PHILADELPHIA — New data from three subanalyses of the Atherosclerosis Risk in Communities study have identified several novel risk factors for type 2 diabetes, including a cardiovascular hormone, liver enzymes and alternative glycemic markers, researchers said here at the American Diabetes Association’s 72nd Scientific Sessions.
Influence of NT-proBNP
Recent studies suggesting a link between natriuretic peptide levels and diabetes prompted Mariana Lazo, MD, PhD, and colleagues to evaluate the prospective association of N-terminal b-type natriuretic peptide (NT-proBNP) with incidence of diagnosed diabetes in those without diabetes or CVD at baseline. They conducted a prospective analysis of 7,822 participants (mean age, 62 years) in the Atherosclerosis Risk in Communities (ARIC) study.
During a median follow-up of 12 years, results revealed lower incidence of diabetes in participants with NT-proBNP levels in the upper quartile when compared those in the lowest quartile. Data also showed that those in the lowest quartile were much more likely to develop diabetes than those in the upper quartiles. Moreover, these trends persisted after adjustment for sociodemographics, BMI and height, CVD risk factors, fasting glucose and family history of diabetes, with patients in the upper quartile remaining 22% less likely to develop diabetes.
“We found a strong independent inverse association between NT-proBNP and incidence of diabetes, showing a potential causal effect of NT-proBNP on glucose metabolism,” Lazo said during her presentation.
Stearoyl CoA desaturase activity
Lisa Chow, MD, of the University of Minnesota, also presented results from an analysis of participants enrolled in ARIC. She and colleagues aimed to assess the potential association of stearoyl CoA desaturase (SCD-1) — the rate-limiting enzyme in monounsaturated fatty acid synthesis — with incident diabetes.
The researchers used plasma fatty acid ratios in cholesterol esters (SCD16c=16:1n-7/16:0, SCD18c=18:1n-9/18:0) and in phospholipids (SCD16p=16:1n-7/16:0, SCD18p=18:1n-9/18:0) to approximate hepatic SCD-1 activity and then examined the development of incident diabetes over time.
Of the nearly 2,800 participants included in their analysis, 7.6% developed diabetes during an average of 8 years of follow-up. After adjustment for age and sex, the researchers found positive associations between higher levels of SCD16c and SCD16p and incident diabetes, but an inverse association for SCD18p and incident diabetes. After further adjustment for parental history of diabetes, smoking, blood pressure, activity, carbohydrate intake, fiber intake, fat intake, lipid composition, waist-to-hip ratio, education, alcohol and BMI, only SCD16c remained positively associated with incident diabetes (HR=1.1: 95% CI, 1.01-1.30; P=.03) — a trend that persisted after adjustment for baseline insulin resistance (P=.05).
“Of all the different measurements of SCD-1 activity, SCD16c had the strongest association with incident diabetes, which is further supported by a positive association of SCD16c with known type 2 diabetes risk factors such as BMI, waist-hip ratio and baseline insulin resistance. These findings suggest a possible role between SCD-1 and incident diabetes in humans,” Chow said. “But further refinement of SCD-1 measurements and validation in other cohorts is recommended.”
Beyond traditional glycemic markers
Another analysis of data from ARIC evaluated the utility of alternatives to conventional indicators of diabetes, including HbA1c and fasting glucose.
Stephen P. Juraschek, of Johns Hopkins University, and colleagues examined 1,229 ARIC participants (mean age, 70 years) without diabetes at baseline. They measured three alternative markers of glycemic control — glycated albumin, fructosamine and 1,5-anhydroglucitol (1,5-AG) — in stored serum samples and followed participants for approximately 3 years.
During follow-up, 119 participants self-reported a diagnosis of diabetes. Results indicated that participants with fructosamine and glycated albumin levels in the upper quartiles had a higher risk for diabetes than those in the lower quartiles. Further, risk for the disease rose as these levels increased. Data also showed that participants with 1,5-AG levels in the lowest quartile had a significantly lower risk for diabetes when compared with those in the upper quartiles. These trends, Juraschek said, persisted even after adjustment for multiple factors, including baseline HbA1c, and were on par with the performance of traditional markers for predicting diabetes risk.
“Significant associations between fructosamine, glycated albumin and 1,5-AG and diabetes risk were independent of fasting glucose, HbA1c,” Juraschek said. “Future studies should look at alternative markers and long-term complications of diabetes. Furthermore, they should evaluate the performance of these markers in patient populations where traditional markers are less valid.” – by Melissa Foster
For more information:
- Drs. Chow and Lazo and Mr. Juraschek report no relevant financial disclosures.