than the patients were eating at baseline, presumably with a goal of weight loss. The article abstract implies the diets overall each provided the same number of calories. They probably adjusted the calories for each patient individually. (I haven’t seen the full text of the article.) Participants were also enrolled in a serious exercise program: 60 minutes of aerobic and resistance training thrice weekly.

Kayaking is an aerobic exercise if done seriously

Kayaking is an aerobic exercise if done seriously

The very low-carb diet (LC diet) provided 14% of total calories as carbohydrate (under 50 grams/day). The high-carb diet (HC diet) provided 53% of total calories as carbohydrate and 30% of calories as fat. The typical Western diet has about 35% of calories from fat.

Both groups lost weight, about 10 kg (22 lb) on average. Hemoglobin A1c, a reflection of glucose control over the previous three months, dropped about 1% (absolute reduction) in both groups.

Compared to the HC diet group, the LC dieters were able to reduce more diabetes medications, lower their triglycerides more, and increase their HDL cholesterol (“good cholesterol”). These triglyceride and HDL changes would tend to protect against heart disease.


You can lose weight and improve blood sugar control with reduced-calorie diets—whether very low-carb or high-carb—combined with an exercise program. No surprise there.

I’m surprised that the low-carb group didn’t lose more weight. I suspect after two months of dieting, the low-carbers started drifting back to their usual diet which likely was similar to the high-carb diet. Numerous studies show superior weight loss with low-carb eating, but those studies are usually 12 weeks or less in duration.

diabetic diet, low-carb diet, paleobetic diet

Low-Carb Brian Burger and Bacon Brussels Sprouts (in the Paleobetic Diet)

The low-carb diet improved improved lipid levels that might reduce risk of future heart disease, and allowed reduction of diabetes drug use. Given that we don’t know the long-term side effects of many of our drugs, that’s good.

If I have a chance to review the full text of the paper, I’ll report back here.

Steve Parker, M.D.

Reference: Jeannie Tay, et al. Comparison of low- and high-carbohydrate diets for type 2 diabetes management: a randomized trial. First published July 29, 2015, doi: 10.3945/​ajcn.115.112581    Am J Clin Nutr

Which Diet for a 41-Year-Old Asian Indian With Prediabetes?

The CulinaryRx blogger at MedPageToday asked two physicians what diet modifications they’d recommend for a 41-year-old Asian-Indian man with prediabetes. (To read the article you may need to do a free sign-up.)

The moderator asked his experts twice whether carbohydrate restriction is important, and never got a straight answer. These experts must not think it’s important since they push legumes, lentils, fruits, and whole grains. Dr. Nadeau said he believes there is no specific diet for folks with diabetes. I almost fell off my chair when I read one comment recommending cookies and sweets, because they’re traditional. They also recommend low glycemic load, nuts, higher protein consumption, vegetables, and “good oils” like olive oil (ghee not even  mentioned).

Read this blog post for prior comments that include advice from possible clinicians.

I’m confident that Dr. Ronesh Sinha in Silicon Valley, California, would disagree with the advice of MedPageToday’s experts. Dr. Sinha would likely recommend limiting digestible carbohydrates to 50–150 grams/day as the most important dietary step.

I’m still looking for clinical studies of various diets for South Asians with prediabetes and diabetes.

Steve Parker, M.D.

Getting Bariatric Surgery to Improve Your Type 2 Diabetes? RYGB May Beat LAGB

An article at Diabetes Care suggests that insulin-treated T2 diabetics getting bariatric surgery were almost twice as likely to get off insulin if they had roux-en-Y gastric bypass rather than laparoscopic adjustable gastric banding. The former procedure is also generally more effective for weight loss.

If you think bariatric surgery is a sure-fire cure for type 2 diabetes, it’s not. I would go as far as I could with diet and exercise before going under the knife.

Steve Parker, M.D.

Cabbage: A Natural Laxative

There’s something about cabbage…

I spent 30 minutes surfing the ‘Net to find out why cabbage soup can help fight constipation and even cause diarrhea. The answer is raffinose.

Raffinose is sometimes called a fiber but more often is characterized as a trisaccharide, oligosaccharide, or complex carbohydrate. It’s all four.

A typical bowl of cabbage soup has three grams of fiber. If you eat two bowls, that’s six grams, still not all that much, but can predictably cause loose stools or diarrhea in  many folks because of a particular type of fiber: raffinose.

The thing about raffinose is that it passes through the small intestine undigested because we lack the enzyme alpha-galactosidase. When raffinose hits the colon, bacteria start digesting it (i.e., fermenting it), potentially leading to gas, bloating, and/or diarrhea. If your “dose” of raffinose is small enough, you won’t have any symptoms. To use cabbage soup as a constipation preventative or remedy, you have to experiment to see what dose works for you.

Raffinose is also found in beans and cruciferous vegetables like brussels sprouts and cauliflower

Steve Parker, M.D.

PS: Ever heard of Beano? The active ingredient is the enzyme alpha-galactosidase. It breaks down raffinose in the small intestine, to simple sugars we can absorb.

PPS: Raffinose is one of the oligosaccharides to avoid if you’re on a low FODMAPs diet.

Could Fructose Cause Diabetes?

Lumps of Diabetes

Cubes of Diabetes?

A Pharm.D (Dr of Pharmacology) and a pair of MD’s surveyed much of the available scientific literature—both animal and human studies—and concluded that fructose is a major culprit in the rise of type 2 diabetes and prediabetes. Fructose does its damage by increasing insulin resistance. ScienceDaily has the details.

Be aware that their conclusion is certainly not universally accepted. I read “Pathogenesis of type 2 diabetes mellitus” at a few months ago and saw no mention of fructose. Under dietary factors, they mainly talked about obesity and how that increases insulin resistance, leading to elevated blood sugars, while the reverse happens with weight loss. I haven’t looked at all the research so I have no definite opinion yet on the fructose-diabetes theory; I’m skeptical.

Fructose is a type of simple sugar. Common dietary sources of fructose are fruits, table sugar (aka sucrose, a 50:50 combination of glucose and fructose molecules), and high-fructose corn syrup (which is usually 42 or 55% fructose).

Damaging effects, if any, of fructose in these fruits may be mitigated by the fiber

Damaging effects, if any, of fructose in these fruits may be mitigated by the fiber

A few quotes from ScienceDaily:

“At current levels, added-sugar consumption, and added-fructose consumption in particular, are fueling a worsening epidemic of type 2 diabetes,” said lead author James J. DiNicolantonio, PharmD, a cardiovascular research scientist at Saint Luke’s Mid America Heart Institute, Kansas City, MO. “Approximately 40% of U.S. adults already have some degree of insulin resistance with projections that nearly the same percentage will eventually develop frank diabetes.”

*   *   *

While fructose is found naturally in some whole foods like fruits and vegetables, consuming these foods poses no problem for human health. Indeed, consuming fruits and vegetables is likely protective against diabetes and broader cardiometabolic dysfunction, explained DiNicolantonio and colleagues. The authors propose that dietary guidelines should be modified to encourage individuals to replace processed foods, laden with added sugars and fructose, with whole foods like fruits and vegetables. “Most existing guidelines fall short of this mark at the potential cost of worsening rates of diabetes and related cardiovascular and other consequences,” they wrote.

If you’re eating a typical Western or American diet, you’ll reduce your fructose consumption by adopting the Paleobetic DietMediterranean diet, or Low-Carb Mediterranean Diet.


Steve Parker, M.D.

Dietary Saturated Fat Doesn’t Influence Future Course of Coronary Heart Disease


Most heart attacks occur in folks with pre-existing coronary artery disease that’s been present for years

If you already have coronary artery disease, Dr. Axel Sigurdsson says that ongoing saturated fat intake probably doesn’t matter, in terms of future cardiac events (like heart attacks) or risk of death from any cause.

Dr. Sigurdsson is a cardiologist in Iceland.

Some quotes from his blog:

For decades, cardiologists have advised patients with heart disease to restrict the intake of saturated fats and dietary cholesterol. Many patients still believe this to be the cornerstone of their lifestyle modification.

The main reason for avoiding saturated fats is the assumption that they adversely affect the lipid profile of our patients.

*   *   *

Recent studies suggest that the recommendation to avoid saturated fats may have been premature and not based on solid scientific evidence.

Now, a recently published Norwegian study shows that dietary intake of saturated fatty acids was not associated with risk of future events or death among patients with established coronary artery disease.

It is important to keep in mind that most of the patients were receiving secondary prevention drug therapy including aspirin, beta blockers and statins.

Anyhow, the results of the study certainly suggest that high intake of saturated fats is not a risk factor among patients with coronary heart disease receiving modern-day treatment.

These recent scientific data don’t imply hat we should urge our patients to consume high amounts of saturated fats. They only tell us that there is no association and accordingly, restriction won’t help.

So, it’s certainly a lifeline for those who believe red meat, whole-fat milk, cheese, cream, butter and eggs can be a part of a healthy diet.

On the other hand we must realise that scientific studies often provide contradictory results. A US study published last year suggested that greater adherence to a low carbohydrate diet high in animal sources of fat and protein was associated with higher all-cause and cardiovascular mortality following acute heart attack.

It appears the jury is still out…


Steve Parker, M.D.

Book Review: “Stop the Clock: The Optimal Anti-Aging Strategy”

dementia, memory loss, Mediterranean diet, low-carb diet, glycemic index, dementia memory loss

“I wish we could have read PD Mangan’s book thirty years ago!”

I read P.D. Mangan’s 2015 book, Stop the Clock: The Optimal Anti-Aging Strategy. I give it five stars in Amazon’s rating system. High recommended.

♦   ♦   ♦

I approached this book with trepidation. I like PD Mangan even though I’ve never met him. We’ve interacted on Twitter and at our blogs. You can tell from his blogging that he’s very intelligent. I don’t know his educational background but wouldn’t be surprised if he has a doctorate degree. My apprehension about the book is that I was concerned it would be brimming with malarkey and scams. Fortunately, that’s not the case at all.

Twin studies have established that 25% of longevity is genetic. That leaves a lot of lifestyle factors for us to manipulate.

I’m not familiar with the anti-aging scientific literature and don’t expect it will ever be something I’ll spend much time on. But it’s an important topic. I’ll listen to what other smart analysts—like Mr. Mangan—have to say about it.

It’s quite difficult to do rigorous testing of anti-aging strategies on free-living humans. So the best studies we have were done with worms, rodents, and monkeys; the findings may or may not apply to us. For example, long-term calorie restriction—about 30% below expected energy needs—is known to prolong life span in certain worms and rodents, with mixed results in rhesus monkeys. It’s the rare person who would follow such a low-calorie diet for years as an experiment. I doubt I would do it even if proven to give me an extra five years of life. I like to eat.

There are several prominent theories of how and why animals age. The author thinks the major factors are:

  1. oxidative stress
  2. inflammation
  3. a decline in autophagy (perhaps most important)

An effective anti-aging program should address these issues.

In the anti-aging chapter of his book, The South Asian Health Solution, internist Ronesh Sinha says that “Lifestyle practices that reduce excess inflammation in the body will help delay the aging process.” Dr. Sinha is a huge exercise advocate and low-carb diet proponent.

Mr. Mangan makes a convincing argument that a good way to forestall aging is to apply hormetic stress. Hormesis is a phenomenon whereby a beneficial effect (e.g., improved health, stress tolerance, growth, or longevity) results from exposure to low doses of an agent or activity that is otherwise toxic or lethal when given at higher doses.

Needs a bit more hormetic stress

Needs a bit more hormetic stress

In case you’re not familiar with hormesis, here’s a major example. Lack of regular exercise leads is linked to premature death from heart disease and cancer. Starting and maintaining an exercise program leads to greater resistance to injury and disease and longer life span. On the other hand, too much exercise is harmful to health and longevity. We see that in professional athletes and excessive marathon runners. Something about exercise—in the right amount—enhances the body’s intrinsic repair mechanisms. That’s the hormetic effect of exercise; one mechanism is by turning on autophagy.

Autophagy is the body’s natural process for breaking down and removing or recycling worn-out cellular structures. This wearing-out occurs daily and at all ages.

If you’re thinking Mr. Mangan recommends exercise as an anti-aging strategy, you’re exactly right. Especially resistance training and high intensity training. His specific recommendations are perfectly in line with what I tell my patients.

Calorie restriction is another form of hormesis; the body reacts by up-regulating stress defense mechanisms. As a substitute for calorie restriction, the author recommends intermittent fasting. Intermittent fasting increases insulin sensitivity, which leads to enhanced autophagy. Fasting seems perfectly reasonable if you think about it, which very few do. Many of us eat every three or four hours while awake, whether a meal or a snack. If you think about it, that’s not a pattern that would be supported by evolution. In the Paleolithic era, we often must have gone 12–16 hours or even several days without food. Hominins without the resiliency to do that would have died off and not passed their genes down to us.

Steve Parker MD, Advanced Mediterranean DIet

Naturally low-carb Caprese salad: mozzarella cheese, tomatoes, basil, extra virgin olive oil

Another anti-aging trick is a low-carb diet, defined as under 130 grams/day, or under 20% of total calories. It may work via insulin signaling and weight control.

Glutathione within our cells is a tripeptide antioxidant critical for clearing harmful reactive oxygen species (free radicals). We need adequate glutathione to prevent or slow aging. Cysteine is the peptide that tends to limit our body’s production of glutathione. We increase our cysteine supply either through autophagy (which recycles protein peptides) or diet. Dietary sources of cysteine are proteins, especially from animal sources. Whey protein supplements and over-the-counter n-acetyl cysteine are other sources. Fasting is another trick that increases cysteine availability via autophagic recyling.

I don’t recall the author ever mentioning it, but if you hope to maximize longevity, don’t smoke. Even if it has hormetic effects. Maybe that goes without saying in 2015.

When I read a book like this, I always run across tidbits of information that I want to remember. Here are some:

  • those of us in the top third of muscular strength have a 40% lower risk of cancer (NB: you increase your strength through resistance training not aerobics)
  • exercise helps prevent cognitive decline and dementia, at least partially via enhanced autophagy
  • exercise increases brain volume (in preparing to do this review I learned that our brains after age 65 lose 7 cubic centimeters of volume yearly)
  • optimal BMI may be 20 or 21, not the 18.5-25 you’ll see elsewhere (higher BMI due to muscle mass rather than fat should not be a problem)
  • Scientist Cynthia Kenyon: “Sugar is the new tobacco.” (in terms of aging)
  • phytochemicals (from plants, by definition) activate AMPK, a cellular energy sensor that improves stress defense mechanisms and increases metabolic efficiency
  • curcumin (from the spice turmeric) activates AMPK
  • coffee promotes autophagy
  • he does not favor HGH supplementation
  • in the author’s style of intermittent fasting, you’re not reducing overall calorie intake, just bunching your calories together over a shorter time frame (e.g., all 2,500 calories over 6-8 hours instead of spread over 24)
  • mouse studies suggest that intermittent fasting could reduce risk of Alzheimer’s disease and Parkinsons disease
  • consider phytochemical supplements: curcumin, resveratrol, green tea extract
  • calorie-restriction mimetics include resveratrol, curcumin, nicotinamide, EGCG, and hydroxycitrate
  • supplemental resveratrol at 150 mg/day improved memory and cognition in humans

The author provides very specific anti-aging recommendations that could be followed by just about anyone. Read the book for details. Scientists are working feverishly to develop more effective anti-aging techniques. I look forward to a second edition of this book in three to five years.

Steve Parker, M.D.

PS: People with certain medical conditions, such as diabetics taking drugs that can cause hypoglycemia, should not do intermittent fasting without the blessing of their personal physician. If you have any question about your ability to fast safely, check with your doctor.

PPS: If you have diabetes or prediabetes and want to reduce your carbohydrate consumption, consider my Low-Carb Mediterranean Diet or Paleobetic Diet.

QOTD: Don’t Let Gravity Get You Down

Average age of study subjects was 71

A good resistance training program will strengthen her bones, improve her balance, and prevent that hip fracture 60 years from now

Adult life is a battle against gravity. Weight training postpones your inevitable defeat.

—Steve Parker, M.D.