bluuebunny/crossref_metadata_2025_split huggingface dataset:
1465-P: Application of the New Cluster-Based Classification of Adult-Onset Diabetes in a South Texas Veteran Population, Increased Incidence of Diabetic Nephropathy in Veterans with Severe Insulin Resistance
Authors: TREJO JONATHAN , PINKSON SHEILA , GONDIN LYAN , ESTEVE LUCY , CHEN XI , TRIPATHY DEVJIT 
Published: June 2020

Recently, cluster analysis has been proposed to classify adult onset diabetes which can better predict diabetes associated complications. Individuals with primarily insulin resistant phenotype have been associated with increased incidence of nephropathy while those with insulin deficient phenotype are associated with retinopathy. We evaluated the application of this classification in a VA diabetes clinic. Ninety patients who had C-peptide and anti-GADab, and detailed clinical follow-up, were included in the analysis. Additionally we defined patients with severe insulin resistance as those who required &gt; 200 units of insulin a day and those with insulin doses &lt; 0.5 U/kg/day were categorized as mild insulin resistance. Six subjects belonged to the Severe Autoimmune Diabetes (SAID) cohort, with average GADab 713±301IU; 66% of the cohort had nephropathy, 33% had retinopathy. The Severe Insulin Deficiency (SIDD) cohort had 9 patients, of which 4 had retinopathy, 3 had nephropathy. Thirty subjects had severe insulin resistance (n=30, M/F=29/1 age 61±2 yr), duration of diabetes 18.3±0.3 yr, HbA1c -8.4±0.2%, total daily insulin dose (TDD) 301±31U) and 32 had mild insulin resistance (N=32, M/F: 28/2, age 61±2 yr, BMI 30±1 kg/m2, duration of diabetes 12±1.2 yr, HbA1c 7.2±0.2%, TDD 17±2U). Insulin resistant subjects had a higher BMI, (41 ± 2 vs. 30 ±1 kg/m2, p&lt;0.05), and higher plasma triglyceride (325±0.3 vs. 202±0.3 mg/dl, p=0.04). Prevalence of nephropathy was higher in the insulin resistant group vs. the mild insulin resistant group (76% vs. 43%, p&lt;0.05). There was no difference in prevalence of retinopathy (p=0.09) or CAD (p=0.6) between the groups. Our results support the higher prevalence of diabetic nephropathy in patients with severe insulin resistance. Long-term follow up of these patients may provide insight into the underlying mechanisms of these complications.

Disclosure
J. Trejo: None. S. Pinkson: None. L. Gondin: None. L. Esteve: None. X. Chen: None. D. Tripathy: None.
147-OR: Long-Term Effect of GLP-1 on Pancreas Endocrine Function after Gastric Bypass in Individuals with and without Diabetes Remission
Authors: PRASAD MALINI A. , SHAH ANKIT , MARK VICTORIA M. , NAIR NANDINI , HOLST JENS J. , LAFERRERE BLANDINE 
Published: June 2020

The contribution of GLP-1 on glucose control after gastric bypass (GBP) is not fully elucidated.
Hypotheses: The improvement in β-cell glucose sensitivity (BCGS) to oral glucose after GBP is GLP-1 mediated, weight loss independent, and varies according to diabetes (T2D) remission status; The administration of exendin 9-39 (EX9), a GLP-1 receptor blocker, has minimal effect on blood glucose.
Methods: Patients with T2D (n=29) underwent a 75 g OGTT prior to and at 3, 12 and 24 months (M) after GBP. Glucose, insulin secretion rates (ISR), BCGS, and glucagon were measured with and without EX9. The cohort was retrospectively divided into 3 groups based on T2D remission status determined at the latest study time point (24 or 12M): remitters (REM, n=5), persistent T2D (P-T2D, n=8), impaired (IGT, n=16).
Results: Prior to GBP, patients were 42.9±8.3y old, had a BMI of 42.4±4.6 kg/m2, 7.7±7.3 y known T2D duration, an HbA1c of 7.8±1.1% (35% on insulin) and an HOMA-IR of 11.5±5.8. Both magnitude and temporal increases in BCGS varied according to remission status: greater (up to 6.5 fold, p&lt;0.03) and sustained in REM, variable in IGT (∼3 fold, p&lt;0.01), minimal and only transient (3M, p=0.014) in P-T2D. These differences were not explained by weight-loss since it did not differ between the 3 groups at any time. EX9 reversed the effect of GBP on ISR at 3, 12 and 24M (p&lt;0.003); it further enhanced the rise in post-prandial glucagon, but this effect was only significant at 3M (p=0.005). Both effects varied in magnitude overtime and by remission status. Glucose improved after GBP, as expected; EX9 decreased glucose levels at 3M in the whole cohort (p&lt;0.001), but had no effect on glucose at 12 and 24M. EX9 increased significantly, albeit minimally, glucose at 120 and/or 180 minutes during the OGTT in REM and IGT, but not in P-T2D.
Conclusions: Our data suggest that the effect of endogenous GLP-1 on pancreatic endocrine function and glucose varies with time and according to remission status after GBP.

Disclosure
M.A. Prasad: None. A. Shah: None. V.M. Mark: None. N. Nair: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics.

Funding
National Institutes of Health (R01DK67561, DK007559, P30DK26687, UL1RR024156, UL1TR000040, F32DK113747)
148-OR: Empagliflozin Improves Insulin Sensitivity of the Hypothalamus in Humans with Prediabetes
Authors: HENI MARTIN , KULLMANN STEPHANIE , WAGNER ROBERT , HUMMEL JULIA , DANNECKER CORINNA , VOSSELER ANDREAS , FRITSCHE LOUISE , KANTARTZIS KONSTANTINOS , MACHANN JÜRGEN , HAERING HANS-ULRICH , FRITSCHE ANDREAS , PREISSL HUBERT 
Published: June 2020

Insulin action in the human brain reduces food intake, improves whole-body insulin sensitivity, and modulates adiposity. In most cases of obesity and diabetes, the brain becomes insulin resistant with impaired brain-derived modulation of peripheral metabolism. As treatment with the SGLT2-inhibitor empagliflozin not only improves glucose metabolism but also reduces body weight and cardiovascular risk, we hypothesized that improved brain insulin sensitivity could be involved.
Methods: In this double blind study, 40 participants with prediabetes (according to ADA’s OGTT criteria) were 1:1 randomized to receive 25 mg empagliflozin qd or placebo (mean ± SD: age: 60 ± 9 years; BMI: 31.5 ± 3.8 kg/m²). Before and after 8 weeks of treatment, brain insulin sensitivity was assessed by functional MRI combined with the intranasal administration of insulin to the brain.
Results: In healthy persons, intranasal insulin administration significantly decreases cerebral blood flow in the hypothalamus. In the current study, volunteers with prediabetes were unresponsive to this, as insulin could not induce hypothalamic inhibition prior treatment. We identified a significant interaction between treatment and the hypothalamic response to insulin (p&lt;0.05, corrected for multiple comparisons). Post-hoc analyses showed that only participants on empagliflozin showed a significant insulin-induced decrease in hypothalamic blood flow after treatment. The group receiving placebo showed no such improvement.
Conclusion: Our current results corroborate insulin resistance of the human hypothalamus in humans with prediabetes. Treatment with empagliflozin for 8 weeks was able to restore hypothalamic insulin sensitivity; a favorable response that could contribute to the positive effects of SGLT2 inhibitors. These findings reveal that brain insulin resistance is treatable by pharmacological interventions with potential benefits for cognition, adiposity, and whole-body metabolism.

Disclosure
M. Heni: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker’s Bureau; Self; Novo Nordisk A/S. S. Kullmann: None. R. Wagner: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Eli Lilly and Company. J. Hummel: None. C. Dannecker: None. A. Vosseler: None. L. Fritsche: None. K. Kantartzis: None. J. Machann: None. H. Haering: None. A. Fritsche: None. H. Preissl: None.

Funding
Boehringer Ingelheim
1495-P: Incidence of Early Diabetes Complications among Patients Newly Diagnosed with Type 2 Diabetes
Authors: AN JAEJIN , NICHOLS GREGORY A. , QIAN LEI , LI ZHUOXIN , MUNIS MERCEDES A. , WEI RONG , HARRISON TERESA , WEISS TRACEY , RAJPATHAK SWAPNIL , REYNOLDS KRISTI 
Published: June 2020

Patients with type 2 diabetes mellitus (T2D) are at risk of various comorbidities. We investigated the timing of incident T2D complications over the course of 15 years and clinical characteristics associated with those complications in a large U.S. integrated healthcare system.
We identified incident T2D between 2003-2014 with a validated algorithm using electronic health records. T2D complications included micro- and macro-vascular diseases, depression, and all-cause mortality. We calculated incidence rates per 1000 person-years and median time to developing each complication through 2018. Multivariable Poisson regression models were used to investigate factors associated with early T2D complications defined as shorter than the median time to incidence.
We identified 135,199 patients with newly diagnosed T2D and followed them for a median six years [mean age 58 years, 48% female, 36% White, 35% Hispanic, 12% Black, 13% Asian]. Median times to incidence of depression, peripheral vascular disease, stable angina, and chronic kidney disease (CKD) were shorter than median times to incidence of lower extremity amputation, stroke, and heart failure (Table). Having hypertension and lower eGFR were associated with shorter time to CKD whereas male was associated with shorter time to composite cardiovascular events. Older age and a higher comorbidity score were associated with shorter time to both.

Disclosure
J. An: Research Support; Self; Merck & Co., Inc., Novartis AG. G.A. Nichols: Research Support; Self; Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Merck & Co., Inc. L. Qian: None. Z. Li: None. M.A. Munis: None. R. Wei: None. T. Harrison: None. T. Weiss: Employee; Self; Merck & Co., Inc. S. Rajpathak: Employee; Self; Menarini Group. K. Reynolds: Research Support; Self; CSL Behring, Merck & Co., Inc., National Institutes of Health, Novartis Pharmaceuticals Corporation.
15-OR: Self-Efficacy and Mood in Youths with T1D before and after a Curriculum-Based Group Intervention
Authors: MUNOZ CYNTHIA E. , HSIN OLIVIA , GAMEZ SARAH H. , RAYMOND JENNIFER , FISHER LYNDA K. 
Published: June 2020

Introduction: Youths with type 1 diabetes (T1D) are at significant risk for diabetes burnout and distress, as well as depressive symptoms. These social-emotional vulnerabilities have been linked with suboptimal child health outcomes. TEEN POWER® is a 10-week curriculum-based group intervention for youths with T1D and their family. This intervention was developed to reduce psychosocial barriers that negatively impact T1D management.
Objective: To examine whether this group intervention had beneficial implications for the empowerment and mood of youths with T1D.
Methods: Ninety youths with T1D completed the Children’s Hope Scale, a 6-item questionnaire focused on self-efficacy at the beginning and end of this group intervention. Higher scores corresponded with greater levels of self-efficacy or the belief that one has the capacity and motivation to achieve one’s goals. Answers are rated on a Likert-scale from 1 (none of the time) to 6 (all of the time). Scores at the beginning and end of the group intervention were compared using paired t-tests. Bivariate correlations between self-efficacy scores and depression ratings on the CDI and PHQ at the end of intervention were also examined.
Results: Youths’ self-efficacy scores at the end of intervention (mean=25.13) were significantly higher than at the beginning of the intervention (mean=23.84) (t(69)=-2.191, p=0032). At the end of intervention, self-efficacy scores were associated with lower depression ratings based on both the CDI (ρ=-.375, p&lt;0.0001) and the PHQ (ρ=-.599, p&lt;0.001).
Conclusions: This analysis included data obtained for youths with T1D who participated in a 10-week curriculum-based group intervention. The data suggest that this intervention is associated with an increase in self-efficacy and improved self-efficacy is associated with reduced depressive symptoms. TEEN POWER® may be indicated for youths with T1D who report low levels of self-efficacy such as youths who may be experiencing diabetes burnout and distress.

Disclosure
C.E. Munoz: Board Member; Self; American Diabetes Association. O. Hsin: None. S.H. Gamez: None. J. Raymond: None. L.K. Fisher: None.

Funding
HumanGood Foundation/Beatson-ABHOW Type 1 Diabetes Fund; Sugar Ray Leonard Foundation; George & Marcia Good Family Foundation
150-OR: Brain Insulin Sensitivity Is Modulated by Menstrual Cycle
Authors: BENKENDORFF CHARLOTTE F.C. , HUMMEL JULIA , VOSSELER ANDREAS , KULLMANN STEPHANIE , FRITSCHE LOUISE , BIRKENFELD ANDREAS L. , PREISSL HUBERT , HAERING HANS-ULRICH , FRITSCHE ANDREAS , PETER ANDREAS , WAGNER ROBERT , HENI MARTIN 
Published: June 2020

Insulin action in the human brain modulates whole-body metabolism by increasing peripheral insulin sensitivity and suppressing endogenous glucose production. In brain insulin resistance, this modulatory function of the brain is impaired. Experimental evidence from rodents and first observations in humans suggest major differences in brain insulin action between women and men. We therefore investigated effects of brain insulin delivery on peripheral metabolism in the follicular and luteal phase of the menstrual cycle.
Eleven natural cycling women (age: 19-29 years, BMI: 17.8 - 23.8 kg/m²) underwent four hyperinsulinemic-euglycemic clamps. On two days during both the follicular and the luteal cycle phase, participants received intranasal insulin spray and placebo 90 min after initiation of the 210 min clamp in randomized, blinded order. Insulin spillover into the blood was mimicked by an appropriate iv insulin bolus on placebo days.
The phase of the menstrual cycle interacted with the type of spray on the subsequent change of glucose infusion rates (GIR) (p=0.01). During the follicular phase, more glucose had to be infused after insulin delivery to the brain as nasal spray compared to placebo administration (p&lt;0.0001; β=0.40±0.06). This difference remained significant after adjustment for plasma glucose and insulin concentrations (p&lt;0.0001). During the luteal phase, GIR were only transiently higher after nasal insulin (p=0.005; β=0.16±0.06), but this depended on the circulating glucose and insulin levels as the difference was no longer present after respective adjustments (p=0.1).
In the follicular phase of the menstrual cycle, insulin delivery to the brain improves peripheral insulin sensitivity in lean women, comparable to what has previously been described in lean men. However, this response was not detected in the luteal phase, suggesting brain insulin resistance. Brain insulin resistance could therefore contribute to the long known peripheral insulin resistance in the luteal phase of the menstrual cycle.

Disclosure
C.F.C. Benkendorff: None. J. Hummel: None. A. Vosseler: None. S. Kullmann: None. L. Fritsche: None. A.L. Birkenfeld: None. H. Preissl: None. H. Haering: None. A. Fritsche: None. A. Peter: None. R. Wagner: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Novo Nordisk A/S. Other Relationship; Self; Eli Lilly and Company. M. Heni: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker’s Bureau; Self; Novo Nordisk A/S.

Funding
German Federal Ministry of Education and Research (01GI0925)
1506-P: Nonalcoholic Fatty Liver Disease (NAFLD) in Type 2 Diabetes Mellitus (T2DM) Patients in India: A Real-World Perspective
Authors: SINGH VIKRAM JIT , SINGH MANMOHAN , PATIDAR HEMANT 
Published: June 2020

Objective: NAFLD is highly prevalent in T2 DM patients. In addition to diabetes, factors like age (&gt; 45 years), obesity (body mass index &gt; 30 kg/m2), dyslipidemia, hypertriglyceridemia, hypertension and poor control of diabetes contribute to higher risk of having NAFLD. Therefore, the study was designed to evaluate the profile of T2DM patients with NAFLD in India alongwith determining high risk factors for having NAFLD.
Methodology: Ultrasonographic (USG) records (1985) of patients with available liver function test (LFT) reports were analyzed after excluding alcoholic liver disease (ALD) and other known causes of liver injury. Various clinical and diagnostic parameters were assessed. Univariate and multivariate logistic regression was used to determine significant risk factors (P value &lt;0.05).
Results: Out of 1985 patients, 72.24% patients had NAFLD. Most were males (65%), &gt;40 years (82.99%) and obese/overweight (92%). Most had normal SGOT (89.33%) and SGPT (74%) levels. The ratio of SGOT/SGPT was less than 1 in 77.20% patients. Most (51.62%) patients had poor control of diabetes (HbA1c &gt;7.5%). Dyslipidemia and hypertriglyceridemia were seen in 80% and 48.16% patients. On univariate logistic regression analysis, age (P&lt;0.001), uric acid (P&lt;0.05), SGOT (P&lt;0.001), SGPT (P&lt;0.001), triglycerides (P&lt;0.001), HDL (P&lt;0.001) and LDL (P&lt;0.001) levels were significantly associated. On multivariate analysis, only HDL (P&lt;0.001), SGOT (P&lt;0.001), SGPT (P&lt;0.001) and SGOT/SGPT ratio (P&lt;0.001) were significantly associated. A predictive algorithm using the above was designed and validated.
Conclusion: NAFLD was seen to be highly prevalent in diabetes patients in India. Most of these patients had normal LFT values which highlight the need for routine screening and management of these patients, especially those with high risk factors.

Disclosure
V. Singh: None. M. Singh: None. H. Patidar: None.
1507-P: Dose–Response Relationship between Periodontal Inflamed Surface Area and Glycated Haemoglobin Level in Patients with Type 2 Diabetes Mellitus on Insulin Therapy and on Oral Antidiabetic Therapy
Authors: VADAKKEKUTTICAL ROSAMMA J. , PATTAYIL SIMNA , RADHAKRISHNAN CHANDNI 
Published: June 2020

A bidirectional inflammatory link exists between periodontitis and diabetes mellitus. Diabetes increases the prevalence and severity of periodontitis and periodontitis affects glycemic control. Treatment of diabetes is with oral antidiabetic drugs (OAD), insulin or their combinations. Insulin achieves faster glycemic control and has other beneficial effects. This study was undertaken to compare the prevalence, extent and severity of periodontal disease, to correlate periodontal inflamed surface area (PISA) with Glycated Hb (HbA1c) and to find the dose response relationship between PISA and HbAic in type 2 diabetes mellitus (T2DM) on insulin therapy and on OAD therapy. The study comprised of 130 T2DM patients on oral antidiabetic drugs therapy (OAD group) and 130 T2DM patients on insulin therapy (INSULIN group). All subjects were assessed for periodontal parameters (BOP, PPD, CAL, OHI-S Index, PI Index and PISA) and systemic parameters (HbA1c, FPG, PPG). The proportion of periodontitis was lower in INSULIN group (46.2%) as compared to OAD group (83.1%). Extent and severity of periodontitis and PISA were lower in INSULIN group as compared to OAD group. HbA1c was positively correlated with PISA in OAD group(r=0.391)(p &lt;0.001) and in INSULIN group (r=0.492) (p &lt;0.001). A dose response relationship between PISA and HbA1c has been observed and an increase in HbA1c of 1% is associated with an increase in PISA of 195mm2 (p &lt;0.001). Multiple linear regression models showed that shifting from OAD to INSULIN results in the decrease of PISA by 605.4mm² (p &lt;0.001). This indicates to the beneficial effects of insulin on periodontal tissues. Dose response relationship between HbA1c and PISA confirm the bidirectional relationship between diabetes mellitus and periodontal disease.

Disclosure
R.J. Vadakkekuttical: None. S. Pattayil: None. C. Radhakrishnan: None.
1512-P: Severe Hypoglycemia and Hyperglycemia among U.S. Adults with Diabetes and ESRD on Dialysis, 2010-2015
Authors: GALINDO RODOLFO J. , ALI MOHAMMED K. , SHAH NILAY , FUNNI SHEALEIGH , UMPIERREZ GUILLERMO E. , MCCOY ROZALINA G. 
Published: June 2020

Glycemic management in patients with diabetes and end-stage renal disease (ESRD) is challenging. There is limited evidence about the incidence of severe hypoglycemia and hyperglycemia in this population. Here, we examine rates of emergency department visits and hospitalizations for severe hypoglycemia and hyperglycemia (ascertained using validated ICD-9/10 codes) in a national cohort of adults with diabetes and incident ESRD, included in the United States Renal Data System, between 2010-2015. We then examine risk factors for these events using logistic regression. Among 678,376 patients with ESRD, 59.5% (n=403,490) had diabetes (63.6±13.0 years, 56.4% male, 26.8% Black, and 18.0% Hispanic). Rates of severe hypoglycemia and hyperglycemia were 126.2 and 35.5 per 1000 person-years, respectively. Strongest risk factors for hypoglycemia were insulin therapy (OR 4.5 [95% CI, 4.4-4.6] vs. no medications) and non-insulin diabetes medications (OR 3.7 [3.6-3.8]); Black race (OR 1.3 [1.3-1.4] vs. Caucasian); older age: 65-74 years (OR 1.2 [1.1-1.3] and ≥75 years OR 1.1 [1.1-1.1] vs. 18-44 years); and history of amputation (OR 1.4 [1.4-1.5]) or retinopathy (OR 1.2 [1.2-1.3]). Strongest risk factors for hyperglycemia were insulin (OR 7.7 [7.4-8.2]) and non-insulin diabetes medication use (OR 2.8 [2.6-3.1]) and retinopathy (OR 1.5 [1.4-1.5]). Older age was protective for hyperglycemia (OR 0.1 [0.1-0.1] for age ≥75 and 0.2 [0.2-0.2] for age 65-74 vs. 18-44 years). Patients on peritoneal dialysis had a lower risk (OR 0.8 [0.8-0.9]) of hypoglycemia, but no difference in odds of hyperglycemia, compared to patients on hemodialysis.
Hypoglycemia requiring ED/hospital care was 3.6-fold more prevalent than severe hyperglycemia, greatly exceeding rates previously reported for older adults and those with non-end stage chronic kidney disease. There is a critical need for proactive interventions to reduce hypoglycemia and related ED/hospital use in this high-risk population.

Disclosure
R.J. Galindo: Advisory Panel; Self; Lilly Diabetes. Consultant; Self; Valeritas, Inc. Research Support; Self; Novo Nordisk Inc. Other Relationship; Self; UpToDate. M.K. Ali: Research Support; Self; Merck & Co., Inc. N. Shah: None. S. Funni: None. G.E. Umpierrez: None. R.G. McCoy: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK111024)