Lysophosphatidylserine receptor P2Y10: A G protein-coupled receptor that mediates eosinophil degranulation.

BACKGROUND: P2Y10, along with GPR34 and GPR174, is a G protein-coupled receptor that is activated by an endogenous lipid mediator lysophosphatidylserine (LysoPS). Its expression pattern and its function are completely unknown. We have previously shown that P2Y10 is one of the highly up-regulated genes at the late differentiation stage during in vitro eosinophilopoiesis. OBJECTIVE: We explored the expression and functions of P2Y10 in human cord blood (CB)-derived and peripheral blood (PB) eosinophils. METHODS: Real-time PCR, FACS, Western blot, ELISA, and chemotaxis assays were performed to determine the expression and function of P2Y10. RESULTS: As CB cells differentiated towards eosinophils, P2Y10 mRNA and protein were abundantly expressed. P2Y10 was the most highly expressed in the granulocytes from PB, to a lesser extent in monocytes, and least in lymphocytes. Further fractionation of granulocytes revealed that eosinophils express P2Y10 much more strongly than do neutrophils. PB eosinophils solely expressed P2Y10 among the three LysoPS receptors, while PB neutrophils expressed the three at comparable levels. LysoPS activated both CB and PB eosinophils to induce a robust ERK phosphorylation. Importantly, LysoPS was capable of triggering degranulation of ECP in PB eosinophils. This response was significantly reduced by pharmacological inhibitors of TNF-alpha-converting enzyme (TACE), epidermal growth factor receptor (EGFR), and ERK1/2, which were known to be required in P2Y10-mediated signalling pathways. However, LysoPS had no effect on chemotaxis, differentiation, or eosinophil survival. CONCLUSIONS AND CLINICAL RELEVANCE: LysoPS provokes eosinophil degranulation through P2Y10. Therefore, P2Y10 is a potential therapeutic target to control eosinophil-associated diseases.

Insulin degludec/insulin aspart once daily in Type 2 diabetes: a comparison of simple or stepwise titration algorithms (BOOST® : SIMPLE USE).

AIMS: To compare the efficacy and safety of two titration algorithms for insulin degludec/insulin aspart (IDegAsp) administered once daily with metformin in participants with insulin-naïve Type 2 diabetes mellitus. METHODS: This open-label, parallel-group, 26-week, multicentre, treat-to-target trial, randomly allocated participants (1:1) to two titration arms. The Simple algorithm titrated IDegAsp twice weekly based on a single pre-breakfast self-monitored plasma glucose (SMPG) measurement. The Stepwise algorithm titrated IDegAsp once weekly based on the lowest of three consecutive pre-breakfast SMPG measurements. In both groups, IDegAsp once daily was titrated to pre-breakfast plasma glucose values of 4.0-5.0 mmol/l. Primary endpoint was change from baseline in HbA1c (%) after 26 weeks. RESULTS: Change in HbA1c at Week 26 was IDegAspSimple -14.6 mmol/mol (-1.3%) (to 52.4 mmol/mol; 6.9%) and IDegAspStepwise -11.9 mmol/mol (-1.1%) (to 54.7 mmol/mol; 7.2%). The estimated between-group treatment difference was -1.97 mmol/mol [95% confidence interval (CI) -4.1, 0.2] (-0.2%, 95% CI -0.4, 0.02), confirming the non-inferiority of IDegAspSimple to IDegAspStepwise (non-inferiority limit of ≤ 0.4%). Mean reduction in fasting plasma glucose and 8-point SMPG profiles were similar between groups. Rates of confirmed hypoglycaemia were lower for IDegAspStepwise [2.1 per patient years of exposure (PYE)] vs. IDegAspSimple (3.3 PYE) (estimated rate ratio IDegAspSimple /IDegAspStepwise 1.8; 95% CI 1.1, 2.9). Nocturnal hypoglycaemia rates were similar between groups. No severe hypoglycaemic events were reported. CONCLUSIONS: In participants with insulin-naïve Type 2 diabetes mellitus, the IDegAspSimple titration algorithm improved HbA1c levels as effectively as a Stepwise titration algorithm. Hypoglycaemia rates were lower in the Stepwise arm.

Distal hyperintense vessel sign is associated with neurological deterioration in acute ischaemic stroke.

BACKGROUND AND PURPOSE: The aim was to evaluate the relationship between distal hyperintense vessel sign (HVS) and early neurological deterioration (END) in acute ischaemic stroke with large vessel steno-occlusion. METHODS: Acute ischaemic stroke patients with symptomatic severe steno-occlusion in the middle cerebral artery or internal carotid artery were recruited within 24 h from symptom onset. Stroke outcomes were evaluated using the National Institutes of Health Stroke Scale (NIHSS) score at the time of admission and at 72 h and 7 days. END was defined as an increment of ≥1 in the motor NIHSS score or ≥2 in the total NIHSS score. Distal HVS was defined as hyperintensity on fluid-attenuated inversion recovery image, located distal to the Sylvian fissure. The extent of distal HVS was divided into absent, subtle and prominent. RESULTS: Amongst a total of 325 participants, END was found in 103 (32%) patients. END was associated with age, atrial fibrillation, initial NIHSS score, initial infarct volume, severe leukoaraiosis, hemorrhagic infarction and distal HVS. In multivariate analysis, distal HVS remained an independent predictor of END [adjusted odds ratio (aOR) 2.86, 95% confidence interval (CI) 1.65-4.97, P < 0.001]. Initial infarct volume (aOR = 1.01, 95% CI 1.01-1.02, P < 0.001) and severe leukoaraiosis (aOR = 3.16, 95% CI 1.77-5.65, P < 0.001) were also associated with END, independently of distal HVS. In the analysis of the burden of distal HVS and stroke outcomes, prominent distal HVS was associated with stroke severity and infarct volume in a dose-response manner. CONCLUSIONS: Distal HVS is associated with END in acute ischaemic stroke patients with large vessel steno-occlusion.

Association of lipid parameters and insulin resistance with bone health in South Korean adolescents.

UNLABELLED: This study investigated the association between lipid profiles and insulin resistance and bone mineral content (BMC) in Korean adolescents and found that BMC was inversely associated with triglyceride (TG) and homeostasis model assessment of insulin resistance (HOMA-IR). This association did not differ according to obesity status in either boys or girls. INTRODUCTION: To prevent future osteoporosis, it is important to identify factors that affect bone health in adolescents as well as adults. This study aimed to examine the association between lipid profiles and insulin resistance and BMC in Korean adolescents. METHODS: Data from 706 boys and 621 girls, who participated in the Korea National Health and Nutrition Examination Survey from 2008 to 2011, were analyzed. Lipid profiles were measured, and HOMA-IR was calculated to assess insulin resistance. BMC was measured for the total femur, femur neck, and lumbar spine by using whole-body dual-energy X-ray absorptiometry (DXA). RESULTS: TG level and HOMA-IR were negatively correlated with BMC at all three sites in boys. In girls, TG level showed a negative correlation with BMC at the femur neck and lumbar spine, and HOMA-IR was negatively associated with BMC at the femur neck only. These inverse associations did not differ according to obesity status in either sex. Adjusted means of BMC at the three sites in boys tended to decrease in the higher tertile groups of TG and HOMA-IR, and the adjusted means of BMC for the total femur in girls tended to decrease in the higher tertile groups of TG and HOMA-IR. CONCLUSIONS: BMC was inversely associated with TG and HOMA-IR in Korean adolescents, and this association was more pronounced in boys. This association did not differ according to obesity status in either sex.

Diagnostic value of haemoglobin A1c in post-partum screening of women with gestational diabetes mellitus.

AIMS: The aim of this study was to evaluate whether women with gestational diabetes mellitus could be screened using HbA1c for glucose metabolism status at 6-12 weeks post-partum. METHODS: We enrolled 699 pregnant women diagnosed with gestational diabetes mellitus from October 2005 to December 2013. A 75-g oral glucose tolerance test (OGTT) and HbA1c measurement were performed at 6-12 weeks after delivery. RESULTS: The prevalence of overt diabetes and pre-diabetes were 5.2% (n = 36) and 49.1% (n = 343), respectively, when using the 75-g OGTT as the gold standard. HbA1c alone identified 2.9% (n = 20) as having overt diabetes and 32.2% (n = 225) as having pre-diabetes. When American Diabetes Association cut-offs were applied, the sensitivity and specificity for HbA1c to diagnose overt diabetes were 19.4% and 98.0%, respectively. Pre-diabetes, according to the HbA1c criterion, had 41.2% sensitivity and 72.2% specificity. The misclassifications identified 97 positive differences, 233 negative differences and 369 ties (P < 0.05). The area under the receiver operating characteristic curves for detecting diabetes and pre-diabetes were 0.615 [95% confidence interval (95% CI), 0.515 to 0.716] and 0.588 (95% CI, 0.545 to 0.630), respectively. CONCLUSIONS: HbA1c may not be sensitive enough for an accurate diagnosis, but it is highly specific for diagnosing overt diabetes at 6-12 weeks post-partum in women with previous gestational diabetes mellitus.

Efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus: a 24-week multicentre, randomized, double-blind, placebo-controlled phase III trial.

We assessed the 24-week efficacy and safety of teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, in Korean patients with type 2 diabetes mellitus (T2DM) that was inadequately controlled with diet and exercise. The present study was designed as a multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study. Patients (n = 142) were randomized 2 : 1 into two different treatment groups as follows: 99 received teneligliptin (20 mg) and 43 received placebo. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. Teneligliptin significantly reduced the HbA1c level from baseline compared with placebo after 24 weeks. At week 24, the differences between changes in HbA1c and fasting plasma glucose (FBG) in the teneligliptin and placebo groups were -0.94% [least-squares (LS) mean -1.22, -0.65] and -1.21 mmol/l (-1.72, -0.70), respectively (all p < 0.001). The incidence of hypoglycaemia and adverse events were not significantly different between the two groups. This phase III, randomized, placebo-controlled study provides evidence of the safety and efficacy of 24 weeks of treatment with teneligliptin as a monotherapy in Korean patients with T2DM.

Isolation and analysis of bioactive compounds in Capsicum peppers.

An overview of the state of the art in the extraction, isolation, and analytical determination of bioactive compounds in peppers of the genus Capsicum is presented. The review is structured by classes of phytochemicals. Both major and minor constituents of peppers are considered. Modern trends in analytical chemistry of nutrients in regard to pepper analysis with particular focus on chromatographic and related methods are discussed. Attention was paid to controversial questions of pepper analysis, including but not limited to problems of sample degradation and the completeness of extraction of target analytes. The rationale for choosing an optimal strategy of analysis is given.

Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group, active-controlled, phase III clinical trial with a 28-week extension.

We aimed to compare the efficacy and safety of lobeglitazone and pioglitazone as add-ons to metformin in patients with type 2 diabetes. Patients who were inadequately controlled by metformin were randomized and treated once daily with either lobeglitazone (0.5 mg, n = 128) or pioglitazone (15 mg, n = 125) for 24 weeks, with a 28-week extension trial of lobeglitazone treatment in patients who consented. The primary endpoint was the change in glycated haemoglobin (HbA1c) concentration from baseline to week 24. At week 24, the mean change from baseline in HbA1c was -0.74% for the lobeglitazone group and -0.74% for the pioglitazone group, with a mean difference of 0.01% [95% confidence interval (CI) of difference, -0.16 to 0.18]. The effects of lobeglitazone on lipid variables and the adverse events associated with lobeglitazone were similar to those observed with pioglitazone. Lobeglitazone was not inferior to pioglitazone as an add-on to metformin in terms of their efficacy and safety.

Anagliptin and sitagliptin as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, active-controlled, phase III clinical trial with a 28-week extension.

We conducted a 24-week, multicentre, double-blind, randomized study with a 28-week extension to compare the efficacy and safety of anagliptin and sitagliptin as an add-on to metformin in patients with type 2 diabetes. Patients inadequately controlled on metformin were randomized to either anagliptin (100 mg twice daily, n = 92) or sitagliptin (100 mg once daily, n = 88). The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24. The mean changes in HbA1c were -0.85 ± 0.70% (p < 0.0001) for anagliptin and -0.83 ± 0.61% (p < 0.0001) for sitagliptin, with a mean difference of -0.02% (95% confidence interval of difference, -0.22 to 0.18%). In both groups, the fasting proinsulin : insulin ratio significantly decreased from baseline, with improved insulin secretion. Safety profiles were similar in each group. In conclusion, the non-inferiority of the efficacy of anagliptin to sitagliptin as an add-on therapy was established with regard to efficacy and safety.

Esophageal mucosal mast cell infiltration and changes in segmental smooth muscle contraction in noncardiac chest pain.

Mast cells release potent mediators that alter enteric nerve and smooth muscle functions and may contribute to the pathogenesis of functional gastrointestinal disorders. The goal of this study was to determine if mucosal mast cell infiltration was associated with smooth muscle segmental changes in esophageal contraction. All patients with noncardiac chest pain (NCCP) were divided into two groups consisting of patients with non-erosive reflux disease or functional chest pain (FCP) according to the results of ambulatory 24 hours esophageal pH monitoring and high-resolution manometry. Pressure-volume (PV) was calculated by multiplying the length of the esophageal segment, duration of the contraction, and mean pressure over the entire space-time box (P mean). Quantification of mast cells was performed in five consecutive nonoverlapping immunostained sections. Spearman correlation analysis showed that the distal segment PV correlated with the mast cell count in all of the patients combined and in patients with FCP with correlation coefficients of 0.509 and 0.436, respectively (P = 0.004 and P = 0.042). Similar findings were observed for the segmental ratio of distal to proximal smooth muscle PV in all patients and in patients with FCP (correlation coefficients 0.566; P = 0.001 and correlation coefficients 0.525; P = 0.012, respectively). Mucosal mast cell infiltration was associated with distal esophageal contraction as a key pathophysiologic factor of NCCP.

Association of serum C1q/TNF-Related Protein-9 (CTRP9) concentration with visceral adiposity and metabolic syndrome in humans.

BACKGROUND: C1q/TNF-Related Protein (CTRP) family members are novel adipokines that have anti-inflammatory, immunomodulatory, glucose-regulating and vascular effects. However, the metabolic effects of CTRP9 remain unclear in humans. OBJECTIVES: The aims of this study were to investigate whether serum CTRP9 concentrations are associated with glucose tolerance, metabolic parameters and abdominal fat accumulation. In addition, the authors investigated whether the aforementioned effects of CTRP9 are independent of serum adiponectin levels. METHODS: A total of 221 subjects (140 men and 81 women), 25-72 years of age (mean age 46.0 years), were randomly selected from two different study populations. The normal glucose tolerance group (n=120) was selected from one study population and the prediabetes/type 2 diabetes group (n=101) was selected from the other study population. Serum CTRP9, total adiponectin concentrations and abdominal fat via computed tomography scan were measured in all subjects. RESULTS: Subjects in the lower serum CTRP9 tertile were older, had metabolically unhealthy profiles and had lower serum total adiponectin levels when compared with subjects in the middle or upper serum CTRP9 tertiles. In addition, serum CTRP9 concentration were inversely correlated with age, blood pressure, fasting glucose, homeostasis model assessment for insulin resistance, total cholesterol, triglyceride and low-density lipoprotein cholesterol levels (all P<0.01) and positively correlated with serum total adiponectin levels (P=0.03). In terms of abdominal fat accumulation, serum CTRP9 concentrations were inversely correlated with visceral fat amount (P<0.01), but no correlation was observed with subcutaneous fat amount. Finally, serum CTRP9 was inversely associated with the presence of metabolic syndrome, independent of age, sex, body mass index, smoking status, total cholesterol, visceral fat and serum total adiponectin concentrations (odds ratio per 1 s.d. 0.47; 95% confidence interval 0.32-0.70; P<0.01). CONCLUSIONS: Serum CTRP9 concentrations were positively associated with favorable glucose or metabolic phenotypes and absence of metabolic syndrome, independent of serum total adiponectin concentrations.

Atherogenic dyslipidaemic profiles associated with the development of Type 2 diabetes: a 3.1-year longitudinal study.

AIMS: While there is thought to be an association between glucose and lipid metabolism, it is largely unknown whether apolipoprotein B and non-high density lipoprotein (HDL) cholesterol are associated with the development of Type 2 diabetes. It is also unknown whether these atherogenic dyslipidaemic profiles have a stronger association with diabetes risk compared with conventional lipid measurements. METHODS: A total of 118 429 subjects without diabetes (70 980 men and 47 449 women), aged 17-90 years (mean age 39.6 years), were enrolled in this study and followed for a mean duration of 3.1 years. RESULTS: Apolipoprotein B and non-HDL cholesterol levels showed a strong association with the development of Type 2 diabetes compared with conventional lipid measurements and their ratios [hazard ratio per 1 sd; 1.39 (95% CI 1.37-1.42) and 1.38 (95% CI 1.35-1.40), respectively; both P < 0.001]. The Kaplan-Meier survival curve demonstrated that Type 2 diabetes developed more frequently as apolipoprotein B or non-HDL cholesterol levels increased across quartiles (both P < 0.001). In multivariate Cox regression analyses, both apolipoprotein B and non-HDL cholesterol were associated with the development of Type 2 diabetes, independent of other risk factor including age, sex, waist circumference, family history of diabetes, fasting serum glucose and insulin levels, HbA1c , systolic blood pressure and other conventional lipid measurements [hazard ratio per 1 sd; 1.14 (95% CI 1.11-1.18) and 1.13 (95% CI 1.10-1.16), respectively; both P < 0.001]. CONCLUSIONS: Atherogenic dyslipidaemia was more strongly associated with the development of Type 2 diabetes than conventional lipid measurements, and this effect was independent of other well-established risk factor for diabetes.

An epidemiological study of androgenic alopecia in 3114 Korean patients.

BACKGROUND: Androgenetic alopecia (AGA) is the most common type of hair loss, and is characterized by the transformation of terminal scalp hair into vellus hair. The epidemiology of AGA is not fully understood. A strong genetic basis has long been identified, although little is known of its nongenetic causes. AIM: To evaluate the association of AGA with a number of environmental factors, including smoking, drinking and sleeping habit. METHODS: In total, 3114 Korean individuals with AGA who attended any one of 17 dermatology clinics in 6 cities in South Korea between March 2011 and February 2012 were enrolled in the study. Epidemiologic a data were collected using a standard questionnaire. RESULTS: No association was seen between eating or sleeping habits and severity of hair loss. However, drinking and smoking were associated with the severity of AGA in male patients. We also found that patients of both genders with a family history had more advanced types of hair loss, and the age of onset of AGA in male patients with a family history was earlier than that in male patients without a family history. CONCLUSIONS: Although the evidence for an environmental influence on AGA remains very weak, we did find an association between hair loss severity and certain environmental factors, such as smoking and drinking. Family history with more severe hair loss and an earlier age of onset.

Apolipoprotein A1 potentiates lipoxin A4 synthesis and recovery of allergen-induced disrupted tight junctions in the airway epithelium.

BACKGROUND: Asthma is characterized by chronic airway inflammation triggered by various allergens in the environment. Defects in the bronchial epithelial interface with the external environment are the hallmark of asthma. Apolipoprotein A-1 (ApoA1) or ApoA1 mimetics have demonstrated anti-inflammatory activity and preventive effects in mouse models. OBJECTIVE: We investigated airway levels of ApoA1 in asthmatics and the possible role of ApoA1 in protection of the bronchial epithelium and in resolution of inflammation in cellular and animal models of asthma. METHODS: ApoA1 levels were measured in bronchoalveolar lavage fluid (BALF) from asthmatics and healthy controls. With treatment of ApoA1, mouse model of house dust mite (HDM)-driven asthma and cultured primary bronchial epithelial cells obtained from asthmatics were examined. Tight junction (TJ) expression in the bronchial epithelial cells was assessed by using confocal microscopy and immunoblot. RESULTS: Asthmatics showed significantly lower ApoA1 levels in bronchoalveolar lavage fluid than did healthy controls. Local ApoA1 treatment significantly decreased lung IL-25, IL-33, and thymic stromal lymphopoietin levels in HDM-challenged mice and inhibited allergen-induced production of these cytokines in cultured primary bronchial epithelial cells. ApoA1 promoted recovery of disrupted TJ proteins zonula occludens-1 and occludin in cultured primary bronchial epithelium obtained from asthmatics. ApoA1-induced increases in the TJ proteins were dependent on increased production of lipoxin A4 (LX A4). CONCLUSIONS AND CLINICAL RELEVANCE: ApoA1 enhances resolution of allergen-induced airway inflammation through promoting recovery of damaged TJs in the bronchial epithelium. ApoA1 could be a therapeutic strategy in chronic airway inflammatory diseases that are associated with a defective epithelial barrier, including asthma.

Randomized comparison of the Pentax AirWay Scope and Macintosh laryngoscope for tracheal intubation in patients with obstructive sleep apnoea.

BACKGROUND: Patients with obstructive sleep apnoea (OSA) can often present difficulties in intubation. This study aimed to compare the efficacy of the Pentax AirWay Scope (AWS) with that of the Macintosh laryngoscope for tracheal intubation in patients with OSA. METHODS: Forty-six patients undergoing uvulopalatopharyngoplasty were randomly allocated to tracheal intubation with either the Macintosh laryngoscope or the Pentax AWS. In all patients, intubation was performed by one of two anaesthetists experienced with both devices. The primary and secondary endpoints of this study were the intubation difficulty scale (IDS) score and success/failure and duration of the first successful intubation attempt. RESULTS: With the Pentax AWS, tracheal intubation was successful on the first attempt in all patients whereas four patients required repeated attempts at intubation with the Macintosh laryngoscope. The IDS score was significantly lower using the Pentax AWS and glottic exposure was better (the Cormack and Lehane grade 1 in all patients vs grade 2 or higher in all patients, P<0.0001). Average duration of successful intubation was shorter (12.9 vs 29.9 s, P=0.0002), and fewer manoeuvres were needed to improve the glottic exposure (0 in all patients vs 1 or more in 16 patients, P<0.0001) with the Pentax AWS, compared with the Macintosh laryngoscope. CONCLUSIONS: In this study of patients with OSA, tracheal intubation by experienced anaesthetists was facilitated using the Pentax AWS compared with the Macintosh laryngoscope.

Risk of microbial transmission by reusing gloves after alcohol-based hand hygiene.

BACKGROUND: Disinfection of gloves might reduce the workload of healthcare workers, protect the environment, and bring economic benefits. Thus, the safety of hand hygiene of gloved hands is an important issue. AIM: We aimed to evaluate the risk of microbial transmission by comparing residual micro-organisms after multiple patient contacts, with or without gloves, in clinical practice. METHODS: Researchers, two with gloved hands (single or double gloves) and one with bare hands, made rounds of patients, followed by alcohol-based hand rub. Hand imprints were obtained before and after the rounds and cultured. The number of colony-forming units (cfu) of gloved and bare hands was compared, and the colony distribution was evaluated semi-quantitatively by hand region. FINDINGS AND CONCLUSION: A total of 108 imprints were obtained after 10 rounds. The median cfu counts were significantly higher in the gloved hands (single and double) than in the bare hands (9.00 vs 3.50, P=0.028). The cfu counts of single- and double-gloved hands were higher after than before contact (P=0.044 and P=0.001, respectively). Carbapenem-resistant Acinetobacter baumannii was identified in a pair of double gloves after a round, which included patients with the same organism with identical antibiotic susceptibility results. The mean percentage of colony-growing compartments from gloved hands was significantly higher than that of bare hands in the finger and wrist regions (P=0.019 and P=0.049, respectively). Compared with bare hands, reuse of gloves increased residual microbial colonies and potential for transmission of multi-drug-resistant organisms, even after using alcohol-based hand rub.

Identification of 11 novel mutations in 49 Korean patients with mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPS II) or Hunter syndrome is a rare lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS). As MPS II is X-linked, patients are usually males with heterogeneous mutations ranging from point mutations to gross deletions and recombination. In 2003, we reported a mutation analysis of 25 patients with MPS II. In this study, 31 mutations in another 49 Korean patients (45 families) with MPS II are reported: 12 missense, nine deletions, four splicing, two nonsense, two insertions, one deletion/insertion, and IDS-IDS2 recombination mutations. Among these mutations, 11 were novel ones (4 missense mutations: Ser61Pro, Pro97Arg, Pro228Ala, and Pro261Ala; 5 deletions: c.344delA, c.420delG, c.768delT, c.1112delC and c.1402delC; 1 deletion/insertion: c.1222delinsTA; and 1 insertion mutation: c.359_360insATCC). The IDS-IDS2 recombination mutations were most frequently observed; all patients with this mutation had the severe MPS II phenotype. However, most of the patients (5/7) with the G374G splicing mutation had an attenuated phenotype, except for two sibling cases with the severe phenotype. Except for a few recurrent mutations such as the G374G, R443X, L522P, and recombination mutations, each patient had a unique individual mutation. Therefore, careful interpretation of genotype-phenotype correlations is warranted.

Increased apoB/A-I ratio independently associated with Type 2 diabetes mellitus: cross-sectional study in a Korean population.

AIMS: The aim of this study was to investigate whether increased apolipoprotein B/apolipoprotein A-I ratio is associated with Type 2 diabetes mellitus independent of other risk factors for Type 2 diabetes. METHODS: A total of 70,063 subjects (41,391 men and 28,672 women; mean age 41.5 years) who visited the Health Screening Center at Kangbuk Samsung Hospital for a routine medical check-up between January 2009 and December 2009 were enrolled in this study. RESULTS: The mean apolipoprotein B/apolipoprotein A-I ratio in the study subjects was 0.66 ± 0.18. The prevalence of Type 2 diabetes increased across the apolipoprotein B/apolipoprotein A-I ratio quartiles (1.0%, 1.6%, 2.9%, and 4.8% for the 1st through 4th quartiles, respectively, P < 0.001) and homeostasis model assessment-insulin resistance (HOMA2-IR) also showed an increasing tendency by quartile (P < 0.001). The apolipoprotein B/apolipoprotein A-I ratio was correlated with age, adiposity, blood pressure, HOMA2-IR value, fasting glucose levels, and other inflammatory marker, including high-sensitivity C-reactive protein, and lipoprotein (a) levels (all P < 0.001). In a multiple logistic regression model, the highest apolipoprotein B/apolipoprotein A-I ratio quartile was associated with Type 2 diabetes, even after controlling for other risk factors for diabetes, such as age, gender, BMI, systolic blood pressure, HOMA2-IR values, high-sensitivity C-reactive protein levels, family history of diabetes, presence of metabolic syndrome, and conventional lipid parameters (odds ratio 1.31; 95% confidence interval 1.17-1.46, P < 0.001). CONCLUSIONS: The apolipoprotein B/apolipoprotein A-I ratio was found to be associated with Type 2 diabetes independent of other risk factors for diabetes and conventional lipid parameters.

Serum 1,5-anhydroglucitol is associated with diabetic retinopathy in Type 2 diabetes.

AIMS: To determine whether there is a relationship between 1,5-anhydroglucitol (1,5-AG), a marker of postprandial hyperglycaemia and glycaemic variability, and the presence of diabetic retinopathy and albuminuria in patients with Type 2 diabetes. METHODS: Five hundred and sixty-seven patients with Type 2 diabetes (serum creatinine < 133 µmol/l), who were enrolled in the Seoul Metro-City Diabetes Prevention Program (SMC-DPP), were cross-sectionally assessed by multivariate logistic regression analysis. RESULTS: After controlling for age, sex, binary HbA(1c) levels, duration of diabetes, triglyceride, systolic blood pressure, smoking status, history of hypertension and dyslipidaemia, and the use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker medication, the odds ratios (95% CI) of diabetic retinopathy were 2.86 (1.12-7.25) for the first (lowest) quartile of 1,5-anhydroglucitol, 2.87 (1.25-6.61) for the second quartile and 0.88 (0.35-2.22) for the third quartile compared with the fourth quartile (P for trend = 0.010). Conversely, the associations between 1,5-anhydroglucitol and clinical albuminuria were non-significant after adjustment. Subjects with low 1,5-anhydroglucitol (< 10.0 µg/ml) were more likely to experience diabetic retinopathy than those with high 1,5-anhydroglucitol (≥ 10.0 µg/ml) under moderate glucose control (HbA(1c) < 8%, 64 mmol/mol) and there were no significant differences in the prevalence of diabetic retinopathy between the subgroup with HbA(1c) < 8% (64 mmol/mol) and low 1,5-anhydroglucitol and the subgroup with HbA(1c) ≥ 8% (64 mmol/mol). CONCLUSIONS: 1,5-Anhydroglucitol levels show close associations with diabetic retinopathy, especially among patients under moderate glucose control, but not with albuminuria. These results suggest that 1,5-anhydroglucitol might be a complementary marker for targeting higher risk group.