Differences Between the Tolbutamide-Boosted and the Insulin-Modified Minimal Model Protocols

Saad, Mohammed F.; Steil, Garry M.; Kades, Wagdy W; Ayad, Maged F.; Elsewafy, Wagih A; Boyadjian, Rima; Jinagouda, Sujata; Bergman, Richard N.

doi:10.2337/diab.46.7.1167

Cited by 46 publications

(12 citation statements)

References 27 publications

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“…FSIGT with MINMOD analysis was conducted to evaluate S I using one of the following three methods: no modification (regular), additional insulin administration at 20 min (insulin modified), or tolbutamide administration at 20 min (tolbutamide boosted). Two studies (12,13) have reported that S I measured by the insulin-modified protocol was systematically lower (16–29%) than that measured using tolbutamide, while another reported no significant difference between S I (insulin) and S I (regular) (14). Most of the studies in our meta-analysis used the insulin-modified or regular protocol (Supplementary Table 1 ) .…”

Section: Methodsmentioning

confidence: 99%

“…It was used in two cohorts for all of the participants (2 Caucasian) in the IGR and for none in the T2D. To correct the effects of the tolbutamide studies, we converted their values of S I (tolbutamide) to the approximate estimates of S I (insulin) using the average rate of decline (25.9%) calculated from the data in the two references noted above (12,13).…”

Section: Methodsmentioning

confidence: 99%

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Ethnic Differences in the Relationship Between Insulin Sensitivity and Insulin Response

et al. 2013

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OBJECTIVEHuman blood glucose levels have likely evolved toward their current point of stability over hundreds of thousands of years. The robust population stability of this trait is called canalization. It has been represented by a hyperbolic function of two variables: insulin sensitivity and insulin response. Environmental changes due to global migration may have pushed some human subpopulations to different points of stability. We hypothesized that there may be ethnic differences in the optimal states in the relationship between insulin sensitivity and insulin response.RESEARCH DESIGN AND METHODSWe identified studies that measured the insulin sensitivity index (SI) and acute insulin response to glucose (AIRg) in three major ethnic groups: Africans, Caucasians, and East Asians. We identified 74 study cohorts comprising 3,813 individuals (19 African cohorts, 31 Caucasian, and 24 East Asian). We calculated the hyperbolic relationship using the mean values of SI and AIRg in the healthy cohorts with normal glucose tolerance.RESULTSWe found that Caucasian subpopulations were located around the middle point of the hyperbola, while African and East Asian subpopulations are located around unstable extreme points, where a small change in one variable is associated with a large nonlinear change in the other variable.CONCLUSIONSOur findings suggest that the genetic background of Africans and East Asians makes them more and differentially susceptible to diabetes than Caucasians. This ethnic stratification could be implicated in the different natural courses of diabetes onset.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Ethnic Differences in the Relationship Between Insulin Sensitivity and Insulin Response

et al. 2013

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“…Because this modi cation can only be applied to subjects with preserved beta cell response to secretagogues, the identi cation of S i in subjects with impaired insulin secretion such as type 1 and insulin-de cient type 2 diabetes patients has often forced several authors to replace tolbutamide by insulin. [137][138][139][140][141] Studies comparing the insulin sensitivity estimates derived from the insulinmodi ed FSIVGT with the tolbutamide-modi ed FSIVGT found good correlation between the two (r 0.85, P 0.001), although S i (insulin) appears to be persistently lower than S i (tolbutamide) and M values from clamp studies, [141][142][143] pointing to an underestimation of insulin sensitivity by the model. 35,139,144 This is thought to be due to a combination of oversimpli cation of the physiology in the model, [145][146][147][148] and because of shorter exposure of tissues to hyperinsulinemia in the FSIVGT when compared with the glucose clamp.…”

Section: Frequently Sampled Intravenous Glucose Tolerance Test (Fsivgmentioning

confidence: 99%

Evaluation of Insulin Sensitivity in Clinical Practice and in Research Settings

2003

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Insulin resistance is the core metabolic abnormality in type 2 diabetes. Its high prevalence and its association with dyslipidemia, hypertension, hyperinsulinemia, and high coronary and cerebrovascular mortality put it in the forefront as the plausible target for aggressive intervention. Measurements of insulin sensitivity provide clinicians and clinical researchers with invaluable instruments to objectively evaluate the efficiency of both current and potentially useful interventional tools. Although several methods had been developed and validated to evaluate insulin sensitivity, none of these methods can be universally used in all patients. Nonetheless, a method suitable for use in clinical or basic research may not necessarily be a practical method for use in clinical practice or for epidemiologic research. We reviewed the currently used methods for assessment of insulin sensitivity. For each method, we summarized its procedure, normal value, cut-off value for defining insulin resistance, advantages and limitations, validity, accuracy for each patient population, and suitability for use in clinical practice and in research settings. The methods reviewed include fasting plasma insulin, homeostatic model assessment, quantitative insulin sensitivity check index, glucose-to-insulin ratio, continuous infusion of glucose with model assessment, indices based on oral glucose tolerance test, insulin tolerance test, and the so called "gold standard" methods, the hyperinsulinemic euglycemic clamp and the frequently sampled-intravenous glucose tolerance test.

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“…Further, they infused intravenous tolbutamide rather than insulin at 20 minutes. Differences in S I determined from the tolbutamide-boosted versus the insulin-modified FSIGTs are well recognized18.…”

Section: Discussionmentioning

confidence: 99%

Validity of the reduced-sample insulin modified frequently-sampled intravenous glucose tolerance test using the nonlinear regression approach

et al. 2009

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The Disposition Index, the product of the insulin sensitivity index (S I ) and the acute insulin response to glucose, is linked in African-Americans to chromosome 11q. This link was determined with S I calculated with the nonlinear regression approach to the minimal model and data from the ReducedSampled-Insulin-Modified-Frequently-Sampled-Intravenous-Glucose-Tolerance-Test (ReducedSample-IM-FSIGT). However, the application of the nonlinear regression approach to calculate S I using data from the Reduced-Sample-IM-FSIGT has been challenged as being not only inaccurate but also having a high failure rate in insulin-resistant subjects. Our goal was to determine the accuracy and failure rate of the Reduced-Sample-IM-FSIGT using the nonlinear regression approach to the minimal model. With S I from the Full-Sample-IM-FISGT considered the standard and using the nonlinear regression approach to the minimal model, we compared the agreement between S I from the Full and Reduced-Sample-IM-FSIGT protocols. One hundred African-Americans, (BMI 31.3 ±7.6 kg/m 2 (mean±SD), range 19.0-56.9 kg/m 2 ) had FSIGTs. Glucose (0.3g/kg) was given at baseline. Insulin was infused from 20 to 25 minutes (total insulin dose 0.02U/kg). For the FullSample-IM-FSIGT, S I was calculated based on the glucose and insulin samples taken at -1, 1, 2, 3, 4, 5,6,7,8,10,12,14,16,19, 22, 23, 24, 25, 27, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, 180. For the Reduced-Sample-FSIGT, S I was calculated based on the timepoints which appear in bold. Agreement was determined by Spearman correlation, concordance and the Bland-Altman method. In addition, for both protocols, the population was divided into tertiles of S I . Insulin resistance was defined by the lowest tertile of S I from the Full-Sample-IM-FSIGT. The distribution of subjects across tertiles was compared by rank order and kappa statistic. We found that the rate of failure of resolution of S I by the Reduced-Sample-IM-FSIGT was 3%(3/100). For the remaining 97 subjects, S I for the Full and Reduced-Sample-IM-FSIGT were: 3.76±2.41 L.mU -1 .min -1 , range 0.58-14.50 and 4.29±2.89 L.mU -1 .min -1 , range 0.52-14.42, relative error 21±18%, Spearman r=0.97, concordance 0.94, (both P<0.001). After log transformation the Bland Altman limits of agreement were: -0.29 and 0.53. The exact agreement for distribution of the population in the insulin-resistant tertile versus the insulin-sensitive tertiles was 92%, kappa 0.82±0.06. Using the nonlinear regression approach and data from the Reduced-Sample-IM-FSIGT in subjects with a wide range of insulin Corresponding Author: Anne E. Sumner, MD, NIDDK, 9000 Rockville Pike, Bethesda, MD 20892-1612, Phone: 301-402-4240, FAX: 301-435-5873, e-mail: AnneS@intra.niddk.nih.gov. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it i...

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Differences Between the Tolbutamide-Boosted and the Insulin-Modified Minimal Model Protocols

Cited by 46 publications

References 27 publications

Ethnic Differences in the Relationship Between Insulin Sensitivity and Insulin Response

Ethnic Differences in the Relationship Between Insulin Sensitivity and Insulin Response

Evaluation of Insulin Sensitivity in Clinical Practice and in Research Settings

Validity of the reduced-sample insulin modified frequently-sampled intravenous glucose tolerance test using the nonlinear regression approach

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