Abstract
BackgroundThe changes in β-cell function in high-risk populations who are apparently in the normal glucose tolerant stage are still under investigation for designing earlier prevention strategies. This study analyzes changes in β-cell function and insulin sensitivity across fasting and two-hour glucose categories spanning normal glucose tolerance (NGT) to impaired glucose tolerance (IGT), in offspring of subjects with type-2 diabetes mellitus (T2DM) compared to the controls without a known family history of T2DM.MethodsOffspring of T2DM patients (cases) and individuals without a family history of T2DM (controls) were the subjects for this cross-sectional study. All participants underwent a 75 g oral glucose tolerance test and blood samples were collected for plasma glucose, insulin, C-peptide and proinsulin, at zero, 30, 60, and 120 minutes. ResultsA total of 358 cases (age 23.0 ± 10.8 years, 54% males) and 287 controls (age 28.4 ± 8.10 years, 65% males) were the subjects of this study. Cases and controls were divided into subgroups based on fasting and two-hour glucose categories spanning NGT to IGT. Compared to the reference category of controls (< 80 mg/dL for fasting glucose and < 84 mg/dL for two-hour glucose), cases with IGT had ~60% decline in both β-cell compensation (as measured as disposition index {0-120}) and insulin sensitivity (as measured as whole-body insulin sensitivity index {0-120}); adjusted for age, gender, and body mass index. From lower to higher fasting and two-hour glucose categories, there was a continuous and significant decline in β-cell compensation in both cases and controls. Significant reduction in first-phase insulin secretion, as measured as insulinogenic (0-30) index, was only observed among two-hour glucose categories, not among the fasting glucose categories. In the transition from late NGT cases to IGT cases, there was a significant decline in β-cell compensation, first-phase insulin secretion (more prominent than a decline in overall β-cell secretion) and the changes in whole-body insulin sensitivity were not statistically significant.ConclusionsThe decline in β-cell compensation was continuous and significant in offspring of subjects with type-2 diabetes and controls without a known family history of diabetes from early normal glucose tolerant ranges to impaired glucose tolerant ranges. Compared to the strictest glucose controlled category of controls, approximately 60% decline was observed in β-cell compensation and insulin sensitivity, in impaired glucose tolerant offspring of subjects with type-2 diabetes mellitus.
Highlights
Maintenance of normal glucose tolerance depends on a finely tuned balance between insulin sensitivity and β-cell function [1]
Cases and controls were divided into subgroups based on fasting and twohour glucose categories spanning normal glucose tolerance (NGT) to impaired glucose tolerance (IGT)
In the transition from late NGT cases to IGT cases, there was a significant decline in βcell compensation, first-phase insulin secretion and the changes in whole-body insulin sensitivity were not statistically significant
Summary
Maintenance of normal glucose tolerance depends on a finely tuned balance between insulin sensitivity and β-cell function [1]. The concept that a feedback loop governs the interaction of the insulin-sensitive tissues and the β-cell, as well as the elucidation of the hyperbolic relationship between insulin secretion and insulin sensitivity, explains the elevated insulin response in insulin-resistant subjects and a lower response in insulin-sensitive subjects [2]. Consideration of this hyperbolic relationship has helped to recognize the. This study analyzes changes in β-cell function and insulin sensitivity across fasting and two-hour glucose categories spanning normal glucose tolerance (NGT) to impaired glucose tolerance (IGT), in offspring of subjects with type-2 diabetes mellitus (T2DM) compared to the controls without a known family history of T2DM
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