Seong-Su Moon

Association of periodontitis with insulin resistance, β-cell function, and impaired fasting glucose before onset of diabetes

Periodontitis and insulin resistance (IR) show bidirectional relationship. No studies have assessed the associations of periodontitis with IR, impaired β-cell function, and impaired fasting glucose (IFG) in the general population. We investigated these associations in a representative sample of the Korean population. The subjects were 8,248 males and 10,874 females, who were ≥ 20 years of age and participants in the third, fourth, and fifth Korea National Health and Nutritional Examination Surveys (2008-2010). Periodontitis was defined as community periodontal index (CPI) ≥ code 3 according to World Health Organization criteria. Homeostasis model assessments of IR and β-cell function (HOMA-IR and HOMA-β) were calculated. Participants with periodontitis showed a higher prevalence of diabetes than those without periodontitis. Among subjects without diabetes, after adjustment for confounding factors including age, gender, body mass index, systolic blood pressure, serum total cholesterol, smoking status, alcohol consumption, region, and regular exercise, a comparison of participants with periodontitis vs those without showed a significantly higher prevalence of IFG (28.5% vs. 17.7%, p<0.001) and lower HOMA-β (115.2 vs. 130.8, p<0.001). Periodontitis was identified as a risk factor for IFG (OR, 1.301; 95% CI, 1.193∼1.418; p<0.001). Conversely, participants with and without periodontitis had similar HOMA-IR. In conclusion, periodontitis showed an association with decreased β-cell function and increased prevalence of IFG before onset of diabetes as well as increased prevalence of diabetes in the Korean population. Future longitudinal studies are warranted to elucidate the shared pathophysiology between periodontal disease and diabetes mellitus.

Serum thyrotropin as a risk factor for thyroid malignancy in euthyroid subjects with thyroid micronodule.

An elevated thyroid stimulating hormone (TSH) level is a risk factor for differentiated thyroid cancer. The present study investigated whether TSH is a risk factor for thyroid microcarcinoma (TMC) in euthyroid subjects with a micronodule.

Association of pyruvate dehydrogenase kinase 4 gene polymorphisms with type 2 diabetes and metabolic syndrome

AIMS Pyruvate dehydrogenase kinase 4 (PDK4) plays a crucial role in glucose utilization and lipid metabolism by regulating the pyruvate dehydrogenase complex (PDC) and is an emerging therapeutic target for type 2 diabetes. To date, no study has specifically examined the relationship between PDK4 gene polymorphisms and type 2 diabetes or metabolic syndrome. METHODS The association of common single nucleotide polymorphisms (SNPs) was examined in PDK4 [-208A/G (rs10085637), IVS3+192C/T (rs3779478), IVS6+31A/G (rs2301630), IVS7+514A/G (rs12668651), IVS10+75C/T (rs10247649)] with type 2 diabetes and metabolic syndrome in 651 Korean subjects with type 2 diabetes and 350 nondiabetic Korean subjects. The association of these SNPs with clinical parameters related to metabolic syndromes including obesity, hyperglycemia, hypertension, and dyslipidemia was also examined. RESULTS No significant association was found between the studied SNPs and type 2 diabetes, metabolic syndrome, or clinical parameters. The PDK4 gene haplotype ACAGC showed a modest association with type 2 diabetes. However, the significance of this association was lost after considering for multiple comparisons. CONCLUSIONS PDK4 polymorphisms may not be associated with type 2 diabetes or metabolic syndrome. Further studies utilizing a larger study population are required to confirm these results.

Algae Undaria pinnatifida Protects Hypothalamic Neurons against Endoplasmic Reticulum Stress through Akt/mTOR Signaling

Increased endoplasmic reticulum (ER) stress is known to be one of the causes of hypothalamic neuronal damage, as well as a cause of metabolic disorders such as obesity and diabetes. Recent evidence has suggested that Undaria pinnatifida (UP), an edible brown algae, has antioxidant activity. However, the neuroprotective effect of UP has yet to be examined. In this study, to investigate the neuroprotective effect of UP on ER stress-induced neuronal damage in mouse hypothalamic neurons, mice immortal hypothalamic neurons (GT1-7) were incubated with extract of UP. ER stress was induced by treating with tunicamycin. Tunicamycin induced apoptotic cell death was compared with the vehicle treatment through excessive ER stress. However UP protected GT1-7 cells from cell death, occurring after treatment with tunicamycin by reducing ER stress. Treatment with UP resulted in reduced increment of ATF6 and CHOP, and recovered the decrease of phosphorylation of Akt/mTOR by tunicamycin and the increment of autophagy. These results show that UP protects GT1-7 cells from ER stress induced cell death through the Akt/mTOR pathway. The current study suggests that UP may have a beneficial effect on cerebral neuronal degeneration in metabolic diseases with elevated ER stress.

Association of the DDAH2 gene polymorphism with type 2 diabetes and hypertension

AIMS The aim of this study was to investigate whether the polymorphism of DDAH2 is associated with type 2 diabetes and hypertension in Korean population. METHODS Total 605 subjects were included in this study: 403 patients with type 2 diabetes and 202 non-diabetic control subjects. The SNP rs805304 and rs2272592 in DDAH2 were analyzed. We examined the association of SNP rs805304 and rs2272592 in DDAH2 with type 2 diabetes and hypertension. RESULTS SNP rs2272592 was significantly associated with type 2 diabetes (P<0.001) while SNP rs805304 was not (P=0.716). We observed that the prevalence of the AG+GG genotypes were significantly greater than AA homozygotes in type 2 diabetes (AA vs AG+GG; OR 20.74, 95% CI 6.48-66.35, P<0.001). Significance was maintained after adjusting for age, sex, BMI, DBP and BUN (OR 21.03, 95% CI 2.83-151.14, P=0.003). Both SNP rs805304 and rs2272592 in DDAH2 were not significantly associated with hypertension. CONCLUSIONS In the present study, we found that SNP rs2272592 in DDAH2 is associated with type 2 diabetes but SNP rs805304 in DDAH2 is not. DDAH2 SNP rs2272592 AG+GG genotypes are associated with genetic susceptibility to type 2 diabetes in Korean population.

Intraventricular administration of Tenebrio molitor larvae extract regulates food intake and body weight in mice with high-fat diet–induced obesity

We recently reported the in vitro and in vivo antiobesity effects of Tenebrio molitor larvae, a traditional food in many countries, but it remains unknown how the larvae affect appetite regulation in mice with diet-induced obesity. We hypothesized that the extract of T molitor larvae mediates appetite by regulating neuropeptide expression. We investigated T molitor larvae extracts (TMEs) effects on anorexigenesis and endoplasmic reticulum (ER) stress-induced orexigenic neuropeptide expression in the hypothalami of obese mice. Intracerebroventricular TME administration suppressed feeding by down-regulating the expression of the orexigenic neuropeptides neuropeptide Y and agouti-related protein. T molitor larvae extract significantly reduced the expression of ER stress response genes. These results suggest that TME and its bioactive components are potential therapeutics for obesity and ER stress-driven disease states.

Association of hearing impairment with insulin resistance, β-cell dysfunction and impaired fasting glucose before onset of diabetes.

Diabetes is a known risk factor for hearing impairment. No study regarding the association of insulin resistance (IR), β–cell dysfunction and impaired fasting glucose (IFG) with hearing impairment has been reported in the population without diabetes. We examined these associations using a representative sample of the Korean population.

Acute anti-obesity effects of intracerebroventricular 11β-HSD1 inhibitor administration in diet-induced obese mice

The hypothalamus is the regulatory centre of both appetite and energy balance and endoplasmic reticulum (ER) stress in the hypothalamus is involved in the pathogenesis of obesity. Recently, inhibition of 11 β hydroxysteroid dehydrogenase type1 (11β‐HSD1) was reported to have an anti‐obesity effect by reducing fat mass. However, the link between the role of 11β‐HSD1 in the hypothalamus and obesity has yet to be determined. In the present study, embryonal primary hypothalamic neurones and high‐fat diet (HFD) fed mice were used to investigate the anorexigenic effects of 11β‐HSD1 inhibitors both in vitro and in vivo. In hypothalamic neurones, carbenoxolone (a non selecitve 11β‐HSD inhibitor) alleviated ER stress and ER stress‐induced neuropeptide alterations. In HFD mice, i.c.v. administration of carbenoxolone or KR67500 (nonselective and selective 11β‐HSD1 inhibitors, respectively) was associated with less weight gain compared to control mice for 24 hours after treatment, presumably by reducing food intake. Furthermore, glucose regulated protein (Grp78), spliced X‐box binding protein (Xbp‐1s), c/EBP homologous protein (chop) and ER DnaJ homologue protein (Erdj4) expression was decreased in the hypothalami of mice administrated 11β‐HSD1 inhibitors compared to controls. Conversely, the phosphorylation of protein kinase B (PKB/Akt), signal transducer and activator of transcription 3 (Stat3), mitogen‐activated protein kinase (MAPK/ERK) and S6 kinase1 (S6K1) in the hypothalamus was induced more in mice treated using the same regimes. In conclusion, acute 11β‐HSD1 inhibition in the hypothalamus could reduce food intake by decreasing ER stress and increasing insulin, leptin, and mammalian target of rapamycin complex 1 (mTORC1) signalling.

Association between diabetic peripheral neuropathy and heart rate variability in subjects with type 2 diabetes

AIM This study evaluated the association of Heart rate variability (HRV) measurements with diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes. METHODS This study included 102 Korean subjects with type 2 diabetes. The Michigan neuropathy screening instrument (MNSI) questionnaire score, the MNSI examination score (MNSIES) and the total symptom score were examined for DPN evaluation. Noninvasive HRV measurements were performed using photoelectric plethysmography. Patients with a MNSIES > 2 were considered to have DPN. RESULTS The MNSIES showed significant negative associations with the high frequency (HF) (r = -0.212, p = 0.033) and low frequency (LF) (r = -0.286, p = 0.004) powers. Multiple linear regression analysis revealed that only HF power maintained a significant negative association with the MNSIES (β = -0.184; 95% CI -0.365 to -0.003; p = 0.047), after controlling for significant related confounders, with HRV parameters in male patients with type 2 diabetes. The HF (p = 0.010) and LF (p = 0.025) powers differed significantly between male patients without and those with DPN according to the MNSIES. CONCLUSIONS This study revealed a negative association of DPN, as assessed by the MNSIES, with HF power in male patients with type 2 diabetes. DPN defined by foot examination was predictive of cardiac autonomic neuropathy.

Negative Association of Hepatitis B Virus With Hearing Impairment

Purpose Hearing impairment is one of the most common chronic diseases causing deterioration of the quality of life in elderly individuals. Several viral infections have been suggested to cause hearing impairment. We investigated association of hepatitis B virus (HBV) infection with hearing impairment using a representative sample of the Korean population. Method Participants included 6,583 men and 8,702 women, who were ≥ 20 years of age from the Korea National Health and Nutritional Examination Surveys of the Korean population (2010-2012). Air-conduction pure-tone thresholds were measured in a soundproof booth using an automatic audiometer for each ear at 6 frequencies (500, 1000, 2000, 3000, 4000, and 6000 Hz). An audiometric test and a laboratory examination, including an HBV surface antigen (HBsAg) test, were performed. Results Subjects who are HBsAg positive had lower average of pure-tone thresholds and lower prevalence of hearing impairment at both low/mid and high frequency compared with those without. Adjusted means of hearing thresholds were also lower among subjects who are HBsAg positive compared with subjects who are HBsAg negative. After the adjustment for age and gender, the odds of high-frequency mild hearing impairment were lower for subjects with HBV infection. In the multiple logistic regression analyses adjusting for confounding variables, the significant negative association between HBV infection and high-frequency mild hearing impairment still remained. Conclusions Contrary to previous reports, subjects who are HBsAg positive had a lower prevalence of hearing impairment compared with subjects who are HBsAg negative. Further studies are warranted to investigate the underlying mechanism regarding their negative relationship.