Table 4.
Descriptions of plasma-based measures commonly used in humans to assess β-cell responses, insulin sensitivity, and β-cell function
| Measure | Description | References |
|---|---|---|
| Measures Based on an OGTT | ||
| β-cell responses | ||
| ∆Insulin0-30/ ∆glucose0-30 | Early insulin response, also known as the insulinogenic index and insulin-to-glucose ratio (IGR). It is measured as the ratio of the increment in insulin relative to glucose during the first 30 minutes following glucose ingestion. It represents a mixture of first- and second-phase insulin secretion as initially defined from intravenous glucose administration. | (477-479) |
| ∆C-peptide0-30/ ∆glucose0-30 | Early C-peptide response, which is similar to the early insulin response but is less affected by differences in hepatic insulin clearance. | |
| IncAUCinsulin/IncAUCglucose | Ratio of the incremental area under the curve (IncAUC) for the insulin response during the whole OGTT as a function of the IncAUC for the glucose response. It provides an estimate of the efficiency of the β-cell’s responsiveness over a prolonged period of glucose exposure. The incremental insulin response is preferred to the total insulin response because the latter includes fasting insulin and is thus not as reflective of the β-cell’s response to the glucose stimulus. | (478, 480) |
| IncAUCC-peptide/IncAUCglucose | Similar to the measure obtained using insulin, but less affected by differences in hepatic insulin clearance. | |
| CIR (corrected insulin response) | Calculated as (100 × 30-min insulin)/(30-min glucose × [30-min glucose − 70 mg/dl]) | (481) |
| Insulin sensitivity | ||
| HOMA1-IR | Equation simplified to allow calculation as HOMA1-IR = (FPI × FPG)/22.5, where fasting plasma insulin (FPI) is in µU/mL and fasting plasma glucose (FPG) is in mmol/L. This measure provides a fasting-based measure of insulin sensitivity. As it is an index of “insulin resistance,” low values indicate insulin sensitive and high values insulin resistant. | (482) |
| IS (insulin sensitivity index) | Calculated as 22.5/(FPI x FPG), where fasting plasma insulin (FPI) is in µU/mL and fasting plasma glucose (FPG) in mmol/L]. It is the inverse of HOMA-IR. Thus, high values indicate insulin sensitive and low values insulin resistant. | |
| 1/fasting insulin | A surrogate measure of insulin sensitivity in humans that is highly correlated with the insulin sensitivity index determined using the minimal model of glucose kinetics developed by Bergman and colleagues. | (109) |
| Matsuda index | This measure is calculated from the glucose and insulin values during an OGTT using the formula 104/(I0 × G0 × Im × Gm)1/2, where G0 and Gm are the fasting and mean glucose and I0 and Im are the fasting and mean insulin. | (483) |
| β-cell function (integrating insulin response and insulin sensitivity) | ||
| HOMA1-%B | Based on fasting samples, a simplified equation to calculate HOMA1-%B = (20 × FPI)/(FPG − 3.5), where fasting plasma insulin (FPI) is in µU/mL and fasting plasma glucose (FPG) is in mmol/L. This measure provides a fasting-based measure of the β-cell’s function relative to the prevailing glucose concentration. | (482) |
| DIo (oral disposition index) | Product of the insulinogenic index and either 1/fasting insulin or HOMA-IR to provide a measure of β-cell function. Importantly, one cannot simply multiply 2 variables together unless it has been proven that the relationship is hyperbolic with a slope not different to −1. | (110) |
| ISSI-2 (insulin secretion-sensitivity index-2) | Ratio of the area under the insulin curve to the area under the glucose curve (as a measure of the β-cell response) multiplied by the Matsuda index to provide an estimate of β-cell function. | (484) |
| Model-derived parameters from an OGTT | ||
| β-cell responses | ||
| HOMA2-%B | Based on fasting samples, a nonlinear model that utilizes either C-peptide or insulin with paired glucose measurement to provide an estimate of the β-cell’s function. This version incorporates an estimate of proinsulin secretion and thus allows use of either total or specific insulin assays. Further, it accounts for renal glucose losses, thus allowing its use in hyperglycemic subjects. Available at https://www.dtu.ox.ac.uk/homacalculator/. | (485) |
| Glucose sensitivity | The slope of the curve relating the rate of insulin secretion to standardized glucose concentrations during the test. It is calculated from the glucose and C-peptide data using a model developed by Mari and colleagues. | (486) |
| Rate sensitivity | An index of early insulin release that represents the dependence of the rate of insulin secretion on the rate of change of glucose concentration. It is calculated from the glucose and C-peptide data using a model developed by Mari and colleagues. | (486) |
| Potentiation | A time-varying factor expressing a potentiation effect upon insulin secretion. It accounts for the physiological processes that can acutely modify insulin secretion. It is calculated from the glucose and C-peptide data using a model developed by Mari and colleagues. | (486) |
| φ d | “Dynamic sensitivity,” a measure of the stimulatory effect of the rate of increase in glucose on the secretion of stored insulin, calculated using a model developed by Cobelli and colleagues. | (487) |
| φ s | “Static sensitivity” is a measure of the effect of glucose on β-cell secretion calculated using a model developed by Cobelli and colleagues. | (487) |
| Insulin sensitivity | ||
| HOMA2-%S | Nonlinear model that utilizes either C-peptide or insulin with paired glucose measurement to provide an estimate of insulin sensitivity. Available at https://www.dtu.ox.ac.uk/homacalculator/. | (485) |
| OGIS (oral glucose insulin sensitivity) | A simple method for calculating insulin sensitivity using glucose and insulin data that is in good agreement with clamp-based measurements. Available at http://webmet.pd.cnr.it/ogis/. | (488) |
| Measures based on intravenous glucose testing | ||
| β-cell responses | ||
| First-phase insulin response | The insulin response to an intravenous bolus of glucose, also known as the acute insulin response to glucose (AIRglucose). This response occurs over the first 10 minutes following glucose administration. This measure can also be determined using C-peptide. | (55, 477, 489, 490) |
| Second-phase insulin response | This insulin response commences shortly after glucose administration, but is not readily discernible until the first-phase response has ended, ie, at about 10 minutes. This measure can also be determined using C-peptide. | (477, 490) |
| AIRmax | Acute insulin response at maximal glycemic potentiation (≥25 mmol/L), typically measured using arginine as the secretagogue. This measure represents β-cell secretory capacity. It has been considered a measure of β-cell mass, but data in humans demonstrate it can change acutely when mass would not be changing. Arginine-induced responses can also be measured at lower glucose concentrations, but these do not usually represent the maximal β-cell response. | (127) |
| Insulin sensitivity | ||
| SI (insulin sensitivity index) | An index of insulin sensitivity calculated from parameters determined using the minimal model of glucose kinetics developed by Bergman and colleagues. Determined from a frequently sampled intravenous glucose tolerance test lasting 3 hours. | (108) |
| M/I | A measure of whole-body insulin sensitivity calculated from clamp studies as the rate of glucose infusion (M) corrected for body size/plasma insulin (I) attained at a steady-state typically achieved after about 2 hours. Addition of tracers (eg, [6,6-2H2]-glucose) allow the measurement of Ra and Rd. Ra denotes rate of tracer appearance when making use of labeled glucose, providing a measure of hepatic insulin sensitivity. Rd denotes rate of tracer disappearance when making use of labeled glucose, providing a measure of skeletal muscle insulin sensitivity. | (491, 492) |
| β-cell function | ||
| DI (disposition index) | A measure that examines the β-cell response relative to insulin sensitivity, the latter a major determinant of secretory demand on the β cell. Importantly, one cannot simply multiply 2 variables together unless it has been proven that the relationship is hyperbolic with a slope not different from −1. | (109) |
Abbreviations: ∆C-peptide0-30/∆C-peptide0-30, C-peptide index/early C-peptide response; ∆Insulin0-30/∆glucose0-30, insulinogenic index/early insulin response; HOMA, homeostatic model assessment; OGTT, oral glucose tolerance test.