Real-time continuous glucose monitoring in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): a multicentre, randomised controlled trial

Insulin Pumps

Real-World Diabetes Technology: Overcoming Barriers and Disparities.

The impressive progress achieved in recent years in diabetes technologies has made diabetes technological devices such as continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) a significant part of diabetes treatment. Many studies conducted in recent years emphasized the advantages of using these technologies. The concept of the “human factor” in diabetes technologies as discussed in this chapter has several different aspects. First, it can refer to the way patients are satisfied with the use of the device and whether it is perceived convenient or inconvenient. For example, is the device perceived as “user friendly” (easy to learn and to operate, comfortable, does not cause many hassles). Second, there is the issue of effectiveness of the technology as it relates to their day-to-day diabetes management. For example, there is an improvement in glycemic control when one diabetes treatment regimen is compared to another (i.e., CSII vs. multiple daily injections (MDI)). Those two fundamental aspects may have different meanings for different groups. For example, different age groups (toddlers, children, adolescents, young adults, adults, and older people) can see different advantages and disadvantages in technological devices. The feasibility and utility of technological devices also need to fit the environments in which they will be used, such as school, the work place, and/or home. Specific subgroups such as diabetic youth with eating disorders can have unique interactions with diabetes technologies. In addition, diabetes technologies can be used as a measurement device, providing more rich and accurate data about patients' self-care that can contribute to our understanding of concepts such as adherence and satisfaction, and they can provide measurement tools to assess how glycemic control can effect cognition and intelligence. The present chapter will review articles published in the last year that have studied some of these issues.

Continuous glucose monitoring for patients with type 1 diabetes and impaired awareness of hypoglycaemia (IN CONTROL): a randomised, open-label, crossover trial

Pharmacotherapy in Type 1 Diabetes

The Comparison of Optimized MDI Versus Pumps With or Without Sensors in Severe Hypoglycemia (HypoCOMPaSS) trial was a prospective, multicenter, randomized controlled trial examining the restoration of impaired awareness of hypoglycemia (IAH) and the prevention of severe hypoglycemia (SH) in adults with type 1 diabetes using multiple daily injections (MDI) compared with continuous subcutaneous insulin infusion (CSII), with or without adjunctive real-time continuous glucose monitoring (RT-CGM), using a 2 × 2 factorial design (1). Few studies are currently available to compare the difference in glucose variability (GV) between MDI and CSII and between self-monitored blood glucose (SMBG) and RT-CGM (2–4). These studies showed an improvement in GV in favor of CSII and RT-CGM. However, none of them included participants with IAH or history of SH. The aim of this study is to compare the changes in GV between MDI and CSII and between SMBG and RT-CGM group in this specific patient group with type 1 diabetes with IAH or recurrent SH. A total of 96 participants were recruited for the study. Each participant undertook 7 days of blinded CGM using Medtronic iPro at baseline and prior to each of the four weekly visits during the 24-week randomized controlled trial period. GV was measured as glucose SD and coefficient of variation (%CV), calculated using available Excel formulas published online (5). Overall, there were decreases in GV between baseline and week …

BackgroundSevere hypoglycaemia (SH) is one of the most feared complications of type 1 diabetes (T1DM) with a reported prevalence of nearly 40%. In randomized trials of Multiple Daily Injections (MDI) and Continuous Subcutaneous Insulin Infusion (CSII) therapy there is a possible benefit of CSII in reducing SH. However few trials have used basal insulin analogues as the basal insulin in the MDI group and individuals with established SH have often been excluded from prospective studies. In published studies investigating the effect of Real Time Continuous Glucose Monitoring (RT-CGM) benefit in terms of reduced SH has not yet been demonstrated. The primary objective of this study is to elucidate whether in people with T1DM complicated by impaired awareness of hypoglycaemia (IAH), rigorous prevention of biochemical hypoglycaemia using optimized existing self-management technology and educational support will restore awareness and reduce risk of recurrent SH.Methods/designThis is a multicentre prospective RCT comparing hypoglycaemia avoidance with optimized MDI and CSII with or without RT-CGM in a 2×2 factorial design in people with type 1 diabetes who have IAH. The primary outcome measure for this study is the difference in IAH (Gold score) at 24 weeks. Secondary outcomes include biomedical measures such as HbA1c, SH incidence, blinded CGM analysis, self monitored blood glucose (SMBG) and response to hypoglycaemia in gold standard clamp studies. Psychosocial measures including well-being and quality of life will also be assessed using several validated and novel measures. Analysis will be on an intention-to-treat basis.DiscussionMost existing RCTs using this study’s interventions have been powered for change in HbA1c rather than IAH or SH. This trial will demonstrate whether IAH can be reversed and SH prevented in people with T1DM in even those at highest risk by using optimized conventional management and existing technology.Trial RegistrationISRCTN52164803 Eudract No: 2009-015396-27

To determine whether impaired awareness of hypoglycemia (IAH) can be improved and severe hypoglycemia (SH) prevented in type 1 diabetes, we compared an insulin pump (continuous subcutaneous insulin infusion [CSII]) with multiple daily injections (MDIs) and adjuvant real-time continuous glucose monitoring (RT) with conventional self-monitoring of blood glucose (SMBG). A 24-week 2 × 2 factorial randomized controlled trial in adults with type 1 diabetes and IAH was conducted. All received comparable education, support, and congruent therapeutic targets aimed at rigorous avoidance of biochemical hypoglycemia without relaxing overall control. Primary end point was between-intervention difference in 24-week hypoglycemia awareness (Gold score). A total of 96 participants (mean diabetes duration 29 years) were randomized. Overall, biochemical hypoglycemia (≤3.0 mmol/L) decreased (53 ± 63 to 24 ± 56 min/24 h; P = 0.004 [t test]) without deterioration in HbA1c. Hypoglycemia awareness improved (5.1 ± 1.1 to 4.1 ± 1.6; P = 0.0001 [t test]) with decreased SH (8.9 ± 13.4 to 0.8 ± 1.8 episodes/patient-year; P = 0.0001 [t test]). At 24 weeks, there was no significant difference in awareness comparing CSII with MDI (4.1 ± 1.6 vs. 4.2 ± 1.7; difference 0.1; 95% CI -0.6 to 0.8) and RT with SMBG (4.3 ± 1.6 vs. 4.0 ± 1.7; difference -0.3; 95% CI -1.0 to 0.4). Between-group analyses demonstrated comparable reductions in SH, fear of hypoglycemia, and insulin doses with equivalent HbA1c. Treatment satisfaction was higher with CSII than MDI (32 ± 3 vs. 29 ± 6; P = 0.0003 [t test]), but comparable with SMBG and RT (30 ± 5 vs. 30 ± 5; P = 0.79 [t test]). Hypoglycemia awareness can be improved and recurrent SH prevented in long-standing type 1 diabetes without relaxing HbA1c. Similar biomedical outcomes can be attained with conventional MDI and SMBG regimens compared with CSII/RT, although satisfaction was higher with CSII.

Severe hypoglycemia is a feared complication of type 1 diabetes; yet, few trials have targeted prevention using optimized self-management (educational, therapeutic, and technological support). We aimed to investigate whether improved awareness and reduced severe hypoglycemia, achieved during an intensive randomized clinical trial (RCT), were sustained after return to routine care. Ninety-six adults with type 1 diabetes (29 ± 12 years' duration) and impaired awareness of hypoglycemia at five U.K. tertiary referral diabetes centers were recruited into a 24-week 2 × 2 factorial RCT (HypoCOMPaSS). Participants were randomized to pump (continuous subcutaneous insulin infusion [CSII]) or multiple daily injections (MDIs) and real-time continuous glucose monitoring (RT-CGM) or self-monitoring of blood glucose (SMBG), with equal education/attention to all groups. At 24 weeks, participants returned to routine care with follow-up until 24 months, including free choice of MDI/CSII; RT-CGM vs. SMBG comparison continued to 24 months. Primary outcome was mean difference (baseline to 24 months [between groups]) in hypoglycemia awareness. Improvement in hypoglycemia awareness was sustained (Gold score at baseline 5.1 ± 1.1 vs. 24 months 3.7 ± 1.9; P < 0.0001). Severe hypoglycemia rate was reduced from 8.9 ± 12.8 episodes/person-year over the 12 months prestudy to 0.4 ± 0.8 over 24 months (P < 0.0001). HbA1c improved (baseline 8.2 ± 3.2% [66 ± 12 mmol/mol] vs. 24 months 7.7 ± 3.1% [61 ± 10 mmol/mol]; P = 0.003). Improvement in treatment satisfaction and reduced fear of hypoglycemia were sustained. There were no significant differences between interventions at 24 months. Optimized insulin replacement and glucose monitoring underpinned by hypoglycemia-focused structured education should be provided to all with type 1 diabetes complicated by impaired awareness of hypoglycemia.

Real-time continuous glucose monitoring (rtCGM) improves glycemic control in type 1 diabetes (T1D) patients treated with continuous subcutaneous insulin infusion (CSII). However, the benefits of rtCGM in T1D patients treated with multiple daily insulin injection (MDI) therapy has not been well studied. We explored the effects of rtCGM versus self-monitoring of blood glucose (SMBG) on clinical outcomes within a large T1D population treated with either CSII or MDI therapy. This retrospective, longitudinal analysis utilized datasets from T1D patients enrolled in a commercial health plan to assess changes in HbA1c in 187 naïve to rtCGM users and 6260 SMBG users. Propensity score modeling was used to assess inpatient admissions, emergency room (ER) visits in 1130 patients (565 rtCGM, 565 SMBG). Differences in HbA1c reduction (rtCGM+MDI vs rtCGM+CSII) were evaluated. Larger, clinically meaningful HbA1c reductions were seen among rtCGM versus SMBG users: -0.5% ( P = .004) versus -0.2% ( P < .0001); 0.3% diff in diff, P = .03. All-cause inpatient admissions were lower for rtCGM users: -42%, P = .013. Emergency room visits coded for diabetic ketoacidosis (DKA) were four times higher for SMBG patients than rtCGM patients: 17 versus 4, P = .0318. HbA1c reductions were most notable with rtCGM+MDI versus rtCGM+CSII treatment: -0.6% ( P = .01) versus -0.3% ( P = .16). Use of rtCGM in T1D patients facilitates greater HbA1c improvements and reduced health care system utilization compared with traditional SMBG use regardless of insulin administration method. Treatment with rtCGM in conjunction with MDI confers similar or greater glycemic benefits without the additional costs associated with CSII therapy.

BackgroundInsulin therapy is required to prevent diabetic ketoacidosis and to optimise blood glucose levels in order to to minimise vascular complications in all Children and Young People with Type 1...

Impaired awareness of hypoglycaemia (IAH) is a major risk factor for severe hypoglycaemia in Type 1 diabetes. Although biochemical hypoglycaemia is asserted to be more frequent in IAH, this has not been estimated accurately. The aim of this study was to use Continuous Glucose Monitoring (CGM) to quantify hypoglycaemia in IAH and evaluate its use in identifying impaired awareness of hypoglycaemia. Ninety-five patients with Type 1 diabetes were classified as having normal (n = 74) or impaired awareness (n = 21) using an established method of assessing hypoglycaemia awareness. Hypoglycaemia exposure was assessed prospectively over 9-12 months using weekly 4-point capillary home blood glucose monitoring (HBGM), 5 days of CGM and prospective reporting of severe hypoglycaemia. The frequencies of biochemical and severe hypoglycaemia were compared in patients with normal and impaired awareness of hypoglycaemia. Patients with impaired awareness had a 3-fold higher incidence of severe hypoglycaemia than those with normal awareness [incidence rate ratio (IRR) 3.37 (95% CI 1.30-8.7); P = 0.01] and 1.6-fold higher incidence of hypoglycaemia on weekly HBGM [IRR 1.63 (95% CI 1.09-2.44); P = 0.02]. No significant differences were observed with CGM [IRR for sensor glucose < or = 3.0 mmol/l 1.47 (95% CI 0.91-2.39); P = 0.12; IRR for sensor glucose < or = 2.2 mmol/l 1.23 (95% CI 0.76-1.98); P = 0.40]. Patients with Type 1 diabetes with impaired awareness had a 3-fold higher risk of severe hypoglycaemia and 1.6-fold higher incidence of biochemical hypoglycaemia measured with weekly glucose monitoring compared with normal awareness, but 5 days of CGM did not differentiate those with impaired from those with normal awareness.

Background: The I HART CGM study showed that real-time continuous glucose monitoring (RT-CGM) has greater beneficial impact on hypoglycemia than intermittent flash glucose monitoring (flash) in adults with type 1 diabetes (T1D) at high risk. The impact of continuing RT-CGM or switching from flash to RT-CGM for another 8 weeks was then evaluated.Methods: Prospective randomized parallel group study with an extension phase. After a 2-week run-in with blinded CGM, participants were randomized to either RT-CGM or flash for 8 weeks. All participants were then given the option to continue with RT-CGM for another 8 weeks. Glycemic outcomes at 8 weeks are compared with the 16-week endpoint.Results: Forty adults with T1D on intensified multiple daily insulin injections and with impaired awareness of hypoglycemia or a recent episode of severe hypoglycemia were included (40% female, median [IQR] age 49.5 [37.5–63.5] years, diabetes duration 30.0 [21.0–36.5] years, HbA1c 56 [48–63] mmol/mol, and Gold Score 5 [4–5]), of whom 36 completed the final 16-week extension. There was a significant reduction in percentage time in hypoglycemia (<3.0 mmol/L) in the group switching from flash to RT-CGM (from 5.0 [3.7–8.6]% to 0.8 [0.4–1.9]%, P = 0.0001), whereas no change was observed in the RT-CGM group continuing with the additional 8 weeks of RT-CGM (1.3 [0.4–2.8] vs. 1.3 [0.8–2.5], P = 0.82). Time in target (3.9–10 mmol/L) increased in the flash group after switching to RT-CGM (60.0 [54.5–67.8] vs. 67.4 [56.3–72.4], P = 0.02) and remained the same in the RT-CGM group that continued with RT-CGM (65.9 [54.1–74.8] vs. 64.9 [49.2–73.9], P = 0.64).Conclusions: Our data suggest that switching from flash to RT-CGM has a significant beneficial impact on hypoglycemia outcomes and that continued use of RT-CGM maintains hypoglycemia risk benefit in this high-risk population.

Prevalence of severe hypoglycemia in a cohort of patients with type 1 diabetes

Prevalencia de hipoglucemia grave en una cohorte de pacientes con diabetes tipo 1