Abstract
Context
Adults with type 1 diabetes (T1D) face the necessity of balancing the benefits of exercise with the potential hazards of hypoglycemia.
Objective
This work aimed to assess whether ...impaired awareness of hypoglycemia (IAH) affects exercise-associated hypoglycemia in adults with T1D.
Methods
We compared continuous glucose monitoring (CGM)-measured glucose during exercise and for 24 hours following exercise from 95 adults with T1D and IAH (Clarke score ≥4 or ≥1 severe hypoglycemic event within the past year) to 95 “aware” adults (Clarke score ≤2 and no severe hypoglycemic event within the past year) matched on sex, age, insulin delivery modality, and glycated hemoglobin A1c. A total of 4236 exercise sessions, and 1794 exercise days and 839 sedentary days, defined as 24 hours following exercise or a day without exercise, respectively, were available for analysis.
Results
Participants with IAH exhibited a nonsignificant trend toward greater decline in glucose during exercise compared to “aware” (−21 ± 44 vs −19 ± 43 mg/dL −1.17 ± 2.44 vs −1.05 ± 2.39 mmol/L, adjusted group difference of −4.2 95% CI, −8.4 to 0.05 mg/dL −0.23 95% CI, −.47 to 0.003 mmol/L; P = .051). Individuals with IAH had a higher proportion of days with hypoglycemic events below 70 mg/dL 3.89 mmol/L (≥15 minutes <70 mg/dL <3.89 mmol/L) both on exercise days (51% vs 43%; P = .006) and sedentary days (48% vs 30%; P = .001). The increased odds of experiencing a hypoglycemic event below 70 mg/dL (<3.89 mmol/L) for individuals with IAH compared to “aware” did not differ significantly between exercise and sedentary days (interaction P = .36).
Conclusion
Individuals with IAH have a higher underlying risk of hypoglycemia than “aware” individuals. Exercise does not appear to differentially increase risk for hypoglycemia during the activity, or in the subsequent 24 hours for IAH compared to aware individuals with T1D.
Prior exposure to hypoglycemia and exercise may each dampen the sympathoadrenal response to subsequent hypoglycemia, leading to impaired awareness of hypoglycemia (IAH) and increased risk for ...experiencing clinically significant hypoglycemia. Whether glucose changes during exercise differ in those with IAH vs. intact awareness of hypoglycemia (Aware) has not been assessed in a large sample of ambulatory adults with type 1 diabetes, nor is the risk for hypoglycemia events in the next 24 hours known in such individuals. Using a case-control design, we compared participants with IAH (Clarke score ≥4 or ≥1 severe hypoglycemic event SHE within the past year) to Aware participants (Clarke score of ≤2 and no SHE within the past year), matching on sex, insulin modality, baseline HbA1c, and age. The analysis cohort included 95 adults with IAH matched to 95 Aware adults (in both groups, 74% female, mean ± SD age of 43 ± 14 yr, and HbA1c of 6.5 ± 0.7%) with a total of 4,236 exercise sessions and 1,794 post-exercise and 839 sedentary days available for analysis. IAH had a trend toward a greater but not clinically significant decline in glucose during exercise compared to Aware (−21 ± 44 vs. −19 ± 43 mg/dL, adjusted group difference of −4.2 95% CI: −8.7 to 0.3 mg/dL, p=0.06). IAH had a higher proportion of hypoglycemic events (≥15 minutes <70 mg/dL) vs. Aware on both post-exercise days (51% vs. 43%, p=0.008) and sedentary days (48% vs. 30%, p=0.002). There was no evidence that the increased odds of hypoglycemia for IAH compared with Aware differed between post-exercise and sedentary days (interaction p=0.36).
In summary, participants with IAH have an overall higher baseline risk of hypoglycemia than Aware participants. However, for those with IAH exercise itself does not appear to differentially increase the risk for hypoglycemia during the activity, or in the subsequent 24 hours compared to Aware individuals with type 1 diabetes.
Disclosure
J.L. Jo Kamimoto: None. Z. Li: None. R.L. Gal: None. J.R. Castle: Research Support; Dexcom, Inc. Advisory Panel; Novo Nordisk. Stock/Shareholder; Pacific Diabetes Technologies. Advisory Panel; Zealand Pharma A/S. F.J. Doyle: Stock/Shareholder; Mode AGC. Other Relationship; Insulet Corporation, Roche Diabetes Care, Dexcom, Inc. P.G. Jacobs: Other Relationship; Pacific Diabetes Technologies. Board Member; Pacific Diabetes Technologies. Research Support; Dexcom, Inc. C.K. Martin: Research Support; Pack Health, Evidation Health, Lilly. Board Member; EHE Health, Wondr Health. Other Relationship; ABGIL. Research Support; WW International, Inc. R. Beck: Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company. Consultant; Eli Lilly and Company. Research Support; Novo Nordisk. Consultant; Novo Nordisk, Diasome, Insulet Corporation. P. Calhoun: None. M. Riddell: Stock/Shareholder; Supersapiens. Advisory Panel; Zealand Pharma A/S. Speaker's Bureau; Dexcom, Inc. Consultant; Lilly Diabetes. Speaker's Bureau; Novo Nordisk, Sanofi. Stock/Shareholder; Zucara Therapeutics. Advisory Panel; Zucara Therapeutics, Indigo Diabetes. Consultant; Eli Lilly and Company, Jaeb Center for Health Research. M.R. Rickels: Consultant; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S. Research Support; Dompé.
Funding
The Leona M. and Harry B. Helmsley Charitable Trust; Verily Life Sciences; Dexcom, Inc.
The Cornea Donor Study (CDS) showed that donor age is not a factor in survival of most penetrating keratoplasties for endothelial disease. Secondary analyses confirm the importance of surgical ...indication and presence of glaucoma in outcomes at 10 years.
To assess the relationship between donor and recipient factors and corneal graft survival in the CDS.
Multicenter prospective, double-masked, controlled clinical trial conducted at 80 clinical sites. One hundred five surgeons enrolled 1090 participants undergoing corneal transplant for a moderate-risk condition, principally Fuchs dystrophy or pseudophakic or aphakic corneal edema (PACE). Forty-three eye banks provided corneas.
Corneas from donors younger than 66 years and donors 66 years or older were assigned, masked to donor age. Surgery and postoperative care were performed according to the surgeons' usual routines. Participants were followed up for as long as 12 years.
Graft failure, defined as a regrafting procedure or a cloudy cornea for 3 consecutive months.
The 10-year cumulative probability of graft failure was higher in participants with PACE than in those with Fuchs dystrophy (37% vs 20%; hazard ratio HR, 2.1 99% CI, 1.4-3.0; P < .001) and in participants with a history of glaucoma before penetrating keratoplasty, particularly with prior glaucoma surgery (58% with prior glaucoma surgery and use of medications to lower intraocular pressure at the time of surgery vs 22% with no history of glaucoma surgery or medication use; HR, 4.1 99% CI, 2.2-7.5; P < .001). We found trends toward increased graft failure in recipients who were 70 years or older compared with those younger than 60 years (29% vs 19%; HR, 1.2 99% CI, 0.7-2.1; P = .04) or were African American (HR, 1.5; P = .11) or who had a history of smoking (35% vs 24%; HR, 1.6 99% CI, 0.9-2.8; P = .02). Lower endothelial cell density (ECD) and higher corneal thickness (CT) at 6 months (6% vs 41% for ECD ≥2700 vs <1700 cells/mm2 P < .001; 14% vs 36% for CT <500 vs ≥600 μm P = .001), 1 year (4% vs 39% for ECD ≥2700 vs <1700 cells/mm2 P < .001; 18% vs 28% for CT <500 vs ≥600 μm P = .04), and 5 years (2% vs 29% for ECD ≥1500 vs <500 cells/mm2 P < .001; 7% vs 34% for CT <550 vs ≥650 μm P < .001) were associated with subsequent graft failure.
Most penetrating corneal grafts for Fuchs dystrophy or PACE remain clear at 10 years. The risk for failure is greater for graft recipients with PACE and those with a history of glaucoma. Measurements of ECD and CT during the course of postkeratoplasty follow-up are associated with a risk for failure. However, even with very low ECD and high CT at 5 years, most corneas remain clear at 10 years.
Nocturnal hypoglycemia is a known challenge for people with type 1 diabetes, especially for physically active individuals or those on multiple daily injections. We developed an evidential neural ...network (ENN) to predict at bedtime the probability and timing of nocturnal hypoglycemia (0-4 vs 4-8 h after bedtime) based on several glucose metrics and physical activity patterns. We utilized these predictions in silico to prescribe bedtime carbohydrates with a Smart Snack intervention specific to the predicted minimum nocturnal glucose and timing of nocturnal hypoglycemia.
We leveraged free-living datasets collected from 366 individuals from the T1DEXI Study and Glooko. Inputs to the ENN used to model nocturnal hypoglycemia were derived from demographic information, continuous glucose monitoring, and physical activity data. We assessed the accuracy of the ENN using area under the receiver operating curve, and the clinical impact of the Smart Snack intervention through simulations.
The ENN achieved an area under the receiver operating curve of 0.80 and 0.71 to predict nocturnal hypoglycemic events during 0-4 and 4-8 h after bedtime, respectively, outperforming all evaluated baseline methods. Use of the Smart Snack intervention reduced probability of nocturnal hypoglycemia from 23.9 ± 14.1% to 14.0 ± 13.3% and duration from 7.4 ± 7.0% to 2.4 ± 3.3% in silico.
Our findings indicate that the ENN-based Smart Snack intervention has the potential to significantly reduce the frequency and duration of nocturnal hypoglycemic events.
A decision support system that combines prediction of minimum nocturnal glucose and proactive recommendations for bedtime carbohydrate intake might effectively prevent nocturnal hypoglycemia and reduce the burden of glycemic self-management.
See also Watson HG. RVO – Real value obscure. This issue, pp 1116–8; Le Gal G, Carrier M, Kovacs MJ, Betancourt MT, Kahn SR, Wells PS, Anderson DA, Chagnon I, Solymoss S, Crowther M, Righini M, ...Delluc A, White RH, Vickars L, Rodger M. Residual vein obstruction as a predictor for recurrent thromboembolic events after a first unprovoked episode: data from the REVERSE cohort study. This issue, pp 1126–32.
Summary. Background: Residual vein obstruction (RVO) detected on compression ultrasonography of the leg after a few months of anticoagulation therapy might be able to identify patients with deep vein thrombosis (DVT) at high risk of having a recurrent venous thromboembolism (VTE). Aim: To determine whether RVO is associated with an increased risk of recurrent events in patients with DVT. Patients and Methods: A systematic literature search strategy was conducted using MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials. We selected 14 articles (nine prospective cohort studies and five randomized controlled trials) that included patients with DVT who had an assessment for RVO with the use of compression ultrasonography. Two reviewers independently extracted data onto standardized forms. Results: Overall, the presence of RVO was not associated with an increased risk of recurrent VTE (odds ratio OR 1.24, 95% confidence interval CI 0.9–1.7) in patients with unprovoked DVT who stopped oral anticoagulation therapy at the time of RVO assessment. However, RVO was significantly associated with recurrent VTE in patients with any (unprovoked or provoked) DVT (OR 1.5, 95% CI 1.1–2.0). Conclusions: RVO was associated with a modestly increased risk of recurrent VTE in patients with DVT (unprovoked and provoked). However, RVO did not seem to be a predictor of recurrent VTE in patients with unprovoked DVT following anticoagulation discontinuation. Further prospective studies are needed to assess the role of RVO in patients with unprovoked DVT.
The impact of a telemedicine model for a virtual diabetes clinic was assessed 6 months following completion of a 6-month intervention of education and support for diabetes self-management, including ...initiation and use of CGM. One hundred and sixty-one participants ≥18 years old with T1D (N=109) or T2D (N=52) using MDI/pump participated in the 12-month study. At the end of the 6-month intervention period, mean HbA1c decreased from 7.6% at baseline to 7.0% in T1D and from 8.1% to 7.0% in T2D (P<0.001). At 12 months (6 months after discontinuation of the intervention), mean HbA1c was 7.0% for T1D and 7.2% for T2D (P<0.001 compared with baseline). Mean time in range 70-180 mg/dL was 51% at baseline, increasing to 62% at 6 months (P<0.001) and 64% at 12 months in T1D (P<0.001) and from 49% to 66% (P<0.001) and 68% (P<0.001), respectively, in T2D. Similar improvements were observed for mean glucose and hyperglycemia metrics. A sustained reduction in hypoglycemia also was observed. The virtual diabetes clinic intervention was successful in promoting improved glycemic outcomes, which were sustained 6 months after the intervention was completed. These findings demonstrate the impact that virtual care and education can have on self-management over time and provide opportunity to expand care models that could minimize barriers to specialty care access.
Disclosure
R. L. Gal: None. S. Oser: Advisory Panel; Cecelia Health, Dexcom, Inc., Consultant; Medscape, Research Support; Abbott Diabetes. T. Oser: Advisory Panel; Cecelia Health, Consultant; Dexcom, Inc., Medscape, Research Support; Abbott. K. K. Hood: Consultant; Cecelia Health. T. L. Cushman: None. M. L. Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research. C. Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. R. Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. D. Raghinaru: None. G. Aleppo: Advisory Panel; Medscape, Consultant; Bayer Inc., Insulet Corporation, Research Support; Dexcom, Inc., Eli Lilly and Company, Emmes, Insulet Corporation, Fractyl Health, Inc., WellDoc, Speaker's Bureau; Dexcom, Inc. B. A. Olson: Stock/Shareholder; Abbott. D. F. Kruger: Advisory Panel; Abbott Diabetes, Lilly, Medtronic, Novo Nordisk, Research Support; Dexcom, Inc., Beta Bionics, Inc., Speaker's Bureau; Dexcom, Inc., Lilly, Xeris Pharmaceuticals, Inc., Novo Nordisk. R. M. Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. R. S. Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. A. Bradshaw: None. T. S. Mcarthur: None.
The Virtual Diabetes Specialty Clinic (VDiSC) provided type 1 (T1D) and type 2 diabetes (T2D) adults taking insulin virtual care with remote CGM training and support. HbA1c improved from baseline to ...6 months in T1D (7.8% to 7.0%) and T2D (8.2% to 7.0%) with increased time in range (70-180 mg/dL; TIR). Here we compare glycemic outcomes (Table 1) and duration of remote CGM training visits (Table 2) in adults ages <40 yr, 40-59 yr and ≥ 60 yr. HbA1c and %TIR improved in each group. Limitations include a small sample size that was mostly White. Results suggest that both T1D and T2D adults ≥60 years of age experience glycemic benefit after remote training and support in the use of CGM from CDCESs, but when compared to young adults, older adults require more time for training. Support for approaches that address the individual needs of older adults with diabetes is required.
Disclosure
R.S.Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. T.S.Mcarthur: None. B.A.Olson: Stock/Shareholder; Abbott. S.Oser: Advisory Panel; Cecelia Health, Dexcom, Inc., Consultant; Medscape, Research Support; Abbott Diabetes. T.Oser: Advisory Panel; Cecelia Health, Consultant; Dexcom, Inc., Medscape, Research Support; Abbott. D.Raghinaru: None. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. G.Aleppo: Advisory Panel; Medscape, Consultant; Bayer Inc., Insulet Corporation, Research Support; Dexcom, Inc., Eli Lilly and Company, Emmes, Insulet Corporation, Fractyl Health, Inc., WellDoc, Speaker's Bureau; Dexcom, Inc. Z.Thompson: None. R.M.Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. T.L.Cushman: None. R.L.Gal: None. C.Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. D.F.Kruger: Advisory Panel; Abbott Diabetes, Lilly, Medtronic, Novo Nordisk, Research Support; Dexcom, Inc., Beta Bionics, Inc., Speaker's Bureau; Dexcom, Inc., Lilly, Xeris Pharmaceuticals, Inc., Novo Nordisk. K.K.Hood: Consultant; Cecelia Health. M.L.Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research.
Funding
The Leona M. and Harry B. Helmsley Charitable Trust; Dexcom, Inc.
Behavioral health support can benefit those living with diabetes, but there is limited information on patient reported outcomes (PROs) associated with a virtual clinic. Adults with diabetes (n=234) ...received virtual care including support for CGM initiation and management over a 6-month study period. Care was led by a CDCES with support from a behavioral team. Participants completed PROs surveys 1) at baseline and 6 months to evaluate change and 2) each month on diabetes distress (DD), fear of hypoglycemia (FOH), and depression (DEP). Full list of PROs surveys included in table. A positive screen led to recommendation for a brief behavioral intervention. Participants with T1D (n=160) were 44(±14) years and mean baseline A1c of 7.8%. Participants with T2D (n=74) were 55(±12) years and mean baseline A1c of 8.1%. Participants screened positive for DD, FOH, or DEP 67% of the time with FOH as the most common concern. Of those with a positive screen, 70% of T1D and 59% of T2D participants had at least one behavioral team contact. Virtual clinic care was associated with a benefit on 7 of 9 PROs for T1D and 7 of 9 PROs for T2D (p values < 0.05; see table). For these virtual clinic adults with diabetes, PROs improved 78% of the time with noteworthy benefits of less FOH, less DD, and more glucose monitoring satisfaction. Paired with the glycemic improvements observed in this virtual clinic study, there were robust benefits on the quality of life of adults with diabetes.
Disclosure
K.K.Hood: Consultant; Cecelia Health. S.Oser: Advisory Panel; Cecelia Health, Dexcom, Inc., Consultant; Medscape, Research Support; Abbott Diabetes. T.Oser: Advisory Panel; Cecelia Health, Consultant; Dexcom, Inc., Medscape, Research Support; Abbott. D.Raghinaru: None. Z.Thompson: None. R.S.Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. G.Aleppo: Advisory Panel; Medscape, Consultant; Bayer Inc., Insulet Corporation, Research Support; Dexcom, Inc., Eli Lilly and Company, Emmes, Insulet Corporation, Fractyl Health, Inc., WellDoc, Speaker's Bureau; Dexcom, Inc. R.M.Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. T.L.Cushman: None. R.L.Gal: None. C.Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. D.F.Kruger: Advisory Panel; Abbott Diabetes, Lilly, Medtronic, Novo Nordisk, Research Support; Dexcom, Inc., Beta Bionics, Inc., Speaker's Bureau; Dexcom, Inc., Lilly, Xeris Pharmaceuticals, Inc., Novo Nordisk. M.L.Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research. T.S.Mcarthur: None. B.A.Olson: Stock/Shareholder; Abbott.
Funding
The Leona M. and Harry B. Helmsley Charitable Trust; Dexcom, Inc.
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