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Low blood levels of adiponectin before pregnancy were associated with a five-fold increased risk of developing gestational diabetes, a study found.
Compared with the highest quartile of adiponectin level, the risk of gestational diabetes increased with each decreasing quartile (P for trend <0.001), from an odds ratio of 1.5 (95% CI 0.7-2.9) for the second-highest quartile to 3.7 (95% CI 1.9-7.2) for the third-highest quartile, to 5.2 (95% CI 2.6-10.1) for the lowest quartile, according to , PhD, of Kaiser Permanente Northern California, in Oakland, and colleagues.
Action Points
- Note that adiponectin is an adipocyte-derived hormone which has been demonstrated to have actions consistent with protection against insulin resistance.
- Be aware that this study suggests that low adiponectin concentrations prior to pregnancy are associated with increased risk of gestational diabetes.
These results came after adjusting for family history of diabetes, body mass index (BMI), parity, race/ethnicity, cigarette smoking, glucose and insulin concentrations, they .
"Our findings are among the first to suggest that low circulating adiponectin concentrations may predict [gestational diabetes] years prior to pregnancy," the authors wrote.
The nested case-control study was based on data collected from 27,743 healthy women from whom an extra serum sample had been collected during a comprehensive voluntary checkup at the Kaiser Permanente Oakland Medical Center between 1985 and 1996.
Using the Kaiser Permanente database, the researchers then identified 4,098 of the women who gave birth between 1984 and 2009, 256 of whom had developed gestational diabetes during their pregnancies. Two controls, matched for year of blood draw, age at exam, age at pregnancy, and number of intervening pregnancies, were selected for each case.
Being overweight heightened the risk, the authors wrote. Having adiponectin levels below the median (<10.29 mg/mL) and being overweight or obese (BMI ≥ 25.0) were associated with a seven-fold increased risk for gestational diabetes compared with normal-weight women with adiponectin levels above the median (OR 6.7; 95% CI 3.6-12.5).
Adiponectin is an adipocyte-derived hormone believed to protect against insulin resistance, inflammation, and atherosclerosis. It circulates in the bloodstream as three discrete complexes. Evidence suggests that one of them -- the high molecular weight complex, or HMW -- is responsible for adiponectin's insulin-sensitizing effects.
"We found similar associations between total and HMW adiponectin and [gestational diabetes] (P for trend <0.001) even when the measurement occurred 6 or more years before pregnancy, confirming the robustness of the association," said the authors.
Women who develop gestational diabetes are at a seven-fold higher risk for developing type 2 diabetes after birth, and their children are at increased risk of obesity and diabetes. Because of this, and because of the success of some prevention strategies for type 2 diabetes, there is increasing interest in identifying pre-pregnancy risk factors and biomarkers for gestational diabetes, the authors wrote.
Other studies have documented an association between low adiponectin and risk of type 2 diabetes. And a couple of studies have suggested an association between low adiponectin and gestational diabetes. But those studies relied on blood samples taken during pregnancy. Because both total adiponectin and HMW adiponectin are known to decrease even during normal pregnancies, the results of these studies were not definitive, the authors wrote.
"The findings of our prospective study suggest that altered adiponectin levels in women with normal glucose metabolism years before pregnancy may lead to decreased glucose tolerance during pregnancy," they said. "Future studies designed to ... assess the sensitivity and specificity of adiponectin in predicting [gestational diabetes] will be valuable to help further clarify the clinical utility of these biomarkers."
There were several limitations to the study. The researchers lacked measures of adiposity beyond BMI, such as waist circumference and body fat percentage, and they were not able to assess whether the association between adiponectin and gestational diabetes was mediated by visceral fat. They also lacked information regarding changes in diet and physical activity between the baseline measure and pregnancy, so they were unable to measure the impact of lifestyle changes on gestational diabetes risk.
Additionally, the researchers had only a single measure of adiponectin, and the majority of their samples were nonfasting. Most evidence, however, suggests that fasting has either no or minimal effect on adiponectin concentrations, the authors wrote.
Disclosures
The authors disclosed no conflicts of interest.