Glucose (GL) Appearance in Impaired Glucose Tolerance (IGT) from a 75 G Oral Glucose Tolerance Test (GTT) Is Similar to That in Overt Diabetes and Is an Additional Reason for Hyperglycemia in (IGT) Patients

Presentation Number: MON 625
Date of Presentation: April 3rd, 2017

John Stephens Melish*
John A. Burns School of Medicine, University of Hawaii at Manoa, Kailua, HI


Carbohydrate counting (CC) is the basis for teaching insulin administration to patients with diabetes mellitus. However, to create an effective GL: insulin ratio, CC requires expertise, time, practice, and extra data resources. Studies show well-instructed diabetic patients performed poorly in CC. This study uses quantitative pharmacokinetic estimates of GL appearance using frequently sampled glucose tolerance data as an alternative way to determine CC and insulin need.. This method quantitates extracellular GL appearance for both mainly CHO diets by determining a GL volume of distribution (Vd). This may be estimated from population data or from patient specific data such as kilogram body weight, hematocrit, and the general estimate of extracellular fluid volume (200 mL/kg body weight). GL appearance (Ka, milligrams/dL) can be estimated from the peak GL concentration and the baseline concentration multiplied by "e" and "e-1", respectively. Subtracting the latter from the former concentration value and multiplying by Vd = GL appearance (mg). This novel methodology was applied to data presented by Varghese, et al (JCEM 2016) who studied volunteers with normal or impaired glucose tolerance. Baseline and peak glucose values were obtained from frequently monitored 2 hour 75 g glucose tolerance data. With an estimated hematocrit of 35% the Vd was determined to be 18.25% of kilogram body weight (79 kg normal; 84 kg prediabetic). Only 78 % of the glucose ingested by normal patients could be accounted for in the Vd whereas 97% appeared in the pre-diabetic patients. When applied to a separate study by Wolpert, et al., Type 1 patients on a high CHO low fat, low protein diet exhibited the same phenomenon with nearly 100% of the ingested available glucose appearing in the Vd. This extends the suggestion by Cobelli, et al. that in diabetics, there is little or no first pass hepatic GL uptake; the majority of available GL appears in the extracellular space. This present analysis shows the same phenomenon in patients with IGT as compared to normal. This simple calculation works nicely and reproducibly when available carbohydrate is administered alone. A more complex additional calculation must be used when mixed diets of protein and/or fat are added to CHO. Varghese used radioisotope techniques to determine that gluconeogenesis and glycogenolysis were within normal limits in both groups. Elevated prediabetic glucose combined curves were explained by reduced GL disposal. This present analysis uniquely demonstrates 1) first pass hepatic GL uptake is minimal in prediabetic as well as diabetic patients as an additional contribution to elevated postprandial letter GL values. 2) an alternative method to CC for assessing insulin need. 3) further calculation is needed to assess glucose appearance from mixed diets.


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