bluuebunny/crossref_metadata_2025 huggingface dataset:
1548-P: High Prevalence of Glaucoma and Cataract with Uncommon Diabetic Retinopathy in Haitian Youth with Diabetes
Authors: BAPTISTE EDDY JEAN , LARCO PHILIPPE , CHARLES LARCO MARIE-NANCY , VON OETTINGEN JULIA E. , ROCOURT FRANCOISE , HUDICOURT BRIGITTE , MOISE KEDDY , PAUL RODOLPHE , CHARLES RENE
Published: June 2019

Aim: Data on glaucoma and cataract in Afro-Caribbean youth with diabetes are scarce. We sought to determine the prevalence of ocular complications and their risk factors in a group of Haitian youth with diabetes.

Methods: A cross-sectional study was conducted on youth aged 0-25 years with insulin-treated diabetes from one diabetes clinic in Haiti. We performed on both eyes visual acuity, Ishihara test, tonometry by Goldmann applanation, corneal pachymetry, slit lamp, refraction, gonioscopy, dilated fundoscopy and retinography, Humphrey visual field (VF), and spectral domain optical coherence tomography (Cirrus SD-OCT). We carried out Michigan Neuropathy Screening Instrument and neurothesiometer tests, and measured hemoglobin A1c (HbA1c), fasting lipid profile, and spot urinary albumin-to-creatinine ratio (UACR) twice 6 weeks apart. Primary open-angle glaucoma (POAG) was based on characteristic changes in: 1- optic disc, 2- retinal nerve fiber layer/combined macular ganglion cell and inner plexiform layers, 3- VF. Possible, suspected and overt POAG were diagnosed in the presence of 1, ≥ 2 and ≥ 2 criteria plus visual acuity loss, respectively.

Results: We enrolled 51 patients: Age 18.4 ± 4.7 y, male 52.9%, diabetes duration 5.0 ± 3.2 y, HbA1c 11.2 ± 2.9%, normal lipid profile. Background diabetic retinopathy (DR), cataract, diabetic peripheral neuropathy, and increased UACR were found in 2.0%, 13.7%, 29.4%, and 7.8%, respectively. No color vision impairment was detected. Intraocular pressure was 17.3 ± 3.7 (R) and 17.1 ± 2.8 (L) mmHg. Ocular hypertension was found in 5.9%. POAG was overt in 3.9% and suspected in 17.7%. On regression analyses, none of the studied variables predicted POAG or cataract.

Conclusion: POAG and cataract are common and precocious in Haitian youth with diabetes, without detectable risk factors. DR is uncommon. Comprehensive eye examination with VF and OCT when available is suggested early after diabetes diagnosis.

Disclosure

E. Jean Baptiste: None. P. Larco: None. M. Charles Larco: None. J.E. von Oettingen: None. F. Rocourt: None. B. Hudicourt: None. K. Moise: None. R. Paul: None. R. Charles: None.
1556-P: Gender Differences in Glycemic Control, Microvascular and Macrovascular Complications in Hospitalized Patients with Diabetes
Authors: PATEL NEETI , PINKHASOVA DIANA , DONIHI AMY , FRENCH ESRA KARSLIOGLU , SIMINERIO LINDA M. , DELISI KRISTIN , HLASNIK DEBORAH S. , KORYTKOWSKI MARY T.
Published: June 2019

Gender differences have been described for glycemic control and prevalence of diabetes related complications in the outpatient setting but have not been examined in the hospitalized population. To address this, we investigated gender differences in demographics, glycemic control and variability (GV), macrovascular and microvascular complications, and admission diagnosis in non-critically ill hospitalized patients with a secondary diagnosis of diabetes recruited for the Readmission and Comprehension of Diabetes Education at Discharge (ReCoDED) Study. To date, 111 men and 87 women have been recruited, with the majority having type 2 DM (86 vs. 79%). Participants age (men vs. women) was 60.6 ± 11.7 vs. 57.6 ± 11.8 years, BMI 32.2 ± 8.4 vs. 32.1 ± 10.6 kg/m2, systolic (SBP) 136 ± 26 vs. 127 ± 23 mmHg, diastolic (DBP) 77 ± 13 vs. 75 ± 14 mmHg, HbA1c 8.0 ± 2.3 vs. 8.3% ± 2.5%, and DM duration 14.5 ± 10.4 vs. 14.1 ± 11.6 years. Race, education, and employment were similar. Men had more retinopathy (23 vs. 16%) and nephropathy (40 vs. 28%), but not neuropathy (60 vs. 63%). Women had a lower prevalence of CAD (49 vs. 36%), but a similar prevalence of CHF (37 vs. 37%), stroke (15 vs. 18%), and PVD (18 vs. 17%). The most frequent admission diagnoses were CVD (37 vs. 22%) and infection (10 vs. 19%). Mean blood glucose (BG) (198 ± 51 vs. 200 ± 54 mg/dl), GV (177 ± 80 vs. 182 ± 112 mg/dl), frequency of hypoglycemia (BG < 70 mg/dl) and hyperglycemia (BG >250 mg/dl) were similar in the 48 hours prior to discharge. Length of stay was 7.8 ± 6.9 vs. 8.3 ± 7.4 days.

In summary, this gender-based description of glycemic control and prevalence of diabetes-related complications in an inpatient population demonstrates that hospitalized women with DM have fewer microvascular complications, a lower prevalence of CAD but a similar prevalence of CHF, stroke and PVD when compared to men, despite similar BMI and DM duration. These findings will be examined as a risk factor for hospital readmissions in this ongoing study.

Disclosure

N. Patel: None. D. Pinkhasova: None. A. Donihi: None. E. Karslioglu French: None. L.M. Siminerio: None. K. Delisi: None. D.S. Hlasnik: None. M.T. Korytkowski: None.
1559-P: Differential Effects of Type 1 (T1D) and Type 2 Diabetes (T2D) on the Growth Hormone (GH)-Insulin-Like Growth Factor (IGF) Axis in Youth
Authors: SNELL-BERGEON JANET K. , REUSCH JANE E.B. , BAUMGARTNER AMY D. , CREE-GREEN MELANIE , NADEAU KRISTEN J.
Published: June 2019

T1D and T2D are characterized by hyperglycemia and insulin resistance (IR), but in T1D the IR occurs even in the absence of metabolic syndrome features. The loss of β-cell insulin secretion in T1D results in lower portal and thus hepatic insulin concentrations in T1D than in T2D or nondiabetic (non-DM) individuals, affecting the GH-IGF axis, as exogenous insulin is subcutaneously delivered in T1D. In this study, we examined how the GH-IGF axis differs by diabetes type, and how it relates to IR. This study included youth (mean age 15±2 years, 37% female) with T1D (n=16), T2D (n=27) and non-DM controls (n=38). A morning fasting blood sample was obtained to measure GH, IGF-1, and IGF binding proteins (IGF BP-1, 2 and 3). Hyperinsulinemic euglycemic clamps were performed to measure glucose infusion rate (GIR), an estimate of skeletal muscle IR, and serum free fatty acid (FFA) suppression. GH, IGF BP-1 and IGF BP-2 were higher in T1D compared to non-DM youth (Figure). Higher IGF BP-3 was associated with lower GIR (more muscle IR) in all youth, but lower IGF BP-1 and 2 were associated with lower GIR in non-DM youth only. Higher GH, IGF BP-1 and IGF BP-3 were associated with less FFA suppression (more adipose IR) in T1D youth only. The GH-IGF-1 axis is altered and is differentially correlated to IR in T1D versus T2D. These data provide clues regarding the unique phenotype of IR in T1D.

Disclosure

J.K. Snell-Bergeon: None. J.E.B. Reusch: Board Member; Self; American Diabetes Association. Other Relationship; Self; Merck & Co., Inc. A.D. Baumgartner: None. M. Cree-Green: None. K.J. Nadeau: None.

Funding

American Diabetes Association (7-13-CD-10 to J.K.S-B.)
1566-P: Clinical Characteristics, Antihyperglycaemic Treatment Patterns, and Blood Glucose Control in Older Type 2 Diabetes Mellitus (T2DM) Patients in China: A Nationwide Cross-Sectional Study
Authors: SHEN JIE , LIU MENG , YE BINQI , LI QIANG , CLARK DOUGLAS , JI LINONG
Published: June 2019

Aim: China has the largest diabetes population in the world at 114.4 million in 2017. However, data on the overall characteristics of older T2DM patients in China is limited. We aimed to investigate blood glucose control, potential factors associated with glucose control, albuminuria incidence, treatment patterns and hypoglycemia prevalence in Chinese T2DM patients, aged over 60 years.

Method: This nationwide cross-sectional study collected data from T2DM outpatients in 18 hospitals in China between March and December 2017. Descriptive analyses and logistic regression were performed to summarize data and identify potential associations, respectively.

Results: Our study included 1520 patients (mean age: 67.7± 5.86 years). Overall, 43.4% (660/1520) of patients had well controlled blood glucose (defined as HbA1c <7%). Older age, albuminuria and longer duration of diabetes were associated with decreased HbA1c control. Albuminuria was reported in 34.7% of patients (27.6% with micro-albuminuria and 7.1% with macro-albuminuria). The most commonly-used OADs were biguanide (42.6%), α-glucosidase inhibitors (AGI [33.5%]) and sulfonylureas (SU [22%]) and the most common dual OAD-combinations were biguanide combined with SU, biguanide combined with AGI, and AGI combined with SU. Additionally, 43.8% of patients received insulin. Only 4.7% of patients received DPP-4 inhibitors; no patient received SGLT2 inhibitors. The proportion of patients who reported a history of hypoglycemia was 28.0%.

Conclusion: In this cross-sectional study of older Chinese T2DM patients, fewer than half had an HbA1c of <7%. Around one third of patients had albuminuria, which was associated with a lower rate of HbA1c control. Given the relatively high risk of hypoglycemia in this population, increased use of OADs with low risk of hypoglycemia, such as DPP-4 inhibitors and SGLT2 inhibitors, should be considered.

Disclosure

J. Shen: None. M. Liu: None. B. Ye: None. Q. Li: None. D. Clark: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi.

Funding

Boehringer Ingelheim; Eli Lilly and Company
1590-P: Parental and Sibling Age at Diabetes Diagnosis and the Risk of Diabetes in Denmark
Authors: SILVERMAN RETANA JOSE OMAR , HULMAN ADAM , NIELSEN JANNIE , CARSTENSEN BENDIX , SIMMONS REBECCA K. , BJERG LASSE , JOHNSTON LUKE , WITTE DANIEL R.
Published: June 2019

Background: We assessed the effect of parental and sibling age at diabetes diagnosis on index individuals’ risk of developing diabetes.

Methods: We carried out a register-based closed cohort analysis of 869,489 initially diabetes-free index individuals living in Denmark between 1995 and 2012. We assessed the effect of parents’ and full siblings’ age at diabetes diagnosis on the incidence of diabetes in the index individual, beyond the general effect of a positive family history. We calculated incidence rate ratios (IRR) in sex-stratified Poisson regression models.

Results: A total of 58,339 index individuals developed diabetes during 14 million person-years of follow-up. Diabetes risk was highest when parents had a diabetes diagnosis at a younger age. Men and women with a mother diagnosed with diabetes at age 50 had an IRR of 3.62 (95% CI: 2.86 to 4.57) and 5.03 (95% CI: 3.90 to 6.49) respectively compared to people of the same age and sex without a mother with diabetes. At a maternal diagnosis age of 70, the IRRs were 1.56 (95% CI: 1.46 to 1.57) and 1.67 (95% CI: 1.53 to 1.82) for men and women respectively.

Conclusions: Diabetes early detection strategies might consider that younger parental age at diabetes diagnosis may reflect more severe forms of diabetes, conferring a higher risk of developing the disease.

Disclosure

J. Silverman Retana: Other Relationship; Self; Danish Diabetes Academy, Steno Diabetes Center Aarhus. A. Hulman: None. J. NIelsen: None. B. Carstensen: Consultant; Self; Leo Pharma. Speaker's Bureau; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. R.K. Simmons: None. L. Bjerg: None. L. Johnston: None. D.R. Witte: None.

Funding

Danish Diabetes Academy (to J.O.S.R.); Novo Nordisk Foundation; Steno Diabetes Center Aarhus
1599-P: Glycated Albumin Identifies Dysglycemia Not Detected by A1C: The Case for Combining Glycated Albumin and A1C in Africans
Authors: MUGENI REGINE , ADUWO JESSICA Y. , BRIKER SARA M. , HORLYCK-ROMANOVSKY MARGRETHE F. , MABUNDO LILIAN , DUBOSE CHRISTOPHER , SUMNER ANNE E.
Published: June 2019

As the diabetes (DM) epidemic spreads in Africa, affected adults are younger and less obese than in high-income regions of the world. A1C, a nonfasting marker of glycemia, is used to diagnose dysglycemia, a summary term for prediabetes and DM. However, independent of glycemia, A1C increases with age and BMI. Conversely, hemoglobinopathies common in Africa such as sickle cell trait (SCT) can lead to artefactually low A1C levels. Because of the challenges surrounding A1C, attention is turning to glycated albumin (GA). Our goal was to determine in Africans the value of A1C and GA when a) performed individually and b) combined. OGTT was performed and A1C and GA levels were measured in 366 African-born blacks currently living in the Washington, DC area (male: 67%). Diagnosis of dysglycemia was based on fasting glucose≥100 mg/dL or 2h glucose≥140 mg/dL. The ability of A1C≥5.7% and GA≥14.2% to diagnose dysglycemia was evaluated. Both A1C≥5.7% and GA≥14.2% represent the upper quartile cut-off for their distribution in the population. To assess the value of performing both GA and A1C, people with dysglycemia were divided into 2 groups: 1) A1C-group detected by A1C only or A1C and GA; 2) GA-group identified by GA only and not detected by A1C. Dysglycemia occurred in 36% (135/366) of participants. SCT occurred in 17% (62/366) of the cohort and 20% (27/135) of people with dysglycemia. Sensitivities of A1C and GA were only 43% and 33%, resp. However, combining A1C and GA led to a sensitivity of 60% and this was better than either test alone (P<0.01). People identified by GA but not A1C were younger (age: 42±10 vs. 47±9y (mean±SD), P=0.05) and less obese (BMI: 26.7±2.5 vs. 30.3±4.5, P<0.01). A1C identified 52% (14/27) of the people with SCT and dysglycemia. GA identified an additional 22% (6/27) of people with SCT and dysglycemia not detected by A1C. Overall, combining GA with A1C leads to improved detection of dysglycemia in Africans from three groups: SCT, the nonobese and younger adults.

Disclosure

R. Mugeni: None. J.Y. Aduwo: None. S.M. Briker: None. M.F. Horlyck-Romanovsky: None. L. Mabundo: None. C. DuBose: None. A.E. Sumner: None.
16-LB: N-Hydroxylethyl-1-Deoxynojirimycin (Miglitol) Infusion Rescues the Sympathoadrenal Response to Hypoglycemia following Antecedent Hypoglycemia in Rats
Authors: JOKIAHO ANNE J. , WINCHESTER MATTHEW , DONOVAN CASEY
Published: June 2019

Antecedent hypoglycemia leads to a blunting of the sympathoadrenal response during subsequent hypoglycemia, which can largely be prevented by normalizing portal-mesenteric vein (PMV) glycemia during the antecedent bout. As SGLT3 has recently been implicated in PMV glucosensing, we hypothesized that PMV infusion of the imino sugar N-hydroxylethyl-1-deoxynojirimycin (miglitol), a potent SGLT3 agonist, during hypoglycemia would prevent or rescue the sympathoadrenal response to subsequent hypoglycemia.

Wistar rats underwent hyperinsulinemic-hypoglycemic clamps on two consecutive days. Control animals were exposed to either euglycemia (EUG-CON: 5.73 ± 0.37 mM) or hypoglycemia (HYPO-CON: 2.39 ± 0.07 mM) on Day 1 without miglitol infusion, followed by a hypoglycemic bout on Day 2. Treatment groups were exposed to hypoglycemia (2.52 ± 0.07 mM) on both days with miglitol (1.45 μmol/kg/min) infused either upstream, perfusing the PMV glucosensors (PORups), or adjacent to the liver, bypassing the PMV glucosensors (PORadj), on Day 1 (PORups1, PORadj1) or Day2 (PORups2, PORadj2). Serial plasma samples drawn on the Day 2 experiment were assayed for glucose, insulin, epinephrine (EPI) and norepinephrine (NE). Compared to EUG-CON, peak EPI responses for HYPO-CON on Day 2 were significantly blunted (34.1 ± 4.3 vs. 15.4 ± 3.5 nmol/L; P < 0.05). EPI responses for PORups1 (11.8 ± 4.7 nmol/L) and PORadj1 (12.83 ± 3.4 nmol/L) were also suppressed on Day 2 compared with HYPO-CON (P<0.05). In contrast, EPI responses for PORups2 (31.5 ± 8.2 nmol/L) and PORadj2 (32.9 ± 13.2 nmol/L) were not significantly different from HYPO-CON (P = 0.74 and 0.90, respectively). NE demonstrated a similar trend to EPI.

Conclusion: The impaired sympathoadrenal response following antecedent hypoglycemia in rats is restored by miglitol (NEOH-DNJ) treatment during a subsequent bout of hypoglycemia. Whether this is mediated via PMV glucosensors remains unclear.

Disclosure

A.J. Jokiaho: None. M. Winchester: None. C. Donovan: None.

Funding

JDRF
1603-P: Fasting Metabolomic Profiles Are Altered by Three Days of Standardized Diet and Restricted Physical Activity
Authors: PYLE LAURA , CARREAU ANNE-MARIE , RAHAT HASEEB , REYES YESENIA GARCIA , NADEAU KRISTEN J. , CREE-GREEN MELANIE
Published: June 2019

Metabolomics has been used to identify biomarkers of diabetes development and progression and to investigate pathophysiological mechanisms; however, metabolomics profiles can be affected by diet and physical activity. We evaluated the effects of acute diet and physical activity on metabolomics profiles in a cohort of obese adolescent girls. Obese adolescents (n=21, 14.2 ± 1.6 years, BMI %ile 98.0 ± 1.7) were studied. At the first study visit (fasting visit), participants fasted for 12 hours prior to sample collection. Prior to the second visit (controlled visit), participants were provided a 3-day standardized isocaloric weight maintenance diet, and were asked to avoid exercising for 3 days, and samples were drawn after 12 hours of fasting. Untargeted metabolomics was performed in plasma samples. Multilevel sPLS-DA was used to identify compounds that discriminated between fasting and controlled visits. The sPLS-DA analysis showed excellent discrimination (Figure 1) between the fasting and controlled samples, resulting in 0% misclassification error. In ROC analysis, the AUROC of the sPLS-DA model was 1.00 (p<0.0001). Acute diet and physical activity affect fasting metabolic profiles, and differences identified between samples may not be a result of underlying metabolism. Caution should be used in interpreting fasting metabolomics unless diet and physical activity are controlled.

Disclosure

L. Pyle: None. A. Carreau: Advisory Panel; Self; Pfizer Inc. H. Rahat: None. Y. Garcia Reyes: None. K.J. Nadeau: None. M. Cree-Green: None.

Funding

National Institutes of Health; University of Michigan
1605-P: Profiling Risk among Sepsis Survivors with Diabetes in Home Care
Authors: WHITEHOUSE CHRISTINA R. , JORDAN LIZEYKA , BOWLES KATHRYN , MURTAUGH CHRISTOPHER M.
Published: June 2019

Diabetes mellitus (DM) increases the risk of developing infectious complications, including sepsis. Little is known about sepsis survivors with DM. Overall, there are limited and conflicting information regarding outcomes of patients with diabetes after a hospitalization for sepsis. The purpose of this study was to profile the characteristics and outcomes for sepsis survivors with (n = 80,312) and without DM (n = 84,916). The sample included Medicare beneficiaries discharged from the hospital to home health care (HHC) after a sepsis admission between July 1, 2013 and June 30, 2014. We utilized Medicare administrative claims and the Outcome and Assessment Information Set Version C start of care assessments. The incidence of older adults with DM and sepsis in HHC was 48.6%; a much higher rate than the 20-30% reported in the general hospitalized population. Those with DM and sepsis had a higher proportion of 30-day rehospitalization (24.3% verse 20.8%, p < .001) and were more likely to have a prior sepsis admission (9.28% verse 3.35%, p < .001) than sepsis patients without DM. They had more comorbid conditions (5.19 versus 3.8, p<.001) including higher rates of depression, vision loss, obesity, hypertension, heart failure, pulmonary disease, and renal failure than non-DM sepsis survivors. Approximately 50% were taking injectable medications and only 12.8% of them were able to do so independently. For those who required caregiver assistance over 25% of caregivers reported needing additional training. Sepsis survivors with DM experience significantly higher readmission rates than non-DM patients. HHC clinicians should flag the sepsis survivor with DM as high risk and target interventions to manage the increased comorbid conditions, medication management, and caregiver training issues that may be contributing to the higher readmission rates.

Disclosure

C.R. Whitehouse: None. L. Jordan: None. K. Bowles: None. C.M. Murtaugh: None.

Funding

National Institute of Nursing Research (R01NR016014); Visiting Nurse Service of New York; Ruth L. Kirschstein National Research Service Award; University of Pennsylvania School of Nursing
161-LB: Inhibition of Kidney SGLT2 Expression following Bariatric Surgery in Mice
Authors: AKALESTOU ELINA , LOPEZ NORIEGA LIVIA , CHABOSSEAU PAULINE L. , LECLERC ISABELLE , RUTTER GUY A.
Published: June 2019

Background: Bariatric surgery is known to improve glucose tolerance and weight loss, but can also cause a postprandial increase in renal glucose excretion following oral glucose tolerance test. Both effects have also been observed following treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors.

Aim: To investigate whether there is an effect of bariatric surgery (Vertical Sleeve Gastrectomy; VSG) on renal SGLT2 expression in mice.

Methods: Fourteen lean mice underwent VSG (n=8) or sham (n=6) surgery. Glucose Tolerance tests with or without treatment with the SGLT2 inhibitor dapagliflozin were performed four weeks post operatively, in order to assess if exogenous SGLT2 inhibition has the same euglycemic effects as bariatric surgery. Kidneys were harvested from fed mice and analysed using Quantitative real-time PCR (qRT-PCR) and immunofluorescence.

Results: VSG did not cause any weight loss when compared to sham operated mice (p=0.37, Mann-Whitney test). However, VSG mice displayed significantly improved glucose tolerance (AUC=103 ±6.8; AUC =66.6 ±2.9 in control and VSG mice, respectively; p<0.001), which was not further affected by dapagliflozin (10 mg/kg; p>0.05). In contrast, treatment of sham mice with dapagliflozin increased glucose tolerance, though to a lesser extent than VSG. Nevertheless, qPCR and immunofluorescence analysis on mouse kidneys demonstrated a significant lowering of SGLT2 expression at both the protein (n=5, p=0.0007) and mRNA (n=7, 0<0.0001) levels four weeks after VSG. Correspondingly, glycosuria was observed in 2/5 VSG mice, but not in controls.

Conclusions: Both gastric and intestinal surgery in lean animals causes a significant inhibition of SGLT2 in the kidney cortex. These findings are in line with our previous results on the effects of Duodenal Jejunal Bypass in lean rats, and point towards a physiologically-relevant gut-kidney axis. SGLT2 inhibition may thus be an important mechanism through which bariatric surgery improves glucose tolerance in man.

Disclosure

E. Akalestou: None. L. Lopez Noriega: None. P.L. Chabosseau: None. I. Leclerc: None. G.A. Rutter: Consultant; Self; Sun Pharma.

Funding

UK Wellcome Trust
1627-P: Glycemic Control From 2013 to 2016 among U.S. Adults with Type 2 Diabetes (T2D): A National Estimate Stratified by Age, eGFR Category, and Comorbidities
Authors: XI YUZHI , WANG TONGTONG , KORO CAROL
Published: June 2019

The adequacy of adherence to ADA guidelines, as reflected in glycemic control, has not been assessed for the U.S. adult T2D population by different risk factors, such as age, CVD, obesity and eGFR categories. The aim of this study was to provide such estimates. Using NHANES 2013-2016 data, we conducted a cross-sectional analysis of an adult sample with diagnosed and undiagnosed T2D (n=1705), aged ≥ 18 years. We aggregated HbA1c measures to 4 levels: <7%, 7-<8%, 8-<9%, and ≥9%. Appropriate sample weights were used to obtain national projections. Results of glycemic control stratified by age, eGFR categories and comorbidities in U.S. adults with T2D are presented in Table 1. The overall glycemic control rate, defined as HbA1c <7%, was 51.9%. Among T2D aged 45-64 years, 46.6% had an HbA1c <7%; while 60.3% of T2D aged ≥75 years had an HbA1c <7%. Among T2D with renal impairment, the glycemic control rate was similar across eGFR categories, remaining at above 50%. Among T2D with different comorbidities, glycemic control rate ranged from 48.5% for those with both obesity and CVD to 69.5% for those with CVD only. Overall, 14.8% of T2D had an HbA1c ≥9%, with 22.7% among aged 18-44 years and 20.3% among those with eGFR >90 ml/min/1.73m2. Our data shows only about 50% of T2D patients are at HbA1c goal of <7% with currently available treatments, ranging from 47-70% depending on risk factors.

Disclosure

Y. Xi: Research Support; Self; Merck & Co., Inc. T. Wang: Employee; Spouse/Partner; Johnson & Johnson. Employee; Self; Merck & Co., Inc. C. Koro: Speaker's Bureau; Self; Merck & Co., Inc.
163-LB: Impact of SGLT2 Inhibitors on Liver Function Test in Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Systemic Review and Meta-analysis
Authors: THAVARAPUTTA SUBHANUDH , WIRUNSAWANYA KAMONKIAT , LAOVEERAVAT PASSISD
Published: June 2019

Background: Nonalcoholic fatty liver disease (NAFLD) has been found to be a chronic and precarious metabolic complication from diabetes mellitus. Due to the limitation of treatment options for NAFLD, we postulated that SGLT2 inhibitors would have a potential benefit for NAFLD. None of the previous studies have comprehensively addressed multiple different classes of SGLT2 inhibitor in type 2 DM individuals with NAFLD. We conducted the first meta-analysis investigating the impact of SGLT2 inhibitors on liver function test in type2DM and NAFLD.

Methods: We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane databases. The inclusion criteria were published randomized control trials (RCT), prospective studies, and retrospective studies comparing SGLT2 inhibitors to placebo or controls in NAFLD and type 2 DM individuals. The primary outcome was the differences in the change of ALT and AST. We also examined the changes of NAFLD risk factors including body composition, lipid profile, HbA1C as secondary outcomes. Pooled odds ratio and 95% confidence interval were calculated using a random-effects model (generic inverse variance method). The between-study heterogeneity of effect size was quantified using the Q statistic and I.

Results: Eight RCTs, one prospective study, and one retrospective study with 4698 patients were included in the analysis. There was a statistically significant reduction of AST (MD=-2.09, 95% CI:-3.65to-0.52) and ALT (MD=-6.02, 95% CI: -8.35to-3.70) favoring SGLT2 inhibitor groups.

Conclusion: SGLT2 inhibitor groups were shown to have a statistically significant reduction of ALT and AST compared to placebo or control groups. SGLT2 inhibitor might be considered as a conjunctive treatment for NAFLD in type2DM individuals. Further studies regarding the optimal dosage and duration of SGLT2 inhibitors are helpful to assess potentially favorable effects in type 2 DM individuals and NAFLD.

Disclosure

S. Thavaraputta: None. K. Wirunsawanya: None. P. Laoveeravat: None.
1631-P: Glycaemic Deterioration, a Clue to Occult Cancer
Authors: KANEKO SHIZUKA , UEDA YOUHEI , TAHARA YUMIKO
Published: June 2019

Background/Objective: Hyperglycemia/hyperinsulinemia promote carcinogenesis. Cancer associated factors worsen insulin resistance. Either way, glycaemic control of cancer bearing diabetic patients often deteriorates, which is believed to help in finding occult cancer in diabetic patients.

Methods: We investigated whether it applies to every type of cancer. We analysed cancer bearing type 2 diabetes patients (T2DM) medical records going back 10 years. HbA1c levels in connection with occult cancer were analysed in relation to organs and stages of cancer based on TMN criteria. Cancers with 20+ diagnosed patients were analysed.

Result: 1155 T2DM patients were newly diagnosed with cancer. Lung cancer totaled 247, colorectal 218, gastric 218, hematologic (leukemia/lymphoma) 81, prostate 75, pancreas 65, hepatocellular 60, kidney or urethro-bladder 49, and uterine 43, breast cancers 32, esophageal 29, gall-bladder/biliary tree 28. No patients were diagnosed with pancreatic cancer at stage 1. The HbA1c of pancreatic cancer patients rose significantly. The HbA1c of lung cancer patients was not elevated even in stage 4, although HbA1c tended to rise significantly as the stage advanced. HbA1c was mildly elevated in almost all stages of colon/rectum and gastric cancer. Gastrointestinal bleeding causes apparent decreases in HbA1c regardless of elevated glycaemic levels in stage 3 and may mask these cancers. HbA1c of hepatocellular carcinoma (HCC) patients decreased with advanced stages.

Discussion: HbA1c elevation can be promising in pancreatic cancer detection. However, lung, prostate, gastrointestinal cancers had little effect on it even in advanced stages with no relation to food intake. Due to masking effects, it was recommended colorectal and gastric cancer patients undergo periodic testing for gastrointestinal bleeding. HCC patients with liver cirrhosis do not have elevated HbA1c levels due to masking effects. The ability to focus on these tests may also save medical expenditure in future. Previous version was presented at EASD.

Disclosure

S. Kaneko: Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd. Y. Ueda: None. Y. Tahara: None.
1636-P: Incidence and Predictors of Diabetes and Prediabetes among South Asians in the United States: The MASALA Study
Authors: UNJALI GUJRAL , VENKAT NARAYAN K.M. , KANDULA NAMRATHA R. , LIU KIANG , KANAYA ALKA M.
Published: June 2019

South Asians are at high risk for type 2 diabetes (T2DM). There is a paucity of data on prediabetes and T2DM incidence and related predictors in U.S. South Asians. We estimated prediabetes and T2DM incidence after five years of follow-up in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study (n=758) and examined the associated correlates. We defined T2DM and prediabetes using the ADA criteria. Prediabetes included isolated impaired fasting glucose (iIFG), isolated impaired fasting glucose (iIGT), and combined IFG+IGT. Overall, 482 (64%) individuals progressed, either from normal glucose tolerance (NGT) to prediabetes/T2DM, or from prediabetes to T2DM (Table 1). In standardized logistic regression models controlled for age and sex, only hepatic fat attenuation (OR: 0.69 (95% CI: 0.55, 0.87), visceral fat mass area (OR: 1.34 (95% CI: 1.05, 1.71), and hypertension (OR: 2.28 (95% CI: 1.49, 3.49) were associated with any glycemic progression. Hepatic fat attenuation was associated with progression from prediabetes to T2DM (OR: 0.56 (95% CI: 0.38, 0.82), and visceral fat mass area was associated with progression from NGT to prediabetes/T2DM (OR: 1.72 (95% CI: 1.23, 2.41). South Asians in the U.S. have a high incidence of dysglycemia. Hepatic fat attenuation may be a factor in the conversion from prediabetes to T2DM, and prevention efforts should target ectopic fat reduction.

Disclosure

U. Gujral: None. K. Narayan: None. N.R. Kandula: None. K. Liu: None. A.M. Kanaya: None.

Funding

National Institutes of Health (R01HL093009, K24HL112827, UL1RR024131)
1638-P: Urinary Polycyclic Aromatic Hydrocarbon Concentrations and Risk of Diabetes Mellitus in Korean Adults
Authors: NAM YON JU , KIM SHIN-HYE
Published: June 2019

Background: Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental chemicals with aromatic rings and are generated by the incomplete combustion of organic materials. A few animal and occupational studies suggested a possible association between PAHs exposure and increased risk of diabetes mellitus.

Objectives: We aimed to investigate the associations of urine levels of PAHs with diabetes mellitus in Korean adults.

Methods: We examined cross-sectional data from the Korean National Environmental Health Survey (KoNEHS) 2012-2014. The study population consisted of 6478 adult subjects (≥20 years of age) from 400 sampling districts in South Korea. The urinary levels of 1-hydroxypyrene, 2-naphthol, 1-hydroxyphenathrene, and 2-hydroxyfluorene were measured in the study subjects. Analyses were adjusted for gender, age, BMI, household income, alcohol consumption, physical activity, urinary creatinine, and urinary cotinine.

Results: We observed a positive association between urinary PAHs and cotinine after adjusting for all covariates. A higher geometric mean value of urinary 2-naphthol was observed in subjects with diabetes mellitus compared with controls (2.67 vs. 2.24 μg/L). There was no significant difference in other urinary PAHs according to the presence of diabetes mellitus. According to the elevation of urinary 2-naphthol quartile, the multivariate-adjusted odds ratio (OR) of diabetes mellitus significantly increased in both male and female adults (P-for-trend <0.05). Compared with subjects with urinary 2-naphthol in the lowest quartile, the OR (95% confidence interval) of diabetes mellitus in those in the highest quartile was 1.8 (1.24-2.63).

Conclusions: Urinary 2-naphthol levels were positively associated with diabetes mellitus in Korean general populations. Prospective studies are needed to determine a potential causal relationship between PAHs exposure and diabetes mellitus in human.

Disclosure

Y. Nam: None. S. Kim: None.
1644-P: Novel Subgroups of Prediabetes and Their Clinical Outcomes: A Data-Driven Analysis
Authors: ZOU XIANTONG , ZHU ZHANXING , LUO YINGYING , LI YUFENG , ZHOU XIANGHAI , JI LINONG
Published: June 2019

The progression of prediabetes to diabetes and the reversion of them to NGT are highly heterogeneous. To develop a refined classification of prediabetes, we used data-driven K-means clustering in patients diagnosed with IGT and IFG according to WHO 1999 criteria in Pinggu Study (a prospective population-based survey for diabetes in suburban Beijing, n=628), NHANES III study (a cross-sectional population-based survey in the U.S., n=1532) and Beijing Prediabetes Reversion Program (BPRP, a RCT to evaluate the efficacy of lifestyle and/or pioglitazone on prediabetes reversion, n=1905). Based on five variables including HbA1c, BMI, age, HOMAIR and HOMAB, we identified four replicable clusters across all three datasets including high glucose group (HGG), lean group (LG), early-onset group (EOG) and insulin resistant group (IRG) (Figure). HRG had significant higher 1-year diabetes progression rate (15.4% in BPRP and 25.6% in Pinggu study) and the LG had the lowest diabetes progression rate (7.1% in BPRP and 11.1% in Pinggu Study). In BPRP, HGG treated with Intensive lifestyle plus pioglitazone had significant higher reversion rate to NGT and EOG treated with intensive life style plus placebo had least reversion rate compared to other treatment. Our study provides risk stratification for prediabetes and can potentially facilitate clinical decision, representing a first step towards precision management.

Disclosure

X. Zou: None. Z. Zhu: None. Y. Luo: None. Y. Li: None. X. Zhou: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi.

Funding

The Major Chronic Non-Communicable Disease Prevention and Control Research of China; Beijing Science and Technology Committee; National Natural Science Foundation of China
1648-P: The Association between Uric Acid Level and Mortality Risks in Diabetes Population in U.S.
Authors: CHEN PO-HSUN , LEE CHIA LIN , CHEN CHING-HSIEN
Published: June 2019

Objective: Elevated serum uric acid (UA) level has been associated with increased coronary heart disease mortality. The optimal UA level in patients with diabetes remains uncertain. We compared the mortality risk across UA levels among adults with and without diabetes.

Methods: We analyzed data from adults aged >18 years without coronary heart disease and chronic renal disease (n= 29,226) from the National Health and Nutrition Examination Survey (1999-2010) and the associated mortality data (up to December 2011). We used the Cox proportional hazards models to examine the risk of all-cause and cause-specific (cardiovascular disease [CVD] and cancer) mortality at different UA levels between adults with diabetes and without diabetes.

Results: Over a median follow-up of 6.6 years, 2,069 participants died (495 from CVD and 520 from cancers). Compared with nondiabetes adults with UA level of 5-7mg/dL (reference), the hazard ratios (HR) for all-cause mortality were significantly greater for adults without diabetes at UA levels of 7-9mg/dL (HR=1.39) and ≥9mg/dL (HR=2.31). In diabetes patients, HRs were 2.10 (95% CI 1.61, 2.73), 1.28 (95% CI 0.93, 1.77), 2.88 (95% CI 2.13, 3.89), and 2.65 (95% CI 1.18, 5.96) for UA <5mg/dL, 5-7mg/dL, 7-9mg/dL, and ≥9mg/dL, respectively. Compared to reference, CVD mortality risk in diabetes participants were significantly higher at every UA category (HR=2.33, 2.24, 5.03, and 1.70 for UA <5mg/dL, 5-7mg/dL, 7-9mg/dL, and ≥9mg/dL, respectively). In diabetes adults, the participants with UA 7-9mg/dL had higher risk than those with UA 5-7mg/dL (p=0.038). Regarding cancer mortality risk, no significant difference was found at different UA levels no matter with or without diabetes.

Conclusions: At UA level of >7mg/dL, increased risk of all-cause and CVD mortality occurred in both diabetes and nondiabetes participants. Without accounting for the effect of glycemic control, our results support all-cause mortality risk in diabetes adults was lowest at UA level of 5-7mg/dL.

Disclosure

P. Chen: None. C. Lee: None. C. Chen: None.
165-OR: The Mechanisms by Which Adiponectin Reverses Insulin Resistance in High-Fat Diet Fed Mice
Authors: LI XIRUO , ZHANG DONGYAN , PERRY RACHEL J. , VATNER DANIEL F. , GOEDEKE LEIGH , ZHANG YE , SHULMAN GERALD I.
Published: June 2019

Adiponectin has emerged as an antidiabetic adipokine, and a potential therapy to treat type 2 diabetes. However, the mechanism by which adiponectin improves insulin sensitivity remains unclear. To address this question, we examined the effects of a 2-week continuous infusion of globular adiponectin (gAcrp30) or saline (CON) on glucose and lipid metabolism in a high fat diet fed (HFD) mouse model. Whole-body and tissue-specific insulin action was assessed by a hyperinsulinemic-euglycemic clamp (HEC). gAcrp30-treated mice displayed reduced fasting plasma glucose and insulin concentrations (both P<0.05 vs. CON) and increased glucose infusion rate (14 vs. 22 mg/(kg-min), P<0.001) during the HEC reflecting increased whole-body insulin-sensitivity. Increased insulin sensitivity could be attributed to reduced endogenous glucose production (16.7 vs.14.2 mg/(kg-min), P<0.05), increased glucose uptake in muscle (191 vs. 285 nmol/(kg-min), p=0.006) and adipose tissues (BAT: 112 vs. 217, WAT: 11 vs. 22 nmol/(kg-min), both P<0.05) during the HEC. These improvements in liver and muscle insulin sensitivity were associated with ∼50% reductions in liver and muscle triglyceride (TAG) and ∼40% diacylglycerol (DAG) (both P<0.01 vs. CON) content but no changes in hepatic ceramide content. Reduced tissue TAG/DAG content occurred independent of changes in WAT lipolysis, hepatic AMPK activation, ACC phosphorylation or mitochondrial oxidation. Reduced tissue DAG content was associated with decreased PKCε activation in liver and PKCθ activation in muscle and increased insulin signaling in liver, muscle and white adipose tissue.

Conclusion: Taken together these data support the hypothesis that adiponectin improves insulin sensitivity in liver and muscle of HFD fed mice by reducing ectopic lipid (DAG) content in these tissues leading to decreased nPKC activity and increased insulin signaling, and contrary to prior studies, is independent of changes in hepatic ceramide content.

Disclosure

X. Li: None. D. Zhang: None. R.J. Perry: Research Support; Self; AstraZeneca. D.F. Vatner: None. L. Goedeke: None. Y. Zhang: None. G.I. Shulman: Advisory Panel; Self; AstraZeneca, Janssen Research & Development, Merck & Co., Inc. Advisory Panel; Spouse/Partner; Merck & Co., Inc. Board Member; Self; Novo Nordisk A/S. Consultant; Self; Aegerion Pharmaceuticals, IMetabolic BioPharma Corporation, Longitude Capital, Nimbus Discovery, Inc., Staten Biotechnology B.V.

Funding

American Heart Association (19PRE34380268); National Institutes of Health (R01DK116774)
166-LB: Canagliflozin but Not Empagliflozin Activates AMPK and Suppresses Colon Cancer Cell Growth
Authors: YAGI TAKASHI , TANAKA TOMOHIRO , KUBOTA EIJI , KOYAMA HIROYUKI , GUO TINGTING , OGAWA KENTO , AOTANI DAISUKE , KATAOKA HIROMI
Published: June 2019

Background: Recent increase in the relative proportion of cancer death in diabetic patients has become a major issue. A hypoglycemic agent, sodium-glucose cotransporter (SGLT) 2 inhibitor has attracted attention because of its potency in reducing cardiovascular risks. Several lines of evidence has emerged suggesting a potential anti-oncotic effect. Here we address potential effects of canagliflozin (Cana) on human colon cancer cell growth and underlying mechanisms and compared with empagliflozin (Empa).

Material and Methods: We examined the effects of Cana and Empa on 1) cell proliferation using colon cancer cell lines, SW480 and HCT116 by MTT assay, 2) DNA synthesis by flow cytometry-based analysis of bromodeoxyuridine (BrdU) uptake. We further examined 3) the expression of SGLT1 and 2 in these cells and 4) investigated molecules of signal transduction pathways with established roles in cancer cell growth such as AMPK, 4EBP1, mTOR by western blotting. Finally, we analyzed 5) time-dependent changes of metabolomic signatures after the treatment with Cana.

Results: While SGLT1 and 2 mRNA and protein expression was detected in both cell lines, Cana but not Empa significantly inhibited cell proliferation and in a dose-dependent manner. Cana suppressed BrdU positive cells and enhanced AMPK phosphorylation with a consequent suppression of 4EBP1 and mTOR activity. Metabolomic profiling revealed that, as a function of time, intermediate metabolites of glycolysis especially phosphoenolpyruvate was decreased with an acute rise in ADP and gradual decrease in ATP and GSSG.

Conclusion: We demonstrate that Cana deprives human colon cancer cells of energy and anti-oxidative capacity possibly through an inhibition of SGLT1-mediated glucose influx, and thereby activates AMPK and inhibits cancer cell growth. Our data herein suggest a potential beneficial effect of Cana in suppressing colon cancer progression especially in patients with diabetes.

Disclosure

T. Yagi: None. T. Tanaka: Research Support; Self; Japan Society for the Promotion of Science. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Taisho Toyama Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited. E. Kubota: None. H. Koyama: None. T. Guo: None. K. Ogawa: None. D. Aotani: None. H. Kataoka: None.
1668-P: The Impact of Ethnicity on Clinical Characteristics and Autoantibody Status at Clinical Onset of Type 1 Diabetes—From the ADDRESS-2 Study
Authors: WALKEY HELEN C. , KAUR AKAAL , GODSLAND IAN F. , WILLIAMS ALISTAIR J. , OLIVER NICK , JOHNSTON DESMOND G. , MISRA SHIVANI
Published: June 2019

Introduction: The phenotype of type 1 diabetes (T1D) has been explored mainly in white populations. People of non-white ethnicity are reportedly less likely to be antibody positive, but phenotypic differences are not well characterised. We investigated ethnic group differences in the clinical characteristics and antibody (Ab) status at clinical onset of T1D.

Methods: We studied people of white European (WE), Asian (A) and black African/Caribbean (AC) ethnicity with clinically-assigned T1D, age ≥5 years, recruited ≤ 6 months after diagnosis, and with Abs (GADA, IA-2A and ZnT8A) measured by radioimmunoassay.

Results: Ethnic breakdown: WE n=1,997, A n=50, AC n=41. Median (IQR) ages were: WE 23(14-24), A 18(12-29), AC 26 (15-41) years p=0.007. Presentation with DKA was more common in AC (65%) than WE (42%) or A (53%) p=0.006; otherwise clinical presentation (polyuria/dipsia, weight loss, fatigue, symptom duration) was similar. Proportions with 0, 1 and ≥2 Abs differed by ethnicity: WE (15%, 24%, 61%); A (28%, 26%, 46%); AC (36%, 32%, 32%) p<0.001. For Ab negative (0 Abs), ethnic groups differed in BMI (p=0.001) and presentation with DKA (<0.001), but other characteristics, including daily insulin dose, were similar. For Ab positive (≥1 Ab), there were differences in parental history of diabetes p=0.02; otherwise ethnicity had no impact. Also, differences were seen in the frequency of IA-2A: WE (67%), A (53%), AC (50%) p=0.03 and ZnT8A: WE (60%), A (39%), AC (42%) p=0.01, but not GADA: WE (83%), A (94%) AC (92%) p=0.09.

Conclusion: Although clinical presentation of T1D was remarkably similar across ethnic groups, variations were found in the proportions with Ab positivity and frequencies of individual Abs. Antibody negativity was more common in non-white ethnic groups and the presence of >1 Ab most common in white ethnicity. Practitioners should be alert to differences in phenotype according to antibody status that may impact classification in some ethnic groups.

Disclosure

H.C. Walkey: None. A. Kaur: None. I.F. Godsland: None. A.J. Williams: None. N. Oliver: Advisory Panel; Self; Roche Diabetes Care. Research Support; Self; Dexcom, Inc., Roche Diabetes Care. Speaker's Bureau; Self; Dexcom, Inc., Sanofi. D.G. Johnston: None. S. Misra: None.

Funding

Diabetes UK; JDRF