The anti-inflammatory and immunological properties of SGLT-2 inhibitors.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are antidiabetic oral drugs that act on proximal renal tubules promoting renal glucose excretion. Although SGLT-2i belong to the class of hypoglycemic agents, in the last years great interest has emerged in studying their pleiotropic effects, beyond their ability to lower glucose levels. PURPOSE: In this review we are describing the anti-inflammatory and immunological properties of SGLT-2i; furthermore, we are addressing how the mechanisms associated with the aforementioned anti-inflammatory properties may contribute to the beneficial effects of SGLT-2i in diabetes. METHODS: A systematic search was undertaken for studies related the properties of SGLT-2i in reducing the inflammatory milieu of acute and chronic disease by acting on the immune system, independently by glycemia. RESULTS: Recently, some data described the anti-inflammatory and immunological properties of SGLT-2 in both pre-clinical and clinical studies. Numerous data confirmed the cardio- and -renal protective effects of SGLT-2i in patients with heart failure and kidney diseases, with or without diabetes. CONCLUSIONS: SGLT-2i are promising drugs with anti-inflammatory and immunological properties. Despite the mechanism of action of SGLT-2i is not fully understood, these drugs demonstrated anti-inflammatory effects, which may help in keeping under control the variety of complications associated with diabetes.

Anti-inflammatory effects of diet and caloric restriction in metabolic syndrome.

BACKGROUND: Weight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear. AIM: To determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles. METHODS: Eighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2 were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss. RESULTS: After weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1ß, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change. CONCLUSION: Weight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.

Bone involvement and mineral metabolism in Williams' syndrome.

CONTEXT: The previous studies suggested a possible increased risk of hypercalcaemia and reduced bone mineral density (BMD) in Williams' syndrome (WS). However, an extensive study regarding bone metabolism has never been performed. OBJECTIVE: To investigate bone health in young adults with WS. DESIGN: Cross-sectional study. SETTINGS: Endocrinology and Metabolic Diseases and Medical Genetic Units. PATIENTS: 29 WS young adults and 29 age- and sex-matched controls. MAIN OUTCOME MEASURES: In all subjects, calcium, phosphorus, bone alkaline phosphatase (bALP), parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHVitD), osteocalcin (OC), carboxyterminal cross-linking telopeptide of type I collagen (CTX), 24-h urinary calcium and phosphorus, femoral-neck (FN) and lumbar-spine (LS) BMD and vertebral fractures (VFx) were assessed. In 19 patients, serum fibroblast growth factor-23 (FGF23) levels were measured. RESULTS: WS patients showed lower phosphorus (3.1 ± 0.7 vs 3.8 ± 0.5 mg/dL, p = 0.0001) and TmP/GFR (0.81 ± 0.32 vs 1.06 ± 0.25 mmol/L, p = 0.001), and an increased prevalence (p = 0.005) of hypophosphoremia (34.5 vs 3.4%) and reduced TmP/GFR (37.9 vs 3.4%). Moreover, bALP (26.3 ± 8.5 vs 35.0 ± 8.0 U/L), PTH (24.5 ± 12.6 vs 33.7 ± 10.8 pg/mL), OC (19.4 ± 5.3 vs 24.5 ± 8.7 ng/mL), and FN-BMD (- 0.51 ± 0.32 vs 0.36 ± 0.32) were significantly lower (p < 0.05), while CTX significantly higher (401.2 ± 169.3 vs 322.3 ± 122.4 pg/mL, p < 0.05). Serum and urinary calcium and 25OHVitD levels, LS-BMD and VFx prevalence were comparable. No cases of hypercalcemia and suppressed FGF23 were documented. Patients with low vs normal phosphorus and low vs normal TmP/GFR showed comparable FGF23 levels. FGF23 did not correlate with phosphorus and TmP/GFR values. CONCLUSIONS: Adult WS patients have reduced TmP/GFR, inappropriately normal FGF23 levels and an uncoupled bone turnover with low femoral BMD.