Yong Seong Kim

Effect of lifestyle modification on serum chemerin concentration and its association with insulin sensitivity in overweight and obese adults with type 2 diabetes

Chemerin, a recently identified adipokine, has been linked to adiposity, insulin resistance, metabolic syndrome risk factors and inflammation. Here, we evaluated whether a 12‐week lifestyle intervention in overweight and obese adults with type 2 diabetes could significantly affect the average blood glucose and serum chemerin levels over time.

Development and Validation of a Semi-Quantitative Food Frequency Questionnaire to Assess Diets of Korean Type 2 Diabetic Patients

Background Our aim was to assess the validity of a semi-quantitative food frequency questionnaire (FFQ) by comparison with the 3-day diet record (DR) in patients with type 2 diabetes. Methods Eighty five type 2 diabetic patients (aged 33 to 70 years) from the Korean National Diabetes Program (KNDP) completed 3-day DR and FFQ. The FFQ was designed to reflect the eating pattern of Korean type 2 diabetic patients, and was based on the 2003 Korean National Health and Nutrition Examination Survey. The FFQ consists of 85 food items and 12 food groups. The validity of FFQ was assessed by comparison with the 3-day DR. Results The mean age was 49 ± 10 years. Clinical characteristic including body weight, diabetic duration, and HbA1c were not different from the total cohort subjects (n = 1,478). There were no significant differences in the mean intake of protein, fat and calcium estimated by the FFQ and the 3-day DR. Energy and carbohydrate estimated by the FFQ were higher than those estimated by the 3-day DR. The correlation coefficient was highest for energy (r = 0.740; P < 0.00) and lowest for iron (r = 0.269; P < 0.05). The Kappa values for energy, carbohydrate, protein, fat and calcium were 0.54, 0.37, 0.36, 0.46, and 0.19, respectively. Conclusion The FFQ is a reasonable instrument for assessing the intake of most macronutrients in Korean type 2 diabetes, although careful consideration is required for the food groups and nutrients for which the FFQ had low validity.

Metformin-Associated Lactic Acidosis: Predisposing Factors and Outcome

Background Metformin is considered the first choice oral treatment for type 2 diabetes patients in the absence of contraindications. Rarely, life-threatening complications associated with metformin treatment are seen in some patients with underlying diseases. The aim of this study was to further investigate the clinical profiles and risk factors for metformin-associated lactic acidosis (MALA) and the treatment modalities according to survival. Methods To identify MALA, we performed a retrospective study in seven diabetic patients who were taking metformin and had been diagnosed with lactic acidosis at Inha University Hospital between 1995 and 2012. For each patient, we recorded the age, sex, daily metformin dosage, laboratory test results, admission diagnosis, and risk factors. Also, concurrent conditions, treatment modalities, and outcomes were evaluated. Results Six patients had risk factors for lactic acidosis before admission. All patients had renal impairment on admission as a precipitating risk factor. Five patients survived and two patients died despite early renal replacement therapy. Older patients tended to have a poorer prognosis. Conclusion Renal function must be monitored in elderly type 2 diabetes mellitus patients with underlying diseases and conditions causing renal impairment who begin metformin treatment. Accurate recognition of MALA and initiation of renal replacement are essential for treatment.

Safety and Efficacy of Modern Insulin Analogues

Background A1chieve® was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. Methods Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints. Results Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7±15.9 to 72.5±13.5) while the mean body weight was slightly increased (0.6±3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%±2.2%, 2.5±4.7 mmol/L, and 4.0±6.4 mmol/L, respectively. Conclusion The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.

Change of Bone Mineral Density and Biochemical Markers of Bone Turnover in Patients on Suppressive Levothyroxine Therapy for Differentiated Thyroid Carcinoma

Untreated hyperthyroidism and high-dose thyroid hormone are associated with osteoporosis, and increased bone mineral density (BMD) has been demonstrated in postmenopausal females with hypoparathyroidism. Studies on the effect of suppressive levothyroxine (LT4) therapy on BMD and bone metabolism after total thyroidectomy in patients with differentiated thyroid carcinoma have presented conflicting results, and few studies in relation to the status of hypoparathyroidism have been studied. One hundred postmenopausal women and 24 premenopausal women on LT4 suppression therapy were included in this study. BMD of lumbar spine and femur and bone turnover markers were measured at the baseline and during the follow-up period up to 18 months using dual energy X-ray absorptiometry. Biochemical marker of bone resorption was measured by urine deoxypyridinoline and bone formation by serum osteocalcin. The age ranged from 36 to 64 years old. Thyroid stimulating hormone (TSH) was suppressed during the study. The results showed that BMD of femur and lumbar spine were not significantly changed in both pre- and postmenopausal women except femur neck in postmenopausal women without hypoparathyroidism. Patients with hypoparathyroidism had higher BMD gain than those without hypoparathyroidism in total hip (1.25 vs. -1.18%, P=0.015). Biochemical markers of bone turnover, serum osteocalcin, and urine deoxypyridinoline did not show significant change. In conclusion, patients with well differentiated thyroid carcinoma are not at a great risk of bone loss after LT4 suppressive therapy. The state of hypoparathyroidism is associated with increased BMD, particularly in postmenopausal women.

Measurement of diabetes-related emotional distress using the Problem Areas in Diabetes scale: psychometric evaluations show that the short form is better than the full form

BackgroundThe Problem Areas in Diabetes (PAID) scale is widely used for measuring diabetes-related emotional distress. There has been debate over the last 2 decades about the underlying factorial-construct validity of the PAID, with one- to four-factor structures being reported. A short form of the PAID, which comprises five items (PAID-5), was recently developed using Western patients with type 2 diabetes. This study measured the psychometric properties of the full and short forms of the PAID in Korean patients with type 2 diabetes, with the aim of determining which form is preferable.MethodsThe PAID and PAID-5 were translated into Korean (K-PAID and K-PAID-5, respectively) using a forward-and-backward translation technique. The study participants were recruited from university hospitals. The factorial-construct, convergent, and known-groups validity, and internal-consistency and test-retest reliability of both the K-PAID and K-PAID-5 were evaluated.ResultsFor the K-PAID, confirmatory factor analysis revealed a marginal fit to the one-, two-, three-, and four-factor models. The three- and four-factor models of the K-PAID partially satisfied the internal-consistency and test-retest reliability, and convergent and known-groups validity. For the K-PAID-5, confirmatory factor analysis demonstrated an excellent fit to the one-factor model, with a Cronbach’s alpha of 0.87 and an intraclass correlation coefficient of 0.89. The K-PAID-5 satisfied the convergent validity, as evaluated using the Center for Epidemiologic Studies Depression Scale and hemoglobin A1c. Known-groups validity by gender was also satisfied.ConclusionsThe K-PAID-5 demonstrated excellent psychometric properties as a one-factor scale. The brevity of the K-PAID-5 represents a major advantage in a practical context in that it may impose a minimum burden upon patients with diabetes.

R1467H Variants of Rho Guanine Nucleotide Exchange Factor 11 (ARHGEF11) are Associated with Type 2 Diabetes Mellitus in Koreans

Background The human Rho guanine nucleotide exchange factor 11 (ARHGEF11) functions as an activator of Rho GTPases and is thought to influence insulin signaling. The R1467H variant of ARHGEF11 has been reported to be associated with susceptibility to type 2 diabetes mellitus (T2DM) in Western populations. Methods We investigated the effects of the R1467H variant on susceptibility to T2DM as well as related traits in a Korean population. We genotyped the R1467H (rs945508) of ARHGEF11 in 689 unrelated T2DM patients and 249 non-diabetic individuals and compared the clinical and biochemical characteristics according to different alleles. Results The H allele was significantly more frequent in T2DM cases than in controls (P = 0.037, 17.1% and 13.1%; respectively). H homozygocity was associated with a higher risk of T2DM compared to those with R/R or R/H genotype (odds ratio, 5.24; 95% confidence interval, 1.06 to 25.83; P = 0.042). The fasting plasma glucose, HbA1c, fasting insulin, HOMA2-IR and HOMA2-%β levels did not differ significantly between different genotypes. Conclusion Our study replicated associations of the ARHGEF11 polymorphism with increased risk of T2DM in a Korean population and thus supports previous data implicating a potential role of ARHGEF11 in the etiology of T2DM. Further studies revealing the underlying mechanism for this association are needed.

The effects of adiponectin and inflammatory cytokines on diabetic vascular complications in obese and non-obese patients with type 2 diabetes mellitus

AIMS To evaluate the associations between inflammatory cytokines and adiponectin and various vascular complications in type 2 diabetes mellitus (T2DM). METHODS A total of 761 patients with T2DM were divided into a non-obese group and an obese group to enable the effects of obesity and T2DM on vascular complications to be differentiated. The serum levels of circulating inflammatory cytokines, that is, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, total adiponectin, and high molecular weight (HMW) adiponectin were measured, and carotid intima media thickness (IMT), the presence of carotid plaque, and the severities of retinopathy and nephropathy, were assessed. RESULTS The obese group had significantly lower serum total and HMW adiponectin levels than the non-obese group. In the obese group, serum levels of total and HMW adiponectin, and TNF-α were significantly higher in patients with proliferative retinopathy than in those without retinopathy after adjusting for covariates. In the non-obese group, only IL-6 levels were significantly higher in patients with proliferative retinopathy than in those without. Serum levels of total and HMW adiponectin were significantly higher in patients with macroalbuminuria than in those with normoalbuminuria. No significant difference of three cytokines levels were observed depending on the carotid IMT or the presence of plaque. Logistic regression analysis revealed that serum total adiponectin (OR=1.209, P=0.038), diabetes duration (OR=1.230, P=0.014), and HbA1c (OR=2.359, P=0.006) were significantly associated with proliferative retinopathy in the obese group. CONCLUSION The study shows total adiponectin may influence proliferative retinopathy in obese patient with T2DM.

The Effect of Lowering the Threshold for Diagnosis of Impaired Fasting Glucose

Purpose The aim of this study was to evaluate the effect of lowering the fasting plasma glucose (FPG) criteria for impaired fasting glucose (IFG) on the prevalence of IFG and the risk for the development of diabetes associated with IFG in Koreans. Materials and Methods A total of 7,211 subjects who had normal glucose tolerance (NGT) or IFG were recruited. Subjects were evaluated at baseline and after two years follow up. Clinical data including total cholesterol, FPG and blood pressure were examined. Results Lowering the criteria for IFG from 6.1 mmol/L (110 mg/dL) to 5.6 mmol/L (100 mg/dL) increased the prevalence of IFG from 6.6% (494 subjects) to 24.4% (1829 subjects). After the 2 years follow up period, 91 subjects (1.3%) developed diabetes. Twenty one (0.3%) subjects developed diabetes among 5,382 NGT subjects and 70 (3.8%) subjects developed diabetes among 1,829 IFG (5.6 - 7.0 mmol/L) subjects. Lowering the IFG threshold from 6.1 mmol/L to 5.6 mmol/L resulted in a 18.4% decrease in specificity and 23.9% increase in sensitivity for predicting diabetes. The baseline FPG for predicting the development of diabetes after 2 years at a point on the receiver operating characteristic curve that was closest to the ideal 100% sensitivity and 100% specificity was 5.7 mmol/L (103 mg/dL). Conclusion Lowering the FPG criterion of IFG should have benefits in predicting new onset type 2 diabetes mellitus in Koreans. The economic and health benefits of applying the new IFG criteria should be evaluated in future studies.

Serum Chemerin Levels Are Associated with Abdominal Visceral Fat in Type 2 Diabetes.

Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.