Hak Yeon Bae

A multicenter, randomized, placebo-controlled, double-blind phase II trial evaluating the optimal dose, efficacy and safety of LC 15-0444 in patients with type 2 diabetes

Aim: The objective of this study was to evaluate the optimal dose, efficacy and safety of a novel dipeptidyl peptidase‐4 (DPP‐IV) inhibitor, LC15‐0444, in Korean subjects with type 2 diabetes mellitus treated by diet and exercise.

Clinical marker of platelet hyperreactivity in diabetes mellitus.

Atherothrombotic complications are important causes of morbidity and mortality in diabetic patients. Diabetes has been considered to be a prothrombotic status. Several factors contribute to the prothrombotic condition, such as increasing coagulation, impaired fibrinolysis, endothelial dysfunction, and platelet hyperreactivity. Among the factors that contribute to the prothrombotic status in diabetes, altered platelet function plays a crucial role. Although understanding platelet function abnormalities in diabetes still remains as a challenge, more attention should be focused on platelet function for effective management and the prediction of atherothrombotic events in diabetic patients. This review will provide an overview on the current status of knowledge of platelet function abnormalities and clinical marker of platelet hyperreactivity in patients with diabetes.

Impact of Age at First Childbirth on Glucose Tolerance Status in Postmenopausal Women: The 2008–2011 Korean National Health and Nutrition Examination Survey

OBJECTIVE The objective of the current study was to determine whether there was an association between age at first childbirth and glucose tolerance status in postmenopausal women. RESEARCH DESIGN AND METHODS This study was based on the data from the Korean National Health and Nutrition Examination Survey, conducted by the Korean Ministry of Health and Welfare from 2008–2011. Of 37,753 participants, data for 4,965 postmenopausal women were included in the analysis. Subjects were subdivided according to the age at first childbirth as follows: ≤19, 20–24, 25–29, and ≥30 years. Multivariate logistic regression analyses were used to identify whether there was an independent association between age at first childbirth and glucose tolerance status by adjusting for potential confounding factors. RESULTS The prevalence of impaired fasting glucose (IFG) and diabetes was 21.8% (1.066 of 4.965) and 15.3% (774 of 4,965), respectively. Diabetes prevalence differed significantly between the subgroups and was higher with earlier age at first childbirth: it was 10.9% in subjects aged ≥30 years and 23.8% in subjects aged ≤19 years at first childbirth. After fully adjusting for potential confounding factors, including lifestyle, sociodemographic factors, known diabetes risk factors, and reproductive factors, age at first childbirth ≤19 years was significantly associated with diabetes (odds ratio 1.492 [95% CI 1.005–2.215]). No significant associations were found between age at first childbirth and IFG. CONCLUSIONS Age at first childbirth influenced diabetes risk in postmenopausal women, and adolescent pregnancy was independently associated with a higher risk of diabetes in postmenopausal women.

The Mean Platelet Volume Is Positively Correlated with Serum Thyrotropin Concentrations in a Population of Healthy Subjects and Subjects with Unsuspected Subclinical Hypothyroidism

BACKGROUND A possible prothrombotic effect of elevated thyrotropin (TSH) has been suggested. The mean platelet volume (MPV), which is used to measure the platelet size, can reflect platelet activity. Although limited and inconsistent data regarding the effects of thyroid function on the MPV are available from small-scale case-control studies, no study has been based on a general population, particularly in euthyroid states. The objective of the present study was to determine whether there is an association between the MPV and serum TSH concentrations in an apparently healthy Korean population without overt thyroid disease, but including subjects with unsuspected subclinical hypothyroidism (SCH). METHODS We retrospectively studied 6893 asymptomatic Korean adults who were 20 years of age or older and who underwent voluntary regular health check-ups at the Health Promotion Center of Chosun University Hospital. The subjects who met the inclusion and exclusion criteria were subdivided into four groups, such as tertile groups for the TSH reference range and an SCH (TSH ≥4 μIU/mL with a normal free T4 concentration) group according to the TSH level. We compared the mean values of the MPVs among the groups. Multivariate logistic regression analyses were used to identify associations between the highest tertile of the MPV and the TSH subgroups. RESULTS The mean level of the MPV in all study subjects was 8.12±0.75 femtoliters (fL), and the mean value of the MPV was significantly different in each group. The mean MPV in SCH was significantly higher compared with those of the first tertile (T1) and second tertile (T2). Moreover, the mean MPV increased statistical significantly by increasing tertiles of the TSH concentration and was highest in SCH (T1, 8.08±0.81 fL; T2, 8.09±0.62 fL; T3, 8.13±0.77 fL; SCH, 8.21±0.81 fL; p for trend=0.012). After adjusting for risk factors associated with increasing MPVs and platelet counts, SCH was independently associated with the highest tertile of the MPV (all subjects, odds radio (OR) 1.58 [95% confidence interval (CI) 1.19-2.09]; men, OR 1.70 [CI 1.10-2.64]; women, OR 1.55 [CI 1.06-2.26]). CONCLUSIONS The MPV was positively correlated with the TSH level. SCH is an independently associated factor with the highest tertile of MPV in a general Korean population. We propose that the MPV may contribute to the prothrombotic condition that is associated with SCH and perhaps even in putative euthyroid states where the TSH level is the higher part of the normal range.

The relationship between mean platelet volume and fasting plasma glucose differs with glucose tolerance status in a Korean general population: Gender differences

Mean platelet volume (MPV), which is used to measure platelet size, can reflect platelet activity. The objective of the present study was to evaluate the relationship between MPV and fasting plasma glucose (FPG) according to glucose tolerance (GT) status in a general population. We retrospectively studied 3098 Korean adults who underwent voluntary regular health check-ups at the Health Promotion Center of our hospital from January 2009 to December 2011. MPV was analysed within 2 hours of blood collection. A multiple linear regression analysis indicated that MPV had a significant negative correlation with FPG when the confounding variables of normal glucose tolerance (β ± SE, −0.112 ± 0.033, R2, 0.109, men; −0.102 ± 0.034, 0.132, women) and intermediate hyperglycemia (−0.072 ± 0.027, 0.130, men; −0.111 ± 0.035, 0.100, women) were adjusted for. However, MPV had a significant positive relationship with FPG after adjusting for diabetes in women as a confounding factor (0.097 ± 0.037, 0.442). We observed a contrasting relationship between MPV and FPG in the presence and absence of diabetes. This result suggests that the positive relationship between an increased glucose level and increased MPV is a unique phenomenon of diabetes itself. To our knowledge, this is the first study to demonstrate a different relationship between MPV and FPG according to glucose tolerance status in a general population.

Discordance between HbA1c and fasting plasma glucose criteria for diabetes screening is associated with obesity and old age in Korean individuals

We evaluated the agreement between HbA1c- and FPG-based criteria for screening of diabetes in an asymptomatic Korean population and identified independent factors associated with discordance. The discordance between the two diabetic criteria was significantly associated with obesity and older age.

Hemoglobin A1c Is Positively Correlated with Framingham Risk Score in Older, Apparently Healthy Nondiabetic Korean Adults

Background Several studies have suggested that elevated levels of hemoglobin A1c (HbA1c) are associated with cardiovascular disease (CVD) in nondiabetic individuals. However, it is unclear whether HbA1c levels can serve as a simple screening marker for increased CVD risk in nondiabetic individuals. Our objective was to evaluate the relationship between HbA1c levels and CVD risk using the Framingham risk score (FRS) in older, apparently healthy nondiabetic Korean adults. Methods We retrospectively studied 2,879 Korean adults between the ages of 40 and 79 who underwent voluntary health check-ups at the Health Promotion Center of our hospital from July 2009 to June 2011. Subjects were subdivided based on their HbA1c levels into four groups: tertiles within the HbA1c normal tolerance range and a group for subjects with an increased risk for diabetes (IRD). Results The mean FRS for the upper tertile (9.6±3.8) group was significantly higher than that of the middle tertile (8.4±4.0) and lower tertile (7.6±3.8) groups. In addition, FRS was highest in the IRD group (10.5±3.7). Multiple linear regression analysis demonstrated that HbA1c levels exhibited a significant positive correlation with FRS when adjusted for confounding variables in all subjects (β±standard error [SE], 0.018±0.002; R2, 0.131), women (β±SE, 0.023±0.003; R2, 0.170), and men (β±SE, 0.016±0.004; R2, 0.109). Conclusion HbA1c levels were positively correlated with FRS in older, apparently healthy nondiabetic Korean adults. We propose that HbA1c levels may reflect CVD risk in nondiabetic individuals.

Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin

Background We compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes. Methods The present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin. Results The mean changes in HbA1c levels from baseline were –0.94% in the vildagliptin group and –0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were –60.2 mg/dL in the vildagliptin group and –38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040). There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL), and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was –0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002). Conclusion As an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.

Symptomatic calcification of a thyroid lobe and surrounding tissue after radioactive iodine treatment to ablate the lobe.

BACKGROUND Fine-needle aspiration diagnosis of follicular carcinoma presents a dilemma because malignancy is confirmed when vascular or capsular invasion is present. Completion thyroidectomy may be necessary when the diagnosis of follicular carcinoma is made following hemithyroidectomy. Ablation of the remaining lobe with radioactive iodine has been used as an alternative to completion thyroidectomy. Here we report an unusual apparent complication of this treatment. PATIENT FINDINGS A 51-year-old woman presented in September 24, 2009 with a stony, hard calcification of left thyroid gland. She complained of recent progressive hoarsening of her voice. Her medical history was positive for a subtotal thyroidectomy on September 6, 1993. Histologic analysis identified follicular carcinoma. Two months postoperatively, the remaining tissue was ablated with (131)I (150 mCi) as an alternative to completion thyroidectomy. We performed computed tomography of the neck, which demonstrated 1.6  x 1.9 x  2.2 cm dense speculated calcification of the entire left residual thyroid gland. The calcification infiltrated the trachea wall. Completion thyroidectomy, including resection of the calcification, was performed. Histologic examination revealed dystrophic calcification. CONCLUSION We report an unusual replacement of the thyroid remnant with calcification that developed over a period of 16 years following radioactive iodine lobe ablation as an alternative to completion thyroidectomy for thyroid follicular carcinoma. To our knowledge, this is the first such case in the English language literature.

Urinary Albumin Excretion Reflects Cardiovascular Risk in Postmenopausal Women without Diabetes: The 2011 to 2013 Korean National Health and Nutrition Examination Survey

Background The objective of the current study was to determine whether there was an association between urinary albumin excretion and cardiovascular disease (CVD) risk by estimating the Framingham Risk Score (FRS) in postmenopausal women without diabetes. Methods This study was based on data from the Korea National Health and Nutrition Examination Survey, which was conducted by the Korean Ministry of Health and Welfare in 2011 to 2013. Data on 2,316 postmenopausal women from a total of 24,594 participants was included in the analysis. Results The mean FRS was significantly different in each of the urinary albumin to creatinine ratio (UACR) subgroups, and it increased with UACR. The FRS was 12.69±0.12 in the optimal group, 14.30±0.19 in the intermediate normal group, 14.62±0.26 in the high normal group, and 15.86±0.36 in the microalbuminuria group. After fully adjusting for potential confounding factors, high normal levels and microalbuminuria were significantly associated with the highest tertile of FRS ([odds ratio (OR), 1.642; 95% confidence interval (CI), 1.124 to 2.400] and [OR, 3.385; 95% CI, 2.088 to 5.488], respectively) compared with the optimal subgroup. High normal levels and microalbuminuria were also significantly associated with a ≥10% 10-year risk of CVD ([OR, 1.853; 95% CI, 1.122 to 3.060] and [OR, 2.831; 95% CI, 1.327 to 6.037], respectively) after adjusting for potential confounding covariates. Conclusion Urinary albumin excretion reflects CVD risk in postmenopausal women without diabetes, and high normal levels and microalbuminuria were independently associated with a higher risk of CVD.