bluuebunny/crossref_metadata_2025_split huggingface dataset:
210-OR: Cerebral Morphometric Alterations in Painless and Painful Diabetic Peripheral Neuropathy
Authors: SLOAN GORDON P. , SELVARAJAH DINESH , TEH KEVIN , SHILLO PALLAI RAPPAI , WILKINSON IAIN D. , TESFAYE SOLOMON 
Published: June 2021

Aims: Neuroimaging studies have found structural alterations in brain regions involved in the somatomotor system in diabetic peripheral neuropathy (DPN) and painful-DPN (pDPN). However, most of these studies have had small cohorts of subjects, without consideration of pDPN phenotypes. Here we present the largest DPN neuroimaging study, which examines differences in brain morphology in DPN and phenotypes of painful-DPN.
Methods: 229 participants were enrolled, 177 with diabetes (46 no-DPN, 56 painless-DPN and 75 pDPN; 25 irritable [IR] and 50 non-irritable [NIR] phenotype), and 52 healthy volunteers underwent detailed clinical, neurophysiological and quantitative sensory testing (DFNS) assessments, and 3-dimensional T1-weighted brain MRI (3.0T, Phillips). Brain volumetry was performed using Freesurfer.
Results: At the post-central gyrus, in comparison with HV (1.92mm±0.11) and NoDPN (1.90mm±0.14), there was a significantly reduced cortical thickness in DPN (1.85mm±0.14), in pDPN (1.87mm±0.12) cortical thickness was reduced compared with HV. At the precentral gyrus, both DPN (2.29mm±0.16) and pDPN (2.28mm±0.16) had significantly reduced cortical thickness compared with HV (2.37mm±0.14) and NoDPN (2.36mm±0.13). At the insula, compared with HV (2.93mm±0.15) the cortical thickness was reduced in DPN (2.85mm±0.18) and pDPN (2.84mm±0.17). The cortical thickness at the pre and postcentral gyrus, and insula correlated with measures of nerve conduction. Moreover, the mean anterior cingulate cortical (ACC) thickness was significantly reduced in the IR- (2.40mm±0.23) compared to NIR-pDPN (2.58mm±0.20; p=0.003).
Conclusions: Key somatomotor brain regions have a reduced cortical thickness in patients with DPN and pDPN, which correlate with neurophysiological measures suggestive of an ascending axonopathy. Moreover, the cortical thickness at the ACC differentiated IR and NIR, suggesting neuroplasticity in this region may play a role determining clinical phenotypes in pDPN.

Disclosure
G. P. Sloan: None. D. Selvarajah: None. K. Teh: None. P. Shillo: None. I. D. Wilkinson: None. S. Tesfaye: Advisory Panel; Self; Angellini, Bayer AG, Eva Pharma, Wörwag Pharma, Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, MSD Corporation, Novo Nordisk, Pfizer Inc.
22-LB: Use of a Novel Virtual Patient Simulation Application to Assess Providers’ Knowledge in Management of T2 Diabetes
Authors: DRAZNIN BORIS , IANCU IGAL 
Published: June 2021

The goals of Type 2 diabetes (T2DM) management include achievement of glycemic, blood pressure (BP), and lipid control. All three variables must be addressed adequately in order to prevent diabetic complications. Aim: Using a proprietary smartphone-based application (APP) developed by Edocate Ltd, that simulates virtual visits, we assessed how well healthcare providers (HCPs) manage T2DM.
Materials & Methods: A total of 461 HCPs (247 MD, MD/PhD, or DO and 214 NPs) downloaded and used the APP to treat their virtual patients over multiple visits. All patients presented with poorly controlled T2DM, hypertension (HTN) and hyperlipidemia. HCPs chose the first, second and third lines of medications, made diagnostic adjustments, initiated appropriate referrals to specialists, and ordered laboratory tests of their choice. Based on their selections, the APP simulated the course of diabetes and its complications, requiring diverse management decisions on the subsequent virtual visits.
Results: In the Edocate virtual clinic, only 53% of HCPs achieved good glycemic control (A1c &lt; 7%), 41% achieved BP control (&lt;130/80 mmHg), and 66% prescribed high-intensity statins. NPs performed slightly but not significantly better than the physician cohort. Only 48% of HCPs checked microalbuminuria, 54% ordered creatinine and 55% ordered LDL. Interestingly, 79% of HCPs either kept or started Metformin as the first line medication. The most commonly ordered second line of medications for glycemic control was either GLP-1 receptor agonists (39%) or SGLT2 inhibitors (36%), while 23% of HCPs kept their patients on or added sulfonylurea or basal insulin (11%).
Conclusions: Despite a worldwide effort in diabetes education, the knowledge of T2DM management remains suboptimal (as assessed by the simulation APP) and underscores the need for better professional education. Innovative patient simulation-based learning applications can dramatically improve the level of competency in HCPs.

Disclosure
B. Draznin: None. I. Iancu: None.
222-LB: Canonical Wnt Signaling Regulates Beta-Cell Neogenesis from Pancreatic Duct Cells
Authors: AFELIK SOLOMON , YU ZHAN 
Published: June 2021

Diabetes results from loss or insufficient numbers of insulin producing beta cells. Thus, restoration of beta cell mass can offer a lasting cure for diabetes. Physiological conditions such as obesity and pregnancy are known to induce compensatory increase in beta cell mass; suggesting the presence of an endogenous mechanism for beta cell regeneration. Significant progress has been made in understanding the regeneration of beta-cells through proliferation of existing beta-cells. In addition to proliferation of existing beta-cells, there is mounting evidence, from both animal models and human tissue, indicating that adult pancreatic duct cells can regenerate endocrine cells, including insulin producing cells. However, the molecular mechanisms governing the regeneration of pancreatic endocrine cells, especially beta cell from pancreatic duct cells remain to be defined. We have found that adult pancreatic duct cells are active in both Notch and Wnt/beta-catenin signaling. Transcriptional profiling revealed Hes1 as the predominant Notch target gene in adult mouse pancreatic duct cells. Using lineage-tracing mouse models, we found that duct-specific deletion of Hes1 in vivo resulted in the conversion of pancreatic duct cells into predominantly somatostatin+ cells. Conversely, pancreatic duct-specific deletion of the canonical Wnt signaling effector, beta-catenin, in vivo resulted in downregulation of Hes1 expression, and the conversion of pancreatic duct cells into predominantly insulin producing cells. Taken together our results demonstrate that Notch and Wnt signaling maintain the adult pancreatic duct state, with duct-derived beta-cell neogenesis requiring the loss of Wnt/beta-catenin signaling.

Disclosure
S. Afelik: None. Z. Yu: None.
225-LB: Targeting ß-Cell Endoplasmic Reticulum (ER) TALK-1 Channels to Restore Ca2+ Homeostasis and Reduce ER Stress in Diabetes
Authors: NAKHE ARYA Y. , DADI PRASANNA , WESTOVER DAVID , DAYS EMILY , DENTON JEROD , JACOBSON DAVID 
Published: June 2021

Perturbations in Ca2+ homeostasis contribute to β-cell failure in diabetes, limiting insulin secretion and exacerbating hyperglycemia. TALK-1 is the most islet-restricted and most abundantly expressed K+ channel of the β-cell. ER TALK-1 channels provide K+ countercurrent for [Ca2+]ER release, thereby tuning [Ca2+]ER storage and release. During β-cell Ca2+ influx, TALK-1-enhanced [Ca2+]ER release leads to activation of the hyperpolarizing Ca2+ activated K+ channels, thus increasing the silent phase duration between Ca2+ oscillations. A gain-of-function mutation in TALK-1(L114P) causes MODY, by disrupting cytoplasmic and ER Ca2+ handling. However, the ability to probe ER TALK-1 channels as a therapeutic target to normalize β-cell Ca2+ handling and reduce ER stress in diabetes has not been determined. Here, using a high throughput fluorescence-based thallium (TI+) flux assay (z’ =0.64) in a TALK-1 overexpression cell line, we identified 80 TALK-1 selective inhibitors from a small molecule library of 50,000 compounds. 4 potent inhibitors that also inhibited the ER membrane TALK-1 channels were identified by monitoring cyclopiazonic acid-induced [Ca2+]ER release (e.g. K2P16-i7(IC50=5.3μM); 63.36% [Ca2+]ER recovery, p-value=0.02). We also tested these inhibitors for their efficacy in controlling mouse islet [Ca2+]ER storage as well as cytosolic Ca2+ oscillations. TALK-1 inhibitors significantly increased islet [Ca2+]ER storage and Ca2+ oscillation frequency (e.g.K2P16-i7; [Ca2+]ER AUC=60.9a.u., peaks/min=0.45 vs. DMSO; [Ca2+]ER AUC=49.7a.u., peaks/min= 0.17, p-value&lt;0.05). Importantly, the inhibitors did not alter [Ca2+]ER and glucose-stimulated Ca2+ oscillation frequency in TALK-1 KO islets. In summary, we have identified the first ER TALK-1 selective inhibitors that can not only be utilized to assess the role of TALK-1 in human β-cell Ca2+ handling and GSIS, but also potentially reduce ER dysfunction during diabetes pathogenesis.

Disclosure
A. Y. Nakhe: None. P. Dadi: None. D. Westover: None. E. Days: None. J. Denton: None. D. Jacobson: None.
226-LB: Elimination of the Progesterone Receptor in ß Cells Improves ß-Cell Function and Glucose Tolerance during Pregnancy and Diet-Induced Insulin Resistance in Female Mice
Authors: DE SA PAULA MOTA , QADIR MIRZA MUHAMMAD FAHD , MAUVAIS-JARVIS FRANCK 
Published: June 2021

We showed that the gonadal hormones estradiol and testosterone influence islet β-cell function and survival in a sex-specific manner via estrogen and androgen receptors expressed in islet β-cells. The progesterone receptor (PR) is a ligand-activated transcription factor and is believed to be involved in the β-cell adaptation to pregnancy. Leveraging public single-cell RNA-seq datasets we observe PR mRNA expression in α- β- and γ-cells in male and female human pancreatic endocrine cells. Using immunohistochemistry, we observe that, unlike in the uterus where PR is nuclear, PR is localized in the cytoplasm of β-cells in male and female human and mouse islets. We investigated the role of progesterone and PR in β-cell physiology in male and female mice with conditional deletion of PR in β-cells (βPRKO) by crossing PR-Lox/lox and MIP-Cre transgenic mice. Male βPRKO mice exhibited no alteration in glucose homeostasis on normal chow (NC) or following western-diet (WD)-induced insulin resistance and obesity compared to littermate PR-Lox/lox controls. Similarly, NC-fed female βPRKO mice exhibited no abnormality of glucose or insulin homeostasis compared to littermate PR-Lox/lox controls. However, during pregnancy or WD feeding, female βPRKO mice developed enhanced IP-glucose-stimulated insulin secretion, associated with improved IP glucose tolerance compared to littermate PR-Lox/lox controls. These results reveal that PR is a cytosolic receptor in β-cells, and suggest that in conditions of high insulin demand, such as pregnancy and diet-induced insulin resistance, elimination of PR action in β-cells of females improves the ability of β-cells to produce insulin and lowers blood glucose. PR may be involved in the pathogenesis of gestational diabetes.

Disclosure
P. Mota de sa: None. M. Qadir: None. F. Mauvais-jarvis: None.

Funding
National Institutes of Health (DK074970, DK107444); U.S. Department of Veterans Affairs (BX003725)
227-LB: GLP-1 Activation of HCN Channels Increases Glucose-Stimulated β- and δ- Cell Ca2+ Oscillation Frequency
Authors: ZABORSKA KAROLINA E. , JORDAN KELLI L. , DADI PRASANNA , DICKERSON MATTHEW , GRAFF SARAH M. , JACOBSON DAVID 
Published: June 2021

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control human β-cell insulin secretion. Here, we examined if HCN channels impact glucagon-like-peptide 1 (GLP-1) receptor modulation of islet Ca2+ handling. We found that Liraglutide (100nM LIRA), a GLP-1 analog, increased mouse β-cell Ca2+ oscillation frequency and cAMP levels in high (11 mM) but not low glucose. Similarly, a subset of human β-cells (65%) show LIRA-induced elevations in Ca2+ oscillation frequency (by 70%, P&lt;0.001) under stimulatory glucose (7 mM) conditions. While mouse islet HCN inhibition (20 μM ivabradine) did not alter glucose-stimulated (9 mM) Ca2+ oscillation frequency, it prevented LIRA-induced changes of islet Ca2+ fluctuations. As LIRA is used to treat type-2-diabetes, we examined and demonstrated that islets from high fat diet-fed, glucose intolerant mice also responded to LIRA with increased Ca2+ oscillation frequency (by 93%, P&lt;0.01). These changes in β-cell Ca2+ handling may contribute to LIRA-mediated increased insulin secretion, which could also play a role in LIRA inhibition of glucagon secretion. However, as somatostatin also inhibits glucagon secretion, we next investigated the influence of LIRA on &#120575;;-cells. Interestingly, LIRA increased Ca2+ oscillation frequency equivalently in β- and &#120575;;-cells (by 85%, P&lt;0.0001), which showed synchronized Ca2+ fluctuations. To establish the origin of synchronization cues, we ablated either β- or δ-cells and determined the LIRA-mediated effect on Ca2+ handling in remaining δ- or β-cells, respectively. Although δ-cell ablation did not affect the LIRA-mediated elevations in β-cell Ca2+ oscillation frequency, β-cell ablation interfered with glucose- and LIRA-mediated δ-cell Ca2+ fluctuations. As the kinetics of pulsatile insulin secretion dictate insulin sensitivity, the data presented here suggests that GLP-1 stimulation of islet HCN channels may improve peripheral insulin sensitivity in diabetics treated with LIRA.

Disclosure
K. E. Zaborska: None. K. L. Jordan: None. P. Dadi: None. M. Dickerson: None. S. M. Graff: None. D. Jacobson: None.
229-LB: Quantification of GLP-1R Internalization and Recycling in Live ß Cells
Authors: GRAY SARAH M. , SLOOP KYLE , RAVN PETER , CAMPBELL JONATHAN , D’ALESSIO DAVID A. 
Published: June 2021

The glucagon-like peptide 1 receptor (GLP-1R) is a class B G-protein coupled receptor that is predominantly expressed on pancreatic β-cells in mice. Endogenous and synthetic ligands for GLP-1R exhibit distinct intracellular signaling cascades and promote insulin secretion to various degrees. Ligand binding typically induces receptor internalization followed by recycling back to the membrane or degradation within the lysosome. We hypothesized that endogenous and synthetic GLP-1R ligands would have distinct rates of internalization and recycling in β-cells. To test this hypothesis, we combined a recently-validated, highly-specific GLP-1R antibody (Glp1r0017) with flow cytometry and applied ligands (GLP-1, exendin-4 [Ex4], glucagon, and tirzepatide [TZP]) to characterize GLP-1R trafficking in freshly-isolated mouse islet cells. Under basal conditions, ~90% of β-cells were GLP1R+, with very low or absent binding in α- and δ-cells. Increasing ligand concentrations (0.01-100 nM) demonstrated distinct rates of internalization between ligands. Most potent was Ex4, followed by the native ligand GLP-1. TZP, a dual-receptor ligand for GLP-1R and GIPR, was more modest in inducing internalization. While showing different potencies, Ex4, GLP-1, and TZP were able to induce maximal internalization. In contrast, maximal treatment with glucagon only resulted in ~70% of β-cells being GLP-1R+. To test the rate of recycling back to the plasma membrane, we treated islet cells with Ex4 or GLP-1 with a dose that induced ~50% internalization, removed the ligand, and then monitored GLP1R+ β-cells over time. Within the first 15 minutes, GLP1R+ β-cells increased linearly and rapidly. This plateaued from 30-60 minutes, resulting in 60-70% of β-cells being GLP1R+ at the end of the experiment. In summary, our assay allows for investigation of GLP-1R trafficking in live β-cells. Understanding into the factors that regulate GLP-1R internalization and recycling may shed light on the insulinotropic properties of these ligands.

Disclosure
S. M. Gray: None. K. Sloop: Employee; Self; Eli Lilly and Company. P. Ravn: None. J. Campbell: None. D. A. D’alessio: Advisory Panel; Self; Eli Lilly and Company, Sun Pharmaceutical Industries Ltd., Research Support; Self; Eli Lilly and Company, Merck & Co., Inc.

Funding
National Institutes of Health (F32DK121420, R01DK123075, R01DK101991); Lilly Research Award Program
229-OR: Physical Fitness and Cardiovascular Risk Factors in Diabetes Subgroups
Authors: SAATMANN NINA , ZAHARIA OANA P. , STRASSBURGER KLAUS , PESTA DOMINIK , BURKART VOLKER , SZENDROEDI JULIA , RODEN MICHAEL 
Published: June 2021

Physical inactivity promotes insulin resistance and increases the risk of diabetes and cardiovascular disease. Clustering based on simple clinical measures has been introduced for identifying diabetes subgroups with different risk of complications. However, little is known about physical fitness and cardiovascular risk factors in these clusters. We hypothesized that the insulin resistant diabetes (SIRD) cluster would associate with lower physical fitness and increased cardiovascular risk factors. Cycling spiroerogometry, physical activity questionnaire (Baecke index) and cardiovascular risk scores (Framingham Risk Scores (FRS) and triglycerides to high-density lipoproteins (TG:HDL) ratio) were analyzed in 746 participants with newly diagnosed diabetes of the German Diabetes Study (GDS). SIRD showed lower VO2max compared to the severe autoimmune diabetes (SAID), moderate age-related (MARD) and moderate obesity-related (MOD) clusters (all p&lt;0.01) but was not different to the severe insulin deficient (SIDD) cluster (p= 0.87). Further, Baecke index was lower in SIRD [7.3 (6.8-8.4)] than SAID [8.5 (7.6-9.5)] and MARD [8.4 (7.3-9.4)] and SIRD had the highest TG:HDL ratio compared to all other groups (p&lt;0.05) after adjustments for age, sex and BMI. This was underlined by a strong association between estimates of insulin resistance (HOMA-IR) and TG:HDL ratio (r= 0.59 p= &lt;.0001) across all groups. Finally, SIRD showed higher FRS [33.1 (25.3-54.9)%] compared to MOD [16.2 (7.4-24.4)%], SAID [3.9 (1.6-9.4)%] and SIDD [12.4 (4.7-34.9)%].
In conclusion, SIRD and MARD showed lowest physical fitness and SIRD was least physically active and has the highest risk scores for diabetes-related cardiovascular diseases.

Disclosure
N. Saatmann: None. O. P. Zaharia: None. K. Strassburger: None. D. Pesta: None. V. Burkart: None. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Allergan plc, Bristol-Myers Squibb Company, Novo Nordisk A/S, Research Support; Self; Boehringer Ingelheim International GmbH, Danone Nutricia, Sanofi-Aventis Deutschland GmbH.
230-OR: Exercise Training Improved Antilipolytic Sensitivity to Insulin in Obese Adults with Low Sensitivity to Insulin before Training
Authors: AHN CHEEHOON , SCHLEH MICHAEL W. , RYAN BENJAMIN J. , LUDZKI ALISON , VARSHNEY PALLAVI , GILLEN JENNA B. , CHEN SHIQI , HOROWITZ JEFFREY F. 
Published: June 2021

Low sensitivity to the antilipolytic effects of insulin in adipose tissue has been linked with impaired insulin-mediated glucose uptake in skeletal muscle. The aims of this study were: 1) to compare adipose tissue morphology in obese adults with high- (HIGH) vs. low-sensitivity (LOW) to the antilipolytic effects of insulin, and 2) compare the effects of exercise training on adipose tissue from HIGH vs. LOW subjects. Using isotopic dilution methods before and during a hyperinsulinemic-euglycemic clamp, we measured the antilipolytic response to insulin in a total of 36 obese adults - and we identified sub-cohorts of 13 LOW (64±7% lipolytic suppression by insulin; BMI: 34±4kg/m2) and 13 HIGH (82±3% lipolytic suppression by insulin; BMI:33±3kg/m2). Abdominal subcutaneous adipose tissue (aSAT) samples were collected before the clamp (non-insulin stimulated). Measurements were made before and after a 12-week endurance exercise training program (4 days/week). Before training, capillary density (# of capillaries/mm2) in aSAT samples for LOW was significantly lower than HIGH (p=0.004). Collagen abundance in aSAT extracellular matrix (ECM) was lower in LOW (p=0.013). In response to training, the antilipolytic response to insulin was significantly improved in LOW (72±5% lipolytic suppression by insulin; p&lt;0.001) but not HIGH. This was accompanied by an increased capillary density (p=0.03), and collagen abundance in ECM (p = 0.02), along with a slight reduction in fat mass (1±1kg; p=0.05). Adipocyte size was reduced in both groups (p=0.02).
In summary, aSAT from obese adults with low antilipolytic sensitivity to insulin displayed lower capillarization and ECM collagen abundance compared with obese adults with high sensitivity to the antilipolytic effects of insulin. Importantly, morphological adaptations to exercise training accompanied an increased antilipolytic sensitivity to insulin in subjects with low antilipolytic sensitivity before training.

Disclosure
C. Ahn: None. M. W. Schleh: None. B. J. Ryan: None. A. Ludzki: None. P. Varshney: None. J. B. Gillen: None. S. Chen: None. J. F. Horowitz: None.

Funding
National Institutes of Health (R01DK077966, P30DK089503, T32DK007245, F32DK117522); Canadian Institutes of Health Research (DFS146190, 338735)
233-OR: Circulating Inflammatory Biomarkers Are Not Improved with Combined Low-Volume High-Intensity Interval Training and Progressive Resistance Training in Prediabetes
Authors: BAKER CALLUM J. , MIN DANQING , GEROFI JAMES , WANG XIAOYU , HOCKING SAMANTHA L. , COLAGIURI STEPHEN , JOHNSON NATHAN A. , TWIGG STEPHEN M. 
Published: June 2021

In prediabetes (PD), circulating inflammatory biomarkers are associated with increased CVD1 risk. Exercise (Ex) has a positive effect on cardiovascular fitness and metabolic outcomes in PD but Ex effects on inflammation markers in PD are not fully known and were investigated in this study. Adults with PD (n=34) and normal fasting glucose (NG) (n=34) were randomised into one of four groups: NG control (NGC, n=16), NG Ex (NGE, n=18), PD control (PC, n=16) and PD Ex (PE, n=18). NGE/PE completed 12 weeks of supervised HIIT and progressive resistance training (PRT) 2 times/week, and NGC/PC unsupervised stretching 3 times/week. Baseline, age and weight were similar in PD and NG. Compared with NG, FPG and HbA1c were higher and VO2peak was significantly lower in PD (29±7 vs. 33±8 mL/kg/min, p=0.03). Comparing NG and PD at baseline, serum IL-1β was higher in NG (11.4±9.0 vs. 7.9±2.8 pg/mL, p=0.04), IL-12p70 and IL-22 were higher in PD (respectively, 5.7±3.6 vs. 4.4±2.2 pg/mL; 164.6±90.3 vs. 122.2±83.2 pg/mL, both p&lt;0.05) and IL-1α, IL-6, IL-8, IL-15, M-CSF and TNFα were similar. At follow-up, HbA1c was reduced by -0.07±0.11% in NGE and -0.09±0.17% in PC (both p&lt;0.05) and not changed in PE or NGC. PE had an increase in VO2peak (5.5±7.5mL/kg/min, p=0.01). Inflammatory biomarkers were unchanged in PE but NGE had reduced IL-12p70 (4.3±1.9 to 3.5±0.8 pg/mL, p=0.05) and M-CSF (124.5±58.2 to 93.8±36.2 pg/mL, p=0.02). Analysis of Ex with &gt;80% adherence revealed that IL-1α, IL-1β, IL-8 and IL-15 were reduced in NGE, however no change was seen in PE despite a reduction in HbA1c of -0.14±0.17% (p=0.02). PD is associated with reduced cardiorespiratory fitness and increased IL-12p70 and IL-22. Ex reduced IL-12p70 and M-CSF in those with NG but not PD, even after stratifying by adherence and despite improvements in clinical markers. This study indicates low volume HIIT with PRT may not be adequate to reduce serum inflammatory biomarkers in prediabetes.

Disclosure
C. J. Baker: None. D. Min: None. J. Gerofi: None. X. Wang: None. S. L. Hocking: Advisory Panel; Self; Eli Lilly and Company, Inova, Novo Nordisk, Pfizer Inc. S. Colagiuri: None. N. A. Johnson: None. S. M. Twigg: Advisory Panel; Self; Abbott Diabetes, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis, Consultant; Self; Aktivo Labs, Sanofi-Aventis, Research Support; Self; Abbott Diabetes, Speaker’s Bureau; Self; Abbott Diabetes, AstraZeneca.

Funding
National Health and Medical Research Council (APP1113612)