Thursday, April 25, 2013

Nigel Kinbrum’s T2 diabetes control method discussed with my Doctor.

Hi Doc, hi Eddie take a seat, what can I do for you today? I want to start using Insulin. Why is that? Because a guy called Nigel reckons it’s the best way to control my diabetes. But you have been controlling your diabetes perfectly for five years, what do think you will gain by going onto insulin ? Well, I will be able to eat lots of junk food, and I am worried about the long term effects of lowcarbing, Nigel reckons it makes you go bat shit ! Eddie, there has never been a major long term trial on the effects of a lowcarb diet re diabetes control, how would Nigel know what the effects of lowcarb are ! Is Nigel an expert on diabetes control ? No Doc, is he a long term well controlled diabetic ? No Doc. So how does he know? A bloke called Anthony Colpo told him. Ah, Colpo he is a diabetes expert ! No Doc. What is he ? He is a sort of body builder and weight lifter that writes  on a blog. I see, but he is a well controlled long term diabetic? Err… Doc.

Eddie, you are one of the best controlled type two diabetics on my books, non diabetic HbA1c, good lipids, stable safe weight, >90 kidney GFR, and all 40 blood test markers in the normal range. Insulin will do nothing for you. In fact it could wreck what you have  achieved over the last five years. Do you miss eating the food that made you ill, overweight and a type two diabetic ? No Doc. Do you realise you could lose your driving license, that all sorts of insurance costs could go thought the roof? Yes Doc. Do you realise many employers may not employ you as they see you as a health and safety risk? Yes Doc. Do you realise so many type two’s that go onto insulin gain weight and that leads back to high insulin resistance? Err….yes Doc.

Eddie, you do realise, there is no way I would put a patient with your non diabetic HbA1c status on Insulin don’t you? We don’t doll out potentially dangerous drugs to people that don’t need them. What about statins Doc ? Are you taking the piss Eddie ? You know me Doc. Eddie forget about using insulin, save it for a time you may need it, at the moment you are doing very well, take it from me it isn’t a get out of jail free card, and stop listening to the Nigel’s of this world. Tell me, this Nigel his surname isn’t Kinbrum is it? Yes. Jeez that bloke is a complete lunatic, he spends his entire life galloping around the blogosphere spouting complete nonsense, seriously he is a  menace to society. You do know he is one of Evelyn Kocur’s eunuchs don’t you, yes Doc. Goodbye Eddie you’re wasting my time, sorry Doc it won’t happen again.

Doctor presses intercom button. Make a note on Mitchell’s records, the mans gone completely batshit !

Wednesday, April 24, 2013

Blood Sample Mismatch Leads 'Anguished' Authors To Retract Three Lipitor Papers

Three substudies of the influential TNT (Treating to New Targets) trial have been retracted after the sponsor of the trial, Pfizer, discovered that blood samples from the study had been matched to the wrong participants.
The main results of TNT, published in 2005 in the New England Journal of Medicine, had a major impact on clinical practice and statin prescription patterns. The trial supported the increasingly aggressive use of statins and helped to solidify the enormous commercial success of atorvastatin (Lipitor, Pfizer).
The 3 newly-retracted substudies do not appear to affect the main finding of TNT. Two papers were published in the Journal of the American College of Cardiology. The third was published in the American Heart Journal. (TheAHJ retraction notice has not yet been published, but the editors have confirmed the retraction.) Here are the 3 retracted articles:
Plasma PCSK9 Levels and Clinical Outcomes in the TNT (Treating to New Targets) Trial: A Nested Case-Control Study
Roeland Huijgen, MD; S. Matthijs Boekholdt, MD, PhD; Benoit J. Arsenault, PhD; Weihang Bao, PhD; Jean-Michel Davaine, MD; Fatiha Tabet, PhD; Francine Petrides, BSc; Kerry-Anne Rye, PhD; David A. DeMicco, PharmD; Philip J. Barter, MD, PhD; John J.P. Kastelein, MD, PhD; Gilles Lambert, PhD
J Am Coll Cardiol. 2012;59(20):1778-1784. doi:10.1016/j.jacc.2011.12.043
Prediction of Cardiovascular Events in Statin-Treated Stable Coronary Patients by Lipid and Nonlipid Biomarkers
Benoit J. Arsenault, PhD; Philip Barter, MD, PhD; David A. DeMicco, PharmD; Weihang Bao, PhD; Gregory M. Preston, PhD; John C. LaRosa, MD; Scott M. Grundy, MD, PhD; Prakash Deedwania, MD, PhD; Heiner Greten, MD; Nanette K. Wenger, MD; James Shepherd, MD; David D. Waters, MD; John J.P. Kastelein, MD, PhD
J Am Coll Cardiol. 2011;57(1):63-69. doi:10.1016/j.jacc.2010.06.052
Vitamin D levels do not predict cardiovascular events in statin-treated patients with stable coronary disease
Vera Bittner, MD, MSPH, Nanette K. Wenger, MD, David D. Waters, MD, David A. DeMicco, PharmD, Michael Messig, PhD, John C. LaRosa, MD
American Heart Journal, Volume 164, Issue 3 , Pages 387-393, September 2012
Here is the main text of the retraction:
"The main findings of the TNT Trial were published in 2005 (1). Since that time, members of the Steering Committee and other investigators have published 32 papers based upon additional analyses of TNT. The data for these papers were derived from analyses of the TNT clinical database, managed by Pfizer. The clinical database has been crosschecked many times and the data in it is valid. During the trial, blood samples were drawn from the patients at regular intervals for subsequent analysis. We performed a nested case-control study that included 507 patients who experienced a CV event and 1,020 control patients in the main biomarker analysis, and 496 patients who experienced a CV event and 1,117 control patients in the PCSK9 analysis. The biomarker database was separate from the clinical database. An anonymization code was run in 2007 to link patients from one database to the other.
In late 2012, the TNT frozen blood samples were integrated into a large automated biobank that includes samples from other Pfizer trials. At that time discrepancies were noted among the samples, indicating that an error had occurred when the samples were anonymized in 2007. Further investigation revealed that the code created to manually anonymize the data was accidentally run twice. During the first run, anonymized subject identifiers were successfully assigned to both biosamples and clinical data. However, after this first run had passed quality control checks, the anonymization code was re-run inadvertently, replacing the first correct set of identifiers with a random and incorrect set. We do not understand how or why the code was re-run. The study team, who were blinded as to patient identity, thus reported on mismatched clinical and biomarker data. The investigators of the biomarkers study were puzzled that none of the 18 biomarkers were predictive of cardiovascular events. However we were reassured because on-treatment LDL-cholesterol, HDL-cholesterol and triglyceride levels were all strongly predictive of events, and we reported this in the paper. These lipid levels were part of the clinical database, and thus were not subject to the error that occurred with the biomarkers. In the PCSK9 analysis, PCSK9 levels were predictive of events in the atorvastatin 10-mg group (p = 0.039) but not in the 80-mg group. This finding, which we now realize is totally spurious, was not unexpected and raised no red flags. Similarly, the failure of vitamin D levels to predict events, as reported in the AHJ paper, was not surprising.
Since the error was discovered, we have created a new anonymized clinical and biomarker database by restoring the original set of anonymized identifiers. We are currently reanalyzing the data according to our original study plans. However, the nested case-control feature of the original study design has been lost because the patient selection for biomarker sampling was random. Only approximately one tenth of patients now had an event, compared to one third in the original study design. Thus, the power to detect a difference in the level of a biomarker between patients with and without events has been attenuated.
All authors of these manuscripts are anguished to have made this mistake and publishing incorrect information."
 TNT investigator John Kastelein,  an author of two of the papers, toldRetraction Watch:
Since the retraction was the result of a sample mix up and the results of our analysis were negative with regards to the predictive ability of the biomarkers in question, I, in fact, do hope that with the corrected sample labels and a new analysis we will be able to make better sense of the data.


Death of medical student Sarah Houston after taking banned slimming drug Dinitrophenol highlights dangers of buying pills online, warns Government

Slimming pills which led to the death of a medical student will claim more lives unless regulators launch an urgent crackdown, campaigners warned yesterday as it emerged that a legal loophole has allowed the hazardous tablets to remain on sale.

Jim Dobbin, a microbiologist who is also the Labour and Co-operative MP for Heywood and Middleton, called for a review of the law concerning DNP (2,4-dinitrophenol) – an unregulated weight-loss product taken by the Leeds University student Sarah Houston. It was linked to 62 deaths around the world in a study published last year in The Journal of Medical Toxicity.

“It is unacceptable that lives are being put at risk by ineffective legislation and control of internet trade in potentially lethal products,” Mr Dobbin said.

More on this story here.

Anyone want to buy my house ?

London home set to smash property price record by going on sale for a staggering £250m The house, which is on Carlton House Terrace, enjoys views of St James's Park and is 30 times bigger than a typical London family house. A London home is set to smash the record for the most expensive property in Britain by going on sale for a staggering £250?million. The Grade I listed Regency property in central London would cost potential buyers 700 times more than the £370,000 average property value in the capital.


 More here.

Tuesday, April 23, 2013

Low-glycemic diet seen to reverse diastolic dysfunction of diabetes !

Vienna, Austria - A diet that was short on carbohydrates and long on protein, given to diabetic patients engaged in a supervised exercise and weight-loss program, appeared not only to cut proinsulin levels and postprandial glucose and triglyceride levels, it seemed to improve LV diastolic function [1].

In the study that compared the "low-carb" diet to a traditionally recommended low-fat diet, the one designed to flatten out resulting insulin and glucose curves also allowed them to take far fewer oral diabetes medications and apparently cut both systolic and diastolic pressures. The low-fat diet had no apparent effect on diastolic function or med use or on blood pressures.

On the other hand, the two diets led to about the same declines in weight and waist circumference and lipoprotein-cholesterol levels, reported Prof Helene von Bibra (Technical University Munich, Germany) here at the Prediabetes and the Metabolic Syndrome 2013 Congress.

Many patients with insulin resistance, diabetes, or both have subclinical diastolic dysfunction, with severe prognostic implications if it becomes symptomatic, von Bibra reminded heartwire. About 65% of the 32 patients in the study had abnormal diastolic function as defined echocardiographically by low early diastolic myocardial velocity. That measure in most cases nearly normalized after the low-carb diet, but not after the low-fat diet, she said.

Of 32 overweight or obese diabetic patients (mean body-mass index, 34) without cardiac disease who were engaged in a "rehabilitation program in order to lose weight" that included two hours of supervised aerobic exercise per day, half followed a low-glycemic diet (25% carbohydrate, 45% fat, 30% protein) and the other half a low-fat diet (55% carbohydrate, 25% fat, and 20% protein) for three weeks. The diets provided the same amount of calories. Those on the low-fat diet then switched to the low-glycemic diet for an additional two weeks. Cardiac function by echo and metabolic parameters were assessed daily before and after a 400-kcal breakfast.

From baseline to three weeks, patients on the low-carb diet reduced their use of conventional oral antidiabetic medication by 86%. Those on the low-fat diet reduced them by only 6% by the end of three weeks, but intake went down another 57% by the end of their two-week low-glycemic diet phase. "And still they had improvements in glucose," von Bibra said. Medications other than oral ones for diabetes, such as antihypertensive drugs, were not changed in anyone during the study.

In the low-glycemic-diet group, mean systolic blood pressure declined from 127 mm Hg to 118 mm Hg (p<0.002) after three weeks; diastolic pressures also fell (p<0.04). Neither changed after three weeks for those initially on the low-fat diet, but both "improved in the same direction" as those in the low-glycemic group after two weeks on the low-glycemic diet, von Bibra said.

Laboratory and echo changes in overweight/obese diabetic patients assigned to low-glycemic (n=16) and low-fat (n=16) diets

Initial assigned diet Baseline 3 wk 2 wk after crossover to low-carb 
Triglycerides (mg/dL)150111<0.005
Postprandial glucose (mg/dL)141125<0.04
E' (cm/s)9.510.4<0.03
Triglycerides (mg/dL)208194138<0.003 vs 3 wk, <0.004 vs baseline
Postprandial glucose (mg/dL)168137127<0.008 vs baseline
E' (cm/s)10.810.711.4<0.02 vs 3 wk

E'=early diastolic myocardial velocity by tissue-Doppler echocardiography

The gains in diastolic function probably were not independently related to the associated blood-pressure reductions; rather, she proposed, they reflected improvements in myocardial energy utilization on the low-glycemic diet. Insulin resistance can lead to diastolic dysfunction via several pathways, she noted, but the most prominent seems to be myocardial energy deficiency secondary to microvascular dysregulation and mitochondrial imbalances of glucose vs fat oxidation.


Monday, April 22, 2013

Nigel Kinbrum and other numbskulls !

If you get around the bloggosphere, especially on some of the sites in the US, you must have come across Nigel Kinbrum, or as he prefers to call himself Nigeepoo. From such diverse blogs such as Free The Animal, to the skid row blog of CarbSane the all knowing. In all fairness our Nigeepoo is a pretty harmless sort of guy, and not bright enough to cause any grief to the thinking man or woman. He reminds me very much of a dog my Father once owned. It was a lot of fun and full of mischief, but when it got old, it went batshit and had to be put down.

So, where is this post going, what’s it all about. Well every now and again, I find a person that makes a lot of noise, they stand for nothing and talk complete nonsense re the best way to control type two diabetes. They talk a lot about diet, but don’t come close to knowing the basic fundamentals. In my opinion these people cause confusion, they suck the kneecaps of idiots such as Evelyn Kocur and I use these dullards to promote the lowcarb cause. I wind them up and lampoon them, always posting under my own name which links directly to our lowcarb diabetic website. Which also links to our main and lowcarb recipe blogs. Recently I have had various run ins with Nigel, mainly on the Free The Animal blog. I recently lampooned him in a couple of cartoons on this blog. One of his replies.

“Someone is a little slow on the uptake and that someone's name is Eddie Mitchell.

I try to not use rude words on my blog, as anyone can read it. Therefore I will merely state that Mr Mitchell is feeling extremely hard done by, as he has to eat a diet virtually devoid of carbohydrates, because he's either too thick or too stubborn to inject some insulin after his beta cells got fed up with his constant whining and decided to down tools.

I, on the other hand, can eat whatever I like and maintain perfect blood glucose regulation after doing the things listed in  Insulin Resistance: Solutions to problems. It must really suck being Eddie Mitchell.”

As I said earlier, he knows nothing whatsoever re diet, or the safe control of type two diabetes. My diet is not devoid of carbs, I use around fifty per day, almost all from low starch vegetables and a small amount of lowcarb fruits. Fifty carbs, two Metformin pills and moderate exercise. This gives me non diabetic HbA1c, safe stable weight and the trigs of an athlete. What sort of numbskull would recommend upping the carbs and shooting insulin ? Our Nigel eh. I do not fear the day insulin may be my only option, but my way of diabetes control has kept me insulin free for over five years. If Nigel knew the ramifications of shooting insulin, even he would not have made the statement “he's either too thick or too stubborn to inject some insulin” There is probably not an Insulin using diabetic in the world, who would not wish to be free of having to use insulin and all it entails.

One last point, Nigel is not a diabetic. He stated on the Free The Animal blog recently, he was once nearly a type two diabetic. I suspect Nigel was nearly a lot of things.


Sunday, April 21, 2013

Troubling New Signals? Diabetes Drugs & Adverse Event Reports !

For the past two months, there has been rising controversy over the extent to which certain diabetes drugs called GLP-1 inhibitors may cause pancreatitis and pancreatic cancer. Although links to pancreatitis are actually not new, one of two recent papers suggested pre-cancerous cell growth may be cause for concern, prompting both the FDA and the European Medicines Agency to start investigations.
Now,  a watchdog group is calling for a reassessment of the entire class of drugs after analyzing adverse events data that was reported to the FDA and finding distinctly higher odds that GLP-1 drugs are generating reports for these illnesses compared with a control group consisting of older drugs, such as metformin, that are used to treat diabetes.   
Specifically, the analysis found the odds were roughly 25 times higher for the following drugs: Merck’s Januvia (MRK), which is the biggest seller in this group; Onglyza, which is sold by Bristol-Myers Squibb (BMY) and AstraZeneca (AZN); Byetta, which is also marketed by Bristol-Myers; the Tradjena treatment sold by Eli Lilly (LLY) and Boehringer Ingelheim, and Novo Nordisk’s Victoza.
“I think the future of the whole class is in question,” says Thomas Moore, senior scientist for drug safety and policy with the Institute for Safe Medication Practices, which published the data in its QuarterWatch report. While he says further study should be undertaken, “if results are confirmed in a broader patient population, it raises questions about the entire class of drugs.”
In reaching this conclusion, ISMP examined 1,723 serious adverse events reported to the FDA between July 1, 2011, and June 30, 2012 for all five of the GLP-1 drugs, which mimic a hormone called GLP-1 to stimulate natural insulin production. There were 831 cases of pancreatitis; 105 case of pancreatic cancer; 32 cases of thyroid cancer and 101 cases indicating a hypersensitivity reaction.
When breaking down the adverse event reports, ISMP found that after adjusting for differences, the odds that a report would be filed indicating pancreatitis was 28.5 times higher for the two injectable drugs – Byetta and Victoza – compared with older diabetes meds. By contrast, the odds of such a report being filed in connection with the pills were 20.8 times higher.
Overall, the odds the GLP-1 drugs would cause an adverse event report of pancreatitis to be filed was 25.6 times higher than for the metformin or sulfonulyreas. Similarly, the injectable drugs were associated with reports of thyroid cancer, while the pills were not, according to ISMP. Athough all of the GLP-1 yielded hypersensitivity reports, the odds that Victoza would do so was nearly 8 times higher than the older meds and the only one to show a statistically significant difference.
“There are some important signals here,” says Moore, who maintains the analysis is the most comprehensive analysis to date of adverse events for this class of drugs. “The hypersensitive issue needs more than AE reports to validate, but it’s a pretty big signal. And our analysis also provides preliminary evidence of the risks of the (injectables) could be higher than the oral agents” (here is the ISMP report).
He added that the results “build on” what was seen in the recent studies that prompted regulatory probes. In one study, which was published in Diabetes, researchers found the drugs caused “marked” cell proliferation and damage, and displayed a potential for eventually transforming into cancer. However, the study was small – researchers examined the pancreas of 20 deceased human organ donors with type 2 diabetes.
The other study, which was published in JAMA Internal Medicine, examined insurance records for more than 2,500 diabetics between February 2005 and December 2008, and found that patients hospitalized with pancreatitis were twice as likely to have taken either Januvia or Byetta than a control group of type 2 diabetics who did not have pancreatitis. The other drugs were not analyzed (read more here and here is another interesting angle).
This study generated considerable pushback from not only the drugmakers, but also Wall Street analysts and the American Association of Endocrinologists and the American Diabetes Association over concerns that physicians may change treatment practices and objections to the study design. They also noted pancreatitis was not a new issue.
But when the next study appeared in Diabetes, the dissension was muted, although the Public Citizen watchdog group called for the FDA to ban the class of drugs (read here). Not surprisingly, several of the drugmakers last night defended their medicines and noted the ISMP analysis had limitations, since the FDA adverse event reporting system does not demonstrate causality.
The FDA database is “subject to reporting biases and (is) often limited by a lack of information concerning important variables such as confirmation of diagnosis, specific patient characteristics and co-morbidities, duration of a patient’s disease, prior drug exposures, and concomitant medication use. The authors themselves caution that their analysis ‘should be interpreted in light of the known limitations of a reporting system that does not collect data systematically,’ “ a Bristol-Myers spokesman writes us.
He adds that “direct comparison of event rates of different agents generated from this type of analysis should be interpreted with caution, as the authors themselves acknowledge.  These data need to be put into context with data from clinical trials and epidemiology studies, which are better suited to assess risk.”
And a Novo Nordisk spokesman sent us this: “We have reviewed the totality of safety information available to us, and remain confident in the safety profile of Victoza.  We continue to work closely with the FDA to provide an on-going assessment of Victoza’s risk-benefit profile.”
And a Boehringer spokeswoman wrote this: "Numerous factors can increase spontaneous adverse event reporting. Comparison of reporting rates across products is not methodologically supported due to biases that cannot be adequately controlled... The FDA’s Adverse Event Reporting System specifically states that data should not be used to compare findings across compounds. Products may be approved for different indications in patient populations that are inherently different, and therefore, the outcomes across these patients may also be different."
"...It is not appropriate to compare new users of a product with patients who have been treated with a product for a longer period of time as it introduces critical bias due to depletion of susceptibles (healthy survivor bias); the initially treated group of patients has a higher risk of adverse events than that after some years of market presence because patients with side effects may, for example, discontinue treatment," she adds.
Think I'll stick with LowCarb !