Introduction: Obstructive sleep apnea (OSA) is a prevalent sleep disorder linked to high type 2 diabetes risk. Positive airway pressure (PAP) therapy is the standard of care for OSA, but it inconsistently improves glucose homeostasis. Senescent cells are common in adipose tissue (AT) of patients with OSA and may impair insulin signaling. However, the effects of PAP therapy on AT senescence are not known. Addition of metformin, an insulin-sensitizer with anti-senescent effects, may be a good adjuvant therapeutic strategy to improve glycemic control in patients with OSA. Methods: We randomly assigned 16 nondiabetic participants with OSA (Mean± SD; age: 50.9 ± 6.7 y, BMI: 36.5 ± 2.9 kg/m2) in a 1:1 ratio to receive either 2g metformin or placebo daily along with PAP therapy for 3 months in a double-blind pilot study. Whole body and AT insulin sensitivity was determined by 2h oral glucose tolerance test (OGTT). AT biopsy was obtained to estimate tissue insulin signaling and senescence. Results: The metformin and placebo groups had comparable age, BMI and OSA severity at baseline. PAP compliance was 38% and 75% in the metformin and placebo groups, respectively. Matsuda Index, glucose area under the curve (2h AUC), and free-fatty acid suppression at baseline and follow-up were not different in metformin or placebo treated groups. Compared to baseline, insulin AUC and insulin to glucose AUC ratio during OGTT was unchanged in the metformin but increased in the placebo group. Metformin, but not placebo, was associated with increased insulin mediated AKT phosphorylation and decreased senescence biomarkers (p21 and MCP1) in AT during the follow-up visit. Conclusion: Metformin, as adjunct to PAP therapy, attenuated insulin rises during OGTT, improved AT insulin signaling, and lowered senescence biomarkers in OSA patients. Larger trials of longer treatment duration are needed to determine if metformin can prevent diabetes in OSA patients. Disclosure S. Rodrigues: None. W.S. Dantas: None. R.A. Beyl: None. R.C. Hebert: None. I. Griffith: None. M. Tanksley: None. E.C. Mader: None. J.P. Kirwan: None. C.L. Axelrod: None. E. Ravussin: Research Support; Eli Lilly and Company, Novartis AG. Advisory Panel; Novartis. P. Singh: None. Funding National Institutes of Health (P30DK072476, U54GM104940); CAPES (88887.470405/2019-00 to S.R.)
The transition period from pediatric to adult care is associated with worsening glycemic control and poor attendance with adult providers, which has only been complicated by the COVID-19 pandemic. Diabetes transition clinics and model programs may improve outcomes, but they remain few in number and underutilized. The aim of our cross-sectional, retrospective study was to compare diabetes control in our diabetes transition clinic (DTC) patients versus those who remained in pediatric endocrine care (non-DTC) over a 5 year period. A random sample of 82 patients ages 16 to 25 years seen in clinic from 9/11/2017 to 9/10/2022 were included. Each patient had at least one visit before and after 3/11/2020, when COVID-19 was declared a global pandemic. Those who attended DTC were similar to the non-DTC group except for insurance status (Table). The DTC group had a mean HbA1c of 8.8% vs. 9.0% (p=0.80) and a mean of 4.1 vs. 3.8 visits (p=0.69); whereas, the non-DTC group had a mean HbA1c of 10% vs. 9.6% (p=0.27) and a mean of 5.2 vs. 4.2 visits (p=0.19) before versus after 3/11/2020. Telehealth visits consisted of 15.7% of the visits in the DTC group versus 13.3% in the non-DTC group after 3/11/2020 (p=0.56). Despite the challenges of the COVID-19 pandemic, patients who moved to DTC during this time maintained glycemic control and continued to attend clinic visits consistently similar to those who remained in pediatric endocrine care. Disclosure D. S. Hsia: None. R. A. Beyl: None. R. Rumsey: None. Funding National Institute of General Medical Sciences (U54GM104940)
Background: Clinical weight loss interventions improve glycemic control in adults with type 2 diabetes (T2D) , but are costly and have limited accessibility. The objective of this trial was to test the efficacy of a diabetes-tailored widely available weight management program (WW, formerly Weight Watchers) on glycemic control in adults with T2D. Methods: This was a prospective 24-week single arm, three-site clinical trial. Participants (n= 136) had T2D, a baseline HbA1c between 7-11%, and a BMI between 27-50 kg/m2. All participants received the 24-wk intervention, which consisted of the WW digital + workshop program tailored for people with T2D, and included weekly virtual workshops and use of the WW App. Assessments occurred at baseline, wk 12 (83.8% retention) , and wk 24 (83.1%) . Primary outcome was change in HbA1c at 24 weeks. Secondary endpoints were changes in body weight and the Diabetes Distress Scale (DDS) . Generalized linear effects models were used for statistical analysis (MAR) and used an intent-to-treat analysis. Results: Participants were 56.8 ± 0.8 y (Mean ± SEM) , 80.2% Female, 62.2% non-Hispanic white. Baseline BMI was 36.2±0.6 kg/m2. Baseline HbA1c, weight, and total DDS score were 7.9±0.1%, 104.3±1.8 kg, and 2.2±0.1, respectively. HbA1c decreased 0.6±0.1% at wk 12 and 0.8±0.1% at wk 24 (both p <.0001) . Body weight decreased 4.6±0.5% at wk 12 and 5.7±0.5% at wk 24 (both p <.0001) . Total DDS score decreased 0.2±0.1 at wk 12 and 0.3±0.1 at wk 24 (both p <.0001) . Conclusions: The widely available WW program, modified for those with T2D, had favorable and clinically meaningful effects on glycemic control, body weight, and diabetes distress at 12 and 24 weeks. Disclosure J.W.Apolzan: Research Support; Mizkan Holdings, LLC , WW International, Inc. T.Bullard: Employee; WW International, Inc. G.D.Foster: Employee; WW International, Inc. M.Cardel: Employee; WW International, Inc. J.G.Larose: Research Support; WW International, Inc. S.D.Anton: None. R.A.Beyl: None. F.L.Greenway: Advisory Panel; General Nutrition Corporation, Jenny Craig, NovMeta Pharma, Nutraceutical Corporation, Pfizer Inc., Plensat, UR Labs, Consultant; Basic Research, Dr. Reddy’s Laboratories Ltd., Energesis, Gedeon Richter, Jazz Pharmaceuticals, Rejuvenate Bio, Other Relationship; Academic Technology Ventures, Inc., Melior Discoveries, Stock/Shareholder; Energesis, Ketogenic Health Systems, NovMeta Pharma, Plensat, Rejuvenate Bio, Slim Health Nutrition, UR Labs. E.P.Wickham: Board Member; American Board on Obesity Medicine, Research Support; National Institutes of Health, WW International, Inc. A.Lanoye: Research Support; WW International, Inc. M.N.Harris: None. A.Kaufman: Employee; WW International. Funding WW International, Inc.
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