Glucose and Counterregulatory Responses to Exercise in Adults With Type 1 Diabetes and Impaired Awareness of Hypoglycemia Using Closed-Loop Insulin Delivery: A Randomized Crossover Study.

OBJECTIVE: To evaluate exercise-related glucose and counterregulatory responses (CRR) in adults with type 1 diabetes with impaired awareness of hypoglycemia (IAH) using hybrid closed-loop (HCL) insulin delivery to maintain glucose homeostasis. RESEARCH DESIGN AND METHODS: Twelve participants undertook 45-min high-intensity intermittent exercise (HIIE) and moderate-intensity exercise (MIE) in random order. The primary outcome was continuous glucose monitoring (CGM) time in range (70-180 mg/dL) for 24-h post-exercise commencement. RESULTS: CGM time in range was similar for HIIE and MIE (median 79.5% [interquartile range 73.2, 87.6] vs. 76.1% [70.3, 83.9], P = 0.37), and time with levels <54mg/dL post-exercise commencement was 0%. HIIE induced greater increases in cortisol (P = 0.002), noradrenaline (P = 0.005), and lactate (P = 0.002), with no differences in adrenaline, dopamine, growth hormone, or glucagon responses. CONCLUSIONS: IAH adults using HCL undertaking HIIE and MIE exhibit heterogeneity in CRR. Novel findings were a preserved cortisol response and variable catecholamine responses to HIIE.

Closed-Loop Insulin Delivery for Adults with Type 1 Diabetes Undertaking High-Intensity Interval Exercise Versus Moderate-Intensity Exercise: A Randomized, Crossover Study.

BACKGROUND: We aimed to compare closed-loop glucose control for people with type 1 diabetes undertaking high-intensity interval exercise (HIIE) versus moderate-intensity exercise (MIE). METHODS: Adults with type 1 diabetes established on insulin pumps undertook HIIE and MIE stages in random order during automated insulin delivery via a closed-loop system (Medtronic). Frequent venous sampling for glucose, lactate, ketones, insulin, catecholamines, cortisol, growth hormone, and glucagon levels was performed. The primary outcome was plasma glucose <4.0 mmol/L for ≥15 min, from exercise commencement to 120 min postexercise. Secondary outcomes included continuous glucose monitoring and biochemical parameters. RESULTS: Twelve adults (age mean ± standard deviation 40 ± 13 years) were recruited; all completed the study. Plasma glucose of one participant fell to 3.4 mmol/L following MIE completion; no glucose levels were <4.0 mmol/L for HIIE (primary outcome). There were no glucose excursions >15.0 mmol/L for either stage. Mean (±standard error) plasma glucose did not differ between stages pre-exercise; was higher during exercise in HIIE than MIE (11.3 ± 0.5 mmol/L vs. 9.7 ± 0.6 mmol/L, respectively; P < 0.001); and remained higher until 60 min postexercise. There were no differences in circulating free insulin before, during, or postexercise. During HIIE compared with MIE, there were greater increases in lactate (P < 0.001), catecholamines (all P < 0.05), and cortisol (P < 0.001). Ketones increased more with HIIE than MIE postexercise (P = 0.031). CONCLUSIONS: Preliminary findings suggest that closed-loop glucose control is safe for people undertaking HIIE and MIE. However, the management of the postexercise rise in ketones secondary to counter-regulatory hormone-induced insulin resistance observed with HIIE may represent a challenge for closed-loop systems.

"It Is Definitely a Game Changer": A Qualitative Study of Experiences with In-home Overnight Closed-Loop Technology Among Adults with Type 1 Diabetes.

BACKGROUND: This qualitative study explored trial participants' experiences of four nights of in-home closed loop. METHODS: Sixteen adults with type 1 diabetes, who completed a randomized crossover trial, were interviewed after four consecutive nights of closed-loop. Interviews were audio recorded, transcribed, and analyzed with a coding framework developed to identify the main themes. RESULTS: Participants had a mean age of 42 ± 10 years, nine were women; mean diabetes duration was 27 ± 7 years, and all were using insulin pumps. Overall, first impressions were positive. Participants found closed-loop easy to use and understand. Most experienced more stable overnight glucose levels, although for some these were similar to usual care or higher than they expected. Compared with their usual treatment, they noticed the proactive nature of the closed-loop, being able to predict trends and deliver micro amounts of insulin. Most reported technical glitches or inconveniences during one or more nights, such as transmission problems, problematic connectivity between devices, ongoing alarms despite addressing low glucose levels, and sensor inaccuracy. Remote monitoring by the trial team and their own hypoglycemic awareness contributed to feelings of trust and safety. Although rare, safety concerns were raised, related to feeling unsure whether the system would respond in time to falling glucose levels. CONCLUSIONS: This study provides relevant insights for implementation of closed-loop in the real world. For people with diabetes who are less familiar with technology, remote monitoring for the first few days may provide reassurance, strengthen their trust/skills, and make closed-loop an acceptable option for more people with type 1 diabetes.

Glycemia, Treatment Satisfaction, Cognition, and Sleep Quality in Adults and Adolescents with Type 1 Diabetes When Using a Closed-Loop System Overnight Versus Sensor-Augmented Pump with Low-Glucose Suspend Function: A Randomized Crossover Study.

BACKGROUND: We compared glycemia, treatment satisfaction, sleep quality, and cognition using a nighttime Android-based hybrid closed-loop system (Android-HCLS) with sensor-augmented pump with low-glucose suspend function (SAP-LGS) in people with type 1 diabetes. MATERIALS AND METHODS: An open-label, prospective, randomized crossover study of 16 adults (mean [SD] age 42.1 [9.6] years) and 12 adolescents (15.2 [1.6] years) was conducted. All participants completed four consecutive nights at home with Android-HCLS (proportional integral derivative with insulin feedback algorithm; Medtronic) and SAP-LGS. PRIMARY OUTCOME: percent continuous glucose monitoring (CGM) time (00:00-08:00 h) within target range (72-144 mg/dL). Secondary endpoints: percent CGM time above target (>144 mg/dL); below target (<72 mg/dL); glycemic variability (SD); symptomatic hypoglycemia; adult treatment satisfaction; sleep quality; and cognitive function. RESULTS: The primary outcome for all participants was not statistically different between Android-HCLS and SAP-LGS (mean [SD] 59.4 [17.9]% vs. 53.1 [18]%; p = 0.14). Adults had greater percent time within target range (57.7 [18.6]% vs. 44.5 [14.5]%; p < 0.006); less time above target (42.0 [18.7]% vs. 52.6 [16.5]%; p = 0.034); lower glycemic variability (35 [10.7] mg/dL vs. 46 [10.7] mg/dL; p = 0.003); and less (median [IQR]) time below target (0.0 [0.0-0.4]% vs. 0.80 [0.0-3.9]%; p = 0.025). In adolescents, time below target was lower with Android-HCLS vs. SAP-LGS (0.0 [0.0-0.0]% vs. 1.8 [0.1-7.9]%; p = 0.011). Nocturnal symptomatic hypoglycemia was less (1 vs. 10; p = 0.007) in adolescents, but not adults (5 vs. 13; p = 0.059). In adults, treatment satisfaction increased by 10 points (p < 0.02). Sleep quality and cognition did not differ. CONCLUSIONS: Android-HCLS in both adults and adolescents reduced nocturnal hypoglycemia and, in adults, improved overnight time in target range and treatment satisfaction compared with SAP-LGS.

New treatments for type 2 diabetes: cardiovascular protection beyond glucose lowering?

The health burden of type 2 diabetes mellitus (T2DM) is increasing worldwide, with a substantial portion of this burden being due to the development of cardiovascular (CV) disease. Multiple individual randomised clinical trials of intensive versus conventional glucose control, based on the use of traditional oral hypoglycaemic agents, have failed to convincingly show that intensive glucose control significantly reduces CV disease outcomes. In recent times, two new approaches to lowering glucose levels have become available. One targets the "incretin effect" which involves the modulation of peptide hormones that normally regulate glucose levels when nutrients are given orally. The other approach is based on inhibiting the sodium-glucose co-transporter 2 (SGLT-2) in the tubules of the kidney to promote glycosuria. Incretin-based therapies, especially glucagon-like peptide-1 receptor analogues, reduce glucose levels, with a low risk of hypoglycaemia, by increasing insulin secretion, inhibiting glucagon release and increasing satiety. Clinical and experimental studies have also shown favourable effects on CV disease risk factors such as dyslipidaemia, blood pressure, and improvements in endothelial function and cardiac contractility. Similarly, SGLT-2 inhibitors reduce glucose levels with a low risk for hypoglycaemia and have positive effects on multiple CV disease risk factors. Whether the beneficial effects of these new glucose lowering approaches on surrogate markers of CV disease risk translates to an improvement in CV events remains unknown. Several CV outcome trials are currently being performed to show that at a minimum, these novel glucose lowering agents are safe, but also have positive CV benefits.