Table 2 Evidence on metabolic diseases and caries

Human studies on metabolic diseases and caries

 Diabetes

  Hegde et al. [34]

Evaluate salivary composition in caries-active (>10 decayed teeth) diabetic patients when compared to caries-active (>10 decayed teeth) controls

Case-control

120 (60 cases and controls)

India

Outcomes: Salivary alkaline phosphatase was significantly higher in diabetic caries-active patients when compared to controls (p < 0.001) and salivary calcium ions were significantly higher in non-diabetic caries-active patients (controls) when compared to diabetic caries-active individuals (p < 0.001)

Conclusion: Salivary composition with regards to calcium and alkaline phosphatase is significantly different between caries-active diabetic and non-diabetic individuals

  Lai et al. [35]

Evaluate caries prevalence [International Caries Detection and Assessment System (ICDAS)], dietary and oral hygiene variables, diabetic control (HbA1c), oral microbiota (DNA-DNA) and plaque acidogenicity by comparing non-diabetic and diabetic (good control with HbA1c ≤ 7.5; poor control with HbA1c ≥ 7.5) pediatric cohorts.

Case-control

204 (68 cases, 136 controls)

Italy

Outcomes: Consumption of sugary beverages and snacks were significantly higher in diabetic group compared to non-diabetic group (p = 0.03 and p = 0.04 respectively) and similarly, diabetics with poor control consumed significantly higher sugary beverages and snacks compared to diabetics with good control (p>0.01 and p = 0.03 respectively); significantly higher caries free participants in diabetics with good control when compared to diabetics with poor control (p < 0.01); significant difference in use of fluoridated toothpaste and tooth brushing ≥ 2 mins were noted between the diabetic subgroups (p = 0.03 each); significant differences were noted between diabetic subgroups for all primary cariogenic bacteria except ‘other mutans streptococci’; pH values of plaque were significantly different between both groups and diabetic subgroups (p < 0.01 each)

Conclusion: Diabetic children with good control may be considered low caries risk while diabetic children with poor control may be considered high caries risk.

  Majbauddin et al. [36]

Investigate association between dental caries (DMFT) and HbA1c [controlled diabetes mellitus type II (T2DM) with HbA1c ≤ 7; and uncontrolled T2DM ≥ 7]

Cross sectional

91 (46 controlled and 45 uncontrolled diabetics)

Philippines

Outcomes: Significantly worse oral hygiene parameters including frequency of tooth brushing (p = 0.04), frequency of flossing (p = 0.002), lack of oral health education (p < 0.001) and irregular dental visits (p < 0.001) were noted in uncontrolled T2DM groups; significantly higher decayed teeth (DT) (p = 0.04), MT (p = 0.002) and DMFT(p < 0.001) were noted in uncontrolled T2DM group; absolute value of DT was significantly correlated with serum HbA1c levels (p = 0.005) and education level (p = 0.04) and significant correlation of DMFT index were noted between serum HbA1c and regular dental visits (p < 0.001) and receiving oral health education (p = 0.004)

Conclusion: There is association between markers of dental caries and serum HbA1c levels

  Singh-Hüsgen et al. [37]

Evaluate caries (DMFS/dmfs) prevalence, periodontal parameters (Silness & Löe and papillary bleeding indexes) and subgingival microbiota in diabetic [diabetes mellitus type 1 (T1DM)] and phenylketonuria pediatric cohorts by comparing it with a control group

Case-control

238 (138 cases, 100 controls)

Germany

Outcomes: Statistically significant difference was noted for caries prevalence in primary dentition between the three groups but no statistically significant difference was noted in permanent dentition; Silness and Löe index was statistically significantly higher in diabetic group compared the other two groups; papillary bleeding index was significantly higher in diabetic group compared to controls; statistically significant differences were noted for Lactobacillus sp., Lactobacillus casei and Porphyromonas gingivalis between groups

Conclusion: Children with phenylketonuria demonstrated a higher caries experience in their primary dentition and diabetic children showed a slightly higher risk of developing periodontal disease

  Al-Badr et al. [38]

Compare prevalence of dental caries between 6-12-year-old type 1 diabetic children and controls matched by age and gender. Diabetic and non-diabetic participants were compared for oral hygiene, socioeconomic status, caries burden (DFT/dft), salivary microbiota and salivary pH

Case-control

173 (69 cases, 104 controls)

Saudi Arabia

Outcomes: Mean DFT/dft scores between groups were non-significantly different between groups. Diabetic children showed significantly higher dentist visits (p = 0.04) and lower consumption of sugary foods (p = 0.003). Further, diabetic children had significantly lower salivary pH (p = 0.01) and higher Lactobacillus counts (p = 0.04) when compared to non-diabetics

Conclusion: There was non-significant difference in caries burden between type 1 diabetic and non-diabetic children. The reduced salivary pH and higher Lactobacillus counts may indicate a higher risk in type 1 diabetic children.

  Kamran et al. [39]

Compare dental caries burden (DMFT) in type 1 diabetic children and healthy controls. Participants were recruited, ranging in age from 9-14 years. Additionally, oral hygiene habits, duration of diabetes and HbA1c levels were recorded

Case-control

200 (100 cases and controls)

Iran

Outcomes: Mean DMFT in diabetic and control groups were 2.60 ± 1.25 and 2.52 ± 1.26 respectively. No significant difference between groups was noted for DMFT (p = 0.654). For oral hygiene, participants who flossed regularly showed significantly lower DMFT when compared to individuals who did not use dental floss (p = 0.001). No significant difference was found in mean DMFT due to diabetes duration or HbA1c levels.

Conclusion: Type 1 diabetes alone may not affect dental caries burden, but oral hygiene is important in controlling dental caries

  Pachonski et al. [40]

Compare caries burden (DMFT) in type 1 diabetic participants (10-18 years) when compared to controls. Cases were divided into poorly (PC) and well controlled (WC) sub-groups based on glycemic control (HbA1c of 7.5% cutoff).

Case-control

75 ( 50 cases, 25 controls)

Poland

Outcomes: Statistically significant difference in DMFT was noted between PC and WC subgroups (p = 0.04) with PC subgroup showing highest mean DMFT values (5.8 ± 3.75). No other statistically significant differences were noted.

Conclusion: Type 1 diabetic patients may show significantly higher caries burden.

  Schmolinsky et al. [41]

Assess effects of type 2 diabetes and metabolic control on coronal caries. This study was a 11-year follow up. DMFS, HbA1c, behavioral, socioeconomic, education level, smoking status and dental home care data was recorded. Parameters from poorly controlled, well controlled diabetes and non-diabetic controls were compared

Longitudinal

2028

Germany

Outcomes: For dental caries, progression of DMFS rates were significantly higher in poorly controlled diabetics compared to other groups (p = 0.01). Importantly, rate of DMFS change differed significantly when duration of diabetes was ≥ 5 years and non-significantly different for duration of diabetes ≤ 5 years. Rate of change of HbA1c levels increased proportional to DMFS index (B=0.046, linear effects model)

Conclusion: Participants with poorly controlled diabetes and longer duration of disease (≥ 5 years) are at increased risk for caries progression (ΔDMFS)

 Obesity

  Alm et al. [42]

Investigate association between body weight [body mass index (BMI)] and caries prevalence [decayed, extracted, and filled surfaces(defs)/ decayed and/or filled approximal surfaces (DFS_a)] followed from pre-school years to young adulthood at 3, 6, 15 and 20 years of age

Longitudinal

402

Sweden

Outcomes: At 3 years of age, no association was noted between overweight/obesity and caries; at 6 years of age, significantly higher caries prevalence was noted in obese children when compared to normal weight children (p = 0.04) with a OR=2.5 times that of normal weight children; at both 15 and 20 years of age, overweight/obese children had significantly higher caries prevalence when compared to normal weight young adults (p < 0.05)

Conclusion: Overweight and obese adolescents and young adults had significantly more caries than normal-weight individuals. Emphasis should be placed on need for preventive approaches that address lifestyle factors that affect obesity and dental caries

  Basha et al. [43]

Assess association between obesity (BMI) and dental caries (DMFS/DMFT) prevalence and increments in 13 year-old adolescents with 3 years follow up

Longitudinal

764

India

Outcomes: Significantly higher number of girls were overweight/obese compared to boys (p = 0.04) and prevalence of dental caries was significantly more in boys compared to girls (p = 0.04 ); after 3 years, significantly more adolescents had dental caries compared to baseline (p = 0.001); mean caries scores were higher in obese and overweight children compared to normal weight children at both examinations-baseline and 3 years (p < 0.05); children with obesity and overweight status had a 3.7 times greater chance of developing caries after adjusting for confounders

Conclusion: Obese and overweight adolescents were at a higher risk of developing new caries in a 3 year follow up period

  Chala et al. [44]

Evaluate non-linear associations between BMI and dental caries (untreated dental decay). BMI was treated as continuous variable and a multivariable Poisson regression model was established

Cross sectional

101

Morocco

Outcomes: Adjusted multivariate analysis revealed that age at beginning tooth brushing and BMI, both below and above the normal range were associated with increase of number of dental caries. A significant quadratic effect between BMI and the rate of untreated dental decay was noted (p value for non-linearity was <0.001 and for overall effect was <0.001)

Conclusion: A U-shaped trend in the association between dental decay and BMI was found which means an increased rate of untreated dental decay was associated with both under- and over-weight status

  Costacurta et al [45]

Evaluate the association between obesity (BMI, body fat mass and body fat free mass) and dental caries (DMFT/dmft) and the impact of lifestyle, dietary and oral hygiene parameters on dental caries in obese pediatric patients by comparing four groups-normal weight with and without caries and pre-obese-obese with and without caries

Cross sectional

96

Italy

Outcomes: Pre-obese-obese children had higher DMFT (p = 0.04) and dmft (p = 0.03) indexes compared to normal weight participants; significant correlation was noted between dmft/DMFT and body fat mass (p = 0.03/0.02 respectively); for lifestyle and diet, there were significant differences between groups for intake of sugary drinks (p = 0.005), frequency of sugar intake limited to main meals (p < 0.001) and sedentary lifestyle (p = 0.01) with higher percentage of participants in the preobese-obese group with caries

Conclusion: There is a direct association between dental caries and obesity and specific dietary habits may be considered risk factors that are common to both dental caries and childhood obesity

  Goodson et al. [46]

Evaluate association of childhood obesity (BMI) and dental caries [DT and filled teeth (FT)] by comparing obese, overweight, normal weight and underweight children

Cross sectional

8275

Kuwait

Outcomes: The percentage of DT and FT varied inversely to body weight and the differences between groups for DT and FT were statistically significant; reduced prevalence of dental decay in obese children was significant for both primary and permanent dentition but was comparably less in permanent teeth than in primary teeth

Conclusion: An inverse relationship between obesity and dental caries argues against the hypothesis that sugar is necessary and sufficient for dental decay and is a leading co-factor in obesity. The reasons for the inverse relationship noted in this study are not entirely clear

  Hall-Sculin et al. [47]

Evaluate association between caries (DMFT) in late childhood (7-9 years) and obesity (BMI) in adolescence (12-16 years) and define strategy for prevention

Longitudinal

2953

England

Outcomes: BMI categories in adolescence were not significantly associated with presence of caries in late childhood (p = 0.6) or adolescence (p = 0.06); obesity was not significantly associated with gender (p = 0.9); statistically significant association was not seen between BMI and ethnicity (p = 0.02)

Conclusion: Caries in late childhood was not shown to be associated with obesity in adolescence and no association was noted between obesity and diabetes in adolescence.

  Li et al. [48]

Evaluate associations between obesity (BMI, waist circumference, waist-height ratio, waist-hip ratio) and dental caries (DMFT) in adolescents (12 years) with 3 and 6 year follow ups

Longitudinal

282

China (Hong Kong)

Outcomes: Significant increase in percentage of underweight adolescents were noted during the period of observation (p < 0.001); BMI, waist circumference, waist-hip ratio and waist-height ratio were associated with frequency of tooth brushing at 3 and 6 years follow ups; prevalence of dental caries increased with increase in duration of follow up (25.5% at baseline to 62.1% at 18 years of age); at 6 years follow up, mean DMFT score of participants with waist-hip ratio below median was significantly lower than mean DMFT score of participants with waist-hip ratio above median at previous follow up (p = 0.03)

Conclusion: Longitudinal association was noted between central obesity and dental caries among adolescents between 15 and 18 years of age

  Modéer et al. [49]

Evaluate if childhood obesity (BMI-adjusted for age and gender) is associated with reduced stimulated salivary flow rate and dental caries (DMFT/DMFS) by comparing obese and normal weight (control) groups

Case-control

130 (65 cases and controls)

Sweden

Outcomes: Obese participants showed significantly higher number of decayed surfaces (p = 0.008) and significantly lower flow rate of stimulated whole saliva (p < 0.001) compared to controls; obesity (BMI-adjusted for age and gender) as a continuous variable was significantly associated with decayed surfaces (OR=1.3)

Conclusion: Childhood obesity is associated with reduced stimulated whole saliva flow rate and dental caries.

  Peng et al. [50]

Evaluate association between adiposity (general, central and peripheral) and dental caries (DMFT and significant caries index-SiC) in early adolescence. Metrics of adiposity used were BMI, waist and hip circumferences, triceps skinfold thickness, waist-height and waist-hip ratios

Cross sectional

514

China (Hong Kong)

Outcomes: Gender was associated with adiposity with boys having significantly higher waist-height ratio (p < 0.01), BMI (p < 0.05), waist circumference (p < 0.001) and waist-hip ratio (p < 0.001) than girls; children brushing less than once daily had significantly higher BMI, waist circumference and waist-hip ratio than those brushing at least once daily (p < 0.05); parental education was associated with prevalence of dental caries (p < 0.01), SiC index prevalence (p < 0.05) and mean DMFT (p < 0.01); dental caries experience was associated with adiposity and there was a significant correlation between DMFT and waist-hip ratio (p = 0.03); regression models identified that dental caries was associated with adiposity

Conclusion: Dental caries experience was associated with central and peripheral adiposity but not general adiposity

  Sánchez-Pérez et al. [51]

Evaluate effect of BMI on tooth eruption in a pediatric cohort (n=88) by studying dental caries (DMFT/dmft and DMFS/dmfs), BMI and tooth eruption timings

Longitudinal

88

Mexico

Outcomes: Significant increase in children with 85^th percentile of BMI over the follow up period (p < 0.001); significant association was noted between number of erupted teeth and BMI (p < 0.001) and longitudinal effect estimated by mixed model indicated higher eruption rate with increase in BMI over time; mixed model fitted for caries (dmfs) showed that children with high BMI had significantly lower levels of dental caries (p < 0.01) and participants from lower socioeconomic resources had significantly higher dmfs scores (p = 0.01)

Conclusion: Children who were overweight had increased eruption rate and lower caries index.

  Akarsu et al. [52]

Evaluate association between BMI and dental caries in 20-30-year-old adults without any chronic diseases. 394 participants were divided into groups based on BMI (normal weight, overweight and obese) and compared

Cross sectional

394

Turkey

Outcomes: Mean DMFT was statistically significantly higher in obese group when compared to normal and overweight groups (p = 0.001 each). No statistically significant difference was noted between mean DMFT of normal and overweight groups (p > 0.05)

Conclusion: A positive relationship was noted between obesity and higher DMFT index.

  Fraiz et al. [53]

Determine association between overweight/obesity (excess body weight, measured as BMI) and prevalence of dental caries (dmft) in a cohort of 4-5-year-old school children. In addition, information on SES, schooling of parent/caregiver and snack consumption limits were collected

Cross sectional

686

Brazil

Outcomes: 16.6% were overweight and 10.9% were obese. A multivariate model showed household income per capita [PR=0.804 (0.665-0.972)], age of the child [PR=2.025 (1.001-1.029)]and snack consumption limit [PR=0.839 (0.732-0.962)] were associated with greater prevalence of dental caries.

Conclusion: Excess body weight was not associated with dental caries. Dental caries was significantly higher in older preschoolers, participants with lower household income and in households where parents had lower limit on snack consumption.

  Frias-Bulhosa et al. [54]

Determine associations between BMI and dental caries (DMFT) in 13-year-old participants.

Cross sectional

181

Portugal

Outcomes: No significant difference was found for dental caries (DMFT) between groups by BMI (underweight, normal, overweight, and obese). However, frequency of oral hygiene was significantly associated with DMFT ≤ 6 (p = 0.041). For severe dental caries (DMFT > 6), no oral hygiene at night was a significant risk factor (p = 0.006)

Conclusion: No significant association was found between BMI and dental caries in cohort of 13-year-old participants.

  Guare et al. [55]

Compare caries [dentin (DC) and enamel (EC)] and caries risk between normal weight (NW) and overweight/obese (OW) 6-12-year-old children. BMI, caries using ICDAS system (two categories: EC/DC and DC) and caries risk using the caries management by risk assessment (CAMBRA) system were recorded and analyzed by logistic regression.

Case-control

91 (41 cases, 50 controls)

Brazil

Outcomes: Caries burden was similar in both groups for EC/DC threshold but higher in NW group for DC threshold (p = .009). Further, caries risk classification was similar to both groups and logistic regression analysis showed that OW group was less likely to demonstrate proximal caries (OR=0.33), thick biofilm (OR=0.36) and have high (OR=0.367)/moderate-high (OR=0.19) caries risk

Conclusion: Children in the OW group had lower caries experience and risk compared to NW children.

  Karki et al. [56]

Evaluate associations of untreated dental caries [grade of severity of untreated dental caries (GUDC)] in groups based on BMI and stratified based on three systems [WHO, International Obesity Task Force (IOTF), Nepalese growth reference] in WHO index age groups of 5-6, 12 and 15-year-old school children. Additionally, demographic information, oral hygiene and food consumption habits were noted

Cross sectional

1135

Nepal

Outcomes: Untreated dental caries was common in youngest age group (5-6-year-old) (p < 0.001), in participants with infrequent tooth brushing (p = 0.007), and frequent consumption of sugary foods (p = 0.014). BMI (low or high) was associated with severity of untreated dental caries (GUDC) [for low BMI, RR=1.09; for high BMI, RR=1.07]

Conclusion: Children with high or low BMI may be at risk for dental caries due to shared common risk factors, prominently dietary factors.

  Kennedy et al. [57]

Evaluate associations between BMI and severe early childhood caries (S-ECC) (dmfs) in children under 6 years of age.

Longitudinal

150

Canada

Outcomes: Multiple linear regression analyses showed no significant relationship between dmfs and BMI z-scores. However, a significant relationship between BMI z-scores and family income (< $28,000/year), registered first nation status, reporting of inadequate physical activity (p = .008, .005 and .02 respectively)

Conclusion: No significant relationship between BMI and S-ECC was noted but socioeconomic status was an important confounding variable.

  Lock et al. [58]

Evaluate association between obesity (BMI) and change in dental caries (ΔDMFS) in 12-year-old schoolchildren. This study was a 2.5-year follow-up of a cross-sectional study (baseline) and 801 participants were followed up

Longitudinal

801

Brazil

Outcomes: DMFS increased by 0.86 (0.65-1.07), 0.91 (0.59-1.23) and 0.42 (0.03-0.80) for normal, overweight, and obese groups respectively. Further, obese group had significantly lower ΔDMFS compared to normal weight group (p < 0.05). While no significant association was noted between BMI categories (normal, overweight, and obese) and ΔDMFS, a polynomial model showed inverse relationship between increasing BMI and decreasing ΔDMFS (p < 0.05).

Conclusion: An inverse association was seen between obesity and Δ DMFS in this longitudinal follow-up.

  Serrano-Pina et al. [59]

Determine associations between obesity (BMI) and dental caries [DMFT/deft and TD (total decay)] in 8-12-year-old schoolchildren.

Cross sectional

331

Mexico

Outcomes: Dental caries prevalence was 32.4% (29.7-35.2) and mean DMFT was 0.64 ± 1.00. Further, statistically significant negative correlation was noted between BMI and TD (r = -0.127, p = 0.021); BMI and deft (r = -0.195, p ≤ 0.001).

Conclusion: This study showed high prevalence of obesity in 8-12-year-old schoolchildren and the association between caries and obesity

  Sharma et al. [60]

Evaluate correlation between dental caries (dmft) and obesity (BMI) in 3-6-year-old schoolchildren from urban and rural dwellings.

Cross sectional

1000

India

Outcomes: Male participants and urban residents had significantly higher BMI than female and rural residents respectively (p < 0.05 each). Dental caries was non-significantly different between groups

Conclusion: No significant correlation was noted between dental caries and BMI and obesity was more prevalent in urban group when compared to rural group.

  Shen et al. [61]

Determine association between severe dental caries [dmft, PUFA (pulpal involvement, ulceration, fistula, and abscess)] and overweight/underweight status (BMI-for-age z-score). For overweight status, BMI cutoff was >2 SD for children under 60 months and >1 SD for over 60 months. For underweight status, BMI cutoff was < -2 SD regardless of age

Longitudinal

772

China

Outcomes: Children in the age range of 24.6-71.1 months were included in the study and median follow up time was approximately 10 months. There was higher odds for underweight status in children with severe dental caries (OR = 4.08). Further, severe caries at baseline had higher odds for overweight status (OR = 2.33).

Conclusion: A U-shaped relationship between severe dental caries and both overweight and underweight status was noted.

  Swaminathan et al. [62]

Determine correlation between BMI (overweight and underweight) and dental caries (DMFT/DEFT) in 3-12-year-old schoolchildren (2 subgroups by age: 3-5; 6-12).

Cross sectional

2200

India

Outcomes: No significant differences were found for dental caries between overweight and underweight groups (by BMI)

Conclusion: No association between BMI and dental caries was found in children in both primary and mixed dentition stages.

Tschammler et al. [63]

Evaluate prevalence and severity of erosive wear (basic erosive wear examination, BEWE) and dental caries (DMFT/dmft, ICDAS) in participants (4-17-year-old) with increased BMI and compare to normal BMI participants. Further, oral hygiene and food consumption habits along with demographic and socioeconomic information was recorded.

Case-control

223 (170 cases, 53 controls)

Germany

Outcomes: Erosive tooth wear and caries burden was significantly higher in obese and extremely obese children when compared to normal weight children (p < 0.05). Increased BMI, older children, male gender, and consumption of erosive foods conferred significantly increased risk for erosive tooth wear and dental caries. Additionally, lower socioeconomic status and poor toothbrushing habits were risk factors for dental caries only.

Conclusion: Increased BMI in children and adolescents was significantly associated with increased risk for erosive tooth wear (BEWE) and dental caries (DMFT/dmft, ICDAS)

 Metabolic syndrome

  Iwasaki et al. [64]

Evaluate association between metabolic syndrome, diet and dental caries in Japanese adults by comparing participants with and without metabolic syndrome

Cross sectional

937

Japan

Outcomes: For diet, significant differences were noted between participants with and without metabolic syndrome for consumption of dairy products (p < 0.01), bean products, sweets and coffee (p < 0.05 each); for clinical parameters, significant differences were noted between groups for gender, age, Brinkman index, BMI, waist circumference, blood pressure-both systolic and diastolic, serum fasting blood glucose, high-density lipoproteins (HDL) cholesterol and CRP (p < 0.001 each); for oral disease, significant difference was noted between periodontitis and DMFT (p < 0.05 each); multivariate logistic regression analysis after adjusting for confounders showed association between metabolic syndrome prevalence and DMFT (first vs. fourth quartile, OR=1.8 and p>0.05)

Conclusion: There appears to be positive association between caries and metabolic syndrome in Japanese adults. This association was strong in those with higher DMFT regardless of dietary habits

  Adachi et al. [65]

Human prospective study of one-year duration to understand relationship between dental caries, periodontitis, and metabolic syndrome (MetS). Adult participants, ≥ 35 years without MetS underwent assessment by survey, medical and dental examinations and were followed up at one-year interval.

Longitudinal

136

Japan

Outcomes: 30 adult participants demonstrated one or more components for MetS diagnosis. In these participants, DT were significantly associated with development of at least one MetS determining component [RR=3.25 (1.59-6.63)]. No associations between periodontitis and other components of DMFT index were noted.

Conclusion: DT may impart an increased risk for subsequent development of MetS.

Animal studies on metabolic diseases and caries

 Diabetes

  Abbassy et al. [20]

Animal study to evaluate morphological and mineral content change of teeth by comparing observations from experimentally induced T1DM and control rats (n=10 each)

Outcomes: T1DM rats showed significant decrease in early weight (day 14 onwards) compared to controls (p < 0.05); microtomography of the mandible showed significant reduction in enamel and dentin thickness (p < 0.05) when compared to controls; histomorphometry showed significant decrease in mineral apposition and dentin formation rates (p < 0.05) when compared to controls

Conclusion: T1DM has detrimental influence on the formation of enamel and dentin in early growth stage in a diabetes rat model

  Claudino et al. [21]

Animal study to evaluate influence of uncontrolled diabetes on loss of tooth structure by comparing diabetic rat model with controls (n=25 each) over a one-year period

Outcomes: Significantly increased loss of tooth structure was noted in diabetic group at all observation intervals (3,6,9,12 months) when compared to controls; morphometric evaluation of dental pulp showed significant reduction in volumetric density of collagen fibers and fibroblasts when compared to controls (p < 0.05) as early as 3 months; non-significant differences in other histological and radiographic criteria were noted between groups, including inflammatory cell infiltrate, necrosis, other connective tissue changes and periapical lesions

Conclusion: Uncontrolled diabetes possibly triggers loss of tooth structure and progressive changes of the dental pulp. Therefore, diabetes may be considered a risk factor for development of dental caries and alterations of dental pulp

  Nakahara et al. [22]

Animal study to evaluate if hyperglycemia induces periodontal inflammation by comparing results between T1DM diabetic rats (n=30, 10 each in 3 groups) and non-diabetic rats (n=30, 10 in each group) administered variable concentrations of fluoride. Also, a T2DM mouse model (n=30, 10 in each group) was compared with non-diabetic mice (n=30, 10 in each group).

Outcomes: In T1DM rat model, fluoride treatment significantly reduced dental caries, gingivitis and marginal periodontitis in 10 and 50ppm fluoride groups when compared to no fluoride group (p < 0.01); the T2DM mouse model, similar results were noted; in fluoride-untreated diabetic rats and mice, marginal periodontitis was always accompanied by moderate caries and alveolar bone resorption or marginal periodontitis was not noted in the absence of caries, regardless of diabetic status

Conclusion: Long-term hyperglycemia induces dental caries but not periodontal disease in type 1 and 2 diabetic rodent models

  Nakahara et al. [23]

Animal study to evaluate dental caries and periodontal disease in an alloxan induced hyperglycemia (T1DM) rat model (n=30) compared with non-diabetic group (n=17)

Outcomes: Caries score was worse in diabetic group when compared to non-diabetic group; caries severity worsened with age with significantly higher scores at 26 weeks for maxillary (p < 0.05) and mandibular (p < 0.01) teeth when compared to 13 weeks; mean caries score was significantly higher in mandibular molars when compared to maxillary molars at 13 and 26 weeks (p < 0.05 and p < 0.01 respectively); alveolar bone resorption was significantly higher in mandible compared to maxilla after 26 weeks (p < 0.01) in diabetic group and alveolar bone resorption was noted adjacent to carious molars only; positive correlation was noted between alveolar bone resorption and caries score for both maxilla and mandible (p < 0.01 each)

Conclusion: Alloxan-induced severe hyperglycemia can cause rapid and progressive dental caries and periodontitis in diabetic rat models

  Nakahara et al. [24]

Animal study (n=60, 15 in each group) to evaluate relationship between hyperglycemia and dental caries and preventive effect of glycemic control on progression of caries in diabetic rat model by comparing four groups [spontaneous diabetes-with (INS) and without (C) insulin intervention, alloxan induced diabetes with (AL+INS) and without insulin intervention (AL)]

Outcomes: Mean caries score and mean bone resorption of the maxilla were significantly lower (p < 0.01 each) in the INS group when compared to C group; mean caries score and mean bone resorption were significantly lower (p < 0.01 each) in the AL+INS group when compared to AL group; positive correlation was noted between alveolar bone resorption and caries scores (p < 0.01 for both maxilla and mandible); incidence of marginal periodontitis was significantly lower in INS and AL+INS groups when compared to C and AL groups (p < 0.05 and p < 0.01 respectively); no periodontal lesions were noted adjacent to a non-carious molar and non-carious molars were comparable in C and INS groups

Conclusion: Glycemic control by insulin prevented occurrence and progression of dental caries and caries-related periodontitis in spontaneously and alloxan induced rodent diabetes model, suggesting that hyperglycemia may be a major factor influencing the development of dental caries

  Nishimoto et al. [25]

Animal study (n=23, n=13 in diabetic group and n=10 in non-diabetic group) to evaluate relationship between hyperglycemia and early dental caries (7 weeks after alloxan administration) and the role of saliva and salivary glands in a rat diabetes model

Outcomes: Mean weight of saliva (after pilocarpine administration) was significantly lower in diabetic group when compared to non-diabetic group at all time points of sample collection (p < 0.01); mean cusp height of molars (a measure of wear) in the diabetic group was approximately half that of non-diabetic group and that difference was significant (p < 0.01) as was the incidence and severity of caries; the incidence and severity of histologic change in diabetic group was significantly more than non-diabetic group (p < 0.01) and this change was predominantly in terms of vacuolation of acinar cells

Conclusion: In this rodent diabetic model, hyperglycemia induces initial caries development and enhances occlusal wear. Also, parotid gland dysfunction may be involved in pathogenesis of occlusal wear and caries

  Sano et al. [26]

Animal study to determine if diabetes affects onset and progression of dental caries and periodontal disease over long follow up (20 to 50 weeks). Also, clinical presentation of caries and periodontal disease in a rodent diabetic model were studied by comparing diabetic and non-diabetic mice

Outcomes: Significantly higher incidence and severity of dental caries was noted in diabetic mice at 30 to 50 weeks of follow ups when compared to non-diabetic mice (p < 0.05 at 30 and 40 weeks and p < 0.001 at 50 weeks); mean caries score was significantly higher (p < 0.001) in diabetic mice when compared to non-diabetic mice; severity of gingivitis was positively correlated with severity of molar caries (p < 0.001 for both genders and both jaws)

Conclusion: There is a strong relationship between diabetes and dental caries in this rodent diabetes model. It is possible that onset of periodontal disease was secondary to dental caries

  Yeh et al. [27]

Animal study to elucidate mechanisms of dental caries by studying type 1 diabetic mice model with point mutation in Ins2 gene and clinically demonstrates hyperglycemia and xerostomia. The disease model mice were compared with wild-type littermates

Outcomes: Mouse model for type 1 diabetes showed progressive changes in tooth appearance and wear when compared to wild type mice. No differences were noted in tooth development, suggesting these changes occurred due to hyperglycemia and xerostomia. In salivary glands, saliva production was little to none in type 1 diabetic mice after pilocarpine stimulation demonstrating significant xerostomia.

Conclusion: Hyperglycemia and xerostomia in type 1 diabetes mouse model leads to excessive dental wear and demineralization.