Pregnant women with type 1 diabetes have a preeclampsia risk 2 to 4 times higher than that of women without the condition, and now researchers think they have identified some novel markers that may help identify diabetic women most at risk.
Valerie A. Holmes, PhD, senior lecturer at the Centre for Public Health, School of Medicine, Dentistry, and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, and colleagues assessed levels of angiogenic and antiangiogenic compounds found in the maternal serum of women with type 1 diabetes in their second trimester and found that abnormal levels of these markers were present in those who developed preeclampsia.
The study, the largest of its kind to date, “would suggest that these markers may have additional predictive risk above and beyond traditional clinical risk factors,” said Dr. Holmes. The study waspublished online August 6, 2013 in Diabetes Care.
“Previous studies have reported altered angiogenic profiles in women at risk of preeclampsia, but few have specifically looked at women with type 1 diabetes,” Dr. Holmes told Medscape Medical News in an email. “Our findings, in a carefully characterized population of women with type 1 diabetes, demonstrate that adding measures of [these] factors to established clinical risk factors significantly improves the prediction of preeclampsia. These results are an important step on the road to establishing a preeclampsia ‘risk score’ for women with type 1 diabetes.”
Some Interest in Commercial Development of Tests
The researchers studied 540 women participating in the Diabetes and Preeclampsia Intervention Trial (DAPIT), which enrolled patients from 25 centers across Scotland, Northern Ireland, and England between April 2003 and June 2008. Blood samples were taken at 26 weeks’ gestation and analyzed by laboratory staff members who were blinded to each woman’s preeclampsia status.
The association of angiogenic factors, such as placental growth factor (PlGF) and antiangiogenic factors — such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) — with preeclampsia was determined through logistic regression analysis adjusted for age, body mass index (BMI), diabetes duration, parity, history of preeclampsia, current smoking, and clinical parameters such as blood pressure, hemoglobin A1c, and renal function.
Of the 540 women included in this study, 94 (17%) developed preeclampsia, and 198 (37%) gave birth prematurely (before 37 weeks’ gestation), including 61 women with preeclampsia (65% of women with preeclampsia, compared with 31% of women without preeclampsia; P < .001).
The scientists observed significantly higher levels of sFlt-1 and sEng and significantly lower levels of PlGF, as well as altered ratios of these antiangiogenic and angiogenic factors, during the second trimester in women who later developed preeclampsia compared with those who did not.
“Our findings show that established clinical risk factors, such as previous history of preeclampsia, age, BMI, diabetes duration, parity, blood glucose control, and blood pressure, are indeed reliable indicators of risk in this population,” Dr. Holmes told Medscape Medical News. But the results “also suggest that angiogenic factors provide added clinical value when predicting risk,” she said.
“These findings need to be validated in another group of women with diabetes before incorporating routine testing into the clinical context. Once they are validated, the next step would be to develop a ‘risk score’ for women with diabetes, based on a combination of established risk factors and angiogenic-factor results.”
The tests for angiogenic factors are currently restricted mainly to research settings, she noted, but there is commercial interest in developing such assays.
“With increasing evidence of the role of angiogenic factors in the pathogenesis of preeclampsia, several companies have developed commercially available assays for at least one of the angiogenic factors we investigated, PlGF, to assist with preeclampsia diagnosis and screening. It is possible that in the future, and with further testing, these assays may emerge as part of routinely available screening test to assist clinicians in determining risk,” she said.
Source: Diabetes Care.
,”san�9rf0����east-font-family:”Times New Roman“; color:black’> ABCG2 (p<0.01), the group writes. In the 134 patients on atorvastatin, explainable blood-level variability was split between two polymorphisms in SLCO1B1 (p<0.01 and p<0.05, respectively) and the activity of cytochrome P3A (CYP3A). The analyses were adjusted for gender, age, body mass index, ethnicity, statin dose, and time from last dose, and echo a 2008 study which concluded that two SLCO1B1 variants were associated with simvastatin-related myopathy, as reported by heartwire . The screening concept is currently being applied to simvastatin therapy at least at one major center.
The group retrospectively tested their ideas, looking at the relationships between genotypic and clinical variables and statin dose, in a validation cohort of 579 patients taking either drug in a primary care setting in the US and at a referral clinic in Canada.
The group found that the transporter genotypes that raise statin concentrations were homogeneously distributed among patients taking a range of atorvastatin and rosuvastatin dosages. That is, the prescribing physicians, armed primarily with their clinical judgment to decide dosage levels, failed to achieve optimal dosing with respect to serum drug levels. But it seemed to be only patients receiving the highest dosages who showed higher-than-safe serum levels according to genotype- and age-based criteria.
“Although we didn’t quite get to the sample size we needed, it did seem like people with the wrong genetic makeup are more likely to stop a statin or switch to [another dyslipidemia drug],” Kim said, at least among patients on the highest statin dosages.
The group’s proposed management algorithm recommends a maximum statin dosage that will result in plasma concentrations below the 90th percentile (reflecting an assumption that 10% of patients will have statin-related muscle issues) based on patient age and transporter-related genotype.
The algorithm is based on data predominantly from whites; the group cautions that some other ethnicities, “particularly Asians,” have increased sensitivity to statins.