Basu et al Effects of Type 2 Diabetes on Insulin Secretion, Insulin Action, Glucose Effectiveness and Postprandial Glucose Metabolism

Table A1: Volunteer Characteristics at screening:

Diabetic / Non-diabetic
Age (yrs) / 57.3±3 / 53±4
Weight (kg) / 90±5 / 82±6
FFM (kg) / 54±3 / 47±5
BMI (kg/m2) / 31.2±2 / 29±2
% body fat (%) / 37±3 / 38±3
Total abdominal fat (cm2) / 429.3±52 / 343±67
Visceral fat (cm2) / 201.3±33* / 111.7±29
Fasting glucose (mM) / 8.2±0.4* / 5.3±0.2
HbA1c (%) / 6.8±0.3* / 5.5±0.1
Diabetes duration (yrs) / 6.5±1.2 / N/A
Diabetes therapy / 2 on diet; 7 metformin;
5 metformin + glipizide / N/A

BMI: Body Mass Index. FFM: Fat Free Mass. TAF: Total Abdominal Fat. VF: Visceral Fat; FPG: Fasting Plasma Glucose obtained during screening visit. * denotes significance with p<0.05 vs. non-diabetic subjects.

Calculation of Meal indices:

Indices of net insulin action (Si), glucose effectiveness (Sg) and of the ability of insulin (Si*) and glucose (Sg*) to stimulate glucose disposal were calculated using the oral minimal model as previously described (1-3). Estimation of Si in most individuals with type 2 diabetes, particularly in those who are very insulin resistant, is difficult due to poor precision. Since Sg is well estimated in all subjects, to improve numerical accuracy of the model we used the constraints Sg=(GEZI+SI Ib)/V (GEZI: glucose effectiveness at zero insulin; Ib: basal insulin concentration; V: volume), to link Si to Sg through parameter GEZI. In all these subjects, a Bayesian parameter estimation was employed by assuming GEZI to be normally distributed with mean=0.025 dl/kg/min and CV=10%. This value was the average of GEZI in those subjects in whom the model was successfully identified by weighted nonlinear least squares. However, the sensitivity of the estimates to the prior average was low, e.g. GEZI converged to very similar values using a mean estimate of 0.036, the average GEZI in normal subjects (2). A similar approach was used to estimate Si* (GEZI* was assumed to be normally distributed with mean=0.0125 dl/kg/min and CV=10%). Indices of insulin secretion including total (total response to the glycemic stimuli), dynamic (response to a change in glucose concentration), and static (response to a given glucose concentration) were calculated using the oral C-peptide secretion model as previously described (2). Disposition indices (DI) were calculated by multiplying indices of insulin secretion times indices of insulin action in order to determine whether insulin secretion was appropriate for the degree of insulin resistance.

References:

1. Basu R, Breda E, Oberg AL, Powell CC, Dalla Man C, Basu A, Vittone JL, Klee GG, Arora P, Jensen MD, Toffolo G, Cobelli C, Rizza RA: Mechanisms of the age-associated deterioration in glucose tolerance: contribution of alterations in insulin secretion, action, and clearance. Diabetes 52:1738-1748, 2003

2. Basu R, Dalla Man C, Campioni M, Basu A, Klee G, Toffolo G, Cobelli C, Rizza RA: Effects of age and sex on postprandial glucose metabolism: differences in glucose turnover, insulin secretion, insulin action, and hepatic insulin extraction. Diabetes 55:2001-2014, 2006

3. Dalla Man C, Caumo A, Basu R, Rizza R, Toffolo G, Cobelli C: Measurement of selective effect of insulin on glucose disposal from labeled glucose oral test minimal model. Am J Physiol Endocrinol Metab 289:E909-914, 2005