Clinical Trials Logo

Clinical Trial Summary

Insulin resistance and beta cell dysfunction are the major core defects responsible for the development of type 2 diabetes (T2DM). Although insulin resistance is the early metabolic defect detected in subjects destined to develop T2DM, it is the beta cell failure which is responsible for the development of hyperglycemia.

Longitudinal and cross-sectional studies have demonstrated that, initially, the compensatory hyperinsulinemia is sufficient to offset the insulin resistance and maintain normal glucose tolerance. However, when the beta cell fails to adequately compensate for the insulin resistance, glucose homeostasis deteriorates. Initially, this is manifest as impaired glucose tolerance (IGT) and later as overt diabetes. It follows that the level of beta cell failure at which hyperglycemia becomes evident depends upon the prevailing level of insulin resistance. A more severe insulin resistance results in development of overt hyperglycemia at lower level of beta cell failure. The investigators previously have shown that the severity of insulin resistance varies amongst different ethnic groups (Arabs versus Indians). Thus, the level of beta cell failure at which overt hyperglycemia becomes evident amongst each ethnic group also varies. Thus, individuals/ethnic groups with more severe insulin resistance, overt hyperglycemia becomes evident at lower level of beta cell dysfunction. Conversely, severe beta cell dysfunction is required for evert hyperglycemia to develop in individuals/ethnicities with less severe insulin resistance.

In the present study, the investigators aim to quantitate beta cell function with the gold standard technique (i.e. hyperglycemic clamp) in Arab and Indian non-diabetic individuals and relate the level of beta cell function to the prevailing level of insulin resistance measured as the glucose infusion rate divided by the mean plasma insulin concentration during the clamp.


Clinical Trial Description

Insulin resistance and the accompanying hyperinsulinemia also lead to the development of multiple metabolic abnormalities which are responsible, at least in part, for the excessive risk of coronary heart disease in T2DM , non-alcoholic steatohepatitis (NASH), and impaired diastolic left ventricular (LV) function. Thus, insulin resistance contributes, not only to increased T2DM risk, but also to the morbidity and mortality associated with the disease.

Etiology of Insulin Resistance Insulin resistance is closely related to obesity. Multiple mechanisms contribute to insulin resistance in obese individuals. Accumulation of fat in insulin target tissues (i.e. ectopic fat), e.g. in myocytes and hepatocytes, plays a central role in the pathogenesis of insulin resistance. When energy intake exceeds energy expenditure, the energy excess is stored in subcutaneous adipocytes in the form of triglycerides. However, under conditions of persistent positive energy balance, subcutaneous fat stores become filled and the excess energy spills over into the circulation in the form of FFA, leading to increased fat content in lean tissues, i.e. ectopic fat. Many studies have documented the important role of ectopic fat content in the pathogenesis of insulin resistance in obese individuals. The severity of insulin resistance in skeletal muscle and liver strongly correlates with ectopic fat content in myocytes and hepatocytes, respectively. Further, therapies that deplete ectopic fat, e.g. weight loss and pioglitazone, significantly improve insulin sensitivity.

Fat spill over and the subsequent increase in ectopic fat content in lean tissues could result from subcutaneous fat cells that are filled to capacity or the inability of the subcutaneous fat stores to expand. Consistent with this hypothesis, several studies have demonstrated increased fat cell size in subcutaneous fat in insulin resistant obese individuals compared to insulin sensitive controls. Moreover, large fat cells have a higher rate of lipolysis and decreased rate of FFA esterification compared to small fat cells, suggesting decreased ability of large fat cells to further store fat in subcutaneous adipose tissue in obese individuals. Of note, large fat cell size is a strong predictor of future T2DM risk in non-diabetic individuals, independent of insulin resistance. Collectively, these results have led to the hypothesis that inability of subcutaneous fat tissue to expand results in fat spill over into muscle, liver, heart, etc and the subsequent development of insulin resistance. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04268862
Study type Observational
Source Dasman Diabetes Institute
Contact Ebaa AlOzairi, Md, PhD
Phone +965 22242999
Email ebaa.alozairi@dasmaninstitute.org
Status Recruiting
Phase
Start date March 1, 2020
Completion date December 31, 2021

See also
  Status Clinical Trial Phase
Completed NCT01317134 - Endothelial Function in Patients With Pulmonary Arterial Hypertension N/A
Completed NCT03997721 - Pathophysiology of Perioperative Fluid Management in Emergency Laparotomy
Completed NCT04791566 - Preoperative High-dose Dexamethasone and Emergency Laparotomy Phase 4
Completed NCT03675100 - Neurotrophic Factors, Tight Junction Proteins, and Cytokines in IBS N/A
Recruiting NCT03283839 - Consequences of Temporomandibular Disorder on Balance Control N/A
Recruiting NCT06234761 - Immunological Mechanisms Underlying Mucosal IgE Responses
Completed NCT05118542 - Effect of Hyperthyroidism and Its Treatment in Graves' Disease to Early Marker of Atherosclerosis Phase 3
Completed NCT04520802 - Neuroinflammation in Cognitive Decline Post-cardiac Surgery
Recruiting NCT06435585 - Responders and Non-responders in the Management of Heart Failure - Significance of Genetic Influence and Identification of Novel Informative Biomarkers
Completed NCT01728974 - Mechanisms of Pharyngeal Collapse in Sleep Apnea, Study A N/A
Recruiting NCT04776642 - Biobank for "Arrhythmia and Conduction Disorders: TowArd Pathophysiology Based Treatment"