bluuebunny/crossref_metadata_2025_split huggingface dataset:
258-OR: Sustainability of HbA1c Control of Tirzepatide vs. Insulin Glargine in People with Type 2 Diabetes and Increased Cardiovascular Risk (SURPASS-4)
Authors: PEARSON EWAN , DEL PRATO STEFANO , PAVO IMRE , FRANCO DENISE R. , YANG ZHENGYU , WIESE RUSSELL , KAHN STEVEN E. 
Published: May 2022

Tirzepatide (TZP) is a novel dual GIP/GLP-1 receptor agonist in development for glucose-lowering in T2D. The open-label SURPASS-4 trial examined TZP vs. insulin glargine (iGlar) in adults with T2D inadequately controlled on oral medications. Participants (N=1989) with baseline HbA1c 7.5-10.5% and BMI ≥25 kg/m2 were randomized 1:1:1:3 to once weekly TZP (5, 10, 15 mg) or iGlar (100 U/mL) titrated to &lt;100 mg/dL fasting glucose. This post hoc analysis evaluated the sustainability of glycemic control after the 52-week (wk) primary endpoint (last on-treatment visit post-52 wks, up to 1wks) , (median=85 wks) . After achieving the 52-wk HbA1c targets of &lt;7%, ≤6.5%, or &lt;5.7%, a participant was considered to have sustained long-term HbA1c control if the final, post-52-wk, on-treatment HbA1c measurement increased ≤0.2% from the 52-wk HbA1c target (Table) . More participants in all 3 TZP dose groups maintained each of the 3 HbA1c targets beyond 52 wks vs. iGlar (all TZP, p&lt;0.05) . Thus, even for the lowest TZP dose (5 mg) , 59% of participants achieved an HbA1c ≤6.5% at 52 wks, with 75% of these having ≤0.2% increase at their last visit. In contrast, for iGlar, 29% achieved an HbA1c ≤6.5%, with 66% of these having ≤0.2% increase.
In conclusion, TZP treatment results in improved long-term HbA1c control for a significantly greater percentage of adults with T2D compared to iGlar.

Disclosure
E.Pearson: Speaker's Bureau; Sanofi. S.Del prato: Advisory Panel; Applied Therapeutics, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Consultant; Menarini Group, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi, Stock/Shareholder; Novo Nordisk A/S. I.Pavo: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. D.R.Franco: Advisory Panel; Abbott Diabetes, Medtronic, Novo Nordisk, Sanofi, Research Support; Eli Lilly and Company, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Medtronic, Roche Diabetes Care, Sanofi. Z.Yang: Employee; Eli Lilly and Company. R.Wiese: Employee; Eli Lilly and Company. S.E.Kahn: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc.
26-LB: Risk Factors of Retinal Oxygen Metabolism and Hemodynamics for Retinopathy in Diabetes
Authors: JIN ZI , ZHOU ZIXIA , ZHANG BIN , WANG FEI , CHEN JIABAO , LIAO DINGYING , LU YUFEI , YANG YUETING , LI JINYING , ZHOU CHUANQING , REN QIUSHI 
Published: May 2022

Purpose: Alterations in retinal oxygen metabolism and hemodynamics are signs of impending diabetic retinopathy (DR) . The study aimed to investigate risk factors of the retinal oxygen metabolism and hemodynamics for non-proliferative DR (NPDR) .
Method: The study included 166 eyes from 50 age-matched healthy subjects, 80 diabetic patients without DR (Non-DR) , and 36 NPDR. Each subjects underwent basic medical history and dilated fundal examinations including colour fundus photography, and custom-built multimodal ophthalmic device with function of retinal oximetry and laser speckle flowgraphy. Retinal metabolism was evaluated by retinal arteriolar (SO2a) , and venular (SO2v) oxygen saturation, while retinal hemodynamics was evaluated by related parameters such as diastolic duration, flow acceleration index (FAI) and resistance index (RI) . Continuous variables were analyzed by one-way analysis of variance, and categorical variables were analyzed by the chi-square test for three groups. The logistic regression model was used to obtain the risk factors of Non-DR developing into NPDR.
Result: The SO2a and SO2v of NPDR and Non-DR were higher significantly than controls (p&lt;0.05) . There were significant difference among three groups in hemodynamics parameters, including diastolic duration, FAI, blowout score, and RI. The greatest risk factors of Non-DR developing into NPDR descending order were higher RI (odds ratio (OR) =5.84, 95% confidence interval (CI) =1.32-25.78) , shorter diastolic duration (OR= 3.46, 95% CI=1.35-8.87) , higher glycosylated hemoglobin A1c (OR=1.82, 95% CI=1.15-2.88) , lower body mass index (OR=1.74, 95% CI=1.19-2.55) , longer duration of diabetic mellitus (OR=1.21, 95% CI=1.05-1.39) , smaller age (OR=1.17, 95% CI=1.04-1.32) , higher SO2v (OR=1.16, 95% CI=1.00-1.34) , higher systolic blood pressure (OR=1.05, 95% CI=1.00-1.10) .
Conclusion: Both NPDR and Non-DR show abnormality in retinal oxygen metabolism and hemodynamics. Diastolic duration, RI, and SO2v are independent risk factors in NPDR.

Disclosure
Z. Jin: None. C. Zhou: None. Q. Ren: None. Z. Zhou: None. B. Zhang: None. F. Wang: None. J. Chen: None. D. Liao: None. Y. Lu: None. Y. Yang: None. J. Li: None.

Funding
Guangdong Basic and Applied Basic Research Foundation (2021A1515110747) .
263-OR: Glycemic Gap Predicts Mortality in a Large Multicenter Diabetes Cohort Hospitalized with COVID-19
Authors: MCDONNELL MARIE E. , SIMONSON DONALD C. , GOPALAKRISHNAN GEETHA , GARG RAJESH , MITRI JOANNA , WEINSTOCK RUTH S. , GREENFIELD MARGARET , PALERMO NADINE E. , RADHAKRISHNAN RAMYA , WESTCOTT GREGORY P. 
Published: May 2022

While diabetes and admission blood glucose (BG) are established risk factors for adverse outcomes during hospitalization for COVID-19, reports on the impact of prior glycemic control have been variable. We examined the relationship between acute and chronic glycemia on risk of ICU admission, mechanical ventilation (MV) , and mortality among 1,786 patients with diabetes or hyperglycemia (BG &gt; 180 mg/dl twice during any 24-hr period during hospitalization) admitted from March 2020 to February 2021 with COVID-at 5 large university hospitals in the eastern U.S. The cohort was 51.3% male, 53.3% White, 18.8% Black, 29.3% Hispanic, with age = 64.8 ± 13.8 y, BMI = 31.5 ± 7.9 kg/m2, admission BG = 216 ± 134 mg/dl, and HbA1c = 8.1 ± 2.2%. During hospitalization, 38.9% were admitted to the ICU, 22.9% received MV, and 10.6% died. In multivariate regression analysis, among demographic factors, age was the strongest risk factor for in-hospital mortality (OR = 1.per year [95% CI: 1.04, 1.06]) , and Hispanic ethnicity was the greatest risk factor for ICU admission (OR = 1.45 [95% CI: 1.16, 1.80]) and intubation (OR = 1.64 [95% CI: 1.28, 2.10]) . Higher BMI (p = 0.005) and admission BG (p = 0.014) were associated with increased risk of mortality, but HbA1c was not. The glycemic gap (GG) , defined as admission BG minus estimated average BG based on HbA1c, was a stronger predictor of mortality than either admission BG or HbA1c alone. Mortality rate was 5.7% for GG &lt; -20 mg/dl; 12.2% for GG = -20 to &lt; 20 mg/dl; 12.4% for GG = 20 to &lt; 100 mg/dl; and 16.1% for GG ≥ 100 mg/dl (p for trend &lt; 0.001) . Conclusion: Among patients with diabetes or hyperglycemia admitted for COVID-19, in addition to previously established risk factors for poor outcomes (age, Hispanic ethnicity, and BMI) , we found that GG is a stronger predictor of in-hospital mortality than blood glucose alone. This suggests that relative hyperglycemia, as measured by the admission GG, is an important marker of disease severity in COVID-and potentially other serious illnesses.

Disclosure
M.E.Mcdonnell: Advisory Panel; Everlywell, Inc., Research Support; Lilly, Stock/Shareholder; Abbott Diabetes. G.P.Westcott: None. D.C.Simonson: Stock/Shareholder; GI Windows, Phase V Technologies, Inc. G.Gopalakrishnan: Research Support; Eli Lilly and Company, Spruce Biosciences. R.Garg: None. J.Mitri: Consultant; dairy management, Lnutra. R.S.Weinstock: Research Support; Boehringer Ingelheim International GmbH, Dexcom, Inc., Diasome, Eli Lilly and Company, Insulet Corporation, Kowa Pharmaceuticals America, Inc., Medtronic, Novo Nordisk, Tandem Diabetes Care, Inc., Tolerion, Inc. M.Greenfield: None. N.E.Palermo: Research Support; Dexcom, Inc. R.Radhakrishnan: None.

Funding
Brigham-TechFoundation, Cambridge, MA 2021
265-OR: Impact of the COVID-Pandemic on Diabetes Screening from 20to 2021 in Ontario, Canada
Authors: FAZLI GHAZAL S. , MOINEDDIN RAHIM , LING VICKI , BOOTH GILLIAN L. 
Published: May 2022

Diabetes incidence is expected to increase following the COVID-pandemic due to widespread changes in physical activity, diet, and access to health care services. We used administrative health care databases from Ontario, Canada to examine monthly changes in diabetes screening during the pandemic (Mar 2020-Feb 2021) compared to the pre-pandemic period (Mar 2019-Feb 2020) among adults aged 20-85 without prior diabetes. The eligible population was 9,599,079 in Mar 20 and 9,941,336 in Feb 2021. Overall, the number of people screened for diabetes was 25.3% lower in the pandemic (N=4,060,348) versus pre-pandemic (N=5,437,284) period. However, the number of people screened each month declined by 65.6% between February and April 2020 (Figure 1; 1.53 vs. 4.44 per 100, -2.91 per 100) . Screening rates recovered by July 2020 (3.88 per 100) but remained 15.6% lower than in the pre-pandemic period. Similar patterns were observed in all age groups but declines in screening rates between February and April 2020 were greatest in adults aged 35-49 (-69.4%) and 50-64 (-69.5%) . Findings were also consistent across income groups.
In summary, we observed a sudden decline in diabetes screening in Ontario, Canada, where laboratory tests and other health care services are universally insured. This may lead to delays in prediabetes and diabetes diagnosis, resulting in missed opportunities for diabetes prevention and early management.

Disclosure
G.S.Fazli: None. R.Moineddin: None. V.Ling: None. G.L.Booth: None.

Funding
Canadian Institute for Health Research
271-OR: Hepatic Glucagon Resistance in Mice with Nonalcoholic Fatty Liver Disease
Authors: CEUTZ FREDERIK R. , CHRISTENSEN EMILIE E. , WINTHER-SOERENSEN MARIE , VILSTRUP HENDRIK , HOLST JENS J. , WEWER ALBRECHTSEN NICOLAI J. 
Published: May 2022

Patients with nonalcoholic fatty liver disease (NAFLD) have elevated fasting levels of glucagon (gcg) and amino acids (AA) . Gcg regulates hepatic AA catabolism by augmenting ureagenesis. We hypothesized that hepatic steatosis causes gcg resistance and impaired gcg-induced hepatic ureagenesis. To address this, we developed an isolated liver perfusion model in mice and used it to investigate gcg’s direct effect on hepatic glucose production (HGP) and ureagenesis in 9 male mice with hepatic steatosis (NAFLD mice) (B6.Vlepob/ob/JRj) and healthy controls (CON) (C57bl6/JRj) . NAFLD mice had higher body mass (50 vs. 26 g, P&lt;0.0001) and higher hepatic fat triglycerides (1vs. µmol/g, P&lt;0.0001) compared to CON. Catheters were place in the portal vein and the inferior vena cava and the liver was perfused with Krebs Henseleit buffer with and without 5 mM AA mixture (Vamin) , nM gcg or both. Samples were collected every minute and analyzed for urea and glucose concentrations. Results were normalized to liver tissue protein content. AA administration increased hepatic urea production from baseline in both groups within six minutes (NAFLD mice: 2.4 vs. 5.3 mmol/min × µg protein, P=0.01) , (CON: 3.4 vs. 7.4 mmol/min × µg protein, P=0.02) . Gcg increased the AA-stimulated ureagenesis compared to AA administration alone in CON (7.4 vs. 9.4 mmol/min × µg protein, P&lt;0.0001) but not in NAFLD mice (5.3 vs. 5.1 mmol/min × µg protein, P=0.66) . During the gcg administration (50 minutes) the total HGP was far greater in CON compared to NAFLD mice (309.5 vs. 195.5 µmol/min/µg protein, P=0.03) . The difference in glucose output could not be explained by hepatic glycogen content, as the NAFLD mice showed higher glycogen content than CON (1.7 vs. 0.8 µg/mg liver mass, P=0.02) . Our data support 1) that glucagon acutely increases the substrate-induced ureagenesis and 2) that hepatic steatosis causes resistance to the acute metabolic actions of glucagon on ureagenesis.

Disclosure
F.R.Ceutz: None. E.E.Christensen: None. M.Winther-soerensen: None. H.Vilstrup: None. J.J.Holst: Advisory Panel; Novo Nordisk, Board Member; Antag Therapeutics, Bainan Biotech. N.J.Wewer albrechtsen: Research Support; Mercodia AB, Novo Nordisk, Regeneron Pharmaceuticals Inc., Speaker's Bureau; Merck & Co., Inc., Mercodia AB.

Funding
Nicolai J. Wewer Albrechtsen were financed by NNF Excellence Emerging Investigator Grant – Endocrinology and Metabolism (Application No. NNF19OC0055001) , EFSD Future Leader Award (NNF21SA0072746) and DFF Sapere Aude.
282-OR: The Emotional Burden of Diabetes during Emerging Adulthood: “Cost. Everything Else Is Secondary.”
Authors: VITALE REBECCA J. , WENTZELL KATHERINE , LAFFEL LORI M. 
Published: May 2022

Emerging adults (EA) with type 1 diabetes (T1D) have multiple developmental stage-specific challenges in diabetes management, including the transition to financial independence. The recently validated Problem Areas in Diabetes-EA (PAID-EA) survey is the first measure of diabetes distress (DD) in EA to include financial concerns. A sample of 287 participants with T1D ages 18-30 years completed an online survey including the 25-item PAID-EA, measures of DD and depressive symptomology, and clinical and demographic questions. To evaluate content validity, 2 open-ended questions asked for the most important worry mentioned and what worries were missed in the questions. Responses were analyzed using directed qualitative content analysis. As cost emerged as a major contributor to DD, responses to the PAID-EA item 21 (“I worry about the cost of diabetes”) were analyzed using Chi-square or Fisher’s exact test to assess participant factors associated with cost-related DD. Most participants (89%) provided open-ended responses (78% female, mean age 24 years) . Cost was the most frequent code in the qualitative analysis: 15% reported DD related to cost and 6% to insurance. Responses included worries about aging out of parents’ insurance and limitations on career choices to ensure payment for diabetes supplies. In all survey respondents, 90% replied “Agree” or “Somewhat agree” to PAID-EA item 21. Responses to this item did not differ by gender, age (&lt; vs. &gt;=25) , continuous glucose monitor use (Y/N) , insulin pump use (Y/N) , student status (full time vs. part time vs. no) , income (&lt; vs ≥$75k) , or insurance status (parent vs. own vs. uninsured) . A greater proportion of those with HbA1c ≥ 7% endorsed worry about cost than with HbA1c &lt; 7% (94% vs. 87%, p = 0.008) . Diabetes cost was a major contributor to DD in this sample of EA with T1D. Worry about diabetes costs was endorsed by nearly all participants, especially those not meeting glycemic targets. Managing the cost of diabetes care for EA may be an avenue to reduce DD.

Disclosure
R.J.Vitale: None. K.Wentzell: None. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc.

Funding
NIH T32DK007260NIH T32DK007529NIH P30DK036836
29-LB: Investigating the Molecular Basis of the Microbiota-Mediated Regulation of Postprandial Chylomicron Production
Authors: ABDALQADIR NYAN H.S. , ADELI KHOSROW 
Published: May 2022

Obesity and insulin resistance have been identified as major global health concerns. They are associated with increased intestinal chylomicron production and subsequent remnant lipoprotein accumulation which lead to postprandial dyslipidemia. Dietary composition influences metabolic output of the gut microbiota by digesting dietary nutrients and producing various metabolites, which affects host metabolism. Understanding the mechanistic roles of the microbiota in regulating host lipid metabolism is therefore critical in addressing the pathogenesis of dyslipidemia. In this study, we aimed to investigate the effects of microbiota on lipid and lipoprotein metabolism in Syrian golden hamsters which is a more relevant animal model to human. Microbiota depletion was induced in male and female hamsters given either standard chow or a low fat/high fructose (HF) diet via antibiotic oral gavage administration. The results showed that feeding a HF diet increased plasma triglyceride (TG) and cholesterol (CH) levels while substantially reduced microbiota in antibiotic-administered groups led to significant reduction in circulating TG and CH in both diets. Then, we intended to look at the role of dysbiosis on postprandial lipid accumulation. Interestingly, in both sexes postprandial and TRL-TG levels were dramatically reduced after antibiotic administration; the effect was associated with significantly decreased ApoB48 protein levels. These changes appear to be due to a modulation of genes involved in farnesoid X receptor (FXR) receptor signaling in the ileum. Additionally, some critical genes implicated in lipid synthesis and absorption were also altered in the jejunum, with the most remarkable discovery being the extremely substantial down regulation of Scavenger Receptor Class B type 1“SR-B1” at both the mRNA and protein levels in all antibiotic-treated groups independent of sex and diet.
In summary, our results suggest a novel role for the gut microbiota in regulating lipid and lipoprotein metabolism in the gut, urging further studies to determine the underlying mechanisms.

Disclosure
N. H. S. Abdalqadir: None. K. Adeli: None.

Funding
Canadian Institutes of Health Research
29-OR: Impact of Carbohydrate-Restricted Nutrition Therapy Delivered via Continuous Remote Care on Metabolic Markers in Veterans with Type 2 Diabetes: A Nationwide, Real-World Study
Authors: VANTIEGHEM MICHELLE , MCKENZIE AMY L. , RATNER ROBERT E. 
Published: May 2022

Type 2 Diabetes (T2D) affects one in four Veterans and often occurs with dyslipidemia, chronic kidney disease, and nonalcoholic fatty liver disease (NAFLD) . In a pilot program, the Veterans Health Administration partnered with Virta Health to provide carbohydrate restricted nutrition therapy via continuous remote care to Veterans to reverse T2D by reducing glucose and dependence on medication, as demonstrated in prior research. This retrospective analysis assessed the 1- and 2-year effects on lipids and renal and hepatic markers in a real-world sample of Veterans with T2D using medical record data. Changes in metabolic markers from enrollment to 1- and 2-years (E, 1y, 2y) were assessed with paired t-tests with Holm-Bonferroni correction for multiple comparisons. Veterans retained at least two years at time of analysis were included (n=254, 58.5% of 434 eligible enrolled, 60±8 years, 12% female) . HDL-C (E: 42±16, 1y: 46±12, 2y: 44±11 mg/dl; ps&lt;0.001) and triglycerides (E: 205±168, 1y: 186±184, 2y: 160±119 mg/dl; 2y p&lt;0.05) improved. Total cholesterol (E: 165±46 mg/dl) and nonHDL-C (E: 124±46 mg/dl) were unchanged. Serum creatinine (E: 1.0±0.3 mg/dl) and eGFR (E: 85±18 ml/min/1.73m2) were stable; BUN increased (E: 17.3±6.1; 1y: 19.6±8.4, 2y: 18.9±7.6 mg/dl, ps&lt;0.05) but remained within normal limits. Liver enzymes (ALP at E: 77.8±24.6 U/L; ALT at E: 32.3±17.1 U/L) were within normal limits and unchanged except AST decreased (E: 26.6±14.1, 1y: 21.7±8.7, 2y: 21.8±9.3 U/L, 2y p&lt;0.05) . Veterans with T2D who underwent two years of diabetes reversal treatment improved atherogenic dyslipidemia and AST with no adverse effects on other markers of NAFLD and renal function, suggesting long term broad metabolic health benefit of this care model in the real world.

Disclosure
M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp.
30-OR: Effects of Vitamin D Supplementation by Race and Weight Status on Serum Vitamin D Measures and Diabetes Risk in the D2d Study
Authors: MONTGOMERY RANEE CHATTERJEE , DAVENPORT CLEMONTINA A. , JOHNSON KAREN C. , KASHYAP SANGEETA , LEBLANC ERIN S. , NELSON JASON P. , VICKERY ELLEN , DAGOGO-JACK SAMUEL , PITTAS ANASTASSIOS G. , DAWSON-HUGHES BESS ,   D2D RESEARCH GROUP
Published: May 2022

Higher blood 25 (OH) D is associated with lower risk of type 2 diabetes (T2D) in people with prediabetes. Blood 25 (OH) D can vary due to skin color and weight. It is not known if blood 25 (OH) D levels have similar impact on T2D risk for people of color or higher weight.
The vitamin D and type 2 diabetes (D2d) study is a randomized clinical trial of participants with high-risk prediabetes and overweight/obesity who were randomized to vitamin D3 4000 IU daily vs. placebo and followed for 2.5 years for the primary outcome of T2D. We compared baseline and intra-trial (mean achieved) serum 25 (OH) D among race-weight groups. We used Cox models to determine the associations between intra-trial serum 25 (OH) D and T2D risk by race-weight groups; we additionally tested for interactions between intra-trial serum 25 (OH) D and race or weight.
Of 2362 D2d participants with self-reported race, Black (n = 616) and White (n = 1616) participants were included in analyses. Baseline serum 25 (OH) D was lower in Black (24.2 ng/mL ± 10.9) compared to White (29.6 ng/mL ± 9.5) participants (P&lt;0.001) ; and were lower in those with higher vs. lower BMI in both races. Intra-trial serum 25 (OH) D was lower in Black participants (P&lt;0.001) overall and those with higher baseline BMI. Both Black and White participants with intra-trial serum 25 (OH) D ≥ 40 ng/mL had significantly reduced risk of T2D [HR (95% CI) ]; Black: 0.51 (0.29, 0.92) ; White 0.42 (0.30, 0.60) ] with no significant race*BMI interaction. Participants with baseline BMI ≤ 40 kg/m2 who achieved intra-trial serum 25 (OH) D levels ≥ 40 ng/mL had significantly reduced risks of T2D but not those with a BMI &gt; 40 kg/m2 with no significant BMI*race interaction.
Conclusions: An intra-trial mean serum 25 (OH) D level ≥ 40 ng/mL was associated with significantly reduced risk of T2D in Black and White D2d participants, but only among those with BMI &lt; 40 kg/m2. Targeting a serum 25 (OH) D level ≥ 40 ng/mL would optimize T2D prevention efforts among people with high-risk prediabetes.

Disclosure
R.Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. B.Dawson-hughes: None. D2d research group: n/a. C.A.Davenport: None. K.C.Johnson: None. S.Kashyap: Advisory Panel; Fractyl Health, Inc., GI Dynamics, Research Support; Janssen Pharmaceuticals, Inc. E.S.Leblanc: n/a. J.P.Nelson: None. E.Vickery: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. A.G.Pittas: None.

Funding
American Diabetes Association (1-14-D2d-01) ; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases and Office of Dietary Supplements (U01DK098245)