Relationship Between Hepatic Glucose Production and Fasting Plasma Glucose Concentration in Patients With NIDDM

Jeng, Chii; Sheu, Wayne H‐H; Fuh, Martin Mao-Tsu; Chen, Y-D. Ida; Reaven, Gerald M.

doi:10.2337/diab.43.12.1440

Cited by 96 publications

(64 citation statements)

References 21 publications

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“…This seems to preclude acute saturation effects of glucose concentrations on MCR in these diabetic patients, as might have been anticipated from the nonlinear relation between R d and C [29±31]. It is consistent, however, with previous estimates of the time course of MCR when they have been reported [3] and with the fact that very good priming of the tracer concentrations was possible in a similar group of patients [10,13,14]. This would only occur if k was constant in equation (7).…”

Section: Discussionsupporting

confidence: 77%

Production and metabolic clearance of glucose under basal conditions in Type II (non-insulin-dependent) diabetes mellitus

Radziuk

Pye

2001

Diabetologia

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The relative importance of glucose over-production and inadequate peripheral removal in the postabsorptive (fasting) hyperglycaemia of Type II (non-insulin dependent) diabetes mellitus has produced diverse estimates. Some studies show that a strong correlation exists between fasting glucose concentrations and its production over a wide range of glycaemia, suggesting a causative role for excessive glucose output in hyperglycaemia [1,8]. Other measurements, however, show almost no correlation between glucose production rates and concentrations [9±14], Diabetologia (2001) AbstractAims/hypothesis. The pathogenesis of fasting hyperglycaemia in Type II (non-insulin-dependent) diabetes mellitus has yet to be clarified. Rates of glucose production (R a ), utilization and metabolic clearance rate were therefore measured during an extended fast, in control subjects and in Type II diabetic patients. Methods. Nine subjects with newly-diagnosed or diettreated diabetes and seven control subjects matched for age and weight (BMI 36.0 2.4 and 35.3 3.1 kg/ m 2 respectively) underwent an overnight fast followed by a 10-h unprimed infusion of [6-3 H]glucose. Plasma tracer concentrations were fitted by a singlecompartment model. Results. The metabolic clearance rate was near-constant [61.7 + 2.4 ml/(min-m 2 )] in diabetic patients and [75.5 3.3 ml/(min-m 2 )] in control subjects (p < 0.05). It was correlated to the glucose concentrations both at t = 0 (r = ±0.752, p = 0.0008) and t = 10 h (r = ±0.675, p = 0.004). The calculated volume of distribution was 17.3 1.4 l (18.2 % weight, diabetes), 19.6 2.4 l (18.4 % weight, control). Glycaemia fell from 10.7 0.8 mmol/l to 6.5 0.3 mmol/l by 10 h (p < 0.05) in diabetes and from 5.6 0.6 to 4.8 0.1 mmol/l in control subjects (p < 0.05). The rate of glucose production decreased in parallel, from 563 33 to 363 23 mmol/(min-m 2 ) (p < 0.05) in diabetes from 419 20 to 347 32 mmol/(min-m 2 ) in control subjects. Initial R a was higher in diabetic patients than in control subjects (p < 0.05) and was highly correlated to glycaemia (r = 0.836, p = 0.0001). By 10 h, R a had converged in diabetic patients and control subjects and all correlation with glycaemia was lost (r = 0.0017, p = 0.95). Conclusions/interpretation. In relatively early diabetes, the more ªlabileº portion of fasting hyperglycaemia, which subsequently decreased, was closely related to the simultaneously decreasing R a . The 25 % increase in glucose concentrations which persisted as stabilized R a , resulted from about a 20 % lower metabolic clearance rate. [Diabetologia (2001) 44: 983± 991]

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Section: Discussionsupporting

confidence: 77%

Production and metabolic clearance of glucose under basal conditions in Type II (non-insulin-dependent) diabetes mellitus

Radziuk

Pye

2001

Diabetologia

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“…There appears to be a small increase above normal in the contribution of GNG in subjects with non-insulindependent diabetes mellitus (Wajmgot et al 1999). However, glucose production, while normal or near normal in mild hyperglycaemia (fasting plasma glucose concentrations 8-10 mM/l) increases with more acute hyperglycaemia (Hother-Nielsen & Beck-Nielsen, 1990;Jeng et al 1994).…”

Section: Heavy Watermentioning

confidence: 99%

Quantifying the contribution of gluconeogenesis to glucose production in fasted human subjects using stable isotopes

Landau

1999

Proc. Nutr. Soc.

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The contribution of gluconeogenesis to glucose production is estimated from the enrichment of the H bound to C-5 of glucose relative to either that bound to C-2 of glucose or the enrichment in body water on ingesting 2H2O in the fasted state. Contributions of all gluconeogenic substrates are included in the estimate and the limitation of an uncertain precursor enrichment removed. The half-life of 2H2O in body water precludes a repeat study for many weeks. Glycogen cycling could result in underestimation, but there is evidence that glycogen cycling does not occur in liver in the fasted state. Gluconeogenesis has been estimated by mass-isotopomer-distribution analyses, usually by administering 13C-labelled glycerol. Underestimates emphasize the major limitation of the method, i.e. the need to assume a single enrichment of the precursor pool. Estimates of gluconeogenesis from isotopomer distribution in arterial-blood glucose and lactate on infusing [U-13C6] glucose are unreliable, as a proportion of the glucose is formed from glycerol and from amino acids not converted to glucose via pyruvate. Loss of label in the Krebs cycle and relying on enrichment of arterial-blood lactate as a measure of hepatic pyruvate further add to the uncertainty. Estimates of the rate of gluconeogenesis by NMR are obtained by subtraction of the rate of glycogenolysis determined by NMR from the rate of glucose production. Estimates are then the mean rate for the period over which glycogen contents are measured. Technical considerations can limit the accuracy of analyses and result in overestimates.

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“…The role of an increased rate of EGP in the pre-diabetic state is controversial. In most studies, including the one on Pima Indians, enhanced EGP has been a relatively late event [3,6,7,8,9]. However, as EGP is extremely sensitive to insulin [10], normal rates of EGP in the face of fasting hyperinsulinaemia could be a sign of hepatic insensitivity to insulin.…”

Section: Introductionmentioning

confidence: 99%

Parallel manifestation of insulin resistance and beta cell decompensation is compatible with a common defect in Type 2 diabetes

et al. 2004

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Aims/hypothesis. The aim of the study was to evaluate the relationship between insulin sensitivity, beta cell function and glucose tolerance, and its dependence on variants in the newly identified Type 2 diabetes susceptibility gene, calpain-10 (CAPN10). Methods. We studied 203 men of the same age but with varying degrees of glucose tolerance. These men participated in (i) an oral glucose tolerance test, (ii) a euglycaemic clamp combined with indirect calorimetry and infusion of [3-3 H]-glucose and (iii) a stepwise assessment of acute insulin response to arginine (AIR) at three different glucose concentrations (fasting, 14 and 28 mmol/l).Results. There was a linear increase in NEFA levels (p<0.0005) and WHR (p<0.0005) and decrease in glucose uptake due to a reduction in glucose storage over the entire range of glucose tolerance (r=−0.404; p<0.005). No increase in endogenous glucose production (EGP) was seen until patients had manifest diabetes. However, when EGP was expressed relative to fasting insulin concentrations, there was a linear deterioration of basal hepatic insulin sensitivity (r= −0.514; p<0.005). The AIR followed a bell-shaped curve with an initial rise and subsequent decrease. However, AIR adjusted for insulin sensitivity (disposition index) showed a linear decrease with increasing glucose concentrations (r=−0.563; p<0.001) starting already in subjects with normal glucose tolerance. There was an inverse correlation between increase in WHR and NEFA and peripheral as well as hepatic insulin sensitivity. Subjects with the genotype combination of CAPN10 consisting of SNP44 TT and SNP43 GG genotypes had significantly lower insulin-stimulated glucose uptake than carriers of the other genotype combinations (5.3±0.4 vs 7.2±0.4 mg·ffm kg −1 min −1 ·mU·l −1 ; p<0.005). Conclusions/interpretation. We conclude that the prediabetic state is characterised by a similar linear deterioration of peripheral and hepatic insulin sensitivity as beta cell function and that variants in the CAPN10 gene modify this relationship. These findings are compatible with a common defect in muscle, liver and beta cells in the pathogenesis of Type 2 diabetes.

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Relationship Between Hepatic Glucose Production and Fasting Plasma Glucose Concentration in Patients With NIDDM

Cited by 96 publications

References 21 publications

Production and metabolic clearance of glucose under basal conditions in Type II (non-insulin-dependent) diabetes mellitus

Production and metabolic clearance of glucose under basal conditions in Type II (non-insulin-dependent) diabetes mellitus

Quantifying the contribution of gluconeogenesis to glucose production in fasted human subjects using stable isotopes

Parallel manifestation of insulin resistance and beta cell decompensation is compatible with a common defect in Type 2 diabetes

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