Eu Jeong Ku

Trabecular Bone Score as an Indicator for Skeletal Deterioration in Diabetes

CONTEXT Trabecular bone score (TBS) is a novel texture index that evaluates the pixel gray-level variations in lumbar spine dual-energy X-ray absorptiometry images and is related to bone microarchitecture independent of bone mineral density (BMD). OBJECTIVE We investigated lumbar spine TBS as an indicator for skeletal deterioration in diabetes. DESIGN AND SETTING Cross-sectional data were collected from subjects participating in an ongoing prospective, community-based, cohort study from 2009 to 2010. PARTICIPANTS We included 1229 men and 1529 postmenopausal women older than 50 years in the Ansung cohort. OUTCOME MEASURES Biochemical parameters, lumbar spine TBS, and BMD from dual-energy X-ray absorptiometry images were measured. RESULTS Lumbar spine TBS was lower in men with diabetes than in nondiabetic men (1.287 ± 0.005 vs 1.316 ± 0.003, P < .001), whereas lumbar spine BMD was higher in men with diabetes (1.135 ± 0.010 vs 1.088 ± 0.006 g/cm(2)). Lumbar spine TBS was lower in women with diabetes than in nondiabetic women only in an unadjusted model (1.333 ± 0.004 vs 1.353 ± 0.003). However, women younger than 65 years (n = 707) with diabetes had a lower TBS than those without diabetes, even after adjusted for covariates (P < .001). Diabetes was not associated with BMD at femur sites in both genders. TBS was negatively correlated with glycated hemoglobin, fasting plasma glucose, fasting insulin, and homeostasis model assessment for insulin resistance but not with homeostasis model assessment for β-cell function in both genders. CONCLUSIONS The inverse association between lumbar spine TBS and insulin resistance may make it an indicator for determining skeletal deterioration in diabetic patients who have high BMD.

Regional body fat depots differently affect bone microarchitecture in postmenopausal Korean women

SummaryIn a prospective community-based cohort study, we investigated the relationship between trabecular bone score (TBS) and regional fat depots in 1474 Korean postmenopausal women. TBS was positively related with subcutaneous fat and negatively related with visceral fat.IntroductionThe effect of fat distribution (visceral/subcutaneous) on bone quality or microarchitecture has rarely been investigated due to measurement difficulty. We aimed to investigate the relationship between TBS reflecting bone microarchitecture and regional fat depots in Korean women.MethodsCross-sectional data evaluation was made from subjects participating in an ongoing prospective community-based cohort study since 2001. A total of 1474 postmenopausal women in the Ansung cohort were analyzed. Regional body fat mass, bone mineral density (BMD) at the lumbar spine, and total hip and lumbar spine TBS were measured by dual energy X-ray absorptiometry (DXA).ResultsIn an age-adjusted partial correlation analysis, TBS was not associated with total fat mass, but negatively associated with trunk fat mass. However, TBS was positively related with leg (r = 0.102, P < 0.05) and gynoid fat mass (r = 0.086, P < 0.05) and negatively related with android fat mass (r = −0.106; P < 0.05). In linear regression models controlling age, BMI, and physical activity, android fat was inversely associated with TBS (β = −0.595, P < 0.001), whereas gynoid fat was positively associated with TBS (β = 0.216, P < 0.001). Lumbar spine and total hip BMDs revealed positive associations with total and all regional fat depots regardless of fat distribution.ConclusionOur findings suggest that relatively large visceral fat and small subcutaneous fat may have a detrimental effect on TBS, a bone microarchitecture index.

Counterintuitive relationship between visceral fat and all-cause mortality in an elderly Asian population.

Abdominal obesity is considered to be a risk factor for mortality. However, recent studies indicate that overweight may be negatively associated with mortality (“obesity paradox”). The relationships between mortality and various obesity markers in an elderly Asian cohort were evaluated.

Germline mutations and genotype–phenotype correlations in patients with apparently sporadic pheochromocytoma/paraganglioma in Korea

The aim of our study was to assess the frequency of germline mutations and develop the genetic testing strategy in patients with apparently sporadic pheochromocytoma/paraganglioma (PPGL) in Korea. We included 53 patients diagnosed with non‐syndromic PPGL without a family history of PPGLs in three referral centers from 2004 to 2011. Succinate dehydrogenase complex B (SDHB), SDHD, Von Hippel–Lindau (VHL), and rearranged during transfection (RET) genes were examined by direct sequencing and multiple ligation‐dependent probe amplification. The study patients were composed of 26 men and 27 women, and mean age was 50.1 ± 13.5 years. The frequency of germline mutations was 13.2% (7/53): RET (n = 2), VHL (n = 1), SDHB (n = 2), and SDHD (n = 2). Six of seven mutation carriers were diagnosed before the age of 50. One of two patients harboring an SDHB mutation had malignant PPGLs. One patient with multifocal head and neck paraganglioma (PGL) and pheochromocytoma (PHEO) carried a SDHD mutation. The carriers of germline mutations in patients with apparently sporadic PPGL were 13.2% in our study. We recommend genetic testing in patients below 50 years and SDHD genetic testing in patients with multifocal PPGLs. In malignant PPGLs, SDHB genetic testing may be performed.

Clinical risk factors of postoperative hyperkalemia after adrenalectomy in patients with aldosterone-producing adenoma

OBJECTIVE Unilateral adrenalectomy is the first-line treatment for aldosterone-producing adenomas (APA). Hyperkalemia after adrenalectomy because of contralateral zona glomerulosa insufficiency has been reported. We investigated clinical risk factors to predict postoperative hyperkalemia in patients with APA undergoing adrenalectomy. DESIGN AND METHODS This study was conducted by retrospectively reviewing medical records from 2000 to 2012 at Seoul National University Hospital and two other tertiary centers. Data from 124 patients who underwent adrenalectomy were included. Hyperkalemia was defined as serum potassium >5.5 mmol/l. Clinical preoperative risk factors included age, blood pressure, plasma renin activity (PRA), plasma aldosterone concentration (PAC), serum potassium, serum creatinine, glomerular filtration rate (GFR), the mass size on pathology, and mineralocorticoid receptor (MR) antagonist use. RESULTS Out of 124 patients, 13 (10.5%) developed postoperative hyperkalemia. The incidences of transient and persistent hyperkalemia were 3.2 and 7.3% respectively. Preoperative PRA and PAC were not significantly different in postoperative hyperkalemic patients compared with normokalemic patients. Patients with persistent hyperkalemia were older, had a longer duration of hypertension, larger mass size on pathology, and lower GFR (all P<0.05). The incidence of postoperative hyperkalemia was not different between MR antagonist users and non-users. CONCLUSION Older age (≥53 years), longer duration of hypertension (≥9.5 years), larger mass size on pathology (≥1.95 cm), and impaired preoperative renal function (GFR <58.2 ml/min) were associated with prolonged postoperative hyperkalemia in patients with APA. MR antagonist use did not prevent postoperative hyperkalemia.

Four-Year Durability of Initial Combination Therapy with Sitagliptin and Metformin in Patients with Type 2 Diabetes in Clinical Practice; COSMIC Study

Objectives We investigated the efficacy of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes for 4 years in clinical practice. Methods Between 2009 and 2010, we reviewed 1,178 patients with type 2 diabetes (HbA1c ≥7.5% or 58 mmol/mol) prescribed initial combination therapy with sitagliptin and metformin. After excluding 288 patients without a second follow-up, 890 individuals (age, 58.0 ± 12.5 years; BMI, 25.4 ± 3.5 kg/m2; HbA1c, 8.6 ± 1.1%) were followed up with every 3–6 months for 4 years. Homeostasis model assessments for insulin resistance and β-cell function (HOMA-β) were recorded at baseline. The response criterion was HbA1c reduction by ≥0.8% from baseline or attainment of the target HbA1c (≤7.0% or 53 mmol/mol). At the end of every year of treatment, changes in HbA1c from the baseline were assessed. Results After 1 year, 72.2% of patients with initial combination therapy had responded, defined as HbA1c reduction ≥0.8% or attainment of the target HbA1c ≤7.0%. After 4 years, 35.4% of the patients still showed a response, with an HbA1c level of 7.0 ± 0.9%. A high HbA1c level at baseline was the most significant independent predictor of the long-term response (P<0.001). In addition, low HOMA-β was a significant predictor of a greater reduction in HbA1c. This treatment was generally well tolerated over the 4-year follow-up period, without any serious adverse events. Conclusions This real-world follow-up study shows a persistent glucose-reducing effect of initial combination therapy with sitagliptin and metformin for up to 4 years.

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

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

The amount of C1q–adiponectin complex is higher in the serum and the complex localizes to perivascular areas of fat tissues and the intimal–medial layer of blood vessels of coronary artery disease patients

BackgroundThe complement component C1q triggers activation of the classical immune pathway and can bind to adiponectin (APN). Recently, some studies have been reported that serum C1q-APN/total APN ratio correlates with atherosclerosis and coronary artery disease (CAD). We assessed the relationships between C1q related variables and the severity of CAD, and investigated the localization of the C1q–APN complex.MethodsThe sample included 153 subjects comprising healthy controls and patients with subclinical or overt CAD. We measured the serum concentrations of C1q, total APN, and high-molecular weight (HMW)-APN, and the amount of C1q–APN complex. We identified the sites of C1q–APN complex deposition in various adipose tissues and blood vessels.ResultsSerum concentrations of C1q and HMW-APN and the C1q/HMW-APN ratio were independently associated with the severity of coronary stenosis. The amount of C1q–APN complex was significantly higher in patients with CAD compared with controls. C1q and APN co-localized in perivascular areas of subcutaneous, visceral, and pericardial fat tissues, and the internal mammary artery of patients with severe CAD.ConclusionsSerum C1q concentration and the C1q/HMW-APN ratio were independent markers of coronary artery stenosis. The amount of C1q–APN complex was significantly greater in serum from CAD patients. C1q and APN co-localized to perivascular areas in adipose tissue and blood vessels. The association between the increased amount of the C1q–APN complex and CAD should be investigated further.

Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes

AIMS The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes. METHODS We recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3-6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7-6.4%, 39-46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated. RESULTS Eighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥ 165 mg/dL and a 30-min C-peptide < 5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98-26.16) of developing diabetes than other prediabetic subjects. CONCLUSIONS In Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population.

Comparison of Abdominal Visceral Adipose Tissue Area Measured by Computed Tomography with That Estimated by Bioelectrical Impedance Analysis Method in Korean Subjects.

We evaluated the concordance between visceral fat area (VFA) estimated by bioelectrical impedance analysis (BIA) or computed tomography (CT) in Korean subjects with a wide range in age and body mass index (BMI). In 1006 individuals (mean age 55.2 ± 11.8 (19–87) years, mean BMI 26.0 ± 3.5 (17–46) kg/m2, 48.9% men), VFA quantified by CT was compared with VFA using multifrequency BIA machines within 15 days. Concordance rates were compared by age or BMI using correlation analysis, Bland-Altman plots, and intraclass correlation coefficient (ICC). Using BIA data, we established a regression formula to reflect CT-VFA. The mean VFAs by CT and BIA were 131.9 ± 57.3 cm2 and 110.5 ± 33.9 cm2, respectively (r = 0.605, p < 0.001). The mean difference was 21.4 ± 45.6 cm2, tending to increase with BMI. In women with BMI <25 kg/m2 or age <50 years, the VFAs by BIA were similar to those by CT (ICC = 0.496 in BMI <25 kg/m2 and ICC = 0.638 in age <50 years). However, the difference was greater in men with BMI ≥25 kg/m2 or age ≥50 years. Applying our formula, the difference between estimations decreased to 0.2 ± 38.2cm2. VFA estimated by BIA correlated well with that by CT, but a more accurate formula is needed to match CT data, particularly in older men or subjects with a high BMI.