Real-World Analysis of Rapid-Acting Insulin Analog Use and Its Blood Glucose Lowering Effect in Patients with Type 2 Diabetes Mellitus: Results from PASSION Disease Registry in Korea.

Purpose: Although rapid-acting insulins (RAIs) are used frequently in Korean clinical settings, evidence on their use is limited. This study explores the pattern and clinical effectiveness of the use of RAIs in Korean patients with type 2 diabetes mellitus (T2DM). Patients and Methods: This non-interventional, observational study enrolled patients (aged >18 years) with T2DM who were prescribed RAIs. The pattern of use and effectiveness of RAI analogs were evaluated over 6 months. Results: A total of 299/451 patients were analyzed. Approximately 90% (n/N=270/299) of the patients received insulin glulisine, which significantly reduced their levels of glycated hemoglobin (HbA1c: n=270, mean± standard deviation [SD]; -1.16±6.02%, p=0.0017), fasting plasma glucose (n=40; mean±SD: -54.9±90.89 mg/dl, p=0.0005), and post prandial blood glucose (n=35, mean±SD: -89.46± 105.68 mg/dl, p<0.0001) at 6 months, with a corresponding increase in body weight (BW) (n=197, mean±SD:1.45±3.64 kg, p<0.0001). At 6 months, more patients receiving an intensive regimen (basal insulin+≥2 RAI injections/day) had HbA1c <7% than those receiving a non-intensive regimen (basal insulin+1 RAI injection/day) (20.69% vs 7.46%; p=0.0333); the corresponding reduction in HbA1c was also higher in patients receiving the intensive regimen (p<0.0001). About one-fourth patients (n/N=22/95) were switched to the intensive regimen (from 1 to ≥2 RAI injections/day), and only 4.41% (n/N=9/204) of the patients were switched to 1 RAI injection/day. The patients receiving the intensive regimen showed higher levels of HbA1c reductions (mean±SD: -1.27±1.96%) compared with the maintenance group-1 RAI injection/day (mean±SD: -0.72±1.66%) (p=0.0459), without a significant increase in BW and body mass index. Conclusion: The insulin glulisine intensification regimen showed glycemic target achievement and can be considered a therapeutic tool in the management of T2DM patients.

Framingham Risk Score Assessment in Subjects with Pre-diabetes and Diabetes: A Cross-Sectional Study in Korea.

BACKGROUND: This study aimed to evaluate cardiovascular risk in subjects with pre-diabetes and diabetes in Korea. METHODS: In this pan-Korean, non-interventional, cross-sectional study, data were collected from medical records of 10 hospitals between November 2013 and June 2014. Subjects (aged ≥40 years) with medical records of dysglycemia and documentation of total cholesterol level, high-density lipoprotein cholesterol level, systolic blood pressure, and smoking status in the past 6 months were included. The primary endpoint was to determine the Framingham risk score (FRS). The relationships between FRS and cardiovascular risk factors, glycated hemoglobin, and insulin usage were determined by multiple linear regression analyses. RESULTS: Data from 1,537 subjects with pre-diabetes (n=1,025) and diabetes (n=512) were analyzed. The mean FRS (mean±standard deviation) in subjects with pre-diabetes/diabetes was 13.72±8.77. FRS was higher in subjects with diabetes than pre-diabetes (P<0.001). FRS in men with pre-diabetes was comparable to that in women with diabetes (13.80±7.37 vs. 13.35±7.13). FRS was elevated in subjects who consumed alcohol (2.66, P=0.033) and with obesity-class II (6.10, P=0.015) among subjects with diabetes (n=199), and was elevated in patients with left ventricular hypertrophy (11.10, P=0.005), those who consumed alcohol (3.06, P=0.000), were pre-obese (3.21, P=0.002), or were obesity-class I (2.89, P=0.002) among subjects with pre-diabetes (n=306) in comparison to subjects without these coexisting risk factors. CONCLUSION: Overall, Korean subjects with pre-diabetes and diabetes have an increased cardiovascular risk, which is significantly higher in those subjects with diabetes than with pre-diabetes. The present data can be used to develop measures to prevent and manage cardiovascular complications in Koreans with impaired glucose metabolism.

Association of breastfeeding with thyroid function and autoimmunity in postmenopausal women.

OBJECTIVE: Whether breastfeeding influences thyroid function and autoimmunity is not elucidated. We examined the association of history of breastfeeding with thyroid hormones and thyroperoxidase antibody (TPOAb). DESIGN: Cross-sectional study of data from the 2013-2015 Korea National Health and Nutrition Examination Survey. METHODS: A total of 816 postmenopausal women were stratified into three groups according to the duration of breastfeeding and number of breastfed children. Thyroid hormones levels, TPOAb titers, and the prevalence of hypothyroidism and TPOAb positivity were evaluated in each group. RESULTS: Subjects with a history of prolonged breastfeeding had lower levels of thyrotropin (TSH) and TPOAb than the others. After adjusting for multiple confounding factors, the estimated means of TSH and TPOAb were associated with cumulative duration of breastfeeding. Duration of breastfeeding per child was associated with TSH levels, and number of breastfed children was associated with TPOAb titers. The odds ratio (OR) of hypothyroidism was significantly lower in group for ≥36 months of cumulative duration of breastfeeding, and the OR of TPOAb positivity was significantly lower in group with ≥3 breastfed children. In addition, duration of breastfeeding and the number of breastfed children were linearly correlated with log TSH and TPOAb each other in the multivariate model. CONCLUSIONS: The present study showed that prolonged breastfeeding was inversely associated with TSH and the prevalence of hypothyroidism. Moreover, TPOAb and the prevalence of TPOAb positivity were inversely associated with number of breastfed children. These results indicate that breastfeeding may exert a protective effect on thyroid function and autoimmunity.

Efficacy and safety of lobeglitazone versus sitagliptin as an add-on to metformin in patients with type 2 diabetes with two or more components of metabolic syndrome over 24 weeks.

We aimed to evaluate the efficacy and safety profile of lobeglitazone compared with sitagliptin as an add-on to metformin in patients with type 2 diabetes as well as other components of metabolic syndrome. Patients inadequately controlled by metformin were randomly assigned to lobeglitazone (0.5 mg, n = 121) or sitagliptin (100 mg, n = 126) for 24 weeks. The mean changes in HbA1c of the lobeglitazone and sitagliptin groups were -0.79% and -0.86%, respectively; the between-group difference was 0.08% (95% confidence interval, -0.14% to 0.30%), showing non-inferiority. The proportion of patients having two or more factors of other metabolic syndrome components decreased to a greater extent in the lobeglitazone group than in the sitagliptin group (-11.9% vs. -4.8%; P < .0174). Favourable changes in the lipid metabolism were also observed with lobeglitazone, which had a similar safety profile to sitagliptin. Lobeglitazone was comparable with sitagliptin as an add-on to metformin in terms of efficacy and safety.

Effects of Yukmijihwang-tang, a Polyherb, on the Pharmacokinetics of Metformin.

Metformin is one of the most common medicines for the treatment of type 2 diabetes, however, recent studies suggest that concomitant antihyperglycemic agents should be administered for better efficacy. Yukmijihwang-tang (YMJHT) is a nephroprotective polyherb prescribed for renal disorders or diabetic mellitus in traditional Korean medicine. Therefore, the pharmacokinetics between metformin and YMJHT were examined for their coadministration. Rats were orally coadministered with metformin and YMJHT as a combination group or metformin and distilled water as the corresponding control. Then, the metformin concentration in plasma and its pharmacokinetic parameters including maximum concentration (Cmax) and area under the plasma concentration time curve (AUC) were analyzed. There were no interactions between metformin and YMJHT in the single coadministration at intervals within 5 min. However, pretreatments with YMJHT for 6 days increased the metformin concentration and its Cmax and AUC (p<0.05). The repeated coadministration for 8 days increased the Cmax of metformin (p<0.05). Conversely, when the combination was coadministered at 2h -intervals, there were no interactions between metformin and YMJHT after a single dosing or repeated dosing of coadministration for 7 days. These results of the present study will help structure proper dosing regimens for the concomitant therapy of metformin and YMJHT.

Delay of insulin initiation in patients with type 2 diabetes mellitus inadequately controlled with oral hypoglycemic agents (analysis of patient- and physician-related factors): A prospective observational DIPP-FACTOR study in Korea.

AIMS/INTRODUCTION: To assess the time to initiation of insulin therapy, and concurrently investigate both patient- and physician-related factors associated with delaying insulin therapy in Korean patients with type 2 diabetes uncontrolled by oral hypoglycemic agents (OHAs). MATERIALS AND METHODS: This prospective, observational disease registry study was carried out across 69 centers in Korea. Type 2 diabetes patients who had received two or more OHAs within the past 5 years, had a glycated hemoglobin ≥8% in the past 6 months and had not received insulin were included. Data recorded on data collection forms during a 12-month period were analyzed. RESULTS: Of 2168 patients enrolled, 1959 were evaluated and classified as the insulin-initiated or insulin-delayed group. Insulin was prescribed for just 20% of the patients during a 1-year follow-up period, and less than half (44.5%) of the patients who were taking two OHAs started insulin after 6 years. Patient-related factors for delay in insulin initiation included older age, shorter duration of diabetes and lower glycated hemoglobin. Physician-related factors included age (~50 to <60 years), sex (women) and number (<1000) of patients consulted per month. Patient refusal (33.6%) and physicians' concerns of patient non-compliance (26.5%) were the major physician-reported reasons for delaying insulin therapy. Inconvenience of insulin therapy (51.6%) and fear of injection (48.2%) were the major reasons for patient refusal. CONCLUSIONS: Insulin initiation is delayed in patients with type 2 diabetes uncontrolled by two or more OHAs in Korea. Patient- and physician-related factors associated with this delay need to be addressed for better diabetes management.

Primary Mucosa-Associated Lymphoid Tissue Lymphoma of Thyroid with the Serial Ultrasound Findings.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) of the thyroid gland is uncommon. Even though its natural history is not well defined, it is known to be indolent course. We present a case of primary MALT thyroid lymphoma with the serial sonographic findings in the patient presenting as the focal nodule. A 45-year-old woman visited our hospital for neck examination. Initially, fine-needle aspiration cytology in the focal hypoechoic lesion in the left thyroid lobe on ultrasound sonography was performed and consistent with Hashimoto's thyroiditis. However, the results of serial ultrasounds and core-needle biopsy revealed an extranodal marginal zone lymphoma of MALT on 4-year follow-up. Patients with a focal hypoechoic nodule with linear echogenic strands and segmental pattern in the background of Hashimoto's thyroiditis on ultrasonography should undergo careful surveillance for malignancy. Serial sonographic features in this case are meaningful in the understanding of the natural history of the extranodal marginal zone lymphoma of MALT of the thyroid.

Ultrasonographic Characteristics of the Follicular Variant Papillary Thyroid Cancer According to the Tumor Size.

Follicular variant papillary thyroid cancer (FVPTC) is the second most common subtype after conventional PTC. We compared ultrasonographic (US) features of FVPTC to those of conventional PTC according to tumor size. We reviewed US findings, pathologic reports, and medical charts of 249 PTC patients with surgically proven disease (83 FVPTCs, 166 conventional PTCs) at our institution from January 2007 to December 2012. FVPTCs were divided into PTC-like and follicular neoplasm (FN)-like based on sonographic characteristics. PTC-like features were defined as having at least one malignant feature (taller-than-wide shape, infiltrative margin, marked hypoechogenicity, and micro-calcifications), whereas FN-like cancers showed oval solid features without malignant features. FVPTCs showed a higher rate of FN-like features than conventional PTCs. Of 166 conventional PTCs, 13 (7.8%) had FN-like features and 153 (92.2%) had PTC-like features, whereas of the 83 FVPTCs, 31 (37.3%) had FN-like features and 52 (62.7%) had PTC-like features. Macro-FVPTCs showed a higher rate of FN-like features than micro-FVPTCs (P < 0.001). Of 21 macro-FVPTCs, 18 (85.7%) had FN-like features and 3 (14.3%) had PTC-like features, whereas of the 62 micro-FVPTCs, 13 (21%) had FN-like features and 49 (79%) had PTC-like features. There were no differences in multifocality, extrathyroidal invasion, and lymph node metastasis between PTC-like FVPTCs and FN-like FVPTCs. FVPTCs showed fewer sonographic malignant features than conventional PTCs. In particular, FVPTCs larger than 1 cm had a more frequent benign sonographic appearance. Therefore, if fine-needle aspiration result is suspicious for PTC in a nodule larger than 1 cm with no suspicious US features, the possibility of FVPTC might be considered.

Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes.

AIMS/INTRODUCTION: Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients. MATERIALS AND METHODS: The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed. RESULTS: Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P < 0.0001). Fasting and postprandial blood glucose levels were reduced by 0.89 ± 3.79 and 2.59 ± 4.77 mmol/L (both P < 0.0001). The most frequently reported adverse drug reactions were flatulence (0.37%) and abnormal gastrointestinal sounds (0.37%), and all were mild in intensity and transient. In the satisfaction evaluation, 79.0% of physicians and 77.3% of patients were 'very satisfied' or 'satisfied' with the combined basal insulin and acarbose therapy. CONCLUSIONS: Combination therapy of basal insulin and acarbose in patients with type 2 diabetes improved glucose control, and had no drug-specific safety concerns, suggesting that the treatment might benefit individuals who cannot control blood glucose with basal insulin alone.

Effects of Chungsinoryungsan, a polyherbal complex, on the pharmacokinetic profiles of perindopril in rats.

For sufficient antihypertension with less adverse effects, numerous clinical trials have recommended combination therapy using two or more hypertensive drugs. Chungsinoryungsan (CSORS) is a polyherbal complex based on oriental medicine, which has shown therapeutic potentials for antihypertension and additional renal improvement. Therefore, the affect of CSORS on the pharmacokinetic profiles of perindopril, an antihypertensive drug, was analyzed as a novel combination of hypertensive drugs. Rats received perindopril with CSORS as the combination or distilled water as the control. The co-administration of perindopril with CSORS or distilled water was performed by single dosing or repeated dosing for a week at a 2-h interval. The analyzed pharmacokinetic parameters included peak concentration (Cmax), time to reach the Cmax (Tmax), area under the plasma concentration-time curve, terminal half-life (t1/2) and mean residence time to infinity (MRTinf). In the single oral co-administration within 5 min, the pharmacokinetics of perindopril demonstrated an increased Tmax and MRTinf but reduced t1/2 in the combination compared to the control treatment, indicating drug-drug interactions between perindopril and CSORS. However, in the repeated co-administration for a week at a 2-h interval, which was more than perindopril MRTinf in the control treatment (1.5±0.1 h), the initial co-administration showed no differences in the pharmacokinetics between the combination and control treatments. Furthermore, the repeated co-administration also showed no differences between the combination and control treatment. The results indicate that CSORS can be co-administered at a 2-h interval that was more than perindopril MRTinf and further clinical studies may provide detailed information for developing a drug regimen that generates enhanced combination effects of CSORS with hypertensive drugs.

Trend analysis of diabetic prevalence and incidence in a rural area of South Korea between 2003-2008.

UNLABELLED: Aims/Introduction: This study determined the change in prevalence of diabetes and prediabetes over a period of 5 years in South Korea. The incidence of diabetes and prediabetes and risk factors associated with the development of diabetes were also investigated. MATERIALS AND METHODS: The Dalseong population-based cohort survey recruited 1806 subjects who were over 20-years-old in 2003. Five years later, 1287 of the original subjects were re-evaluated and 187 new subjects were added to the study. All participants completed a questionnaire, were given a physical examination, and provided blood samples for analysis including 2 h oral glucose tolerances. RESULTS: Age-adjusted prevalence of diabetes rose from 6.7% in 2003 to 9.1% in 2008. The prevalence of prediabetes also increased from 18.5% in 2003 to 28.4% in 2008. The incidence rates of diabetes and prediabetes were 18.3 per 1000 person-years and 55.4 per 1000 person-years, respectively. The development of diabetes was associated with impaired fasting glucose (IFG) (odds ratio [OR] 5.661), impaired glucose tolerance (IGT) (OR: 6.013), age (OR 1.013), and waist-to-hip ratio (OR 1.513). After excluding the IFG and IGT, systolic blood pressure (OR 1.023), high-sensitivity C-reactive protein (hsCRP; OR 1.097), triglyceride (OR 1.002) and waist-to-hip ratio (OR 1.696) were statistically significant risk factors in a multivariate logistic regression analysis. CONCLUSIONS: A significant rise in the prevalence of diabetes and prediabetes was observed between 2003 and 2008. In addition, this study newly demonstrated that waist-to-hip ratio and hsCRP were associated with the development of diabetes after adjusting for several confounding factors. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00045.x, 2010).

Assessment of clinical risk factors to validate the probability of osteoporosis and subsequent fractures in Korean women.

This cross-sectional, observational study was designed to identify clinical risk factors of osteoporosis and fractures in Korean women to validate the probability of osteoporosis and subsequent fractures. A total of 1541 Korean women were recruited nationally. Fracture history of any site, risk factors of osteoporosis, and fall-related risk factors were surveyed and physical performance tests were conducted. Peripheral dual-energy X-ray absorptiometry was used to measure calcaneus bone mineral density (BMD). The number of positive responses on the modified 1-min osteoporosis risk test was related to the risk of osteoporosis. The frequency of osteoporosis was higher in those with a height reduction of >4 cm and a reduced body mass index (BMI). Multivariate analysis showed that older age and lower BMI were related to higher relative risk of osteoporosis. Time required to stand up from a chair and questions related to fall injury were significantly related to clinical fracture history of any site. Multivariate analysis showed that the relative risk of fractures at any site was higher in older subjects with a lower T-score and parental hip fracture history. This study shows that age and BMI are the most significant clinical risk factors for osteoporosis and that age, BMD, and parental history of hip fracture are highly applicable risk factors for validating the probability of osteoporotic fractures in Korean women.

Free T4 is negatively correlated with body mass index in euthyroid women.

BACKGROUND/AIMS: Overt thyroid dysfunction is well known to affect weight. However, the influence of normal-range changes in thyroid status on body mass index (BMI) is unclear. We sought to evaluate thyroid function (free T4, TSH) and its possible relationship with BMI and lipid profiles in euthyroid subjects. METHODS: A total of 1572 euthyroid women (mean age 46.2 years) who visited Daegu Catholic University Medical Centre for primary health screening participated in this cross-sectional study. Women who were not euthyroid and women who took thyroid medication were excluded. TSH, free T4, and lipid profile [total-cholesterol, triglyceride (TG), HDL-C, LDL-C] were evaluated. RESULTS: Obese euthyroid women had lower free T4 levels than did lean euthyroid women. After adjustment for age and smoking, free T4, but not TSH, was significantly negatively correlated with BMI. After adjustment for age, smoking, and BMI, free T4 was negatively correlated with TG to a significant degree. CONCLUSIONS: We demonstrated a negative correlation between free T4 within the normal range and BMI in euthyroid subjects. These findings suggest that low free T4 is associated with obesity in euthyroid subjects.

A case of McCune-Albright syndrome with associated multiple endocrinopathies.

McCune-Albright syndrome (MAS) is a rare disorder that develops from an activating mutation in the Gs gene. It is characterized by an association with Polyostotic fibrous dysplasia, and precocious puberty, Caf-au-lait pigmentation, and other endocrinopathies that result from the hyperactivity of a variety of endocrine glands. Recently we encountered a patient with MAS with fibrous dysplasia, skin pigmentation, acromegaly, hyperprolactinemia and a thyroid nodule. A 23-year-old male presented for an evaluation of a change in his facial structures. Fibrous dysplasia was diagnosed by a bone biopsy and radiographic studies. The GH level increased paradoxically after an oral glucose load. The plasma prolactin, IGF-1 and alkaline phosphatase were high. Thyroid ultrasonography revealed multiple nodules. The brain MRI demonstrated a mass in the left pituitary gland. Genetic analysis identified a change from Arg (CGT) at codon 201 to Cys (TGT).

Management of a pregnant patient with Graves' disease complicated by propylthiouracil induced agranulocytosis.

Relapse and exacerbation of Graves' disease during pregnancy is rare, and thionamide induced agranulocytosis is an uncommon side effect. We report a case of a pregnant woman in her 24th week of gestation that experienced a relapse of Graves' disease that was complicated by propylthiouracil induced agranulocytosis. Following the discontinuation of propylthiouracil and administration of a broad-spectrum of antibiotics, agranulocytosis subsided within 10 days. A total thyroidectomy to avoid any future relapse was planned and a short course of a beta-adrenergic blocker and Lugol solution were prescribed before the operation. At the 28th week of gestation, a total thyroidectomy was performed without complications and thyroxine replacement therapy was commenced. At the 40th week of gestation, labor was induced and a 3,370 g healthy male infant was born without clinical features of thyrotoxicosis. We report herein on the patient and the treatment options for this rare and complicated case.

A typical Korean case of Carney complex.

Carney complex is a multiple neoplasia syndrome, inherited in an autosomal dominant manner, that is characterized by lentigines, cardiac myxoma, and numerous endocrine and other tumors, including primary pigmented nodular adrenocortical disease. Here, we describe a typical case of Carney complex in a 27-year-old female who exhibited spotty skin pigmentation on the lips, oral mucosa, fingers, and toes and several manifestations of Cushing's syndrome due to primary pigmented nodular adrenocortical disease. She also had pituitary adenoma, breast tumor and thyroid nodule. Only a few cases of this disorder have been reported in the Korean literature. All of them, however, had only two components of Carney complex: composed of skin pigmentation and primary pigmented nodular adrenocortical disease. Therefore, the present case seems to be the first true case of Carney complex reported in Korea.