Human adenovirus-36 is uncommon in type 2 diabetes and is associated with increased insulin sensitivity in adults in Sweden

Abstract

Background. Human adenovirus-36 (Adv36) increases adiposity, but also upregulates distal insulin signaling in vitro in human adipose and muscle tissue and in vivo in the rodent independently of adiposity. Accordingly, healthy adults and children with antibodies against Adv36 had increased insulin sensitivity and reduced hepatic lipid accumulation. We hypothesized that Adv36 infection would be less frequent in individuals with type 2 diabetes or impaired glycemic control.

Methods. Presence of antibodies against Adv36 was analyzed for association to type 2 diabetes or impaired glycemic control in a two-wave population-based sample of well-characterized adults (n = 1734). Indices of impaired glycemic control included oral glucose tolerance, and circulating fasting levels of glucose, insulin, and insulin-like growth factor binding protein-1 (IGFBP-1).

Results. Adv36 seropositivity was more common in those with normal glucose tolerance (NGT) than in those with diabetes (females: OR 17.2, 95% CI 4.0–74.3; males: OR 3.5, 95% CI 1.8–6.7). Also, females with NGT had higher frequency of Adv36 seropositivity than females with prediabetes (impaired glucose tolerance and/or impaired fasting glucose; OR 1.8, 95% CI 1.1–3.1). Within the female prediabetes group Adv36 seropositivity was associated with higher insulin sensitivity reflected by reduced HOMA-IR and increased IGFBP-1.

Conclusion. Adv36 infection is associated with lower occurrence of type 2 diabetes and better insulin sensitivity in adults, particularly among females.

Key words::

• Ad36
• Adv36
• glucose tolerance
• infection

Acknowledgements

We thank Elisabeth Norén-Krog, Elvi Sandberg, Yvonne Strömberg, and Margareta Andersson at Karolinska University Hospital for their experimental support and the nurses of the health care centers who carried out the OGTTs. This work was supported by grants from the VINNOVA (2009-00223, www.vinnova.se), the Swedish Research Council (2010-3631, www.vr.se), the Karolinska Institutet Foundation (www.ki.se), the Swedish Council for Working Life and Social Research (2008-0375, www.forte.se), the Swedish Diabetes Association (www.diabetes.se), the Family Erling Persson Foundation, and the Obetech Obesity Research Center (www.obesityvirus.com).

C.L., M.A., R.L.A., M.S., C.-G.Ö., and A.H. conceived and designed the experiments. M.A. performed the experiments (guided by J.H.). C.L. analyzed the data. C.-G.Ö., A.H., J.H., and R.L.A. contributed reagents and materials. C.L. wrote the paper. M.A., A.H., R.L.A., C.-G.Ö., M.S., J.H., and K.B. revised the manuscript.

Declaration of interest: Richard L. Atkinson is the owner of Obetech, LLC which provided ELISA assay reagents to Karolinska Institutet for this study. All the analyses in this manuscript were performed at Karolinska Institutet independently of Obetech. Jia He was an employee of Obetech. The other authors report no conflicts of interest.