Jae-Hwan Jee

Metabolic syndrome as a predictor of cardiovascular diseases and type 2 diabetes in Koreans

BACKGROUND The purpose of this study was to investigate whether the presence of the NCEP-ATP III defined metabolic syndrome (MS) is associated with the future development of cardiovascular disease (CVD) and diabetes in Koreans. METHODS The study subjects were recruited from among those who visited the Health Promotion Center at the Samsung Medical Center. 2435 subjects (1761 men and 674 women), 20 to 78 years of age, were enrolled and evaluated for the development of new onset CVD (coronary heart disease [CHD] and stroke) during a mean 8.7 years of follow-up. RESULTS The prevalence of the MS at baseline was 21.7% (382/1761) and 11.4% (77/674) in men and women respectively, and the MS was found to be associated with the risk for CVD in both men and women (OR, 1.98; 95% CI, 1.30-3.03 in men, 4.04; 95% CI, 1.78-9.14 in women). More specifically, the MS was associated with the risk for future CHD (OR, 3.68; 95% CI, 1.93-7.01) in men and stroke (OR, 3.96; 95% CI, 1.58-9.94) in women. However, no statistical differences were found between the HOMA-IR tertiles with regard to the risk for CVD. After controlling for fasting plasma glucose (FPG) levels, the predictive power of the MS for an increased risk for diabetes was dramatically decreased (OR, from 3.69 to 1.77) in men, and it no longer was a predictor in women. CONCLUSIONS The NCEP-defined MS was found to be associated with the risk for future CVD, i.e., CHD in men and stroke in women.

The favorable outcome of human islet transplantation in Korea: experiences of 10 autologous transplantations.

Background. Cystic neoplasms of the pancreas are an increasingly diagnosed entity, and surgical resection of the pancreas is advocated. Islet autotransplantation is a therapeutic approach used to prevent diabetes in cases of pathologically benign neoplasm after major pancreatectomy. Methods. A total of 10 patients underwent pancreatectomy with islet autotransplantation. To evaluate islet transplantation efficiency, the authors compared 23 subjects who did not undergo islet transplantation after partial pancreatectomy with 87 subjects with normal glucose tolerance and with 77 diabetic subjects that did not undergo pancreatectomy. Results. Ten female patients with nine cystic neoplasms and one patient with pancreatic injury underwent transplantation. Their mean islet equivalents (IEQ) was 3,159 IEQ/kg. During follow-up, two recipients required insulin or oral agents. At the 12-month follow-up, homeostasis model assessment (HOMA)-β was 77.36±17.68, the insulinogenic index (INSindex) was 0.49±0.11, and fasting C-peptide and hemoglobin A1c were 1.28±0.18 ng/mL and 5.73±0.26%, respectively. Islet replacement was found to increase HOMA-β by approximately 17% compared with distal pancreatectomy in normal glucose tolerance subjects without islet autotransplantation and by 46% compared with distal pancreatectomy diabetes subjects without islet autotransplantation. Factors different in the two insulin and oral hypoglycemic agent (OHA)-requiring recipients and the eight insulin- and OHA-free recipients were pancreatectomy extent, preoperative glucose metabolism insufficiency, age, and underlying cystic neoplasm disease. Conclusions. Even partial islet graft function can have a beneficial metabolic effect on the recipient in terms of metabolic parameters such as HOMA-β and INSindex. This study suggests that islet replacement should be considered for experimental procedures in benign pancreatic conditions.

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.

Metformin enhances glucagon-like peptide 1 via cooperation between insulin and Wnt signaling

One aspect of the effects of metformin on glucagon-like peptide (GLP)-1 might be associated with the mechanism by which the cross talk between insulin and Wnt signaling enhances GLP1 secretion, due to the action of metformin as an insulin sensitizer. However, this remains completely unknown. In this study, we have investigated the mechanisms of the action of metformin on cross talk between insulin and Wnt signaling. GLP1 enhancement by meformin was determined in human NCI-H716 intestinal L-cells and hyperglycemic db/db mice treated with metformin (0.25 and 0.5 mM and/or 12.5 mg/kg body weight) for 24 h and 2 months. Metformin increased GLP1 secretion in L-cells and db/db mice. Metformin stimulated the nuclear translocation of β-catenin and TOPflash reporter activity, and gene depletion of β-catenin or enhancement of mutation of transcription factor 7-like 2 binding site offset GLP1. In addition, insulin receptor substrate 2 gene depletion blocked metformin-enhanced β-catenin translocation. These effects were preceded by an increase in glucose utilization and calcium influx, the activation of calcium-dependent protein kinase, and, in turn, the activation of insulin signaling, and the inhibition of glycogen synthase kinase 3β, a potent inhibitor of β-catenin. Furthermore, high blood glucose levels were controlled via GLP1 receptor-dependent insulinotropic pathways in db/db mice, which were evidenced by the increase in GLP1 and insulin levels at 30 min after oral glucose loading and pancreatic insulinotropic gene expression. Our findings indicate that the cooperation between Wnt and its upstream insulin signaling pathways might be a novel and important mechanism underlying the effects of metformin on GLP1 production.

A better yield of islet cell mass from living pancreatic donors compared with cadaveric donors

Abstract:  Studies in rats have shown that brain death decreases β‐cell function and causes islet cell death during islet isolation and transplantation. Because a direct comparison of human islet cells between living and cadaveric donors has not been reported to date, we studied the effects of brain death on islet cell yield. A total of 36 pancreas specimens from 20 living donors and 16 cadaveric donors were used for analysis. Islets were isolated with a Ricordi chamber, and counted as equivalent islet numbers (EIN). Living donors were predominantly female, and cadaveric donors were mainly male. Although the cold ischemic time, pancreas distensibility and digestion time were not different, islet yield was observed to be higher in living donors compared with cadaveric donors (5800 ± 3500 vs. 1900 ± 2000 EIN/g pancreas). Islet isolation success rates (when defined as more than 2000 EIN/g) were 94.1% and 42.9%, respectively. Post‐Ficoll islet recovery rates and purity were also better in living donors. However, islet viability and in vitro function of isolated islets showed no significant differences between the groups. These results suggested that brain death negatively affected the processes of islet isolation from the pancreas.

Delayed improvement of insulin secretion after autologous islet transplantation in partially pancreatectomized patients

The purpose of this study was to evaluate the effects of autologous islet transplantation (ITx) on glucose homeostasis and insulin secretory function after partial pancreatectomy (Px). Fourteen nondiabetic patients who underwent distal Px and autologous ITx for benign pancreatic tumors were enrolled in the study (Px + ITx group). Fourteen normal glucose-tolerant controls and 6 Px without ITx controls were recruited, and all groups were followed over a 24-month period. They performed the 75-g oral glucose tolerance test and the 1-mg glucagon stimulation test. Hemoglobin A(1c) was measured, and indices of insulin secretion were calculated. In the Px + ITx group, insulin secretion increased after a nadir at 6 months. Glucose tolerance, which had been abruptly impaired immediately after Px, recovered until 6 months and stabilized thereafter. As a result, differences in glucose intolerance emerged between the subjects in the Px group and those in the Px + ITx group at 24 months after Px. Characteristic variables in the better insulin secretory subjects in the Px + ITx group included younger age, less extensive pancreas resection, and a greater number of total islets. In summary, delayed amelioration of glucose intolerance was induced by autologous ITx after partial Px, even with a small number of islets.

High Dietary Sodium Intake Assessed by 24-hour Urine Specimen Increase Urinary Calcium Excretion and Bone Resorption Marker

Background The average dietary sodium intake of Koreans is 2.6 times higher than the World Health Organizations recommended amount. The effect of a diet high in sodium on the skeletal system, especially osteoporosis, has not previously been examined in Korean postmenopausal women with low bone mass. We assessed the daily sodium intake, and determined the impact of sodium intake on urinary calcium excretion and bone resorption marker. Methods A retrospective review of medical records was performed for 86 postmenopausal subjects who were initially diagnosed with osteopenia or osteoporosis at the health promotion center. They were subsequently referred to the Division of Endocrinology and Metabolism between 2010 and 2013. All subjects completed a modified food frequency questionnaire. Twenty-four hour urine collection for sodium, calcium and creatinine excretion, and serum C-terminal telopeptides of type I collagen (CTX-I) were also obtained. Results The average amount of daily sodium and calcium intake were 3,466 mg and 813 mg, respectively. Average dietary sodium intake and 24-hour urinary sodium excretion showed significant positive linear correlation (r=0.29, P=0.006). There was also a significant positive linear correlation between 24-hour urine sodium and calcium excretion (r=0.42, P<0.001); CTX-I and 24-hour urinary calcium excretion (r=0.29, P=0.007). Conclusions Excessive sodium intake assessed by 24-hour urine specimen is associated with high calcium excretion in urine. High calcium excretion is also related to increasing bone resorption marker.