Glycolipid metabolism disorder are major threats to human health and life. Genetic, environmental, psychological, cellular, and molecular factors contribute to their pathogenesis. Several studies demonstrated that neuroendocrine axis dysfunction, insulin resistance, oxidative stress, chronic inflammatory response, and gut microbiota dysbiosis are core pathological links associated with it. However, the underlying molecular mechanisms and therapeutic targets of glycolipid metabolism disorder remain to be elucidated. Progress in high-throughput technologies has helped clarify the pathophysiology of glycolipid metabolism disorder. In the present review, we explored the ways and means by which genomics, transcriptomics, proteomics, metabolomics, and gut microbiomics could help identify novel candidate biomarkers for the clinical management of glycolipid metabolism disorder. We also discuss the limitations and recommended future research directions of multi-omics studies on these diseases.

Repositioning or repurposing drugs account for a substantial part of entering approval pipeline drugs, which indicates that drug repositioning has huge market potential and value. Computational technologies such as machine learning methods have accelerated the process of drug repositioning in the last few decades years. The repositioning potential of type 2 diabetes mellitus (T2DM) drugs for various diseases such as cancer, neurodegenerative diseases, and cardiovascular diseases have been widely studied. Hence, the related summary about repurposing antidiabetic drugs is of great significance. In this review, we focus on the machine learning methods for the development of new T2DM drugs and give an overview of the repurposing potential of the existing antidiabetic agents.

Cardiometabolic disease (CMD), characterized with metabolic disorder triggered cardiovascular events, is a leading cause of death and disability. Metabolic disorders trigger chronic low-grade inflammation, and actually, a new concept of metaflammation has been proposed to define the state of metabolism connected with immunological adaptations. Amongst the continuously increased list of systemic metabolites in regulation of immune system, bile acids (BAs) represent a distinct class of metabolites implicated in the whole process of CMD development because of its multifaceted roles in shaping systemic immunometabolism. BAs can directly modulate the immune system by either boosting or inhibiting inflammatory responses via diverse mechanisms. Moreover, BAs are key determinants in maintaining the dynamic communication between the host and microbiota. Importantly, BAs via targeting Farnesoid X receptor (FXR) and diverse other nuclear receptors play key roles in regulating metabolic homeostasis of lipids, glucose, and amino acids. Moreover, BAs axis per se is susceptible to inflammatory and metabolic intervention, and thereby BAs axis may constitute a reciprocal regulatory loop in metaflammation. We thus propose that BAs axis represents a core coordinator in integrating systemic immunometabolism implicated in the process of CMD. We provide an updated summary and an intensive discussion about how BAs shape both the innate and adaptive immune system, and how BAs axis function as a core coordinator in integrating metabolic disorder to chronic inflammation in conditions of CMD.

Diabetes mellitus, a group of metabolic disorders characterized by persistent hyperglycemia, affects millions of people worldwide and is on the rise. Dietary proteins, from a wide range of food sources, are rich in bioactive peptides with antidiabetic properties. Notable examples include AGFAGDDAPR, a black tea-derived peptide, VRIRLLQRFNKRS, a β-conglycinin-derived peptide, and milk-derived peptide VPP, which have shown antidiabetic effects in diabetic rodent models through variety of pathways including improving beta-cells function, suppression of alpha-cells proliferation, inhibiting food intake, increasing portal cholecystokinin concentration, enhancing insulin signaling and glucose uptake, and ameliorating adipose tissue inflammation. Despite the immense research on glucoregulatory properties of bioactive peptides, incorporation of these bioactive peptides in functional foods or nutraceuticals is widely limited due to the existence of several challenges in the field of peptide research and commercialization. Ongoing research in this field, however, is fundamental to pave the road for this purpose.

Proteins and peptides (PPs) have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity and efficacy, but fewer side effects. Owing to the poor stability and limited permeability through gastrointestinal (GI) tract and epithelia, the therapeutic PPs are usually administered by parenteral route. Given the big demand for oral administration in clinical use, a variety of researches focused on developing new technologies to overcome GI barriers of PPs, such as enteric coating, enzyme inhibitors, permeation enhancers, nanoparticles, as well as intestinal microdevices. Some new technologies have been developed under clinical trials and even on the market. This review summarizes the history, the physiological barriers and the overcoming approaches, current clinical and preclinical technologies, and future prospects of oral delivery of PPs.

Hypoglycemia and acute metabolic complications (AMCs; ketoacidosis, hyperosmolarity, and coma) are glycemic outcomes that have high cost and high morbidity; these outcomes must be taken into consideration when choosing initial second-line therapy after metformin. We conducted a retrospective cohort study analyzing national administrative data from adults with type 2 diabetes mellitus who started a second-line diabetes medication (sulfonylureas [SFUs], thiazolidinediones [TZDs], glucagon-like peptide 1 [GLP-1] agonists, dipeptidyl peptidase 4 [DPP-4] inhibitors, basal insulin, or sodium-glucose contransporter 2 [SGLT-2] inhibitors) between April 1, 2011 and September 30, 2015 (N=43,288) and compared rates of hypoglycemia and AMCs. Most patients (24,506 [56.6%]) were prescribed sulfonylurea as second-line treatment, followed by DPP-4 inhibitors (7953 [18.4%]), GLP-1 agonists (3854 [8.9%]), basal insulin (2542 [5.9%]), SGLT-2 inhibitors (2537 [5.9%), and TZDs (1896 [4.4%]). Baseline rates of hypoglycemia varied more than 5-fold across initial second-line antidiabetic medication classes, and rates of AMCs varied 7-fold. Compared with patients taking an SFU, lower adjusted rates of hypoglycemia were associated with taking a DPP-4 inhibitor (63% lower rate; incidence rate ratio [IRR], 0.37; 95% CI, 0.25 to 0.57), SGLT-2 inhibitor (54% lower; IRR, 0.46; 95% CI, 0.22 to 0.94), or TZD (79% lower; IRR, 0.21; 95% CI, 0.08 to 0.56) but not a glucagon-like peptide 1 agonist or basal insulin. For AMCs, only initiation of a DPP-4 inhibitor (43% lower rate; IRR, 0.57; 95% CI, 0.41 to 0.81) was associated with a lower adjusted rate compared with SFU. Use of SGLT-2 inhibitors was not associated with a substantially increased rate of acute metabolic complications compared with SFU. Special attention still needs to be paid to glycemic outcomes when choosing a second-line diabetes therapy following metformin.

FFA2 and FFA3 are receptors for short-chain fatty acids which are produced in prodigious amounts by fermentation of poorly digested carbohydrates by gut bacteria. Understanding the roles of these receptors in regulating enteroendocrine, metabolic and immune functions has developed with the production and use of novel pharmacological tools and animal models. A complex (patho)physiological scenario is now emerging in which strategic expression of FFA2 and FFA3 in key cell types and selective modulation of their signalling might regulate body weight management, energy homoeostasis and inflammatory disorders.

A large proportion of older adults are affected by impaired glucose metabolism. Previous studies with fish protein have reported improved glucose regulation in healthy adults, but the evidence in older adults is limited. Therefore, we wanted to assess the effect of increasing doses of a cod protein hydrolysate (CPH) on postprandial glucose metabolism in older adults. The study was a double-blind cross-over trial. Participants received four different doses (10, 20, 30 or 40 mg/kg body weight (BW)) of CPH daily for 1 week with 1-week washout periods in between. The primary outcome was postprandial response in glucose metabolism, measured by samples of serum glucose and insulin in 20 min intervals for 120 min. The secondary outcome was postprandial response in plasma glucagon-like peptide 1 (GLP-1). Thirty-one subjects aged 60-78 years were included in the study. In a mixed-model statistical analysis, no differences in estimated maximum value of glucose, insulin or GLP-1 were observed when comparing the lowest dose of CPH (10 mg/kg BW) with the higher doses (20, 30 or 40 mg/kg BW). The estimated maximum value of glucose was on average 0·28 mmol/l lower when the participants were given 40 mg/kg BW CPH compared with 10 mg/kg BW (P = 0·13). The estimated maximum value of insulin was on average 5·14 mIU/l lower with 40 mg/kg BW of CPH compared with 10 mg/kg BW (P = 0·20). Our findings suggest that serum glucose and insulin levels tend to decrease with increasing amounts of CPH. Due to preliminary findings, the results require further investigation.

Co-ingestion of almonds with carbohydrate prevents excessive increase in plasma glucose level (PGL), but information about the functional fraction is limited. Identifying the functional fraction is necessary to use almonds more efficiently in terms of controlling postprandial glycaemia after a high-carbohydrate meal. In the present study, we evaluated the effects of almond skin, oil, water-soluble fraction and water-insoluble fraction on both postprandial glycaemia and insulinaemia. The effect of almond skin was tested by comparing the effect of whole almonds with the effect of skinless almonds. Male ICR mice were administered dextrin and 4 g/kg body weight test samples. After the administration, 2-h postprandial changes in glycaemia and insulinaemia were measured. Oil was the only fraction being able to blunt postprandial glycaemia. Interestingly, when co-ingesting with dextrin, almond oil did not change the insulin level compared with the control but whole almonds or skinless almonds triggered a 4-fold increase in insulin level. The co-ingestion of whole almonds or skinless almonds similarly suppressed the PGL at 15 and 30 min (P < 0·05), which means almond skin has no effect on postprandial glycaemia. Neither soluble nor insoluble fractions lead to any significant changes in postprandial glycaemia and insulinaemia. In conclusion, oil is the main functional component accounting for the glycaemia-lowering effect without altering insulin level.

The increased prevalence of lifestyle diseases, such as the metabolic syndrome and type 2 diabetes mellitus (T2DM), calls for more knowledge on dietary treatments targeting the specific metabolic pathways involved in these conditions. Several studies have shown a protein preload before a meal to be effective in lowering the postprandial glycaemic response in healthy individuals and patients with T2DM. The aim of the present study was to assess the effect of a marine protein hydrolysate (MPH) from Atlantic cod (Gadus morhua) on postprandial glucose metabolism in healthy, middle-aged to elderly subjects. This double-blind cross-over trial (n 41) included two study days with 4-7 d wash-out in between. The intervention consisted of 20 mg of MPH (or casein as control) per kg body weight given before a breakfast meal. The primary outcome was postprandial response in glucose metabolism, measured by samples of serum glucose, insulin and plasma glucagon-like peptide 1 (GLP-1) in 20 min intervals for 180 min. In a mixed-model regression analysis, no differences were observed between MPH and control for postprandial glucose concentration (mean difference: -0·04 (95 % CI -0·17, 0·09) mmol/l; P = 0·573) or GLP-1 concentration (mean difference between geometric means: 1·02 (95 % CI 0·99, 1·06) pmol/l; P = 0·250). The postprandial insulin concentration was significantly lower after MPH compared with control (mean difference between geometric means: 1·067 (95 % CI 1·01, 1·13) mIU/l; P = 0·032). Our findings demonstrate that a single dose of MPH before a breakfast meal reduces postprandial insulin secretion, without affecting blood glucose response or GLP-1 levels, in healthy individuals. Further studies with repeated dosing and in target groups with abnormal glucose control are warranted.