March 7, 2010 · 2:58 PM

Book Review: The New Atkins for a New You

Here’s my review of The New Atkins for  a New You, a weight-loss book by Dr. Eric Westman, Dr. Stephen Phinney, and Dr. Jeff Volek released a week ago.  The copyright holder is Atkins Nutritionals, Inc.  Under Amazon.com’s five-star rating system, I give it four stars (“I like it”).  

♦   ♦   ♦ 

The most exciting nutritional medicine development in recent memory is the fact that saturated fat consumption is not a significant cause of heart disease and premature death. The same goes for for total fat and cholesterol.  When enough physicians, nutritionists, and dietitians learn this, low-carb eating will take off like a rocket.

For those unfamiliar with the Atkins diet, it is designed for weight loss via high fat consumption and major carbohydrate restriction.  Protein intake is a bit higher than average.  As long as carbohydrates (carbs) are kept low, other foods are mostly unlimited.  Atkins has four phases.  As you graduate from one phase tothe next, more carbs are allowed, adding some carb sources before others (the Carb Ladder). 

Atkins has been around for years.  It’s not just a weight-loss diet; it’s a lifetime way of eating.

Doctors Westman, Phinney, and Volek are leaders in low-carb nutritional science.  The last time Atkins peaked (2003), we didn’t have the scientific studies backing up safety of the diet.  Now we do, in large part thanks to these guys. 

Physicians see beaucoup patients with overweight-related medical conditions.  We’re not going to recommend a diet that causes heart attacks, strokes, and other major medical complications.  Published research over the last eight years has established the relative safety of very low-carb diets, particularly Atkins.  Low-carb diets may even be healthier than the low-fat, high-carb diet that has been recommended by U.S. public health authorities for the last forty years.  Come to think of it, our current obesity and diabetes epidemics started around that same time.

The book covers nutrition basics, day-to-day practical application of Atkins eating, recipes and detailed meal plans, and the science behind the program.    

What’s New Since Dr. Atkins’ 2002 Book?

  • adaptations for vegetarians and vegans
  • adaptations for Latinos
  • coffee is now OK
  • introduction of the term “foundation vegetables” and almost doubling the amount of vegetables allowed in Phase 1: “approximately six cups of salad and up to two cups of cooked vegetables, depending upon the ones you select”
  • more flexility, such as the option to skip Phase 1 (induction)
  • focus on adequate protein intake, based on your height
  • emphasis on getting enough omega-3 fatty acids
  • no emphasis on supplements and low-carb products sold by Atkins Nutritionals,Inc.
  • diet journals—a personal record of your weight-loss journey—are recommended
  • eliminate or minimize “induction flu” and constipation (in Phase 1) by eating at least 1/2 teaspoon of salt daily [I’m skeptical.]
  • discussion of the trendy omega-6/omega-3 fatty acid ratio
  • favor monounsaturated fatty acids (e.g., olive oil, canola oil) over certain polyunsaturated fats, as in oils from corn, soybeans, sunflower, cottonseed, and peanuts
  • no mention of testing urine for ketosis
  • more discussion of psychological aspects of weight

The lack of ads for Atkins Nutritionals products is welcome and refreshing.  Too many of the official Atkins books read like infomercials, which diminishes credibility.

A vegetarian or vegan “Atkins diet” is just not something I can visualize.

What Could Have Been Done Better?

  • no specific amounts given for these recommended supplements: calcium, vitamin D, omega-3 fats, multivitamin, magnesium and other minerals (except “no iron”).  [Is the idea to encourage a visit the official Atkins website?]
  • little guidance for physicians who are to advise diabetics doing Atkins.  Few physicians are familiar enough with the program to make the necessary changes in particular diabetic medications.
  • little discussion of the constipation and leg cramps that often accompany very low-carb diets
  • the hype on the cover: “How would you like to LOSE UP TO 15 POUNDS IN TWO WEEKS!”  [To their credit, the authors note that such results are not typical.]
  • nearly all the measurements are U.S. Customary.  Metric users are out of luck.
  • four phases seem a bit much.  The beauty of Atkins Phase 1 is its simplicity. 

My favorite sentence: “White flour is better suited to glue for kindergarten art projects than to nutrition.”

My least favorite sentence: “We can’t stress strongly enough that the best diet for you is one composed of foods you love.”  I love apple pie and Cinnabon cinnamon rolls, but they won’t help me manage my weight.

The only error I found worth mentioning is minor.  The authors state that the American Heart Association recommends consumption of fish three times a week. The official policy is still “at least twice weekly.”

The book is very practical and easily understood by average people.  Most will skip the science chapters at the end.  I know the basic Atkins program works at least short-term; many of my patients have done it.

In summary, the book has nearly everything you need to be successful with the Atkins diet. 

As far as I know, there are no comprehensive long-term studies (e.g., 10+ years) regarding health outcomes of Atkins-style eating.  In other words, does Atkins have any effect on longevity, cancer, heart attacks, strokes, etc.?  But very few of the popular diets have these data either.  The best researched ways of eating in this respect are the Mediterranean diet and vegetarian diets.

Steve Parker, M.D.

Disclosure:  I was given nothing of value for this review by the authors, publisher, or Atkins Nutritionals, Inc.  I wrote it for the benefit of my patients and readers.

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March 6, 2010 · 2:00 AM

My Ketogenic Mediterranean Diet and Low-Carb Eating: Six-Month Summary

I started my Ketogenic Mediterranean Diet on September 1, 2009.  After two months, I stopped compulsive record-keeping and food measurement and made a few other intentional tweaks: fish five times a week instead of seven miminum, more nuts (often two ounces a day—I like nuts and they’re convenient), less salad, more dark chocolate.  Otherwise the last four months have been similar to the initial two months of strict KMD.  My daily digestible carbohydrate intake has probably crept up to 40 g compared to 20-25 g on the strict KMD—this is still considered very low-carb. 

Accomplishments

Starting weight was 170 pounds (77.3 kg) on September 1.   After two months—8.6 weeks—my weight clearly stabilized at 155 lb (70.5 kg).  I lost the 15 lb (6.8 kg) over the first six weeks then just hovered around 155 lb.  So average weekly weight loss over the six weeks was 2.5 pounds.  Also lost a couple inches (5 cm) off my waist.

For the last four months—November through February—I’ve been eating the aforementioned liberalized KMD.  Weight has stayed around 155-157 lb (71 kg).  No calorie counting.  I eat as much as I want, except for carbs.  The experience of the first two months taught me how to eat 20-25 g of carbs in a day; it’s the gauge by which I estimate I’m eating 40 g daily now.

Has It Been Easy?

Yeah, relatively easy.  Two other adults in my house are also eating low-carb, which definitely helps.  Blogging here also helps me maintain compliance.  I promised myself to report everything—the good, the bad, and the ugly—honestly.  Accountability is important. 

Staying with the program may be easier for me than for others because I am heavily invested in it, psychologically and time-wise. 

It’s also been helpful for me to participate at two low-carb online communities: LowCarbFriends and Active Low-Carber Forums.  We support each other.  Thanks, guys.

I took diet holidays twice, for three days at both Thanksgiving and Christmas.  Gained three to five pounds (1.8 kg) each time on high-carb eating, but lost it over the next week by returning to the strict KMD.

Any Surprises?

Induction flu.  I’d never heard of it before.  Occurs typically on days 2–5 of very low-carb dieting: achiness and fatigue.  Others also experience headaches and dizziness, and it may last 1–2 weeks.

Rapid weight gain during my diet holidays (aka cheat days).  I was not gorging.  I figure the weight was mostly new glycogen in liver and muscle.  And water.

Eating fish more than once a day is a lot of fish!  Quickly boring, even unappetizing.  But that’s just me.  I need to be a more creative.  Most of my fish lately has been canned tuna.

Assuming that the Daily Values of various nutrients recommended by the U.S. Food and Drug Administration are valid, the KMD foods come up short in many vitamins and minerals.  I bet this is an issue (a problem?) with many, if not most, very low-carb diets if supplements aren’t used.  Those Daily Values are debatable, of course.  For instance, Gary Taubes argues that you don’t need much vitamin C if eating few carbs.  My nocturnal leg cramps and constipation were proof enough for me that I needed at least some supplements.  The recommended KMD supplements remedy the DailyValue shortfall in vitamins and minerals.  Dr. Richard K. Bernstein has a 30-gram carbohydrate diet for his diabetic patients and himself, as outlined in his Diabetes Solution book: no supplements are required.  

As time passes, I worry less about getting enough of various micronutrients.   I feel fine.  I’m still taking the recommended KMD supplements (5 pills a day) plus sugar-free Metamucil.   

I never had hunger that I couldn’t satisfy within the guidelines of the diet. 

No major trouble with cravings or longing for carbs.  I’ve gone six months now without whole grain bread, oatmeal, pizza, and pasta—very unusual for me.  I’d be OK never eating them again.  What I do miss are sweet, often fat-laced, carbohydrates: pie, cookies, cinnamon rolls, candy bars, cake, ice cream.  I doubt that desire will ever disappear, although it does for some who eat very low-carb.   

I counted calories only during the first two months of this experiment.  Remember, fats and proteins are unlimited.  Nevertheless, I ate fewer calories than my baseline intake.   This calorie reduction is a well-documented effect of very low-carb diets.  Fats and proteins are more satiating than carbohydrates.  It’s possible I’ve limited total calories subconsciously. 

[An interesting experiment would be to try to gain weight by over-eating fats and proteins while keeping total digestible carbs under 30 g/day.  Has it been done already?]

What’s Next?

I’d like to answer some intriguing questions.

Why did my weight loss stop where it did, at 155 lb (70.5 kg)? 

If I’d started the KMD at 270 lb (123 kg) instead of 170 lb (77.3 kg), would my weight loss have stopped at 255 lb (116 kg), 210 lb (95.5 kg) or 155 lb (70.5 kg)? 

Will two people, 300 lb each (136 kg), end up at the same final weight when following the program religiously?  Probably not, but why not?    

Six months ago, I believed many scientific studies supported the idea that a higher intake of carbohydrates is healthier, long-term, than the very low-carb Ketogenic Mediterranean Diet and other very low-carb diets.  Studies seemed to support higher carbohydrate intake in the form of traditional fruits, vegetables, legumes, and whole grains.  After reviewing the scientific literature over the last few months, I’m not so sure that higher carb consumption is necessary or beneficial for long-term health and longevity.  The evidence is weak.  Nearly all the pertinent studies are observational or epidemiologic—not the most rigorous science. 

On the other hand, I still can’t help feeling that the recommended eating styles of people like Monica Reinagel, Darya Pino, and Holly Hickman may be healthier than the KMD over the long run, at least for people free of diabetes and prediabetes.  What features unify those three?  Food that is minimally processed, fresh, locally produced when able, including a variety of fruits, vegetables, nuts, whole grains, and legumes. 

It seems that the human body is marvelously designed to survive, even thrive, with multiple ways of eating—but not all ways.   

The strongest evidence for higher carb consumption supports whole grains as a preventative for heart disease (coronary artery disease).  But the effect is modest. 

The argument against higher carb consumption is simple for people with diabetes and prediabetes: carbs raise blood sugar levels, sometimes to an unhealthy degree.  

I don’t see much role for highly processed, refined carbohydrates except as a cheap source of energy (calories).

What’s next for me is to formalize an opinion on which carbs, if any, and in what amount, to add back into the diet of those who have lost weight with the Ketogenic Mediterranean Diet.  The answer will probably be different for two groups:

  1. those who have diabetes, prediabetes, or metabolic syndrome
  2. healthy people who just need to control weight

The goal is to maximize health and longevity without tipping over into excessive carb intake that leads to overweight and obesity with associated illnesses.  

The traditional Mediterranean diet—long associated with health and longevity—is rich in carbohydrates.  The Ketogenic Mediterranean Diet—much lower in carbs—has great potential to help with loss of excess weight and control of blood sugar levels.  Does the KMD incorporate enough of the healthy components of the Mediterranean diet?  We may never know for sure.

Steve Parker, M.D.

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March 5, 2010 · 2:15 PM

My New Pedometer: Accusplit Eagle AE 170 XLG

Regular physical activity is a great way to help prevent regain of lost weight.  One activity available to most of us is easy, inexpensive, generally safe, and available in all climates:

Walking

I received my Accusplit Eagle AE 170 XLG pedometer in the mail today, having ordered from Amazon.com a week ago.  About $25 USD, and I got free shipping.  I thought I ordered the AE 170 instead, because I didn’t want the extra bells and whistles of the XLG.  Same price for both.  What’s extra?  You can set goals for total distance, total steps, walking time, and calories burned on the XLG.  A graph shows your progress. 

Initial Impressions

It’s smaller than I imagined: 2 x 1.3  x 0.5 inches.

Over four pages of instructions.  This will be a little intimidating for some folks.  I’m sure I’ll have to refer back to the instructions at some point.  Do you tend to lose instructions, like me?  The well-designed Accusplit website has them.

For accurate estimates of distance and calories burned, you have to input your stride length and weight.  If you just want your step count, no need to input data.  Instructions on measuring stride length are good, resulting in x feet and xx inches.  The data input screen seems to request the stride length purely in inches, however.  This was the most confusing thing about setup.  I’m still not sure I entered my stride length properly.

It’s a good thing to see an estimate of calories burned.  You might think twice about that Snickers bar if you know you have to walk five miles to burn it off.

I usually think in English units.  You can switch the device to metric  if you prefer.

I clipped the Accusplit onto my jeans and thrice walked 200 steps.  Each time the device was right on the money.  I’m happy so far.

Steve Parker, M.D.

Disclosure: I received nothing of value from Accusplit or Amazon.com for writing this review.  It’s for the benefit of my patients and readers.

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February 28, 2010 · 2:00 AM

Which Pedometer Should I Get?

Setting a goal of walking 10,000 steps a day could motivate you to become active enough to gain the health benefits of exercise.  You count steps automatically with a pedometer.  Regular exercise also helps keep lost weight from returning.

Thanks to the Internet, you can waste spend hours reviewing features of pedometers before you make a purchase. 

Consumer Reports magazine in February, 2009, reviewed pedometers and their #1 Best Buy recommendation was the Omron HJ 112, which you can clip to your belt or waistband, or carry in your purse.  Available for around $15-30 (U.S. dollars). 

No. 2 was the Accusplit AE 170 XLG ($30-35).  The Accusplit AE 170 is probably just as good.  The only differences I see are that you can enter specific goals into the XLG and it tracks your progress and the time you’re moving. 

The Omron HIP (HJ 150, $20) is also very popular and probably the simplest one to use on this page.

The guys at Obesity Panacea blog recommend the Omron HJ-303 ($35), which you can carry in your pocket instead of clipped to your waistband.

You don’t have to be a marathoner or gym rat to gain most of the health benefits of exercise.  Why not start a walking program today?

Steve Parker, M.D.

Disclosure:  I was not paid to mention these products.  I haven’t owned or used any of them.  If you are a device manufacturer or sales representative and would like me to try your pedometer, please contact me by e-mail.

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February 27, 2010 · 4:05 AM

Alcohol Habit (Especially Wine) Started in Middle-Age Reduces Heart Attack and Stroke

Jesus turned water into wine at a wedding.  His mother asked him to do it.  Of all the miracles he performed and could have performed, I wonder why this is the first one recorded in the Holy Bible.

We have known for years that low or moderate alcohol consumption tends to lower the risk of cardiovascular disease such as heart attack and stroke, and prolongs life span.  Physicians have been hesitant to suggest that nondrinkers take up the habit.  We don’t want to be responsible for, or even accused of, turning someone into an alcoholic.  We don’t want to be held accountable for someone else’s drunken acts.  Every well-trained physician is quite aware of the ravages of alcohol use and abuse.  We see them up close and personal in our patients.

A scientific study published in 2008, however, lends support to a middle-aged individual’s decision to start consuming moderate amounts of alcohol on a regular basis.  It even provides a positive defense if a doctor recommends it to carefully selected patients.

This research, by the way, was supported by a grant from the National Heart, Lung, and Blood Institute, not the wine/alcohol industry.

Methodology

Researchers at the Medical University of South Carolina examined data on 15,637 participants in the Atherosclerosis Risk in Communities (ARIC) study over a 10-year period.  These men and women were 45 to 64 years old at the time of enrollment, living in four communities across the U.S.  Of the participants, 27% were black, 73% nonblack, 28% were smokers, and 80% of them had high blood pressure, high cholesterol, or diabetes.

Out of 15,637 participants at the time of enrollment, 7,359 indicated that they didn’t drink alcohol.  At baseline, these 7,359 had no cardiovascular disease except for some with high blood pressure.    Subsequent interviews with them found that six percent of the nondrinkers – 442 people – decided independently to become moderate alcohol drinkers.  Or at least they identified themselves as such.

“Moderate” intake was defined as 1-14 drinks per week for men, and 1-7 drinks a week for women.  Incidentally, 0.4% of the initial non-drinking cohort – 21 people – became self-identified heavy drinkers.

93.6% of the 7,359 non-drinkers said that they continued to be non-drinkers.  These 6,917 people are the “persistent nondrinkers.”

Type of alcohol consumed was also surveyed and broken down into 1) wine-only drinkers, or 2) mixed drinkers: beer, liquor, wine.

Researchers then monitored health outcomes for an average of 4 years, comparing the “new moderate drinkers” with the “persistent nondrinkers.”

Results

  •  Over 4 years, 6.9% of the new moderate drinkers suffered a cardiovascular event, defined as a heart attack, stroke, a coronary heart disease procedure (e.g, angioplasty), or death from cardiovascular disease.
  • Over 4 years, 10% of the persistent nondrinkers suffered a cardiovascular event.
  • The new moderate drinkers were 38% less likely than persistent nondrinkers to suffer a new cardiovascular event (P = 0.008, which is a very strong association).  The difference persisted even after adjustment for demographic and cardiovascular risk factors.
  • There was no difference in all-cause mortality (death rate) between the new moderate drinkers and the persistent nondrinkers.
  • New  drinkers had modest but statistically significant improvements in HDL and LDL cholesterol and mean blood pressure compared with persistent nondrinkers.
  • 133 new moderate drinkers consumed only wine
  • 234 new moderate drinkers consumed mixed types of alcohol
  • Wine-only drinkers were 68% less likely than nondrinkers to suffer a cardiovascular event.
  • “Consumers of moderate amounts of beer/liquor/mixed (which includes some wine) tended to also be less likely to have had a subsequent cardiovascular event than nondrinkers…but the difference was not significant.”

A Few Study Limitations

  • Four years is a relatively brief follow-up, especially for cancer outcomes.  Alcohol consumption is associated with certain types of cancer.
  • If moderate alcohol consumption indeed lowers death rates as suggested by several other studies, this study may not have lasted long enough to see it.
  • The alcohol data depended on self-reports.

Take-Home Points

The study authors cite four other studies that support a slight advantage to wine over other alcohol types.  It’s a mystery to me why they fail to stress the apparent superiority of wine in the current study.  Several other studies that found improved longevity or cardiovascular outcomes in low-to-moderate drinkers suggest that the type of alcohol does not matter.  Perhaps “the jury is still out.”  In the study at hand, however, it is clear that the reduced cardiovascular disease rate in new moderate drinkers is associated with wine.

In all fairness, other studies show no beneficial health or longevity benefit to alcohol consumption.  But at this point, the majority of published studies support a beneficial effect.

Wine is a component of the traditional healthy Mediterranean diet.  The Mediterranean diet is associated with prolonged life span and reduced cardiovascular disease.  This study strongly suggests that wine is one of the health-promoting components of the Mediterranean diet.

Starting a judicious wine habit in middle age is relatively safe for selected people and may, in fact, improve cardiovascular health, if not longevity.

Now the question is, red or white.  Or grape juice?

Steve Parker, M.D.

Reference:  King, Dana E., et al.  Adopting Moderate Alchohol Consumption in Middle Age: Subsequent Cardiovascular Events.  American Journal of Medicine, 121 (2008): 201-206.

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February 24, 2010 · 5:41 AM

Recipe: Arizona’s Baked Cheesecake (low-carb)

My daughter, Arizona, enjoys baking.  I’m nudging her into low-carb baking since I miss my sweets.  I’m still low-carbing, so I can’t eat a lot of what she bakes.  

Arizona is used to the commercial cheesecakes based on a pre-mixed box: you mix then refrigerate.  The one below is more work, but I think well worth the effort.  We had fun making this together. 

Arizona’s Low-Carb Baked Cheesecake    

Ingredients for crust:

Ground nuts (pecan, walnut, or almond), 1.5 cups (226 g)

Butter, melted, 4 tbsp (10 g)

Cinnamon, ground, 1/2 tsp (2g)

Egg white, one (33 g)

Splenda No Calorie Sweetener, Granulated, 1 tbsp (optional)

Ingredients for filling:

Cream cheese, 24 oz (675 g)

Sour cream, 1 cup (230 g)

Eggs, 4 large (50 g each)

Splenda No Calorie Sweetener, Granulated, 1 cup (28 g  I think)

Lemon juice from 1 lemon (47 g)

Vanilla extract, 2 tsp (4 g)

Preparation

Have the following ingedients at room temperature before you start: eggs, cream cheese, sour cream.

Preheat oven to 350.

Crust first: Put ground pecans, 4 tbsp melted butter (fine to microwave briefly), cinnamon, 1 tbsp Splenda (granulated), and egg white in bowl, then blend all.  Spread onto bottom of greased (with melted butter 1.5 tbsp) 9″ springform pan. Cover with plastic wrap to aid spreading evenly.  Bake in 350 degree oven for 10-15 minutes then remove.  Then reduce heat to 325.

Filling: Use a mixer on low to medium setting to beat the cream cheese until fluffy.  Blend in the Splenda incrementally, a little at a time, beating until creamy.  Then mix in the lemon juice and vanilla extract.  Gently mix in one egg at a time and beat on low speed after each egg.  Mix in the sour cream last.  Pour cream cheese mixture into the crusted springorm pan.  Place on the top rack in the 325 degree preheated oven for 50-60 minutes. On the rack below that, place a pie pan full of water.  [The water pan and gentle handling of the eggs help prevent cracking of the finalproduct.]  When time is up, turn off the oven and open the oven door but leave the cake in the oven to cool slowly.  After an hour, remove from oven.  After it cools to room temperature, put it in the refrigerator to age for 24 hours.

NOTES:

  • The filling has one cup of Splenda, which I estimate is one ounce (28 g). This has 96 calories, which I assume is mostly from maltodextrin rather than sucralose.
  • Many cooks just use a glass pie pan instead of the springform pan. The volume of this recipe is likely too much for a 9″ pie pan, so you could reduce the amounts; or make a larger pie or two smaller ones.
  • Some cooks don’t bother to bake the crust first.
  • Reduce the carb count even further by omitting the crust. 
  • For higher fiber, substitute flaxmeal for about  a third or 1/2 of the ground nuts. 
  • The Splenda in this recipe is not the same as in the individual serving packets.

Nutritional Analysis (thanks to NutritionData.com):

Recipe makes 12 servings.  Each serving has 444 calories (382 calories from fat), 8 g of carbohydrate, 2 g of fiber, 6 g of digestible carbohydrate.

Steve Parker, M.D.

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February 19, 2010 · 2:00 AM

Drug Review: Insulin

I was going to do a brief review of insulin therapy here, but I found a good one at About.com.  So why re-invent the wheel?

If interested, click through to the article by Michael Bihari, M.D.: Insulin for type 2 diabetes: What you need to know.

Steve Parker, M.D.

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February 17, 2010 · 2:00 AM

Brief Drug Review: Pramlintide

Pramlintide is sold in the U.S. as Symlin.  It’s only used in patients already taking meal-time rapid-acting insulin.  Pramlintide may have a role in treatment of overweight type 2 diabetics inadequately controlled on insulin, or who experience weight gain refractory to diet and exercise.

Remember that drug names vary by country and manufacturer.  This is a brief review; consult your physician or pharmacist for details.

Class:  amylin analogue

How does it work?

Amylin is a hormone stored in pancreas beta cells and is secreted along with insulin.  It affects glucose levels by several mechanisms, including slowed stomach emptying, regulation of glucagon secretion after meals, and by reducing food intake.  Amylin and insulin levels rise and fall together,working jointly to control blood sugar levels.   Amylin is relatively deficient in many cases of type 2 diabetes.

Pramlintide is a chemical similar in structure to amylin, and causes similar effects.  It allows insulin therapy to more easily match the body’s needs in the after-meal period.  It also promotes modest weight loss in obese patients. 

Pramlintide therapy reduces hemoglobin A1c by 0.5 to 1% (absolute decrease, not relative).

We have no data on long-term outcomes with this drug.

Uses

Pramlintide is FDA-approved for use in both type 1 diabetes and insulin-requiring type 2 diabetes.  It can be used with metformin and/or sulfonylureas as long as insulin is also part of the regimen.  It’s probably best not to use it with exenatide and other GLP-1-based therapies.

Dosing

It’s injected subcutaneously just before meals, starting with 60 mcg in type 2 diabetics.  To avoid hypoglycemia at the start of treatment, the pre-meal rapid-acting injected insulin dose is usually reduced by half.  Pramlintide should only be administered before meals that contain at least 30 grams of carbohydrate or 250 calories.  The maximum dose is 120 mcg with each meal. 

Side effects

Nausea is the most common side effect but clears up in a few weeks.  Pramlintide by itself does not cause hypoglycemia, but since it is always used with injectable insulin, hypoglycemia may occur—usually within three hours.

Don’t use if you have . . .

. . . gastroparesis or hypoglycemia unawareness.

Steve Parker, M.D.

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February 15, 2010 · 2:00 AM

Drug Review: Colesevelam

Colesevelam is used primarily to reduce elevated levels of LDL cholesterol.  It’s sold in the U.S. as WelChol.  Remember that drug names vary by country and manufacturer.  This is a brief review; consult your physician or pharmacist for details.

Class:  Bile acid sequestrant

How does it work?  Unclear

Uses

Colesevelam is FDA-approved for treatment of type 2 diabetes in conjunction with insulin or diabetic pills.

Dosing

Three tablets twice daily with meals, or six tablets once daily with a meal.

Side effects

Constipation in one of every 10 users.

Do not use if you have . . .

. . . serum triglycerides over 500 mg/dl, or have gastroparesis, other gastrointestinal motility disorders, risk factors for bowel obstruction, or recent major gastrointestinal procedures.

Steve Parker, M.D.

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February 13, 2010 · 2:00 AM

Drug Review: Dipeptidyl-Peptidase-4 Inhibitors (sitagliptin, saxagliptin, linagliptin, alogliptin)

The four dipeptidyl-peptidase-4 inhibitors available in the U.S. are sitagliptin (sold as Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), and alogliptin (Nesina). Vildagliptin is available in other countries.

Remember that drug names vary by country and manufacturer.  This is a brief drug review; consult your physician or pharmacist for details.

How do they work?

DPP-4 inhibitors decrease both fasting and after-meal blood sugar levels primarily by increasing insulin release from pancreas beta cells.  How they do it is complicated.

First off, you need to know that two gastrointestinal hormones levels—glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide—increase in response to a meal.  These hormones increase insulin secretion by pancreas beta cells, suppress glucagon secretion from pancreas alpha cells after meals, help suppress glucose production by the liver, and improve glucose uptake by tissues outside the liver.  GLP-1 also slows emptying by the stomach and reduces food intake.  All this tends to lower glucose levels after meals.

Did I mention it was complicated?

If we could make these gut hormones hang around longer, their glucose-lowering action would be enhanced.  How can we make them hang around and work longer?  Easy: suppress the enzyme that degrades them: dipeptidyl-peptidase-4.  That’s what DPP-4 inhibitors do.

The small intestine hormone GLP-1 is a major player in normal carbohydrate metabolism.  GLP-1 levels, by the way, are decreased in type 2 diabetes.

For the DPP-4 inhibitors, we have no data on long-term safety, mortality, or diabetic complications.

Uses

Sitagliptin is FDA-approved as initial drug therapy for the treatment of type 2 diabetes, and as a second agent in those who do not respond to a single agent, such as metformin, a sulfonylurea, or a thiazolidinedione.  It can also be used as a third agent when dual therapy with a sulfonylurea and metformin doesn’t provide adequate blood sugar control.

Saxagliptin, linagliptin, and alogliptin are FDA-approved as initial drug therapy for the treatment of type 2 diabetes (in adults) or as add-on drugs for those who do not respond to a single drug, such as metformin, a sulfonylurea, or a thiazolidinedione.  In case you’re wondering, you wouldn’t use several of the DPP-4 inhibitors at the same time.  In the summer of 2012, the FDA approved linagliptin as an add-on drug for type 2 diabetics already taking insulin.  Linagliptin and alogliptin haven’t been studied in nursing or pregnant women; I’m not sure about sitagliptin and saxagliptin in those settings.  Alogliptin is approved for combined use with metformin, pioglitazone, insulin, and perhaps sulfonylureas.

Dosing

The DPP-4 inhibitors are given by mouth.   The usual dose of sitagliptin is 100 mg once daily, with reduction to 50 mg for moderate to severe kidney impairment and 25 mg for severe kidney impairment.  The usual dose of saxagliptin is 2.5 or 5 mg once daily, with the 2.5 mg dose recommended for patients with moderate to severe kidney impairment.  Linagliptin’s dose is 5 mg daily, regardless of liver or kidney funtion.  The alogliptin dose is 25 mg daily, with lower doses for those with kidney impairment.

Side Effects

Generally well-tolerated.  No risk of hypoglycemia when used as the sole diabetes drug.  They do not cause weight gain.  Sitagliptin, linagliptin, and alogliptin might cause pancreatitis.  Alogliptin may cause liver disease or abnormal liver function blood tests. Saxagliptin and alogliptin may increase the risk of heart failure, particularly in those with pre-existing heart or kidney disease.

Don’t use if you have . . .

. . . moderate or severe kidney impairment (sitagliptin) or severe kidney impairment (saxagliptin).
Use sitagliptin or alogliptin with caution and careful monitoring if you have a history of pancreatitis.

Steve Parker, M.D.

Updated April 7, 2016

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