A high baseline transcutaneous oximetry (TcPO₂) measurement predicts optimal response to hyperbaric oxygen therapy (HBOT) in diabetic patients with chronic foot ulcers, show Swedish study results.

Previous studies have shown that HBOT can be highly beneficial for promoting healing of chronic diabetic foot ulcers, as reported by MedWire News, but the treatment is more successful in some patients than others.

As HBOT is an expensive treatment, Magnus Lohndahl (Skane University Hospital, Lund) and colleagues investigated factors with potential to predict HBOT efficacy.

Using data from the 75 patients enrolled in the HODFU (HBOT in Diabetic Patients with Chronic Foot Ulcers) study who completed at least 36 out of the 40 scheduled HBOT or placebo treatment sessions, the team assessed TcPO₂, toe blood pressure (TBP), and ankle-brachial index (ABI) as possible outcome predictors.

Ulcer healing rate was measured 9- and 12-months after the last treatment. Ulcers were considered to be completely healed if completely epithelialized at 9 months, remaining so at 12 months.

For patients in the HBOT group (n=38), TcPO₂ was significantly lower in those with an unhealed compared with a healed ulcer.

Healing rate was also lower with decreased TcPO₂. More specifically, at a TcPO₂ of less than 25 mmHg the healing rate was 0%, increasing to 50% with a TcPO₂ of 26-50 mmHg, and increasing still further to 100% with a TcPO₂ of 75 mmHg or above.

Of note, TBP and ABI were not significantly associated with HBOT outcome in this study.

Writing in the journal Diabetologia, the authors conclude: “We suggest hyperbaric oxygen therapy as a feasible adjunctive treatment modality in selected diabetic patients with chronic non-healing foot ulcers when basal TcPO₂ at the dorsum of the foot is above 25 mmHg.”

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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Efficacy of HBOT therapy for diabetic foot ulcer is dose dependent
Hyperbaric oxygen therapy helps heal diabetic foot ulcers

Ranibizumab is effective for improving best corrected visual acuity (BCVA) and central retinal thickness (CRT) and is well tolerated in patients with diabetic macular edema (DME), show results from the RESOLVE study.

The Ranibizumab in Diabetic Macular Edema (RESOLVE) study included 151 patients with Type 1 or 2 diabetes and DME who were assigned in a 1:1:1 fashion to three monthly injections with ranibizumab 0.3 or 0.5 mg or sham treatment. The patients had a CRT of greater than or equal to 300 µm and a BCVA of 73-39 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale.

After the three injections, treatment could be stopped or re-initiated with an opportunity for rescue laser photocoagulation. The participants were followed up for 12 months.

Sebastian Wolf (University of Bern, Switzerland) and colleagues report that BCVA had improved by 10.3 letters from baseline in the pooled ranibizumab group compared with a reduction of 1.4 letters in the sham treatment group, a statistically significant difference.

CRT was also significantly reduced at 12 months in the pooled ranibizumab group compared with the sham group, by 194.2 versus 48.4 µm.

BCVA improved by 10 letters or more in 60.8% of the ranibizumab versus 18.4% of the sham treatment group.

Ranibizumab was well tolerated and the rates of adverse events did not differ significantly between the two groups.

“This study appears promising for the use of ranibizumab in the treatment of DME, with a good safety profile,” commented Pedro Romero-Aroca (Universitat Rovira i Virgili, Reus, Spain) the author of an accompanying editorial.

“Anti-Vascular endothelial growth factor (VEGF) drugs seem to be a promising alternative for the treatment of DME, but it is still necessary to define the dose and the time between injections.”

He concluded: “A clinical trial directly comparing the efficacy and safety of anti-VEGF treatment with conventional laser therapy is warranted.”

The results of this study are published in the journal Diabetes Care.

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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Ranibizumab plus laser treatment effective for diabetic macular edema

The combination of a large waist circumference and elevated plasma triglyceride (TG) levels in patients with Type 2 diabetes can predict the presence of coronary artery disease (CAD), study results show.

This combination, termed “hypertriglyceridemic waist,” could provide “a simple, low-cost biomarker for CAD, enabling the identification of patients who are at increased cardiovascular risk,” say Jeroen Bax (Leiden University Medical Center, The Netherlands) and colleagues in the American Journal of Cardiology.

Bax and colleagues aimed to see if the Quebec Cardiovascular Study finding of an association between the hypertriglyceridemic waist phenotype and the “atherogenic metabolic triad,” defined as increased insulin, small dense low-density lipoprotein particles, and apolipoprotein B, could be extended to patients with diabetes.

They assessed waist circumference and TG levels in 202 patients with Type 2 diabetes who were clinically referred for tomographic coronary angiography (CTA).

The patients were divided into four groups using threshold values for waist circumference (?88 or >88 cm for women and ?102 or >102 cm for men) and TG levels (<1.7 or ?1.7 mmol/l for both men and women) as previously described by the National Cholesterol Education Program Adult Treatment Panel III.

Patients with elevated waist circumference and TG levels (n=61, 31%) were considered to have the hypertriglyceridemic waist phenotype, while patients with low waist circumference and TG levels (n=49, 24%) served as the reference group.

Bax and colleagues found that in patients with hypertriglyceridemic waist, plasma cholesterol levels were significantly elevated while high-density lipoprotein cholesterol was significantly reduced compared with the reference group.

The presence of any CAD and obstructive CAD was significantly increased in patients with hypertriglyceridemic waist relative to the reference group, at odds ratios of 3.3 and 2.9, respectively.

In addition, a significantly larger number of noncalcified and mixed plaques was observed in the hypertriglyceridemic waist group relative to the reference group.

Discussing the findings, Bax et al note that screening for CAD in patients with Type 2 diabetes in the presence of two or more additional traditional cardiovascular risk factors has been endorsed by the American Diabetes Association, although evidence for the effectiveness of routine screening of patients is lacking.

“In this setting, the hypertriglyceridemic waist phenotype may potentially serve as a practical biomarker for CAD to increase risk stratification in this patient population,” Bax and colleagues comment.

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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Results from a population-based cohort study suggest that individuals who are screened for Type 2 diabetes have lower long-term mortality than those who are not.

Simon Griffin (Institute of Metabolic Science, Cambridge, UK) and colleagues assessed the impact on long-term mortality of inviting 1705 of 4936 patients from a single practice in Ely, Cambridgeshire, UK to Type 2 diabetes screening.

The initial screening took place in 1990-1992 when the participants were aged 40-65 years. They had an oral glucose tolerance test and related cardiovascular risk factors such as lipids and blood pressure were also measured.

A further 1705 individuals from the rest of the cohort were selected for screening in 2000-2003, leaving 1526 who were not screened. All participants were followed-up for mortality until January 2008.

In total, 345 deaths occurred from 1990-1999 and 291 from 2000-2008. Individuals invited to the first round of screening had a nonsignificant 21% reduction in all-cause mortality at study completion in 2008 versus those who did not undergo screening. However, no mortality difference was observed between invited and noninvited participants for the second screened group in 2008.

The researchers note that only 68% and 45% of those invited to the first and second screening sessions, respectively, actually attended. When this was taken into account, participants who attended either diabetes screening session had significantly lower (46-48% decrease) and those who were invited but did not attend had significantly higher (36-73% increase) mortality than those who were not screened.

“While results from this analysis are promising, it remains unclear whether early detection and treatment of diabetes and related cardiovascular disease risk factors is beneficial and produces sufficient improvement in long-term health outcomes to justify the economic costs,” write the authors in the journal Diabetologia.

“In view of the extensive organizational, technical, and financial input that a national Type 2 diabetes screening program would demand, evidence of the cost effectiveness of screening from prospective randomized controlled trials prior to implementation would be desirable.”

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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Type 2 diabetes patients with gated myocardial perfusion single-photon computed tomography (SPECT) imaging abnormalities who are otherwise asymptomatic are at high risk for cardiovascular (CV) events and death, say researchers.

The Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS) study previously showed diabetes to be the most important predictor of CV events in Japan.

Yoshimitsu Yamasaki (Osaka University, Suita, Japan) and co-workers therefore used SPECT imaging, which was recently validated for detecting myocardial ischemia and assessing prognosis, to stratify 485 at-risk, but asymptomatic, Type 2 diabetes patients into high and low CV risk categories.

Those with a SPECT summed stress score (SSS) of less than 9 were considered to have normal or mildly abnormal results and those with a score of 9 or more to have moderately or severely abnormal results, as described in the J-ACCESS trial.

The cohort was then followed up for 3 years, during which time five cardiac deaths and 57 CV events (heart failure, revascularization, angina, transient ischemic attack, stroke, and peripheral artery disease) occurred.

Patients with a SSS score of 9 or more had a significantly higher incidence of death or CV events than those with lower scores, at 23% versus 12%. Other significant risk factors were having a low estimated glomerular filtration rate and being a current smoker.

“The prevalence of diabetes in the Japanese population is rapidly increasing as the lifestyle becomes more Westernized. Therefore, the cardiovascular event rate among asymptomatic diabetic Japanese patients is a matter of considerable concern,” write the researchers.

“The present data indicate that myocardial ischemia would be useful for risk stratification of cardiovascular events in asymptomatic diabetic patients,” they suggest.

The results of this study are published in the journal Diabetes Care.

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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Younger age at diagnosis, female gender, and high body mass index (BMI) and glycated hemoglobin (HbA1c) at initial clinic visit predict switching to insulin therapy in patients with Type 2 diabetes, say researchers.

Mohsen Janghorban and Masoud Amini from Isfahan University of Medical Sciences in Iran followed up 6896 non-insulin treated patients with Type 2 diabetes for a mean period of 9.3 years for incidence of progression to insulin therapy. At baseline, the participants were aged 51.2 years and had a mean diabetes duration of 5.8 years.

Over a total of 64,540 patient-years of follow-up, 1599 (23.2%) patients switched from diet and exercise (24.4%) or oral antidiabetes (75.6%) medication to insulin therapy, a rate of 2.5 per 100 patient years.

The researchers found that each additional year of age was associated with a significant 3% reduction in risk for switching to insulin, whereas each additional unit of BMI (kg/m²) at baseline significantly increased the risk for switching by 2%.

Each additional follow-up visit over the study period decreased the risk for switching by a significant 3%, while each 1% increase in HbA1c at baseline was linked with a significant 8% increase in risk for switching.

Finally, female gender increased the risk for switching to insulin by a significant 20%.

Writing in the journal Diabetes Research and Clinical Practice, the team concludes: “The findings of this study illustrate for the first time the switching rates and its predictors to insulin from a non-insulin regimen in patients with Type 2 diabetes in Iran.”

They suggest: “These findings may be taken into account in future treatment decisions.”

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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Adolescent girls with Type 1 diabetes who have poor glycemic control are at increased risk for oligomenorrhea, show study findings.

The researchers also found that diabetic girls had later menarche and a generally higher rate of oligomenorrhea compared with nondiabetic girls.

Women with Type 1 diabetes have a higher frequency of menstrual problems than nondiabetic women, but links with glycemic control are less clear.

In this study, Anna Deltsidou (Technological Educational Institute, Lamia, Greece) and colleagues recruited 81 female adolescent Type 1 diabetics, aged 15 years on average, and 205 age-matched healthy controls.

Menstruation data were collected by questionnaire, and the investigators defined oligomenorrhea as having a menstrual cycle longer than 36 days 5/6 times in the previous year.

Girls with Type 1 diabetes had a significantly greater age at menarche compared with healthy controls, at a mean of 12.2 versus 11.7 years.

The team also found that diabetic girls were 7.8 times more likely to have oligomenorrhea compared with healthy controls.

Further analysis within the Type 1 diabetic group showed that each incidence of hypoglycemia and each 1% increase in glycated hemoglobin (HbA1c) increased the risk for oligomenorrhea 5.3 and 4.8 fold, respectively.

“Several reasons may explain the high frequency of menstrual disorders in adolescents with type 1 diabetes, such as a relative decrease in luteinizing hormone pulsatility, or delay in the appearance of the positive estrogen feedback loop on the hypothalamic-pituitary axis,” write the authors in the European Journal of Obstetrics and Gynecology and Reproductive Biology.

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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Retrospective cohort study results suggest that treatment with exenatide or sitagliptin is not associated with an increased risk for acute pancreatitis.

Postmarketing surveillance has indicated that treatment with the dipeptidyl peptidase-4 inhibitor sitagliptin or the glucagon-like peptide-1 receptor agonist exenatide may increase the risk for acute pancreatitis, as reported by MedWire News.

However, other studies have suggested that the increased incidence of acute pancreatitis is likely to be due to an increased occurrence in patients with Type 2 diabetes compared with the general population, regardless of medication type.

For the current study, Merri Prendergrass (University of Texas Southwestern Medical Center, Dallas, USA) and colleagues carried out a retrospective analysis of a large medical and pharmacy claims database including 786,656 patients.

In total, 748,041 individuals were nondiabetic and 38,615 were diabetic, with a mean age of 52 years overall. Of the diabetic patients, 6545 were treated with exenatide and 15,826 with sitagliptin, and 16,244 diabetic ‘controls’ were treated with alternative medication. The participants had a minimum follow-up of 12 months for incidence of pancreatitis.

As reported in the journal Diabetes Care, the team found that the combined diabetic group had a significant 2.1-fold higher risk for acute pancreatitis than the nondiabetic group.

However, the risk for acute pancreatitis in the exenatide (adjusted hazard ratio [aHR]=0.9) and the sitagliptin (aHR=1.0) groups versus the diabetic control group over the follow-up period were not significantly different.

The incidence of acute pancreatitis was 1.9, 5.6, 5.7, and 5.6 cases per 1000 patient years in the nondiabetic, diabetic control, exenatide, and sitagliptin groups, respectively.

“Our findings did not reveal any increased risk of acute pancreatitis with exenatide and sitagliptin, but this retrospective study cannot rule out with certainty the existence of such an association,” write the authors.

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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Type 2 diabetics have increased risk for acute pancreatitis
FDA to revise prescribing information for exenatide, sitagliptin

Impaired heart rate recovery within 1 minute of finishing exercise in patients with Type 2 diabetes is associated with an increased likelihood of having multivessel coronary artery atheroma, study results show.

However, this finding was not independent of the UK Prospective Diabetes Study (UKPDS) risk score, say David Halon (Ruth and Bruce Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel) and co-authors who suggest that the observed correlation was due to the generally poor patient risk profiles of those with low peak heart rate at 1 min after completion of exercise (HRR1).

Halon and team investigated HRR1 in 549 patients with Type 2 diabetes (54.9% women) and no history of coronary artery disease (CAD) who were enrolled in an ongoing prospective outcomes study. They were aged 55-74 years and had at least one risk factor for CAD.

HRR1 was assessed after maximal graded treadmill stress testing carried out using a Bruce protocol. Presence of coronary atheroma was detected using cardiac computed tomographic angiography.

Writing in the International Journal of Cardiology, the investigators report that presence of any coronary atheroma, multivessel coronary atheroma, or coronary stenosis was associated with significantly lower HRR1, at 22.1, 21.6, and 20.7 beats/first minute, respectively, compared with the absence of these conditions, at a respective 24.9, 24.2, and 23.3 beats/first minute.

The median HRR1 value was 21 beats/first minute, and significantly more patients with values below the median had multivessel coronary plaque than those above, at 61.7% versus 49.3%.

Following adjustment for age and gender, HRR1 remained a significant predictor of multivessel CAD in men, but not women. However, adjustment for the UKPDS risk score invalidated the association.

The team notes that poor HRR1 was linked to the presence of several factors associated with poor diabetes prognosis, such as a long history of diabetes, high glycated hemoglobin, large waist circumference, hypertension, and current smoking, but did not independently predict multivessel CAD in these patients.

Halon and co-authors conclude that in this study “the correlation of HRR1 with CAD appeared to be related to the adverse patient risk profile.”

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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Lipid ratios may be more useful than other lipoprotein measurements for assessing the risk for early atherosclerosis in Japanese patients with Type 2 diabetes, research suggests.

The ratios of low- to high-density lipoprotein (LDL/HDL) cholesterol and total to HDL (total/HDL) cholesterol were most closely associated with carotid intima-media thickness (IMT) of all the lipid parameters assessed.

There was also a positive, linear association between the two ratios and the prevalence of carotid plaque, report Naoto Katakami (Osaka University Graduate School of Medicine, Japan) and co-workers.

They say: “These results suggest that total/HDL cholesterol and LDL/HDL cholesterol ratios are better lipid indices than the other standard lipid parameters in assessing the risk of early-stage atherosclerosis.”

The team studied the relationship between various lipid parameters and carotid atherosclerosis evaluated using ultrasonography in 934 Japanese individuals with Type 2 diabetes, but without apparent atherosclerotic disease.

Overall, 71.7% of the group were men, and the mean age was 59.6 years.

Stepwise multivariate regression analysis demonstrated that HDL cholesterol, and the total/HDL cholesterol and LDL/HDL cholesterol ratios each significantly determined IMT, even after adjusting for other conventional risk factors.

However, there was no significant correlation between IMT and levels of total cholesterol, triglycerides, LDL cholesterol, and non-HDL cholesterol.

The ratios of total/HDL cholesterol and LDL/HDL cholesterol as well as levels of non-HDL cholesterol were significantly higher in patients with carotid plaque than in those without, while the reverse was true for HDL cholesterol.

However, there were no significant differences for total or LDL cholesterol, or triglyceride levels.

There was a positive and linear relationship between carotid plaque prevalence and total/HDL cholesterol and LDL/HDL cholesterol ratios, with odds ratios of 1.34 and 1.54, respectively, regardless of adjustment for covariates.

Reporting in the journal Atherosclerosis, the researchers conclude: “These data suggest that these lipoprotein ratios are recommended as a tool to assess the risk of early-stage atherosclerosis in Type 2 diabetic patients in regular 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

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