bluuebunny/crossref_metadata_2025_split huggingface dataset:
22-OR: Nasal Glucagon: A Viable Alternative to Treat Insulin-Induced Hypoglycemia in Japanese Patients with Type 1 and Type 2 Diabetes
Authors: MATSUHISA MUNEHIDE , TAKITA YASUSHI , NASU RISA , OHWAKI KENJI , NAGASHIMA HIROTAKA 
Published: June 2019

Background/Objective: Currently available glucagon products for rescue treatment of severe hypoglycemia require cumbersome multistep reconstitution and injection procedures in an emergency situation. Nasal glucagon (NG) is a nasally administered, single-use, drug-device combination containing 3 mg glucagon dry powder. We aimed to evaluate noninferiority of NG to intramuscular glucagon (IMG) for treatment of insulin-induced hypoglycemia in patients with type 1 and type 2 diabetes (T1D/T2D) (NCT03421379).
Methods: This was a randomized, two-period, crossover trial with NG and IMG. Hypoglycemia was induced by an intravenous insulin infusion; insulin was stopped once plasma glucose (PG) reached &lt;60 mg/dL. Approximately 5 minutes (min) after stopping insulin either 3 mg NG or 1 mg IMG was administered followed by PG measurements up to 4 hours. Treatment success was defined as an increase in PG to ≥70 mg/dL or an increase of ≥20 mg/dL from the PG nadir within 30 min after receiving glucagon. Spontaneously reported adverse events (AEs) and a Nasal and Non-Nasal Symptom Questionnaire (NNSQ) assessed local tolerability of NG.
Results: Of the 68 evaluable patients (T1D 32, T2D 36) who received both NG and IMG, all patients achieved treatment success with a mean time of 12.0 min (NG) and 11.0 min (IMG). Noninferiority of NG to IMG was demonstrated. PG responses were similar between T1D and T2D. During the treatment period 26 treatment-emergent AEs (TEAEs) occurred with NG and 13 with IMG. Most TEAEs were mild in severity and none was severe. TEAEs with an incidence ≥5% were rhinalgia (NG 8.5%, IMG 0%), nausea (NG 5.6%, IMG 11.4%), and blood pressure increase (NG 5.6%, IMG 0%). With NG, very common (≥10%) symptoms from NNSQ were watery eyes and nasal congestion.
Conclusion: NG was noninferior compared to IMG for the treatment of insulin-induced hypoglycemia in Japanese patients with T1D/T2D supporting the use of NG as a rescue treatment for severe hypoglycemia.

Disclosure
M. Matsuhisa: Advisory Panel; Self; Eli Lilly and Company. Board Member; Self; Daiichi Sankyo Company, Limited. Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Astellas Pharma Inc., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited. Y. Takita: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. R. Nasu: None. K. Ohwaki: Employee; Self; Eli Lilly and Company. H. Nagashima: None.
220-OR: Is There Any Prognostic Value of Diabetes-Associated Autoantibody Levels for Predicting Islet Graft Function in Patients with Long-Standing Type 1 Diabetes Mellitus?
Authors: BACHUL PIOTR J. , GOLEBIEWSKA JUSTYNA E. , ANTIC FILIP , PARA MONICA , BASTO LINDSAY , LUCANDER AARON C. , GOLAB KAROLINA , PEREA LAURENCIA , TIBUDAN MARTIN L. , WANG LING-JIA , THOMAS CELESTE C. , WITKOWSKI PIOTR 
Published: June 2019

Introduction: Correlation between increasing titers for GADA, IA-2A, and ZnT8A and graft loss due to recurrent autoimmunity has been reported, but not confirmed in other studies. Here, we assessed the prognostic value of DAA levels for predicting graft function in our cohort of islet transplant recipients.
Methods: Twelve patients with T1DM with hypoglycemic unawareness underwent islet allotransplantation (ITx). Eight of those patients were randomly assigned to receive Reparixin (CXCR1/2 inhibitor) and remaining 4 to placebo in addition to thymoglobulin, tacrolimus and mycophenolate mofetil for immunosuppression. Titers of DAAs were monitored before IT and 0, 7, and 75 days and every 3 months post-operatively.
Results: IA-2A and ZnT8A levels were undetectable prior to and after IT in all 12 T1DM patients at any time points, median follow-up of 56 months (24-66) so had no value in islet monitoring. No difference was observed for trends of GADA titers between 4 patients with long-term insulin independence after IT and the remaining 8 who experienced a decline in islet graft function. Prior to and after IT, GADA levels did not vary between patients receiving Reparixin and placebo with most GADA negative (65% and 50%, respectively). Most patients converted from GADA seronegative to seropositive or increased antibody titers [5/8 (62.5%) and 4/4 (100%), respectively] and converted back to seronegative by 1 year post-transplant and maintained partial or complete islet function over 4 years.
Conclusion: We found no correlation between trends of anti-GAD65 autoantibody levels and IT outcome in our 12-patient cohort. Levels of DAAs targeting IA-2 and ZnT8 were not detectable in all patients prior to and after IT and did not correlate with IT outcome. Differences in immunosuppression and anti-inflammatory regimens and patient characteristics between studies may contribute to inconsistency among reported results.

Disclosure
P.J. Bachul: None. J.E. Golebiewska: None. F. Antic: None. M. Para: None. L. Basto: None. A.C. Lucander: None. K. Golab: None. L. Perea: None. M.L. Tibudan: None. L. Wang: None. C.C. Thomas: None. P. Witkowski: None.

Funding
State of Illinois; Dompé
2206-PUB: Reducing Rates of Hypoglycemic Events through a Multidisciplinary Coordination of Care in a Teaching Hospital in Phoenix, AZ
Authors: CHMELNIK SANDRA , ABDOLLAHI SHAGHAYEGH , NEAL CHANTÉ N. , CAMERON DEBORAH R. 
Published: June 2019

The challenge of controlling hyperglycemia and hypoglycemia in hospitalized patients drives cost increase, length of stay, morbidity and mortality. Between 10% of patients on antihyperglycemic agents suffer at least one hypoglycemic event during hospitalization, adding 31% to the overall cost of care. One cause relates to poor coordination of meal delivery and insulin administration. After internal data collection and analysis, the average time between point of care glucose testing (POCT) and insulin administration was 60 minutes. In January 2018, the overall percentage of severe hypoglycemic events (defined as &lt;50 mg/dL) reached 9.1%. A pilot project started at the Medicine-Oncology units in March 2018 to improve coordination between POCT, meal tray delivery and insulin administration. Expected process outcomes were: effective communication between Dietary and Nursing when meal is ordered on-demand, POCT within 30 minutes of meal order and insulin administration within 15 minutes before tray delivery. Also, a branded visual cue was developed as “Insulin tents,” placed on the meal tray, encouraging patients to alert Nursing if medication was needed. Timely insulin coverage was operationalized as within 15 minutes of the first bite due to pharmacokinetics of rapid acting insulin. Our study included adults (≥18 years) admitted to the Medicine-Oncology unit who presented with hyperglycemia. Post intervention POCT data was collected March 2018 to November 2018 and compared to analogous data prior intervention (October 2016 to February 2018). We observed a reduction of hypoglycemic events, from 4.7% pre-intervention to 2.2% post intervention, and 3 months with 0 hypoglycemic events. POCT after patient’s meal order call was successful 52% of the time, and the POCT time improved from expected goal of 30 minutes to 16.6 minutes average. We concluded that the pilot project can reduce hypoglycemic events and improve patient outcomes and costs related to care.

Disclosure
S. Chmelnik: None. S. Abdollahi: None. C.N. Neal: None. D.R. Cameron: None.
2210-PUB: Despite Optimal Use of Angiotensin Receptor Blockers There Exists Substantial Cardiovascular Risk as Suggested by Elevated NT-ProBNP in 259 T2DM Patients
Authors: GUPTA VISHAL , TELI VAISHALI 
Published: June 2019

259 T2DM patients with microalbuminuria eUACR &gt;30 irrespective of their A1c, on standard glucose lowering, lipid lowering and ARB (telmisartan TM or valsartan Vs as first line BP lowering therapy until optimal dose was achieved, were followed-up for 2 years. Renal (Cr, eGFR, UACR) and CV (BP, BMI, Lipid profile, hs-CRP) parameters were assessed every 6 months. NT-ProBNP was measured at the end of 2 years. Patients with history of major surgery, coronary intervention, IHD or hospitalization in last 1 year, eGFR &lt;45, hyperkalemia &gt;5.3 were excluded Data was analyzed using PSPP version 1.0.1 and represented as Mean (SD) and paired-t test was used, p-value of 0.05 was considered to be significant.
Results: 42.1% used TM and 57.9% used Vs. Average dose of TM 66.76mg (±52.63) and Vs 165.33 (±89.94) Baseline characteristics: 259 patients (females 45.6%, male 54.4%), mean age 61.22 years (±9.50); weight 78.91kg (±15.78), BMI 30.63 (5.81±), DOD 12.9 years (7.52±), SBP 137.09mm (±20.60), DBP 77.54 (±11.31). There was a significant mean reduction observed in HbA1c 1.21% (95% CI 1.02-1.39, p-&lt;0.001), SBP 3.37mm (95% CI 0.66-6.08, p-0.015), TC 14.13mg% (95% CI 8.43-19.83, p &lt;0.001), LDL 10.64mg% (95% CI 5.87-15.41, p &lt;0.001), TG 19.52mg% (95% CI 11.50-27.55, p&lt;0.001), non-HDL 25.31mg% (95% CI 18.95-31.66, p&lt;0.001), Chol remnant 8.25mg% (95% CI 5.27-11.22, p &lt;0.001), UACR 147.5mg% (95% CI 61.27-233.79, p 0.001). There was no significant change seen in weight, BMI, DBP, HDL, Cr, eGFR, potassium. The NT-ProBNP was 166.30 pg/ml (±242.72) remained elevated after 2 years.
Conclusion: Despite optimal use of ARB and reduction in renal (UACR, maintenance of renal function) and CV risk factors there remains a significant risk for future CV mortality as suggested by elevated NT-ProBNP in T2DM with microalbuminuria.

Disclosure
V. Gupta: None. V. Teli: None.
2212-PUB: The Prevalence of Nonalcoholic Fatty Liver Disease Is Increased in Patients with Type 2 Diabetes but Not in Those with Peripheral Artery Disease
Authors: SAELY CHRISTOPH H. , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN-PURIN DANIELA , SCHINDEWOLF MARC , BAUMGARTNER IRIS , LARCHER BARBARA , MADER ARTHUR , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ 
Published: June 2019

Nonalcoholic fatty liver disease (NAFLD) is a feature of the metabolic syndrome and is associated with an increased risk of cardiovascular disease. Whether the prevalence of NAFLD is increased independently from the presence of type 2 diabetes (T2DM) in patients with peripheral artery disease (PAD) is unknown and is addressed in the present study. We assessed the prevalence of NAFLD as estimated by the validated fatty liver index in four groups of patients, including 216 who neither had PAD nor T2DM, 56 without PAD but with T2DM, 157 with PAD but without T2DM and 119 with the combination of T2DM and PAD. Both, among patients without PAD and among those with PAD, T2DM was associated with an increased prevalence of NAFLD (71.4 vs. 39.4%; p&lt;0.001 and 70.6 vs. 40.8%; p&lt;0.001, respectively). However, the prevalence of NAFLD neither among those with nor among those without T2DM was significantly associated with the presence of PAD (p=0.783 and p=0.909, respectively). The prevalence of NAFLD was significantly higher in patients with T2DM but without PAD than in PAD patients who did not have diabetes (p&lt;0.001). T2DM after multivariate adjustment remained significantly associated with NAFLD (OR 3.23 [1.77-5.90]; p&lt;0.001). We conclude that the prevalence of NAFLD disease is increased in patients with T2DM but not in those with PAD.

Disclosure
C.H. Saely: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin-Purin: None. M. Schindewolf: None. I. Baumgartner: None. B. Larcher: None. A. Mader: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None.
2217-PUB: Type 2 Diabetes Is a Strong Predictor for LDL Cholesterol Target Achievement in Patients with Peripheral Artery Disease
Authors: STERNBAUER SIMON , VONBANK ALEXANDER , HEINZLE CHRISTINE , ZANOLIN-PURIN DANIELA , DOPHEIDE JÖRN F. , BAUMGARTNER IRIS , LARCHER BARBARA , MADER ARTHUR , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H. 
Published: June 2019

Patients with peripheral artery disease (PAD) are at a very high risk of cardiovascular events and strongly benefit from lowering LDL cholesterol (LDL-C). Current guidelines recommend an LDL-C target of at least &lt;70mg/dl for these patients. PAD patients who also have diabetes are at an extremely high risk of cardiovascular events, and an LDL-C target of &lt;55 mg/dl has been proposed for these patients. Whether the presence of type 2 diabetes (T2DM) affects LDL-C target achievement in PAD patients is unknown and is addressed in the present study. We investigated an unselected consecutive series of 481 patients with sonographically proven PAD, of whom 214 (44.5%) had T2DM. An LDL-C target of &lt;70 mg/dl was met by 26.4% of PAD patients with T2DM and by 9.0% of nondiabetic PAD patients (p&lt;0.001); an LDL-C target &lt;55 mg/dl was met by 11.8% of T2DM patients and by 2.7% of nondiabetic patients (p&lt;0.001). Logistic regression analysis showed that the presence of T2DM was an independent and strong predictor of LDL-C target achievement after multivariate adjustment including age, gender and statin use both for the &lt;70 mg/dl target (OR 3.31 [1.93-5.68]; p&lt;0.001) and for the &lt;55 mg/dl target (OR 4.40 [1.83-10.51]; p&lt;0.001). We conclude that T2DM is a strong and independent predictor of LDL-C target achievement among PAD patients; however, also among PAD patients with T2DM the majority does not even meet the liberal LDL-C target of &lt;70 mg/dl.

Disclosure
S. Sternbauer: None. A. Vonbank: None. C. Heinzle: None. D. Zanolin-Purin: None. J.F. Dopheide: None. I. Baumgartner: None. B. Larcher: None. A. Mader: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.
223-LB: Beta-Cell Function but Not Insulin Sensitivity Is Impaired in Nondiabetic Cystic Fibrosis Adults Assessed with the Oral Minimal Model Method
Authors: SCHIAVON MICHELE , TOFFOLO GIANNA MARIA , COBELLI CLAUDIO , NAIR K. SREEKUMARAN , MORAN ANTOINETTE 
Published: June 2019

Insulin deficiency in cystic fibrosis (CF) is the primary cause of impaired glucose tolerance and diabetes. However, along with insulin deficiency, insulin sensitivity may also play an important role. Herein we aimed to quantify insulin action and secretion in nondiabetic CF adults in comparison with healthy controls after an oral glucose tolerance test (OGTT) with the oral minimal model method. Sixteen nondiabetic CF (7F; age=22±2 y; BMI=22±2 kg/m2; BW=66±10 kg) and seven healthy adults (3F; age=22±2 y; BMI=22±2 kg/m2; BW=66±9 kg) underwent an OGTT. Plasma glucose, insulin and C-peptide were measured for 5 h. The oral glucose and C-peptide minimal models were used to quantify indices of glucose absorption, insulin sensitivity, β-cell responsiveness and disposition index.
Insulin sensitivity was similar (mean±SE; p-value from two-sample t-test) in CF and healthy (23±3 and 16±3 10-4 dL/kg/min per uU/mL; NS), while percentage of glucose absorbed within the first two hours was significantly higher in CF (70±3 vs. 53±4 %; p&lt;0.005). In contrast, β-cell responsiveness was significantly reduced in CF (42±4 vs. 118±16 10-9 min-1) due to a reduction both in the dynamic (320±45 vs. 1316±172 10-9; p&lt;0.005) and static (42±4 vs. 118±16 10-9 min-1; p&lt;0.005) component. The delay in the static component was also higher, but not significantly, in CF (15±4 vs. 8±3 min; NS). As a consequence, the disposition index was significantly reduced in CF (1659±423 vs. 3303±426 10-14 dL/kg/min2 per pmol/L; p&lt;0.05). Of note, no difference in incremental Area Under Curve (0-5 h) of glucose (6186±884 vs. 3680±1113 mg/dL*min; NS), insulin (4901±559 vs. 8577±2032 uU/mL*min; NS) and C-peptide (331±33 vs. 349±82 nmol/L*min; NS) in CF vs. healthy was observed.
In conclusion, the oral minimal model method showed that abnormal glucose tolerance in our cohort of CF patients is due to an impaired β-cell function, while insulin action is similar and glucose absorption is higher.

Disclosure
M. Schiavon: None. G.M. Toffolo: None. C. Cobelli: None. K. Nair: None. A. Moran: Other Relationship; Self; Novo Nordisk Inc.

Funding
National Institutes of Health (R01DK101402); National Center for Advancing Translational Sciences (UL1-TR-000114)
2234-PUB: A Risk Prediction Model for End-Stage Renal Disease in Patients with Type 2 Diabetes Mellitus
Authors: GEBA DANIELA , CORDOVA JEANINE M. , SHETTY SHARASH , WILLIAMS BRENT 
Published: June 2019

End-stage renal disease (ESRD) is the most severe form of chronic kidney disease (CKD) and requires dialysis or renal transplant for survival. ESRD affects more than 600,000 individuals in the United States and over 40% of cases are diabetes-related. Results from recent clinical trials consistently showed that sodium-glucose cotransporter-2 (SGLT2) inhibitors improve renal outcomes among patients with type 2 diabetes mellitus (T2DM). Cost considerations, however, emphasize the need for designing cost-effective strategies to use the medicine in this class for ESRD prevention. Therefore, the goal of this project was to develop a risk prediction model that would help identify T2DM patients at high risk to develop ESRD. The study is based on a retrospective cohort of patients with T2DM who received health care services at a large, integrated healthcare system for at least two years between 2001 and 2016. Cox regression was used to identify the strongest predictors of ESRD among 93 candidate predictors (e.g., medical history, laboratory tests) obtained from the electronic medical records. The “high-risk” group included the highest risk 10% of patients according to the final model predictors. The study sample included 58,428 patients with a mean age of 61 years. Of these, 6350 (11%) had CKD at baseline. During a mean follow-up of 6.8 years, 2208 (3.8%) patients were diagnosed with ESRD. Estimated event rates were 0.4% at 1 year and 2.7% at 5 years. The corresponding rates for the high-risk group were 2.8% and 15.1%. The predictors of ESRD included in the final model were: blood urea nitrogen, CKD, albumin, pulse pressure, hemoglobin A1c, anemia, glomerular filtration rate, and preexisting diabetes (vs. newly diagnosed) (c-statistic: 0.706). The proposed risk prediction model for ESRD demonstrates strong predictive capabilities. Applied in clinical settings, the model could help clinicians identify T2DM patients most likely to benefit from SGLT2 inhibitors to prevent or delay progression to ESRD.

Disclosure
D. Geba: None. J.M. Cordova: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. S. Shetty: None. B. Williams: None.
2238-PUB: Small-Fiber Neuropathy Is Prevalent in Diabetes with Albuminuria
Authors: OH TAE JUNG , KANG SUNYOUNG , CHOI SUNGHEE , JANG HAK CHUL 
Published: June 2019

Diabetic neuropathy is one of microvascular complications of diabetes. Among many types of diabetic neuropathy small-fiber neuropathy is believed to be the earliest sign of nerve dysfunction. Albuminuria, the other microvascular complication, is common and precedes renal dysfunction in diabetes and the early detection of these two complications is important. In this study, we investigated whether the small-fiber nerve dysfunction would be prevalent in subjects with diabetes and albuminuria. If so, we could discover a common etiology of these two conditions. We enrolled adult type 2 diabetes (n = 311) and measured their feet electrochemical skin conductance (ESC) by SUDOSCAN, and albumin to creatinine ratio (ACR) using random urine samples. The subjects were categorized according to their albuminuria status: no albuminuria, newly detected albuminuria, and persistent albuminuria. We defined small-fiber neuropathy if the feet ESC levels were less than 60 uS. Mean ages of subjects were 57.9 years and 58.8% were male. Among them, 13.5% and 20.6% of subjects had newly detected and persistent albuminuria, respectively. Mean ESC levels were decreased in subjects with albuminuria than those without albuminuria. In addition, more subjects had small-fiber neuropathy in albuminuria groups than normal counterpart (47.6% vs. 56.3% vs. 26.8% in newly detected albuminuria, persistent albuminuria, and no albuminuria groups, respectively, P &lt;0.001). Feet ESC levels were negatively correlated with ACR and it can detect the presence of albuminuria with 58.5% of sensitivity and 70.2% of specificity. The feet ESC levels were independently associated with albuminuria after adjusting for diabetes duration, HbA1c, systolic blood pressure, triglyceride, and LDL-cholesterol.
In conclusion, small-fiber neuropathy was more prevalent in diabetes with albuminuria compared to diabetes without albuminuria. The small-fiber neuropathy might be an independent risk factor for diabetic nephropathy.

Disclosure
T. Oh: None. S. Kang: None. S. Choi: None. H. Jang: None.
2249-PUB: Current Practices and Gaps in Management of Dyslipidemia in Indian Participants with Type 2 Diabetes Mellitus (T2DM) in Alignment with American Association of Clinical Endocrinologists (AACE) Guidelines in LEADD (Learning with Experts to Advance Diabetes
Authors: UNNIKRISHNAN AMBIKA GOPALAKRISHNAN , DAS ASHOK KUMAR , SABOO BANSHI D. , KALRA SANJAY , AYYAR VAGEESH , TIWASKAR MANGESH HARIHAR 
Published: June 2019

Background: Dyslipidemia is a common co-morbid condition in participants with T2DM. AACE guidelines advocate moderate to high intensity statins in T2DM unless contraindicated.
Objective: Assess evaluation practices and treatment patterns for dyslipidemia with statin intensity usage in the T2DM population as per AACE guidelines.
Methods: Sub-analysis of prospective, cross sectional, observational LEADD study in T2DM participants, conducted at 226 sites Participants stratified basis risk status and mean LDL was compared to recommended LDL levels as per AACE guidelines. “n”=number of participants analyzed for each parameter.
Results: Total of 4002 participants were evaluated and had mean (±SD) LDL - C levels of 117.7 ± 37.66 mg/dl. AACE Risk stratification with available data (n = 3538/4002) of participants was conducted on stratification 0.3% (n = 11/3538) participants were in high risk, 87.0% (n = 3077/3538) in very high risk and 12.7% (450/3538) in extreme risk category. Mean(±SD) LDL - C was 116.8 (± 36.41), 118.1 (±38.04) and 118.4 (± 41.39) mg/dl as against goal of &lt;100, &lt;70 and &lt;55mg/dl for high risk, very high risk and extreme risk groups. 77.5% (n = 1523/1964) participants evaluated for dyslipidemia received Rosuvastatin. Percentage participants not on LDL- C goal were 54.54%, 89.88% and 94.77% in high risk, very high risk and extreme risk. 87.44% (n = 1962/2244), and 77.69% (n = 282/363 in very high risk and extreme risk group did not receive moderate to high intensity statin as recommended by AACE.
Conclusion: AACE guidelines adherence for evaluation and management of diabetic dyslipidemia is sub-optimal in study population. Although population falling in very high to extreme risk, they were not treated with moderate to high intensity statins. Reasons for these findings require further research.

Disclosure
A. Unnikrishnan: Other Relationship; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Dr. Reddys Laboratories, Eli Lilly and Company, Eris Pharmaceuticals, Ipca Laboratories Ltd., MSD, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi. A.K. Das: None. B.D. Saboo: None. S. Kalra: None. V. Ayyar: None. M.H. Tiwaskar: None.

Funding
Diabetes Care India; Dr. Reddy's Laboratories