Role of Heat Shock Proteins in Increasing risk of hyperglycemia/diabetes in First/Second degree relatives of diabetics

Abstract

Type II diabetes mellitus or adult-onset diabetes is a collection of disarray distinguished by hyperglycemia, micro-vascular, macro-vascular and neuropathic problems. The World Health Organization reported in 2004 that more than 170 million people have diabetes and the projected number could be as high as 370 million by 2030. The increased incidence of diabetes in developing countries is due to poor diet, obesity and inactive lifestyle. Diabetes is a condition that increases oxidative stress and inflammation, which may lead to damage of pancreas resulting in failure of beta cell function. It is a serious health problem that may lead to complications and can increase the risk of mortality. It also brings substantial economic losses, such as loss of work which effects productivity, wages and increase medical expenditure, the intial point of living a normal life with diabetes is an early diagnosis, longer a person lives with undiagnosed and untreated diabetes, the worse their health outcomes are likely to be. Present study was designed to find out the role of heat shock proteins, hormone and metal ions in developing hyperglycemia/diabetes in first degree relatives of diabetics. Study also tried to find out the relationship of heat shock protein, insulin, insulin resistance; hormones, cytokines and lastly metal ions. Link of heat shock proteins with risk of diabetes is not studied as of yet. The study included 200 relatives of diabetic patients. The seventy subjects (with no history of diabetes) with same sex, age and socioeconomic status were included as control. Both control and diabetes related subjects were between the ages of 14 -50 years. Study was divided into 2 units i.e. primary and secondary. In primary unit, the subjects were divided in three groups based on age i.e. groups, A (14-25 years), group B (26-35 years) and group C (36-50 years). Laboratory tests i.e., fasting plasma glucose, oral glucose tolerance test; and HbA1c, serum insulin were performed. Then according to these parameters the age group suitable for further study was decided (secondary study). The secondary study was based on the estimation of biochemical parameters (level of insulin, insulin resistance, level of adiponectin; visfatin, elastase, metal ions and different heat shock proteins) related to pancreatic endocrine and exocrine function; as the impairment of these parameters may increase the risk of diabetes. In primary study comparisons between group A, B and C showed that group B, was more aberrant due to release of insulin, results in impairing the oral glucose tolerance test, and caused progressive loss of beta-cell function. It is confirmed that prevalent risk, associated with diabetes, is greater in relatives within age group of 26-35 (group B). Therefore, there is a need to check heat shock proteins as an early indicator of diabetes, in the age group between 26-35 years. Data was entered in SPSS 20 and analyzed by student ‗t‘ test and Pearson correlation coefficient.Results showed that the level of fasting blood sugar, HbA1c, insulin and values of insulin resistance were increased in FDR within age group of 26-35 years. On the other hand, a decreased level of HSP 60 and mild increased level of HSP 70 (reactive oxidative intermediates) were observed in first degree relatives of diabetics as compared to the controls. Oxidative stress in first degree relatives of diabetic subjects were determined by estimating the levels of adiponectin, visfatin and elastase. The Raw volume of adiponectin and visfatin may be associated with higher intra-cellular reactive oxygen levels, elicited by mitochondrial dysfunction which resulted in impairment of the functions of adipocytes in the maintenance of glucose homeostasis. On the other hand the decreased level of elastase represents pancreatic exocrine insufficiency. A positive correlation between HSP70 and calcium whereas weak negative correlation between SP60 and calcium showed the importance of this relationship, as differential calcium signaling may be accounted for the differential induction of HSP. A moderately strong negative correlation between HSP70 and magnesium, confirmed, that plasma magnesium concentrations may inversely correlate with degree of hyperglycemia and insulin sensitivity; which may be due to increased oxidative stress. The study revealed a weak negative correlation between phosphate and HSP70. Furthermore, the research also confirmed that dietary lack of phosphorus lead to organ specific induction of HSP. It is therefore concluded that in FDR, besides genetic modification, there is an increased oxidative stress due to mitochondrial dysfunction which is confirmed by impaired level of HSPs. The increased oxidative stress may be the major factor causing impaired fasting glucose, impaired glucose tolerance, increase level of insulin; increase insulin resistance and decrease elastase activity i.e. an impair endocrine and exocrine function of pancreas. The Increased oxidative stress also has an effect on the function of adipocytes by decreasing the secretion of visfatin and adiponectin which also have a role in glucose metabolism.