Elevations of inflammatory cytokines during and after pregnancy in gestational diabetes

Increased insulin resistance in Type 2 diabetes relates to systemic inflammation. Gestational diabetes mellitus (GDM), a known risk factor for Type 2 diabetes, can coincide with high inflammatory marker levels (1). One suggested model sees obesity as mediating the systemic inflammation causing insulin resistance and impaired glucose tolerance (2-4). Little is known about the anti-inflammatory pattern in GDM patients (5). Hence our interest in evaluating inflammatory and anti-inflammatory markers in GDM and normal glucose-tolerant (NGT) women during and after pregnancy. Thirty GDM and 30 NGT women were enrolled among women routinely screened for GDM at our Diabetic Care Unit according to American Diabetes Association recommendations (6). Cases of chronic inflammatory disease or infections, or on antiinflammatory drugs were excluded. Our GDM women had higher inflammatory marker levels in late pregnancy, as reported elsewhere (1); this lowgrade inflammation persisted 6 months after delivery (8), but no relationship emerged between BMI and inflammatory markers, in contrast with Winkler (4) and Retnakaran (2), but consistent with Leipold (3), suggesting that impaired glucose metabolism is important per se in causing subclinical inflammation, as well as obesity (3). Though our GDM patients had a higher insulin resistance than controls, no such relationship emerged between HOMA and inflammatory marker levels (1-3); insulin resistance may still be important, however, since HOMA mainly reflects changes in hepatic insulin sensitivity (9). The high IL6/IL10 ratio in pregnancy suggests inflammatory cytokine downregulation and antiinflammatory cytokine upregulation, a situation amplified in GDM, and the high IL10 levels seen in pregnant women (5) suggest a role for IL10 in maintaining pregnancy. After delivery, our GDM women had normal glucose tolerance and HOMA, but higher IL6 and IL10 levels. Despite persistently high IL10 levels (protecting against or delaying the onset of Type 2 diabetes), the IL6/IL10 ratio suggests ongoing inflammation. This study has some limitations, e.g. relatively few patients and a short follow-up, and having considered only HOMA as a marker of insulin resistance. Its strength and novelty lie in our assessing women both during and after pregnancy, considering inflammatory and anti-inflammatory markers. In conclusion, we found an inflammatory and anti-inflammatory marker modulation in women with GDM, the possible role of which in any future onset of Type 2 diabetes needs to be clarified.