Hyperbolic correlation between insulin sensitivity and insulin secretion fades away in lean subjects with superb glucose regulation

Aizawa, Toru; Yamada, Masayuki; Katakura, Masafumi; Funase, Yoshiko; Yamashita, Koh; Yamauchi, Kazuyo

doi:10.1507/endocrj.ej11-0162

Cited by 9 publications

(15 citation statements)

References 41 publications

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“…However, it is difficult to obtain independent measures of SI and β in cases of OGTTs. Therefore, FIRI‐derived indices for SI and post‐loading insulin‐derived indices for β have been appreciated in previous studies and also in the present study.…”

Section: Discussionmentioning

confidence: 59%

“…When SI and β are in a hyperbolic relationship, the disposition index (DI), which is calculated by multiplying SI with β, reflects beta cell function adjusted for SI . 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 .…”

Section: Introductionmentioning

confidence: 99%

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

Murai

Saito

Kodama

et al. 2019

Clinical Endocrinology

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Background Ghrelin is involved in feeding regulation and energy metabolism and is also known to inhibit insulin secretion (β). However, few clinical studies have demonstrated the relationship between β and ghrelin dynamics. This study tested the hypothesis that, in oral glucose tolerance tests (OGTT), ghrelin dynamics are associated with β. Methods Subjects were 1145 healthy individuals <40 years old who tested normal on the 75‐g OGTT. The following indicators and the ghrelin suppression ratio (GSR) during OGTT were calculated: insulin sensitivity (SI) [1/homoeostasis model assessment of insulin resistance, insulin sensitivity index‐Matsuda and 1/fasting insulin (1/FIRI)]; and β [Stumvoll first‐phase index (Stumvoll‐1), Stumvoll second‐phase index and insulinogenic index]. From nine combinations of SI and β, combinations that produce hyperbolic relationships were identified. Results Stumvoll‐1 and 1/FIRI showed a hyperbolic relationship in nonobese subjects, and the product of Stumvoll‐1 and 1/FIRI was used as the disposition index (DI). When analyzed by BMI quartiles, post‐loading glucose and insulin levels at each time point increased from Q1 (low BMI) through Q4 (high BMI), whereas the DI, ghrelin levels at each time point, and GSR decreased from Q1 to Q4. On multivariate and bivariate analysis, GSR and DI were positive and independent, and fasting ghrelin and FIRI were negatively and independently correlated. Conclusions Ghrelin dynamics were associated with beta cell function in subjects with normal glucose tolerance. Glucose intolerance in obesity may be due not only to insulin resistance but also to impaired beta cell function associated with abnormalities of ghrelin dynamics.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

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

Murai

Saito

Kodama

et al. 2019

Clinical Endocrinology

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“…As alternative indices of GSIS, Stumvoll 1st (Stumvoll-1) and 2nd phase (Stumvoll-2) indices, respectively, were also used: Stumvoll-1 = 1283 + 1.829∙IRI 30 – 138.7∙PG 30 + 3.772∙FIRI and Stumvoll-2 = 287 + 0.4164∙IRI 30 – 26.07∙PG 30 + 0.9226∙FIRI, in which the unit of IRI and PG was pmol/L and mmol/L, respectively (Stumvoll et al 2000). BCF was estimated by oral disposition indices (DI O ): a product of insulinogenic index and ISI Matsuda (DIoII) (Nagasaka et al 2012; Aizawa et al 2012) and a product of Stumvoll-1 and ISI Matsuda (DIoST-1) (Oka et al 2014a; Yamauchi et al 2013) were employed. As an index of Sg, SgI O which is derived from OGTT (Nagasaka et al 2012) was calculated.…”

Section: Methodsmentioning

confidence: 99%

Longitudinal changes in insulin sensitivity, insulin secretion, beta cell function and glucose effectiveness during development of non-diabetic hyperglycemia in a Japanese population

2014

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Since there had been no previous studies of alterations in insulin sensitivity, glucose-stimulated insulin secretion, beta cell function and glucose effectiveness during the development of non-diabetic hyperglycemia in Asian populations, we conducted a longitudinal study of such changes in 244 Japanese adults with normal glucose tolerance (median BMI 23.3 kg/m2 and age 51 yrs). The median follow-up period was 3.3 yrs. One hundred and eighty-two subjects maintained normal glucose tolerance (nonprogressors). After excluding the 3 subjects who progressed to diabetes, we analyzed the 59 who developed non-diabetic hyperglycemia (progressors), of which 31 progressed to impaired fasting glucose and 28 to impaired glucose tolerance. Whole body insulin sensitivity was estimated by ISIMatsuda, glucose-stimulated insulin secretion by [δIRI0-30/δPG0-30] and Stumvoll indices, hepatic insulin sensitivity by quantitative insulin sensitivity check index (QUICKI) and 1/fasting IRI, beta cell function by oral disposition index (DIO) ([δIRI0-30/δPG0-30]∙[ISIMatsuda]), and glucose effectiveness by an OGTT-derived index (SgIO). ISIMatsuda (p <0.05), [δIRI0-30/δPG0-30], DIO and SgIO (both p <0.01), but not QUICKI, 1/fasting IRI, or Stumvoll-1st and -2nd phases, were lower in the progressors at baseline. This group was also characterized by the following: 1) ISIMatsuda, DIO and SgIO were reduced by 34%, 32% and 11%, respectively (all p <0.01); 2) QUICKI and 1/fasting IRI diminished by 21% and 5%, respectively (both p <0.01); and 3) no significant changes were found in [δIRI0-30/δPG0-30], Stumvoll-1st and -2nd phases or BMI during the follow-up. In the nonprogressors, no indices changed significantly during the follow-up. Our study concluded that during the transition from normal glucose tolerance to non-diabetic hyperglycemia in this non-obese population, whole body insulin sensitivity, hepatic insulin sensitivity, beta cell function, and glucose effectiveness were all attenuated, but no significant changes in glucose-stimulated insulin secretion occurred. Also of note is the fact that the transition took place without any accompanying increase in BMI.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-252) contains supplementary material, which is available to authorized users.

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“…Characteristics of the Aizawa cohort, which was stratified according to age (<45, 45–54, 55–64, ≥65), are presented in Table . Characteristics of the Chikuma cohort (N = 502), which was divided into two groups (<65, ≥65), have been reported elsewhere . The hospital review boards of Aizawa Hospital and Chikuma Hospital approved the study protocol.…”

Section: Effect Of Age On Prediction Of Diabetes By Body Mass Index (mentioning

confidence: 99%

“…Insulin secretion was determined in the Chikuma cohort, and serum immunoreactive insulin was determined using an insulin‐specific radioimmunoassay at 0, 30, and 120 minutes during the OGTT. In the Aizawa cohort, median age was 52, fasting plasma glucose (PG) was 5.1 mmol/L, 2‐hour PG was 6.7 mmol/L, BMI was 23.1 kg/m 2 , and HbA 1c was 5.6% (38 mmol/mol).…”

Section: Effect Of Age On Prediction Of Diabetes By Body Mass Index (mentioning

confidence: 99%

Equivocal Association Between Body Mass Index and Diabetes Mellitus in Elderly Adults

Sato

Nakasone

Miyakoshi

et al. 2016

J American Geriatrics Society

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Hyperbolic correlation between insulin sensitivity and insulin secretion fades away in lean subjects with superb glucose regulation

Cited by 9 publications

References 41 publications

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

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

Longitudinal changes in insulin sensitivity, insulin secretion, beta cell function and glucose effectiveness during development of non-diabetic hyperglycemia in a Japanese population

Equivocal Association Between Body Mass Index and Diabetes Mellitus in Elderly Adults

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