Individuals with Type 2 diabetes have more extensive and severe coronary artery disease (CAD) than those with Type 1 diabetes, suggest results from a small study.

“It is unclear whether the coronary atherosclerotic plaque burden is similar in patients with Type 1 and Type 2 diabetes,” explain Jeroen Bax (Leiden University Medical Center, The Netherlands) and co-researchers.

To investigate further, the team recruited 135 asymptomatic Type 2 (n=70) and Type 1 (n=65) diabetics. Multislice computed tomography, as well as coronary artery calcium (CAC) scoring, was used to determine the presence, degree, and morphology of CAD.

Writing in the journal Diabetes Care, the researchers report that there was no significant difference in CAC score (217 vs 174) or prevalence of coronary atherosclerosis (65% vs 71%) between participants with Type 1 and Type 2 diabetes.

However, more patients with Type 2 diabetes had obstructive atherosclerosis (34% vs 17%) and multivessel disease (59% vs 29%) than those with Type 1 diabetes.

Type 2 diabetics also had a significantly higher mean number of lesions than Type 1 diabetics (9.9 vs 3.4), as well as a higher number of obstructive plaques (1.7 vs 0.5).

The team also notes that patients with Type 2 diabetes had a higher percentage of noncalcified plaques than Type 1 individuals (66% vs 27%), leading to a higher burden per CAC score.

“Although CAC scores and the prevalence of coronary atherosclerosis were similar between patients with Type 1 and Type 2 diabetes, CAD was more extensive in the latter,” conclude Bax et al.

“These observations may be valuable in the development of targeted management strategies adapted to diabetes type,” they add.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Patients who have a glycated hemoglobin (HbA1c) level below 6.0% when tested for Type 2 diabetes do not require retesting at intervals shorter than 3 years, show study results.

However, those with an HbA1c between 6.0% and the diagnostic threshold of 6.5% are likely to benefit from more frequent testing, write the investigators in the journal Diabetes Care.

Osamu Takahashi (St Luke’s International Hospital, Tokyo, Japan) and colleagues carried out a retrospective cohort study of 16,313 apparently healthy Japanese adults, aged 49.7 years on average, who were not taking glucose-lowering medication when they entered the study. The participants had annual health checks, including HbA1c testing, between 2005 and 2008.

At baseline, mean HbA1c was 5.4%. The team found that at 3 years the cumulative incidence of Type 2 diabetes was 0.05%, 0.05%, 1.20%, and 20.0% in participants with baseline HbA1c levels of less than 5.0%, 5.0-5.4%, 5.5-5.9%, and 6.0-6.4%, respectively.

There has been a recent shift towards using HbA1c for diagnosis of diabetes as it “integrates longer-term glucose levels and has better preanalytic stability” than fasting and post-glucose challenge blood glucose levels, say the authors.

The current diagnostic threshold for Type 2 diabetes is 6.5%, based on retinopathy risk, but optimal retesting intervals for at-risk individuals with an HbA1c level below 6.5% are less clear.

Takahashi and team say their results show that people with an HbA1c level below 6.0% are very unlikely to develop Type 2 diabetes during the subsequent 3 years and therefore more frequent testing than this is likely to be unnecessary.

They add that for those with an HbA1c level above 6.0% the risk is significantly greater, and therefore yearly testing in this group is not unreasonable.

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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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

An elevated microaneurysm score is an important prognostic indicator for progression of diabetic retinopathy and reduced likelihood of regression, suggest study findings.

The researchers say that treatment of microaneurysms using renin-angiotensin system inhibitors may be effective for improving mild retinopathy.

Writing in the journal Diabetic Medicine, Anne Sjølie (Odense University Hospital, Denmark) and team report results from a post-hoc analysis of the DIabetic REtinopathy Candesartan Trials (DIRECT) study.

They included 893 patients with Type 1 (454 placebo; 439 candesartan treated) and 526 patients with Type 2 diabetes (264 placebo; 262 candesartan treated) with microaneurysms and diabetic retinopathy who were assessed for progression.

In addition, 438 patients with Type 1 and 216 with Type 2 diabetes who had significant potential to regress (Early Treatment Diabetic Retinopathy Study [ETDRS] severity scale score level 20 in both eyes) were also assessed for regression of retinopathy.

The researchers found that each additional microaneurysm observed at baseline on retinal photographs increased the risk for progression of retinopathy by 8% and 7% in Type 1 and Type 2 diabetes, respectively.

Chance of regression of retinopathy was reduced by a corresponding 21% and 15% per additional aneurysm scored at baseline.

Use of a renin-angiotensin system inhibitor, in this case candesartan, was observed to reduce the risk for microaneurysm score progression, note the authors.

“Our findings support the use of microaneurysm score as a useful surrogate clinical endpoint for progression and regression of retinopathy in clinical trials and may be more sensitive than the ETDRS in earlier stages,” write Sjølie et al.

“It should be emphasized that this is not applicable to screening for sight-threatening retinopathy in clinical practice,” 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

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Study findings show that women with previous gestational diabetes mellitus (GDM) have increased prevalence of non-alcoholic fatty liver disease (NAFLD) compared with women who have not experienced GDM.

NAFLD is known to be common in patients with Type 2 diabetes, but whether women at high risk for Type 2 diabetes, such as those who have previously experienced GDM, are at increased risk is less clear.

For the purposes of this study, Shareen Forbes (University of Edinburgh, UK) and colleagues recruited 110 women with previous GDM (within previous 10 years) and 113 without prior GDM (controls). They had liver ultrasound examinations, blood tests to assess liver function, lipid, and glucose levels, and had anthropometric factors measured.

As reported in the journal Diabetologia, prevalence of NAFLD was significantly greater in women with prior GDM than controls, at 38% versus 17%.

Body mass index (BMI) was not significantly different between the two groups. However, women with previous GDM had significantly higher fasting (5.3 vs 5.1 mmol/l) and 2-hour glucose (6.8 vs 5.8 mmol/l) concentrations following an oral glucose tolerance test (75 g) than controls.

In addition, GDM women were more likely to have dyslipidemia, lower insulin sensitivity, and higher insulin secretion than controls.

“As these women are at significant risk of Type 2 diabetes, this result may be consistent with NAFLD preceding Type 2 diabetes in this cohort,” write Forbes et al.

They add: “Diminished insulin sensitivity and raised alanine aminotransferase activity may all contribute to the development of NAFLD in these women.”

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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A weight-loss program combining diet, exercise, and telemonitoring, and only moderate cost can offer multiple benefits for patients with Type 2 diabetes, a small trial suggests.

The Active Body Control (ABC) program significantly lowered body weight, glycated hemoglobin (HbA1c) levels, and the use of anti-diabetic drugs during a period of 6 months compared with standard therapy.

Sabine Westphal and co-workers from the Otto-von-Guericke-University Magdeburg in Germany, randomly assigned 70 overweight patients with Type 2 diabetes and a mean age of 57.5 years to the ABC program or standard therapy.

ABC participants were advised to lower their calorie intake by 500 kcal/day and preferentially consume low GI-carbohydrates, as well as increase their physical activity. Telemonitoring of weight and physical activity was also conducted, with a weekly feedback letter to inform and motivate participants. The cost to the patient of the ABC program was €150 (US $196).

After 6 months, patients on the ABC program had lost a statistically significant mean of 11.8 kg in weight versus no significant change for those on standard therapy.

Glucose levels in ABC patients decreased by 1.0 mmol/l and HbA1c levels by 0.8%, with respective reductions of just 0.2 mmol/l and 0.2% with standard therapy.

The proportion of patients with HbA1c of more than 7% fell from 57% to 26% with the ABC program, but increased in the standard-therapy group. Antidiabetic drugs were discontinued in 39% of the ABC group and reduced in 42% versus far smaller changes with standard therapy.

Reporting in the journal Diabetes Research and Clinical Practice, the researchers summarize: “The ABC program combines innovative telemonitoring with additional sensible measures.

“In obese diabetic patients it leads not only to a pronounced weight loss but also to relevant metabolic improvements and reductions in antidiabetic drug use.”

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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Findings from a study in humans demonstrate no evidence for promotion of C-cell proliferation, which is associated with increased medullary thyroid cancer risk, by the glucagon-like peptide (GLP)-1 receptor agonist liraglutide.

Liraglutide has been shown to be highly effective for reducing glycated hemoglobin and weight in patients with Type 2 diabetes.

However, preclinical studies of this drug in rats and mice showed an increased level of serum calcitonin, a marker of C-cell proliferation, and increased incidence of C-cell hyperplasias, adenomas, and carcinomas were observed in rats given liraglutide.

To assess if this is a rodent-specific effect, Laszlo Hegedüs (Odense University Hospital, Denmark) and co-workers evaluated data on the serum calcitonin levels of 4456 participants of the six Liraglutide Effect and Action in Diabetes (LEAD) trials and 1242 participants of three additional trials.

All the trials compared treatment with liraglutide (in various combinations with other therapies) and placebo or a comparator in patients with Type 2 diabetes. Calcitonin levels were measured at baseline and 12-week intervals for up to 2 years.

All treatment groups had serum calcitonin levels at the low end of the normal range at study initiation. They remained so throughout the trials and at 2 years the estimated mean values were 1.0 ng/l or lower, considerably lower than the upper normal range for both men and women.

Less than 2% of participants in any treatment group (liraglutide, comparator, or placebo) had a calcitonin level at or above 20 ng/l, a clinically relevant cutoff by the end of the study.

“Together, these data do not support any significant risk for the activation or growth of C-cells in humans in response to GLP-1 receptor agonists including liraglutide over the 2-year period that it has been studied,” write the authors in the Journal of Clinical Endocrinology and Metabolism.

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; 2011

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African-American Type 1 diabetes patients with an elevated retinal vein diameter are at increased risk for proliferative diabetic retinopathy (DR) and associated complications, report US researchers.

Monique Roy (University of Medicine and Dentistry, New Jersey Medical School, Newark) and colleagues assessed the association between retinal arteriolar and venular diameter in 486 African-American patients with Type 1 diabetes and progression of DR 6 years later.

At baseline, 41.5% of the participants had no DR, 35.7% had mild, 13.0% had moderate, and 9.8% had severe DR, as defined by the Early Treatment of Diabetic Retinopathy Study scoring system.

The mean retinal arteriolar and venular diameters for both eyes were 168.8 and 254.2 µm, respectively, measuring 7-14 of each vessel type for each eye on retinal photos.

Roy and team found that having a larger retinal venular, but not arteriolar, diameter in either eye was associated with an increased risk for progression to proliferative DR at 6 years. More specifically, patients in the first, second, third, and fourth quartile of venular diameter at baseline had a proliferative DR incidence of 8.6%, 14.2%, 14.2%, and 23.7%, respectively, at 6 years.

The team notes that the increased risk for progression to proliferative DR was only significant in individuals with mild-to-moderate or no DR at baseline.

“Limitations of the study include the fact that measurement of retinal vessel diameter from color retinal photographs may underestimate the true vascular width because only the red blood cell column is being measured,” write the authors in the Archives of Ophthalmology.

“It remains to be seen whether such a measure may be used in the future to monitor treatments for diabetes mellitus and other vascular diseases that specifically target the microvasculature,” conclude Roy et al.

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; 2011

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Exposure to acrylamide in foodstuffs and from smoking is associated with decreased serum insulin and insulin resistance, report researchers.

Acrylamide is a highly reactive carbonyl compound that is used in industry and has been found in a variety of fried and oven-baked foods as a result of the cooking process. It is also a component of cigarette smoke.

Lian-Yu Lin (National Taiwan University Hospital, Taipei) and colleagues evaluated the effects of acrylamide exposure on 1356 individuals with accurate measures of glucose homeostasis and hemoglobin measures of acrylamide (HbA) and its byproduct glycidamide. The participants all took part in the National Health and Nutrition Examination Survey, 2003??”2004.

As reported in the journal Diabetes Care, the team found that a 1-unit increase in log HbA was associated with a significant decrease in serum insulin (beta coefficient=-0.20) and homeostasis model assessment of insulin resistance (HOMA-IR; beta coefficient=-0.23). The associations were still valid following adjustment for various confounders.

When the participants were analyzed by subgroup, a stronger association between acrylamide exposure and insulin levels or HOMA-IR was noted in White participants and those who had ever smoked, had a low education level, or had a body mass index of less than 25 but more than 30 kg/m².

“We present the first report that acrylamide exposure is associated with both reduced blood insulin and insulin resistance,” write the authors.

“Because exposure to acrylamide in foodstuffs and smoking has become a worldwide concern, further longitudinal clinical and in vitro studies are urgently needed to elucidate the putative causal relationship,” they conclude.

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; 2009

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Poor glycemic control, presence of the metabolic syndrome, and dyslipidemia all increase the risk for erectile dysfunction (ED) in men with Type 2 diabetes, report researchers.

However, they add that increased physical activity appears to be protective against ED in these individuals.

Previous research has shown that men with diabetes have a significantly increased risk for ED, as reported by MedWire News.

In this study, Katherine Esposito (Second University of Naples, Italy) and colleagues investigated the prevalence and factors associated with ED in a group of 555 men with Type 2 diabetes, aged 35??”70 years, who were recruited consecutively on attendance of a diabetes outpatient clinic.

All the men had a body mass index of 24 kg/m2 or higher and a glycated hemoglobin (HbA1c) level of 6.5% or higher. ED was assessed using the international index of erectile function (IIEF-5) instrument.

Of the men in the cohort, 9% had mild, 11.2% had mild-to-moderate, 16.9% had moderate, and 22.9% had severe ED. The team observed that ED became more severe with increasing age.

Esposito and co-authors found that high HbA1c, presence of the metabolic syndrome, hypertension, dyslipidemia (high triglycerides, low high-density lipoprotein cholesterol), and depression were all significantly associated with ED.

Interestingly, physical activity appeared to be protective against ED in these men, as those who were most physically active were 10% less likely to have ED compared with the men who were least physically active.

“These results agree with, and encourage for implementation of current medical guidelines that put intensive lifestyle changes as the first step of the management of Type 2 diabetes,” conclude the investigators in the International Journal of Impotence Research.

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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Men with Type 2 diabetes and ED have elevated cardiometabolic risk
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Poor glycemic control linked to increased erectile dysfunction risk