POSTERIOR EYE SEGMENT COMPLICATIONS RELATED TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION.

PURPOSE: To identify complications in the posterior eye segment in patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This retrospective cohort study enrolled 747 patients with hematologic disease who had undergone allogeneic HSCT at Seoul St. Mary's Hospital from January 2009 to December 2012. The posterior eye segment complications were evaluated by reviewing information in medical records at the Department of Hematology and Ophthalmology, including the types, onset times, locations, and resolution times of the complications according to the treatment periods for HSCT; in addition, a subgroup analysis was performed. RESULTS: Among the 635 included patients, 48 (7.6%) experienced complications related to HSCT in the posterior eye segment. Twenty patients were diagnosed with retinal hemorrhage, 16 with cytomegalovirus (CMV) retinitis, and 5 with uveitis. Six patients (37.5%) with retinal hemorrhage had a lesion in Zone 1 and took more time to recover from this complication. Retinal tear (1/16, 6.3%) and rhegmatogenous retinal detachment (2/16, 12.5%) were observed in the patients with CMV retinitis. Among the 20 patients with retinal hemorrhage, 18 (90.0%) had thrombocytopenia, 14 (70.0%) had pancytopenia, and 7 (35.0%) had profound cytopenia. Cytomegalovirus viremia was detected in 16 (72.7%) of the 22 patients with inflammation-associated complications. CONCLUSION: Understanding of each patient's general condition, which is affected by the specific procedures used for HSCT, is important for the diagnosis and management of transplantation-related complications in the posterior eye segment.

Long-term trends in intraocular pressure after combined vitrectomy with sub-tenon injection of triamcinolone acetonide.

PURPOSE: To evaluate the long-term effect of vitrectomy by itself and combined vitrectomy with sub-Tenon injection of triamcinolone acetonide (TA) on intraocular pressure (IOP). METHODS: In a retrospective cohort study, the medical records of 56 eyes of 56 patients who underwent nonemergent vitrectomy and were followed up for at least 24 months were reviewed. Thirty-two eyes of 32 patients underwent combined vitrectomy with sub-Tenon injection of TA. Twenty-four eyes of 24 patients underwent vitrectomy only. Increased IOP of >4 mmHg from the baseline, change in IOP from the baseline, and preoperative and postoperative measured IOPs were recorded and compared between the two groups, and with fellow eyes. RESULTS: Minimum follow-up period was 24 months. Except the IOP at postoperative 1 day, there were no significant differences between vitrectomized eyes and nonvitrectomized fellow eyes. There were also no differences between vitrectomized eyes and eyes that underwent combined vitrectomy with sub-Tenon injection of TA. And in the comparison of the vitrectomy-only eye group and the vitrectomy with sub-Tenon TA eye group, there was also no significant difference during the whole follow-up period. CONCLUSION: Vitrectomy by itself or combined vitrectomy with sub-Tenon injection of TA does not seem to increase IOP in the long term.

The cross-linguistic comparison of perceptual strength norms for Korean, English and L2 English.

This study aimed to establish perceptual strength norms for 1,000 words in the languages of Korean, English, and L2 English, in order to investigate the similarity and difference across languages as well as the influence of the environment on semantic processing. The perceptual strength norms, which are a collection of word profiles that summarize how a word is experienced through different sensory modalities including the five common senses and interoception, provide a valuable tool for testing embodiment cognition theory. The results of this study demonstrated that language users had parallel sensory experiences with concepts, and that L2 learners were also able to associate their sensory experiences with linguistic concepts. Additionally, the results highlighted the importance of incorporating interoception as a sensory modality in the development of perceptual strength norms, as it had a negative correlation with both vision and concreteness. This study was the first to establish norms for Korean and L2 English and directly compare languages using the identical and translation-equivalent word list.

Continuous glucose monitoring: current clinical use.

Four kinds of subcutaneous continuous glucose monitoring (CGM) machines have been currently introduced in clinical practice. These machines exhibit real-time glucose on the monitor every 5 minutes and have alarms to indicate hypoglycaemia and hyperglycaemia. However, thus far, there is no clear consensus about the clinical indications for CGM in actual clinical practice. CGM should be an ideal and powerful tool for monitoring glucose variability. Glycaemic variability has become a major concern over the years with growing evidence on its detrimental impact with respect to the risk of diabetic complications. Although the HbA1c level is ubiquitously measures in clinical practice, this level does not adequately represent glycaemic variability. Currently available evidence indicates that CGM aids in lowering the HbA1c level without increasing the incidence of severe hypoglycaemic episodes in patients with type 1 diabetes. Thus far, CGM has not been indicated for preventing severe hypoglycaemia or for treating type 2 diabetes because sufficient supporting evidence has not been obtained. Promising results have been obtained for the use of CGM for pregnant women with diabetes and for patients with hospital hyperglycaemia. Predictions regarding the feasibility of the closed-loop system have proven to be optimistic. CGM-integrated communication systems using information technology such as smart phone help controlling blood glucose more easily and effectively.

Prevention of diabetes: a strategic approach for individual patients.

The 'diabetes epidemic' is an important health and socioeconomic problem worldwide. Type 2 diabetes is a chronic disease with gradual deterioration in glucose metabolism which causes multiple systemic complications. Therefore, early intervention in the prediabetic stage is a valuable approach to reduce diabetes development and related complications. Many clinical trials have suggested that lifestyle intervention, including moderate-intensity exercise and diet control, and pharmacologic intervention using metformin, α-glucosidase inhibitors, thiazolidinediones, anti-obesity drugs and incretin mimics, are effective in preventing diabetes development. However, an individualized approach with careful consideration of the patient's risk status and health economics is needed to perform a successful intervention programmes. In this review, we will summarize the known evidence on treatment- and cost-effectiveness of drug and lifestyle treatment. Additionally, we will propose a strategic approach algorithm that is applicable to clinical practice.

Structural Priming and Inverse Preference Effects in L2 Grammaticality Judgment and Production of English Relative Clauses.

This study investigated inverse preference effects in L2 structural priming of English relative clauses and their potential influences on subsequent learning of target structures. One hundred fourteen Chinese learners of English at a low-to-intermediate proficiency level participated in a structural priming experiment with a pretest-posttest design. The experimental group underwent a priming task in which they orally produced syntactic structures immediately after viewing English object or passive relative clauses as primes, whereas the control group only read sentences unrelated to English relative clauses. A grammaticality judgment task and a sentence completion task were used to measure the inverse preference effect and its subsequent effects on L2 learning. The results showed the presence of structural priming and inverse preference effects in immediate production, which extended to subsequent learning of L2. In subsequent grammaticality judgments and production, L2 learners performed better with English object relative clauses than with English passive relative clauses in comparison with the pretest. The results are discussed in terms of the structural frequency in both L1 and L2 as well as the implicit learning mechanisms of structural priming.

Transforming growth factor-ß induces epithelial to mesenchymal transition and suppresses the proliferation and transdifferentiation of cultured human pancreatic duct cells.

Pancreatic duct cells are considered a potential source of ß-cell regeneration, and transforming growth factor-ß (TGF-ß) has been suggested to perform an important role in these processes, but the underlying mechanism of the signal pathways, especially in humans, remains poorly understood. To evaluate the role of TGF-ß1, pancreatic duct cells were isolated from three brain-dead organ donors. Pancreatic cell clusters harvested after islet isolation were dispersed to single cells and cultured in monolayers, then treated with TGF-ß1. We analyzed the characteristics of the cultured cells, the TGF-ß1 intracellular signaling pathway, the proliferation, and transdifferentiation rates of the duct cells. We also evaluated the genes and protein expression patterns after TGF-ß1 treatment. After TGF-ß1 treatment, typical morphologic changes representative of EMT were observed and Erk1/2, JNK, and AKT phosphorylation, Ras downstream effectors, were increased. ß cell-specific transcription factors including PDX-1, Beta2/NeuroD, Ist-1, and NGN3 were markedly suppressed and the rate of transdifferentiation into ß cells was also suppressed. Genomic and proteomic analyses suggested that TGF-ß1 induces marked changes in a variety of structural genes and proteins associated with EMT. In conclusion, TGF-ß1 induces EMT in cultured human pancreatic duct cells, but suppresses its proliferation and transdifferentiation into ß cells. Our results are the first report of TGF-ß1 effects for EMT and ductal cell transdifferentiation and proliferation at the protein level in human pancreatic duct cells.

Surgical Outcomes of Vitrectomy for Macular Hole-induced Retinal Detachment According To Various Surgical Methods: A Multicenter Retrospective Study.

PURPOSE: To investigate the surgical outcomes of vitrectomy for macular hole-induced retinal detachment(MHRD), with respect to the surgical adjunctive method used. METHOD: We performed retrospective multicenter study of patients who underwent vitrectomy for MHRD. The visual/anatomical outcomes after vitrectomy were analyzed. We also analyzed these outcomes according to surgical method and the presence of persistent macular hole after the vitrectomy. RESULT: Thirty-four patients (34 eyes) from 6 hospitals were included in this study. The mean age of the patients was 64.56 ± 12.23 years; 31 patients (91.2%) were female. The mean LogMAR best-corrected visual acuity (BCVA) significantly improved 6 months after vitrectomy (p < .001). Retinal detachment completely improved in 32 eyes (94.1%). The visual prognoses and macular hole closure rates were not different depending on subretinal fluid drainage site. The presence or absence of a persistent macular hole after vitrectomy did not affect the visual outcomes. However, the recurrence of MHRD was significantly higher in eyes with persistent macular holes(p = .015). CONCLUSION: The surgeries to treat MHRD differed in terms of the procedure depending on the surgeons, but the visual outcomes did not differ depending on the surgical adjunctive method employed. There were no differences in the visual prognoses, regardless of whether there was a persistent macular hole; however, recurrence was significantly higher in eyes with persistent macular holes. Therefore, further surgical treatment might be considered for eyes with persistent macular holes after MHRD surgery.

Therapeutic Efficacy of Autologous Platelet Concentrate Injection on Macular Holes with High Myopia, Large Macular Holes, or Recurrent Macular Holes: A Multicenter Randomized Controlled Trial.

We aimed to evaluate the anatomical and functional outcomes of pars-plana vitrectomy (PPV) with or without autologous platelet concentrate (APC) injection in patients with recurrent macular holes (MHs), large MHs, or MHs with high myopia. This multicenter, prospective, interventional randomized controlled trial was conducted from March 2017 to April 2020. Participants were randomly allocated to a PPV group or a PPV+APC group. All participants underwent standard 25-gauge PPV, and eyes in the PPV+APC group underwent PPV with intravitreal APC injection before air-gas exchange. A total of 117 patients were enrolled (PPV group: n = 59, PPV+APC group: n = 58). Hole closure was achieved in 47 participants (79.7%) in the PPV group and 52 participants (89.7%) in the PPV+APC group. There were no between-group differences in the anatomical closure rate or functional outcomes including best-corrected visual acuity, metamorphopsia, pattern-reversal visual evoked potential, or Visual Function Questionnaire-25 score. The use of APC injection does not improve the anatomical and functional outcomes of surgery for large MHs, recurrent MHs, or MHs with high myopia. The adjunctive use of APC can be considered in selected cases because it is not inferior to conventional MH surgery, is relatively simple to perform, and is not affected by the surgeon's skill.

Genetic effect of CysLTR2 polymorphisms on its mRNA synthesis and stabilization.

BACKGROUND: We previously demonstrated that single nucleotide polymorphism (SNP) and haplotypes were associated with aspirin hypersensitivity in asthmatics. We investigated the genetic effects of the SNPs and haplotypes on the expression of the CysLTR2 gene. METHODS: We measured CysLTR2 protein and mRNA expression in EB virus-infected B cell lines from asthmatics having ht1+/+ and ht2+/+. A gel retardation assay was used to identify nuclear protein binding to the c.-819 promoter site. The function of promoter and 3'-UTR were assessed using pGL3 luciferase and pEGFP reporter system, respectively. RESULTS: We found that the expression of CysLTR2 protein was higher in B cell lines of asthmatics having ht2+/+ than in those having ht1+/+. PMA/ionomycin induced higher mRNA expression of CysLTR2 in B cell lines from ht2+/+ asthmatics than those from ht1+/+ asthmatics. A nuclear protein from the B cell lines showed stronger DNA binding affinity with a probe containing c.-819T than one containing c.-819G. The luciferase activity of the c.-819T type of CysLTR2 promoter was higher than that of the c.-819G type. EGFP expression was higher in the EGFP-c.2078T 3'-UTR fusion construct than in the c.2078C construct. CONCLUSION: The sequence variants of CysLTR2 may affect its transcription and the stability of its mRNA, resulting in altered expression of CysLTR2 protein, which in turn causes some asthmatics to be susceptible to aspirin hypersensitivity.

Effects of Ranibizumab, Bevacizumab, and Aflibercept on Senescent Retinal Pigment Epithelial Cells.

PURPOSE: Anti-vascular endothelial growth factor (VEGF) agents have been used for the last 10 years, but their safety profile, including cytotoxicity against various ocular cells such as retinal pigment epithelial (RPE) cells, remains a serious concern. Safety studies of VEGF agents conducted to date have primarily relied on healthy RPE cells. In this study, we assessed the safety of three anti-VEGF agents, namely, ranibizumab, bevacizumab, and aflibercept, on senescent RPE cells. METHODS: Senescent human induced pluripotent stem cell-derived RPE cells were generated by continuous replication and confirmed with senescence biomarkers. The viability, proliferation, protein expression, and phagocytosis of the senescent RPE cells were characterized 3 days after anti-VEGF treatment with clinical doses of ranibizumab, bevacizumab, or aflibercept. RESULTS: Clinical doses of ranibizumab, bevacizumab, or aflibercept did not decrease the viability or alter proliferation of senescent RPE cells. In addition, the anti-VEGF agents did not induce additional senescence, impair the protein expression of zonula occludens-1 and RPE65, or reduce the phagocytosis capacity of senescent RPE cells. CONCLUSIONS: Clinical dosages of ranibizumab, bevacizumab, or aflibercept do not induce significant cytotoxicity in senescent RPE cells.

Ocular Manifestations of Biopsy-Proven Pulmonary Sarcoidosis in Korea.

PURPOSE: To investigate the clinical features and ocular manifestations of biopsy-proven pulmonary sarcoidosis in Korea. METHODS: 55 patients diagnosed with pulmonary sarcoidosis by bronchoscopic or excisional biopsy were included. By retrospective clinical chart review, we investigated features of uveitis, ocular and systemic treatments, visual acuity, angiotensin-converting enzyme level, chest radiography, and pulmonary function tests. Clinical features were analyzed by presence of uveitis, site of biopsy, and first manifested sign of sarcoidosis. RESULTS: The group with uveitis (n = 39) presented with higher systemic (71.8%) and immunosuppressive treatment rates (35.9%) than the group without uveitis (31.3%, 0%, resp.) (P = 0.007, P = 0.005, resp.). There were no significant differences in clinical features, including systemic treatment rate, by type of biopsy. Of 39 patients with uveitis, the group with ocular manifestation as a first sign of sarcoidosis showed higher systemic and immunosuppressive treatment rates (88.9%, 55.6%) compared to the group with pulmonary manifestation as a first sign (57.1%, 19.0%) (P = 0.037, P = 0.018, resp.). CONCLUSIONS: In patients with biopsy-proven pulmonary sarcoidosis, the presence of ocular involvement and uveitis as a first sign could be significant factors associated with higher systemic treatment rate, especially with immunosuppressive agents. Biopsy site determined by location and size had no influence on clinical features.

5-aminolevulinic acid biosynthesis in Escherichia coli coexpressing NADP-dependent malic enzyme and 5-aminolevulinate synthase.

5-aminolevulinate (ALA) synthase (E.C. 2.3.1.37), which mediates the pyridoxal phosphate-dependent condensation of glycine and succinyl-CoA, encoded by the Rhodobacter sphaeroides hemA gene, enables Escherichia coli strains to produce ALA at a low level. To study the effect of the enhanced C4 metabolism of E. coli on ALA biosynthesis, NADP-dependent malic enzyme (maeB, E.C. 1.1.1.40) was coexpressed with ALA synthase in E. coli. The concentration of ALA was two times greater in cells coexpressing maeB and hemA than in cells expressing hemA alone under anaerobic conditions with medium containing glucose and glycine. Enhanced ALA synthase activity via coupled expression of hemA and maeB may lead to metabolic engineering of E. coli capable of large-scale ALA production.

The Association of Metabolic Syndrome with Diabetic Retinopathy: The Korean National Health and Nutrition Examination Survey 2008-2012.

AIMS: To explore gender differences and associations between metabolic syndrome (MetS) and its components, and diabetic retinopathy (DR) in Korean adults aged 40 years and older with diabetes. METHODS: We analyzed data from the Korean National Health and Nutrition Examination Surveys (2008-2012). In total, 2,576 type 2 diabetic participants, aged 40 and older, were evaluated. Seven standard retinal fundus photographs were obtained after pupil dilation in both eyes. DR was graded using the modified Airlie House classification system. Vision-threatening diabetic retinopathy (VTDR) included proliferative diabetic retinopathy and clinically significant macular edema. MetS was defined according to the Joint Interim Statement, proposed in 2009, by the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute. Multivariate logistic regression analysis was used to assess the relationship between MetS and its individual components with DR and VTDR. RESULTS: After controlling for confounders, MetS was not associated with DR in men or women. Moreover, the risk for DR or VTDR did not increase with increasing MetS components. However, high waist circumference was significantly inversely associated with VTDR (adjusted odds ratio = 0.36; 95% confidence interval = 0.14-0.93) only in men. CONCLUSIONS: MetS was not associated with DR or VTDR in a Korean diabetic population. However, among MetS components, it seems that abdominal obesity was inversely associated with VTDR in Korean diabetic men.

Reduction of Sulfonylurea with the Initiation of Basal Insulin in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Undergoing Long-Term Sulfonylurea-Based Treatment.

BACKGROUND: There were a limited number of studies about ß-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of ß-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin. METHODS: In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT. RESULTS: Among 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group. CONCLUSION: Long-acting basal insulin replacement could improve the glycemic status and restore ß-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.

Retinal Nerve Fiber Layer Converges More Convexly on Normal Smaller Optic Nerve Head.

PURPOSE: To investigate retinal nerve fiber layer (RNFL) configuration in the optic nerve head (ONH) and peripapillary area according to disc size and to determine whether it explains cup discrepancy among eyes with different disc sizes. METHODS: Horizontal and vertical RNFL curvature and mean thickness were measured using confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph) in 63 normal subjects grouped by disc size. Average and quadrant RNFL thickness, disc size, average cup-to-disc ratio (CDR), and convergence angle at the optic disc were also measured using Cirrus HD-optical coherence tomography. The relationships between disc size and RNFL curvature, thickness, angle at optic disc, and CDR were evaluated. RNFL curvature and convergence angle reflects convexity "on" and "into" the optic disc, respectively. RESULTS: CDR was smaller for small discs and was positively correlated with disc size (P<0.001). Horizontal and vertical RNFL curvatures were significantly more convex for small than large discs (P=0.001, 0.017). Horizontal and vertical RNFL angles at the optic disc were positively correlated with disc size (P<0.001, P=0.012). Optic disc area was negatively correlated with mean RNFL thickness at the optic disc margin measured by HRT (P=0.002), but not in the peripapillary area by optical coherence tomography. CONCLUSIONS: Using imaging techniques, we demonstrated that the shape of the RNFLs converging "on" and entering "into" the optic disc was more convex for small optic discs compared with large discs. A low CDR for small discs could be mediated by these RNFL profiles at the ONH, which may guide the clinical evaluation of glaucomatous ONH damage.

The association between chronic kidney disease and diabetic retinopathy: the Korea National Health and Nutrition Examination Survey 2008-2010.

PURPOSE: To explore the relationship between chronic kidney disease and diabetic retinopathy in a representative population of Korean diabetic adults. METHODS: We analyzed data from the Korea National Health and Nutrition Examination Surveys (2008-2010). A total of 15,409 individuals (weighted frequency, 32,168,636) aged 19 and over who completed ophthalmologic and renal functional examinations were evaluated. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate of < 60 ml/min/1.73 m2 or proteinuria greater than 1+. Seven standard photographs from the Early Treatment for Diabetic Retinopathy Study were obtained from each eye after pharmacological pupil dilatation. Diabetic retinopathy (DR) was defined as the presence of 1 or more retinal microaneurysms or retinal blot hemorrhages with or without more severe lesions. Vision-threatening diabetic retinopathy (VTDR) was defined as the presence of a clinically significant macular edema (CSME) or proliferative diabetic retinopathy. RESULTS: CKD was significantly associated with DR and VTDR (odds ratio (OR), 95% confidence interval (CI); 2.49(1.43-4.35) and 3.74(1.56-8.95), respectively) in the diabetic population. After controlling for confounders, however, CKD was significantly associated only with DR [adjusted OR (aOR), 95% CI; 2.34(1.04-5.28)]. In the subgroup analysis for CKD, only proteinuria was significantly associated with DR and VTDR (aOR, 95% CI; 4.56(1.51-13.77) and 5.61(1.06-29.87), respectively) in this population. CONCLUSIONS: Our results show that CKD appears to be associated with DR and VTDR in a Korean diabetic population. In particular, proteinuria, not decreased eGFR, is more significantly associated with DR or VTDR.

The Relationship between Visual Impairment and Health-Related Quality of Life in Korean Adults: The Korea National Health and Nutrition Examination Survey (2008-2012).

INTRODUCTION: To evaluate health-related quality of life (HRQoL) in Korean adults with visual impairment(VI) using various measures based on a nationally distributed sample. METHODS: Using the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2012) data, we compared EuroQol five-dimensional questionnaire (EQ-5D) and EQ-visual analogue scale (VAS) scores after adjusting for socio-demographic and psychosocial factors as well as for comorbidities with VI. Logistic regressions were used to elucidate determinants for the lowest quintile HRQoL scales according to VI severity. Uncorrected visual acuity (VA) which implies vision of ordinary life was measured using an international standard vision chart based on Snellen scale. RESULTS: 28,825 participants (sum of weights; 37,562,376) were included in the analysis. The mean EQ-5D and EQ-VAS scores were significantly lower in the VI groups than in the normal vision (defined as VA 20/20-20/25) group based on the better or worse seeing eye (P<.0001 and P<.0001, respectively). Participants with moderate (VA 20/80-20/160) and severe VI (VA ≤20/200) had higher scores of multivariate-adjusted odd ratios (aORs) for the lowest quintile than did the normal vision group which was particularly evident in the results from EQ-5D, whereas the results of the mild VI (VA 20/32-20/63) group did not identify significant differences from the normal vision group independent of classification according to the better or the worse seeing eye. Conversely, EQ-VAS revealed significantly higher score of multivariate-aORs for the lowest quintile in participants with mild VI either for the better or worse seeing eye. CONCLUSIONS: The severity of VI was definitely associated with impaired HRQoL compared with the normal vision population. The analyses presented here elicited even mild VI could potentially deteriorate the health-related quality of life (or subjective perception of health quality) and therefore, therapeutic approaches should also focus on the subjective perception and better management of health condition.

The Insulin Resistance but Not the Insulin Secretion Parameters Have Changed in the Korean Population during the Last Decade.

BACKGROUND: This study aimed to compare the patterns of insulin secretion and resistance between Korean subjects in the 1990s and 2000s. METHODS: Insulin secretion and resistance indices were calculated from subjects who underwent 75-g oral glucose tolerance tests in the year 1997 to 1999 and 2007 to 2011 at the Seoul St. Mary's Hospital, Korea. RESULTS: A total of 578 subjects from the 1990s (mean age, 48.5 years) and 504 subjects from the 2000s (mean age, 50.2 years) were enrolled. Compared with the subjects from the 1990s, those from the 2000s exhibited increased insulin resistance (increased homeostatic model assessment for insulin resistance), and reduced insulin sensitivity (reduced Matsuda index and quantitative insulin sensitivity check index), regardless of their glucose tolerance status. However, insulinogenic index did not reveal significant differences between the 2 decades in subjects with or without diabetes. A distinct relationship was confirmed between Matsuda index and total area under the curve (insulin/glucose) in each glucose tolerance group. The mean product of the Matsuda index and the total area under the curve (insulin/glucose) as well as the oral disposition index, was lower in subjects with normal glucose tolerance from the 2000s than in those from the 1990s. CONCLUSION: After rapid economic growth and changes in lifestyle patterns, insulin resistance has worsened across the glucose tolerance status; however, the insulin secretory function remained unchanged, which resulted in an increase in the susceptibility to the development of type 2 diabetes mellitus among Korean subjects without diabetes. We could not rule out the potential selection bias and therefore, further studies in general Korean population are needed.

Association between Lower Normal Free Thyroxine Concentrations and Obesity Phenotype in Healthy Euthyroid Subjects.

We investigated whether thyroid function could identify obesity phenotype in euthyroid subjects. A cross-sectional analysis was performed among nondiabetic, euthyroid subjects. We stratified subjects into four groups by BMI and insulin resistance (IR). Of 6241 subjects, 33.8% were overweight or obese (OW/OB) and 66.2% were normal weight (NW). Free thyroxine (FT4) levels were negatively associated with body mass index, waist circumference, triglyceride, c-reactive protein, and HOMA-IR and positively with high-density lipoprotein cholesterol in both genders. In multivariate regression analysis, FT4 level, a continuous measurement, was negatively correlated with HOMA-IR (ß = -0.155, P < 0.001 in men; ß = -0.175, P < 0.001 in women). After adjustment for age, sex, metabolic, and life style factors, subjects in the lowest FT4 quartile had an odds ratio (OR) for IR of 1.99 (95% confidence interval 1.61-2.46), as compared to those in the highest quartile. The association between low FT4 and IR remained significant in both NW and OW/OB subgroups. In conclusion, low normal FT4 levels were independently related to IR in NW and OW/OB euthyroid subjects. Further studies are needed to investigate the mechanisms by which low FT4 levels are linked to high IR in euthyroid ranges.