When a patient is diagnosed with type 2 diabetes, the disease has usually already progressed over several years and damage to areas such as blood vessels and eyes has already taken place. To find a test that indicates who is at risk at an early stage would be valuable, as it would enable preventive treatment to be put in place. Researchers at Lund University have now identified a promising candidate for a test of this kind
‘We have shown that individuals who have above-average levels of a protein called SFRP4 in the blood are five times more likely to develop diabetes in the next few years than those with below-average levels’, says Anders Rosengren, a researcher at the Lund University Diabetes Centre (LUDC), who has led the work on the risk marker.
It is the first time a link has been established between the protein SFRP4, which plays a role in inflammatory processes in the body, and the risk of type 2 diabetes.
Studies at LUDC, in which donated insulin-producing beta cells from diabetic individuals and non-diabetic individuals have been compared, show that cells from diabetics have significantly higher levels of the protein.
It is also the first time the link between inflammation in beta cells and diabetes has been proven.
‘The theory has been that low-grade chronic inflammation weakens the beta cells so that they are no longer able to secrete sufficient insulin. There are no doubt multiple reasons for the weakness, but the SFRP4 protein is one of them’, says Taman Mahdi, main author of the study and one of the researchers in Anders Rosengren’s group.
The level of the protein SFRP4 in the blood of non-diabetics was measured three times at intervals of three years. Thirty-seven per cent of those who had higher than average levels developed diabetes during the period of the study. Among those with a lower than average level, only nine per cent developed the condition.
‘This makes it a strong risk marker that is present several years before diagnosis. We have also identified the mechanism for how SFRP4 impairs the secretion of insulin. The marker therefore reflects not only an increased risk, but also an ongoing disease process’, says Anders Rosengren.
The marker works independently of other known risk factors for type 2 diabetes, for example obesity and age.
Motivation for lifestyle changes
‘If we can point to an increased risk of diabetes in a middle-aged individual of normal weight using a simple blood test, up to ten years before the disease develops, this could provide strong motivation to them to improve their lifestyle to reduce the risk’, says Anders Rosengren, adding:
‘In the long term, our findings could also lead to new methods of treating type 2 diabetes by developing ways of blocking the protein SFRP4 in the insulin-producing beta cells and reducing inflammation, thereby protecting the cells.’ Lund University

About 10 percent of kids born with kidney defects have large alterations in their genomes known to be linked with neuro-developmental delay and mental illness, a new study by Columbia University Medical Center (CUMC) researchers has shown.
Congenital defects of the kidney and urinary tract account for nearly 25 percent of all birth defects in the US and are present in about 1 in every 200 births. Eventually, an evaluation for genomic alterations will be part of the standard clinical workup. Patients with congenital kidney disease—who are currently lumped into one category—will be placed in subgroups based on their genetic mutations and receive a more precise diagnosis.
‘This changes the way we should handle these kids,’ said kidney specialist Ali Gharavi, MD, associate professor of medicine at CUMC, associate director of the Division of Nephrology, and an internist and nephrologist at NewYork-Presbyterian Hospital.’
‘If a physician sees a child with a kidney malformation, that is a warning sign that the child has a genomic disorder that should be looked at immediately because of the risk of neuro-developmental delay or mental illness later in life,’ he said. ‘This is a major opportunity for personalising medical care. As we learn which therapies work best for each subgroup, the underlying genetic defect of the patient will dictate what approach to take.’
The current study was the result of a large collaborative effort of CUMC and other medical centers in the US, Italy, Poland, Croatia, Macedonia, and the Czech Republic. It was led by Dr. Gharavi and his colleague Simone Sanna-Cherchi, MD, an associate research scientist in CUMC’s Department of Medicine.
Until now, no studies have linked congenital kidney disease with neuro-developmental disorders.
‘If you talk to clinicians, they tell you that some of these kids behave differently,’ Dr. Sanna-Cherchi said. ‘There has been a general assumption, though, that behavioural or cognitive issues in children with chronic illnesses such as kidney disease stem from the child’s difficulty in coping with the illness. Our study suggests that in some cases, neuro-developmental issues may be attributable to an underlying genomic disorder, not the kidney disease.’
The mutations discovered by Drs. Gharavi and Sanna-Cherchi and their colleagues belong to a class of mutations called copy number variations (CNVs). CNVs are extra copies or deletions of DNA just large enough to contain several genes. When CNVs are present, the ‘dose’ of the affected genes is either lower or higher than normal, potentially leading to a health disorder.
Until the mid-2000s, when effective techniques for detecting CNVs were developed, scientists thought that CNVs caused only a small number of health disorders. Today, tens of thousands of different CNVs have been discovered and linked to several disorders—including autism, schizophrenia, and Parkinson’s disease.
To see if CNVs are involved in congenital kidney defects, Drs. Gharavi and Sanna-Cherchi scanned the genomes of 522 individuals with small and malformed kidneys from medical centres in Europe and United States. About 17 percent of the patients carried a CNV that appeared to contribute to their kidney disorder.
In studies of children with previously discovered CNVs, most of the CNVs had been linked to developmental delays or mental illness. In the current study, about 1 in 10 children had a CNV linked to developmental delays or mental illness.
Though it remains unclear why kidney malformations and neurodevelopment are linked in some cases, it is possible that the same genes involved in kidney development are involved in brain development, Dr. Gharavi said. University of Columbia

In a comparison of novel cardiovascular risk markers, coronary artery calcium, ankle-brachial index, high-sensitivity C-reactive protein, and family history were independent predictors of coronary heart disease/cardiovascular disease in intermediate-risk individuals beyond traditional risk factors, with coronary artery calcium providing superior discrimination and risk reclassification compared with other risk markers, according to a study.
‘Current trends in primary prevention of cardiovascular disease (CVD) emphasise the need to treat individuals based on their global cardiovascular risk. Accordingly, practice guidelines recommend approaches to classify individuals as high, intermediate, or low risk using the Framingham Risk Score (FRS) or other similar CVD risk prediction models. However, there is increasing recognition of the imprecision of these classifications such that the intermediate-risk group actually represents a composite of higher-risk individuals for whom more aggressive (i.e., drug) therapy might be indicated. The intermediate-risk group also contains lower-risk individuals in whom CVD might be managed with lifestyle measures alone. This recognition has motivated researchers to identify markers that could offer greater discrimination of higher- and lower-risk patients within the intermediate-risk group,’ according to background information in the article.
‘Risk markers including coronary artery calcium (CAC), carotid intima-media thickness (CIMT), ankle-brachial index (ABI), brachial flow-mediated dilation (FMD), high-sensitivity C-reactive protein (CRP), and family history of coronary heart disease (CHD) have been reported to improve on the Framingham Risk Score for prediction of CHD, but there are no direct comparisons of these markers for risk prediction in a single cohort,’ the authors write.
Joseph Yeboah, M.D., M.S., of the Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues assessed the improvements in CHD/CVD prediction accuracy and reclassification to high- and low-risk categories using CIMT, CAC, FMD, ABI, high-sensitivity CRP, and family history of CHD in asymptomatic adults classified as intermediate risk who participated in the Multi-Ethnic Study of Atherosclerosis (MESA). Of 6,814 MESA participants from 6 U.S. field centres, 1,330 were intermediate risk, without diabetes mellitus, and had complete data on all 6 markers. Recruitment spanned July 2000 to September 2002, with follow-up through May 2011. Analysis was conducted to compare incremental contributions of each marker when added to the FRS, plus race/ethnicity. Incident CHD was defined as heart attack, angina followed by revascularisation, resuscitated cardiac arrest, or CHD death. Incident CVD additionally included stroke or CVD death.
After a median (midpoint) follow-up of 7.6 years, 94 participants (7.1 percent) experienced a CHD event and 123 (9.2 percent) experienced a CVD event. After analyses, the researchers found that each of the novel risk markers was associated with incident CHD; however, after adjusting for confounders, the associations with CIMT and FMD were no longer significant. Among all of the risk markers, CAC had the strongest association. Similarly, for incident CVD, each of the markers was associated with events except high-sensitivity CRP. However, after adjusting for confounders, the associations between CIMT and FMD were no longer significant. CAC also had the strongest association in the multivariable models for CVD.
‘The current study shows that among 6 of the most promising novel risk markers, CAC provides the highest improvement in discrimination over the FRS and Reynolds score (RS) in individuals classified as intermediate risk. The present study provides additional support for the use of CAC as a tool for refining cardiovascular risk prediction in individuals classified as intermediate risk by the FRS or the RS,’ the authors write. ‘Additional research is warranted to explore further both the costs and benefits of CAC screening in intermediate-risk individuals.’
Catalan researchers identify a key component of cell division EurekAlert

Women who begin snoring during pregnancy are at strong risk for high blood pressure and preeclampsia, according to research from the University of Michigan.
The research showed pregnancy-onset snoring was strongly linked to gestational hypertension and preeclampsia, says lead author Louise O’Brien, Ph.D., associate professor in U-M’s Sleep Disorders Center.
‘We found that frequent snoring was playing a role in high blood pressure problems, even after we had accounted for other known risk factors,’ says O’Brien. ‘And we already know that high blood pressure in pregnancy, particularly preeclampsia, is associated with smaller babies, higher risks of pre-term birth or babies ending up in the ICU.’
The study is believed to be the largest of its kind, with more than 1,700 participants. It is the first study to demonstrate that pregnancy-onset snoring confers significant risk to maternal cardiovascular health.
Habitual snoring, the hallmark symptom of sleep-disordered breathing, was defined as snoring three to four nights a week. About 25 percent of women started snoring frequently during pregnancy and this doubled the risk for high blood pressure compared to non-snoring women.
O’Brien writes that these results suggest that up to 19 percent of hypertensive disorders during pregnancy might be mitigated through treatment of any underlying sleep-disordered breathing.
Pregnant women can be treated for sleep-disordered breathing using CPAP (continuous positive airway pressure). It involves a machine, worn during sleep, that uses mild air pressure to keep the airways open. It is possible that use of CPAP may decrease high blood pressure in pregnant women, and O’Brien has such a study currently underway to test this hypothesis.
‘Hypertensive disorders of pregnancy are a leading global cause of maternal and infant deaths and cost billions of dollars annually to treat,’ O’Brien says. University of Michigan Health System

Favourable results have led to crizotinib gaining approval for the treatment of advanced stage ALK-positive non-small cell lung cancer (NSCLC) in Japan, the United States, Canada, and several other countries in Europe and Asia. Now, the identification of an effective therapy for ALK-positive NSCLC places great emphasis on rapid, accurate, and cost-effective way to find patients with this subtype of lung cancer. A recent study concludes immunohistochemistry (IHC) is a reliable screening tool for identification of ALK rearrangement.
Fluorescence in situ hybridisation (FISH) is the current standard method to detect ALK rearrangement. However, FISH is not readily available as a routine method of pathology practice in most laboratories because it is time consuming and requires advanced technical and professional expertise. In contrast, IHC is relatively inexpensive, faster, and is perfectly adapted for routine practice by academics and most community hospitals.
Researchers screened 377 stage I or II NSCLC cases, diagnosed between 1978 and 2002. Tissue microarray results were available on 377 cases by IHC and 273 cases by FISH. Eleven cases were positive or possibly positive by either IHC or FISH, and three cases were positive or possibly positive by both methods.
They found, ‘that all cases exhibiting ALK rearrangement demonstrated adenocarcinoma histology.’ Their results report a sensitivity of 100 percent and high specificity with the IHC with no false-negative results. While researchers acknowledge that further study involving a larger cohort is recommended, IHC is a valid screening test. The International Association for the Study of Lung Cancer