Kyu Jeung Ahn

The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced β‐cell function in middle‐aged male subjects

Recent human studies support the notion that serum osteocalcin increases β‐cell proliferation and insulin secretion, and improves insulin sensitivity. However, no study has examined the effects of serum osteocalcin γ‐carboxylation status on these associations or determined the role of uncarboxylated osteocalcin in glucose metabolism in humans.

Sarcopenia is independently associated with cardiovascular disease in older Korean adults: the Korea National Health and Nutrition Examination Survey (KNHANES) from 2009.

Background The association between sarcopenia and cardiovascular disease (CVD) in elderly people has not been adequately assessed. The aim of this study was to investigate whether CVD is more prevalent in subjects with sarcopenia independent of other well-established cardiovascular risk factors in older Korean adults. Method This study utilized the representative Korean population data from the Korea National Health and Nutrition Examination Survey (KNHANES) which was conducted in 2009. Subjects older than 65 years of age with appendicular skeletal muscle mass (ASM) determined by dual energy X-ray absorptiometry were selected. The prevalence of sarcopenia in the older Korean adults was investigated, and it was determined whether sarcopenia is associated with CVD independent of other well-known risk factors. Results 1,578 subjects aged 65 years and older with the data for ASM were selected, and the overall prevalence of sarcopenia was 30.3% in men and 29.3% in women. Most of the risk factors for CVD such as age, waist circumference, body mass index, fasting plasma glucose and total cholesterol showed significant negative correlations with the ratio between appendicular skeletal muscle mass and body weight. Multiple logistic regression analysis demonstrated that sarcopenia was associated with CVD independent of other well-documented risk factors, renal function and medications (OR, 1.768; 95% CI, 1.075–2.909, P = 0.025). Conclusions Sarcopenia was associated with the presence of CVD independent of other cardiovascular risk factors after adjusting renal function and medications.

Prevalence of Chronic Complications in Korean Patients with Type 2 Diabetes Mellitus Based on the Korean National Diabetes Program

Background The Korean National Diabetes Program (KNDP) cohort study is performing an ongoing large-scale prospective multicenter investigation to discover the pathogenesis of type 2 diabetes in Korean patients. This study was performed to examine the prevalence of chronic complications in patients with type 2 diabetes among those registered in the KNDP cohort within the past 4 years. Methods This study was performed between June 2006 and September 2009 at 13 university hospitals and included 4,265 KNDP cohort participants. Among the participants, the crude prevalence of microvascular and macrovascular diseases of those checked for diabetes-related complications was determined, and the adjusted standard prevalence and standardization of the general population prevalence ratio (SPR) was estimated based on the 2005 Korean National Health and Nutrition Examination Survey (KNHANES) population demographics. Results Among the KNDP registrants, 43.2% had hypertension, 34.8% had dyslipidemia, 10.8% had macrovascular disease, and 16.7% had microvascular disease. The SPR of the KNDP registrants was significantly higher than that of the KNHANES subjects after adjusting for demographics in the KNHANES 2005 population. However, with the exception of cardiovascular disease in females, the standardized prevalence for the most complicated items in the survey was significantly higher than that in the KNHANES subjects. Conclusion The prevalence of macrovascular disease and peripheral vascular disease were significantly higher in Korean patients with type 2 diabetes than in the normal population. However, no significant difference was noted in the prevalence of cardiovascular disease in females.

Circulating Osteocalcin Level Is Not Associated With Incident Type 2 Diabetes in Middle-Aged Male Subjects Mean 8.4-year retrospective follow-up study

OBJECTIVE Recent human studies suggested that serum osteocalcin is associated with the cross-talk between bone and energy metabolism. The aim of this study was to determine whether serum osteocalcin level is independently associated with the development of type 2 diabetes. RESEARCH DESIGN AND METHODS A retrospective cohort study was performed of 1,229 nondiabetic men, aged 25–60 years, who were recruited from the Health Promotion Center, Samsung Medical Center, between January 1997 and December 1997. They were followed regularly at the center on an out-patient basis and during hospitalization for a mean of 8.4 years, and the development of type 2 diabetes was determined. RESULTS In the baseline analysis, BMI, body fat percentage, triglyceride, homeostasis model assessment of insulin resistance value, and plasminogen activator inhibitor-1 levels varied inversely with the osteocalcin tertiles, and serum high-density lipoprotein cholesterol levels increased with the osteocalcin tertiles. However, no differences were observed in fasting glucose and glycated hemoglobin levels across the osteocalcin tertiles. Incident type 2 diabetes occurred in 90 (7.3%) of the study subjects. In Cox proportional hazards models, however, no statistical differences in the development of type 2 diabetes across the osteocalcin tertiles were evident after adjustment of other risk factors for incident diabetes. CONCLUSIONS Despite baseline associations with favorable metabolic parameters, the serum osteocalcin level was not associated with the development of type 2 diabetes in middle-aged males.

Direct Medical Costs for Patients with Type 2 Diabetes and Related Complications: A Prospective Cohort Study Based on the Korean National Diabetes Program

We analyzed the direct medical costs for Korean patients with type 2 diabetes according to the type of complications and the number of microvascular complications. We analyzed costs for type 2 diabetes and associated complications in 3,125 patients. These data were obtained from the Korean National Diabetes Program (KNDP), a large, ongoing, prospective cohort study that began in 2005. The cost data were prospectively collected, using an electronic database, for the KNDP cohort at six hospitals. The costs were analyzed according to complications for 1 yr from enrollment in the study. Among 3,125 patients, 918 patients had no vascular complications; 1,883 had microvascular complications only; 51 had macrovascular complications only; and 273 had both complications. The annual direct medical costs for a patient with only macrovascular, only microvascular, or both macrovascular and microvascular complications were 2.7, 1.5, and 2.0 times higher than the medical costs of patients without complications. Annual direct medical costs per patient increased with the number of microvascular complications in patients without macrovascular complications. The economic costs for type 2 diabetes are attributable largely to the management of microvascular and macrovascular complications. Proper management of diabetes and prevention of related complications are important for reducing medical costs.

Comparison of the Efficacy of Glimepiride, Metformin, and Rosiglitazone Monotherapy in Korean Drug-Naïve Type 2 Diabetic Patients: The Practical Evidence of Antidiabetic Monotherapy Study

Background Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated. Methods We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels. Results HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (P<0.001), from 7.9% to 7.0% in the metformin group (P<0.001), and from 7.8% to 7.0% (P<0.001) in the rosiglitazone group. Glimepiride and rosiglitazone significantly increased body weight and metformin reduced body weight during the study period. Symptomatic hypoglycemia was more frequent in the glimepiride group and diarrhea was more frequent in the metformin group. Conclusion The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.

Bisphenol A reduces differentiation and stimulates apoptosis of osteoclasts and osteoblasts.

AIMS Bisphenol A (BPA), a major component of epoxy resins used in protective coatings, is a known endocrine-disrupting chemical. BPA has the ability of binding to estrogen receptors. In the current paper, we examine the direct effects of bisphenol A on in vitro osteoclast and osteoblast culture systems. MAIN METHODS We evaluated the effects of BPA on osteoclast formation using bone marrow-derived macrophages and RAW 264.7 cells and on osteoblast differentiation using MC3T3-E1 cells. KEY FINDINGS BPA significantly inhibited RANKL-induced, TRAP-positive multinucleated cell formation in bone marrow-derived macrophages and RAW 264.7 cell cultures in a dose-dependent manner (0.5 μM to 12.5 μM). We observed suppression of ERK, JNK, AKT, and p38 mitogen-activated protein kinases induced by RANKL in Western blotting after BPA treatment in RAW 264.7 cells. Furthermore, BPA suppressed Bcl-2 (anti-apoptotic) while stimulating Bax (pro-apoptotic) protein expression in RAW 264.7 cells. Bisphenol A also significantly suppressed ALP activities and bone nodule formation in MC3T3-E1 cell cultures. Specifically, the expression of Bcl-2 protein was decreased, and changes in expression of caspases 3, 8, and 9 were detected by BPA treatment in both cells. SIGNIFICANCE We found that bisphenol A directly suppressed both osteoclastic and osteoblastic activities in vitro. Our data suggest that bisphenol A suppresses cell differentiation and survival.

Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

Background Type B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans. Methods To evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patients dialyzed serum before and after immunosuppressive therapy. Results In the patients pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%. Conclusion We treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patients insulin receptor antibodies by measuring the inhibition of insulin binding.

Characteristics of insulin resistance and insulin secretory capacity in Korean subjects with IFG and IGT

Both IFG and IGT are prediabetic conditions that can progress to type 2 DM. However, previous studies have shown that these are not identical. This study was conducted on 307 drug naïve prediabetic adults who did not meet the diagnostic criteria for diabetes based on the OGTT. According to the OGTT, the subjects were divided into isolated IFG (i-IFG), isolated IGT (i-IGT), and combined glucose intolerance (CGI) group. We also measured insulin resistance indices (HOMA-IR, WBISI), an insulin secretion indices (insulinogenic index [IGI], AUC I/G(0-120), disposition index [DI]), and compared each of the three groups. The OGTT measurements showed that 87 subjects were diagnosed with i-IFG, 75 subjects had i-IGT, and 145 subjects had CGI. With respect to the insulin resistance indices, HOMA-IR and WBISI were not significantly different. However, insulin secretory capacity, the IGI and DI were significantly higher for the i-IFG group. Moreover, after confounders were adjusted, HOMA-IR, IGI, AUC I/G(0-120), and the DI were significantly higher for the i-IFG group and WBISI was significantly higher for the i-IGT group. These results demonstrate that the pathogenesis of IFG is more closely associated with insulin resistance, and the pathogenesis of IGT is more closely associated with impaired insulin secretion.

Changes in Serum Osteocalcin are Not Associated with Changes in Glucose or Insulin for Osteoporotic Patients Treated with Bisphosphonate

Background Bisphosphonate is used in osteoporosis treatment to repress osteoclast activity, which then decreases levels of osteocalcin (OC). OC, a protein secreted by osteoblasts and released from the bone matrix during osteoclastic bone resorption, has been found to control blood glucose levels by increasing insulin production and sensitivity. The question addressed in this study is whether decreasing OC through bisphosphonate treatment will provoke a change in glucose homeostasis. Methods Eighty-four patients with osteoporosis were treated with once-weekly risedronate 35 mg and cholecalciferol 5,600 IU. We measured fasting plasma glucose (FPG), insulin, and undercarboxylated (Glu) and carboxylated (Gla) OC levels at baseline and after 16 weeks. To estimate insulin resistance (IR) and β-cell function (B)%, homeostasis model assessment (HOMA)-IR and HOMA-B% were also calculated, respectively. Results The mean FPG level in total subjects increased significantly from 5.3 to 5.5 mmol/L, but no changes in blood glucose were noted in the 24 subjects with impaired fasting glucose. Glu and Gla OC levels declined significantly after treatment. No correlations were observed between changes in OC and changes in glucose, however. Conclusions Bisphosphonate treatment for osteoporosis reduced OC, but this change was not associated with changes in glucose metabolism.