Tag Archives: hemoglobin A1c

When Is the Hemoglobin A1c Test Misleading?

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? Sometimes the patient, usually a young one, is trying to pull the wool over my eyes. But there are other potential explanations.

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 isn’t always an accurate reflection of blood sugar levels.

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

Pregnancy

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).

Race

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

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Low-Carb Diet Improves Glucose Control in Japanese Type 2 Diabetics

Mt. Fuji in Japan

Mt. Fuji in Japan

I don’ know anything about Japanese T2 diabetes. I’ve never studied it. Their underlying physiology may or may not be the same as in North American white diabetics, with whom I am much more familiar.

For what it’s worth, a small study recently found improvement of blood sugar control and triglycerides in those on a carbohydrate restricted diet versus a standard calorie-restricted diet.

Only 24 patients were involved. Half were assigned to eat low-carb without calorie restriction; the other half ate the control diet. The carbohydrate-restricted group aimed for 70-130 grams of carb daily, while eating more fat and protein than the control group. The calorie-restricted guys were taught how to get 50-60% of calories from carbohydrate and keep fat under 25% of calories. At the end of the six-month study, the low-carbers were averaging 125 g of carb daily, compare to 200 g for the other group. By six months, both groups were eating about the same amount of calories.

Average age was 63. Body mass index was 24.5 in the low-carb group and 27 in the controls. (If you did the research, I bet you’d find Japanese T2 diabetics have lower BMIs than American diabetics.) All were taking one or more diabetes drugs.

The calorie-restricted group didn’t change their hemoglobin A1c (a standard measure of glucose control) from 7.7%. The low-carb group dropped their hemoglobin A1c from 7.6 to 7.0% (statistically significant). The low-carb group also cut their triglycerides by 40%. Average weights didn’t change in either group.

Bottom Line

This small study suggests that mild to moderate carbohydrate restriction helps control diabetes in Japanese with type 2 diabetes. The improvement in hemoglobin A1c is equivalent to that seen with initiation of many diabetes drugs. I think further improvements in multiple measures would have been seen if carbohydrates had been restricted even further.

Steve Parker, M.D.

Link to reference.

h/t Dr Michael Eades

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Hemoglobin A1c Test May Miss Many Cases of Diabetes

…according to a report at MedPageToday. If there’s any doubt about a new case of diabetes, consider a fasting blood sugar test or glucose tolerance test.

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Aerobic Versus Strength Training for People With Diabetes

“Resistance training, similarly to aerobic training, improves metabolic features and insulin sensitivity and reduces abdominal fat in type 2 diabetic patients,” according to a report in the current issue of Diabetes Care.

Italian researchers randomized 40 type 2 diabetics to follow either an aerobic or strength training program for four months.  The increase in peak oxygen consumption (VO2 peak) was greater in the aerobic group, whereas the strength training group gained more strength.  Hemoglobin A1c was similarly reduced in both groups, about 0.37%.  Body fat content was reduced in both groups, and insulin sensitivity and lean limb mass were similarly increased.  Pancreas beta-cell function didn’t change.

Per this one study, neither type of training seems superior overall.  If you’re just going to do one type of exercise program, choose your goal.  Do you want more strength, or more sustainable “windpower”? 

The Pennington Biomedical Research Center found somewhat different results in their larger and more complex study published in 2010.  However, they were primarily testing for diabetes control (as judged by hemoglobin A1c improvement), rather the improvements in strength or aerobic power.  The found the combination of aerobic and strength training is needed to improve diabetic blood sugar levels.  Both types of exercise—when considered alone—did not improve diabetes control. 

As for me, I do both strength and aerobic training.

By the way, I only read the abstract of the current research, not the full report. High-intensity intervals on a treadmill help me git’r done quicker.

Steve Parker, M.D.

PS: PWD = people or person with diabetes.  Do you like that term or would you prefer “diabetic”?

Reference:  Bacchi. Elizabeth, et al.  Metabolic Effects of Aerobic Training and Resistance Training in Type 2 Diabetic Subjects
A randomized controlled trial (the RAED2 study)
Diabetes Care.  Published online before print February 16, 2012, doi: 10.2337/dc11-1655

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Severe Carb Restriction in Type 2 Diabetes

U.K. researchers found major metabolic improvements in obese type 2 diabetics following a very low-carbohydrate diet, compared to a low-fat portion-controlled diet.  The latter is a standard recommendation in the U.S. for overweight type 2 diabetics.
 
This study is an oldie (2005) but a goodie.
 
Methodology
 
The investigators randomly assigned 102 poorly controlled diabetics to follow one of the two diets for three months.  Participants had average weights of 224 pounds (102 kg),  body mass index 36, age 58, hemoglobin A1c’s of 9%.  Half of them were men.  About 40% of the diabetics in both groups were on unspecified oral diabetic drugs; 20% were on insulin and 40% were using a combination of the two.  Sulfonylurea was mentioned, but not metformin. 
 
Participants were randomly assigned to either a low-fat portion-controlled weight-loss diet or a low-carbohydrate diet.  The goal with the low-carb diet was “up to 70 g of carbohydrate per day,” including at least a half a pint of milk and one piece of fruit.  (Is a UK pint the same as in the US?).  Increased physical activity was recommended to both groups. 
 
Only 79 of the 102 participants made it through the three-month diet intervention.  Drop-out rate was the same for both groups.
 
What Did They Find?
 
(Differences are statistically significant unless otherwise noted.)
Weight loss for the low-carb group was 3.55 kg (7.8 lb) compared to only 0.92 kg (2 lb) for the low-fat cohort.
 
The total/HDL cholesterol ratio improved for the low-carb group (absolute decrease of 0.48 versus 0.10). 
 
Hemoglobin A1c and systolic blood pressure tended to decrease more for the low-carb group, but did not reach statistical significance.  For instance, HgbA1c dropped 0.55% (in absolute terms) for the low-carb group, and 0.23% for the low-fat group.  Lower HgbA1c indicates improved blood sugar control.
 
Caloric intake was not different between the groups (about 1350 cals/day by diet recall method).
 
The low-carb group reduced carbs to 109 g/day compared to 168 g in the  low-fat cohort.
 
The low-carb group consumed 33% of energy as carbs compared to 45% for the low-fat group.
 
The low-carb group consumed 40% of energy as fat compared to 33% in the low-fat cohort.
 
Protein intake was 26% of energy for the low-carbers compared to 21% for the low-fatters.
 
Absolute saturated fatty acid intake was higher for the low-carbers, but still considered moderate.
 
Insulin dose was reduced in about 85% of the insulin users in the low-carb group but in only 22% of the low-fat group.  Oral diabetic pill use was unchanged in both groups.
 
Comments
 
This is a classic research report that I cited in Conquer Diabetes and Prediabetes: The Low-Carb Mediterranean Diet.
 
The improved total/HDL cholesterol ratio in the low-carbers may reduce risk of heart and vascular disease.  These investigators didn’t look at LDL particle size.  Other studies have found that low-carb eating tends to shift LDL cholesterol (bad stuff) from small dense particles to light fluffy particles, which are thought to be less harmful to arteries.
 
The authors considered reduction of carbs to 109 grams a day to be “severe.”  That compares to 275 grams a day eating by the typical U.S. citizen.  I agree that a reduction of carbs by two-thirds is major restriction.  Dr. Richard Bernstein and I consider severe restriction to be 20–30 grams, or perhaps up to 50 g.
 
I suspect the improved metabolic numbers in the low-carbers would have been even more dramatic if they had reduced carbs well below 100 grams a day.  The Ketogenic Mediterranean Diet reduces digestible carbs to 20–30 grams daily.  Many diabetics start losing control of their blood sugars when daily carbs exceed 60–80 grams.
 
Low-carb diets often yield better weight loss than low-fat calorie-restricted diets, as was seen here.  This is often attributed to lower calorie consumption on the low-carb diets.  These investigators didn’t see that here.
 
Low-carb diets are often criticized as being hard to stick with.  The low-carbers here didn’t have any more drop-outs than the low-fat group.  Granted, it was only a three-month study.
 
Based on what we know today, the reduced need for insulin in these patients was entirely predictable. 
 
The authors had some concern about the higher relative saturated fatty acid consumption in the low-carbers.  In 2011, we know that’s not much, if any, cause for concern.
 
 
 
 
Reference: Daly, M.E., et al.  Short-term effects of severe dietary carbohydrate-restriction advice in Type 2 diabetes—a randomized controlled trialDiabetic Medicine, 23 (2006): 15-20.  doi: 10.1111/j.1464-5491.2005.01760.x

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Aerobic vs Strength Training: Which Improves Diabetes More?

Judging from improvement in hemoglobin A1c, the combination of aerobic and strength training is needed to improve diabetic blood sugar levels.  Both types of exercise—when considered alone—did not improve diabetes control, according to the latest research in the Journal of the American Medical Association.

One type of resistance training

One of the things that impressed me about Dr. Richard Bernstein’s book, Diabetes Solution, was his strong advocacy of weight training, also known as resistance training and strength training.  Weight lifting is a typical example.

Prior studies had shown exercise-induced  improvements (reductions)  in hemoglobin A1c, a great test for overall diabetes control, in the range of o.66% to 1.0% (absolute change, not relative).  That’s comparable to what we see with many drugs.  Much easier to pop a pill though, huh?

One earlier study showed hemoglobin A1c lowered by 0.4% with resistance training, 0.5% with aerobic training, and 1.0% with combined resistance/aerobic.  But folks doing both aerobic and resistance were exercising 270 minutes a week—39 minutes a day—which was significantly more than the people just doing one type of exercise. [This was the DARE study: Diabetes Aerobic and Resistance Exercise.] 

Investigators at the Pennington Biomedical Research Center in Louisiana wondered which type of exercise would be more effective, comparing the same minutes per week of activity.

Methodology

They randomized 262 sedentary type 2 diabetics to one of four groups: control, aerobic exercise, resistance training 3 days a week, or combined aerobic and resistance training (resistance twice weekly).  All three groups exercised for about 140 minutes a week—just 20 minutes a day, on average—for nine months.  Exercise intensity was 50 to 80% of maximum oxygen consumption (determined by a baseline treadmill stress test).  Nearly all participants were on diabetic drugs; 18% were on insulin.  I think the aerobic group exercised on treadmills.

Participant characteristics:  Women were 64% of the total.  Average age 56. Forty-seven percent were non-white (114 black, 10 Hispanic/other).  Average body mass index was 35.  Average hemoglobin A1c was 7.7%.  Not too many people dropped out of the study before it was over.

Results

No serious adverse event occurred during exercise.  The authors didn’t mention the occurence of hypoglycemia.

The combination training group dropped their hemoglobin A1c average by 0.34% (p = 0.03). The pure resistance and aerobic exercisers didn’t show any improvement over the control group.

The combination group lost 1.6 kg body weight on average compared to the control group.  Pure resistance and aerobic exercisers’ weights didn’t differ from the control group. [Remember, this was not a weight-loss study.]

Comments

The authors write:

The failure of the aerobic group to lose a substantial amount of weight (or fat) has been reported in numerous aerobic exercise trials, which may be due to aerobic training resulting in [higher] energy intake, expenditure compensation, or both.

If you’re trying to lose excess fat weight, resistance training appears to win over aerobic exercise.

Doing either aerobic execise or resistance exercise for an average of 20 minutes a day will not improve hemoglobin A1c levels in most type 2 diabetics.  We can assume blood sugars aren’t lower either.  It takes a combination of both types of exercise to lower hemoglobin A1c.

A hundred and forty minutes of exercise weekly—just 20 minutes a day—is not too much to ask for, if improved health and weight management are the goals.  More would be better.

Over nine months, the control group ended up needing more diabetic drugs.  The combination training group decreased its drug use.

Dr. Bernstein may still by right to stress resistance training over aerobic.  I bet he’d say these folks weren’t exercising enough.  The study at hand suggests that it’s important to do both types of exercise, especially if you’re not going to put much time into it.

The details of the resistance training program are probably important.  You can read the study yourself and decide if participants were on a good regimen.  I’ve little expertise in that area. 

ResearchBlogging.orgDiabetics taking insulin, sulfonylureas, and meglitinides are at risk for hypoglycemia during exercise. The study authors made little mention of this, so it may be safe to assume it wasn’t a problem. Certified diabetes educators saw participants monthly, which may have nipped the problem in the bud.

Steve Parker, M.D.

Reference: Church, T., Blair, S., Cocreham, S., Johannsen, N., Johnson, W., Kramer, K., Mikus, C., Myers, V., Nauta, M., Rodarte, R., Sparks, L., Thompson, A., & Earnest, C. (2010). Effects of Aerobic and Resistance Training on Hemoglobin A1c Levels in Patients With Type 2 Diabetes: A Randomized Controlled Trial JAMA: The Journal of the American Medical Association, 304 (20), 2253-2262 DOI: 10.1001/jama.2010.1710

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Using Hemoglobin A1c to Diagnose Diabetes

In July, 2009, an expert committee composed partially of representatives from the American Diabetes Association proposed that hemoglobin A1c be used as a diagnostic test for diabetes in non-pregnant adults and children. 

The expert committee proposed that diabetes is present when hemoglobin A1c is 6.5% or greater.  The test should be repeated for confirmation unless the individual has clear symptoms of diabetes.

The committee also recommended that the term “prediabetes” be phased out.  They indicated that a person with hemoglobin A1c of at least 6% but less that 6.5% is at risk (high risk?) of developing diabetes, yet they don’t want to give that condition a name (such as prediabetes). 

In December, 2009, the American Diabetes Association established a hemoglobin A1c criterion for the diagnosis of diabetes: 6.5% or higher.  Diagnosis of prediabetes involves hemoglobin A1c between 5.7 and 6.4%.  These numbers don’t apply to pregnant women. 

Previously established  blood sugar criteria can also be used to diagnose diabetes and prediabetes.

This step is a major change in the diagnosis of diabetes.   

Steve Parker, M.D.

Reference:  International Expert Committee.  International Expert Committee report on the role of the A1c assay in the diagnosis of diabetesDiabetes Care, 32 (2009): 1-8.

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How Well Should Diabetes Be Controlled?

Researchers in the U.K. suggest that a hemoglobin A1c of 7.5% may be optimal in terms of longevity for type 2 diabetics treated with drugs, according to a study published recently in The Lancet.

Hemoglobin A1c (HgbA1c) is a blood test widely used as a gauge of blood sugar control, reflecting average blood sugars over the previous three months.  The American Diabetes Association recommends a HgbA1c goal of 7% or less.  The American Association of Clinical Endocrinologists recommends 6.5% or less.  Dr. Richard K. Bernstein, a diabetologist and himself a type 1 diabetic, recommends HgbA1c’s as near normal as possible (about 5%). 

Many physicians believe that keeping blood sugar levels as close to normal as possible—often referred to as “tight control”— will help prevent certain diabetes complications such as blindness, kidney failure, and nerve damage.  We have good supportive evidence.

We assume tight control would also help prevent premature death from heart attacks and strokes, too.  Several recent studies—the ACCORD and ADVANCE trials—call this into question, however.  The ACCORD trial, for example, achieved near-normal glucose control with multiple medication options, yet found that the effort was linked to increased death rates from cardiovascular disease and from any cause (all-cause mortality).

The scariest thing about tight control is hypoglycemia, which can kill you quickly, for example,  if you’re operating dangerous machinery (e.g., driving), scuba-diving, or rock-climbing.

U.K. researchers recently reviewed records of diabetics treated either with 1) two oral medications (usually metformin and a sulfonylurea), or 2) a regimen containing insulin.  Each group had over 20,000 subjects.  They found that risk of death for those with an average HgbA1c of 6.4% (the lowest blood sugar levels in this study) was 52% higher than those with HgbA1c of 7.5%.  Those with the highest blood sugar levels over time—HgbA1c over 10% if I recall correctly—had the highest risk of death.  In general, those taking insulin had higher rates of death than those on pills.

It’s extremely difficult to interpret studies like this.  There are myriad ways to treat diabetes.  We have 10 classes of drugs for treatment of diabetes: this study looked at three.  There are at least three types of “diabetic diet” in common use: low-fat/high-carb, low-carb, and just regular eating, which depends on where you live.  Exercise, too, plays a role in treatment and longevity. 

With all these variables, should we put much stock in a study that looks at longevity from the perspective of just two therapeutic regimens?  How well would a football team do with just two plays in its play-book?

You’d think we would have a definite answer to the “tight versus loose control” issue by 2010.  We don’t.  It’s still very appealing to me to think that, if done right, tight control would yield the better outcomes.  Problem is, we don’t always know what’s right. 

One thing is clear: Having a HgbA1c of 7.5% is better than 10% in terms of health and longevity. 

But is 7.5% really better than 6.5 or 5.5 or 5.0% for a particular individual on a particular treatment program?  Probably not.  That’s why the ADA and AACE emphasize that treatment programs be tailored to the individual patient.        

Maybe controlling blood sugar levels is like controlling high blood pressure.  The ideal may be 120/80, but you gain very little, if any, by reducing high blood pressure below 140/90 (130/85 for diabetics).  HgbA1c of 5.0% may be ideal, but not necessary.

Steve Parker, M.D. 

References:

Currie, Craig, et al.  Survival as a function of HgA1c in people with type 2 diabetes: a retrospective cohort study.  The Lancet, January 27, 2010.  Early online publication   doi: 10.1016/S0140-6736(09)61969-3

Dluhy, Robert and McMahon, Graham.  Intensive glycemic control in the ACCORD and ADVANCE trials.  New England Journal of Medicine, 358 (2008):2630-2633.

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Low-Carb Mediterranean Diet Beats Low-Fat For Recent-Onset Type 2 Diabetes

MPj03417870000[1]A low-carbohydrate Mediterranean diet dramatically reduced the need for diabetic drug therapy, compared to a low-fat American Heart Association diet.  The Italian researchers also report that the Mediterranean dieters also lost  more weight over the first two years of the study.

Investigators suggest that the benefit of the Mediterranean-style diet is due to greater weight loss, olive oil (monunsaturated fats increase insulin sensitivity), and increased adiponectin levels.

The American Diabetes Association recommends both low-carbohydrate and low-fat diets for overweight diabetics.  The investigators wondered which of the two might be better, as judged by the need to institute drug therapy in newly diagnosed people with diabetes.

Methodology

Newly diagnosed type 2 diabetics who had never been treated with diabetes drugs were recruited into the study, which was done in Naples, Italy.  At the outset, the 215 study participants were 30 to 75 years of age, had body mass index over 25 (average 29.5), had average hemoglobin A1c levels of 7.73, and average glucose levels of 170 mg/dl.

Participants were randomly assigned to one of two diets:

  1. Low-carb Mediterranean diet (“MED diet”, hereafter):  rich in vegetables and whole grains, low in red meat (replaced with poultry and fish), no more than 50% of calories from complex carbohydrates, no less than 30% of calories from fat (main source of added fat was 30 to 50 g of olive oil daily).  [No mention of fruits or wine.  BTW, the traditional Mediterranean diet derives 50-60% of energy from carbohydrates.]
  2. Low-fat diet based on American Heart Association guidelines:  rich in whole grains, restricted additional fats/sweets/high-fat snacks, no more than 30% of calories from fat, no more than 10% of calories from saturated fats.

Both diet groups were instructed to limit daily energy intake to 1500 (women) or 1800 (men) calories.

All participants were advised to increase physical activity, mainly walking for at least 30 minutes a day.

Drug therapy was initiated when hemoglobin A1c levels persisted above 7% despite diet and exercise.

The study lasted four years.

Results

By the end of 18 months, twice as many low-fat dieters required diabetes drug therapy compared to the MED dieters—24% versus 12%.

By the end of four years, seven of every 10 low-fat dieters were on drug therapy compared to four of every 10 MED dieters. 

The MED dieters lost 2 kg (4.4 lb) more weight by the end of one year, compared to the low-fat group.  The groups were no different in net weight loss when measured at four years: down 3–4 kg (7–9 lb).

Compared to the low-fat group, the MED diet cohort achieved significantly lower levels of fasting glucose and hemoglobin A1c throughout the four years.

The MED diet group saw greater increases in insulin sensitivity, i.e., they had less insulin resistance.

The MED group had significantly greater increases in HDL cholesterol and decreases in trigylcerides throughout the study.  Total cholesterol decreased more in the MED dieters, but after the first two years the difference from the low-fat group was not significantly different. 

The Mediterranean group’s intake of carbohydrates was 8-9% lower than baseline, monounsaturated fat was 5.5% higher than baseline, and polyunsaturated fat was 2.5% higher than baseline.  Compared with their baseline, the low-fat group didn’t make much change in these nutrient groups.  These numbers hold up for all four years of the study. 

Comments

The MED diet here includes “no more than 50% of calories from complex carbohydrates.”  The authors don’t define complex carbs.  Simple carbohydrates are monosaccharides and disaccharides.  Complex carbs are oligosaccharides and polysaccharides.  Another definition of complex carbs is “fruits, vegetables, and whole grains,” which I think is definition of complex carbs applicable to this study. 

The editors of the Annals of Internal Medicine conclude that:

A low-carbohydrate, Mediterranean-style diet seems to be preferable to a low-fat diet for glycemic control in patients with newly diagnosed type 2 diabetes.

I’m sure the American Diabetes Association will take heed of this study when they next revise their diet guidelines.  If I were newly diagnosed with type 2 diabetes, I wouldn’t wait until then.

This study dovetails nicely with others that show prevention of type 2 diabetes with the Mediterranean diet, reversal of metabolic syndrome—a risk factor for diabetes—with the Mediterranean diet (supplemented with nuts), and prevention of type 2 diabetes and pre-diabetes in people who have had a heart attack.

For instruction on how to lose weight with a Mediterranean-style diet, click here (it’s not the low-carb diet used in the study at hand).

For general information on Mediterranean eating, visit Oldways.

Steve Parker, M.D.

Reference:  Esposito, Katherine, et al.  Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetesAnnals of Internal Medicine, 151 (2009): 306-314.

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