Clinical Characteristics and Prevalence of Comorbidities according to Metformin Use in Korean Patients with Type 2 Diabetes.

METHODS: This cross-sectional study based on the Korean National Diabetes Program 2 registry used its baseline clinical data collected from seven participating university hospitals in Korea. Patients with no significant changes in their oral hypoglycemic agents and no diabetes-related complications within the year prior to participation were enrolled. Patients' clinical characteristics according to metformin use were analyzed. RESULTS: Among 858 subjects included in the analyses, 706 were metformin users and 152 were nonmetformin users. Metformin users were significantly younger and had higher and glycated hemoglobin with significantly lower rates of accompanying microvascular complications such as retinopathy, cataracts, overt proteinuria, renal insufficiency, and peripheral neuropathy than nonusers. Meanwhile, there was a significantly lower prevalence of malignancy and depression among metformin users. These associations remained significant in multivariate analyses. The prevalence rate of macrovascular complications was not significantly different between the two groups. CONCLUSIONS: There were significant differences with respect to clinical characteristics and comorbidity prevalence according to metformin use among Korean type 2 diabetes patients. Long-term follow-up of these patients is necessary to observe how this difference will affect clinical outcomes for these patients.

Pharmacokinetics and Safety of Two Voriconazole Formulations after Intravenous Infusion in Healthy Korean Volunteers.

BACKGROUND: Voriconazole, a triazole antifungal agent exhibits broad-spectrum antifungal activity. It is used to treat severe, invasive fungal infections, including invasive aspergillosis and candidemia. The aim of this study was to assess the pharmacokinetic equivalence of a test formulation (Vorico® Injection) and reference formulation (Vfend® IV) of voriconazole. MATERIALS AND METHODS: This was a randomized, open-label, single-dose, three-group, two-treatment, two-sequence, two-period, crossover phase I trial with 7-day washout periods (ClinicalTrials.gov identifier NCT02631954). Twenty-four healthy Korean male subjects were recruited. In each group, eight subjects were randomized in a 1:1 manner to receive a single dose of 200 mg test or reference formulation intravenously over 1.5 h. Blood samples were collected over 24 h post-dose, and plasma drug concentrations were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined using a non-compartmental analysis, and safety was evaluated. RESULTS: Twenty-three subjects completed the study. The geometric mean ratio (90% confidence interval) of the test formulation to reference formulation was 0.9570 (0.8178 - 1.1199) for the maximum plasma concentration (Cmax) and 1.0720 (1.0262 - 1.1198) for the area under the concentration-time curve from dosing to the last quantifiable concentration (AUClast). The mean plasma concentration-time profiles, pharmacokinetic parameters, and safety were comparable between the two formulations. CONCLUSION: Equivalent pharmacokinetic characteristics that satisfied the criteria of bioequivalence and similar safety profiles were observed for both test and reference formulations of voriconazole.

A Randomized, Double-Blind Trial Comparing the Pharmacokinetics of CT-P16, a Candidate Bevacizumab Biosimilar, with its Reference Product in Healthy Adult Males.

BACKGROUND: CT-P16 is a candidate biosimilar of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor that is used in the treatment of a range of advanced solid cancers. OBJECTIVE: The objective of this study was to demonstrate the pharmacokinetic equivalence of CT-P16 and European Union (EU)-approved bevacizumab (EU-bevacizumab) and US-licensed bevacizumab (US-bevacizumab) reference products. METHODS: In this double-blind, parallel-group phase I trial (ClinicalTrials.gov identifier NCT03247673), healthy adult males were randomized (1:1:1) to receive a single dose of CT-P16 5 mg/kg, EU-bevacizumab 5 mg/kg, or US-bevacizumab 5 mg/kg. Primary study endpoints were area under the concentration-time curve (AUC) from time zero to infinity (AUC∞), AUC from time zero to the last quantifiable concentration (AUClast), and maximum serum concentration (Cmax). Pharmacokinetic equivalence was shown if the 90% confidence intervals (CIs) of the geometric mean (GM) ratios of the AUC∞, AUClast, and Cmax were within the predefined bioequivalence margin of 80-125%. Safety and immunogenicity were also evaluated. RESULTS: A total of 144 subjects were randomized: 47 to CT-P16, 49 to EU-bevacizumab, and 48 to US-bevacizumab. The 90% CIs for the GM ratios of AUC∞, AUClast, and Cmax for CT-P16/EU-bevacizumab, CT-P16/US-bevacizumab, and EU-bevacizumab/US-bevacizumab comparisons were all within the bioequivalence margin. Mean serum concentration-time profiles, secondary pharmacokinetic parameters, and safety and immunogenicity profiles were comparable across all three treatment groups. CONCLUSION: CT-P16 demonstrated pharmacokinetic equivalence to EU-bevacizumab and US-bevacizumab. Safety and immunogenicity profiles were similar for CT-P16, EU-bevacizumab, and US-bevacizumab. These data support the further clinical evaluation of CT-P16 as a bevacizumab biosimilar. CLINICAL TRIALS REGISTRATION: NCT03247673.

Importance of family history of diabetes in computing a diabetes risk score in Korean prediabetic population.

Prediabetic subjects represent a vulnerable population, requiring special care to reduce the risk of diabetes onset. We developed and validated a diabetes risk score for prediabetic subjects using the Korea National Diabetes Program (KNDP) cohort. Subjects included in the multicenter and prospective cohort (n = 1162) had high diabetes risk at baseline (2005) and were followed until 2012. Survival analysis was performed to analyze the prospective cohort over time, and the bootstrap method was used to validate our model. We confirmed our findings in an external cohort. A diabetes risk score was calculated and the cut-off defined using a receiver operating characteristic curve. Age, body mass index, total cholesterol, and family history of diabetes were associated with diabetes. The model performed well after correction for optimism (Cadj = 0.735). A risk score was defined with a cut-off of ≥5 that maximized sensitivity (72%) and specificity (62%), with an area under the curve of 0.73. Prediabetic subjects with a family history of diabetes had a higher probability of diabetes (risk score = 5) irrespective of other variables; this result was confirmed in the external cohort. Hence, prediabetic subjects with a family history of diabetes have a higher probability of developing diabetes, regardless of other clinical factors.

Impact of Socioeconomic Status on Health Behaviors, Metabolic Control, and Chronic Complications in Type 2 Diabetes Mellitus.

BACKGROUND: The aim of the study was to assess the impact of socioeconomic status (SES) on health behaviors, metabolic control, and chronic complications in people with type 2 diabetes mellitus (T2DM) from South Korea, a country with universal health insurance coverage and that has experienced rapid economic and social transition. METHODS: A total of 3,294 Korean men and women with T2DM aged 30 to 65 years, participating in the Korean National Diabetes Program (KNDP) cohort who reported their SES and had baseline clinical evaluation were included in the current cross-sectional analysis. SES included the level of education and monthly household income. RESULTS: Lower education level and lower income level were closely related, and both were associated with older age in men and women. Women and men with lower income and education level had higher carbohydrate and lower fat intake. After adjustment for possible confounding factors, higher education in men significantly lowered the odds of having uncontrolled hyperglycemia (glycosylated hemoglobin ≥7.5%) (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.43 to 0.91 for highest education; P(trend)=0.048), while higher household income in men significantly lowered the odds of having diabetic retinopathy (OR, 0.59; 95% CI, 0.37 to 0.95 for highest income level; P(trend)=0.048). In women, lower income was associated with a higher stress level. CONCLUSION: Men with lower SES had higher odds of having diabetic retinopathy and uncontrolled hyperglycemia, showing the need to improve care targeted to this population.

Metformin reduces the risk of cancer in patients with type 2 diabetes: An analysis based on the Korean National Diabetes Program Cohort.

The epidemiological literature suggests that insulin resistance, hyperinsulinemia, and increased levels of insulin-like growth factors place patients with type 2 diabetes mellitus (T2DM) at greater risk of cancer. The association between cancer incidence and the use of antidiabetic medications in patients with T2DM has been recently examined. There have been conflicting reports regarding an association between metformin and cancer risk. The aim of this study was to investigate the relationship between metformin use and the incidence of cancer in Koreans with T2DM.Data from The Korean National Diabetes Program (KNDP, 2006-2014), a nationwide, large-scale, prospective, multicenter cohort study in Korea, were used to study patients with T2DM. Patients ≥30 years old whose complete medical records were available were included in this study. Patients with a history of any cancer on KNDP registration or those who had been diagnosed with any type of cancer within 1 year of metformin use were excluded. Survival curves with respect to the incidence of cancer were plotted using the Kaplan-Meier method. Hazard ratios and 95% confidence intervals for cancer were estimated in a Cox proportional hazards regression analysis.During a mean 5.8 years of follow-up, 164 of the 1918 study patients (335 metformin nonusers and 1583 metformin users) developed cancer. The incidence per 1000 person-years was 21.8 in metformin nonusers and 13.2 in metformin users. Metformin users had a reduced risk of cancer, even after adjustment for demographic characteristics, metabolic parameters, diabetic complications, and other antidiabetic medications (hazard ratio 0.513, 95% confidence interval 0.318-0.826, P = .0060). Subgroup analysis of metformin users showed a reduced risk of cancer in males, patients < 65 years of age, patients with a T2DM duration < 5 years, nonobese patients, nonsmokers, and good glycemic control group.This large-scale, prospective, multicenter cohort study demonstrated an association between metformin use and reduced cancer risk in patients with T2DM.

Asymmetric dimethylarginine (ADMA) is identified as a potential biomarker of insulin resistance in skeletal muscle.

To unravel metabolic determinats of insulin resistance, we performed a targeted metabolomics analysis in Korean Children-Adolescent Cohort Study (KoCAS, n = 430). Sixty-seven metabolites were associated with insulin resistance in adolescents and the association also found in an adult population (KoGES, n = 2,485). Functional interactions of metabolites with gene/proteins using biological pathway with insulin resistance were not identified biological significance and regulatory effects of asymmetric dimethylarginine (ADMA). However, ADMA showed a higher association with adolescent obesity (P < 0.001) and adult diabetes (P = 0.007) and decreased after obesity intervention program. Functional studies in cellular and mouse models demonstrated that an accumulation of ADMA is associated with the regulation of obesity-induced insulin resistance in skeletal muscle. ADMA treatment inhibited dimethylarginine-dimethylaminohydrolase (DDAH) activity and mRNA expression in insulin resistance muscle cell. Moreover, the treatment led to decrease of phosphorylation of insulin receptor (IR), AKT, and GLUT4 but increase of protein-tyrosine phosphatase 1B (PTP1B). Accordingly, increased ADMA significantly inhibited glucose uptake in myotube cell. We suggest that accumulation of ADMA is associated with modulation of insulin signaling and insulin resistance. ADMA might expand the possibilities of new therapeutic target for functional and clinical implications in the control of energy and metabolic homeostasis in humans.

Long-term effects on glycaemic control and ß-cell preservation of early intensive treatment in patients with newly diagnosed type 2 diabetes: A multicentre randomized trial.

AIM: To determine the effects of early intensive glycaemic control with intensive insulin treatment (IIT) or initial combined oral antidiabetic drug (COAD) therapy on long-term glycaemic control and the preservation of ß-cell function in people with type 2 diabetes mellitus (T2DM). METHODS: Newly diagnosed drug-naïve patients with T2DM from 8 outpatient diabetes centres were randomized to receive either IIT (n = 50; glargine/glulisine) or COAD (n = 47; glimepiride/metformin) as intensive treatment until the termination criteria to ensure euglycaemia were met. After intensive treatment, the patients completed a follow-up period with either lifestyle modification (LSM) alone or rescue therapy to maintain target glycated haemoglobin levels of <7% (53 mmol/mol) up to week 104. The primary outcomes were analysed after excluding participants who were anti-glutamic acid decarboxylase autoantibody-positive. RESULTS: Both intensive treatment methods were effective for short-term glycaemic control, but improvements in the disposition index (DI) were significantly greater in the IIT group than in the COAD group (P = .021). During the follow-up period after intensive treatment, the two groups significantly differed in rescue method regarding the maintenance of comparable levels of glycaemic control (P = .010) and more participants who received IIT exhibited well-controlled glycaemia with LSM alone. Additionally, the IIT group maintained a higher DI than the COAD group during the follow-up period. Cox regression analysis showed that the IIT method was associated with a 52.5% lower risk of failing to maintain drug-free glycaemic remission compared with the COAD method (P = .015). CONCLUSIONS: The findings indicate that outpatient clinic-based IIT to ensure euglycaemia in newly diagnosed patients with T2DM might be an effective initial therapeutic option for improvements in ß-cell function and glycaemic control over the long term, without serious adverse events.

Effects of foot complications in patients with Type 2 diabetes mellitus on public healthcare: An analysis based on the Korea National Diabetes Program Cohort.

AIM: Diabetes mellitus (DM) patients are susceptible to foot injury or foot diseases such as diabetic foot and peripheral arterial disease. Although these conditions are considered important, few studies have investigated them in detail. Therefore, we investigated the epidemiology of diabetic foot complications (DFC) with respect to the effects on the public healthcare system. METHODS: We evaluated the incidence, clinical characteristics, health service utilization frequency and medical expenses of DFC in type 2 DM patients in the Korea National Diabetes Program (KNDP), the largest multi-center, prospective cohort in Korea (n=4405). To determine precise outcomes, we used national representative databases, including claims data from the Health Insurance Review & Assessment Service of Korea. RESULTS: During a median follow-up period of 3.30years, 528 patients (12.0%) were newly diagnosed with DFC at an incidence rate of 43.02 cases per 1000 person-years. The patients with DFC were significantly older than patients without DFC, but other clinical characteristics were similar between the two groups. The patients with DFC had more hospital visits (p<0.001), longer duration of hospitalization (p<0.001), and increased expenses (p<0.001) compared to patients without DFC. After multiple adjustments, the differences in number of hospital visits and medical expenses were consistent. In a before and after comparison within the DFC group, all three variables increased significantly after the onset of DFC (p<0.001). CONCLUSIONS: DFC were significantly associated with poor clinical outcomes and caused a substantial burden to the national healthcare system in Korea. Therefore, intervention to prevent DFC is important.

Hypoglycemia is associated with dementia in elderly patients with type 2 diabetes mellitus: An analysis based on the Korea National Diabetes Program Cohort.

AIM: Although hypoglycemia is associated with cognitive dysfunction, including dementia, in patients with type 2 diabetes mellitus (DM), the data are equivocal. The purpose of this study was to investigate the association between hypoglycemia, dementia, and other cognitive dysfunctions. METHODS: This was a prospective observational study based upon the Korea National Diabetes Program (KNDP). Among the 4540 participants in the KNDP cohort, individuals aged ⩾60years without any history of hypoglycemia or cognitive dysfunction (n=1957) were included. Nationally representative data from the Health Insurance Review and Assessment Service of Korea claim database were used to obtain a more precise determination of patient outcome. RESULTS: During a mean follow-up period of 3.4±0.9years, 118 subjects experienced hypoglycemia-related events. The incidence of dementia and cognitive dysfunction was 7.5 cases per 1000 person-years (PY) and 0.61 cases per 1000 PY, respectively. In the subjects who experienced hypoglycemic events (relative to those who did not), the incidence of dementia was significantly higher (P=0.0139), but the incidence of cognitive dysfunction was not (P=0.1106). Hypoglycemic events were associated with dementia (HR, 2.689; 95% CI, 1.080-6.694, P=0.0335) following multiple adjustments. There was also a significant linear trend toward an increased dementia risk commensurate with an increasing number of hypoglycemic events (P=0.0286). CONCLUSIONS: Hypoglycemia is significantly associated with the risk of dementia in Korean type 2 DM patients aged ⩾60years.

Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin-Angiotensin System Blockade: A 16-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To determine the effect of probucol on urine albumin excretion in type 2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. APPROACH AND RESULTS: This was a 16-week, phase II, randomized, placebo-controlled, parallel-group study in type 2 diabetes mellitus patients with a urinary albumin/creatinine ratio of ≥300 mg/g using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, conducted in 17 tertiary referral hospitals. Eligible patients were randomized to probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in a ratio of 1:1:1 after block randomization procedures, keeping the treatment assignment blinded to the investigators, patients, and study assistants. The primary end point was change in the geometric mean of urinary albumin/creatinine ratio from baseline to week 16 (ClinicalTrials.gov identifier NCT01726816). The study was started on November 8, 2012, and completed on March 24, 2014. The least squares mean change±SE from baseline in urinary albumin/creatinine ratio at week 16 was -7.2±639.5 mg/g in the probucol 250 mg/d group (n=43; P=0.2077 versus placebo group), 9.3±587.4 mg/g in the probucol 500 mg/d group (n=40; P=0.1975 versus placebo group), and 259.0±969.1 mg/g in the placebo group (n=41). Although the majority of subjects were on statins, probucol treatment significantly lowered total cholesterol and low-density lipoprotein cholesterol levels. QT prolongation occurred in one and two subjects in control and probucol 250 mg/d groups, respectively. CONCLUSIONS: Four months of probucol up to 500 mg/d failed to reduce urinary albumin excretion.

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 (ß = 0.001, P < 0.001), serum triglyceride (ß = 0.001, P < 0.001), CCr (ß = -0.003, P = 0.001), hsCRP (ß = 0.157, P = 0.001), fibrinogen (ß = 0.001, P < 0.001) and BMI (ß = 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.

Hypoglycemia and Medical Expenses in Patients with Type 2 Diabetes Mellitus: An Analysis Based on the Korea National Diabetes Program Cohort.

BACKGROUND AND AIMS: Hypoglycemia is one of the most important adverse events in individuals with type 2 diabetes mellitus (T2DM). However, hypoglycemia-related events are usually overlooked and have been documented less in clinical practice. MATERIALS AND METHODS: We evaluated the incidence, clinical characteristics, and medical expenses of hypoglycemia related events in T2DM patients based on the Korea National Diabetes Program (KNDP), which is the largest multi-center, prospective cohort in Korea (n = 4,350). For accurate outcomes, the KNDP data were merged with claims data from the Health Insurance Review and Assessment Service (HIRA) of Korea. RESULTS: During a median follow-up period of 3.23 years (95% CI: 3.14, 3.19), 88 subjects (2.02%) were newly diagnosed with hypoglycemia, and the incidence of hypoglycemia was 6.44 cases per 1,000 person-years (PY). Individuals with hypoglycemia were significantly older (59.7±10.7 vs. 53.3±10.4 years, p < 0.001), had more hospital visits (121.94±126.88 days/PY, p < 0.001), had a longer hospital stays (16.13±29.21 days/PY, p < 0.001), and incurred greater medical costs ($2,447.56±4,056.38 vs. $1,336.37±3,403.39 /PY, p < 0.001) than subjects without hypoglycemia. CONCLUSION: Hypoglycemia-related events were infrequently identified among the medical records of T2DM subjects. However, they were associated significantly with poor clinical outcomes, and thus, hypoglycemia could have a substantial burden on the Korean national healthcare system.

Direct injection LC-MS/MS method for the determination of teicoplanin in human plasma.

A direct injection-based, simple, accurate, and robust LC-MS/MS method was developed and validated for the determination of teicoplanin in human plasma. Patient plasma samples were diluted in an aqueous buffer prior to injection into the LC-MS/MS system. Chromatographic separation was achieved using a Cadenza HS-C18 column and a gradient mixture of acetonitrile-water (both containing 0.1% formic acid) as the mobile phase at a flow rate of 0.5mL/min. The analytes were detected in multiple reaction monitoring mode with positive ion electrospray ionization. The concentration of teicoplanin was determined as the sum of six components (A3-1, A2-1, A2-2, A2-3, A2-4, and A2-5). The calibration curve was linear over a concentration range of 1-50mg/L, which covered the clinically accepted trough and therapeutic plasma levels. The intra- and inter-day precision and accuracy values were both less than 15%. This validated method was successfully applied to therapeutic drug monitoring of teicoplanin in routine clinical practice. Thus, we expect it to be useful for the determination of teicoplanin concentration in human plasma.

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.

Glucosamine enhances body weight gain and reduces insulin response in mice fed chow diet but mitigates obesity, insulin resistance and impaired glucose tolerance in mice high-fat diet.

OBJECTIVE: This study investigated the potential of glucosamine (GlcN) to affect body weight gain and insulin sensitivity in mice normal and at risk for developing diabetes. METHODS: Male C57BL/6J mice were fed either chow diet (CD) or a high fat diet (HFD) and the half of mice from CD and HFD provided with a solution of 10% (w/v) GlcN. Total cholesterol and nonesterified free fatty acid levels were determined. Glucose tolerance test and insulin tolerance test were performed. HepG2 human hepatoma cells or differentiated 3T3-L1 adipocytes were stimulated with insulin under normal (5 mM) or high glucose (25 mM) conditions. Effect of GlcN on 2-deoxyglucose (2-DG) uptake was determined. JNK and Akt phosphorylation and nucleocytoplasmic protein O-GlcNAcylation were assayed by Western blotting. RESULTS: GlcN administration stimulated body weight gain (6.58±0.82 g vs. 11.1±0.42 g), increased white adipose tissue fat mass (percentage of bodyweight, 3.7±0.32 g vs. 5.61±0.34 g), and impaired the insulin response in livers of mice fed CD. However, GlcN treatment in mice fed HFD led to reduction of body weight gain (18.02±0.66 g vs. 16.22±0.96 g) and liver weight (2.27±0.1 vs. 1.85±0.12 g). Furthermore, obesity-induced insulin resistance and impaired Akt insulin signaling in the liver were alleviated by GlcN administration. GlcN inhibited the insulin response under low (5 mM) glucose conditions, whereas it restored the insulin response for Akt phosphorylation under high (25 mM) glucose conditions in HepG2 and 3T3-L1 cells. Uptake of 2-DG increased upon GlcN treatment under 5 mM glucose compared to control, whereas insulin-stimulated 2-DG uptake decreased under 5 mM and increased under 25 mM glucose in differentiated 3T3-L1 cells. CONCLUSION: Our results show that GlcN increased body weight gain and reduced the insulin response for glucose maintenance when fed to normal CD mice, whereas it alleviated body weight gain and insulin resistance in HFD mice. Therefore, the current data support the integrative function of the HBP reflecting the nutrient status of lipids or glucose and further implicate the importance of the pathway in insulin signaling for the regulation of metabolism.

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.

BACKGROUND: The 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. METHODS: The 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. RESULTS: For 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. CONCLUSIONS: The 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.

Serum magnesium level is associated with type 2 diabetes in women with a history of gestational diabetes mellitus: the Korea National Diabetes Program study.

Gestational diabetes mellitus (GDM) is a strong predictor of postpartum prediabetes and transition to overt type 2 diabetes (T2DM). Although many reports indicate that low magnesium is correlated with deteriorated glucose tolerance, the association between postpartum serum magnesium level and the risk for T2DM in women with a history of GDM has not been evaluated. We analyzed postpartum serum magnesium levels and development of prediabetes and T2DM in women with prior GDM according to American Diabetes Association (ADA) criteria using the Korean National Diabetes Program (KNDP) GDM cohort. During a mean follow-up of 15.6 ± 2.0 months after screening, 116 women were divided into three groups according to glucose tolerance status. Ultimately, eight patients (6.9%) were diagnosed with T2DM, 59 patients (50.9%) with prediabetes, and 49 patients (42.2%) with normal glucose tolerance (NGT) after follow-up. The T2DM group had the lowest serum magnesium level (0.65 [0.63-0.68] mM/L) in the postpartum period, but there was no significant difference between the prediabetes group (0.70 [0.65-0.70] mM/L) and the NGT group (0.70 [0.65-0.70] mM/L) (P=0.073) Multiple logistic regression analysis showed that postpartum HOMA-IR was a significant predictor of both prediabetes and T2DM. Moreover, we found that postpartum serum magnesium level was also a possible predictor for T2DM development. Serum magnesium level in the postpartum period may be a possible predictor for T2DM development in women with a history of GDM.

Measurement equivalence of touch-screen computerized and paper-based diabetes-specific quality-of-life questionnaires.

Current advances in technology have enabled the development of a computer-based questionnaire that provides advantages over the paper-based mode of administration, such as automatic data entry, storage and calculations. However, before implementing a computer-based questionnaire, its equivalence with the original paper-based questionnaire must first be demonstrated. The purpose of this study was to evaluate the measurement equivalence of the computerized Diabetes-Specific Quality-of-Life questionnaire (cD-QOL) with its original paper-based counterpart. A two-period crossover design was used in this study. The measurement equivalence was evaluated using quadratic weighted kappa coefficients, intraclass correlations and Cronbach's alpha comparisons. The cD-QOL was equivalent to its original paper-based counterpart. Participants preferred the cD-QOL over the paper-based questionnaire and reported that it was easy to use.

Implication of circulating omentin-1 level on the arterial stiffening in type 2 diabetes mellitus.

Omentin-1 is an adipokine implicated in diabetes, inflammation, and cardiovascular disease. However, no prospective studies have examined the impact of circulating omentin-1 levels on arterial stiffening in patients with type 2 diabetes mellitus. For the purpose of this study, we recruited 120 patients with type 2 diabetes mellitus and measured serum omentin-1, adiponectin, and high-sensitivity C-reactive protein levels as well as other cardiovascular risk factors. Arterial stiffness was assessed by brachial ankle pulse wave velocity (baPWV). An increase in the level of circulating omentin-1 over a period of 1 year was positively correlated with changes in levels of HbA1c and serum adiponectin as well as baPWV. Subjects with higher baseline serum omentin-1 levels tended to have a reduced arterial stiffness after 1 year (P for linear trend = 0.03). In the group with increased baPWV after 1 year, the magnitude of increase of circulating omentin-1 levels was significantly higher than in the group with a lower baPWV after 1 year (134.3 [16.6, 277.1] ng/mL vs. 15.9 [-67.6, 145.7] ng/mL, P < 0.01). Multiple stepwise logistic regression analysis revealed that an increase in systolic blood pressure and an increase in serum omentin-1 level were independently correlated with arterial stiffening, even after adjusting for other cardiovascular risk factors and medication history. Baseline serum omentin-1 levels can predict arterial stiffness changes occurring within a year. Furthermore, changes in serum omentin-1 levels after a year can function as independent markers of arterial stiffening in patients with type 2 diabetes mellitus.