Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5'-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets.

Type 2 diabetes mellitus is a complex disease characterized by β-cell failure in the setting of insulin resistance. In early stages of the disease, pancreatic β-cells adapt to insulin resistance by increasing mass and function. As nutrient excess persists, hyperglycemia and elevated free fatty acids negatively impact β-cell function. This happens by numerous mechanisms, including the generation of reactive oxygen species, alterations in metabolic pathways, increases in intracellular calcium and the activation of endoplasmic reticulum stress. These processes adversely affect β-cells by impairing insulin secretion, decreasing insulin gene expression and ultimately causing apoptosis. In this review, we will first discuss the regulation of β-cell mass during normal conditions. Then, we will discuss the mechanisms of β-cell failure, including glucotoxicity, lipotoxicity and endoplasmic reticulum stress. Further research into mechanisms will reveal the key modulators of β-cell failure and thus identify possible novel therapeutic targets.

Introduction Clinically significant weight loss is defined as a ≥5% of initial body weight loss within a 6-month period. The purpose of this study was to assess body weight change from a 12-week telehealth-based weight loss program that integrated health coaching via video conferencing. Methods A total of 25 obese participants (12 males, 13 females) were recruited for this fully online 12-week weight loss program. Participants were randomly assigned to either an intervention group or control group ( n = 13 intervention, body mass index (BMI) = 34.7 ± 4.5 kg/m; n = 12 control, BMI = 34.4 ± 4.43 kg/m). All participants were given access to a secure platform for data tracking and video conferencing with the research team. The intervention group met with the medical doctor once per month and with a registered dietitian, weekly. Control participants met with the research team at baseline and at 12 weeks. Independent samples t-tests and Chi-square tests were used via SPSS version 24 with significance set to p < 0.05. Results There was a significant difference between the intervention and control groups for body weight loss (7.3 ± 5.2 versus 1.2 ± 3.9 kg, respectively, p < 0.05) as well as for percent body weight loss (7.16 ± 4.4 versus 1.5 ± 4.1%, respectively, p < 0.05). Clinically significant weight loss was achieved in 9 out of 13 (69.2%) in the intervention group versus 1 out of 12 (8%) in the control group. Discussion Mobile phone-based health coaching may promote weight loss. Weekly video conferencing with education may be an applicable tool for inducing significant body weight loss in obese individuals.

Patients with Type 2 diabetes mellitus (T2DM) show cognitive and mood impairment, indicating potential for brain injury in regions that control these functions. However, brain tissue integrity in cognition, anxiety, and depression regulatory sites, and their associations with these functional deficits in T2DM subjects remain unclear. We examined gray matter (GM) changes in 34 T2DM and 88 control subjects using high-resolution T1-weighted images, collected from a 3.0-Tesla magnetic resonance imaging scanner, and assessed anxiety [Beck Anxiety Inventory], depressive symptoms [Beck Depression Inventory-II], and cognition [Montreal Cognitive Assessment]. We also investigated relationships between GM status of cognitive and mood control sites and these scores in T2DM. Significantly increased anxiety (p = 0.003) and depression (p = 0.001), and reduced cognition (p = 0.002) appeared in T2DM over controls. Decreased GM volumes appeared in several regions in T2DM patients, including the prefrontal, hippocampus, amygdala, insular, cingulate, cerebellum, caudate, basal-forebrain, and thalamus areas (p < 0.01). GM volumes were significantly associated with anxiety (r = −0.456,p = 0.009), depression (r = −0.465,p = 0.01), and cognition (r = 0.455,p = 0.009) scores in regions associated with those regulations (prefrontal cortices, hippocampus, para hippocampus, amygdala, insula, cingulate, caudate, thalamus, and cerebellum) in T2DM patients. Patients with T2DM show brain damage in regions that are involved in cognition, anxiety, and depression control, and these tissue alterations are associated with functional deficits. The findings indicate that mood and cognitive deficits in T2DM patients has brain structural basis in the condition.

Background At the onset of the COVID-19 pandemic, there was a rapid increase in the use of telehealth services at the US Department of Veterans Affairs (VA), which was accelerated by state and local policies mandating stay-at-home orders and restricting nonurgent in-person appointments. Even though the VA was an early adopter of telehealth in the late 1990s, the vast majority of VA outpatient care continued to be face-to-face visits through February 2020. Objective We compared telehealth service use at a VA Medical Center, Greater Los Angeles across 3 clinics (primary care [PC], cardiology, and home-based primary care [HBPC]) 12 months before and 12 months after the onset of COVID-19 (March 2020). Methods We used a parallel mixed methods approach including simultaneous quantitative and qualitative approaches. The distribution of monthly outpatient and telehealth visits, as well as telephone and VA Video Connect encounters were examined for each clinic. Semistructured telephone interviews were conducted with 34 staff involved in telehealth services within PC, cardiology, and HBPC during COVID-19. All audiotaped interviews were transcribed and analyzed by identifying key themes. Results Prior to COVID-19, telehealth use was minimal at all 3 clinics, but at the onset of COVID-19, telehealth use increased substantially at all 3 clinics. Telephone was the main modality of patient choice. Compared with PC and cardiology, video-based care had the greatest increase in HBPC. Several important barriers (multiple steps for videoconferencing, creation of new scheduling grids, and limited access to the internet and internet-connected devices) and facilitators (flexibility in using different video-capable platforms, technical support for patients, identification of staff telehealth champions, and development of workflows to help incorporate telehealth into treatment plans) were noted. Conclusions Technological issues must be addressed at the forefront of telehealth evolution to achieve access for all patient populations with different socioeconomic backgrounds, living situations and locations, and health conditions. The unprecedented expansion of telehealth during COVID-19 provides opportunities to create lasting telehealth solutions to improve access to care beyond the pandemic.