Category Archives: diabetes

Infertility to Acne: Treatment and Prevention of Polycystic Ovarian Syndrome. Part 2


Worried about pregnancyIn part one of this series we looked at the cause of polycystic ovarian syndrome (PCOS) and the many complications it causes. Weight gain, acne, excess hair growth on the face and body,  high cholesterol and high blood sugar due to insulin resistance are among the problems associated with PCOS.  One particular area of concern for PCOS sufferers is infertility due to lack of ovulation. PCOS is the cause of anovulatory infertility in  3 out of 4 cases. Before the acceptance of medical therapy for infertility due to PCOS  a surgical approach referred to as a wedge resection of the ovary was performed which allowed patients with PCOS to ovulate and conceive normally. Low success rates with this procedure, complications of surgery and improved medical therapies have all resulted in the end of this type of treatment in most situations.  At present, treatment of infertility associated with PCOS generally consists of using a drug to combat insulin resistance known as metformin often in combination with the fertility drug clomid, which has a high rate of success.

Treatment of the excess hair growth associated with PCOS often consists of using the drug spironalactone and the use of birth control pills. Spironalactone is a very interesting drug used for decades as a salt depleting diuretic but also has an effect to block the action of the male hormone testosterone. The action of spironalactone to block testosterone was discovered when it was noticed that men using this diuretic developed tender nipples and breast enlargement (gynecomastia). Oral contraceptive agents are also useful to combat hirsutism because these agents also cause reduce testosterone levels by putting the ovary in a dormant “resting” state.  Cosmetic procedures are always another option to treat unwanted hair growth. Laser hair removal appears to be replacing the older modality of electrolysis for this purpose.

Can PCOS be cured? Once PCOS develops it can be controlled but not cured unless the ovaries are removed. At menopause  PCOS-related problems diminish as the ovary stops making sex hormones including testosterone which is one of the culprits during the reproductive years. A recent study published this year in the journal Pediatric Endocrinology showed that using metformin treatment in pre-adolescent girls thought to be at risk for PCOS reduces the risk and/or the severity of PCOS in later years. It may do this by blocking fat accumulation in the abdomen and liver which seems to set off the insulin resistance. Metformin is not FDA approved for this purpose and as a generic drug there is little profit potential in developing this treatment. I expect it will be many years before preventive therapy for PCOS will come before the FDA for approval .

This information is strictly for educational purposes. Due to high risk of toxicity of medical therapy in young women who can potentially become fertile under treatment for PCOS, no drug should be taken without the close supervision of a physician. The reader agrees to the Terms of Service of this website, metabolism.com

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Polycystic Ovarian Syndrome Is Common in Adolescent Girls


Polycystic Ovarian Syndrome (PCOS) sounds like a rare disorder but it is surprisingly common. This is a disorder with onset in early adolescence effecting up to 10% of young women. Characteristic signs and symptoms include increasing facial and body hair, hair loss from the scalp, muscular or heavy build, acne, thickening and darkening of the skin known as acanthosis nigricans, blood sugar problems including type 2 diabetes, high cholesterol and irregular menstrual cycles and infertility. In older women with PCOS coronary artery disease is more common. In severe cases deepening of the voice and enlargement of the clitoris (clitoromegaly) can be seen. Before the underlying hormone disorders were clarified, the main method of diagnosing this disorder was by finding multiple cysts on the ovary. We now understand that the main problem is not the ovarian cysts but metabolic disorders including insulin resistance and elevated male hormone levels (testosterone) in the blood.

Another misconception about PCOS is that it only occurs in overweight women. Obesity is common in PCOS but thin women are also capable of developing PCOS. The underlying hormone problems are complex but are thought to be at least in part due to high insulin levels in the blood resulting from insulin resistance. With insulin resistance the body requires high levels of insulin due to insensitivity of the tissues to insulin’s presence.
What treatments are available for PCOS? There are very few, if any, drugs specifically approved for the treatment of PCOS. This is probably because of the low profit potential for treating this disorder. Drug companies cannot afford to invest millions of dollars in research because almost all of the existing standard therapies are generic drugs. Some of the most useful medications for treating PCOS are drugs used to treat type 2 diabetes because of their effect to reduce insulin resistance. These drugs are metformin and Actos. Metformin is the most popular oral medication for diabetes treatment in the U.S. Actos has been available for about 10 years but due to recent negative publicity about an unproven risk of bladder cancer, its popularity is declining. Neither drug is approved by the FDA for treatment of PCOS but multiple studies confirm the clinical and hormonal benefits of using these medications in this disorder. In 2011 research was published in the Journal of Clinical Endocrinology and Metabolism suggesting that the generic cholesterol lowering drug, simvastatin may also show benefits similar to metformin for the treatment of PCOS.

In the late 1980’s, I along with Dr. Lester Gabrilove at Mt. Sinai Hospital in New York, published our research showing that an anti-fungal medication, ketoconazole, could reverse the hormonal, physical and metabolic problems associated with PCOS. Due to the potential toxicity of ketoconazole this therapy never gained wide spread acceptance. The manufacturer refused to fund additional studies to determine how to more effectively use this drug, due to the low profit potential and liability concerns.

This information is strictly for educational puroses. Due to high risk of toxicity of medical therapy in young women who can potentially become fertile under treatment for PCOS, no drug should be taken without the close supervision of a physician. The reader agrees to the Terms of Service of this website, metabolism.com

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Getting the Right Amount of Sleep Helps Prevent Diabetes


One aspect of lifestyle that is often overlooked is time spent sleeping. Getting adequate sleep is often sacrificed due to the demands of job and family. In the Sleep Heart Health Study over 1400 men and women were surveyed about their sleep habits and its relationship to diabetes and prediabetes. It was found that sleeping less than 6 hours per night was associated with increased risk of having diabetes. Interestingly, in those sleeping more than 9 hours per night there was an increased risk of diabetes and prediabetes.The authors of the study recommend trying to get between 7 and 8 hours of sleep per night to minimize the chances of developing blood sugar problems. To learn more about ways of preventing diabetes see pages 90 to 98 in my ebook “Metabolism.com”

Maintaining ideal body weight with diet and exercise is also crucial for avoiding diabetes and prediabetes.In overweight adults for each2.2 pounds(1 kilogram) gained per year the risk of developing diabetes increases about 50% over the next ten years. By losing 2.2 pounds per year the risk of developing diabetes is reduced about33% for the next 10 years (J Epidemiol Community Health. 2000; 54(8):596-602).

Speak to your healthcare professional to find out if you are at risk for developing diabetes and to learn ways you can avoid it.

Gary Pepper M.D.

Editor-in-Chief, Metabolism.com

The terms of service for metabolism.com apply to this and all posts; http://www.metabolism.com/2008/09/06/terms-conditions-service-agreement/

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Novartis Blood Pressure Medication Runs into Trouble


Novartis Blood Pressure Medication Runs into Trouble
by Gary Pepper, M.D.
Editor, Metabolism.com

In 2007 a new type of blood pressure lowering medication was brought to market by Novartis Pharmaceutical Company. This medication by the brand name Tekturna (aliskiran) works by blocking hormones that make up a circuit from the kidney to the blood vessels know as the RAAS system. This mechanism is distinct from all other blood pressure lowering medications available. By working via a completely novel pathway to lower blood pressure doctors were given another potent weapon in the war on high blood pressure. A second medication, Valturna, which combines an established blood pressure medication with Tekturna, was released by Novartis to the public in 2009. These drugs have been extremely popular due to their effectiveness and apparent freedom from serious side effects.
A warning about this class of drug was issued by Novartis, 2 weeks ago when it was forced to end the Altitude drug study due to apparent unforeseen complications in patients using Tekturna and Valturna. The study found a small but significant increase in stroke in diabetics with renal disease who were using these drugs. Although the group of patients in the Altitude study are up to 12 times more likely to develop stroke or heart attack under normal circumstances, Novartis had no choice but to end the study and issue a warning to the health care community about limiting the use of these drugs.

In my own practice I have found Tekturna and Valturna to be extremely effective and well tolerated. A survey of my colleagues revealed the same findings. Diabetes and high blood pressure very commonly occur together and national guidelines stress the need for excellent blood pressure control for diabetics to help prevent heart, kidney and eye complications of this disease. For doctors treating diabetics who recognize these patients as particularly high risk, having to significantly cut back or eliminate the use of Tekturna and Valturna is creating major concerns. Within the past week I have had to counsel numerous individuals about these issues and the solution is far from easy. For instance, one man with diabetes and early kidney disease and heart disease, with borderline high blood pressure despite using 4 different types of blood pressure medication including Tekturna has to decide with me, which is the greatest risk, going off the medication resulting in a rise in his blood pressure or continuing a drug which may pose a risk of its own.

These discussions are going on in doctor’s offices throughout the country with no good solution in sight. The only certainty is a flood of ads by lawyers which begin, “Have you ever been on Tekturna or Valturna….”.

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Bariatric Surgery Benefits Last for Years


One of the biggest problems with weight loss programs and diets is that even if they work the weight tends to come back on within a year or two. A recent study from the University of Utah of people who underwent bariatric surgery shows that not only do they lose weight quickly, after 6 years they continue to maintain their lower weight. After undergoing bariatric surgery the average weight drop was 35% of the original weight and after 6 years weight loss was still a very encouraging 28%. 75% of diabetics who had bariatric surgery were able to go off their diabetic medications, while improvements were generally seen in cholesterol levels and blood pressure.

Although this study shows a very high success rate, in the real world medical practice I have seen many people who are able to eat their way out of weight loss success after bariatric surgery. Eating small amounts of very high calorie food is still possible and unfortunately is not all that uncommon. Not to say that bariatric surgery is not helpful, because when it works the results can be spectacular, but as always the degree of motivation of the patient is crucial to success.

Gary Pepper, M.D.
Editor-in-Chief, metabolism.com

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Diabetes Medications, One Old and One New, Run into Trouble


A potential new treatment for type 2 diabetes, dapagliflozin, recently failed to gain approval from the FDA. What makes this rejection noteworthy is that the new medication works by a completely new mechanism causing the kidney to excrete sugar from the blood into the urine. Reasons for the rejection were the increased risk of bladde and breast cancer in those taking the medication, increased urine and genital infections and possible liver toxicity. That list of problems seems pretty convincing to me. This is unfortunate because the drug appears to cause weight loss and does not cause low blood sugar (hypoglycemia). However, a drug that works by “poisoning” the kidney so that it dumps sugar into the urine strikes me as a drug that is going to cause a lot of other problems.

The other established diabetes medication generating new warnings is Actos (pioglitazone). I have written a number of articles on the sister drug Avandia, defending its usefulness despite possible cardiovascular risks, but the cancer warning for Actos is a new angle on this class of drugs (thiazolidinediones). Actos has been withdrawn in France due to concerns that it may cause bladder cancer but no such action has been taken in the U.S. The FDA this month did issue a warning that individuals with bladder cancer or at risk for bladder cancer, should be advised not to use Actos. If Actos is hit hard by these actions this whole class of diabetes drugs will have been eliminated from use.
A sure sign of trouble for Actos is that a “google search” for Actos is now showing lawyer websites as the first 5 citations.

Being sick is dangerous. Treating illness also has dangers. I am concerned that our cultural zeal for uncovering scandals and for pursuing litigation will lead us to sterile treatment options and doctors who are unwilling to risk helping.

Gary Pepper, M.D.
Editor in Chief, metabolism.com

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Avandia Law Suit Brings Out the Opportunists


The lawsuits against Avandia are being prepared and opportunists are lining up for a payday. Unfortunately, everyone else will wind up a loser, and here’s why.

Avandia, one of only two available medicines with unique properties to treat diabetes, was approved in 1999. From the very first day Avandia was approved a heated debate arose whether Avandia or its sister drug, Actos, was the better drug for diabetes treatment. Both had similar abilities to lower blood sugar and both had the same downside of causing significant weight gain and fluid retention. Avandia showed a slightly worse effect on cholesterol profiles which convinced many diabetes specialists to choose Actos over Avandia. The choice between drugs has also been heavily influenced by cost considerations such as whether the drug was covered by the patient’s insurance carrier. I personally treated numerous patients with both drugs and found them about equal in all respects.

The lawsuits against Avandia will contend that the medication caused heart attack or stroke. The truth of this contention is very much in question, but the murkiness of the water doesn’t stop the lawyers from trying to take a bite out of the flesh of GSK (GlaxoSmithKline), the maker of Avandia.

Several years ago research studies seemed to indicate a small increased risk of heart attacks in users of Avandia. Ever since there has been a heated debate about whether this was a true risk or just the result of overly aggressive interpretation of the available data. There are two major analyzes on the subject of heart attack risk with Avandia. One, written by a doctor on the payroll of a competing drug company, looked at results from 14 thousand patients on Avandia and found a small increased risk of heart attack or stroke and the other study analyzed another 14 thousand Avandia users and found no such association. Under pressure from the public, in 2007 the FDA placed a strong warning on the label of Avandia regarding the possibility of the drug causing heart disease, but Avandia was permitted to remain on the market. The FDA warning was updated and upgraded in 2010. The publicity surrounding Avandia’s potential risks basically halted the use of the drug in the U.S.

Now enter the opportunists. Advertisements fill my email in-box from lawyers looking for customers who want to sue the drug manufacturer in class action law suits. Try goggling “Avandia side-effects” and you will find the first several pages of results are ads looking for lawsuit clients. In the last month I received two requests for patient records from these lawyers. Both patients had heart disease at the time they started the medication. One patient who recently died was over 80 years old, and the other who had significant heart disease and other diabetes complication to begin with, is still alive more than 7 years after treatment with Avandia. I wonder how much benefit these patients received from the medication which allowed them to survive as long as they did despite all the other problems they had related to their diabetes.

Why should you care about whether a small army of opportunists each get a few thousand dollars from the drug manufacturer and a few lawyers become millionaires? Because it is just this sort of legal action which is convincing drug makers to back away from developing other potential diabetes treatments. It takes a decade and a billion dollars to bring a new drug in front of the FDA. This doesn’t include the cost of developing drugs which fail to even make it to FDA review. Then the FDA approval process is tortuous and uncertain. Passing this hurdle, any new drug can come under attack (like Avandia) for “possible” side effects making the company vulnerable to devastating legal costs and bad publicity. It isn’t economically feasible to develop new diabetes drugs in the United States. As a result, new drug development is grinding to a halt. We will all suffer due to lack of innovation, not only for diabetes treatment but for treatment of many other dangerous diseases.

Gary Pepper, M.D.
Editor in Chief, Metabolism.com

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To Be Fair, New Diabetes Medications Have Some Use


In my last article on the newest generation of diabetes pills (the DPP-4 inhibitors), I basically said that their benefits were not impressive and the costs were too high. I stand by those comments, but I need to add some clarifying thoughts. I continue to use drugs like Januvia, Onglyza and Trajenta because certain individuals seem to get a better effect from them than I generally expect. If, for instance, a diabetic is on maximum dose of the older (and cheaper) diabetic medications and the glucose control is not good, instead of going directly to insulin as the next step, I will try the DPP-4 inhibitors (gliptins). If the glycohemoglobin A1c level drops by a percentage point (e.g from 9% to 8%) I will continue the new drug therapy. If the change is minor (less than a percentage point) then there is little reason to continue spending my patients’ money on a therapy which has failed. In these cases, insulin needs to be started. The nice thing about insulin treatment is that it almost always results in a swift and dramatic improvement in blood sugar. Few of my patients willingly accept insulin at the beginning and are glad they were given one more chance to stay on pill therapy, even if it is just a temporary reprieve.

These comments are for educational purposes only and do not constitute medical advice.

Gary Pepper
Editor in Chief, Metabolism.com

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Are New Diabetes Medications Worth the Money?


(I don’t think so, and here’s why.)

The FDA just announced its approval of linagliptin (Tradjenta), a new diabetes medication developed by Eli Lilly and Company and Boehringer Inglheim. Linagliptin is the third drug to be approved in the class of medications commonly known as gliptins (scientifically known as dipeptidyl peptidase-4 (DPP-4) inhibitors) which block the destruction of a glucose controlling hormone, GLP-1. Januvia, developed by Merck and Company, was the first of the gliptins to be approved in 2006. Three years later in 2009, Onglyza, developed by AstraZeneca was approved while two other similar drugs were withdrawn from the approval process in the meantime.

Diabetes drugs are evaluated by the FDA for safety and for their ability to combat diabetes by lowering blood sugar. Assuming the drug being evaluated is safe then we will want to know how effectively the new medicine lowers the blood sugar. The glycohemoglobin A1c blood test represents the average blood sugar for the prior 3 months, and is the most concise way of assessing an individuals over all blood sugar control. By determining the ability of a medicine to lower the “glycoA1c” we can get a very accurate idea of the strength of the medicine for diabetes treatment. In general, physicians set a glycoA1c goal of 7% or less for their diabetic patients which equates to an average blood sugar level of 154 mg/dl or 8.6 mmol/L.

Linagliptin passed the FDA’s strigent safety review. Several large studies sponsored by the drug developers show the linagliptin lowers glycohemoglobin A1c by about 0.5. For example, if a person has a glycoA1c of 7.5 % before starting linagliptin, they can anticipate it will be 7.0% when on the medication. This translates to an average blood sugar of 169 mg/dl dropping to 154. This is virtually the same effect found with Januvia and Onglyza, the other medicines in this group.This amount of blood sugar lowering seems feeble but the benefit is even worse then that. Here’s why.

Blood tests are accurate enough for the clinical purposes of physician’s diagnosing and treating their patients. “Clinical purposes” allow for some fuzziness in measurements. Does it matter to a patient’s health if the blood sugar is 200 or 210? Not really. In general, a variation of 10% is acceptable for clinical blood tests, meaning that if a result is given as 100, a repeat measurement of the same blood sample could read between 95 and 105. For the glycohemoglobin A1c test a variation of 0.5 is common with standard laboratory techniques. For an individual on linagliptin there is virtually no way to determine if the change in glycoA1c is due to the medication or is simply within the variation of the blood test. Not very impressive is it?

How much is the average person going to pay for this unimpressive effect? I researched the retail cost of Januvia, the sister drug to linagliptin. Drugstore.com lists a price of $216 for 30 pills after a 18% saving. $7 per pill….wow!! I assume linagliptin will be priced competitively. Compare this to the price of $13 for a month’s supply of metformin, currently the most prescribed oral agent for treating diabetes. In contrast, metformin shows a 1.5% to 2% drop in glycohemoglobin A1c, more than three times that of the gliptins such as linagliptin.

I have used both Januvia and Onglyza in my medical practice. As advertised, I haven’t encountered significant side effects. Also, as advertised the effect of these medicines to lower blood sugar has been disappointing and complaints by patients about the cost has been a constant theme. At the same time my email inbox is stuffed with invitations to join online symposiums with paid experts inevitably focusing on how to ramp up my use of these drugs. The sales pitch is given in inflated marketing lingo as a “change in the treatment paradigm” for treating diabetes. Buyer beware, is my advice for the health care consumer starting a new medication for treating type 2 diabetes.

Gary Pepper, M.D.
Editor-in-Chief, metabolism.com

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Can Actos Really Prevent Type 2 Diabetes?


Diagnosing diabetes is simple. If the blood sugar is found to be elevated you are diabetic. Increasing or decreasing the cut off level between normal and diabetic will dramatically change the number of people diagnosed with diabetes. In 1997 the American Diabetes Association lowered the criterion of diabetes (type 2) to a fasting blood sugar above 126 mg/dl instead of 140 mg/dl. Suddenly 1.7 million Americans became “diabetic” under the new definition.

In the latest issue (March 24, 2011) of the New England Journal of Medicine research was published stating that Actos (pioglitazone), a popular medication used to treat type 2 diabetes, could substantially reduce the percentage of people at high risk for developing diabetes who progress to actual diabetes. 600 people with a form of pre-diabetes known as impaired fasting blood sugar (fasting blood sugar levels between 95 and 125), were divided into one group given placebo and the other group given Actos. After 2.5 years Actos reduced the incidence of developing type 2 diabetes by 72% compared to placebo. Initially, I was very impressed with these results.

Actos is the sister drug to Avandia and Rezulin. All of these drugs show similar ability to reduce blood sugar in diabetics. Rezulin and Avandia fell into disfavor due to the potential for side effects. Actos is considered safer.

It seems almost a little too obvious that if diabetes is defined as elevated blood sugar that if the test medication reduces blood sugar, diabetes can be “prevented”. Since Actos lowers blood sugar, the conclusion that Actos reduces the progression of pre-diabetes to actual diabetes seems inevitable. A substance that does not already lower blood sugar which prevented elevated blood sugar from developing would be far more impressive.

Side-effects of taking Actos need to be considered, as well. In this research study (New England J of Medicine 364; 12, 2011) the group taking Actos gained an average of about 9 pounds. That doesn’t include the 3% of test subjects who dropped out of the study because they gained too much weight. Edema (puffy ankles) was also more common in those taking Actos. We know that weight gain, particularly in pre-diabetics, is not a good thing. What are we hoping to accomplish by using Actos to prevent diabetes when at the same time, we make people chunkier and puffier?

To be fair, the family of medications known as “glitazones” which contain Actos, Avandia and Rezulin, have some intriguing properties. Years ago, the Triad Study, showed that women with gestational diabetes who received Rezulin, did not go on to develop type 2 diabetes nearly as often, even years after stopping this medication. This does seem like a true preventive benefit.

I am dubious about using Actos to prevent diabetes at this time. My patients, I suspect, will agree with that decision. I don’t think I would survive very long in practice, if my patients gain 10 or more pounds as I try to “prevent” their progression to diabetes.

This information is for educational purposes only and is not intended as medical advise or treatment. Always consult with your physician when deciding whether to use a prescription drug.

Gary Pepper, M.D.

Editor-in-Chief, Metabolism.com

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