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Abstract Background Treatment of the older diabetic individual comprises a therapeutic challenge. Currently little scientific evidence exists depicting the best approach to type 2 diabetes treatment in this growing sub-population of patients. The purpose of this study is to assess the effects of a modified plant-based Mediterranean diet (“vegeterranean” diet), circuit resistance training (CRT) and empagliflozin, separately or in combination, on body composition and physical function in older subjects with type 2 diabetes. The rationale for this study is to assess three interventions associated with a negative energy/caloric balance (increased caloric use in exercise, caloric restriction in the “vegeterranean” diet and caloric wasting by glycosuria with empagliflozin), their interaction and effect on body composition and physical function. Methods One hundred and twenty men and women ≥65 years of age with type 2 diabetes, and low levels of physical activity will be randomized (1:1:1 manner, gender stratified) for 10 weeks to one of 3 parallel arms: CRT consisting of 3 home sessions/week; ad-libitum plant-based Mediterranean diet (limited consumption of eggs, dairy and fish, avoidance of red meat and poultry) or empagliflozin 10 mg/day. After 10 weeks CRT will be added to the empagliflozin and diet arms for an additional 10 weeks. Allocation concealment and blinding of primary outcome assessors will be implemented. Efficacy will be determined by assessment of lean body mass, body weight, frailty and functional status, sarcopenia, HbA1c and quality of life questionnaires. Safety will be evaluated by routine monitoring of adverse events. This study was approved by the Tel-Aviv Sourasky Medical Center Institutional Review Board. Discussion The combination and comparison of these diverse interventions to metabolic control may lead to better understanding of their mechanism of action with potential clinical implications in older individuals. Also, this study will provide evidence of the effectiveness of these interventions on delaying the progression from diabetes to sarcopenia and/or frailty. Trial registration ClinicalTrials.gov PRS: NCT03560375. Last registration date (last update): 06/06/2018. The trial was a-priori registered before actual recruitment of subjects.

Background: Sex hormone-binding globulin (SHBG) is the main transporter of sex hormones in most vertebrates. Low SHBG levels have been linked to increased risk for diabetes and metabolic syndrome. Polymorphisms of the SHBG gene linked to low SHBG protein levels also strongly predicted increased risk of type 2 diabetes, thus raising the possibility that SHBG may play a role in the pathogenesis of insulin resistance and diabetes. Aim: To examine whether expression of human SHBG in mice may ameliorate the development of diabetes and metabolic syndrome in response to a high-fat diet (HFD). Methods: Transgene mice expressing a human SHBG transgene (SHBG+) (N = 10/11; males/ females) and their wild type littermates (N = 12/8; males/females) were fed HFD for 4.5 months. Results: HFD induced comparable obesity in control and SHBG+ mice. Male transgenes had higher muscle mass after 2–3.5 months HFD (0.43 ± 0.028 (n = 4) vs 0.38 ± 0.053 g (n = 7), P = 0.05). Fasting blood glucose, as well as insulin or HOMA-IR, was not different in transgenic vs wild-type males after 4–5 months HFD. Female transgenes had higher fasting glucose (152 ± 29 (n = 7) vs 115 ± 27 mg/dL, P = 0.01 (n = 8)), but mean insulin and HOMA-IR were not different. Likewise, insulin tolerance test and intra-peritoneal glucose tolerance test (GTT) were not different. Finally, SHBG+ mice were not different from controls in terms of liver enzymes, serum triglyceride levels and blood pressure. Conclusion: In mice with diet-induced obesity, human SHBG did not protect against development of obesity or dysglycemia.

The liver is the main metabolic organ in the body, serving as a significant hormonal secretory gland and functioning to maintain hormone balance and homeostasis. Steroid hormones regulate various biological pathways, mainly in the reproductive system and in many metabolic processes. The liver, as well as steroid hormones, contribute significantly, through functional intertwine, to homeostasis maintenance, and proper responses during stress. Malfunction of either has a significant impact on the other and may lead to severe liver diseases as well as to several endocrine syndromes. Thus, the regulation on liver functions as on steroid hormones levels and activities is well-controlled. p53, the well-known tumor suppressor gene, was recently found to regulate metabolism and general homeostasis processes, particularly within the liver. Moreover, p53 was shown to be involved in steroid hormones regulation. In this review, we discuss the bi-directional regulation of the liver and the steroid hormones pointing to p53 as a novel regulator in this axis. A comprehensive understanding of the molecular mechanisms of this axis may help to prevent and treat related disease, especially with the increasing exposure of the population to environmental steroid hormones and steroid hormone-based medication.