bluuebunny/crossref_metadata_2025 huggingface dataset:
1126-P: A New Prostate-Specific Antigen Threshold for Screening Prostate Cancer among Diabetic Patients
Authors: LIU CHUNYAN , CHEN YI , LIU JIASHU , YIN JIAJING , ZHA XIAOJUAN , SU BIN , LI HONG
Published: May 2022

Background: The level of prostate-specific antigen (PSA) was reported to be reduced in type 2 diabetes mellitus (T2DM) . Possible low PSA levels in T2DM patients reduce the sensitivity of prostatic cancer (PCa) screening. To improve the effectiveness of early PCa screening inT2DM, it is necessary to establish a new PSA threshold for T2DM patients.

Methods: We retrospectively analyzed the clinical data of 2151 patients who underwent prostate biopsy for the first time admitted to Shanghai Tenth People′s Hospital from January 20to March 2020. The distribution of PSA was estimated by fitting a probability function. Machine learning methods was used to find a new threshold for PCa screening in T2DM.

Results: This study found that the PSA level in T2DM was lower than the regular patients. The new PCa screening threshold for T2DM was PSA=3.27 ng/mL. Meanwhile, the possible influence of age and body mass index (BMI) on the threshold were excluded. Compared with 4ng/mL, the sensitivity and specificity of the new threshold in T2DM patients for PCa screening were 94.53% (vs.91.54%) and 41.36% (vs.46.78%) , area under the curve (AUC) 0.83 (vs.0.83, P>0.5) .

Conclusion: The serum PSA levels in T2DM patients reduced. The new PCa screening threshold in T2DM based on machine learning is 3.27ng/mL. Lowering the PSA screening threshold for T2DM has a better early warning effect on PCa, which is conducive to improving the early diagnosis rate of PCa in T2DM patients.

Disclosure

C.Liu: None. Y.Chen: None. J.Liu: None. J.Yin: None. X.Zha: None. B.Su: None. H.Li: None.
1130-P: A Prospective Cohort Study on the Predictive Value of Controlled Attenuation Parameter Measured by FibroScan to the Transition of Metabolic Status
Authors: LI JIANGHONG , HUANG ZHIMIN , DENG WANPING , ZHANG ZHI , LI YANBING
Published: May 2022

Aims: Our previous study validated that controlled attenuation parameter (CAP) was a sensitive surrogate marker for evaluating metabolic derangement. However, prospective studies are needed to assess its usefulness for transition of metabolic status over time. In this study, predictive effect of CAP and its change over time was investigated by following up of medical staff volunteered for MAFLD study over 3 years.

Subjects and Methods: Volunteers were recruited from our hospital to undergo FibroScan examination in 2018 and followed up in 2021. Anthropometric data, CAP and hematological indices for metabolic profiles and insulin resistance were collected. Metabolic syndrome (MetS) components were scored. CAP≥238 dB/m denoted hepatic steatosis. Number of MetS component increased by 1 or more was denoted ‘progression’ , whereas decreased by 1 or more denoted ‘regression’ of metabolic status.

Results: A total of 922 subjects volunteered for FibroScan examination in 2018, and 466 of them were followed in 2021. At baseline, the median age was 49.0 years, BMI was 23.3kg/m2, waist circumference was 80cm. CAP were 240 (216, 275) dB/m, LSM were 3.9 (3.4, 4.7) Kpa, 242 (51.9%) subjects were with CAP≥238 dB/m. During the follow up, 124 (26.6%) subjects had progression, while 81 (17.3%) had regression of metabolic status. Logistic regression showed that CAP at baseline [1.0 (1.001, 1.011) , P = 0.019], change in waist circumference [1.1 (1.047, 1.165) , P = 0.000] and change in CAP [1.0 (1.004, 1.0150) , P = 0.001] were independent predictors for progression. In contrast, CAP at baseline [1.012 (1.006, 1.018) , P= 0.000], change in waist circumference [0.9 (0.857, 0.967) , P = 0.002] and change in LSM [0.813 (0.667, 0.990) , P = 0.040] were significant in predicting regression of metabolic status.

Conclusions: CAP at baseline, changes in CAP and waist circumference are useful surrogate markers for predicting transition of metabolic status over time.

Disclosure

J.Li: None. Z.Huang: None. W.Deng: None. Z.Zhang: None. Y.Li: None.

Funding

National Natural Science Foundation of China (82070918)
1135-P: Concomitant Use of Sulfonylureas and Beta-Blockers and the Risk of Severe Hypoglycemia: A Population-Based Cohort Study
Authors: DIMAKOS JENNY , CUI YING , PLATT ROBERT W. , RENOUX CHRISTEL , FILION KRISTIAN B. , DOUROS ANTONIOS
Published: May 2022

Background: Beta-blockers may interact with sulfonylureas (SU) and increase their hypoglycemic risk. Our study assessed the potential association between concomitant use of SU and beta-blockers and the risk of severe hypoglycemia.

Methods: We used the UK's Clinical Practice Research Datalink linked to hospitalization and vital statistics data of patients with type 2 diabetes initiating SU between 1998 and 2020, excluding those with beta-blocker use in the past 6 months. Time-dependent Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycemia associated with current concomitant use of SU and beta-blockers compared to current SU use alone, adjusted for baseline confounders. To address potential residual confounding, we repeated the analysis with current concomitant use of SU and thiazide diuretics as reference group. We also compared current concomitant use of SU and non-cardioselective (propranolol, carvedilol, sotalol, labetalol) vs. cardioselective beta-blockers (acebutolol, atenolol, bisoprolol, metoprolol, nebivolol, esmolol) to explore the role of beta-blocker cardioselectivity in this association.

Results: Our cohort included 252,869 SU initiators. The crude incidence rate of severe hypoglycemia was 7.8 per 1000/year. Concomitant use of SU and beta-blockers was associated with an increased risk of severe hypoglycemia compared to SU use alone (HR, 1.53; 95% CI, 1.42-1.65) . Changing the reference group led to consistent findings (HR, 1.69; 95% CI, 1.42-2.01) . There was no difference in the risk when comparing concomitant use of SU and non-cardioselective beta-blockers to concomitant use of SU and cardioselective beta-blockers (HR, 0.95; 95% CI, 0.74-1.24) .

Conclusion: Our large cohort study showed an increased risk of severe hypoglycemia associated with concomitant use of SU and beta-blockers compared to SU use alone. This association did not vary with beta-blocker cardioselectivity.

Disclosure

J.Dimakos: None. Y.Cui: None. R.W.Platt: Consultant; Amgen Inc., Biogen, Merck & Co., Inc., Nant Pharma, Pfizer Inc. C.Renoux: None. K.B.Filion: None. A.Douros: None.

Funding

Canadian Institutes of Health Research (PJT-165882)
1139-P: The Association between Age of Onset of Type 2 Diabetes and the Long-Term Risk for Major Diabetes-Related Complications
Authors: MORTON JEDIDIAH I. , LAZZARINI PETER , POLKINGHORNE KEVAN , MAGLIANO DIANNA J. , SHAW JONATHAN E.
Published: May 2022

We evaluated the association between age of onset of type 2 diabetes and the risk for major diabetes complications. We included 1.1 million people with type 2 diabetes from the Australian diabetes registry, followed from 2010-2019. We evaluated the incidence of hospitalization for, or death from, myocardial infarction (MI) , stroke, and heart failure (HF) , and hospitalization for lower extremity amputation (LEA) ; the incidence of end-stage kidney disease (ESKD; including kidney replacement therapy or death from ESKD) ; and all-cause mortality (ACM) . Poisson regression was used to model rates by age of diabetes onset, current age, and diabetes duration. During 6.9 million person-years of follow-up, 72338, 46533, 101023, 20024, 13331, and 203542 MI, stroke, HF, LEA, ESKD, and ACM events occurred, respectively. The risk for all outcomes increased exponentially with diabetes duration (Figure) . The effects of age and duration differed for each: age was the stronger risk factor for MI, stroke, HF, and ACM, while duration was the predominant determinant of ESKD and LEA risk. At a given age, a 10-year younger age of onset was associated with a 1.1-1.5-fold increased risk of stroke and ACM, a 1.5-2-fold increased risk of MI and HF, and a 2-4-fold increased risk of LEA and ESKD. Thus, the increase in prevalence of young-onset type 2 diabetes may shift the burden of diabetes complications in coming decades.

Disclosure

J.I.Morton: None. P.Lazzarini: None. K.Polkinghorne: None. D.J.Magliano: None. J.E.Shaw: Advisory Panel; Abbott Diagnostics, AstraZeneca, Eli Lilly and Company, Pfizer Inc., Roche Diagnostics, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi.

Funding

JIM is supported by an Australian Government Research Training Program (RTP) Scholarship and Monash Graduate Excellence Scholarship. PAL is supported by a National Health and Medical Research Council Early Career Fellowship. DJM is supported by a National Health and Medical Research Council Senior Research Fellowship. JES is supported by a National Health and Medical Research Council Investigator Grant. This work is partially supported by the Victorian Government’s Operational Infrastructure Support Program.
114-OR: A Randomized Clinical Trial of Etanercept and Alpha-1 Antitrypsin in TPIAT
Authors: ABDEL-KARIM TASNEEM R. , HODGES JAMES S. , PRUETT TIMOTHY L. , RAMANATHAN KARTHIK , BEILMAN GREG , BELLIN MELENA
Published: May 2022

Total pancreatectomy with islet auto-transplant (TPIAT) can relieve pain for patients with intractable pancreatitis. However, inflammatory damage to transplanted islets from the instant blood mediated inflammatory response (IBMIR) limits the IAT's success. We hypothesized blockade of IBMIR would improve islet engraftment, resulting in improved islet function.

We randomized 43 participants to A1AT (90 mg/kg IV x6 doses) , or etanercept (50 mg then 25 mg SQ x 5 doses) , or standard care in a 1:1:1 ratio. Islet graft function was assessed with mixed meal tolerance test (MMTT) , intravenous glucose tolerance test (IVGTT) , glucose-potentiated arginine-induced insulin secretion (GPAIS) , HbA1c, and insulin use 3 months and 1 year after TPIAT. Acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) 3 months after TPIAT were higher in the etanercept-treated group (p<0.025, Fig 1) , but neither treatment differed significantly from controls at 1 year (Fig 1) . MMTT, GPAIS, HbA1c, and insulin use did not differ between groups. Multivariate modelling suggested a sex-specific response, with females on A1AT showing the most robust insulin secretion from GPAIS at 1 year (p≤0.033) .

In conclusion, this randomized pilot study suggests etanercept may improve early islet engraftment. The long-term effect of etanercept or A1AT on islet engraftment is less clear, though speculatively females may have a sex-specific benefit.

Disclosure

T.R.Abdel-karim: None. J.S.Hodges: None. T.L.Pruett: None. K.Ramanathan: None. G.Beilman: None. M.Bellin: Advisory Panel; Insulet Corporation, Research Support; Dexcom, Inc., Viacyte.

Funding

National Institute of Health (R01DK109914)
115-LB: Dorzagliatin Showed Sustained Remission in an Observational Study after Discontinuation of Treatment in T2D Patients Who Achieved Good Glycemic Control with Dorzagliatin Monotherapy
Authors: ZENG JIAOE , GAN SHENGLIAN , DONG XIAOLIN , LIU YUNFENG , SU XIAOFEI , LUO JIANFENG , MA JIANHUA
Published: May 2022

Diabetes remission is the optimal goal for treating T2D. While most remission studies focused on metabolic surgery, lifestyle interventions, and intensive insulin therapy, little evidence was found with oral antidiabetic drugs. Dorzagliatin is an oral dual-acting glucokinase activator which has shown effective glycemic control with significant improvements in early-phase insulin secretion and β-cell function. DREAM was an observational, non-pharmacological, non-interventional diabetes remission study, an extension study of a phase 3 monotherapy trial (SEED) with dorzagliatin. Initiated by investigators from 5 in 40 study sites in SEED, DREAM aimed to observe whether patients who had completed SEED and achieved good glycemic control were able to achieve diabetes remission without any antidiabetic medication. In total, 69 subjects previously with drug-naïve T2D and treated with dorzagliatin for 28 or 52 weeks in SEED were enrolled. The primary endpoint was the diabetes remission rate after 52 weeks of dorzagliatin withdrawal, estimated by the Kaplan-Meier method. At week 52, 36 subjects maintained stable glycemic control and the remission rate was 65.2% (95% CI, 53.4 to 77.0) . These 36 patients had shown improvement of early-phase insulin secretion (C30/G30) after dorzagliatin treatment in SEED. Improvements of β-cell function and insulin resistance were sustained during DREAM (indicated by HOMA2-β of 43.8 at baseline and 56.6 at week 52, HOMA2-IR of 1.58 at baseline and 1.46 at week 52) . According to a consensus released in Aug 2021 by ADA, diabetes remission was defined as HbA1c<6.5% measured at least 3 months after cessation of glucose-lowering pharmacotherapy. Based on this definition, the remission rate was 52.0% (95% CI, 31.2 to 69.2) . DREAM observed sustained glycemic control in a high proportion of subjects after withdrawal of dorzagliatin monotherapy, indicating that improvements of early-phase insulin secretion and β-cell function may be a potential mechanism for diabetes remission.

Disclosure

J. Zeng: None. S. Gan: None. X. Dong: None. Y. Liu: None. X. Su: None. J. Luo: None. J. Ma: None.
1156-P: Ischaemic Heart Disease in Type 2 Diabetes Before and After Diagnosis: Impact on Expected Lifetime and Trends 1996–2020
Authors: CARSTENSEN BENDIX , CLEMMENSEN KIM K. , AMADID HANAN
Published: May 2022

Background: Complications can be present at type 2 diabetes (T2D) diagnosis or develop later. We describe trends in burden of ischaemic heart disease (IHD) in T2D.

Methods: T2D cases in Denmark 1996-2020 in a national diabetes register were used. Events of IHD 1994-2020 were from the National Patient Register. Prevalence of IHD at time of T2D was described by a binomial model. New IHD and death during follow-up were analysed by rate models and used to estimate the time in the states (no IHD / IHD at T2D / IHD after T2D) .

Results: 410,4 persons with T2D 1996-2020 were included; 61,378 with pre-existing IHD. Prevalence of IHD at T2D diagnosis was increasing 1.7%/year. Incidence rates of IHD after diagnosis was decreasing 5.7%/year. Mortality among T2D persons without IHD decreased 5.7%/year; for those with IHD it decreased 3.5%/year. During the first years, expected lifetime was 8.1 and 8.8 years for men diagnosed at age 65 in 1998 and 2018, respectively. Time without IHD was 6.2 and 6.9 years, with new IHD 0.9 and 0.5 years and with preexisting IHD 1.0 and 1.5 years in 1998 and 2018. We saw an increase in expected lifetime, partly as increase in lifetime with preexisting IHD. Similar patterns were seen for women and for persons diagnosed in other ages.

Conclusions: We saw an increase in expected lifetime, as well as decreasing mortality rates regardless of IHD status. Prevalence of IHD at the time of diagnosis was increasing, possibly due to more detailed diagnoses of IHD; in our data only IHD complications after 1994 are included which may be a partial explanation of the increase in prevalent IHD at the date of T2D diagnosis. In general the IHD burden in T2D in Denmark is decreasing.

Disclosure

B.Carstensen: Stock/Shareholder; Novo Nordisk A/S. K.K.Clemmensen: Employee; Novo Nordisk A/S, Research Support; AstraZeneca, Novo Nordisk Foundation, Stock/Shareholder; Lundbeck, Novo Nordisk A/S. H.Amadid: Stock/Shareholder; Novo Nordisk.
1165-P: Combined Severe Diabetic Complications: The New Life-Altering Outcome
Authors: YAGUCHI YUTA , FUJIHARA KAZUYA , YAMADA MAYUKO H. , MATSUBAYASHI YASUHIRO , YAMADA TAKAHO , IWANAGA MIDORI , KITAZAWA MASARU , YAMAMOTO MASAHIKO , KODAMA SATORU , SONE HIROHITO
Published: May 2022

Since advanced microangiopathy of diabetes severely impairs activities of daily living (ADL) and quality of life (QoL) and macroangiopathy is life-threatening regardless of severity, treatment of diabetes requires appropriate risk management to avoid all such complications. However, current studies have analyzed and reported diabetes complications separately, despite varying incident rates and impacts on ADL/QoL and severity of illness. It is difficult to determine which predictors should be prioritized when extrapolating the results of these studies to the comprehensive care of individual patients. We defined the combined severe diabetic complications as a new life-altering outcome and determined the association of established risk factors with combined severe diabetic complications. We analyzed data from a nationwide database involving 36,994 participants with diabetes mellitus without any prior life-altering complication of diabetes during 2008-19. Combined severe diabetic complications included severe diabetic eye disease, initiating dialysis, coronary artery disease (CAD) , cerebrovascular disease (CVD) , heart failure (HF) , or amputation which were determined according to ICD-codes, medication and medical procedures. During a median follow-up period of 5.0 years, the following events occurred: severe diabetic eye disease, 774; dialysis initiated, 134: CAD, 703; CVD, 535; HF, 161; and amputations, 31. Multivariate Cox regression model showed the HRs per 1SD for combined severe diabetic complications of HbA1c, SBP, current smoking, HDL-C, BMI and LDL- C were 1.54 (1.49-1.59) , 1.37 (1.31-1.42) , 1.35 (1.23-1.48) , 0.83 (0.79-0.88) , 0.85 (0.81-0.90) and 1. (1.06-1.16) , respectively. We found that HbA1c was the most strongly associated with combined severe diabetic complications among established risk factors. Also, our results implied the necessity of revisiting the value of BMI in risk management for combined severe diabetic complications.

Disclosure

Y.Yaguchi: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. K.Fujihara: None. M.H.Yamada: None. Y.Matsubayashi: None. T.Yamada: None. M.Iwanaga: None. M.Kitazawa: None. M.Yamamoto: None. S.Kodama: None.
1169-P: Circulating MicroRNA-378a-5p and Improvement in Glucose Homeostasis in Response to Weight-Loss Diets: The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) Trial
Authors: XUE QIAOCHU , HEIANZA YORIKO , LI XIANG , DENG HONG-WEN , ROOD JENNIFER , BRAY GEORGE , SACKS FRANK , QI LU
Published: May 2022

Background: MicroRNA-378a (MiR-378a) has been identified as a key regulator of glucose homeostasis and emerging as a promising target for the improvement of glycemic dysregulation including type 2 diabetes. Hypothesis: We assessed associations of circulating miR-378a-5p with improvements in insulin sensitivity and glucose metabolism in a 2-year dietary intervention trial.

Methods: Circulating miR-378a-5p levels were measured at baseline and 6 months among 5participants with overweight or obesity. Outcome measurements including fasting glucose, hemoglobin A1c (HbA1c) , fasting insulin, and homeostasis model assessment-of-insulin resistance (HOMA-IR) were assessed at baseline, 6 and 24 months.

Results: Higher level of miR-378a-5p was associated with greater fasting glucose (p =0.031) at baseline. Greater decrease in miR-378a-5p was significantly associated with greater improvements in fasting insulin (p =0.012) and HOMA-IR (p =0.017) over 6 months. The initial (6-months) decrease of miR-378a-5p was also significantly related to long-term (24-months) improvements in glucose, insulin, and HOMA-IR (p <0.for all) . Individuals in the lowest tertile group of the baseline miR-378a-5p showed consistently improved fasting insulin and HOMA-IR over 2 years, as compared to those with higher levels of miR-378a-5p (p time*miR-378a-5p =0.015 and 0.007, respectively) . We also found significant interactions between baseline miR-378a-5p and dietary fat in the 6-months change in HbA1c (p = 0.003) ; a lower level of baseline miR-378a-5p showed a greater reduction of HbA1c at 6 months among participants who consumed a low-fat diet.

Conclusions: In conclusion, decreased circulating miR-378a-5p levels were related to significant improvements in insulin sensitivity and glucose metabolism in response to dietary weight-loss interventions; and dietary fat intake modified such associations.

Disclosure

Q.Xue: None. Y.Heianza: None. X.Li: None. H.Deng: None. J.Rood: None. G.Bray: None. F.Sacks: None. L.Qi: None.

Funding

National Heart, Lung, and Blood Institute (HL071981, HL034594, and HL126024) ;National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, and DK100383) ;Fogarty International Center (TW010790)
1171-P: Food Insecurity and Glycemic Goals among Medicare Beneficiaries with Type 2 Diabetes
Authors: NG BOON PENG , STEWART MORGAN P. , LAMANNA JACQUELINE B. , PARK CHANHYUN
Published: May 2022

Food insecurity, a modifiable risk factor, has a significant impact on individuals' health and well-being. This study examined the association between food insecurity and glycemic goals among Medicare beneficiaries aged ≥65 years with type 2 diabetes (T2D) , using the 20Medicare Current Beneficiary Survey (n=1,340) . The binary dependent variable was whether beneficiaries' blood glucose (BG) was at target (i.e., having A1C ≤7.5% or average fasting BG of ≤140 mg/dL, all/most of the time) . Food insecurity, a binary variable, was defined as having ≥2 affirmative responses on 4 selected questions of the USDA's food security questionnaire. A survey-weighted multivariable logistic model, adjusted for socio-demographics and comorbidities, was conducted to estimate predictive margins for comparing prevalence of having higher than target BG levels across groups. Of study beneficiaries with T2D, 20.9% reported not achieving glycemic targets. Beneficiaries not meeting BG goals were more likely to be: female (60.5% vs. 49.1%, p=0.002) , less educated (<high school, 21.9% vs. 13.4%, p=0.013) , and experiencing food insecurity (20.4% vs. 8.9%, p<0.001) . In the adjusted analysis, the predictive marginal prevalence of having higher than target BG levels was significantly greater in females over males (23.8% [95% CI, 20.0-27.5] vs. 16.6% [13.4-19.8]) ; those with less than high school education over those with greater education (30.9% [23.6-38.3] vs. 18.5% [14.7-22.3]) ; and those reporting food insecurity over their counterparts (33.4% [24.5-42.3] vs. 19.1% [16.5-21.6]) . This study identified that females, those with low education levels, and those experiencing food insecurity may be less likely to achieve BG goals, placing them at-risk of developing potentially preventable complications and incurring higher overall healthcare costs. Routine screening and interventions to reduce these disparities should be considered by all healthcare team members caring for Medicare beneficiaries with T2D.

Disclosure

B.Ng: None. M.P.Stewart: None. J.B.Lamanna: None. C.Park: None.
1172-P: Higher Dairy Consumption Is Associated with Lower Risk of Type 2 Diabetes among U.S. Adults: A Nationally Representative Study
Authors: TOMAH SHAHEEN , HAMDY OSAMA
Published: May 2022

Dairy consumption has been associated with a modestly lower risk of type 2 diabetes and other components of the metabolic syndrome in few cohort studies. However, confounding by overall diet quality and physical activity levels remains present. We evaluated 4,934 adults who participated in the 2017-2018 National Health and Nutrition Examination Surveys (NHANES) and underwent two 24-hr dietary recalls in addition to general health questionnaires, examinations, and laboratory assessments. Dairy intake data (milk, yogurt, and cheese but not dairy-based desserts) were extracted and transformed into USDA-defined serving sizes then categorized based on number of servings: non-consumers, <1 serving, 1 to <2 servings, and ≥2 servings. We defined diabetes mellites (DM) as physician-diagnosed DM, A1c ≥6.5%, or fasting plasma glucose ≥126 mg/dL. We calculated the Healthy Eating Index-2015 (HEI-2015) , an indicator of overall diet quality. The average age of this cohort was 49.6±18.5 yrs, 51% were female, 73.5% were overweight or obese, and 17% had DM. After multivariate adjustment for age, gender, BMI, smoking, vigorous physical activity, and HEI-2015, intake of ≥2 servings of dairy was associated with lower risk of DM (OR: 0.9, 95% CI 0.81-0.99, p=0.049) compared with non-consumers. In sensitivity analysis, the association between intake of ≥2 servings of dairy and prevalent DM showed directionally dissimilar results when adding dairy type-specific servings to the model (Milk, OR: 0.9, 95% CI 0.77-1.05, p=0.vs. combined cheese and yogurt, OR: 0.87, 95% CI 0.76-0.99, p=0.036) . In conclusion, higher dairy intake is associated with lower risk of DM among US adults while adjusting for diet quality. This association seems to be driven by cheese and yogurt intake rather than by milk. These findings need to be evaluated in randomized prospective intervention trials.

Disclosure

S.Tomah: None. O.Hamdy: Advisory Panel; L-Nutra Inc., Nestlé, Consultant; Abbott, Sanofi, Research Support; Eli Lilly and Company, Gilead Sciences, Inc., National Dairy Council, Novo Nordisk, Stock/Shareholder; Healthimation.

Funding

The authors received specific funding for this research
1173-P: Metabolomic Signatures of Refined Grains Intake and Risk of Gestational Diabetes
Authors: ZHU YEYI , ZHENG SIWEN , NGO AMANDA , CHEHAB RANA F. , WANG EMILY Z. , FIEHN OLIVER , FERRARA ASSIAMIRA
Published: May 2022

Previous studies linked refined grains intake to risk of gestational diabetes (GDM) ; however, the underlying mechanisms remain understudied. We aimed to identify and validate refined grains-related metabolites as biomarkers for GDM. In a nested case-control study of 91 women with GDM and 180 non-GDM controls (discovery set) in the Pregnancy Environment and Lifestyle Study (PETALS) cohort, we assessed dietary intake of refined grains by a validated food frequency questionnaire and measured fasting serum untargeted metabolomics at gestational weeks (GW) 10-13. We identified metabolites associated with refined grains intake using multivariable linear regression and examined prospective associations of refined grains-related metabolites at GW 10-13 with risk of GDM in later pregnancy using conditional logistic regression. We further examined incremental predictivity of refined grains-related metabolites selected by 10-fold cross-validated LASSO regression beyond conventional risk factors in the discovery set and a random PETALS subsample (38 GDM, 336 non-GDM) as the validation set. Among 821 known metabolites, 42 (mostly lipids/lipid-like molecules and organic oxygen/acids compounds) were associated with refined grains intake in early pregnancy, of which 17 were significantly associated with GDM risk (all FDR < 0.05) . Adding seven out of 17 metabolites selected by LASSO regression to a conventional risk factor-based prediction model increased the C-statistic from 0.71 (95% CI 0.64-0.77) to 0.77 (0.71-0.83) ; P-for-difference < 0.05. Similar improvement was observed in the validation set [0.77 (0.69-0.86) to 0.81 (0.74-0.89) ; P-for-difference < 0.05]. Refined grains intake may be associated with risk of GDM via perturbed metabolic pathways of glycerolipids, glycerophospholipids, and sphingolipids. Refined grains-related metabolites might help improve prediction of GDM risk and inform diet-related preventive strategies. Further validation studies are warranted.

Disclosure

Y.Zhu: None. S.Zheng: None. A.Ngo: None. R.F.Chehab: None. E.Z.Wang: None. O.Fiehn: None. A.Ferrara: n/a.

Funding

National Institutes of Health Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Program (K12HD052163) ; National Institute of Diabetes and Digestive and Kidney Diseases (K01DK120807)
1177-P: Mediterranean Diet Is Associated with a Better Estimated Renal Function in Overweight, but Not in Obese, Adults with Impaired Fasting Glucose
Authors: LEONE ALESSANDRO , DE AMICIS RAMONA , FOPPIANI ANDREA , BERTOLI SIMONA , BATTEZZATI ALBERTO
Published: May 2022

Background: Impaired fasting glucose (IFG) is a risk factor for renal function, whereas adherence to the Mediterranean diet may be protective.

Methods: Cross-sectional study on 1016 overweight (OW) and 1297 obese (OB) adults (52 ± 12 yrs, 55% women) with IFG (s-glucose: 100-125 mg/dl) . Anthropometry, fat-free mass by BIA, s-creatinine, blood pressure, marital status, education, familiarity for diabetes and CVD, smoking and physical activity were evaluated. The 14-item MEDiterranean Diet Adherence Screener (MEDAS, score: 0-14 points) was used to assess Mediterranean diet. Glomerular filtration rate (eGFR) was estimated by CKD-EPI formula. Normal renal function was defined as eGFR ranged 90-140 ml/min/1.73m2, so that both cases of loss of renal function and cases of glomerular hyperfiltration were considered at risk of renal damage. Logistic regression stratified for BMI class and adjusted for above confounders was fitted to assess association of Mediterranean diet with normal renal function.

Results: The prevalence of normal renal function was 55% (60% in OW, 52% in OB) . Compared to the first tertile, the highest tertile of MEDAS score was associated to higher odds being normal renal function in OW (OR 1.48, 95%CI 1.07, 2.04, Ptrend=0.014) but not in OB patients.

Conclusion: Mediterranean diet is associated with a better renal function in OW patients with IFG.

Disclosure

A.Leone: None. R.De amicis: None. A.Foppiani: None. S.Bertoli: None. A.Battezzati: None.
1179-P: Secular Trends in Dietary Intake Over a Five-Year Period in People with Type 2 Diabetes in Japan: Japan Diabetes Complications Study (JDCS)
Authors: HORIKAWA CHIKA , AIDA REI , KAMADA CHIEMI , FUJIHARA KAZUYA , TANAKA SHIRO , ARAKI ATSUSHI , YOSHIMURA YUKIO , AKANUMA YASUO , SONE HIROHITO
Published: May 2022

To provide effective medical nutrition therapy (MNT) , it is necessary to consider dietary intake, which can change over time. This longitudinal study analyzed changes in the dietary intakes of Japanese patients with type 2 diabetes over a 5-year period. The JDCS is a nationwide study of Japanese patients with type 2 diabetes conducted in 1996. Participants were aged 40-70 years from outpatient clinics in 59 universities and general hospitals. Analyzed were 922 responders to a dietary survey assessed by the Food Frequency Questionnaire based on food groups at baseline and 5 years after registration. Paired samples t-test was used for analysis. Over a 5-year period, patients with type 2 diabetes maintained almost the same body mass index (BMI) (baseline: 22.9±3.0; 5 years later: 22.8±3.0 kg/m2) . Differences in energy intake, fat-to-energy ratio, and carbohydrate-to-energy ratio were small although significant. Neither the mean intake of fiber nor salt met the required intake for MNT for persons with diabetes both at baseline and after 5 years. As for food groups, there was a significant decrease in intakes of vegetables, seaweed, soybeans/soy products, and milk/dairy products. Details are shown in the Table. Results showed that Japanese patients with type 2 diabetes need to pay special attention to dietary fiber intake and salt intake on an ongoing basis.

Disclosure

C.Horikawa: None. R.Aida: None. C.Kamada: None. K.Fujihara: None. S.Tanaka: None. A.Araki: None. Y.Yoshimura: None. Y.Akanuma: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited.

Funding

Japan Society for the Promotion of Science (19H04028)
118-LB: The Antipsychotic D2 Receptor Antagonist Diphenylbutylpiperidines Improve Glycemia in Experimental Obesity by Inhibiting Succinyl-CoA—3-Ketoacid CoA transferase
Authors: TABATABAEI DAKHILI SEYED AMIRHOSSEIN , ABOU FARRAJ RABIH , GREENWELL AMANDA A. , SAED CHRISTINA T. , YANG KUNYAN , GOPAL KESHAV , CHAN JORDAN S.F. , LEE CRYSTAL , EATON FARAH , VELAZQUEZ CARLOS A. , CRAWFORD PETER A. , GLOVER MARK , AL BATRAN RAMI , USSHER JOHN R.
Published: May 2022

Purpose: Despite significant progress in understanding the pathogenesis of type 2 diabetes (T2D) , it remains difficult to manage, hence, new therapeutic options are required. We previously observed that elevated skeletal muscle succinyl CoA:3-ketoacid CoA transferase (SCOT) activity, the rate-limiting enzyme of ketone (KB) oxidation, contributes to obesity-induced hyperglycemia. Moreover, we identified that the antipsychotic agent, pimozide, is a SCOT inhibitor with glucose-lowering actions. In silico molecular modeling determined that a wide range of DPBPs can theoretically inhibit SCOT activity, therefore, we determined whether the DPBP drug class could be repurposed for the treatment of T2D.

Methods: 8-week-old male wild-type and muscle-specific/brain-specific SCOT knockout (SCOTMuscleKO, SCOTBrainKO) mice were subjected to experimental obesity via consumption of a high fat, high sugar diet for 12-weeks. Lean control mice received a low fat, low sugar diet. At 8-weeks, lean and obese mice were treated with DPBPs (penfluridol, fluspirilene, pimozide (10mg/kg)) once every 2 days via oral gavage for 14-days, following which circulating KB levels and glucose homeostasis were assessed. To rule out a contribution of the canonical actions of DPBPs as dopamine 2 (D2) receptor antagonists to DPBP-mediated glucose-lowering, obese mice were treated with the structurally unrelated D2 receptor antagonist, lurasidone (10 mg/kg) .

Results: All tested DPBPs improved glucose homeostasis in obese mice through a mechanism dependent on the inhibition of both brain and muscle SCOT activity. Treatment with lurasidone failed to improve glycemia in obese mice, thus consistent with a SCOT-dependent mechanism of action.

Conclusions: Our findings suggest all DPBPs have glucose-lowering actions and therefore may have clinical utility in being repurposed for the treatment of T2D.

Disclosure

S. Tabatabaei dakhili: None. C. A. Velazquez: None. P. A. Crawford: Advisory Panel; Abbott Diabetes, Johnson & Johnson Global Services. M. Glover: None. R. Al batran: None. J. R. Ussher: None. R. Abou farraj: None. A. A. Greenwell: None. C. T. Saed: None. K. Yang: None. K. Gopal: None. J. S. F. Chan: None. C. Lee: None. F. Eaton: None.

Funding

Canadian Institutes of HealthResearch
1180-P: Diet Quality and ABC Goals among U.S. Adults with Diabetes: 2013–2018
Authors: CHEN YU , SIEGEL KAREN R. , BULLARD KAI M. , ROLKA DEBORAH B.
Published: May 2022

A healthy diet can help attain hemoglobin HbA1c (A1C) , blood pressure (BP) , and cholesterol goals (ABC goals) in people with diabetes. We examined the association of diet quality with achievement of ABC goals (defined as A1C<8%, BP <140/90 mmHg, non-HDL cholesterol <130 mg/dL, and meeting all three goals) among adults with diabetes. Our analysis included non-pregnant adults aged ≥18 years with a self-reported diabetes diagnosis who had complete data on the 24-hour dietary recalls in the 2013-2018 National Health and Nutrition Examination Surveys. We used the Healthy Eating Index-2015 (HEI-2015) to measure diet quality. Overall, the median HEI-2015 among adults with diabetes was 51.1 points; a score larger than the median was positively associated with achievement of the A1C goal (Figure) . After adjusting for age, sex, race/ethnicity, education, marital status, health status, health insurance status, and smoking status using logistic regressions, we found that an interquartile increase in HEI-2015 (from 43.0 to 60.2 points) was significantly associated with 4.5 percentage points larger probability (74.3% compared with 78.8%, p=0.02) of meeting the A1C goal. No significant associations were found between HEI-2015 and achievement of BP, cholesterol, or combined ABC goals. Public health efforts to improve dietary quality among people with diabetes may help to increase the proportion of individuals with diabetes who achieve A1C goals.

Disclosure

K.R. Siegel: None. K.M. Bullard: None. D.B. Rolka: None.
1182-P: Is Prediabetes Awareness Associated with Leisure-Time Physical Activity and Dietary Behaviors?
Authors: SIEGEL KAREN R. , PAVKOV MEDA E. , BENOIT STEPHEN R. , IMPERATORE GIUSEPPINA , BULLARD KAI M.
Published: May 2022

Lifestyle modification –healthy diet and physical activity– can help prevent or delay type 2 diabetes in adults with prediabetes (preDM) . However, 84% of US adults with preDM are unaware they have it. Whether preDM status awareness is associated with leisure-time physical activity (LTPA) levels and dietary intake is unknown. Using data from US adults without DM ≥18 y from the National Health and Nutrition Examination Surveys 2013-2018, we classified preDM as ‘aware’ (self-report of preDM and 5.7%≤A1c<6.5%, n=456) , ‘unaware’ (no self-report; 5.7%≤A1c<6.5%, n=2,223) , and ‘normoglycemic’ (A1c<5.7% but self-reported as preDM, n=191) . We calculated means or medians for LTPA (self-reported minutes of moderate to vigorous physical activity per week) , dietary intake (total calories, fruit, vegetables, whole grains, added sugars, processed meat, unprocessed red meat from one day of 24-h recall data) , and the Healthy Eating Index (HEI) 2015, a marker of overall healthy diet (higher score indicates healthier diet) . Of adults with or reporting preDM, 77.9% were unaware (mean age [years]: 51.2 [standard error, 0.5]; 44.6% [1.4] female; mean BMI: 30.3 kg/m2[0.2]) , 14.3% were aware (mean age: 57.4 [0.9]; 56.5% [2.6] female; mean BMI: 31.8 kg/m2 [0.5]) , and 7.8% were normoglycemic (mean age: 43.6 [1.4]; 71.1% [3.7] female; mean BMI: 30.6 kg/m2 [0.6]) . PreDM-aware and normoglycemic adults consumed less calories (p=0.002) , added sugars (p<0.001) , and unprocessed red meat (p<0.001) than preDM-unaware adults. PreDM-aware and preDM-unaware adults consumed more processed meat than normoglycemic adults (p=0.002) . HEI scores and fruit, vegetables, and whole grains intake were low overall and across groups (all p>0.05) . Mean LTPA levels did not significantly vary across the 3 groups (p=0.22) . Overall, preDM awareness is associated with lower added sugars, red meat, and total overall calories intake, suggesting that efforts to increase awareness may lead to healthier eating among those with preDM.

Disclosure

K.R.Siegel: None. M.E.Pavkov: None. S.R.Benoit: None. G.Imperatore: None. K.M.Bullard: None.
1201-P: Glycemic Response Phenotypes on Metformin Monotherapy in Real-World Diabetes Care
Authors: RAGHAVAN SRIDHARAN , LIU WENHUI , WARSAVAGE THEODORE , PHILLIPS LAWRENCE S. , REUSCH JANE E. , CAPLAN LIRON
Published: May 2022

Metformin is the most prescribed initial treatment for type 2 diabetes in many parts of the world. Glycemic response to metformin has been described based on glycemic change - a measure that ignores potential differences in glycemic trajectories or paths between the start and end of metformin monotherapy. We examined HbA1c trajectories over two years in adults treated with metformin and developed prediction models for treatment response. We studied adults treated with metformin alone for >30 days after diabetes diagnosis in the US VA Health System from 20to 2016 who had a minimum of two HbA1c measurements from 90 days prior to two years after the first metformin prescription (N=140,413) . We included all HbA1c measurements (487,6total) during two years after metformin initiation, censoring at addition of a 2nd diabetes medication, metformin discontinuation, nursing home admission, death, or 90-day metformin non-adherence (medication possession ratio <80%) . We used latent class mixed models to identify HbA1c trajectory classes, then used random forests machine learning to predict trajectory class membership based on demographic, laboratory, vital sign, and comorbidity data at the time of diabetes diagnosis. We found three HbA1c trajectories: stably low (89.7% of sample, mean HbA1c decrease from 7.2% to 6.6%) , brisk response (7.1% of sample, mean HbA1c decrease from 11.4% to 7.0%) , and non-response (3.1% of sample, mean HbA1c increase from 8.9% to 10.8%) . Of those in the stably low and brisk response classes at 2 years, 91% maintained HbA1c at ∼7% on metformin alone for 5 years after drug initiation. Random forests yielded prediction models that accurately predicted brisk response (91% accuracy) but not non-response (59% accuracy) . CONCLUSION: Three glycemic response phenotypes were evident by 6 months after metformin monotherapy initiation in real world data and persisted in the vast majority out to 5 years. Early HbA1c surveillance can inform diabetes treatment optimization with durable impact.

Disclosure

S.Raghavan: None. W.Liu: None. T.Warsavage: None. L.S.Phillips: Other Relationship; Cystic Fibrosis Foundation, Diasyst Inc., Research Support; Abbott Diabetes, AbbVie Inc., Janssen Pharmaceuticals, Inc., Janssen Scientific Affairs, LLC, Pfizer Inc. J.E.Reusch: Advisory Panel; Medtronic. L.Caplan: None.

Funding

US Department of Veterans Affairs (IK2-CX001907)
1205-P: Trends in Insulin Use and Glycemic Control in U.S. Adults with Diabetes, 1988–2020
Authors: VENKATRAMAN SIDDHARTH , SELVIN ELIZABETH , FANG MICHAEL
Published: May 2022

Introduction: Insulin remains a last line therapy for type 2 diabetes, and formulations have improved significantly over the past 30 years. It is unknown whether these advancements have translated into better glycemic control in persons with diabetes.

Methods: We conducted a trends analysis of cross-sectional data from the National Health and Nutrition Examination Survey (NHANES, 1988-2020) . Our analysis included 8,658 nonpregnant adults aged ≥20 with diagnosed diabetes. We examined trends in self-reported diabetes medication use (insulin or oral) and glycemic control (A1c<7.0%) , overall and by race/ethnicity.

Results: From 1988-1994 to 2013-2020, there was an increase in the proportion of US adults with diabetes using only oral glucose-lowering medications (43.5% to 55.2%, p=0.003) . The proportion of patients using insulin did not change over the same period (30.5% to 28.2%, p=0.81) . Glycemic control improved among users of oral medications (p<0.001) (Figure 1a) . Among insulin users, glycemic control was unchanged (p=0.87) . Mexican American insulin users had a decrease in glycemic control (25.1% in 1988-94 to 9.9% in 2013-20, p=0.004) and had poorer glycemic control, overall, as compared to their non-Hispanic White or Black counterparts (Figure 1b-1d) .

Conclusions: Despite improvements in insulin formulations, insulin users have not seen improved glycemic control.

Disclosure

S.Venkatraman: None. E.Selvin: Other Relationship; Wolters Kluwer. M.Fang: n/a.
1236-P: Cardiometabolic Disease Risk in Metabolically Unhealthy vs. Healthy in Normal Weight and Obesity: Results from 2015 and 20KNHNES Data
Authors: SEO MYONG-WON , CHO WONHEE , ROSENBERG JARED , WHITE LINDSEY , KIM JOON YOUNG
Published: May 2022

The concept of metabolically unhealthy vs. healthy obese (MUO vs. MHO) was expanded to non-obese individuals as obesity-related comorbidities exist in a subgroup of metabolically unhealthy vs. healthy normal-weight (MUNW vs. MHNW) . It is unclear if MUNW differs from MHO with respect to cardiometabolic health. Here, we applied a widely accepted definition of metabolic health (JAMA 20285: 2486) and examined differences in cardiometabolic risk factors among 4 subgroups of Korean adults (N=7,594) . Individuals with NW vs. obesity (BMI ≥25 kg/m2) were categorized as either MU or MH if those met one or more of the following criteria: triglyceride ≥150 mg/dl; fasting glucose ≥100 mg/dl; HDL <40 mg/dl in men or <50 mg/dl in women; and SBP ≥130 mmHg or DBP ≥85 mmHg. Despite a gradual increase in BMI and visceral adiposity index from MHNW to MUNW to MHO to MUO, surrogates of insulin resistance (TG/HDL) and arterial stiffness (estimated pulse wave velocity) were higher in MUNW vs. MHO (Table) . HOMA-IR was highest in MUO with no difference between MUNW and MHO (Table) . Individuals with MUNW vs. MHO are at least similar to or more vulnerable to cardiometabolic disease. Our data indicate that cardiometabolic risk is not solely dependent on adiposity, suggesting that early preventive efforts for chronic disease are needed for individuals with normal-weight, yet metabolically unhealthy.

Disclosure

M.Seo: None. W.Cho: None. J.Rosenberg: None. L.White: None. J.Kim: n/a.
1238-P: Diabetes Treatment Using Metformin Is Associated with Protective Effect for Emphysema Progression in Smokers
Authors: LI YISHA , CONWAY REBECCA B. , YOUNG KENDRA , PRATTE KATHERINE A. , FOER DINAH , RENNARD STEPHEN , AUSTIN ERIN , GWON YEONGJIN , KINNEY GREGORY L.
Published: May 2022

Rationale: Type 2 Diabetes (T2D) is one of the leading chronic diseases among smokers. Chronic obstructive pulmonary disease (COPD) is common among people with diabetes, with the lung posited as an additional target organ of diabetes. Previous literature suggests that some medications treating comorbidities of COPD patients may also benefit lung function.

Objectives: We used a novel statistical method to identify comorbidity medications associated with pulmonary function progression and assess potential effects using an adjusted mixed effect model among smokers with and without COPD.

Methods: Participants from the COPDGene cohort who completed initial visit (P1) , and 5-year follow up (P2) from 20through 2017 with complete demographics, clinical information, and medication history were included in the study. A least absolute shrinkage and selection operator (LASSO) model with false discovery rate control by a knockoff filter was used to identify medication classes associated with COPD progression in participants with and without T2D treatment. An adjusted linear mixed model was then used to confirm the association between selected medication and the change in percent emphysema and other lung function variables from P1 to P2.

Results: A total of 3,786 out of 10,198 smokers with complete information from P1 and P2 were included. Overall, 359 out of 3,786 smokers reported having T2D at P1, 2out of 359 patients were treated with the class of biguanides (metformin) at P1. The LASSO selection identified metformin as strongly associated with percent emphysema change. Adjusted linear mixed models confirmed that metformin use is associated with the reduction of emphysema in smokers (p<0.0001) from P1 to P2.

Conclusions: Our study identified and confirmed an association between metformin and reduced emphysema progression among smokers with and without COPD. Metformin, a common treatment for diabetes, may also have protective effect on lung function.

Disclosure

Y.Li: Employee; Vertex Pharmaceuticals Incorporated. R.B.Conway: None. K.Young: None. K.A.Pratte: None. D.Foer: Research Support; IBM Watson Health. S.Rennard: Advisory Panel; GlaxoSmithKline plc., Sanofi, Verona, Verona, Consultant; Bergenbio, Boehringer Ingelheim International GmbH, NovoVentures. E.Austin: None. Y.Gwon: None. G.L.Kinney: None.

Funding

U01HL089897U01HL089856