by yoly Sun Aug 17 2014, 20:11
Another interesting paper;
http://diabetes.diabetesjournals.org/content/51/suppl_1/S117.fullUnfortunately, in the past, these variables were generally not taken into consideration and because of this, the concept that insulin resistance precedes ß-cell failure in the progression to type 2 diabetes became widely believed (14) and consequently so did the concept that insulin resistance was the primary genetic component of type 2 diabetes (15). Such a concept fails to explain why most obese individuals, who of course are insulin resistant, do not develop diabetes. If one accepts that the normal ß-cell adjusts its function to compensate for insulin resistance, then one could explain the development of IGT and type 2 diabetes as a failure of ß-cell compensation and that this may be the genetic basis for type 2 diabetes. Acceptance of this proposition does not exclude that environmental/acquired factors (e.g., glucose toxicity [16], lipotoxicity [17], and amyloid accumulation in islets [18]) might also be involved.
In this article, previously published work of the author’s laboratory is reviewed as is that of other investigators that relates to the questions of whether first-phase insulin release is the earliest detectable defect in ß-cell function and whether impaired ß-cell function precedes insulin resistance in the pathogenesis of type 2 diabetes.
<>
As shown in Table 2, both first- and second-phase insulin release were reduced in people with IGT, as was insulin sensitivity. These data therefore do not provide evidence for priority for reductions in first-phase insulin release versus second-phase insulin release or for insulin resistance preceding impaired β-cell function. However, because first-phase insulin release was reduced by ∼35% and second-phase insulin release was reduced by ∼28%, whereas insulin sensitivity was reduced by ∼15%, it appears that the decrement in β-cell function was greater than that in insulin sensitivity.
Table 2 also provides data on differences in the phases of insulin release and insulin sensitivity in individuals with and without a family history of diabetes. As has been previously reported (19–28), there was clear-cut evidence for reduced β-cell function in individuals with a family history of diabetes. Both phases of insulin release were reduced: first phase slightly more than second phase (∼19 vs. ∼12%). It is of note that insulin sensitivity was not reduced in these subjects.
We have not as yet analyzed these data to examine the coincidence of reductions in first- and second-phase insulin release, but in an earlier study of subjects with normal glucose tolerance, differing only in whether they had a first-degree relative with type 2 diabetes (19), we also found that people with a first-degree relative with type 2 diabetes had reduced β-cell function (but no insulin resistance) and that some had reductions in only first-phase insulin release; some had reductions only in second-phase insulin release, whereas others had reductions in both phases of insulin release. We interpret these results to be consistent with genetic heterogeneity for impaired β-cell function.
Home
