Coronary Artery Calcium Score as a Sensitive Indicator of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus: A Long-Term Cohort Study

Background@#Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden. @*Methods@#We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease. @*Results@#The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100. @*Conclusion@#CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.

Clinical characteristics of infants younger than 90 days diagnosed with invasive group B streptococcal infection in the emergency department

Purpose@#We aimed to characterize invasive group B streptococcal infection (IGBSI) in young infants hospitalized through the emergency department. @*Methods@#We analyzed medical records of infants younger than 90 days with IGBSI, defined as group B streptococcus bacteremia or meningitis, who visited the emergency department from January 2009 through December 2021. Their clinical features were compared as per 2 criteria, neonates and meningitis. For the comparisons, we defined 2 composite outcomes, “clinically important abnormality (any of the followings: temperature > 38.5℃, leukocytes 15,000/mm3, absolute neutrophils > 4,000/mm3 or C-reactive protein > 2.0 mg/dL)”and “poor outcomes (any of the followings: intensive care unit, transfer, seizure or complications).”Percentages are rounded to the first decimal places. @*Results@#A total of 35 infants, of whom 15 (43%) were neonates and 17 (49%) were boys, had IGBSIs, including 23 infants (66%) with isolated bacteremia, 11 (31%) with bacteremia with meningitis, and 1 (3%) with isolated meningitis. Ill appearances were noted in 27 infants (77%) who encompassed all with meningitis. The other 8 infants (23%) looking well had 1 or more components of the clinically important abnormality. The neonates showed a higher frequency of vaginal delivery (87% vs. 35%; P = 0.002) and a lower frequency of a temperature > 38.5℃, compared to their counterparts (47% vs. 80%; P = 0.040). The infants with meningitis had a longer median time required to visit (5.0 vs. 2.0 hours; P = 0.011), and higher frequencies of ill appearance (100% vs. 65%; P = 0.032), leukocytes < 5,000/mm3 (67% vs. 13%; P = 0.002), and the poor outcomes (75% vs. 0%; P < 0.001). @*Conclusion@#Young infants with ill-looking appearance or abnormality in any of the fever or inflammatory markers may have IGBSIs, particularly meningitis.

Neonatal Atrial Flutter: Clinical Characteristics of 14 Cases in a Single Center

Purpose@#Atrial flutter is an uncommon arrhythmia in the neonatal period. This study aimed to describe the cause and clinical course of atrial flutter in neonates. @*Methods@#The medical records of 14 patients diagnosed with atrial flutter at Ulsan University Hospital Neonatal Intensive Care Unit (NICU) between March 2008 and August 2020 were reviewed retrospectively. @*Results@#All 14 cases occurred on the first day of birth. Of these, two were term infants, and 12 were preterm infants. Causes of atrial flutter included three cases of the umbilical venous catheter misplacement, one with a diabetic mother, and one ivolving atrial flutter after an intravenous aminophylline injection. Thirteen patients had structurally normal hearts with no congenital heart diseases. The patient, born to a diabetic mother, had an atrial septal defect and ventricular hypertrophy. Adenosine was administered first to differentiate it from paroxysmal supraventricular tachycardia. Synchronized cardioversion was attempted in 11 patients, while one received it after an esmolol injection that failed to convert to sinus rhythm. One patient had a recurrence after the intrusion of a peripherally inserted central catheter; however, atrial flutter disappeared after repositioning it. No patient had a recurrence after discharge. @*Conclusion@#Neonatal atrial flutter is a rare tachyarrhythmia with the risk factors often unknown; however, it could occur in structural heart disease, mispositioning of the umbilical venous catheter, and if the mother has diabetes. During umbilical venous catheterization, clinicians should be cautious and ensure appropriate monitoring of infants in the NICU as it may cause complications.

Intussusception in Neonates: Clinical Characteristics of Eight Cases in a Single Center

Purpose@#Intussusception is the most common cause of bowel obstruction in children; however, it is rarely diagnosed in newborn infants. This study aimed to describe the clinical features of intussusception in newborn infants. @*Methods@#Medical records of eight patients diagnosed with intussusception during the newborn period at Ulsan University Hospital between March 2007 and March 2020 were retrospectively reviewed. @*Results@#Among the eight cases, two occurred in the intrauterine period and six occurred in the postnatal period. Intrauterine intussusception presented with symptoms of bowel obstruction within 1 to 2 days after birth, and ileal atresia was diagnosed simultaneously through exploratory laparotomy. All the postnatal patients were extremely low birth weight infants (median gestational age and birth weight: 25+6 weeks and 745 g, respectively). Four cases were diagnosed preoperatively using abdominal ultrasonography. One patient was diagnosed by exploratory laparotomy because the clinical symptoms were nonspecific and difficult to differentiate from those of necrotizing enterocolitis, a more prevalent complication in preterm infants. The site of intussusception in all six patients was the small bowel. Meckel’s diverticulum (one case) and meconium obstruction (two cases) were found to be the lead point. @*Conclusion@#Neonatal intussusception tends to show different clinical features according to its period of occurrence. Intussusception, especially in preterm infants, has nonspecific clinical features; therefore, clinicians should always be cautious of this disease for its early diagnosis.

Intussusception in Neonates: Clinical Characteristics of Eight Cases in a Single Center

Purpose@#Intussusception is the most common cause of bowel obstruction in children; however, it is rarely diagnosed in newborn infants. This study aimed to describe the clinical features of intussusception in newborn infants. @*Methods@#Medical records of eight patients diagnosed with intussusception during the newborn period at Ulsan University Hospital between March 2007 and March 2020 were retrospectively reviewed. @*Results@#Among the eight cases, two occurred in the intrauterine period and six occurred in the postnatal period. Intrauterine intussusception presented with symptoms of bowel obstruction within 1 to 2 days after birth, and ileal atresia was diagnosed simultaneously through exploratory laparotomy. All the postnatal patients were extremely low birth weight infants (median gestational age and birth weight: 25+6 weeks and 745 g, respectively). Four cases were diagnosed preoperatively using abdominal ultrasonography. One patient was diagnosed by exploratory laparotomy because the clinical symptoms were nonspecific and difficult to differentiate from those of necrotizing enterocolitis, a more prevalent complication in preterm infants. The site of intussusception in all six patients was the small bowel. Meckel’s diverticulum (one case) and meconium obstruction (two cases) were found to be the lead point. @*Conclusion@#Neonatal intussusception tends to show different clinical features according to its period of occurrence. Intussusception, especially in preterm infants, has nonspecific clinical features; therefore, clinicians should always be cautious of this disease for its early diagnosis.

Serum Transferrin Predicts New-Onset Type 2 Diabetes in Koreans: A 4-Year Retrospective Longitudinal Study

Background@#It is well known that high serum ferritin, a marker of iron storage, predicts incident type 2 diabetes. Limited information is available on the association between transferrin, another marker of iron metabolism, and type 2 diabetes. Thus, we investigated the association between transferrin and incident type 2 diabetes. @*Methods@#Total 31,717 participants (mean age, 40.4±7.2 years) in a health screening program in 2005 were assessed via cross-sectional analysis. We included 30,699 subjects who underwent medical check-up in 2005 and 2009 and did not have type 2 diabetes at baseline in this retrospective longitudinal analysis. @*Results@#The serum transferrin level was higher in the type 2 diabetes group than in the non-type 2 diabetes group (58.32±7.74 μmol/L vs. 56.17±7.96 μmol/L, P<0.001). Transferrin correlated with fasting serum glucose and glycosylated hemoglobin in the correlational analysis (r=0.062, P<0.001 and r=0.077, P<0.001, respectively) after full adjustment for covariates. Transferrin was more closely related to homeostasis model assessment of insulin resistance than to homeostasis model assessment of β cell function (r=0.042, P<0.001 and r=–0.019, P=0.004, respectively) after full adjustment. Transferrin predicted incident type 2 diabetes in non-type 2 diabetic subjects in a multivariate linear regression analysis; the odds ratio (95% confidence interval [CI]) of the 3rd tertile compared to that in the 1st tertile of transferrin for incident diabetes was 1.319 (95% CI, 1.082 to 1.607) after full adjustment (P=0.006). @*Conclusion@#Transferrin is positively associated with incident type 2 diabetes in Koreans.

Deficiency of Sphingosine-1-Phosphate Reduces the Expression of Prohibitin and Causes β-Cell Impairment via Mitochondrial Dysregulation

BACKGROUND: Emerging evidence suggests that sphingolipids may be involved in type 2 diabetes. However, the exact signaling defect through which disordered sphingolipid metabolism induces β-cell dysfunction remains unknown. The current study demonstrated that sphingosine-1-phosphate (S1P), the product of sphingosine kinase (SphK), is an essential factor for maintaining β-cell function and survival via regulation of mitochondrial action, as mediated by prohibitin (PHB). METHODS: We examined β-cell function and viability, as measured by mitochondrial function, in mouse insulinoma 6 (MIN6) cells in response to manipulation of cellular S1P and PHB levels. RESULTS: Lack of S1P induced by sphingosine kinase inhibitor (SphKi) treatment caused β-cell dysfunction and apoptosis, with repression of mitochondrial function shown by decreases in cellular adenosine triphosphate content, the oxygen consumption rate, the expression of oxidative phosphorylation complexes, the mitochondrial membrane potential, and the expression of key regulators of mitochondrial dynamics (mitochondrial dynamin-like GTPase [OPA1] and mitofusin 1 [MFN1]). Supplementation of S1P led to the recovery of mitochondrial function and greatly improved β-cell function and viability. Knockdown of SphK2 using small interfering RNA induced mitochondrial dysfunction, decreased glucose-stimulated insulin secretion (GSIS), and reduced the expression of PHB, an essential regulator of mitochondrial metabolism. PHB deficiency significantly reduced GSIS and induced mitochondrial dysfunction, and co-treatment with S1P did not reverse these trends. CONCLUSION: Altogether, these data suggest that S1P is an essential factor in the maintenance of β-cell function and survival through its regulation of mitochondrial action and PHB expression.

The Association between Persistent Hypertriglyceridemia and the Risk of Diabetes Development: The Kangbuk Samsung Health Study

BACKGROUND: Hypertriglyceridemia is known to have an association with increased risks of insulin resistance and diabetes. The aim of this study was to investigate the risk of diabetes mellitus, according to changes in the concentrations of triglycerides, over time. METHODS: A total of 15,932 non-diabetic participants (mean age 43.2 years, 68% men) who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital, between January 2010 and December 2014, were recruited. Participants were classified according to their triglyceride concentrations; normal ( < 150 mg/dL) and abnormal (≥150 mg/dL). According to the triglyceride levels in 2010 and 2012, subjects were divided into four groups: normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal. The risk for incident diabetes was assessed in 2014. RESULTS: Among the total subjects, 67.5% belonged to the normal-normal group, 8.6% to the normal-abnormal group, 9.4% to the abnormal-normal group, and 14.5% to the abnormal-abnormal group. A total of 234 subjects (1.5%) were newly diagnosed with diabetes, between 2010 and 2014. Over 4 years, 1%, 1.5%, 2.1%, and 3.0% of the subjects developed diabetes in the normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal groups, respectively. When the risk for incident diabetes was analyzed in the groups, after adjusting the confounding variables, a 1.58-fold increase in the risk of diabetes (95% confidence interval [CI], 1.10 to 2.26) was observed in the participants with persistent hypertriglyceridemia (abnormal-abnormal group). This was attenuated by further adjustments for body mass index (BMI) (hazard ratio, 1.25; 95% CI, 0.86 to 1.80). CONCLUSION: In this large study population, persistent hypertriglyceridemia, over a period of 2 years, was significantly associated with the risk of incident diabetes, which was attenuated after adjustment for BMI.

Pioglitazone Attenuates Palmitate-Induced Inflammation and Endoplasmic Reticulum Stress in Pancreatic β-Cells

BACKGROUND: The nuclear receptor peroxisome proliferator-activator gamma (PPARγ) is a useful therapeutic target for obesity and diabetes, but its role in protecting β-cell function and viability is unclear. METHODS: To identify the potential functions of PPARγ in β-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPARγ agonist pioglitazone in conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation. RESULTS: Palmitate-treated cells incubated with pioglitazone exhibited significant improvements in glucose-stimulated insulin secretion and the repression of apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the palmitate-induced expression of inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], and IL-1β) and ER stress markers (phosphor-eukaryotic translation initiation factor 2α, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the expression of ATF6α, GRP78, and monocyte chemoattractant protein-1, prevented α-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in β-cells. Moreover, the preservation of β-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels. CONCLUSION: Altogether, these results support the proposal that PPARγ agonists not only suppress insulin resistance, but also prevent β-cell impairment via protection against ER stress and inflammation. The activation of PPARγ might be a new therapeutic approach for improving β-cell survival and insulin secretion in patients with diabetes mellitus

Changes in Body Composition According to Age and Sex among Young Non-Diabetic Korean Adults: the Kangbuk Samsung Health Study

BACKGROUND: Age-related decreases in lean mass represent a serious health problem. We aimed to analyze the risks of rapid decreases in lean mass by age and sex in relatively young Korean adults during a 4-year follow-up study. METHODS: A total of 65,856 non-diabetic participants (59.5% men, mean age 39.1 years) in a health screening program were subjected to bioimpedance body composition analyses and metabolic parameter analyses at baseline and after 4 years. The participants were sub-divided according to age, and additionally to six groups by age and the degree of body weight change over the 4-year period. The actual changes in body weight, lean mass, and fat mass and the percent changes over the 4-year period were assessed. RESULTS: The percent change in lean mass decreased and the percent change of fat mass increased with increasing age in every age and sex group. However, the annual percent decrease in lean mass and percent increase in fat mass were significantly higher among women than among men (−0.26% vs. −0.15% and 0.34% vs. 0.42%, respectively; P<0.01). Participants who were older than 50 years and had a weight loss <−5% during the 4 years had significantly greater decreases in lean mass and smaller decreases in fat mass, compared to those who were younger than 50 years. An odds ratio analysis to determine the lowest quartile of the percent change in lean mass according to age group revealed that participants older than 60 years had a significantly increased risk of a rapid decrease in the lean mass percentage (2.081; 95% confidence interval, 1.678 to 2.581). CONCLUSION: Even in this relatively young study population, the lean mass decreased significantly with age, and the risk of a rapid decrease in lean mass was higher among women than among men. Furthermore, the elderly exhibited a significantly more rapid decrease in lean mass, compared with younger participants.

Korean Society for Bone and Mineral Research Task Force Report: Perspectives on Intermittent High-dose Vitamin D Supplementation

An adequate supply of vitamin D is considered necessary for osteoporosis management and fracture prevention. Intermittent high-dose vitamin D supplementation is an effective and convenient way to achieve and maintain sufficient vitamin D status. However, the long-term effectiveness of supplementation for preventing falls and fractures is unclear, and some deleterious effects of such treatments have been reported. Concerning these issues, the Korean Society for Bone and Mineral Research task force team reviewed previous clinical trials and provided the following perspectives based on current evidence: 1) An adequate supply of vitamin D is necessary for preventing falls and fractures in postmenopausal women and men older than 50 years. An oral intake of 800 to 1,000 IU/day of vitamin D is generally recommended. 2) Care should be taken concerning the routine use of intermittent high-dose vitamin D, as large-scale clinical trials showed increased risk of falls or fractures after high-dose vitamin D administration. Intermittent high-dose vitamin D supplementation is recommendable only in cases of malabsorption or when oral administration is not suitable. 3) Monitoring of the serum level of 25-hydroxy-vitamin D (25[OH]D) is advisable, especially when intermittent high-dose vitamin D is used for supplementation. The task force team suggests that a serum 25(OH)D level of >20 ng/mL is generally appropriate for the prevention of osteoporosis, and that a serum 25(OH)D level of >30 ng/mL is probably helpful both for the management of osteoporosis and the prevention of fractures and falls. However, serum 25(OH)D level >50 ng/mL (this value can vary depending on the measurement method used) is unnecessary and may be undesirable. These perspectives are relevant for the management of osteoporosis, falls, or fractures. Other metabolic bone diseases or non-skeletal disorders are not within the scope of these perspectives.

Waist Circumference as a Marker of Obesity Is More Predictive of Coronary Artery Calcification than Body Mass Index in Apparently Healthy Korean Adults: The Kangbuk Samsung Health Study

BACKGROUND: We aimed to assess the risk for coronary artery calcification (CAC) according to groups subdivided by body mass index (BMI) and waist circumference (WC) in apparently healthy Korean adults. METHODS: Thirty-three thousand four hundred and thirty-two participants (mean age, 42 years) in a health screening program were divided into three groups according to BMI: 25 kg/m² (obese). In addition, the participants were divided into two groups according to WC. Coronary artery calcium score (CACS) was measured with multi-detector computed tomography in all participants. Presence of CAC was defined as CACS >0. RESULTS: When logistic regression analysis was performed with the presence of CAC as the dependent variable, the risk for CAC increased as BMI increased after adjusting for confounding variables (1.102 [95% confidence interval (CI), 1.000 to 1.216]; 1.284 [95% CI, 1.169 to 1.410]; in the overweight and obese groups vs. the normal weight group). When the participants were divided into six groups according to BMI and WC, the subjects with BMI and WC in the obese range showed the highest risk for CAC (1.321 [95% CI, 1.194 to 1.461]) and those with BMI in the overweight range and WC in the obese range showed the second highest risk for CAC (1.235 [95% CI, 1.194 to 1.461]). CONCLUSION: Participants with obesity defined by both BMI and WC showed the highest risk for CAC. Those with BMIs in the overweight range but with WC in the obese range showed the second highest risk for CAC, suggesting that WC as a marker of obesity is more predictive of CAC than BMI.

The Relationship between 10-Year Cardiovascular Risk Calculated Using the Pooled Cohort Equation and the Severity of Non-Alcoholic Fatty Liver Disease

BACKGROUND: We investigated the association between the severity of non-alcoholic fatty liver disease (NAFLD) and the estimated 10-year risk of cardiovascular disease (CVD) calculated by Pooled Cohort Equation (PCE) and Framingham risk score (FRS). METHODS: A total of 15,913 participants (mean age, 46.3 years) in a health screening program were selected for analysis. The presence and severity of fatty liver was assessed by abdominal ultrasonogram. Subjects who drank alcohol more than three times a week were excluded from the study. RESULTS: Among the participants, 57.6% had no NAFLD, 35.4% had grade I, 6.5% had grade II, and 0.5% had grade III NAFLD. Mean estimated 10-year CVD risk was 2.59%, 3.93%, 4.68%, and 5.23% calculated using the PCE (P for trend <0.01) and 4.55%, 6.39%, 7.33%, and 7.13% calculated using FRS, according to NAFLD severity from none to severe (P for trend <0.01). The odds ratio for ≥7.5% estimated CVD risk calculated using the PCE showed a higher correlation with increasing severity of NAFLD even after adjustment for conventional CVD risk factors (1.52, 2.56, 3.35 vs. the no NAFLD group as a reference, P<0.01) compared with calculated risk using FRS (1.65, 1.62, 1.72 vs. no NAFLD group as a reference, P<0.01). CONCLUSION: In our study of apparently healthy Korean adults, increasing severity of NAFLD showed a higher correlation with estimated 10-year CVD risk when calculated using the PCE than when calculated using FRS.

Association of Waist-Height Ratio with Diabetes Risk: A 4-Year Longitudinal Retrospective Study

BACKGROUND: Waist-to-height ratio (WHtR) is an easy and inexpensive adiposity index that reflects central obesity. In this study, we examined the association of various baseline adiposity indices, including WHtR, with the development of diabetes over 4 years of follow-up in apparently healthy Korean individuals. METHODS: A total of 2,900 nondiabetic participants (mean age, 44.3 years; 2,078 men) in a health screening program, who repeated the medical check-up in 2005 and 2009, were recruited. Subjects were divided into two groups according to development of diabetes after 4 years. The cut-off values of baseline body mass index (BMI), waist circumference (WC), and WHtR for the development of diabetes over 4 years were calculated. The sensitivity, specificity, and mean area under the receiver operator characteristic curve (AUROC) of each index were assessed. The odds ratio (OR) for diabetes development was analyzed for each of the three baseline adiposity indices. RESULTS: During the follow-up period, 101 new cases (3.5%) of diabetes were diagnosed. The cut-off WHtR value for diabetes development was 0.51. Moreover, WHtR had the highest AUROC value for diabetes development among the three adiposity indices (0.716, 95% confidence interval [CI], 0.669 to 0.763; 0.702, 95% CI, 0.655 to 0.750 for WC; 0.700, 95% CI, 0.651 to 0.750 for BMI). After adjusting for confounding variables, the ORs of WHtR and WC for diabetes development were 1.95 (95% CI, 1.14 to 3.34) and 1.96 (95% CI, 1.10 to 3.49), respectively. No significant differences were observed between the two groups regarding BMI. CONCLUSION: Increased baseline WHtR and WC correlated with the development of diabetes after 4 years. WHtR might be a useful screening measurement to identify individuals at high risk for diabetes.

C-Peptide-Based Index Is More Related to Incident Type 2 Diabetes in Non-Diabetic Subjects than Insulin-Based Index

BACKGROUND: Diabetes can be efficiently prevented by life style modification and medical therapy. So, identification for high risk subjects for incident type 2 diabetes is important. The aim of this study is to identify the best β-cell function index to identify high risk subjects in non-diabetic Koreans. METHODS: This is a retrospective longitudinal study. Total 140 non-diabetic subjects who underwent standard 2-hour 75 g oral glucose tolerance test from January 2007 to February 2007 at Kangbuk Samsung Hospital and followed up for more than 1 year were analyzed (mean follow-up, 54.9±16.4 months). The subjects were consist of subjects with normal glucose tolerance (n=44) and subjects with prediabetes (n=97) who were 20 years of age or older. Samples for insulin and C-peptide levels were obtained at 0 and 30 minutes at baseline. RESULTS: Thirty subjects out of 140 subjects (21.4%) developed type 2 diabetes. When insulin-based index and C-peptide-based index are compared between progressor and non-progressor to diabetes, all C-peptide-based indices were statistically different between two groups, but only insulinogenic index and disposition index among insulin-based index were statistically different. C-peptide-based index had higher value of area under receiver operating characteristic curve (AROC) value than that of insulin-based index. "C-peptidogenic" index had highest AROC value among indices (AROC, 0.850; 95% confidence interval, 0.761 to 0.915). C-peptidogenic index had significantly higher AROC than insulinogenic index (0.850 vs. 0.731 respectively; P=0.014). CONCLUSION: C-peptide-based index was more closely related to incident type 2 diabetes in non-diabetic subjects than insulin-based index.

Eligibility for Statin Treatment in Korean Subjects with Reduced Renal Function: An Observational Study

BACKGROUND: The purpose of this study was to investigate the relationship between statin eligibility and the degree of renal dysfunction using the Adult Treatment Panel (ATP) III and the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines in Korean adults. METHODS: Renal function was assessed in 18,746 participants of the Kangbuk Samsung Health Study from January 2011 to December 2012. Subjects were divided into three groups according to estimated glomerular filtration rate (eGFR): stage 1, eGFR ≥90 mL/min/1.73 m2; stage 2, eGFR 60 to 89 mL/min/1.73 m2; and stages 3 to 5, eGFR <60 mL/min/1.73 m2. Statin eligibility in these groups was determined using the ATP III and ACC/AHA guidelines, and the risk for 10-year atherosclerotic cardiovascular disease (ASCVD) was calculated using the Framingham Risk Score (FRS) and Pooled Cohort Equation (PCE). RESULTS: There were 3,546 (18.9%) and 4,048 (21.5%) statin-eligible subjects according to ATP III and ACC/AHA guidelines, respectively. The proportion of statin-eligible subjects increased as renal function deteriorated. Statin eligibility by the ACC/AHA guidelines showed better agreement with the Kidney Disease Improving Global Outcomes (KDIGO) recommendations compared to the ATP III guidelines in subjects with stage 3 to 5 chronic kidney disease (CKD) (κ value, 0.689 vs. 0.531). When the 10-year ASCVD risk was assessed using the FRS and PCE, the mean risk calculated by both equations significantly increased as renal function declined. CONCLUSIONS: The proportion of statin-eligible subjects significantly increased according to worsening renal function in this Korean cohort. ACC/AHA guideline showed better agreement for statin eligibility with that recommended by KDIGO guideline compared to ATP III in subjects with CKD.

Efficacy of a Once-Monthly Pill Containing Ibandronate and Cholecalciferol on the Levels of 25-Hydroxyvitamin D and Bone Markers in Postmenopausal Women with Osteoporosis

BACKGROUND: The present study evaluated the efficacy of a combination of ibandronate and cholecalciferol on the restoration of the levels of 25-hydroxyvitamin D (25[OH]D) and various bone markers in postmenopausal women with osteoporosis. METHODS: This was a randomized, double-blind, active-controlled, prospective 16-week clinical trial conducted in 20 different hospitals. A total of 201 postmenopausal women with osteoporosis were assigned randomly to one of two groups: the IBN group, which received a once-monthly pill containing 150 mg ibandronate (n=99), or the IBN+ group, which received a once-monthly pill containing 150 mg ibandronate and 24,000 IU cholecalciferol (n=102). Serum levels of 25(OH)D, parathyroid hormone (PTH), and various bone markers were assessed at baseline and at the end of a 16-week treatment period. RESULTS: After 16 weeks of treatment, the mean serum levels of 25(OH)D significantly increased from 21.0 to 25.3 ng/mL in the IBN+ group but significantly decreased from 20.6 to 17.4 ng/mL in the IBN group. Additionally, both groups exhibited significant increases in mean serum levels of PTH but significant decreases in serum levels of bone-specific alkaline phosphatase and C-telopeptide of type 1 collagen (CTX) at 16 weeks; no significant differences were observed between the groups. However, in subjects with a vitamin D deficiency, IBN+ treatment resulted in a significant decrease in serum CTX levels compared with IBN treatment. CONCLUSION: The present findings demonstrate that a once-monthly pill containing ibandronate and cholecalciferol may be useful for the amelioration of vitamin D deficiency in patients with postmenopausal osteoporosis. Moreover, this treatment combination effectively decreased serum levels of resorption markers, especially in subjects with a vitamin D deficiency, over the 16-week treatment period.

Metabolic Health Is More Important than Obesity in the Development of Nonalcoholic Fatty Liver Disease: A 4-Year Retrospective Study

BACKGROUND: The aim of this study is to compare the risk for future development of nonalcoholic fatty liver disease (NAFLD) according to different status of metabolic health and obesity. METHODS: A total of 3,045 subjects without NAFLD and diabetes at baseline were followed for 4 years. Subjects were categorized into four groups according to the following baseline metabolic health and obesity statuses: metabolically healthy, non-obese (MHNO); metabolically healthy, obese (MHO); metabolically unhealthy, non-obese (MUHNO); and metabolically unhealthy, obese (MUHO). Being metabolically healthy was defined as having fewer than two of the following five components: high blood pressure, high fasting blood glucose, high triglyceride, low high density lipoprotein cholesterol, and being in the highest decile of the homeostasis model assessment-insulin resistance index. Obesity was defined as a body mass index >25 kg/m2. The presence of NAFLD was assessed by ultrasonography. RESULTS: The proportions of subjects included in the MHNO, MHO, MUHNO, and MUHO groups were 71.4%, 9.8%, 13.0%, and 5.8%, respectively. The proportions of subjects who developed NAFLD were 10.5%, 31.4%, 23.2%, and 42% in the MHNO, MHO, MUHNO, and MUHO groups, respectively. The risk for developing NAFLD was highest in subjects who were metabolically unhealthy both at baseline and after 4 years compared with subjects who were consistently metabolically healthy during the follow-up period (odds ratio, 2.862). Using the MHNO group as reference, the odds ratios for the MHO, MUHNO, and MUHO groups were 1.731, 1.877, and 2.501, respectively. CONCLUSION: The risk for NAFLD was lower in MHO subjects than in MUNO subjects.

Exendin-4 Inhibits the Expression of SEPP1 and Fetuin-A via Improvement of Palmitic Acid-Induced Endoplasmic Reticulum Stress by AMPK

BACKGROUND: Selenoprotein P (SEPP1) and fetuin-A, both circulating liver-derived glycoproteins, are novel biomarkers for insulin resistance and nonalcoholic fatty liver disease. However, the effect of exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, on the expression of hepatokines, SEPP1, and fetuin-A, is unknown. METHODS: The human hepatoma cell line HepG2 was treated with palmitic acid (PA; 0.4 mM) and tunicamycin (tuni; 2ug/ml) with or without exendin-4 (100 nM) for 24 hours. The change in expression of PA-induced SEPP1, fetuin-A, and endoplasmic reticulum (ER) stress markers by exendin-4 treatment were evaluated using quantitative real-time reverse transcription polymerase chain reaction and Western blotting. Transfection of cells with AMP-activated protein kinase (AMPK) small interfering RNA (siRNA) was performed to establish the effect of exendin-4-mediated AMPK in the regulation of SEPP1 and fetuin-A expression. RESULTS: Exendin-4 reduced the expression of SEPP1, fetuin-A, and ER stress markers including PKR-like ER kinase, inositol-requiring kinase 1alpha, activating transcription factor 6, and C/EBP homologous protein in HepG2 cells. Exendin-4 also reduced the expression of SEPP1 and fetuin-A in cells treated with tunicamycin, an ER stress inducer. In cells treated with the AMPK activator 5-aminoidazole-4-carboxamide ribonucleotide (AICAR), the expression of hepatic SEPP1 and fetuin-A were negatively related by AMPK, which is the target of exendin-4. In addition, exendin-4 treatment did not decrease SEPP1 and fetuin-A expression in cells transfected with AMPK siRNA. CONCLUSION: These data suggest that exendin-4 can attenuate the expression of hepatic SEPP1 and fetuin-A via improvement of PA-induced ER stress by AMPK.

Comparison of Serum Adipocytokine Levels according to Metabolic Health and Obesity Status

BACKGROUND: Metabolic health is an emerging concept that is highly correlated with various metabolic complications, and adipocytokines have been causally linked to a wide range of metabolic diseases. Thus, this study compared serum adipocytokine levels according to metabolic health and obesity status. METHODS: Four hundred and fifty-six nondiabetic subjects (mean age, 40.5 years) were categorized into four groups according to metabolic health and obesity status: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUHNO), and metabolically unhealthy obese (MUHO). Being metabolically healthy was defined as the presence of fewer than two of the following five metabolic abnormalities: high blood pressure, high fasting blood glucose, high triglyceride, low high density lipoprotein cholesterol, and being in the highest decile of the homeostatic model assessment of insulin resistance index. Obesity status was assessed using body mass index (BMI), with obesity defined as a BMI higher than 25 kg/m2. Levels of serum interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha), and adipocyte fatty acid binding protein (A-FABP) were also evaluated. RESULTS: Of the 456 subjects, 247 (54.2%) were in the MHNO group, 66 (14.5%) were in the MHO group, 66 (14.5%) were in the MUHNO group, and 77 (16.9%) were in the MUHO group. There were no significant differences in IL-6 or MCP-1 levels among the groups, but levels of TNF-alpha and A-FABP were significantly higher in the MUHNO group compared to the MHNO group. CONCLUSION: High TNF-alpha and A-FABP levels are significantly associated with metabolically unhealthiness in nonobese Korean individuals.