Metabolic Consequences Of Insulin Resistance Research Articles

Study of the Relationship between Platelet Distribution Width, Red Blood Cell Distribution Width and Insulin Resistance in Type 2 Diabetic Patients with Non-Alcoholic Fatty Liver Disease

Abstract Background Insulin resistance is identified as an impaired biological response to insulin stimulation of target tissues, primarily the liver, muscle, and adipose tissue. The metabolic consequences of insulin resistance can result in hyperglycaemia, hypertension, dyslipidaemia, visceral adiposity, hyperuricemia, elevated inflammatory markers, endothelial dysfunction, and a prothrombotic state. Progression of insulin resistance can lead to metabolic syndrome, non- alcoholic fatty liver disease, and type 2 diabetes mellitus. Aim of the Work We aimed by our study to assess the relationship of platelet distribution width and red blood cell distribution width with insulin resistance in patients with type 2 diabetes with and without non-alcoholic fatty liver disease (NAFLD) and to check if platelet distribution width or red blood cell distribution width could be easy predictors of insulin resistance. Patients and Methods The present study is a Case Control Study was conducted in Ain Shams University Hospital. This study includes 80 subjects with matched age and sex. Results The present study results confirmed that low RDW was associated with increased risk of developing diabetes mellitus. Their study found that RDW is negatively correlated with waist and FG, insulin and TG concentrations. We also found that the group with the lowest quartile of RDW had the highest glucose, insulin and HOMA levels. Moreover, our results were found that there is a significant negative correlation of RDW with poor glycemic control. Our results also found that decreased levels of red blood cell distribution widths (RDW) were all associated with increased fasting insulin. Our study was documented a negative correlation between HbA1c and the platelet index PDW. Conclusion In our study, we found a relation between insulin resistance and red blood cell distribution width. RDW (fl) could be used to discriminate between patients with type II diabetes and controls.

Abstract #1324374: Relationship Between Platelet Distribution Width (PDW), Red Blood Cell Distribution Width (RDW), and Insulin Resistance in People With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease (NAFLD)

Insulin resistance is identified as an impaired biologic response to insulin stimulation of target tissues, primarily the liver, muscle, and adipose tissue. The metabolic consequences of insulin resistance can result in hyperglycemia, hypertension, dyslipidemia, visceral adiposity, hyperuricemia, elevated inflammatory markers, endothelial dysfunction, and a prothrombotic state. Progression of insulin resistance can lead to metabolic syndrome, nonalcoholic fatty liver disease, and type 2 diabetes mellitus. Several techniques are used to measure insulin sensitivity. However, we are in need for easy inexpensive measure. RDW and PDW are numerical measures reported as part of standard compete blood count. To further explore if RDW and PDW could be easy predictors of insulin resistance, we have analyzed in this study the relationship between RDW, PDW and insulin resistance in people with type 2 diabetes with nonalcoholic fatty liver disease.

Clinical Trials Evaluating Turmeric Dietary Supplement Treatment of Obesity-Associated Disorders of Glucose Metabolism or Bone

Abstract Curcumin-enriched turmeric dietary supplements (DS) are one of the top selling botanicals in the United States. Recent observational studies by our research group have documented turmeric DS use by almost a quarter of breast cancer survivors concurrent with anti-estrogen therapy and a third of those with rheumatoid arthritis. However, some recent reviews have suggested that there is no evidence of any biological effect of curcumin in humans, albeit without rigorous review of published reports. A scoping review of the literature was therefore undertaken to identify clinical trials testing oral curcumin-containing turmeric dietary supplements in humans. Using a defined search strategy, eight databases were reviewed (thru 05/29/2019), identifying 4767 potential English language reports for inclusion, from which all but n = 315 were excluded after review by three independent observers. The majority of studies reported significant effects of turmeric DS on clinical endpoints. Obesity-associated disorders of glucose and lipid metabolism (n =69, including type 2 diabetes mellitus [T2DM], metabolic syndrome and/or hyperlipidemia) or musculoskeletal disorders (n = 46), of which half related to osteoarthritis, were among the most commonly studied diseases in turmeric DS clinical trials, with reported benefits related to inhibition of inflammation, amelioration of hyperlipidemia, increases in adiponectin, and improved glucose control. As is common for botanical clinical trials, the quality of the studies were variable due to lack of clarity about product content as well as study design (e.g. only 60% of T2DM trials and 74% of osteoarthritis trials were randomized, placebo-controlled and double-blinded). However, particularly with respect to treatment of osteoarthritis and metabolic consequences of insulin resistance, the preponderance of the data were suggestive of beneficial physiologic effects. Given the current widespread use of turmeric DS by Americans and existing evidence of possible clinical benefits, further evaluation of turmeric DS efficacy and safety may be warranted.

Insulin Resistance in Osteoarthritis: Similar Mechanisms to Type 2 Diabetes Mellitus.

Osteoarthritis (OA) and type 2 diabetes mellitus (T2D) are two of the most widespread chronic diseases. OA and T2D have common epidemiologic traits, are considered heterogenic multifactorial pathologies that develop through the interaction of genetic and environmental factors, and have common risk factors. In addition, both of these diseases often manifest in a single patient. Despite differences in clinical manifestations, both diseases are characterized by disturbances in cellular metabolism and by an insulin-resistant state primarily associated with the production and utilization of energy. However, currently, the primary cause of OA development and progression is not clear. In addition, although OA is manifested as a joint disease, evidence has accumulated that it affects the whole body. As pathological insulin resistance is viewed as a driving force of T2D development, now, we present evidence that the molecular and cellular metabolic disturbances associated with OA are linked to an insulin-resistant state similar to T2D. Moreover, the alterations in cellular energy requirements associated with insulin resistance could affect many metabolic changes in the body that eventually result in pathology and could serve as a unified mechanism that also functions in many metabolic diseases. However, these issues have not been comprehensively described. Therefore, here, we discuss the basic molecular mechanisms underlying the pathological processes associated with the development of insulin resistance; the major inducers, regulators, and metabolic consequences of insulin resistance; and instruments for controlling insulin resistance as a new approach to therapy.

Targeting Metabolic Consequences of Insulin Resistance in Polycystic Ovary Syndrome by D-chiro-inositol and Emerging Nutraceuticals: A Focused Review.

Polycystic ovary syndrome (PCOS) is a complex disorder associated with ovarian dysfunction, infertility, menstrual irregularity, and hormonal impairments. Over the last decade, several studies have shown that some PCOS women have insulin resistance (InsR) and hyperinsulinemia, apart from being overweight or obese. Therefore, a crucial clinical aspect is that PCOS patients might develop glucose intolerance and type 2 diabetes. Insulin-sensitizing drugs have been used as first-line treatment to improve hyperinsulinemia in women with PCOS. Although reducing PCOS symptoms and signs, several used insulin-sensitizer drugs may induce side effects, which reduces compliance. D-chiro-inositol (DCI), which is a naturally occurring stereoisomer of inositol, has been classified as an insulin-sensitizer and seems to mitigate multiple InsR-related metabolic alterations in PCOS with a safe profile. However, according to a multi-targeted design, the supplementation with DCI can be synergistically integrated by combining other potential insulin-sensitizing drugs and/or nutraceuticals. The literature provides the initial support for using several unexplored nutraceutical interventions that may target relevant metabolic abnormalities associated with InsR in PCOS. With a need to promote interest in clinical research, this review aims to discuss the efficacy of DCI and the role of emerging nutraceuticals for managing InsR in PCOS.

Recent advances in managing/understanding the metabolic syndrome.

The metabolic syndrome (MetS) concept gathers in a single entity a set of metabolic abnormalities that have in common a close relationship with ectopic deposit of lipids, insulin resistance, and chronic low-grade inflammation. It is a valuable teaching tool to help health professionals to understand and integrate the consequences of lipotoxicity and the adverse metabolic consequences of insulin resistance. Also, it is useful to identify subjects with a high risk for having incident type 2 diabetes. Systems biology studies have gained a prominent role in understanding the interaction between adipose tissue dysfunction, insulin action, and the MetS traits and co-morbidities (that is, non-alcoholic steatohepatitis, or NASH). This approach may allow the identification of new therapeutic targets (that is, de novo lipogenesis inhibitors for NASH). Treatment targets on MetS are the adoption of a healthy lifestyle, weight loss, and the control of the co-morbidities (hyperglycemia, dyslipidemia, arterial hypertension, among others). The long-term goals are the prevention of type 2 diabetes, cardiovascular events, and other MetS-related outcomes. In the last few decades, new drugs derived from the identification of innovative treatment targets have come on the market. These drugs have positive effects on more than one MetS component (that is, hyperglycemia and weight control). New potential treatment targets are under study.

Insulin Resistance the Link between T2DM and CVD: Basic Mechanisms and Clinical Implications.

Insulin resistance (IR) is a cardinal feature of type 2 diabetes mellitus (T2DM). It also is associated with multiple metabolic abnormalities which are known cardiovascular disease (CVD) risk factors. Thus, IR not only contributes to the development of hyperglycemia in T2DM patients, but also to the elevated CVD risk. Improving insulin sensitivity is anticipated to both lower the plasma glucose concentration and decrease CVD risk in T2DM patients, independent of glucose control. We review the molecular mechanisms and metabolic consequences of IR in T2DM patients and discuss the importance of addressing IR in the management of T2DM.

Adipose-brain crosstalk: do adipokines have a role in neuroprotection?

Accumulating evidence from epidemiological and experimental studies indicate that obesity, and its related metabolic consequences of insulin resistance and type 2 diabetes, are associated with accelerated cognitive decline (Yates et al., 2012). The etiology of neurodegeneration in obesity is undoubtedly complex, with vascular, metabolic, inflammatory, and structural changes all likely to play a role (Yates et al., 2012). The discovery of leptin in 1994 and the subsequent advancement in our understanding that adipose tissue is an endocrine organ that can communicate with the brain to regulate appetite (Zhang et al., 1994) brings about the intriguing possibility that adipose-brain crosstalk can regulate aspects of neuronal physiology and pathology (Aguilar-Valles et al., 2015). Indeed neurons have been shown to express receptors for various adipokines, indicating that factors released from adipose tissue have the potential to communicate directly with the brain. Research in this area is relatively new, and while epidemiological data points towards the negative consequences of adipose-brain crosstalk (Whitmer et al., 2005), some intriguing new studies highlight that the secretory profile of adipose tissue might be involved in reduction in neurodegeneration via maintenance of neuronal viability (Tezapsidis et al., 2009; Wan et al., 2015).

E IGFBP-1 upregulates vascular nitric oxide via PI-3-K activation and rescues endothelial function in murine models of insulin resistance: Abstract E Table 1

<h3>Background</h3> Low circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) predict the development of diabetes and cardiovascular disease. Whether IGFBP-1 has direct influences on the vasculature remains unknown however. We previously showed that transgenic over-expression of IGFBP-1 in lean mice conferred favourable effects on endothelial function and blood pressure. We now present data demonstrating that IGFBP-1 increases nitric oxide (NO) production in endothelial cells via PI-3-K activation, and protects against the cardiovascular consequences of insulin resistance in mice. <h3>Methods</h3> Male IGFBP-1 transgenic C57Bl/6 mice and littermate controls were challenged by two models of insulin resistance: (i) diet-induced obesity (DIO) and; (ii) crossing with heterozygous insulin receptor knockout mice (IRKO). Cardiovascular function was assessed by tail cuff blood pressure, aortic ser¹¹⁷⁷eNOS phosphorylation following in vivo insulin bolus, and aortic vasomotion ex vivo. Metabolic function was also assessed in DIO mice by insulin- and glucose-tolerance testing, and skeletal muscle Akt⁴⁷³ phosphorylation following in vivo insulin bolus. To dissect the mechanisms by which IGFBP-1 modulates endothelial function, complementary in vitro studies were conducted with exogenous IGFBP-1. Thus, after incubation with IGFBP-1, we tested vasomotion in intact aorta (organbath), NO generation in HUVECs (citrulline assay) and ser¹¹⁷⁷eNOS phosphorylation in HUVECs (western blot and immunofluorescence). Upstream signalling pathways were further probed using targeted signalling inhibitors. <h3>Results</h3> Both DIO and IRKO mice predictably developed endothelial dysfunction and hypertension. In contrast, IGFBP-1 transgenic mice with DIO or IRKO had preserved endothelial function, normal blood pressure, and improved gluco-regulation in DIO despite equal weight gain (see Abstract E table 1). In HUVECs and intact aorta, IGFBP-1 induced dose- and time-dependent ser¹¹⁷⁷ phosphorylation of eNOS and NO generation via PI-3-K activation. No IGF-I was present in these in vitro assays and these findings were reproducible in vessels with homozygous knockout of the endothelial IGF-receptor, indicating that the actions of IGFBP-1 on the vasculature are independent of IGF-I. <h3>Implications</h3> IGFBP-1 improves endothelial function independently of IGF-I and protects against the cardiovascular and metabolic consequences of insulin resistance. Restoration of IGFBP-1 levels may thus be a novel therapeutic target to mitigate cardiovascular risk.

Mechanisms of Vascular Insulin Resistance

See related article, pages 1085–1094 Insulin resistance is characterized by the diminished ability of insulin to initiate intracellular signaling. It is a common manifestation of obesity and a prelude to type 2 diabetes. The primary targets of insulin are skeletal muscle, adipose, and the liver. Impaired insulin signaling in these tissues reduces glucose uptake and promotes a metabolic syndrome that is characterized by elevated levels of insulin, inappropriate synthesis of glucose, and dyslipidemia.1 However, insulin receptors and insulin signaling are not exclusively restricted to metabolically active tissue and can be observed in most cell types including vascular cells. Individuals with insulin resistance have compromised endothelial cell function and increased frequency and severity of cardiovascular disease.2 Although it is clear that the metabolic consequences of insulin resistance are sufficient in themselves to induce cardiovascular dysfunction, the local actions of insulin on blood vessels are also thought to be of significance. Insulin directly stimulates nitric oxide (NO) release from the vascular endothelium in a phosphatidylinositol 3-kinase (PI3K)-dependent manner that involves the Akt-mediated phosphorylation of endothelial NO synthase (eNOS).3 Alternatively, insulin can stimulate the mitogen-activated protein kinase (MAPK) pathway to promote cellular proliferation.3 Selective or “pathway-specific” insulin resistance has also been described in blood vessels.4 This refers to the selective reduction in the ability of insulin to stimulate PI3K signaling while permitting or even enhancing MAPK activation (see the Figure). These effects are further magnified in insulin-resistant states where there is increased pancreatic secretion of insulin and by angiotensin II, which promotes MAPK signaling at the expense of the PI3K pathway. The reduction in PI3K signaling is proposed to attenuate eNOS activity and thus diminish the buffering …

Clinical use of thiazolidinediones: recommendations

Type 2 diabetes mellitus is characterized by progressive β-cell secretory dysfunction against a background of insulin resistance, which is present many years before the onset of hyperglycemia in most patients. Intensive treatment of diabetes reduces the risk of the onset and progression of microvascular complications and may impact the risk of development of macrovascular complications, notably coronary artery disease. Therefore, aggressive treatment with the goal of achieving serum glucose concentrations as close to normal as possible is warranted. Although medical nutritional therapy and exercise remain the cornerstones of therapy for type 2 diabetes, >90% of patients ultimately require pharmacologic therapy, and most need >1 agent to achieve therapeutic objectives. When considering which agent or agents to use to treat type 2 diabetes, one must consider the mechanism of action of the drug, its ability to lower serum glucose concentrations, the durability of effect, and potential adverse effects. In addition, some medications have potential benefits that extend beyond glucose lowering. These include beneficial effects on the adverse metabolic consequences of insulin resistance and possibly β-cell preservation. Thiazolidinediones should be considered as early as possible in the natural history of type 2 diabetes because of their persistent glucose-lowering effect and their ability to reduce insulin resistance as well as because these agents may preserve β-cell function and reverse some of the adverse metabolic consequences of insulin resistance.