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Objective:  Individuals with type 1 diabetes (T1D) have increased risk for cognitive dysfunction and high rates of sleep disturbance. Despite associations between glycemia and cognitive performance using cross-sectional and experimental methods few studies have evaluated this relationship in a naturalistic setting, or the impact of nocturnal versus daytime hypoglycemia. Ecological Momentary Assessment (EMA) may provide insight into the dynamic associations between cognition, affective, and physiological states. The current study couples EMA data with continuous glucose monitoring (CGM) to examine the within-person impact of nocturnal glycemia on next day cognitive performance in adults with T1D. Due to high rates of sleep disturbance and emotional distress in people with T1D, the potential impacts of sleep characteristics and negative affect were also evaluated., Methods:  This pilot study utilized EMA in 18 adults with T1D to examine the impact of glycemic excursions, measured using CGM, on cognitive performance, measured via mobile cognitive assessment using the TestMyBrain platform. Multilevel modeling was used to test the within-person effects of nocturnal hypoglycemia and hyperglycemia on next day cognition., Results:  Results indicated that increases in nocturnal hypoglycemia were associated with slower next day processing speed. This association was not significantly attenuated by negative affect, sleepiness, or sleep quality., Conclusions:  These results, while preliminary due to small sample size, showcase the power of intensive longitudinal designs using ambulatory cognitive assessment to uncover novel determinants of cognitive fluctuation in real world settings, an approach that may be utilized in other populations. Findings suggest reducing nocturnal hypoglycemia may improve cognition in adults with T1D.

Background: The Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) study demonstrated continuous glucose monitoring (CGM) reduced hypoglycemia over 6 months among older adults with type 1 diabetes (T1D) compared with blood glucose monitoring (BGM). We explored heterogeneous treatment effects of CGM on hypoglycemia by formulating a data-driven decision rule that selects an intervention (ie, CGM vs BGM) to minimize percentage of time <70 mg/dL for each individual WISDM participant., Method: The precision medicine analyses used data from participants with complete data (n = 194 older adults, including those who received CGM [n = 100] and BGM [n = 94] in the trial). Policy tree and decision list algorithms were fit with 14 baseline demographic, clinical, and laboratory measures. The primary outcome was CGM-measured percentage of time spent in hypoglycemic range (<70 mg/dL), and the decision rule assigned participants to a subgroup reflecting the treatment estimated to minimize this outcome across all follow-up visits., Results: The optimal decision rule was found to be a decision list with 3 steps. The first step moved WISDM participants with baseline time-below range >1.35% and no detectable C-peptide levels to the CGM subgroup (n = 139), and the second step moved WISDM participants with a baseline time-below range of >6.45% to the CGM subgroup (n = 18). The remaining participants (n = 37) were left in the BGM subgroup. Compared with the BGM subgroup (n = 37; 19%), the group for whom CGM minimized hypoglycemia (n = 157; 81%) had more baseline hypoglycemia, a lower proportion of detectable C-peptide, higher glycemic variability, longer disease duration, and higher proportion of insulin pump use., Conclusions: The decision rule underscores the benefits of CGM for older adults to reduce hypoglycemia. Diagnostic CGM and laboratory markers may inform decision-making surrounding therapeutic CGM and identify older adults for whom CGM may be a critical intervention to reduce hypoglycemia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RSW participated in multicenter clinical trials through her institution, sponsored by Insulet, Medtronic, Eli Lilly, Novo Nordisk, and Boehringer Ingelheim, and has used donated DexCom CGMs in projects sponsored by NIH and the Leona M. and Harry B. Helmsley Charitable Trust. KMM has used donated DexCom CGMs in projects sponsored by NIH and the Leona M. and Harry B. Helmsley Charitable Trust. REP reports consulting fees from Bayer AG, Corcept Therapeutics Incorporated, DexCom, Hanmi Pharmaceutical Co., Merck, Novo Nordisk, Pfizer, Sanofi, Scohia Pharma Inc., and Sun Pharmaceutical Industries, and grants/research support from Hanmi Pharmaceutical Co., Janssen, Metavention, Novo Nordisk, Poxel SA, and Sanofi. All funds are paid directly to Dr Pratley’s employer, AdventHealth, a nonprofit organization that supports education and research.

Introduction: Severe hypoglycemia (SH) in older adults (OAs) with type 1 diabetes is associated with profound morbidity and mortality, yet its etiology can be complex and multifactorial. Enhanced tools to identify OAs who are at high risk for SH are needed. This study used machine learning to identify characteristics that distinguish those with and without recent SH, selecting from a range of demographic and clinical, behavioral and lifestyle, and neurocognitive characteristics, along with continuous glucose monitoring (CGM) measures., Research Design and Methods: Data from a case-control study involving OAs recruited from the T1D Exchange Clinical Network were analyzed. The random forest machine learning algorithm was used to elucidate the characteristics associated with case versus control status and their relative importance. Models with successively rich characteristic sets were examined to systematically incorporate each domain of possible risk characteristics., Results: Data from 191 OAs with type 1 diabetes (47.1% female, 92.1% non-Hispanic white) were analyzed. Across models, hypoglycemia unawareness was the top characteristic associated with SH history. For the model with the richest input data, the most important characteristics, in descending order, were hypoglycemia unawareness, hypoglycemia fear, coefficient of variation from CGM, % time blood glucose below 70 mg/dL, and trail making test B score., Conclusions: Machine learning may augment risk stratification for OAs by identifying key characteristics associated with SH. Prospective studies are needed to identify the predictive performance of these risk characteristics., Competing Interests: Competing interests: RW participated in multicenter clinical trials through her institution, sponsored by Insulet, Medtronic, Eli Lilly, Novo Nordisk, and Boehringer Ingelheim, and has used donated DexCom CGMs and Tandem insulin pumps in projects sponsored by the NIH and the Leona M and Harry B Helmsley Charitable Trust., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Continuous glucose monitoring (CGM) can reduce hypoglycemia in older adults with type 1 diabetes (T1D). We aimed to characterize factors that influence effective use in this age group., Methods: Older adults with type T1D (age ≥ 65) and their caregivers participated in one of a series of parallel group model building workshops, a participatory approach to system dynamics involving drawing and scripted group activities. Data were synthesized in a qualitative model of the hypothesized system of factors producing distinct patterns of CGM use in older adults. The model was validated through virtual follow-up interviews., Results: Data were collected from 33 participants (four patient-caregiver dyads, mean age 73.8 ± 4.4 years [range 66-85 years]; 16 % non-CGM users, 79 % pump users). The system model delineates drivers of CGM uptake, drivers of ongoing CGM use, and feedback loops that either reinforce or counteract future CGM use. Participants emphasized the importance of different sets of feedback loops at different points in the duration of CGM use., Conclusions: The holistic system model underscores that factors and feedback loops driving effective CGM use in older adults are both individualized and dynamic (e.g., changing over time), suggesting opportunities for staged and tailored age-specific education and support., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: To investigate whether an increased bolus: basal insulin ratio (BBR) with liver-targeted bolus insulin (BoI) would increase BoI use and decrease hypoglycaemic events (HEv)., Patient Population and Methods: We enrolled 52 persons (HbA1c 6.9% ± 0.12%, mean ± SEM) with type 1 diabetes using multiple daily injections. Hepatic-directed vesicle (HDV) was used to deliver 1% of peripheral injected BoI to the liver. A 90-day run-in period was used to introduce subjects to unblinded continuous glucose monitoring and optimize standard basal insulin (BaI) (degludec) and BoI (lispro) dosing. At 90 days, BoI was changed to HDV-insulin lispro and subjects were randomized to an immediate 10% or 40% decrease in BaI dose., Results: At 90 days postrandomization, total insulin dosing was increased by ~7% in both cohorts. The -10% and -40% BaI cohorts were on 7.7% and 13% greater BoI with 6.9% and 30% (P = .02) increases in BBR, respectively. Compared with baseline at randomization, nocturnal level 2 HEv were reduced by 21% and 43%, with 54% and 59% reductions in patient-reported HEv in the -10% and -40% BaI cohorts, respectively., Conclusions: Our study shows that liver-targeted BoI safely decreases HEv and symptoms without compromising glucose control. We further show that with initiation of liver-targeted BoI, the BBR can be safely increased by significantly lowering BaI dosing, leading to greater BoI usage., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: To evaluate glycemic outcomes in the Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) randomized clinical trial (RCT) participants during an observational extension phase. Research Design and Methods: WISDM RCT was a 26-week RCT comparing continuous glucose monitoring (CGM) with blood glucose monitoring (BGM) in 203 adults aged ≥60 years with type 1 diabetes. Of the 198 participants who completed the RCT, 100 (98%) CGM group participants continued CGM (CGM-CGM cohort) and 94 (98%) BGM group participants initiated CGM (BGM-CGM cohort) for an additional 26 weeks. Results: CGM was used a median of >90% of the time at 52 weeks in both cohorts. In the CGM-CGM cohort, median time <70 mg/dL decreased from 5.0% at baseline to 2.6% at 26 weeks and remained stable with a median of 2.8% at 52 weeks ( P  < 0.001 baseline to 52 weeks). Participants spent more time in range 70-180 mg/dL (TIR) (mean 56% vs. 64%; P  < 0.001) and had lower hemoglobin A1c (HbA1c) (mean 7.6% [59 mmol/mol] vs. 7.4% [57 mmol/mol]; P  = 0.01) from baseline to 52 weeks. In BGM-CGM, from 26 to 52 weeks median time <70 mg/dL decreased from 3.9% to 1.9% ( P  < 0.001), TIR increased from 56% to 60% ( P  = 0.006) and HbA1c decreased from 7.5% (58 mmol/mol) to 7.3% (57 mmol/mol) ( P  = 0.025). In BGM-CGM, a severe hypoglycemic event was reported for nine participants while using BGM during the RCT and for two participants during the extension phase with CGM ( P  = 0.02). Conclusions: CGM use reduced hypoglycemia without increasing hyperglycemia in older adults with type 1 diabetes. These data provide further evidence for fully integrating CGM into clinical practice. Clinicaltrials.gov (NCT03240432).

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes., Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes., Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes., Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100)., Main Outcomes and Measures: The primary outcome was CGM-measured percentage of time that sensor glucose values were less than 70 mg/dL during 6 months of follow-up. There were 31 prespecified secondary outcomes, including additional CGM metrics for hypoglycemia, hyperglycemia, and glucose control; hemoglobin A1c (HbA1c); and cognition and patient-reported outcomes, with adjustment for multiple comparisons to control for false-discovery rate., Results: Of the 203 participants (median age, 68 [interquartile range {IQR}, 65-71] years; median type 1 diabetes duration, 36 [IQR, 25-48] years; 52% female; 53% insulin pump use; mean HbA1c, 7.5% [SD, 0.9%]), 83% used CGM at least 6 days per week during month 6. Median time with glucose levels less than 70 mg/dL was 5.1% (73 minutes per day) at baseline and 2.7% (39 minutes per day) during follow-up in the CGM group vs 4.7% (68 minutes per day) and 4.9% (70 minutes per day), respectively, in the standard BGM group (adjusted treatment difference, -1.9% (-27 minutes per day); 95% CI, -2.8% to -1.1% [-40 to -16 minutes per day]; P <.001). Of the 31 prespecified secondary end points, there were statistically significant differences for all 9 CGM metrics, 6 of 7 HbA1c outcomes, and none of the 15 cognitive and patient-reported outcomes. Mean HbA1c decreased in the CGM group compared with the standard BGM group (adjusted group difference, -0.3%; 95% CI, -0.4% to -0.1%; P <.001). The most commonly reported adverse events using CGM and standard BGM, respectively, were severe hypoglycemia (1 and 10), fractures (5 and 1), falls (4 and 3), and emergency department visits (6 and 8)., Conclusions and Relevance: Among adults aged 60 years or older with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in hypoglycemia over 6 months. Further research is needed to understand the long-term clinical benefit., Trial Registration: ClinicalTrials.gov Identifier: NCT03240432.

Context: Use of continuous glucose monitoring (CGM) is increasing for insulin-requiring patients with diabetes. Although data on glycemic profiles of healthy, nondiabetic individuals exist for older sensors, assessment of glycemic metrics with new-generation CGM devices is lacking., Objective: To establish reference sensor glucose ranges in healthy, nondiabetic individuals across different age groups using a current generation CGM sensor., Design: Multicenter, prospective study., Setting: Twelve centers within the T1D Exchange Clinic Network., Patients or Participants: Nonpregnant, healthy, nondiabetic children and adults (age ≥6 years) with nonobese body mass index., Intervention: Each participant wore a blinded Dexcom G6 CGM, with once-daily calibration, for up to 10 days., Main Outcome Measures: CGM metrics of mean glucose, hyperglycemia, hypoglycemia, and glycemic variability., Results: A total of 153 participants (age 7 to 80 years) were included in the analyses. Mean average glucose was 98 to 99 mg/dL (5.4 to 5.5 mmol/L) for all age groups except those over 60 years, in whom mean average glucose was 104 mg/dL (5.8 mmol/L). The median time between 70 to 140 mg/dL (3.9 to 7.8 mmol/L) was 96% (interquartile range, 93 to 98). Mean within-individual coefficient of variation was 17 ± 3%. Median time spent with glucose levels >140 mg/dL was 2.1% (30 min/d), and median time spent with glucose levels <70 mg/dL (3.9 mmol/L) was 1.1% (15 min/d)., Conclusion: By assessing across age groups in a healthy, nondiabetic population, normative sensor glucose data have been derived and will be useful as a benchmark for future research studies., (Copyright © 2019 Endocrine Society.)

Background: Hypoglycemia and hypoglycemia unawareness are common in long-standing type 1 diabetes (T1D). This pilot study examined the real-world use of a smartphone application (app), which receives meter readings and logs hypoglycemic symptoms, causes, and treatments to reduce hypoglycemia., Methods: Adults with T1D and recent hypoglycemia synchronized their glucose meter to their smartphone and used the Joslin HypoMap™ app powered by Glooko to track hypoglycemic events. At baseline, and after 6 and 12 weeks of using the app, a blinded continuous glucose monitor (CGM; Dexcom G4) was used for 2 weeks and surveys administered., Results: Participants (n = 22) at baseline had mean (SD) age 43 (14) years, duration of diabetes 26 (13) years, A1c 8.0% (0.87) and 21/22 had reduced hypoglycemia awareness per Clarke Hypoglycemia Unawareness survey scores; 13 (59%) were "CGM completers" (CGM data available at baseline and follow-up). Most noncompletion related to time required/difficulties using the mobile app. After 6 weeks, 8/13 completers (62% of CGM completers, 36% of total participants) had reduced daytime minutes with glucose <54 mg/dL (mean ↓331 minutes) and 10/13 (77% of CGM completers; 45% of total participants) had reduced time ≤ 70 mg/dL (mean ↓449 minutes). This was not sustained at 12 weeks, at which time half of the completers had less time ("improved"). Five participants reported improved hypoglycemia awareness; 9 stated the app helped them better recognize hypoglycemia., Conclusions: Use of this phone app has the potential to help reduce daytime hypoglycemia in a subset of T1D adults with reduce hypoglycemia awareness; larger studies are needed.

Context: Standard treatment of hypoglycemia is oral carbohydrate, but it often results in hyperglycemia and entails extra caloric intake., Objective: To evaluate low-dose glucagon to treat mild hypoglycemia in ambulatory adults with type 1 diabetes (T1D)., Design: Randomized crossover trial (two 3-week periods)., Setting: Five U.S. diabetes clinics., Patients: Twenty adults with T1D using an insulin pump and continuous glucose monitor (CGM) and experiencing frequent mild hypoglycemia., Intervention: Nonaqueous mini-dose glucagon (MDG) (150 µg) to treat nonsevere hypoglycemia., Main Outcome Measures: Successful treatment was defined as blood glucose (BG) ≥50 mg/dL 15 minutes and ≥70 mg/dL 30 minutes after intervention, on the study meter. Two authors, blinded to treatment arm, independently judged each event as a clinical success or failure., Results: Sixteen participants (mean age 39 years, 75% female, mean diabetes duration 23 years, mean hemoglobin A1c 7.2%) had 118 analyzable events with initial BG of 50 to 69 mg/dL. Successful treatment criteria were met for 58 (94%) of 62 events during the MDG period and 53 (95%) of 56 events during the glucose tablets (TABS) period (adjusted P = 0.99). Clinical assessments of success for these events were 97% and 96%, respectively. CGM-measured time in range did not differ between treatment groups during the 2 hours after events, but TABS resulted in higher maximum glucose (116 vs 102 mg/dL; P = 0.01) over the first hour., Conclusions: Low-dose glucagon can successfully treat mild hypoglycemia and may be a useful alternative to treatment with oral carbohydrate when trying to avoid unnecessary caloric intake., (Copyright © 2017 Endocrine Society)

Background: Hypoglycemia is a major concern in older adults with type 1 diabetes (T1D) and there is limited knowledge in this population. We examined data from 199 adults, ≥60 years of age, who participated in a T1D Exchange study assessing factors associated with severe hypoglycemia (SH) in older adults with T1D: 100 with SH in the prior year and 99 with no SH in prior 3 years (mean age 68; mean diabetes duration 40 years; 47% female; 92% non-Hispanic white). Hypoglycemia was assessed with up to 14 days of blinded continuous glucose monitoring (CGM). Linear regression models were performed to assess the association between biochemical hypoglycemia [defined as percentage of time below specific cutoffs (<70/60/50 mg/dL)] and various factors., Results: Overall, participants had CGM values <70 mg/dL for a median of 91 min per day. On 53% of days, glucose levels continuously were <70 mg/dL for ≥20 min. Hypoglycemia was found to be strongly associated with glucose variability (r = 0.76; P < 0.001). Time spent in hypoglycemia was greater in those who were younger (P = 0.004), had shorter diabetes duration (P = 0.008), lower HbA1c (P < 0.001), and undetectable C-peptide (P = 0.001), but did not differ by insulin method, education level, number of blood glucose checks per day, cognition, activities of daily living, or fear of hypoglycemia., Innovation: This study adds valuable data on the frequency of hypoglycemia in older adults with T1D., Conclusion: Future studies need to focus on how to prevent hypoglycemia in this vulnerable population of older adults with long-standing T1D.

Objective: Severe hypoglycemia is common in older adults with long-standing type 1 diabetes, but little is known about factors associated with its occurrence., Research Design and Methods: A case-control study was conducted at 18 diabetes centers in the T1D Exchange Clinic Network. Participants were ≥60 years old with type 1 diabetes for ≥20 years. Case subjects (n = 101) had at least one severe hypoglycemic event in the prior 12 months. Control subjects (n = 100), frequency-matched to case subjects by age, had no severe hypoglycemia in the prior 3 years. Data were analyzed for cognitive and functional abilities, social support, depression, hypoglycemia unawareness, various aspects of diabetes management, C-peptide level, glycated hemoglobin level, and blinded continuous glucose monitoring (CGM) metrics., Results: Glycated hemoglobin (mean 7.8% vs. 7.7%) and CGM-measured mean glucose (175 vs. 175 mg/dL) were similar between case and control subjects. More case than control subjects had hypoglycemia unawareness: only 11% of case subjects compared with 43% of control subjects reported always having symptoms associated with low blood glucose levels (P < 0.001). Case subjects had greater glucose variability than control subjects (P = 0.008) and experienced CGM glucose levels <60 mg/dL for ≥20 min on 46% of days compared with 33% of days in control subjects (P = 0.10). On certain cognitive tests, case subjects scored worse than control subjects., Conclusions: In older adults with long-standing type 1 diabetes, greater hypoglycemia unawareness and glucose variability are associated with an increased risk of severe hypoglycemia. A study to assess interventions to prevent severe hypoglycemia in high-risk individuals is needed., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: Little is known about the frequency of depression in adults with type 1 diabetes (T1D) or its relationship to diabetes outcomes. The T1D Exchange clinic registry allowed us to explore depression in a large, heterogeneous sample., Research Design and Methods: Participants ≥18 years old (N = 6,172; median age 34 years; median diabetes duration 16 years; 55% female; and 89% non-Hispanic white) completed the eight-item Patient Health Questionnaire (PHQ-8), a validated, reliable measure of current depression. Probable major depression was defined in four ways: PHQ-8 ≥10, PHQ-8 ≥12, per diagnostic algorithm, and as a continuous variable. Characteristics and clinical outcomes of those with and without depression were compared using logistic and linear regression models., Results: A total of 4.6-10.3% of participants were classified as probable major depression depending on how defined. Participants classified as depressed were more likely female, nonwhite race/ethnicity, to have a lower household income and lower education level, to exercise less often, to miss insulin doses, and to have one or more complications (neuropathy, nephropathy, treatment for retinopathy, or cardiovascular/cerebrovascular disease) (all P < 0.01). HbA1c was higher in the depressed versus not depressed groups (8.4 ± 1.7% [68 ± 8.6 mmol/mol] vs. 7.8 ± 1.4% [62 ± 15.3 mmol/mol]; P < 0.001). Occurrence of one or more diabetic ketoacidosis events (11 vs. 4%; P < 0.001) and one or more severe hypoglycemic events (18 vs. 9%; P < 0.001) in the past 3 months was higher among depressed participants., Conclusions: In the T1D Exchange clinic registry, adults with probable major depression have worse clinical outcomes than those not depressed. Whether identification and treatment of depression improves diabetes outcomes requires study. Depression is common in T1D, and better identification and treatment of this comorbid condition is needed., (© 2014 by the American Diabetes Association.)

Context: Few studies have assessed factors associated with severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D)., Objective: Our objective was to determine frequency of and factors associated with the occurrence of SH and DKA in adults with T1D., Design and Setting: We conducted a cross-sectional analysis from the T1D Exchange clinic registry at 70 U.S. endocrinology centers., Patients: Analysis included 7012 participants in the T1D Exchange clinic registry aged 26 to 93 years old with T1D for ≥2 years., Results: Higher frequencies of SH and DKA were associated with lower socioeconomic status (P < .001). SH was strongly associated with diabetes duration (P < .001), with 18.6% of those with diabetes ≥40 years having an event in the past 12 months. SH frequency was lowest in those with hemoglobin A1c (HbA1c) levels of 7.0% (53 mmol/mol) to 7.5% (58 mmol/mol), being higher in those with HbA1c levels <7.0% (<53 mmol/mol) or >7.5% (>58 mmol/mol). DKA frequency increased with higher HbA1c levels (P < .001), with 21.0% of those with HbA1c ≥10.0% (≥86 mmol/mol) having an event in the past 12 months., Conclusions: SH and DKA are more common in those with lower socioeconomic status. DKA, most common in those with HbA1c ≥10.0% (≥86 mmol/mol), should be largely preventable. In contrast, SH, most frequent with diabetes ≥40 years duration, cannot be abolished given the limitation of current therapies. To reduce SH in adults with longstanding diabetes, consideration should be given to modifying HbA1c goals, particularly in patients with very low HbA1c levels.

The goal of this pilot study was to assess the effects of acute hypoglycemia on retinal function and contrast sensitivity in individuals with and without diabetes. Hyperinsulinemic hypoglycemic and euglycemic clamp procedures were performed in subjects without diabetes (n=7) and with controlled type 1 diabetes (n=5). Mean age was 28 years, and none had retinal disease. During euglycemia (glucose 95-110 mg/dl) and acute hypoglycemia (glucose 50-55 mg/dl), contrast sensitivity was measured and spatial retinal responses were recorded with multifocal electroretinograms (mfERG), a rapid technique for mapping sensitivity from the foveal, macular and peripheral areas of the retina. During hypoglycemia, retinal responses (mfERG P1 wave) were decreased in both type 1 diabetes subjects and subjects without diabetes. The dominant effect was in the amplitude of the responses in the central macular retina, not in their temporal properties. Responses from the central region, central 10(0), were on average 1.8-fold lower than those from the periphery for both groups. All diabetes subjects and 3/7 without diabetes reported central scotoma. Decreases in mfERG amplitude were accompanied by decreases in contrast sensitivity. These changes were immediately reversed with the restoration of euglycemia. Overall, this study demonstrates that the acute effects of hypoglycemia in the human eye predominantly involve central vision, and these visual effects originate, at least in part, in the retina. The association between low blood glucose levels and impaired central vision underscores the importance of avoiding when possible and promptly treating hypoglycemia, particularly in individuals with diabetes., (Published by Elsevier Ltd.)

Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This phase 3 study aimed to assess the efficacy and safety of efsitora compared with insulin degludec (degludec) in adults with type 1 diabetes. This randomised, 52-week, parallel-design, open-label, treat-to-target non-inferiority study conducted at 82 global health-care centres, randomly assigned (1:1) adults (ie, those aged ≥18 years) with type 1 diabetes glycated haemoglobin A 1c (HbA 1c) 7·0–10·0% (53·0–85·8 mmol/mol) to efsitora (n=343) or, degludec (n=349), both in combination with insulin lispro. The primary endpoint was the change in HbA 1c from baseline to week-26 (non-inferiority margin=0·4%). The trial was registered at ClinicalTrials.gov (NCT05463744) and is completed. Between Aug 12, 2022, and May 7, 2024, of 893 participants enrolled, 692 (77%) participants were randomly assigned to once-weekly efsitora or once-daily degludec, and 623 (90%) participants completed the study. Mean HbA 1c decreased from 7·88% (62·66 mmol/mol) at baseline to 7·41% (57·5 mmol/mol) at week 26 with efsitora and from 7·94% (63·3 mmol/mol) at baseline to 7·36% (56·9 mmol/mol) at week 26 with degludec. Mean HbA 1c change from baseline to week 26 was –0·51% with efsitora and –0·56% with degludec (estimated treatment difference 0·052%, 95% CI –0·077 to 0·181; p=0·43), confirming a non-inferiority margin of 0·4% for efsitora compared with degludec. Rates of combined level 2 (<54 mg/dL [3·0 mmol/L]) or level 3 severe hypoglycaemia were higher with efsitora compared with degludec (14·03 vs 11·59 events per patient year of exposure; estimated rate ratio 1·21, 95% CI 1·04 to 1·41; p=0·016) during weeks 0–52, with the highest rates during weeks 0–12. Severe hypoglycaemia incidence was higher with efsitora (35 [10%] of 343) versus degludec (11 [3%] of 349) during weeks 0–52. Overall incidence of treatment-emergent adverse events was similar across treatment groups. One death not related to the study treatment occurred in the degludec group. In adults with type 1 diabetes, once-weekly efsitora showed non-inferior HbA 1c reduction compared with daily insulin degludec. Higher rates of combined level 2 or level 3 hypoglycaemia and greater incidence of severe hypoglycaemia in participants treated with efsitora compared with participants treated with degludec might suggest the need for additional evaluation of efsitora dose initiation and optimisation in people with type 1 diabetes. Eli Lilly and Company. [ABSTRACT FROM AUTHOR]

Objective. To further evaluate glycemic outcomes during the observational extension phase of the Continuous Glucose Monitoring (CGM) Intervention for Teens and Young Adults randomized clinical trial (RCT). Subjects and Methods. Following a 26-week RCT comparing CGM with blood glucose monitoring (BGM) in 153 adolescents and young adults aged 14 to <25 years old with suboptimally controlled type 1 diabetes, 70 (89%) participants in the BGM group initiated use of CGM (referred to as BGM–CGM cohort), and 70 (95%) participants in the CGM group continued to use of CGM (CGM–CGM cohort) for an additional 26 weeks. Results. In the CGM–CGM cohort, mean hemoglobin A1c (HbA1c) decreased from 8.9% ± 0.9% (74 ± 9.8 mmol/mol) at randomization to 8.3% ± 1.3% (67 ± 14.2 mmol/mol) at 52 weeks (p < 0.001); however, significant improvement in time in target range (TIR) 70–180 mg/dL was not observed from prerandomization (38% ± 13%) to 52 weeks (41% ± 18%). Median percent time <70 mg/dL decreased from 3.0% before randomization to 1.1% at 52 weeks (p < 0.001). In the BGM–CGM cohort, mean HbA1c decreased from 8.9% ± 1.2% (74 ± 13.1 mmol/mol) before CGM initiation to 8.5% ± 1.3% (69 ± 14.2 mmol/mol) after 26 weeks of CGM use (p < 0.001) and mean TIR increased from 34% ± 12% to 38% ± 15% (p = 0.01). The median percent time <70 mg/dL decreased from 3.3% before CGM initiation to 1.2% after 26 weeks of CGM use (p < 0.001). No participants discontinued CGM use during the extension phase. Conclusions. This further evaluation of CGM supports the findings of the preceding RCT that use of CGM improves glycemic control and reduces hypoglycemia in adolescents and young adults with type 1 diabetes. This trial is registered with NCT03263494. [ABSTRACT FROM AUTHOR]

Importance: Adolescents and young adults with type 1 diabetes exhibit the worst glycemic control among individuals with type 1 diabetes across the lifespan. Although continuous glucose monitoring (CGM) has been shown to improve glycemic control in adults, its benefit in adolescents and young adults has not been demonstrated.Objective: To determine the effect of CGM on glycemic control in adolescents and young adults with type 1 diabetes.Design, Setting, and Participants: Randomized clinical trial conducted between January 2018 and May 2019 at 14 endocrinology practices in the US including 153 individuals aged 14 to 24 years with type 1 diabetes and screening hemoglobin A1c (HbA1c) of 7.5% to 10.9%.Interventions: Participants were randomized 1:1 to undergo CGM (CGM group; n = 74) or usual care using a blood glucose meter for glucose monitoring (blood glucose monitoring [BGM] group; n = 79).Main Outcomes and Measures: The primary outcome was change in HbA1c from baseline to 26 weeks. There were 20 secondary outcomes, including additional HbA1c outcomes, CGM glucose metrics, and patient-reported outcomes with adjustment for multiple comparisons to control for the false discovery rate.Results: Among the 153 participants (mean [SD] age, 17 [3] years; 76 [50%] were female; mean [SD] diabetes duration, 9 [5] years), 142 (93%) completed the study. In the CGM group, 68% of participants used CGM at least 5 days per week in month 6. Mean HbA1c was 8.9% at baseline and 8.5% at 26 weeks in the CGM group and 8.9% at both baseline and 26 weeks in the BGM group (adjusted between-group difference, -0.37% [95% CI, -0.66% to -0.08%]; P = .01). Of 20 prespecified secondary outcomes, there were statistically significant differences in 3 of 7 binary HbA1c outcomes, 8 of 9 CGM metrics, and 1 of 4 patient-reported outcomes. The most commonly reported adverse events in the CGM and BGM groups were severe hypoglycemia (3 participants with an event in the CGM group and 2 in the BGM group), hyperglycemia/ketosis (1 participant with an event in CGM group and 4 in the BGM group), and diabetic ketoacidosis (3 participants with an event in the CGM group and 1 in the BGM group).Conclusions and Relevance: Among adolescents and young adults with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in glycemic control over 26 weeks. Further research is needed to understand the clinical importance of the findings.Trial Registration: ClinicalTrials.gov Identifier: NCT03263494. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Little is known about the psychosocial challenges of adults living with type 1 diabetes or its impact on partner relationships. This qualitative study was undertaken to gain better understanding of these issues. RESEARCH DESIGN AND METHODS--Four focus groups were held, two with adult type 1 diabetic patients (n = 16) and two with partners (n = 14). Two broad questions were posed: "What are the emotional and interpersonal challenges you have experienced because you have (your partner has) type 1 diabetes?" and "How does the fact that you have (your partner has) type 1 diabetes affect your relationship with your partner, positively and/or negatively?" Sessions were recorded and transcribed, and analyzed by a team of four researchers, using constant comparative methods to identify core domains and concepts. RESULTS--Four main domains were identified: 1) impact of diabetes on the relationship, including level of partner involvement, emotional impact of diabetes on the relationship, and concerns about child-rearing; 2) understanding the impact of hypoglycemia; 3) stress of potential complications; and 4) benefits of technology. Themes suggest that, although partner involvement varies (very little to significant), there exists significant anxiety about hypoglycemia and future complications and sources of conflict that may increase relationship stress. Partner support is highly valued, and technology has a positive influence. CONCLUSIONS--Adults with type 1 diabetes face unique emotional and interpersonal challenges. Future research should focus on gaining a better understanding of how they cope and the effect of psychosocial stressors and coping on adherence, quality of life, and glycemic control. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- The purpose of the study was to investigate the effect of comorbid depression on glycemic control and on response to a telemedicine case management intervention for elderly, ethnically diverse diabetic patients. RESEARCH DESIGN AND METHODS-- Medicare beneficiaries in underserved areas were participants (n = 1,665) in the Informatics for Diabetes Education and Telemedicine (IDEATel) project and randomized to a telemedicine case management intervention or usual care. The data analyzed include baseline demographics (age, sex, race/ethnicity, marital status, insulin use, years of education, years of diabetes, and pack-years smoked) and measures of glycemic control (HbA1c [A1C]), comorbidity, diabetes symptom severity, functional disability and depression, and 1-year (n = 1,578) A1C. The association between depression and glycemic control was analyzed cross-sectionally and prospectively. RESULTS -- At baseline, there was a significant correlation between depression and A1C and a trend for depression to predict A1C when other factors were controlled. However, in prospective analyses, depression did not predict change in A1C, either in the control or intervention group. CONCLUSIONS -- In this large sample of elderly diabetic patients, a weak relationship between depression and A1C was found, but depression did not prospectively predict change in glycemic control. Thus, there is no evidence that depression should be used to exclude patients from interventions. Also, we should evaluate the impact of depression on outcomes other than glycemic control. [ABSTRACT FROM AUTHOR]

Delivering diabetes care to prisoners presents unique challenges. We report our experience using telemedicine to help care for 44 diabetic males incarcerated in 12 institutions of the New York State Penal System. Mean age was 43.2 yr (range 16.7-68.9), duration of diabetes was 16.5 yr (1-51), 36.4% of patients (pts) had type 1 diabetes, and many had significant comorbidities such as HIV, hepatitis, cardiovascular disease, and end-stage renal disease. Therapy consisted of basal/bolus insulin (27.3%), NPH/Regular insulin 1-3 injections daily (31.8%), pre-mixed insulin bid (13.6%), oral agents + insulin (9.1%), and oral agents alone (13.6%). There were 111 televisits from 2004-2006; 27% (n=12) of pts had only one consultation. The remaining 73% (n=32) were followed a median of 7.1 mon (range 1.4-38.5) with 3.1 (mean) televisits each (2-10); 53.1% had ≥ 3 televisits and 16% were followed for ≥1 year. Mean interval between visits was 4.5 mon (0.9-20.3); 7% (n=3) of pts lacked an initial A1c and 22% (n=7) of pts with ≥2 televisits had only 1 A1c. Fifty-six percent (n=23) of patients had an initial A1c ≥ 9%. Follow up A1c levels were available for 14 of these pts, of which half (n=7) achieved an A1c < 9%. Goal A1c (<7%) was attained by 31.8% (n=14) of pts. Mean time to goal was 4.7 mon (2.1-9.1). Mean duration of A1c < 7% was 6.7 mon (6.1-7.0). Eleven (25%) pts had an A1c < 7% at baseline and were followed a mean of 5.9 mon (0-22.3). Nine remained at goal. One patient's A1c was 7.1% at 7 months. Another had erratic control with A1cs of 9.6%, 6.1%, and 11.0% at 7, 11, and 15 months. Those initially not at goal with ≥2A1c value s (n=19) had an initial mean A1c of 10.0% (7.5%-15.4%) and final mean A1c of 9.3% (range of A1c change - 2.6% to + 1.4%). Overall, those reaching goal (n=14) tended to be seen more frequently (57% every 4 mon) and were followed longer [mean 8.2 mon (0-37.3)]. Therapeutic recommendations were made in 86% of visits, and were known to have been followed 45% of the time. Lack of follow-up data was primarily due to patient turnover (changing institution, parole), limited access (ie solitary confinement), and death. Other difficulties included limited access to laboratory data and lack of data concerning hypoglycemia. Our results demonstrate the feasibility of this approach and the need for further study of the delivery of diabetes care to this vulnerable population. We suggest that telemedicine can be helpful in the management of diabetes in incarcerated individuals. [ABSTRACT FROM AUTHOR]

Aims: Little is known about cognition in older adults with type 1 diabetes. The aim of this study was to identify correlates of clinically significant cognitive impairment.Methods: Neuropsychological, diabetes-related and glycemic (HbA1c, Continuous Glucose Monitoring; CGM) data were collected from 201 older adults (≥60 years) with longstanding type 1 diabetes.Results: Clinically significant cognitive impairment (≥2 cognitive tests ≥1.5 SD below normative data) occurred in 48% of the sample. After controlling for age, gender, education and diabetes duration, we found that hypoglycemia unawareness, recent severe hypoglycemic events, any microvascular complication, higher HbA1c and CGM average nocturnal glucose were all associated with increased odds of clinically significant cognitive impairment (ORs = 1.01-2.61), while CGM nocturnal % time below 60 mg/dL was associated with a decreased odds of cognitive impairment (OR = 0.94). Diabetes duration, diagnosis age, daytime CGM, and lifetime severe hypoglycemic events were not related to cognitive impairment status.Conclusions: Clinically significant cognitive impairment was common in older adults with type 1 diabetes. Diabetes-related correlates of cognitive impairment were identified, including hypoglycemia unawareness, recent severe hypoglycemic events, and CGM variables. Longitudinal research is needed to determine if these variables predict cognitive decline and if their modification alters outcomes. [ABSTRACT FROM AUTHOR]

Aims: To assess prevalence of, and factors associated with, medication adherence of young adults with youth-onset type 2 diabetes.Methods: Oral hypoglycaemia agent (OHA) adherence was measured with unannounced telephone pill counts, insulin adherence was self-reported. Those taking ≥ 80% of pills/insulin were classified "high-adherent," <80% of pills/insulin "low-adherent." Analyses included unadjusted, and adjusted linear and logistic regressions assessing associations of participant factors with adherence.Results: For people taking OHAs (N = 212, mean age 26 yrs, 67% women, 18% non-Hispanic White, 35% non-Hispanic Black, 41% Hispanic), 69.8% were low-adherent. HbA1c was lower in the high-adherent group (9.2%/77 mmol/mol vs. 10.0%/86 mmol/mol, p < 0.04). More non-Hispanic Blacks were low-adherent (85.7%) than Hispanics (60.2%) and non-Hispanic whites (55.3%, p < 0.002); 91.4% of participants without healthcare coverage were low-adherent vs. 65.5% of those with coverage (p < 0.004). After adjustment, gender (p = 0.024), race/ethnicity (p < 0.001) and healthcare coverage (p = 0.001) remained related to OHA adherence. For insulin (N = 192), 37% were low-adherent. HbA1c was associated with insulin adherence (low = 11.2%/99 mmol/mol vs. high = 10.0%/86 mmol/mol, p < 0.001) with and without adjustment.Conclusions: Young adults with youth-onset type 2 diabetes, especially females, non-Hispanic Blacks and those without healthcare coverage, commonly had low-OHA adherence. Glycaemic control was also poor. Interventions to improve medication adherence are needed for this vulnerable group. [ABSTRACT FROM AUTHOR]