bluuebunny/crossref_metadata_2025 huggingface dataset:
1292-P: Serum Thrombospondin-2 Level as a Novel Liver Fibrosis Biomarker That Changes with Liver Stiffness Improvement in Patients with Type 2 Diabetes
Authors: MAK JIMMY H.C. , YI CAROL FONG HO , WONG YING , TAN KATHRYN C. , LING KAREN LAM SIU , LEE CHI-HO
Published: June 2023

Introduction: High baseline circulating thrombospondin-2 (TSP2) level was recently found to associate with both the development and progression of liver fibrosis in patients with co-existing nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. Here, we investigated whether circulating TSP2 levels changed with improvement in liver fibrosis.

Methods: Serum TSP2 levels were measured in all participants of the DISTINCTION study (NCT 03959501), a randomized 1:1 open-label intervention study, at baseline and after treatment with either 10mg dapagliflozin (N=30) or 100mg sitagliptin daily (N=30) for 24 weeks. Liver stiffness (LS) and controlled attenuation parameter (CAP) were measured using vibration-controlled transient elastography for evaluation of hepatic fibrosis and steatosis, respectively.

Results: Among these 60 participants with similar clinical characteristics at baseline (mean HbA1c 8.9%, CAP 289 dB/m and LS 5.9 kPa), despite similar HbA1c lowering, treatment with dapagliflozin, but not sitagliptin, led to significant improvements in body weight (BW) (p=0.012), CAP (p=0.015) and LS (p=0.011) after 24 weeks. Serum TSP2 level significantly decreased from 3.07 to 2.90 ng/mL (p=0.012), whereas no significant change in TSP2 was observed with sitagliptin. In Pearson correlation analysis, change in serum TSP2 levels positively correlated with change in LS in the dapagliflozin group (r=0.388, p=0.034), but not with changes in BW, CAP or HbA1c after dapagliflozin treatment.

Conclusion: Serum TSP2 level decreased with LS after dapagliflozin treatment, and was independent of improvements in BW, glycemic control and liver steatosis, further supporting the potential of serum TSP2 level as a novel liver fibrosis biomarker in type 2 diabetes.

Disclosure

J.H.C. Mak: None. H. Fong: None. Y. Wong: None. K.C. Tan: None. S. Lam: None. C. Lee: None.
1293-P: Diagnosing GDM in the Indian Population with Country-Specific Glucose Cut-Off Values
Authors: JHA SUDHIR C. , KUMAR NAWEEN
Published: June 2023

Introduction: In India, about 5 million pregnancies are affected with gestational diabetes mellitus (GDM), which triggers unfavourable pregnancy outcomes. Infants that experience intrauterine hyperglycemia are more likely to develop obesity and diabetes. Insulin resistance is associated with the Indian phenotype's propensity to accumulate excessive central fat. This study aimed to ascertain how different plasma glucose concentrations affected the ability of participants in an Indian birth cohort to predict unfavourable outcomes for both mothers and babies.

Methods: We looked at a prospective cohort of pregnant women in public hospitals in Bihar, India. Pregnant women between 24 and 36 weeks underwent a 2-hour 75g oral glucose tolerance test. Following delivery, we measured the skinfold thickness of infants at the biceps, triceps, and subscapular regions of the body. For predicting the risk of SSFT new-borns and caesarean deliveries with the FBS and PPBS, 240 reliable Poisson models were built. FBS≥87 up to 92 mg/dL and PPBS≥134 up to 153 mg/dL with a one-unit increase were tested with sum of skinfold thickness (SSST) and C section delivery.

Results: We discovered that 46.91% of the mothers underwent caesarean sections, and 10.65% of the new-borns had SSFT. Results show that after correcting for age, parity, socioeconomic status, height, and maternal obesity, FBS87 mg/dL and PPBS of 134 mg/dl were linked with risk of higher SSST in new-borns and caesarean delivery.

Conclusion: In India, pregnant women are more likely to experience negative birth outcomes due to lower glucose cut-off readings than in other international classification systems. These results provide information for revising the cutoff points in light of the contextual conditions in LMIC nations.

Disclosure

S.C.Jha: None. N.Kumar: None.
1295-P: The Association between Risk of Gout Flares and Monosodium-Urate Burden Assessed Using Musculoskeletal Ultrasound in Patients with Gout
Authors: YANG SHAOLING , LIN XIAOJING , GAO YINING , LIANG NAN , HAN YALI , SUN HANG , QU SHEN , CHEN HAIBING
Published: June 2023

Objective: We aimed to investigate the association between the risk of gout flares and ultrasound (US)-detected monosodium urate (MSU) burden using two different US score.

Methods: Patients with gout were consecutively recruited to undergo musculoskeletal ultrasound examinations of their knees, ankles, and feet. The Outcome Measure in Rheumatology (OMERACT) and musculoskeletal ultrasound features-based (MSUS) score were used to quantify the MSU burden of gout. Odds ratios for the risk of frequent gout attacks were calculated.

Results: We enrolled 1253 patients with gout (median age, 46 years; gout duration, 5 years; males, 95.9%) and a median of 3 flares over the past year. Of these, 275 (21.9%) patients had frequent (≥7) gout attacks. The OMERACT and MSUS median scores were 6 and 9, respectively. For each 5-point OMERACT and MSUS score increase, the risk of frequent gout attack increased 1.13-fold and 1.27-fold, respectively. The area under the curve (AUC) for the OMERACT and MSUS score was 0.654 (95% confidence interval [CI] 0.617-0.691) and 0.699 (95% CI: 0.663-0.735), respectively, (AUC difference 0.046, P-value for AUC difference, 0.013).

Conclusions: The OMERACT and MSUS score were significantly associated with the risk of frequent gout attacks. The MSUS score outperformed the OMERACT in terms of frequent gout attack discrimination.

Disclosure

S.Yang: None. X.Lin: None. Y.Gao: None. N.Liang: None. Y.Han: None. H.Sun: None. S.Qu: None. H.Chen: None.

Funding

Key Technologies Research and Development Program of China (2019YFA0904500); National Natural Science Foundation of China (81870606, 82170904); Three-Year Action Plan (2022-2024) to Promote Clinical Skills and Innovation in Municipal Hospitals of Shanghai
1296-P: Comparison of Fingerstick and Venous Plasma Glucose in the Ugandan Diabetes in Low-Resource Populations Study
Authors: NIWAHA ANXIOUS J. , SUMNER ANNE E. , NKABURA HUBERT , MUKASA ROGERS J. , MUBIRU NATHAN , BALUNGI PRISCILLA A. , SEKITOLEKO ISAAC , MPAIRWE BERNARD
Published: June 2023

As Africa is experiencing the most rapid rise in the world of type 2 diabetes (T2D), identifying feasible, accurate ways to measure glucose is imperative. While venous glucose (ven-glucose) is recommended, cost and lack of access to pre-analytical processing often rules out this option. Fingerstick measurement of capillary glucose (fs-glucose) is a potential alternative. But data on the correlation between fs-glucose and ven-glucose are scant. Hence OGTT were performed in 512 Ugandans (Male: 46% (234/512), age: 43±17y (mean±SD) enrolled in the Diabetes in Low Resource Populations Study with fs-glucose (Contour Plus Glucometer) and ven-glucose (Glucokinase Method, Roche Cobas 6000) obtained at 0h and 2h. To determine correlation, bias and levels of agreement, Pearson’s correlations and Bland Altman analyses were performed. T2D, preT2D and normal glucose tolerance occurred in 2% (9/512), 18% (92/512) and 80% (411/512), resp. At 0h, fs-glucose and ven-glucose were modestly correlated (r= 0.56) (Fig) with a modest bias for lower glucose by fs-glucose 0.28 mmol/L (95% CI: 0.23, -0.34). At 2h, glucose, fs-glucose and ven-glucose were highly correlated (r=0.92) (Fig) with modest bias for higher glucose by fs-glucose 0.60 mmol/L (95% CI: 0.53, 0.66) mmol/L. Overall, fs-glucose may be an alternative to ven-glucose in Africans where the prevalence of undetected T2D is high and resources are limited.

Disclosure

A.J.Niwaha: None. A.E.Sumner: None. H.Nkabura: None. R.J.Mukasa: None. N.Mubiru: None. P.A.Balungi: None. I.Sekitoleko: None. B.Mpairwe: None.
1299-P: Predictors of Glucagon-Like Peptide-1 Responses following OGTT in Treatment-Naïve Type 2 Diabetes Mellitus among Three Ethnic Groups in Malaysia
Authors: CHIN CHONG SHIAU , SUKOR NORLELA , ROBERT SARAH A. , FONG NG KIM , KAMARUDDIN NOR A.
Published: June 2023

Introduction: Predictors of glucagon-like peptide-1 (GLP-1) responses following OGTT in treatment-naïve type 2 diabetes mellitus (T2DM) have not been fully elucidated. In this respect, we aim to investigate the various predictors of GLP-1 responses following OGTT in treatment-naïve T2DM.

Aim: To assess the clinical and biochemical predictors of GLP-1 responses following OGTT in treatment-naïve T2DM among three ethnic groups in Malaysia.

Methods : Thirty-one treatment-naive T2DM subjects underwent a 75-g OGTT. Total GLP-1 concentrations were measured at 0, 30 and 120 min. By using area under the curve (AUC) for GLP-1 (AUCGLP-1) as an index of GLP-1 secretory response, predictors of GLP-1 responses following OGTT were assessed using multiple linear regression analysis.

Results: Majority of the treatment-naïve T2DM patients were newly-diagnosed (n=28, 96.6%). The GLP-1 levels at 0, 30- and 120-min were 25.59 ± 10.87 pmol/L, 46.86 ± 18.36 pmol/L and 27.02 ± 13.37 pmol/L respectively. There was a positive correlation between increasing age and AUCGLP-1 (Β = 8.55, p<0.001). Male had higher GLP-1 response to OGTT than female (Β = -303.04, p<0.001). The Indian ethnicity exhibited higher GLP-1 secretion than the Malays (Β = 244.17, p<0.001). Fasting insulin was positively correlated with AUCGLP-1 (Β = 8.73, p=0.001). AUCGLP-1 was positively correlated with increased systolic blood pressure (Β = 3.65, p=0.03), total cholesterol (Β = 174.32, p=0.004) and LDL-cholesterol (Β = 202.35, p=0.002).

Conclusions: Older age, male and Indian ethnicity were independent predictors of GLP-1 responses following OGTT in treatment-naïve T2DM. The positive correlation between risk factors associated with insulin resistance and GLP-1 suggested that these risk factors are responsible for driving GLP-1 secretion.

Disclosure

S.Chong: None. N.Sukor: None. S.A.Robert: None. K.Ng: None. N.A.Kamaruddin: Advisory Panel; Zuellig Pharma Holdings Pte. Ltd., Other Relationship; American Association of Clinical Endocrinologists, Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk.

Funding

National University of Malaysia (GUP-2017-066); Malaysian Endocrine & Metabolic Society (L12-MEMS6)
1300-P: Glucagon-Like Peptide-1 Levels Mirror Insulin Resistant States in Treatment-Naïve Type 2 Diabetes Mellitus
Authors: CHIN CHONG SHIAU , SUKOR NORLELA , ROBERT SARAH A. , FONG NG KIM , KAMARUDDIN NOR A.
Published: June 2023

Introduction: In some Asian populations incretin system has been shown to be preserved in type 2 diabetes mellitus (T2DM). The association between fasting and post-OGTT glucagon-like peptide-1 (GLP-1) levels and insulin resistance in treatment-naïve T2DM population has not been clearly defined.

Aim: To assess the insulin resistant states (IRS) by means of insulin resistance index (HOMA-IR) and relate this to the fasting and post-OGTT GLP-1 responses in treatment-naïve T2DM.

Methods : Thirty-one treatment-naive T2DM subject underwent a 75-g OGTT. Fasting plasma glucose and insulin levels were obtained for HOMA-IR analyses along with plasma total GLP-1 concentrations measured at 0, 30 and 120 min.

Results: Majority of the treatment-naïve T2DM patients were newly-diagnosed (n=28, 96.6%). The GLP-1 levels at 0, 30- and 120-min were 25.59 ± 10.87 pmol/L, 46.86 ± 18.36 pmol/L and 27.02 ± 13.37 pmol/L respectively. Fasting GLP-1, incremental GLP-1 at 30 min (∆GLP-130min) and ∆GLP-1120min were positively correlated with HOMA-IR (r=0.654, p<0.001; r=0.421, p=0.018; r=0.574, p=0.001 respectively).

Conclusions: The novel finding of this study is that fasting and post-OGTT GLP-1 levels increased proportionately to IRS. This suggests an adaptive compensatory GLP-1 responses to overcome the worsening insulin resistance in treatment-naïve newly-diagnosed T2DM patients.

Disclosure

S.Chong: None. N.Sukor: None. S.A.Robert: None. K.Ng: None. N.A.Kamaruddin: Advisory Panel; Zuellig Pharma Holdings Pte. Ltd., Other Relationship; American Association of Clinical Endocrinologists, Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk.

Funding

National University of Malaysia (GUP-2017-066); Malaysian Endocrine & Metabolic Society (L12-MEMS6)
1301-P: Glucagon Stimulation Test—Is It Time for an Easy Interpretation Proposal?
Authors: RIZZI ALESSANDRO , TARTAGLIONE LINDA , GUGLIANDOLO SHAWN , DI STASIO ENRICO , BARBERIO ANNARITA , PITOCCO DARIO
Published: June 2023

Background and Aims. Guidelines suggest the use of c-peptide in case of ambiguous diabetes. Glucagon stimulation test (GST), with the intravenous administration of glucagon 1 mg, is a 10-minutes test and it is suitable in clinical practice. It can describe residual beta-cell function although an easy way to identify from this test the type of diabetes or need for insulin in the short term is not available. The aims of this pilot study were to describe c-peptide response during GST and to identify classes of subjects corresponding to different types of diabetes or need of insulin.

Methods: We retrospectively recorded c-peptide levels of adults with ambiguous diabetes who underwent to GST. We divided subjects in 4 classes according to basal c-peptide (BCP) and to mean stimulated c-peptide increase (SCPi): class 1 (BCP <0.5 and SCPi <0.7 mmol/L from basal levels); class 2 (BCP <0.5 mmol/L and SCPi ≥0.7 mmol/L), class 3 (BCP ≥0.5 mmol/L and SCPi <0.7 mmol/L); class 4 (BCP ≥0.5 mmol/L and SCPi ≥0.7 mmol/L). Data about antibody positivity for anti-GAD and I.C.A. (Ab+) and need for insulin within two months were recorded.

Results: We enrolled 61 subjects, age 48.4 (14.6) years [mean (standard deviation)]. 7 subjects (11%) were included in class 1. Mean basal c-peptide was 0.3 mmol/L. 5 subjects (71%) were Ab+ and all required insulin. None of the participants were included in class 2. 18 subjects (29.5%) were included in class 3. Mean basal c-peptide was 1.0 mmo/L. 11 (61%) of class 3 subjects were Ab+ and required insulin within 2 months. 36 subjects (59.5%) were included in class 4. Mean basal c-peptide was 1.8 mmol/L. 5 (13%) of them required insulin therapy within 2 months and 4 (11%) were Ab+. Class 1 and 3 presented with lower BMI than class 4 (p<0.001).

Conclusions: In those preliminary data subjects in class 1 are more likely type 1 diabetes, while subjects in class 3 are more likely T1DM or LADA requiring insulin in the short term. Those preliminary data suggest an easy interpretation for GST to include it more frequently in clinical practice.

Disclosure

A.Rizzi: None. L.Tartaglione: None. S.Gugliandolo: None. E.Di stasio: None. A.Barberio: None. D.Pitocco: None.
1302-P: Predicting Insulin Time-Course Profiles for Early Prediabetes Interception Using a Mechanistic Mathematical Model
Authors: HOR CHENG KOH , CHAN JAMES C.Y.
Published: June 2023

Early detection of prediabetes using blood glucose remains difficult as individuals often present with slight elevations or even normoglycaemia. However, their insulin profiles usually show marked elevations, suggesting that insulin is a more sensitive biomarker for prediabetes. We developed a mechanistic whole-body model that can predict an individual’s insulin time-course and insulin sensitivity from a given glucose time-course. The model describes the absorption, distribution, metabolism and excretion of glucose and the relevant hormones, while various homeostatic processes such as insulin secretion were dynamically represented by sub-models. Matched glucose and insulin data were obtained from 7 oral glucose tolerance test studies. Model predictions of insulin time-course using glucose data as inputs were compared with observed data for validation (Fig 1). Both population and individual simulation results indicated robust prediction of insulin profiles and demonstrate that it is possible to utilize glucose data (easy to obtain) to predict insulin data (difficult to obtain) for prediabetes screening.

Disclosure

K.Hor cheng: None. J.C.Y.Chan: None.
1305-P: The Effect of Limited Pregnancy Weight Gain on Fetal Growth during Dietary Therapy in Gestational Diabetes Mellitus–Affected Women
Authors: KUMAR NAWEEN , JHA SUDHIR C.
Published: June 2023

Aims: We aimed to evaluate how diet-related maternal weight gain (GWG) affected foetal growth in gestational diabetes (GDM)-complicated pregnancies.

Methods: This study involved 182 women who were sequentially diagnosed with GDM before 34 weeks of pregnancy and gave birth to live singletons at our hospital. To gauge compliance with an energy-limited “diabetic diet,” the women were divided into three groups based on their restricted (53%), appropriate (16%), and excessive (31%) weekly GWG. If necessary, insulin therapy was started in accordance with regional clinical recommendations.

Results: At the time of the diagnosis of GDM at 276 ± 51 weeks, the three groups' glucose tolerance, HbA1c, weekly GWG before dietary treatment, and SD score for foetal abdominal circumference were comparable. The women were monitored for 100 ± 51 weeks, during which time 54% of them got further insulin medication, and the average GWG during dietary therapy varied amongst the three groups, weighing 0 kg, 3 kg, and 5 kg. Increased HbA1c between the time of GDM diagnosis and late pregnancy was associated with excessive weekly GWG during dietary treatment, reflecting poor dietary adherence, and newborns had a birthweight-SD score of 0.59 ± 1.6.

Conclusions: In women with GDM, restricted GWG during nutritional therapy was linked to improved foetal growth. Clinical determinants of infant birthweight-SD score that are possibly modifiable include GWG during nutritional therapy and late-pregnancy HbA1c.

Disclosure

N.Kumar: None. S.C.Jha: None.
1306-P: Body-Worn Motion Sensors Detect Gait Deficits in People with Impaired Fasting Glucose Who Have Normal 400-Meter Walk Time
Authors: SHAH VRUTANGKUMAR V. , CARLSON-KUHTA PATRICIA , SOWALSKY KRISTEN , MANCINI MARTINA , HORAK FAY B.
Published: June 2023

Background: Gait is increasingly recognized as a marker of general health status. Abnormal gait characteristics have been observed in people with diabetes, but it is unclear if subtle changes in specific gait characteristics can be found in people with impaired fasting glucose (IFG), who are not yet classified as diabetic (prediabetic).

Aim: The aim of this study was to investigate if digital gait measures discriminate people with IFG from healthy control subjects (HC) who have a normal 400-meter walk time.

Methods: One-hundred and eight people with IFG (mean age: 71.20 years) and 63 healthy control participants (mean age: 70.40 years) wore 6 inertial sensors (Opals by APDM, a Clario Company) while performing a 400-meter fast walk test. In total, 56 measures were derived from the 400-meter walk test, including time to complete the test. Analysis of Covariance (ANCOVA) was used to investigate the differences between the prediabetic and healthy control groups while adjusting for body mass index (BMI) as a covariate.

Results: After controlling for BMI as a covariate, 9 out of 55 gait measures were significantly different (p<10-4) between IFG and HC groups. Step duration, cadence, and turn velocity were the most discriminative measures. In contrast, there was no significant difference between groups for stopwatch timed for 400-meter walk test.

Conclusion: Specific gait measures using body-worn sensors could be abnormal in people with IFG, even when stop watch time for the 400-meter walk test is normal. Thus, digital gait measures show promise to be used as endpoints for clinical trials in people with prediabetes.

Disclosure

V.V.Shah: Employee; APDM Wearable Technologies, A Clario Company. P.Carlson-kuhta: None. K.Sowalsky: Employee; Clario. M.Mancini: Consultant; Clario. F.B.Horak: Employee; APDM Precision Motion, division of Clario.

Funding

National Institutes of Health (5IK2CX000729-05)
1307-P: To What Extent Are the Risks in Prediabetes Explained by Progression to Diabetes?
Authors: ROONEY MARY R. , ECHOUFFO TCHEUGUI JUSTIN , LUTSEY PAMELA , FANG MICHAEL , HU JIAQI , GRAMS MORGAN , CORESH JOSEF , SELVIN ELIZABETH
Published: June 2023

Introduction: Prediabetes is associated with elevated risks of microvascular and macrovascular complications but it is unknown to what extent progression from prediabetes to diabetes explains these associations.

Methods: In 11536 participants from the Atherosclerosis Risk in Communities (ARIC) Study (aged 46-70, ~55% women, ~20% Black) without diabetes at baseline (1990-2), we used Cox regression to characterize associations of prediabetes (A1C 5.7-6.4%) with incident atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), non-traumatic amputation, and all-cause mortality before and after accounting for time-varying diabetes. We calculated the excess risk in prediabetes explained by progression to diabetes.

Results: Of the ~20% of adults with prediabetes at baseline, ~40% progressed to diabetes (median time to diabetes, ~15 years). Over ~25 years of follow-up, there were 2195 ASCVD and 2307 HF events, 100 amputations, and 5556 deaths. Prediabetes was associated with modestly elevated risks of all outcomes (Figure). Incident diabetes accounted for 15% of CVD risk, 19% of HF risk, 24% of amputation risk, and 29% of mortality risk in persons with baseline prediabetes.

Conclusion: Progression to diabetes explained an important fraction of the risks of clinical outcomes associated with prediabetes. Prediabetes contributes to risk of clinical outcomes even when persons do not progress to overt diabetes.

Disclosure

M.R.Rooney: None. J.Echouffo tcheugui: None. P.Lutsey: None. M.Fang: None. J.Hu: None. M.Grams: None. J.Coresh: Consultant; Healthy.io Ltd, SomaLogic. E.Selvin: None.
1308-P: Glutamic Acid Decarboxylase Autoantibodies (GADA) in Type 2 Diabetes Do Not Predict Long-Term Diabetes Complications
Authors: PILLA SCOTT J. , KNOWLER WILLIAM C. , BALASUBRAMANYAM ASHOK , HAMPE CHRISTIANE S. , PIETROPAOLO SUSAN , ANDERSON ANDREA M. , LI MO , ZHAO NI , ZEGER SCOTT L. , RAMELIUS ANITA , BENNET RASMUS , LERNMARK ÅKE , MATHIOUDAKIS NESTORAS N. , CLARK JEANNE , MARUTHUR NISA M.
Published: June 2023

Some adults with type 2 diabetes (T2D) have islet autoantibodies that may explain clinical heterogeneity, yet limited long-term studies have examined their relationship with diabetes outcomes. We investigated the association between GADA, the most prevalent islet autoantibody, and diabetes complications and mortality in Look AHEAD (Action for Health in Diabetes), a trial that randomized adults with clinically-diagnosed T2D to intensive lifestyle intervention vs. control for 9.6 years, and then followed them observationally. GADA was measured by radioligand binding assay in 87% of the cohort at baseline and categorized as negative, low-level (35-199 U/mL) or high-level (≥200 U/mL). We used Cox proportional hazards regression adjusted for age, sex, race/ethnicity, and study arm to analyze the association between GADA category and time-to-event outcomes: CVD (MI, stroke, hospitalized angina, CVD death), incident eGFR <45 ml/min/1.73m2, incident end stage kidney disease, and all-cause mortality. Among 4,492 participants, the median age was 59 years and diabetes duration 5 years. GADA was low-level and high-level positive in 131 (2.9%) and 85 (1.9%), respectively. Over a median follow-up of 17 years, there was no significant association between GADA levels and outcomes (Table). Overall, the presence of GADA above 35 U/mL was not predictive of CVD, or renal outcomes or mortality.

Disclosure

S.J.Pilla: None. A.Ramelius: None. R.Bennet: None. Å.Lernmark: Advisory Panel; Diamyd Medical. N.N.Mathioudakis: None. J.Clark: None. N.M.Maruthur: Other Relationship; Johns Hopkins HealthCare Solutions. W.C.Knowler: None. A.Balasubramanyam: None. C.S.Hampe: Employee; Immusoft corp. S.Pietropaolo: None. A.M.Anderson: None. M.Li: None. N.Zhao: None. S.L.Zeger: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK126825, K23DK128572)
1310-P: Causes of Death among Australians with Type 1 or Type 2 Diabetes, 2002–2019
Authors: TOMIC DUNYA , CHEN LEI , MAGLIANO DIANNA J. , SHAW JONATHAN E.
Published: June 2023

Objective: We sought to explore the conditions driving the diversification in causes of death among people with diabetes.

Methods: We linked Australians with type 1 or type 2 diabetes of all ages on the National Diabetes Services Scheme (Diabetes Registry) to the National Death Index for 2002-2019. We investigated causes of death over time across eight categories of causes of death. Underlying causes of death were classified according to the International Classification of Diseases, Tenth Revision codes.

Results: Between 2002-2019, there was a shift in the underlying cause of death among Australians with diabetes. The proportion of deaths attributed to cardiovascular disease declined in both sexes (Ptrend < 0.001), most substantially among females with type 2 diabetes from 48.2% in 2002 to 30.7% in 2019 (Figure). Among males, cancer overtook cardiovascular disease as the leading cause of death. The proportion of deaths due to dementia increased among all people with diabetes, from 2% in 2002 to 7% in 2019, across all age-groups, notably from 1% to 4% in those aged 70-79. The proportion of deaths due to falls also increased.

Conclusions: We are seeing a shift of causes of death among those with diabetes away from cardiovascular and renal disease towards conditions such as dementia, falls, and respiratory disease, which may have serious consequences for health systems and will require consideration in resource allocation.

Disclosure

D.Tomic: None. L.Chen: None. D.J.Magliano: None. J.E.Shaw: Advisory Panel; Abbott Diagnostics, Lilly, Zuellig Pharma Holdings Pte. Ltd., Mylan, Research Support; AstraZeneca, Speaker's Bureau; AstraZeneca, Roche Diagnostics, Lilly, Amgen Inc., Sanofi, Zuellig Pharma Holdings Pte. Ltd.
1311-P: Insulin Resistance in Non-obese Young Adults with Type 1 Diabetes
Authors: CHARTIER-LOGAN CATHERINE J. , SCHAUER IRENE E. , CREE-GREEN MELANIE , PYLE LAURA , BERGMAN BRYAN C. , SNELL-BERGEON JANET K.
Published: June 2023

Insulin resistance has been noted in youth and adults with type 1 diabetes (T1D) and is associated with higher levels of cardiovascular and kidney complications. Obesity is increasing in populations with T1D, and the degree of insulin resistance in younger adults with T1D who are free from complications and non-obese isn’t clear. We performed hyperinsulinemic euglycemic clamps in non-obese adults aged 20-45 with and without T1D. Inclusion criteria included diabetes duration > 5 years and HbA1c <9% among people with T1D, or no diabetes based on fasting glucose and HbA1c among controls; Body mass index (BMI) < 30 kg/m2, no use of statins or other medication affecting insulin sensitivity, non-smokers and normal thyroid function. Participants were given a fixed macronutrients study diet for 2 days and were asked to refrain from vigorous exercise for 72 hours. Clamps were performed by a single investigator after an overnight stay. A sliding scale insulin infusion was used overnight for participants with T1D. Arterial stiffness (brachial artery distensibility, pulse wave velocity and reactive hyperemia index) was assessed. There were 47 participants, 24 with T1D and 23 without diabetes. 53% were women (25/47), and the average age did not differ between controls and people with T1D (31 ± 6 years vs. 28 ± 6 years, p=0.12). Whole body insulin sensitivity estimated by glucose infusion rate (GIR) per kg fat free mass was reduced by more than half in adults with T1D (LS mean ± SE =5.4 ± 1.0 mg/kg FFM/min) compared to adults without diabetes (12.7 ± 1.0 mg/kg FFM/min, p<0.0001). In contrast, there were no differences in BMI, body fat, urinary albumin, or measures of arterial stiffness by diabetes status. Young, non-obese adults with T1D are profoundly insulin resistant compared to nondiabetic adults, even when no differences in vascular stiffness or kidney complications are apparent. These results suggest that insulin resistance may occur earlier than vascular or kidney complications in people with T1D and is independent of obesity.

Disclosure

C.J. Chartier-Logan: None. I.E. Schauer: None. M. Cree-Green: Consultant; Pollie Inc. Research Support; Amino Corp LLC. L. Pyle: None. B.C. Bergman: Research Support; Eli Lilly and Company. J.K. Snell-Bergeon: None.

Funding

JDRF (2-SRA-2019-849-S-B)
1312-P: Relationship between Progression of Diabetic Nephropathy and Seasonal Fluctuation of Estimated GFR
Authors: YUKI MASAHIRO , YAMAZAKI TSUTOMU , MIYASHITA KAZUTOSHI , SAKAMOTO MASAYA
Published: June 2023

Introduction: The seasonal fluctuation of estimated glomerular filtration rate (GFR) in type2 diabetes mellitus (T2DM) patients remains unknown. The present study is first to examine seasonal fluctuation of eGFR and its relationship to the progression of diabetic nephropathy (DN).

Methods: This retrospective study initially analyzed data on 21,307 T2DM patients with hypertension (HT). Seasonal fluctuation of eGFR were evaluated using the intrapersonal coefficient of variation (CV) of 20 or more serial measurements of body weight, Blood pressure and HbA1c during a 5-year period from 2014-2018. The primary objective was to determine if there is seasonal fluctuation of eGFR or not. Secondary objective is to examine the relationship between progression of DN and seasonal fluctuation of eGFR. DN was assessed by eGFR and urinary albumin excretion (UAE) changes.

Results: The figure shows the changes of eGFR monthly averages. eGFR is significantly lower in summer each year (vs winter, P<0.001). Classified into two groups based on median CV of eGFR, eGFR decrease was obvious in the group with large CV of eGFR (vs group with small CV, P<0.001). In addition, UAE increase was also obvious in the group with large CV of eGFR (vs group with small CV, P<0.001).

Conclusion: This study suggests that eGFR is fluctuated by season in T2DM patients with HT. The seasonal fluctuation of eGFR was associated with the progression of DN.

Disclosure

M.Yuki: None. T.Yamazaki: None. K.Miyashita: None. M.Sakamoto: None.
1313-P: The Prevalences of NAFLD and Liver Fibrosis Are High in Individuals with Type 1 Diabetes and Increase with Disease Progression
Authors: FUHRI SNETHAGE COCO , MEIJNIKMAN ABRAHAM S. , DE GROEN PLEUN , CALLENDER CENGIZ , RAMPANELLI ELENA , BROUWER CATHERINE B. , VAN RAALTE DANIËL , NIEUWDORP MAX , HANSSEN NORDIN
Published: June 2023

Introduction: Approximately 30% of the global population has nonalcoholic fatty liver disease (NAFLD). This can result in nonalcoholic steatohepatitis (NASH) and liver fibrosis (2% in general population). NAFLD with fibrosis increases overall morbidity and mortality significantly. T2D increases the risk of fibrosis progression in NAFLD, but little is known about NAFLD in T1D. Therefore, the aim of this study was to assess the prevalence of NAFLD and liver fibrosis in T1D.

Methods: In this cross-sectional study 453 individuals with T1D were included for analyses (41.0 ±14years old, 64% female, HbA1c 55.6 ±12mmol/mol, median T1D duration 14 [IQR: 6-29] years. Participants underwent a FibroScan® to assess liver stiffness, with a cut-off of 238 dB/m for steatosis and 7.0 kPa for fibrosis. Data analyses was performed in R studio, using a Students T- or Mann-Whitney U test, as appropriate.

Results: Prevalence of liver steatosis was 29.5% and fibrosis was 7.7%. Steatosis was significantly higher in individuals with longer T1D duration (median:15 [IQR:7-25] vs. 23 [9-33] years), higher 24-hour insulin dose (34 [24-47] vs. 46 [33-62] units), higher BMI (mean 24.3±SD 3.5 vs. 27.9±4.6 kg/m2), higher CRP levels (1.0 [0.5-2.1] vs. 1.6 [0.8, 3.7] mg/L), higher triglyceride levels (0.6±0.3 vs. 0.8±0.5 mmol/L) and lower TIR (67 [51-82] vs. 62 [48-75] %). Presence of fibrosis was associated with a longer duration of T1D (16 [7-27] vs. 30 [20-39] years) a higher 24-hour insulin (36.0 [26-50] vs. 42 [34-63] units), higher BMI (25.1±4.1 vs. 27.8±4.6 kg/m2), higher CRP levels (1.2 [0.6-2.4] vs 1.5 [0.8-3.9] mg/L) and lower TIR (67 [51, 8] vs. 58 [46, 71] %).

Conclusion: The prevalence of NAFLD and liver fibrosis was 7.7% in individuals with T1D. Duration of T1D, markers of insulin resistance, glycemic control and inflammation are likely contributors to this high prevalence and more attention should be paid to this possible complication.

Disclosure

C. Fuhri Snethage: None. A.S. Meijnikman: None. P. de Groen: None. C. Callender: None. E. Rampanelli: None. C.B. Brouwer: None. D. van Raalte: Consultant; Boehringer Ingelheim and Eli Lilly Alliance, AstraZeneca, Merck & Co., Inc. Research Support; Boehringer Ingelheim and Eli Lilly Alliance, AstraZeneca, Merck & Co., Inc. M. Nieuwdorp: Advisory Panel; caelus health. N. Hanssen: Research Support; Novo Nordisk. Consultant; Novo Nordisk.

Funding

DNF DON Grant 2020 (2020.10.002)
1314-P: Adherence to Life’s Essential 8 and Incident Chronic Kidney Disease—A Prospective Study of 142,567 UK Biobank Participants
Authors: TANG RUI , WANG XUAN , LI XIANG , MA HAO , HEIANZA YORIKO , QI LU
Published: June 2023

Background: The American Heart Association (AHA) recently updated an improved method for evaluating cardiovascular health (CVH): Life’s essential 8 (LE8). We aimed to investigate the association between levels of CVH and the risk of CKD in UK biobank.

Methods: A total of 142,567 participants free of CKD and CVD were included. LE8 score at baseline was created including DASH diet, physical activity, smoking, sleep, BMI, non-HDL cholesterol, HbA1c, and BP. CVH levels were categorized as low, moderate, and high. Cox proportional hazard model was used to investigate the association between LE8 and CKD.

Results: During a median follow-up of 11.8 years, 4,914 CKD cases were documented. We observed a linear dose-response relationship. Compared to participants with a low CVH, those with a moderate CVH were associated with a 35% lower risk of developing CKD (HR=0.65, 95% CI: 0.59, 0.73). Participants with a high CVH had a 48% lower risk of CKD incidence (HR=0.52, 95% CI: 0.45, 0.60) after adjustment for covariates. Additionally, the HR (95% CI) for each SD increment in behavior subscale score was 0.46 (0.39, 0.53) for CKD, and the HR (95% CI) for each SD increment in biological subscale score was 0.86 (0.76, 0.98) for CKD.

Conclusion: Participants with high CVH, defined by LE8, were significantly associated with a lower risk of CKD. The burden of CKD may be reduced by promoting adherence to optimal CVH levels.

Disclosure

R.Tang: None. X.Wang: None. X.Li: None. H.Ma: None. Y.Heianza: None. L.Qi: None.
1315-P: Examining Excess Hospitalizations in People With vs. Without Diabetes—A National U.S. Study
Authors: HARDING JESSICA L. , UPPAL TEG S. , TOMIC DUNYA , ALI MOHAMMED K. , MAGLIANO DIANNA J.
Published: June 2023

Background: A diversification of diabetes-related complications has been observed due, in part, to declines in cardiovascular mortality and increases in time spent living with diabetes. We examined leading causes of excess hospitalizations among people with vs. without diabetes.

Methods: We used the 2019 National Inpatient Sample (numerator) and the 2019 Behavioral Risk Factor Surveillance Survey (denominator), weighted to reflect the U.S. population, to estimate rates of cause-specific hospitalizations in adults (≥18 years) with and without diabetes defined by ICD codes (numerator) and self-report (denominator). Annual age-standardized hospitalization rates were determined using three-digit ICD-10 codes, with excess risk and rate ratios reported. We grouped the top ten causes of excess hospitalizations as 1) traditional (e.g., vascular diseases); 2) emerging (e.g., liver disease); or 3) other complications.

Results: Americans with diabetes are at increased risk of hospitalization for most conditions, ranging from a 3% [rate ratio (RR): (1.00-1.05)] to a 9-fold increased risk [RR: 9.00 (8.96-9.04)]. The major causes for excess hospitalization in people with vs. without diabetes, according to traditional, emerging, or other complications are reported in Table 1.

Conclusions: The conditions responsible for excess hospitalizations in people with diabetes are more diverse than previously recognized.

Disclosure

J.L. Harding: None. T.S. Uppal: None. D. Tomic: None. M.K. Ali: Research Support; Merck & Co., Inc. Advisory Panel; Bayer Inc., Eli Lilly and Company. D.J. Magliano: None.
1318-P: Type 2 Diabetes as a Risk Factor for Dementia—An Analysis of Australian National Registries
Authors: MEHTA KANIKA , SALIM AGUS , SACRE JULIAN W. , ANSTEY KAARIN J. , MAGLIANO DIANNA J. , SHAW JONATHAN E.
Published: June 2023

High dementia prevalence and associated disability have necessitated a focus on the identification of potentially modifiable risk factors. One such example is type 2 diabetes; however, there are not enough large population-based studies that can provide an accurate estimate of the strength of the association. Therefore, we investigated prospective associations between diabetes and dementia using Australian national registries. The study included ~850,000 people with type 2 diabetes (median age=66.2 years, females=45.5%) registered on the National Diabetes Services Scheme (NDSS) during the period 2002-2014 and followed up for at least 1 year (median 7.0 years). Propensity score matching (based on logistic regression with birth year, sex, socio-economic index and medication history as predictors) was then conducted to match (1:1) people with diabetes to a general population control group without diabetes. The latter comprised people with no registration history on NDSS or record of taking glucose lowering drugs on the Pharmaceutical Benefits Scheme (median age=67.3 years, females=43.9%, median follow up=7.5 years). Dementia was defined either by dementia drug use (cholinesterase inhibitors or memantine) or dementia-related death. The association between diabetes and dementia was examined using Cox’s proportional hazard model that treated each individual with diabetes and their matched control as one stratum. Diabetes was associated with an increased risk of dementia-related death (HR 1.19, 95% CI 1.17, 1.22), while no significant association was observed between diabetes and dementia medication use (HR 0.99, 95% CI 0.97, 1.02). When both dementia-related death and dementia drug use were included in the outcome, diabetes was still associated with an increased risk of dementia (HR 1.11, 95% CI 1.09, 1.14). These findings highlight the need for clinicians to be vigilant in identifying and managing diabetes as a potentially modifiable risk factor for cognitive decline and dementia.

Disclosure

K.Mehta: None. A.Salim: None. J.W.Sacre: None. K.J.Anstey: Speaker's Bureau; Nutricia. D.J.Magliano: None. J.E.Shaw: Advisory Panel; Abbott Diagnostics, Lilly, Zuellig Pharma Holdings Pte. Ltd., Mylan, Research Support; AstraZeneca, Speaker's Bureau; AstraZeneca, Roche Diagnostics, Lilly, Amgen Inc., Sanofi, Zuellig Pharma Holdings Pte. Ltd.

Funding

Deakin University (to K.M.); Alicia Baker and Eleanor Shaw Gender Equity Fellowship (to D.J.M.); National Health and Medical Research Council (APP1173952 to J.E.S.); Victorian Government’s Operational Infrastructure Support Program
132-LB: Real-World Effectiveness of My Dose Coach (MDC)-Assisted Basal Insulin (BI) Titration in People with Type 2 Diabetes (PWT2D) in Saudi Arabia and Kuwait
Authors: AL-SOFIANI MOHAMMED , ALMEHTHEL MOHAMMED , ALOZAIRI EBAA S. , SADIK JAMAA , HAO LICHEN , AKIL YASSER
Published: June 2023

Insulin titration inertia is a key barrier to optimal glycemic control, particularly in areas where diabetes is highly prevalent and specialized healthcare professionals (HCP) are limited. MDC is a US FDA-approved digital smartphone application designed to help PWT2D to titrate BI according to HCP-prescribed individualized titration plan. This real-world analysis evaluated clinical outcomes in PWT2D in Saudi Arabia (SA) and Kuwait who were on BI therapy, registered on MDC from 05/01/2021 to 08/31/2022, and recorded ≥2 FBG readings in the app over a 2-week period. FBG target achievement, change in FBG, and hypoglycemia were assessed. A total of 197 MDC users with mean (SD) age of 51.5 (14.4) years were included (Table). Overall, 116 (58.9%) users achieved their individualized FBG target, 14 (7.1%) were still titrating and 67 (34.0%) stopped using MDC. The mean (SD) time to reach FBG target was 16.3 (20.8) days. Mean (SD) FBG decreased from 172.4 (75.7) mg/dL at baseline to 136.5 (54.3) mg/dL and BI dose increased from 21.9 (16.8) U to 25.1 (16.2) U. Moreover, high usage of MDC app was associated with a greater reduction in FBG versus moderate or low usage. Overall, hypoglycemia events were reported in 7 (3.6%) participants. PWT2D from SA and Kuwait were able to successfully utilize MDC app to titrate their BI doses and achieve FBG target with low risk of hypoglycemia

Disclosure

M. Al-sofiani: Consultant; Eli Lilly and Company, Speaker's Bureau; Sanofi, Medtronic, Vitalair. M. Almehthel: None. E. S. Alozairi: None. J. Sadik: Employee; Sanofi. L. Hao: Employee; Sanofi. Y. Akil: Employee; Sanofi.

Funding

Sanofi
132-OR: Ten-Year Evaluation of Diabetes Categories in Youth Shows a Continuous Increase in Frequency of Newly Diagnosed Type 2 Diabetes—Results from the Worldwide SWEET Registry
Authors: CHERUBINI VALENTINO , ECKERT ALEXANDER J. , AMED SHAZHAN , BESANÇON STÉPHANE , CAVALLO AITA FRED , CRIMMINS NANCY A. , GEVERS EVELIEN F. , JEFFERIES CRAIG A. , KIM JAEHYUN , SHAH SEJAL , VAMVAKIS ANASTASIOS , GESUITA ROSARIA , BEHALF OF THE SWEET STUDY GROUP ON
Published: June 2023

Background: To evaluate the frequency of youth with type 2 diabetes (T2D) using data from the multinational consortium SWEET e.V.

Methods: The frequency of newly diagnosed T2D across all categories of diabetes in youth under 21 registered in the SWEET database during 2012-2021 was analysed. Trends in biennial proportions in five world regions (Europe, EU; Australia/New Zealand, AU/NZ; South America, SA; North America/Canada, NA; Asia/Africa, AS/AF) were estimated using logistic regression models adjusted for age at onset and sex.

Results: Table 1 shows the proportion of patients across diabetes categories over the study period in two-year steps. The increase in T2D rate was 9.0% per two years [95% CI 5.7-12.3] and was significant in EU (10.4% [3.8-17 .3]), AU/NZ (13.6% [3.5-24.7]), and NA (8.7% [3.8-14.0]). The overall increase in T2D during COVID-19 pandemic was similar to the previous biennial increase, while AU/NZ and NA showed the highest increase (respectively from 9.5% to 12.2%, p=0.999; from 7.7% to 13.2%, p<0.001).

Conclusions: There has been a steady increase in T2D observed worldwide over time. Findings suggest that more prevention efforts are needed to contain the public health impact in the near future. The Covid-19 pandemic did not affect the overall trend in frequency of youth with T2D observed over the 10-year period.

Disclosure

V.Cherubini: None. S.Shah: Research Support; Boehringer-Ingelheim, Takeda Pharmaceutical Co., Ltd. A.Vamvakis: None. R.Gesuita: None. On behalf of the sweet study group: n/a. A.J.Eckert: None. S.Amed: None. S.Besançon: None. F.Cavallo aita: None. N.A.Crimmins: None. E.F.Gevers: Other Relationship; Novo Nordisk, Speaker's Bureau; Novo Nordisk. C.A.Jefferies: None. J.Kim: None.
1320-P: Causal Mediators of Underlying Socioeconomic Status Disparities in Hospitalization Risk among Patients with Type 2 Diabetes (T2D)
Authors: CHEN WEI-HAN , HUANG YU , DONAHOO WILLIAM T. , BIAN JIANG , GUO JINGCHUAN
Published: June 2023

Socioeconomically disadvantaged groups carry a disproportionally increased risk of T2D-related adverse outcomes, yet few studies have addressed how modifiable social risk factors drive such health disparities. We aimed to estimate to what extent housing instability explained unemployment or education disparities in hospitalization risk in patients with T2D. We used electronic health records data from the University of Florida Health System and identified patients with T2D in 2015-2020. We conducted causal mediation analyses using marginal structural models to test the causal mediator role of housing insecurity in the association between education or employment and hospitalization risk. Of 9,144 eligible patients, mean (SD) age was 58 (13) years, and 17% were hospitalized in the follow-up year. We observed an increased hospitalization risk in those who were unemployed (odds ratio [OR]: 1.21, 95% CI: 1.04-1.41) and those with lower education levels (1.38 [1.17-1.62]). Housing insecurity, as a causal mediator, explained 11% of the unemployment-hospitalization association, but it had minimal contribution to the education-hospitalization association (2%). Unemployment status and lower education were associated with an increased risk of hospitalization in T2D. Housing insecurity modestly contributed to unemployment disparities in hospitalization risk in T2D.

Disclosure

W.Chen: None. Y.Huang: None. W.T.Donahoo: None. J.Bian: None. J.Guo: Consultant; Pfizer Inc., Research Support; PhRMA Foundation, NIH - National Institutes of Health.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK133465)
1324-P: Mortality and Glycemic Control in Chronic Pancreatitis With and Without Diabetes—A Single Center, Referral Population Study in the United States
Authors: RAZA RIZVI SHAFAQ , JEET KAUR RAVINDER , AGGARWAL MANIK , ZANILETTI ISABELLA , REID COREY , KUDVA YOGISH C.
Published: June 2023

Introduction: To our knowledge, limited data are available regarding mortality and glycemic control in patients with chronic pancreatitis (CP) and diabetes mellitus (DM) in the United States.

Methods: After IRB approval, we retrospectively studied 496 subjects with CP at Mayo Clinic, Rochester between 01/01/2013 and 12/31/2015. DM was identified using ICD 9 and 10 codes in 250 patients (CPDM cohort).

Results: CPDM cohort had identified F/M 91/159 with median age of 56 yrs., BMI 24.2 kg/m2 and DM for 9.5 yrs. whereas CP without DM (CPWODM) cohort had F/M 106/140 with median age of 51 yrs. and BMI 26 kg/m2. In CPDM cohort, mean HbA1c was > 7 % from baseline to 5 yrs., hospitalizations due to any reason were highest within 1 yr. of DM diagnosis (Table). CP patients who developed DM had higher rates of 10 yr. mortality compared with those without DM (20.8% vs. 13.4%, Odd ratio 1.7, 95% CI=1.05-2.73, P= 0.03).

Conclusion: Other studies outside the U.S have reported high mortality among CPDM subjects as compared to DM without CP. We report a unique comparison of mortality in CPDM vs. CPWODM in the U.S. CP patients who developed DM had 70% higher risk of 10-year mortality as compared to those who did not develop DM. Studies with larger sample size need to be conducted to confirm these findings. Clinical trials to improve diabetes in CP are warranted and could impact morbidity and mortality.

Disclosure

S.Rizvi: None. R.Kaur: None. M.Aggarwal: None. I.Zaniletti: None. C.Reid: None. Y.C.Kudva: Advisory Panel; Novo Nordisk, Research Support; Dexcom, Inc.