There is still controversy about the meaningfulness of HbA1c reduction in diabetics upon non-surgical periodontal therapy. One may get the impression that the number of systematic reviews (SR) on the issue surpasses the number of quality randomized clinical trials (RCT). The most current update by the Cochrane Collaboration (Simpson et al. 2015) had concluded that,
There is low quality evidence that the treatment of periodontal disease by SRP [scaling and root planing] does improve glycaemic control in people with diabetes, with a me an percentage reduction in HbA1c of 0.29% at 3-4 months; however, there is insufficient evidence to demonstrate that this is maintained after 4 months.
I will stick to that statement although I am fully aware that attempts are being made by representatives of our profession of considering rather systematic reviews of SRs as if that would lead to other research outcomes. For still interested readers, I have reported and discussed the issue in numerous blog posts, see e.g. here, here and here.
Treating all kinds of systemic ailments by proper scaling and root planing has been an illusion of certain periodontists for some time. As a healthy antidot, one should carefully read an interview with Jan Lindhe, published some time ago, where he warned us:
I think that the dentist’s area is pretty well described – it’s intraoral and also maxillofacial in a sense but the dentist shouldn’t be a pseudo-doctor for all types of disorders. (Emphasis added.)
In a recent editorial in Quintessence’s Oral Health & Preventive Dentistry, Kocher & Holtfreter (2017) had asked, “Is the prevalence of periodontitis declining or not?” and had referred to the “landmark paper” by Kassebaum et al. (2014) in which the “global burden of severe periodontitis” was estimated at about 11%, or 743 million. The first Kassebaum paper had sparked considerable interest claiming that severe periodontitis was, in 2010, “the sixth most prevalent condition in the world.”
As with all Global Burden of Disease (GBD) reports, in the paper by Kassebaum et al. (2014) data of a large number of very heterogenous epidemiological studies was used from all over the world and metaregression done. Published studies were supplemented with hand searches of reference lists of relevant publications and textbooks, government and international health organizations web pages, even conference reports, theses, government reports and unpublished survey data (gray literature).
Based on 65 prevalence studies, but only 2 (or 3; reported numbers differ in the flow chart describing selection of studies, and text) incidence studies as well as 5 (or 6) mortality (sic!) studies, Kassebaum et al. (2014) were able to estimate prevalence patterns in 1990 and 2010 (which strangely appear to be static) and made the strong claim (based on 2 or 3 studies) that incidence of severe periodontitis peaks at about age 38 years with more than 2000 new cases per year among 100,000.
Garbage in, garbage out?
A few words on heterogeneity of data. Kassebaum et al. (2014) had “identified 3 comparable quantitative indicators” of severe periodontitis, i.e. CPITN score of 4, attachment loss of >6 mm, and pocket depth of >5 mm. Taken as a singular observation, none of these indicators, per se, would actually point to “severe periodontitis” which would be considered a much more serious disease. Extent of the disease is of importance when describing periodontal disease, something which periodontists are or should be aware of. Mixing partial and full-mouth probing in the various studies considered is another caveat (or flaw) in Kassebaum’s analysis. One might instantly think, garbage in – garbage out.
In a recent commentary in the Journal of Periodontology, Merchant and Josey (2016) had suggested directed acyclic graphs to better comprehend the partly conflicting results from randomized controlled trials (RCT) on diabetic control after periodontal treatment in diabetic patients. In particular the influence of obesity caught their attention.
As a matter of fact, a remarkable number of systematic reviews (whose varying quality have recently been reviewed in at least two further SRs of SRs) have shown that numerous small-scale, single-center, often poorly designed RCTs had shown that the marker for diabetic control, HbA1c, might be reduced by, say 0.4% 3 months after in essence non-surgical periodontal therapy. The only large-scale, multi-center trial (DPTT) by Engebretson et al. (2013) couldn’t confirm that, though, which sparked harsh criticism of a large number of our thought leaders. A professor in the Department of Epidemiology and Biostatistics at the University of South Carolina, Columbia, Dr. Anwar Merchant himself had written a letter to the editors of JAMA pointing first to the fact that most participants in the paper by Engebretson et al. were utterly obese. He had further noticed that, “[i]n RCTs conducted among mostly nonobese individuals, periodontal treatment has been shown to reduce systemic inflammation2,4 and improve glycemic control among those with type 2 diabetes.2 However, periodontal treatment has not been shown to affect glycemic control in RCTs conducted among predominantly obese individuals with type 2 diabetes.1,3”
Obesity is positively correlated with inflammatory markers in the blood and strongly related to insulin resistance and metabolic dysregulation mediated by chronic systemic inflammation.5 These findings, taken together with results from RCTs evaluating the effects of periodontal treatment, suggest that the lack of effect of periodontal treatment on glycemic control observed in the study by Engebretson et al may be attributed to the high level of obesity in the study population. Therefore, the findings may be generalizable only to predominantly obese populations with type 2 diabetes.
Currently, teachers experience a general problem, a surge of published systematic reviews where slightly modified search criteria have led to slightly different bunch of papers with slightly different results of meta-analyses. Systematic reviews have once been welcomed as valuable tool to either end a story once and forever (if evidence for or against a certain treatment or association was overwhelming), or call for more conclusive randomized controlled trials (RCT) after still open questions had been identified. If, after any new RCT, editors of our professional journals would accept considering a new systematic review for publication, which basically ruminates already published RCT summaries but adds just another study without changing main conclusions, it will in fact become difficult to keep pace with what some call “emerging evidence”.
One main reason why evidence based medicine has to be taught to undergraduate students is to provide future health care workers with proper tools and train specific skills to conduct brief systematic reviews of identified randomized controlled trials themselves. Here on this blog, I had posted a couple of quick examples, see here, here and here.
In particular the latter of the above examples has dealt with the question whether the large multi-center trial by Engebretson et al. (2013), which had reported no effects of periodontal therapy on HbA1c levels in diabetics, would nullify the conclusion (that nonsurgical periodontal treatment may reduce HbA1c levels by about 0.4%) of previous meta-analyses of smaller and mainly single-center RCTs with similar settings.
Engebretson et al. (2013) had listed possible shortcomings of their study. However, that oral hygiene of study participants had not improved was considered by most of our professional leaders scandalous. Further issues for unprecedented criticism included “nearly normal” HbA1c levels at the outset and extreme obesity of participants. Engebretson’s unwelcome results had been reviled by an armada of 21 editors of our key journals, presidents of our main scientific societies, and further periodontal experts. Criticism had culminated in a very strange recommendation.
“Given the inconlusive nature of these data, we recommend that the existing body of evidence in which meta-analyses consistently conclude that successful periodontal therapy appears to improve glycemic control, should instruct us until results from future studies are reported. We urge all interested parties to refrain from using these study results as a basis for future scientific texts, new research projects, guidelines, policies, and advice regarding the incorporation of necessary periodontal treatment in diabetes management.” (My emphasis.)
In other words, forget about Engebretson et al. and continue quoting more favorable results from existing meta-analyses of RCTs on the effect of periodontal therapy on diabetes control. A quick analysis revealed that it won’t nullify a mean HbA1c reduction in diabetics by nonsurgical periodontal therapy, but that considerable heterogeneity was introduced by including Engebretson’s study which may in fact lower the grade of evidence. I had entered meta-data of Engebretson and Kocher 2013 in an amazing tool for meta-analysis and had added findings by Engebretson et al. (2013). That might have been premature, see below.
In an announcement for his talk about periodontal treatment effects on type 2 diabetes at Europerio 8 in London later this year, exasperated Professor Thomas Kocher of Greifswald University in Germany promises to “dissect” the large multicenter trial by Engebretson et al. (2013) who could not find an effect on glycated hemoglobin in type 2 diabtes mellitus. The study had been published in late 2013 in JAMA, not in New England (Journal of Medicine). The large multicenter trial had long been attacked for not yielding the desired results (“a publication which we were really waiting for”).
Kocher was asked to talk in London about “why all the other small studies showed an effect” and he wants to find out “the issues why we [?] couldn’t see anything in the Engebretson study”. Well, it was actually Wenche Borgnakke who had got 20 other “reviewers” aboard who had already dissected the study by Engebretson et al. and has called for censorship.
As noted by Engebretson and Kocher 2013 in one of the numerous previous systematic reviews of RCTs on the effect of nonsurgical periodontal therapy and reported in Table 1 of their article, problems with the design of these small-scale, mainly single-center studies, which included some trials with adjunctive antibiotics, were plentiful. Problems with low and high baseline HbA1c levels and with questionable periodontal outcomes had been reported as well. Engebretson and Kocher (2013) report possible publication bias which means nothing else that studies without an effect on HbA1c might have gone unpublished. Based on this particular and numerous other systematic reviews, the evidence that nonsurgical periodontal therapy in fact has a relevant beneficial effect on HbA1c levels in type 2 diabetics may actually be regarded moderate. The study by Engebretson et al. adds heterogeneity to any meta-analysis which may downgrade this evidence to low. That is what our thought leaders alerts. That’s why censorship.