2015年 · 第07卷第06期

Patients with type 2 diabetes mellitus (T2DM) are often accompanied by cardiovascular disease, which becomes the main cause of disability and death. Vascular endothelial dysfunction is an early predictor of vascular disease in diabetic patients, and can independently predict the risk of cardiovascular disease in patients with T2DM^[1]。 The pathological mechanism of endothelial dysfunction in patients with T2DM is very complex. The main pathophysiological factors causing diabetic endothelial dysfunction include insulin resistance, oxidative stress, inflammatory response, protein kinase C activation and epigenetics. Therefore, this paper mainly discusses the molecular mechanism of vascular endothelial dysfunction in T2DM.

Type 2 diabetes mellitus (T2DM), often associated with hepatic microvascular disease and hepatic inflammation, is an independent risk factor for non-alcoholic fatty liver disease (NAFLD)^[1]。 In recent years, the prevalence of NAFLD in T2DM patients has increased year by year. According to the latest research report, the prevalence of NAFLD in T2DM patients is 42.6% ~76.0%, and about 33% of NAFLD patients have diabetes^[2]。 Microcirculation disorder is one of the important reasons for the formation of NAFLD, and hepatic sinusoidal endothelial cell (LSEC) dysfunction is the initiation and key link of hepatic microcirculation disorder^[3]。 LSEC is the main component of hepatic sinus wall, which has the physiological functions of providing multi-pore barrier, scavenging, maintaining the resting state of hepatic stellate cells (HSC) and mediating the self-repair of liver injury^[4]。 The fenestral structure of LSEC is a unique marker distinguishing it from vascular endothelial cells, and it plays an important role in regulating the substance exchange between sinusoidal blood flow and surrounding tissues. LSEC dysfunction can cause abnormal sinusoidal blood flow, lipid metabolism disorder, sinusoidal capillarization and hepatocyte metabolism disorder, etc., resulting in abnormal liver structure and function. The persistent high glucose and lipotoxicity in the diabetic state exacerbates the impairment of LSEC function, therefore, the role of LSEC dysfunction in the formation of NAFLD cannot be ignored. This paper focuses on analyzing the mechanism of LSEC function in the occurrence and development of hepatic microcirculation disorder and NAFLD in diabetic patients.

Uric acid is the end product of purine metabolism, and human blood uric acid levels gradually increase in the process of evolution. The reasons are, on the one hand, genetic factors. The uricase gene and promoter of human beings have undergone genetic variation, so the uricase level is lower than that of other mammals; On the other hand, environmental factors, the westernization of modern human lifestyle and the large intake of high fructose diet are important reasons for the increase of blood uric acid. At present, hyperuricemia (HUA) is defined as: blood uric acid concentration>7 mg/dl in men and postmenopausal women (the conversion factor from old unit mg/dl to new unit μ mol/L is 59.5, the same below), and blood uric acid concentration>5.8 mg/dl in premenopausal women^[1]。

neonatal diabetes mellitus (NDM) refers to a type of monogenic diabetes in which patients develop within 6 months after birth and need to receive insulin therapy for at least 2 weeks^[1]。 There are two types of NDM: transient neonatal diabetes mellitus (TNDM) and permanent NDM (permanent neonatal diabetes mellitus (PNDM). TNDM Most of them achieve complete remission within 18 months of onset, but about half of them develop T2DM in childhood or later and persist for life. According to the known genetic pathogenesis, TNDM can be roughly divided into three types: TNDM1, TNDM2 and TNDM3. TNDM1, namely 6q24 TNDM, accounts for the majority of TNDM, and is related to the abnormality of the 6q24 region of chromosome.

With the development of economy, the lifestyle of our residents has changed tremendously, and the prevalence of diabetes is rising rapidly. More and more evidence shows that diabetes can cause damage to the central nervous system, damage to the integrity and function of brain tissue, and cognitive dysfunction, so it is also called diabetic encephalopathy (DE). In recent years, it has been suggested that diabetes mellitus may be a chronic inflammatory response mediated by cytokines, and inflammation plays an important role in the pathogenesis of diabetes mellitus^[1]。 High mobility group protein B1 (HMGB1) is a pro-inflammatory factor that acts on advanced glycosylation end products (AGEs) and Toll-like receptors (TLRs), activating nuclear factor-κ B (NF-κ B), leading to a series of cascade metabolic reactions. High mobility group protein B1-AGEs/TLR-NF-κ B (HMGB1-RAGE/TLR-NF-κ B) signaling pathway may play an important role in the development and development of diabetic inflammation^[2]In this paper, the research progress of this pathway and DE in recent years is briefly summarized.

Diabetes is one of the major health problems that endanger the development of society. Although the etiology is complex, the central role of pancreatic islets in the regulation of blood glucose homeostasis is unquestionable. Restoring the function and number of pancreatic islet beta cells has been the key to clinical treatment of diabetes. Cell cycle analysis showed that islet β cells proliferated very slowly, and the vast majority (97% ~99%) were in G0/1 phase^[1,2,3]。 The molecular mechanisms that prevent beta cells from switching through the G1/S phase cycle are unknown. Retinoblastoma protein (Rb) is an important molecule that regulates cell cycle transition in G1/S phase. It has similar pocket-shaped DNA binding regions with retinoblastoma-like protein 1 (p107) and retinoblastoma-like protein 2 (p130), and belongs to the pocket protein family^[3,4,5]。 Research on the family of pocket proteins has mainly focused on the field of oncology. Recent studies have shown that the expression of islet Rb gene in patients with type 2 diabetes mellitus is significantly reduced^[6]Its role in the expansion of pancreatic islet cells is receiving increasing attention. This paper reviews the research progress of pocket protein family in the regulation of islet development and homeostasis.

In recent years, with the change of diet and lifestyle, the incidence of diabetes in the population has shown an increasing trend. According to the latest report of the International Diabetes Federation (IDF), the total number of diabetic patients worldwide was about 381.8 million in 2013, and this number will reach 591.9 million in 2035^[1]。 With the progression of the disease, stepped treatment regimens are often recommended by domestic and foreign guidelines for blood glucose management in patients with type 2 diabetes mellitus (T2DM). In 2012, the American Diabetes Society (ADA) and the European Society for Diabetes Research (EASD) issued a position statement entitled "Hyperglycemic Management in Type 2 Diabetes: A Patient-Centered Pathway", recommending that basal insulin therapy should be initiated when single or combined oral hypoglycemic drugs fail to satisfactorily control blood glucose^[2]。

Ninety years ago, the discovery of insulin brought a great turn in the fate of diabetics. With the development of insulin and its preparations, safe and effective control of blood sugar is no longer out of reach. Because type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and impaired insulin secretion at diagnosis, and progressive decline in islet beta cell function as the disease progresses. Therefore, in addition to the timely initiation of insulin therapy to maintain glycemic control to prevent and reduce complications, the adjustment process of insulin dose is also of interest in the treatment protocol.