Beta-cell function and insulin sensitivity contribute to the shape of plasma glucose curve during an oral glucose tolerance test in non-diabetic individuals

Background: Insulin resistance and impaired beta-cell function are associated with type 2 diabetes mellitus (T2DM). Many insulin resistance and beta-cell function indices have been developed using the data from an oral glucose tolerance test (OGTT) with insulin assay. However, insulin assays are not widely used along with the OGTT in primary prevention outpatient clinics. We aimed to evaluate the association of having impaired fasting glucose (IFG), impaired glucose tolerance (IGT), isolated or combined, with insulin resistance and impaired beta-cell function in subjects at risk for T2DM. Methods: This is a cross-sectional study that included 376 subjects who underwent an OGTT who had at least two risk factors for T2DM without any chronic disease. Results: Participants were 51.6±8.2 years old, 71.8% were women, had a mean body mass index (BMI) of 30.1±6.5 kg/m2, 42.4% had obesity and 26.7% hypertension. A HOMA-IR ≥2.5 was independently associated with male sex, BMI>25kg/m2, and with isolatedIFG, isolated-IGT, or combined (p<0.05 for all). On the other hand, only overweight, but not obesity, was independently associated with impaired beta-cell function (disposition index <1.24). Additionally, combined IFG and IGT had 29.7 higher odds to have impaired beta-cell function compared with those that had a normal OGTT. Conclusions: IFG alone, IGT alone, or the presence of both, are associated with higher odds to have insulin resistance and impaired beta-cell function in asymptomatic subjects at risk for T2DM without any chronic disease. Further studies are needed to evaluate this associations with the risk to develop T2DM, cardiovascular events and mortality.

Download Full-text

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.

Download Full-text

Value of the intravenous and oral glucose tolerance tests for detecting subtle impairments in insulin sensitivity and beta-cell function in former gestational diabetes

Clinical Endocrinology ◽

10.1111/j.1365-2265.2008.03178.x ◽

2008 ◽

Vol 69 (2) ◽

pp. 237-243 ◽

Cited By ~ 15

Author(s):

A. Tura ◽

A. Mari ◽

T. Prikoszovich ◽

G. Pacini ◽

A. Kautzky-Willer

Keyword(s):

Insulin Sensitivity ◽

Gestational Diabetes ◽

Glucose Tolerance ◽

Beta Cell ◽

Beta Cell Function ◽

Cell Function ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Oral Glucose Tolerance Tests ◽

Glucose Tolerance Tests

Download Full-text

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

Acta Endocrinologica ◽

10.1530/eje-10-1003 ◽

2011 ◽

Vol 165 (1) ◽

pp. 69-76 ◽

Cited By ~ 21

Author(s):

A Battezzati ◽

A Mari ◽

L Zazzeron ◽

G Alicandro ◽

L Claut ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Glucose Tolerance Test ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Β Cell ◽

Β Cell Function

BackgroundCystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance.AimTo evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population.MethodsA total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas β-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration.ResultsFifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. β-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6 pmol/min per m2 per mM, P<0.001) and decreased significantly with age by −2.7 pmol/min per m2 per mM per year (confidence interval (CI) −4.5 to −0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower β-cell function and higher insulin sensitivity.ConclusionThe major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining β-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.

Download Full-text

Beyond the morphology of the glucose curve following an oral glucose tolerance test in obese youth

Acta Endocrinologica ◽

10.1530/eje-11-0827 ◽

2012 ◽

Vol 166 (1) ◽

pp. 107-114 ◽

Cited By ~ 26

Author(s):

Giuseppe Nolfe ◽

Maria Rita Spreghini ◽

Rita Wietrzycowska Sforza ◽

Giuseppe Morino ◽

Melania Manco

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Insulin Action ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Obese Youth ◽

Glucose Curve

BackgroundTo describe the morphology of glucose curve during the oral glucose tolerance test (OGTT) and any association with glucose tolerance, insulin action and secretion in obese youth.Study designCross-sectional.MethodsOGTT data of 553 patients were analysed. Subjects were divided in groups based on the morphology (i.e. monophasic, biphasic, triphasic and upward monotonous) of glucose curve. Insulin action was estimated by the homeostasis model assessment of insulin resistance, the insulin sensitivity, the muscle insulin sensitivity and the hepatic insulin resistance indexes (HIRI), and the oral glucose insulin sensitivity (OGIS). Insulin secretion was estimated by the insulinogenic index (IGI). Disposition index, including the insulin secretion–sensitivity index-2, and areas under glucose (AUCG) and insulin (AUCI) curves were computed.ResultsIn patients with normal glucose tolerance (n=522), prevalent morphology of the glucose curve was monophasic (n=285, 54%). Monophasic morphology was associated with the highest concentration of 1 h plasma glucose (P<0.0001) and AUCG (P<0.0001); biphasic morphology with better insulin sensitivity as estimated by OGIS (P<0.03) and lower AUCI (P<0.0001); triphasic morphology with the highest values of HIRI (P<0.02) and IGI (P<0.007).By combining morphologies of glucose and insulin curves or time of the glucose peak, a deeper characterisation of different phenotypes of glucose metabolism emerged.ConclusionsMorphologies of the glucose curve seem reflecting different metabolic phenotypes of insulin action and secretion, particularly when combined with morphologies of insulin curve or time of glucose peak. Such findings may deserve validation in cohort study, in which glucose metabolism would be estimated by using gold standard techniques.

Download Full-text