A team at Joslin has been looking for more MODY genes and has found one they say should be added to the six currently tested for. This gene is named BLK. One of its many functions is to trigger insulin production.
The discovery is reported here:
Mutations at the BLK locus linked to maturity onset diabetes of the young and β-cell dysfunction. Maciej Borowie et al. PNAS, Published online before print August 10, 2009, doi: 10.1073/pnas.0906474106
You can read a slightly more informative report on this study here:
Joslin Study Identifies Gene Linked To Rare Form Of Diabetes
MODY is believed to cause 2% to 3% of all cases of diabetes. As reported there are currently eight genes known to cause MODY, but these account for only 85% of those whose family histories are suggestive. Joslin's researchers are looking for the genes that cause the other 15%.
I had volunteered for this study but was unable to participate because one requirement is that participants have a fairly large number of relatives with diabetes. My extended family was too small to qualify.
Unfortunately, when I contacted them two years ago, the Joslin researchers were not willing to share findings with the study subjects. So whatever the benefits of this study for science, it won't help those of you with clear-cut MODY family histories who don't test for the known genes.
For those of you who aren't familiar with MODY, you can find a detailed description of what it is here: MODY: It's Not Type 1 or Type 2 but Something Else.
Because I maintain this MODY page I get a lot of mail from people diagnosed with Type 2 Diabetes who are not fat who are wondering if they have MODY. Most of them do not. Slow onset autoimmune diabetes (LADA) is much more common than MODY and is a much more likely cause for high blood sugars in normal weight people in their 30s and older.
One key thing to understand about MODY is that if you have it, you will have had abnormal blood sugars all your life in some form or other. Blood sugar problems that emerge suddenly and deteriorate over a year or two are much more likely to be autoimmune in nature. The blood sugars associated with MODY tend to stay relatively stable.
So if you are a thin or normal weight person diagnosed with Type 2 diabetes, don't even consider MODY as a possible cause for your diabetes unless you have had a full set of Type 1 antibody tests that are negative, a normal fasting C-peptide test (several forms of MODY only affect insulin secretion in response to meals), have no history of any other autoimmune disease, and have a life long history suggestive of abnormal glucose tolerance.
Unfortunately, as you can see from the reporting of this story in Medical News Today, the only reason scientists are working on MODY is because they hope to find genes implicated in Type 2 diabetes. Once they find a new gene that affects insulin secretion they are done. This means that once you are diagnosed with MODY by a gene test you rarely will be able to find out anything further about the probable course of the kind of MODY you have or even about the best treatments.
This is because all the money in diabetes is in treating the millions with Type 2 and the funding goes into studies that could turn into blockbuster drugs for Type 2.
Meanwhile we people with MODY have to muddle along on our own, often without the help of doctors who have any knowledge of what MODY is.
One thing I would like to make clear before I leave this discussion is this: It is not true that "MODY is simpler to diagnose and treat than the other forms of diabetes," as stated in the Medical News Today article. In fact, most of us with MODY go through years of misdiagnosis and inappropriate treatment.
Each genetic form of MODY is different, and they each require different treatment approaches. Finding the one that works for your own specific case can take a lot of work and because prescription drugs are involved you will need the support of an endocrinologist willing to work with you.
Since many endos have zero knowledge about MODY, many people with MODY get the same miserably poor treatment as the rest of the Type 2 community, and end up with the 8%+ A1cs that guarantee they will develop complications.
Because contrary to what you may read online, every form of MODY causes complications, it is only a matter of which one. MODY-2 (GCK) doesn't cause neuropathy or retinopathy, just fatal heart attacks, often striking the young. The HNF MODYs cause blood sugars high enough to produce all the classic -pathies and the sulfonylurea drugs often prescribed for them do not give the normal blood sugars that will prevent these complications. Only meal-time insulin can do this though some people with MODY-3 respond very well to Byetta. The gene responsible for MODY-3 can also cause congenital kidney malformations that lead to an early death if not diagnosed correctly.
So if you are diagnosed with MODY in any form, you will have to fight very hard to get appropriate treatment. If you just rely on your doctor and believe that MODY is "easy to treat" and that A1cs near 7% are all you need to attain, you are deluding yourself.
I have written to the researchers who identified this latest MODY gene to see if I can find out anything more about BLK MODY, but my guess is that having found the gene they will move on and those who have the gene will be left in the dark as to what it means and how to best treat it.
August 12, 2009
August 11, 2009
More Insight into What Blood Pressure Level is Safe
People with diabetes have been told for the past five years that they should shoot for a lower blood pressure target than the normal population, ideally one under 120/80. However, recent research is refining the usefulness of this recommendation.
Blood pressure control is the second most import step a person with diabetes can take. That is because high blood pressure promotes both heart attack and kidney failure. These are among the most dreaded complications of diabetes.
But, as I have learned the through my own experience, for some of us striving for the 120/80 blood sugar target can be a problem, because blood pressure tends to drop during the night. When my blood pressure is under the 120/80 target in the daytime I am prone to wake up at 4 AM with the pounding pulse and throbbing heart that occur when my blood pressure has dropped so low that a counterregulatory response kicks in to raise it. I also tend to develop postural hypotension when I am taking blood pressure drugs and may keel over and nearly black out when working in my garden if I kneel down and stand up too often.
So the latest news about how low blood pressure needs to be to maintain health is very reassuring.
The first piece of it is a Cochran Review look at blood pressure studies. The chief researcher here concluded, "'At present there is no evidence from randomized trials to support aiming for a blood pressure target lower than 140/90, in the general population of patients with elevated blood pressure.'"
You can read more about this in the Science Daily report: Blood Pressure Targets: Aiming Lower Produces No Benefit Review Finds.
As reported in Science Daily,
Another study published in the American Journal of Kidney Diseases may provide a bit more insight into when borderline blood pressure becomes dangerous.
Prehypertension, Obesity, and Risk of Kidney Disease: 20-Year Follow-up of the HUNT I Study in Norway. John Munkhauge et al. American Journal of Kidney Diseases doi:10.1053/j.ajkd.2009.03.023 Article in press 8/11/2009.
This study is particularly compelling because it is a huge epidemiological study that studied the relationship of borderline blood pressure and kidney failure over a period of 20 years.
The subjects were 88.2 percent of all inhabitants 20 years or older in Nord-Trøndelag county, in mid-Norway. This kind of broad reach means that the study was more likely to include all kinds of people of all social and economic classes. The one major limitation is that being they were in Norway, the racial mix of the population would have been very limited compared to the population you'd find in a county in middle America.
This study's findings are informative for people with diabetes because, though they did not examine risk specifically relative to diabetes (the medical definition of which has changed greatly over the 20 year period of the study), they did look at risk relative to obesity.
What the Norway study found was this: Borderline blood pressure, defined as blood pressures between 120/80 and 139/89 were not associated with a higher risk of kidney failure or cardiovascular related death until BMI rose over 30.*
This BMI correlates to a weight of 175 lbs in a woman 5' 4" tall or of 203 lbs in a man 5' 9" tall. You can compute your own BMI HERE.
However, while risk rose in the borderline blood pressure category the study also found "In participants with BP less than 120/80 mm Hg, risk did not increase with increasing BMI." [emphasis mine]
BMI can be very deceptive because it doesn't distinguish between body fat and muscle mass, so an athlete may be classified as obese while having a normal or even low body weight percentage.
For example, when my son was playing college football he had a BMI of 32 which is well into the "obese" category, but his body fat was measured at 17%, which is far from obese. But if you aren't a teenaged boy who leg presses 700 lbs, the BMI is usually a pretty good guide to how fat you are.
This study points to two important conclusions.
If you are not obese as defined by BMI, you are probably fine maintaining a blood pressure lower than 139/89.
If you are obese, you should shoot for a blood pressure of 120/80.
This robust long term epidemiological data also appears to back up the NHANES finding that I've blogged about before that overweight is a healthy weight, especially for people in the latter half of life. Overweight is officially defined as having a BMI of 25-29.
If you are trying to lose weight this data might convince you that it is worth shooting for a weight that gives you a BMI under 30. For any of us is an attainable goal--and one we are far more likely to reach than the dream weights suitable for people in their early 20s most obese dieters shoot for.
Choosing an attainable realistic goal is one of the keys to successful dieting. This is because unrealistically low weight goals often derail people's diets. A goal set too low is a goal the dieter can't reach. That failure often frustrates otherwise successful dieters to the point where they often blow off their diet because they still think they are fat--even if they have lost 20, 30 or even 100 lbs.
If you can get to a BMI of 29 you have succeeded, as far as your health goes. For that matter, if you have lost any significant amount of weight you've done something positive for your health. Risk for many conditions rises along with weight as it continues to rise over that 30 BMI.
Set that 30 BMI weight as your first and most important goal. If you can do better. Great! If not, you can rest assured that you have done what you need to do to maintain your health.
One nice thing about blood pressure is that, unlike the case with blood sugar, you can buy a blood pressure meter for a one time charge and test your blood pressrue as often as you want without ever having to pay for a single consumable.
It is a good idea for any person with diabetes to invest in a blood pressure meter and get into the habit of checking your blood pressure now and then to make sure it isn't rising dangerously high without your realizing it. If you see blood pressures over 139/89 make an appointment to talk to your doctor about it. Doctors are much better at treating blood pressure than blood sugar.
I recommend a blood pressure meter that plugs into the wall not the slightly cheaper meters that run on batteries. Long term they are cheaper and you don't end up with unpredictable results from failing batteries. Use a meter that measures arm pressure, not wrist pressure. The arm meters are more accurate. I like the Omrons, personally. They are a lot cheaper on Amazon than at the drug store.
----
* The mention of cardiovascular related deaths comes from the report of this study in Science Daily: Prehypertension, Obesity And Kidney Disease Risks
Blood pressure control is the second most import step a person with diabetes can take. That is because high blood pressure promotes both heart attack and kidney failure. These are among the most dreaded complications of diabetes.
But, as I have learned the through my own experience, for some of us striving for the 120/80 blood sugar target can be a problem, because blood pressure tends to drop during the night. When my blood pressure is under the 120/80 target in the daytime I am prone to wake up at 4 AM with the pounding pulse and throbbing heart that occur when my blood pressure has dropped so low that a counterregulatory response kicks in to raise it. I also tend to develop postural hypotension when I am taking blood pressure drugs and may keel over and nearly black out when working in my garden if I kneel down and stand up too often.
So the latest news about how low blood pressure needs to be to maintain health is very reassuring.
The first piece of it is a Cochran Review look at blood pressure studies. The chief researcher here concluded, "'At present there is no evidence from randomized trials to support aiming for a blood pressure target lower than 140/90, in the general population of patients with elevated blood pressure.'"
You can read more about this in the Science Daily report: Blood Pressure Targets: Aiming Lower Produces No Benefit Review Finds.
As reported in Science Daily,
The review is based on the results of seven trials, which together involved 22,089 people. Whilst patients aiming for targets below 135/85 mmHg did succeed in achieving greater reductions in blood pressure than those in the standard target group, there was no difference between the two groups in terms of the number of patients dying or suffering heart attacks, strokes, heart failure or kidney failure.The researchers noted that they did not break out the data for people with diabetes separately. The study also did not draw conclusions about whether it is safe to lower blood pressure aggressively.
Another study published in the American Journal of Kidney Diseases may provide a bit more insight into when borderline blood pressure becomes dangerous.
Prehypertension, Obesity, and Risk of Kidney Disease: 20-Year Follow-up of the HUNT I Study in Norway. John Munkhauge et al. American Journal of Kidney Diseases doi:10.1053/j.ajkd.2009.03.023 Article in press 8/11/2009.
This study is particularly compelling because it is a huge epidemiological study that studied the relationship of borderline blood pressure and kidney failure over a period of 20 years.
The subjects were 88.2 percent of all inhabitants 20 years or older in Nord-Trøndelag county, in mid-Norway. This kind of broad reach means that the study was more likely to include all kinds of people of all social and economic classes. The one major limitation is that being they were in Norway, the racial mix of the population would have been very limited compared to the population you'd find in a county in middle America.
This study's findings are informative for people with diabetes because, though they did not examine risk specifically relative to diabetes (the medical definition of which has changed greatly over the 20 year period of the study), they did look at risk relative to obesity.
What the Norway study found was this: Borderline blood pressure, defined as blood pressures between 120/80 and 139/89 were not associated with a higher risk of kidney failure or cardiovascular related death until BMI rose over 30.*
This BMI correlates to a weight of 175 lbs in a woman 5' 4" tall or of 203 lbs in a man 5' 9" tall. You can compute your own BMI HERE.
However, while risk rose in the borderline blood pressure category the study also found "In participants with BP less than 120/80 mm Hg, risk did not increase with increasing BMI." [emphasis mine]
BMI can be very deceptive because it doesn't distinguish between body fat and muscle mass, so an athlete may be classified as obese while having a normal or even low body weight percentage.
For example, when my son was playing college football he had a BMI of 32 which is well into the "obese" category, but his body fat was measured at 17%, which is far from obese. But if you aren't a teenaged boy who leg presses 700 lbs, the BMI is usually a pretty good guide to how fat you are.
This study points to two important conclusions.
If you are not obese as defined by BMI, you are probably fine maintaining a blood pressure lower than 139/89.
If you are obese, you should shoot for a blood pressure of 120/80.
This robust long term epidemiological data also appears to back up the NHANES finding that I've blogged about before that overweight is a healthy weight, especially for people in the latter half of life. Overweight is officially defined as having a BMI of 25-29.
If you are trying to lose weight this data might convince you that it is worth shooting for a weight that gives you a BMI under 30. For any of us is an attainable goal--and one we are far more likely to reach than the dream weights suitable for people in their early 20s most obese dieters shoot for.
Choosing an attainable realistic goal is one of the keys to successful dieting. This is because unrealistically low weight goals often derail people's diets. A goal set too low is a goal the dieter can't reach. That failure often frustrates otherwise successful dieters to the point where they often blow off their diet because they still think they are fat--even if they have lost 20, 30 or even 100 lbs.
If you can get to a BMI of 29 you have succeeded, as far as your health goes. For that matter, if you have lost any significant amount of weight you've done something positive for your health. Risk for many conditions rises along with weight as it continues to rise over that 30 BMI.
Set that 30 BMI weight as your first and most important goal. If you can do better. Great! If not, you can rest assured that you have done what you need to do to maintain your health.
One nice thing about blood pressure is that, unlike the case with blood sugar, you can buy a blood pressure meter for a one time charge and test your blood pressrue as often as you want without ever having to pay for a single consumable.
It is a good idea for any person with diabetes to invest in a blood pressure meter and get into the habit of checking your blood pressure now and then to make sure it isn't rising dangerously high without your realizing it. If you see blood pressures over 139/89 make an appointment to talk to your doctor about it. Doctors are much better at treating blood pressure than blood sugar.
I recommend a blood pressure meter that plugs into the wall not the slightly cheaper meters that run on batteries. Long term they are cheaper and you don't end up with unpredictable results from failing batteries. Use a meter that measures arm pressure, not wrist pressure. The arm meters are more accurate. I like the Omrons, personally. They are a lot cheaper on Amazon than at the drug store.
----
* The mention of cardiovascular related deaths comes from the report of this study in Science Daily: Prehypertension, Obesity And Kidney Disease Risks
August 9, 2009
Who Is Really Getting Euthanized
UPDATE: Health Care Protesters Largely From Out of District
The forces trying to keep us from getting a new health care system are bussing operatives in to disrupt congresspeople's meetings. These protesters are not people who live in the district. The pattern of using violence to shut down discourse is very disturbing. Contact your congresspeople and let them know you don't want policy set in response to gun toting people brought in from outside to threaten violence.
The right wing fringe is trying to frighten the public with the claim that health reform will mean those close to death will be forced to die because medical care will be withheld.
They prefer the old system, where only those who are poor, unemployed, or have a chronic condition are forced to die because care is withheld.
Shame on them.
Next time some fear monger tries to tell you that health reform means rationing care, remind them we already ration care.
Those with high status jobs get it. Those who work for small business, are laid off for more than 18 months, or are self-employed in businesses that don't earn enough to pay $12,000 a year for an insurance plan do not. Those with a preexisting diagnosis can't get insurance in many states no matter what they are willing to pay.
I get mail every week from people in their 30s and 40s who have LADA (a slow form of Type 1) and severe Type 2 diabetes who have lost their jobs or have jobs without health insurance who cannot afford to see a doctor or pay for the drugs they need.
The media tells you that there are programs for these people. Try finding one when you are faced with a person whose average blood sugar is running around 400 mg/dl but who the emergency room doctor diagnosed as "Type 2." Until they are in DKA or a hyperosmolar state, or have gangrene or kidney failure, they aren't considered in danger. So if cutting carbs doesn't bring down their sugars, they are SOL.
That looks a lot more like euthanasia to me than denying open heart surgery to a demented 90 year old who can no longer recognize her own family.
Who benefits from the current system? Someone, obviously, because a lot of money is going into funding the noisy rent-a-mob protests against health reform.
A country that can pay billions to bail out banks can afford to provide adequate health coverage for every single citizen. My stomach is turned by the arguments that health care reform must save money, while bank bailouts and car bailouts can lose as much as it takes to "keep our economy stable."
Where is it written that some people have a god given right to get wealthy off the sickness and suffering of others? What sick religious belief tells us that we should only help the suffering if we can do it without it costing us money?
The right wing uses fear, lies, violence and name calling when they have no real arguments left. Anyone familiar with the history of fascism should recognize the patterns. Perhaps the right wing is flinging the word "Nazi" around because they have been dipping so freely into the very techniques the Nazis used to rise to power. Scream your lie loud enough, gather a violent mob to attack those who attempt to argue with you, and you can take over a country. For a while.
I think the American people are better than that. If you agree, contact your representatives in congress and let them know what you want to see in health care reform. Let them know that you don't make death threats to those who disagree with you but that you vote and that your friends with diabetes vote and you will be voting for those who do not let the huge corporate interests define "health care" as "The right to profit from the wealthy, employed, privileged sick."
The forces trying to keep us from getting a new health care system are bussing operatives in to disrupt congresspeople's meetings. These protesters are not people who live in the district. The pattern of using violence to shut down discourse is very disturbing. Contact your congresspeople and let them know you don't want policy set in response to gun toting people brought in from outside to threaten violence.
The right wing fringe is trying to frighten the public with the claim that health reform will mean those close to death will be forced to die because medical care will be withheld.
They prefer the old system, where only those who are poor, unemployed, or have a chronic condition are forced to die because care is withheld.
Shame on them.
Next time some fear monger tries to tell you that health reform means rationing care, remind them we already ration care.
Those with high status jobs get it. Those who work for small business, are laid off for more than 18 months, or are self-employed in businesses that don't earn enough to pay $12,000 a year for an insurance plan do not. Those with a preexisting diagnosis can't get insurance in many states no matter what they are willing to pay.
I get mail every week from people in their 30s and 40s who have LADA (a slow form of Type 1) and severe Type 2 diabetes who have lost their jobs or have jobs without health insurance who cannot afford to see a doctor or pay for the drugs they need.
The media tells you that there are programs for these people. Try finding one when you are faced with a person whose average blood sugar is running around 400 mg/dl but who the emergency room doctor diagnosed as "Type 2." Until they are in DKA or a hyperosmolar state, or have gangrene or kidney failure, they aren't considered in danger. So if cutting carbs doesn't bring down their sugars, they are SOL.
That looks a lot more like euthanasia to me than denying open heart surgery to a demented 90 year old who can no longer recognize her own family.
Who benefits from the current system? Someone, obviously, because a lot of money is going into funding the noisy rent-a-mob protests against health reform.
A country that can pay billions to bail out banks can afford to provide adequate health coverage for every single citizen. My stomach is turned by the arguments that health care reform must save money, while bank bailouts and car bailouts can lose as much as it takes to "keep our economy stable."
Where is it written that some people have a god given right to get wealthy off the sickness and suffering of others? What sick religious belief tells us that we should only help the suffering if we can do it without it costing us money?
The right wing uses fear, lies, violence and name calling when they have no real arguments left. Anyone familiar with the history of fascism should recognize the patterns. Perhaps the right wing is flinging the word "Nazi" around because they have been dipping so freely into the very techniques the Nazis used to rise to power. Scream your lie loud enough, gather a violent mob to attack those who attempt to argue with you, and you can take over a country. For a while.
I think the American people are better than that. If you agree, contact your representatives in congress and let them know what you want to see in health care reform. Let them know that you don't make death threats to those who disagree with you but that you vote and that your friends with diabetes vote and you will be voting for those who do not let the huge corporate interests define "health care" as "The right to profit from the wealthy, employed, privileged sick."
August 8, 2009
GSK Marketed Paxil Heavily to Pregnant Women Though It Causes Birth Defects
This isn't a diabetes story, but I am writing about it because the manufacturer involved in this case, GlaxoSmithKline (GSK), is the same company that sells and promotes Avandia and Avandamet to people with diabetes. The behavior of GSK in the way it is promoting blockbuster profit maker Paxil is very similar to what we saw with Avandia: complete disregard for the damage the company's drug caused patients.
You can read an excellent discussion of the problems with Paxil in this story published in today's Guardian. It's important to note that these stories appear in a British publication, not a US publication. The reason may have something to do with the fact that US print publications rely heavily on drug company advertising which is illegal in the UK.
Antidepressants once seen as miracle drugs: now risks are becoming evident US courts to hear claims that insufficient attention was paid to dangers to foetus.
What is most disturbing here is that the company specifically marketed Paxil, an SSRI which is notoriously difficult to quit, to pregnant women and women of childbearing age, even when there was growing evidence that the drug caused severe withdrawal symptoms in newborns and possibly was causing heart defects.
Even now the company spokesmen continue to downplay the dangers.
This is the same company that used threats of lawsuits to silence those who attempted to inform the public of the heart-attack potential of Avandia. While intelligent people can debate the facts about Avandia's link to heart attack, the heavy handed Mafia-like tactics the company employed to prevent that discourse from taking place speaks far louder than any research study about what the company really knew about Avandia's side effect profile.
If you are taking any SSRI and are thinking about becoming pregnant or have friends or relatives in that situation, you need to read this article and get the word out about what SSRIs may do to a baby. These drugs can be extremely difficult to stop (which in my youth was the definition of "addictive drug"--a definition which the SSRI manufacturers have managed to change). So women on these drugs should get their doctor's help to detox months before becoming pregnant.
And the rest of us have one more reason to distrust drug companies who prove month in and month out that they are willing to boost profits even if it means ruining the lives of innocent men, women, and now it appears, children.
You can read an excellent discussion of the problems with Paxil in this story published in today's Guardian. It's important to note that these stories appear in a British publication, not a US publication. The reason may have something to do with the fact that US print publications rely heavily on drug company advertising which is illegal in the UK.
Antidepressants once seen as miracle drugs: now risks are becoming evident US courts to hear claims that insufficient attention was paid to dangers to foetus.
What is most disturbing here is that the company specifically marketed Paxil, an SSRI which is notoriously difficult to quit, to pregnant women and women of childbearing age, even when there was growing evidence that the drug caused severe withdrawal symptoms in newborns and possibly was causing heart defects.
Even now the company spokesmen continue to downplay the dangers.
This is the same company that used threats of lawsuits to silence those who attempted to inform the public of the heart-attack potential of Avandia. While intelligent people can debate the facts about Avandia's link to heart attack, the heavy handed Mafia-like tactics the company employed to prevent that discourse from taking place speaks far louder than any research study about what the company really knew about Avandia's side effect profile.
If you are taking any SSRI and are thinking about becoming pregnant or have friends or relatives in that situation, you need to read this article and get the word out about what SSRIs may do to a baby. These drugs can be extremely difficult to stop (which in my youth was the definition of "addictive drug"--a definition which the SSRI manufacturers have managed to change). So women on these drugs should get their doctor's help to detox months before becoming pregnant.
And the rest of us have one more reason to distrust drug companies who prove month in and month out that they are willing to boost profits even if it means ruining the lives of innocent men, women, and now it appears, children.
August 3, 2009
Onglyza: Just Like Januvia but with More Serious Side Effects?
NOTE (April 2, 2013): Before you take Onglyza or Januvia please read about the new research that shows that they, and probably all incretin drugs, cause severely abnormal cell growth in the pancreas and precancerous tumors. You'll find that information HERE.
When the FDA approves a new drug it requires no proof that the drug is more effective than similar, existing drugs, only that it is better than placebo. Which is something to keep in mind as Bristol-Myers Squibb unveils what is sure to be a saturation advertising campaign for its new DPP-4 inhibitor, Onlgyza.
This mellifluous moniker is the brand name for Saxagliptin, which alert followers of drug news remember as the Januvia clone developed at the same times as Januvia whose release has been blocked due to its ability to cause "skin lesions" some of which necrotized (i.e. died and fell off) in monkeys.
I have read through the Prescribing Information for Onglyza and cannot see any benefit it offers in comparison to Januvia, the other DPP-4 inhibitor currently on the market.
Setting aside for the time being the advisability of controlling your blood sugar by turning off a tumor suppressor gene Onglyza offers nothing not offered by Januvia.
Both inhibit the expression of the DPP-4 gene for a full 24 hours--which means that if your body was fighting a new, very small DPP-4 sensitive tumor, like ovarian cancer, melanoma, prostate cancer or lung cancer, the drug would keep DPP-4 from killing off the tumor cells.
1. Feeble impact on blood sugar: Onglyza lowered A1cs that averaged 8% by .5%, which does not bring them anywhere near a safe level even by the anemic standards of the ADA. When the highest dose of Onglyza was compared to a placebo, it allowed only 14% more of those taking it to achieve 7% A1cs.
To better understand how "Effective" it is, consider what that A1c really meant: Onglyza lowered the average fasting glucose in those who took it from 171 mg/dl to 162 mg/dl (9.5 mmol/L) to 162 mg/dl (9 mmol/L). It lowered the average two hour post-meal blood sugar reading from a damaging 278 mg/dl (15.4 mmol/L) to an equally complication-guaranteeing 235 mg/dl (13 mmol/L).
So my immediate question would be: Why take this drug which is likely to cost 3 or 4 dollars a day to "achieve" blood sugars that are still high enough to lead to amputation, blindness and kidney failure when for the same money or less you could use insulin to get normal blood sugars?
2. Negative impact on the immune system. Inhibiting the DPP-4 gene, which produces an enzyme that rids the body of GLP-1 by chopping it up, lowers blood sugar because GLP-1 lowers blood sugar. However DPP-4 is used by the immune system for other functions most doctors know nothing about. Januvia's initial testing showed that it caused changes in white blood cell counts which the drug company dismissed as being of unknown significance.
Onglyza has a stronger impact on your immune system's white blood cells. In the prescribing information we read:
Translated into English, this means than in 1 person in 100 who take it, Onglyza lowers the white blood count to a dangerously low level.
If your doctor prescribes Onglyza without requiring that you have a blood count periodically, you can be sure the doctor has not read the prescribing information. Few doctors do.
3. Onglyza conflicts with common drugs and grapefruit juice Because of the way it is removed from the body Onglyza may build up in the blood stream when taken with common yeast medication, ketoconazole, as well as with erythromycin, calcium channel blocker verapamil, and grapefruit juice. Onglyza levels also rise in people with poorly functioning kidneys. The manufacturer says that dose must be cut back in people using these drugs. Whether busy doctors will know this and warn patients about lowering the dose when needed is another story.
4. Onglyza raises the peak Concentration of Sulfonylureas and TZDs. This makes it more likely people whose doctors prescribe this new drug with a sulfonylurea drug will experience hypos. Onglyza also reduces the peak concentration of metformin.
5.Side effects The main side effects reported with Onglyza are the headache and runny nose that are also found with Januvia and which result from the inhibition of the immune system these drugs cause. Over time, my experience with taking Januvia for several months was that the headaches increased in intensity in a way that made me glad to stop taking the drug.
However, Onglyza also causes other immune reactions: As reported, "Hypersensitivity-related events, such as urticaria [rash] and facial edema [swelling] in the 5-study pooled analysis up to Week 24 were reported in 1.5%, 1.5%, and 0.4% of patients."
Januvia also turns out to cause rashes, including, very rarely, the life threatening Stevens-Johnson syndrome where people's skin peels off the body. It is significant, though that rash did not appear as a side effect of Januvia until after the approval testing was complete. That Onglyza produced such a high rate of rash during testing seems to suggest that it has a higher potential to disrupt the immune system.
6. No evidence that this or any other DPP-4 inhibitor preserves beta cells I mention this because the drug reps are selling these drugs to doctors claiming, based on weak animal evidence that these drugs preserve beta cells. No drug can preserve or regenerate beta cells when blood sugars are rising over 140 mg/dl for long periods of time, because sustained high blood sugars cause glucotoxicity--poisoning of beta cells. With the many years that BMS has been testing Onglyza you can be sure they have run every test they could find to demonstrate beta cell preservation and the complete lack of any cite to this in the prescribing information suggests they could not find it.
Why Take Onglyza?
Nothing in the prescribing information suggests any advantage in taking Onglyza compared to Januvia, while at the same time suggesting strongly that Onzglya's impact on the immune system is stronger than Januvia's. No research was done into whether Onglyza increases the incidence of tumors in those who take it, and because of the very small numbers involved in the clinical trials and the way the drug companies bury tumor incidence (combining benign and cancerous tumors in one category, as in the Januvia trials), that data is not likely to emerge.
Nevertheless, I'm sure a BMS drug rep is hard at work motivating doctors to switch patients to their new drug. Don't be surprised if your doctor suggests you enroll in a "study" using Onglyza, as this is a common way to divert patients from an existing drug. The "study" will provide you with one or two month's free supply of the drug because the companies know that once you are used to taking it you are likely to continue taking it. You'll be seeing free samples and eventually saturation advertising on diabetes web sites and TV.
The really sad part is that the net effect of all this will be only that patients with A1cs of 8% whose fasting blood sugar is well over 150 mg/dl and whose post meal blood sugars are in the range the ADA long ago defined as causing blindness (over 200 mg/dl two hours after eating) will take another expensive drug that ensures they won't get the kind of control that prevents the classic complications.
If you have blood sugars that high before you pay a couple hundred bucks a month for a potentially harmful new drug try the following:
1. Try the technique described here: How to Get Your Blood Sugar Under Control. It really works. Even for people who have had diabetes for as long as a decade.
2. Add extended release metformin if you can tolerate it and have no kidney or liver problems. Metformin is much more effective and less prone to cause digestive distress when used along with a diet lower in carbohydrate.
3. If cutting back on the carbs in your meals and adding metformin doesn't lower your blood sugar to safe levels (Under 140 mg/dl after eating) demand that your doctor send you to an endocrinologist so that you can get a tailored insulin regimen that gives you normal blood sugars.
Do not settle for the kind of insulin regimen family doctors usually prescribe which almost always leave you with blood sugars that are damagingly high. These inadequate insulin regimens are designed to keep your blood sugar high so as to avoid hypos--and to avoid the need to give you the kind of diabetes education routinely offered people with Type 1. With proper diabetes education you can avoid hypos and get great control. But for most Type 2s, to get the right kind of insulin regimen prescribed you will have to find a young, knowledgeable endocrinologist who will take the time to work with you on tuning your insulin regimen.
If your doctor won't help you get normal blood sugars, and insists that all you need are oral drugs fire him or her and find one who will give you the help you need.
Every person with diabetes can achieve normal blood sugars and normal blood sugars produce normal health.
When the FDA approves a new drug it requires no proof that the drug is more effective than similar, existing drugs, only that it is better than placebo. Which is something to keep in mind as Bristol-Myers Squibb unveils what is sure to be a saturation advertising campaign for its new DPP-4 inhibitor, Onlgyza.
This mellifluous moniker is the brand name for Saxagliptin, which alert followers of drug news remember as the Januvia clone developed at the same times as Januvia whose release has been blocked due to its ability to cause "skin lesions" some of which necrotized (i.e. died and fell off) in monkeys.
I have read through the Prescribing Information for Onglyza and cannot see any benefit it offers in comparison to Januvia, the other DPP-4 inhibitor currently on the market.
Setting aside for the time being the advisability of controlling your blood sugar by turning off a tumor suppressor gene Onglyza offers nothing not offered by Januvia.
Both inhibit the expression of the DPP-4 gene for a full 24 hours--which means that if your body was fighting a new, very small DPP-4 sensitive tumor, like ovarian cancer, melanoma, prostate cancer or lung cancer, the drug would keep DPP-4 from killing off the tumor cells.
1. Feeble impact on blood sugar: Onglyza lowered A1cs that averaged 8% by .5%, which does not bring them anywhere near a safe level even by the anemic standards of the ADA. When the highest dose of Onglyza was compared to a placebo, it allowed only 14% more of those taking it to achieve 7% A1cs.
To better understand how "Effective" it is, consider what that A1c really meant: Onglyza lowered the average fasting glucose in those who took it from 171 mg/dl to 162 mg/dl (9.5 mmol/L) to 162 mg/dl (9 mmol/L). It lowered the average two hour post-meal blood sugar reading from a damaging 278 mg/dl (15.4 mmol/L) to an equally complication-guaranteeing 235 mg/dl (13 mmol/L).
So my immediate question would be: Why take this drug which is likely to cost 3 or 4 dollars a day to "achieve" blood sugars that are still high enough to lead to amputation, blindness and kidney failure when for the same money or less you could use insulin to get normal blood sugars?
2. Negative impact on the immune system. Inhibiting the DPP-4 gene, which produces an enzyme that rids the body of GLP-1 by chopping it up, lowers blood sugar because GLP-1 lowers blood sugar. However DPP-4 is used by the immune system for other functions most doctors know nothing about. Januvia's initial testing showed that it caused changes in white blood cell counts which the drug company dismissed as being of unknown significance.
Onglyza has a stronger impact on your immune system's white blood cells. In the prescribing information we read:
There was a dose-related mean decrease in absolute lymphocyte count observed with ONGLYZA. From a baseline mean absolute lymphocyte count of approximately 2200 cells/microL, mean decreases of approximately 100 and 120 cells/microL with ONGLYZA 5 mg and 10 mg, respectively, relative to placebo were observed at 24 weeks in a pooled analysis of five placebo-controlled clinical studies. Similar effects were observed when ONGLYZA 5 mg was given in initial combination with metformin compared to metformin alone. There was no difference observed for ONGLYZA 2.5 mg relative to placebo. The proportion of patients who were reported to have a lymphocyte count ≤750 cells/microL was 0.5%, 1.5%, 1.4%, and 0.4% in the saxagliptin 2.5 mg, 5 mg, 10 mg, and placebo groups, respectively. In most patients, recurrence was not observed with repeated exposure to ONGLYZA although some patients had recurrent decreases upon rechallenge that led to discontinuation of ONGLYZA.
Translated into English, this means than in 1 person in 100 who take it, Onglyza lowers the white blood count to a dangerously low level.
If your doctor prescribes Onglyza without requiring that you have a blood count periodically, you can be sure the doctor has not read the prescribing information. Few doctors do.
3. Onglyza conflicts with common drugs and grapefruit juice Because of the way it is removed from the body Onglyza may build up in the blood stream when taken with common yeast medication, ketoconazole, as well as with erythromycin, calcium channel blocker verapamil, and grapefruit juice. Onglyza levels also rise in people with poorly functioning kidneys. The manufacturer says that dose must be cut back in people using these drugs. Whether busy doctors will know this and warn patients about lowering the dose when needed is another story.
4. Onglyza raises the peak Concentration of Sulfonylureas and TZDs. This makes it more likely people whose doctors prescribe this new drug with a sulfonylurea drug will experience hypos. Onglyza also reduces the peak concentration of metformin.
5.Side effects The main side effects reported with Onglyza are the headache and runny nose that are also found with Januvia and which result from the inhibition of the immune system these drugs cause. Over time, my experience with taking Januvia for several months was that the headaches increased in intensity in a way that made me glad to stop taking the drug.
However, Onglyza also causes other immune reactions: As reported, "Hypersensitivity-related events, such as urticaria [rash] and facial edema [swelling] in the 5-study pooled analysis up to Week 24 were reported in 1.5%, 1.5%, and 0.4% of patients."
Januvia also turns out to cause rashes, including, very rarely, the life threatening Stevens-Johnson syndrome where people's skin peels off the body. It is significant, though that rash did not appear as a side effect of Januvia until after the approval testing was complete. That Onglyza produced such a high rate of rash during testing seems to suggest that it has a higher potential to disrupt the immune system.
6. No evidence that this or any other DPP-4 inhibitor preserves beta cells I mention this because the drug reps are selling these drugs to doctors claiming, based on weak animal evidence that these drugs preserve beta cells. No drug can preserve or regenerate beta cells when blood sugars are rising over 140 mg/dl for long periods of time, because sustained high blood sugars cause glucotoxicity--poisoning of beta cells. With the many years that BMS has been testing Onglyza you can be sure they have run every test they could find to demonstrate beta cell preservation and the complete lack of any cite to this in the prescribing information suggests they could not find it.
Why Take Onglyza?
Nothing in the prescribing information suggests any advantage in taking Onglyza compared to Januvia, while at the same time suggesting strongly that Onzglya's impact on the immune system is stronger than Januvia's. No research was done into whether Onglyza increases the incidence of tumors in those who take it, and because of the very small numbers involved in the clinical trials and the way the drug companies bury tumor incidence (combining benign and cancerous tumors in one category, as in the Januvia trials), that data is not likely to emerge.
Nevertheless, I'm sure a BMS drug rep is hard at work motivating doctors to switch patients to their new drug. Don't be surprised if your doctor suggests you enroll in a "study" using Onglyza, as this is a common way to divert patients from an existing drug. The "study" will provide you with one or two month's free supply of the drug because the companies know that once you are used to taking it you are likely to continue taking it. You'll be seeing free samples and eventually saturation advertising on diabetes web sites and TV.
The really sad part is that the net effect of all this will be only that patients with A1cs of 8% whose fasting blood sugar is well over 150 mg/dl and whose post meal blood sugars are in the range the ADA long ago defined as causing blindness (over 200 mg/dl two hours after eating) will take another expensive drug that ensures they won't get the kind of control that prevents the classic complications.
If you have blood sugars that high before you pay a couple hundred bucks a month for a potentially harmful new drug try the following:
1. Try the technique described here: How to Get Your Blood Sugar Under Control. It really works. Even for people who have had diabetes for as long as a decade.
2. Add extended release metformin if you can tolerate it and have no kidney or liver problems. Metformin is much more effective and less prone to cause digestive distress when used along with a diet lower in carbohydrate.
3. If cutting back on the carbs in your meals and adding metformin doesn't lower your blood sugar to safe levels (Under 140 mg/dl after eating) demand that your doctor send you to an endocrinologist so that you can get a tailored insulin regimen that gives you normal blood sugars.
Do not settle for the kind of insulin regimen family doctors usually prescribe which almost always leave you with blood sugars that are damagingly high. These inadequate insulin regimens are designed to keep your blood sugar high so as to avoid hypos--and to avoid the need to give you the kind of diabetes education routinely offered people with Type 1. With proper diabetes education you can avoid hypos and get great control. But for most Type 2s, to get the right kind of insulin regimen prescribed you will have to find a young, knowledgeable endocrinologist who will take the time to work with you on tuning your insulin regimen.
If your doctor won't help you get normal blood sugars, and insists that all you need are oral drugs fire him or her and find one who will give you the help you need.
Every person with diabetes can achieve normal blood sugars and normal blood sugars produce normal health.
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