bluuebunny/crossref_metadata_2025 huggingface dataset:
1497-P: Secular Trends in Incidence and One-Year Mortality Rates of Lower Extremity Amputation in People with Diabetes in Hong Kong between 2001 and 2016
Authors: WU HONGJIANG , YANG AIMIN , LAU ERIC S. , MA RONALD C. , KONG ALICE P. , CHOW ELAINE , SO WING YEE , CHAN JULIANA C. , LUK ANDREA
Published: June 2020

Objective: Diabetes is a leading cause of nontraumatic lower extremity amputation (LEA). We describe the secular trends in incidence rates of LEA and one-year mortality rates after LEA in people with diabetes in Hong Kong between 2001 and 2016.

Methods: The Hong Kong Diabetes Surveillance Database (HKDSD) is a territory-wide population-based diabetes cohort identified from the Hong Kong Hospital Authority electronic medical system. We identified LEA events using ICD-9 procedure codes and that of one-year mortality after LEAs from the linkage to the Hong Kong Death Registry. We used Joinpoint regression models to describe the trends in incidence of LEAs from 2001 to 2016 and one-year mortality rates after LEAs from 2001 to 2015.

Results: Between 2001 and 2016, a total of 390,071 men and 380,007 women with diabetes aged 20 years or older were included in the HKDSD, among whom 6,113 LEAs in men and 4,149 LEAs in women were recorded. The event rates of minor LEAs declined by 48.6% (average annual percent change [AAPC]: -3.8, 95% CI -5.7, -1.9) from 14.0 to 7.2 per 10,000 in men and by 59.5% (AAPC: -6.3, 95% CI -10.6, -1.8) from 7.9 to 3.2 per 10,000 in women. The rates of major LEAs declined by 77.9% (AAPC: -8.0, 95% CI -9.6, -6.5) from 19.5 to 4.3 per 10,000 in men and by 79.3% (AAPC: -10.4, 95% CI -13.1, -7.6) from 11.6 to 2.4 per 10,000 in women. The one-year mortality rates after both minor and major LEAs remained constant during the surveillance period in both sexes. The AAPC for one-year mortality rates was 1.5 (95% CI -3.0, 6.1) in men and 0.6 (95% CI -4.7, 6.1) in women after minor LEAs, and was -2.1 (95% CI -4.8, 0.6) in men and 2.6 (-1.4, 6.7) in women after major LEAs.

Conclusions: Although the event rates of LEAs have declined overall in people with diabetes in Hong Kong, there was no improvement in one-year mortality rates after LEAs. Urgent action to improve the quality of care and ongoing surveillance after LEAs in people with diabetes is needed.

Disclosure

H. Wu: None. A. Yang: None. E.S. Lau: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. A.P. Kong: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Abbott, AstraZeneca, Sanofi. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. E. Chow: None. W. So: None. J.C. Chan: None. A. Luk: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Roche Pharma. Other Relationship; Self; Merck Sharp & Dohme Corp.
1498-P: A Feedback Loop between miRNA Processing Complex and miR-3975 in Western Diet–Induced Brown Adipose Tissue Dysfunction
Authors: PARK MIN HI , MERUVU SUNITHA , ZHANG JIAN , CHOUDHURY MAHUA
Published: June 2020

Brown adipose tissue (BAT) is considered as promising therapeutic targets for obesity and metabolic disorder through modulation of energy homeostasis. microRNAs (miRNAs) are established as essential modulators of biological processes in many tissues, including the differentiation and function of BAT. Here we demonstrated that high-fat/high fructose associated dysfunction of BAT coincides with impaired miRNA-processing pathway in a feedback loop with miR-3975 activation. Eight-week-old male C57BL/6 mice were fed a low-fat diet (10% fat and 17% sucrose; LFD) and high fat-high fructose (45% fat, 17% sucrose, and 17% fructose; HFHFD) for 4, 12, and 20 weeks (n=6-9 per group). We evaluated expression levels of apoptosis markers, thermogenesis markers, miRNA biogenesis regulators, and miRNAs in BAT. Mice fed an HFHFD showed a gradually significance increased body weight and brown adipose tissue weight when compared to the mice fed with LFD. BAT of HFHFD fed mice has a pale appearance versus feeding period matched LFD fed mice. The protein expression of thermogenesis markers, UCP1 (P <0.05), and PGC1α (P <0.05) were shown to decrease after 12 weeks of HFHFD diet feeding. The apoptosis marker, the Bax/Bcl-2 ratio, was upregulated at 12 weeks (P < 0.01). Mice fed HFHFD for 12 and 20 weeks showed a significant decrease in Dicer (P < 0.01 for 12 and 20 weeks) and TRBP2 (P < 0.01 for 12 weeks and P < 0.0001 for 20 weeks). miR-3975, which is predicted miRNA to regulate both Dicer and TRBP2 by IPA was activated at 12 weeks (P < 0.01), while inactivated at 20 weeks (P < 0.001). Our results suggest that miR-3975 acts as a component of a negative feedback loop that blocks miRNA biogenesis machinery through the inhibition of Dicer and TRBP2 expression. Therefore, long-term HFHFD may disturb miRNA processing and contribute to brown adipose tissue dysfunction and apoptosis by modulation of miRNA expression. We are currently investigating the novel feedback loop in brown adipocyte primary cells.

Disclosure

M. Park: None. S. Meruvu: None. J. Zhang: None. M. Choudhury: None.
1499-P: Hepatobiliary Disease in Type 2 Diabetes: Is It Increasing and Is Fatty Liver Important?
Authors: DAVIS TIMOTHY , DAVIS WENDY A.
Published: June 2020

Objective: To determine whether the incidence/adverse outcomes of hepatobiliary disease (HPD) has increased over recent decades in community-based Australians.

Methods: Longitudinal data from the Fremantle Diabetes Study Phase I (FDS1; recruitment 1993-1996) and Phase II (FDS2; 2008-2011) were analyzed. Participants with type 2 diabetes from both Phases were age-, sex- and zip code-matched 1:4 to people without diabetes. Incident HPD and associated mortality were ascertained from hospitalization, cancer registration and/or death certification for an ICD-coded diagnosis (principal/secondary) of liver disease, viral hepatitis, primary malignancy, and gallbladder/biliary tract disease. Incidence rates (IRs) and IR ratios (IRRs) for those with versus without diabetes in FDS1 and FDS2 were calculated.

Results: Data relating to IRs for HPD and associated mortality are shown in the Table. HPD IRs for people without diabetes did not change between Phases but the IRR increased, reflecting an IRR (95% CI) for people with diabetes in FDS2 versus FDS1 of 1.30 (1.01-1.68). Nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) accounted for <20% of HPD and <10% of liver-related deaths in both Phases.

Conclusions: HPD is more frequent in people with versus without type 2 diabetes. This discrepancy has increased in the 15 years between FDS Phases. Hospitalizations/deaths due to NAFLD/NASH remain uncommon.

Disclosure

T. Davis: Advisory Panel; Self; Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker’s Bureau; Spouse/Partner; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Lilly Diabetes, Merck Sharp & Dohme Corp., Mylan, Novo Nordisk A/S, Sanofi-Aventis. Other Relationship; Self; Protemics International. Other Relationship; Spouse/Partner; Protemics International. W.A. Davis: Advisory Panel; Spouse/Partner; Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Spouse/Partner; Lilly Diabetes, Merck Sharp & Dohme Corp., Mylan, Novo Nordisk A/S, Sanofi-Aventis. Other Relationship; Self; Proteomics International. Other Relationship; Spouse/Partner; Proteomics International.

Funding

Raine Foundation; University of Washington; National Health and Medical Research Council (513781, 1042231); Medical Research Future Fund Practitioner Fellowship
1500-P: Prevalence of Nonalcoholic Fatty Liver Disease in Unselected Patients with Type 1 Diabetes Mellitus Using Transient Elastography
Authors: VRIES MARIEKE DE , WESTERINK JAN , KAASJAGER KARIN , DE VALK HAROLD W.
Published: June 2020

Background: Worldwide NAFLD prevalence is approximately 25% in the general population and 56% in patients with type 2 diabetes mellitus (T2DM). The relationship between NAFLD and type 1 diabetes mellitus (T1DM) is less clear, with widely varying prevalence estimates (0 to 50%), dependent on the study population, NAFLD definition and diagnostic method. Data on assessment of hepatic steatosis (HS) as well as fibrosis stage with transient elastography (TE) as single diagnostic method are lacking.

Methods: We assessed NAFLD using TE in an unselected group of adult patients with T1DM. Patients attending the outpatient clinic were eligible if they did not have any known secondary cause of liver disease including excessive alcohol consumption. We calculated a required group size of 150 patients. All patients underwent TE (M- or XL-probe when applicable). NAFLD was defined as isolated HS and/or fibrosis/cirrhosis. HS was assessed by controlled attenuation parameter: S0 (no HS) to S3 (severe HS). Fibrosis stage was assessed by liver stiffness measurement: F0/F1 (no fibrosis) to F4 (cirrhosis). Potential associated factors of NAFLD were explored using a multivariate logistic regression model, stepwise including predefined covariates.

Results: We prospectively enrolled 150 consecutive subjects with T1DM (mean age 46 ± 13 years, female 46%). The prevalence of NAFLD was 34% (51/150). Fifty-one patients (34%) had HS (S1 n=21, S2 n=4, S3 n=26). Six patients (4%) had HS with fibrosis/cirrhosis (F2 n=2, F3 n=2, F4 n=2). After stepwise adjustment for age and BMI, waist circumference remained statistically significantly associated with the presence of NAFLD (OR 1.16, 95% CI 1.02.-1.32).

Conclusions: Overall NAFLD prevalence in patients with T1DM is slightly increased at 34% compared to the general population. The prevalence of NAFLD in patients with T1DM is associated with visceral adiposity.

Disclosure

M. de Vries: None. J. Westerink: None. K. Kaasjager: None. H.W. de Valk: None.
1509-P: Development of a Noninvasive Fibrosis Score for Chinese Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease
Authors: LEE CHI HO , SETO WAI KAY , IEONG KELLY , LUI DAVID T.W. , FONG HO YI , WAN HELEN , CHOW WING SUN , WOO YU CHO , YUEN MAN FUNG , LAM KAREN S.
Published: June 2020

Objective: In NAFLD, non-invasive serum-based fibrosis scores are often recommended as first-line assessment tools, followed by transient elastography to identify patients at high risk of liver fibrosis for consideration of liver biopsy. However, some studies had reported lower accuracy of these scores in diabetes. Therefore, we conducted this cross-sectional study to develop a non-invasive fibrosis score specifically for type 2 diabetes to improve risk stratification.

Research Design and Methods: A total of 815 adults with type 2 diabetes and NAFLD was recruited from the diabetes clinic in Hong Kong. A random sample of 643 individuals were included in the training set, and the remaining 172 in the testing set. All participants had transient elastography for assessment of liver fibrosis. Diabetes Fibrosis Score (DFS) was developed to identify patients with advanced fibrosis (AF) on transient elastography, defined as liver stiffness (LS) >9.5kPa, using significant determinants of LS with variables selected based on Akaike information criteria. The performance of DFS was compared with conventional liver fibrosis scores (NAFLD fibrosis score [NFS], Fib-4 and APRI), based on their area under the receiver operating characteristic (AUROC) curve, sensitivity (Sn), specificity (Sp), positive (PPV) and negative predictive values (NPV).

Results: The variables included in DFS consisted of body mass index, platelet, alanine and aspartate aminotransferase levels. The AUROC of DFS for AF on transient elastography was 0.822, while those of NFS, APRI and Fib-4 were 0.629, 0.643 and 0.788, respectively. In the testing set, the AUROC of DFS was 0.852, with 76.7% Sn, 82.3% Sp, PPV 48.2% and NPV 94.3%.

Conclusions: Compared to conventional non-invasive fibrosis scores, DFS more accurately identified, amongst patients comorbid with type 2 diabetes and NAFLD, those who should undergo transient elastography to evaluate their risk of liver fibrosis.

Disclosure

C. Lee: None. W. Seto: None. K. Ieong: None. D.T.W. Lui: None. H. Fong: None. H. Wan: None. W. Chow: None. Y. Woo: None. M. Yuen: None. K.S. Lam: Advisory Panel; Self; Merck Sharp & Dohme Corp.
151-LB: A Pilot Randomized Controlled Trial to Reduce Hospital Readmission Risk of Patients with Diabetes: 90-Day Outcomes
Authors: RUBIN DANIEL J. , WATTS SAMANTHA , DEAK ANDREW , VAZ CHERIE LISA , TANNER SAMUEL , RECCO DOMINIC , TIVON MADELINE , DILLARD FELICIA R. , BRZANA EMILY , JOYCE KATHERINE E. , KARUNAKARAN ABHIJANA , IWAMAYE AMY , MILLER ELI , MATHAI CHRISTINE , KONDAMURI NEIL , ALBURY BONNIE S. , ALLEN SHANEISHA , NAYLOR MARY D. , GOLDEN SHERITA , WU JINGWEI
Published: June 2020

Unplanned hospital readmission is a high-priority quality measure and target for cost reduction. Patients with diabetes are at higher risk of readmission than patients without diabetes. We previously presented results of a pilot randomized controlled trial (RCT) of an intervention designed to reduce readmission risk (the Diabetes Transition of Hospital Care [DiaTOHC] program) with outcomes assessed 30 days after hospital discharge. Here we present secondary outcomes assessed 90 days after discharge.

Patients predicted to be high risk (>=27%) for readmission based on a validated readmission risk tool (DERRITM) were randomized 1:1 to the intervention (INT) or usual care (UC). The intervention consisted of inpatient diabetes education, coordination of care, post-discharge support by a nurse practitioner, adjustment of diabetes therapy, and weekly phone calls for 30 days after discharge.

There were 45 INT and 46 UC patients randomized and analyzed by intention-to-treat. Twenty-one INT and 23 UC patients had a readmission (46.7% vs. 50%) while 25 INT and 27 UC patients had a readmission or Emergency Department (ED) visit (55.6% vs. 58.7%). The ratio of the mean estimated cost of readmissions, ED visits, and the intervention in the INT group was 0.51 (0.25-1.02)95%CL the cost of readmissions and ED visits in the UC group.

Among the 69 patients with an admission A1C >7%, 14 INT and 17 UC patients had a readmission (41.2% vs. 48.6%), and 18 INT and 21 UC patients had a readmission or ED visit (52.9% vs. 60.0%), yielding relative risk reductions of 15.2% and 11.8%. The INT:UC group ratio of the mean estimated cost was 0.50 (0.22-1.12)95%CL. No differences were statistically significant in this pilot study.

The DiaTOHC intervention may modestly reduce readmission risk and cut costs by half within 90 days after discharge among patients with an admission A1C >7%. This merits further investigation in a larger RCT.

Disclosure

D.J. Rubin: None. S. Watts: None. A. Deak: None. C. Vaz: None. S. Tanner: None. D. Recco: None. M. Tivon: None. F.R. Dillard: None. E. Brzana: None. K.E. Joyce: None. A. Karunakaran: None. A. Iwamaye: None. E. Miller: None. C. Mathai: None. N. Kondamuri: None. B.S. Albury: None. S. Allen: None. M.D. Naylor: None. S. Golden: None. J. Wu: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K23DK102963)
1511-P: Diabetic Kidney Disease and Visit-to-Visit Variability of HbA1c, Blood Pressure, and Body Mass Index: A Nationwide Population-Based Study (ABB-DKD Study, JDDM)
Authors: MATSUTANI DAISUKE , MINATO SOICHIRO , TSUJIMOTO YUKI , MAEGAWA HIROSHI , SAKAMOTO MASAYA
Published: June 2020

Aim: The present study is the first to investigate association between Diabetic Kidney Disease (DKD) and Visit-to-Visit Variability (VVV) of HbA1c, blood pressure (BP), and body mass index (BMI) in patients with T2DM whose HbA1c, BP, and BMI were measured ≥12 times during a 2-year period.

Material and Methods: This retrospective clinical trial initially analyzed data on 104,601 persons with T2DM in 38 clinical centers. We included 20- to 75-year-old patients whose HbA1c, systolic BP (SBP), and BMI were measured ≥12 times during a 2-year period. VVV was calculated using the coefficient of variation. VVVs of HbA1c, SBP, and BMI respectively, were divided into two groups by median value (high or low VVV). Risk of DKD were analyzed by multivariate logistic regression analysis. DKD was defined as urine albumin-to-creatinine ratio ≥30mg/g Cr or eGFR <60 mL/min/1.73 m2.

Results: A total of 12,575 patients who met the inclusion criteria were finally analyzed. Adjusted odds ratios (ORs) for high risk of DKD were 1.33 (95% CI 1.22-1.46, p < 0.001) for high VVV of HbA1c, 1.18 (1.08-1.28, p < 0.001) for high VVV of SBP, and 1.19 (1.10-1.30, p < 0.001) for high VVV of BMI. Male sex 1.29 (1.12-1.34, p < 0.001), advanced age, longer diabetes duration, presence of hypertension 1.19 (1.03-1.38, p = 0.02), anti-hypertensive agent use 1.40 (1.22-1.61, p < 0.001), presence of dyslipidemia 1.24 (1.11-1.39, p < 0.001), higher 2-year mean HbA1c, higher 2-year mean SBP, and higher 2-year mean BMI were also related to high risk of DKD. Additionally, the analysis of antidiabetic drug use revealed that particularly use of insulin 1.50 (1.34-1.68, p < 0.001) and sulfonylurea use 1.24 (1.13-1.37, p < 0.001) were associated with high risk of DKD.

Conclusion: High VVV of HbA1c, SBP, and BMI were associated with DKD independently of mean HbA1c, SBP, and BMI values.

Disclosure

D. Matsutani: None. S. Minato: None. Y. Tsujimoto: None. H. Maegawa: Speaker’s Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Sanofi K.K., Takeda Pharmaceutical Company Limited. M. Sakamoto: None.
1524-P: Prevalence of Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes in a Spanish Population
Authors: SANCHEZ BAO ANA M. , BELLIDO VIRGINIA , TEJERA CRISTINA , BELLIDO DIEGO
Published: June 2020

Introduction: The prevalence of liver disease due to nonalcoholic fatty deposits (NAFLD) has doubled in the last 20 years in parallel to the increased prevalence of obesity and type 2 diabetes mellitus (T2DM). Insulin resistance is a central element in the pathogenesis of NAFLD and it is known that the prevalence of NAFLD is higher among patients with T2DM.

Objective: To assess the prevalence of NAFLD in a sample of patients with T2DM and define the associated clinical characteristics.

Methods: Observational, retrospective and multicenter study in routine clinical practice with SLGT2 inhibitor (dapaglifozin) and DPP-4 inhibitor (sitagliptin) in patients with T2DM in Spain (DAPA-RWE study). Protocol code:FIS-DAP-2016-01. Inclusion criteria were patients between 18-75 years old on treatment with sitagliptin or dapaglifozin for at least 6 months, minimum data set available. Data were analyzed with SSPPSS® version 24 (statistical significance level 0.05, mean data ± standard deviation).

Results: Data from 1040 patients, belonging to 22 different centers, were analyzed. The average age of the patients is 59.6 ± 8.9, 50% were women and 45.7% were receiving treatment with insulin. In our sample, 8% of patients are diagnosed with NAFLD. Among patients with NAFLD the average BMI was 35 kg/m2 and the waist circumference was 111.83 cm compared to patients without NAFLD with an average BMI of 31 kg/m2 and a waist circumference of 102.36 mm. No statistically significant relationship was found between NAFLD and the development of ischemic heart attack (patients with NAFLD and Myocardial infarction were 11.9%) or neurovascular disease (patients with NAFLD and neurovascular disease were and 8.3%).

Conclusions: In our sample, patients with NAFLD had higher BMI and waist circumference compared to patients without NAFLD. It has not been possible to demonstrate the relationship between NAFLD and cardiovascular or neurovascular disease, although the potency is limited by the low prevalence in our sample.

Disclosure

A.M. Sanchez Bao: None. V. Bellido: None. C. Tejera: None. D. Bellido: None.
1526-P: Time-Dependent Effect of Kidney Disease on All-Cause and CVD Mortality in Adults with Type 2 Diabetes: A Secondary Analysis of the Look AHEAD Clinical Trial
Authors: WILLS ANDREW C. , KNOWLER WILLIAM C.
Published: June 2020

The Look AHEAD trial compared an intensive lifestyle intervention (ILI) for weight loss with diabetes support and education in adults with T2DM and BMI ≥ 25 kg/m2. During 10 years of follow-up, ILI had no significant effect on mortality or incidence of CVD. Here we present a secondary analysis of urine albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) as predictors of all-cause mortality (361 deaths among 4865 participants) using time varying covariates proportional hazards models adjusted for age, sex, race/ethnicity, and ILI. Both ACR and eGFR predicted mortality (Figure 1a/b, respectively). In a joint analysis of ACR and eGFR, mortality was highest among groups with low eGFR and high ACR. Interestingly, high eGFR was also associated with higher mortality (Figure 1c). Effects of eGFR on mortality were nonlinear, but in each eGFR group, ACR was positively associated with mortality. In each analysis, ILI was beneficial, but not significantly so. There were no significant interactions between ACR or eGFR and insulin treatment, history of CVD, beta-blocker treatment, or age at baseline on mortality.

In conclusion, ACR and eGFR predicted mortality in time varying models. Results were similar for CVD mortality (106 deaths) and for the primary trial outcome of fatal or nonfatal CVD (796 events).

Disclosure

A.C. Wills: None. W.C. Knowler: None.
1527-P: Trends in Diabetic Ketoacidosis in Kentucky, 2008-2018
Authors: LACY MARY E. , BENITEZ JOSEPH , FOWLKES JOHN , SOHN MIN-WOONG
Published: June 2020

Background: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes. In the U.S., DKA hospitalizations are increasing. We estimated DKA hospitalization rates in Kentucky across key subgroups.

Methods: Using the statewide Kentucky Inpatient Claims Files, we examined rates of DKA hospitalization in Kentucky for adults aged ≥18 in 2008-2018. In each year, the denominator was all diabetes-related hospitalizations (any position; ICD-9 250; ICD-10 E10, E11, E13). The numerator was all DKA-related hospitalizations (any position; ICD-9 250.1; ICD-10 E10.1, E11.1, E13.1).

Results: In 2008-2018, rates of DKA hospitalizations in Kentucky increased by 100% (from 2.2% in 2008 to 4.4% in 2018; Fig A). In certain subgroups, rates were markedly higher. In the subset of Medicaid-insured patients DKA rates surpassed 10% of all diabetes-related hospitalizations (Fig B). Compared to patients covered by commercial insurance or Medicare, Medicaid-insured patients show dramatic increase following Medicaid expansion (2014). In non-Hispanic (NH) blacks, rates reached 6% by 2018 (Fig C). Rates for urban and rural populations were mostly parallel but diverged slightly following Medicaid expansion (Fig D).

Conclusions: Consistent with previous studies, DKA rates were higher in NH black, Medicaid-insured, and urban patients. Rates increased in all subgroups. The trends for Medicaid enrollees may show the effect of the 2014 Medicaid expansion.

Disclosure

M.E. Lacy: None. J. Benitez: None. J. Fowlkes: None. M. Sohn: None.
153-OR: Glucose-Dependency of Insulinotropic and Glucagonostatic Effects of Glucagon-Like Peptide-1 after Gastric Bypass and Sleeve Gastrectomy
Authors: HONKA HENRI , AL ZUBAIDI ANAS M. , GASTALDELLI AMALIA , DEFRONZO RALPH A. , SALEHI MARZIEH
Published: June 2020

Increased prandial GLP-1-induced insulin secretion after gastric bypass (GB), especially in those with late-complication of hypoglycemia, is well characterized. We previously reported that meal ingestion increases insulin and GLP-1 secretion during a sub-basal glycemic clamp in individuals after GB. Here, we investigated whether altered meal-stimulated β-cell output in this setting is due to the enhanced glucose-independent actions of GLP-1 using a potent GLP-1 receptor (GLP-1R) antagonist, exendin-(9-39) (Ex-9). Nine subjects with history of GB, 6 with prior sleeve gastrectomy (SG), and 4 non-operated healthy subjects were studied twice with and without Ex-9 infusion during a 5-hr hyperinsulinemic (120mU/m2/min) hypoglycemic (55mg/dl) clamp. The GB, SG, and CN groups were matched for BMI, FFM, A1c, and age; and the GB and SG for weight loss and time postsurgery; none had diabetes. Islet and gut hormones were measured before and after a liquid meal (280kcal, 20% glucose) at 2 hr of clamp studies. Fasting levels of glucose, islet and GI hormones were similar between 2 studies and among 3 groups. Insulin sensitivity (M/I) didn’t differ among the groups but insulin clearance was larger in surgical patients (P=0.08). Blocking GLP-1R did not affect β-cell secretory response before or after meal ingestion whereas α-cell responses to hypoglycemia alone or to meal ingestion were increased during Ex-9 infusion (pre-meal: 18, 9, 47%, and post-meal: 42, 14, 13% in GB, SG, and CN, respectively, P<0.05). Prandial GIP was similar among 3 groups and not affected by Ex-9. GLP-1 response was larger in GB compared to SG and CN, and was further increased by Ex-9 (P<0.01). Our findings indicate that in nondiabetic subjects with prior history of GB and SG, endogenous GLP-1 contribution to prandial β-cell secretion is glucose-dependent. Glucagonostatic effect of endogenous GLP-1, on the other hand, is preserved during hypoglycemic condition after these surgeries.

Disclosure

H. Honka: None. A.M. Al Zubaidi: None. A. Gastaldelli: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Inventiva Pharma, Novo Nordisk Inc. R.A. DeFronzo: None. M. Salehi: None.

Funding

Finnish Cultural Foundation (00180071); National Institutes of Health (DK105379)
1531-P: Impact of Hurricanes Irma/Maria on Changes in Glucose Abnormalities and Diabetes Care
Authors: MARTINEZ-LOZANO MARIJULIE , NOBOA CARLAMARIE , JOSHIPURA KAUMUDI J.
Published: June 2020

Aims: To evaluate the impact of hurricanes Irma/María on changes in glucose abnormalities and diabetes care.

Methods: Participants from the San Juan Overweight Adults Longitudinal Study (SOALS) aged 40-65 years and free of diabetes at baseline completed a follow-up exam. Of these, 324 participants without diabetes were enrolled in the Preparedness to Reduce Exposures and diseases Post-hurricanes and Augment Resilience (PREPARE) study evaluating risk and resiliency factors. Self-reported physician diagnosed diabetes data and blood samples were collected at all three visits. Paired t-tests were conducted to compare within person changes from baseline to follow up (pre-hurricanes) versus follow up to PREPARE visits (post hurricanes), both roughly similar 3 years follow-up periods, for fasting glucose, insulin and HbA1c. PREPARE participants with diabetes (N=56) recruited from another cohort were interviewed.

Results: At baseline, mean age was 54 years (SD=6.84), 77% were women and mean BMI was 33.5 (SD=6.30). The 3-year cumulative incidence of diabetes was 0.012 pre hurricanes and was 0.056 post hurricanes (p=.003). The increase in HbA1c post hurricane (M=0.66%, SD=5.49) was significantly higher than the changes pre hurricane (M=-0.18%, SD=0.23). The changes in fasting insulin post hurricanes (M=1.51uIU/mL, SD=8.69) was also significantly higher than pre hurricanes (M=0.38uIU/mL, SD=5.58). There were no significant differences for glucose. Of the 56 participants with diabetes, 18.9% had problems obtaining and storing insulin (median=112 days). Also, 16.7% had trouble getting good medical care for diabetes or related complications (median= 61 days), and needed to change their healthcare provider/facility, and/or find alternatives for insulin.

Conclusion: Hurricanes had a detrimental impact, increasing the incidence of diabetes, and fasting insulin and HbA1c. Among people with diabetes, hurricanes could disrupt healthcare and medications both short-term and long-term impact.

Disclosure

M. Martinez-Lozano: None. C. Noboa: None. K.J. Joshipura: None.

Funding

National Institutes of Health (R21MD013666, U54MD007587, R01DE010111)
1538-P: Prevalence of Late-Evening and Nighttime Eating in Individuals with Type 2 Diabetes
Authors: QUIST JONAS S. , BLOND MARTIN B. , FÆRCH KRISTINE , EWERS BETTINA
Published: June 2020

Introduction: Late-evening food intake associates with metabolic risk. We assessed the prevalence of late-evening and night-time eating in individuals with type 2 diabetes and its association with BMI and HbA1c.

Methods: This cross-sectional analysis includes 348 individuals with type 2 diabetes from an outpatient diabetes clinic in Denmark. Frequency of late-evening and night-time eating was assessed from a food frequency questionnaire and clinical data were obtained from electronic medical records. Participants were divided into those reporting to eat frequently (≥3 times/week) during the evening after dinner and/or night (late-eaters) and those who did not (reference) and BMI and HbA1c were compared between groups with and without adjustment for diabetes duration and antidiabetic medication.

Results: Forty-two% reported to eat frequently (≥3 times/week) during late evening and 8% reported to do so during the night (Figure 1). Most late-eaters reported to eat breakfast regularly suggesting a long eating window and short fasting period. BMI and HbA1c did not differ between late-eaters and the reference group (Figure 1).

Conclusion: Eating late was prevalent among individuals with type 2 diabetes across BMI and HbA1c levels. Whether restriction of eating during evening and night-time can induce weight loss and improve glycemic control in individuals with type 2 diabetes needs testing in randomized controlled trials.

Disclosure

J.S. Quist: None. M.B. Blond: None. K. Færch: None. B. Ewers: None.

Funding

Steno Diabetes Center
1541-P: Dietary Patterns Significantly Associated with Obesity in Japanese with Type 2 Diabetes: JDDM
Authors: HATTA MARIKO , FUJIHARA KAZUYA , IKEDA IZUMI , TAKEUCHI MIZUKI , NEDACHI RINA , MORIKAWA SAKIKO Y. , HORIKAWA CHIKA , KATO MITSUTOSHI , KATO NORIKO , MAEGAWA HIROSHI , SONE HIROHITO
Published: June 2020

Although both average BMI and foods vary greatly between Asian and Western countries, few studies have examined the relationship between dietary patterns and obesity in Asians. We investigated dietary patterns significantly associated with obesity in Japanese with diabetes. Cross-sectionally analyzed were 2070 Japanese with type 2 diabetes (mean age, 62 y; men, 62%) who completed the Food Frequency Questionnaire. Principal component analysis was performed on 20 food groups to elucidate dietary patterns significantly associated with obesity. We also divided participants into quintiles according to factor scores of each dietary pattern. The adjusted odds ratios (ORs) for obesity, defined as BMI ≥25 according to the Asian cutoff, were calculated with other covariates including energy intake. Six dietary patterns were determined from eigenvalues (≥1) and screen plots. For Factor 1, characterized by a well-balanced food group with high intake of light-colored vegetables, green and yellow vegetables, sugar, seaweed, beans, fish and seafood, fruit and potato, the OR for obesity in Quintile5 compared to Quintile1 was 0.34 (95% CI: 0.22-0.53). Conversely, that of Factor 2, characterized by high intake of seasoning and spices, sugar-sweetened beverages, rice and eggs, was 2.56 (1.69-3.89) (Table).

In conclusion, a balanced diet with various food groups might help to avoid obesity in Japanese with type 2 diabetes.

Disclosure

M. Hatta: None. K. Fujihara: None. I. Ikeda: None. M. Takeuchi: None. R. Nedachi: None. S.Y. Morikawa: None. C. Horikawa: None. M. Kato: None. N. Kato: None. H. Maegawa: Speaker’s Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Sanofi K.K., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.
1550-P: Whole-Exome Sequencing in Children with Suspected Maturity-Onset Diabetes of the Young (MODY)
Authors: TOSUR MUSTAFA , SABO ANIKO , KHAYAT MICHAEL M. , JHANGIANI SHALINI N. , REFAEY AHMAD K. , MUZNY DONNA , GIBBS RICHARD A. , BALASUBRAMANYAM ASHOK , REDONDO MARIA J.
Published: June 2020

The yield of commercial gene panels for MODY has been reported as low as 27% suggesting the role of un-identified gene variants in MODY. We aimed to study novel genetic factors of MODY. We identified 10 probands who had clinical characteristics suggestive of MODY (i.e., positive family history of diabetes, negative islet autoantibodies, and diagnosis of diabetes at <25 y/o) but negative genetic test results on a commercial MODY gene panel. We performed whole-exome sequencing (WES) in probands and their parents. In each trio, we prioritized rare protein-altering variants (stop-gain, frameshift indels, splicing and missense variants) in 70 neonatal diabetes and MODY candidate genes. Mean age at diabetes diagnosis was 10 (± 3.8) years. Six were females; 4 were non-Hispanic white, 5 Hispanic, and 1 Asian. Previously assigned diabetes types were type 1 diabetes (T1D) (n=7), unknown (n=2) and ketosis-prone diabetes (n=1). We found a likely pathogenic, de novo variant in INS gene (c.94G>A, p.Gly32Ser), confirmed by Sanger sequencing, in a proband who was previously diagnosed with T1D at 3 y/o. This very rare variant, absent in the general population (gnomAD database), has been reported previously in multiple individuals with neonatal diabetes. We also identified a frameshift deletion (c.2650delC, p.Gln884AsnfsTer57) in RFX6 gene in a child with a previous diagnosis of T1D at 12 y/o. The variant was inherited from the mother, who was diagnosed with diabetes of unknown etiology at 25 y/o. Heterozygous protein-truncating variants in RFX6 gene have been recently reported in individuals with MODY.

In conclusion, we identified two new MODY cases, with a novel variant not previously associated with MODY in one of them, using WES in children who were initially diagnosed with T1D. Our study demonstrates clinical utility of exome sequencing in atypical cases of diabetes suspected of MODY.

Disclosure

M. Tosur: None. A. Sabo: None. M.M. Khayat: None. S.N. Jhangiani: None. A.K. Refaey: None. D. Muzny: None. R.A. Gibbs: None. A. Balasubramanyam: None. M.J. Redondo: None.

Funding

Mike Hogg Fund
1552-P: Machine Learning Approach to Decision-Making for Initial Insulin Use in Japanese Patients with Type 2 Diabetes
Authors: FUJIHARA KAZUYA , YAMADA MAYUKO H. , MATSUBAYASHI YASUHIRO , YAMAMOTO MASAHIKO , IIZUKA TOSHIHIRO , MIYAMURA KOSUKE , HASEGAWA YOSHINORI , YAMAZAKI TATSUYA , KODAMA SATORU , SONE HIROHITO
Published: June 2020

We examined whether the machine learning approach could be used as support for decision-making by general physicians as to whether to use insulin as an initial therapy for patients with type 2 diabetes. Prescription data on different antidiabetic agents from December 2009 to March 2015 from diabetes specialists’ patient registries were used to compare the machine learning decision of initial insulin use to that of general physicians. Gold standard was defined as consensus, that is, 80% agreement among nine diabetes specialists based on patients’ information. Twenty-two general physicians chose the most suitable medication according to the patients’ information. Analyzed were data on 4,860 patients who received initial monotherapy with either insulin (293 patients) or non-insulin (4,567 patients) and had laboratory data. Accuracy was calculated by 5-fold cross validation in machine learning. The average predictive values of initial insulin use by machine learning were 0.40, 0.50 and 0.82, respectively, for under-sampling ratios of 1:2, 1:4 and 1:8. General physicians achieved a mean accuracy for initial insulin use of 51%. The overall accuracy was 43%, 57% and 86% for under-sampling ratios of 1:2, 1:4 and 1:8. The difference in the accuracy between general physicians and machine learning in the under-sampling ratio of 1:8 was significant (P<0.05).

In conclusion, accuracy of machine learning with the sampling ratio of 1:8 was higher compared with that of general physicians in initial insulin use defined by diabetes specialists’ choice as the gold standard. Assistance by machine learning may be beneficial to any general physician in deciding upon initial insulin usage.

Disclosure

K. Fujihara: None. M.H. Yamada: None. Y. Matsubayashi: None. M. Yamamoto: None. T. Iizuka: None. K. Miyamura: None. Y. Hasegawa: None. T. Yamazaki: None. S. Kodama: None. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.

Funding

Japan Society for the Promotion of Science (18K17897)
1557-P: Eye Exam Rates for Patients with T2DM from a Large Population with Employer-Sponsored Insurance
Authors: SCHEUFELE ELISABETH , ROSARIO BEDDA L. , ROBERTS FREDERICK J. , RAJMANE AMOL B. , GEORGE JUDY , FELDMAN HENRY J. , RHEE KYU B.
Published: June 2020

The ADA recommends eye exams for patients (Pt) with type 2 diabetes mellitus (T2DM) at diagnosis and annually thereafter, with an option to extend the timeline if the Pt has little to no retinopathy and is in good glycemic control. This retrospective descriptive study utilized the claims and member data from IBM® MarketScan® Commercial Research Database to examine the proportion of members with employer-sponsored insurance with T2DM, aged 18-64 years and in the U.S., who have medical claims for retinal or dilated eye exams in 2017. The dataset consists of 396,396 T2DM members enrolled continuously for 24 months in 2016-2017, with the following attributes: mean age is 54 years; females at 44.3%; ages of 18-44 at 18.1%, and 45-64 at 81.9%; regions of Midwest at 21.8%, Northeast at 16.7%, South at 49.8%, and West at 12.0%. The proportion of T2DM members with medical claims for eye exam is 35.8%. The proportion of T2DM Pts with eye exams by gender, age, and regional attributes are: females at 37.0% (numerator = 65,078), males at 34.8% (76,710); 18-44 at 25.0% (18,241), 45-64 at 38.0% (125,969); Midwest at 36.6% (31,578), Northeast at 43.6% (28,836), South at 33.6% (66,469) and West at 32.2% (15,362). About 2.1% (8,282) of T2DM Pts had a diagnosis of retinopathy, and of those, with eye exams by age group, are: 18-44 at 63.8% (812/1,272) and 45-64 at 72.8% (5,103/7,010). The average total cost per member by CPT codes are: $0.44 (Intermediate New Pt), $11.57 (Comprehensive New Pt), $9.50 (Intermediate Established Pt) and $34.06 (Comprehensive Established Pt). In this study, predominant factors for a higher rate of having a medical claim for an eye exam by members with T2DM are being female, ages 45-64, and from Northeast. There was a higher prevalence of retinopathy in the older age group. In this large sample, the majority of T2DM members did not have an eye exam. Future research should investigate the extent to which members with T2DM defer or obtain ADA recommended eye exams outside of their medical insurance coverage.

Disclosure

E. Scheufele: Employee; Self; IBM. B.L. Rosario: None. F.J. Roberts: None. A.B. Rajmane: None. J. George: Employee; Self; IBM Watson Health. H.J. Feldman: Employee; Self; IBM. K.B. Rhee: Employee; Self; IBM.
1558-P: Sex-Specific Associations of Blood and Urinary Manganese with Glucose Levels, Insulin Resistance, and Kidney Function among U.S. Adults: Use of 2011-2016 NHANES Data
Authors: YANG JINGLI , YANG AIMIN , CHENG NING , BAI YANA
Published: June 2020

Although the role of manganese (Mn) in the development of diabetes has been a concern, epidemiological studies directly linking Mn exposures to glucose homeostasis in a sex-dependent context are rare. We evaluated the associations of Mn levels in both blood and urine with glucose levels, insulin resistance, and kidney function among general populations and potential heterogeneities by sex. We performed a cross-sectional analysis of population-based data in the National Health and Nutrition Examination Survey (NHANES) involving 1417 adults in 2011-2016. We estimated the associations between blood and urinary Mn levels with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), insulin, and estimated glomerular filtration rate (eGFR) by using categorical and spline analyses. There were significant positive linear relationships between urinary Mn with FPG (P<overall=0.003, P<nonlinear=0.817) and HbA1c (P<overall=0.023, P<nonlinear=0.854) among women, while blood Mn levels were associated HOMA-IR (P<nonlinear=0.042) and insulin (P<nonlinear=0.014) with J-shaped dose-responses among men. For eGFR, positive linear relationships were observed with blood Mn in women (P<overall=0.032, P<nonlinear=0.549), and with urinary Mn in both men (P<nonlinear=0.058) and women (P<nonlinear=0.892). In sensitivity analysis, after excluding participants with diabetes, we still observed sex differences in the association between urinary Mn levels with FPG, HbA1c, insulin, HOMA-IR and eGFR.

In summary, blood and urinary Mn levels were independently associated with glucose-related biomarkers with potential heterogeneities by sex. The findings emphasize the probable role of Mn for the glucose-related biomarkers and kidney function, and call for more studies on the risk of diabetes in a sex-specific manner.

Disclosure

J. Yang: None. A. Yang: None. N. Cheng: None. Y. Bai: None.
156-LB: Effect of Maternal Obesity and GDM on Children’s Obesity and Fat Distribution
Authors: MARTIN SAMANTHA
Published: June 2020

Background: Women with obesity or gestational diabetes (GDM) and their children are at risk for type 2 diabetes. Given that obesity and fat distribution are correlated with insulin resistance, we examined whether there are differences in total adiposity and fat distribution among women who were lean (NW) or obese (Ob) with no GDM history, verses women with prior GDM, and their children. We hypothesized that dyads in the GDM group would have greater adiposity and more centralized fat distribution compared to dyads in the NW and Ob groups.

Methods: Mother-child dyads were enrolled 4-10 years after a pregnancy complicated by GDM (N=73), or without GDM and NW (N=76) or Ob (N=76). Body weight, height, and anthropometric measures of adiposity were collected. ANCOVA were used to assess group differences in BMI, BMIz (in children), sum of skinfolds (SS), waist to hip ratio (WHR), and central (suprailiac + subscapular) to peripheral (thigh + tricep) skinfold ratio (CvP). Models were adjusted for age and race for mothers, along with tanner stage and sex for children.

Results: Women with prior GDM had greater BMI and SS compared to women in the NW group (P<0.0001), but did not differ from Ob. Despite similar total adiposity for GDM and Ob groups, the GDM group had greater WHR and CvP as compared to Ob (P<0.05). Among children, BMIz and WHR were greater in the GDM versus NW offspring (P<0.05), with children in the Ob group having a mean BMIz and WHR that was in between NW and GDM.

Conclusion: Results support the hypothesis that women with prior GDM exhibit more central adiposity despite having similar BMI as women with Ob without prior GDM. Among children, BMIz and central adiposity increased progressively when comparing offspring of NW, Ob, and GDM mothers. The results indicate that both Ob and GDM in mothers during pregnancy may affect total and central adiposity in children. While additional research is needed, attention to maternal health before and during pregnancy is vital to mitigate against a cardiometabolic disease phenotype in children.

Disclosure

S. Martin: None.

Funding

American Heart Association (336101011); University of Alabama at Birmingham (DK079626, DK056336)
1569-P: Prevalence, Risk, and Management of Diabetes in Friedreich’s Ataxia
Authors: TAMAROFF JACLYN , DEDIO ANNA , WADE KRISTIN L. , RUMMEY CHRISTIAN , PINNEY SARA E. , LYNCH DAVID , KELLY ANDREA , MCCORMACK SHANA
Published: June 2020

Background: Friedreich’s Ataxia (FA) is a neuromuscular disorder caused by either GAA triplet repeat expansions of both alleles of the gene frataxin, or less commonly, by a point mutation in one allele and triplet expansion on the other. FA is associated with an increased incidence of diabetes (DM), but risk factors and management are not well described.

Objective: To report the prevalence of, identify risk factors for, and describe management of DM in FA using the large (N=1,020) multi-site, longitudinal, observational FA Outcomes Measures Study (FACOMS).

Methods: FACOMS was queried for self-reported DM status and the modified FA Rating Scale (mFARS), which rates severity. For the subset at the Children’s Hospital of Philadelphia (CHOP), past medications were noted via EMR. Point mutation status and mFARS were compared in DM vs. non DM with chi-square and Wilcoxon signed rank tests, respectively. Independent risk factors for DM were tested by logistic regression including mFARS, age, point mutation, and age of FA diagnosis (dx).

Results: Median age of FA dx was 14y (IQR 10-21), 5.7% had a point mutation, and 8.8% had DM. In those with DM, median age at DM dx was 27y (IQR 17-41) and mean HbA1c since dx was 7% (SD 1). Point mutations were more common in DM vs. non DM (13.9% vs. 4.9%; p<0.001). Those with DM had more severe disease (median mFARS, 70, IQR 58,78) vs. without (55, IQR 41,68) (p<0.001). In logistic regression, severe disease (mFARS 4th vs. 1st quartile, OR 4.54, 95%CI: 1.75,11.77, p=0.002), older age (OR 1.05, 95%CI: 1.02,1.07, p<0.001), and point mutation (OR 4.49, 95%CI: 2.11,9.53, p<0.001) were associated with a greater risk of DM. In FACOMS, 76% (61/80 with DM and current medication data) used insulin. At CHOP, 47% (14/30 with DM and past medication data) had ever tried Metformin.

Conclusions: DM in FA was associated with more severe disease, older age, and a point mutation. Many require insulin. Future studies will evaluate the pathophysiology of FA-related DM to inform screening practices and management decisions.

Disclosure

J. Tamaroff: None. A. DeDio: None. K.L. Wade: None. C. Rummey: None. S.E. Pinney: None. D. Lynch: None. A. Kelly: None. S. McCormack: Advisory Panel; Self; Reata Pharmaceuticals, Rhythm Pharmaceuticals. Other Relationship; Self; Levo Pharmaceuticals.

Funding

National Institutes of Health (T32DK063688-16); Uplifting Athletes; McCormack Children’s Hospital of Pittsburgh Metabolism, Nutrition, and Development Research Affinity Group; McCormack Friedreich’s Ataxia Research Alliance