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Similar to the general population, lifestyle interventions focused on nutrition and physical activity form the foundation for treating obesity caused by rare genetic disorders. Additional therapies, including metreleptin and setmelanotide, that target defects within the leptin signaling pathway can effectively synergize with lifestyle efforts to treat monogenic disorders of leptin, leptin receptor, proopiomelanocortin (POMC), and proprotein convertase subtilisin/kexin type 1 (PCSK1) and syndromic conditions, such as the ciliopathies Bardet-Biedl and Alström syndromes, whose pathophysiological mechanisms also converge on the leptin pathway. Investigational treatments for Prader-Willi syndrome target specific defects caused by reduced expression of paternally derived genes within the chromosome 15q region., Competing Interests: Disclosure J.C. Han is a clinical trial investigator for multi-site research studies sponsored by Rhythm Pharmaceuticals. A.M. Haqq is a clinical trial investigator for multi-site research studies sponsored by Rhythm Pharmaceuticals, Levo Therapeutics, and Eli Lilly. She has received grants from the Weston Family Microbiome Initiative and Canadian Institutes of Health Research, Canada, payment as a speaker for Pfizer Canada, and is a member of advisory boards for Pfizer, Rhythm Pharmaceuticals, and Novo Nordisk Canada. The remaining authors have no disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Who never had a type 2 obese diabetic patient, treated by several oral antidiabetic drugs and insulin, with consequent weight gain associated with the therapeutic escalation and uncontrolled diabetes? The arrival of GLP-1 agonists and SGLT-2 inhibitors allows to reevaluate the management of these patients, with their favorable effects on glycemic control, weight and the risk of hypoglycemia and their complementary mechanisms to conventional treatments. The vicious cycle of weight gain and increased need of insulin is limited. The choice between these two molecules must be based on several factors (glycemic target, weight, comorbidities, route of administration, side effects, etc.), and the balanced enthusiasm of these new treatments with the insufficient data regarding their long-term safety and their impact on micro- and macrovascular complications.

Aims: To determine the effects of experimental jaw-muscle pain on jaw movements., Methods: Mandibular mid-incisor point was tracked in 22 asymptomatic subjects during standardized (at 2.2 mm/s) protrusion, contralateral excursion, and open jaw movements, as well as free, right-sided chewing and chewing standardized for timing (900 ms/cycle). Tonic infusion of 4.5% hypertonic saline into the right masseter muscle maintained pain intensity between 30 and 60 mm on a 100-mm visual analog scale. Subjects performed tasks in 3 sessions on the same experimental day: control condition (baseline trials), test condition 1 (during hypertonic or 0.9% isotonic saline infusion), and test condition 2 (during isotonic or hypertonic saline infusion)., Results: In comparison with control, there were no significant effects of hypertonic saline infusion on amplitude or velocity for protrusion or contralateral jaw movements or on velocity for jaw opening. Jaw-opening amplitude was significantly smaller in comparison with control during hypertonic, but not isotonic, saline infusion. During free but not standardized chewing, subjects chewed faster and exhibited larger amplitude gapes during hypertonic and isotonic infusion in comparison with control. Therefore, it was unlikely that pain had an effect on the kinematic parameters of jaw movement during free chewing. Qualitatively, individual subject data revealed considerable variability in the effects of hypertonic saline on movement parameters, which suggests that the effect of pain on jaw movement may not be uniform between individuals., Conclusions: The data indicate that the effect of pain on jaw movement may vary with the task performed.

To study the effects of masseter muscle pain on jaw muscle electromyographic (EMG) activity during goal-directed tasks. Mandibular movement was tracked and EMG activity was recorded from bilateral masseter, and right posterior temporalis, anterior digastric, and inferior head of lateral pterygoid muscles in 22 asymptomatic subjects at postural jaw position, and during three tasks: (a) protrusion, (b) contralateral (left), (c) open jaw movement. Tasks were performed during three conditions: control (no infusion), test 1 [continuous infusion into right masseter of 4.5% hypertonic saline to achieve 30-60 mm pain intensity on 100-mm visual analog scale (VAS)], and test 2 (isotonic saline infusion; in 16 subjects only); the sequence of hypertonic and isotonic saline was randomized. The average EMG root-mean-square values at 0.5 mm increments of mid-incisor-point displacement were analysed using linear mixed effects model statistics (significance: P < 0.05). Right masseter hypertonic saline infusion resulted in significantly (P < 0.0005) more pain (mean +/- SD VAS 47.3 +/- 14.3 mm) than isotonic infusion (12.2 +/- 17.3 mm). Although there was evidence of inter-subject variation, the principal EMG findings were that the significant effects of hypertonic saline-induced pain on EMG activity varied with the task in which the muscle participated irrespective of whether the muscle was an agonist or an antagonist in the tasks. The direction of the hypertonic saline-induced pain effect on EMG activity (i.e., whether the hypertonic saline-induced EMG activity was less than or greater than control EMG activity) could change with the magnitude of jaw displacement. Hypertonic saline infusion had no significant effect on postural EMG activity in any of the recorded jaw muscles. The data suggest that under constrained goal-directed tasks, the pattern of pain-induced changes in jaw muscle EMG activity is not clear cut, but can vary with the task performed, jaw displacement magnitude, and the subject being studied.