Inflammation is an important contributor to the pathogenesis of obesity-related type 2 diabetes (T2D). Adipose tissue-resident immune cells have been observed, and the potential contribution of these cells to metabolic dysfunction has been appreciated in recent years. This review focused on adipose tissue-resident immune cells that are dysregulated in the context of obesity and T2D. We comprehensively overviewed emerging knowledge regarding the phenotypic and functional properties of these cells and local factors that control their development. We discussed their function in controlling the immune response cascade and disease progression. We also characterized the metabolic profiles of these cells to explain the functional consequences in obese adipose tissues. Finally, we discussed the potential therapeutic targeting of adipose tissue-resident immune cells with the aim of addressing novel therapeutic approaches for the treatment of this disease.
Compared with placebo, metformin was not associated with glycaemic control in T1D patients. Although it exhibited other benefits, such as lower BMI and reduced insulin requirements, total cholesterol, and low-density lipoprotein cholesterol, negative outcomes, such as gastrointestinal adverse effects and severe hypoglycaemia, should also be considered in the use of metformin for T1D patients.
Summary Sodium‐glucose cotransporter (SGLT) inhibitors added to insulin therapy have been proposed as treatment strategy for type 1 diabetes (T1D). We thus conducted a meta‐analysis of randomized controlled trials (RCTs) to assess the efficacy and adverse effects of this combination in T1D. We searched the PubMed, EMBASE, and Cochrane Library databases and http://ClinicalTrials.gov for RCTs. Statistical analyses were performed using STATA 15. Ten eligible placebo‐controlled trials involving 5961 patients were included. Compared with placebo, SGLT inhibitors were associated with a reduction in HbA1c of −0.39% (95% CI, −0.43 to −0.36), an improved mean amplitude of glucose excursion (MAGE) of −14.81 mg/dL (95% CI, −19.08 to −10.54), and a reduction in body weight of −3.47% (95% CI, −3.78 to −3.16), as well as no increased relative risk of hypoglycaemia (1.01; 95% CI, 0.99‐1.02) or severe hypoglycaemia (0.91; 95% CI, 0.77‐1.07). SGLT inhibitors decreased fasting plasma glucose and insulin requirement but increased the risk of genital infection (3.57; 95% CI, 2.97‐4.29) and diabetic ketoacidosis (3.11; 95% CI, 2.11‐4.58). However, the very low dose empagliflozin (2.5 mg) did not increase the risk of diabetic ketoacidosis (risk ratio [RR] 0.67; 95% CI, 0.11‐3.95). SGLT inhibitors had no effect on overall adverse events, urinary tract infection, or bone fracture but slightly increased the risk of serious adverse events (1.35; 95% CI, 1.16‐1.58), severe adverse events (1.84; 95% CI, 1.20‐2.84), adverse events leading to discontinuation (1.50; 95% CI, 1.22‐1.84), drug‐related adverse events (1.78; 95% CI, 1.44‐2.19), and diarrhoea (1.54; 95% CI, 1.15‐2.05). Although adverse events exist, the available data provide evidence that the combination of SGLT inhibitors with basal insulin treatment is beneficial in patients with T1D.
With the growing use of immune checkpoint inhibitors (ICIs), case reports of rare yet life‐threatening pituitary‐adrenal dysfunctions, particularly for hypopituitarism, are increasingly being published. In this analysis, we focus on these events by including the most recent publications and reports from early phase I/II and phase III clinical trials and comparing the incidence and risks across different ICI regimens. PubMed, Embase, and the Cochrane Library were systematically searched from inception to April 2019 for clinical trials that reported on pituitary‐adrenal dysfunction. The rates of events, odds ratios (ORs), and 95% confidence intervals (CIs) were obtained using random effects meta‐analysis. The analyses included data from 160 trials involving 40 432 participants. The rate was 2.43% (95% CI, 1.73%‐3.22%) for all‐grade adrenal insufficiency and 3.25% (95% CI, 2.15%‐4.51%) for hypophysitis. Compared with the placebo or other therapeutic regimens, ICI agents were associated with a higher incidence of serious‐grade adrenal insufficiency (OR 3.19, 95% CI, 1.84 to 5.54) and hypophysitis (OR 4.77, 95% CI, 2.60 to 8.78). Among 71 serious‐grade hypopituitarism instances in 12 336 patients, there was a significant association between ICIs and hypopituitarism (OR 3.62, 95% CI, 1.86 to 7.03). Substantial heterogeneity was noted across the studies for the rates of these events, which in part was attributable to the different types of ICIs and varied phases of the clinical trials. Although the rates of these events were low, the risk was increased following ICI‐based treatment, particularly for CTLA‐4 inhibitors, which were associated with a higher incidence of pituitary‐adrenal dysfunction than PD‐1/PD‐L1 inhibitors.
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