Association between periodontitis and fibrotic progression of non-alcoholic fatty liver among Japanese adults.

AIM: Non-alcoholic fatty liver (NAFL) is known to develop into liver fibrosis, which increases the risk of liver cirrhosis and liver cancer. The association between periodontal condition and fibrotic progression of NAFL is unclear. This study aimed to clarify this longitudinal association. MATERIALS AND METHODS: Among 4812 participants aged 35-64 years undergoing annual health check-ups between 2003 and 2004, and follow-up 5 years later, 392 participants were diagnosed with NAFL. After excluding participants with liver fibrosis at baseline, 341 participants were followed up for 5 years. NAFL disease fibrosis score of ≥-1.455 was used to evaluate the probability of the presence of liver fibrosis. RESULTS: During the follow-up period, 10.6% of participants progressed to liver fibrosis. A higher clinical attachment level (CAL) tended to be associated with the incidence of liver fibrosis in the logistic regression analysis (odds ratio [OR] 1.82, 95% confidence interval [CI], 0.94-3.49, p = .074). The stratified analysis by obesity revealed a significant association with higher CAL in obese participants (OR 2.87, 95% CI, 1.23-6.69, p = .015), but not in non-obese participants. CONCLUSION: Higher CAL was associated with an increased probability of liver fibrosis in obese adults with NAFL.

Longitudinal Associations of Toothbrushing With Obesity and Hyperglycemia.

BACKGROUND: Toothbrushing is a health-related lifestyle habit and has been reported to contribute not only to oral health but also to some parameters of general health; however, little research has been conducted to understand the association of the frequency and timing of toothbrushing with the development of comprehensive metabolic abnormalities, with consideration of oral health condition. In this study, using longitudinal data, we examined this association in Japanese adults, adjusting for periodontal condition. METHODS: A 5-year longitudinal study was performed with 4,537 participants between 35 and 64 years old who underwent an annual dental examination in both 2003 and 2008. Data about toothbrushing habits and metabolic abnormalities, such as obesity, hyperglycemia, diabetes, hypertension, hypertriglyceridemia, and low levels of high-density lipoprotein-cholesterol, were analyzed using Poisson regression analysis. RESULTS: The percentage of participants with a toothbrushing frequency ≤1 time/day was 29.4%, and that for those not brushing their teeth at night was 21.4%. The incidences of obesity and hyperglycemia after 5 years were 5.5% and 28.4%, respectively. A toothbrushing frequency ≤1 time/day was associated with development of obesity (prevalence rate ratio [PRR] 1.77; 95% confidence interval [CI], 1.12-2.80), after adjusting for periodontal condition and potential risk factors. A significant association between not brushing teeth at night and hyperglycemia (PRR 1.30; 95% CI, 1.02-1.66) was observed in participants with toothbrushing frequency of 1 time/day. No association was found between toothbrushing habits and other metabolic abnormalities. CONCLUSIONS: This study suggests that toothbrushing habits are associated with the development of obesity and hyperglycemia.

Relationship of toothbrushing to metabolic syndrome in middle-aged adults.

AIM: To examine the effect of toothbrushing on the development of metabolic syndrome (MetS), including assessment of periodontal status, in middle-aged adults. METHODS: This 5-year follow-up retrospective study was performed in 3,722 participants (2,897 males and 825 females) aged 35-64 years who underwent both medical check-ups and dental examinations. Metabolic components included obesity, elevated triglycerides, blood pressure, fasting glucose and reduced high-density lipoprotein. Toothbrushing frequency was assessed using a questionnaire. Periodontal disease was defined as having at least one site with a pocket depth of ≥4 mm. Logistic regression analysis was performed to evaluate the relationship between toothbrushing frequency at the baseline examination and the development of MetS (≥3 components). RESULTS: During follow-up, 11.1% of participants developed MetS. After adjusting for potential confounders including periodontal disease, participants with more frequent daily toothbrushing tended to have significantly lower odds of developing MetS (p for trend = .01). The risk of development of MetS was significantly lower in participants brushing teeth ≥3 times/day than in those brushing teeth ≤1 time/day (odds ratio = 0.64, 95% confidence interval = 0.45-0.92). CONCLUSIONS: Frequent daily toothbrushing was associated with lower risk of development of MetS.

Tooth loss and metabolic syndrome in middle-aged Japanese adults.

AIM: Metabolic syndrome is associated with periodontal disease and dental caries; however, little attention has been given to the association between metabolic syndrome and tooth loss, which is the endpoint of these two diseases. This study examined this association in middle-aged adults over a 5-year period. METHODS: A retrospective study was performed in 2107 participants (1718 males and 389 females) aged 35-60 years who underwent annual dental check-ups, to evaluate tooth loss and metabolic components, including obesity, elevated triglycerides, blood pressure, fasting glucose, and reduced high-density lipoprotein. Logistic regression analysis was performed to evaluate the association between metabolic syndrome (≥3 components) at the baseline examination and tooth loss. RESULTS: Over a 5-year period, 10.8% of the participants lost at least one tooth. Compared to those with no metabolic components, participants with ≥3 components had an increased risk of tooth loss (odds ratio = 1.54; 95% confidence interval: 1.01-2.37), adjusting for age, gender, dental caries experience, attachment loss, oral hygiene status, number of teeth, tooth brushing frequency, smoking, and occupational status. CONCLUSIONS: Metabolic syndrome was associated with the incidence of tooth loss among middle-aged adults.

Association of periodontal status with liver abnormalities and metabolic syndrome.

Although an association between periodontal status and liver abnormalities has been reported, it has not been described in relation to metabolic syndrome (MetS), which often coexists with non-alcoholic fatty liver disease. We examined the association of a combination of liver abnormality and MetS with periodontal condition in Japanese adults, based on the level of alcohol consumption. In 2008, 4,207 males aged 45.4 ± 8.9 years and 1,270 females aged 45.9 ± 9.7 years had annual workplace health check-ups at a company in Japan. Periodontal status was represented as periodontal pocket depth at the mesio-buccal and mid-buccal sites for all teeth. Alanine aminotransferase (ALT), and metabolic components were examined. Multiple linear regression analysis showed a significant association between deep pocket depth and the coexistence of elevated ALT and MetS in males with low alcohol consumption. Females showed no such relationship. In conclusion, the association between periodontal condition and the combination of elevated ALT and MetS was confirmed in males. That is, a clear association between liver abnormalities and periodontal condition was seen in male subjects with no or low alcohol consumption and MetS, providing new insights into the connection between liver function and periodontal health.

Periodontal status and metabolic syndrome in middle-aged Japanese.

BACKGROUND: Metabolic syndrome (MetS) increases the risk of various lifestyle-related diseases. Although some studies have reported a significant relationship between periodontal status and MetS, little information exists about the nature of the relationship between periodontal health status and MetS. METHODS: Comprehensive health examinations of 6,421 Japanese individuals (aged 34 to 77 years) were performed. Five components (obesity, high blood pressure, low high-density lipoprotein cholesterol, hypertriglyceridemia, and high plasma glucose) of MetS were evaluated, and individuals with ≥3 positive components were defined as having MetS. The periodontal parameters were periodontal probing depth (PD) and clinical attachment level (CAL), and each parameter was divided into three categories (none/mild: ≤3 mm; moderate: 4 to 5 mm; and severe: ≥6 mm). RESULTS: When PD and CAL were analyzed separately in multivariate models, both parameters were significantly associated with MetS. In a multivariate logistic regression analysis using a combination of PD and CAL as an independent variable, individuals with severe PD and severe CAL or with moderate PD and moderate CAL had significantly higher odds ratios for MetS, but severe CAL without severe PD was not significantly associated with MetS. CONCLUSION: The results of this study suggest that periodontal status, particularly in individuals suspected to have untreated periodontal infection indicated by ≥4 mm PD, is significantly associated with MetS.

Relationship between receiving a workplace oral health examination including oral health instruction and oral health status in the Japanese adult population.

OBJECTIVES: Dental caries and periodontal disease are highly prevalent in the Japanese adult population. Oral examination is an effective method to find various oral health problems in their early stages. However, workplace oral examination is not common in Japan. The purpose of this study was to examine the relationship between receiving workplace oral health examination, including oral health instruction, and oral health status in the Japanese adult population. METHODS: This study was performed using data from 4,484 Japanese employees aged 35-74 yr. The proportion of teeth with a probing depth (PD) ≥4 mm and the number of decayed teeth were used for periodontal disease and dental caries parameters. The subjects were asked by questionnaire about past experiences with workplace oral health examination. RESULTS: The subjects who received a workplace oral health examination every year had better periodontal health status than those receiving an examination for the first time. The odds ratio for having ≥10% of teeth with PD ≥4 mm in the subjects who received workplace oral health examination every year was 0.63 (p<0.05) after adjustment for age, sex, smoking habits, tooth-brushing habits, routine visits to dental clinics, number of missing teeth, and oral hygiene status, in a multivariate, multinomial logistic regression analysis. On the other hand, no significant relationship was found between workplace oral health examination and number of decayed teeth. CONCLUSIONS: These results suggest that workplace oral health examination accompanied by oral health instruction may be effective for maintenance of periodontal health.

Novel intronic CYP21A2 mutation in a Japanese patient with classic salt-wasting steroid 21-hydroxylase deficiency.

Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder caused by the defective CYP21A2 gene that leads to various degrees of impaired secretion of both cortisol and aldosterone. In the present study, we analyzed the CYP21A2 gene in a Japanese male patient with 21-OHD and functionally characterized the mutant CYP21A2 gene. The patient presented with hypoglycemia and a salt-losing crisis during the neonatal period, and was diagnosed as having the salt-wasting form of 21-OHD based on the clinical and laboratory findings. Analysis of the CYP21A2 gene revealed that the patient is homozygous for a novel C to A conversion at -9 position of intron 9 (IVS9-9C>A) and that his parents are heterozygous for the IVS9-9C>A mutation. Transient expression of the IVS9-9C>A mutant CYP21A2 gene in COS-1 cells demonstrated that the mutation creates an aberrant splice acceptor site at -7 position of intron 9 and totally inactivates the authentic splice acceptor site of intron 9, which results in complete deficiency of 21-hydroxylase activity and loss of immunoreactive 21-hydroxylase protein. Clinical presentations of the patient as the severe salt-wasting form of 21-OHD are in good agreement with these results of the expression study. In conclusion, the patient is a homozygote for the novel intronic IVS9-9C>A mutation, which affects messenger RNA splicing and totally inactivates 21-hydroxylase to give rise to clinically manifest classic salt-wasting 21-OHD.

A case report of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas and literature review.

Osteoclast-like giant cell tumors rarely arise in the pancreas. Here we report the case of a 78-year-old woman who was diagnosed with a well-defined 3 cm multilocular mass in the pancreatic body by the use of ultrasonography, computed tomography and magnetic resonance imaging. The rim and the septa of the tumor were well enhanced. The distal pancreas was removed with the spleen and the peripancreatic lymph nodes. Macroscopically, the mass was composed predominantly of a multilocular cystic tumor filled with hemorrhagic necrosis, and partly composed of solid components. A histopathological study showed a proliferation of multinucleated osteoclast-like giant cells and spindle cells. Although the predominant tumor cells were strongly positive for vimentin and CD68 and negative for epithelial markers, there were some sparsely scattered cytokeratin-positive neoplastic glands. Seventeen months after surgery, the patient is still alive and has had no recurrence. Below we review 32 cases of osteoclast-like giant cell tumor of the pancreas that have been reported in English literature since 2000.

Nonclassic steroid 21-hydroxylase deficiency due to a homozygous V281L mutation in CYP21A2 detected by the neonatal mass-screening program in Japan.

Since 1989, neonatal mass screening for congenital adrenal hyperplasia (CAH) has been carried out in Japan. The mass screening has detected not only the patients with the classic form of steroid 21-hydroxylase deficiency (21-OHD), but also those with the nonclassic (NC) form of 21-OHD, and the molecular basis in these patients has been elucidated. However, the homozygous V281L mutation in CYP21A2, the common mutation in the NC form in Caucasians, has not been described in Japanese patients, implying at least two possibilities; 1) the V281L mutation itself might be very rare in Japanese, and 2) nonclassic 21-OHD patients bearing the V281L mutation might be barely detectable by the mass-screening program, hence overlooked in Japan. In the present study, we describe a Brazilian girl with the NC form of 21-OHD, who was pointed out to have mildly elevated 17 alpha-hydroxyprogesterone in blood by the mass screening in Japan. Genetic analysis revealed that the patient was homozygous for the V281L mutation, and that the parents were heterozygous for the V281L mutation. Thus, the NC patients due to the homozygous V281L mutation can be detectable by the mass-screening program for CAH in Japan, and further accumulation and analysis of the NC patients should elucidate the frequency of the V281L allele in Japan.