The effect of dietary fiber on insulin resistance in obesity: A literature review

Introduction Obesity has become a significant public health problem in developing countries such as Indonesia. According to WHO, 13% of adults aged 18 years and over were obese in 2016. In Indonesia, 21.8% of adults were obese. In obesity, the body's resistance to insulin will develop. Some studies showed a probable link between dietary fiber and insulin resistance. This research aims to investigate the role of the dietary fiber on insulin resistance in obesity. Methods: This study is a literature study to determine the effect of dietary fiber on insulin resistance in obesity with sources from scientific publications 10 years back. The databases were PubMed and Google Scholar. The search term used was using the explode function for subgroup terms with operators (“and,” or) for “dietary fiber”, “obesity”, “insulin resistance”. Hand-searching was used to identify further potential eligible studies. There were no language restrictions, however only publications with full texts available were included. Total 138 publications titles and abstract were screened for their relevance to this literature review. Results: A total of 25 publications were finally included. There are cross-sectional studies, randomized clinical trial, cohort studies, and article review. Some studies showed that dietary fiber had an effect on improve insulin resistance, but other studies did not find this effect. Conclusion: The studies of dietary fiber effect on insulin resistance have inconsistent results. In the future, further studies are required for better understanding about the effect of dietary fiber on insulin resistance in obesity

Diabetes Mellitus and Heart Failure

Diabetes mellitus (DM) is a major risk factor for new-onset heart failure (HF) and vice versa. The pathogenesis of new-onset HF in DM is complex and has been largely attributed to the toxic cardiovascular effects of hyperglycemia and relevant metabolic abnormalities (diabetic cardiomyopathy) as well as the frequently coexisting morbidities such as hypertension (HTN), coronary artery disease (CAD), and diabetic nephropathy. In patients with type 1 DM (T1DM), HF develops in the setting of a dysregulated immune response, whereas in most patients with type 2 DM (T2DM), against a background of overweight/obesity. HF prevention in DM is feasible with rigorous treatment of cardiovascular risk factors and selective antidiabetic agents. Conversely, development of new-onset T2DM in HF (cardiogenic DM) is common and has been attributed to an increase in the resistance to insulin, especially in the skeletal muscle, liver, and adipose tissue as well as in diminished insulin secretory response to hyperglycemia by pancreatic β-cells. Cardiogenic DM further deteriorates cardiac dysfunction and adversely affects outcome in HF. Novel lifesaving medications employed in HF management such as sacubitril/valsartan and sodium glucose cotransporter 2 inhibitors (SGLT-2i) have a favorable metabolic profile and lower the incidence of cardiogenic diabetes. Whether mitigation of cardiogenic DM should be a treatment target in HF deserves further investigation.

Clusterin and Its Role in Insulin Resistance and the Cardiometabolic Syndrome

The cardiometabolic syndrome involves a clustering of metabolic and cardiovascular factors which increase the risk of patients developing both Type 2 Diabetes Mellitus and cardio/cerebrovascular disease. Although the mechanistic underpinnings of this link remain uncertain, key factors include insulin resistance, excess visceral adiposity, atherogenic dyslipidemia, and endothelial dysfunction. Of these, a state of resistance to insulin action in overweight/obese patients appears to be central to the pathophysiologic process. Given the increasing prevalence of obesity-related Type 2 Diabetes, coupled with the fact that cardiovascular disease is the number one cause of mortality in this patient population, a more thorough understanding of the cardiometabolic syndrome and potential options to mitigate its risk is imperative. Inherent in the pathogenesis of insulin resistance is an underlying state of chronic inflammation, at least partly in response to excess adiposity. Within obese adipose tissue, an immunomodulatory shift occurs, involving a preponderance of pro-inflammatory immune cells and cytokines/adipokines, along with antigen presentation by adipocytes. Therefore, various adipokines differentially expressed by obese adipocytes may have a significant effect on cardiometabolism. Clusterin is a molecular chaperone that is widely produced by many tissues throughout the body, but is also preferentially overexpressed by obese compared lean adipocytes and relates strongly to multiple components of the cardiometabolic syndrome. Herein, we summarize the known and potential roles of circulating and adipocyte-specific clusterin in cardiometabolism and discuss potential further investigations to determine if clusterin is a viable target to attenuate both metabolic and cardiovascular disease.

Effect of Statins Therapy in Diabetogenesis

Statins are widely used in the management or inhibition of several processes that lead to the development of cardiovascular diseases. Increased statin therapy has been related to the induction of type II diabetes (DM), a state which predisposes to cardiovascular disease (CVD). Statins are well-known to possess anti-inflammatory properties and the ability to disrupt de novo biosynthesis of cholesterol and lipid homeostasis has been implicated in the induction of inflammatory responses within pancreatic β-cells. Inhibition of β-hydroxy β-methyl glutaryl-CoA (HMG-CoA) results an increased level of low-density lipoproteins (LDL) receptors. Increased LDL receptor numbers will replenish exhausted intracellular supplies, resulting in higher levels of intracellular cholesterol. Therefore, stimulating immunological response and inflammatory reactions, disrupt the functional integrity of the β-cell via oxidation of the plasma-derived low-density lipoprotein. Despite the pleiotropic effects of statins on the pancreatic β-cell, they have also been reported to affect a number of other cell types associated with the development of diabetes. Inhibition of the biosynthesis of isoprenoid by statins has been associated with the down-stream regulation of glucose transporter (GLUT 4) in adipose tissues, which facilitates the uptake of glucose. This effect resulted in increasing resistance to insulin in the liver, muscle, and adipose tissue. Adiponectin, a plasma protein released by adipocytes, alters fatty acids and carbohydrate metabolism both in the muscle cells and liver. This process indirectly influences resistance to insulin by the attendant decrease in hepatic gluconeogenesis and to upregulate muscular β-oxidation and glucose uptake.

Some results of studying of mechanisms of effect of drinking mineral waters and prospect of further development of this problem

In article the main achievements in a problem of studying of mechanisms of treatment-and-prophylactic use of drinking mineral waters are analysed. The important role of their nonspecific influence due to existence of a stressorny component, activation of digestive organs and increase in products of gastrointestpnalny and pancreatic hormones is proved. Increase in activity of enteroinsulyarny interrelations at intake of mineral waters provides optimization of the broken metabolic reactions. It is revealed that against the background of course intake of mineral waters the resistance to insulin due to optimization of hormonal and receptor interaction decreases. The role of activization of pro-oxidatic reactions in improvement of sensitivity of fabrics to insulin is discussed. Various methods of increase in medical potential of mineral waters due to change of algorithms of their use, enrichment are analyzed by vitamins and phytodrugs, nanoparticles of metals. The scheme of realization of biological potential of mineral water at its internal reception is offered.

Chronic Alcohol Consumption is Inversely Associated with Insulin Resistance and Fatty Liver in Japanese Males

We aimed to elucidate the effect of chronic alcohol consumption on fatty liver. We assessed the consumption of alcohol in 2429 Japanese males (mean age: 54.2 ± 9 years); they were classified according to average consumption into non-drinkers (ND), light drinkers (LD), moderate drinkers (MD), and heavy drinkers (HD). The prevalence of fatty liver was the lowest in the MD and highest in the ND group (p < 0.001), while obesity was not significantly different among the groups (p = 0.133). Elevated levels of alanine aminotransferase (ALT) were the lowest in the MD group (p = 0.011) along with resistance to insulin (homeostasis model assessment-insulin resistance (HOMA-IR)), which was highest in the ND group (p = 0.001). Chronic consumption of alcohol was independently and inversely associated with fatty liver and insulin resistance after adjusting for obesity, hypertension, fasting hyperglycemia, habit of drinking sweet beverages, physical activity, and age (odds ratios are as follows: ND, 1; LD, 0.682; MD, 0.771; HD, 0.840 and ND, 1; LD, 0.724; MD, 0.701; HD, 0.800, respectively). We found that regardless of the type of alcoholic beverage, chronic consumption of alcohol is inversely associated with insulin resistance and fatty liver in Japanese males. This study had limitations, most notably the lack of investigation into diet and nutrition.

The Receptor Tyrosine Kinase RON and Its Isoforms as Therapeutic Targets in Ewing Sarcoma

The receptor tyrosine kinase (RTK) RON is linked to an aggressive metastatic phenotype of carcinomas. While gaining interest as a therapeutic target, RON remains unstudied in sarcomas. In Ewing sarcoma, we identified RON among RTKs conferring resistance to insulin-like growth factor-1 receptor (IGF1R) targeting. Therefore, we explored RON in pediatric sarcoma cell lines and an embryonic Tg(kdrl:mCherry) zebrafish model, using an shRNA-based approach. To examine RON–IGF1R crosstalk, we employed the clinical-grade monoclonal antibody IMC-RON8, alone and together with the IGF1R-antibody IMC-A12. RON silencing demonstrated functions in vitro and in vivo, particularly within micrometastatic cellular capacities. Signaling studies revealed a unidirectional IGF1-mediated cross-activation of RON. Yet, IMC-A12 failed to sensitize cells to IMC-RON8, suggesting additional mechanisms of RON activation. Here, RT-PCR revealed that childhood sarcomas express short-form RON, an isoform resistant to antibody-mediated targeting. Interestingly, in contrast to carcinomas, treatment with DNA methyltransferase inhibitor did not diminish but increased short-form RON expression. Thus, this first report supports a role for RON in the metastatic progression of Ewing sarcoma. While principal molecular functions appear transferrable between carcinomas, Ewing sarcoma and possibly more common sarcoma subtypes, RON highlights that specific regulations of cellular networks and isoforms require better understanding to successfully transfer targeting strategies.

A STUDY ON EFFECT OF DRUG DURING IN CLINICAL MANAGEMENT OF DIABETES

Diabetes is defined as a state in which homeostasis of carbohydrate, protein and lipid metabolism is improperly regulated as a consequence of a relative or absolute deficiency of insulin secretion, resistance to insulin action or both at one or more center in tedious pathways of hormones activity. Diabetes is deadly disease in both developed and developing countries. In 2000, there were a probable 175 million people with diabetes universal and by 2030, the projected estimate of diabetes is 354 million. The most widely recognized unfavorable responses to insulin are weight addition and hypoglycaemia (Henry et al, 1993; Kudlacek et al, 1992). Weight increase in the wake of beginning insulin treatment for uncontrolled diabetes is an inescapable outcome and is the consequence of expanded truncal fat and muscle mass and severe side effects of biguanides include diarrhoea, abdominal discomfort, nausea, metallic taste, and anorexia. Keywords: Diabetes, Insulin, Biguanides and Hypoglycaemia

SUN-336 Obesity and Impaired Glucose Metabolism in Adult Patients with X-Linked Hypophosphatemia

Background: X-linked hypophosphatemia (XLH) is characterized by increased activity of circulating FGF23 resulting in renal phosphate wasting and abnormal bone mineralization. Epidemiologic studies suggest a relationship between FGF23, obesity and metabolic syndrome. However, the prevalence of metabolic complications in adult XLH patients is not known. Study design: We conducted a prospective cohort study (CNIL 2171036 v 0) in a single tertiary referral center. Subjects: Patients were adult subjects with XLH, defined as hypophosphatemia due to renal phosphate wasting with either documented PHEX mutation (92%) and/or family history of rickets. Healthy controls were selected among adult participants of the AcroCut cohort and matched for sex, age and body mass index (BMI). Methods: Prevalence of obesity and diabetes in patients was compared with the general French population (ObEpi 2012; Bonaldi C. et al., Bulletin épidemiologique hebdomadaire 2016) and prevalence of glucose intolerance in patients, assessed by standard 75-g OGTT, was compared to matched controls. Resistance to insulin was evaluated with HOMA-IR index. Results: 107 patients (79 women and 28 men) were recruited. Median age at evaluation was 35.5 years (range 16.9-74.2) and median BMI was 25 kg/m2 (range 18-48). Thirty-eight (35.5%) patients were overweight (29 women) and 22 (20.5%) patients were obese (16 women). Distribution of normal weight, overweight and obesity in adult XLH patients differed from that seen in the general French population. We observed an excess of overweight and obesity (+20%, 95% CI [+6; +33], P=0.013) in comparison to general population, especially in younger age categories (under 45 years of age). Three (2.8%) out of the 107 patients were treated for diabetes which did not differ from the expected frequency of type 2 diabetes of 5% in the French population. Twelve (13%) out of 90 patients with available OGTT were glucose intolerant or diabetic compared to ten (12%) of the 82 matched controls (P=0.995). Decreased insulin sensitivity assessed by HOMA-IR was found in fourteen (15.6%) adult XLH patients. Comparison of insulin and glucose curves obtained during the OGTT in patients and matched controls are planned to analyze insulin sensitivity in both populations. Conclusion: Adult XLH patients are prone to develop overweight and obesity, particularly adolescents and young adults. This excess of weight does not seem to result in increased prevalence of metabolic disorders. Insulin sensitivity, yet, needs to be further evaluated in these patients and compared to appropriate controls. FGF23 concentrations will also be assessed to search for determinants of insulin sensitivity in patients. Lifestyle recommendations to prevent obesity, promoting physical activity, are thus essential in the management of XLH patients.

Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm

The current paradigm of type 2 diabetes (T2D) is gluco-centric, being exclusively categorized by glycemic characteristics. The gluco-centric paradigm views hyperglycemia as the primary target, being driven by resistance to insulin combined with progressive beta cells failure, and considers glycemic control its ultimate treatment goal. Most importantly, the gluco-centric paradigm considers the non-glycemic diseases associated with T2D, e.g., obesity, dyslipidemia, hypertension, macrovascular disease, microvascular disease and fatty liver as ‘risk factors’ and/or ‘outcomes’ and/or ‘comorbidities’, rather than primary inherent disease aspects of T2D. That is in spite of their high prevalence (60–90%) and major role in profiling T2D morbidity and mortality. Moreover, the gluco-centric paradigm fails to realize that the non-glycemic diseases of T2D are driven by insulin and, except for glycemic control, response to insulin in T2D is essentially the rule rather than the exception. Failure of the gluco-centric paradigm to offer an exhaustive unifying view of the glycemic and non-glycemic diseases of T2D may have contributed to T2D being still an unmet need. An mTORC1-centric paradigm maintains that hyperactive mTORC1 drives the glycemic and non-glycemic disease aspects of T2D. Hyperactive mTORC1 is proposed to act as double-edged agent, namely, to interfere with glycemic control by disrupting the insulin receptor-Akt transduction pathway, while concomitantly driving the non-glycemic diseases of T2D. The mTORC1-centric paradigm may offer a novel perspective for T2D in terms of pathogenesis, clinical focus and treatment strategy.