Impact of one-hour postchallenge glucose on the relationship between insulin sensitivity and secretion

Abstract

The impact of postchallenge glucose on the relationship between insulin sensitivity (SI) and secretion (β) is unknown. We analyzed data from 2,264 health examinees (male/female 1,524/740, median age 54 yrs) with normal glucose tolerance (NGT, n = 1,623), non-diabetic hyperglycemia (NDH, n = 555), or diabetes (DM, n = 86) using OGTT-derived indices of SI (insulin sensitivity index [ISI]-Matsuda, 1/HOMA-IR, and 1/fasting IRI) and β (δIRI0-30/δPG0-30, and Stumvoll 1st [Stumvoll-1] and 2nd [Stumvoll-2] phases). The combination of 1/HOMA-IR and Stumvoll-1 recapitulated the hyperbolic SI-β relationship with the slope of the fitted line -1.000 in NGT subjects, and therefore it was utilized in the following analysis of the SI-β correlation. In multiple regression analysis of the relationship between SI and β, an independent correlation was found for 1 h-plasma glucose (PG; PG60) but not for 2 h-PG. When the NGT subjects were grouped by PG60 quartile (Q), the fitted line was flat in Q1 but progressively steeper from Q2 to Q4, with a slope (95%CI) of -0.663 (-0.726~-0.605), -0.680 (-0.745~-0.622), -0.847 (-0.922~-0.779), and -1.259 (-1.370~-1.158) (P for trend < 0.05). The fitted line steepened further in the NDH and DM groups, with a slope of -1.545 and -1.915, respectively (P < 0.01 for the difference). The intercept of the fitted line for SI-β correlation was also progressively lower across the PG60 Q for NGT, NDH, and DM. In conclusion, using the 1/HOMA-IR-Stumvoll-1 pair for an analysis of the SI-β relationship, elevated PG60 was associated with steepening and downward shifting of the fitted line for the SI-β correlation. The finding suggests impaired beta cell function.

Aldosterone excess may inhibit insulin secretion: A comparative study on glucose metabolism pre- and post-adrenalectomy in patients with primary aldosteronism

“…The following indices were utilized in this study: Insulinogenic index = ΔIRI 0-30 / Δplasma glucose (PG) 0-30 [16]; homeostasis model assessment of insulin resistance (HOMA-IR) = [fasting plasma glucose (FPG) × fasting IRI (FIRI)] / 405 [17]; ISI matsuda = 10,000 / [sqrt (FPG × FIRI × mean PG × mean IRI)] [18], where mean PG and mean IRI represent mean glucose and insulin concentrations during the OGTT; and the disposition index = Stumvoll-1 / HOMA-IR, which was shown to have the best-fit hyperbolic line for insulin sensitivity and insulin secretion in Japanese [19]. Stumvoll-1 = 1,283 + 1.829 × IRI 30 -138.7 × PG 30 + 3.772 × FIRI [20].…”

Comparison of HOMA-IR, HOMA-β% and disposition index between US white men and Japanese men in Japan in the ERA JUMP study: was the calculation of disposition index legitimate?

“…It is obvious that one cannot a priori assume that individuals with a low FPG have robust beta cell function and vice versa. The idea of defining DI as HOMA-β%/HOMA-IR might have arisen from the authors' understanding that 'DI is assumed to be hyperbolic (the constant product of insulin sensitivity and insulin secretion) for individuals with the same degree of glucose tolerance,' which is not always correct [4,5]. A hyperbolic relationship between indices of insulin sensitivity (SI) and insulin secretion exists for a certain combination of the two, but not for all combinations [4,5].…”

“…The idea of defining DI as HOMA-β%/HOMA-IR might have arisen from the authors' understanding that 'DI is assumed to be hyperbolic (the constant product of insulin sensitivity and insulin secretion) for individuals with the same degree of glucose tolerance,' which is not always correct [4,5]. A hyperbolic relationship between indices of insulin sensitivity (SI) and insulin secretion exists for a certain combination of the two, but not for all combinations [4,5]. There is certainly ethnic diversity, as inferred by Simonson et al [6], such that the relationship between the two in the Japanese population is different from that in white people [5].…”

“…A hyperbolic relationship between indices of insulin sensitivity (SI) and insulin secretion exists for a certain combination of the two, but not for all combinations [4,5]. There is certainly ethnic diversity, as inferred by Simonson et al [6], such that the relationship between the two in the Japanese population is different from that in white people [5]. It is strongly recommended that the legitimacy of the calculation of DI using any combination of indices of SI (or IR) and insulin secretion should be verified, before utilising the DI value as a measure of beta cell function.…”

Association of ghrelin dynamics with beta cell function in Japanese subjects with normal glucose tolerance

“…Studies have shown that, in intravenous glucose tolerance tests and oral glucose tolerance tests (OGTTs), SI and β of individuals with NGT and those with glucose intolerance demonstrate hyperbolic relationships . Recently, the relationship between SI and β was analyzed for middle‐aged Japanese subjects predominantly with NGT . According to this study, 1/homoeostasis model assessment of insulin resistance (1/HOMA‐IR) and the Stumvoll first‐phase index (Stumvoll‐1) were selected as the best SI and β combination that produces a hyperbolic relationship.…”