Hirsch, Irl B.

Objective: To evaluate the function and safety of the SteadiSet™ infusion set over a continuous 7-day wear period in adults with type 1 diabetes. Research Design and Methods: Participants used a SteadiSet infusion set with a t:slim X2™ insulin pump with Control-IQ™ technology, and either insulin aspart or insulin lispro, for a target of 7 days for 12 consecutive wear periods. Each set removed before 7 days was adjudicated by an independent committee to assess the cause of early removal and to determine whether criteria for primary or key secondary endpoints were met. Results: There were 260 participants who inserted 3028 infusion sets. For the primary endpoint, the Kaplan–Meier 7-day survival estimate was 95% (95% CI 94% to 96%). For the key secondary endpoint, which expanded the reasons for a failed infusion set, the Kaplan–Meier 7-day survival estimate was 84% (95% CI 82% to 86%). For both endpoints, the P value was <0.001 compared with a prespecified survival rate of 75%. Time-in-range 70–180 mg/dL (TIR) increased through day 3 of set wear and then decreased through day 7, with the average TIR being 70.6% over the entire wear period across all infusion sets, including those that failed. An increase in total daily insulin was observed from day 4 through day 7. Conclusions: The 7-day survival of the SteadiSet infusion set was very high for the primary endpoint and at an acceptable level with respect to early removal for any reason related to the device.

OBJECTIVE The Centers for Medicare & Medicaid Services (CMS) requires a low C-peptide level for insulin pump coverage unless the individual is β-cell autoantibody positive, which precludes coverage of automated insulin delivery (AID) systems for many people with type 2 diabetes. RESEARCH DESIGN AND METHODS In the Randomized Trial Evaluating the Efficacy and Safety of Control-IQ+ Technology in Adults With Type 2 Diabetes Using Basal-Bolus Insulin Therapy study evaluating the t:slim X2 insulin pump with Control-IQ+ technology, adults with insulin-treated type 2 diabetes were categorized into high C-peptide (n = 195) and low C-peptide (n = 59) groups based on CMS criteria. RESULTS In the AID group, mean HbA1c decreased from baseline by 0.8%, which was significantly greater than in the control group with both high (P &lt; 0.001) and low (P = 0.02) C-peptide levels. Results were similar in participants ≥65 years old. CONCLUSIONS The benefit of AID is present with high and low C-peptide levels. Thus, requiring a low C-peptide level as a prerequisite for AID therapy is not warranted.

OBJECTIVE To evaluate a regimen of inhaled Technosphere insulin (TI) plus insulin degludec in adults with type 1 diabetes, who prestudy were predominately using either an automated insulin delivery (AID) system or multiple daily insulin injections (MDI) with continuous glucose monitoring. RESEARCH DESIGN AND METHODS At 19 sites, adults with type 1 diabetes were randomly assigned to TI plus insulin degludec (N = 62) or usual care (UC) with continuation of prestudy insulin delivery method (N = 61) for 17 weeks. RESULTS Prestudy, AID was used by 48% and MDI by 45%. Mean ± SD HbA1c was 7.57% ± 0.97% at baseline and 7.62% ± 1.06% at 17 weeks in the TI group and 7.59% ± 0.80% and 7.54% ± 0.77%, respectively, in the UC group (adjusted difference 0.11%, 95% CI −0.10 to 0.33, P value for noninferiority = 0.01). HbA1c improved from baseline to 17 weeks by &gt;0.5% (5.5 mmol/mol) in 12 (21%) in the TI group and in 3 (5%) in the UC group and worsened by &gt;0.5% (5.5 mmol/mol) in 15 (26%) in the TI group and in 2 (3%) in the UC group. The most common TI side effect was a brief cough; eight participants discontinued TI due to side effects. CONCLUSIONS In adults with type 1 diabetes, HbA1c after 17 weeks with a regimen of TI and degludec was noninferior to UC, which consisted predominately of either AID or MDI. TI should be considered an option for people with type 1 diabetes, particularly those who are motivated to further reduce postprandial hyperglycemia.

Abstract Background Adult patients with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. These patients are at increased risk for adverse clinical outcomes in the absence of defined approaches to glycemic management. Objective To review and update the 2012 Management of Hyperglycemia in Hospitalized Patients in Non-Critical Care Settings: An Endocrine Society Clinical Practice Guideline and to address emerging areas specific to the target population of noncritically ill hospitalized patients with diabetes or newly recognized or stress-induced hyperglycemia. Methods A multidisciplinary panel of clinician experts, together with a patient representative and experts in systematic reviews and guideline development, identified and prioritized 10 clinical questions related to inpatient management of patients with diabetes and/or hyperglycemia. The systematic reviews queried electronic databases for studies relevant to the selected questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. Results The panel agreed on 10 frequently encountered areas specific to glycemic management in the hospital for which 15 recommendations were made. The guideline includes conditional recommendations for hospital use of emerging diabetes technologies including continuous glucose monitoring and insulin pump therapy; insulin regimens for prandial insulin dosing, glucocorticoid, and enteral nutrition–associated hyperglycemia; and use of noninsulin therapies. Recommendations were also made for issues relating to preoperative glycemic measures, appropriate use of correctional insulin, and diabetes self-management education in the hospital. A conditional recommendation was made against preoperative use of caloric beverages in patients with diabetes. Conclusion The recommendations are based on the consideration of important outcomes, practicality, feasibility, and patient values and preferences. These recommendations can be used to inform system improvement and clinical practice for this frequently encountered inpatient population.

Background: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data. Methods: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low–glucose and low-glucose hypoglycemia; very high–glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation. Results: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals. Conclusion: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

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)