Background:
We tested the safety and performance of the “insulin-only” configuration of the bionic pancreas (BP) closed-loop blood-glucose control system in a home-use setting to assess glycemic ...outcomes using different static and dynamic glucose set-points.
Method:
This is an open-label non-randomized study with three consecutive intervention periods. Participants had consecutive weeks of usual care followed by the insulin-only BP with (1) an individualized static set-point of 115 or 130 mg/dL and (2) a dynamic set-point that automatically varied within 110 to 130 mg/dL, depending on hypoglycemic risk. Human factors (HF) testing was conducted using validated surveys. The last five days of each study arm were used for data analysis.
Results:
Thirteen participants were enrolled with a mean age of 28 years, mean A1c of 7.2%, and mean daily insulin dose of 0.6 U/kg (0.4-1.0 U/kg). The usual care arm had an average glucose of 145 ± 20 mg/dL, which increased in the static set-point arm (159 ± 8 mg/dL, P = .004) but not in the dynamic set-point arm (154 ± 10 mg/dL, P = ns). There was no significant difference in time spent in range (70-180 mg/dL) among the three study arms. There was less time <70 mg/dL with both the static (1.8% ± 1.4%, P = .009) and dynamic set-point (2.7±1.5, P = .051) arms compared to the usual-care arm (5.5% ± 4.2%). HF testing demonstrated preliminary user satisfaction and no increased risk of diabetes burden or distress.
Conclusions:
The insulin-only configuration of the BP using either static or dynamic set-points and initialized only with body weight performed similarly to other published insulin-only systems.
There is growing evidence to suggest that the brain is an important target for insulin action, and that states of insulin resistance may extend to the CNS with detrimental effects on cognitive ...functioning. Although the effect of systemic insulin resistance on peripheral organs is well-studied, the degree to which insulin impacts brain function in vivo remains unclear.
This randomized, single-blinded, 2-way-crossover, sham-controlled, pilot study determined the effects of hyperinsulinemia on fMRI brain activation during a 2-back working memory task in 9 healthy older adults (aged 57-79 years). Each participant underwent two clamp procedures (an insulin infusion and a saline placebo infusion, with normoglycemia maintained during both conditions), to examine the effects of hyperinsulinemia on task performance and associated blood-oxygen-level dependent (BOLD) signal using fMRI.
Hyperinsulinemia (compared to saline control) was associated with an increase in both the spatial extent and relative strength of task-related BOLD signal during the 2-back task. Further, the degree of increased task-related activation in select brain regions correlated with greater systemic insulin sensitivity, as well as decreased reaction times and performance accuracy between experimental conditions.
Together, these findings provide evidence of insulin action in the CNS among older adults during periods of sustained cognitive demand, with the greatest effects noted for individuals with highest systemic insulin sensitivity.
This work was funded by the National Institutes of Health (5R21AG051958, 2016).
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