bluuebunny/crossref_metadata_2025 huggingface dataset:
Kebijakan Pemerintah Kabupaten Sukoharjo dalam Menciptakan Iklim Investasi yang Kondusif
Authors: Dona Fery
Published: May 2022

Penelitian ini bertujuan untuk mengetahui kebijakan Pemerintah Daerah Kabupaten Sukoharjo dalam menciptakan iklim investasi yang kondusif, dan untuk mengetahui apa saja hambatan yang dihadapi Pemerintah Daerah Kabupaten Sukoharjo dalam menciptakan iklim investasi yang kondusif.
Penelitian ini menggunakan jenis penelitian empiris, yang diteliti pada awalnya adalah data sekunder kemudian dilanjutkan dengan penelitian terhadap data primer. Analisis data menggunakan deskripsi kualitatif, yaitu hasil pengelolahan data kualitatif ini digambarkan dengan kalimat dipisahkan berdasarkan kategori untuk memperoleh kesimpulan.
Hasil penelitian menunjukan bahwa kebijakan Pemerintah Daerah Kabupaten Sukoharjo dalam menciptakan iklim investasi yang kondusif antara lain membangun gedung pusat promosi potensi daerah, menetapkan Peraturan Bupati No. 38 tahun 2015 tentang Rencana Umum Penanaman Modal Kabupaten Sukoharjo tahun 2015-2025, menetapkan Peraturan Bupati Sukoharjo No. 2 tahun 2017 tentang Standar Pelayanan Pada Dinas Penanaman Modal dan Pelayanan Terpadu Satu Pintu Kabupaten Sukoharjo, menetapkan Peraturan Bupati Sukoharjo No. 4 tahun 2017 tentang Layanan Perizinan Online dan Secara  Mandiri di Kabupaten Sukoharjo, menetapkan Peraturan Bupati Sukoharjo No. 32 tahun 2017 tentang Pendelegasian Kewenangan Di Bidang Perizinan dan Non Perizinan Kepada Kepala Dinas Penanaman Modal dan Pelayanan Terpada Satu Pintu, menetapkan Peraturan Bupati Sukoharjo No. 1 tahun 2018 tentang Perubahan Atas Peraturan Daerah Kabupaten Sukoharjo No. 14 tahun 2011 tentang Rencana Tata Ruang Wilayah Kabupaten Sukoharjo tahun 2011-2031, mengikuti promosi investasi. Kemudian juga diperoleh hasil mengenai hambatan yang dihadapi Pemerintah Daerah Kabupaten Sukoharjo dalam menciptakan iklim investasi yang kondusif antara lain Sukoharjo belum mempunyai terminal peti kemas, ada penolakan dari masyarakat terhadap izin tertentu salah satunya adalah izin menara telekomunikasi, adanya protes dari masyarakat kepada pelaku usaha yang disebabkan kelalaian pelaku usaha.
A Theory of Relativity in Donor Organ Ischemia
Authors: Joyce David
Published: May 2022

Changes in the heart allocation system have led to transplant programs
traveling greater distances for donor organs. At the same time, several
new technologies have emerged to provide improvements in donor organ
protection when compared with traditional strategies. These new
developments have increased the need for a better understanding of risks
associated with donor injury related to various types of ischemia.
Increasing plant species richness by seeding has marginal effects on ecosystem functioning in agricultural grasslands
Authors: Freitag Martin , Hölzel Norbert , Neuenkamp Lena , Plas Fons van der , Manning Peter , Abrahão Anna , Bergmann Joana , Boeddinghaus Runa , Bolliger Ralph , Hamer Ute , Kandeler Ellen , Kleinebecker Till , Knorr Klaus-Holger , Marhan Sven , Neyret Margot , Prati Daniel , Provost Gaëtane Le , Saiz Hugo , Kleunen Mark van , Schäfer Deborah , Klaus Valentin
Published: May 2022

Experimental evidence shows that grassland plant diversity enhances
ecosystem functioning. Yet, the transfer of results from controlled
biodiversity experiments to naturally assembled ‘real world’ ecosystems
remains challenging. Here, we address this issue by experimentally
sowing locally absent plant species in 73 agricultural grasslands along
a land-use intensity gradient, to test how ecosystem functions related
to productivity and nutrient cycling respond to species enrichment. We
found that only one of 12 ecosystem functions responded to changes in
species richness. In fact, ecosystem functioning was rather driven by
environmental conditions and land-use intensity. This suggests that the
functionally-relevant niche space is saturated in naturally assembled
grasslands, and that competitive, high-functioning species are already
present. While nature conservation and cultural ecosystem services
certainly benefit from species enrichment, our study indicates that
plant species enrichment may deliver only weak increases in ecosystem
functioning in both moderately intensive and traditionally managed
agricultural grasslands.
Toxic epidermal necrolysis associated with apalutamide: a case report and brief review of the literatures
Authors: Huang Ya , Luo Jimin , Luo Jisheng , Leng Yao , Han Qingfu , Wen Juanjuan , Qu Huilin , Wang Wei , Zhang Jinhang , Zhang Enjuan
Published: May 2022

Apalutamide is a novel competitive inhibitor of the androgen receptor
for the treatment of non-metastatic castration-resistant prostate cancer
or metastatic castration-sensitive prostate cancer. Rash is the most
common skin adverse reaction of apalutamide. If rash is paid
insufficient attention, further developing life-threatening
Stevens–Johnson Syndrome/Toxic Epidermal Necrolysis. Here, we reported
a case of toxic epidermal necrolysis caused by apalutamide. An
86-year-old male patient developed a Nikolsky-positive maculopapular
rash, skin exfoliation and mucosal erosion involving 60% body surface
area 24 days after treatment of oral apalutamide (180mg/d) for prostate
cancer with bone metastases. The skin manifestations aggravated after
discontinuation of apalutamide and treatment of methylprednisolone
(0.8mg/kg/d) and immunoglobulin (400mg/kg/d) for 2 days. Then, clinician
increased the dose of methylprednisolone and immunoglobulin. The skin
symptoms improved after treatment of methylprednisolone (1.2mg/kg/d) and
immunoglobulin (600mg/kg/d) for 5 days. This is the first to report a
dose-dependent response to methylprednisolone and immunoglobulin in the
treatment of apalutamide-caused toxic epidermal necrolysis. Since the
number of prostate cancer patients treated with apalutamide increases,
it is necessary to summarize and analyze the clinical characteristics
and treatment experience in cases of severe skin adverse reactions
caused by apalutamide.
Influence of edaphic conditions on aboveground biomass in areas post-mining in the Colombian pacific
Authors: Mosquera Harley Quinto , Torres Jhon Jerley Torres , MAchado Mayira Guerrero
Published: May 2022

Mining is one of the main drivers of deforestation of tropical forests.
This activity affects the storage of aboveground biomass of these
ecosystems; and, therefore, its ability to contribute to the mitigation
of global climate change. The influence of soils on the aboveground
biomass of areas post-mining in the Colombian Pacific was evaluated. For
this, plots were established in areas post-mining and with different
successional ages (12-15 years, 30-35 years and mature forest). The
aboveground biomass and physicochemical parameters of the soil were
measured. A aboveground biomass of 15.58 t ha-1, 35.17 t ha-1, and
178.32 t ha-1 was recorded at 12-15 years, 30-35 years and mature
forest, respectively. The aboveground biomass was positively correlated
with organic matter (OM), calcium (Ca), magnesium (Mg), CICE, total
nitrogen (N) and silt; whereas, with sand, aluminum (Al) and potassium
(K) content the relationship was negative. It was evidenced that the
relationship between aboveground biomass and soils was different in each
successional age. When evaluating the changes of aboveground biomass and
soils in the successional, it was observed that the aboveground biomass
and total N increased with the recovery time; while the P and K
decreased with succession. On the other hand, the contents of OM, Mg,
Al, Ca and CICE, showed curvilinear tendencies, since they increased in
the first stages, and then in the advanced successional stages they
decreased. In summary, the results showed that the aboveground biomass
of areas post-mining was limited by multiple soil nutrients.
Healthy Diet and Regular Physical Activities for Support Endurance and Fitness
Authors:   Riga Stradins University, Plavina Liana
Published: May 2022

Balanced diet and regular physical activities are essential for support health status, physical fitness and endurance, and decrease the risk of health disorders and morbidity. Balanced diet that cover physiological requirements and needs is a very important for support physical fitness and improve the quality of recovering processes after physical load. Knowledge and skills of individuals allow making good and right choice of daily essential nutrients and keeping optimal health status and improve physical endurance. The aim of the study to analyse cadets` daily dietary habits and knowledge in nutritional education on the base of questionnaire and elaborate adapted to respondents. Cadets` daily dietary habits and knowledge in nutritional education analysed on the base of questionnaire that elaborated and adapted to respondents of study group. The study group included 73 persons of both gender (male N= 65, and female N= 7) in aged from 20 years until 35 years. Questionnaire included 22 questions about daily dietary habits, menu planning, nutrients levels, food products consumption, and composition. Only 30.5 % of respondents interested into eating adapted dietary patterns and follow to dietary recommendations. Supervision of dietary habits, water consumption, dietary patterns are essential for health capacity support done by 73.6% of respondents. Quality and quantity characteristics of dietary patterns are essential for support physical and mental activity. Balanced and moderate diet is essential for improving working capacities, diminished fatigue, improve concentration capacities and support mental activity as a result provide wellbeing and welfare of individuals.
Sonolith Extracorporeal Shock wave Lithotriptor for the Treatment of Urinary Calculi
Authors: Hwang Eun-Ju , Huh Jung-Sik
Published: May 2022

Purpose: The electroconductive lithotriptor (ECL) is a new concept for shockwave generation in which a conductive solution channels the discharge between the anode and cathode. To evaluated the effectiveness and safety of extracorporeal shock wave lithotripsy (ESWL), with a Sonolith lithotriptor, in patients with urinary stones.Materials and methods: Out of 183 patients treated, complete follow up data were available on 177 patients, between August 2001 and January 2004. The study group comprised of 105 men and 72 women (1.46:1), mean ages of 47.70 and 52.83, respectively. The number of sessions and success rates according to the stone sizes and location of stones were analysed. Auxiliary measures, other treatment modalities and complications were also reviewed.Results: The overall success rate of ESWL was 96.05% (170 of 177 patients). For the stones of calyx and renal pelvis, regardless of stone size, the ESWL was 100% successful. For upper ureter stones, the success rates ranged from 90%, for stones ll-15mm in size, to 100%, for stones less than 5mm and more than 15 mm in size. For lower ureter stones, the success rates ranged from 50%, for stones 11-15mm in size, to 100%, for stones less than 5mm and more than 15mm in size. The success rates of midureter, staghorn and multiple lesion were 100%, 66.67% and 66.67%, respectively. The number of sessions correlated the stone size. Post-ESWL complications were observed in 4 cases (2.26%).Conclusions: The success rate of ESWL was 96.05%. In our experience, ESWL has proved to be an effective and safe method to treat the urinary stones.
Characteristics of Sites and Morphology of the stomach cancer incidents in Jejudo, 2000
Authors: Bae Jong-Myon , Kang Hyun-Wook , Chang Weon young , Hong Seong-Chul , Lee Sang-Yi
Published: May 2022

Objectives: The aim of this study is to describe the distribution of sites and morphologic findings of the stomach cancer in Jejudo.Methods: From the Jejudo Regional Cancer Registry databases, the subjects were constructed by condition of the incidents of stomach cancer in 2000 among Jejudo residents. The databases also supplied the individual information of the topology and morphology on subjects.Results: The order of ranks in the topology and morphology of stomach cancer was nearly same as that of Korea Central Cancer Registry databases, which represented the nationwide condition of cancer incidence. However, there were some differences in dominant site and morphology between men and women.Conclusions: The results showed that the occurring mechanism of stomach cancer would not be different between Jejudo and other area of Korea. But some further studies to evaluate sex-related risk factors of stomach cancer should be necessary near future.
A Case of Overlap Syndrome with Rheumatoid arthritis and Polymyositis
Authors: Lim Hyung Woo , Shin Ji-Nam , Kang Hyun Wook , Kim Jinseok
Published: May 2022

Overlap syndrome is a combination of major features of more than one rheumatic disease present in the same patient such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and polymyositis. Polymyositis and RA are independent rheumatic diseases that may have a variety of overlapping clinical, radiological, and pathological manifestations according to different accepted criteria. Overlap syndrome with RA and polymyositis is rarely reported worldwide. We reported a rare case of overlap syndrome RA and polymyositis with relevant literatures.
A Case of Uterus Didelphys with Unilateral Obstructed Hemivagina and Ipsilateral Renal Agenesis
Authors: Kim Sung Yob , Choi Gukmvung
Published: May 2022

Double vagina in association with uterus didelphys and kidney agenesis is a rare Mullerian duct malformation. Progressive dysmenorrhea after menarch, abdominal pain in association with pelvic mass are common symptom. Accurate diagnosis is needed to prevent laparotomy and hemihysterectomy by mistakenly. We report a case of double vagina in association with uterus didelphys and kidney agenesis with a brief review of concerned literature.
Association between the basal core promoter mutation and the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection
Authors: Song Byung-Cheol
Published: May 2022

It has been suggested that the A to T mutation at nucleotide 1762 and/or the G 10 A mutation at nucleotide 1764 (A1762T/G1764A) in the basal core promoter (BCP) in hepatitis B virus (HBV) might be associated with the development of hepatocellular carcinoma (HCC) This study investigated the association between the A 1762T/G1764A mutations of HBV and the development of HCC by adjusting age, sex, and genotypes of HBV. A total of 106 HCC patients were studied. Age, sex, and genotype-matched patients were assigned in a 2:1:1 ratio (HCC: inactive HBsAg carrier: liver cirrhosis) The prevalence of A 1762T/G1764A mutations was higher in LC (94.3%) (P=0.004) and HCC patients (96.2%) (P <0.001) than inactive HBsAg carriers (73.6%). There was no difference in the prevalence of A 1762T/G1764A mutations between LC and HCC patients (P=0.691. In multivariate analysis, patients with cirrhosis (odds ratio rOR1, 6.0; 95% confidence interval [CI], 1.6-22.3) and HCC (OR. 9.2; 95% CI,2.8-29.5) had a greater likelihood of A 1762T/G 1764A mutations than in inactive HBsAg carriers. There was no increased likelihood of A1762T/G1764A mutations in HCC patients compared with LC patients (OR, 1.7: 95% CI, 0.4-8.4: P=0.5). These data suggest that A 1762T/G1764A mutations themselves might not be associated with the development of HCC, especially in patients with genotype C.
Novel therapeutic agents for Sjögren ’s syndrome
Authors: Kim Jinseok
Published: May 2022

Sjögren ’s syndrome (SS) is a chronic autoimmune disorder of the exocrine gland that predominantly affects salivary and lacrimal glands. The principal target is the tubular epithelium of salivary and lacrimal glands, leading to the characteristic symptoms of dry eyes and mouth. The decreased functional capacity. of the lacrimal and salivary glands which is the result of the inflammatory process and Iymphocytic infiltration observed in SS. SS is one of the three most common autoimmune disorders. but there are currently no effective systemic therapies. Recent studies have broadened our understanding of the etiopathogenesis and immunopathology of primary SS. Systemic therapy includes treatment of the underlying systemic disorder with steroidal and non-steroidal agents, disease modifying drugs, and cytotoxic therapy to address the extra glandular manifestations. In spite of intensive research in other systemic treatments including biologic therapies，there is limited evidence to support their use in routine clinical practice. This article reviews existing data on the use of local and systemic treatments for glandular and extraglandular manifestations of primary SS
1234-P: Serum Fatty Acid Composition as a Biomarker of Diabetes Development: Tokushima Cohort Study
Authors: HATA AKIKO , AKI NANAKO , ICHIHARA TAKAKO , TAMURA AYAKO , MINAGAWA TAKAKO , KUWAMURA YUMI , FUNAKI MAKOTO
Published: May 2022

Few prospective cohort studies still exist on the association between serum fatty acid (FA) proportions and the enzymes involved in their synthesis and the onset of type 2 diabetes (T2D) . Thus, the aim of the present study was to investigate whether or not serum FA proportions or FA ratios, which reflect desaturase activities, are associated with the incidence of T2D. Here we analyzed data of a prospective cohort study, which was conducted during 2010-20in Japan. A total of 872 male workers without diabetes aged over 20 years were followed up prospectively. Diabetes was defined as having either: 1) fasting plasma glucose ≥ 126 mg/dl, 2) HbA1c ≥ 6.5%, 3) medication for hyperglycemia or 4) postprandial plasma glucose ≥ 200 mg/dl during the follow-up period. We measured serum FA levels and estimated the activity of ⊿5desaturase (D5D) by calculating the ratio of serum arachidonic acid to dihomo-γ-linolenic acid (DGLA) . The subjects were also divided into two groups by the cutoff point of waist circumference (WC) ≥ 90 cm. In multivariate analysis, the HR of developing diabetes was 2.81 [95%CI: 1.to 7.15, P=0.03] in the highest quartile of serum DGLA proportion and 0.28 [95%CI: 0.to 0.90, P=0.03] in the highest quartile of D5D, compared with their lowest quartiles, respectively. In stratified analysis, the multivariate adjusted risk of diabetes was higher in participants with low D5D/low WC (2.56 [0.96 to 6.82]) or high D5D/high WC (2.77 [0.68 to 11.32]) , and was significantly higher in participants with low D5D/high WC (6.30 [1.95 to 20.33, P=0.002]) than in participants with high D5D/low WC. Our findings suggest that the combination of increased serum DGLA proportion and attenuated D5D activity is a risk factor for the incidence of diabetes in male Japanese, especially in those with WC ≥ 90 cm. Thus, the significance of serum FA measurements in predicting T2D is suggested.

Disclosure

A.Hata: None. N.Aki: None. T.Ichihara: None. A.Tamura: None. T.Minagawa: None. Y.Kuwamura: None. M.Funaki: Board Member; Mechanogenic, Inc.

Funding

Grants-in-aid for research from Tokushima Prefecture Local Government
1288-P: Increased Adipose Tissue Expression of IL-23 and Its Association with Inflammation in Individuals with High LDL Cholesterol
Authors: AHMAD RASHEED , KOCHUMON SHIHAB P. , HASAN AMAL , SINDHU SARDAR T. , AREFANIAN HOSSEIN , ALRASHED FATEMA , ALMULLA FAHD
Published: May 2022

Obesity induced chronic low-grade inflammation is a central risk factor for the development of metabolic syndrome. It has been well documented that high LDL-c induces inflammation. The proinflammatory cytokine Il-23 plays a pivotal role in the pathogenesis of inflammatory diseases. IL-23 and its relationship with LDL- c has not been reported yet. In this cross-sectional study we investigated whether adipose tissue expression of IL-23 associated with the other inflammatory mediators in individuals with high serum levels of low-density lipoprotein cholesterol (LDL-c) . Subcutaneous adipose samples were collected from 67 individuals and divided into two groups based on their serum LDL-c levels (LDL-c: < 2.9 or ≥2.9 mmol/L) . Expression of IL-23 and inflammatory markers was determined using real-time RT-PCR. Plasma lipid measurements included total cholesterol (TC) , triglyceride (TG) , high-density lipoprotein cholesterol (HDL-c) and LDL-c by standard methods, and serum adiponectin was measured by enzyme-linked immunosorbent assay (ELISA) . Individuals with increased serum levels of LDL-c showed high IL-23 expression levels in adipose tissue (p < 0.011) . AT IL-23 expression was correlated positively with LDL-c (r= 0.39, p < 0.0001) . IL-23 expression levels were positively correlated with macrophage markers (CD11c, CD68, CD86, CD127; (r ≥0.37, p≤ 0.02) , TLRs (TLR8, TLR10; (r ≥ 0.39, p ≤ 0.022) , IRF3 (r= 0.46, p< 0.01) , cytokines (TNF-α, IL-12, IL-18; (r ≥ 0.35, p ≤ 0.04) , chemokines (CXCL8, CCL3, CCL5, CCL15, CCL20; (r ≥0.43, p ≤ 0.01) . Notably, IL-23 is negatively correlated with adiponectin (r=-0.44, p < 0.03) in the individuals with high LDL-c. However, such association of IL-23 with inflammatory markers was not found in the individuals with low LDL-c.

In conclusion, adipose tissue IL-23 may be a biomarker for inflammation progression in the individuals with high LDL-c and could be used as a therapeutic target for the treatment of metabolic syndrome.

Disclosure

R.Ahmad: None. S.P.Kochumon: None. A.Hasan: None. S.T.Sindhu: None. H.Arefanian: None. F.Alrashed: None. F.Almulla: None.

Funding

Kuwait Foundation for Advancement of Sciences (RA-2010-003)
1296-P: Adipose Tissue Insulin Resistance in RISE: Divergence between Youth and Adults, and Females and Males
Authors: ARSLANIAN SILVA A. , CAPRIO SONIA , NADEAU KRISTEN J. , TEMPLE KARLA A. , WANDER PANDORA , CREE-GREEN MELANIE , HANNON TAMARA S. , KAHN STEVEN E. , GHORMLI LAURE EL ,   THE RISE CONSORTIUM
Published: May 2022

Adipose tissue insulin resistance (Adipose-IR) is a pathophysiological component of type 2 diabetes (T2D) . We examined:1) Adipose-IR (calculated as fasting insulin x free fatty acids [FFAs]) in youth and adults with impaired glucose tolerance (IGT) or recently diagnosed T2D;2) sexual dimorphism in Adipose-IR in each age group;3) the association of Adipose-IR with β-cell function (βCF) in youth and adults.In RISE, 91 youth [BMI 36.7±24.4 (SD) kg/m2, 59.3% IGT] and 355 adults [BMI 35.1±5.1 kg/m2, 70.7% IGT] had baseline Adipose-IR measured. The relationship of Adipose-IR to hyperglycemic-clamp-derived-βCF and insulin sensitivity (IS) were assessed. Adipose-IR was 2.2-fold higher in youth vs. adults (p<0.001; Fig A) , higher in females than males in both age groups (p<0.05; Fig B) , and higher in T2D vs. IGT in youth (p<0.05; Fig C) . In adults, Adipose-IR correlated positively with all clamp-derived βCF parameters, while in youth it only correlated with steady-state C-peptide. In both age groups, Adipose-IR correlated inversely with clamp-IS. Youth, whether males or females, have 100% higher adipose tissue insulin resistance compared with adults. Moreover, within each age group, females have greater Adipose-IR than males. The higher Adipose-IR in youth vs. adults across a wide range of BMI is suggestive of other yet unknown factors, possibly puberty-related, potentially modulating Adipose-IR.

Disclosure

S.A.Arslanian: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Other Relationship; AstraZeneca, Research Support; Eli Lilly and Company, Novo Nordisk. T.Consortium: None. S.Caprio: None. K.J.Nadeau: None. K.A.Temple: None. P.Wander: None. M.Cree-green: None. T.S.Hannon: Advisory Panel; Eli Lilly and Company. S.E.Kahn: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc. L.El ghormli: None.

Funding

American Diabetes Association (1-20-RISE-01) ; NIDDK, Department of Veterans Affairs, and Kaiser Permanente Southern California
1299-P: Novel Tools to Dissect the Metabolic Roles of Central and Peripheral Dopamine D2-Like Receptors
Authors: BONIFAZI ALESSANDRO , ELLENBERGER MICHAEL P. , FARINO ZACHARY , RAIS RANA , MANTILLA-RIVAS JOSÉ , ASLANOGLOU DESPOINA , JANOWSKY AARON , SLUSHER BARBARA , SCHWARTZ GARY J. , NEWMAN AMY H. , FREYBERG ZACHARY
Published: May 2022

Dopamine (DA) D2-like receptors are key physiological modulators of metabolism under healthy and disease states. While D2-like receptors are expressed both in the central nervous system (CNS) and within the periphery, the respective metabolic roles of CNS and peripheral D2-like receptors remain poorly understood. Therefore, to disentangle these CNS versus peripheral contributions, we synthesized a series of new peripherally-limited D2-like receptor agonists. We selected bromocriptine methiodide, a quaternary methiodide (MeI) analog of bromocriptine as our lead compound based on preservation of its binding and functional efficacy at D2-like receptors and its diminished blood brain barrier permeability. Systemic administration of bromocriptine, with unrestricted access to both CNS and peripheral targets, significantly improved both insulin sensitivity and glucose tolerance in obese, insulin-resistant mice in vivo. In contrast, metabolic improvements were abolished when bromocriptine’s access was restricted either to the CNS through intracerebroventricular administration or to the periphery via the peripherally-limited bromocriptine MeI. Our findings therefore suggest that the coordinated actions of both CNS and peripheral D2-like receptors are required for bromocriptine’s therapeutic efficacy in correcting dysglycemia. Overall, bromocriptine MeI may serve as a useful new tool to further dissect these mechanisms of peripheral DA signaling.

Disclosure

M.P. Ellenberger: None. Z. Farino: None. J. Mantilla-Rivas: None. B. Slusher: None.

Funding

Department of Defense (PR141292) , National Institutes of Health (R01DK124219)
1420-P: Gestational Diabetes Glyburide Treatment and Glycemic Control: Associations with Risk of Subsequent Child Obesity
Authors: JOSEFSON JAMI L. , SUN BAIYANG , GREENBERG MARA , GREENSPAN LOUISE , DAVIS JAIMIE N. , METZGER BOYD E. , LO JOAN C. , FAITH MYLES S. , LOWE WILLIAM , GUNDERSON ERICA P.
Published: May 2022

Gestational diabetes mellitus (GDM) increases offspring obesity risk. GDM severity, treatment, glycemic control and postnatal feeding behaviors increase or alleviate child obesity risk. This study sought to evaluate GDM treatment (glyburide vs. diet) and glycemic control related to overweight/obesity risk in toddlers of mothers with GDM. In a diverse prospective cohort of 786 GDM mother-child dyads (78% minority: Hispanic, Asian, Black and 22% White) , we measured prenatal glycemic control (daily home testing) , GDM severity, treatment, postnatal diet, and child BMI at age 2-5 y. Maternal glycemia was categorized as optimal control (≥80% of fasting & post-prandial blood glucose tests met target) or not optimal control (<80%) . Child weight and height was categorized by BMI percentiles (age, sex) ; normal weight (<85th) , overweight (85-95th) or obese (>95th) . Multinomial logistic regression estimated odds ratios (OR) 95%CI of overweight and obesity associated with treatment and glycemic control adjusted for prenatal, newborn and postnatal covariates. On average, mothers were 33.3 (SD 4.7) y at delivery with prepregnancy BMI 29.3 (7.1) kg/m2 and 74% had optimal glycemic control. Children were age 40.5 (6.3) months at BMI measurement; 76% normal weight, 13% overweight and 11% obese. Glyburide was associated with higher risk of obesity, 1.75 (1.05-2.91) independent of glycemic control. Stratifying by glycemic control, glyburide was associated with borderline higher odds of obesity (2.79, 0.94-8.33, p=0.065) among those not in optimal control adjusted for GDM severity, pre-pregnancy BMI, sociodemographic, newborn size and infant diet. Longer breastfeeding was associated with lower odds of obesity (0.83, 0.75-0.93) and sugary drink or fruit juice intake birth to 1 y was associated with higher odds of obesity (4.14, 1.06-16.19) . Glyburide treatment of GDM and sugary infant diet may contribute to obesity in young children if maternal glycemic control was not optimal.

Disclosure

J.L.Josefson: n/a. E.P.Gunderson: None. B.Sun: None. M.Greenberg: None. L.Greenspan: None. J.N.Davis: None. B.E.Metzger: None. J.C.Lo: None. M.S.Faith: None. W.Lowe: None.

Funding

National Institutes of HealthRDK122700
1435-P: Identifying the Continuing Educational Needs of U.S. Physicians in Managing Patients with T2DM and Obesity
Authors: CERENZIA WENDY , STACY SYLVIE , WILEY SHERETA
Published: May 2022

Most people with type 2 diabetes (T2D) also have obesity and the prevalence of both continues to increase. This study sought to understand approaches of endocrinologists (ENDOs) and primary care physicians (PCPs) in managing patients with both T2D and obesity to identify areas where physicians may benefit from continued education. A patient case-based survey assessing approaches to managing patients with T2D and obesity was fielded in October 2021, with responses from US-practicing ENDOs (n=181) and PCPs (n=350) . Survey questions included free response, multiple choice, and rating scales. Descriptive analysis was performed. When presented with a patient with poorly controlled T2D, obesity, and other clinical concerns (eg, elevated blood pressure (BP) , hyperlipidemia, and cigarette use) , improving HbA1c was among the top three goals in 93% of physicians, while BP control was a top goal for just over half and weight loss was a top goal for only 45%. In another patient presenting with T2D and unchanged BMI of 37 kg/m2, despite 6 months of lifestyle intervention, 9% of ENDOs and 15% of PCPs would continue current weight management without change. If the patient’s BMI been higher at 47 kg/m2, both ENDOs and PCPs were more likely to begin a weight loss medication and PCPs were more likely to defer management to a specialist. Most physicians (63%) agreed that effectively managing T2D leads to weight loss and 83% agreed that GLP-1 receptor agonists are effective for obesity. However, only half of ENDOs and 29% of PCPs have a certain percentage of body weight loss goal when managing obesity in patients with T2D. Further, 19% of ENDOs and 30% of PCPs reported that they trial diet, exercise, and behavioral modifications for 6 months or longer. Results show physicians may benefit from continuing education focused on the importance of addressing weight in combination with glycemic control for patients with T2D and obesity, and the benefits of pharmacotherapy as a component of weight management.

Disclosure

W.Cerenzia: None. S.Stacy: None. S.Wiley: None.
192-OR: T-Type Calcium Channel Cav3.2 in GABAergic Neurons Regulates Rhythmic Glucose Metabolism
Authors: FENG BING , HARMS JERNEY , XU PINGWEN , ZHOU WENJUN , SUN ZHENG , HE YANLIN
Published: May 2022

Systemic insulin sensitivity shows a diurnal rhythm with a peak upon waking. The GABAergic (γ-aminobutyric acid-producing) neurons in the suprachiasmatic nucleus (SCN) (SCNGABA neurons) were reported to control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice in earlier work1. SCNGABA neural firing activity displays a diurnal rhythm, with the intrinsic ionic mechanism underlying this temporal pattern not completely understood. Here we provided evidence supporting a role of the T type voltage-gated calcium ion channel subunit 3.2 (Cav3.2) in SCNGABA neurons in regulating rhythmic neural firing and glucose homeostasis. We found that Cav3.2 global knockout (Cav3.2KO) mice displayed disrupted diurnal rhythm of blood glucose levels. Selective deletion of Cav3.2 in the SCNGABA neurons abolished the oscillatory firing activity of SCNGABA neurons and led to glucose intolerance. Furthermore, our real-time calcium imaging data in freely moving mice showed that SCN GABA neuronal activity displayed a circadian rhythm pattern in WT control mice but not Cav3.2KO mice or mice with Cav3.2 selectively deleted in the SCNGABA neurons. These findings provide insights into how the calcium ion channel regulates the central circadian clock and glucose metabolism, with implications in the extended dawn phenomenon in type 2 diabetes.

Keywords: Type 2 diabetes, calcium channel, Cav3.2, GABA neurons, circadian rhythm

Reference: 1 Ding, G. et al. REV-ERB in GABAergic neurons controls diurnal hepatic insulin sensitivity. Nature 592, 763-767, doi:10.1038/s41586-021-03358-w (2021) .

Disclosure

P. Xu: None. W. Zhou: None. Z. Sun: None. Y. He: None.

Funding

NIH (P20 GM135002)
221-OR: Safety and Effectiveness of Insulin Aspart vs. Other Bolus Insulins in Women with Preexisting Type 1 Diabetes during Pregnancy: A Post Hoc Analysis of the EVOLVE Study
Authors: MATHIESEN ELISABETH , ALIBEGOVIC AMRA CIRIC , ANIL GAYATHRI , DUNNE FIDELMA P. , HALASA TARIQ , IVANISEVIC MARINA , MCCANCE DAVID R. , NORDSBORG RIKKE BAASTRUP , DAMM PETER ,   ON BEHALF OF THE EVOLVE STUDY GROUP
Published: May 2022

Aims: This post hoc analysis of the real-world EVOLVE study investigated safety and effectiveness of insulin aspart (IAsp) vs. other bolus insulins in pregnant women with pre-existing type 1 diabetes.

Methods: Maternal, pregnancy and infant outcomes were assessed in women receiving bolus insulins on enrolment and during pregnancy in a prospective cohort, by estimating risk differences following adjustment for potential confounders using propensity score matching.

Results: Insulin treatment in early pregnancy and maternal, pregnancy and infant outcomes are presented (Table) . In total, 1434 women were treated with IAsp and 4with other bolus insulins on enrolment. Significantly lower mean A1c values in the third trimester were observed with IAsp vs. other bolus insulins (adjusted % point difference -0.16% [95% CI -0.28;-0.05]; p=0.005) . No significant differences were seen with IAsp vs. other bolus insulins in the risk of adverse maternal-fetal outcomes including major maternal hypoglycemia, abortion, pre-term delivery, pre-eclampsia, birthweight large for gestational age, major congenital malformations and perinatal or neonatal death, in the matched dataset.

Conclusion: Compared with other bolus insulins, IAsp was associated with significantly lower A1c during the third trimester and a similar risk of adverse pregnancy outcomes.

Disclosure

E.Mathiesen: Consultant; Novo Nordisk A/S, Speaker's Bureau; Novo Nordisk A/S. On behalf of the evolve study group: n/a. A.Alibegovic: Employee; Novo Nordisk A/S, Novo Nordisk A/S. G.Anil: Employee; Novo Nordisk Global Business Services. F.P.Dunne: None. T.Halasa: Employee; Novo Nordisk A/S. M.Ivanisevic: None. D.R.Mccance: None. R.Baastrup nordsborg: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. P.Damm: Advisory Panel; Novo Nordisk A/S.

Funding

Novo Nordisk A/S
277-OR: Increased Liver Fat Is Associated with Severe Metabolic Perturbations in Men Born with a Low Birth Weight
Authors: ELINGAARD-LARSEN LINE OHRT , JUSTESEN LOUISE , VILLUMSEN SOFIE O. , THUESEN ANNE CATHRINE B. , STØRLING JOACHIM , SPARKS LAUREN M. , KIM MIN , LEGIDO-QUIGLEY CRISTINA , DANIELSEN ELSE R. , HANSEN TORBEN , BRØNS CHARLOTTE , VAAG ALLAN A.
Published: May 2022

Background: Ectopic fat deposition resulting from impaired subcutaneous adipose tissue expandability may take center stage in the pathophysiological events linking low birth weight (LBW) with increased risk of developing Type 2 diabetes (T2D) . However, the extent to which adult LBW subjects exhibit increased hepatic fat accumulation is controversial.

Methods and Results: Using 1H MR spectroscopy, we found a significantly increased hepatic fat content (P=0.014) in 26 early middle-aged and non-obese LBW males compared with 21 BMI- and age-matched normal birth weight (NBW) controls. Interestingly, 5 LBW (20%) versus no NBW subjects, had previously unrecognized overt nonalcoholic fatty liver disease (NAFLD) with a median hepatic fat content of 9.45%. The LBW w/NAFLD displayed widespread metabolic changes compared with both NBW and LBW w/o NAFLD subjects including hepatic insulin resistance (P=0.02) , increased fasting plasma triglycerides (TGs) (P=0.03) , cholesterol (P=0.05) , leptin, C-peptide and GLP-1 levels, as well as decreased adiponectin levels (P-range: 0.02-0.007) . Among 65 distinct metabolites and 279 lipids identified by untargeted serum metabolomic and lipidomic analyses, the levels of 7 metabolites including ornithine and citrulline, were different (P<0.05) between LBW w/NAFLD and NBW subjects, pointing towards increased urea cycling in the LBW w/NAFLD subjects. Moreover, the LBW w/NAFLD subjects displayed disproportionately increased levels of phosphatidylcholines and TGs (P<0.05) , with both lipid species qualitatively changed in the LBW w/NAFLD subjects consisting of an increased amount of long chain fatty acids as well as fewer double bonds. These structural lipid characteristics are known to be associated with T2D.

Conclusion: The data support a role for ectopic fat deposition in the pathophysiological events and trajectories linking LBW with increased risk of developing T2D and associated cardiometabolic traits including dyslipidemia.

Disclosure

L.Elingaard-larsen: None. T.Hansen: None. C.Brøns: Stock/Shareholder; Novo Nordisk. A.A.Vaag: Stock/Shareholder; AstraZeneca. L.Justesen: None. S.O.Villumsen: None. A.B.Thuesen: None. J.Størling: None. L.M.Sparks: None. M.Kim: None. C.Legido-quigley: None. E.R.Danielsen: None.

Funding

Novo Nordisk Foundation (NNF15OC0016692) , Aase and Ejnar Danielsens Fond, Augustinus Foundation, Simon Spies Fonden, TrygFonden.
3-LB: A Free-Living Walking-Based Exercise Programme Improves HbA1c in Individuals with Obesity, with Additional Benefits of Nutritional Status on Metabolic Health
Authors: BARRETT JENNIFER S. , SHEPHERD SAM O. , WAGENMAKERS ANTON , CUTHBERTSON DANIEL , STRAUSS JULIETTE
Published: May 2022

Background: Regular exercise improves insulin resistance and glycaemic control, but ‘real world’ programmes are not universally effective. Laboratory studies show that post-breakfast exercise improves postprandial glucose excursions with subsequent meals while pre-breakfast exercise augments whole-body fat oxidation. Whether these acute effects translate to greater changes in metabolic health with exercise training is not clear.

Aim: To investigate if exercise before/after breakfast leads to differential improvements in metabolic health and/or postprandial glycaemic response.

Methods: Thirty-four people with obesity (43±12 y, BMI 35.1±5.1 kg/m2) undertook a 12-week walking-based programme, with two continuous and two interval sessions each week (for 30-60 min, at 50% HRmax vs. alternating 3 min at 85% HRmax and 3 min 50% HRmax respectively) . Participants exercised before (FAST) or after (FED) breakfast (n=17 per group) . Body composition, HbA1c, blood lipids and liver transaminases (ALT/AST) were assessed pre- and post-intervention. Postprandial glucose responses were assessed in week 1 and 12 using flash glucose monitoring.

Results: Adherence (FAST: 93%, FED: 95%) and compliance (FAST: 85%, FED: 88%) was high in both groups. Body mass, BMI, waist-to-hip ratio and HbA1c decreased similarly between groups (all P >0.001, HbA1c P=0.01) . However, ALT decreased after FAST (-16%; P=0.001) , but not FED training (-2%; P=0.720) . In week 1, continuous exercise lowered postprandial responses to lunch (FAST; P=0.064) and dinner (FED; P=0.047) versus interval exercise. In week 12, the postprandial glucose responses to lunch and dinner after interval exercise were lower compared to week 1 (P=0.008) .

Conclusions: Free living exercise, pre- or post-breakfast improved body composition, glycaemic control and enhanced the postprandial-lowering effect of interval exercise but pre-breakfast exercise had a greater impact on liver biochemistry. Exercise, pre-breakfast, may be advantageous for people with obesity and fatty liver.

Disclosure

J. S. Barrett: None. S. O. Shepherd: None. A. Wagenmakers: None. D. Cuthbertson: Other Relationship; AstraZeneca, Novo Nordisk. J. Strauss: None.
430-P: Remnant Cholesterol Predicts Major Cardiovascular Events in Patients with Coronary Artery Disease Both among Patients with Type 2 Diabetes and in Nondiabetic Individuals
Authors: MADER ARTHUR , SPRENGER LUKAS , VONBANK ALEXANDER , LARCHER BARBARA , MAECHLER MAXIMILIAN , LEIHERER ANDREAS , MUENDLEIN AXEL , DREXEL HEINZ , SAELY CHRISTOPH H.
Published: May 2022

Remnant cholesterol, which is calculated as total cholesterol minus LDL cholesterol minus HDL cholesterol has attracted interest as a marker of cardiovascular event risk. The power of remnant cholesterol to predict major cardiovascular events (MACE) in patients with established coronary artery disease is unclear and is addressed in the present study. We enrolled 1472 consecutive patients with established coronary artery disease. Prospectively, cardiovascular events were recorded over a mean follow-up period of 8.0±5.03 years. At baseline, remnant cholesterol was significantly higher in patients with T2DM (n=446) than in non-diabetic subjects (27±24 vs. 21±23 mg/dl; p<0.001) . During follow-up, 493 of our patients suffered MACE; the event rate was significantly higher in patients with T2DM than in non-diabetic subjects (62.5 vs. 37.5%; p<0.001) . Remnant cholesterol in Cox regression models adjusting for age, sex, hypertension, smoking, body mass index and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.17 [1.09-1.28], p<0.001) , and in patients with T2DM as well as in non-diabetic subjects (standardized adjusted HRs 1.24 [1.07-1.44], p=0.0 and 1.14 [1.02-1.26], p=0.017, respectively) . From our data we conclude that remnant cholesterol in patients with established coronary artery disease predicts MACE both among patients with T2DM and among non-diabetic subjects.

Disclosure

A.Mader: None. L.Sprenger: None. A.Vonbank: None. B.Larcher: None. M.Maechler: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None. C.H.Saely: None.
53-LB: Youth and Parents’ Experiences Using the Insulin-Only Bionic Pancreas
Authors: HOWARD KELSEY R. , GARZA KIMBERLY P. , FELDMAN MARISSA , WEISSBERG-BENCHELL JILL ,   BIONIC PANCREAS RESEARCH GROUP
Published: May 2022

The Insulin-only Bionic Pancreas (BP) Pivotal Trial compared the BP initialized only with body weight vs. standard-of-care (SC) . The BP autonomously determines all insulin doses. Meals are announced without carbohydrate counting. For youth aged 6-17 the mean adjusted difference of HbA1c at 13 weeks between BP and SC was -0.5% (95% CI: -0.7, -0.2, P<0.001) : percent of time <54 mg/dl was not different between groups. Focus groups with youth who used the BP and their parents were conducted at the trial’s end. Youth reported positive experiences: improved A1c, increased independence, less parent worry and texting about glucose, less family diabetes conversations, less cognitive and emotional burden, less time managing diabetes, less worries about nighttime lows, more sleep, easier mealtimes, and easier school management. Children felt parents trusted them more and parents spent less time managing glucose at night. Some reported increased lows and others less. Some found challenges with exercise while others found it managed exercise well. Some found the BP took too long to learn their body and to correct high glucose. Concerns included: not having a snack announcement, site change frequency, small insulin capacity, lack of insulin-on-board information, poor backlighting, screen timing out too fast, and not having a clip or being waterproof. Parents reported positive experiences: pride in the child’s independence, less cognitive and emotional burden, less time managing diabetes, less diabetes conversations, and better school experiences. Most reported improved sleep and easier mealtimes. Some found challenges with exercise while others found it managed exercise well. Some found improved TIR and less lows while others found more lows or delays in correcting highs. Some found the system learned their child while others felt the system struggled. Parents were concerned that the low insulin warning did not go to parents’ phones. Youth and parent perspectives highlight experiences in learning and using the BP and offer insights related to multiple psychosocial domains which can guide future innovations.

Disclosure

K. R. Howard: None. K. P. Garza: None. M. Feldman: None. J. Weissberg-benchell: None. Bionic pancreas research group: n/a.

Funding

National Institute of Diabetes Digestive and Kidney Diseases (#1UC4DK108612-01)
651-P: Continuous Glucose Monitoring in Primary Care: Explaining Characteristics Associated with CGM Prescription
Authors: OSER TAMARA , HALL TRISTEN , WARMAN MEREDITH K. , FILIPPI MELISSA K. , MANNING BRIAN , CALLEN ELISABETH , DICKINSON L. MIRIAM , MICHAELS LEANN C. , NEASE DONALD E. , OSER SEAN
Published: May 2022

Background: Continuous glucose monitors (CGM) provide clearer, more actionable data than self-monitoring of blood glucose and are associated with improved outcomes (e.g., reduced HbA1c) . Barriers to endocrinology care create disparities in CGM access. Expanding CGM use in primary care can improve outcomes and reduce disparities. We explored barriers and facilitators to CGM use in primary care.

Methods: Mixed-methods sequential explanatory study of U.S. primary care clinicians, with survey (n=632) followed by semi-structured interviews (n=55) .

Analysis: Multivariable linear and logistic regression, followed by rapid qualitative analysis of interviews to offer a deeper understanding of quantitative data.

Results: Qualitative analysis helped explain quantitative findings that residents were less likely than others to have prescribed CGM but had greater intent to prescribe: lack of resident knowledge about CGM hindered prescribing. While quantitative analysis found clinicians >40 miles from endocrinologists were somewhat more likely to prescribe CGM (coef .18, p=.041) , qualitative analysis offered nuance: results were mixed, with many interviewees noting distance as a barrier due to having no endocrinologist to help manage the CGM; for others, proximity was a barrier because they referred patients to endocrinology for CGM rather than prescribing themselves. While survey results showed an association between higher proportion of Medicare patients and greater confidence in using CGM to manage diabetes, qualitative themes around prescribing barriers included lack of public insurers covering CGM, suggesting that, for some, having Medicare may make CGM prescription more difficult.

Conclusion: Primary care clinicians can benefit from education and support for CGM use. Targeting recent trainees and clinicians in regions lacking endocrinology could increase CGM use, extending its benefits to more people with diabetes.

Disclosure

T. Oser: Advisory Panel; Cecelia Health, Dexcom, Inc. T. Hall: None. M.K. Warman: None. M.K. Filippi: None. B. Manning: None. E. Callen: None. L. Dickinson: None. L.C. Michaels: None. S. Oser: Advisory Panel; Cecelia Health, Children with Diabetes, Inc., Dexcom, Inc. Consultant; American Diabetes Association, Association of Diabetes Care & Education Specialists, Jaeb Center for Health Research. Research Support; American Academy of Family Physicians, Leona M. and Harry B. Helmsley Charitable Trust.

Funding

The Leona M. and Harry B. Helmsley Charitable Trust