Diabetes Technology & Therapeutics

Safe Options for the Treatment of Mothers and Babies with Pregestational Diabetes
Benhalima K, Mathieu C, Napoli A, Kudva YC, Cypryk K, Hammond P, Cukierman-Yaffe T, Cyganek K, Divakar H and Hod M
Evaluation of an Automated Priming Bolus for Improving Prandial Glucose Control in Full Closed Loop Delivery
Moscoso-Vasquez M, Colmegna P, Barnett C, Fuller M, Koravi CLK, Brown SA, DeBoer MD and Breton MD
Automated insulin delivery (AID) is widely available to people with type 1 diabetes (T1D), providing superior glycemic control versus traditional methods. The next generation of AID devices focus on minimizing user/device interactions, especially around meals ("full closed loop," [FCL]). Our goal was to assess the postprandial glycemic impact of the bolus priming system (BPS), an algorithm delivering fixed insulin doses based on the likelihood of a meal having occurred, in conjunction with UVA's latest AID. Eleven adults with T1D participated in a supervised randomized-crossover trial assessing glycemic control during two 24-h sessions with identical meals and activity-with and without BPS. On the day in-between study sessions, participants underwent food and activity challenges to test BPS safety and robustness. Continuous glucose monitor (CGM) outcomes and total insulin doses were assessed overall and following meals with potential for BPS to dose additional insulin (CGM >90 mg/dL for 1 h prior). Daytime CGM outcomes were similar with and without BPS: time-in-range (TIR) 70-180 mg/dL 70.6% [62.2-76.5] versus 65.7% [58.6%-80.6%]; time-below-range <70 mg/dL 0% [0-2.1] versus 0% [0-1.3]; respectively. Insulin delivery during 3 h postprandial was indistinguishable 33.5 U [26.4-47.0] versus 35.7 U [28.7-44.9]. Among 43 out of 66 meals with potential to trigger BPS (24/19 BPS/no-BPS), postprandial incremental area-under-the-curve (iAUC) was lower for BPS versus no-BPS (2530 ± 1934 versus 3228 ± 2029, = 0.047), but CGM outcomes were inconclusive: 4-h-TIR 51.2% [19.8-83.3] versus 40.2% [20.8-56.3] ( = 0.24). There were no severe adverse events. While there was no difference in TIR, when BPS was active an improved postprandial AUC in FCL was obtained via earlier insulin injection.
Effect of Interrupting Prolonged Sitting with Frequent Activity Breaks on Postprandial Glycemia and Insulin Sensitivity in Adults with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy: A Randomized Crossover Pilot Trial
Larsen R, Taylor F, Dempsey PC, McNarry M, Rickards K, Sethi P, Homer A, Cohen N, Owen N, Kumareswaran K, MacIsaac R, McAuley SA, O'Neal D and Dunstan DW
This study examined acute effects of interrupting prolonged sitting with short activity breaks on postprandial glucose/insulin responses and estimations of insulin sensitivity in adults with type 1 diabetes (T1D). In a randomized crossover trial, eight adults (age = 46 ± 14 years [mean ± SD], body mass index [BMI] = 27.2 ± 3.8 kg/m) receiving continuous subcutaneous insulin infusion (CSII) therapy completed two 6-h conditions as follows: uninterrupted sitting (SIT) and sitting interrupted with 3-min bouts of simple resistance activities (SRAs) every 30 min. Basal and bolus insulin were standardized across conditions except in cases of hypoglycemia. Postprandial responses were assessed using incremental area-under-the-curve (iAUC) and total AUC (tAUC) from half-hourly venous sampling. Meal-based insulin sensitivity determined from glucose sensor and insulin pump (S) was assessed from flash continuous glucose monitor and insulin pump data. Outcomes were analyzed using mixed models adjusted for sex, BMI, treatment order, and preprandial values. Glucose iAUC did not differ by condition (SIT: 19.8 ± 3.0 [estimated marginal means ± standard error] vs. SRA: 14.4 ± 3.0 mmol.6 h.L; = 0.086). Despite CSII being standardized between conditions, insulin iAUC was higher in SRA compared to SIT (137.1 ± 22.7 vs. 170.9 ± 22.7 mU.6 h.L; < 0.001). This resulted in a lower glucose response relative to the change in plasma insulin in SRA (tAUCglu/tAUCins: 0.32 ± 0.02 vs. 0.40 ± 0.02 mmol.mU; = 0.03). Si was also higher at dinner following the SRA condition, with no between-condition differences at breakfast or lunch. Regularly interrupting prolonged sitting in T1D may increase plasma insulin and improve insulin sensitivity when meals and CSII are standardized. Future studies should explore underlying mechanistic determinants and the applicability of findings to those on multiple daily injections. Australian and New Zealand Clinical Trial Registry Identifier-ACTRN12618000126213 (www.anzctr.org.au).
Temporary Target Versus Suspended Insulin Infusion in Patients with Type 1 Diabetes Using the MiniMed 780G Advanced Closed-Loop Hybrid System During Aerobic Exercise: A Randomized Crossover Clinical Trial
Gómez AM, Henao DC, Muñoz OM, Romero DM, León JDS, Jaramillo PE, Moscoso E, Parra Prieto DA, Robledo S, Jaramillo MG and Rondón Sepúlveda M
To compare the safety in terms of hypoglycemic events and continuous glucose monitoring (CGM) metrics during aerobic exercise (AE) of using temporary target (TT) versus suspension of insulin infusion (SII) in adults with type 1 diabetes (T1D) using advanced hybrid closed-loop systems. This was a randomized crossover clinical trial. Two moderate-intensity AE sessions were performed, one with TT and one with SII. Hypoglycemic events and CGM metrics were analyzed during the immediate (baseline to 59 min), early (60 min to 6 h), and late (6 to 36 h) post-exercise phases. In total, 33 patients were analyzed (44.6 ± 13.8 years), basal time in range (%TIR 70-180 mg/dL) was 79.4 ± 12%, and time below range (%TBR) <70 mg/dL was 1.8 ± 1.7% and %TBR <54 mg/dL was 0.5 ± 0.9%. No difference was found in the number of hypoglycemic events, %TBR <70 mg/dL and %TBR <54 mg/dL between TT and SII. Differences were found in the early phase, with better values when using TT for %TIR 70-180 mg/dL (83.0 vs. 65.3, = 0.005), time in tight range (%TITR 70-140 mg/dL) (56.3 vs. 41.5, = 0.04), and time above range (%TAR >180 mg/dL) (15.3 vs. 31.8, = 0.01). In the diurnal period, again %TIR was better for TT use (82.1 vs. 73.1, = 0.02) and %TAR (15.0 vs. 22.96, = 0.04). No significant differences were found in the CGM metrics during the different phases of AE. Our data appear to show that the use of TT compared with SII is equally safe in all phases of AE. However, the use of TT allows for a better glycemic profile in the early phase of exercise.
Impact of Continuous Glucose Monitoring Versus Blood Glucose Monitoring to Support a Carbohydrate-Restricted Nutrition Intervention in People with Type 2 Diabetes
Willis HJ, Asche SE, McKenzie AL, Adams RN, Roberts CGP, Volk BM, Krizka S, Athinarayanan SJ, Zoller AR and Bergenstal RM
Low- and very-low-carbohydrate eating patterns, including ketogenic eating, can reduce glycated hemoglobin (HbA1c) in people with type 2 diabetes (T2D). Continuous glucose monitoring (CGM) has also been shown to improve glycemic outcomes, such as time in range (TIR; % time with glucose 70-180 mg/dL), more than blood glucose monitoring (BGM). CGM-guided nutrition interventions are sparse. The primary objective of this study was to compare differences in change in TIR when people with T2D used either CGM or BGM to guide dietary intake and medication management during a medically supervised ketogenic diet program (MSKDP) delivered via continuous remote care. IGNITE (Impact of Glucose moNitoring and nutrItion on Time in rangE) study participants were randomized to use CGM ( = 81) or BGM ( = 82) as part of a MSKDP. Participants and their care team used CGM and BGM data to support dietary choices and medication management. Glycemia, medication use, ketones, dietary intake, and weight were assessed at baseline (Base), month 1 (M1), and month 3 (M3); differences between arms and timepoints were evaluated. Adults ( = 163) with a mean (standard deviation) T2D duration of 9.7 (7.7) years and HbA1c of 8.1% (1.2%) participated. TIR improved from Base to M3, 61-89% for CGM and 63%-85% for BGM ( < 0.001), with no difference in change between arms ( = 0.26). Additional CGM metrics also improved by M1, and improvements were sustained through M3. HbA1c decreased by ≥1.5% from Base to M3 for both CGM and BGM arms ( < 0.001). Diabetes medications were de-intensified based on change in medication effect scores from Base to M3 ( < 0.001). Total energy and carbohydrate intake decreased ( < 0.001), and participants in both arms lost clinically significant weight ( < 0.001). Both the CGM and BGM arms saw similar and significant improvements in glycemia and other diabetes-related outcomes during this MSKDP. Additional CGM-guided nutrition intervention research is needed.
Comparison of Computational Statistical Packages for the Analysis of Continuous Glucose Monitoring Data with a Reference Software, "Ambulatory Glucose Profile," in Type 1 Diabetes
Karakus KE, Snell-Bergeon JK and Akturk HK
To compare the accuracy of commonly used continuous glucose monitoring (CGM) analysis programs with ambulatory glucose profile (AGP) and Dexcom Clarity (DC) in analyzing CGM metrics in patients with type 1 diabetes (T1D). CGM data up to 90 days from 152 adults using the same CGM and automated insulin delivery system with T1D were collected. Six of the 19 CGM analysis programs (CDGA, cgmanalysis, Glyculator, iglu, EasyGV, and GLU) were selected to compare with AGP and DC. Metrics were compared etween all tools with two one-sided -tests equivalence testing. For the equivalence test, the acceptable range of deviation was set as ±2 mg/dL for mean glucose, ±2% for time in range (TIR), ±1% for time above range (TAR), time above range level 1 (TAR1), time above range level 2 (TAR2), and coefficient of variation (CV). All packages were compared with each other for all CGM metrics, and most of them had statistically significant differences for at least some metrics. All tools were equivalent to AGP for mean glucose, TIR, TAR, TAR1, and TAR2 within ±2 mg/dL, ±2%, ±1%, ±1% and 1%, respectively. CDGA, Glyculator, cgmanalysis, and iglu were not equivalent to AGP for CV within ±1%. All tools were equivalent to DC for mean glucose, TIR, and TAR2 within ±2 mg/dL, ±2%, and ±1%, respectively. Glyculator was not equivalent for TAR1, TAR, and CV. CGDA, cgmanalysis, and iglu were not equivalent to DC for TAR1 and TAR. EasyGV and GLU were not equivalent for TAR within ±1%. CGM analysis programs reported CGM metrics statistically differently, but these differences may not be applicable in clinical practice. The equivalence test also confirmed that the differences are negligible for TIR and mean glucose, while they can be important for hyperglycemic ranges and CV. A standardization for CGM data handling and analysis is necessary for clinical studies reporting CGM-generated outcomes.
Transitioning from Self-Monitoring of Blood Glucose to Continuous Glucose Monitoring in Combination with a mHealth App Improves Glycemic Control in People with Type 1 and Type 2 Diabetes
Zivkovic J, Mitter M, Theodorou D, Kober J, Mueller-Hoffmann W and Mikulski H
Integrating mobile health (mHealth) apps into daily diabetes management allows users to monitor and track their health data, creating a comprehensive system for managing daily diabetes activities and generating valuable real-world data. This analysis investigates the impact of transitioning from traditional self-monitoring of blood glucose (SMBG) to real-time continuous glucose monitoring (rtCGM), alongside the use of a mHealth app, on users' glycemic control. Data were collected from 1271 diabetes type 1 and type 2 users of the mySugr app who made a minimum of 50 SMBG logs 1 month before transitioning to rtCGM and then used rtCGM for at least 6 months. The mean and coefficient of variation of glucose, along with the proportions of glycemic measurements in and out of range, were compared between baseline and 1, 2, 3, and 6 months of rtCGM use. A mixed-effects linear regression model was built to quantify the specific effects of transitioning to a rtCGM sensor in different subsamples. A novel validation analysis ensured that the aggregated metrics from SMBG and rtCGM were comparable. Transitioning to a rtCGM sensor significantly improved glycemic control in the entire cohort, particularly among new users of the mySugr app. Additionally, the sustainability of the change in glucose in the entire cohort was confirmed throughout the observation period. People with type 1 and type 2 diabetes exhibited distinct variations, with type 1 experiencing a greater reduction in glycemic variance, while type 2 displayed a relatively larger decrease in monthly averages.
GLP-1 Receptor Agonist Therapy in Cystic Fibrosis-Related Diabetes: A Case Report
Ayada G, Zolotov S, Cohen R, Lavi T, Abdul-Ghani M, Shehadeh N and Nakhleh A
Insulin Pump Use and Diabetic Ketoacidosis Risk in Type 1 Diabetes: Secular Trends over Four Decades
Budhram DR, Bapat P, Bakhsh A, Abuabat MI, Verhoeff NJ, Mumford D, Cheema W, Orszag A, Jain A, Cherney DZI, Fralick M, Alamri BN, Weisman A, Lovblom LE and Perkins BA
Continuous subcutaneous insulin infusion (CSII) in type 1 diabetes has been regarded as a major diabetic ketoacidosis (DKA) risk factor. We aimed to determine secular trends in risk since CSII implementation in the 1980s. We assessed the relationship between time-varying CSII use and DKA events from 1983 to 2017 and by each decade in the 1441 Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study participants using crude and adjusted Cox proportional hazards models. Time-varying CSII exposure was associated with significantly higher DKA risk in the 1980s (adjusted hazard ratio [HR] 5.81; 95% confidence interval [CI] 3.28-10.29; < 0.001), but in the 2010s, this risk was not significantly elevated (adjusted HR 1.24; 95% CI 0.73-2.12; = 0.43). DKA risk associated with CSII in type 1 diabetes has declined substantially since the 1980s such that the remaining risk in the past decade appears to be of low magnitude.
The Feasibility of an Experimental Hypobaric Simulation to Evaluate the Safety of Closed-Loop Insulin Delivery Systems in Flight-Related Atmospheric Pressure Changes
Fan KS, Shojaee-Moradie F, Manoli A, Baumann PM, Koehler G, Edwards V, Lee V, Mathieu C, Mader JK, Russell-Jones D and
Hybrid closed-loop (HCL) systems remain underexplored within aviation, and as atmospheric pressure changes can independently affect insulin pumps and continuous glucose monitoring readings, this preliminary study assessed the feasibility of HCL safety evaluation, in both fasting and post-prandial states, by using hypobaric chamber to simulate flights. Participants with type 1 diabetes and on HCL were studied: Medtronic Guardian 4-Medtronic 780G-SmartGuard ( = 4), Dexcom G6-Omnipod DASH-Android APS ( = 1), and Dexcom G6-Ypsomed Pump-CamAPS ( = 1). Flight cabin pressures of 550 mmHg and 750 mmHg were simulated in a hypobaric chamber. Seven-hundred-50 glucose measurements were taken, with glucose levels demonstrating a stable decline to 4 mmol/L during fasting. To maintain a tight fasting and post-prandial glucose range across the different pressure settings, the HCL administered insulin as expected. While not demonstrating any apparent issues, repeating flight simulation protocol with other systems, examining longer flights, and undertaking larger, powered randomised controlled trials can confirm their safety in aviation.
Possible Glycemic Effects of Vagus Nerve Stimulation Evaluated by Continuous Glucose Monitoring in People with Diabetes and Autonomic Neuropathy: A Randomized, Sham-Controlled Trial
Kufaishi H, Bertoli D, Kornum DS, Ranjan AG, Nørgaard K, Krogh K, Brock B, Okdahl T, Frøkjær JB, Drewes AM, Brock C, Krag Knop F, Hansen TW, Hansen CS and Rossing P
Autonomic neuropathy is associated with dysglycemia that is difficult to control. We investigated if transcutaneous vagus nerve stimulation (tVNS) could improve glycemic levels. We randomized 145 individuals with type 1 diabetes (T1D) ( = 70) or type 2 diabetes (T2D) ( = 75) and diabetic autonomic neuropathy (DAN) to self-administered treatment with active cervical tVNS ( = 68) or sham ( = 77) for 1 week (4 daily stimulations) and 8 weeks (2 daily stimulations), separated by a wash-out period of at least 2 weeks. Continuous glucose monitoring (CGM) indices were measured for 104 participants starting 5 days prior to intervention periods, during the 1-week period, and at end of the 8-week period. Primary outcomes were between-group differences in changes in coefficient of variation (CV) and in time in range (TIR 3.9-10 mmol/L). Secondary outcomes were other metrics of CGM and HbA1c. For the 1-week period, median [interquartile range] changes of CV from baseline to follow-up were -1.1 [-4.3;2.0] % in active and -1.5 [-4.4;2.5] % in sham, with no significance between groups ( = 0.54). For TIR, the corresponding changes were 2.4 [-2.1;7.4] % in active and 5.1 [-2.6;8.8] in sham group ( = 0.84). For the 8-week treatment period, changes in CV and TIR between groups were also nonsignificant. However, in the subgroup analysis, persons with T1D receiving active tVNS for 8 weeks had a significant reduction in CV compared with the T1D group receiving sham stimulation (estimated treatment effect: -11.6 [95% confidence interval -20.2;-2.0] %, = 0.009). None of the changes in secondary outcomes between treatment groups were significantly different. Overall, no significant changes were observed in CGM metrics between treatment arms, while individuals with T1D and DAN decreased their CV after 8 weeks of tVNS treatment.
Safety of Options to "Boost" (Enhancing Insulin Infusion Rates) and "Ease-Off" (Reducing Insulin Infusion Rates) in CamAPS FX Hybrid Closed-Loop System: A Real-World Analysis
Royston C, Bergford S, Calhoun P, Sibayan J, Ruan Y, Boughton C, Wilinska ME and Hovorka R
The usage and safety of the Boost and Ease-off features in the CamAPS FX hybrid closed-loop system were analyzed in a retrospective analysis of real-world data from 7,464 users over a 12-month period. Boost was used more frequently than Ease-off, but for a shorter duration per use. Mean starting glucose was above range for Boost (229 ± 51 mg/dL), and within range for Ease-off (114 ± 29 mg/dL). Time spent below 70 mg/dL was low during Boost periods [median (interquartile range; IQR) 0.0% (0.0, 0.5%)], and lower than during no Boost periods [2.1% (1.2, 3.4%)], while time spent above 180 mg/dL was lower during Ease-off periods (15 ± 14%) compared with no Ease-off periods (25 ± 12%). There were no episodes of severe hypoglycemia or diabetic ketoacidosis attributed to Boost or Ease-off use. Boost and Ease-off allow users to engage safely with CamAPS FX to manage their glucose levels during periods of more-than-usual and less-than-usual insulin needs.
Clinical Utility of Serum C-Peptide Concentration for Hospitalized Patients with Hyperglycemia
Costa DN, Kudva YC, Jensen MD and Shah P
Serum C-peptide concentration is often utilized for diagnostic, prognostic, or therapeutic assessment in diabetes mellitus. However, there are limited clinical data regarding diagnostic and predictive value of C-peptide measured during hospitalizations for hyperglycemia. Adults admitted to Mayo Clinic inpatient facilities due to an acute hyperglycemic emergency between January 2017 and November 2022 were included in our study. Predictive capacity of C-peptide for discontinuation of therapeutic insulin was examined in the entire cohort and the subgroup of non-autoimmune non-pancreatitis diabetes (NANP-DM). We included 187 patients (63 women) in our study. During hospitalization, patients with type 1 diabetes antibodies displayed diminished serum C-peptide concentration ( = 0.014), correlating inversely with subsequent hemoglobin A1c% [ = (-0.22), = 0.005]. Initial C-peptide concentrations did not differ between patients requiring insulin therapy during follow-up and those who did not ( = 0.16). C-peptide concentrations showed limited predictive capacity for achieving glycemic control. Subgroup analyses in NANP-DM exhibited similar limited capacity for anticipating therapeutic insulin needs and achieving glycemic controls. C-peptide concentration did not exhibit a robust predictive capability for future need of insulin therapy and achieving glycemic control, limiting its utility in clinical practice within inpatient settings.
Glycemic Variability and Disordered Eating Among Adolescents and Young Adults with Type 1 Diabetes: The Role of Disinhibited Eating
Propper-Lewinsohn T, Shalitin S, Gillon-Keren M, Yackobovitch-Gavan M, Liberman A, Phillip M and Elran-Barak R
Disordered eating behaviors (DEB) are common among individuals with type 1 diabetes (T1D). Glycemic variability, potentially harmful in T1D, may reveal distinct characteristics between those with higher versus lower variability, particularly concerning DEB. Our aim was to evaluate the prevalence of DEB and associated risk factors among adolescents and young adults with T1D and to investigate unique factors associated with DEB across different levels of glycemic variability. An observational, cross-sectional study was conducted with 147 individuals with T1D, aged 13-21 years. Data were collected from medical charts, personal technological devices for assessing glycemic variability, and self-reported questionnaires, including assessments of DEB. DEB were found in 62 (42.1%) individuals, and 41.5% achieved the glycemic variability (% coefficient of variation) target ≤36%. Among individuals with low glycemic variability, DEB were positively associated with diabetes distress (odds ratio [OR]: 1.14 [95% confidence interval or CI: 1.05-1.22], < 0.001), longer diabetes duration (OR: 1.34 [95% CI: 1.05-1.70],  = 0.016) and lower socioeconomic-status (OR: 0.53 [95% CI: 0.31-0.90],  = 0.019). Among those with high glycemic variability, body mass index Z score (OR: 3.82 [95% CI: 1.48-9.85], = 0.005), HbA1c (OR: 4.12 [95% CI: 1.33-12.80],  = 0.014), disinhibited eating (OR: 1.57 [95% CI: 1.14-2.15], = 0.005), and tendency to lower socioeconomic status (OR: 0.75 [95% CI: 0.56-1.01],  = 0.065). DEB are prevalent among adolescents and young adults with T1D and are associated with various risk factors. Factors associated with DEB vary across different levels of glycemic variability. Both low and high glycemic variability are associated with specific risk factors for DEB. One notable risk factor is diabetes-specific disinhibited eating among individuals with high glycemic variability, in contrast to those with low glycemic variability. Given these different risk factors, it may be prudent to adjust intervention programs to reduce DEB among T1D adolescents according to their glycemic variability levels.
Comment on Rilstone et al: A Randomized Controlled Trial Assessing the Impact of Continuous Glucose Monitoring with a Predictive Hypoglycemia Alert Function on Hypoglycemia in Physical Activity for People with Type 1 Diabetes (PACE)
Seibold A
MiniMed 780G System Use in Type 1 Diabetes During Ramadan Intermittent Fasting: A Systematic Literature Review and Expert Recommendations
Elbarbary N, Alguwaihes A, Zarif H, Hassanein M, Deeb A, Petrovski G, Al Dahash R, Alamoudi R, Hussain S, Ibrahim M, Shaikh S, Zainudin SB, Chaar W, van den Heuvel T and Al-Sofiani ME
This article offers a systematic literature review (SLR) on the use of the MiniMed 780G automated insulin delivery system (MM780G) in people with type 1 diabetes (PwT1D) during Ramadan intermittent fasting. It also presents consensus recommendations on the use of MM780G during the Ramadan period. The SLR was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. The recommendations resulted from a consensus-forming process involving a panel of experts. The process considered evidence found in the SLR as well as the expert opinions. In total, six studies were included in the SLR. The evidence and expert opinions led to recommendations related to (a) pre-Ramadan counseling of MM780G users who plan to fast; (b) suggested MM780G settings, meal announcement strategy, and safety aspects during Ramadan (including a contingency plan); and (c) post-Ramadan transition into and out of Eid-al-Fitr festivities. The SLR findings showed that the MM780G maintains glycemic control at target in PwT1D during Ramadan (meeting continuous glucose monitoring-based clinical targets proposed by the International Consensus on Time-in-Range) while ensuring low rates of hypoglycemia and diabetic ketoacidosis. Automated insulin delivery also helps PwT1D fast more days of Ramadan compared with users of other less advanced modalities of treatment. Pre-Ramadan guidance on specific aspects of the MM780G along with the International Diabetes Federation and Diabetes and Ramadan International Alliance counseling guidelines is recommended. There is still a challenge with post-Iftar hyperglycemia, which could potentially be mitigated by following the recommendations outlined in this article.
Novel Glucose Metric "Latest Spike Time" Correlated with Weight Loss at Six Months in People with Obesity Using the Signos System
Dixon W, Kim S, Levonian D, Gusz D, Fouladgar-Mercer S and Skyler JS
The rise of digital health applications utilizing continuous glucose monitoring (CGM) allows for novel assessments of glucose management and weight changes in people without diabetes. The Signos System incorporates a digital health app paired with a CGM to provide information and prompts aimed to help people without diabetes to manage weight. The primary objective of this study was to determine whether the average timing of the latest chronological glucose excursion ("spike") was correlated with amount of weight loss. This was a retrospective analysis of prospectively obtained glucose and weight data from people without diabetes who enrolled in the Signos System from November 2021 to August 2023. Participants were provided CGMs as well as encouraged to use the Signos app with personalized advice and logging capabilities for weight, food, physical activity, heart rate, sleep, and activities. "Latest spike time" (LST) was retrospectively derived from CGM data and compared with weight changes at 6 months. Nine hundred and twenty-six subjects met the inclusion criteria including sufficient days wearing a CGM and a weight log within 15 days of 6 months from their first weight log. There was a strong correlation between an earlier spike time and increased weight loss. The top quintile of subjects, with an average LST before 5:41 PM, lost over three times as much weight as the bottom quintile of users, with LST after 8:40 PM; this separation was predictable within 1 month of data. In a large population of obese people without diabetes, continuous glucose data, specifically a novel metric "LST," was highly correlated with percentage of total body weight loss at 6 months. This research suggests that for people attempting weight loss, review and alteration of behaviors relating to later glucose excursions may be of specific benefit.
What Really Matters?: How Insulin Dose, Timing, and Distribution Relate to Meal Composition in Free-Living People with Type 1 Diabetes
Toschi E, Edwards S, Kao CY, Xue J, Atakov-Castillo A, Wang W, Steil G and Wolpert H
Optimizing postprandial glucose control in persons with type 1 diabetes (T1D) is challenging. We hypothesized that in free-living individuals, meal composition (high and low glycemic index [HGI and LGI], high and low fat [HF and LF]) may impact insulin requirements. Adults ( = 25) with T1D using open-loop insulin and continuous glucose monitoring were provided a meal-tagging app and prepackaged meals with defined macronutrient content. Data from 463 meals were analyzed. LGI meals required significantly more insulin than HGI meals ( = 0.01). Furthermore, the mean (±standard deviation) carbohydrate-to-insulin ratio (CIR) was significantly different overall among the LGI-LF (5.5 ± 3.4), LGI-HF (4.5 ± 3.8), HGI-LF (7.6 ± 5.1), and HGI-HF (8.7 ± 5.8) meals ( = 0.001). The risk of nocturnal hypoglycemia is associated with daytime hypoglycemia and amount of insulin administered prior to the evening and exercise. This exploratory study designed to examine the impact of different meal types on insulin dosing requirements in free-living adults with T1D emphasizes the need for individualized adjustment of the CIR depending on meal composition.
From Stability to Variability: Classification of Healthy Individuals, Prediabetes, and Type 2 Diabetes Using Glycemic Variability Indices from Continuous Glucose Monitoring Data
Cichosz SL, Kronborg T, Laugesen E, Hangaard S, Fleischer J, Hansen TK, Jensen MH, Poulsen PL and Vestergaard P
This study aims to investigate the continuum of glucose control from normoglycemia to dysglycemia (HbA1c ≥ 5.7%/39 mmol/mol) using metrics derived from continuous glucose monitoring (CGM). In addition, we aim to develop a machine learning-based classification model to classify dysglycemia based on observed patterns. Data from five distinct studies, each featuring at least two days of CGM, were pooled. Participants included individuals classified as healthy, with prediabetes, or with type 2 diabetes mellitus (T2DM). Various CGM indices were extracted and compared across groups. The data set was split 70/30 for training and testing two classification models (XGBoost/Logistic Regression) to differentiate between prediabetes or dysglycemia and the healthy group. The analysis included 836 participants (healthy: = 282; prediabetes: = 133; T2DM: = 432). Across all CGM indices, a progressive shift was observed from the healthy group to those with diabetes ( < 0.001). Statistically significant differences ( < 0.01) were noted in mean glucose, time below range, time above 140 mg/dl, mobility, multiscale complexity index, and glycemic risk index when transitioning from health to prediabetes. The XGBoost models achieved the highest receiver operating characteristic area under the curve values on the test data set ranging from 0.91 [confidence interval (CI): 0.87-0.95] (prediabetes identification) to 0.97 [CI: 0.95-0.98] (dysglycemia identification). Our findings demonstrate a gradual deterioration of glucose homeostasis and increased glycemic variability across the spectrum from normo- to dysglycemia, as evidenced by CGM metrics. The performance of CGM-based indices in classifying healthy individuals and those with prediabetes and diabetes is promising.
Simplified Meal Management in Adults Using an Advanced Hybrid Closed-Loop System
Minsky N, Shalit R, Benedetti A, Laron-Hirsh M, Cohen O, Kurtz N, Roy A, Grosman B and Tirosh A
The advanced hybrid closed-loop (AHCL) algorithm combines automated basal rates and corrections yet requires meal announcement for optimal performance, which poses a challenge for some. We aimed to compare glucose control in adults with type 1 diabetes (T1D) using the MiniMed 780G AHCL system, utilizing simplified meal announcement versus precise carbohydrate (CHO) counting. In a study involving 14 adults with T1D, we evaluated glycemic control during a 13-week "precise phase," followed by two 3- to 4-week simplified meal announcement phases: "fixed one-step" (preset of one personalized fixed CHO amount) and "multistep" (entry of multiples of one, two, or three of these presets depending on meal size estimate). The mean age was 45.7 ± 12.4, and 10 participants were male (71%). Mean baseline HbA1c was 6.8% ± 1.2% and time in range (TIR) was 67.5% ± 16.7%. Comparing the fixed one-step to the precise study phase, TIR was similar (75.4 ± 13% vs. 77.7 ± 9%, = 0.12), and glucose management indicator (GMI) was slightly higher (6.8 ± 0.4 vs. 6.6 ± 0, = 0.01). Furthermore, there was less level 1 and 2 hypoglycemia (1.6 ± 1% vs. 2.8 ± 2%, = 0.03 and 0.3 ± 5% vs. 0.65 ± 1%, = 0.08) but slightly more level 1 and 2 hyperglycemia (17.1 ± 8% vs. 15.0 ± 7%, = 0.05 and 5.5 ± 5% vs. 3.6 ± 3%, = 0.04). When comparing the multistep with the precise phase, GMI was identical (6.6%) and TIR superior (80.5 ± 10% vs. 77.7 ± 9%, = 0.02). Additionally, there was less level 1 hypoglycemia (1.9 ± 1% vs. 2.8 ± 2%, = 0.01) and a trend for less level 2 hypoglycemia (0.4 ± 0.7% vs. 0.65 ± 1%, = 0.08). A simplified meal announcement strategy for adults using the MiniMed 780G system, relying on three increments of a fixed one-step CHO amount, may offer a way to improve glycemic control and ease self-care. For patients with more limitations, using one fixed one-step CHO amount could be a safe alternative to meeting most consensus glycemic targets.
Association of Race and Ethnicity with Prescriptions for Continuous Glucose Monitoring Systems Among a National Sample of Veterans with Diabetes on Insulin Therapy
Lipska KJ, Oladele C, Zawack K, Gulanski B, Mutalik P, Reaven P, Lynch JA, Lee KM, Shih MC, Lee JS and Aslan M
Continuous glucose monitoring (CGM) can improve glycemic control in people with diabetes on insulin therapy. We assessed rates of prescriptions for CGM in a national sample of Veterans across subgroups defined by race and ethnicity. This cross-sectional analysis of data from the U.S. Veterans Health Administration included adults with type 1 or type 2 diabetes on insulin therapy. Main exposures included self-reported race and ethnicity, and primary outcome was the percentage of patients with at least one CGM prescription between January 1, 2020, and December 31, 2021. Association of race and ethnicity categories with CGM prescription was examined using multilevel, multivariable mixed-effects models. Among 368,794 patients on insulin (mean age, 68.5 years; 96% male; 96.8% type 2 diabetes; 0.8% American Indian or Alaska Native, 0.7% Asian, 18.9% Black or African American, 0.9% Native Hawaiian or other Pacific Islander, 70.2% White, 2.8% multiracial, 5.7% with unknown race, and 7.0% Hispanic or Latino ethnicity), 11.2% were prescribed CGM. CGM was prescribed for 10.4% American Indian or Alaska Native, 9.7% Asian, 9.2% Black or African American, 9.3% Native Hawaiian or other Pacific Islander, 11.8% White, 11.8% multiracial, and 10.1% patients with unknown race. CGM was prescribed for 8.3% Hispanic or Latino, 11.4% non-Hispanic, and 11.5% of patients with unknown ethnicity. After accounting for patient-, clinical-, and system-level factors, Black or African American patients had significantly lower odds of CGM prescription compared with White patients (adjusted odds ratio [aOR] 0.62, 95% confidence interval [CI] 0.59-0.64), whereas Hispanic or Latino patients had significantly lower odds compared with non-Hispanic patients (aOR 0.79, 95% CI 0.74-0.84). Findings were consistent across subgroups with clinical indications for CGM use. Among Veterans with diabetes on insulin therapy, there were significant disparities in prescribing of CGM technology by race and ethnicity, which require further study and intervention.