bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroprotective Effects of HM15211, a Novel Long-Acting GLP-1/GIP/Glucagon Triple Agonist in the Neurodegenerative Disease Models
Authors: KIM JEONG A. , LEE SANGDON , LEE SANG HYUN , JUNG SUNG YOUB , KIM YOUNG HOON , CHOI IN YOUNG , KIM SUN JIN
Published: June 2018

HM15211 is a novel long-acting GLP-1/GIP/Glucagon triple agonist that is being developed for the treatment of obesity and nonalcoholic fatty liver disease (NASH). Accumulating evidences have shown that obesity, type 2 diabetes, and NASH increase the risk of developing progressive neurodegenerative disease such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). In addition to peripheral contributions, each of incretins consisting HM15211 have neuroprotective effects in several brain diseases like AD, PD, and ischemia. Previously, we demonstrated that HM15211 exerted neuroprotective effects in MPTP induced subacute PD mice model. Here, we evaluated 1) the neuroprotective effects of HM15211 in chronic MPTP/probenecid PD model, and 2) the protection of AD progression in db/db mice. Chronic PD mice model was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in combination with probenecid injection, twice a week for 5 weeks and HM15211 was administered once a week for 6 weeks. Dopaminergic neuronal death by MPTP/probenecid was protected by HM15211, which was derived from anti-inflammatory and anti-oxidative stress effect by HM15211. Also HM15211 decreased alpha synuclein in striatum of chronic mice PD model. Together with these efficacies, HM15211 significantly improved the MPTP/probenecid induced motor impairments in behavior. A db/db mice are well-established diabetic model and reported that db/db mice develop hyperphosphorylation of tau as they grew older. Thus we chose db/db mice to elucidate the prophylactic effect of HM15211 on AD. After once every 2 days subcutaneous administration for 12 weeks, HM15211 reversed inflammatory cytokines and oxidative stress marker, which were increased in db/db mice. Also, increased phosphorylated tau in db/db mice was decreased by HM15211. Based on these observations, HM15211 might be a potential therapeutic option for the neurodegenerative disease.

Disclosure

J.A. Kim: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. S. Lee: Employee; Self; Hanmi Pharmaceutical. S. Jung: None. Y. Kim: Employee; Self; Hanmi Pharmaceutical. I. Choi: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical. S. Kim: Employee; Self; Hanmi Pharmaceutical. Stock/Shareholder; Self; Hanmi Pharmaceutical.
LIK066, a Dual SGLT1/2 Inhibitor, Reduces Weight and Improves Multiple Incretin Hormones in Clinical Proof-of-Concept Studies in Obese Patients With or Without Diabetes
Authors: HE YANLING , HAYNES WILLIAM G. , MEYERS CHARLES D. , AMER AHMED , ZHANG YIMING , MAHLING PING C. , MENDONZA ANISHA E. , MA SHENGLIN , CHUTKOW WILLIAM , BACHMAN ERIC S.
Published: June 2018

Background: LIK066 is a potent dual inhibitor of SGLT1/2 (IC50: 20.6 and 0.58 nM for SGLT1 and SGLT2). We studied mechanistic effects of dual SGLT1/2 inhibition of SGLT1 in the gut and SGLT1/2 in the kidneys.

Methods: Effects of LIK066 on weight, glucose and a variety of incretin hormones (GLP-1, PYY, GIP, glucagon, insulin) were investigated in: 1) a single dose cross-over study in T2DM, 2) a 14 day randomized, double-masked study in T2DM, 3) a 12-week randomized, double-masked, placebo-controlled study in obese subjects with normoglycemia (NG) or dysglycemia (DG; HbA1c: ≥5.7% and <10%).

Results: LIK066 (2.5, 30, 300 mg single dose) significantly reduced glucose excursion and insulin secretion (p<0.01 at 30 and 300 mg) following oral glucose tolerance test (OGTT) in patients with T2DM (n=12), with the 300 mg dose completely suppressing glucose and insulin excursions. In patients with T2DM (n=30), LIK066 15 mg qd for 14 days reduced blood glucose (41 mg/dL by continuous glucose monitoring) and increased 24-hour urinary glucose excretion (100 g/d on day 14). Furthermore total GLP-1 and PYY increased (AUC0-3hrs >1.5-fold; p<0.05) post-OGTT, while GIP levels were reduced (>50%; p<0.05). In obese subjects (n=88), LIK066 150 mg qd for 12 weeks reduced weight by 5.70% (p<0.001) compared to placebo, with higher effects in DG (6.85%) vs. NG (4.55%). Additionally multiple metabolic parameters improved (reduced waist circumference, postprandial glucose and insulin, and increased postprandial glucagon). LIK066 was generally safe and well tolerated. The most common AEs were headache, flatulence and diarrhea.

Conclusions: LIK066 treatment leads to favorable changes in a variety of metabolic hormones (increased GLP-1, PYY and glucagon, reduced GIP, glucose and insulin), all contributing to WL effects of LIK066. The dual inhibition of SGLT1/2 in both the gut and kidneys is an attractive strategy for obesity or diabetes treatment.

Disclosure

Y. He: None. W.G. Haynes: Employee; Self; AstraZeneca. C.D. Meyers: Employee; Self; Janssen Research & Development. A. Amer: Employee; Self; Novartis Pharmaceuticals Corporation. Stock/Shareholder; Self; Novartis AG. Y. Zhang: Employee; Self; Novartis Pharmaceuticals Corporation. P.C. Mahling: None. A.E. Mendonza: None. S. Ma: None. W. Chutkow: Employee; Self; Novartis Pharmaceuticals Corporation. E.S. Bachman: None.
Triple vs. Dual Therapy with Low-Dose Dapagliflozin plus Saxagliptin vs. Each Monocomponent Added to Metformin in Uncontrolled Type 2 Diabetes
Authors: ROSENSTOCK JULIO , PERL SHIRA , JOHNSSON EVA K. , JACOB STEPHAN
Published: June 2018

Triple therapy with dapagliflozin (DAPA) 10 mg/d + saxagliptin (SAXA) 5 mg/d added to metformin (MET) has greater efficacy than dual therapy in type 2 diabetes (T2D) inadequately controlled by MET alone. We tested triple therapy with the lower starting dose of DAPA in a randomized, parallel-group, double-blind, 24-week trial (NCT02681094) to evaluate the efficacy and safety of DAPA 5 mg/d + SAXA 5 mg/d add-on therapy vs. add-on of either agent in patients with T2D (A1C 7.5-10%) uncontrolled with stable MET ≥1500 mg/d monotherapy. The primary end point was change in A1C from baseline to week 24; secondary end points were the proportion of participants achieving A1C <7% at week 24 and changes in FPG and body weight from baseline to week 24. At baseline, mean±SD patient characteristics were similar in all arms: age, 56.7±10.5 years; A1C, 8.2±0.9%; BMI, 31.9±5.4 kg/m2; T2D duration, 7.6±6.1 years. Triple therapy resulted in significant decreases in A1C and FPG vs. both dual therapies, and reduced body weight vs. SAXA + MET (Table). Incidences of genital infections were 3.4%, 1.7% and 0%; urinary tract infections 3.1%, 2.0% and 2.4%; hypoglycemia 5.8%, 2.7% and 3.4% for DAPA + SAXA + MET, DAPA + MET and SAXA + MET, respectively.

In conclusion, DAPA 5 mg/d + SAXA 5 mg/d added to MET led to greater improvement in glycemic control vs. either agent added to MET in T2D uncontrolled with MET monotherapy.

Disclosure

J. Rosenstock: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Consultant; Self; Sanofi. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Consultant; Self; Intarcia Therapeutics, Inc.. Research Support; Self; Merck & Co., Inc., Pfizer Inc., Sanofi, Novo Nordisk Inc., Bristol-Myers Squibb Company, Eli Lilly and Company, Intarcia Therapeutics, Inc., Genentech, Inc. S. Perl: Employee; Self; AstraZeneca. E.K. Johnsson: Employee; Self; AstraZeneca. S. Jacob: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, AstraZeneca, Eli Lilly and Company. Board Member; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk Foundation. Advisory Panel; Self; MSD K.K.. Speaker's Bureau; Self; MSD K.K., Menarini Group, Roche Diabetes Care Health and Digital Solutions.
Disparity of the Efficacy of DPP-4 Inhibitors in Combination with Metformin vs. High Dose Metformin as Initial Treatment between Asian and Caucasian T2DM Patients
Authors: HUANG XIUTING , GAO XUEYING , CAI XIAOLING , JI LINONG
Published: June 2018

Background: To evaluate the efficacy and safety of DPP-4 inhibitors (DPP-4i) in combination with metformin as initial treatment vs. high or low dose of metformin in type 2 diabetes patients.

Methods: Studies were identified by search of MEDLINE and EMBASE until Nov. 2017. Inclusion criteria were: T2DM; initial treatment; comparing metformin monotherapy vs.s DPP-4i in combination with metformin therapy; the primary endpoint was the change in HbA1c.

Results: A total of 9 studies were included. In Asian drug-naïve T2DM patients, compared with high dose metformin monotherapy(2g/day), high dose metformin initial combine with DPP-4i therapy led to significant decrease in HbA1c (WMD -0.22%), while in Caucasian, combination therapy resulted in -0.53% change. The difference in the reduction of HbA1c between Asian and Caucasian of combination therapy vs. monotherapy was 0.31% with significance in favor of Caucasian population. In terms of fasting plasma glucose (FPG), in Asian patients, combination therapy vs. monotherapy led to -0.40mmol/L change, while in Caucasian, combination therapy vs. monotherapy led to -0.95mmol/L change. The difference in FPG reduction between Asian and Caucasian was 0.55mmol/L with significance in favor of Caucasian patients. The difference in postprandial glucose (PPG) reduction between Asian and Caucasian was 0.94mmol/L in favor of Caucasian. The difference in body weight changes between Asian and Caucasian was 0.50kg with significance body weight gain of Asian patients. Adverse effects were not increased when compared with combination therapy vs. monotherapy.

Conclusion: DPP-4i with metformin as initial treatment was superior to metformin given alone in glycemic control of drug-naïve T2DM. The glucose-lowering efficacy of DPP-4i combination therapy was greater in Caucasian patients than in Asian.

Disclosure

X. Huang: None. X. Gao: None. X. Cai: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Eli Lilly and Company, Bristol-Myers Squibb Company, Novartis AG, Novo Nordisk A/S, Merck & Co., Inc., Bayer AG, Merck Sharp & Dohme Corp., Takeda Development Center Asia, Pte. Ltd., Sanofi, Roche Pharma, Boehringer Ingelheim GmbH. Research Support; Self; AstraZeneca, Roche Pharma, Sanofi, Merck Sharp & Dohme Corp., Novartis AG, Eli Lilly and Company, Bristol-Myers Squibb Company.
Effects of SGLT2 Inhibitors on Renin-Aldosterone System for One Month and Six Months in Type 2 Diabetes
Authors: MORI ICHIRO , ISHIZUKA TATSUO
Published: June 2018

Previous study has shown SGLT2 inhibitors affect tubule-glomerular feedback in macula densa associated with decreased glomerular filtration rate. Thereby, plasma renin activity(PRA) may acutely increase after treatment with SGLT2 inhibitors. However chronic activation of PRA-aldosterone system may introduce deterioration of atherosclerosis and fibrosis of heart muscle. The purpose of this study is to examine alterations of PRA and aldosterone concentration (PAC) after treatment with SGLT2 inhibitor in type 2 diabetic patients (T2D). We measured PRA and PAC in T2D (age 68±18 years old, men: female = 12:6) after treatment with SGLT2 inhibitors (tofogliflozin: 7 cases, empagliflozin: 6cases, canagliflozin: 3 cases) for 1 months and 6months (8 cases, age 63±16 years old, men: female = 7:1) from 2014 to 2017. Moreover, we could measured each metabolic parameters such as blood glucose, HbA1c, urinary Na/creatinine and blood pressure before and after treatment with SGLT2 inhibitors (SGLT2i) for 1month and 6months in T2D. We analyzed these results with paired t test using JMP12.2.0. SGLT2i significantly increased PRA for only 1month, but not PAC for 1 month and 6 months as follows; before PRA 1.9±2.4 ng/ml/h, 5.8±9.2 ng/ml/h for 1month (p<0.05) and 2.5±3.1 ng/ml/h for 6months, before PAC 104±65 pg/ml, 105±55 pg/ml for 1 month and 123±85 pg/ml for 6 months, respectively. Moreover, when we examined each metabolic parameter before and after treatment for 1 month, each body weight, BS, and HbA1c was significantly decreased (p<0.05). SGLT2i increases urinary sodium excretion, which affects macula densa in juxta-glomerular apparatus, and finally stimulates secretion of renin for 1month, but not for 6 months. The alteration of aldosterone were not observed after treatment with SGLT2 inhibitors for 1 and 6 months. These results suggest that SGLT2 inhibitors acutely affects PRA but not PAC, and chronic activation of PRA and PAC, which might cause cardiovascular events are not found.

Disclosure

I. Mori: None. T. Ishizuka: None.
The Safety of Continuing Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor during Ramadan Fasting in Muslim Patients with Type 2 Diabetes
Authors: YANLI YANLI SHAO , LIM GWYNETH J. , CHUA CHIN LIAN , WONG YIP FONG , YEOH ESTER , SERENA LOW KIAT MUN , SUM CHEE FANG
Published: June 2018

Methods: This is a single-centre, prospective observational controlled cohort study. Muslim patients aged 18 to 75 years with type 2 diabetes and estimated glomerular rate (eGFR) ≥ 45 ml/min/1.73 m2 were eligible if they had no contraindication to observe Ramadan fasting. Patients in study group received stable dose of SGLT2 Inhibitor for ≥ 3 months prior to enrolment and during study period, while patients in control group were not on SGLT2 inhibitor before and during study period. All participants were to attend baseline visit within 2 months before Ramadan and follow-up visit during Ramadan.

Results: A total of 68 patients of similar baseline characteristics were included in the study: 35 in study group and 33 in control group. During Ramadan fasting, patients from study and control group had similar change in weight (LS mean change of -1.8 vs. -1.1kg, p=0.205), eGFR (LS mean change of -6.0 vs. -4.2ml/min/1.73m2; p= 0.399), sitting systolic BP (LS mean change of - 8.0 vs. -10.4mmHg, p=0.569), sitting diastolic BP (LS mean change of -3.7 vs. - 3.5mmHg, p=0.934) and plasma β-hydroxybutyrate level (LS mean change of -0.01 vs. -0.02mmol/L, p=0.649).

Conclusions: Continued use of SGLT2 Inhibitors during Ramadan in the study had no increased risk in eGFR deterioration, ketonemia, hypoglycaemia and postural hypotension.

Disclosure

Y. Shao Yanli: None. G.J. Lim: None. C. Chua: None. Y. Wong: None. E. Yeoh: None. K. Low: None. C. Sum: None.
Eldecalcitol, a Vitamin D Analog, for Diabetes Prevention in Impaired Glucose Tolerance (DPVD Study)
Authors: KAWAHARA TETSUYA
Published: June 2018

Background: In cohort and observational studies, it was clear that vitamin D deficiency is associated with insulin resistance and risk of future diabetes. However, randomized controlled trials with vitamin D supplementation for improving glucose tolerance or prevention of type 2 diabetes is still controversial.

Methods: We conducted the Diabetes Prevention on Vitamin D (DPVD) study which was a large, randomized, double-blind, placebo-controlled study to examine whether eldecalcitol, an active form of vitamin D analog, can reduce the risk of type 2 diabetes in patients with impaired glucose tolerance. Participants were randomly assigned to receive eldecalcitol or placebo. The primary endpoint was the incidence of type 2 diabetes and the secondary endpoint was the conversion to normal glucose tolerance. The study duration was 3 years.

Results: The mean follow-up was 2.6 years. A total of 1256 participants were enrolled in the study. 57 of 630 (9.0%) participants in the eldecalcitol and 64 of 626 (10.2%) in the placebo group developed type 2 diabetes (hazard ratio, 0.87; 95% confidence interval, 0.68 to 1.09; p=0.37). In the subgroup participants with vitamin D deficiency (serum 25-hydroxyvitamin D<20 ng/ml), the difference of the incidence of type 2 diabetes between the two groups was greater; however, there was no statistical significance. Two hundred ninety-five of 630 (46.8%) participants in the eldecalcitol and 267 of 626 (42.7%) in the placebo group achieved normal glucose tolerance (hazard ratio, 1.10; 95% confidence interval, 0.93 to 1.31; p=0.45). No serious adverse events related to the intervention were recorded.

Conclusion: Our study showed that treatment with eldecalcitol was not associated with a reduction in the incidence of type 2 diabetes or an increase in the conversion to normal glucose tolerance among patients with impaired glucose tolerance.

Disclosure

T. Kawahara: None.
Canagliflozin Ameliorates Arterial Stiffness by Reducing Serum Uric Acid in Type 2 Diabetic Patients
Authors: SANCHEZ RAMIRO A. , SANCHEZ MARIA J. , RAMIREZ AGUSTIN J.
Published: June 2018

We have previously shown a strong relation between high serum uric acid and pulse wave velocity (PWV) as expression of arterial stiffness. This relation was even stronger than with blood pressure. In addition to its hypoglycemic effect, sodium-glucose transport protein 2 inhibitors (SGLT2i) may reduce serum uric acid (SUA) by a uricosuric effect.

Aims: to evaluate in type 2 diabetic patients with hypertension and normal renal function the effect of canagliflozin on SUA and carotid femoral PWV.

Methods: 20 patients with type 2 diabetes mellitus (DM) 10 females, 59±4y received metformin 2000mg, canagliflozin 100-300mg and amlodipine 10mg daily during 6 months. Laboratory parameters including HbA1C, fasting blood glucose level, glomerular filtration rate, SUA, 24h ambulatory blood pressure monitoring (ABPM) and PWV were determined at baseline and after a 6-month treatment course with canagliflozin 100-300mg.

Results: After 6 months of treatment, PWV dropped from 12±3 to 8.5±4 m/sec, p<0.05, HbA1C decreased from 8.1% to 7.0%, p<0.05, SUA decreased from 7.9mg%±1 to 6.7±2%, p<0.and 24h ABPM decreased from 154±6/96±5mmHg to 141±3/86±4mmHg, p<0.05.

Conclusions: Canagliflozin ameliorates arterial stiffness in patients with type 2 DM and hypertension. This effect seems to be related, among other mechanisms, such as blood pressure drop and plasma volume contraction to the reduction in serum uric acid level. Since SUA has been shown to predict the risk of cardiovascular morbidity and mortality in hypertension and DM, lowering serum uric acid by SGLT2i might be contributing to cardiovascular protection.

Disclosure

R.A. Sanchez: None. M.J. Sanchez: None. A.J. Ramirez: None.
Suppressive Effect of Angiotensin II Receptor Blockers on Progression of Atherosclerosis as Assessed by 3-Dimensional Carotid Ultrasound
Authors: TAKI KENTARO , NISHIMURA RIMEI , NISHIOKA MAKIKO , MIYASHITA YUMI , YOKOTA TAMOTSU , DAISUKE TSUJINO , MORIMOTO AYA , TAJIMA NAOKO , UTSUNOMIYA KAZUNORI
Published: June 2018

The effect of antihypertensive therapy with ARB on carotid endothelium in diabetic patients with hypertension by using 2- and 3-dimensional ultrasonography has received little attention.

We investigated whether significant differences exist between telmisartan and valsartan or not in carotid intima-media thickness and plaque volume. Eighty-six type 2 diabetic, hypertensive patients received nateglinide and Telmisartan 40 mg or Valsartan 80 mg for 6 months and were evaluated for bilateral maximum IMT and plaque volume by 2-/3-dimensional ultrasonography.

Baseline characteristics in groups telmisartan and valsartan(n=43 each) were: age, 62.0 and 65.0 years; Body Mass Index, 24.6 and 24.4kg/m2; duration of diabetes, 7.0 and 9.0 years; and HbA1c, 7.0 and 6.9%, respectively. Systolic/diastolic blood pressures in group telmisartan vs. valsartan were 143.0/84.0 vs. 144.0/83.0 at baseline and 127.0/76.0 vs. 130.0/74.0 mmHg after antihypertensive therapy, with all later values significantly lower than those at baseline(all P<0.001).

Bilateral maximum IMT in group telmisartan vs. valsartan, as assessed by 2-dimensional ultrasonography, were 1.54 vs. 1.72 at baseline and 1.51 mm vs. 1.62 mm after antihypertensive therapy, without significant differences between groups.

Plaque volume in group telmisartan vs. valsartan, as assessed by 3-dimensional ultrasonography, at baseline and post-antihypertensive therapy, based on 15 measurements, were 57.3 and 42.6 mm3(P<0.001) vs. 70.8 and 47.9 mm3(P<0.001), respectively, with significant reductions revealed after antihypertensive therapy in both groups, but without significant differences between groups.

Significant reductions in plaque volume demonstrated that ARB-based antihypertensive therapy with telmisartan or valsartan was efficacious in suppressing the progression of carotid atherosclerosis as assessed by 3-dimensional ultrasonography.

Disclosure

K. Taki: None. R. Nishimura: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Astellas Pharma US, Inc., Eli Lilly and Company, Abbott, Medtronic, MSD K.K., Novo Nordisk A/S, Sanofi, Takeda Development Center Asia, Pte. Ltd., Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.. M. Nishioka: None. Y. Miyashita: None. T. Yokota: None. T. Daisuke: None. A. Morimoto: None. N. Tajima: None. K. Utsunomiya: None.
Metformin Activates AMPK Signaling but Inhibits Mitophagy in the Mouse Heart
Authors: ZHANG YAWEN , CHANG MICHAEL M. , PINKHASOVA POLINA R. , ZHAO FENGYI , KOBAYASHI TAMAYO , HUANG YUAN , KOBAYASHI SATORU , LIANG QIANGRONG
Published: June 2018

Metformin, a commonly prescribed first-line drug for the treatment of type 2 diabetes mellitus, has been shown to reduce cardiac injury under diabetic and other pathological conditions. However, the mechanisms that mediate the cardioprotective effects of metformin remain controversial. One prevailing hypothesis suggests that metformin activates AMPK-autophagy pathway which eliminates protein aggregates and damaged mitochondria, thus protecting the heart from injury. In the present study, we tested this hypothesis using both in vivo and in vitro models. FVB/N mice were administered 200 mg/kg of metformin through gavage once a day for two days. As expected, metformin activated AMPK signaling in the heart as shown by the increased phosphorylation of AMPK alpha at Thr172 and its downstream effecter Acetyl-CoA Carboxylase at Ser79. Autophagy and mitophagy were determined by Western blot analysis of LC3-II, a well-established marker of autophagic vesicles. Surprisingly, however, metformin did not affect LC3-II levels in total tissue lysates and significantly reduced LC3-II in mitochondrial fractions, suggesting that metformin actually inhibited rather stimulated mitophagy, contrary to the current belief. This was confirmed by measuring mitophagy flux using lysosomal inhibitors pepstatin A and E64d. The ability of metformin to inhibit mitophagy was also corroborated by a novel dual fluorescent mitophagy reporter showing reduced degradation rate of mitochondria in the lysosomes. All these results were reproduced in H9c2 rat cardiac myoblast cells. Collectively, our results show that metformin is able to activate AMPK signaling but paradoxically inhibits mitophagy in the heart, suggesting that the cardioprotective benefit of metformin observed in many different models may be mediated through mechanisms other than autophagy and mitophagy. Future studies will explore the mechanisms by which metformin inhibits mitophagy and protects the heart.

Disclosure

Y. Zhang: None. M.M. Chang: None. P.R. Pinkhasova: None. F. Zhao: None. T. Kobayashi: None. Y. Huang: None. S. Kobayashi: None. Q. Liang: None.
Simplified Transition Algorithm from Intravenous to Subcutaneous Insulin in Nondiabetic Cardiac Surgery Patients with Stress Hyperglycemia
Authors: CARDONA SAUMETH , GALINDO RODOLFO J. , TSEGKA KATERINA G. , URRUTIA MARIA A. , VELLANKI PRIYATHAMA , FAYFMAN MAYA , SONYA HAW J. , PASQUEL FRANCISCO J. , PENG LIMIN , UMPIERREZ GUILLERMO E.
Published: June 2018

Intravenous (IV) insulin is recommended to treat stress hyperglycemia (SH) in nondiabetic (non-DM) patients after cardiac surgery. Many patients with SH require transition to subcutaneous (SQ) insulin after stopping IV drip in the ICU. We report a simplified protocol for the transition from IV to SQ insulin in cardiac surgery patients with SH. Patients requiring IV insulin >2 U/hour were transitioned to SQ basal bolus regimen at 70% of calculated daily insulin requirement. Patients requiring ≤ 2 U/hour were treated with sliding scale insulin (SSI), if >2 episodes of BG > 140 mg/dl patients were started on rescue therapy with basal insulin.

Among 150 non-DM patients with SH in the ICU, 30 patients (20%) required >2 U/hour and were transitioned to SQ basal/bolus at a mean SQ dose of 0.34 U/kg/day for a duration of treatment of 5.5±3.6 days. A total of 120 (80%) patients required ≤ 2 U/hour and were transitioned to SSI. Of them, the mean blood glucose (BG) was 129.8±16 mg/dl and only 3 (2.5%) patients required a single dose of basal insulin during the hospital stay. There were no differences in LOS or in a composite of complications between groups.

Our results indicate that cardiac surgery patients with SH requiring continuous IV insulin ≤ 2 U/hour in the ICU can be safely transitioned to SSI; however, patients requiring > 2 U/hour should be transitioned to basal insulin to maintain glycemic targets.

 Transition to SSITransition to Basalp-valuePatients, n (%)120 (80)30 (20)BMI, Kg/m228.8 ± 6.530.3 ± 5.40.15HbA1c, %5.6 ± 0.45.8 ± 0.70.047ICUDaily BG during IV insulin drip, mg/dl133.9 ± 17142.9 ± 150.004Total insulin in the ICU, U/day57.4 ± 8973.8 ± 640.005TRANSITIONAverage BG after transition, mg/dl123.4 ± 12129.8 ± 160.022Patients who required SQ SSI99 (83)30 (100)<0.001Patients with BG < 70 mg/dl, n (%)13 (10.8)2 (6.7)0.74Composite of complications53 (44)14 (47)0.81Data are n (%) or mean ± SD. Composite complications: major CV events, infections, respiratory failure and acute kidney injury.

Disclosure

S. Cardona: None. R.J. Galindo: None. K.G. Tsegka: None. M.A. Urrutia: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., AstraZeneca. M. Fayfman: None. J. Haw: None. F.J. Pasquel: Consultant; Self; Merck Sharp & Dohme Corp., Sanofi, Boehringer Ingelheim Pharmaceuticals, Inc.. L. Peng: None. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc..
A Phase 3 Comparison of a Novel Liquid Glucagon Autoinjector to Glucagon Emergency Kit for the Treatment of Severe Hypoglycemia
Authors: CHRISTIANSEN MARK P. , CUMMINS MARTIN J. , PRESTRELSKI STEVEN J. , STRANGE POUL
Published: June 2018

Objective: To prevent medical complications and serious sequalae of severe hypoglycemic emergencies, prompt and reliable rescue intervention is critically important. A novel ready-to-use stable liquid glucagon autoinjector (GAI; Xeris Pharmaceuticals) was evaluated for the rescue treatment of severe hypoglycemia.

Research Design and Methods: A randomized, controlled, double-blind, crossover clinical trial was conducted in 80 adults with T1D (mean age 43.6 years) to compare subcutaneous 1 mg doses of GAI vs. Glucagon Emergency Kit (GEK; Eli Lilly) for the treatment of insulin-induced severe hypoglycemia. Efficacy was evaluated as either an increase in plasma glucose to ≥70 mg/dL or an increase in plasma glucose ≥20 mg/dL from a baseline glucose <50 mg/dL, within 30 min of dosing.

Results: On an intent-to-treat basis, efficacy was comparable between the groups (97.4% GAI, 100% GEK, p=NS), and all subjects were rescued from severe hypoglycemia without additional measures. GAI was similar to GEK in terms of glucose Cmax, Tmax, and AUC (0-90 min). The incidence of AEs was low in both groups; the most commonly reported AE was nausea [GAI (20.5%), GEK (12.7%); p=NS], followed by vomiting and headache.

Conclusions: These results demonstrate that GAI is an effective, safe, and well tolerated rescue treatment for severe hypoglycemia and is a viable alternative to GEK.

Disclosure

M.P. Christiansen: Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Abbott, Novo Nordisk Inc., Senseonics, REMD Biotherapeutics, Xeris Pharmaceuticals, Inc. M.J. Cummins: Employee; Self; Xeris Pharmaceuticals, Inc. S.J. Prestrelski: Employee; Self; Xeris Pharmaceuticals, Inc. P. Strange: Other Relationship; Self; AstraZeneca. Consultant; Self; Valeritas, Inc.. Stock/Shareholder; Self; Valeritas, Inc..
Simplici-T1—First Clinical Trial to Test Activation of Glucokinase as an Adjunctive Treatment for Type 1 Diabetes
Authors: BUSE JOHN B. , VALCARCE CARMEN , FREEMAN JENNIFER L. , DUNN IMOGENE , DVERGSTEN CHRIS , SUE KIRKMAN M. , KASS ALEXANDER , DINER JAMIE , BERGAMO KATHERINE A.
Published: June 2018

TTP399 is an oral liver selective Glucokinase Activator (GKA). Because it exhibits an insulin-independent mechanism of action, it may be suitable as an adjunctive treatment for type 1 diabetes (T1DM).

In clinical trials in type 2 diabetes (T2DM), TTP399 has shown significant reduction in postprandial glucose, increased percentage time in range and decreased percentage time in hypo or hyperglycemia. Moreover, TTP399 significantly reduced HbA1c without significant hypoglycemia, dyslipidemia, or ketoacidosis.

The Simplici-T1 trial (NCT03335371) is an adaptive three-part (sentinel, learning phase and confirming phase) Phase 1b/2 Proof of Concept study designed to explore the effect of TTP399 as adjunctive therapy for the treatment of T1DM. The aims of the study are to: (1) evaluate the safety of TTP399 and (2) evaluate whether TTP399 can replace or reduce mealtime insulin bolus and improve A1c in patients with T1DM.

The sentinel phase, an open label, dose escalation study in 5 adults with T1DM on insulin pump therapy and continuous glucose monitoring (CGM), showed that TTP399 was well tolerated. No incidents of severe hypoglycemia or diabetic ketoacidosis were observed. When compared to baseline, trends toward improved glycemic control while reducing insulin dose (Table) were observed with TTP399 treatment, supporting continuing to the randomized, placebo controlled phase of the study.

Disclosure

J.B. Buse: Other Relationship; Self; ADOCIA, AstraZeneca, Dexcom, Inc., Elcelyx Therapeutics, Inc., Eli Lilly and Company, Fractyl Laboratories, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Metavention, NovaTarg, Novo Nordisk A/S, Sanofi, VTV Therapeutics. Research Support; Self; Boehringer Ingelheim GmbH, Johnson & Johnson Services, Inc., Theracos, Inc.. Other Relationship; Self; Shenzhen Hightide Biopharmaceutical, Ltd.. Research Support; Self; National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association. Research Support; Self; Patient-Centered Outcomes Research Institute. Other Relationship; Self; National Institute of Environmental Health Sciences. C. Valcarce: Employee; Self; VTV Therapeutics. J.L. Freeman: Employee; Self; VTV Therapeutics. Stock/Shareholder; Self; VTV Therapeutics. Stock/Shareholder; Spouse/Partner; VTV Therapeutics. I. Dunn: Employee; Self; VTV Therapeutics. C. Dvergsten: Employee; Self; VTV Therapeutics. M. Kirkman: Research Support; Self; Bayer AG, Theracos, Inc.. Consultant; Self; National Institutes of Health. Research Support; Self; National Institutes of Health, Centers for Disease Control and Prevention. A. Kass: None. J. Diner: None. K.A. Bergamo: None.
The Effectiveness of Text Message Support for Weight Loss to Reduce Diabetes Risk
Authors: FISCHER HENRY , RAGHUNATH SILVIA , DURFEE JOSH , RITCHIE NATALIE
Published: June 2018

Objective: To reach the estimated 84.1 million U.S. adults with prediabetes, lower-cost alternatives to the National Diabetes Prevention Program (NDPP) are needed, which is estimated to cost $500 per person. In a previous randomized controlled trial, we demonstrated efficacy of a 12-month text message support program (SMS4PreDM) in individuals with prediabetes. We now explore effectiveness in a pragmatic study in a healthcare system, in addition to calculating per-person costs of SMS4PreDM.

Research Design and Methods: English- and Spanish-speaking patients with diabetes risks (e.g., A1C 5.7-6.4) were referred by their healthcare providers and offered NDPP classes, SMS4PreDM, or both. This analysis focused on comparing weight outcomes among SMS4PreDM-only participants to a usual care control group of patients with diabetes risks who were not referred. As a pragmatic study, weights for both groups were collected from electronic health records at baseline and 12 months. Rates of achieving ≥3% weight loss were compared using logistic regression, including a sub-analysis by language.

Results: Among 183 SMS4PreDM-only participants, 51.4% (N=94) had documented pre- and post-intervention weights and 30.9% (N=29) achieved ≥3% weight loss, compared with 23.4% of 1,871 control patients (p=0.10). English-speakers receiving SMS4PreDM trended toward ≥3% weight loss at a higher rate than English-speaking controls (36.5% vs. 25.6%, p=.07). There was no significant difference among Spanish-speakers. In an intention-to-treat analysis that assumed no weight loss among participants with missing data, there was no significant difference in achieving ≥3% weight loss as compared to controls (20.8% vs. 20.2%, p=.49). Costs of SMS4PreDM were $100.92 per capita.

Conclusions: SMS4PreDM trends toward greater achievement of ≥3% weight loss compared to usual care and at a lower cost than the NDPP. However, results may not be sufficiently robust or generalizable to support long-term implementation.

Disclosure

H. Fischer: None. S. Raghunath: None. J. Durfee: None. N. Ritchie: None.
Real-World Comparative Effectiveness, Treatment Patterns, and Costs in Type 2 Diabetes Mellitus (T2DM) Patients Initiated on Canagliflozin 300 mg (CANA) or a Glucagon-Like Peptide-1 Receptor Agonist (GLP-1)
Authors: SINGHAL MUKUL , TAN HIANGKIAT (JASON) , COLEMAN CRAIG I. , HERMAN WILLIAM H. , CAI JENNIFER , HAN MICHELLE , INGHAM MIKE
Published: June 2018

This study compared HbA1c control, treatment patterns, and costs in adults with T2DM initiated on CANA or a GLP-1 based on administrative claims data from the HealthCore Integrated Research Database (4/2013-02/2016) augmented with laboratory data. The analysis included adult patients with ≥1 HbA1c result at baseline (BL) and in the 12-month follow-up period; statistical analysis was performed at 3-month intervals. Inverse probability of treatment weighting (IPTW) accounted for differences in BL characteristics. From 12 months pre- to 12 months post-index (Figure), there were no significant differences in HbA1c at each 3-month interval in patients initiated on CANA (n = 750) or GLP-1 (n = 2417); results were consistent regardless of BL HbA1c (≥7%, ≥8%, or ≥9%) (data not shown). A greater proportion of patients were adherent to index medication (proportion of days covered ≥80%) over 12 months with CANA vs. GLP-1 (47.5% vs. 37.5%; P <0.001). The likelihood of discontinuation from index medication was lower with CANA than GLP-1 (49.6% vs. 57.4%; HR [95% CI]: 0.78 [0.70, 0.88]). Continuous 12-month pharmacy costs were $1,421 lower with CANA vs. GLP-1.

In summary, CANA initiation resulted in similar HbA1c values, greater adherence, less discontinuation, and lower treatment cost compared to GLP-1 in T2DM patients.

Disclosure

M. Singhal: Other Relationship; Self; Janssen Scientific Affairs, LLC. H. Tan: Other Relationship; Self; Janssen Scientific Affairs, LLC. C.I. Coleman: Research Support; Self; Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc. W.H. Herman: Other Relationship; Self; Merck Sharp & Dohme Corp., Lexicon Pharmaceuticals, Inc.. Consultant; Self; Janssen Scientific Affairs, LLC.. Research Support; Spouse/Partner; Nestlé. Other Relationship; Self; American Diabetes Association. Advisory Panel; Self; National Committee for Quality Assurance (NCQA). J. Cai: Employee; Self; Janssen Scientific Affairs, LLC. M. Han: Employee; Self; Janssen Scientific Affairs, LLC. M. Ingham: Employee; Self; Janssen Scientific Affairs, LLC..
First Assessment of the Performance of an Implantable CGM System through 180 Days in a Primarily Adolescent Population with Type 1 Diabetes
Authors: ARONSON RONNIE , RASTOGI RAVI , MDINGI COLLEEN , CHEN XIAOXIAO , TWEDEN KATHERINE
Published: June 2018

Background: An implantable continuous glucose monitoring (CGM) system (Eversense® XL, Senseonics, Maryland U.S.A) recently received CE Mark for 180-day duration in adults. The current study is the first investigation of the performance of the Eversense XL through 180 days in a primarily adolescent population with type I diabetes (T1D).

Methods: This study was a prospective, single-center, single-arm, 180-day evaluation of the effectiveness and safety of the implantable CGM system among Canadian adolescent and adult participants with T1D. Effectiveness measures included mean absolute relative difference (MARD), system agreement with Yellow Springs Instrument (YSI) glucose values, and Clarke Error Grid analysis using paired CGM and reference YSI glucose analyzer values. Adult participants were inserted with two sensors and adolescent participants were inserted with one sensor in the upper arm. CGM system accuracy studies were performed every 30 days. The safety assessment included the incidence of insertion or removal procedure-related and device-related serious adverse events (SAEs) through 180 days post-insertion.

Results: Thirty-Six participants (30 adolescent/6 adult, 13 female/23 male, mean age 17±9.2 years, mean BMI 22±4 kg/m2) received the CGM system. One subject withdrew at Day 1 due to intravenous access issues. CGM system agreement with YSI glucose within 15 mg/dL or 15% of YSI glucose values (N = 7163) through 60, 120 and 180 days was 82.9% (95% CI: 78.4%-86.1%), 83.6% (95% CI: 80.4%-85.7%) and 83.4% (95% CI: 79.7%-85.5%), respectively. Overall MARD was 9.4% (95% CI: 8.6%-10.5%). Clarke Error Grid analysis showed 99% of paired values in clinically acceptable error zones A and B. No insertion/removal or device-related SAEs were reported.

Conclusions: The Eversense XL CGM system is safe and accurate through 180 days of Sensor wear in a primarily adolescent population.

Disclosure

R. Aronson: Other Relationship; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi, AstraZeneca. Research Support; Self; Eli Lilly and Company, Becton, Dickinson and Company, Merck & Co., Inc., Senseonics, Boehringer Ingelheim Pharmaceuticals, Inc. R. Rastogi: Employee; Self; Senseonics. C. Mdingi: Employee; Self; Senseonics. X. Chen: Employee; Self; Senseonics. K. Tweden: Employee; Self; Senseonics.
The Pros and Cons of Gastric Bypass Surgery in Obese Individuals with Type 2 Diabetes—Nationwide, Matched, Observational Cohort Study
Authors: LIAKOPOULOS VASILEIOS , SVENSSON ANN-MARIE , NASLUND INGMAR , ELIASSON BJORN
Published: June 2018

Introduction: Long-term effects of gastric bypass (GBP) surgery have been presented in observational and randomized studies, but there is still only limited data for obese persons with type 2 diabetes (T2DM), in particular regarding postoperative complications. We investigated postoperative outcomes after GBP in a nation-wide cohort.

Research Design and Methods: In this observational study, we merged data from the Scandinavian Obesity Surgery Registry, the National Diabetes Register and national databases. We matched persons with type 2 diabetes who had undergone GBP with persons not surgically treated for obesity, based on sex, age, BMI and propensity score. The risks of postoperative outcomes were assessed using Cox regression model adjusted for sex, age, BMI and socioeconomic status.

Results: 5321 T2DM patients who had undergone GBP and 5321 control persons were followed for up to 9 years. We confirm lower risks of all-cause mortality (49%) and cardiovascular disease (34%), found positive effects on severe kidney disease, but also demonstrate significantly increased risks (2 to 9-fold) of several short-term complications after GBP. There were higher rates of abdominal pain and gastrointestinal conditions frequently requiring additional surgical procedures, apart from reconstructive plastic surgery. Long-term, the risk of anemia was 92% higher, malnutrition appeared approximately 3-fold more often, while psychiatric diagnoses were 33% increased, and alcohol abuse was 3-fold higher than in the control group.

Conclusions: This nation-wide study confirms the benefits but also describes the panorama of adverse events after bariatric surgery in obese persons with T2DM. In order to maximize the benefit and minimize the risk of unfavorable results after bariatric surgery, a thorough and long-term follow-up and support of these patients seems paramount. Better selection of patients for such treatment could probably also improve results.

Disclosure

V. Liakopoulos: None. A. Svensson: None. I. Naslund: Other Relationship; Self; Baricol Bariatrics AB, Sweden. B. Eliasson: Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Novo Nordisk A/S. Consultant; Self; Sanofi.
T1D and T2D Youth in the Pediatric Diabetes Consortium (PDC) Registries—Comparing Clinical Characteristics and Glycemic Control
Authors: TAMBORLANE WILLIAM V. , CHENG PEIYAO , GAL ROBIN L. , KOLLMAN CRAIG , VAN NAME MICHELLE A. , LYNCH JANE L. , NELSON BRYCE A.
Published: June 2018

Objective: To compare characteristics of youth with T1D (n = 484) vs. T2D (n = 1169) in the PDC.

Methods: Participants were 10 to <21 years at diagnosis. Mann-Whitney U and Chi-square tests were used to compare demographics. Linear regression models were used to compare BMI and HbA1c at diagnosis; logistics regression was used to compare DKA at diagnosis. Post-diagnosis HbA1c differences between cohorts were assessed through repeated measures.

Results: T2D youth were more likely to be female (62 vs. 45%, p<0.001), overweight/obese (99 vs. 16%, p<0.001) and from low income (75 vs. 30%, p<0.001), minority (82 vs. 29%, p<0.001) families. T1D youth were more likely to present with DKA (32 vs. 11%, p<0.001) and have higher mean HbA1c levels (12.0 vs. 10.0%, p<0.001) at diagnosis. More than 70% in both cohorts achieved target HbA1c levels <7.5% within 6 months but fewer T1D patients were able to maintain HbA1c target after 6 months (Figure). In 410 participants with T2D duration ≥ 24 months at enrollment, 185 (45%) required no insulin therapy; c-peptide was 1.45 mmol/l in the subset of 74 measured at enrollment.

Conclusion: While families of youth with T2D face greater socio-economic obstacles and risk factors for poor diabetes outcomes, the greater retention of residual endogenous insulin secretion likely contributes to the increased ability of T2D youth to to maintain target HbA1c levels over time.

Disclosure

W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceuticals U.S.A., Inc.. P. Cheng: None. R.L. Gal: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Development Center Americas, Inc., Novo Nordisk Inc. C. Kollman: Research Support; Self; JDRF, Bigfoot Biomedical, Dexcom, Inc., Tandem Diabetes Care, Inc., Medtronic MiniMed, Inc., Helmsley Charitable Trust. M.A. Van Name: None. J.L. Lynch: Other Relationship; Self; Novo Nordisk Inc.. Research Support; Self; Daiichi Sankyo Company, Limited. B.A. Nelson: Speaker's Bureau; Self; Dexcom, Inc..
Development of a National Minimal Set of Patient-Important Outcome Domains for Value-Based Diabetes Care in Denmark
Authors: SKOVLUND SOREN E. , TROELSEN LISE , DØMGAARD MIKALA , JAKOBSEN POUL ERIK O. , EJSKJAER NIELS
Published: June 2018

Aim: To identify a minimal set of patient-reported (PRO) domains for use in value-based diabetes care in Denmark.

Methodology: A structured mixed-methods research protocol was applied to ensure an evidence-based approach to involvement of people with diabetes in the identification of patient-centered outcome domains. 20 people with diabetes and 4 caregivers of people with diabetes selected for representativeness in age, gender, type of therapy, duration of diabetes, type of diabetes, and disease burden were recruited for qualitative research and co-creation to examine 1) psychological, physical and social impacts of diabetes and desired outcomes of treatment, 2) dis-utilities of therapy and 3) factors enabling sustainability in line with the value based care model. Qualitative research based on interviews, structured focus group and co-creation workshop sessions together with desk research on patient, clinical, health economic, and societal relevance of identified domains informed the final identification of domains by a multi-disciplinary and multi-sector working group using strict criteria of patient importance, clinical relevance and applicability, measurability and mutability.

Results: The following PRO domains were selected to complement the clinical outcome domains: Self-reported health, psychological well-being, symptom burden (e.g., sleep, sexual dysfunction, complications), multi-faceted impact of diabetes on life including diabetes distress, treatment burden and impacts of hypoglycemia, and specific indicators of care confidence, quality and diabetes self-care ability.

Conclusions: The assessment of patient-important outcomes for value based diabetes care in Denmark require the implementation of PRO questionnaires in standard diabetes care.

Disclosure

S.E. Skovlund: None. L. Troelsen: None. M. Dømgaard: None. P.O. Jakobsen: None. N. Ejskjaer: None.
Obstructive Sleep Apnea in Pediatric Type 2 Diabetes—Prevalence, Demographics, and Screening Practices
Authors: MATLOCK KRISTAL A. , GUO YUPING , KHOURY JANE C. , GURBANI NEEPA , CRIMMINS NANCY A.
Published: June 2018

Background: Managing pediatric type 2 diabetes (T2D) requires provider proficiency in addressing co-morbidities. Adults with T2D are at high risk for obstructive sleep apnea (OSA) but data is limited in children. Study aims were to 1) develop a screening process to assess OSA symptom prevalence in children with T2D and 2) characterize patients with T2D and proven OSA (confirmed by polysomnography [PSG]).

Methods: Michigan Sleep-Disordered Breathing questionnaire was implemented for patients age 8-18 years with T2D (2017). A score >0.33 defined positive screening for OSA symptoms, resulting in Sleep Medicine referral. Data collected included age, sex, race/ethnicity, duration of T2D, surgical and medication history, body mass index (BMI), blood pressure, lipid profile and hemoglobin A1c. Patients with positive screenings were followed prospectively to describe clinical course.

The same data was collected on patients with T2D and proven OSA via retrospective chart review (2010-2016). Wilcoxon rank sum or Fisher’s exact test were used to compare 1) patients with and without OSA symptoms and 2) patients with and without proven OSA.

Results: Over 10 months, 43 children with T2D completed OSA screening. Forty percent (17/43) screened positive for OSA symptoms leading to referral. Thus far, four children have completed PSG; three had OSA and 1 had primary snoring. No significant differences between youth with or without OSA symptoms were detected.

Chart review of 225 children with T2D showed 42 had PSG and 29/42 (69%) had proven OSA. Only BMI and associated z-score were significantly higher when comparing children with proven OSA to those without OSA.

Conclusion: Prevalence of OSA symptoms is high (40%) in children with T2D when routinely screened in a small cohort. Furthermore, the majority who complete PSG have proven OSA. There were no consistent factors that identified children with OSA symptoms; thus, screening all patients is crucial to prevent complications of delayed diagnosis.

Disclosure

K.A. Matlock: None. Y. Guo: None. J.C. Khoury: None. N. Gurbani: None. N.A. Crimmins: None.