Progression Of T2DM Research Articles

Irisin levels in the progression of diabetes in sedentary women

ContextThe recently discovered peptide irisin has been hypothesized to be a regulator of body metabolism. However, studies ended up with controversial results. In the present study, we aimed to investigate irisin levels in sedentary women at different stages of prediabetes. Design, setting, and subjectsWe performed a cross-sectional analysis of circulating levels of irisin in 263 females similar for age and body mass index (BMI) and the groups included 52 normal glucose tolerance (NGT), 60 isolated impaired fasting glucose (IFG), 36 isolated impaired glucose tolerance (IGT), 65 both IFG and IGT and 50 type 2 diabetic patients. All patients were exercising less than 150min/week. ResultsPlasma irisin levels were significantly lower in IFG+IGT (2.86±0.6μg/mL, p: 0.019) and T2DM (2.83±0,5μg/mL, p: 0.005) patients compared to NGT (3.16±0.3μg/mL) patients. After age adjustment there was a negative correlation between irisin and BMI (r: −0.141; p: 0.031), postprandial glucose (PPG) (r: −0.142; p: 0.030), low density lipoprotein-cholesterol (LDL-C) (r: −0.138; p: 0.035) and triglyceride (TG) (r: −0.214; p: 0.001) and a positive correlation between irisin and high density lipoprotein-cholesterol (HDL-C) (r:.142; p: 0.030). After adjustment for age and BMI; PPG (r: −0. 137; p: 0.037), LDL-C (r: −0. 143; p: 0.029) and TG (r: −0.203; p: 0.002) were considered to correlate with irisin levels. Subgroup analysis revealed that TG levels were correlated with irisin levels in IFG (r: −0.347; p: 0.014) and IGT (r: −0.397; p: 0.030) patients. ConclusionIn our cohort of sedentary women, irisin levels were lower in patients with IFG+IGT and with diabetes than in patients with NGT. There is no correlation between irisin levels and BMI. Irisin is a myokine decreasing gradually with the progression of glucose intolerance and T2DM and is not correlated with BMI in sedentary women.

Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer's Disease.

Type 2 diabetes (T2DM), Alzheimer's disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer's disease (AD) is the most common subtype of dementia. Reduced release (for T2DM) and decreased action of insulin are central to the development and progression of both T2DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T2DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic inflammatory response and oxidative stress associated with T2DM, amyloid-β (Aβ) protein accumulation, and mitochondrial dysfunction link T2DM and AD.

Quantitative metabolomic and lipidomic profiling reveals aberrant amino acid metabolism in type 2 diabetes

Type 2 diabetes (T2DM) is a multi-factorial disease with a complex pathogenic mechanism; however a complete understanding of precise biochemical alterations accompanying the onset and progression of T2DM is lacking. Using a combination of untargeted and targeted metabolomic profiling approach we were able to delineate significantly altered metabolites in the diabetic (T2DM) group. Our results indicate significant perturbations in amino acid metabolism, TCA cycle and glycerol-phospholipid metabolism possibly impacting the overall glucose homeostasis in T2DM. A systems approach offers promise towards identification of clinically relevant markers of T2DM and novel molecular targets to foster drug discovery for effective therapeutic development for diabetes.

Role of Insulin Resistance in the Pathogenesis and Development of Type 2 Diabetes in WBN/Kob-<i>Lepr<sup>fa</sup></i> Rats

ABSTRACTWBN/Kob-Leprfa (fa/fa) rats have been identified as a new animal model of type 2 diabetes (T2DM), as they are characterized by impaired pancreatic insulin secretion and severe insulin resistance. Our previous study demonstrated impaired insulin secretion and its involvement in hyperglycemia in fa/fa rats. The present study was aimed at elucidating the role of insulin resistance in the development and progression of diabetes in these animals. Troglitazone (TGZ) was used as an insulin sensitizer. Insulin resistance and insulin secretory capacity were measured by a homeostasis model assessment of insulin resistance and the area under the blood concentration–time curve for plasma insulin levels after intravenous glucose tolerance testing, respectively. The fa/fa rats exhibited marked insulin resistance between 5 and 11 weeks of age, compared with age-matched Wistar rats. The insulin secretory capacity of fa/fa rats was higher than that of Wistar rats at 5 weeks of age, but decreased by 50% between 9 and 11 weeks of age. The fa/fa rats were fed a standard diet, with or without 0.2% w/w TGZ, for 4 weeks. Treatment with TGZ significantly improved insulin resistance, hyperglycemia and hypertriglyceridemia in both prophylactic and therapeutic study groups. These results suggest that insulin resistance is markedly involved in the development and progression of T2DM in fa/fa rats.

Future detection and monitoring of diabetes may entail analysis of both β-cell function and volume: how markers of β-cell loss may assist.

Disease heterogeneity is as major issue in Type II Diabetes Mellitus (T2DM), and this patient inter-variability might not be sufficiently reflected by measurements of glycated haemoglobin (HbA1c).Β-cell dysfunction and β-cell death are initiating factors in development of T2DM. In fact, β-cells are known vanish prior to the development of T2DM, and autopsy of overt T2DM patients have shown a 60% reduction in β-cell mass.As the decline in β-cell function and mass have been proven to be pathological traits in T2DM, methods for evaluating β-cell loss is becoming of more interest. However, evaluation of β-cell death or loss is currently invasive and unattainable for the vast majority of diabetes patients. Serological markers, reflecting β-cell loss would be advantageous to detect and monitor progression of T2DM. Biomarkers with such capacities could be neo-epitopes of proteins with high β-cell specificity containing post translational modifications. Such tools may segregate T2DM patients into more appropriate treatment groups, based on their β-cell status, which is currently not possible. Presently individuals presenting with adequately elevated levels of both insulin and glucose are classified as T2DM patients, while an important subdivision of those is pending, namely those patients with sufficient β-cell capacity and those without. This may warrant two very different treatment options and patient care paths.Serological biomarkers reflecting β-cell health status may also assist development of new drugs for T2DM and aid physicians in better characterization of individual patients and tailor individual treatments and patient care protocols.

ROS Acts as a Double-Edged Sword in the Pathogenesis of Type 2 Diabetes Mellitus: Is Nrf2 a Potential Target for the Treatment?

Although the clear mechanism of T2DM is still to be elucidated, it has been well established that reactive oxygen species (ROS) derived from multiple sources plays a causal role in multiple types of insulin resistance and contributes to β-cell dysfunction thus enhances the development and progression of T2DM. What is incomprehensible is that the detrimental ROS also plays a substantial role in the normal insulin signal transduction and glucose-stimulated insulin secretion (GSIS) in β-cell, which forces us to re-recognize the role of ROS under physiological and pathological conditions in a more broad way. Redox homeostasis is tightly controlled by the transcriptional factor nuclear factor erythroid 2-related factor 2 (Nrf2), whose abnormality is believed to be related with diabetes. Accumulating evidences suggest that there are important cross-talks between Nrf2 and PPARγ, PGC1α, PI3K/Akt on regulating antioxidant enzymes and the development of diabetes. Therefore, these evidences indicate that Nrf2 may be a critical element in taking survival and death decisions when cells are exposed to an oxidant environment. In conclusion, enhancing GSIS and insulin sensitivity through the regulation of Nrf2 levels is a potential avenue for developing new therapeutics. Nrf2 may become a promising target for the treatment of T2DM.

Clinical research for the significance of inflammatory factors and adiponectin in type 2 diabetes complicated with non-alcoholic fatty liver disease

ObjectiveTo investigate the clinical significance of inflammatory factors and adiponectin in type 2 diabetes milletus complicated with non-alcoholic fatty liver disease.MethodsTwo hundred and ten subjects aged 25 to 65-years-old including...

Development of multiple complications in type 2 diabetes is associated with the increase of multiple markers of chronic inflammation.

Patients with type 2 diabetes (T2DM) are known at risk for developing cardiovascular disease (CVD), nephropathy, and cancer. We were interested to find out whether multiple markers associated with chronic inflammation are detectable in patients with T2DM and are increased in patients with T2DM who developed additional clinical complications. A sequence of multiple risk markers for atherogenesis, associated with chronic inflammation, was measured in patients with T2DM before and after the development of clinical complications. We found that multiple clinical complications frequently developed simultaneously in patients with T2DM. At the early stage of T2DM, only low levels and low percent elevations of multiple risk markers were detected. However, both the level and the percent elevation of these markers were found to increase with disease progression and the development of clinical complications. We believe that chronic inflammation not only contributes to the pathogenesis of T2DM but also continues to increase in T2DM patients who are developing additional clinical complications. It appears that these multiple markers are potentially useful not only for monitoring the progression of T2DM but also predicting the risk of developing macro- and microvascular disease, nephropathy, and cancer.

Metabolic syndrome in youths

The metabolic syndrome (MetS), characterized by a clustering of cardiovascular disease and type 2 diabetes (T2DM) risk factors, has become prevalent in children and adolescents in recent years. However, the reported prevalence data on the MetS in youths has varied markedly, in large part, because of the disagreement among the variously proposed definitions of the MetS. Obesity is defined by using body mass index, waist circumference, or percent overweight, pointing to the need for standardized use of anthropometric variables to define obesity with a well-defined reference year for each ethnic population. In addition, slightly different cutoff values are used for triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting plasma glucose. Therefore, International Diabetes Federation recently proposed unified, easy-to-use criteria for diagnosing the MetS in youths. To provide insight into the mechanisms underlying the MetS in youths, the degree of insulin sensitivity/resistance and its correlation with the serum lipid and blood pressure levels have been evaluated. In addition, the serum levels of adipocytokines, such as adiponectin, leptin, tumor necrosis factor-alpha, resistin, interleukin-6, plasminogen activator inhibitor-1, and their correlation with childhood obesity have been extensively investigated. Recommendations for future research include exploring ways to assess visceral adiposity, to identify better biochemical markers for prediction of T2DM and disease progression, and to effectively intervene to prevent the MetS in youths.

Detecting of mtDNA Mutations at Position A3243G and G3316A in Pa-tients with type 2 Diabetes Mellitus in Wenzhou

To investigate the frequencies of mitochondria DNA (mtDNA) tRNA(Leu (UUR)) point mutation A3243G and NADH dehydronase subunit 1(ND1) gene point mutation G3316A in Wenzhou area of Zhejiang Province, and to explore the correlation between these mutations and the clinical manifestations in patients with type 2 mellitus diabetes(T2DM). Two hundreds and forty-four unrelated patients with T2DM and 156 healthy subjects without family history of T2DM were enrolled in Wenzhou area in this study and screened for the point mutations mentioned above with polymerase chain reaction (PCR) and restricted fragment length polymorphism(RFLP) analysis. The heterogeneous mutations were confirmed with DNA sequencing and denaturing high performance liquid chromatography (DHPLC) following T-A cloning of PCR products. The percentage of A3243G mutation in group of patients with T2DM and control were 0.410% and 0.0% (1/244 vs 0/156), respectively; however, there's not any significant difference between these two groups in frequency of A3243G mutation (P>0.05). G3316A mutation was detected in 4 of 244 cases with T2DM (1.639%) and 2 of 156 healthy controls (1.282%), showing that there's also no statistic difference between these two groups in frequency of G3316A mutation (P>0.05). It's shown that the frequency of mtDNA tRNA(Leu (UUR)) A3243G mutation is fairly low in patients with T2DM in Wenzhou area. Thus it's reasonable to assume that this mutation may not be involved in the development and progression of T2DM. Furthermore, it's demonstrated that the rate of G3316A mutation of mtDNA ND1 gene is rare in patients with T2DM in Wenzhou area and this mutation also happened in healthy control. It's suggested that G3316A mutation is just a gene polymorphism of mtDNA and not related to the pathogenesis of T2DM.

Use of Chromium Picolinate and Biotin in the Management of Type 2 Diabetes: An Economic Analysis

This paper addresses the potential economic benefits of chromium picolinate plus biotin (Diachrome) use in people with Type 2 diabetes (T2DM). The economic model was developed to estimate the impact on health care systems' costs by improved HbA1C levels with chromium picolinate plus biotin (Diachrome). Lifetimes cost savings were estimated by adjusting a benchmark from the literature, using a price index to adjust for inflation. The cost of diabetes is highly dependent on the HbA1C level with higher initial levels and higher annual increments increasing the cost. Improvement in glycemic control has proven to be cost-effective in delaying the onset and progression of T2DM, reducing the risk for diabetes-associated complications and lowering utilization and cost of care. Chromium picolinate plus biotin (Diachrome) showed greater improvement of glycemic control in poorly controlled T2DM patients (HbA(1C) > or = 10%) compared to their better controlled counterparts (HbA(1C) < 10%). This improvement was additive to that achieved by oral hypoglycemic medications and correlates to calculated levels of cost savings. Average 3-year cost savings for chromium picolinate plus biotin (Diachrome) use could range from 1,636 dollars for a poorly controlled patient with diabetes without heart diseases or hypertension, to 5,435 dollars for a poorly controlled patient with diabetes, heart disease, and hypertension. Average 3-year cost savings was estimated to be between 3.9 billion dollars and 52.9 billion dollars for the 16.3 million existing patients with diabetes. Chromium picolinate plus biotin (Diachrome) use among the 1.17 million newly diagnosed patients with T2DM each year could deliver lifetime cost savings of 42 billion dollars, or 36,000 dollars per T2DM patient. Affordable, safe, and convenient, chromium picolinate plus biotin (Diachrome) could prove to be a cost-effective complement to existing pharmacological therapies for controlling T2DM.