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Role of insulin receptors in obesity-related diabetes
Abstract:
Insulin binding to monocytes was assessed before and after plasma insulin suppression by diazoxide in 14 obesity-related diabetic subjects. Four of the five patients with mild carbohydrate intolerance (FBS less than 150 mg%) and hyperinsulinism exhibited low monocyte insulin binding. Despite an increase in insulin binding after 7 days of diazoxide therapy, no improvement in carbohydrate tolerance could be demonstrated. Lack of improvement may have been related to persistent diazoxide effect. An additional group of 4 patients with low plasma insulin values and more severe carbohydrate intolerance (FBS greater than 150 mg%) had high monocyte insulin binding. This group, as well as a group of patients with intermediate insulin responses, tolerated diazoxide poorly and developed moderate ketonuria or severe hyperglycemia (plasma glucose greater than 350 mg%) necessitating discontinuation of the drug after 3-6 days. The studies in these patients suggest that obesity-related diabetes may be characterized early by mild elevation of plasma glucose, hyperinsulinism and impaired monocyte insulin binding. As beta cell exhaustion occurs, more severe hyperglycemia intervenes and insulin binding to monocytes increases.
Insights
Obesity-related diabetes shows impaired monocyte insulin binding early on, with binding increasing as the condition worsens. Diazoxide treatment did not improve carbohydrate tolerance in these patients.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Diabetes Research
Background:
- Obesity-related diabetes is characterized by complex metabolic dysregulation.
- Insulin resistance and impaired insulin secretion are key features.
- Monocyte insulin binding is a potential biomarker for assessing insulin sensitivity.
Purpose of the Study:
- To investigate monocyte insulin binding in obesity-related diabetes.
- To assess the effect of plasma insulin suppression using diazoxide.
- To correlate insulin binding with carbohydrate tolerance and disease progression.
Main Methods:
- Assessed insulin binding to monocytes before and after diazoxide administration.
- Measured fasting blood sugar (FBS) and plasma glucose levels.
- Monitored patients for ketonuria and hyperglycemia during diazoxide therapy.
Main Results:
- Mildly carbohydrate-intolerant diabetic subjects with hyperinsulinism showed low monocyte insulin binding.
- Diazoxide therapy increased insulin binding but did not improve carbohydrate tolerance.
- Severely carbohydrate-intolerant patients with low insulin values had high monocyte insulin binding.
- Some patients experienced adverse effects like ketonuria or severe hyperglycemia with diazoxide.
Conclusions:
- Early-stage obesity-related diabetes may present with hyperinsulinism and impaired monocyte insulin binding.
- As beta-cell function declines, hyperglycemia worsens, and monocyte insulin binding increases.
- Diazoxide's efficacy may be limited by its persistent effects or patient-specific responses.