Quantification of the Relationship Between Insulin Sensitivity and  -Cell Function in Human Subjects: Evidence for a Hyperbolic Function

States of insulin resistance are characterized by hyperinsulinemia that often appears to be out of proportion to the minimal degree of hyperglycemia. One possible explanation for these findings is that mild hyperglycemia per se can cause an adaptive increase in islet sensitivity to glucose, leading to increased insulin output at a given glucose level. To test this hypothesis, we compared acute insulin responses (AIR) and acute glucagon responses (AGR) to 5-g arginine injections before and after 20-h glucose infusions (200 mg X m-2 X min-1) in 11 healthy men of varying age and degree of adiposity. The 20-h glucose infusion caused an increase in fasting plasma glucose (PG) in all subjects (95 +/- 2 vs. 130 +/- 3 mg/dl). PG was clamped at three levels (approximately 95, 165, and 235 mg/dl) before and after the 20-h glucose infusion. Despite matching of PG levels, consistent increases of AIR were observed after the 20-h glucose infusion: 86 +/- 10 vs. 57 +/- 8 at PG = 95 (P = 0.002); 241 +/- 20 vs. 192 +/- 22 at PG = 165 (P = 0.02); and 508 +/- 59 vs. 380 +/- 50 microU/ml at PG = 235 mg/dl (P = 0.009). In addition, the slope of the relationship between AIR and PG level (potentiation slope), a measure of B cell sensitivity to glucose, increased consistently from 2.28 +/- 0.35 (control) to 3.07 +/- 0.45 (P = 0.004) after the 20-h infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

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Estimation of β-cell function from the data of the oral glucose tolerance test

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00341.2006 ◽

2007 ◽

Vol 292 (6) ◽

pp. E1575-E1580 ◽

Cited By ~ 9

Author(s):

Shinji Sakaue ◽

Shinji Ishimaru ◽

Daisuke Ikeda ◽

Yoshinori Ohtsuka ◽

Toshiro Honda ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Glucose Tolerance Test ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Sensitivity Index ◽

Β Cell ◽

Β Cell Function ◽

The Relationship

Although a hyperbolic relationship between insulin secretion and insulin sensitivity has been shown, the relationship has been often questioned. We examined the relationship using oral glucose tolerance test (OGTT)-derived indexes. A total of 374 Japanese subjects who had never been given a diagnosis of diabetes underwent a 75-g OGTT. In subjects with normal glucose tolerance (NGT), the ln [insulinogenic index (IGI)] was described by a linear function of ln ( x) ( x, insulin sensitivity index) in regression analysis when the reciprocal of the insulin resistance index in homeostasis model assessment, Matsuda's index, and oral glucose insulin sensitivity index were used as x. Because the 95% confidence interval of the slope of the regression line did not necessarily include −1, the relationships between IGI and x were not always hyperbolic, but power functions IGI × xα = a constant. We thought that IGI × xα was an appropriate β-cell function estimate adjusted by insulin sensitivity and referred to it as β-cell function index (BI). When Matsuda's index was employed as x, the BI values were decreased in subjects without NGT. Log BI had a better correlation with fasting plasma glucose (PG; FPG) and 2-h PG in non-NGT subjects than in NGT subjects. In subjects with any glucose tolerance, log BI was linearly correlated with 1-h PG and glucose spike (the difference between maximum PG and FPG). In conclusion, the relationship between insulin secretion and insulin sensitivity was not always hyperbolic. The BI is a useful tool in the estimation of β-cell function with a mathematical basis.

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Analysis of the relationship between fasting serum leptin levels and estimates of beta-cell function and insulin sensitivity in a population sample of 380 healthy young Caucasians

Acta Endocrinologica ◽

10.1530/eje.0.1400180 ◽

1999 ◽

pp. 180-185 ◽

Cited By ~ 9

Author(s):

SM Echwald ◽

JO Clausen ◽

T Hansen ◽

SA Urhammer ◽

L Hansen ◽

...

Keyword(s):

Insulin Sensitivity ◽

Beta Cell Function ◽

Cell Function ◽

Serum Insulin ◽

Population Based ◽

Sensitivity Index ◽

Insulin Sensitivity Index ◽

Fasting Serum ◽

Serum Leptin ◽

The Relationship

OBJECTIVE: Circulating leptin levels correlate positively with the degree of obesity and prolonged hyperinsulinaemia increases serum leptin levels. Moreover, insulin secreting beta-cells express functional leptin receptors indicating a functional relationship between leptin and insulin. The aim of this study was to examine the relationship between fasting serum leptin levels and measures of insulin sensitivity and beta-cell function in a population-based sample of 380 young healthy Caucasians. DESIGN AND METHODS: Multiple regression analysis was employed to analyse the relationship between fasting serum leptin levels and levels of fasting serum insulin, insulin sensitivity index and acute insulin response (AIR) in a population-based study of 380 young healthy Caucasians who underwent a combined intravenous glucose and tolbutamide tolerance test. RESULTS AND CONCLUSION: Serum leptin levels were positively correlated to measures of adiposity and were 3.2 times higher in women than in men (P<0.00001). In multiple regression analyses adjusting for age, percentage body fat, waist circumference and maximal aerobic capacity, a significant positive correlation was observed between the fasting serum leptin concentrations and both fasting serum insulin levels (P<0.0001) and AIR (P = 0.014) for women. No significant interrelation of these variables was found in men. However, for both genders a significant negative correlation was observed between fasting serum leptin levels and measures of insulin sensitivity index (P = 0.007).

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The Relationship between Serum 25-Hydroxy Vitamin D and Insulin Sensitivity and β-Cell Function in Newly Diagnosed Type 2 Diabetes

Journal of Diabetes Research ◽

10.1155/2015/636891 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 10

Author(s):

Yuan Gao ◽

Xinchi Wu ◽

Qi Fu ◽

Yanyun Li ◽

Tao Yang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Vitamin D ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Cell Function ◽

Newly Diagnosed ◽

25 Hydroxy Vitamin D ◽

The Relationship ◽

Diabetes Patients

The aim of this study was to investigate the relationship between serum 25-hydroxy vitamin D (25-OHD) and insulin sensitivity andβ-cell function in newly diagnosed type 2 diabetes. 395 newly diagnosed type 2 diabetes patients were enrolled in this study. Venous blood samples were collected at 0 min, 30 min, and 120 min of OGTT to measure serum glucose and insulin. Matsuda ISI and HOMA-IR were used to determine insulin sensitivity. The ratio of 0–120 min area under curve of insulin to glucose (insulin release index, INSR) was calculated as surrogate index ofβ-cell insulin secretion function. The products of insulin secretion indices multiplied by Matsuda insulin sensitivity index were used as disposition indices. Patients were divided into three groups according to tertiles (T1, T2, and T3) of 25-OHD concentration. There was significant difference among three groups for HOMA-IR, Matsuda ISI, and INSR. HOMA-IR, Matsuda ISI, INSR, and DI were undifferentiated among three groups in male patients. But HOMA-IR, Matsuda ISI, and INSR were significantly different among three groups in female patients after being adjusted by confounding factors. In conclusion, serum 25-OHD is associated with insulin sensitivity andβ-cell function for female newly diagnosed type 2 diabetes patients, and the association is ambiguous in males.

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Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess beta cell function in clinical studies

Acta Endocrinologica ◽

10.1530/eje.0.1500097 ◽

2004 ◽

pp. 97-104 ◽

Cited By ~ 152

Author(s):

B Ahren ◽

G Pacini

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Beta Cell ◽

Beta Cell Function ◽

Glucose Tolerance Test ◽

Cell Function ◽

Tolerance Test ◽

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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Postnatal insulin secretion and sensitivity after manipulation of fetal growth by embryo transfer in the horse

Journal of Endocrinology ◽

10.1677/joe.0.1810459 ◽

2004 ◽

Vol 181 (3) ◽

pp. 459-467 ◽

Cited By ~ 29

Author(s):

AJ Forhead ◽

JC Ousey ◽

WR Allen ◽

AL Fowden

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Beta Cell ◽

Embryo Transfer ◽

Plasma Glucose ◽

Cell Function ◽

The Other ◽

Intrauterine Growth ◽

Cell Responses ◽

The Relationship

This study examined the effects of intrauterine growth on insulin secretion and resistance in newborn foals. Embryo transfer between small pony and large Thoroughbred mares was used to produce four groups of foals with different birth weights (pony in pony n=7; pony in Thoroughbred n=7; Thoroughbred in Thoroughbred n=8; Thoroughbred in pony n=8). On day 2 after birth, glucose (0.5 g/kg) was administered intravenously to the foal and blood samples were taken for 2 h to determine plasma glucose and insulin concentrations. On day 3, insulin sensitivity was assessed by giving insulin (0.75 U/kg i.v.) and measuring the decrement in plasma glucose in the foals. There were no significant differences in insulin secretion, insulin sensitivity or glucose tolerance between the control and growth-retarded Thoroughbred foals. Overgrown pony foals delivered by Thoroughbred mares had higher basal insulin levels and greater beta cell responses to glucose than the other groups of foals. The relationship between plasma glucose and insulin was also significantly steeper in overgrown pony foals than in the other groups. Variations in intrauterine growth rate, therefore, affect postnatal insulin secretion in the horse. More specifically, it is overgrowth, not growth retardation in utero that alters equine beta cell function in the immediate neonatal period.

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