Autoantibodies against oxidized apolipoprotein (Apo) B peptides are potential biomarkers for diabetic retinopathy and peripheral neuropathy, while antibodies against the corresponding native peptides are potential biomarkers for macrovascular complications, report researchers in the journal Diabetologia.

There is increasing interest in identifying novel biomarkers that can be used to predict the risk of development of and monitor treatment for diabetic vascular complications.

Oxidation of low-density lipoprotein (LDL) plays a key role in the development of atherosclerosis and autoantibodies against oxidised LDL antigens such as Apo B have been linked with disease severity and the risk for developing acute cardiovascular events.

Jan Nilsson (Lund University, Malmo, Sweden) and colleagues investigated whether there is an association between autoantibodies against Apo B peptide sequences targeted by autoimmune responses (Apo B antigens p45 and p210) and vascular complications in patients with Type 2 diabetes, a disease associated with increased oxidative stress.

They assessed a total of 487 individuals with Type 2 diabetes and no history or symptoms of coronary heart disease, measuring their levels of oxidised LDL autoantibodies against native and immunogenic malondialdehyde (MDA)-modified Apo B peptides p45 and p210 using custom-made enzyme-linked immunosorbent assays.

Coronary artery calcium score was used as a surrogate marker for diabetic macrovascular complications and patients were stratified according to low-to-moderate or severe-to-extensive coronary calcification. Individuals were followed up for a mean of 2.5 years.

Patients affected by retinopathy had significantly higher levels of immunoglobulin (Ig)G against MDA-p45 and MDA-p210 than patients without retinopathy. They also had significantly higher levels of IgG against native p210 and a trend for higher IgG against native p45.

MDA-p210 IgG was also an independent predictor of the presence of neuropathy.

In contrast, patients with low-to-moderate coronary calcification had higher plasma levels of both IgG and IgM against native p45 and native p210 than patients with severe-to-extensive coronary calcification, but only IgG against p210 remained independently associated with the severity of coronary calcification after adjustment for confounding factors.

Follow-up imaging in 398 patients revealed that 119 (30%) patients with coronary calcium progression had lower plasma levels of IgG against native p45 than patients without progression; there was no association between antibodies against p210 and coronary calcium progression.

“The present observations suggest that autoantibodies against the MDA-modified ApoB peptide p210 are possible biomarkers for diabetic retinopathy and peripheral neuropathy, while antibodies against the corresponding native peptides are potential biomarkers for macrovascular complications,” conclude the authors.

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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Type 2 diabetes patients who are exposed to anti-inflammatory medication such as aspirin or statins are more than twice as likely to lose weight as those who are not, suggest investigators.

Both obesity and Type 2 diabetes have been linked to chronic inflammation and higher levels of various inflammatory markers. It has therefore been suggested that anti-inflammatory medications such as aspirin and statins may have a positive influence on obesity in Type 2 diabetic patients.

In this study, Mona Boaz (E Wolfson Medical Center Holon, Israel) and colleagues compared exposure to anti-inflammatory medication between a group of 100 Type 2 diabetes patients who lost weight (mean weight loss 3.3 kg) and 102 Type 2 diabetes patients who maintained or gained weight, over a 1-year follow-up study.

Anti-inflammatory medication consisted of aspirin ??” mean dose 78.7 mg/day, statins ??” mean dose 12.3 mg/day, or both.

As reported in the journal Diabetic Medicine, 79% of the study population overall were exposed to anti-inflammatory medication over the study period, with the proportion higher in those who had lost weight compared with those who had not at 85.0% versus 71.5%, respectively.

Boaz and team calculated that participants who had been exposed to anti-inflammatory medication during the follow-up period were 2.14-fold more likely to have lost weight than individuals who had not. This relationship was still valid after adjusting for age, gender, baseline body mass index, years since diagnosis, and comorbidities.

Individuals who were exposed to anti-inflammatory medication were older, had longer diabetes duration, and a greater prevalence of cardiovascular risk factors such as dyslipidemia, hypertension, and cardiovascular disease. The authors caution that this may be an alternative explanation for the increased weight loss seen in this group as they may have had more nutrition advice and incentive to lose weight than the other patients.

“The present findings underline the need to conduct a randomized, placebo controlled clinical trial including measures of anti-inflammatory treatment and dietary compliance to more definitively ascertain the role of anti-inflammatory treatment exposure on weight loss in obese Type 2 diabetic patients,” conclude the researchers.

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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Diabetic statin users have a lower risk for colorectal cancer than nonusers, report US researchers.

Colorectal cancer is the third most common cause of cancer and second most common cause of death in the USA. It is also particularly prevalent in diabetic individuals.

“Experimental studies indicate a potential cancer prevention effect for statins,” say Hashem El-Serag (Baylor College of Medicine, Houston, Texas) and colleagues. “However, the available epidemiological data are conflicting.”

In this study, the researchers assessed the influence of statin use on risk for colorectal cancer among 30,400 veterans with diabetes. The data were taken from national databases of the Department of Veterans Affairs and Medicare-linked files.

Overall, 6080 diabetic patients with colorectal cancer and 24,320 without the cancer were examined. The cohort members were aged 74 years on average, were 88% Caucasian, and were 99% male.

Filled statin prescriptions (87% simvastatin) were recorded for 49% of cases and 52% of controls. Mean duration of statin use was also lower in cases at 274 versus 296 days for controls.

The team calculated that the presence of a filled prescription for any statin was associated with a significant 12% reduction in risk for colorectal cancer. This association remained significant after adjustment for factors such as diabetes severity, inflammatory bowel disease, cholecystectomy, liver disease, and filled prescriptions for sulfonylurea of aspirin.

However, the significant inverse association was restricted to Caucasian patients suffering from colon cancer (not rectal cancer) who were 65 years or older and who had no previous history of polyps.

Of note, non-statin related cholesterol level and use of triglyceride-lowering medication were not linked to risk for colorectal cancer. In addition, the use of insulin did not significantly affect the influence of statins on colon cancer risk.

El-Serag and co-investigators caution that the reduction in risk observed in this study is small and likely restricted to colon cancer. They emphasize that they did not see “a clear dose??”response or duration??”response relationship between filled statin prescriptions and colorectal cancer risk.”

The results of this study are published in the American Journal of Gastroenterology.

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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