Glycemic Control and Oral Health Outcomes in Patients With Diabetes: Insights From a Nationwide Korean Survey.

BACKGROUND: Diabetes is recognized as a risk factor for various inflammatory conditions, including periodontitis. There exists a bidirectional relationship between glycemic control and oral health in individuals with diabetes. This study aimed to analyze the link between glycemic control and oral health status among Korean patients with diabetes. METHODS: Using data from a population-based nationwide survey conducted between 2007 and 2019, we identified 70,554 adults with diabetes-related information. The study population included 9,090 individuals diagnosed with diabetes and 61,164 healthy controls. The association between glycemic control, defined by mean glycated hemoglobin (HbA1c) values, and various oral health measures, such as tooth brushing frequency, periodontitis, denture wearing, Decayed, Missing, and Filled Teeth (DMFT) index, number of remaining teeth, and past-year dental clinic visits, was evaluated using multivariate logistic regression analyses. RESULTS: Compared to the control group, patients with diabetes exhibited a higher prevalence of periodontitis (88.6% vs. 73.3%), complete dentures (5.0% vs. 1.5%), and elevated DMFT index (33.2% vs. 26.7%) (all P < 0.001). Multivariate analyses revealed significant associations between diabetes and several oral health factors: denture status (No denture: adjusted odds ratio [aOR], 0.784; 95% confidence interval [CI], 0.627-0.979), and having fewer permanent teeth (0-19) (aOR, 1.474; 95% CI, 1.085-2.003). Additionally, a positive correlation was found between higher HbA1c levels and the risk of having fewer remaining teeth (0-19) (HbA1c < 6.5%: aOR, 1.129; 95% CI, 0.766-1.663; 6.5% ≤ HbA1c < 8.0%: aOR, 1.590; 95% CI, 1.117-2.262; HbA1c ≥ 8%: aOR, 1.910; 95% CI, 1.145-3.186) (P for trends = 0.041). CONCLUSION: We found a positive association between diabetes and poor oral health, as well as a noteworthy relationship between reduced permanent teeth (≤ 19) and glycemic control. These insights emphasize the critical role of oral health management in diabetic care and underscore the importance of maintaining effective glycemic control strategies for overall health and well-being in patients with diabetes.

The Efficacy and Safety of Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitors in Real-World Clinical Practice: Potential Cautionary Use in Elderly Patients with Type 2 Diabetes (T2D).

INTRODUCTION: Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown safe and therapeutic efficacy in randomized controlled trials (RCT) to reduce adverse cardiorenal events in high-risk patients with type 2 diabetes (T2D). In this study, we investigated the efficacy and safety of SGLT2 intervention in patients with T2D in a real-world clinical practice to confirm the validity of the RCT results. METHODS: As a retrospective study, we evaluated medical records from 596 patients with T2D treated with SGLT2 inhibitors (dapagliflozin or empagliflozin) in addition to their prior drug regimen to improve glucose control between 2015 and 2019 in the Endocrinology Department at Chungbuk National University Hospital. No control arm was evaluated to compare the effects of adding SGLT inhibitors to the pre-existing regimen. The primary objective was the measurement of glycated hemoglobin (HbA1c) from each individual patient over a 36-month period at 6-month intervals. The secondary parameters were the measurement of fasting plasma glucose (FPG) and body weight (Bwt) changes, as well as the monitoring of adverse events (AEs) and determining the reasons for drug discontinuation. RESULTS: HbA1c levels were reduced at each of the time points throughout the 36-month period and were significantly reduced by 12.5% (P < 0.01) from time 0 (8.8 ± 1.3%) to 36 months (7.7 ± 1.0%). FPG levels [from basal (180 ± 60 mg/dL) to 36 months (138 ± 38 mg/dL)] and Bwt [from basal (74 ± 15 kg) to 36 months (72 ± 15 kg)] were also significantly reduced (P < 0.01) for both measurements in the SGLT2 inhibitor add-on group. Similar to HbA1c profile, the FPG and Bwt were measured at a consistently lower level at 6 months until the end of the study. The most common AEs were hypoglycemia (n = 57), genitourinary infection (GUI) (n = 31), and polyuria (n = 28). In the elderly population (≥ 75 years old), AEs (31%) were generally more prevalent (P < 0.001) than those (21%) in the adult (< 75 years old) patients. Over the study period, 211 (35%) patients either dropped or completely discontinued the use of the SGLT2 inhibitor, and the elderly patients tended to have a higher discontinuation rate (52%; P = 0.005) than the adults (33%). CONCLUSIONS: In this study, we demonstrated that SGLT2 inhibitors are an effective and durable hypoglycemic agent to control blood glucose levels with reduced maintenance of Bwt, but their use in the elderly (≥ 75 years old) patients with T2D may warrant some additional caution due to increased probability of AEs and discontinuation of drug use.

Influenza vaccination trend and related factors among patients with diabetes in Korea: Analysis using a nationwide database.

Background: Subjects with diabetes are at higher risk of serious influenza-related complications. We aimed to investigate the yearly trend of influenza vaccination and factors associated with being unvaccinated for influenza in subjects with diabetes using a nationwide observational study performed within the recent decade. Methods: Among 105,732 subjects from the Korea National Health and Nutrition Examination Survey between 2007 and 2019, 8,632 with diabetes were included. We investigated the yearly trend of influenza vaccination and factors associated with being unvaccinated for influenza. Results: During the study period, the prevalence of influenza vaccination in subjects with diabetes showed a tendency to increase every year, reaching almost 60% in 2019, which was higher than the rate in subjects without diabetes. Younger age (adjusted hazard ratio (aHR) [95% CI] 11.29 [8.63-14.75] for < 50 years; 6.16 [5.21-7.29] for 50-65 years), male (aHR 1.67 [1.52-1.87]), current smoker (aHR 1.31 [1.00-1.72], lower-income status (aHR 1.46 [1.17, 1.84]), and high education level (aHR 1.30 [1.01-1.67]) were associated with being unvaccinated. Also, a poorer glycemic control with HbA1c ≥ 9% was found to be correlated with unvaccinated status (aHR 1.48 [1.15-1.90]). Conclusion: The influenza vaccination rate is still unsatisfactory in subjects with diabetes. Young age, males, low-income level, high education level, and poor glycemic control were associated with unvaccinated status. Considering the risk-benefits of influenza vaccination in patients with diabetes, physicians should make an effort to increase vaccination rates, especially in low vaccination rate groups.

Association between the triglyceride-glucose (TyG) index and increased blood pressure in normotensive subjects: a population-based study.

BACKGROUND: Insulin resistance (IR) is an important contributor to the development of hypertension (HTN), and the triglyceride-glucose (TyG) index has been proposed as a simple, reliable marker of IR. This study investigated the association between the TyG index and blood pressure (BP) elevation in a large general population. METHODS: The study enrolled 15,721 adults with no history of cardiometabolic diseases from the 2016-2019 Korea National Health and Nutrition Examination Survey. Participants were classified into quartiles based on the TyG index and BP was categorized as normal BP, elevated BP, pre-HTN, and HTN. The associations of the TyG index with BP categories were assessed using multivariate multinomial logistic regression models with normal BP as the reference group. RESULTS: The mean systolic/diastolic BP and prevalence of HTN increased with the TyG index (P for trend < 0.001). The continuous TyG index had a strong dose-response relationship with increased odds of elevated BP, pre-HTN, and HTN. Compared with the lowest TyG index quartile, the highest TyG index quartile was significantly associated with higher odds of having elevated BP (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.24-1.87; P for trend < 0.001), pre-HTN (OR, 2.22; 95% CI, 1.95-2.53; P for trend < 0.001), and HTN (OR, 4.24; 95% CI, 3.49-5.16; P for trend < 0.001). CONCLUSION: We found that a higher TyG index was positively associated with the risk of increased BP in normal healthy individuals. This study suggests that the TyG index might serve as a potential predictor of HTN. However, further studies with larger sample sizes and various target populations in longitudinal designs are needed.

Which factors are helpful for the early determination of treatment level in patients with interstitial lung disease in the intensive care unit to minimize the suffering in their end of life?: A retrospective study.

Interstitial lung disease (ILD) is widely known to be associated with high mortality and poor prognosis, especially in patients admitted to the intensive care unit (ICU). The objective of this study was to investigate clinical predictors for assisting relatively early decision of treatment level in the ICU. We retrospectively investigated patients with ILD who were admitted to the ICU between January 1, 2014, and September 30, 2019. A total of 64 patients were analyzed. We found the ICU and hospital mortality rates to be 67.2% and 69.8%, respectively. Nonsurvivors had a higher fraction of inspired oxygen (FiO2) on days 1 (79 ±â€…21 vs 60% ±â€…21%, P = .001) and 3 (61 ±â€…31 vs 46% ±â€…19%, P = .004). They showed lower partial pressure of oxygen/FiO2 (PF) ratio on days 1 (134 ±â€…80 vs 173 ±â€…102, P = .049) and 3 (147 ±â€…74 vs 235 ±â€…124, P = .003) than the survivor group. The lactic acid levels obtained on day 1 and PF ratio measured on day 3 were associated with mortality (odds ratio, 1.89; 95% confidence interval 1.03-3.47 and odds ratio, 0.99; 95% confidence interval 0.98-1.00, respectively). Among the 31 ICU survivors, 10 patients died in the general ward, 12 patients died after hospital discharge; only 9 patients survived after 1 year. We suggest that these clinical predictors could be used to determine the level of further treatment or withdrawal on day 3 of admission in patients with ILD admitted to the ICU to minimize the prolonged suffering in a relatively early period.

Optimal blood pressure target in the elderly: rationale and design of the HOW to Optimize eLDerly systolic Blood Pressure (HOWOLD-BP) trial.

BACKGROUND/AIMS: The optimal systolic blood pressure (SBP) goal for elderly patients with hypertension, especially to reduce cardiovascular disease (CVD) incidence and improve outcome, is unclear. This study aimed to evaluate the beneficial effects of intensive treatment for hypertension on the incidence of CVD in elderly Korean patients. METHODS: The HOW to Optimize eLDerly systolic Blood Pressure (HOWOLD-BP) trial is a multicenter, parallel-design, open-label, randomized controlled trial designed to evaluate whether intensive treatment (SBP ≤ 130 mmHg) will provide more benefits in lowering the incidence and mortality associated with CVD than standard treatment (SBP ≤ 140 mmHg) in elderly patients with hypertension aged ≥ 65 years. For this study, eleven university hospitals in Korea will enroll approximately 3,176 elderly patients with hypertension between 2019 and 2022. Patients will be requested to visit the clinic every 4 months for the first year and every 6 months thereafter for 36 months. Parameters, including clinic and home blood pressure, anthropometric and laboratory findings, and frailty assessments, will be collected according to the standardized protocol. The primary outcome is a composite of CVD (acute coronary syndrome, stroke, and heart failure) incidence and cardiovascular deaths. RESULTS: As of December 2021, 1,655 participants had been enrolled in the study, including 831 patients in the standard group and 824 patients in the intensive group. CONCLUSION: The HOWOLD-BP trial is the first study performed in Korea to evaluate the beneficial effects of intensive blood pressure treatment on CVD in elderly patients with hypertension. The results of this study will help clarify the appropriate target SBP for this population.

Female Reproductive Factors and the Risk of Bronchiectasis: A Nationwide Population-Based Longitudinal Study.

Although the oestrogen level is thought to be involved in the occurrence of bronchiectasis, limited data are available on the relationship between female reproductive factors and the risk of bronchiectasis. We performed a population-based retrospective cohort study of 959,523 premenopausal women and 1,362,401 postmenopausal women without a previous history of bronchiectasis who participated in a health screening exam in 2009 in South Korea. In premenopausal women, compared with a later age at menarche (≥16 years), an earlier menarche (<12 years) was associated with a reduced risk of bronchiectasis with an adjusted hazard ratio (aHR) (95% confidence interval (CI)) of 0.74 (0.67-0.81). However, there were no significant associations between other reproductive factors (breastfeeding, parity, or oral contraceptive use) and the risk of bronchiectasis. In postmenopausal women, the risk of bronchiectasis (aHR (95% CI)) was lower in those with an earlier menarche (0.79 (0.72-0.87) for <12 years vs. ≥16 years), a later menopause (0.90 (0.84-0.96) ≥55 years vs. <40 years), and a longer reproductive period (0.90 (0.86-0.94) for ≥40 years vs. <30 years). There was no significant relationship between parity and the risk of bronchiectasis. Although breastfeeding <1 year (aHR (95% CI) = 0.92 (0.87-0.97) for <0.5 years and 0.93 (0.88-0.97) for 0.5-1 years) and oral contraceptive use <1 year (0.97 (0.94-0.99)) reduced the risk of bronchiectasis, hormone replacement therapy ≥5 years increased the risk of bronchiectasis (1.24 (1.18-1.30)). Female reproductive factors are risk factors for developing bronchiectasis, showing a higher risk associated with shorter endogenous oestrogen exposure regardless of the menopausal status.

Nationwide trends in prevalence of underweight, overweight, and obesity among people with disabilities in South Korea from 2008 to 2017.

OBJECTIVES: This study investigated the 10-year trends of weight and prevalence of underweight, overweight and obesity according to disability grade and types compared with those without disabilities. METHODS: This serial cross-sectional analysis was conducted using national disability registration data with national general health checkup data from 2008 to 2017. Age-standardized prevalence of underweight and obesity were analyzed for each year, according to the presence, type, and severity of disabilities. Odds of underweight, overweight, obesity, and severe obesity were examined by multinomial logistic regression after adjusting for socio-demographic and clinical variables using data in 2017. RESULTS: Over 10 million subjects in each year were included in the analysis. In 2017, 14,246,785 people with age between 19 and 110 years were included and 53.1% was men. For 10 years, age-standardized prevalence of obesity and severe obesity showed significant increases regardless of sex and presence of disability. However, age-standardized underweight prevalence in people without disability tended to decrease whereas it was an increase in 2012 and the prevalence has remained steady since in people with disability. People with disabilities had higher odds of underweight compared to those without disability (OR 1.41, 95% CI 1.38-1.44 in male and OR 1.31, 95% CI 1.28-1.34 in female), especially in those with severe disabilities (OR 2.00, 95% CI 1.94-2.06 in male and OR 1.83, 95% CI 1.77-1.89 in female). Women with disabilities are more likely to be obese than those without disabilities regardless of disability severity (OR 1.40, 95% CI 1.38-1.41). Participants with mental disorder showed the highest prevalence of obesity, followed by epilepsy and developmental disability. CONCLUSIONS: Having a disability was associated with higher odds/probability of both obesity and underweight. The intersection of female, severe disability, and mental/developmental disabilities was associated with probability of severe obesity. Simultaneous efforts are needed to develop health policy to reduce both the prevalence of obesity and underweight.

Long-term effectiveness and safety of quadruple combination therapy with empagliflozin versus dapagliflozin in patients with type 2 diabetes: 3-year prospective observational study.

AIMS: To investigate the long-term effectiveness and safety of two distinct sodium-glucose co-transporter 2 (SGLT2) inhibitors, empagliflozin and dapagliflozin, in inadequately controlled type 2 diabetes (T2D) despite a combined administration of metformin, glimepiride and dipeptidyl peptidase-4 inhibitor. METHODS: A total of 362 patients with T2D were enrolled for this 3-year open-label, prospective observational study. Empagliflozin (25 mg/day, n = 185) or dapagliflozin (10 mg/day, n = 177) was added to the existing triple drug regimen. HbA1c, fasting plasma glucose (FPG), body weight, and other cardiometabolic variables and adverse events were evaluated. RESULTS: At 3 years, changes in HbA1c and FPG were -1.7% (standard error [SE] 0.10) and -60.0 mg/dL(2.2), and -1.1%(0.12) and -48.1 mg/dL(3.6), for empagliflozin and dapagliflozin group, respectively (P = 0.001 and P = 0.055). Empagliflozin group showed significantly greater body weight reduction (-4.5 kg [SE 0.35] vs. -1.0 kg [SE 0.40], P = 0.024) and had beneficial effects on HDL cholesterol and LDL cholesterol (both P < 0.05). The overall incidence of adverse events, cardiovascular events and mortality did not differ between the two groups. CONCLUSIONS: Quadruple combination therapy with either empagliflozin or dapagliflozin showed a positive long-term effect in the glycemic control and body weight reduction with generally well tolerance. In general, the use of empagliflozin performed better than dapagliflozin. Clinical Trial Number NCT03748810 (ClinicalTrials.gov).

Effect of Dipeptidyl Peptidase-4 Inhibitors on Bone Health in Patients with Type 2 Diabetes Mellitus.

Patients with type 2 diabetes (T2DM) have a higher risk of bone fracture even when bone mineral density (BMD) values are normal. The trabecular bone score (TBS) was recently developed and used for evaluating bone strength in various diseases. We investigated the effect of DPP-4 inhibitors on bone health using TBS in patients with T2DM. This was a single-center, retrospective case-control study of 200 patients with T2DM. Patients were divided into two groups according to whether they were administered a DPP-4 inhibitor (DPP-4 inhibitor group vs. control group). Parameters related to bone health, including BMD, TBS, and serum markers of calcium homeostasis, were assessed at baseline and after one year of treatment. We found TBS values increased in the DPP-4 group and decreased in the control, indicating a significant difference in delta change between them. The BMD increased in both groups, with no significant differences in delta change between the two groups observed. Serum calcium and 25-hydroxy vitamin D3 increased only in the DPP-4 inhibitor group, while other glycemic parameters did not show significant differences between the two groups. Treatment with DPP-4 inhibitors was associated with favorable effects on bone health evaluated by TBS in patients with T2DM.

RANTES 59029A/G Polymorphisms Associated with Diabetic Compilations in Korean Patients with Type 2 Diabetes for over 15 Years.

BACKGROUND: Polymorphisms in the RANTES gene are known to be associated with several diseases related to insulin resistance. In this study, we investigated the association between RANTES 59029A/G polymorphisms and the prevalence of diabetic complications relative to obesity in Korean patients who had type 2 diabetes (T2D) for over 15 years. METHODS: A single-center, retrospective case-control study was performed. We included 271 patients with a duration of diabetes greater than 15 years. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze RANTES polymorphisms, identifying genotypes as GG, AG, or AA. Obesity was defined using the body mass index with a cutoff value of 25 kg/m2. Both microvascular (retinopathy and nephropathy) and macrovascular (coronary artery disease and cerebrovascular disease) complications were evaluated. RESULTS: The duration of T2D and hemoglobin A1c values at enrollment were 24.4 ± 5.0 years and 7.8 ± 1.6%, respectively, in the non-obese group, and 25.4 ± 6.1 years and 7.7 ± 1.7%, respectively, in the obese group. The prevalence of microvascular complications was significantly higher in the obese group compared with that in the non-obese group (83.5% vs. 72.0%, p = 0.039). Compared to the non-obese group, the obese group showed a higher proportion of the patients with AA or AG genotypes (64.3% vs. 84.5%, p = 0.001). CONCLUSIONS: The A allele of the RANTES gene is associated with obesity and may affect diabetic microvascular complications in patients with T2D for over 15 years.

Being Underweight Increases the Risk of Non-Cystic Fibrosis Bronchiectasis in the Young Population: A Nationwide Population-Based Study.

Although body mass index (BMI) is a potential risk factor for bronchiectasis in young adults, the association between BMI and incident bronchiectasis has not been well elucidated. This study included 6,329,838 individuals aged 20-40 years from the Korean National Health Insurance Service database 2009-2012 who were followed up until the date of the diagnosis of bronchiectasis, death, or 31 December 2018. We evaluated the incidence and risk of bronchiectasis according to the BMI category. The incidence rate of bronchiectasis increased as BMI decreased in a dose-dependent manner (p for trend <0.01). In multivariable Cox regression analysis, being underweight was an independent risk factor for the development of bronchiectasis, with a hazard ratio of 1.24 (95% confidence interval, 1.19-1.30) compared to being normal weight. In subgroup analysis, the effect of being underweight on the development of bronchiectasis was more evident in males and older individuals (30-40 years) than females and younger individuals (20-29 years), respectively (p for interaction <0.01 for both). These results remained significant in subgroup analysis in which subjects with comorbidities related to being underweight were excluded. Being underweight may be a novel risk factor for the development of bronchiectasis in young adults.

Polymorphism in the HaeIII single nucleotide polymorphism of the SLC2A1 gene and cardiovascular disease in the early type 2 diabetes mellitus.

INTRODUCTION: SLC2A1 polymorphism may play a role in the smooth muscle cell proliferation and extracellular matrix synthesis in vessels. However, the role of SLC2A1 polymorphism on diabetic cardiovascular disease (CVD) have not yet been identified. In this study, we aimed to investigate the association between SLC2A1 HaeIII polymorphism and CVD in Korean patients with type 2 diabetes mellitus (T2DM) according to disease duration. METHODS: A total of 846 patients with T2DM who visited the Chungbuk National University Hospital were investigated. The HaeIII polymorphism of SLC2A1 gene was determined by real time polymerase chain reaction method. Genotyping results were presented GG, AG, or AA. Subgroup analysis was performed according to duration of T2DM (⩽10, 11-20, >20 years). RESULTS: The AA genotype was significantly associated with higher prevalence of CVD in patients with DM duration less than 10 years (26.3% vs 9.2%, p = 0.014). There was no significant association between SLC2A1 HaeIII polymorphism and other diabetic complications including, retinopathy, nephropathy, neuropathy, cerebrovascular disease, and peripheral artery disease. CONCLUSIONS: The SLC2A1 HaeIII polymorphism was associated with CVD in Korean patients with T2DM with short disease duration.

Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism.

BACKGROUND: Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominant0.26 after adjusting for other factors. CONCLUSION: CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.

Identification of candidate gene variants of monogenic diabetes using targeted panel sequencing in early onset diabetes patients.

INTRODUCTION: Monogenic diabetes is attributed to genetic variations in a single gene. Maturity-onset diabetes of the young (MODY) is the most common phenotype associated with monogenic diabetes, but is frequently misdiagnosed as either type 1 or type 2 diabetes. Increasing our basic understanding of genetic variations in MODY may help to improve the accuracy of providing the correct diagnosis and personalize subsequent treatment regimens in different racial populations. For this reason, this study was designed to identify nucleotide variants in early onset diabetes patients with clinically suspected MODY in a Korean population. RESEARCH DESIGN AND METHODS: Among 2908 Korean patients diagnosed with diabetes, we selected 40 patients who were diagnosed before 30 years old and were clinically suspected of MODY. Genetic testing was performed using a targeted gene sequencing panel that included 30 known monogenic diabetes genes. The pathogenicity of the identified variants was assessed according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG-AMP) guidelines. RESULTS: A total of six rare missense variants (p.Ala544Thr in HNF1A, p.Val601Ile and p.His103Tyr in ABCC8, p.Pro33Ala in PDX1, p.Gly18Glu in INS, and p.Arg164Gln in PAX4) in five distinct MODY genes were identified in five patients. In addition, a variant was identified in mitochondrial DNA at 3243A>G in one patient. The identified variants were either absent or detected at a rare frequency in the 1000 Genomes Project. These variants were classified as uncertain significance using the ACMG-AMP guidelines. CONCLUSION: Using a targeted gene sequencing panel, we identified seven variants in either MODY genes or mitochondrial DNA using a Korean patient population with early onset diabetes who were clinically suspected of MODY. This genetic approach provides the ability to compare distinct populations of racial and ethnic groups to determine whether specific gene is involved in their diagnosis of MODY.

Longitudinal Changes of High Molecular Weight Adiponectin are Associated with Postpartum Development of Type 2 Diabetes Mellitus in Patients with Gestational Diabetes Mellitus.

BACKGROUND: The influence of serial changes of adipokines on maternal glucose metabolism from pregnancy to postpartum periods in women with previous gestational diabetes mellitus (pGDM) has not been thoroughly explored. We tried to examine the relationship between the serial changes of adipokines and the development of diabetes mellitus (DM) in women with pGDM. METHODS: We longitudinally measured following adipokines: high molecular weight (HMW) adiponectin, retinol-binding protein-4 (RBP-4), lipocalin-2, and chemerin, during pregnancy, and at 2 months and 3 years after delivery. Based on glucose status at postpartum 3 years, we divided into three groups: normal glucose tolerance (GDM-NGT, n=20), impaired glucose tolerance (GDM-IGT, n=23), and GDM-DM (n=22). We analyzed the correlations between adipokines and various metabolic parameters. RESULTS: Plasma HMW adiponectin levels were not different among the three groups during pregnancy. However, HMW adiponectin levels increased at 3 years after the delivery in women with GDM-NGT compared with women with GDM-DM. In the GDM-IGT group, HMW adiponectin levels increased at 2 months postpartum compared to pregnancy period. In contrast, HMW adiponectin levels showed no alternation after parturition in women with GDM-DM. HMW adiponectin was negatively correlated with body mass index and a homeostasis model assessment of insulin resistance. Other adipokines such as RBP-4, lipocalin-2, and chemerin neither showed any differences among the groups nor any significant correlations with 3 years postpartum status of glucose intolerance. CONCLUSION: Serial changes of HMW adiponectin are associated with the maintenance of glucose metabolism in women with pGDM after delivery.

The Associations Between Vitamin D Receptor BsmI and ApaI Polymorphisms and Obesity in Korean Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Vitamin D receptor (VDR) polymorphisms are associated with osteoporosis, diabetes, immunological diseases, and cancers. However, the association of obesity with VDR polymorphisms has shown inconsistent results, and perhaps it depends upon the characteristics of a population. Therefore, we evaluated the association between BsmI (rs1544410) and ApaI (rs7975232) polymorphisms of VDR and obesity in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 506 patients with T2DM participated in the study. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze BsmI and ApaI polymorphisms; the genotypes were presented as BB, Bb, or bb for BsmI and AA, Aa, or aa for ApaI. Obesity was defined using the body mass index (BMI) with a cutoff level of 25 kg/m2. RESULTS: The prevalence of obesity was higher in patients with the bb genotype than in those with BB or Bb genotypes (48.4% vs 33.9%, P = 0.031). The mean BMI was 25.2 ± 3.5 kg/m2 in patients with bb genotype and 24.1 ± 3.1 kg/m2 in patients with BB or Bb genotypes. Patients with Aa or aa genotypes showed a higher prevalence of obesity than patients with AA genotype (47.6% vs 26.1%, P = 0.043). Glycemic control parameters and lipid profiles did not show significant differences with either polymorphism. CONCLUSION: To our knowledge, this is the first study to assess the association between VDR polymorphisms and obesity in Korean patients with T2DM. Further studies in larger populations and multiethnic cohorts are needed to validate our findings.

Tertiary RNA Folding-Targeted Drug Screening Strategy Using a Protein Nanopore.

Bacterial riboswitch RNAs are attractive targets for novel antibiotics against antibiotic-resistant superbacteria. Their binding to cognate metabolites is essential for the regulation of bacterial gene expression. Despite the importance of RNAs as therapeutic targets, the development of RNA-targeted, small-molecule drugs is limited by current biophysical methods. Here, we monitored the specific interaction between the adenine-sensing riboswitch aptamer domain (ARS) and adenine at the single-molecule level using α-hemolysin (αHL) nanopores. During adenine-induced tertiary folding, adenine-bound ARS intermediates exhibited characteristic nanopore events, including a two-level ionic current blockade and a ∼ 5.6-fold longer dwell time than that of free RNA. In a proof-of-concept experiment, tertiary RNA folding-targeted drug screening was performed using a protein nanopore, which resulted in the discovery of three new ARS-targeting hit compounds from a natural compound library. Taken together, these results reveal that αHL nanopores are a valuable platform for ultrasensitive, label-free, and single-molecule-based drug screening against therapeutic RNA targets.