After my recent comment on the concerted action of 19 eminent and self-proclaimed eminent periodontal scientists spearheaded by Drs. Borgnakke and Chapple (2014) aiming at smashing findings of a large multicenter randomized controlled trial by Engebretson et al. 2013 on HbA1c levels in type 2 diabetics with moderate or severe periodontitis, I had honestly decided not to report any more on the issue unless an updated systematic review by the Cochrane Collaboration was published. A reader of my blog had contacted CC’s Dr. Terry Simpson who promised that, due to “logistical problem[s] including difficulties with authors not supplying vital information [sic!],” they would likely be able to publish it around the turn of the year.
Now, the final paper was published yesterday in the Journal of Evidence-Based Dental Practice with a few editorial amendments. Borgnakke’s, well, rant is remarkable since it assembles (as reviewers who are also listed as authors) in essence all editors and many members of the editorial boards of our core journals in periodontology and implant dentistry as well as the editor of Journal of Dental Research. I had reported on the history of the paper here and had noted that, after a first version had been withdrawn by the authors earlier this year, Panos N. Papapanou was no longer listed as reviewer in the version which went online on 13 August 2014. Instead, Fusanori Nishimora (an editorial board member of Journal of Periodontal Research who is involved in the so-called Hiroshima Study, see below) had joined the group. While the online early version of Borgnakke’s paper had got the title “The randomized controlled trial (RCT) published by the Journal of the American Medical Association (JAMA) on the impact of periodontal therapy on glycated hemoglobin (HbA1c) has fundamental flaws,” a slightly moderated version is now provided: “The Multi-Center Randomized Controlled Trial (RCT) Published by the Journal of the American Medical Association (JAMA) on the Effect (sic!) of Periodontal Therapy on Glycated Hemoglobin (HbA1c) Has Fundamental Problems (sic!).”
Well, even Dr. Borgnakke and, I suppose, most honest clinical scientists would easily concede that problems frequently arise when conducting a randomized controlled trial. Problems are even obvious in Borgnakke’s concerns about Engebretson’s RCT. For instance, when criticizing that selected enrollment criteria of HbA1c (7-9%) were violated twice since, upon study commencement, 9 test participants had HbA1c levels in excess of 9% and 12 less than 7%, one has to concede that patients were screened before baseline exam, and HbA1c levels certainly slightly fluctuate. It is a matter of intention to treat, and deliberately omitting randomized patients would have been a rather serious flaw. When criticizing the average HbA1c level of 7.84% in the treatment group as “already close to the goal for good glycemic control,” Borgnakke may recall similar baseline values in some of the studies included in the 7 meta-analyses conducted during the past decade.
Borgnakke’s second concern relates to the modest treatment result as regards periodontal outcome. Well, this is undeniable and has been addressed by Engebretson in some detail. Borgnakke doesn’t mention that Engebretson et al. were not able to identify the slightest biological gradient, or dose-response relationship, in secondary analyses of their data. Moreover, rather than quoting old systematic reviews on what can be achieved by nonsurgical periodontal therapy in patients with chronic periodontitis not suffering from type 2 diabetes mellitus, Dr. Borgnakke should have done her homework first: present data on what can be achieved in diabetics. When looking at the study summaries in recent systematic reviews, just claiming that “previous intervention studies did manage to overcome this challenge and greatly improve periodontal health” is not enough and rather greatly misleading. This is just dishonest and indicates considerable bias.
A final concern deals with high BMI in particular in the test, apparently a common feature of type 2 diabetes mellitus in particular in the U.S. I had quoted the bumpy circular reasoning by Borgnakke et al. in my previous post already but it is worth to read it again.
The Hiroshima Study demonstrated that HbA1c levels improve by resolution of the periodontal infection-related systemic inflammation, but only in subjects with initially elevated levels of the acute-phase inflammatory marker C-reactive protein, measured with high sensitivity (hsCRP) (reference to Munenaga et al. 2013). In fact, the initial hsCRP level is a significantly important independent variable influencing HbA1c reduction rates, and the greatest reduction in HbA1c level is experienced by the group with the highest hsCRP reduction following periodontal treatment (Munenaga et al. 2013). Importantly, the subjects in the Hiroshima study (i.e. Munenaga et al. 2013) were non-obese but had type 2 diabetes. An earlier US study called Atherosclerosis Risk in Communities (ARIC) already reported that, when the BMI of the subjects was in the 20s range, there was a predicted 2-fold difference in hsCRP between severe and no/mild periodontitis groups, but the difference decreased with increasing BMI and became negligible when BMIs reached 35 kg/m2 (reference to Slade et al. 2003).
This might be an interesting finding made in a new clinical trial with an indirect relation to an older study, nothing else. When scanning the abstract it becomes instantly clear that the Hiroshima Study, the results of which have been published in April 2013, cannot easily be compared with Engebretson’s RCT, which was published eight months later.
Regarding the list of authors of Borgnakke’s final published paper I noted that two further periodontists have joined, Steven Offenbacher and Thomas Kocher. Probably desperately sought diabetologists are still missing, and that is really a serious problem of the whole enterprise. The current tempest in a tea pot will probably remain completely unnoticed by those who by definition have to care of their diabetes patients.
Borgnakke, Chapple and Genco had already an opportunity to express their dismay in a letter to the editors of JAMA which was published earlier this year and which gave Engebretson et al. the opportunity to respond. The current assault is published in a journal which is supposed to report the level of evidence or grade of quality of mainly published systematic reviews/meta-analyses. I doubt whether Borgnakke’s intimidation attempt will prevent future systematic reviewers to include Engebretson’s results in a new meta-analysis.
25 September 2014 @ 11:15 am.
Last modified March 30, 2016.