Improved glycemic control in 3,592 adults with type 2 diabetes mellitus initiating a tubeless insulin management system.

AIMS: To compare glycemic outcomes in adults with type 2 diabetes mellitus (T2DM) before and 90 days after initiating Omnipod® or Omnipod DASH® Insulin Management Systems. METHODS: In this retrospective observational study (N = 3,592) change in HbA1c level, total daily dose (TDD) of insulin (n = 3,053), and frequency of self-reported hypoglycemic events (HE, <70 mg/dL, n = 2,922) were assessed overall and by prior treatment modality (multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII)), age group, and baseline HbA1c category. RESULTS: Change (mean ± SD) in HbA1c was -1.3 ± 1.7% [-14 ± 19 mmol/mol] overall, -1.4 ± 1.7% [-15 ± 19 mmol/mol] for prior MDI users, and -0.9 ± 1.5% [-10 ± 16 mmol/mol] for prior CSII users (p<0.0001). The percentage of patients with HbA1c ≥9% [≥75 mmol/mol] decreased (49% to 19%), and with HbA1c <7% [<53 mmol/mol] increased (10% to 22%) (p<0.0001). Prior therapy, age, and baseline HbA1c category were factors affecting change in HbA1c (p<0.05). Reductions in TDD (overall, -33 ± 52U, p<0.0001) and HE per week (overall, -0.5 ± 2.0, p<0.0001), were seen regardless of prior treatment, age, or baseline HbA1c. CONCLUSIONS: Omnipod System use was associated with statistically and clinically meaningful reductions in HbA1c, TDD, and HE compared to prior treatments in T2DM.

Evidence for a task-dependent switch in subthalamo-nigral basal ganglia signaling.

Basal ganglia (BG) can either facilitate or inhibit movement through excitatory and inhibitory pathways; however whether these opposing signals are dynamically regulated during healthy behavior is not known. Here, we present compelling neurophysiological evidence from three complimentary experiments in non-human primates, indicating task-specific changes in tonic BG pathway weightings during saccade behavior with different cognitive demands. First, simultaneous local field potential recording in the subthalamic nucleus (STN; BG input) and substantia nigra pars reticulata (SNr; BG output) reveals task-dependent shifts in subthalamo-nigral signals. Second, unilateral electrical stimulation of the STN, SNr, and caudate nucleus results in strikingly different saccade directionality and latency biases across the BG. Third, a simple artificial neural network representing canonical BG signaling pathways suggests that pathway weightings can be altered by cortico-BG input activation. Overall, inhibitory pathways (striato-pallidal-subthalamo-nigral) dominate during goal-driven behavior with instructed rewards, while facilitatory pathways (striato-nigral and subthalamo-pallidal-nigral) dominate during unconstrained (free reward) conditions.

Threshold mechanism for saccade initiation in frontal eye field and superior colliculus.

In an influential model of frontal eye field (FEF) and superior colliculus (SC) activity, saccade initiation occurs when the discharge rate of either single neurons or a population of neurons encoding a saccade motor plan reaches a threshold level of activity. Conflicting evidence exists for whether this threshold is fixed or can change under different conditions. We tested the fixed-threshold hypothesis at the single-neuron and population levels to help resolve the inconsistency between previous studies. Two rhesus monkeys performed a randomly interleaved pro- and antisaccade task in which they had to look either toward (pro) or 180° away (anti) from a peripheral visual stimulus. We isolated visuomotor (VM) and motor (M) neurons in the FEF and SC and tested three specific predictions of a fixed-threshold hypothesis. We found little support for fixed thresholds. First, correlations were never totally absent between presaccadic discharge rate and saccadic reaction time when examining a larger (plausible) temporal period. Second, presaccadic discharge rates varied markedly between saccade tasks. Third, visual responses exceeded presaccadic motor discharges for FEF and SC VM neurons. We calculated that only a remarkably strong bias for M neurons in downstream projections could render the fixed-threshold hypothesis plausible at the population level. Also, comparisons of gap vs. overlap conditions indicate that increased inhibitory tone may be associated with stability of thresholds. We propose that fixed thresholds are the exception rather than the rule in FEF and SC, and that stabilization of an otherwise variable threshold depends on task-related, inhibitory modulation.