Increased circulating RANTES in type 2 diabetes

Aim

The pro-atherogenic role of RANTES, a chemokine expressing pleiotropic activities, in the course of type 2 diabetes-related atherosclerosis has been well documented. However, it is not known which of the diabetes-related factors primarily influence serum RANTES levels in patients with type 2 diabetes. Our aim was to investigate relationships between several factors known to be related to an increased risk of atherosclerosis and serum RANTES levels in type 2 diabetic patients.

Methods

A total of 168 subjects were examined, which included 138 patients with type 2 diabetes and 30 non-diabetic controls. Measurements of venous, fasting, plasma glucose, HbA₁c, lipid profile, 1,5-anhydro-D-glucitol (1,5-AG) plasma levels, homocysteine and the fasting, serum C-peptide levels were performed. Serum concentrations of RANTES were assayed using BD? Cytometric Bead Array tests. Peripheral insulin resistance was expressed according to a new index defined by Ohkura et al.

Results

RANTES levels in type 2 diabetic patients correlated with 1,5-AG, fasting glycaemia, HbA₁c and the Ohkura index. Multivariate regression analysis was performed taking into consideration several factors related to the inflammatory process and atherosclerosis, namely the patient’s age, diabetes duration, waist circumference, 1,5-AG, HbA₁c, lipid profile parameters, serum homocysteine levels and Ohkura index, as independent variables potentially influencing serum RANTES levels in type 2 diabetic patients. It is shown that RANTES concentrations in the serum is primarily dependent upon 1,5-AG plasma levels.

Conclusion

Our results suggest that increased serum levels of RANTES in type 2 diabetic patients are closely related to postprandial (acute) hyperglycaemia.

     

Prevention of type 2 diabetes

Changes in the human environment and in human behavior and lifestyle, in conjunction with genetic susceptibility, have resulted in a dramatic increase in the incidence and prevalence of diabetes in the world. The rapid escalation of the number of people with type 2 diabetes (T2DM) and diabetes-related cardiovascular disease demands urgent action on prevention. The Finnish Diabetes Prevention Study and The Diabetes Prevention Program showed that the prevention (or delaying) of T2DM is feasible and effective. Both of these trials led to a reduction of 58% in the conversion to diabetes in subjects with impaired glucose tolerance. Compared to lifestyle changes, drug treatment in the prevention of diabetes in people at high risk for T2DM has been less beneficial. Metformin (31%) or acarbose (25%) treatment obtained only about a half of the reduction in the conversion to diabetes compared to lifestyle changes. These drugs require monitoring, and have significant side-effects. Also the effect of orlistat (37%) did not reach the effect of lifestyle modification. Results of the Troglitazone in Prevention of Diabetes study are suggestive for the prevention, but the trial was too small, and included only one ethnic group (Hispanic) and one gender (women). On the basis of the evidence available, we do not have a definite proof that T2DM is prevented in any of these trials. However, we can safely conclude that the current evidence strongly favors the notion that lifestyle changes are the primary means to tackle the epidemic of T2DM.     

Genetics of type 2 diabetes

Identification and characterization of genetic variants that either cause or predispose to diabetes are a major focus of biomedical research. As of early 2007, the molecular basis of most forms of monogenic diabetes resulting from beta-cell dysfunction is known and, in particular, there has been recent success in delineating the genetic aetiology of neonatal diabetes. Finding genes predisposing to more common, multifactorial forms of type 2 diabetes represents a far greater challenge, and only a handful of robust, well-replicated examples have been established. Nevertheless, 2006 heralded identification of the most important type 2 diabetes susceptibility gene known so far, TCF7L2, and in 2007 large-scale genome-wide association studies are destined to provide novel insights into the genetic architecture and biology of type 2 diabetes.     

Anti-atherogenic effects of fibrates in type 2 diabetes

Type 2 diabetes is an increasing cause of premature coronary heart disease. Several trials with lipid-modifying therapy have included sufficient numbers of diabetics to indicate that treatment of diabetic dyslipidaemia with either fibrates or statins reduces the risk of future coronary events in such patients. However, until recently no reported study had been designed specifically to investigate the effects of intervening in patients with type 2 diabetes. The Diabetes Atherosclerosis Intervention Study (DAIS) is an angiographic study in which 418 diabetic subjects were randomized to micronised fenofibrate or placebo groups. After 3 years of treatment, the fenofibrate group had a significantly reduced rate of progression of coronary atherosclerosis. This study, when considered with the results of other studies that have included diabetics, has important implications for the treatment of diabetic dyslipidaemia. The evidence that is currently available supports a place for both fibrates and statins, either as monotherapy or in combination, in the treatment of diabetic dyslipidaemia.     

Muscle glycogen content in type 2 diabetes mellitus

Muscle contains the largest reservoir of glycogen (Glyc), a depot that is closely regulated and with influence on insulin sensitivity. The current study examines muscle Glyc in type 2 diabetes mellitus (T2DM) and obesity and with respect to muscle fiber type, intramyocellular lipid content (IMCL), and mitochondrial function (oxidative enzyme activity; OX-Enz). There is increasing interest in the relation of IMCL and mitochondrial dysfunction with insulin resistance (IR), yet the association with muscle Glyc has not been examined with regard to these parameters. Using a quantitative histological approach specific to muscle fiber types, we assessed muscle Glyc, IMCL, and OX-Enz in vastus lateralis obtained by percutaneous biopsy in lean nondiabetic (L; n = 16), obese nondiabetic (Ob; n = 15), and T2DM volunteers (n = 14). Insulin sensitivity was estimated using homeostasis model assessment (HOMA)-IR. Muscle Glyc was reduced in T2DM, a deficit evident for type IIa fibers, yet minor in types I and IIb fibers. Low Glyc in T2DM correlated with fasting hyperglycemia. Also, in T2DM and Ob, there was significantly higher IMCL and lower OX-Enz in all fiber types. The IMCL-to-OX-Enz ratio, especially for type I fibers, correlated strongly with IR. Similarly, a Glyc-to-OX-Enz ratio correlated with IR, particularly for type IIb fibers. This ratio tended to be higher in Ob and T2DM. In summary, there is decreased muscle Glyc in T2DM yet a disproportional Glyc-to-OX-Enz relationship that is related to IR, although not as robustly as the IMCL-to-OX-Enz ratio.     

N-acetyltransferase 2 polymorphism in patients with diabetes mellitus

The arylamine N-acetyltransferases (NATs) are a unique family of enzymes that catalyse the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of hydrazine and arylamine drugs and carcinogens. Human arylamine NATs are known to exist as two isoenzymes, NAT1 and NAT2. The objective of this study was to identify whether the genetic polymorphism of NAT2 plays a role in susceptibility to Diabetes Mellitus (DM). Ninety-seven patients with DM and 104 healthy controls were enrolled in the study. NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A polymorphisms were detected by using real time PCR with LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). According to our data, the NAT2*5A and NAT2*6A mutant genotypes and NAT2*14A heterozygous genotype were associated with an increased risk of development of DM (OR = 47.06; 95%CI: 10.55-209.77 for NAT 2*5A, OR = 18.48; 95%CI: 3.83-89.11 for NAT2*6A and OR = 18.22; 95%CI: 6.29-52.76 for NAT2*14A). However, the NAT2*7A/B gene polymorphism carried no increased risk for developing DM disease. After grouping according to phenotypes as either slow or fast acetylators, NAT2*6A slow acetylator was found to be a significant risk factor for DM (OR = 6.09; 95%CI: 1.99-18.6, p = 0.02). The results indicate that NAT2 slow acetylator genotypes may be an important genetic determinant for DM in the Turkish population.     

A diet-induced type 2 diabetes model in Drosophila

正Dear Editor.Type 2 diabetes has become a global epidemic.It is a disease characterized by insulin resistance and relative insulin deficiency,resulting in hyperglycemia and various physiological and metabolic abnormalities.Besides genetic risk factors,inappropriate life styles,such as lack of physical activity and imbalanced diet,also contribute to the development of type 2diabetes in human (Jia et al.,2019).Animal models of type 2diabetes are of great value to understand its underlying mechanisms as well as to develop and evaluate potential diagnostic and therapeutic options (Kleinert et al.,2018).The     

Reduced exercise arteriovenous O2 difference in Type 2 diabetes.

Maximal O(2) consumption (Vo(2 max)) is lower in individuals with Type 2 diabetes than in sedentary nondiabetic individuals. This study aimed to determine whether the lower Vo(2 max) in diabetic patients was due to a reduction in maximal cardiac output (Q(max)) and/or peripheral O(2) extraction. After 11 Type 2 diabetic patients and 12 nondiabetic subjects, matched for age and body composition, who had not exercised for 2 yr, performed a bicycle ergometer exercise test to determine Vo(2 max), submaximal cardiac output, Q(max), and arterial-mixed venous O(2) (a-v O(2)) difference were assessed. Maximal workload, Vo(2 max), and maximal a-v O(2) difference were lower in Type 2 diabetic patients (P < 0.05). Q(max) was low in both groups but not significantly different: 11.2 and 10.0 l/min for controls and diabetic patients, respectively (P > 0.05). Submaximal O(2) uptake and heart rate were lower at several workloads in diabetic patients; respiratory exchange ratio was similar between groups at all workloads. Vo(2 max) was linearly correlated with a-v O(2) difference, but not Q(max) in diabetic patients. These data suggest that a reduction in maximal a-v O(2) difference contributes to a decreased Vo(2 max) in Type 2 diabetic patients.     

Impaired cerebral vasoreactivity in type 2 diabetes mellitus

The aim of our study was to assess cerebral vasoreactivity (CVR) in type 2 diabetes mellitus (DM2) and factors which may influence on it. According to previous studies, evaluating CVR in DM2 on the similar way, the results were dubious. For the evaluation CVR we used breath holding index (BHI) and transcranial Doppler ultrasound (TCD) in 50 patients with DM2 and 50 sex- and age-matched healthy controls. We observed epidemiologic and clinic data, other vascular risk factors and laboratory parameters. We found statistically significant difference in BHI between patients with DM2 (BHI = 0.69 +/- 0.31) and age- and sex-matched healthy controls (BHI = 1.33+/-0.28) (p < 0.05 ). Because of a significant correlation between BHI and age (p < 0.001) in healthy controls we made an adjustment of BHI for age before further analyses (BHIadj). In DM2 group we found a significant correlation between BHIadj and age (p = 0.0004), fasting glycemia (p = 0.04), and albuminuria (p = 0.04) (creatinine clearance in multivariate analysis (p = 0.007)). Our study has shown that CVR is impaired in DM2 patients and that it's severity was associated with age, fasting glycemia and renal function. Functional TCD is a very good screening method for detection and monitoring of cerebral microangiopathic changes in DM2 patients.     

Ⅱ型糖尿病易感基因研究的进展

Ⅱ型糖尿病是由基因和环境共同作用所引起的多基因遗传病,随着人类基因组计划的完成和单核苷酸多态性(single-nu-clcotide polymorphisms,SNP)扫描技术的发展,许多SNP位点被证实与Ⅱ型糖尿病相关,因此易感基因的检测是未来糖尿病预防和治疗的关键.本文主要介绍了目前Ⅱ型糖尿病易感基因的检测策略、方法、研究进展及今后的研究方向.