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OBJECTIVETo minimize hypoglycemia in subjects with type 1 diabetes by automated glucagon delivery in a closed-loop insulin delivery system.RESEARCH DESIGN AND METHODSAdult subjects with type 1 diabetes underwent one closed-loop study with insulin plus placebo and one study with insulin plus glucagon, given at times of impending hypoglycemia. Seven subjects received glucagon using high-gain parameters, and six subjects received glucagon in a more prolonged manner using low-gain parameters. Blood glucose levels were measured every 10 min and insulin and glucagon infusions were adjusted every 5 min. All subjects received a portion of their usual premeal insulin after meal announcement.RESULTSAutomated glucagon plus insulin delivery, compared with placebo plus insulin, significantly reduced time spent in the hypoglycemic range (15 ± 6 vs. 40 ± 10 min/day, P = 0.04). Compared with placebo, high-gain glucagon delivery reduced the frequency of hypoglycemic events (1.0 ± 0.6 vs. 2.1 ± 0.6 events/day, P = 0.01) and the need for carbohydrate treatment (1.4 ± 0.8 vs. 4.0 ± 1.4 treatments/day, P = 0.01). Glucagon given with low-gain parameters did not significantly reduce hypoglycemic event frequency (P = NS) but did reduce frequency of carbohydrate treatment (P = 0.05).CONCLUSIONSDuring closed-loop treatment in subjects with type 1 diabetes, high-gain pulses of glucagon decreased the frequency of hypoglycemia. Larger and longer-term studies will be required to assess the effect of ongoing glucagon treatment on overall glycemic control.

The 13th Acromegaly Consensus Conference was held in November 2019 in Fort Lauderdale, Florida, and comprised acromegaly experts including endocrinologists and neurosurgeons who considered optimal approaches for multidisciplinary acromegaly management. Focused discussions reviewed techniques, results, and side effects of surgery, radiotherapy, and medical therapy, and how advances in technology and novel techniques have changed the way these modalities are used alone or in combination. Effects of treatment on patient outcomes were considered, along with strategies for optimizing and personalizing therapeutic approaches.Expert consensus recommendations emphasize how best to implement available treatment options as part of a multidisciplinary approach at Pituitary Tumor Centers of Excellence.

ObjectiveThe Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH).ParticipantsA closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry.EvidenceCurrent literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues.Consensus processFollowing plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors.ConclusionsLAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.

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Abstract-We consider the problem of correlated data gathering in sensor networks with multiple sink nodes. The problem has two objectives. First, we would like to find a rate allocation on the correlated sensor nodes such that the data gathered by the sink nodes can reproduce the field of observation. Second, we would like to find a transmission structure on the network graph such that the total transmission energy consumed by the network is minimized. The existing solutions to this problem are impractical for deployment because they have not considered all of the following factors: 1) distributed implementation; 2) capacity and interference associated with the shared medium; and 3) realistic data correlation model. In this paper, we propose a new distributed framework to achieve minimum energy data gathering while considering these three factors. Based on a localized version of Slepian-Wolf coding, the problem is modeled as an optimization formulation with a distributed solution. The formulation is first relaxed with Lagrangian dualization and then solved with the subgradient algorithm. The algorithm is amenable to fully distributed implementations, which corresponds to the decentralized nature of sensor networks. To evaluate its effectiveness, we have conducted extensive simulations under a variety of network environments. The results indicate that the algorithm supports asynchronous network settings, sink mobility, and duty schedules.

OBJECTIVE -Considerable evidence implicates impaired nitric oxide (NO) generation in the pathogenesis of diabetic neuropathic pain. We therefore conducted a pilot study to examine the effects of isosorbide dinitrate (ISDN), a NO donor with local vasodilating properties, in spray form in the management of chronic neuropathic pain. RESEARCH DESIGN AND METHODS -The study was of double-blind, randomized, placebo-controlled, and two-period cross-over design. After a 2-week run-in period, 22 diabetic patients (13 men, 20 with type 2 diabetes, age [mean Ϯ SE] 63.7 Ϯ 1.8 years, duration of diabetes 9.1 Ϯ 1.5 years, duration of painful neuropathy 2.6 Ϯ 0.4 years) were randomized to receive ISDN or placebo sprays for 4 weeks, exchanging their treatment for a further 4 weeks after a 2-week wash-out period. The patients administered the spray to both feet before bedtime. Biweekly pain and other sensory symptoms were assessed using a visual analog scale (VAS) and the Lickert scale, respectively. RESULTS -ISDN spray reduced overall neuropathic pain (P ϭ 0.02) and burning sensation (P ϭ 0.006). No treatment difference was observed with other sensory modalities (hot/cold sensation, tingling, numbness, hyperesthesia, and jabbing-like sensation). At study completion, 11 patients (50%) reported benefit and wished to continue using the ISDN spray, 4 (18%) preferred the placebo spray, and the remaining 7 (32%) were undecided. CONCLUSIONS -ISDN spray offers an alternative and effective pharmacological option in relieving overall pain and burning sensation in the management of painful diabetic neuropathy. The potential of ISDN spray in alleviating other specific sensory symptoms associated with diabetic peripheral neuropathy merits further study. Diabetes Care 25:1699 -1703, 2002D iabetic peripheral neuropathy, one of the most common late complications of diabetes, is frequently painful, with the pain involving predominantly the lower limbs (1,2). The pain may vary from mild tingling to deepseated lancinating or severe unremitting pain. Night-time exacerbation of pain is common, with sleep deprivation and depression being common sequelae (3). The pathophysiology of the condition remains unclear, although it is associated with peripheral demyelination, a reduction in peripheral nerve conduction, and degeneration of myelinated and unmyelinated sensory fibers (4). Recent data suggest that impaired nitric oxide (NO) synthesis plays an important role in the pathogenesis of painful diabetic neuropathy. Sasaki et al. (5) and Rodella et al. (6) demonstrated that impaired neuronal NO generation in diabetic rats induced hyperalgesia, whereas Pitei et al. (7) showed that decreased NO production contributed to a reduction in endoneurial blood flow in type 2 diabetic patients with peripheral sensory neuropathy. The preservation of endothelialdependent vasodilatory responses to nitroglycerin (8), which directly releases NO, further implicates a defect or defects in endoneurial NO synthesis as the cause of impaired vascular responses in diabetes. ...

Context Long-acting GH (LAGH) preparations are currently being developed in an attempt to improve adherence. The profile of GH action following administration of LAGH raises practical questions about clinical monitoring and long-term safety and efficacy of these new therapeutic agents. Methods Recent literature and meeting proceedings regarding LAGH preparations are reviewed. Results Multiple LAGH preparations are currently at various stages of development, allowing for decreased GH injection frequency from daily to weekly, biweekly, or monthly. Following administration of LAGH, the serum peak and trough GH and IGF-I levels vary depending upon the mechanism used to prolong GH action. Randomized, controlled clinical trials of some LAGH preparations have reported non-inferiority compared with daily recombinant human GH (rhGH) for improved growth velocity and body composition in children and adults with GH deficiency (GHD), respectively. No significant LAGH-related adverse events have been reported during short-term therapy. Conclusion Multiple LAGH preparations are proceeding through clinical development with some showing promising evidence of short-term clinical efficacy and safety in children and adults with GHD. The relationship of transient elevations of GH and IGF-I following administration of LAGH to efficacy and safety remain to be elucidated. For LAGH to replace daily rhGH in the treatment of individuals with GHD, a number of practical questions need to be addressed including methods of dose adjustment, timing of monitoring of IGF-I, safety, efficacy, and cost-effectiveness. Long-term surveillance of efficacy and safety of LAGH preparations will be needed to answer these clinically relevant questions.