The presence of xerostomia and hyposalivation is frequent among diabetes mellitus (DM) patients. It is not clear if the presence of xerostomia and hyposalivation is greater in DM than non-DM patients. The aims of this systematic review are (1) to compare the prevalence rates of xerostomia, (2) to evaluate the salivary flow rate, and (3) to compare the prevalence rates of hyposalivation in DM versus non-DM population. This systematic review was conducted according to the PRISMA group guidelines by performing systematic literature searches in biomedical databases from 1970 until January 18th, 2016. All studies showed higher prevalence of xerostomia in DM patients in relation to non-DM population, 12.5%–53.5% versus 0–30%. Studies that analyzed the quantity of saliva in DM population in relation to non-DM patients reported higher flow rates in non-DM than in DM patients. The variation flow rate among different studies in each group (DM/CG) is very large. Only one existing study showed higher hyposalivation prevalence in DM than non-DM patients (45% versus 2.5%). In addition, quality assessment showed the low quality of the existing studies. We recommend new studies that use more precise and current definitions concerning the determination and diagnosis of DM patients and salivary flow collection.
Diabetes mellitus (DM) is an endocrine disease characterized by a deficit in the production of insulin with consequent alteration of the process of assimilation, metabolism, and balance of blood glucose concentration. DM has become a worldwide public health problem. In recent years, the global prevalence of DM has increased substantially, reaching 8.3% in 2014, which corresponds to 387 million patients [
Xerostomia is a subjective complaint of dry mouth, whereas hyposalivation is an objective decreased of salivary flow. The clinical method most often employed for the diagnosis of salivary dysfunction is a sialometry test. Hyposalivation is considered to appear when salivary flow rates are under 0.1 mL/min at rest (UWS) or 0.7 mL/min under stimulation (SWS). Xerostomia is often associated with hyposalivation, but not always. And many cases of xerostomia have been described in patients with a normal salivary flow rate [
Several factors are capable of inducing salivary disorders in DM patients such as ageing, head and neck radiotherapy, systemic disorders, and several drugs [
Both types of DM, T1DM and T2DM, have been associated previously with xerostomia [
Considerable debate exists surrounding the issue, if the presence of xerostomia and hyposalivation is greater in DM than non-DM patients. No systematic review has been performed up to now. Given the lack of systematic knowledge, we have conducted the first systematic review concerning the prevalence of xerostomia and hyposalivation in DM (compared to non-DM) patients. We also have analyzed the differences in the rate of salivary flow between DM and non-DM patients.
The main objectives of this review were (1) to compare the prevalence rates of xerostomia in the DM and non-DM population, (2) to evaluate the salivary flow rate in the DM and non-DM population, and (3) to compare the prevalence rates of hyposalivation in the DM and non-DM population.
The systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [
Based on the PRISMA guidelines, 3 focused questions were constructed. The addressed focused questions (PICO) were as follows: (1) Do DM patients have higher xerostomia prevalence than non-DM patients? (2) Is the salivary flow rate lower in DM patients compared to non-DM patients? (3) Do DM patients have higher hyposalivation prevalence than non-DM patients?
A comprehensive literature search was conducted by searching the international biomedical literature databases. PubMed/MEDLINE (National Library of Medicine, Bethesda, Maryland), Scopus, and Cochrane database were searched from 1970 until January 18th, 2016, using different combinations of the following keywords: diabetes; xerostomia; dry mouth; hyposalivation; and salivary flow. Moreover, we performed an additional handsearch to find potential eligible studies as reference lists of review articles and relevant studies.
Full-text articles were included if they met the inclusion criteria with respect to types of studies, types of population, and the main outcome/s regardless of the time period of study and the year of publication.
Studies were excluded if they were published in a language other than English. They were also excluded if they solely reported prevalence of xerostomia/hyposalivation and salivary flow rates among persons with DM in relation to the total population (DM and non-DM) and not exclusively to the diabetic (possibly compared to the non-DM) population.
Two authors (Rosa María López-Pintor and Elisabeth Casañas) independently screened all the retrieved titles and abstracts identified through the search strategies to identify potentially eligible articles. Full texts of relevant studies judged by title and abstract were read and independently assessed with reference to the eligibility criteria by two authors (Rosa María López-Pintor and José González-Serrano). Disagreements were resolved by discussion with a third reviewer (Julia Serrano). Data extraction was performed including information about first author, publication year, country, study population, mean age, type of DM, DM diagnosis (if available), definition of xerostomia, definition of hyposalivation (if available), type of flow rate, and data sources of the study. With regard to the results, xerostomia prevalence (%) and salivary flow rate (mL/min), as well as hyposalivation prevalence (%) of DM and non-DM groups, were extracted. The reported statistical signification was extracted if it was available.
In the final selection of eligible studies, we assessed features that could potentially bias the estimates of xerostomia/flow rate/hyposalivation using the Joanna Briggs Institute Prevalence Critical Appraisal Tool (Table
JBI critical appraisal checklist for studies reporting prevalence data.
Assessment items | Yes | No | Unclear | Not applicable |
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Critical appraisal was conducted by two reviewers (Gonzalo Hernández and Lucía Ramírez) independently of each other. The reviewers met to discuss the results of their critical appraisal; if the two reviewers disagreed on the final critical appraisal and could not be resolved through discussion, a third reviewer (Julia Serrano) was required.
Due to the high heterogeneity of the studies, we analyzed the outcomes of interest in accordance with the prevalence of xerostomia or salivary quantity flow rate/hyposalivation (if available), type of DM, and age (adults ≥ 19 years old/children and adolescents). There were studies that reported xerostomia prevalence and flow rate; therefore, there could be two groups. The following categories were the result: (1) xerostomia studies in adults T2DM, (2) xerostomia studies in adults NIDDM, (3) xerostomia studies in children and adolescents T1DM, (4) salivary flow rate studies in adults T1DM, (5) salivary flow rate studies in adults IDDM, (6) salivary flow rate/hyposalivation prevalence studies in adults T2DM, (7) salivary flow rate/hyposalivation prevalence studies in children and adolescents T1DM, and (8) salivary flow rate/hyposalivation prevalence studies in children and adolescents IDDM.
The results of xerostomia prevalence from the included studies were presented as a percentage. The results of quantity salivary flow rate were presented as mean
Due to heterogeneity of results, we did not perform a meta-analysis.
The initial search yielded 53 studies. Thirty-eight studies, which did not fulfill the eligibility criteria, were excluded (the Appendix). A total of 15 articles were included and processed for data extraction. The selection procedure is presented in Figure
Flowchart of the systematic review process.
With regard to the main outcome, 7 papers considered xerostomia prevalence (Table
Xerostomia prevalence studies.
Author, publication year, country | Study population (DM/CG) | Mean age (years) DM/CG | Type of diabetes | DM diagnosis | Definition of xerostomia | Xerostomia DM/CG% | Significant association | Matched variables (DM/CG) | JBI scoring |
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( | |||||||||
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Vasconcelos et al. 2010, |
40/40 |
57.7 ± 8.9/50.2 ± 12.3 | T2DM | NS | Does your mouth feel dry frequently? | 12.5%/2.5% | No | Gender |
3 |
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Bernardi et al. 2007, |
82/18 |
PC 54.3 ± 10.1; |
T2DM | WHO criteria 2006 |
Does your mouth usually feel dry? | 52.43%/0% |
Yes |
Age | 4 |
|
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Sandberg et al. 2001, |
102/102 |
64.8 ± 8.4/64.9 ± 8.5 | T2DM | NS | Patient’s subjective feeling of dry mouth | 53.5%/28.4% | Yes |
Age |
5 |
|
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Chavez et al. 2000, |
29/23 |
(i) Mean age NS |
T2DM | Blood glucose levels ≥ 140 mg/dL at 2 hours after oral glucose tolerance test | Does your mouth frequently feel dry? |
Data not shown | No | Age |
2 |
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( | |||||||||
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Zielinski et al. 2002, |
32/40 |
71 ± 7/74 ± 8 | NIDDM | NS | Does your mouth frequently feel dry? |
50%/30% | No |
Gender |
3 |
|
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( | |||||||||
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Javed et al. 2009, |
48/40 |
15 (10–19)/14.6 (10–19) | T1DM | NS | Does your mouth usually feel dry, especially during meals? | WCDM = 80% |
Yes (DM/CG) | Socioeconomic status | 3 |
DM, diabetes mellitus; WCDM, well controlled diabetes mellitus; PCDM, poorly controlled diabetes mellitus; CG, control group; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; NIDDM, non-insulin-dependent diabetes mellitus; JBI, Joanna Briggs Institute Prevalence Critical Appraisal Tool.
Salivary flow rate/hyposalivation studies.
Author, publication year, country | Study population (DM/CG) | Mean age (years) DM/CG | Type of diabetes | DM diagnosis | Type and QFR mL/min | Definition of hyposalivation | Hyposalivation in DM/CG% | Significant association | Matched variables (DM/CG) | JBI scoring |
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Edblad et al. |
41/41 |
21 (1.6)/21 (1.6) | T1DM | NS | SWS (paraffin, spitting method) |
— | — | Nonsignificant (NS) | Age |
6 |
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Ben-Aryeh et al. |
35/31 |
31.2 ± 7.4/29 ± 6.2 | IDDM | NS | UWS (spitting method) 0.35 ± 0.24/0.48 ± 0.23 | — | — | Yes |
Age |
2 |
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Lasisi and Fasanmade |
20/20 |
58.4 ± 10.6/50.2 ± 9.2 | T2DM | NS | UWS (spitting method) |
— | — | Yes |
Gender | 3 |
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Vasconcelos et al. |
40/40 |
57.7 ± 8.9/50.2 ± 12.3 | T2DM | NS | UWS and SWS (spitting method) |
UWS < 0.1 mL/min |
45%/2.5% | Yes |
Gender |
3 |
|
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de Lima et al. |
30/30 |
60 (9)/63 (12) | T2DM | Fasting blood glucose |
SWS 0.95 (0.61)/1.14 (0.87) | SWS < 0.7 mL/min | NS | Nonsignificant |
Gender |
3 |
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Bernardi et al. |
82/18 |
PC 54.3 ± 10.1; |
T2DM | WHO criteria |
SWS (spitting method), |
— | — | Yes |
Age | 4 |
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Dodds et al. |
243/240 |
Age is specified by sex per group |
T2DM | Modified WHO criteria |
UWS 0.36/0.44 |
— | — | UWS and USP: nonsignificant; USS and SSS: significantly reduced in DM | NS | 5 |
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Chavez et al. |
29/23 |
(i) Mean age NS |
T2DM | Blood glucose levels ≥ 140 g/dL at 2 hours after oral glucose tolerance test | DM/CG/WCDM/PCDM |
— | — | Nonsignificant (DM/CG) |
Age |
2 |
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( | ||||||||||
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Alves et al. |
51/51 |
11.3 ± 3.4/11.9 ± 3.4 | T1DM | American Diabetes Association criteria (2010) | UWS (spitting method) 0.26 ± 0.14/0.41 ± 0.28 | UWS < 0.3 mL/min | NS | Yes |
Socioeconomic status |
2 |
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Javed et al. |
48/40 |
15 (10–19)/14.6 (10–19) | T1DM | NS | UWS (spitting method) |
— | — | DM/CG, yes |
Socioeconomic status | 3 |
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López et al. |
20/21 |
9.4 ± 3.9/8.3 ± 1.8 | IDDM | NS | UWS = saliva 5 min production collected with sterile syringe |
— | — | Yes (NS) | Gender |
1 |
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Belazi et al. |
10/10 |
6.8 (4–15)/10.5 (5–17) | IDDM | NS | UWS (spitting method), 0.79 ± 0.46/1.06 ± 0.37 | NS | — | Nonsignificant ( |
NS | 1 |
DM, diabetes mellitus; CG, control group; QFR, quantity of flow rate; NS, nonspecific; WC, well controlled; PC, poorly controlled; UWS, nonstimulated salivary flow; SWS, stimulated salivary flow; USP, nonstimulated parotid flow; SSP, stimulated parotid flow; USS, nonstimulated submandibular/sublingual flow; SSS, stimulated submandibular/sublingual flow; JBI, Joanna Briggs Institute Prevalence Critical Appraisal Tool.
We found 7 studies about xerostomia prevalence that met our inclusion criteria. Two of them, written by Sandberg et al. [
With respect to the recruitment of patients, three studies had selected their DM patients from an endocrinology service or a diabetic care unit of a specialized medical care or hospital, two from a geriatric center and one (the two studies realized by Sanberg et al. [
DM and CG participants were matched by gender in 4 studies, by age in 5 studies, by race distribution in one, by diuretics and antidepressants treatment in one, and by socioeconomic status in another one. With regard to statistical significance, three studies [
Regarding quality assessment all studies obtained scores ≤5; therefore the studies were evaluated as “low quality” (Table
We found 12 studies about quantity of salivary flow rate that met our inclusion criteria; one of them considered hyposalivation prevalence as outcome (Table
Three studies recruited their DM patients from a diabetes care unit of a hospital, 3 from an endocrine unit, 3 from a pediatric endocrinology service, one from a university dental school, one from an oral health study, and another one from community-living/geriatric centers. Non-DM patients came from varied origins: oral health centers (
Five studies specified the DM diagnosis, two WHO criteria 2006 (fasting blood glucose ≥ 126 mg/dL), one modified WHO criteria 2006 (fasting blood glucose ≥ 126 mg/dL) or currently taking diabetic medications, one blood glucose levels ≥ 140 mg/dL at 2 hours after oral glucose tolerance test, and the last one American Diabetes Association criteria 2010 (
DM and non-DM participants were matched by gender in 7 studies, by age in 6 studies, by race distribution in 2, by socioeconomic status in 3, by living in the same area in two, and by Tanner puberty states in another one. With regard to the type of flow rate 9 studies collected UWS, 4 SWS, 2 USP, one SSS, one USS, and one collected SSP.
Three studies did not explain the hour of collection of saliva and 4 studies did not specify the saliva collection duration. Two studies collected salivary flow during 10 minutes and 6 studies during 5 minutes. Five studies [
Only one study reflected prevalence of hyposalivation as outcome [
The prevalence of xerostomia was analyzed in 7 studies (Table
There was only one study about xerostomia in adults NIDDM [
Only one work was realized in children and adolescents T1DM between 10 and 19 years old. This study showed that prevalence of xerostomia was greater in T1DM patients than non-T1DM patients (0%), and the prevalence was greater in PCDM patients (100%) than WCDM patients (80%).
The quantity of salivary flow rate was analyzed in 12 studies (Table
A considerable part of studies were realized in adults T2DM [
Three studies assessed SWS flow rate in T2DM [
USP flow rates were analyzed in two studies [
There were four studies [
Only one study evaluated this outcome and showed that hyposalivation prevalence was significantly greater in T2DM versus CG patients, 45% versus 2.5%.
Multiple epidemiologic studies have suggested that xerostomia is frequent among DM patients. In addition, there are studies that have showed that DM patients presented lower salivary flow rates than non-DM population [
Selection bias regarding the study population was minimized through the restriction to population-based studies. At the same time, we detected some sources of information bias. Firstly, the majority of studies [
Due to the fact that only articles published in the English language were reviewed, publication (language) bias could not be ruled out. Although we searched three databases, we cannot guarantee that some related papers might not have been identified. However, we did check the reference lists of reviewed articles to identify relevant studies. The studies reviewed presented different types of DM and DM and non-DM patients of different age (see Section
We identified 15 studies reporting prevalence of xerostomia/hyposalivation and rates of salivary flow in DM population. Comparisons between studies were limited due to different types of DM, different types of salivary flow, and heterogeneous demographic characteristics (age, ethnic origin) of the studied individual. In addition, the quality assessment of studies was low. Hence, no quantitative data synthesis was performed. Nevertheless, there are some patterns that can be described.
All studies about this outcome showed higher prevalence of xerostomia in DM patients in relation to non-DM population, 12.5%–53.5% compared to 0–30% [
All studies [
The comparison of the SWS rates between DM and non-DM patients showed that rates were higher in non-DM patients [
Only one study [
The selection of studies for this systematic review was based on a systematic search approach with clearly determined search strategies. We included only those studies reporting xerostomia prevalence/salivary flow rate/hyposalivation within the DM population in relation to a non-DM control group. Moreover, we analyzed these outcomes in separate groups according to age and type of DM. This approach allows limited comparison of the studies despite a high degree of heterogeneity. Our review also has some limitations. Although three databases were searched, we cannot rule out having missed relevant studies, also due to publication bias. The studies published in languages other than English were not included. Most studies reporting our outcomes were conducted in economically developed areas such as USA and Sweden and thus do not represent a worldwide perspective.
In addition, there are studies previous to the year 2000. The change in the diagnostic criteria for DM from 140 mg/dL (7.8 mmol/L) to 126 mg/dL (7.0 mmol/L) in the fasting plasma glucose level in 1997 [
The review conducted demonstrated the considerable variation in prevalence of xerostomia and salivary flow rates among DM population in relation to non-DM patients. Most studies found a higher prevalence of xerostomia and lower salivary flow rates in DM with respect to CG. We found only a study about hyposalivation that showed higher prevalence in DM than non-DM patients. A few studies showed that WCDM patients have lower xerostomia prevalence and higher salivary flow rates than PCDM patients. Owing to the high degree of heterogeneity regarding the types of DM, diagnosis of DM, age of patients, and types and techniques of salivary flow collection, it was difficult to compare the studies. In addition, the quality assessment showed the low quality of the existing studies. Therefore, the results of this systematic review were inconsistent.
We recommend that new studies analyzing the xerostomia and salivary flow rate in the DM population should use more precise and current definitions concerning the determination and diagnosis of DM patients and salivary flow rate collection. New studies should match correctly DM and non-DM patients, keeping in mind xerostomia associated drugs and illness (other than DM). New studies are required that consider hyposalivation in DM patients because a reduction in salivary flow is not always pathological.
The authors declare that there is no conflict of interests regarding the publication of this paper.
Rosa María López-Pintor conceived and designed the experiments. Rosa María López-Pintor, Elisabeth Casañas, José González-Serrano, Julia Serrano, and Lucía Ramírez performed the experiments. Rosa María López-Pintor, Elisabeth Casañas, José González-Serrano, Julia Serrano, Lucía Ramírez, and Gonzalo Hernández analyzed the data. Lorenzo de Arriba contributed reagents/materials/analysis tools. Rosa María López-Pintor wrote the paper. Gonzalo Hernández contributed to the concept, design, and drafting of the protocol. Rosa María López-Pintor, Elisabeth Casañas participated in the development of the systematic search strategies. Gonzalo Hernández, Lorenzo de Arriba made major contributions to the write-up and editing of systematic review. Gonzalo Hernández, Lorenzo de Arriba, and Elisabeth Casañas critically revised the paper for important intellectual content and approved the final version.