A strong and expanding evidence base supports the influence of gut microbiota in human metabolism. Altered glucose homeostasis is associated with altered gut microbiota, and is clearly associated with the development of type 2 diabetes mellitus (T2DM) and associated complications. Understanding the causal association between gut microbiota and metabolic risk has the potential role of identifying susceptible individuals to allow early targeted intervention.

Aim: To conduct a meta‐analysis and systematic review to examine the effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) on clinical biomarkers of inflammation and oxidative stress in patients with type 2 diabetes. Methods: Medline, Embase and the Cochrane Library were searched for randomised controlled trials (RCTs) that examined changes with GLP‐1RAs in a priori selected biomarkers of inflammation: C‐reactive protein (CRP), adiponectin, tumour necrosis factor‐alpha (TNFα), plasminogen activator inhibitor‐1, interleukin‐6, leptin; and of oxidative stress: malondialdehyde (MDA); 8‐iso‐prostaglandin F2α; and 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG). Results: We included 40 eligible RCTs (n = 6749) with a median follow‐up of 6 months, a mean participant age of 53.1 years, 56.3% females, glycated haemoglobin (HbA1c) 55.6 mmol/mol, body mass index 28.8 kg/m ² and diabetes duration 7.46 years. Analysis of GLP‐1RAs versus standard diabetes therapies or placebo revealed significant reductions in CRP, TNFα and MDA, and significant increases in adiponectin for (mean difference −0.54 mg/L [−0.75, −0.34]; standard mean difference [SMD] −0.39 [−0.62, −0.15]; SMD −0.84 [−1.61, −0.06] and SMD 0.30 [0.12, 0.49], respectively [95% confidence intervals]). Systolic blood pressure decreased significantly and was significantly and strongly correlated with a reduction in CRP. Homeostatic model assessment of insulin resistance was also significantly correlated with a reduction in CRP, but HbA1c was not. Conclusions: There is strong evidence supporting clinically relevant anti‐inflammatory and antioxidant effects of GLP‐1RAs. This may be used to guide future targeted clinical use of GLP‐1RAs and the development of medications seeking to target the cardioprotective properties of GLP‐1RAs.

Previous guidelines for the treatment of people with type 2 diabetes mellitus (T2D) have relied heavily upon rigid algorithms for the sequential addition of pharmacotherapies to achieve target glycemic control. More recent guidelines advocate a personalized approach for diabetes treatment, to improve patient satisfaction, quality of life, medication adherence and overall health outcomes. Clinicians should work with patients to develop personalized goals for their treatment, including targeted glycemic control, weight management, prevention and treatment of associated comorbidities and avoidance of complications such as hypoglycemia. Factors that affect the intensity of treatment and choice of pharmacotherapy should include medical and patient influences. Medical considerations include the diabetes phenotype, biomarkers including genetic tests, and the presence of comorbidities such as cardiovascular, renal, or hepatic disease. Patient factors include their treatment preference, age and life expectancy, diabetes duration, hypoglycemia fear and unawareness, psychological and social circumstances. The use of a personalized approach in the management of people with T2D can reduce the cost and failure associated with the algorithmic “one-size-fits-all” approach, to anticipate disease progression, improve the response to diabetes pharmacotherapy and reduce the incidence of diabetes-associated complications. Ultimately, the use of personalized medicine in people with T2D should improve medication adherence, patient satisfaction and quality of life to reduce diabetes distress and improve physical health outcomes.

Obesity and its complications constitute a substantial burden. Considerable published research describes the novel relationships between obesity and gut microbiota communities. It is becoming evident that microbiota behave in a pivotal role in their ability to influence homeostatic mechanisms either to the benefit or detriment of host health, the extent of which is not fully understood. A greater understanding of the contribution of gut microbiota towards host pathophysiology is revealing new therapeutic avenues to tackle the global obesity epidemic. This review focuses on causal relationships and associations with obesity, proposed central mechanisms encouraging the development of obesity and promising prospective methods for microbiota manipulation.

Background: Increased oxidative stress is associated with coronary heart disease (CHD). We examined the association between plasma markers of oxidative stress and CHD in a cross-sectional sample of patients with diabetes and prospective CHD risk in a sample of men predominantly without diabetes. Methods: Plasma total antioxidant status (TAOS) and the ratio of oxidized LDL (Ox-LDL) to LDL-cholesterol (LDL-C) were determined in a cross-section of 761 Caucasian individuals with diabetes (UDACS study). Plasma TAOS was also determined in 310 baseline samples from a 10-year prospective cohort of 3012 healthy males (NPHSII). Results: Within UDACS, males with CHD had lower mean (SD) plasma TAOS [no CHD, 43.4 (13.2)%; CHD, 40.3 (13.8)%; P = 0.04]. The prevalence of CHD was higher in the lowest compared with the upper quartiles (32.7% vs 19.7%; P = 0.004). We observed a significant association between plasma Ox-LDL:LDL-C and CHD status [no CHD vs CHD, 16.9 (3.1) vs 19.3 (5.0) units/mmol; P = 0.04], with the prevalence of CHD being higher among men in the upper compared with lower quartiles (18.4% vs 35.1%; P = 0.003). No association was observed in females. In NPHSII, TAOS was lower in those who developed CHD [35.1 (8.0)% vs 37.1 (7.9)%; P = 0.04]. The odds ratio for CHD in the lowest compared with the upper quartile was 1.91 (95% confidence interval, 0.99–3.70; P = 0.04). This remained unchanged after adjustment for classic risk factors. Conclusions: A cross-sectional and prospective association exists between baseline plasma measures of oxidative stress and CHD risk. The association with prospective CHD risk remained after adjustment for “traditional” risk factors, implying an independent role for oxidative stress in CHD risk.