Tag Archives: type 2 diabetes

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

Have You Heard About Dulaglutide for Diabetes?

I forgot to tell you about a new drug for diabetes that hit the market in the U.S. last fall. My preferred initial treatment approach to type 2 diabetes is diet and exercise in most cases, but in many cases that’s not enough.

If your blood sugar’s 400 mg/dl (22 mmol/l) and you’re fairly symptomatic from it, I’ll probably have to start you out on insulin while initiating dietary changes at the same time. Later we’ll try to get you off insulin, onto metformin, and perhaps off drugs entirely within a couple months. (Type 1 diabetics have to keep taking insulin shots, of course.)

Where this new drug fits into our armamentarium isn’t clear. Click here for links to professional association guidelines on diabetes drug prescribing.

In September, 2014, the Food and Drug Administration approved the fourth drug in the GLP-1 analogue class: dulaglutide. The granddaddy in the class is exenatide (Byetta). The new GLP-1 receptor agonist will be sold in the U.S. under the name of Trulicity. It’s a once-weekly injection.

This is only a summary and is liable to change. Get full information from your prescribing healthcare provider and pharmacist.

Resistance training helps control blood sugar

Resistance training helps control blood sugar


For adults with type 2 diabetes, in conjunction with diet and exercise. It’s not a first-line drug. It can be used by itself or in combination with metformin, pioglitazone, glimiperide (and presumably other sulfonylureas), and insulin lispro (e.g., Humalog, a rapid-acting insulin). The drug has not been tried with basal (long-acting) insulins.


Start with 0.75 mg subcutaneously every week. Can go up to 1.5 mg weekly if needed.

Adverse Effects

Hypoglycemia is rare, but possible, when GLP-1 analogues are used as the sole diabetes drug. When it happens, it’s rarely severe. But the risk increases substantially when dulaglutide is used along with insulin or insulin secretagogues such as sulfonylureas or meglitinides.

Common side effects are nausea, vomiting, diarrhea, abdominal pain, decreased appetite, dyspepsia, and fatigue.

It might cause thyroid tumors and pancreatitis.

Do Not Use If…

…you have a family or personal history of medullary thyroid cancer, or if you have Multiple Endocrine Neoplasia syndrome type 2 or pre-existing severe gastrointestinal disease. Those who are pregnant or nursing babies should probably not take it since we have no data on safety. Don’t use for diabetic ketoacidosis.

Use only with caution if you have a history of pancreatitis or known liver impairment.

Steve Parker, M.D.

Click for full prescribing information.

Short-Term Paleo Diet Improves Glucose Control in Obese Type 2 Diabetes (the Masharani Study)

UCSF is here

UCSF is here

A three-week Paleolithic-style diet improved blood sugars and lipids in obese type 2 diabetics, according to researchers at the University of California—San Francisco. This is the Lynda Frassetto study I’ve been waiting over a year for. The first named author is U. Masharani, so I’ll refer to this work in the future as the Masharani study. Sorry, Lynda.

To understand the impact of this study, you need to know about a blood test called fructosamine, which reflects blood sugar levels over the preceding 2–3 weeks. You may already be familiar with a blood test called hemoglobin A1c: it tells us about blood sugars over the preceding three months. Blood glucose binds to proteins in our blood in a process called glycation. The higher the blood glucose, the more bonding. Glucose bound to hemoglobin molecules is measured in HgbA1c. Glucose bound to plasma proteins (predominantly albumin) is measured as fructosamine. It probably has nothing to do with fructose. Fructosamine is a generic name for plasma ketoamines.

If you’re doing a diabetic diet study over over 2–3 weeks, as in the report at hand, changes in glucose control will mostly be detected in fructosamine rather than HgbA1c levels.

How Was the Research Done?

Twenty-five obese diabetics in the San Francisco Bay area were randomly assigned to either a paleo-style diet or one based on American Diabetes Association (ADA) guidelines. They followed the diets for three weeks, with various measurements taken before and after intervention.

Participants were aged 50-69; you have to guess the sex breakdown. Average body mass index was 34. Over half (63%) were White/European American; there were three each of Asian, African American, and Hispanic ethnicity. They had normal blood pressures and diabetes was well controlled, with hemoglobin A1c’s around 7% and fructosamine levels close to normal. Four subjects were on no diabetes medications; 14 were taking metformin alone, five were on metformin and a sulfonylurea, one was on long-acting insulin and a sulfonylurea. No drug dosages were changed during the study.

Both intervention diets were designed for weight maintenance, i.e., avoidance of weight loss or gain. If participants lost weight, they were instructed to eat more. All food was prepared and provided for the participants. Three meals and three snacks were provided for daily consumption.

Fourteen subjects completed the paleo diet intervention. They ate lean meats, fruits, vegetables, tree nuts, poultry, eggs, canola oil, mayonnaise, and honey. No added salt. No cereal grains, dairy, legumes, or potatoes. Calorie percentages from protein, fat, and carbohydrate were 18%, 27%, and 58%, respectively. Compared to the ADA diet, the paleo diet was significantly lower in saturated fat, calcium, and sodium (under half as much), while higher in potassium (twice as much). These dieters eased into the full paleo diet over the first week, allowing bodies to adjust to higher fiber and potassium consumption. The paleo diet had about 40 grams of fiber, over twice as much as the ADA diet.

[I wonder why they chose canola over other oils.]

Ten subjects completed the ADA diet, which included moderate salt, low-fat dairy, whole grains, rice, bread, legumes, and pasta. Calorie percentages from protein, fat, and carbohydrate were 20%, 29%, and 54%, respectively (very similar to the paleo diet). I don’t have any additional description for you. I assume it included meat, poultry, eggs, and fruit.

Diet compliance was confirmed via urine measurements of sodium, potassium, pH, and calcium.

What Did the Researchers Find?

Both groups on average lost about 2 kg (4-5 lb).

Compared to their baseline values, the paleo group saw reductions in total cholesterol, HDL cholesterol, LDL cholesterol, HgbA1c (down 0.3% absolute reduction), and fructosamine. Fructosamine fell from 294 to 260 micromole/L. [The normal non-diabetic range for fructosamine is 190-270 micromole/L.]

Compared to their baseline values, the ADA diet group saw reductions in HDL cholesterol and HgbA1c (down 0.2% absolute reduction) but no change in fructosamine, total cholesterol, and LDL cholesterol.

Comparing the groups to each other, the difference in fructosamine change was right on the cusp of statistical significance at p = 0.06.

Within each group, insulin resistance trended down, but didn’t reach statistical significance. However, when they looked at the folks who were the most insulin resistant, only the paleo dieters improved their resistance. By the way, insulin resistance was measure via euglycemic hyperinsulinemic clamp instead of the short-cut HOMA-IR method.

Blood pressures didn’t change.

The authors don’t mention hypoglycemia at all, nor alcohol consumption.

They note that some of the paleo dieters complained about the volume of food they had to eat.


I found what I think are a couple misprints. Table 1 has incorrect numbers for the amount of sodium and potassium in the ADA diet. See the text for correct values. Table 2 give fructosamine values in mg/dl; they should be micromoles/L.

Final Thoughts

This particular version of the paleo diet indeed seems to have potential to help control diabetes in obese type 2’s, perhaps even better than an ADA diet, and despite the high carb content. Obviously, it’s a very small study and I’d like to see it tested in a larger population for several months, and in type 1 diabetics. But it will be years, if ever, before we see those research results. Diabetics alive today have to decide what they’ll eat tomorrow.

I wish the researchers had explained why they chose their paleo diet macronutrient breakdown: calorie percentages from protein, fat, and carbohydrate were 18%, 27%, and 58%, respectively. Perhaps they were trying to match the ratios of the ADA diet. But from what I’ve read, the average ancestral paleo diet carbohydrate energy percentage is 30-35%, not close to 60%. My experience is that reducing carb calorie consumption to 30% or less helps even more with glucose control. Reducing carbs that low in this study would have necessitated diabetes drug adjustments and increased the risk of hypoglycemia.

The authors wonder if the high fiber content of the paleo diet drove the lowered glucose levels.

High HDL cholesterol is thought to be protective against coronary artery disease and other types of atherosclerosis. Both diet groups here saw reductions in HDL. That’s something to keep an eye on.

The ADA diet group saw a drop in HgbA1c but not fructosamine. I can’t explain how HgbA1c goes down over three weeks without a change in fructosamine level.

You have to wonder if the paleo diet results would have been more impressive if the test subjects at baseline had been sicker, with poorly controlled blood pressures and HgbA1c’s of 9% or higher. And it sounds like some of these folks would have lost weight if not forced to eat more. The paleo diet is more satiating than some.

The article was well-written and a pleasure to read, in contrast to some I’ve suffered through recently.

Steve Parker, M.D.

Reference: Masharani, U., et al. Metabolic and physiologic effects from consuming a hunter-gatherer (Paleolithic)-type diet in type 2 diabetes. European Journal of Clinical Nutrition, advance online April 1, 2015. doi: 10.1038/ejcn.2015.39

Why Do Diabetics Resist the Paleo Diet?

Dr. Ernie Garcia (MD) posted a passionate essay about his difficulty getting his patients with diabetes to follow a carbohydrate-restricted Paleolithic diet. He makes a good case for carbohydrate addiction. A few quotes:

Today I saw a lady at my office. Fairly typical middle-aged, over weight female with poorly controlled diabetes. She recently started on an insulin pump but her glucose control is no better at all. I had a suspicion why, and again started to question the details of what she eats. Of course, she eats carb after carb after carb. Whole wheat this, and low fat that. She has tried to cut the carbs in the past, and actually had pretty decent success, but quickly falls back into your carbilicious ways. Why? Why go back when a change in diet shows clear improvement in her sugars?

*   *   *

What do addicts do? They generally know what they do is bad for them, and they have periods of clarity where they do better. Eventually though, the pull of their drug of choice draws them back in. Or, they slip up and use just a little and BAM…right back to square one. They feel shame for their addiction, people look down upon them for it, and they wish so badly they could make a permanent change, but they always fall back into old habits. Now, imagine a heroin addict who is advised to control the addition by sticking with “moderation” because of course, everything is good in moderation right?

Another issue that type 2 diabetics have is that they’ve been eating copious carbohydrates for over 40 years. It’s hard to break any habit with that type of longevity. It doesn’t help that they’re immersed in a carb-centric culture.


Steve Parker, M.D.


Do Sugar Substitutes Cause Overweight and T2 Diabetes?

We don’t know with certainty yet. But a recent study suggests that non-caloric artificial sweeteners do indeed cause overweight and type 2 diabetes in at least some folks. The study at hand is very small, so I wouldn’t bet the farm on it. I’m not changing any of my recommendations at this point.

exercise for weight loss and management, dumbbells

Too many diet sodas?


The proposed mechanism for adverse metabolic effects of sugar substitutes is that they alter the mix of germs that live in our intestines. That alteration in turn causes  the overweight and obesity. See MedPageToday for the complicated details. The first part of the article is about mice; humans are at the end.

Some quotes:

“Our results from short- and long-term human non-caloric sweetener consumer cohorts suggest that human individuals feature a personalized response to non-caloric sweeteners, possibly stemming from differences in their microbiota composition and function,” the researchers wrote.

The researchers further suggested that these individualized nutritional responses may be driven by personalized functional differences in the micro biome [intestinal germs or bacteria].


Diabetes researcher Robert Rizza, MD, of the Mayo Clinic in Rochester, Minn., who was not involved with the research, called the findings “fascinating.”

He noted that earlier research suggests people who eat large amounts of artificial sweeteners have higher incidences of obesity and diabetes. The new research, he said, suggests there may be a causal link.

“This was a very thorough and carefully done study, and I think the message to people who use artificial sweeteners is they need to use them in moderation,” he said. “Drinking 17 diet sodas a day is probably a bad idea, but one or two may be OK.”

I won’t argue with that last sentence! (Unless you have phenylketonuria and want to use aspartame.)

Finally, be aware that several clinical studies show no linkage between human consumption of non-caloric artificial sweeteners and overweight, obesity, and T2 diabetes.

Steve Parker, M.D.

Do the Drug Companies Have Too Much Influence on Diagnosis and Management of Type 2 Diabetes?

diabetic mediterranean diet, Steve Parker MD

Pharmacist counting pills

MedPageToday has recently completed a series of articles looking at socioeconomic issues related to diabetes drugs that have come onto the market in the last decade. They call it their Diabetes Drugs Investigation. I recommend the entire series to you if you have type 2 diabetes. The authors’ have five major points:

1. “Diabetes drugs improve lab tests, but not much more, particularly in pre-diabetics.” FDA drug approvals were based mostly on whether hemoglobin A1c or blood sugar levels improved, not on improvements in hard clinical endpoints such as risk of death, heart attacks, stroke, blindness, amputations, etc.

2. “Physicians and drug makers have reported diabetes drugs as the “primary suspect” in thousands of deaths and hospitalizations.”

3. “Diabetes drug makers paid physicians on influential panels millions of dollars.” The implication is that the panelists were not totally unbiased in their assessments of drug effectiveness and safety.

4. “Risk of a risk now equals disease.” This is about the latest redefinition of prediabetes which created many more “patients.” Prediabetes can progress to type 2 diabetes over a number of years: one of every four adults with prediabetes develops diabetes over the next 3 to 5 years. Some doctors are even treating prediabetes with diabetic drugs. (I recommend a “diet and exercise” approach.) The authors think the prediabetic label—one third of U.S. adults, including half of all folks over 65—is over-used and over-treated.

5. “The clinical threshold for diagnosing diabetes has crept lower and lower over the past decade.” For instance, in 1997 expert panels lowered the threshold defining diabetes from a fasting blood glucose level of 140 mg/dl (7.8 mmol/l) to 125 mg/dl (6.9 mmol/l). Four million more American adults became diabetics overnight. In 2003, they lowered the threshold for prediabetes from a fasting blood glucose from 110 mg/dl (6.1 mmol/l) to 100 mg/dl (5.6 mmol/l). Boom! 46 million more American prediabetics.

I fully agree with the authors that we don’t know which drugs for type 2 diabetes are the best in terms of prolonging life, preventing diabetes complications, and postponing heart attacks and strokes. Furthermore, we don’t know all the adverse long-term effects of most of these drugs. For instance, metformin had been on the market for over a decade before we figured out it’s linked to vitamin B12 deficiency.

That’s why I try to convince my patients to do as much as they can, when able, with diet and exercise before resorting to one or more drugs. (All type 1 diabetics and a minority of type 2 diabetics must take insulin.) Maybe it’s healthier to focus primarily on drug therapy…but I don’t think so.


Steve Parker, M.D.

Is a Vegan Diet Better Than Paleo for T2 Diabetes?

We don’t know yet because they’ve never been compared head-to-head.

paleo diet, Steve Parker MD, how to cook asparagus and Brussels sprouts

These might be on the vegan Ma-Pi 2 diet

What we do have is a specific vegan diet (Ma-Pi 2) compared to a low-fat diet in a study published by Nutrition & MetabolismCarbsane Evelyn dove into the study at her blog (recommended reading), or you can read the original research report yourself. Study subjects had fairly well-controlled type 2 diabetes and were elderly (66) and overweight (84 kg or 185 lb). The vegan diet was mostly whole grains, vegetables, legumes, and green tea.  The low-fat and vegan diets both probably supplied 200-300 calories/day fewer than what the subjects were used to: 1900 cals for men, 1700 for women. The study lasted only three weeks.

The vegan group ate 335 grams/day of carbohydrate compared to 235 grams in the low-fat group. In contrast, the Paleobetic Diet provides 60-80 grams/day of digestible carb and the Ketogenic Mediterranean Diet allows a max of 20-30 grams.

The vegans in the study at hand ate 15-20 more grams/day of fiber. High fiber intake is linked to better blood sugar control.

From the study abstract:

After correcting for age, gender, BMI at baseline, and physical activity, there was a significantly greater reduction in the primary outcomes fasting blood glucose and post-prandial blood glucose in those patients receiving the Ma-Pi 2 diet compared with those receiving the control diet. Statistically significantly greater reductions in the secondary outcomes, HbA1c, insulin resistance, total cholesterol, LDL cholesterol and LDL/HDL ratio, BMI, body weight, waist and hip circumference were also found in the Ma-Pi 2 diet group compared with the control diet group. The latter group had a significantly greater reduction of triglycerides compared with the Ma-Pi 2 diet group.

The take-home point for me is that overweight T2 diabetics can improve short-term diabetes numbers despite a high carbohydrate consumption if they restrict calories and eat the “right” carbs. Restrict calories enough—600/day?—and T2 diabetes might be curable

I’ve written before about vegetarian/vegan diets for diabetes. My patients are more resistant to vegan diets than they are to low-carb.

Paleobetic diet, low-carb breakfast

Not allowed not on the Ma-Pi 2 diet. Bacon, eggs, black coffee, and Cholula hot sauce. A caveman wouldn’t recognized any of this except for eggs.

I scanned the original report and don’t see any problems with Evelyn’s summary.

Steve Parker, M.D.

Metformin: More Effective in Blacks Than Whites

Diabetes Self-Management has some of the details.

The implication is that the genetically determined physiology of black diabetics is different from whites. There could be other explanations, admittedly.


Here’s why I bring this to your attention. You don’t see me review many scientific articles involving mice, rats, pigs, or rabbits. In fact, I hardly ever read them. I take care of human patients. I suspect there are too many genetic differences between us and them that clinically pertinent studies are rare.

If you read my blogs carefully, you’ll also note I often hesitate to generalize clinical study results from one ethnic group to others. The different black/white responses to metformin validates my approach.

Type 2 diabetes in whites and blacks may not be the same disease, and it could be different in Asians, Australian aborigines, and North American Native Americans. For that matter, Ethiopian black diabetes may not be the South Africa black diabetes.

You may also be starting to understand why there’s so much confusion about which diabetic drugs are the best. We have 12 different classes of drugs now; what’s best for me may not be best for you.

Steve Parker, M.D.

PS: Type 1 diabetes, on the other hand, is probably more homogenous across ethnic and national boundaries.

Dr. Richard Feinman Doubts Red Meat Causes T2 Diabetes

This looks healthful to me, despite the red meat

This looks healthful to me, despite the red meat

At least one recent study implicated red meat consumption as a cause of type 2 diabetes. Dr. Richard Feinman at his blog takes a close look at the 2013 study and points out the great difficulty in making the leap from red meat to diabetes. I think Dr. Feinman’s point is best made by his graph about half way through the post, showing steadily decreasing red meat consumption as T2 diabetes takes off over the last four decades. (I assume all the figures are based on U.S. data.)

For the opposing viewpoint, read the original study (linked at Dr. F’s blog) or search at Fanatic Cook.

Do I worry that red meat causes diabetes? Not much. I await definitive research.

Steve Parker, M.D.