Debate exists as to whether the higher hemoglobin A1c (HbA1c) levels observed in black persons than in white persons are due to worse glycemic control or racial differences in the glycation of ...hemoglobin.
To determine whether a racial difference exists in the relationship of mean glucose and HbA1c.
Prospective, 12-week observational study.
10 diabetes centers in the United States.
104 black persons and 104 white persons aged 8 years or older who had had type 1 diabetes for at least 2 years and had an HbA1c level of 6.0% to 12.0%.
Mean glucose concentration, measured by using continuous glucose monitoring and compared by race with HbA1c, glycated albumin, and fructosamine values.
The mean HbA1c level was 9.1% in black persons and 8.3% in white persons. For a given HbA1c level, the mean glucose concentration was significantly lower in black persons than in white persons (P = 0.013), which was reflected in mean HbA1c values in black persons being 0.4 percentage points (95% CI, 0.2 to 0.6 percentage points) higher than those in white persons for a given mean glucose concentration. In contrast, no significant racial differences were found in the relationship of glycated albumin and fructosamine levels with the mean glucose concentration (P > 0.20 for both comparisons).
There were too few participants with HbA1c levels less than 6.5% to generalize the results to such individuals.
On average, HbA1c levels overestimate the mean glucose concentration in black persons compared with white persons, possibly owing to racial differences in the glycation of hemoglobin. However, because race only partially explains the observed HbA1c differences between black persons and white persons, future research should focus on identifying and modifying barriers impeding improved glycemic control in black persons with diabetes.
Helmsley Charitable Trust.
Abnormally elevated proinsulin secretion has been reported in type 2 and early type 1 diabetes when significant C-peptide is present. We questioned whether individuals with long-standing type 1 ...diabetes and low or absent C-peptide secretory capacity retained the ability to make proinsulin.
C-peptide and proinsulin were measured in fasting and stimulated sera from 319 subjects with long-standing type 1 diabetes (≥3 years) and 12 control subjects without diabetes. We considered three categories of stimulated C-peptide:
) C-peptide positive, with high stimulated values ≥0.2 nmol/L;
) C-peptide positive, with low stimulated values ≥0.017 but <0.2 nmol/L; and
) C-peptide <0.017 nmol/L. Longitudinal samples were analyzed from C-peptide-positive subjects with diabetes after 1, 2, and 4 years.
Of individuals with long-standing type 1 diabetes, 95.9% had detectable serum proinsulin (>3.1 pmol/L), while 89.9% of participants with stimulated C-peptide values below the limit of detection (<0.017 nmol/L;
= 99) had measurable proinsulin. Proinsulin levels remained stable over 4 years of follow-up, while C-peptide decreased slowly during longitudinal analysis. Correlations between proinsulin with C-peptide and mixed-meal stimulation of proinsulin were found only in subjects with high stimulated C-peptide values (≥0.2 nmol/L). Specifically, increases in proinsulin with mixed-meal stimulation were present only in the group with high stimulated C-peptide values, with no increases observed among subjects with low or undetectable (<0.017 nmol/L) residual C-peptide.
In individuals with long-duration type 1 diabetes, the ability to secrete proinsulin persists, even in those with undetectable serum C-peptide.
Background: Older adults with T1D are a growing population at risk for severe hypoglycemia. Automated insulin delivery (AID) approaches that can reduce risk have not been sufficiently evaluated in ...this population. Methods: We conducted a multicenter, randomized, crossover trial in adults ≥65 years with T1D experiencing hypoglycemia (>1.5% time < 70 mg/dL based on CGM). Participants completed 3 sequential 12-week periods of hybrid-closed (HCL) loop with Tandem Control-IQ technology, predictive low glucose suspend (PLGS) with Tandem Basal-IQ technology, and sensor augmented pump (SAP) insulin delivery. The primary outcome was % time <70 mg/dL measured by Dexcom G6 CGM. Results: 82 randomized participants were 65-86 years, 45% female, with a mean (±SD) baseline HbA1c 7.2±0.9%. AID was active a median of 97% of the time during the HCL period and 96% during the PLGS period. Mean (±SD) time <70 mg/dL was 2.49±1.78% at baseline, 1.58±0.95% during HCL, 1.67±0.96% during PLGS, and 2.57±1.54% during SAP (p<0.001 for HCL vs. SAP and PLGS vs. SAP; Table). CGM hypoglycemic events and time <54 mg/dL were reduced during HCL and PLGS compared to SAP. HCL improved time in range 70-180 mg/dL (TIR), time >180 mg/dL, time >250 mg/dL, and HbA1c compared to SAP and PLGS (Table). Conclusions: In older adults with T1D, HCL and PLGS both reduced hypoglycemia compared to SAP. HCL also improved TIR, hyperglycemia, and HbA1c compared to SAP and PLGS. Disclosure Y.C. Kudva: Research Support; Dexcom, Inc. Other Relationship; Tandem Diabetes Care, Inc., Medtronic. R. Henderson: None. L. Kanapka: None. R.S. Weinstock: Research Support; Eli Lilly and Company, Tandem Diabetes Care, Inc., Diasome, Amgen Inc., MannKind Corporation, Insulet Corporation, Novo Nordisk. Other Relationship; Dexcom, Inc. M.R. Rickels: Consultant; Vertex Pharmaceuticals Incorporated, Sernova, Corp. Research Support; Dompé. R.E. Pratley: Other Relationship; Bayer AG, Dompé, Endogenex, Inc., Gasherbrum Bio, Inc., Hengrui (USA) Ltd., Intas Pharmaceuticals Ltd., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sun Pharmaceutical Industries Ltd. Consultant; AbbVie Inc., AstraZeneca. Other Relationship; Bayer HealthCare Pharmaceuticals, Inc., Biomea Fusion, Carmot Therapeutics, Inc., Corcept Therapeutics, Fractyl Health, Inc., Genprex. Consultant; Getz Pharma. Other Relationship; Lilly USA LLC, Sanofi. Consultant; Scholar Rock, Inc. N. Chaytor: None. K. Janess: None. D. Desjardins: None. V. Pattan: Stock/Shareholder; Tandem Diabetes Care, Inc. A. Peleckis: None. A. Casu: None. S. Rizvi: None. S. Bzdick: None. K.J. Whitaker: None. J.L. Jo Kamimoto: None. K. Miller: Consultant; Dexcom, Inc. Research Support; Dexcom, Inc. R. Beck: Consultant; Insulet Corporation. Research Support; Insulet Corporation. Consultant; Tandem Diabetes Care, Inc. Research Support; Tandem Diabetes Care, Inc. Consultant; Beta Bionics, Inc. Research Support; Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk, Eli Lilly and Company. Consultant; embecta, Vertex Pharmaceuticals Incorporated, Hagar, Ypsomed AG, Sanofi, Zucara Therapeutics, Sequel. Funding Funding provided by NIDDK. Study materials provided by Tandem Diabetes Care and Dexcom.
Introduction and Objective: Assess Omnipod 5 System’s efficacy in managing glycemia during activity, comparing ‘Activity Feature’ initiated 30 (AF-30) or 60 min (AF-60) before exercise to automated ...delivery (Auto). Methods: In this three-way crossover, 50 people with T1D (age 30±15 years, BMI 24.7±4.1 kg/m2, HbA1c 7.5±1.0%, and T1D duration 16±11 years) underwent a 70 min activity session (60 min exercise, 5 min rest at 20 and 45 min), 3hrs post-bolus, under each condition (Auto, AF-30, and AF-60). Pre-activity glucose was 90-200mg/dL. Up to 16g of carbs were provided if glucose was <90mg/dL pre activity or <70mg/dL during activity. Metrics were assessed using generalized estimating equations. Results: Insulin delivery was decreased before and during activity for AF-30 and AF-60 vs Auto (p<0.05, Table). During activity, AF-30 and AF-60 had smaller decreases in glucose, which was significant for Auto vs AF-30, p=0.03. Carb consumption during activity was higher for Auto vs AF-30 (p=0.02) and AF-60 (p=0.04). Time to hypo was delayed by 10 min (16% longer) in AF-30 and AF-60 relative to Auto. Conclusion: Enabling Activity Feature 30 min before activity with Omnipod 5 may effectively mitigate glucose declines. Regardless, carb consumption may be necessary to minimize hypo risk during 60 min of exercise. Disclosure L.V. Turner: None. J.L. Sherr: Consultant; Medtronic. Advisory Panel; Medtronic, Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Vertex Pharmaceuticals Incorporated, MannKind Corporation, StartUp Health T1D Moonshot, Bigfoot Biomedical, Inc., Cecelia Health. Speaker's Bureau; Zealand Pharma A/S. D.P. Zaharieva: Research Support; Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; Dexcom, Inc. Research Support; Insulet Corporation. Speaker's Bureau; Dexcom, Inc. Research Support; International Society for Pediatric and Adolescent Diabetes. Board Member; Juvenile Diabetes Research Foundation (JDRF). J.D. Baran: None. B.W. Bode: Research Support; Omnipod. Speaker's Bureau; Omnipod. Research Support; Medtronic. Advisory Panel; Medtronic. S.A. Brown: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Insulet Corporation, Tolerion, Roche Diagnostics. S. Bzdick: None. M. Church: None. D.W. Hansen: None. R.S. Kingman: None. L.M. Laffel: Consultant; Dexcom, Inc. Advisory Panel; Medscape, Medtronic, Vertex Pharmaceuticals Incorporated. Consultant; Novo Nordisk. Advisory Panel; Lilly Diabetes, Provention Bio, Inc., Sanofi-Aventis U.S., Janssen Pharmaceuticals, Inc., MannKind Corporation. V.N. Shah: Consultant; Dexcom, Inc., Insulet Corporation. Research Support; Insulet Corporation. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi, Medscape. Consultant; embecta, Tandem Diabetes Care, Inc. S.L. Stone: None. T. Vienneau: Employee; Insulet Corporation. Stock/Shareholder; Insulet Corporation. L.M. Huyett: Employee; Insulet Corporation. Stock/Shareholder; Insulet Corporation. B. Dumais: None. T.T. Ly: Employee; Insulet Corporation. M.C. Riddell: Consultant; Eli Lilly and Company. Speaker's Bureau; Novo Nordisk. Advisory Panel; Supersapiens. Consultant; Dexcom, Inc. Speaker's Bureau; Sanofi. Advisory Panel; Zealand Pharma A/S. Speaker's Bureau; Dexcom, Inc. Stock/Shareholder; Zucara Therapeutics. Funding This study was funded by Insulet Corporation.
Very young children with type 1 diabetes often struggle to achieve glycemic targets, putting them at risk for long-term complications and creating an immense management burden for caregivers. We ...conducted the first evaluation of the Omnipod 5 Automated Insulin Delivery System in this population.
A total of 80 children aged 2.0-5.9 years used the investigational system in a single-arm study for 13 weeks following 14 days of baseline data collection with their usual therapy.
There were no episodes of severe hypoglycemia or diabetic ketoacidosis. By study end, HbA1c decreased by 0.55% (6.0 mmol/mol) (P < 0.0001). Time with sensor glucose levels in target range 70-180 mg/dL increased by 10.9%, or 2.6 h/day (P < 0.0001), while time with levels <70 mg/dL declined by median 0.27% (P = 0.0204).
Use of the automated insulin delivery system was safe, and participants experienced improved glycemic measures and reduced hypoglycemia during the study phase compared with baseline.
This study assessed longitudinal change in depression symptoms over ≥4 years in adults with type 1 diabetes and examined the association between change in depression symptom status and glycemia.
...Adults in the T1D Exchange registry with HbA
and Patient Health Questionnaire (PHQ-8) at 1 year (baseline) and 5 years post-enrollment (follow-up;
= 2,744, mean age, 42 years; 57% female, 92% white; mean HbA
, 7.6% 58 mmol/mol) were included. Depression status was defined as Persistent Elevated Depression Symptoms (EDS) (EDS at baseline and follow-up), Resolved EDS (EDS at baseline, no EDS at follow-up), New Onset EDS (no EDS at baseline, EDS at follow-up), and Not Depressed (no EDS at baseline or follow-up).
Overall, 131 (5%) had Persistent EDS, 122 (4%) had Resolved EDS, 168 (6%) had New Onset EDS, and 2,323 (85%) were Not Depressed. Of those with EDS (PHQ ≥ 10) at baseline, 53% had EDS at follow-up; of those not depressed at baseline, 7% had EDS at follow-up. An increase in PHQ-8 was associated with an increase in HbA
(
< 0.001). Although HbA
increased in all groups, the increase was less in the Resolved EDS and Not Depressed groups (
= 0.001). Persistent EDS and New Onset EDS groups were more likely to experience diabetic ketoacidosis (DKA) (
< 0.001).
T1D Exchange registry data provide evidence for relationships over time between persistently, and newly developing EDSs and worsening glycemic control, and suggest relationships between depression symptoms and the occurrence of severe hypoglycemia and DKA. Successful treatment of depression symptoms may lead to better long-term diabetes outcomes.
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.
Standard treatment of hypoglycemia is oral carbohydrate, but it often results in hyperglycemia and entails extra caloric intake.
To evaluate low-dose glucagon to treat mild hypoglycemia in ambulatory ...adults with type 1 diabetes (T1D).
Randomized crossover trial (two 3-week periods).
Five U.S. diabetes clinics.
Twenty adults with T1D using an insulin pump and continuous glucose monitor (CGM) and experiencing frequent mild hypoglycemia.
Nonaqueous mini-dose glucagon (MDG) (150 µg) to treat nonsevere hypoglycemia.
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.
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.
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.
To assess change in depression over ≥4 years in adults with type 1 diabetes (T1D) and the association between change in depression and glycemic outcomes, we examined PHQ-8 data in adults in the T1D ...Exchange Clinic Registry with T1D duration ≥ 1 year (N= 2547; 57% female, 92% non-Hispanic white, year 1 age 43±16 years). PHQ-8 score ≥10 defined “depressed.” Linear regression was used to assess association of continuous outcomes and depression; logistic regression was used for categorical outcomes. At year 1/year 5, 9%/11% were depressed. In this sample, 126 (5%) had Persistent Depression (depressed at year 1 and year 5), 112 (4%) Resolved Depression (depressed at year 1, not at year 5), 148 (6%) New Year 5 Depression (not depressed at year 1, depressed at year 5), and 2161 (85%) Not Depressed at year 1/year 5. Of those depressed at year 1, 53% were depressed at year 5; of those not depressed at year 1, 6% were depressed at year 5. Participants with persistent depression/new year 5 depression had a significant increase (↑) in A1c adj mean ↑ 0.5± 0.2/0.5± 0.2; adj mean 8.1±0.1 for both; adj P’s=0.001; those not depressed at year 1/year 5 showed a trend in ↑A1c 0.3±0.1; adj mean 7.8±0.1; adj P=0.04. Those with resolved depression did not show change in A1c 0.2±0.2; adj mean 7.7±0.2; adj P=0.28. Those with persistent depression/new year 5 depression were more likely to report new year 5 DKA (DKA year 5 | no DKA year 1) than those not depressed at year 1/year 5 (adj P’s=0.03/0.04). There were trends for those with persistent depression to be more likely to report new year 5 severe hypoglycemia (SH) than those not depressed (11.1% vs. 4.8%); and for those with resolved depression to be less likely to report new year 5 SH (3.6 vs. 4.8%, adj P’s=0.09/0.11). Depression category was not associated with change in BMI (adj P=0.80). As a continuous variable, ↑in PHQ-8 was associated with ↑ in A1c (adj P<0.001), but not with new year 5 SH or BMI change (adj P>0.50). Depression (persistent or new year 5) has a negative impact on glycemic control over time. Adults with T1D should be screened and treated for depression.
Disclosure
P.M. Trief: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases. N.C. Foster: None. N. Chaytor: None. M.E. Hilliard: None. J. Kittelsrud: None. S. Jaser: None. S. Majidi: None. S. Corathers: None. S. Bzdick: None. D. Adkins: None. R.S. Weinstock: Research Support; Self; Medtronic MiniMed, Inc., Mylan, Kowa Pharmaceuticals America, Inc., Diasome Pharmaceuticals, Inc., Calibra Medical, Dexcom, Inc., Ultradian Diagnostics LLC., JAEB Center For Health Research, JDRF, National Institute of Diabetes and Digestive and Kidney Diseases.
The purpose of this study was to collect 1 year of real-world data from individuals with type 1 diabetes (T1D) initiating the Medtronic 670G hybrid closed-loop insulin delivery system as part of ...usual care. We sought to expand current knowledge to understand how use of the system impacts patient-reported outcomes, in addition to clinical outcomes, for children and adults with T1D.
Questionnaires were completed by the participant (and/or parent) before initiation of the 670G system (baseline) and at 6 weeks, 6 months, and 12 months from enrollment. Clinical data were obtained at routine clinical visits.
Of 132 participants who initiated Auto Mode, 80 completed the 12-month questionnaires while persisting with the system. Nearly all reported receiving adequate training on the 670G. Participant and parent-reported fear of hypoglycemia decreased by 6 and 11 points, respectively, from baseline to 12 months. More than half reported issues with sleep interruption at night due to alarms and 40% did not like frequent exits from Auto Mode. For the subset who had complete continuous glucose monitor data (
= 27), mean percent time in target range (70-180 mg/dL) was 66% at baseline, and 74% and 68% at 6 and 12 months, respectively.
With this study, we have captured real-time feedback from patients with T1D who initiated the 670G system and continued to use it over 12 months regarding their experience with the system. This has helped to illuminate both benefits and burdens associated with the first commercially available hybrid closed-loop system.
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