bluuebunny/crossref_metadata_2025_split huggingface dataset:
1158-P: The Effect of Surgical Weight Loss on Diabetic Complications in the Severely Obese
Authors: REYNOLDS EVAN L. , WATANABE MAYA , ELAFROS MELISSA , FELDMAN EVA L. , CALLAGHAN BRIAN C. 
Published: May 2022

The aim of this study was to determine the effect of surgical weight loss on chronic kidney disease (CKD) , retinopathy, and cardiovascular autonomic neuropathy (CAN) in people with severe obesity.
We completed a prospective cohort study of participants with severe obesity who underwent bariatric surgery. At baseline and at 2 years following bariatric surgery, participants had outcome measurements and underwent metabolic phenotyping. The updated National Cholesterol Education Program (NCEP) criteria were used to define the metabolic syndrome (MetS) and its individual components. The primary outcome for CKD was the estimated Glomerular Filtration Rate (eGFR) , retinopathy was mean deviation on frequency doubling technology testing, and CAN was the expiration/inspiration (E/I) ratio.
Among 138 baseline participants, 80 (mean (standard deviation) age: 45.6 (11.2) years, 72.5% female) completed 2 years of follow-up. Participants lost 31.9 (17.5) kg. All metabolic syndrome components improved with the exception of blood pressure. CKD worsened (eGFR: baseline: 85.6 (19.7) , 2-year: 82.6 (23.1) , p=0.04) , retinopathy was stable (mean deviation: baseline: −1.2 (4.3) , 2-year: −1.6 (4.2) , p=0.53) , and CAN was stable (E/I ratio: baseline: 1.18 (0.12) , 2-year: 1.18 (0.11) , p=0.95) following bariatric surgery. Greater reduction in fasting glucose was associated with significant improvements to primary CKD (eGFR: point estimate (PE) : -0.22, 95% Confidence Interval (CI) : −0.38, −0.06) and retinopathy (mean deviation: PE: -0.04, 95%CI: −0.08, −0.004) , after adjusting for age, sex, and baseline BMI.
Surgical weight loss was associated with improvements in all metabolic parameters except blood pressure. Despite the improvement to metabolic risk factors, CKD significantly worsened during follow-up, whereas retinopathy and CAN outcomes remained stable. This stability may be an improvement compared to the natural progression of these conditions, however controlled trials are needed to confirm.

Disclosure
E.L.Reynolds: None. M.Watanabe: None. M.Elafros: None. E.L.Feldman: None. B.C.Callaghan: None.

Funding
The project described was supported by Grant Number P30DK020572 (MDRC) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) . Dr. Callaghan is currently funded by a NIH NIDDK R-award (DK115687) . Dr. Reynolds was supported by NIH T32 (NS0007222) . Dr. Feldman was supported by an NIH NIDDK DP3 award (DK094292) and is currently funded by NIH NIDDK (R24082841 and R21 NS102924) and the Novo Nordisk Foundation Center for Basic Metabolic Research (NNF14°C0011633) . Dr. Reynolds, Dr. Callaghan, and Dr. Feldman receive support from the NeuroNetwork for Emerging Therapies and the A. Alfred Taubman Research Institute at the University of Michigan.
124-OR: HbA1c Variability Is Independently Associated with Lower-Extremity Amputation and Death among Patients with Diabetic Foot Ulcers
Authors: JAGANNATHAN RAM , SCHECHTER MARCOS COUTINHO , ALVAREZ JESSICA A. , BLANCO GERARDO , RAJANI RAVI , SANTAMARINA GABRIEL , UMPIERREZ GUILLERMO E. , FAYFMAN MAYA 
Published: May 2022

Background: Higher HbA1c on admission is associated with increased amputation risk in patients with diabetic foot ulcers (DFUs) ; however, the impact of long-term glycemic control and glycemic variability after hospital discharge on amputation risk is unclear.
Methods: We performed retrospective analyses of hospitalized patients with a DFU who were followed for &gt;1 year after index admission with at least two HbA1c measurements and &gt; 1-year follow-up (n=479) . Using multivariable logistic regression analysis, we examined the associations of HbA1c measures [HbA1c nadir change (difference between the baseline HbA1c and the single lowest prospective HbA1c level during the follow-up) , standard deviation (SD-HbA1c) , mean HbA1c change, and HbA1c variability score (HVS) ] with a composite outcome [minor and major lower extremity amputations (LEA) and mortality].
Results: The median age was 55.3 (IQR: 47.9, 62.8) years. During a mean follow-up of 2.4 years, 250 (52.2%) patients had a LEA or death [minor LEA: 116 (24.2%) ; major LEA: 113 (23.4%) ; death: 21 (4.4%) ]. In the fully adjusted model, HbA1c variability metrics were significantly associated with higher LEA and/or death rates, except HVS (Table) .
Conclusion: Our findings indicate that visit-to-visit HbA1c variability, especially HbA1c nadir change, and SD-HbA1c are independent biomarkers of LEA risk in patients with DFU.

Disclosure
R.Jagannathan: None. M.Schechter: None. J.A.Alvarez: None. G.Blanco: None. R.Rajani: None. G.Santamarina: None. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. M.Fayfman: None.

Funding
Emory Medical Care Foundation to MCS and MF
1257-P: Associations of Five-Year Type 1 Diabetes (T1D) Risk with Predictors Using Cross-Sample Validation
Authors: ISMAIL HEBA M. , CUTHBERTSON DAVID D. , ATKINSON MARK A. , REDONDO MARIA J. , SOSENKO JAY ,   TYPE 1 DIABETES TRIALNET
Published: May 2022

We studied 5-yr T1D risk associations using a series of risk factors in an autoantibody positive population of 6,020 in the TrialNet Pathway to Prevention study (PTP) study. We used data from 25 subgroups developed from 5 AUC glucose (&lt;115;115-&lt;130;130-&lt;145;145-&lt;160; ≥160 mg/dl) and 5 AUC C-peptide (&lt;3.5;3.5-&lt;5.0;5.0-&lt;6.5;6.50-&lt;8.0; ≥8.0 ng/ml) categories from baseline OGTT data. Subgroup boundaries were set to provide quantitative power for proper statistical analysis (range: 138 to 487) . We assessed 5-yr T1D risk associations with risk factors among the 25 subgroups using correlation coefficients and linear regression analysis (slope: 5-yr risk/risk factor prevalence) . The table shows the strongest correlation of 5-yr T1D risk with IA-2A (r=0.96) . This was consistent in split sample analyses, as were the linear regression indices (Sample 1 vs. Sample 2: r=0.96 vs. 0.93; intercept=-0.186 vs. -0.228; slope=0.014 vs. 0.015) . Using the regression indices for a cross-sample validation (i.e., predicting 5-yr risk for one sample using its IA-2A prevalence and the other sample's regression indices) , the predicted/actual 5-yr risk was 0.27/0.26 for Sample 1 and 0.27/0.23 for Sample 2.
In summary, in PTP subgroups, 5-yr T1D risk correlated strongly with IA-2A. Further, regression indices predicted 5-yr T1D risk in cross-sample validation, suggesting a tight linkage between active β-cell decline and IA-2A.

Disclosure
H.M.Ismail: n/a. D.D.Cuthbertson: None. M.A.Atkinson: None. M.J.Redondo: Advisory Panel; Provention Bio, Inc. J.Sosenko: None. Type 1 diabetes trialnet: n/a.

Funding
NIH
13-OR: Cystic Fibrosis Donors Exhibit Striking Decrease in Pancreatic Islet and Exocrine Capillaries
Authors: CASTILLO JOSEPH J. , APLIN ALFRED , AKTER REHANA , HULL-MEICHLE REBECCA L. 
Published: May 2022

Glucose intolerance and insulin deficiency are common features of cystic fibrosis (CF) , with nearly half of adult CF patients developing CF-related diabetes (CFRD) , but the underlying pathophysiology remains poorly understood. Extensive destruction of the exocrine pancreas occurs in most CF patients. However, islets are still readily detectable, suggesting β cell loss is not the major driver of impaired insulin release. Islets are normally highly vascularized, and islet capillaries are the source of key growth factors that maintain β cell health and function. Islet capillary morphology is altered in type 1 and type 2 diabetes, with increased capillary density and/or vessel thickening being observed. In the present study we aimed to determine whether islet capillaries are also disrupted in CF/CFRD. Pancreas sections (8 control and 8 CF/CFRD, age-matched) were stained for CD31, a marker of vascular endothelial cells. Islets in microscopy images were manually identified (17.8±2.8[SEM] per sample) and CD31-positive area within islet and exocrine was quantified. Mean islet cross-sectional area did not significantly differ between CF and non-CF pancreas specimens. CD31 positive area, expressed as a fraction of islet area, was significantly decreased in CF pancreas specimens (2.8±0.9% vs. 6.1±1.2%; p=0.05) . Islet capillary density (the number of CD31+ objects normalized to islet area) was also decreased (0.88±0.17x103/μm2 vs. 3.8±0.57x103/μm2; p=0.0004) , as was exocrine tissue CD31 positive area (0.17±0.03% vs. 1.5±0.23%; p&lt;0.0001) . Our data demonstrate a significant deficit in islet and pancreatic vascularity in CF/CFRD. This contrasts markedly with the increase in islet capillary density seen in both T1D and T2D and underscores the presence of distinct features of islet morphology that characterize CF. Given that islet capillaries support β-cell function and survival, their loss likely contributes to impaired β-cell function.

Disclosure
J.J.Castillo: None. A.Aplin: None. R.Akter: None. R.L.Hull-meichle: Research Support; Casma Therapeutics.

Funding
Cystic Fibrosis Foundation Fellowship (CASTIL20F0)
1304-P: Quantification of Preproinsulin and Insulin Isoforms Derived from Upstream Open Reading Frames in Human Clinical Samples by Selected Reaction Monitoring Assay
Authors: LIU QING-RONG , ZHU MIN , GHOSH PARITOSH , CHIA CHEE W. , EGAN JOSEPHINE M. 
Published: May 2022

We recently uncovered a novel human proinsulin containing a amino-acid Cα-peptide and upstream open reading frame (uORF) isoforms whose transcription is initiated from an alternative INS promoter upstream of the conventional INS promoter (Liu et al, 2021, Diabetes, PMID: 34649926) . Post-translational protease processing of preproinsulin is reported to be involved in the pathogenesis of diabetes. However, there are no sensitive and specific assays to quantify unprocessed preproinsulin and insulin originating from uORFs in clinical samples. Hence, we developed an LC-MS/MS based Selected Reaction Monitoring (SRM) assay to quantify the fragments of processed and unprocessed signal peptide in plasma, pancreatic islets, cerebrospinal fluid (CSF) , and brain. Trypsinization of insulin B-chain generates two peptides: peptide-B1 (pep-B1: FVNQHLCGSHLVEALYLVCGER) that requires cleavage by signal peptidase (SPase) , and peptide-B2 (GFFYTPK) that does not require SPase. As a result, the pep-B1 derived from preproinsulin cannot be detected if the signal peptide fails to be cleaved by SPase. Therefore, the pep-B1 could serve as a surrogate for preproinsulin since its quantity is correlated with the signal peptide cleavage efficiency. We also developed an SRM peptide panel to detect and measure insulin derived from uORF isoforms. Our SRM assay allows for measurement of insulin A- and B-chains separately in plasma samples, and levels highly correlate with ELISA after a glucose stimulus to secretion. We detected more unconventional uORF-derived insulin in CSF and cerebrum in comparison with plasma and islets. Furthermore, we found that uORF levels were significantly altered in middle temporal gyrus (MTG) of postmortem brains of Alzheimer Disease patients compared to control MTGs. The newly developed SRM assay could serve to determine preproinsulin and insulin uORF isoforms in clinical biofluid and tissue samples.

Disclosure
Q.Liu: None. M.Zhu: None. P.Ghosh: None. C.W.Chia: None. J.M.Egan: None.

Funding
This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging
1313-P: Short-Chain Fatty Acids Decrease Food Intake through Free Fatty Acid Receptors in the Brain
Authors: LUO PEI , XU PINGWEN , FENG BING , YE HUI , PATEL NIRALI , LAYDEN BRIAN T. , HE YANLIN , KOTA MAYA , DIXIT DEVIN , ANTONY NIMISHA , CARRILLO-SÁENZ LESLIE , TORRES IRIZARRY VALERIA C. , IBRAHIMI LUCAS , SCHAUL SARAH 
Published: May 2022

The influence of gut bacteria on host energy homeostasis is increasingly recognized, but mechanistic links are lacking. The gut microbiota digests and ferments nutrients, which result in short-chain fatty acids (SCFAs) . The body senses these nutrients in large part through free fatty acid receptors 2 (FFA2) and 3 (FFA3) . Accumulating evidence indicates that the gut microbiota/SCFAs interact with the central nervous system (CNS) to regulate brain metabolic function. Consistently, we found that a single acute intracerebroventricular (ICV) injection of acetate (ACE) , propionate (PRO) , or butyrate (BUT) dose-dependently inhibited food intake in an FFA2/3-dependent manner. The reduced food intake induced by ACE, PRO, or BUT was attributed to decreased meal size or increased intermeal interval. These regulatory effects on meal patterns were blunted in FFA2 and FFA3 double-receptor knockout mice, suggesting a mediating role of brain FFA2/3. Interestingly, RNAscope analysis showed that FFA3 but not FFA2 highly expressed in the cerebellar granule neurons. Using brain slice patch-clamp, we consistently showed that PRO or FFA3-selective agonists inhibited these granule neurons. Notably, the hyperpolarization effects of PRO on cerebellar granule neurons were blocked by pertussis toxin (PTX) , a G-protein coupled receptor subunit Gi/o blocker, further supporting an FFA3-Gi/o-mediated inhibition on granule neurons. These results suggest a model that SCFAs inhibit food intake through FFA3 expressed by the cerebellar granule neurons.
Key words: SCFA; Brain; FFA3

Disclosure
P. Luo: None. P. Xu: None. H. Ye: None. B.T. Layden: None. Y. He: None. V.C. Torres Irizarry: None.
1324-P: Short-Term Effects of Glycemia-Lowering Medications on ß-Cell Function in the GRADE Study
Authors: RASOULI NEDA , ALBU JEANINE , COHEN ROBERT M. , DEFRONZO RALPH A. , DIAZ ELSA , GHOSH ALOKANANDA , LUCHSINGER JOSE A. , MCGILL JANET B. , KASSEM LAURE SAYYED , SIVITZ WILLIAM , TAMBORLANE WILLIAM V. , UTZSCHNEIDER KRISTINA , YOUNES NAJI , KAHN STEVEN E. ,   GRADE RESEARCH GROUP
Published: May 2022

Therapies that preserve β-cell function and enhance glycemic control in type 2 diabetes are of great value. We examined β-cell function in GRADE participants after one year of intervention with insulin glargine U-100, glimepiride, liraglutide or sitagliptin. Participants who remained on originally assigned medication and had complete OGTT data at baseline and Year 1 were analyzed (n=3342 of 5047 initially randomized) . OGTT derived β-cell responses were measured as the ratio of the increment of C-peptide to glucose in the first 30 minutes (CPI) and over 120 minutes (CP/G AUC) . At baseline, age (57.7±9.7 y) , sex (63.5% male) , race (66.8% White) , BMI (34.2±6.7 kg/m2) , fasting C-peptide (1.3±0.5 nmol/L) , HOMA-B (87±35.2 %) , CPI (0.08±0.nmol/mg) and CP/G AUC (1.1±0.6 nmol/mg) did not differ by treatment group. At Year 1, measures of β-cell function were different by treatment groups (Table) . After pairwise analysis, glargine had the lowest fasting C-peptide while CP/G AUC was highest in the liraglutide group. When tested for treatment heterogeneity across subgroups, participants with longer duration of diabetes had smaller increases in CPI and CP/G AUC. Decreased fasting C-peptide by glargine is likely due to lower endogenous insulin secretion in the setting of exogenous insulin. Improved β-cell responses with liraglutide may indicate better β-cell function during the first year of treatment.

Disclosure
N. Rasouli: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Sanofi. Research Support; Allergan, Eli Lilly and Company, Novo Nordisk. J. Albu: None. R.M. Cohen: Research Support; Dexcom, Inc. R.A. DeFronzo: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Intarcia Therapeutics, Inc., Novo Nordisk. Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc. Speaker’s Bureau; AstraZeneca. E. Diaz: None. A. Ghosh: None. J.A. Luchsinger: None. J.B. McGill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals. Consultant; Bayer AG, Boehringer Ingelheim International GmbH. Research Support; Dexcom, Inc., Novo Nordisk. L. Sayyed Kassem: None. W.V. Tamborlane: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Medtronic, Novo Nordisk, Sanofi, Takeda Pharmaceutical Company Limited. K. Utzschneider: Consultant; Nevro Corp. N. Younes: None. 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.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (U01DK098246, U34-DK-088043)
1335-P: Deciphering Liver Glycome Regulation by the PGC-1/FN3K Axis
Authors: SAAR EFRAT GLICK , DAIME YOHANNIES G. , TIROSH AMIR , MINSKY NERI 
Published: May 2022

Diabetes in general, and specifically in the context of obesity, is characterized by hyperglycemia resulting in non-enzymatic glycation of proteins, a key event in the pathophysiology of diabetes and its chronic complications. Yet, the full scope of molecular targets for glycation, particularly in liver, is incompletely understood. De-glycation, which removes the attached sugars, is controlled intracellularly by fructosamine-3-kinase (FN3K) , a kinase that phosphorylates the attached sugar and has been proposed to have a protective role against the deleterious effects of glycation related to diabetes. However, FN3K has been suggested to be ubiquitously expressed and to act as a constitutive housekeeping gene. Furthermore, whether intracellular de-glycation is regulated in physiological contexts and what factors are involved in its regulation remain unknown. Our data identify that regulation of protein glycation in liver is controlled by the key metabolic regulators PGC-1s (PGC-1alpha and PGC-1beta) in response to metabolic cues, particularly in the fed state. Liver-specific deletion of PGC-1s results in reduction of Fn3k expression and concomitant increase in specific protein glycation. In accordance, overexpression of PGC-1alpha in liver-derived cells induces Fn3k and a reduction in protein glycation. Purification of glycated proteins followed by mass spectrometric analysis reveals significant alterations in intracellular protein glycation in response to PGC1-alpha expression. Mechanistically, PGC-1alpha effect on Fn3k involves the activity of the transcription factor Foxo1. Thus, in liver, fasting and re-feeding govern intracellular protein glycation via PGC-1 dependent induction of FN3K. Our work reveals the scope and dynamic nature of the liver glycome, establishing the PGC1/FN3K axis as a key regulator of protein glycation.

Disclosure
E.Glick saar: None. Y.G.Daime: None. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker’s Bureau; Eli Lilly and Company. N.Minsky: None.
1374-P: In Type 2 Diabetes, the Exocrine Pancreas Has Greater Fibrosis, Fat, Metaplastic Changes, and Microangiopathy
Authors: WRIGHT JORDAN J. , ESKAROS ADEL , WINDON ANNIKA L. , SAUNDERS DIANE C. , BOTTINO RITA ,   HUMAN PANCREAS ANALYSIS PROGRAM, BRISSOVA MARCELA , POWERS ALVIN C. 
Published: May 2022

Type 2 diabetes (T2D) is associated with increased risk of pancreatic cancer. Our knowledge of exocrine pancreas histopathology in T2D is incomplete. To determine whether T2D is associated with changes in the pancreatic exocrine compartment, we analyzed tissue sections from the pancreatic head, body, and tail of 25 T2D donors (age 51 ± yrs, duration 3.4 ± 2.6 yrs, 9/25 on insulin, BMI 35.5 ± 6.3, A1c 7.5 ± 1.5%) and 26 non-diabetic donors (ND; age 41 ± yrs, BMI 28.7 ± 5.0, A1c 5.3 ± 0.4%) using histochemistry, immunofluorescence, and CODEX multiplexed imaging with automated quantitation and manual review by two pathologists. Compared to ND, T2D pancreata were larger (113.3 ± 6.9 vs. 93.8 ± 6.7 g, p&lt;0.05) and had more exocrine fibrosis (29.4 ± 1.6 vs. 17.3 ± 2.7% area, p&lt;0.01) , inter- and intra-lobular fat (14.6 ± 2.0 vs. 7.6 ± 1.5% area, p&lt;0.01) , acinar-to-ductal metaplasia (ADM; 1.4 ± 0.3 vs. 0.3 ± 0.1 positive lobules/section, p&lt;0.01) , pancreatic intraepithelial neoplasia (PanIN; present in 40.0 vs. 14.8%, p&lt;0.05) , and small vessel angiopathy (7.0 ± 0.5 vs. 3.6 ± 0.6 combined score, p&lt;0.001) . In contrast, exocrine tissue from 16 donors with type 1 diabetes (T1D; age 23 ± 7 yrs, duration 11.5 ± 8.2 years, BMI 23.7 ± 5.4, A1c 9.1 ± 1.7%) had no increase in ADM, PanIN, fat or angiopathy. Though similar in severity, T2D fibrosis was predominantly intralobular, while T1D was interlobular, perivascular, and periductal. T2D tissues with greater fibrosis had more activated stellate cells compared to low fibrosis tissues (5.6 ± 1.1 vs. 1.0 ± 0.2% area, p&lt;0.05) . Endothelial cell density, shape, and size and macrophage abundance and phenotype were similar in T2D and ND, while T cells were greater in T2D (4.1 ± 1.6 vs. 3.9 ± 1.8% of cells, p&lt;0.05) with no change in subtype or activation. Thus, T2D is associated with marked changes in the pancreatic exocrine compartment. Whether these exocrine changes contribute to islet dysfunction or influence the risk of pancreatic cancer in T2D is unknown.

Disclosure
J.J.Wright: None. A.Eskaros: None. A.L.Windon: None. D.C.Saunders: None. R.Bottino: Employee; Imagine Pharma. Human pancreas analysis program: n/a. M.Brissova: None. A.C.Powers: None.
1427-P: Long-Term Treatment with Testosterone Leads to Profound Weight Loss in Men with Hypogonadism and Type 2 Diabetes: Update of Real-World Data from a Registry Study
Authors: HAIDER AHMAD , HAIDER KARIM S. , SAAD FARID 
Published: May 2022

Background: Prevalence of hypogonadism in men with T2DM has been reported as high as 50%. ADA Guidelines recommend measuring testosterone in men with T2DM.
Methods: Of 370 men with hypogonadism and T2DM, 302 (81.6%) were obese, 62 (16.8%) overweight and 6 (1.6%) had normal weight. 190 received injections of testosterone undecanoate 1000 mg/12 weeks (T-group) following an initial 6-week interval, 180 opted against treatment (CTRL) . Means and standard deviations of absolute measures over 13 years of treatment are reported.
Results: Mean baseline age: 62.0±5.2 years, mean (median) follow-up: 9.3±3.1 (10) years. Waist circumference (cm) decreased from 117.9±14.8 to 98.2±4.3 in the T-group (p&lt;0.0001) and increased in CTRL from 116.9±13.5 to 119.0±8.4 (p&lt;0.0001) . Difference between groups at 13 years: 21.8 (p&lt;0.0001) . Weight (kg) decreased from 114.4±13.8 to 88.3±7.6 in the T-group (p&lt;0.0001) and increased in CTRL from 102.7±14.1 to 104.5±10.2 (p&lt;0.0001) . Difference between groups: 21.4 (p&lt;0.0001) .
BMI (kg/m²) decreased from 36.5±4.4 to 28.5±2.4 in the T-group (p&lt;0.0001) and increased in CTRL from 32.8±4.7 to 33.3±3.6 (p&lt;0.0001) . Difference between groups: 6.9 (p&lt;0.0001) .
Weight change from baseline was -21.5±5.2% in the T-group and 9.3±3.0% in CTRL (p&lt;0.00for both) . Difference between groups: 30.4% (p&lt;0.0001) .
Waist:height ratio decreased from 0.67±0.to 0.56±0.03 in the T-group and increased from 0.66±0.to 0.67±0.05) in CTRL (p&lt;0.00for both) . Difference between groups: 0.12 (p&lt;0.0001) .
Visceral adiposity index (VAI) decreased from 5.9±3.1 to 1.8±0.4 in the T-group and increased from 5.2±2.6 to 9.1±4.4 in CTRL (p&lt;0.00for both) . Difference between groups: 7.6 (p&lt;0.0001) .
Adherence to testosterone therapy was 100%.
Conclusions: Long-term treatment with testosterone undecanoate injections results in profound weight loss maintained over up to 13 years. Untreated hypogonadal patients gain weight.

Disclosure
A.Haider: Other Relationship; Bayer AG. K.S.Haider: Other Relationship; Bayer AG. F.Saad: Consultant; Bayer AG, Stock/Shareholder; AbbVie Inc., Bayer AG, GlaxoSmithKline plc.

Funding
Bayer AG