β-Cell Dysfunction, Hepatic Lipid Metabolism, and Cardiovascular Health in Type 2 Diabetes: New Directions of Research and Novel Therapeutic Strategies

Abstract

Cardiovascular disease (CVD) remains a major problem for people with type 2 diabetes mellitus (T2DM), and dyslipidemia is one of the main drivers for both metabolic diseases. In this review, the major pathophysiological and molecular mechanisms of β-cell dysfunction and recovery in T2DM are discussed in the context of abnormal hepatic lipid metabolism and cardiovascular health. (i) In normal health, continuous exposure of the pancreas to nutrient stimulus increases the demand on β-cells. In the long term, this will not only stress β-cells and decrease their insulin secretory capacity, but also will blunt the cellular response to insulin. (ii) At the pre-diabetes stage, β-cells compensate for insulin resistance through hypersecretion of insulin. This increases the metabolic burden on the stressed β-cells and changes hepatic lipoprotein metabolism and adipose tissue function. (iii) If this lipotoxic hyperinsulinemic environment is not removed, β-cells start to lose function, and CVD risk rises due to lower lipoprotein clearance. (iv) Once developed, T2DM can be reversed by weight loss, a process described recently as remission. However, the precise mechanism(s) by which calorie restriction causes normalization of lipoprotein metabolism and restores β-cell function are not fully established. Understanding the pathophysiological and molecular basis of β-cell failure and recovery during remission is critical to reduce β-cell burden and loss of function. The aim of this review is to highlight the link between lipoprotein export and lipid-driven β-cell dysfunction in T2DM and how this is related to cardiovascular health. A second aim is to understand the mechanisms of β-cell recovery after weight loss, and to explore new areas of research for developing more targeted future therapies to prevent T2DM and the associated CVD events.

Hypertriglyceridemia and Other Plasma Lipid Profile Abnormalities among People Living with Diabetes Mellitus in Ethiopia: A Systematic Review and Meta-Analysis

“…In the current study, the pooled prevalence of hypertriglyceridemia among DM patients was 48.15%. This higher percentage could be related with the defects of insulin action [ 60 , 61 ], in that low insulin or insulin resistance leads to reduced fatty acid mobilization into cells and increases lipolysis, both of which contributed to high plasma lipid levels [ 62 ]. Other studies in in Thailand (49.94%) [ 28 ], Botswana (38.9%) [ 63 ], Tanzania (53.8%) [ 57 ], India (56.1%) [ 58 ], Brazil (46.7%) [ 64 ], and Yemen (39.2%) [ 65 ] also reported similar findings.…”

Qingre Yiqi Method along with Oral Hypoglycemic Drugs in Treating Adults with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

“…The Qingre Yiqi method includes some herbs such as Coptis , rhubarb, Radix Scutellariae, and Sophora flavescens , which can effectively reduce the effects of oxidative stress and release of inflammatory factors, therefore alleviating the glucose toxicity [ 7 , 8 ], which may explain the favorable effect of the Qingre Yiqi method when blood glucose baseline is high. In addition, as type 2 diabetes involves multiple pathological processes, such as increasing secretion of glucagon, decreasing secretion of insulin, weakness of incretin effect, reduced glucose uptake, and neurotransmitter dysfunction [ 37 ], combined use of multiple oral hypoglycemic drugs performs significantly better than the single use of the drugs. Rosenstock et al have explored the efficacy and tolerability of initial combination therapy with vildagliptin and pioglitazone compared with component monotherapy.…”

Effect of Weight Loss by Low-Calorie Diet on Cardiovascular Health in Type 2 Diabetes: An Interventional Cohort Study

“…Cardiovascular disease (CVD) remains a major problem for people with type 2 diabetes mellitus (T2DM), and the leading cause of death worldwide [ 1 , 2 , 3 ]. Recognition that substantial dietary weight loss is feasible and effective in achieving lasting remission of T2DM [ 4 , 5 , 6 , 7 ] raises the possibility that clinically useful decrease in cardiovascular risk may follow.…”

“…Non-alcoholic fatty liver disease (NAFLD) increases hepatic triglyceride export via very low-density lipoprotein (VLDL), and this is related to the pathogenesis of T2DM [ 6 , 8 , 9 ]. These abnormalities in lipid metabolism markedly increase CVD risks [ 3 , 10 , 11 ]. Remission of T2DM by weight loss is associated with normalization of liver fat and hepatic VLDL1-TG export [ 4 , 5 , 6 ], and the changes in plasma biomarkers on CVD risk requires to be established after remission.…”