The Doctor's Channel - Diabetes & Endocrinology

Thyroid hormone analogue shows promise for statin-treated dyslipidemia

2010-03-12T21:09:30+00:00

NEW YORK (Reuters Health) – When statins alone can’t reverse dyslipidemia, the thyroid hormone analogue eprotirome may be helpful, new research suggests.

In a 12-week study of 189 dyslipidemic, statin-treated patients, eprotirome safely reduced the levels of various atherogenic lipoproteins, the investigators report in The New England Journal of Medicine for March 11.

In the study, subjects continued to receive simvastatin or atorvastatin and were randomized to receive eprotirome (25, 50, or 100 micrograms/day) or placebo.

With the 25, 50, and 100 microgram doses of eprotirome, mean low density lipoprotein (LDL) cholesterol levels fell by 22%, 28%, and 32%, respectively, from a baseline value of 141 mg/dL. By contrast, placebo produced a mean reduction of just 7%. Eprotirome had a similar effect on levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein.

Eprotirome was generally well tolerated, with no adverse cardiac or bone effects. Although thyroxine levels fell in patients receiving the drug, serum levels of thyrotropin and triiodothyronine did not change.

“This randomized, placebo-controlled, double-blind trial showed that eprotirome is associated with further reductions in serum LDL cholesterol levels in patients who are already receiving statins,” the authors conclude. “Eprotirome also has potent properties for lower levels of apolipoprotein B, triglycerides, and Lp(a) lipoprotein.”

The study was supported, in part, by Kara Bio, the company developing eprotirome.

Reference:
N Engl J Med 2010;362:906-916.

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Cardiac catheterization has low diagnostic yield

2010-03-11T22:49:39+00:00

NEW YORK (Reuters Health) – Just 38% of patients with suspected cardiac disease are found to have obstructive coronary disease on elective cardiac catheterization, new research shows. This low diagnostic yield suggests that clinical assessments and noninvasive tests are not doing their job in selecting patients for cardiac catheterization.

“Guidelines recommend continued observation in the case of patients who are at very low risk, noninvasive stress testing to determine the need for cardiac catheterization in the case of patients at intermediate risk, and direct referral for catheterization in the case of patients at high risk,” lead author Dr. Manesh R. Patel and colleagues note.

But whether these recommendations help limit the number of patients without coronary disease who undergo cardiac catheterization was unclear, according to the report in The New England Journal of Medicine for March 11.

To investigate, Dr. Patel, from Duke University Medical Center, Durham, North Carolina, and colleagues analyzed national registry data on nearly 400,000 patients without known coronary disease who had elective cardiac catheterization at 663 hospitals in the U.S.

Obstructive coronary disease was defined as stenosis of at least 50% of the diameter of the left main coronary artery or stenosis of at least 70% of the diameter of a major epicardial vessel.

The median patient age was 61 years and 52.7% of patients were male. Twenty-six percent of subjects had diabetes and 69.6% had hypertension. Roughly 84% had noninvasive tests before cardiac catheterization.

Only 37.6% of patients had obstructive coronary disease at catheterization, the report indicates. Moreover, 39.2% of patients had no coronary disease (stenosis <20% in all vessels).

A positive noninvasive test result slightly increased the likelihood of finding obstructive disease: 41.0% vs. 35.0% (adjusted odds ratio, 1.28, p < 0.001).

In an editorial, Dr. David J. Brenner from Columbia University Medical Center in New York agrees with the authors that a better “gatekeeper” test is needed to select the best candidate for cardiac catheterization. “Ironically,” he notes, “there is evidence that, in many situations, a better gatekeeper test may be yet another radiographic imaging technique—namely, multidetector-row computed-tomographic angiography.”

Reference:
N Engl J Med 2010;362:886-895,943-945.

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Women benefit as much as men from statins for primary prevention of CVD

2010-03-11T22:44:28+00:00

NEW YORK (Reuters Health) - Statin use by women cuts their risk of primary cardiovascular disease (CVD) events by roughly a third, which is similar to the risk reduction seen in men, research shows.

"Statin therapy in women without CVD is controversial, given the insufficient evidence of benefit," Dr. Samia Mora, from Brigham and Women's Hospital, Boston, and colleagues note in the March 9th issue of Circulation.

Dr. Mora and colleagues analyzed gender-specific outcomes from the randomized JUPITER trial and performed a meta-analysis of statin trials that focused on women.

JUPITER included 6801 women at least 60 years of age, and 11,001 men at least 50 years of age. All had high C-reactive protein levels (at least 2 mg/L) and normal to low levels of low density lipoprotein cholesterol (no higher than 130 mg/dL). Participants took either rosuvastatin or placebo daily.

The meta-analysis included 7 primary prevention trials, with 13,154 women who had 240 CVD events and 216 deaths.

Compared to the men in the JUPITER trial, the women had lower absolute CVD rates per 100 person-years (0.57 vs. 0.88 for rosuvastatin groups and 1.04 vs. 1.54 for placebo groups) - but both genders had relative risk reductions of roughly 44%.

Further analysis showed that statin therapy significantly reduced revascularization and unstable angina in women, but did not affect other CVD events.

In the meta-analysis, statin use by women cut primary CVD events by 37% (p < 0.001), but did not significantly affect total mortality.

When the results of JUPITER and the meta-analysis are taken together, the researchers conclude, "statin therapy resulted in about a one-third relative reduction in primary CVD in women, a benefit similar to that seen in previous meta-analyses of men."

Reference:
Circulation 2010;121:1069-1077.

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Continuous intraperitoneal insulin linked with better quality of life

2010-03-10T16:36:00+00:00

NEW YORK (Reuters Health) - Patients report higher quality of life with continuous intraperitoneal versus subcutaneous insulin, Dutch investigators have found.

The researchers had previously reported that continuous intraperitoneal insulin allows better glycemic control compared to intensified subcutaneous insulin therapy (see Reuters Health story, August 11, 2009).

Their new paper reports on health-related quality of life outcomes and treatment satisfaction in 23 adults with type 1 diabetes who enrolled in a randomized cross-over trial of the two approaches. Patients had 6 months of intensive subcutaneous insulin followed by 6 months of peritoneal infusion, or vice versa. The subcutaneous insulin was given either continuously or via injection - whatever the patient was doing before enrollment.

In their article, published online February 25th in Diabetes Care, lead author Dr. Susan J. Logtenberg, from Isala Clinics, Zwolle, and colleagues write that scores on six subscales of the 36-item Short-Form Health Survey were significantly higher with peritoneal infusion. The only exceptions were in the social functioning and bodily pain domains.

On the World Health Organization-Five Well-Being Index, significantly fewer patients had a score below 50 -- an indication of poor emotional well-being - after peritoneal treatment (6 vs 13, p = 0.02).

Moreover, patients perceived significantly fewer hypoglycemic and hyperglycemic events during their peritoneal infusion phase, leading to greater treatment satisfaction.

As the authors point out, patients preferred the peritoneal approach despite the fact that it requires hospital admission and surgery to insert the pump. It also costs more than twice as much as continuous subcutaneous insulin infusion.

"Continuous intraperitoneal insulin infusion should be (re)considered as a treatment option, at least when satisfactory results of treatment are not reached with subcutaneous intensive insulin treatment regimens," Dr. Logtenberg's team concludes.

Medtronic Europe, which sells insulin pumps, provided an unrestricted grant to the authors.

Reference:
Diabetes Care 2010.

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African American kids with diabetes have higher HbA1c levels

2010-03-08T19:20:13+00:00

NEW YORK (Reuters Health) - As in adult diabetics, hemoglobin (Hb) A1c levels are higher in black children with type 1 disease than in white children, independent of mean blood glucose, according to a February 25th online report in Diabetes Care.

The authors of the report have long been interested in between-individual differences in HbA1c levels. Spurred by reports indicating a role for race and ethnicity in adult diabetic variables, lead author Dr. Jodi L. Kamps and colleagues at Louisiana State University Health Sciences Center in New Orleans looked for a similar pattern in their pediatric patients.

Their study included 276 children (72% Caucasian, 28% African-American) with an average age of 12.5 years and an average disease duration of 4.9 years. Slightly more than half were girls.

Mean blood glucose was determined by averaging data downloaded from patient glucose meters for periods of 30 days or more. Predicted HbA1c was calculated with the following equation:

HbA1c % = (mean blood glucose x 0.021) + 4.3

Hemoglobin glycation index was then calculated by subtracting the predicted HbA1c from the observed HbA1c.

The hemoglobin glycation index was significantly higher in the African-American children (p < 0.001), the authors report. They note that the highest tertile (index > 0.26) contained 57.5% of the African American children but only 24.2% of the Caucasian children. The adjusted mean hemoglobin glycation index values were 0.64 in black children and -0.15 in whites (p < 0.001).

Furthermore, average HbA1c was significantly higher among African Americans than Caucasians after controlling for mean blood glucose, age, and diabetes duration: 9.1% vs 8.3%, respectively (p < 0.001).

These findings may help explain why African Americans are at increased risk of diabetes complications, the authors suggest.

Also, they caution, "Given that mean blood glucose-independent disparity in HbA1c is unlikely to be modifiable by glucose lowering agents, simply increasing insulin doses in order to achieve a lowered target HbA1c could lead to greater risk of hypoglycemia in African American patients."

Dr. Kamps and her associates advise that both HbA1c and mean blood glucose be taken into account when making therapeutic decisions for diabetics, especially for African Americans.

Reference:
Diabetes Care 2010.

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Prostate cancer prevention and nutrition

2010-03-08T15:39:19+00:00

David Heber, MD, Professor of Medicine, Director, UCLA Center for Human Nutrition, discusses prostate cancer prevention, and explains why low fat diets and exercise can reduce inflammation by reducing the amount of circulating cytokines and thereby help prevent this common male cancer.

Reading:
Freedland SJ, Aronson WJ. Dietary intervention strategies to modulate prostate cancer risk and prognosis. Curr Opin Urol. 2009 May;19(3):263-7. Review.
Kristal AR, Arnold KB, Schenk JM, Neuhouser ML, Weiss N, Goodman P, Antvelink CM, Penson DF, Thompson IM. Race/ethnicity, obesity, health related behaviors and the risk of symptomatic benign prostatic hyperplasia: results from the prostate cancer prevention trial.
Rodriguez C, Freedland SJ, Deka A, Jacobs EJ, McCullough ML, Patel AV, Thun MJ, Calle EE. Body mass index, weight change, and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev. 2007 Jan;16(1):63-9. Epub 2006 Dec 19.

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Aspirin prophylaxis not useful for asymptomatic vascular disease

2010-03-05T21:36:50+00:00

NEW YORK (Reuters Health) – Asymptomatic patients with a low ankle brachial index don’t seem to get cardiovascular protection from aspirin, randomized trial results suggest.

The subjects came from a cohort of nearly 29,000 men and women ages 50 to 75 years enrolled in a community health registry in Scotland. All were free of clinical cardiovascular disease at baseline, and each agreed to ankle brachial index screening. The 3350 individuals with an index of no more than 0.95 took either 100 mg of aspirin daily, or placebo, for the next 8.2 years, on average.

In the Journal of the American Medical Association for March 3, lead author Dr. F. Gerald R. Fowkes, from the University of Edinburgh and colleagues report that 357 subjects met the main endpoint (a composite of coronary events, stroke, or revascularization). Rates per 1000 person-years were similar with aspirin (13.7) and placebo (13.3).

Rates of a secondary outcome – a composite of the main endpoint plus angina, intermittent claudication, or transient ischemic attack – were also comparable: 22.8 vs. 22.9 per 1000 person-years with aspirin vs placebo, respectively.

All-cause mortality was similar as well, with 12.8 deaths per 1000 person-years in the aspirin group and 13.5 in the placebo group.

Subjects treated with aspirin were 71% more likely than those given placebo to experience major hemorrhage requiring admission to the hospital: 2.5 vs. 1.5 per 1000 person-years.

“Based on the trial conducted by Fowkes et al and other similar studies, aspirin appears to have marginal benefits for reducing initial cardiovascular events when used for patients without clinically evident cardiovascular disease and is associated with higher rates of bleeding in these patients,” Dr. Jeffrey S. Berger, from New York University School of Medicine, comments in a related editorial.

Dr. Fowkes and colleagues conclude that “given the increased level of risk among those with a low ankle brachial index, the use of alternative therapies, such as statins or more potent antiplatelet agents without attendant hemorrhagic risks may usefully be considered.”

Reference:
JAMA 2010;303:841-848,880-882.

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Benefits of early intensive insulin therapy can persist unless HbA1C levels rise

2010-03-01T17:22:21+00:00

NEW YORK (Reuters Health) - Intensive insulin therapy in type 1 diabetics reduces their risks of neuropathy and retinopathy over the long-term, according to two papers published online February 11th in Diabetes.

Both papers report data from the long-term Epidemiology of Diabetes Interventions and Complications (EDIC) study. Since the early 1990s, the EDIC researchers have followed participants in the landmark Diabetes Control and Complications Trial, which showed that intensive therapy (three or more insulin injections per day or use of a continuous pump) prevented complications more effectively than standard therapy (two injections per day).

In the follow-up study, which has lasted more than 10 years now, all of the subjects have been told to use intensive insulin therapy.

In one of the two papers in Diabetes, Dr. James W. Albers, from the University of Michigan Medical School, Ann Arbor, and colleagues used clinical and nerve conduction studies to compare rates of neuropathy in 603 former intensive-therapy and 583 former conventional-treatment subjects. Over time, both groups have achieved similar HbA1c levels.

Between the end of the original study and years 13-14 of EDIC, the prevalence of neuropathy rose from 9% to 25% in the former intensive therapy group and from 17% to 35% in the former conventional therapy group (p < 0.001). The incidence of neuropathy was also lower in the former intensive treatment group: 22% vs. 28% (p = 0.0125).

On longitudinal analysis, improved HbA1c control was directly linked to lower risks of incident and prevalent neuropathy.

In the second paper, Dr. Neil H. White, from Washington University, Saint Louis, and colleagues assessed the impact of intensive therapy in the original trial on patients' risk of retinopathy. The researchers also looked to see whether any effect on risk was mediated by the patient's age when intensive therapy started.

Among 1055 adults and 156 adolescents, during 10 years of EDIC, there was no significant difference in HbA1c levels between former intensive and conventional therapy patients, nor between adults and teens. In adults, however, former use of intensive therapy cut the risk of retinopathy by 57%, whereas in teens, no benefit of former intensive therapy was noted. Further analysis suggested a possible explanation for this finding: during long-term follow-up, teens who had been given intensive therapy had higher mean HbA1c levels than adults: 8.1% vs. 7.2%.

The current findings, the authors of both studies agree, emphasize the importance of maintaining HbA1c at as close to target values as possible. "The benefits of former intensive therapy treatment wane over time if HbA1C levels rise," Dr. White and his colleagues conclude.

Reference:
Diabetes 2010.

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Nutrition, breast cancer and prevention

2010-02-24T16:48:27+00:00

David Heber, MD, Professor of Medicine, Director, UCLA Center for Human Nutrition, discusses nutrition in breast cancer, and the role of diabetes and obesity in post-menopausal breast cancer, ie breast cancer in women over 50, which accounts for more than 75 percent of all female breast cancer cases. He also discusses breast cancer prevention starting with weight loss.

Reading:
Anderson AS, Caswell S. Obesity management--an opportunity for cancer prevention. Surgeon. 2009 Oct;7(5):282-5.
Schlienger JL, Luca F, Vinzio S, Pradignac A. [Obesity and cancer] Rev Med Interne. 2009 Sep;30(9):776-82. Epub 2009 Jun 12. Review. French.
Howell A, Chapman M, Harvie M. Energy restriction for breast cancer prevention. Recent Results Cancer Res. 2009;181:97-111. Review.

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Avosentan trial cut short, but lower doses may reduce proteinuria in diabetics

2010-02-23T16:45:51+00:00

NEW YORK (Reuters Health) - Researchers cut short a clinical trial of the endothelin blocker avosentan in patients with diabetic nephropathy because it was linked with fluid overload and congestive heart failure. Before the abrupt end, however, it was clear that avosentan cut proteinuria by 40-50%.

Although terminated prematurely, the study provides new information about the effects of a predominant endothelin receptor antagonist in type 2 diabetics with stages 3 to 4 chronic kidney disease, the researchers report in the February 18th online edition of the Journal of the American Society of Nephrology.

Because of the trial's termination, they couldn't tell if the reduction of proteinuria could slow the loss of kidney function. They hope to find, eventually, that lower doses of avosentan will be effective, not to mention more tolerable.

In the discontinued trial, researchers at more than 500 centers in 36 countries treated 1,392 diabetic adults either with avosentan, in doses of 25 or 50 mg per day, or with placebo. All subjects had overt kidney disease. Throughout the trial, all patients continued taking their standard medication, either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

Although scheduled for 42 months, the trial was stopped after a median of four months for those taking avosentan and five months for the placebo group. There was no difference between the groups in the percentages of patients who met the primary composite end point (death, end-stage renal disease, or doubling of baseline creatinine level).

In the avosentan groups, fewer patients progressed to end-stage renal disease, but more died, mainly of cardiovascular causes. Cardiovascular outcomes in general, and particularly congestive heart failure, were more frequent with both doses of avosentan.

Compared to the placebo group, significantly more avosentan patients withdrew from the trial due to adverse effects (19.6% of the 25-mg group, 18.2% of the 50-mg group, and 11.5% of the placebo group).

Albumin-to-creatinine ratios (ACR) fell by a median of 44.3% in the 25-mg group, 49.3% in the 50-mg group, and 9.7% in the placebo group.

"The effect on albuminuria is likely due to inhibition of the renal ETA (endothelin) receptor, because other researchers have found that the mixed type ETA/B receptor antagonists have a weaker or no effect on proteinuria," the researchers write.

In another secondary outcome, the estimated glomerular filtration rate (eGFR) declined in all three groups by 2.5 to 4 ml/min/1.73 m2. The decrease was slightly greater in the group that took the 50-mg dose compared to the placebo group after three months (p = 0.03) and six months (p = 0.02).

"Whether the faster fall in eGFR was the result of avosentan-induced lower intraglomerular pressure, an effect that could translate into long-term benefit, remains a moot point," the authors say, given that any benefit for the kidney "was outweighed by increased early mortality."

In an editorial, Dr. Eberhard Ritz of Ruperto Carola University in Heidelberg, Germany and Dr. Rene Wenzel of A.O. Krankenhaus in Zell am See, Austria write, "We suspect that lower dosages of (endothelin receptor) blockers may be associated with fewer adverse effects, and hopefully those dosages will be clinically effective."

But, they emphasize, "Before making any sweeping suggestions...it is absolutely necessary to have more information on the long-term safety of avosentan in the 5- to 10-mg/d dosage range."

J Am Soc Nephrol 2010;21:527-535.

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