Yul Hwangbo

Prevalence and Clinical Characteristics of Recently Diagnosed Type 2 Diabetes Patients with Positive Anti-Glutamic Acid Decarboxylase Antibody

Background Latent autoimmune diabetes in adults (LADA) refers to a specific type of diabetes characterized by adult onset, presence of islet auto-antibodies, insulin independence at the time of diagnosis, and rapid decline in β-cell function. The prevalence of LADA among patients with type 2 diabetes varies from 2% to 20% according to the study population. Since most studies on the prevalence of LADA performed in Korea were conducted in patients who had been tested for anti-glutamic acid decarboxylase antibody (GADAb), a selection bias could not be excluded. In this study, we examined the prevalence and clinical characteristics of LADA among adult patients recently diagnosed with type 2 diabetes. Methods We included 462 patients who were diagnosed with type 2 diabetes within 5 years from the time this study was performed. We measured GADAb, fasting insulin level, fasting C-peptide level, fasting plasma glucose level, HbA1c, and serum lipid profiles and collected data on clinical characteristics. Results The prevalence of LADA was 4.3% (20/462) among adult patients with newly diagnosed type 2 diabetes. Compared with the GADAb-negative patients, the GADAb-positive patients had lower fasting C-peptide levels (1.2±0.8 ng/mL vs. 2.0±1.2 ng/mL, P=0.004). Other metabolic features were not significantly different between the two groups. Conclusion The prevalence of LADA is 4.3% among Korean adult patients with recently diagnosed type 2 diabetes. The Korean LADA patients exhibited decreased insulin secretory capacity as reflected by lower C-peptide levels.

High-normal free thyroxine levels are associated with low trabecular bone scores in euthyroid postmenopausal women

SummaryTrabecular bone scores (TBS) have recently been developed as a diagnostic tool to assess bone texture. We studied thyroid status and TBS in a population-based cohort and demonstrated that high-normal thyroxine levels are associated with low TBS in healthy euthyroid postmenopausal women.IntroductionIncreased thyroid hormone levels affect bone mineral density (BMD) and, if untreated, increase the risk of fracture. However, the relationship between thyroid function and bone microarchitecture has not yet been established. Trabecular bone scores (TBS) are gray-level textural measurements of dual energy X-ray absorptiometry (DXA) images. The TBS has been proposed as an indirect index of bone microarchitecture. The goal of this study was to characterize the relationship between thyroid function and TBS in euthyroid men and postmenopausal euthyroid women.MethodsA total of 1376 euthyroid subjects (648 postmenopausal women and 728 men) were recruited from a community-based cohort in Korea. Free thyroxine (fT4) levels, thyroid stimulating hormone (TSH) levels, BMD, and TBS were measured and compared.ResultsThere was no significant relationship between either fT4 or TSH levels and BMD in men and women. Multiple linear regression analysis showed that high-normal fT4 levels were negatively correlated with TBS (β = −0.111; P = 0.002, after adjusting for both age and body mass index [BMI]) in postmenopausal women. In men, however, there was no significant correlation between fT4 levels and TBS. TSH levels were not significantly associated with TBS in either men or women.ConclusionHigher fT4 levels within the normal reference range are associated with deterioration of trabecular microarchitecture in healthy euthyroid postmenopausal women.

Comparison of vildagliptin as an add-on therapy and sulfonylurea dose-increasing therapy in patients with inadequately controlled type 2 diabetes using metformin and sulfonylurea (VISUAL study): A randomized trial

The aim of present study is to compare the efficacy and safety of adding vildagliptin with sulfonylurea dose-increasing as an active comparator in patients who had inadequately controlled type 2 diabetes mellitus (T2DM) using metformin plus sulfonylurea in real clinical practice. Patients using metformin plus sulfonylurea were assigned to either vildagliptin add-on (50 mg twice a day, n=172) or sulfonylurea dose-increasing by 50% (n=172) treatment groups. The primary endpoint was a change in HbA(1c) after 24 weeks. The secondary endpoints were patients achieving HbA(1c)≤7.0% (53 mmol/mol) and changes in the fasting plasma glucose (FPG), 2-h postprandial glucose (2pp), lipid profiles, and urine albumin-to-creatinine ratio. Body weight and hypoglycemia were also investigated. The mean HbA(1c) at baseline was 8.6% (70 mmol/mol) in both groups. At week 24, the adjusted mean HbA(1c) levels decreased by -1.19% (-13.09 mmol/mol) with vildagliptin add-on and -0.46% (-5.06 mmol/mol) with sulfonylurea (P<0.001). Significantly more vildagliptin add-on patients achieved HbA(1c)≤7.0% (53 mmol/mol) than did sulfonylurea patients (40.1% vs. 7.9%; P<0.001). Greater reductions in FPG and 2pp were observed with vildagliptin add-on than with sulfonylurea (P<0.001). The vildagliptin add-on group exhibited no clinically relevant weight gain and had a lower incidence of hypoglycemia compared with the sulfonylurea group. Vildagliptin add-on therapy might be a suitable option for patients with T2DM that is controlled inadequately by metformin and sulfonylurea, based on its greater glucose control and better safety profile (ClinicalTrial.gov: NCT01099137).

Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer

Thyroid cancer is the most common cancer in Korea. Several susceptibility loci of differentiated thyroid cancer (DTC) were identified by previous genome-wide association studies (GWASs) in Europeans only. Here we conducted a GWAS and a replication study in Koreans using a total of 1,085 DTC cases and 8,884 controls, and validated these results using expression quantitative trait loci (eQTL) analysis and clinical phenotypes. The most robust associations were observed in the NRG1 gene (rs6996585, P=1.08 × 10−10) and this SNP was also associated with NRG1 expression in thyroid tissues. In addition, we confirmed three previously reported loci (FOXE1, NKX2-1 and DIRC3) and identified seven novel susceptibility loci (VAV3, PCNXL2, INSR, MRSB3, FHIT, SEPT11 and SLC24A6) associated with DTC. Furthermore, we identified specific variants of DTC that have different effects according to cancer type or ethnicity. Our findings provide deeper insight into the genetic contribution to thyroid cancer in different populations.

Long-term Recurrence of Small Papillary Thyroid Cancer and Its Risk Factors in a Korean Multicenter Study

Context: Small papillary thyroid cancer (PTC) generally has an excellent prognosis. However, long-term recurrence is not uncommon and sometimes leads to morbidity or mortality. Objective: To identify high-risk factors for long-term recurrence in patients with small PTC by stratifying their pathologic characteristics. Design, Setting, and Patients: We conducted a nationwide, retrospective, multicenter study of 3282 patients with PTC sized ⩽2 cm from 9 high-volume hospitals in Korea. Main Outcome Measures: The maximally selected &khgr;2 method was used to find the best cutoff points of tumor size, the number of metastatic lymph nodes (LNs), and the ratio of metastatic/examined LNs (LNR) to predict recurrence. Kaplan-Meier analysis and the Cox proportional hazards regression model were used to analyze recurrence and risk factors. Results: The optimal tumor size cutoff was 1.8 cm (10-year recurrence rates for tumors sized 0.1 to 1.7 cm and 1.8 to 2.0 cm: 7.7% vs 17.2%, respectively). Metastatic LNs ⩽1 and ≥2 provided optimal estimates of recurrence (10-year recurrence rates: 4.0% vs 16.8%, respectively). The LNR of 0.19 was the optimal cutoff point for predicting the risk of recurrence (10-year recurrence rates for LNRs of 0 to 0.18 and 0.19 to 1: 2.7% vs 16.2%, respectively). LN metastasis, lobectomy, tumor size ≥1.8 cm, and bilateral tumors were independent risk factors for recurrence. Conclusions: Long-term recurrence was increased in patients who underwent lobectomy or with tumor sized ≥1.8 cm, 2 or more metastatic LNs, or bilateral tumors. For patients with these high-risk features, total thyroidectomy could be considered to avoid reoperation.

Development and Evaluation of a Korean Version of a Thyroid-Specific Quality-of-Life Questionnaire Scale in Thyroid Cancer Patients

Purpose The purpose of this study was to develop a Korean version of the self-reported thyroid-specific quality of life (QoL) questionnaire for thyroid cancer patients (KT-QoL), and to evaluate its reliability and validity. Materials and Methods Two hundred seventy-two patients who underwent thyroidectomy from January to December 2010 were recruited in this study. The original version of the thyroid QoL was translated into Korean and evaluated for its reliability and validity. Using the developed KT-QoL, the postoperative QoL was evaluated until postoperative 1 year. Results At the preoperative baseline, the item internal consistency (IIC) ranged from ‒0.19 to 0.76, with low IIC values for items 2, 17, and 27. Item discriminant validity ranged from 86% to 97%. These values were similar at the postoperative periods. The internal consistency reliability (Cronbach’s α) was high for all dimensions, ranging from 0.90 to 0.95. The test-retest reliability (intraclass correlation coefficient) was acceptable (0.74-0.82). The external validity examined by the correlation between the item 1j (voice changes) of KT-QoL and the voice handicap index-30 ranged from 0.51 to 0.75. Patients’ QoL scores decreased after surgery, which demonstrated the sensitivity of the questionnaire. The QoL scores in patients with lobectomy showed best QoL scores postoperatively and those with receiving radioactive iodine still showed decreased QoL scores along the postoperative periods. Conclusion These results demonstrate that KT-QoL is a valid instrument for evaluating QoL of Korean patients with thyroid cancer.

Genome-wide Association Study Reveals Distinct Genetic Susceptibility of Thyroid Nodules from Thyroid Cancer.

Context Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown. Objective To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer. Design and Setting We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data. Results The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26; P = 6.12 × 10-8) and meta-analysis (OR, 1.28; P = 2.11 × 10-8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 × 10-5; rs944289, P = 8.68 × 10-5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues. Conclusions To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer.

Genetic variations in TAS 2 R3 and TAS 2 R4 bitterness receptors modify papillary carcinoma risk and thyroid function in Korean females

Type 2 taste receptors (T2Rs, TAS2Rs) mediate bitterness perception and are involved in diverse defence mechanisms in extraoral tissues. The thyrocyte-expressed T2Rs control thyroid hormone production, and this regulatory role may be associated with susceptibility to thyroid diseases. This study examined whether the variations in TAS2Rs modify the risk of papillary thyroid carcinoma (PTC) and whether such T2R-related PTC risk is associated with genetically modified thyroid function. We conducted a case-control study with 763 Korean females, including 250 PTC cases. Seventy-three single-nucleotide polymorphisms in 13 TAS2R genes and the pre-diagnosis levels of 4 thyroid-related functional markers [total triiodothyronine (TT3), free thyroxine, thyroid-stimulating hormone and thyroglobulin] were analysed. Individuals with TAS2R3/4 CC haplotype (rs2270009 and rs2234001) were at a lower risk for PTC than those with the remaining haplotypes (odds ratio = 0.59, 95% confidence interval: 0.36–0.97). Furthermore, TT3 levels were significantly reduced for TAS2R3/4 CC haplotype carriers compared with other haplotype carriers (p = 0.005). No other genetic variants exhibited critical associations with the PTC phenotype and biomarkers. In summary, genetic variations in T2R3/4 bitterness receptors may modify the PTC risk, and the genetically modified thyroid hormone level by those variations may be linked with the PTC-T2Rs association.

Interaction between alcohol consumption and methylenetetrahydrofolate reductase polymorphisms in thyroid cancer risk: National Cancer Center cohort in Korea

The effect of alcohol intake on thyroid cancer is unestablished, and its interaction effects with genetic susceptibility are unclear. In this case-control study, the relationship among alcohol intake, the methylenetetrahydrofolate reductase (MTHFR) gene, and thyroid cancer risk has been evaluated. In total, 642 cases and 642 controls of Korean origin were included, and the genetic variants C677T and A1298C of the MTHFR gene were analysed. The interactions between alcohol-consumption behaviour and genetic variants were analysed with a likelihood ratio test, wherein a multiplicative interaction term was added to a logistic regression model. There was an independent association between the C677T polymorphism and thyroid cancer risk but not for drinking history. For C677T C/C homozygotes, individuals with a history of alcohol consumption showed a protective OR (95% CI) of 0.42 (0.15–1.13) when never drinkers were used as the reference. However, this protective association was not observed among individuals with a T+ allele with an OR (95% CI) of 1.27 (0.89–1.82), showing different directions for the association between genotypes with a significant interaction (Pinteraction = 0.009). Based on the genetic characteristics of individuals included, an interaction between alcohol intake and MTHFR C677T may modify the risk of thyroid cancer.

Incidence of Diabetes After Cancer Development: A Korean National Cohort Study

Importance Diabetes is an established risk factor for developing cancer. A limited body of evidence also suggests that cancer can increase the risk of developing new cases of diabetes, but the evidence is inconclusive. Objective To evaluate whether the development of cancer is associated with increasing risk of subsequent diabetes. Design, Setting, and Participants This cohort study included a nationally representative sample of the Korean general population observed for up to 10 years (January 1, 2003, to December 31, 2013). A total of 524 089 men and women 20 to 70 years of age without diabetes and with no history of cancer at baseline were included. Exposures Incident cancer (time-varying exposure). Main Outcomes and Measures Incident type 2 diabetes using insurance claim codes. Results During 3 492 935.6 person-years of follow-up (median follow-up, 7.0 years) in 494 189 individuals (50.0% female; mean [SD] age, 41.8 [12.5] years), 15 130 participants developed cancer and 26 610 participants developed diabetes. After adjustment for age, sex, precancer diabetes risk factors, metabolic factors, and comorbidities, the hazard ratio (HR) for diabetes associated with cancer development was 1.35 (95% CI, 1.26-1.45; P < .001). The excess risk for diabetes was highest in the first 2 years after cancer diagnosis, but it remained elevated throughout follow-up. By cancer type, development of pancreatic (HR, 5.15; 95% CI, 3.32-7.99), kidney (HR, 2.06; 95% CI, 1.34-3.16), liver (HR, 1.95; 95% CI, 1.50-2.54), gallbladder (HR, 1.79; 95% CI, 1.08-2.98), lung (HR, 1.74; 95% CI, 1.34-2.24), blood (HR, 1.61; 95% CI, 1.07-2.43), breast (HR, 1.60; 95% CI, 1.27-2.01), stomach (HR, 1.35; 95% CI, 1.16-1.58), and thyroid cancer (HR, 1.33; 95% CI, 1.12-1.59) was associated with a significantly increased risk of diabetes. Conclusions and Relevance In this large Korean cohort, cancer development increased the risk of subsequent diabetes. These data provide evidence that cancer is associated with an increased risk of diabetes in cancer survivors independent of traditional diabetes risk factors. Physicians should remember that patients with cancer develop other clinical problems, such as diabetes, with higher frequency than individuals without cancer, and should consider routine diabetes screening in these patients.