Diabetes in relation with cardiovascular diseases

Diabetes is an important chronic disease which incidence is globally increasing and however considered as an epidemic. This growth in diabetes prevalence, driven principally by an increased prevalence of type 2 diabetes (T2D), is occurring in both developing and developed countries. The incidence of type 1 diabetes (T1D) is also increasing in parallel to that of T2D worldwide. Individuals with diabetes and with chronically poor metabolic control can experience micro vascular and macro vascular complications leading to a significant burden for the individual and for the society. This burden includes direct costs of medical care and indirect costs, such as loss of productivity, which result from diabetes-related morbidity and premature mortality Health care expenses for people with diabetes is more than double of that for people without diabetes; the direct and indirect expenditures attributable to diabetes. The International Diabetes Federation (IDF) estimated that diabetes accounts for 5–10% of the total healthcare budget in many countries.

Cardiovascular diseases are the most prevalent cause of mortality and morbidity among people with T2D and T1D. The presence of cardiovascular diseases and stroke was found in 68% and 16% of deaths related to diabetes among people older than 65 years, respectively. Adult individuals with diabetes present rates of mortality because of heart disease and stroke from two to four times higher than those without diabetes. It has been stated that patients with T2D without a previous history of myocardial infarction have the same risk of coronary artery disease as nondiabetic subjects with a history of myocardial infarction. However, there is still some uncertainty as to whether the cardiovascular risk given by diabetes is truly equivalent to that of a previous myocardial infarction. In general, patients with diabetes aggregate other comorbidities such as obesity, hypertension, and dyslipidemia which also contribute to increasing the risk for cardiovascular diseases. Although there is strong evidence that supports both the efficacy and cost effectiveness of programs directed towards improvement of glycemic control and other cardiovascular risk factors in patients with T2D and T1D, the majority of these patients never achieve the goals established by guidelines issued by diabetes societies.

Contact details:

Alina Grace

Program Manager | Obesity Middle East 2019

Email id: obesityendo@mehealthevents.org 

Obesity and Clinical Endocrinology

Endocrine disrupting chemicals are commonly found in food and food containers, furniture, plastic products, toys, building materials, carpeting, and cosmetics. They are usually released from the products that contain them and enter the bodies of humans and wildlife through dust or through the food chain. A large volume of studies have shown that Endocrine disrupting chemicals exert their effects by interfering with endogenous hormone action and can impact male and female reproduction, breast development and cancer, prostate cancer, metabolism and obesity, neuroendocrinology, thyroid and cardiovascular endocrinology.

Critical endocrine principles that are relevant to risk assessment as it applies to Endocrine disrupting chemicals. In its Statement of Principles, the Society recommends that endocrine principles be incorporated into programs by the EPA and different agencies charged with evaluating chemicals for endocrine-disrupting potential.

Several endocrine abnormalities are reported in obesity. A number of these abnormalities are considered as causative factors for the development of obesity, whereas others are considered to be secondary effects of obesity and usually are restored after weight loss. Thyroid hormones sometimes are normal in obesity, with the exception of T3 that is elevated. Prolactin is normal but prolactin response to various stimuli is blunted. Growth hormone is low and GH response to stimuli is blunted. IGF-I levels are normal or elevated. Cortisol, ACTH, and urine free cortisol levels are generally normal; however, a hyperresponsiveness of the HPA axis with enhanced cortisol and ACTH response to stimulatory tests is observed in centrally obese individuals. Total testosterone and SHBG levels are low, however free testosterone levels are typically normal in obese men. LH and FSH levels usually are normal and estrogens are elevated. Norepinephrine levels are elevated, though epinephrine levels are low or normal. Aldosterone levels are raised however renin activity is typically normal. Parathyroid hormone levels are elevated with normal serum calcium levels and enhanced urine calcium levels. Monogenic mutations that result in severe obesity have been described in few people. Likewise, several endocrine diseases have obesity as one their clinical signs. Hypothyroidism, GH and testosterone deficiency, Cushing's syndrome, polycystic ovarian syndrome, hypothalamic lesions, insulinoma and genetic syndromes often present with obesity. In most of these conditions, proper treatment of the primary disease results in weight reduction. Also, the fat cell has been observed to be an endocrine organ that produces several peptides that are bioactive and participate in the regulation of adipocyte function.

Contact details:
Alina Grace
Program Manager | Obesity Middle East 2019
Mail Id:obesityendo@mehealthevents.org

Genetics of Obesity

Obesity is a major risk factor for cardiovascular diseases, pulmonary diseases like sleep apnoea, metabolic disorders, osteoarticular diseases, for several of the Similar types of cancer and for serious psychiatric illness. Childhood obesity is associated with early-onset type 2 diabetes and with increased mortality risk for coronary heart disease in adulthood. If the escalating population prevalence of obesity and its serious implications for public health are generally accepted [with some notable exceptions], its causes and physiological consequences at the individual level are still elusive. 

Types:

Rare familial obesity:

Moreover a decade, obesity genetics has been predominantly driven by research into syndromic obesity. The cloning of the mouse gene and its human homologue, leptin, proved to be a paradigm for the field that resulted in the identification of many genes involved in the regulation of appetite via the leptin-melanocortin pathway. These variants account for 5% of morbid human obesity and include leptin and its receptor.

Common polygenic obesity:

The Human Obesity Gene Map summarizes the current situation in the field of common polygenic obesity. In any complex genetic disease, there are many unconfirmed genetic associations as some of these may be due to inadequate sample sizes for association studies of genes of modest effect or caused due to the inadequate examination of the genetic variation within these candidate genes.

GAD2:

The glutamic acid decarboxylase gene (GAD2) was first reported and recorded to be associated with obesity and feeding behaviors in morbidly obese adults, and this result was subsequently replicated in obese children. Moreover, an independent study failed to replicate these findings. These results illustrate the difficulty in determining whether a gene is truly associated with a complex genetic disease. 

Visfatin:

Pre-B cell colony-enhancing factor (PBEF1) was identified as the first protein secreted by lymphocytes over 10 years ago. This finding has now been replicated. The initial visfatin paper was also reported that visfatin had insulin mimetic activity. This was supported by a report where visfatin levels were altered in T2D patients. 

Ghrelin/ghrelin receptor/obestatin:

The growth hormone secretagogue receptor (GHSR) was identified in the year of 1996 and its endogenous ligand ghrelin in 1999. However, the evidence for ghrelin is not required as clear with initial positive results, but latterly, some negative results. 

Bardet–Biedl syndrome genes:

Bardet–Biedl syndrome genes are familial forms of obesity have been associated with common obesity, e.g. leptin, as well as the leptin receptor, were examined BBS gene variants for this possibility. Twelve SNPs along with BBS1, 2, 4 and 6 genes were selected and genotyped in adult and childhood obesity sample sets, with a total of 3242 subjects.

Contact details:
Alina Grace
Program Manager | Obesity Middle East 2019
Email Id: obesityendo@mehealthevents.org 

Obesity and Diabetes

Weight is likely the most essential factor in the advancement of insulin obstruction; however, science's comprehension of the chain of occasions is as yet spotty. Now researchers have developed possible outcomes for obesity sets the stage for diabetes and why thin people can become insulin-resistant. ER (endoplasmic reticulum) stress is the condition which is induced by a high-fat diet and is overly activated in obese people, triggers aberrant glucose production in the liver, an important step on the path for insulin resistance.

In healthy people, a fasting switch possibly flips on glucose production when blood glucose levels run low during fasting. The existence of a second cellular cascade signalling—like an alternate route from A to B—that can modulate glucose production, shows the potential to distinguish new classes of medications that that may bring down glucose by disrupting this alternative pathway. It had been well established that obesity promotes insulin resistance through the inappropriate inactivation of a process called gluconeogenesis, where the liver creates glucose for fuel and which usually happens just during fasting. 

At the point when a cell begins to sense stress a red light goes on, which slows down the generation of proteins. This procedure, which is known as ER stress response, is abnormally active in livers of obese individuals, where it contributes to the development of high blood glucose levels or hyperglycemia. We asked whether chronic endoplasmic reticulum stress in obesity leads to abnormal activation of the fasting switch that usually controls glucose production in the liver. The endoplasmic reticulum, short for endoplasmic reticulum, is a protein factory within the cell. Endoplasmic reticulum stress can induce gluconeogenesis in lean mice. Glucose production is turned on by a transcriptional switch called CRTC2, which typically sits outside the nucleus waiting for the signal that allows it to slip inside and do its work. Once in the nucleus, it collaborates with a protein called CREB and together they switch on the genes necessary to increase glucose output. In insulin-resistant mice, however, the CRTC2 switch seems to get stuck in the "on" position and the cells begin producing glucose like sugar factories in overdrive.  

Contact details:
Alina Grace
Program Manager | Obesity Middle East 2019
Mail Id: obesityendo@mehealthevents.org