bluuebunny/crossref_metadata_2025 huggingface dataset:
1463-P: Relationship between Hepatic and Adipose Tissue Insulin Resistance with Liver Fibrosis in Patients with Type 2 Diabetes Mellitus (T2DM) and Nonalcoholic Fatty Liver Disease (NAFLD)
Authors: KALAVALAPALLI SRILAXMI , LOMONACO ROMINA , GODINEZ EDDISON , FANOUS NADA , TEJERA LAZARO J. , MCCAULEY ALLISON , MANSOUR LYDIA , SHRESTHA SULAV , MARTE JONATHAN S. , FAKHRY JONATHAN , WANG HANNAH , VARGAS ALEJANDRA , BARB DIANA , BRIL FERNANDO , CUSI KENNETH
Published: June 2020

The ADA recommends screening for liver fibrosis in all patients with T2DM and with elevated ALT or steatosis. However, the factors that may predispose to hepatic fibrosis, such as comorbid conditions or insulin resistance (IR), have not been carefully examined. To this end, we studied patients with T2DM and NAFLD/fibrosis screened in an outpatient clinical setting. Screening for steatosis was done by controlled attenuation parameter (CAP), fibrosis by liver stiffness (LSM) with vibration-controlled transient elastography (VCTE). Out of 527 patients screened, 350 (66%) had steatosis (age: 60±12 years; BMI: 33±6 kg/m2; A1c: 7.5±1.7%). Based on VCTE, they were divided into LSM ≥ 7.0 kPa (moderate-to-severe fibrosis; n=69) or LSM ≤ 7.0 kPa (no or mild fibrosis; n=281). We measured hepatic (HOMA) and adipose tissue (Adipo-IR: fasting FFA x insulin) IR, FIB-4 and CK-18 (biomarkers of liver fibrosis).

Results are summarized in the Table. Patients with fibrosis had more steatosis, worse HOMA/Adipo-IR and more severe metabolic syndrome. Presence of fibrosis was not evident in most patients by AST/ALT >40 U/L (elevated in just 26%) or FIB-4, but CK-18 was higher.

In conclusion, clinicians should strongly suspect liver fibrosis in patients with T2DM that have the most unfavorable metabolic profile.

Disclosure

S. Kalavalapalli: None. R. Lomonaco: None. E. Godinez: None. N. Fanous: None. L.J. Tejera: None. A. McCauley: None. L. Mansour: None. S. Shrestha: None. J.S. Marte: None. J. Fakhry: None. H. Wang: None. A. Vargas: None. D. Barb: None. F. Bril: None. K. Cusi: Consultant; Self; Allergan plc., AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., Gilead Sciences, Inc., Merck & Co., Inc. Research Support; Self; Cirius Therapeutics, Echosens, Eli Lilly and Company, Inventiva Pharma, Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Poxel SA, Zydus Pharmaceuticals, Inc.

Funding

Echosens
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 > 200 units of insulin a day and those with insulin doses < 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<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<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<0.03) and sustained in REM, variable in IGT (∼3 fold, p<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<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<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<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<0.0001) and the PHQ (ρ=-.599, p<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<0.0001; β=0.40±0.06). This difference remained significant after adjustment for plasma glucose and insulin concentrations (p<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 (> 45 years), obesity (body mass index > 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 <0.05).

Results: Out of 1985 patients, 72.24% patients had NAFLD. Most were males (65%), >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 >7.5%). Dyslipidemia and hypertriglyceridemia were seen in 80% and 48.16% patients. On univariate logistic regression analysis, age (P<0.001), uric acid (P<0.05), SGOT (P<0.001), SGPT (P<0.001), triglycerides (P<0.001), HDL (P<0.001) and LDL (P<0.001) levels were significantly associated. On multivariate analysis, only HDL (P<0.001), SGOT (P<0.001), SGPT (P<0.001) and SGOT/SGPT ratio (P<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 <0.001) and in INSULIN group (r=0.492) (p <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 <0.001). Multiple linear regression models showed that shifting from OAD to INSULIN results in the decrease of PISA by 605.4mm² (p <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)
1516-P: Microvascular Burden Predicts All-Cause Mortality, Major Vascular Outcomes, and ESRD in Type 2 Diabetes
Authors: GAROFOLO MONIA , GUALDANI ELISA , GIANNARELLI ROSA , LUCCHESI DANIELA , MICCOLI ROBERTO , FRANCESCONI PAOLO , PRATO STEFANO DEL , PENNO GIUSEPPE
Published: June 2020

Microvascular complications (MC) affect CV risk and mortality in T2D. We explored the association of cumulative burden of retinopathy, nephropathy and peripheral neuropathy with mortality, CV events and ESRD in a single-centre, observational study involving 986 T2D over a 12.9±2.7 yrs follow-up. Vital status and rates of outcomes were censored on December 2017. The cohort included 491 (49.8%), 318 (32.3%), 135 (13.7%) and 42 (4.3%) people with no, 1, 2 or 3 MC. All-cause mortality (23.3%) increased from no-MC (15.3%) to 1 MC (23.3%, HR 1.60; 95%CI 1.16-2.20), 2 MC (41.5%, 3.19; 2.25-4.51) and 3 MC (59.5%, 5.32; 3.38-8.36; p<0.0001). After adjustments, HRs were: 1 MC, 1.21 (0.87-1.69); 2 MC, 1.72 (1.15-2.56) and 3 MC, 3.17 (1.89-5.33, p<0.0001). Irrespective of number of baseline CV risk factors not at target (HbA1c ≥7%, LDL ≥100 mg/dl, BP ≥140/90 mmHg), age and sex adjusted HRs raised with MC (p<0.0001). CV events occurred in 276 T2D (28.4%). Incidence raised with MC: no-MC, 20.8%; 1 MC, 31.3% (HR 1.65; 1-25-2.18); 2 MC, 42.7% (2.77; 2.00-3.85); 3 MC, 50.0% (3.78; 2.36-6.05, p<0.0001). After adjustments, HRs for CV events were: 1 MC, 1.37 (1.03-1.82); 2 MC, 1.61 (1.12-2.30) and 3 MC, 2.42 (1.48-3.99, p<0.0001). Rate of heart failure hospitalization (hHF) was 3.3% in no-MC, 11.5% in 1 MC (HR 3.19; 1.83-5.56), 17.6% in 2 MC (5.68; 3.09-10.45) and 14.3% (5.00; 2.00-12.54) in 3 MC (p<0.0001). After adjustments, rate of hHF raised in 1 MC (2.28; 1.30-4.01), 2 MC (3.38; 1.79-6.40) and 3 MC (3.02; 1.19-7.65). Also ESRD raised with MC: no-MC, 4.9%; 1 MC, 6.7% (HR 1.44; 0.80-2.59); 2 MC, 11.5% (2.76; 1.45-5.27); 3 MC, 26.2% (7.67; 3.75-15.70; p<0.0001). After adjustments, ESRD raised with 2 MC (HR 2.34; 1.21-4.53) and 3 MC (6.41; 3.19-13.16, p<0.0001). Incidence of CV events, hHF, and ESRD raised with number of MC after stratification for risk factors not at target (p<0.0001). In T2D, the cumulative burden of MC predicts mortality, CV events, hHF and ESRD, offering an accessible tool for improving risk prediction.

Disclosure

M. Garofolo: None. E. Gualdani: None. R. Giannarelli: None. D. Lucchesi: None. R. Miccoli: None. P. Francesconi: None. S. Del Prato: Advisory Panel; Self; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Takeda Pharmaceutical Company Limited. G. Penno: None.
1520-P: Developing New Risk Equations to Predict Diabetes-Related Complications and Mortality in U.S. Adults with Type 2 Diabetes
Authors: HOERGER THOMAS J. , KAUFMANN MATTHEW , NEUWAHL SIMON , SHAO HUI , CHEN HAIYING , LAXY MICHAEL , CHENG YILING J. , BENOIT STEPHEN R. , ANDERSON ANDREA M. , CRAVEN TIMOTHY , ZHANG PING
Published: June 2020

Risk equations to predict diabetes-related complications and mortality in most type 2 diabetes simulation models were based on data from the UK Prospective Diabetes Study. Two recently completed U.S. diabetes trials, the Action to Control Cardiovascular Risk in Diabetes and the Action for Health in Diabetes and their follow-up studies with >15,000 participants and >7 years follow-up, provide a unique source for developing new risk equations. We estimated parametric hazard models for cardiovascular, neuropathy, nephropathy, vision, and hypoglycemia complications and mortality in persons with type 2 diabetes using longitudinal data from the trials. We included demographic variables, time-varying risk factors, and histories of complications. Variable selection was based on backwards stepwise regression and expert opinion.

We estimated 17 complication and 3 mortality equations. HbA1c was selected in all but one complication/mortality equation, with hazard ratios ranging from 1.09 for stage 3 chronic kidney disease to 1.85 for amputation per 1% increase. Other risk factors were selected less frequently. For mortality, smoking was the risk factor with the largest hazard ratio. At least one lagged complication was selected for every complication/mortality equation. Previous congestive heart failure was associated with increased risk for 13 complications, with hazard ratios as high as 2.6 for amputation. Other lagged complications selected for over half of the complications included microalbuminuria, previous revascularization, macroalbuminuria, and previous stroke. Congestive heart failure, myocardial infarction, and stroke increased mortality in persons with current or previous cardiovascular disease. Kidney-related complications also increased mortality.

Our equations can be used in type 2 diabetes simulation models to estimate costs, outcomes, and cost-effectiveness of interventions for type 2 diabetes, particularly in U.S.-based models.

Disclosure

T.J. Hoerger: Research Support; Self; Centers for Disease Control and Prevention, Centers for Medicare and Medicaid Services. M. Kaufmann: None. S. Neuwahl: None. H. Shao: None. H. Chen: None. M. Laxy: None. Y.J. Cheng: None. S.R. Benoit: None. A.M. Anderson: None. T. Craven: None. P. Zhang: None.

Funding

Centers for Disease Control and Prevention (200-2016-92270)
1521-P: State-Level Trends in Lower Extremity Amputations among U.S. Medicare Beneficiaries with Diabetes, 2000-2017
Authors: ANDES LINDA J. , HARDING JESSICA , ROLKA DEBORAH B. , IMPERATORE GIUSEPPINA , LI YANFENG , GREGG EDWARD W. , ALBRIGHT ANN L.
Published: June 2020

Non-traumatic lower extremity amputations (NLEA) are an important complication of diabetes. After a period of decline, some national U.S. data show that rates of diabetes-related NLEA have recently increased. Whether this varies by state is unknown. We used 100% Medicare claims for beneficiaries enrolled in Parts A and B during 2000-2017 to examine state-specific NLEA trends among adults ≥67 years with diabetes. NLEA was defined as the highest-level amputation per patient per calendar year. All rates were age-sex standardized to the 2000 study population. Trends were assessed using Joinpoint regression. National diabetes-related NLEA rates (per 1,000 persons) decreased from 8.5 in 2000 to 4.4 in 2009 (APC - 7.9, p<0.001), and then increased to 4.8 in 2017 (APC 1.2, p<0.001). However, standardized state-specific rates varied considerably over the entire time period from a maximum of 12.5 in Louisiana to a minimum of 2.6 in Hawaii. Many states showed an initial decline followed by an increase after 2009. Other states did not experience a similar increase. Our findings suggest that the recent national increase in NLEAs may be driven by only some states, while others have been able to maintain low rates. Determining reasons for the increase in some states and not others could help identify interventions to reverse the trend.

Disclosure

L.J. Andes: None. J. Harding: None. D.B. Rolka: None. G. Imperatore: None. Y. Li: None. E.W. Gregg: None. A.L. Albright: None.
1523-P: Chinese T2DM Females Are Prone to Diabetic Retinopathy: Based on a Cross-Sectional Study in Twelve Provinces
Authors: LI MEI , MU PAN-WEI , TAN YING , CHEN YANMING
Published: June 2020

Aims: To investigate if the gender is a risk factor of the prevalence of diabetic retinopathy (DR) among type 2 diabetic patients, we designed and performed a cross-sectional study in twelve provinces in the mainland of China.

Methods: Patients with type 2 diabetes, age of 18 years or older, were recruited from 76 cities/counties of 12 provinces in the mainland of China, during January 2015 to December 2018. All participants received a standard interview, eye examinations and digital fundus photography. The presence and severity of DR were diagnosed and graded by retinal specialists according to the DR domestic typing method.

Results: A total of 12,766 eligible participants (5963 males and 6803 females) were included in this study. The overall prevalence of DR was 30.1%. Females exhibited a significantly higher prevalence of DR than males (31.1%% vs. 29.0%, P=0.011). A multivariate logistic regression analysis confirmed that the female sex was an independent predictor for higher prevalence of DR after adjusting for age, duration of diabetes, economic status and presence of hypertension (OR: 1.096, 95% CI: 1.013-1.186, P=0.023). Even after stratification by diabetic duration, age and economic status, the female sex was still independently associated with the presence of DR in patients whose T2DM history was more than 10 years (OR 1.150, 95% CI:1.012-1.306, P=0.032), whose ages were over 60 years (OR 1.141,95% CI:1.031-1.262, P=0.010) or who were in a relatively intermediate economic area (OR 1.123, 95% CI: 1.001-1.259, P=0.048).

Conclusion: Chinese T2DM females had a higher prevalence of DR than T2DM males. In addition, the female sex remains as an independent predictor for DR in patients with diabetes for more than 10 years, ages over 60 years or a relatively intermediate economic status.

Disclosure

M. Li: None. P. Mu: None. Y. Tan: None. Y. Chen: None.

Funding

Research and Development Plans in Key Areas of Guangdong Province (2019B020227003); National Natural Science Foundation of China (81770826); National Key Research and Development Program of China (2017YFA0105803)
1525-P: Serum Uric Acid Level Is an Independent Risk Factor for Glomerular Filtration Rate Decline in Patients with Untreated Type 2 Diabetes
Authors: OKADA YUKI , SATO KYOKO K. , SHIBATA MIKIKO , UEHARA SHINICHIRO , KOH HIDEO , OUE KEIKO , KAMBE HIROSHI , MORIMOTO MICHIO , HAYASHI TOMOSHIGE
Published: June 2020

Decline in kidney function is a major concern for patients with type 2 diabetes. The importance of serum uric acid level as the risk factor for chronic kidney disease (CKD) remains unconfirmed. We therefore evaluated the relationship between baseline serum uric acid level and the risk of incident CKD among men with untreated type 2 diabetes at baseline examination in a 10-11 years prospective cohort study. We included 717 middle-aged Japanese subjects with fasting plasma glucose level ≥126 mg/dL or HbA1c ≥6.5% at baseline who were not taking hypoglycemic medications nor insulin, who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2, who did not have proteinuria nor malignant tumors, and who were not taking anti-hypertensive medications nor urate-lowering medications at baseline. CKD was defined as eGFR <60 ml/min/1.73 m2. Cox proportional hazards models were used in the multivariate analysis.

During the 5961 person-years follow-up period, 87 subjects developed CKD. Higher serum uric acid level was associated with an increased risk of CKD after adjustment for age, body mass index, systolic blood pressure, diastolic blood pressure, HbA1c, smoking habits (nonsmokers, past smokers, and current smokers), regular leisure-time physical activity (yes/no), daily alcohol consumption (g ethanol/day), and eGFR at baseline. Multiple-adjusted hazard ratios of CKD for quintile 4 (6.2-6.9 mg/dL) and quintile 5 (≥7.0 mg/dL) of serum uric acid levels were 1.30 (95% CI, 0.73-2.30) and 1.80 (95% CI, 1.04-3.11), respectively, compared with quintile 1 to 3 (0.7-6.1 mg/dL). Moreover, when we modeled serum uric acid level as a continuous variable, serum uric acid level per 1.0 mg/dL increase was significantly associated with a 25% increased risk of incident CKD.

In conclusion, higher serum uric acid level is independently and significantly associated with an increased risk of CKD in patients with untreated type 2 diabetes.

Disclosure

Y. Okada: None. K.K. Sato: None. M. Shibata: None. S. Uehara: None. H. Koh: None. K. Oue: None. H. Kambe: None. M. Morimoto: None. T. Hayashi: None.
1533-P: Lower Protein Intake Is Associated with Higher Intakes of Carbohydrate and Lower Diet Quality in Adults with Diabetes: A 2005-2016 NHANES Analysis
Authors: THOMAS SARA , FANELLI STEPHANIE M. , KELLY OWEN , KROK-SCHOEN JESSICA L. , TAYLOR CHRISTOPHER A.
Published: June 2020

Hyperglycemia is associated with an increased risk for sarcopenia. The concurrence of hyperglycemia and sarcopenia may inflate the risk for falls, fractures, and mortality. On average, Americans consume more than the individual protein recommendation (0.8 g/kg/d); however, a large proportion of adults still consume less than recommended levels, which may have negative health implications. Therefore, this study examined the individual protein intake in a nationally representative sample of adults (31+ years) with and without type 2 diabetes to explore protein intakes (g/d) and diet quality (Healthy Eating Index-2015). Data were examined from 23,487 non-institutionalized adults from the 2005-2016 National Health and Nutrition Examination Survey (NHANES). Hemoglobin A1c (%) was used to classify glycemic status: nondiabetes (<5.7%); prediabetes (5.7-6.4%); diabetes (≥6.5%). Dietary data were collected using 24-hour dietary recalls. Participants were further categorized by mean individual protein intake and either ’met’ or ’did not meet’ the protein recommendation of 0.8 g/kg/d. For those without diabetes, 35.9% did not meet protein recommendations, with more adults with prediabetes (46.8%) and diabetes (51.3%) below recommended intakes on the day of record. Adults below the protein recommendation consumed significantly more carbohydrates (13-14 g more across all glycemic groups; p < 0.001) and had worse HEI-2015 diet quality scores across all glycemic groups (nondiabetes: 50.4 v 53.5; prediabetes: 49.9 v 52.8; diabetes: 49.9 v 52.6) compared to those who met the protein recommendation (p < 0.001). Adults with diabetes may have an increased risk for muscle loss, thus assessing and addressing patterns of gaps in protein intakes during patient interactions may help prevent sarcopenia and its associated complications.

Disclosure

S. Thomas: Employee; Self; Abbott. S.M. Fanelli: None. O. Kelly: Employee; Self; Abbott. Employee; Spouse/Partner; Abbott. J.L. Krok-Schoen: None. C.A. Taylor: Research Support; Self; Abbott Laboratories.

Funding

Abbott Nutrition
1536-P: Trends in Eating Patterns among U.S. Adults with Diagnosed Diabetes
Authors: SIEGEL KAREN R. , BULLARD KAI M. , SAYDAH SHARON , MERCADO CARLA , ALI MOHAMMED K. , ALBRIGHT ANN L. , IMPERATORE GIUSEPPINA
Published: June 2020

In 2019, the American Diabetes Association published a consensus report on nutrition therapy for individuals with diabetes (DM), which included a section on five recommended eating patterns: Mediterranean-style, Dietary Approaches to Stop Hypertension, low-fat, low-carbohydrate, and vegetarian. Using data from 4,718 non-pregnant adults aged ≥20 years with self-reported diagnosed DM and complete dietary data (i.e., one day of 24-hour recall) in the National Health and Nutrition Examination Surveys 2001-2016, we examined the proportion who followed each of the recommended eating patterns (including achieving different components/levels of the eating patterns), and whether this has changed over time. We used age-standardized descriptive statistics to calculate the proportion of individuals following each eating pattern across four 4-year time periods, and calculated p-values for trend across the time periods. Overall, the proportion of individuals following the recommended eating patterns was low and did not change significantly over time, although the decline in following the Mediterranean-style diet from the 2001-2004 to the 2013-2016 time period was significant (p=0.04 and p=0.046 for the highest and lowest categories, respectively) (Table). These results suggest more efforts may be considered for improving eating patterns among adults with DM in the United States.

Disclosure

K.R. Siegel: None. K.M. Bullard: None. S. Saydah: None. C. Mercado: None. M.K. Ali: Research Support; Self; Merck & Co., Inc. A.L. Albright: None. G. Imperatore: None.
1548-P: Changes in Glucose-Lowering Medication Use in the Era of Cardiovascular Outcomes Trials: Risk/Treatment Paradox Persists
Authors: MCCOY ROZALINA G. , HOUTEN HOLLY VAN , ROSS JOSEPH , KARACA-MANDIC PINAR , MONTORI VICTOR M. , SHAH NILAY
Published: June 2020

Three new classes of glucose-lowering drugs were introduced into practice over the past 15 years: DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors. These drugs have low hypoglycemia risk, do not cause weight gain, and post-marketing outcomes trials found cardiovascular and renal benefits associated with GLP-1RA and SGLT2i use.

Our objective was to determine whether these drugs are being used by patients with type 2 diabetes most likely to benefit from them. Using OptumLabs Data Warehouse, a de-identified dataset of commercially-insured and Medicare Advantage beneficiaries, we identified adults with type 2 diabetes who first started a DPP-4i (n=140,933), GLP-1RA (n=107,331), SGLT2i (n=112,892), or any other diabetes drug (n=1,743,484) between 2013-2018. After adjustment for age, gender, race/ethnicity, insurance type, baseline medications, year, prescriber specialty, and comorbidities, we found that GLP-1RA and SGLT2i, in particular, were less likely to be started by patients most likely to benefit from them. GLP-1RA initiation was less likely among patients with prior hypoglycemia requiring ED/hospital care (OR 0.86 [95% CI 0.79-0.93]), myocardial infarction (MI; OR 0.93 [0.89-0.97], or stroke (OR 0.88 [0.85-0.91]), though more likely with nephropathy (OR 1.20 [1.17-1.23]). SGLT2i initiation was less likely with prior hypoglycemia (OR 0.81 [0.73-0.89]), nephropathy (OR 0.80 [0.78-0.0.82]), or heart failure (HF; OR 0.85 [0.82-0.87]). However, DPP-4i initiation was more likely with prior hypoglycemia (OR 1.49 [1.41-1.57]), MI (OR 1.09 [1.05-1.12]), stroke (OR 1.09 [1.06-1.11), HF (OR 1.12 [1.09-1.14]), and nephropathy (OR 1.40 [1.37-1.43]).

Our results do not explain why these drugs are not preferentially used in guideline-recommended contexts, but do highlight missed opportunities to reduce the morbidity and mortality associated with hypoglycemia, cardiovascular disease, and kidney disease in highest risk patients.

Disclosure

R.G. McCoy: None. H. Van Houten: None. J. Ross: Research Support; Self; Centers for Medicare and Medicaid Services, Janssen Pharmaceuticals, Inc., U.S. Food and Drug Administration. P. Karaca-Mandic: None. V.M. Montori: None. N. Shah: None.

Funding

National Institutes of Health (K23DK114497); Agency for Healthcare Research and Quality (1U19HS024075, R01HS025164)
1551-P: Optimizing MODY Detection in a Pediatric Diabetes Population
Authors: TOSUR MUSTAFA , REFAEY AHMAD K. , GUFFEY DANIELLE , BALASUBRAMANYAM ASHOK , REDONDO MARIA J.
Published: June 2020

Maturity-onset diabetes of the young (MODY) is under-diagnosed or misdiagnosed as type 1 diabetes (T1D) or type 2 diabetes (T2D), in part due to lack of systematic genetic testing. We aimed to define patient characteristics that could guide the decision to conduct genetic testing for MODY diagnosis in racially/ethnically diverse youth with diabetes. In our electronic health record-based Diabetes Registry, we found 4,752 cases carrying a diagnosis of T1D (78.3%), T2D (20.4%) or MODY (1.3%) seen within the past 3 years. We then screened the Diabetes Registry in an agnostic manner for likely MODY cases (“Study Cohort”) based on: (1) diagnosis of diabetes at age <25 y, (2) family history of diabetes in 3-consecutive generations, (3) absent islet autoantibodies (Ab) except GAD65 Ab. We collected data on their clinical and biochemical characteristics, and results of MODY testing if available. In the Study Cohort (n=350, 7.4% of the Diabetes Registry), 62.3% were female; 57% Hispanic, 13.8% non-Hispanic white, 26.4% non-Hispanic black and 2.9% other. 4.6% had previously received a diagnosis of MODY, 16.6% T1D and 78.8% T2D. Frequency of MODY diagnosis was 3.5 times higher in the Study Cohort than in the Diabetes Registry (p<0.001). At diabetes diagnosis, mean age was 13 y (± 3.2) and HbA1c 9.8% (± 2.6). To further refine characteristics of potential MODY, we performed cluster analysis on the Study Cohort using variables commonly used to establish diabetes type at diagnosis: age, BMI-z score, glucose, C-peptide, HbA1c and islet Ab. The cluster with the highest rate of prior MODY diagnosis (25%) had the lowest age at onset (10.9 ± 2.5 y), BMI-z (0.5 ± 0.9), C-peptide (1.5 ± 1.2 ng/mL) and acanthosis nigricans frequency (12.5%) (all p<0.05). Furthermore, in this cluster, molecular confirmation rate was 75% in those patients who had undergone genetic testing (1/3 of the cluster). The patient characteristics defined by this stepwise approach expands and enhances accurate MODY diagnosis and improves the yield of genetic testing for MODY.

Disclosure

M. Tosur: None. A.K. Refaey: None. D. Guffey: None. A. Balasubramanyam: None. M.J. Redondo: None.

Funding

Mike Hogg Fund