Ji Sun Nam

Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus

Background Sitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects. Methods We obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (ΔHbA1c) and fasting plasma glucose (ΔFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in ΔHbA1c or >20% in ΔFPG levels at 24 weeks. Results We classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70±2.40 vs. 26.00±2.26, P≤0.01) and were younger (58.83±11.57 years vs. 62.87±12.09 years, P=0.03) than the non-responder group. Conclusion In Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders.

Insulin resistance independently influences arterial stiffness in normoglycemic normotensive postmenopausal women.

Objective:Cardiovascular disease risk increases after menopause, which may be related to insulin resistance, and arterial stiffness is a significant predictor of atherosclerosis. We investigated the relationships among insulin resistance, adiponectin, and arterial stiffness in normoglycemic normotensive postmenopausal women. Methods:From 9,555 participants who had routine health checkups, 455 normoglycemic normotensive postmenopausal women were enrolled. Serum concentrations of glucose, total cholesterol, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) and adiponectin were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Pulse wave velocity (PWV) was evaluated to assess arterial stiffness. Results:The women were stratified into three groups according to their HOMA-IR values, and comparisons were made among the three groups. There were significant differences in metabolic parameters between the groups. The mean age, body mass index, waist circumference, fasting plasma glucose, TG, systolic blood pressure (SBP), diastolic blood pressure (DBP), aortic PWV, and peripheral PWV increased sequentially with the degree of insulin resistance. Meanwhile, HDL-C and adiponectin levels decreased with the worsening of insulin resistance. Age, body mass index, fasting plasma glucose, TG, insulin, SBP, HOMA-IR, aortic PWV, and peripheral PWV were significantly higher in women with central obesity, and HDL-C and adiponectin were significantly lower in women with central obesity. Aortic PWV and peripheral PWV were significantly correlated with age, waist circumference, total cholesterol, SBP, DBP, insulin, and HOMA-IR, but adiponectin was not associated with PWV. The results of multiple regression analysis indicated that SBP, DBP, and insulin resistance were independently correlated with PWV. Conclusions:Insulin resistance was independently associated with PWV in normoglycemic normotensive postmenopausal women.

Effects of growth hormone on insulin resistance and atherosclerotic risk factors in obese type 2 diabetic patients with poor glycaemic control

Objective  We aimed to evaluate the combined effects of GH treatment and diet restriction on lipolysis and anabolism, insulin resistance and atherosclerotic risk factors in obese patients with type 2 diabetes mellitus (T2DM).

Effect of pioglitazone on serum concentrations of osteoprotegerin in patients with type 2 diabetes mellitus

Objective Osteoprotegerin (OPG) acts as an important regulatory molecule in atherosclerosis. Recent studies report that thiazolidinediones could affect OPG expression. We investigated the relationship between OPG and inflammatory cytokines and the effects of pioglitazone (a PPARγ (PPARG) agonist) versus metformin on serum OPG levels in type 2 diabetic patients. Design and methods Sixty-seven type 2 diabetic patients were included in this study. They were assigned to pioglitazone (15 mg/day, n=34) or metformin (1000 mg/day, n=33) during 24 weeks. Various anthropometric and metabolic parameters, OPG, interleukin 6 (IL6), C-reactive protein (CRP), adiponectin, and homeostasis model assessment of insulin resistance (HOMA-IR), were measured at baseline and at 6 months of treatment. Results Serum OPG levels correlated significantly with fasting plasma glucose (FPG), HbAlc, HOMA-IR, IL6, and CRP, and inversely correlated with adiponectin after adjusting for age (P<0.05). Multiple regression analysis showed that FPG, HbAlc, and adioponectin were independently correlated with OPG level. After 6 months of treatment, the reduction in FPG and HbAlc levels was similar between the two groups. Pioglitazone treatment significantly increased body mass index (P<0.05) and waist circumference (P<0.05) and decreased triglycerides (P<0.05) and HOMA-IR (P<0.01). The adiponectin concentration was increased (P<0.05), and OPG and CRP levels were decreased in the pioglitazone group (P<0.05), but were unchanged in the metformin group. The changes in serum OPG in the pioglitazone group showed significant correlation with changes in FPG, HbAlc, and adiponectin. Conclusions In type 2 diabetic patients, pioglitazone decreases OPG levels, and this decrease in OPG levels might be associated with the increase in adiponectin.

Usefulness of brachial-ankle pulse wave velocity as a predictive marker of multiple coronary artery occlusive disease in Korean type 2 diabetes patients

Multiple coronary artery occlusive disease (multiple CAOD) is the most fatal and frequently observed coronary artery disease in type 2 diabetes patients, but no simple, non-invasive screening tool is available yet. The aim of this study is to evaluate the arterial stiffness in type 2 diabetes patients using brachial-ankle pulse wave velocity (baPWV), to demonstrate the correlation between arterial stiffness and multiple CAOD, and to suggest the cutoff point of baPWV for predicting multiple CAOD in Korean type 2 diabetes patients. One hundred and eighty-one diabetes and 262 non-diabetes patients were enrolled in the study. Routine anthropometric and serologic data were collected. baPWV was measured the day before coronary angiography, and the severity of CAOD was assessed with Gensini score after angiography. baPWV and Gensini score were significantly increased in diabetes patients and Gensini score had a positive correlation with baPWV. Subjects in the highest tertile of baPWV showed odds ratio of 3.06 for multiple CAOD compared to the lowest tertile. In ROC curve, baPWV at 1635 cm/s showed 73% sensitivity and 75% specificity with AUC 0.76 in diabetes patients in detecting multiple CAOD. Therefore, baPWV may be utilized a screening tool for predicting multiple CAOD, especially in type 2 diabetes patients.

The effects of aerobic exercise training on serum osteocalcin, adipocytokines and insulin resistance on obese young males

Osteocalcin has been proposed to be a novel link between bone and energy metabolism. Previous studies showed its relations to exercise, body fat and glucose metabolism, but their interrelationship remains inconslusive. We evaluated the changes in osteocalcin level following 8‐week exercise programme and assessed how they are related to concomitant changes in body fat composition, insulin resistance and various adipocytokines in a single centre, randomized and prospective design.

The activation of NF-κB and AP-1 in peripheral blood mononuclear cells isolated from patients with diabetic nephropathy

We evaluated the role of oxidative stress in diabetic nephropathy by measuring intracellular reactive oxygen species (ROS) and redox-sensitive transcription factors in isolated peripheral mononuclear cells (PBMC) in 66 diabetic patients with or without diabetic nephropathy (Groups III and II, respectively) and 49 normal controls (Group I). Stimulated ROS was significantly higher in Group III compared to Group II (increment of H(2)O(2)-induced ROS production: 21.8+/-2.2% vs. 11.1+/-2.0%; increment of PMA-induced ROS production 23.5+/-4.5% vs. 21.6+/-2.2%; both respectively), and the activity of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1), but not specificity protein 1 (Sp1) was significantly higher in Group III than in Group II (2.53-fold vs. 2.0-fold vs. 1.43-fold, respectively). Both PBMC- and urinary TGF-beta1 levels were higher in Group III than Group II (3.23+/-0.39 ng/g vs. 1.99+/-0.68 ng/g in PBMCs, 16.88+/-6.84 (ng/g Cr) vs. 5.61+/-1.57 (ng/g Cr) in urine, both respectively), and they correlated with the activity of NF-kappaB and AP-1 and 24-h urine albumin excretion (UAE). Increased intracellular ROS generation in PBMCs of diabetic patients is involved in the pathogenesis of diabetic nephropathy via activation NF-kappaB and AP-1 and an increased expression of TGF-beta1.

The humoral immune response to the inactivated influenza A (H1N1) 2009 monovalent vaccine in patients with Type 2 diabetes mellitus in Korea.

Diabet. Med. 28, 815–817 (2011)

Relationship of low-density lipoprotein (LDL) particle size to thyroid function status in Koreans.

Objective  Dyslipidaemia is a well‐known manifestation of thyroid dysfunction. Recently, small low‐density lipoprotein (LDL) particle size has been linked with development of cardiovascular disease. To better understand the effects of thyroid dysfunction on the development of cardiovascular disease, we examined LDL particle size and lipid profiles in subjects with different thyroid function.

Does birthweight predict adolescent adiponectin levels

Objective Low birthweight is associated with insulin resistance later in life, and adiponectin is known to play an important role in insulin resistance. We have investigated whether birthweight has a relationship with adiponectin levels in adolescence.