Obstructive sleep apnea (OSA) impairs brachial artery endothelial function to a similar degree to Type 2 diabetes, show study results.

Atul Malhotra (Brigham and Women’s Hospital, Boston, Massachusetts, USA) say that treatment of OSA in Type 2 diabetes patients has the potential to improve macro- but not microvascular outcomes, as they found that OSA does not appear to influence brachial endothelium-independent vasodilation or skin microcirculation.

The investigators recruited 153 individuals with a mean age per subgroup ranging from 33 to 59 years. These included 14 healthy normal-weight controls, 33 healthy obese controls, 66 individuals with Type 2 diabetes, and 38 obese individuals with OSA.

The team notes that the diabetic participants and normal-weight controls did not undergo sleep testing for OSA and therefore could have had subclinical OSA.

As reported in the journal Obesity, the researchers found that patients with Type 2 diabetes and OSA had impaired flow mediated dilation (FMD), as assessed by brachial artery ultrasound, compared with normal-weight and obese controls, at 5.8% and 5.4% versus 9.1% and 8.3%, respectively.

Further analysis showed that baseline brachial artery diameter, OSA, and Type 2 diabetes status were significant negative predictors of percentage FMD.

However, OSA did not significantly affect skin microcirculation, as assessed by laser Doppler flowmetry, or nitroglycerin-induced vasodilation of the brachial artery.

“To our knowledge, this is the first study to compare endothelial function between OSA and Type 2 diabetes,” write Malhotra et al.

“These findings represent an important addition to the literature and will be critical to the design of subsequent interventional diabetes studies.”

They conclude: “Future research in the interacting vascular complications of diabetes mellitus and OSA populations may provide new therapeutic options for afflicted patients.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

Group medical clinics help to reduce blood pressure (BP) in patients with Type 2 diabetes and hypertension when compared with usual care, report researchers.

However, they found that reductions in HbA1c were not significantly different between the two groups.

David Edelman (Durham Veterans Affairs Medical Center, North Carolina, USA) and colleagues say that many medical practices lack resources to train individual patients with chronic diseases such as diabetes to participate actively in their own care.

They suggest that a more efficient alternative could be for such patients to attend group visits with other individuals with the same condition to receive training on optimum disease management.

Edelman and team recruited 239 patients with poorly controlled hypertension (systolic/diastolic BP above 140/90 mmHg) and Type 2 diabetes (HbA1c of 7.5% or above) to take part in a study comparing group medical clinic treatment with usual care.

The group clinics included 7??”8 patients and a care team comprising a general internist physician, pharmacist, and a nurse or other qualified diabetes educator. The groups met every 2 months for just over 1 year (7 visits in total over 12.8 months).

Patients were randomly assigned to group care in addition to usual care (n=133) or usual care alone (n=106).

The mean systolic/diastolic BP and HbA1c values at baseline were 152.9/84.4 mmHg and 9.2%, respectively.

By study completion, the mean systolic BP had decreased by 13.7 mmHg in the group care patients compared with a decrease of 6.4 mmHg in the usual care group, a statistically significant difference. Diastolic BP was also reduced to a greater extent in the group care than usual care patients, but the difference was not statistically significant.

However, the mean reduction in HbA1c was not significantly different between the two groups, at 0.8% in the group care and 0.5% in the usual care group.

“Group visits are feasible and can improve outcomes for some, but not all, chronic diseases,” say the authors.

They add that the reduction in systolic BP seen in the group care patients could hold promise for “reducing cardiovascular morbidity and mortality among patients with diabetes.”

Edelman et al conclude in the Annals of Internal Medicine: “If found to be cost-effective and efficient, group medical clinics could be implemented in a wide range of settings and become important in the remodeling of long-term care in the United States.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

Low-dose combination therapy with rosiglitazone and metformin is effective for preventing the onset of Type 2 diabetes in patients with impaired glucose tolerance (IGT), show results from the CANOE trial.

“These results lend support to the notion of use of low-dose combination therapies as an effective means to manage complex metabolic disorders,” say the researchers.

Writing in The Lancet, Bernard Zinman (University of Toronto, Ontario, Canada) and colleagues report results from the CANOE (CAnadian Normoglycemia Outcomes Evaluation) trial.

In total, 207 individuals with IGT, aged 52.5 years on average, were randomly assigned to receive a combination of rosiglitazone 2 mg and metformin 500 mg twice daily (n=103) or matching placebo (n=104). They were followed up for a median period of 3.9 years for incident Type 2 diabetes.

Zinman and team found that incident diabetes was significantly more common in the placebo than in the treatment group, at 39% versus 14%.

Treatment with the combination of rosiglitazone and metformin achieved a reduction in relative and absolute risk for incident Type 2 diabetes of 66% and 26%, respectively, which corresponds to a number needed to treat of 4.

Moreover, 80% of the treatment group had returned to normal glucose status by the end of the study compared with only 53% of the placebo group.

Insulin sensitivity was unchanged in the treatment group, but decreased in the placebo group over the follow-up period. Change in ?-cell function over the study period did not differ significantly between the two groups.

Side effects were generally minimal. No cases of myocardial infarction or heart failure were recorded in the treatment group, with one of each recorded in the placebo group. Incidence of bone fracture was similar in the treatment and placebo groups, as was the likelihood of gain or loss of 2??”3 kg in weight.

“Low-dose combination therapy with rosiglitazone and metformin was highly effective in prevention of Type 2 diabetes in patients with impaired glucose tolerance, with little effect on the clinically relevant adverse events of these two drugs,” conclude the authors.

The authors of an accompanying commentary, Thomas Buchanan and Anny Xiang (University of Southern California, Los Angeles and Kaiser Permanente, Pasadena, USA), suggest: “We need data on more intensive approaches, including high-dose combination therapy, to provide clinicians with a full range of evidence-based approaches to halt or reverse this progressive disease relatively early in its course.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

Women with polycystic ovary syndrome (PCOS) have a four-fold increased prevalence of Type 2 diabetes, independent of body mass index (BMI), show results from a systematic review and meta-analysis.

In addition, the researchers found that women with PCOS have a significantly increased prevalence of impaired glucose tolerance (IGT) and the metabolic syndrome independent of BMI.

Previous research has suggested that women with PCOS have increased risks for Type 2 diabetes, IGT, and the metabolic syndrome, but definitions of these conditions and PCOS vary across the literature and factors such as age, BMI, and ethnicity can influence PCOS phenotype and diagnosis.

Lisa Moran (Monash University, Victoria, Australia) and team therefore carried out a systematic review and meta-analysis to obtain a realistic estimate of the prevalence of these conditions in women with PCOS compared with those without the disorder adjusting for the confounding factor of adiposity.

In total, 35 studies were included in the systematic review and 30 in the meta-analysis. All included studies were observational and employed a cross-sectional or cohort study design.

Most studies assessed overweight or obese (BMI above 25 kg/m²) post- and premenopausal women, with the exception of three that included adolescents only, two that included premenopausal women only, and five that included a lean subgroup of women with a BMI below 25 kg/m². BMI-matched cases and controls were reported in 10 studies.

In non BMI-matched studies, the researchers found that women with PCOS had a 4.48-, 2.48-, and 2.88-fold increased prevalence of Type 2 diabetes, IGT, and the metabolic syndrome, respectively, compared with controls.

In BMI-matched studies, the corresponding prevalence’s were increased a respective 4.00-, 2.54-, and 2.20-fold.

The authors caution that “it is important to note that there are limited studies of high methodological quality assessing the magnitude of this metabolic disturbance and associated CVD risk in BMI- or abdominal obesity-matched groups and in lean women with and without PCOS.”

However, they say that their results support “a greater prevalence of IGT, Type 2 diabetes, and the metabolic syndrome in women with PCOS compared with women without PCOS.”

They conclude in the journal Human Reproduction Update: “Future research in PCOS should identify optimal risk prediction tools for Type 2 diabetes and CVD and optimal definition and utility of the metabolic syndrome for disease prediction.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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Study results show that intensive lifestyle intervention (ILI) reduces cardiovascular disease (CVD) risk factors more than diabetes support and education (DSE), leading to reduced medication use and lower costs.

Previous results from the Look AHEAD (Action for Health in Diabetes) study, reported by MedWire News, showed that ILI improves quality of life, physical fitness, and weight loss more than DSE in overweight individuals with Type 2 diabetes.

In this study, J Bruce Redmon (University of Minnesota, Minneapolis, USA) and colleagues assessed the impact of ILI versus DSE on use and cost of medications for treatment of CVD in 4358 overweight participants of the Look AHEAD trial aged 45??”76 years with complete data at 1 year.

DSE involved general recommendations for healthy eating and increased exercise, attendance at an initial session, and invitations to three additional group sessions over the year. The ILI was more intensive than this, including weekly group treatment and monthly individual sessions with a lifestyle counselor.

As previously reported, patients in the ILI group had significantly greater improvements in CVD risk factors at 1 year than those in the DSE group.

In this study, the team compared use of medications to treat diabetes, hypertension, and hyperlipidemia in the ILI and DSE groups at baseline and at 1 year as well as the estimated monthly costs of the medications.

Writing in the journal Diabetes Care, Redmon and co-workers report that patients in the ILI group had significantly lower medication use and costs than those in the DSE group.

At baseline, the Look AHEAD participants were taking an average of 3.3 medications at a monthly cost of approximately US $155 (€129).

At 1 year, the average number of CVD-related medications prescribed to ILI patients was 3.1 versus 3.6 for DSE patients. This corresponds to approximate total monthly costs of $143 (€120) and $173 (€145), respectively.

ILI patients who met optimal care goals at 1 year ??” glycated hemoglobin below 7%, blood pressure below 130/80 mmHg, and low-density lipoprotein cholesterol below 100 mg/dl ??” were taking an average of 3.2 medications at a mean monthly cost of $154 (€129). This compared with the DSE patients who were taking 3.8 medications on average at a mean monthly cost of $194 (€163).

“Continued intervention and follow-up will determine whether these changes are maintained and reduce cardiovascular risk,” conclude Redmon et al.

“If these changes can be sustained for the long term, the public health benefits would be substantial,” they add.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

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Type 2 diabetics ‘Look AHEAD’ to improved fitness and weight loss after ILI
Weight management program improves quality of life in overweight diabetics

Vildagliptin is an effective and well-tolerated add-on therapy to glimepiride for the treatment of patients with Type 2 diabetes, report Japanese researchers.

The dipeptidyl peptidase-4 inhibitor vildagliptin has previously been shown to significantly improve glycemic control in Type 2 diabetics when added to metformin therapy, as reported by MedWire News.

In the current study, Matthew Goodman (Novartis Pharmaceuticals, Horsham, UK) and colleagues assessed the efficacy of adding vildagliptin (100 mg/day) to the sulfonylurea glimepiride (1 mg/day or more) in Japanese patients with Type 2 diabetes and inadequate glycemic control.

The study took place over 12 weeks, during which time 102 patients were randomly assigned to take vildagliptin and 100 were randomly assigned to take placebo in addition to their existing dose of glimepiride. A total of 99 and 96 patients in the respective groups completed the study.

At baseline, the mean glycated hemoglobin (HbA1c) was 7.9% and average fasting plasma glucose (FPG) was 163.8 mg/dl.

At study completion, HbA1c had decreased by 1.0% in the vildagliptin group compared with just 0.1% in the placebo group, a significant difference.

In addition, 45.0% of patients treated with vildagliptin achieved an HbA1c of 6.5% or below compared with only 3.0% of patients in the placebo group.

The adjusted mean change in FPG at study completion was a 20.9 mg/dl decrease in vildagliptin-treated patients versus a 6.3 mg/dl increase in the placebo group.

Adverse events occurred at a similar frequency in the vildagliptin and placebo groups, at 59.8% and 57.0%, respectively. The corresponding rates of serious adverse events, suspected drug-related adverse events, and discontinuation due to adverse events, were 0.0% versus 2.0%, 21.6% versus 23.0%, and 1.0% versus 3.0%. Two vildagliptin- and one placebo-treated patient experienced hypoglycemia during the study.

Goodman and co-authors conclude that vildagliptin 100 mg/day is “an efficacious and well tolerated addition to pharmacotherapy in the management of diabetes in Japanese patients with Type 2 diabetes mellitus.”

The results of this study are published in the journal Diabetes Research and Clinical Practice.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

Free abstract

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Vildagliptin ‘promising’ adjunct to metformin
Vildagliptin effective as thiazolidinediones as metformin add-on

Study results show that two markers of fatty liver disease, the Fatty Liver Index (FLI) and the non alcoholic fatty liver disease score (NAFLD-FLS), both significantly predict incident Type 2 diabetes.

Beverly Balkau (INSERM, Villejuif, France) and colleagues report the results of the DESIR (Data from an Epidemiological Study on the Insulin Resistance syndrome) study, which evaluated the predictive ability of NAFLD-FLS and FLI for 9 year incident Type 2 diabetes in a French population cohort of 1861 men and 1950 women.

At baseline, the participants were all nondiabetic and were aged 30 to 65 years. Over a 9-year follow-up period, 203 cases of incident Type 2 diabetes (fasting plasma glucose of 7.0 mmol/l or more) were diagnosed in 140 men and 63 women.

The FLI score runs from 0??”100 and estimates the percentage chance of having a fatty liver. It is calculated using a combination of factors including body mass index (BMI), waist circumference, triglycerides, and gamma glutamyl transferase.

The NAFLD-FLS equation also evaluates the percentage chance of having a fatty liver and is calculated according to presence or absence of the metabolic syndrome or diabetes, and differing levels of insulin, alanine aminotransferase, and aspartate aminotransferase.

Compared with participants with a baseline FLI score below 20, men and women with a score of 70 or above had a respective 3.43- and 11.05-fold increased risk for developing incident Type 2 diabetes during the study, following adjustment for baseline glucose and insulin levels, hypertension, alcohol intake, physical activity, and family history of diabetes.

In addition, men with a NAFLD-FLS score of more than -1.15 and women with a NAFLD-FLS score of more than -1.82 had a 2.32- and 3.95-fold increased adjusted risk for Type 2 diabetes, respectively, compared with men and women with lower scores. “These fatty liver indexes are simple clinical tools for evaluating the extent of liver fat and they are predictive of incident diabetes,” conclude the authors in the journal BMC Gastroenterology.

They suggest: “Physicians should screen for diabetes in patients with fatty liver.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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New results from a post-hoc analysis of the
BARI-2D trial show no association between rosiglitazone and
cardiovascular (CV) events.

However, the results confirmed previously reported links between
rosiglitazone and fracture.

Richard Bach (Washington University School of Medicine, St
Louis, Missouri, USA) presented the results of a post-hoc study of
2368 patients enrolled in the BARI-2D (Bypass Angioplasty
Revascularization Investigation 2 Diabetes) study at the American
Diabetes Association 2010 Scientific Sessions held in Orlando,
Florida.

The patients all had Type 2 diabetes and
angiographically-confirmed coronary artery disease (CAD) plus at
least one significant lesion suitable for revascularization. The
trial aimed to assess the long-term outcomes of rosiglitazone
therapy.

The main results of BARI-2D have already been published.
Patients were randomized to treatment with prompt revascularization
and medical therapy versus medical therapy and delayed or no
revascularization, and to insulin sensitization versus insulin
provision. The findings showed that the rate of overall survival
and freedom from CV events did not vary significantly between the
different treatment groups, as previously reported by MedWire
News.

For the purposes of this study, Bach and team compared 992
patients treated with rosiglitazone with 1199 patients who were not
treated with a thiazolidinedione (TZD).

At baseline, the patients were aged 62 years on average, had a
mean glycated hemoglobin level of between 7.5% and 7.8%, and had
had diabetes for approximately 10 years. In addition, a quarter of
patients in both groups had undergone prior revascularization.

Bach reported that, at 4.5 years, patients taking rosiglitazone
had a significantly lower rate of stroke and the combination of
death, myocardial infarction (MI), and stroke per 100 patient years
compared with patients not treated with TZDs. In addition, the rate
of death and MI were non-significantly lower, and chronic heart
failure was non-significantly higher in rosiglitazone-treated
patients.

Co-administration with insulin, metformin, nitrates, and
angiotensin-converting enzyme inhibitors, did not significantly
influence the rate of CV outcomes in rosiglitazone treated
patients.

Notably, as found in previous studies, the relative risk for
fracture was a significant 62% higher in rosiglitazone-treated
patients than in those who took no TZDs. When stratified by gender,
the increase in relative risk was statistically significant in
women only, at 82%.

Bach acknowledged that the study was limited by its
non-randomized nature and added that the fact that many patients on
the study were taking more than one anti-diabetic drug might have
limited the ability of the researchers to discriminate the effects
of any one drug from another.

“I think these data are important because they suggest there is
no significant cardiovascular harm posed by taking rosiglitazone
for patients with Type 2 diabetes and coronary heart disease,” said
Bach.

These new data “contribute to the scientific inquiry regarding
associated events with rosiglitazone.”

He added: ” There is an increase in fractures, but when one
considers the dramatic morbidity and mortality associated with
ischemic cardiovascular events in patients with diabetes, these
data are reassuring.”

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

Meeting website

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Revascularization no better than medical therapy for stable IHD in Type 2 diabetics

Results from a meta-analysis show that
moderate-dose aspirin can significantly reduce all-cause mortality
in diabetic patients.

Low-dose aspirin is recommended for cardiovascular (CV) risk
reduction in at-risk patients with Type 2 diabetes, but there has
been some debate about the ideal dosage to use, and recent studies,
such as JPAD (Japanese Primary prevention of atherosclerosis with
Aspirin for Diabetes) and POPADAD (Prevention Of Progression of
Arterial Disease And Diabetes), indicate that a daily dose of 100
mg/dl or less is not effective for primary prevention.

Scott Simpson (University of Alberta, Edmonton, Canada) and
colleagues performed a meta-analysis to estimate the optimum
aspirin dose required to achieve a significant reduction in
all-cause mortality in diabetic patients. In total, 21 studies
involving 17,522 diabetic patients were included in the
analysis.

Overall, 14.6% (1189 of 8133) of patients who took aspirin and
17.0% (1358 of 8000) of those who did not died. Simpson and team
found that aspirin use was not associated with a statistically
significant reduction in mortality risk in the pooled cohort, and
stratification by daily aspirin dose only led to small decreases in
pooled risk ratios.

However, patients with a history of CV disease who were taking
aspirin achieved a significant 18% reduction in mortality risk,
compared with their peers not taking aspirin.

Further stratification for aspirin dose in patients with a
history of CV disease showed that only patients taking aspirin 325
mg/day or more achieved a significant reduction in all-cause
mortality (23%). When only randomized controlled trials were
considered, however, patients given aspirin 101-325 mg/dl had a
significant reduction in mortality risk.

“The premise of this study is coming from a pharmacologic study
called ASPECT, where patients with diabetes that were using 81 mg
of aspirin had a higher rate of aspirin resistance compared with
those that were using over 100 mg of aspirin daily,” explained
Simpson, who presented the results at the American Diabetes
Association 2010 Scientific Sessions held in Orlando, Florida.

“We wanted to see if that would translate into clinical outcomes
of cardiovascular events or all-cause mortality.”

He suggested that the dose-response relationship seen in this
analysis should be investigated further in a clinical trial.

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

Meeting website

Microvascular markers of kidney, eye, and
peripheral nerve function may benefit from intensive as opposed to
standard treatment for hyperglycemia, show study results.

Faramarz Ismail-Beigi (Case Western Reserve University,
Cleveland, Ohio, USA) and colleagues reported results on
microvascular outcomes from 10,251 participants who were given
intensive glucose control (n=5107; target glycated hemoglobin
[HbA1c] below 6.0%) or standard treatment (n=5108; target HbA1c
7.0-7.9%) in the Action to Control Cardiovascular Risk in Diabetes
(ACCORD) study.

The results were presented at the American Diabetes Association
2010 Scientific Sessions held in Orlando, Florida, USA, and
simultaneously published in The Lancet journal.

The prespecified first composite outcomes evaluated were:
dialysis or renal transplantation, a high serum creatinine level
above 291.7 µmol/l, or retinal photocoagulation or vitrectomy;
and the second composite outcome was a combination of peripheral
neuropathy and the first composite outcome.

The researchers also assessed 13 secondary measures of kidney,
eye, and peripheral nerve function.

Due to higher mortality in the intensive treatment group, at 3.5
years the patients on intensive therapy were given standard therapy
instead for an additional 1.5 years.

At the transition, 443 and 444 of the patients in the intensive
and standard treatment groups, respectively, had the first
composite outcome and a corresponding 1591 and 1659 had the second
composite outcome. Between-group differences for the first and
second composite outcomes were not significant.

At study completion, 556 and 586 of the respective groups had
the first composite outcome and 1956 and 2046 the second composite
outcome, again with no significant between-group differences
observed.

Although the between-group differences for the primary and
secondary composite outcomes were not statistically significant,
seven of the 13 secondary markers of kidney, eye, and peripheral
nerve function significantly favored intensive over standard
treatment. Especially notable was a delay in the onset of
albuminuria and some measures of eye complications and neuropathy
in intensive versus standard glucose control patients.

“Patients who develop macroalbuminuria are prone to renal
failure and cardiovascular events,” said Ismail-Beigi. “Less
protein in the urine is a very good sign.”

Other results from ACCORD were previously reported by MedWire
News and showed that intensive glycemia treatment did not
decrease cardiovascular risk and increased the risk for severe
hypoglycemia.

“The microvascular benefits you see here in the intensive arm
should be weighed against the increase in total and cardiovascular
mortality, weight gain, and a higher risk for severe hypoglycemia,”
he concluded.

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

Free abstract:

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ACCORD intensive glucose-lowering arm stopped