bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness and Tolerability of Vildagliptin plus Metformin Compared with Other Oral Dual Agents in Different Regional Patients with Type 2 Diabetes—A Real-World Study (China PDS)
Authors: ZANG LI , HAN YING , CHEN LIXIAN , HU DAQING , JIN HUI , YANG NAILONG , SHI XIAOYUN , LI QUANMIN , LIANG LINLANG , LIU MINGMING , HE JAMES , MU YIMING
Published: June 2018

Background and Aim: China PDS aims to investigate the real-world effectiveness and tolerability of vildagliptin plus metformin (VM) in patients with type 2 diabetes mellitus (T2DM), compared with other oral dual agents (OD). In this study, we present the results of different regional subgroup analysis.

Materials and Methods: In China PDS, T2DM patients with inadequate glycemic control on monotherapy were assigned to either VM dual therapy or OD therapy according to local physician’s decision. In this prespecified subgroup study, patients were divided into three groups according to their geographic regions (East China, North China, and South China). The primary outcome was the proportion of patients with HbA1c<7% and without tolerability events (hypoglycemia, weight gain, or discontinuation due to gastrointestinal event) at 12th month. Secondary outcomes included the HbA1c change from baseline to study endpoint, and tolerability.

Results: In total, 357 (126 in VM vs. 231 in OD) patients in East China, 499 (292 in VM vs. 207 in OD) patients in North China, and 65 (27 in VM vs. 38 in OD) patients in South Chinawere enrolled. Compared with OD, significantly higher proportion of VM treated patients achieved primary outcome in East China (49.2% vs. 28.1%, P <0.001), North China (52.1% vs. 39.1%, P=0.004), and in South China (66.7% vs. 36.8%, P=0.018). Mean HbA1c changes were significantly greater in VM than in OD in East China (-1.24% vs. -0.55%, P<0.001) and North China groups (-1.35% vs. -0.93%, P=0.011), but not in South China group (-2.12% vs. -1.31%, P=0.147). VM resulted in less tolerability findings than OD in East China (6.3% vs. 18.2) and North China (6.5% vs. 15.0%) groups (P<0.for both), but not in South China group (3.7% vs. 26.3%, P>0.05).

Conclusion: In all regional subgroups, vildagliptin plus metformin dual therapy was generally associated with good glycemic control and was well tolerated.

Disclosure

L. Zang: None. Y. Han: None. L. Chen: None. D. Hu: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. M. Liu: None. J. He: None. Y. Mu: None.
“Alarming" T-Regulatory Cells (Tregs) to Protect from Type 1 Diabetes (T1D)
Authors: SHARMA RAHUL , SABAPATHY VIKRAM
Published: June 2018

Defects in IL-2 signaling and Tregs correlate with susceptibility to T1D. Helminth burden also negatively correlates with the incidence of T1D. The alarmin IL-33 and its receptor ST2 are elicited in anti-helminth immunity, which also increase Tregs, M2 macrophages and Th2 response. We hypothesized that IL-33 may cooperate with IL-2 in promoting Tregs to protect from T1D. Indeed, a major subset of Tregs express ST2, thus enabling a role for IL-33 in Treg biology. Non-obese diabetic (NOD) mice, which have less Tregs than the nondiabetic NOD.Idd3 congenic mice, also exhibit less ST2+ Tregs (13±3%) than NOD.Idd3 (38±11%). For better cooperativity and preferential targeting of Tregs, we generated a hybrid cytokine (IL233) bearing IL-2 and IL-33 activities in a single molecule. Recent-hyperglycemia onset NOD mice (n≥6/group) were treated with daily injections (3.3pmol/g) of IL-2 and/or IL-33 or IL233 for 5 days. IL-33 alone offered a similar, if not better reversal of T1D with a 70% cumulative incidence (CI) compared to IL-2 alone (80% CI), whereas IL233 offered the best protection with 50% of mice remaining in remission 10-weeks post-treatment. There was a robust increase in the proportion of Tregs in pancreatic lymph node in IL233 group (25±3.7%) compared to 10±3.9%, 16±4.1%, 14±4.3% and 19±4.3% in Saline, IL-2 only, IL-33 only and IL-2 and IL-33 groups respectively. IL233 treatment also increased the levels of Tregs and group-2 innate lymphoid cells in an alternate species (rats) and blocked high-dose streptozotocin (STZ)-induced beta-cell death. Interestingly, the average islet size was bigger in the rats treated with IL233 in the STZ model, indicating a role of IL233 in islet growth and repair. Thus, IL233 utilizes the synergy of IL-2 and IL-33 to promote Tregs and bears strong therapeutic potential for T1D.

Disclosure

R. Sharma: None. V. Sabapathy: None.
Diabetes Management in Hospitalized Patients with Type 2 Diabetes (T2D) during Fasting Periods
Authors: RAINER RAPHAEL , ELSAYED HESHAM , ABERER FELIX , BECK PETER , PIEBER THOMAS R. , DONSA KLAUS , PLANK JOHANNES , MADER JULIA K.
Published: June 2018

To date little data exists on diabetes management during fasting periods on the general ward. The aim of the analysis was to assess standardized diabetes management using GlucoTab® - a digital algorithm driven basal-bolus insulin therapy - in hospitalized patients with T2D in the fasting period. Data from two clinical trials were pooled. Patients were included in the analysis if they had at least one fasting period during hospital stay at the general ward. Periods of fasting were compared with periods of regular food intake. Out of 191 T2D patients 91 (48%, 5 on surgical and 86 patients on internal medicine wards, 32 female, age 68 ± 12 years, HbA1c 67 ± 19 mmol/mol, BMI 30 ± 15 kg/m2, diabetes duration 15 ± 11 years, creatinine 1.8 ± 1.4 mg/dl, length of hospital stay 10 ± 6 days) were included comprising overall 131 fasting periods. Mean blood glucose was lower during fasting periods as compared to periods with regular food intake (153 ± 38 vs. 158 ± 24 mg/dl, p = 0.033). Hypoglycemia (<70 mg/dl) was documented in 1.35% (fasting) vs. 1.91% (non-fasting) of all measurements, respectively. In neither period BG <40 mg/dl occurred. Insulin doses during fasting vs. non-fasting were as follows: bolus insulin 18.0 ± 12.7 vs. 26.0 ± 17.1 U; basal insulin 20.7 ± 13.2 vs. 22.3 ± 15.2 U. Fasting is common among patients on a general ward. Our data demonstrate that standardized diabetes management by GlucoTab® using a basal-bolus insulin algorithm is safe and effective in fasting state.

Disclosure

R. Rainer: None. H. Elsayed: None. F. Aberer: None. P. Beck: Employee; Self; decide Clinical Software GmbH. T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. K. Donsa: Stock/Shareholder; Self; decide Clinical Software GmbH. J. Plank: None. J.K. Mader: Speaker's Bureau; Self; Roche Diabetes Care Health and Digital Solutions, Novo Nordisk A/S. Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Becton, Dickinson and Company. Speaker's Bureau; Self; Sanofi. Research Support; Self; ConvaTec Inc., Menarini Group. Speaker's Bureau; Self; Medtronic. Research Support; Self; Novo Nordisk A/S, Sanofi.
A Reusable Cap for Disposable Insulin Pens Protects Insulin against Temperature-Induced Degradation
Authors: PFÜTZNER ANDREAS , NAGAR RON , REEH WOLFGANG
Published: June 2018

Insulin has to be kept at 4-8° C (∼ 39°F to 47°F) until use and once opened, is supposed to be stable for 28 to 30 days at room temperature. Exposure to extreme cold or heat leads to insulin degradation in a very short time with loss of glucose-lowering efficacy. ViVi-Cap (TempraMed Inc.) is a reusable storage device, which is available for all existing disposable pen devices in the U.S. and EU. It works without external power supply requirements based on an ultra-high vacuum insulation and an additional heat consumption by a calorimetry-based phase-change technology.

Five disposable insulin pens (FlexPen, Insulin aspart) were kept for one week under extreme temperature conditions for 5 days (each day: 8 h at 50 °C and 16 h at 22 °C) either without protection, in a frio device (freshly prepared each day) and in the ViViCap. Samples were taken every day and insulin degradation was determined in accordance with U.S. pharmacopoia by appropriate HPLC methods for insulin aspart, and high and low molecular weight degradation molecules. Each experiment was performed in triplicate.

Insulin aspart without protection was shown to have more than 2% impurities already after one day (Frio: 2 days, ViViCap: >5 days). High molecular weight products appeared in measurable quantities after two days without protection (Frio: 3 days, ViViCap > 5 days, p<0.01 against the other 2 storage conditions).

ViVi-Cap was superior to the other tested conditions with respect to stabilizing insulin aspart during storage under extreme temperature conditions. The device provides an easy to use solution for maintaining insulin efficacy under daily life conditions.

Disclosure

A. Pfützner: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Consultant; Self; Lifecare. Speaker's Bureau; Self; Berlin-Chemie AG. Research Support; Self; Boehringer Ingelheim GmbH. R. Nagar: Stock/Shareholder; Self; TempraMed Ltd.. W. Reeh: None.
Evaluation of Insulin Regimen and Glycemic Control in Noncritically Ill Hospitalized Patients with Type 2 Diabetes Receiving Continuous Enteral Nutrition Therapy
Authors: SELEN DARYL J. , HOWARD ALAN B. , GILBERT MATTHEW P.
Published: June 2018

Hyperglycemia is a common complication in hospitalized patients with type 2 diabetes mellitus (T2DM) on continuous enteral nutrition therapy (ENT). The purpose of this study was to identify an insulin regimen for this patient population that provided adequate coverage for hyperglycemia without significant hypoglycemia. A retrospective chart review was conducted at the University of Vermont Medical Center for noncritically ill patients admitted between 07/01/2012 and 09/01/2015 who had T2DM and received continuous ENT for ≥72 hours—209 patients met the inclusion criteria; 117 had received aspart sliding scale only and 92 had received aspart with long-acting glargine. Our results revealed no evidence of severe hypoglycemia (blood glucose <40mg/dL) in either group, and the occurrence of hypoglycemia (blood glucose <70mg/dL) was similar in both groups (p=0.54). However, there was a difference in the percentage of blood glucose values within the optimal range (100 to 180mg/dL): the aspart-only group had 60.3%±27.2% of values within this range compared to 36.6%±24.4% in the aspart+glargine group (p<0.001). The aspart+glargine group had blood glucose levels >180 mg/dL 58.8%±26.9% of the time compared to 33.1%±28.6% in the aspart-only group (p<0.0001).

In conclusion, both insulin regimens resulted in similar efficacy in noncritically ill, hospitalized patients with T2DM receiving continuous ENT without significant hypoglycemia. However, neither regimen resulted in blood glucose values in the optimal range for a sufficient percentage of the 72-hour period. A basal and bolus insulin regimen, rather than sliding scale only, is likely needed to improve overall glycemic control in these patients while preventing hypoglycemia. Further prospective studies are needed in this area to identify the most appropriate insulin program to treat hyperglycemia in hospitalized patients on ENT.

Disclosure

D.J. Selen: Employee; Spouse/Partner; CVS/Caremark. A.B. Howard: None. M.P. Gilbert: Consultant; Self; Sanofi US, Novo Nordisk A/S.
Use of Insulin Degludec in Type 1 Diabetes Clinical Practice in the U.K.—General Practice Data from Two English Regions and Data from the Association of British Clinical Diabetologists (ABCD) Nationwide Degludec Audit
Authors: LUMB ALISTAIR N. , GALLEN IAN W. , BICKERTON ALEX , ABRAHAM RALPH R. , BAIN STEPHEN C. , HARPER ROY , RYDER ROBERT E. ,   ABCD NATIONWIDE DEGLUDEC AUDIT CONTRIBUTORS
Published: June 2018

In clinical trials insulin degludec (Tresiba) was associated with less hypoglycaemia and less day to day glucose variability than older basal insulins. This study assessed the use of insulin degludec in type 1 diabetes in real clinical practice in the UK.

Data were extracted from General Practice records in 2 areas of England for people with type 1 diabetes, prescribed insulin degludec, who had weight and HbA1c measurements at baseline and at least 3 months into treatment. 77 eligible people were identified (43M, 44F). Mean age was 53.3 years (SD 19.9). In this unselected group, there was a significant reduction in HbA1c from 9.5% to 8.9% (p<.001), associated with a significant rise in weight from 78.4 to 80.7kg (P<.005). For individuals, there was no significant association between the change in HbA1c and change in weight.

These data were considered alongside data from the ABCD Nationwide Degludec Audit. In this audit, there were 144 people with type 1 diabetes who had weight and HbA1c measurements at baseline and at least 3 months into treatment at the time of the analysis (65M, 79F). Mean age was 44.1 years (SD 15.7). There was no significant reduction in HbA1c with degludec treatment (8.9% to 8.7%), and no significant increase in weight (77.2 to 77.7 kg).

We have previously shown in the ABCD Nationwide Degludec Audit that there is no significant change in HbA1c or weight in those switched to insulin degludec for reasons of hypoglycaemia (n=88), although hypoglycaemia is significantly improved. A significant reduction in HbA1c and significant increase in weight is seen in those switched to insulin degludec for reasons other than hypoglycaemia (n=56). If the majority of those in the General Practice database were switched to degludec for reasons other than hypoglycaemia, such as to reduce day to day glucose variability, this may explain the observed results.

Disclosure

A.N. Lumb: Other Relationship; Self; Novo Nordisk A/S, Abbott. Consultant; Self; Johnson & Johnson Services, Inc.. I.W. Gallen: None. A. Bickerton: Other Relationship; Self; Novo Nordisk A/S. Advisory Panel; Self; Amgen Inc. R.R. Abraham: Advisory Panel; Self; Novo Nordisk Inc. S.C. Bain: Research Support; Self; Novo Nordisk Inc., AstraZeneca. R. Harper: None. R.E. Ryder: Other Relationship; Self; AstraZeneca. Speaker's Bureau; Self; Bioquest, Janssen Pharmaceuticals, Inc.. Other Relationship; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Novo Nordisk A/S.
Efficacy of a Basal-Plus Regimen
Authors: SABOO BANSHI D.J. , HASNANI DHRUVI , CHANDARANA HARDIK , BHANDARI SUDHIR , JOSHI SHASHANK , KESAVADEV JOTHYDEV , MAHESHWARI ANUJ , THACKER HEMANT
Published: June 2018

Aim: To find out Efficacy of a basal plus regimen.

Objectives: 1. To find out the efficacy of basal plus regime by evaluating the changes in HbA1c at 24 weeks. 2. To find out changes in weight and frequency of hypoglycemia after initiation of the basal plus regime.

Method: The study was a prospective analysis of 24 weeks after initiation of basal plus regime. Inclusion criteria: T2DM>5 Years; On 3OAD + basal insulin, HbA1c- 7.5-8.5%. Exclusion Criteria: critically ill patients, acute infection, pregnant, T1D. All patients matching the inclusion criteria were analyzed on the basis of SMBG chart to find out their highest glycemic excursion of post prandial and fasting readings. Based on the diet recall and sugar reading charts these patients were initiated on bolus insulin with the largest meal of the day where their post prandial corresponded to the highest reading. They were educated on proper insulin injection techniques and SMBG and asked to follow-up with their sugar readings using telemedicine application every day.

Result: We studied 220 patients (F=124 M=96) with HbA1c at baseline 7.5-8.5% (avg-8.0). After addition of bolus insulin at 12 weeks target HbA1c <7% was achieved in 55.9% (n=123) patients with minor dose titrations. Average HbA1c at 12 Weeks was 7.3%. At 24Weeks target HbA1c was achieved in 88.18% (n=194) of patients after uptitration of bolus dose. Average HbA1c at 24Weeks was 6.9%. 5 patients experienced severe hypoglycemic episode. Cases of 15 average mild to moderate hypoglycemic episodes were reported. Regular SMBG and follow-up of the patients through telemedicine applications is continued for insulin dose titration. Fasting sugar target of below 110 mg/dl was achieved through titration of basal insulin in all 220 patients at the end of 12 weeks. Post prandial glycemic readings at the end of 12 weeks were achieved below 160 mg/dl in 167 patients and at 24 weeks in 198 patients.

Conclusion: After failure of OADS and basal insulin a basal plus regime with addition of 1 bolus insulin with the largest meal of the day helped achieve the target HbA1c of <7% effectively.

Disclosure

B.D.J. Saboo: None. D. Hasnani: None. H. Chandarana: None. S. Bhandari: None. S. Joshi: None. J. Kesavadev: Advisory Panel; Self; Novo Nordisk India Private Limited. Speaker's Bureau; Self; Novo Nordisk India Private Limited. Advisory Panel; Self; Medtronic. Speaker's Bureau; Self; Medtronic. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; MSD. Speaker's Bureau; Self; MSD. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. A. Maheshwari: None. H. Thacker: Research Support; Self; Wockhardt LTD.
Insulin Initiation and Concomitant OHA (Oral Hypoglycaemic Agents) in Treatment of Diabetes Mellitus—Results of the Indian Human Insulin Registry (INHIRIT)
Authors: KARADI VEERANNA , PAWAR DILIP , JABEEN SARAH , S. SANDEEP , BOSE SAPTARSHI , WAGH SAGAR P. , BHATTACHARJEE KINGSHUK , ANAND SANTOSH
Published: June 2018

INHIRIT is a multi-centric, prospective, open-label, single-arm, observational, naturalistic registry of diabetes mellitus patients in India with the aim of understanding the criteria for insulins initiation in day to day practice. Patients initiated on human insulin were included in the registry during which their glycaemic parameters and body weight was monitored. The commonly used oral antidiabetic drugs (OADs) used along with insulin therapy and the relevance of BMI as a criterion for insulin selection also was evaluated.

Results: Of the total 668 patients with insulin initiation data, 62 were treatment-naïve. The mean total daily dose of insulin was 36.8 units/d. The daily insulin dose was higher for HbA1C between 7%-8% (42.03 units/d). The most commonly used OADs with insulin were the DPP-4 inhibitors (59.3%), sulfonylureas (50.6%) and metformin (42.7%). Other OADs used are alpha-glucosidase inhibitors (8.5%), thiazolidinedione’s (7.9%), SGLT inhibitors (1.3%) and other OADs (0.4%). Sulfonylureas used in the decreasing order glimepiride, gliclazide, glimepiride, glibenclamide and glipizide. Voglibose was the widely used alpha-glucosidase inhibitor and dapagliflozin was the commonly used SGLT inhibitor. There was found to be no preference of insulin type in underweight patients. However, more overweight and obese patients received human premix 30/70 compared to other insulin preparations.

Conclusion: Our study illustrated the roles that different antidiabetic drugs play in the management of diabetes; chief among them was DPP-4 inhibitors, which represents almost 60% of prescriptions overlapping with insulin and the percentage use of sulfonylurea has decreased.

Disclosure

V. Karadi: None. D. Pawar: Employee; Self; Biocon. S. Jabeen: Employee; Self; Biocon. S. S.: Employee; Self; Biocon. S. Bose: Employee; Self; Biocon. S.P. Wagh: None. K. Bhattacharjee: Employee; Self; Biocon. S. Anand: None.
GLP Analogues Are Superior for Diabetes and Weight Control in Patients on Antipsychotic Plus/Minus Antidepressant Medications
Authors: PERLIS LAUREN , MIEDLICH SUSANNE U.
Published: June 2018

Obesity and diabetes are much more common in patients with mental illnesses compared to the general population and they are linked to adverse cardiovascular (CV) outcomes. Antipsychotic, but also antidepressant medications have been associated with adverse metabolic outcomes. Newer diabetes medications, for example GLP (Glucagon-Like Peptide) analogues, improve not only diabetes control, they also promote weight loss and some (f.i. liraglutide) lower adverse CV outcomes making them ideal agents for mentally diseased patients. Studies of these at-risk patients are scarce and inconclusive. While one study of prediabetic patients on antipsychotics showed improved glucose tolerance and weight loss on a GLP analogue [liraglutide (Larsen JR et al., 2017)], another did not [exenatide (Ishoy PL et al., 2017)]. We thus analyzed diabetic patients on antipsychotics after referral to our diabetes clinic between 2010-2016. Forty five patients were included in this retrospective study; ten were started on GLP analogues (cases), thirty five were treated with alternative diabetic agents (controls). Cases and controls did not significantly differ in age, sex, height, weight and medical therapies at the time of referral. Within one year, a significant reduction in HbA1c (mean±SE) was noted in both groups (-1.25±0.25% for cases, -1.47±0.45% for controls). However, patients on GLP analogues lost 7.1±2.6kg, whereas control patients gained 1.9±1.4kg (p=0.005). Within the entire cohort, we also noted a blunted HbA1c reduction in patients on antidepressants (-0.69±0.33% ON, -2.97±0.6% OFF antidepressants, p=0.001). The opposite trend was observed for patients on GLP analogues, a greater HbA1c reduction was seen for those ON antidepressants.

In summary, GLP analogues are superior for both diabetes and weight control in diabetic patients on antipsychotics plus/minus antidepressants. Future studies are needed to confirm and validate these promising trends.

Disclosure

L. Perlis: None. S.U. Miedlich: None.
Persistence to Liraglutide Therapy Is Associated with Good Glycemic and Body Weight Control in Patients with Type 2 Diabetes
Authors: COHEN CHELI MELZER , CHODICK GABRIEL , HUSEMOEN LISE LOTTE N. , RHEE NICOLAI , SHALEV VARDA , KARASIK AVRAHAM
Published: June 2018

Objective: In both randomized, controlled trials and real-world studies, liraglutide (Victoza®) has demonstrated glycemic and body weight benefits in patients with type 2 diabetes mellitus (T2DM). To achieve long-term beneficial outcomes, persistence with treatment is important; however, this can be challenging with injectable drugs. In this study, we examined the association of long-term adherence to liraglutide and metabolic changes.

Methods: A retrospective analysis of patients with T2DM (≥18 years old) from Maccabi Healthcare Services, Israel, who initiated liraglutide from 2010-2015 and had HbA1c measurements at treatment initiation and after 24 months. Mean change in HbA1c and body weight from initiation to 24 months was compared between patients who received liraglutide regularly for at least 12 months (’continuers’) and those who discontinued liraglutide before 12 months (’discontinuers’). Patients who were treated with another GLP-1 receptor agonist, or who underwent bariatric surgery, were excluded. Adjustment for potential confounding factors (sex, age, years in diabetes registry, HbA1c, body mass index, and insulin use at treatment start) was performed using propensity score matching (1:1 [n=882 in each group]).

Results: Significant reductions in HbA1c were seen in continuers compared with discontinuers (0.80% vs. 0.32%, p<0.0001), despite more using insulin (70.2% vs. 59.0%, p<0.0001) and ≥3 oral antihyperglycemic drugs (20.6% vs. 6.2%, p<0.0001) among discontinuers (in the 3 months preceding the last measurement). Mean body weight reduction was higher in continuers than in discontinuers (3.57 kg vs. 1.25 kg; p<0.0001), but no statistically significant differences were observed in low-density lipoprotein cholesterol (5.72 vs. 2.83 mg/dl [p=0.4717]) and triglycerides (10.37 vs. 6.89 mg/dl [p=0.7896]).

Conclusion: In a real-world setting, persistent use of liraglutide was associated with good glycemic and body weight control.

Disclosure

C. Melzer Cohen: None. G. Chodick: None. L.N. Husemoen: Employee; Self; Novo Nordisk A/S. N. Rhee: Employee; Self; Novo Nordisk A/S. V. Shalev: None. A. Karasik: Stock/Shareholder; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S, AstraZeneca. Research Support; Self; AstraZeneca. Consultant; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Merck & Co., Inc., GlucoMe.
Liraglutide-Based Therapy Shows More Prominent Effect than Conventional Insulin Therapy to Achieve HbA1c Target, Especially in Patients with Short Duration
Authors: KASHIMA KOJI , SHIMIZU HIROYUKI , YAMADA MASANOBU
Published: June 2018

Objective: Despite advanced new medications, the rate of achieving HbA1c target <7% is only around 50%. The aim of study is to evaluate the ability of GLP-1 receptor agonist to achieve this target compared to insulin therapy.

Methods: A total of 154 type 2 diabetic (T2DM) patients on liraglutide (LIRA) based therapy and 124 T2DM patients on insulin based therapy were randomly recruited. The rate of patients achieving the target and background characteristics were compared.

Results: 1) The rate of achieving HbA1c<7% was 41.6% on insulin vs. 61.0% on LIRA. HbA1c<6% was only 7.3% on insulin, but 19.4% on LIRA, although self-blood glucose monitoring (SMBG) was equally done (52.4% vs. 51.9%). 2) Divided into 3 regimes: LIRA mono-injection, LIRA+basal insulin, LIRA+basal bolus (BBT)/pre-mixed insulin therapy, achieving HbA1c<7% rate much varied: 76.3%, 56.9%, and 35.0%. Achieving HbA1c<6% rate was 21.8%, 21.5%, and 5.0% without hypoglycemia. In mono-injection group, the rate of SMBG (30.9%) was lower than other 2 groups (58.2%, 80.0%), and less cost. Moreover, prominent effect was attained in this group, HbA1c improved from 9.9±2.9 to 6.6±0.9% (p<0.01), and BMI improved from 24.5±5.9 to 23.6±5.3kg/m2 (p<0.05) by adding LIRA. In background characteristics, the duration of diabetes was shortest (6.6±6.3 year) in this group, compared with LIRA+basal (11.2±8.8 year) or LIRA+BBT/pre-mixed (15.6±10.6 year) group. But ischemic heart disease (12.7%), chronic kidney disease (30.9%), and obesity (30.9%) complication rates were still high. 4) In one of the patients with a year duration of diabetes, after changing the regime from BBT into LIRA+basal insulin, marked improvement in HbA1c from 8.2% to 5.6% with narrowing blood glucose range 126∼349mg/dL into 79∼145mg/dL was found, and durability for 3 years was confirmed.

Conclusion: Since T2DM is a complex metabolic disorder, LIRA should be started early years to get its maximum benefit of LIRA.

Disclosure

K. Kashima: None. H. Shimizu: Speaker's Bureau; Self; Eli Lilly and Company, MSD K.K., Daiichi Sankyo Company, Limited, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc.. M. Yamada: None.
Gut Microbiome Dysbiosis and Increased Intestinal Permeability in Australian Children with Islet Autoimmunity and Type 1 Diabetes
Authors: HARBISON JESSICA E. , ROTH-SCHULZE ALEXANDRA J. , BARRY SIMON C. , TRAN CUONG D. , NGUI KATRINA , PENNO MEGAN A. , WENTWORTH JOHN , COLMAN PETER G. , THOMSON REBECCA , CRAIG MARIA E. , PAPENFUSS ANTHONY T. , GILES LYNNE , HARRISON LEONARD C. , COUPER JENNY
Published: June 2018

We aimed to characterise the gut microbiome and small intestinal permeability in children with islet autoimmunity and type 1 diabetes (T1D). 88 participants, median age 11.8 (IQR 8.1-13.3) years at baseline were followed 6 monthly for a median of 13 months (range 2-34). 18 had islet autoimmunity, 29 recent-onset T1D, and 41 were age and gender-matched unrelated or sibling controls. Stool samples were collected (Omnigene kit) for 16S rRNA gene sequencing. Small intestinal permeability was measured by blood lactulose:rhamnose ratio (L/R), 90 minutes after drinking a 5gm lactulose/1gm rhamnose solution. Antibodies to insulin, GAD, IA2 and ZnT8 were assayed using IASP standardized radiobinding assays. Statistical analysis used linear mixed models. Differential abundance analysis used limma with total-sum scaling.

Children with islet autoimmunity or T1D had gut microbiome dysbiosis with reduced α diversity and different β diversity compared with controls. Progressors from islet autoimmunity to T1D had lower observed richness (OTUs) (p=0.01) and different β diversity (Adonis, P=0.004), compared with non-progressors. Genus Prevotella, with anti-inflammatory properties, was less abundant in children with T1D (p<0.005) or ≥ 2 islet antibodies (p<0.005) than in controls. Diet did not explain this difference. L/R was higher in T1D than sibling controls (mean difference +3.03±1.02, p=0.003). Progressors had higher L/R than non-progressors (+4.74±1.97, p=0.01) and sibling controls (+4.62±1.69, p=0.006). There was a trend towards a relationship between higher L/R and lower observed richness in the microbiome over time in children with ≥ 2 islet antibodies or T1D (coeff -0.0617, 95% CI -0.1254, 0.002 P=0.058).

Australian children progressing from islet autoimmunity to T1D have gut dysbiosis and increased intestinal permeability. This observation supports a mechanism underlying progression to T1D.

Disclosure

J.E. Harbison: None. A.J. Roth-Schulze: None. S.C. Barry: None. C.D. Tran: None. K. Ngui: None. M.A. Penno: None. J. Wentworth: None. P.G. Colman: None. R. Thomson: None. M.E. Craig: None. A.T. Papenfuss: None. L. Giles: None. L.C. Harrison: None. J. Couper: None.
DPP-4 Inhibitor Gemigliptin in T2DM Patients Uncontrolled on Metformin—Results of Multicenter, National, Randomized, Parallel-Group, Phase 3 Study Alternative
Authors: BIRUKOVA ELENA
Published: June 2018

Gemigliptin a new DPP-4 inhibitor is marketed in Korea since 2012. The study compared the efficacy and safety of gemigliptin (G) 50mg QD vs. vildagliptin (V) 50mg BID as add-on therapy to metformin in type 2 diabetes mellitus Russian patients (pts) uncontrolled on metformin. This was a multicenter comparative randomized (1:1) open-label 24- week non-inferiority trial (predefined equivalence limit difference = 0, 4). Pts with 7% < HbA1c < 9.5% and metformin ≥ 1500mg entered into the study. Change in HbA1c from baseline at 24 weeks was the primary endpoint. Distribution of study populations: randomized-443, of whom G-group-220 (PP population-180), V-group-223 (PP population-196).

Results: Baseline characteristics were comparable between the 2-treatment groups except for BMI in G-treatment group (32.72±4.35 vs. 31.88±3.93 kg/m2, p<0.05). Mean HbA1c change at 24 weeks was -0.77±1.17% for G and -0.79±1.11% for V groups. Between-groups mean difference of HbA1c changes was 0.22% [95% CI 0, 15-0, 29] confirming non-inferiority of G effect vs. V (p<0,001). The 7-points self-monitoring of glucose changes from week 0 to 24 (n=117 for G, n=118 for V): significant glucose level reduction before and 2 hours after dinner was reported in G-group only, but 2 hours after lunch in V-group only*. Eleven cases of symptomatic hypoglycemia were reported in 7 (1.58%) pts: 5 cases in 3 (1, 4%) pts in G-group and 6 cases in 4 pts (1, 8%) in V-group*. No cases of severe or asymptomatic hypoglycemia were reported. 64 AEs including 4 SAEs were reported in 49 pts (11, 1%). 34 (53, 1%) AEs were reported in G-group and 30 AEs in V-group (46, 9%)*.

Conclusion: The clinical efficacy of gemigliptin 50mg was similar to that of vildagliptin 100mg. Both gemigliptin and vildagliptin were well tolerated and did not expose patients to severe hypoglycemias. *- between treatment groups was not statistically significant.

Disclosure

E. Birukova: None.
No Drug–Drug Interaction between Dorzagliatin and Metformin in Type 2 Diabetes Patients
Authors: CHEN LI , ZHAO GUIYU , REN SHUANG , ZHANG YI , DU DANIEL
Published: June 2018

Dorzagliatin (HMS5552) is a new glucokinase activator and showed excellent antidiabetic effects in type 2 diabetes (T2D) patients with good tolerability. It is in Phase 3 clinical development for a new oral antidiabetic drug. Drug-drug interaction (DDI) potential between dorzagliatin and Metformin was investigated in an open-label clinical study in Chinese T2D patients. T2D subjects (n=15) in general good health between 18 and 70 years old, BMI of 22 to 38 kg/m2, fasting C-peptide >0.3 nmol/L, and HbA1c 7% to 12% were randomized in the study. They had been diagnosed of T2D for at least 3 months and were taking a stable daily dose of ≥1000 mg of Metformin for at least 4 weeks. All subjects were standardized to Metformin 500 mg BID for at least two weeks prior to study day 1. In the study, subjects were treated with Metformin (500 mg BID) on days 1-2 and a morning dose only on day 3 before PK samples were collected for 24 hours. On days 4-7, subjects were treated with Metformin (500 mg BID) and dorzagliatin (50 mg BID), and day 8 morning a single dose of each drug was given before PK samplings. Subjects were then treated with dorzagliatin (50 mg BID) on days 9-12, a single dose only on day 13 morning, and followed by PK samplings. Pharmacodynamic (PD) parameters (glucose, insulin and C-peptide levels) were evaluated on days 3, 8 and 13. Study results demonstrated that Metformin had no effect on the exposure of dorzagliatin (Cmax and AUC0-t). The AUC0-t of Metformin remained unchange when co-administered with dorzagliatin while the Cmax was slightly lower than Metformin alone. It is concluded that there was no significant DDI between dorzagliatin and Metformin. Dose adjustment is not warranted when they are co-administered. PK/PD analysis suggested that co-administration of dorzagliatin and Metformin compared to each drug alone can further improve glycemic control in T2D patients. Both drugs were well tolerated in the study.

Disclosure

L. Chen: None. G. Zhao: None. S. Ren: None. Y. Zhang: None. D. Du: None.
Pleiotropic Effects of Totum-63—Simultaneous Targeting of Multiple Diabetes Mediators
Authors: CHAVANELLE VIVIEN , OTERO YOLANDA F. , SIRVENT PASCAL , CANI PATRICE D. , PELTIER SEBASTIEN
Published: June 2018

In 2015, 30.3 million Americans had diabetes, and 84.1 million Americans had prediabetes. Up to 70% of individuals with prediabetes will eventually develop type 2 diabetes (T2D). Additional intervention strategies are needed to manage prediabetes. The pathophysiology of T2D is complex and characterized by alterations in many tissues. We have previously shown that Totum-63 is effective to prevent glucose homeostasis impairments in rodent models of T2D. In an open phase I/II clinical study, Totum-63 also improved glucose and insulin responses to a standardized breakfast in healthy subjects. In order to better understand the mechanisms involved in the beneficial effects of Totum-63, we have conducted early interventions with oral administration of Totum-63 in high fat-fed mice and in db/db mice. Body weight gain and fat mass accumulation, known as early mediators of insulin-sensitivity defectiveness, were markedly lowered. Liver and skeletal muscle insulin signaling pathways were activated in a similar fashion despite lower circulating insulin levels, suggesting an improvement in insulin sensitivity. Hepatic triglyceride content, known as a powerful inductor of liver insulin resistance, was reduced. Totum-63 administration increased liver gene expression of FGF-21, which has been involved in the regulation of many metabolic pathways. In db/db mice, Totum-63 administration delayed the defect of insulin secretion, suggesting a protective role on pancreatic beta-cells. Finally, Totum-63 also showed preventive effects on high fat diet-induced gut microbiota dysbiosis, that has been postulated as a key driver of many metabolic disturbances.

In conclusion, Totum-63 displays pleiotropic beneficial effects on tissues known as major contributors to T2D development. Totum-63 is a promising intervention strategy to prevent T2D development, and is currently under investigation in phase II clinical trial.

Disclosure

V. Chavanelle: Employee; Self; Valbiotis. Y.F. Otero: Employee; Self; Valbiotis. P. Sirvent: Employee; Self; Valbiotis. P.D. Cani: Research Support; Self; Tate&Lyle. Consultant; Self; Biocodex. Stock/Shareholder; Self; A-Mansia Biotech SA. Research Support; Self; Pilèje, Valbiotis. S. Peltier: Board Member; Self; Valbiotis.
Implementation of a Perioperative Insulin Protocol in an Advanced Practice Provider (APP)–Led Limb Salvage Hospitalist Team
Authors: ODEDOSU KEHINDE , OCONNELL KATHLEEN K. , JORDAN MICHELLE C. , GUNASEKARAN UMA , FOX PAMELA E. , MCNULTY JACQUELINE N. , HARDER STEPHEN , MENEGHINI LUIGI
Published: June 2018

We implemented a standardized perioperative insulin management protocol (PIP) for patients with hyperglycemia and acute diabetic foot problems. Our multidisciplinary quality improvement (QI) project retrospectively compared outcomes in the APP-led hospitalist team (TU) using the PIP vs. other hospitalist teams (OT) managing similar patients. We chose glargine U100 as the basal insulin to simplify preoperative dose adjustments. There were no statistical differences in either arm with respect to mean age (53-57 years), female distribution (26-27%), mean weight (85-94 kg) and race/ethnicity (Hispanic 52-62%, Black 34-21% and non-Hispanic white 11-17%). Patients in TU (n=44) and OT (n=42) were started on basal/bolus insulin 80 v 74% of the time, respectively. Initial basal insulin doses (units) were similar (24 ± 12 v 26 ± 24), while initial prandial insulin amounts were higher in TU than OT (21 ± 10 v 13 ± 12; p<0.01), respectively. Use of insulin types were consistent with PIP protocol and hospital formulary guidelines, with TU using glargine and aspart in 89% and 82% of patients, while OT used NPH and Regular in 69% and 76% of patients, respectively. Mean admission A1C (9.1±2.3 v 9.2±2.2 %) and capillary blood glucose (CBG in mg/dl) (239±117 v 257±123) were similar for TU and OT. Mean CBG during hospitalization was lower for TU (163 ± 31 v 187 ± 44; p<0.01). Pre-op (145 ± 49 v 153 ± 50; p=0.48) and immediately post-op (153 ± 74 v 162 ± 81; p=0.59) CBGs were similar for TU and OT, respectively. Hypoglycemia (CBG<70) occurred in 32% of TU and 19% of OT (p=0.18) with only one CBG<50 recorded in each arm. There were no differences in ER visits or readmissions within 30 days of discharge; there was a trend for shorter hospital LOS in TU (14±8 v 18±9 days; p=0.08). A standardized PIP improved perioperative glycemic control without increasing hypoglycemia risk. Wider implementation of this protocol through incorporation into electronic order sets will be the next step in our QI initiative.

Disclosure

K. Odedosu: None. K.K. OConnell: None. M.C. Jordan: Employee; Spouse/Partner; Accenture. U. Gunasekaran: None. P.E. Fox: None. J.N. McNulty: None. S. Harder: None. L. Meneghini: Advisory Panel; Self; Novo Nordisk Inc., Sanofi US. Consultant; Self; Sanofi US, Novo Nordisk Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Other Relationship; Self; American Diabetes Association.
Implementation of the DP-Transfers Project in Catalonia—A Translational Method to Improve Diabetes Screening and Prevention in Primary Care
Authors: COSTA BERNARDO , MESTRE SANTIAGO , BARRIO FRANCISCO , CABRE JOAN-JOSEP , COS FRANCESC XAVIER , AGUILAR SOFIA , SOLE CLAUSTRE , CASTELL CONXA , ARIJA VICTORIA , LINDSTROM JAANA ,   THE CATALAN DIABETES PREVENTION RESEARCH GROUP
Published: June 2018

Background: DP-TRANSFERS(Diabetes Prevention-Transferring findings from European research to society) is a large scale national program aimed at translating a lifestyle diabetes prevention intervention (DE-PLAN-CAT) in primary care centers in Catalonia.

Methods: Multidisciplinary committee evaluated the programme. Participants without diabetes aged 45-75 years (FINDRISC>11 and/or prediabetes) were posible candidates. Implementation was a 4-channel transfer approach (institutional relationships, facilitator WS, collaborative groupware, programme website) and built upon a 3-step (screening, intervention, follow-up) real-life strategy. The 2-year lifestyle intervention program included an initial 9-hour and 15-hour continuity module, 6 and 10 sessions respectively. A 3-level (centre, professionals and participants) descriptive analysis was conducted using cluster sampling by contributing centres to assess results and barriers identified one year after implementation.

Results: Between June2016 and July2017, 103 PHCC 1.4 million inhabitants (27.9% of all centres), 5professionals agreed to participate. After 1 year,83 centres (80.6%) remained active and 3professionals (60.3%) were involved. Implementation was not feasible in 20 centres (19.4%) 5 main barriers: lack of staff support; discontinuity of the initial effort; increase of workload; shift in professional status and lack of acceptance. Overall, 1819 people were screened and 1458 (80.1%) followed the lifestyle intervention, with 1190 (81.6% or 65.4% of those screened) participating in the basic module and 912 in the continuity (62.5% or 50.1%, respectively).

Conclusions: Large-scale lifestyle intervention in primary care can be properly implemented using existing public health resources. Regrettably, one fifth of the centres and more than one third of the professionals showed substantial resistance to performing these additional activities.

Disclosure

B. Costa: None. S. Mestre: None. F. Barrio: None. J. Cabre: None. F. Cos: Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation. Advisory Panel; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Sanofi Pasteur. Speaker's Bureau; Self; Sanofi Pasteur. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Research Support; Self; Eli Lilly and Company. S. Aguilar: None. C. Sole: None. C. Castell: None. V. Arija: None. J. Lindstrom: None.
Out-of-Pocket Costs for Patients with Type 2 Diabetes Mellitus
Authors: DAVIS CHRISTIAN , BURGEN EMILY , CHEN GUOQING J.
Published: June 2018

Objective: Type 2 diabetes mellitus is a growing epidemic in the United States. In 2015 alone, it affected 30.2 million people. Additionally, the cost of managing type 2 diabetes continues to rise. This condition requires long-term management, and the out-of-pocket costs for type 2 diabetes are not well-characterized. The objective of this study was to understand the magnitude of out-of-pocket costs for type 2 diabetes.

Methods: We identified studies in the PubMed databank that were published between 2000 and 2017. From these studies, we examined the amount spent on out-of-pocket costs by type 2 diabetes patients.

Results: Across the ten studies examined, we found a cost range of $143 per year to $2210 per year, a mean cost of $2063 per year, and a median cost of $435 per year. There is a wide range in cost of out-of-pocket costs for people with diabetes.

Conclusion: Clearly, there is not a consistent cost measurement through all of the studies. Some of the variation is accounted for by different definitions of out-of-pocket cost across the studies. To help better inform patients and healthcare policy decision-makers accurately assessing out-of-pocket cost per year in patients with diabetes, there needs to be a consistent definition of out-of-pocket costs, as well as a consistent way to measure out-of-pocket costs.

Disclosure

C. Davis: None. E. Burgen: None. G.J. Chen: None.
Patient Experience after Being Discharged with Newly Prescribed Insulin or Oral Hypoglycemic Agents
Authors: MADHUN NABIL Z. , CALOGERAS ELLEN , NIWATTISAIWONG SOAMSIRI , CECILIA LANSANG M.
Published: June 2018

Objective: To identify issues surrounding discharge from hospitalization in patients newly prescribed insulin or oral hypoglycemic agents.

Methods: We conducted telephone surveys and retrospective chart reviews on adult patients satisfying the aforementioned conditions one week after they were discharged from an academic medical center. Data gathered included glucose levels, logistical issues in obtaining medications or testing supplies, and barriers for testing and treating DM. We compared A1c during and after admission, and identified factors associated with change in A1c.

Results: We attempted to contact 141 eligible patients phone, and reached 98. Of 98 patients, 85 were scheduled with a follow-up with PCP or endocrinology within 60 days of discharge, 13 patients were discharged without follow-up scheduled; 76 were discharged with enough supplies and medication to last until next follow-up. Regarding overall glucose control after discharge, 69 patients were completely to very satisfied, 18 were somewhat satisfied, 11 were slightly to not at all satisfied.

Fifty patients had repeat A1c available after admission (median 116 days, IQR 92, 196). There was a significant decrease in A1c (admission mean 9.5% ± SD 2.7 vs. follow-up 7.0% ± 1.5, p <0.0001). There was no statistically significant change in percentage A1c reduction whether patient received bedside delivery (-22.3% ± 18.8) or not (-23.5% ± 22.0; p = 0.825), or between medical (-25.4% ± 20.4) and surgical services (-16.2% ± 18.7, p = 0.134). Patients utilizing bedside delivery program (pharmacy bringing discharge medications to patient’s room) were more likely to receive the correct diabetes testing supplies and medications (95.2%) than those who did not use the service (71.1%) (p=0.003).

Conclusion: Most patients were satisfied with DM education and readiness upon discharge. Bedside delivery may help improve percentage of discharge with correct supplies and medications.

Disclosure

N.Z. Madhun: None. E. Calogeras: None. S. Niwattisaiwong: None. M. Lansang: None.
Care of the Transgender Adolescent with Type 1 Diabetes
Authors: AVILA JONATHAN , AYE TANDY
Published: June 2018

Approximately 1% of high school aged youth identify as transgender and recent increased societal acceptance of gender dysphoria (GD) has resulted in higher utilization of gender affirming medical interventions. Given that type 1 diabetes (T1D) is one of the most common chronic disease in childhood, it is expected that pediatric diabetes providers will encounter adolescents with both T1D and GD. Pioneering studies from the Netherlands in 1998 described the first use of pubertal suppression with a gonadotropin releasing hormone agonist (GnRHa) in adolescents and the addition of gender affirming sex hormone, testosterone or estrogen, to transition the person to the true gender identity. The Pediatric Endocrine Society, Endocrine Society, and World Professional Association for Transgender Health have published guidelines and standards of care for gender affirming providers. However, very little has been published about the specific considerations in the treatment of these adolescents who have T1D and GD. We report on our experience (n=5) of the unique challenges of managing the T1D during gender transition. There is risk for infection, diabetic ketoacidosis, poor adherence, diabulimia, anxiety and depression in these adolescents. Close monitoring and open conversations between the pediatric diabetes provider and the adolescent with T1D and GD are essential.

Disclosure

J. Avila: None. T. Aye: None.