Evaluation of a Web-Based Simulation Tool for Self-Management Support in Type 1 Diabetes: A Pilot Study.

OBJECTIVE: To develop and evaluate a novel Web-based Simulation Tool (WST) that brings simulation technologies to people with Type 1 Diabetes (T1D), enabling unique patient-data interactions seamlessly on a daily basis. METHODS: A pilot clinical trial was conducted to assess system usability. The study consisted of one week of observation (Phase 1) and four weeks of interaction with WST (Phase 2). Responses to Technology Acceptance (TA) and Diabetes Distress Scale (DDS) questionnaires were collected, and follow-up interviews were conducted after Phase 2. RESULTS: Fifteen participants with T1D using Control-IQ technology (age: 36 ± 13 years, HbA1c: 6.5% ± 0.7%) completed all study procedures. Generated simulation models achieved a median Mean Absolute Relative Difference (MARD) of 6.8% [interquartile range, IQR: 5.1%, 9.1%]. A decrease in expected benefits (likely explained by issues with the third-party data collection system) and an increase in expected burdens were observed. On a 1-5 scale, ease of use, trust, and usefulness scores were 3 [3,4], 4 [3,4], and 4 [3,4], respectively. Time below 70 mg/dL decreased between Phases 1 and 2 (1.6% [0.7%,3.7%] vs 0.8% [0.5%,3.0%]). A reduction in mean emotional burden was also observed (2.5 ± 1.1 vs 2.1 ± 0.8). CONCLUSIONS: Results indicate that there was a learning curve to WST, but also that most participants trusted the system and found it useful in their diabetes care. SIGNIFICANCE: Simulation technologies like WST could be used by educators and patients to facilitate diabetes self-management, leading to better diabetes literacy and reducing associated distress.

Predictors of Time-in-Range (70-180 mg/dL) Achieved Using a Closed-Loop Control System.

Background: Studies of closed-loop control (CLC) in patients with type 1 diabetes (T1D) consistently demonstrate improvements in glycemic control as measured by increased time-in-range (TIR) 70-180 mg/dL. However, clinical predictors of TIR in users of CLC systems are needed. Materials and Methods: We analyzed data from 100 children aged 6-13 years with T1D using the Tandem Control-IQ CLC system during a randomized trial or subsequent extension phase. Continuous glucose monitor data were collected at baseline and during 12-16 weeks of CLC use. Participants were stratified into quartiles of TIR on CLC to compare clinical characteristics. Results: TIR for those in the first, second, third, and fourth quartiles was 54%, 65%, 71%, and 78%, respectively. Lower baseline TIR was associated with lower TIR on CLC (r = 0.69, P < 0.001). However, lower baseline TIR was also associated with greater improvement in TIR on CLC (r = -0.81, P < 0.001). During CLC, participants in the highest versus lowest TIR-quartile administered more user-initiated boluses daily (8.5 ± 2.8 vs. 5.8 ± 2.6, P < 0.001) and received fewer automated boluses (3.5 ± 1.0 vs. 6.0 ± 1.6, P < 0.001). Participants in the lowest (vs. the highest) TIR-quartile received more insulin per body weight (1.13 ± 0.27 vs. 0.87 ± 0.20 U/kg/d, P = 0.008). However, in a multivariate model adjusting for baseline TIR, user-initiated boluses and insulin-per-body-weight were no longer significant. Conclusions: Higher baseline TIR is the strongest predictor of TIR on CLC in children with T1D. However, lower baseline TIR is associated with the greatest improvement in TIR. As with open-loop systems, user engagement is important for optimal glycemic control.

Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.

BACKGROUND: Growth hormone secretion and muscle mass decline from midpuberty throughout life, culminating in sarcopenia, frailty, decreased function, and loss of independence. The decline of growth hormone in the development of sarcopenia is one of many factors, and its etiologic role needs to be demonstrated. OBJECTIVE: To determine whether MK-677, an oral ghrelin mimetic, increases growth hormone secretion into the young-adult range without serious adverse effects, prevents the decline of fat-free mass, and decreases abdominal visceral fat in healthy older adults. DESIGN: 2-year, double-blind, randomized, placebo-controlled, modified-crossover clinical trial. SETTING: General clinical research center study performed at a university hospital. PARTICIPANTS: 65 healthy adults (men, women receiving hormone replacement therapy, and women not receiving hormone replacement therapy) ranging from 60 to 81 years of age. INTERVENTION: Oral administration of MK-677, 25 mg, or placebo once daily. MEASUREMENTS: Growth hormone and insulin-like growth factor I levels. Fat-free mass and abdominal visceral fat were the primary end points after 1 year of treatment. Other end points were body weight, fat mass, insulin sensitivity, lipid and cortisol levels, bone mineral density, limb lean and fat mass, isokinetic strength, function, and quality of life. All end points were assessed at baseline and every 6 months. RESULTS: Daily administration of MK-677 significantly increased growth hormone and insulin-like growth factor I levels to those of healthy young adults without serious adverse effects. Mean fat-free mass decreased in the placebo group but increased in the MK-677 group (change, -0.5 kg [95% CI, -1.1 to 0.2 kg] vs. 1.1 kg [CI, 0.7 to 1.5 kg], respectively; P < 0.001), as did body cell mass, as reflected by intracellular water (change, -1.0 kg [CI, -2.1 to 0.2 kg] vs. 0.8 kg [CI, -0.1 to 1.6 kg], respectively; P = 0.021). No significant differences were observed in abdominal visceral fat or total fat mass; however, the average increase in limb fat was greater in the MK-677 group than the placebo group (1.1 kg vs. 0.24 kg; P = 0.001). Body weight increased 0.8 kg (CI, -0.3 to 1.8 kg) in the placebo group and 2.7 kg (CI, 2.0 to 3.5 kg) in the MK-677 group (P = 0.003). Fasting blood glucose level increased an average of 0.3 mmol/L (5 mg/dL) in the MK-677 group (P = 0.015), and insulin sensitivity decreased. The most frequent side effects were an increase in appetite that subsided in a few months and transient, mild lower-extremity edema and muscle pain. Low-density lipoprotein cholesterol levels decreased in the MK-677 group relative to baseline values (change, -0.14 mmol/L [CI, -0.27 to -0.01 mmol/L]; -5.4 mg/dL [CI, -10.4 to -0.4 mg/dL]; P = 0.026); no differences between groups were observed in total or high-density lipoprotein cholesterol levels. Cortisol levels increased 47 nmol/L (CI, 28 to 71 nmol/L (1.7 microg/dL [CI, 1.0 to 2.6 microg/dL]) in MK-677 recipients (P = 0.020). Changes in bone mineral density consistent with increased bone remodeling occurred in MK-677 recipients. Increased fat-free mass did not result in changes in strength or function. Two-year exploratory analyses confirmed the 1-year results. LIMITATION: Study power (duration and participant number) was insufficient to evaluate functional end points in healthy elderly persons. CONCLUSION: Over 12 months, the ghrelin mimetic MK-677 enhanced pulsatile growth hormone secretion, significantly increased fat-free mass, and was generally well tolerated. Long-term functional and, ultimately, pharmacoeconomic, studies in elderly persons are indicated.

Evidence for acyl-ghrelin modulation of growth hormone release in the fed state.

CONTEXT: The timing and frequency of GH secretory episodes is regulated by GHRH and somatostatin. This study provides evidence for amplification of these GH pulses by endogenous acyl-ghrelin. DESIGN: Blood was sampled every 10 min for 26.5 h during a fed admission with standardized meals and also during the final 24 h of a 61.5-h fast. GH secretion profiles were derived from deconvolution of 10-min sampling data, and full-length acyl-ghrelin levels were measured using a newly developed two-site sandwich assay. SETTING: The study was conducted at a university hospital general clinical research center. PARTICIPANTS: Participants included eight men with mean (+/- sd) age 24.5 +/- 3.7 yr (body mass index 24 +/- 2.1 kg/m(2)). RESULTS: Correlations were computed between amplitudes of individual GH secretory events and the average acyl-ghrelin concentration in the 60-min interval preceding each GH burst. In the fed state, the peak correlations were positive for all subjects and significantly higher than in the fasting state when acyl-ghrelin levels declined [mean (+/- sem): 0.7 (0.04) vs. 0.29 (0.08), P = 0.017]. In addition, long-term fasting was associated with an increase in the GH secretory pulse mass and amplitude but not frequency [fed vs. fasting pulse mass: 0.22 (0.05) vs. 0.44 (0.06) microg/liter, P = 0.002; amplitude: 5.2 (1.3) vs. 11.8 (1.9) microg/liter/min, P = 0.034; pulses per 24 h: 19.4 (0.5) vs. 22.0 (1.4), P = 0.1]. CONCLUSION: Our data support the hypothesis that under normal conditions in subjects given regular meals endogenous acyl-ghrelin acts to increase the amplitude of GH pulses.