Type 2 diabetes (T2D) is a disease characterized by heterogeneously progressive loss of islet β cell insulin secretion usually occurring after the presence of insulin resistance (IR) and it is one component of metabolic syndrome (MS), and we named it metabolic dysfunction syndrome (MDS). The pathogenesis of T2D is not fully understood, with IR and β cell dysfunction playing central roles in its pathophysiology. Dyslipidemia, hyperglycemia, along with other metabolic disorders, results in IR and/or islet β cell dysfunction via some shared pathways, such as inflammation, endoplasmic reticulum stress (ERS), oxidative stress, and ectopic lipid deposition. There is currently no cure for T2D, but it can be prevented or in remission by lifestyle intervention and/or some medication. If prevention fails, holistic and personalized management should be taken as soon as possible through timely detection and diagnosis, considering target organ protection, comorbidities, treatment goals, and other factors in reality. T2D is often accompanied by other components of MDS, such as preobesity/obesity, metabolic dysfunction associated steatotic liver disease, dyslipidemia, which usually occurs before it, and they are considered as the upstream diseases of T2D. It is more appropriate to call “diabetic complications” as “MDS-related target organ damage (TOD)”, since their development involves not only hyperglycemia but also other metabolic disorders of MDS, promoting an up-to-date management philosophy. In this review, we aim to summarize the underlying mechanism, screening, diagnosis, prevention, and treatment of T2D, especially regarding the personalized selection of hypoglycemic agents and holistic management based on the concept of “MDS-related TOD”.

We assessed the serum glucagon-like peptide-1 (GLP-1) levels for Chinese adults with pre-diabetes (PD) and newly-diagnosed diabetes mellitus (NDDM) during oral glucose tolerance test (OGTT). The relationships between total GLP-1 level and islet β cell function, insulin resistance (IR) and insulin sensitivity (IS) were also investigated. A 75g glucose OGTT was given to 531 subjects. Based on the results, they were divided into groups of normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), IFG combined IGT (IFG+IGT) and NDDM. Total GLP-1 levels were measured at 0- and 2-hour during OGTT. Homeostasis model assessment of β cell function (HOMA-β), HOMA of insulin resistance (HOMA-IR), Gutt and Matsuda indexes were calculated. The relationships between GLP-1 level and β cell function, IR and IS were analyzed. The levels of total fasting GLP-1 (FGLP-1), 2h GLP-1 (2hGLP-1) and 2hGLP-1 increments (∆GLP-1) following OGTT reduced significantly in IFG+IGT and NDDM groups (P<0.005). HOMA-β , HOMA-IR, Gutt and Matsuda indexes demonstrated various patterns among NGT, isolated IFG, isolated IGT, IFG+IGT and NDDM groups (P<0.05). Spearman rank correlation analysis and multivariable linear regression model suggested that some levels of correlation between GLP-1 levels, ∆GLP-1 and β cell function, IR (P<0.05). The total GLP-1 levels and its response to glucose load decreased significantly in IFG+IGT group, compared to isolated IFG or IGT group. They were even similar to that of NDDM group. Moreover, there were observable correlations between impaired GLP-1 secretion and β cell function, IR and IS.

Background: Exercise has been recommended as a cornerstone for diabetes management. Supervised exercise is more efficient than unsupervised exercise but is less convenient and accessible. Objective: We aimed to determine the efficiency of exercise using a fitness app and heart rate band to remotely monitor patients with type 2 diabetes in comparison with that of traditional exercise. Methods: Patients with type 2 diabetes without severe complications or comorbidities were recruited to participate in this multicenter randomized controlled trial and were allocated to either the intervention or control group (1:1 ratio). Participants in both groups were asked to engage in moderate to vigorous physical activity for at least 150 minutes per week; each participant was prescribed individualized exercises. Participants in the intervention group were asked to follow exercise videos on the app and to wear a chest band; heart rate, exercise duration, and exercise intensity were recorded by the app. Participants in the control group self-reported exercise intensity and duration. Cardiopulmonary endurance, body composition, blood glucose level, and insulin level were assessed before and after a 3-month exercise program. Results: Of the 101 participants who were enrolled, the majority of them (85/101, 84.2%) completed the study. Both groups had similar baseline characteristics, with the exception that participants in the intervention group were slightly younger and less likely to have hypertension. Self-reported exercise duration was longer than app-recorded exercise duration (control: mean 214 minutes/week; intervention: mean 193 minutes/week); in addition, a higher proportion of participants in the control group (29/41, 71%) than in the intervention group (18/44, 41%) met the 150-minute target for moderate to vigorous physical activity. However, compared with the control group, the intervention group had a larger increase in cardiopulmonary endurance (mean difference –2.0 bpm [beats per minute] vs 1.0 bpm; P=.02) and a larger decrease in body fat percentage (mean difference –1.8% vs –0.8%; P=.01). There was no difference in hemoglobin A1c level reduction between the two groups, yet more participants in the intervention group stopped taking their antidiabetic drugs or had their dosages lowered by an endocrinologist, compared with those in the control group. There were no serious adverse events in either group. Conclusions: This was the first randomized controlled trial in China, to our knowledge, to test the efficiency of exercise using a fitness app and heart rate band to remotely monitor prescribed exercise in patients with type 2 diabetes. The findings of our study suggest that exercise programs may be more efficient if participants are remotely monitored with an app and heart rate band than if participants are not monitored. Trial Registration: Chinese Clinical Trial Register ChiCTR1800015963; http://www.chictr.org.cn/showprojen.aspx?proj=27080

Diabetes mellitus is one of the most significant global burden diseases. It is well established that a chronic, systemic, low-grade inflammatory condition is strongly correlated with type 2 diabetes mellitus (T2D) and the development of target-organ damage (TOD). Sodium-glucose cotransporter inhibitors (SGLTis), novel oral drugs for the treatment of diabetes, act mainly by reducing glucose reabsorption in proximal renal tubules and/or the intestine. Several high-quality clinical trials and large observational studies have revealed that SGLTis significantly improve cardiovascular and renal outcomes in T2D patients. Increasing evidence suggests that this is closely related to their anti-inflammatory properties, which are mainly manifested by a reduction in plasma concentrations of inflammatory biomarkers. This review analyses the potential mechanisms behind the anti-inflammatory effects of SGLTis in diabetes and presents recent evidence of their therapeutic efficacy in treating diabetes and related TOD. Graphic Abstract