Type 2 diabetes mellitus is a disease of complex pathogenesis and pleiotropic clinical manifestations. The greatest clinical challenge in this disease is the prevention of the long-term complications, many of which involve cardiovascular outcomes. The peroxisome proliferator-activated receptor (PPAR) alpha and gamma isoforms of the family of nuclear transcription factors are pharmaceutical targets for therapeutic intervention because they can potentially ameliorate not only the hyperglycemia of diabetes, but also the dyslipidemia that is characteristic of this disorder (low high-density lipoprotein cholesterol, high triglycerides, small, dense low-density lipoprotein particles). Novel drugs with dual PPAR alpha and gamma activity have been under clinical development for type 2 diabetes, and they have shown promise in early studies with regard to glucose lowering and improved lipid profile when compared with the PPAR-gamma-specific thiazolidinediones. Unfortunately, the dual PPARs available to date have some of the PPAR-gamma-associated side effect profile, including fluid retention and weight gain, which have limited the further clinical development of higher doses that show improved efficacy. This review will briefly summarize our understanding of the pathogenesis of type 2 diabetes, the role of the PPAR family of receptors, and the potential for clinical use of this novel emerging class of agents that serve as dual activators of both PPAR-alpha and PPAR-gamma.

Purpose: Diabetes Self-Management Education (DSME) is a crucial aspect of treating type 2 diabetes mellitus (T2DM). Daily individual decisions affect patient health, well-being, and long term outcomes. This pilot study evaluated what best educates and motivates patients to improve glucose control. Method: 17 participants with T2DM were recruited from Penn Rodebaugh Diabetes Center to attend 3 monthly diabetes support group meetings, and receive American Association of Diabetes Educators education. Weight and hemoglobin A1C (A1C) were measured at baseline and completion. Fitbit Activity Trackers were provided, as well as bi-weekly communication to reinforce behavior change. Pre and post-study surveys assessed nutrition, activity, monitoring blood glucose, and taking medication. Two sided paired t-test was performed to compare change in A1C and weight. A type I error rate of 0.was used for statistical significance. Results: 15 participants completed the study. DSME interventions resulted in a statistically significant decrease in mean A1C from 8.5% to 7.7% with a mean A1C reduction of 0.8% in 3 months (p-value=0.01). Mean weight decreased 4.80 lb (p-value=0.0001). 11 remained on same medications, and 1 required reduced insulin. 3 added a glucagon-like peptide receptor agonist (GLP-1RA), with 1 adding a sodium-glucose cotransporter-2 inhibitor. 7 increased daily steps wearing Fitbit, while 8 reported no motivation. 10 increased weekly exercise, and 11 increased daily activity. All benefited from bi-weekly reinforcement, and reported improved nutrition. Food replica models aided visual reinforcement. Conclusion: DSME in a group setting can motivate self-care and reduce both A1C and weight, however, the study met challenges. Time per patient spent coordinating was substantial. Food models and phone communication to reinforce lifestyle modification were useful. Research is needed to determine what provides long-term sustainability in a busy clinical practice. Disclosure L. McLeer Maloney: None. J. Flood: None. N. Alamuddin: Consultant; Self; Novo Nordisk Inc.. M. Al Mukaddam: None.

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Graves disease is an autoimmune disease characterized by the loss of immune tolerance to thyroid antigens and the resulting development of stimulating autoantibodies directed against thyrotropin [thyroid stimulating hormone (TSH)] receptors in the thyroid follicular cells, orbital fibroblasts and adipocytes, and the skin. These antibodies cause thyroid hormone overproduction by the thyroid follicular cells, leading to classic symptoms of hyperthyroidism. The activation of TSH receptors in local fibroblasts in the skin can lead to thyroid dermopathy, characterized by T-cell infiltration, local inflammation, and increased production of glycosaminoglycans leading to tissue swelling and hypertrophy. [1][2][3] The pathogenesis of Graves orbitopathy will be reviewed in a later chapter. ' DefinitionsThyrotoxicosis is a clinical state resulting from inappropriately high thyroid hormone levels and their action on target tissues. 2 Hyperthyroidism more specifically is a form of thyrotoxicosis that results from the inappropriate synthesis and secretion of thyroid hormone by the thyroid gland. The most common causes of hyperthyroidism in the United States are Graves disease, toxic multinodular goiter, and single toxic adenoma. 2 ' Clinical Presentation Upon presentation, patients can have signs and symptoms due to thyrotoxicosis, obstructive symptoms from a goiter such as dysphagia, and/or extrathyroidal manifestations of autoimmunity, as seen in orbitopathy and dermopathy. Thyroid hormone acts by binding to specific thyroid hormone receptors, modifying gene transcription in