Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function

Insulin sensitivity and insulin secretion are mutually related such that insulin resistance is compensated by increased insulin secretion. A correct judgement of insulin secretion therefore requires validation in relation to the insulin sensitivity in the same subject. Mathematical analyses of the relationship between insulin sensitivity and insulin secretion has revealed a hyperbolic function, such that the product of the two variables is constant. This product is usually called the disposition index. Several techniques may be used for its estimation such as data derived from the frequently sampled i.v. glucose tolerance test, the oral glucose tolerance test or the glucose-dependent arginine stimulation test or the euglycemic hyperinsulinemic clamp technique in combination with a test on insulin secretion. Using these techniques the compensatory increase in beta cell function in insulin resistance has been verified in obesity, in pregnancy and after glucocorticoid administration as has the defective beta cell function as the underlying cause of impaired glucose tolerance and type 2 diabetes. Similarly, combined analysis of insulin sensitivity and insulin secretion has shown a down-regulation of beta cell function in increased insulin sensitivity accompanying weight reduction in obesity and following exercise. Acknowledging this inverse relationship between insulin secretion and insulin sensitivity therefore requires estimation of both variables for correct assessment in any individual.

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Disruption of fasting and post-load glucose homeostasis are largely independent and sustained by distinct and early major beta-cell function defects: a cross-sectional and longitudinal analysis of the Relationship between Insulin Sensitivity and Cardiovascular risk (RISC) study cohort

Metabolism ◽

10.1016/j.metabol.2020.154185 ◽

2020 ◽

Vol 105 ◽

pp. 154185 ◽

Cited By ~ 2

Author(s):

Alessandro Mengozzi ◽

Domenico Tricò ◽

Lorenzo Nesti ◽

John Petrie ◽

Kurt Højlund ◽

...

Keyword(s):

Cardiovascular Risk ◽

Insulin Sensitivity ◽

Beta Cell ◽

Glucose Homeostasis ◽

Longitudinal Analysis ◽

Beta Cell Function ◽

Cell Function ◽

Study Cohort ◽

Cross Sectional ◽

The Relationship

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Month-Long Fish Protein Diet Improves Insulin Sensitivity, Beta-Cell Function

Clinical Endocrinology News ◽

10.1016/s1558-0164(06)70415-1 ◽

2006 ◽

Vol 1 (12) ◽

pp. 4

Author(s):

Miriam E. Tucker

Keyword(s):

Insulin Sensitivity ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Protein Diet ◽

Fish Protein

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Effect of troglitazone on insulin sensitivity and pancreatic beta-cell function in women at high risk for NIDDM

Diabetes ◽

10.2337/diabetes.45.11.1572 ◽

1996 ◽

Vol 45 (11) ◽

pp. 1572-1579 ◽

Cited By ~ 19

Author(s):

K. Berkowitz ◽

R. Peters ◽

S. L. Kjos ◽

J. Goico ◽

A. Marroquin ◽

...

Keyword(s):

Insulin Sensitivity ◽

High Risk ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Pancreatic Beta Cell ◽

Pancreatic Beta Cell Function

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Autoantigen Treatment in Type 1 Diabetes: Unsolved Questions on How to Select Autoantigen and Administration Route

International Journal of Molecular Sciences ◽

10.3390/ijms21051598 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1598 ◽

Cited By ~ 3

Author(s):

Johnny Ludvigsson

Keyword(s):

Type 1 Diabetes ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Human Subjects ◽

Subcutaneous Administration ◽

Acid Decarboxylase ◽

Recent Onset ◽

Prevention Trials

Autoantigen treatment has been tried for the prevention of type 1 diabetes (T1D) and to preserve residual beta-cell function in patients with a recent onset of the disease. In experimental animal models, efficacy was good, but was insufficient in human subjects. Besides the possible minor efficacy of peroral insulin in high-risk individuals to prevent T1D, autoantigen prevention trials have failed. Other studies on autoantigen prevention and intervention at diagnosis are ongoing. One problem is to select autoantigen/s; others are dose and route. Oral administration may be improved by using different vehicles. Proinsulin peptide therapy in patients with T1D has shown possible minor efficacy. In patients with newly diagnosed T1D, subcutaneous injection of glutamic acid decarboxylase (GAD) bound to alum hydroxide (GAD-alum) can likely preserve beta-cell function, but the therapeutic effect needs to be improved. Intra-lymphatic administration may be a better alternative than subcutaneous administration, and combination therapy might improve efficacy. This review elucidates some actual problems of autoantigen therapy in the prevention and/or early intervention of type 1 diabetes.

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