The haptoglobin 2-2 genotype is associated with cardiac autonomic neuropathy in type 1 diabetes: the RETRO HDLc study
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The haptoglobin (Hp) 2-2 genotype has been shown to increase the risk of coronary artery disease, kidney dysfunction and mortality from cardiovascular and renal causes in type 1 diabetes (T1D). Similar associations, however, have not been observed in those without diabetes. As cardiac autonomic neuropathy (CAN) is a cardiovascular disease risk factor, we assessed the presence of an association between the Hp 2-2 genotype and CAN.
The study included 216 individuals with childhood-onset T1D and 200 individuals with normal glucose tolerance (NGT) of similar age and gender distribution to their counterparts with T1D. CAN was assessed using an electrocardiogram as an abnormal, age-specific, heart rate response to deep breathing. Multivariable logistic regression models were used to assess the association between the Hp 2-2 genotype and CAN.
Compared with NGT, participants with T1D had a similar proportion of Hp 2-2 carriers (41.5% vs. 32.0%, p = 0.05) but a greater CAN prevalence (28.2% vs. 5.0%, p < 0.0001). In multivariable logistic regression models, those carrying the Hp 2-2 genotype had significantly higher odds of CAN compared with Hp 1-1 or Hp 2-1 carriers (OR = 2.27, p = 0.01). The presence of T1D (OR = 4.20, p = 0.0003), hypertension (OR = 2.08, p = 0.03), eGFR (OR = 0.98, p = 0.01) and WBC count (OR = 1.21, p = 0.02) were also associated with CAN. There was no T1D by Hp interaction (p = 0.92), although in stratified analyses, the Hp–CAN association was significant only in T1D.
The Hp 2-2 genotype was independently associated with greater odds of CAN in T1D though no definitive conclusions could be made in NGT.
KeywordsCardiac autonomic neuropathy Haptoglobin genotype Type 1 diabetes Normal glucose tolerance
We are indebted to study participants and staff for their invaluable contributions to the EDC and RETRO HDLc studies. This research was supported by the National Institutes of Health Grant HL130153 and DK34818, and by the Rossi Memorial Fund.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The study was conducted in accordance with the principles of the Declaration of Helsinki as revised in 2008.
Human and animal rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the responsible institutional and national research committee on human experimentation and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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