�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.
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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.
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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
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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
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