�Disappointing results of modish treatments of blood glucose which get not convincingly reduced problems, apart from sub-clinical micro-vascular disease
Current drugs offer little evidence that treatment of moderate hyperglycaemia is of benefit to patients.
Concerns about side effect of drugs treating hyperglycaemia associated with obesity
A major barrier to obtaining evidence that long-term treatments are good is the short and often insecure drug patent-life offered by regulatory agencies. Short-termism forces regulators to accept surrogates instead of real clinical benefits
Long-term studies are required to establish the best means of treating diabetes
The need for long full term studies to establish the best means of treating Diabetes, was underlined by Prof John Cleland from the University of Hull at the ESC Congress in Munich. Prof Cleland listed the latest discourse available for patients and voiced his concern about the side-effects and efficacy of available anti-diabetic drugs.
Treating Patients with Diabetes Mellitus
Treatment should be based, wheresoever possible, on the results of studies of substantial size and duration that measure outcomes that are meaningful to patients. We know that treatment of hypertension and hyperlipidaemia reduce progression of micro-vascular disease, reduce vascular events associated with expectant vessel disease and improve the prospect of patients with diabetes.
In contrast, treatment of rip glucose has not convincingly reduced any of these problems, apart from subclinical micro-vascular disease. A major barrier to obtaining evidence that semipermanent treatments ar beneficial is the short and ofttimes insecure drug patent-life offered by regulative agencies.
Short-termism forces regulators to accept surrogates instead of real clinical benefits. This deceives manufacturers, scientists, clinicians and patients into believing that blood glucose control is an important goal of treatment rather than a mere surrogate for real success. Longer patent-life is a pre-requisite for obtaining ripe evidence that any treatment (for diabetes, blood press or lipids) designed to reduce long-term morbidity and mortality is safe and effective. Another alternative is to trammel such studies only to patients with established cardiovascular disease and thus senior high school event rates.
Type 1 Diabetes
Originally, diabetes mellitus was conceived as a syndrome of insulin deficiency, mainly affecting jr. people and often associated with weight loss, glycosuria, ketoacidosis and often rapidly fatal. This syndrome requires insulin replacing therapy, which is still predominantly granted by intermittent subcutaneous injections. The evidence that stringent insulin control is superior to a lax regime is weak.
The largest study, DCCT (n = 1,441), reported no reduction in diabetic keto-acidosis or mortality and only humble reductions in vascular events (21 patients difference afterwards 17 days follow-up) with clear benefits only on subclinical micro-vascular disease. This study was not blinded and we know that unblinded studies tend to over-estimate benefit. More intense insulin therapy was associated with substantive weight reach which may obviate whatsoever cardiovascular benefit of improved diabetes control. Insulin pumps, inhaled insulin and pancreatic islet mobile phone transplants ar potential, only mainly theoretical alternatives. Potentially, very long-run studies are required to establish the best means of treating this disease.
Type II Diabetes
Subsequently, a new population of patients with high insulin levels and hyperglycaemia (insulin-resistance) was identified. These were more than commonly senior patients, weighty and had evidence of other cardiovascular diseases including hypertension and hyperlipidaemia. This population has increased markedly over the last 20 years, partly due to the growing proportion of the population who ar elderly, partially because of the increase in fleshiness and partly because of the diminution in glucose thresholds required for diagnosing. Diabetes of this type does not really represent a distinct disease merely rather just now one end of the spectrum of the population. Blood glucose is continuously distributed in a similar way to blood pressure or spunk rate. For each, thither is an ideal natural range. Levels below this range or markedly to a higher place it causal agency acute malady and moderately elevated levels are associated with worse long-term outcome.
It is a giant effrontery to hint that victimisation drugs to get patients back into the normal range is helpful or safe. We know from experience with other diseases that this assumption is no thirster tenable. Unfortunately, there is remarkably little evidence that treatment of moderate hyperglycemia is of benefit to patients and concerns that treating hyperglycaemia associated with obesity, other perhaps than by treating obesity itself, is safe.
Although the micro-vascular complications of diabetes mellitus are of great fear, few older patients with diabetes subsist long enough to train them. For instance, over 10 years follow-up in the 411 patients of UKPDS-34 managed with low-pitched intensity regimen (to maintain fasting blood glucose
Oral Drugs for Treating Hyperglycaemia
Two major drug classes that have been in use for some decades are biguanides (metformin) and sulphonylureas (eg:- chlorpropamide, gliclazide and glyburide). Metformin reduces hepatic synthesis of glucose (considered its main effect) and increases glucose uptake (insulin sensitivity) of peripheral tissues. There is more evidence for a therapeutic benefit with this agent than any other but even that grounds is not strong. Sulphonylureas increase pancreatic insulin secretion. There is little evidence that these agents thin micro- or macro-vascular complications but they do cause obesity.
Newer Agents
Thiazolidinediones (eg:- Pioglitazone, Rosiglitazone)
These agents increase glucose uptake (insulin sensitivity) in peripheral tissues. They typically reduce HbA1c by 0.5-2% compared to placebo. Two solid trials ingest been reported and several meta-analyses. Overall, these suggest little or no force on clinically relevant outcomes in patients with diabetes mellitus. However, these agents can cause fluid holding that may cause peripheral and/or pulmonic oedema. A trial of pioglitazone (PROACTIVE) did hint some clinical benefit only after undermentioned more than 5,000 patients for 3 years there was only 9 deaths difference between active and control groups.
Alpha-Glucosidase Inhibitors (Precose and Miglitol)
These agents slow the digestion of composite carbohydrates and reduce HbA1c by 0.5 to 1.0%. No adequate trial has been conducted to show that they improve outcome.
Glinides (Repaglinide, Nateglinide)
These agents enhance the release of insulin in response to glucose and therefore mimic normal human physiology. This reduces HbA1c by 0.5-2% compared to placebo. They may be combined with glucophage but are not recommended with sulponylureas, which likewise stimulate insulin release. These are short-acting agents and should be taken ahead meals.
Peptidyl peptidase-IV (DDP-IV) Inhibitors (Sitagliptan, Vildagliptin)
These agents block the degradation of incretins (such as GLP-1 see below). This increases insulin release in response to glucose, may better islet-cell mass and function and better peripheral glucose uptake. They reduce HbA1c by virtually 1% and may shrink weight by 1-2kg. There is no evidence yet that these effects translate into clinical benefits.
New Subcutaneous Agents
Glucagonlike Peptide-I (Incretin) Analogues (GLP-1) (Exenatide, Liraglutide)
In healthy citizenry GLP-1 rises along with insulin in response to food intake. Analogues can be exploited to enhance secretion of endogenous insulin in patients with type II diabetes mellitus. They also retard gastric voidance, may increase beta-cell (insulin producing) mass and enhance uptake glucose in the periphery. Treatment is associated with weight unit loss of up to 4-5kg over 2 old age. HbA1c drops by more or less 1%. There is no evidence that these effects translate into clinical benefits for patients.
Amylin Analogues
Insulin is co-secreted with a peptide called amylin, which delays the surge in blood glucose by slowing gastric voidance and reducing glucose production by the liver. Unlike insulin it suppresses appetency and causes weight passing. Unfortunately, it can make a toxic substance called amyloid in animal models. Accordingly, pramlintide, a synthetical analogue of amylin that should non cause this problem, has been developed which may be co-injected with insulin. Studies intimate a 0.5-1.0% reduction in HbA1c associated with a 1-2kg system of weights loss. There is no evidence that this treatment is efficient, or so safe, for long-term use in patients.
EUROPEAN SOCIETY OF CARDIOLOGY (ESC)
The European Heart House
2035 Route diethylstilbesterol Colles
B.P. 179 - Les Templiers
FR-06903 Sophia Antipolis
http://www.escardio.org
View do drugs information on Precose.
More information
Friday, 5 September 2008
Tuesday, 26 August 2008
OK! Exclusive: Michael Lohan to Spar With K-Fed?
The last thing the Lohan family unit needs some other celebrity feud, but OK! has well-educated that the patriarch of the scandal-magnet clan, Michael Lohan, intends to throw down the gauntlet and challenge Kevin Federline to a packing match!
"Everyone wants me to fight K-fed because he�s a notorious celebrity papa and so am I," Michael tells OK! alone. "It�s for charity."
In accession to diverting those world Health Organization want to see these two bullet it kO'd � the money would benefit the organization, Long Island's Fight For Charity.
But, adds Michael, this isn't some touchy-feely event. "It's serious boxing," he explains. "You have to go get a trainer. I have to register with the Mature Boxing Association."
It should be noted that K-Fed wasn't Michael's first choice for a sparring partner: "I called Richard Johnson [editor of the NY Post's Page 6 newsmonger column] and challenged him, but he didn�t accept."�
Say Lindsay's pappa, "I don�t care world Health Organization it is; it�s for charity. I�ve been beaten up by the push, so I don�t care if I get a few shots by a kid half my age.�
Michael, who is sponsored by blackbook2.com, also reveals that, if his girl Erin gets her way, she'll be involved in the fistfight as substantially. "They�re stressful to match her up with Debbie Gibson," he says.
Should K-Fed, wHO sources say does not yet know about the fight, live with the challenge, this wouldn't be the first time he's stepped into the ring to scuffle. In 2006, right around the time his then-wife Britney Spears was filing for divorce, the wannabe rapper appeared four separate multiplication on televised WWE grapple matches.
�
More info
Saturday, 16 August 2008
Three things our writers love this week
DVDs
"The Wire � Fifth Season"
The finish to one of the best shows ever wraps up all the complicated crime storylines � with more Det. McNulty (Dominic West), wHO got shorted in the fourth season � and adds one: the slow, maddening extinction of newspapers personified by a fictional version of creator and ex-journo David Simon's Baltimore Sun. I don't call up major reviewers have written honestly almost that depicting, for emptiness and fear of their bosses' ire (HBO, $59.99).
Mark Rahner, Seattle Times DVD writer
Art
Charles Stokes
Revisit the life history of the late Seattle artist Charles Stokes, world Health Organization died before this class at his New York home. Thirty-five of his early paintings are on view at the Virginia Inn, gathered from the collections of friends and patrons. A memorial gathering for Stokes will be held at the V.I. on Aug. 17, beginning at 5 p.m. The point continues 11:30 a.m.midnight through Sept. 1 at 1937 First Ave., Seattle (206-728-1937 or www.virginiainnseattle.com).
Sheila Farr, Seattle Times art critic
Festivals
Bumbershoot
It's crowded. It's expensive. We love it. Ease the pain and maximize the pleasure by buying your ticket ahead Saturday, when prices go up. Go to wWW.bumbershoot.org for details.
Lynn Jacobson, Seattle Times Arts & Life editor
More information
Thursday, 7 August 2008
Monday, 23 June 2008
Gordie Sampson
Artist: Gordie Sampson
Genre(s):
Other
Discography:
Sunburn
Year: 2004
Tracks: 13
Katie Holmes: Read About Her Wedding Day
Wednesday, 18 June 2008
Madonna's Brother Pens 'Brutal' New Book
Madonna’s brother Christopher Ciccone has penned a new “brutal” book about his pop star sister.
Ciccone has produced the damning new tome with the help of British journalist Wendy Leigh, and the results are said to be set to shock Madonna.
A source tells The Mirror, “It's brutal. He wrote it on the sly without telling Madonna."
Ciccone has produced the damning new tome with the help of British journalist Wendy Leigh, and the results are said to be set to shock Madonna.
A source tells The Mirror, “It's brutal. He wrote it on the sly without telling Madonna."
Saturday, 14 June 2008
U2 to reissue 3 albums with rarities
NEW YORK - Irish rock band U2 will reissue its first three albums next month with a wealth of previously unreleased and rare material."Boy, October and War, all due July 22 via Universal, will be available as remastered single CDs, deluxe sets with a second disc of extras, and on vinyl.U2's 1980 debut album, Boy, features the previously unreleased tracks Speed of Life, Saturday Night and Cartoon World and a previously unreleased mix of I Will Follow. Live versions of Boy-Girl and 11 O'Clock Tick Tock, taped at London's Marquee club, are also included.The new edition of 1981's October boasts a series of tracks drawn from London's Hammersmith Palais and Boston's Paradise Theatre, including Gloria and I Will Follow, a BBC session with Richard Skinner and Common Ground's remix of Tomorrow.""War (1983) includes the previously unreleased track Angels Too Tied to the Ground, several remixes of New Year's Day and Two Hearts Beat as One, as well as the 7-inch single edit of New Year's Day."
U2, which last year reissued its 1987 album The Joshua Tree with various bells and whistles, is recording its next album with producers Brian Eno and Daniel Lanois. No release date has been set, but rumblings are that it may be out before the end of the year via Interscope.- REUTERS/Billboard
U2, which last year reissued its 1987 album The Joshua Tree with various bells and whistles, is recording its next album with producers Brian Eno and Daniel Lanois. No release date has been set, but rumblings are that it may be out before the end of the year via Interscope.- REUTERS/Billboard
math and physics club
Artist: math and physics club
Genre(s):
Indie
Discography:
Comfort Stand Recordings Single #505
Year: 2004
Tracks: 2
Madonna's missing ring fuels marital trouble rumours
Washington (ANI): Madonna has fuelled rumours that her marriage to British director Guy Ritchie by stepping out without her wedding ring. The music icon was seen partying at two of London's most high-profile restaurants celebrating the adoption of Malawian toddler David Banda, but not around was her hubby of 7-years. "She was out at Claridge's on Wednesday night on her own, then on Thursday night Madonna was at Nobu with Gwyneth Paltrow, but no Guy. She was lifting her hand up to the photographers to make it clear she didn't have a wedding ring on," Now magazine quoted a source, as saying. The source also insists that the couple's marriage has come to an amicable end, and they are close to announcing their split.
McCain's daughter pens children's book on her father
LOS ANGELES (Reuters) - Meghan McCain, the daughter of Republican presidential candidate Senator John McCain, is writing a children's book about her father.
Publisher Simon & Schuster said in a statement on Wednesday that McCain, 23, had signed with imprint Aladdin Books for the yet-to-be-titled picture book that will hit stores the first week of September to coincide with the Republican National Convention.
"I am truly excited about the opportunity to write a children's book about my father, who is not only a fantastic dad, but also a great American," McCain, who runs her own blog McCain Blogette, said in a statement.
"This book will offer children the unique opportunity to see the character building events that happened over his lifetime, experiences that led up to his current bid to become the future President of the United States."
McCain, the eldest of John and Cindy McCain's three children, was born and raised in Phoenix and graduated from Columbia University in May last year after majoring in Art History.
She interned at Newsweek magazine and Saturday Night Live.
Her blog, McCain Blogette (http://www.mccainblogette.com/), has received media attention but mixed reviews for chronicling her experiences on the campaign trail as well as her interests in fashion, music, and pop culture.
The publisher, which is part of the CBS Corp., said it will donate a portion of the proceeds from sales of this book to the Intrepid Fallen Heroes Fund that helps military personnel and veterans who have suffered severe traumatic brain injuries.
(Writing by Belinda Goldsmith, Editing by Bob Tourtellotte)
(To read more about our entertainment news, visit our blog "Fan Fare" online at blogs.reuters.com/fanfare)
Publisher Simon & Schuster said in a statement on Wednesday that McCain, 23, had signed with imprint Aladdin Books for the yet-to-be-titled picture book that will hit stores the first week of September to coincide with the Republican National Convention.
"I am truly excited about the opportunity to write a children's book about my father, who is not only a fantastic dad, but also a great American," McCain, who runs her own blog McCain Blogette, said in a statement.
"This book will offer children the unique opportunity to see the character building events that happened over his lifetime, experiences that led up to his current bid to become the future President of the United States."
McCain, the eldest of John and Cindy McCain's three children, was born and raised in Phoenix and graduated from Columbia University in May last year after majoring in Art History.
She interned at Newsweek magazine and Saturday Night Live.
Her blog, McCain Blogette (http://www.mccainblogette.com/), has received media attention but mixed reviews for chronicling her experiences on the campaign trail as well as her interests in fashion, music, and pop culture.
The publisher, which is part of the CBS Corp., said it will donate a portion of the proceeds from sales of this book to the Intrepid Fallen Heroes Fund that helps military personnel and veterans who have suffered severe traumatic brain injuries.
(Writing by Belinda Goldsmith, Editing by Bob Tourtellotte)
(To read more about our entertainment news, visit our blog "Fan Fare" online at blogs.reuters.com/fanfare)
Guy Maddin on Directing a ‘Docu-fantasia’ About His Hometown
Photo: Getty Images
Once a cult director whose rarefied, pseudo-silent films were known only to a select group of cinephiles, Canadian filmmaker Guy Maddin has recently become a mainstay of the art-house circuit. What’s even more impressive is that he has done it through a series of complex, personal films: Last year, his first-person family psychodrama Brand Upon the Brain!, which screened in New York with live narration, music, and sound effects, became a bona fide indie hit. Now Maddin’s back with the funny, powerful film My Winnipeg, a noirish documentary in which Maddin ruminates on the bizarre, often eerie history of his titular hometown. Vulture spoke with Maddin on a recent visit to New York about dead cows, unreliable narrators, and getting (run) the hell out of his own hometown.
You’ve described My Winnipeg as a “docu-fantasia.” Can you explain?
That’s just a label I threw on because I wanted to avoid arguments over whether it’s a documentary or not. But it’s a useful starting point. Rather than having to research facts, I just conducted all my research in my memory and in my heart. I got to rant, I got to squirt some bile.
Which all begs the question a lot of your fans are asking: What’s real and what’s not in My Winnipeg?
Virtually everything in the film is real. It’s either real, or it’s a wish, an opinion, or a legend. There are no outright lies in the film.
Animals don’t fare very well in this film, do they? You keep referring to your dead dog Toby, horses freeze, squirrels get fried on electrical lines, and the bison stampede.
Yeah, and I even left out some stories that were just too disturbing. A friend of mine told me about how she had a family farm right on the edge of the city, with one of those cow ponds, where the cows drink water. And then late one autumn, one of the cows just died. It fell over in the pond, and then the pond froze, with the cow on its side, so that it had two legs under the ice and two legs above the ice. And just happened to make a perfect hockey goal – for a winter’s worth of half-court hockey. Apparently like a million goals were scored on the belly of that poor dead cow that winter. It’s just a Canadian prairie boy’s winter!
How is the Guy Maddin of this movie different from the real Guy Maddin?
Not all that different, actually. My goal with these pictures, masochistic as it might be, is to reveal myself. Not because I’m exhibitionistic, but because my movies have been described as bizarre for so long that I fear I’ll be thought of as some kind of wanker. I don’t mind representing myself as someone who bullies an old woman or outs family members – because that’s exactly what I am doing. By just being as honest as possible about myself, I thought maybe I could achieve something almost literary — about how cowardly I am, how wrong I’ve been about a lot of things.
What prompted this recent personal direction in your work?
It goes back to Cowards Bend the Knee, which I made in 2003. I had just been through a bad, stormy relationship, and I finally got around to reading Euripides around that time. I devoured them like telenovelas. And one of them, Elektra, basically was my relationship with this girl. I couldn’t believe it. All I had to do was rearrange some things — I had to make Orestes into a boyfriend figure who was forced into doing all these horrible things by a temper-tantrum-throwing woman with a daddy complex. Next thing I knew, I had a script. And I felt masochistically liberated — just having to stand behind every craven act, like a confession.
What do the folks in Winnipeg think of the film?
They haven’t seen it yet. I am, in fact, trying to escape from that place. But I’m really hoping that the citizens of Winnipeg will run me out of town on a rail after I screen this thing there at the end of June. It would take all the vacillation out of it.
—Bilge Ebiri
Once a cult director whose rarefied, pseudo-silent films were known only to a select group of cinephiles, Canadian filmmaker Guy Maddin has recently become a mainstay of the art-house circuit. What’s even more impressive is that he has done it through a series of complex, personal films: Last year, his first-person family psychodrama Brand Upon the Brain!, which screened in New York with live narration, music, and sound effects, became a bona fide indie hit. Now Maddin’s back with the funny, powerful film My Winnipeg, a noirish documentary in which Maddin ruminates on the bizarre, often eerie history of his titular hometown. Vulture spoke with Maddin on a recent visit to New York about dead cows, unreliable narrators, and getting (run) the hell out of his own hometown.
You’ve described My Winnipeg as a “docu-fantasia.” Can you explain?
That’s just a label I threw on because I wanted to avoid arguments over whether it’s a documentary or not. But it’s a useful starting point. Rather than having to research facts, I just conducted all my research in my memory and in my heart. I got to rant, I got to squirt some bile.
Which all begs the question a lot of your fans are asking: What’s real and what’s not in My Winnipeg?
Virtually everything in the film is real. It’s either real, or it’s a wish, an opinion, or a legend. There are no outright lies in the film.
Animals don’t fare very well in this film, do they? You keep referring to your dead dog Toby, horses freeze, squirrels get fried on electrical lines, and the bison stampede.
Yeah, and I even left out some stories that were just too disturbing. A friend of mine told me about how she had a family farm right on the edge of the city, with one of those cow ponds, where the cows drink water. And then late one autumn, one of the cows just died. It fell over in the pond, and then the pond froze, with the cow on its side, so that it had two legs under the ice and two legs above the ice. And just happened to make a perfect hockey goal – for a winter’s worth of half-court hockey. Apparently like a million goals were scored on the belly of that poor dead cow that winter. It’s just a Canadian prairie boy’s winter!
How is the Guy Maddin of this movie different from the real Guy Maddin?
Not all that different, actually. My goal with these pictures, masochistic as it might be, is to reveal myself. Not because I’m exhibitionistic, but because my movies have been described as bizarre for so long that I fear I’ll be thought of as some kind of wanker. I don’t mind representing myself as someone who bullies an old woman or outs family members – because that’s exactly what I am doing. By just being as honest as possible about myself, I thought maybe I could achieve something almost literary — about how cowardly I am, how wrong I’ve been about a lot of things.
What prompted this recent personal direction in your work?
It goes back to Cowards Bend the Knee, which I made in 2003. I had just been through a bad, stormy relationship, and I finally got around to reading Euripides around that time. I devoured them like telenovelas. And one of them, Elektra, basically was my relationship with this girl. I couldn’t believe it. All I had to do was rearrange some things — I had to make Orestes into a boyfriend figure who was forced into doing all these horrible things by a temper-tantrum-throwing woman with a daddy complex. Next thing I knew, I had a script. And I felt masochistically liberated — just having to stand behind every craven act, like a confession.
What do the folks in Winnipeg think of the film?
They haven’t seen it yet. I am, in fact, trying to escape from that place. But I’m really hoping that the citizens of Winnipeg will run me out of town on a rail after I screen this thing there at the end of June. It would take all the vacillation out of it.
—Bilge Ebiri
Devlin is dancing to breakfast
Dancing with the Stars contestant Martin Devlin will be high-stepping on to the breakfast television stage.
The Game of Two Halves star is understood to be among the hosts stepping in for Paul Henry, who has taken extended leave from TVNZ.
Henry said last week he was taking a two-month break from his 3.40am starts to spend more time with his three teenage daughters.
He and his daughters are said to be sailing to Fiji to enjoy the warmer climate.
Sunday News understands along with Devlin, Close-Up presenter Mark Sainsbury and TV One's 6pm news anchor Simon Dallow will also fill in beside regular presenter Pippa Wetzell.
Devlin returned to the screen earlier this month on the sports show Game of Two Halves, screening at 10pm on Fridays on TVOne.
Earlier this year, Devlin took a walk on the wild side when he competed in a series of Dancing With The Stars.
After his sabbatical Henry, who has a three-year contract with TVNZ, says he will be "raring to go" in time for coverage of the general election later this year.
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