Postprandial, but not fasting, glucose predicts CV risk in type 2 diabetes

Postprandial blood glucose levels, but not fasting blood glucose, predict cardiovascular events and all-cause mortality in people with type 2 diabetes, according to 14 years of follow-up in the San Luigi Gonzaga Diabetes Study.

HbA_1c was also a predictor of both outcomes over the long term, according to Dr Franco Cavalot (University of Turin, Italy), who presented long-term follow-up data here at the European Association for the Study of Diabetes (EASD) 2011 Meeting.

Franco and colleagues reported five-year findings from this study back in 2006: at that time, postprandial blood glucose was predictive of CVD events after adjustment for HbA_1c and other cardiovascular risk factors.

The study included 505 patients with type 2 diabetes reporting for regular follow-up at the diabetes clinic. Patients underwent blood glucose tests at four time points: fasting, two hours after breakfast, two hours after lunch, and before dinner. Three separate Cox regression models were applied to confirm the results, with one of the models adjusting for age, sex, known diabetes duration, smoking, body-mass index (BMI), systolic and diastolic blood pressure, cholesterol levels, triglycerides, creatinine, and albumin excretion rate.

Over the 14 years of follow-up, 147 patients died and 172 cardiovascular events occurred. Across all of the analyses conducted, HbA_1c and blood glucose levels after lunch predicted both future cardiovascular events and all-cause deaths. Further analyses suggested that the information provided by postprandial blood glucose added to the predictive power of HbA_1c alone for both cardiovascular events and all-cause mortality. For all-cause mortality, the predictive ability of postprandial test was similar to that of HbA_1c.

"The 14-year follow-up of the San Luigi Gonzaga Diabetes Study supports the conclusion that postprandial blood glucose is not only an essential determinant of HbA_1c, but also per se a relevant tool in cardiovascular events and mortality risk stratification in type 2 diabetes mellitus," Cavalot concluded.

Cavalot noted that the lack of an association between future events and blood tests taken after breakfast is not surprising, given that, in Italy, breakfast tends to be a light meal. Asked why the study had not measured blood glucose after supper, he explained that all tests were taken during clinic hours; he speculated that these would likely be similar to the postlunch findings.

 

Shake It Off And Step Up

A parable is told of a farmer who owned an old mule. The mule fell into the farmer's well. The farmer heard the mule 'braying' - or - whatever mules do when they fall into wells. After carefully assessing the situation, the farmer sympathized with the mule, but decided that neither the mule nor the well was worth the trouble of saving. Instead, he called his neighbors together and told them what had happened...and enlisted them to help haul dirt to bury the old mule in the well and put him out of his misery.

 

Initially, the old mule was hysterical! But as the farmer and his neighbors continued shoveling and the dirt hit his back...a thought struck him. It suddenly dawned on him that every time a shovel load of dirt landed on his back...HE SHOULD SHAKE IT OFF AND STEP UP! This he did, blow after blow.

 

"Shake it off and step up...shake it off and step up...shake it off and step up!" he repeated to encourage himself. No matter how painful the blows, or distressing the situation seemed the old mule fought "panic" and just kept right on SHAKING IT OFF AND STEPPING UP!

 

You're right! It wasn't long before the old mule, battered and exhausted, STEPPED TRIUMPHANTLY OVER THE WALL OF THAT WELL! What seemed like it would bury him, actually blessed him...all because of the manner in which he handled his adversity.

 

THAT'S LIFE! If we face our problems and respond to them positively, and refuse to give in to panic, bitterness, or self-pity...THE ADVERSITIES THAT COME ALONG TO BURY US USUALLY HAVE WITHIN THEM THE POTENTIAL TO BENEFIT AND BLESS US! Remember that FORGIVENESS--FAITH--PRAYER-- PRAISE and HOPE...all are excellent ways to "SHAKE IT OFF AND STEP UP" out of the wells in which we find ourselves!

 

- Author Unknown

High marks for novel LVEF-boosting agent stir hope in heart failure

The heart-failure drug development field is so strewn with casualties that researchers tend to express caution rather than optimism when discussing new candidates. Hopes are stirring again, however, for an LVEF-boosting drug with mechanistic underpinnings and safety data suggesting it could be an effective, lower-risk alternative to conventional inotropic agents, and perhaps more.

That potential was on display in two studies published in the August 20, 2011 issue of the Lancet, phase-1 and -2 evaluations aimed at pinning down the most effective and best-tolerated IV dosage of the novel myosin-activator omecamtiv mecarbil (Cytokinetics, San Francisco, CA). In earlier research, the drug was identified as CK-1827452.

Dr John R Teerlink (San Francisco Veterans Affairs Medical Center, CA), lead author of one of the studies, acknowledges that the drug is still early in development but is impressed enough with its positive effect on cardiac output and apparent safety to say that omecamtiv mecarbil "has the potential to completely replace dobutamine and milrinone," which are used only in the most seriously ill patients with heart failure.

But as the same molecule is under investigation in an oral form, Teerlink noted in an interview that it has potential for broader use in acute heart failure as well as stable, chronic heart failure.

Conventional inotropic agents are used sparingly in patients with advanced heart failure because of well-recognized adverse effects. With increased intracellular calcium as their mechanism in strengthening ventricular contractions, they also raise heart rate, are proarrhythmic, and can cause ischemia by raising myocardial oxygen demand.

Omecamtiv mecarbil apparently has none of those metabolic downsides, according to Teerlink. The drug potentiates the effect of myosin in myocyte contractions, boosting cardiac output not by strengthening contractile force but by prolonging systole, thereby making contractions more efficient. And, he says, the effects are predictable and "exquisitely dose-dependent."

The only significant adverse effect in the dose-ranging studies, according to Teerlink, was evidence of myocardial ischemia at the very highest dosages. "It prolonged systole to such an extent that it finally impinged upon coronary filling," he said. "So far, we have not seen any off-target effects or any adverse effects at what we consider now to be a reasonable dose range."

Novel agent reduces emboli after carotid endarterectomy

Inhibition of von Willebrand factor (vWF) activity with the investigational agent ARC1779 (Archemix, Cambridge, MA) has been shown to reduce cerebral embolization after carotid endarterectomy in a randomized trial.

ARC1779 is an aptamer that inhibits the prothrombotic function of vWF by binding to the A1 domain of vWF, blocking its interaction with glycoprotein, the study authors, led by Dr Hugh S Markus (St Georges University of London, UK), write.

"Our results show for the first time that vWF inhibition improves a clinically relevant end point, cerebral embolization in humans," Markus and colleagues conclude. "Further studies are now required to determine whether this treatment approach reduces clinical cardiovascular events and to assess the risk of bleeding complications in a nonoperative situation."

The results are published in the August 2011 issue of Stroke.

 

Multivessel PCI during STEMI associated with higher short- and long-term mortality

Two new studies published this week confirm clinical recommendations that a deferred angioplasty strategy of nonculprit lesions should remain the standard interventional approach in patients with ST-segment elevation MI (STEMI) undergoing primary PCI.

In the first study, an analysis of the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS AMI) study, investigators, led by Dr Ron Kornowski (Tel Aviv University, Israel), observed significantly higher one-year mortality and stent-thrombosis rates among patients undergoing multivessel PCI compared with individuals undergoing staged PCI.

In the second study, a meta-analysis that included 18 studies and more than 40 000 patients, the investigators report that multivessel PCI was associated with the highest rates of death in short- and long-term follow-up when compared with culprit-lesion PCI and staged PCI.

Dr Pieter Vlaar (University Medical Center, Groningen, the Netherlands), the lead researcher of the meta-analysis, told that the results support current guidelines discouraging multivessel primary PCI for STEMI patients. That said, the guidelines are not based on large randomized controlled clinical trials, and this had led to some confusion and variability across different centers. Even at their institution, Vlaar said clinicians differ in their opinions about whether nonculprit lesions should be treated during the initial intervention. However, these new data suggest that when significant nonculprit lesions are suitable for PCI, "they should be treated only during staged interventions."

Both studies, as well as an accompanying editorial, are published in the August 9, 2011 issue of the Journal of the American College of Cardiology.

 

Erosions with ASD devices quantified by FDA

 The US FDA has provided  with figures from its MAUDE database on erosions with Amplatzer septal-occluder devices (St Jude Medical) until July 21, 2011. This follows a report last week in which some doctors expressed concerns about the safety of these devices, particularly with regard to erosions.

Karen Riley (Office of Public Affairs, FDA, Silver Spring, MD) told  that the FDA has received and entered into its database 742 medical device reports for these septal occluders. "Of these, 72 can be considered as either confirmed or possible erosion events. Seven of these were reported as death, and the remaining ones as serious injuries," she says.

The devices have been approved in the US for percutaneous closure of atrial septal defects (ASD) for more than 10 years. Interventionalists are divided as to whether erosions are an issue, with one saying last week that this was the one adverse effect that made him pause before using the devices, because of the potentially serious consequences and the fact that there are no indicators that erosion is about to happen or any way of predicting who will suffer this fate. But another physician said that as long as the devices are used for their intended indication and not off-label, he was confident about using them. And the manufacturer maintains that the septal-occluder devices are safe and reliable.

The FDA was unable to supply with the actual number of Amplatzer devices implanted over the period during which the 72 erosions were reported, so it's difficult to calculate the "rate" of erosion, which St Jude Medical has put at 0.1%. Spokesperson Amy Jo Meyer (St Jude Medical, St Paul, MN) said the company does not disclose sales data by individual product line, so she was unable to provide the number of implantations in the US.

Two years ago, reviewers combed the FDA's MAUDE database and documented 51 known cardiac perforations, erosions, or ruptures with Amplatzer septal-occluder devices between January 2002 and June 2007. At the time, the authors were also unable to obtain the number of implantations from the manufacturer, but they estimated the figure at 18 000 for that five-and-a-half year period.

 

Cochrane salt/blood-pressure message blasted in the Lancet

Two preventive-medicine experts in the UK are crying foul over a recent and controversial meta-analysis that concluded cutting salt consumption would have no clear health benefits [1]. In a Comment published in the July 30, 2011 issue of the Lancet, Dr Feng J He (Queen Mary University, London, UK) and Dr Graham A MacGregor (Wolfson Institute of Preventive Medicine, Barts, London, UK) say that the meta-analysis published simultaneously by Taylor and colleagues in the Cochrane Review [2] and the American Journal of Hypertension [3] and press release that accompanied it "reflect poorly on the reputation of the Cochrane Library and the authors."

As previously reported, Taylor et al's meta-analysis included seven randomized controlled trials of dietary salt reduction in normotensives (three studies), hypertensives (two studies), a mixed population (one study), and one trial of patients with heart failure.

At follow-up, relative risks for all-cause mortality and cardiovascular mortality for both normotensives and hypertensives were only mildly to moderately reduced, and not to a statistically significant degree. In congestive heart failure patients, salt restriction actually significantly increased all-cause death.

He and MacGregor, in their Comment, reanalyze the same data but combined the normotensives and hypertensives. They also omitted the heart-failure trial—a group of "very ill" patients taking large doses of diuretics in whom salt restrictions would seldom be recommended, MacGregor observed. In the combined patient analysis, they find a now statistically significant 20% reduction in cardiovascular events and a nonsignificant reduction in all-cause mortality.

"The results of our reanalysis, contrary to the claims by Taylor and colleagues, support current public-health recommendations to reduce salt intake in the whole population," He and MacGregor conclude.