Efficacy and Safety of a New Sustained-release Pregabalin Formulation Compared With Immediate-release Pregabalin in Patients With Peripheral Neuropathic Pain: A Randomized Noninferiority Phase 3 Trial.

OBJECTIVE: This study investigated whether a new sustained-release (SR) pregabalin formulation is noninferior to immediate-release (IR) pregabalin in alleviating peripheral neuropathic pain in Korean patients. MATERIALS AND METHODS: This was a randomized, double-blind, active-controlled phase 3 study of patients with diabetic peripheral neuropathy or postherpetic neuralgia from 41 sites in South Korea in 2017-2018. Eligible patients were randomized (1:1) to receive once-daily SR pregabalin or twice-daily IR pregabalin (150 to 600 mg/d) in a double-dummy manner for 12 weeks according to a stratified permuted block randomization scheme. The primary endpoint was the Daily Pain Rating Scale score at the end of treatment, averaged from the last 7 available scores. RESULTS: A total of 319 of 371 (86.0%) randomized patients completed the 12-week treatment (SR pregabalin: n=154; IR pregabalin: n=165; per-protocol set: n=296). The least square mean difference between both groups for the primary endpoint was 0.06 (SE 0.19); (95% confidence interval -0.31 to 0.42), with the lower limit of the confidence interval above the pre-specified margin (-0.78; Pnoninferiority<0.0001). Drug-related treatment-emergent adverse events (TEAEs) were comparable between both groups. The incidence of drug-related TEAEs leading to treatment discontinuation was low (SR pregabalin: 2.7%; IR pregabalin: 1.1%). No serious drug-related TEAEs or deaths occurred. DISCUSSION: The results demonstrate that the new once-daily SR pregabalin formulation is noninferior to twice-daily IR pregabalin in reducing peripheral neuropathic pain and is well tolerated in Korean patients with diabetic peripheral neuropathy or postherpetic neuralgia after 12 weeks of treatment.

Effects of DA-9801 on the inflammation and apoptosis induced by angiotensin II in human dermal microvascular endothelial cells.

DA-9801, a plant-based drug used for the treatment of diabetic neuropathy, is known to improve angiotensin II (Ang II)-induced vascular endothelial cell dysfunction. However, the underlying mechanism is not fully understood. We aimed to determine whether the protective effect of DA-9801 against Ang II-induced endothelial cell dysfunction was mediated via inhibition of endothelial cell inflammation and apoptosis. Ang II-induced oxidative stress was attenuated by pretreatment of human dermal microvascular endothelial cells (HDMECs) with DA-9801. This prevented the Ang II-induced upregulation of NAD(P)H oxidase (the NOX4 and p22phox subunits) and reactive oxygen species. Further, pretreatment of HDMECs with DA-9801 ameliorated Ang II-mediated nuclear factor kappa B activity via prevention of the upregulation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. It also decreased the Ang II-stimulated increase in inducible nitric oxide synthase (NOS) and decreased endothelial NOS protein expression. DA-9801 decreased Ang II-induced upregulation of intercellular adhesion molecule 1, vascular adhesion molecule, and E-selectin in HDMECs. Moreover, TUNEL and annexin V-FITC fluorescence staining for apoptosis and the activities of caspases 9, 7, and 3 decreased in HDMECs pretreated with DA-9801, indicating that the drug enhanced anti-apoptotic pathways. Thus, DA-9801 modulated Ang II-induced endothelial cell dysfunction via inflammatory and apoptotic pathways.

γ-Linolenic Acid versus α-Lipoic Acid for Treating Painful Diabetic Neuropathy in Adults: A 12-Week, Double-Placebo, Randomized, Noninferiority Trial.

BACKGROUND: This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN). METHODS: This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS). RESULTS: Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was -0.65 (-1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ1=0.51). For the TSS, the treatment difference was -0.05 (-1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ2=0.054). There were no serious adverse events associated with the treatments. CONCLUSION: GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.

Risk factors for hypothyroidism in euthyroid thyroid nodule patients with lymphocytic thyroiditis on fine needle aspiration cytology.

BACKGROUND/AIMS: Lymphocytic thyroiditis as cytology diagnosis from fine needle aspiration (FNA) is frequently detected in patients with thyroid nodules. However, the clinical outcome for upcoming hypothyroid events has been rarely clarified in euthyroid patients. METHODS: We retrospectively reviewed the data of patient who had lymphocytic thyroitidis on FNA cytology of thyroid nodule from January 2005 to December 2010 at a tertiary referral hospital. In total, 109 patients with follow-up thyroid function tests (TFT) were enrolled. Final outcomes included overt and subclinical hypothyroidism with thyroid stimulating hormone (TSH) levels ≥ 10 mIU/L. Potential parameters predicting clinical hypothyroidism were analyzed by multivariate analysis. RESULTS: Over the mean follow-up duration of 51.6 months, 14 out of 109 patients (12.8%) developed clinical hypothyroidism that required thyroid hormone replacement. The median onset time to hypothyroidism was 16 months (range, 3 to 88) and ≥ 60% of patients experienced clinical hypothyroidism within 1 year. By multivariate analysis, background thyroiditis (relative risk [RR], 9.78; p = 0.004), thyroid peroxidase antibody positivity (RR, 9.90; p = 0.003), nodule size (RR, 1.24; p < 0.001), and initial TSH (RR, 1.47; p = 0.009) were the independent risk factors for predicting hypothyroidism in euthyroid patients. CONCLUSION: Hypothyroidism frequently occurs during the follow-up in euthyroid patients with thyroid nodules which show lymphocytic thyroiditis on FNA cytology. Close surveillance and regular TFT are needed in high-risk patients for upcoming clinical hypothyroidism.

Male-specific association between subclinical hypothyroidism and the risk of non-alcoholic fatty liver disease estimated by hepatic steatosis index: Korea National Health and Nutrition Examination Survey 2013 to 2015.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease encompassing a broad spectrum of pathologic changes in the liver. Metabolic derangements are suggested to be main causes of NAFLD. As thyroid hormone is a main regulator of energy metabolism, there may be a link between NAFLD and thyroid function. In previous studies, the association between NAFLD and thyroid function was not conclusive. The aim of this study was to clarify the relationship between NAFLD and thyroid function, focusing on subclinical hypothyroidism, using nationwide survey data representing the Korean population. NAFLD was defined as a hepatic steatosis index of 36 or higher. Based on the analysis of nationwide representative data, subclinical hypothyroidism was related to a high risk of NAFLD in males, but not in females. Our study showed that thyroid function might play a substantial role in the development of NAFLD, especially in males. Further study to elucidate the underlying mechanism of gender specific association of mild thyroid dysfunction and NAFLD would be required.

Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects with Type 2 Diabetes Mellitus.

BACKGROUND: This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus. METHODS: In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ≥6 measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements. RESULTS: A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%). CONCLUSION: CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.

Comparison of Adherence to Glimepiride/Metformin Sustained Release Once-daily Versus Glimepiride/Metformin Immediate Release BID Fixed-combination Therapy Using the Medication Event Monitoring System in Patients With Type 2 Diabetes.

PURPOSE: The purpose of this study was to compare the adherence of the glimepiride/metformin sustained release (GM-SR) once-daily fixed-dose combination and glimepiride/metformin immediate release (GM-IR) BID fixed-dose combination in type 2 diabetes therapies. METHODS: An open-label, randomized, multicenter, parallel-group study was conducted at 11 hospitals in the Republic of Korea. A total of 168 patients with type 2 diabetes treated with >4 mg of glimepiride and 1000 mg of metformin by using free or fixed-dose combination therapy for at least 2 weeks were enrolled. Patients were randomized to receive GM-SR 4/1000 mg once-daily or GM-IR 2/500 mg BID for 24 weeks. Adherence was compared by using the Medication Event Monitoring System (MEMS). FINDINGS: A significant difference in adherence was observed between the 2 groups. Overall adherence, defined by the number of container openings divided by the number of prescribed doses, was 91.7% in the GM-SR group and 88.6% in the GM-IR group (P < 0.001). The percentage of treatment days with the correct number of doses taken was 85.3% in the GM-SR group and 75.1% in the GM-IR group (P < 0.001). The percentage of missed doses was 11.7% in the GM-SR group and 15.3% in the GM-IR group (P < 0.001). The percentage of doses taken in the correct time window and therapeutic coverage were higher in the GM-SR group (P < 0.001). There was no significant difference in glycosylated hemoglobin changes or number of adverse events between the 2 groups. A total of 168 patients randomized to receive GM-SR once daily (86 patients) or GM-IR twice daily (82 patients). Mean Age were 57.8 ± 9.6 years old. Male : female ratio was 47.6 : 52.4 %. Body mass index were 66.3 ± 12.0 kg/m2, Diabetes duration were 10.5 ± 6.6 years. IMPLICATIONS: This study showed that patient adherence with GM-SR once daily was significantly better than with GM-IR BID. ClinicalTrials.gov identifier: NCT01620489.

Sex differences in risk factors for subclinical hypothyroidism.

OBJECTIVE: To investigate the prevalence of subclinical hypothyroidism (SCH) in Korean adults and identify the risk factors for the occurrence of SCH by sex. DESIGN AND METHODS: This study used data from the Sixth Korea National Health and Nutrition Examination Survey (KNHANES VI), a cross-sectional, nationally representative survey, which comprises a health interview survey, a health examination survey and a nutrition survey. To examine SCH, the reference range of thyroid-stimulating hormone (TSH) was defined using both the range provided by the test kit manufacturer (SCH-M) and a population-based range (SCH-P). We investigated the prevalence of SCH and its risk factors by sex using both reference ranges. RESULTS: The prevalence of SCH in Koreans according to SCH-M (0.35-5.5 µIU/mL) was 5.6%, and 3.3% with SCH-P (0.62-6.68 µIU/mL). For men, smoking significantly reduced the incidence of SCH, positive anti-thyroid peroxidase antibody (TPOAb) significantly increased the risk of SCH, and in an adjusted model, the risk of SCH in all quartiles increased as the urine iodine creatinine ratio (UICR) quartile increased. For women, positive TPOAb was confirmed as a risk factor for SCH, as was the highest UICR quartile. Furthermore, the odds ratio for SCH in urban vs rural residence was 1.78. CONCLUSIONS: The prevalence rates of SCH were similar to those reported in the literature and previously known risk factors were confirmed using both TSH reference ranges. The notable findings from this study are that the increased risk of SCH with increased iodine intake was more marked in men than in women and that residential area may be a risk factor for SCH in women.

Gender specific association of parathyroid hormone and vitamin D with metabolic syndrome in population with preserved renal function.

The association of parathyroid hormone (PTH) and vitamin D with Metabolic syndrome (MetS) was evaluated using representative data from the Korean population. Data from 7004 subjects aged 50 or older with preserved renal function (excluding chronic kidney disease stage 3b to 5) who were included in the Korean National Health and Nutrition Examination Survey between 2008 and 2010 were analysed. Higher PTH levels (pg/ml) were observed in subjects with MetS than in those without MetS among both genders (60.1 (58.6-61.6) vs. 62.4 (60.7-64.2) in males p = 0.018, 60.7 (59.4-62.1) vs. 63.9 (62.4-65.6) in females, p < 0.001). For females, PTH levels were significantly higher in subjects with MetS than in those without MetS after adjustment for possible covariates. Lower 25(OH)D levels were significantly associated with MetS only in male subjects (p = 0.004). As the number of MetS components increased, a significant rise in PTH levels (p for trend 0.005 in males and 0.024 in females) and a decrease in 25(OH)D levels (p for trend < 0.001 in males and 0.053 in females) were observed. In conclusion, among subjects with preserved renal function, PTH levels were possibly associated with MetS in females, whereas vitamin D levels exhibited a possible link to MetS in males.

Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea.

BACKGROUND: Diabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV). METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes. RESULTS: Most of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by -3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms² in the ALA group, whereas it declined by -15.04 ms² in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by -0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events. CONCLUSION: Although a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

Recombinant human TSH stimulated thyroglobulin levels at remnant ablation predict structural incomplete response to treatment in patients with differentiated thyroid cancer.

In patients with differentiated thyroid cancer, stimulated thyroglobulin (sTg) levels after thyroid hormone withdrawal (THW) at remnant ablation (RA) and at 6 to 12 months are known to have good prognostic value. This study aimed to evaluate the prognostic impacts and best cutoff values of sTg levels under recombinant human thyroid stimulating hormone (rhTSH) treatment at RA and at follow-up. A total of 151 patients were enrolled, of whom 77 were followed up with rhTSH-stimulated Tg (rhTSH-sTg) and 74 with THW-stimulated Tg (THW-sTg) at 6 to 12 months after rhTSH-aided RA. Risk stratification, response to treatment (excellent, indeterminate, biochemical incomplete, and structural incomplete response [SIR]), and clinical outcome were accessed by revised American Thyroid Association (ATA) guideline criteria. Seven out of 151 (4.6%) patients were confirmed to have SIR during the median follow-up of 79.0 months; 3 in the rhTSH group and 4 in the THW group. One hundred thirty-two out of 151 (87.4%) patients were confirmed to have excellent response; 68 (51.5%) in the rhTSH group and 64 (48.5%) in the THW group. The cutoff values of sTg for predicting SIR to treatment at rhTSH-aided RA, THW-sTg, and rhTSH-sTg were 4.64 ng/mL (sensitivity 85.7%, specificity 76.4%, negative predictive value [NPV] 99.2%), 2.41 ng/mL (sensitivity 100%, specificity 94.3%, NPV 100%), and 1.02 ng/mL (sensitivity 66.7%, specificity 94.6%, NPV 98.6%), respectively. sTg levels using rhTSH at both RA and follow-up has a high NPV and are as effective as using THW for predicting SIR. The risk classification according to the revised ATA guidelines can be used effectively to supplement rhTSH-aided sTg levels to predict better clinical outcomes.

Physician-Directed Diabetes Education without a Medication Change and Associated Patient Outcomes.

BACKGROUND: When patients with diabetes mellitus (DM) are first referred to a hospital from primary health care clinics, physicians have to decide whether to administer an oral hypoglycemic agent (OHA) immediately or postpone a medication change in favor of diabetes education regarding diet or exercise. The aim of this study was to determine the effect of diabetes education alone (without alterations in diabetes medication) on blood glucose levels. METHODS: The study was conducted between January 2009 and December 2013 and included patients with DM. The glycosylated hemoglobin (HbA1c) levels were evaluated at the first visit and after 3 months. During the first medical examination, a designated doctor also conducted a diabetes education session that mainly covered dietary management. RESULTS: Patients were divided into those who received no diabetic medications (n=66) and those who received an OHA (n=124). Education resulted in a marked decrease in HbA1c levels in the OHA group among patients who had DM for <1 year (from 7.0%±1.3% to 6.6%±0.9%, P=0.0092) and for 1 to 5 years (from 7.5%±1.8% to 6.9%±1.1%, P=0.0091). Those with DM >10 years showed a slightly lower HbA1c target achievement rate of <6.5% (odds ratio, 0.089; P=0.0024). CONCLUSION: For patients who had DM for more than 5 years, higher doses or changes in medication were more effective than intensive active education. Therefore, individualized and customized education are needed for these patients. For patients with a shorter duration of DM, it may be more effective to provide initial intensive education for diabetes before prescribing medicines, such as OHAs.

Prognostic value of preoperative anti-thyroglobulin antibody in differentiated thyroid cancer.

CONTEXT: The coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune disease could represent a better or worse prognosis. This study investigated the prognostic importance of preoperative anti-thyroglobulin antibody (TgAb) in DTC patients. DESIGN AND PATIENTS: This retrospective hospital-cohort study enrolled 1171 consecutive DTC patients with preoperative TgAb data, who underwent total thyroidectomy between January 2006 and December 2011. Clinical parameters studied included demographics, primary tumour characteristics, radioiodine therapy, thyroid function tests, preoperative thyroglobulin (Tg) and TgAb levels, and cancer persistence/recurrence. RESULTS: A total of 254 (21.7%) patients were preoperatively TgAb positive. The percentage positive for thyroid peroxidase (TPO) antibody and lymphocytic thyroiditis was significantly higher in the TgAb-positive group. The TgAb-positive group had a significantly higher rate of lymphatic invasion and lymph node metastasis both overall and in patients without TPOAb and lymphocytic thyroiditis (non-HT group). The mean number of total and central lymph nodes dissected and rate of lateral lymph node dissection were significantly higher in the TgAb-positive group, both overall and in non-HT patients. In regression analysis, preoperative TgAb was an independent risk factor for lateral lymph node metastasis. Over 50.2±14.5 months of follow-up, disease persistence/recurrence was not significantly different between patients with and without TgAb, both overall and in non-HT patients. Preoperative TgAb showed no significant correlation with final disease status. CONCLUSION: Positive preoperative serum TgAb is associated with worse primary tumour characteristics but rarely showed poor prognosis, probably due to more aggressive treatment of these subjects.

Parathyroid hormone and vitamin D are associated with the risk of metabolic obesity in a middle-aged and older Korean population with preserved renal function: A cross-sectional study.

BACKGROUND: In general, obesity is a major contributor to metabolic syndrome (MetS) and is associated with insulin resistance (IR). Metabolically obese but normal weight (MONW) individuals present metabolic abnormalities and features of MetS despite having a normal range of body mass index (BMI). In recent years, different subtypes of obesity have been introduced, including metabolically healthy obese (MHO) and metabolically obese obese (MOO). Also, it has been reported that vitamin D and parathyroid hormone (PTH) are possibly linked with MetS. METHODS AND FINDINGS: In this study, we aimed to evaluate the association between serum 25(OH)D, serum PTH, and the risk of metabolic obesity in four subtypes using nationally representative survey data for a Korean population conducted between 2008 and 2010. Of the 29,235 Korean participants, 18,997 subjects aged under 50 years were excluded. Participants with diabetes (n = 1,520), renal insufficiency (glomerular filtration rate [GFR] < 45 ml/min/1.73 m2, chronic kidney disease [CKD] stage 3b, 4, and 5 according to KDOQI classification [1]) (n = 49), history of treatment for osteoporosis (n = 455), insufficient data (n = 1,613), and fasting time less than 8 hours prior to blood collection (n = 771) were excluded for analysis. Ultimately, 5,830 adults (2,582 men and 3,248 women) were eligible for the present study. And, subtypes of obesity were divided into four types: Metabolically healthy normal weight (MHNW), Metabolically healthy obese (MHO), Metabolically obese but normal weight (MONW), and Metabolically obese obese (MOO). Female subjects with metabolic obesity were more likely to have higher levels of PTH and Male subjects with metabolic health were more likely to have higher serum 25(OH)D levels. CONCLUSION: We concluded that a positive association between serum PTH concentration and metabolic obesity among female subjects and an inverse relationship between serum 25(OH)D levels and the risk of metabolic obesity were found among male subjects. Further prospective studies are necessary to explore the biological mechanisms underlying these sex-specific findings.

Low muscle mass and risk of type 2 diabetes in middle-aged and older adults: findings from the KoGES.

AIMS/HYPOTHESIS: Asians have a propensity to develop type 2 diabetes with a lower BMI than Western populations. This discrepancy may be due to differences in body fat and muscle mass for a given BMI. However, unlike adiposity, it is unclear whether muscle mass affects the risk of type 2 diabetes in Asian populations. METHODS: We conducted a 2-yearly prospective assessment of 6895 participants who were free of diabetes at the baseline examination as part of the Korean Genome Epidemiology Study. The muscle mass index (MMI) was defined as the weight-adjusted appendicular skeletal muscle mass. Using Cox regression models, we evaluated the association between MMI and the risk of developing type 2 diabetes across sex-specific tertiles of MMI. Low muscle mass was defined as the sex-specific lowest tertile of MMI. Main covariates included age, sex, urban or rural residence, family history of diabetes, hypertension, smoking status, education level, monthly income, physical activity, alcohol consumption and diet. In addition, body fat mass, waist circumference and BMI were controlled as categorical variables. Obesity was defined as a BMI of ≥25 kg/m2 or a waist circumference of ≥90 cm for men and ≥85 cm for women. RESULTS: During a median follow-up of 9.06 years, 1336 participants developed type 2 diabetes. At baseline, the mean age was 52.1 years and the mean BMI was 24.4 kg/m2. The mean MMI for men and women was 32.1% and 26.0%, respectively. There was an inverse association between MMI and the risk of type 2 diabetes. Multivariate-adjusted HRs for the risk of developing type 2 diabetes were 2.05 (95% CI 1.73, 2.43), 1.39 (95% CI 1.17, 1.66) and 1.0 from the lowest to highest sex-specific MMI tertile, with an HR of 1.35 (95% CI 1.26, 1.45) per SD decline in MMI. Further adjustments for fat mass, waist circumference and BMI as categorical variables did not modify the relationship (each p < 0.01). In BMI-stratified analyses, the population-attributable fraction of the lowest tertile of MMI for developing type 2 diabetes was increased by 11.9% in the non-obese group and 19.7% in the obese group. CONCLUSIONS/INTERPRETATION: Low muscle mass as defined by MMI was associated with an increased risk of type 2 diabetes, independent of general obesity, in middle-aged and older Korean adults.

Clinical Phenotype of Diabetic Peripheral Neuropathy and Relation to Symptom Patterns: Cluster and Factor Analysis in Patients with Type 2 Diabetes in Korea.

OBJECTIVES: Patients with diabetic peripheral neuropathy (DPN) is the most common complication. However, patients are usually suffering from not only diverse sensory deficit but also neuropathy-related discomforts. The aim of this study is to identify distinct groups of patients with DPN with respect to its clinical impacts on symptom patterns and comorbidities. METHODS: A hierarchical cluster analysis and factor analysis were performed to identify relevant subgroups of patients with DPN (n = 1338) and symptom patterns. RESULTS: Patients with DPN were divided into three clusters: asymptomatic (cluster 1, n = 448, 33.5%), moderate symptoms with disturbed sleep (cluster 2, n = 562, 42.0%), and severe symptoms with decreased quality of life (cluster 3, n = 328, 24.5%). Patients in cluster 3, compared with clusters 1 and 2, were characterized by higher levels of HbA1c and more severe pain and physical impairments. Patients in cluster 2 had moderate pain levels but disturbed sleep patterns comparable to those in cluster 3. The frequency of symptoms on each item of MNSI by "painful" symptom pattern showed a similar distribution pattern with increasing intensities along the three clusters. CONCLUSIONS: Cluster and factor analysis endorsed the use of comprehensive and symptomatic subgrouping to individualize the evaluation of patients with DPN.

Triglyceride glucose index, a marker of insulin resistance, is associated with coronary artery stenosis in asymptomatic subjects with type 2 diabetes.

BACKGROUND: Insulin resistance is one of the most important contributing factors to cardiovascular disease. This study aimed to investigate the association between coronary artery stenosis (CAS) and triglyceride glucose index (TyG index), a simple insulin resistance marker, in asymptomatic subjects with type 2 diabetes. METHODS: We recruited asymptomatic adults with type 2 diabetes but without previous history of coronary heart disease (n = 888). Significant CAS was defined as maximum intraluminal stenosis ≥70 % by coronary CT angiography. TyG index was calculated as log [fasting triglycerides (mg/dl) x fasting glucose (mg/dl)/2]. RESULTS: Mean age was 63.8 ± 9.5 and 58.9 % of the subjects were men. We analyzed the participants according to the tertile of TyG index. The TyG index was correlated with HOMA-IR (r = 0.397, P < 0.001), and subjects with higher tertile of TyG index were younger but showed worse clinical and metabolic parameters. The prevalence of CAS was higher in subjects with higher tertile of TyG compared with those with lower tertile of TyG (14 % vs. 7.8 %, P = 0.022). On multiple regression analysis, the highest tertile of TyG index was an independent risk factor for CAS after adjustment for other confounders (odds ratio, 3.19 [95 % CI, 1.371-7.424]). Subgroup analysis showed that TyG index showed more significant association with CAS in patients with risk factors such as old age, longer duration of diabetes, poor glycemic control, no statin use, and male gender. CONCLUSION: Higher TyG index is associated with increased risk of CAS in asymptomatic subjects with type 2 diabetes, particularly when they have risk factors for cardiovascular disease. TRIAL REGISTRATION: This study was retrospectively registered in ClinicalTrials. gov with the registration number of NCT02070926 in Feb 23, 2014.

Comparative analysis of the efficacy of low- and moderate-intensity statins in Korea.

PURPOSE: The American College of Cardiology/American Heart Association (ACC/AHA) guidelines are based on studies with a limited number of Asian subjects; therefore, they are difficult to apply to Asian patients, including Korean patients. MATERIALS AND METHODS: Data were extracted from the clinical data warehouse system of Seoul St. Mary's hospital (January 2010 - December 2012) to determine the percent change in low-density lipoprotein cholesterol (LDL-C) levels at an average 3 and 6 months from baseline. Statins with statistically similar lowering effects were placed in one group (group A, B, or C). The proportions of patients who achieved LDL-C < 100 mg/dL were compared between baseline LDL-C levels: low (< 130 mg/dL), medium (130 - 160 mg/dL), and high (> 160 mg/dL). RESULTS: The majority of the 9 statins of various doses (2,349 patients) were effective at 3 months, with additional, smaller decreases at 6 months. The LDL-C lowering effect of group A (atorvastatin (20 mg), rosuvastatin (10 mg)) was ~ 45%; that of group B (atorvastatin (10 mg), pitavastatin (2 mg), pravastatin (40 mg), simvastatin (20 mg)) was 35 - 37%. groups A and B contained only moderate-intensity statins (ACC/AHA guidelines). With baseline LDL-C ≥ 130 mg/dL, greater proportions of patients achieved LDL-C < 100 mg with atorvastatin (20 mg) and rosuvastatin (10 mg). CONCLUSION: Because of the demonstrated LDL-C lowering effects and target achievement rates, the ACC/AHA guidelines might not apply to Korean patients. Korean treatment guidelines should consider statins with relatively low potency. Additional studies regarding appropriate statin doses should be conducted with Asian populations.

Obesity, metabolic health, and mortality in adults: a nationwide population-based study in Korea.

BMI, metabolic health status, and their interactions should be considered for estimating mortality risk; however, the data are controversial and unknown in Asians. We aimed to investigate this issue in Korean population. Total 323175 adults were followed-up for 96 (60-120) (median [5-95%]) months in a nationwide population-based cohort study. Participants were classified as "obese" (O) or "non-obese" (NO) using a BMI cut-off of 25 kg/m(2). People who developed ≥1 metabolic disease component (hypertension, diabetes, dyslipidaemia) in the index year were considered "metabolically unhealthy" (MU), while those with none were considered "metabolically healthy" (MH). The MUNO group had a significantly higher risk of all-cause (hazard ratio, 1.28 [95% CI, 1.21-1.35]) and cardiovascular (1.88 [1.63-2.16]) mortality, whereas the MHO group had a lower mortality risk (all-cause: 0.81 [0.74-0.88]), cardiovascular: 0.73 [0.57-0.95]), compared to the MHNO group. A similar pattern was noted for cancer and other-cause mortality. Metabolically unhealthy status was associated with higher risk of all-cause and cardiovascular mortality regardless of BMI levels, and there was a dose-response relationship between the number of incident metabolic diseases and mortality risk. In conclusion, poor metabolic health status contributed more to mortality than high BMI did, in Korean adults.