Glucose Utilization In Patients Research Articles

6: Effect of triple-modulator therapy on glucose utilization in patients with cystic fibrosis

6: Effect of triple-modulator therapy on glucose utilization in patients with cystic fibrosis

Modeling of insulin secretion and insulin mass balance during hemodialysis in patients with and without type 2 diabetes

BackgroundThe secretion, distribution, and elimination of insulin in response to a bolus of glucose injected during regular hemodialysis was modeled to quantify the intra-dialytic mass balance of glucose and insulin in patients without (D0) and with type 2 diabetes (D1). MethodsA two-compartment regional blood flow model with shared compartments and dynamics for glucose, insulin and c-peptide was used to identify parameters of insulin and c-peptide co-secretion, first- and second-pass hepatic insulin extraction, as well as insulin-independent and insulin-dependent glucose utilization. Experimental data from a previous study obtained in 21 D0 and 14 D1 were used to identify kinetic model parameters and the fractions of glucose and insulin removed by dialysis. ResultsModeled gains for insulin secretion (β1 = 0.015 vs. 0.084 L/min, β2 = 0.004 vs. 0.666 L) were lower in D1, resulting in a lower total insulin secretion (Mi = 6.40 vs. 38.0 nmol). Hepatic insulin extraction was high (Eihep = 0.558 vs. 0.638) and only slightly smaller in D1. The fraction of insulin removed by dialysis (Fid = 0.07 vs. 0.05) was small and comparable between D1 and D0. Modeled gains for insulin-dependent glucose uptake (γ = 0.38 vs. 1.34 L2/nmol/min) were lower whereas those for insulin-independent glucose uptake (λ = 0.14 vs. 0.067 L/min) were higher in D1. The fraction of glucose removed by dialysis (Fgd = 0.31 vs. 0.28) was higher in D1. ConclusionApart from expected differences in modeled secretion and glucose utilization in patients with and without diabetes an intravenous bolus of glucose causes only small differences in overall glucose and insulin balance during a typical hemodialysis treatment.

Clinical significance of quantitative assessment of glucose utilization in patients with ischemic cardiomyopathy

BackgroundThe aim of this study was to prospectively quantify the rate of myocardial glucose uptake (MRGlu) in myocardium with different perfusion-metabolism patterns and determine its prognostic value in patients with ischemic cardiomyopathy. Methods and Results79 patients with ischemic cardiomyopathy were prospectively enrolled for dynamic cardiac FDG PET, and then followed for at least 6 months. Perfusion-metabolism patterns were determined based on visual score analysis of 201Tl SPECT and FDG PET. MRGlu was analyzed using the Patlak kinetic model. The primary end-point was cardiovascular mortality. Significantly higher MRGlu was observed in viable compared with non-viable areas. Negative correlations were found between MRGlu in transmural match and a history of hyperlipidemia, statin usage, and triglyceride levels. Diabetic patients receiving dipeptidyl peptidase-4 inhibitors (DPP4i) had a significantly lower MRGlu in transmural match, mismatch, and reverse mismatch. Patients with MRGlu in transmural match ≥ 23.40 or reverse mismatch ≥ 36.90 had a worse outcome. ConclusionsMyocardial glucose utilization was influenced by substrates and medications, including statins and DPP4i. MRGlu could discriminate between viable and non-viable myocardium, and MRGlu in transmural match and reverse mismatch may be prognostic predictors of cardiovascular death in patients with ischemic cardiomyopathy.

Collaborative Activities of Noradrenaline and Natriuretic Peptide for Glucose Utilization in Patients with Acute Coronary Syndrome

Glucose is an important preferential substrate for energy metabolism during acute coronary syndrome (ACS) attack, although insulin resistance (IR) increases during ACS. Increasing evidence indicates that natriuretic peptides (NP) regulate glucose homeostasis. We investigated possible compensatory actions of NP in collaboration with other neurohumoral factors that facilitate glucose utilization during ACS. The study population consisted of 1072 consecutive cases with ischemic heart disease who underwent cardiac catheterization (ACS, n = 216; non-ACS, n = 856). Among ACS subjects, biochemical data after acute-phase treatment were available in 91 cases, defined as ACS-remission phase (ACS-rem). Path models based on covariance structure analyses were proposed to clarify the direct contribution of B-type NP (BNP) and noradrenaline to glucose and HOMA-IR levels while eliminating confounding biases. In non-ACS and ACS-rem subjects, although noradrenaline slightly increased glucose and/or HOMA-IR levels (P < 0.03), BNP did not significantly affect them. In contrast, in ACS subjects, high noradrenaline was a significant cause of increases in glucose and HOMA-IR levels (P < 0.001), whereas high BNP was a significant cause of decreases in both parameters (P < 0.005). These findings indicate that BNP and noradrenaline coordinately activate glucose metabolism during ACS, with noradrenaline increasing glucose levels, as an energy substrate, while BNP improves IR and promotes glucose utilization.

GLUCOSE METABOLISM AS A THERAPEUTIC TARGET IN ALZHEIMER’S DISEASE

Reduced brain glucose metabolism is a consistent feature of Alzheimer's disease (AD), and predicts progression from amnestic mild cognitive impairment (aMCI) to AD dementia. Greater decreases in F18fluorodeoxyglucose uptake with positron emission tomography (FDG-PET) correlate with greater cognitive impairment along the continuum from normal cognitive status to aMCI to AD dementia. In spite of the tight linkage of glucose metabolism to brain function and the decline in AD, only a very limited number of studies have tried to understand why glucose utilization is diminished or tried to reverse this AD-related deficit. Thiamine-dependent enzymes are critical components of glucose metabolism and are reduced in brains of AD patients. Increasing thiamine in humans or animals increases glucose utilization, improves brain metabolism and cognition, including memory. The most effective way to increase blood and brain thiamine is with benfotiamine because of superior pharmacokinetics. Our aim is to test the effect of administering benfotiamine on brain glucose metabolism (FDG-PET) and clinical impact as measured by changes in Assessment Scale-Cognitive subscale (ADAS-Cog) over time in patients with aMCI or AD. A randomized, double-blind, placebo-controlled clinical trial with benfotiamine in patients with aMCI or mild AD was initiated. The primary objective is to determine whether increasing thiamine availability with benfotiamine can slow cognitive decline compared to placebo, as measured by a change in the ADAS Cog score over the twelve-month trial. The secondary objective is to test whether benfotiamine will slow the decline in glucose utilization in patients as measured by FDG-PET. Using blocked, stratified randomization, 76 patients will be assigned to the treatment or placebo group. Stratification is based on Mini Mental Status Exam score (>21) to better understand if treatment responses differ according to initial cognitive impairment. Of the 464 patients screened, 45 patients have been enrolled. Patient characteristics will be detailed in the poster. The trial will determine whether benfotiamine provides clinical or underlying biological benefit for aMCI/AD patients and if this correlates with changes in glucose utilization.

Short-term glucagon stimulation test of C-peptide effect on glucose utilization in patients with type 1 diabetes mellitus.

This work aimed to evaluate the use of a four-point glucagon stimulation test of C-peptide effect on glucose utilization in type 1 diabetic patients using a new mathematical model. A group of 32 type 1 diabetic patients and a group of 10 healthy control subjects underwent a four-point glucagon stimulation test with blood sampling at 0, 6, 15 and 30min after 1mg glucagon bolus intravenous administration. Pharmacokinetic and pharmacokinetic/pharmacodynamic models of C-peptide effect on glucose utilization versus area under curve (AUC) were used. A two-sample t test and ANOVA with Bonferroni correction were used to test the significance of differences between parameters. A significant difference between control and patient groups regarding the coefficient of whole-body glucose utilization and AUC C-peptide/AUC glucose ratio (p≪0.001 and p=0.002, respectively) was observed. The high correlation (r=0.97) between modeled coefficient of whole-body glucose utilization and numerically calculated AUC C-peptide/AUC glucose ratio related to entire cohort indicated the stability of used method. The short-term four-point glucagon stimulation test allows the numerically calculated AUC C-peptide/AUC glucose ratio and/or the coefficient of whole-body glucose utilization calculated from model to be used to diagnostically identify type 1 diabetic patients.

Myocardial Glucose Transport and Utilization in Patients With Type 2 Diabetes Mellitus, Left Ventricular Dysfunction, and Coronary Artery Disease

This research was designed to assess the effect of type 2 diabetes mellitus (T2DM) on myocardial glucose utilization in patients with heart failure secondary to coronary artery disease. Patients with T2DM and coronary artery disease have an increased morbidity and mortality compared with patients with coronary artery disease without diabetes that may relate to a reduction in the ability of the myocardium to utilize glucose. Myocardial blood flow and glucose utilization were assessed during a hyperinsulinemic clamp by 18F-flurodeoxyglucose and positron emission tomography in 54 patients (19 with T2DM) with multivessel coronary artery disease and heart failure. In a subgroup of 18 patients, myocardial biopsies were obtained during coronary bypass surgery to assess glucose transporter (GLUT4) distribution and protein concentration, and compared with myocardium from transplant donor hearts. Myocardial blood flow was similar in patients without diabetes and those with T2DM. Myocardial glucose utilization was lower in patients with T2DM (0.34 +/- 0.16 vs. 0.47 +/- 0.24 micromol x min(-1) x g(-1), p = 0.0002) despite comparable plasma insulin concentrations and a higher blood glucose concentration. Extraction of glucose by the myocardium was reduced in patients with T2DM (7.1 +/- 3.1% vs. 13.5 +/- 5.2%, p < 0.01). Myocardial GLUT4 protein was similar in patients with and without T2DM (p = 0.75). Patients with coronary artery disease and heart failure exhibit myocardial insulin resistance, and this is greater in those with T2DM. This may limit the ability of the myocardium in patients with T2DM to withstand ischemia and may contribute to the increased cardiovascular morbidity and mortality in such patients.

Changes in cerebral glucose utilization in patients with panic disorder treated with cognitive–behavioral therapy

Several neuroanatomical hypotheses of panic disorder have been proposed focusing on the significant role of the amygdala and PAG-related “panic neurocircuitry.” Although cognitive–behavioral therapy is effective in patients with panic disorder, its therapeutic mechanism of action in the brain remains unclear. The present study was performed to investigate regional brain glucose metabolic changes associated with successful completion of cognitive–behavioral therapy in panic disorder patients. The regional glucose utilization in patients with panic disorder was compared before and after cognitive–behavioral therapy using positron emission tomography with 18F-fluorodeoxyglucose. In 11 of 12 patients who showed improvement after cognitive–behavioral therapy, decreased glucose utilization was detected in the right hippocampus, left anterior cingulate, left cerebellum, and pons, whereas increased glucose utilization was seen in the bilateral medial prefrontal cortices. Significant correlations were found between the percent change relative to the pretreatment value of glucose utilization in the left medial prefrontal cortex and those of anxiety and agoraphobia-related subscale of the Panic Disorder Severity Scale, and between that of the midbrain and that of the number of panic attacks during the 4 weeks before each scan in all 12 patients. The completion of successful cognitive–behavioral therapy involved not only reduction of the baseline hyperactivity in several brain areas but also adaptive metabolic changes of the bilateral medial prefrontal cortices in panic disorder patients.

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Quantitative analysis of myocardial glucose utilization in patients with left ventricular dysfunction by means of 18F-FDG dynamic positron tomography and three-compartment analysis

Myocardial glucose utilization (MGU) is altered in various heart diseases. The aim of this study was to quantitatively assess regional myocardial glucose utilization in patients with left ventricular (LV) dysfunction by dynamic( 18)F-fluorodeoxyglucose positron emission tomography (FDG PET). A total of 18 subjects were studied, including ten with LV dysfunction (seven with idiopathic dilated cardiomyopathy and three with aortic regurgitation; NYHA II in 8 and III in 2) and eight healthy normal volunteers. Patients with diabetes mellitus were excluded. A dynamic PET study was performed for 40 min following the injection of 370 MBq of FDG after 50-g glucose loading. On the basis of a three-compartment model, MGU, K1, k2, and k3 were computed on a pixel by pixel basis to generate LV myocardial parametric maps. FDG standardized uptake value (SUV) was also calculated using static images obtained 40 min after FDG injection. These metabolic values were compared with myocardial flow distribution (%Flow), LVEF, LV volumes, and LV wall thickening (WT) determined by gated myocardial single-photon emission computed tomography using QGS software in eight myocardial segments. MGU correlated positively with LV volumes and negatively with LVEF. K(1) was significantly higher in the segments of the patients than in those of the normal volunteers (0.082+/-0.055 vs 0.041+/-0.017 ml min(-1) g(-1), p<0.05), although there was no difference in MGU between the groups. On the other hand, SUV, k2, and k3 did not differ significantly between the groups. Among the patients, the K1 values were significantly higher in the areas with impaired WT (%WT<17%) (0.109+/-0.063 vs 0.069+/-0.062 ml min(-1) g(-1), p<0.05) and in the areas with flow reduction (%Flow<71%) (0.112+/-0.076 vs 0.071+/-0.046 ml min(-1) g(-1), p<0.05). These results indicate that glucose utilization was preserved in the patients with LV dysfunction, mainly due to an increase in glucose transport, particularly in the regions with severely impaired LV function. Thus, the quantitative assessment of myocardial glucose utilization by FDG dynamic PET may provide useful information for assessing the regional myocardial metabolic status in patients with LV dysfunction.

Regional cerebral glucose utilization in patients with a range of severities of unipolar depression

Background: Patients with unipolar depression are most often reported to have decreased regional cerebral glucose metabolism (rCMRglu) in dorsal prefrontal and anterior cingulate cortices compared with healthy control subjects, often correlating inversely with severity of depression. Methods: We measured rCMRglu with fluorine-18 deoxyglucose positron emission tomography (PET) in 38 medication-free patients with unipolar depression and 37 healthy control subjects performing an auditory continuous performance task to further investigate potential prefrontal and anterior paralimbic rCMRglu abnormalities in patients attending to this task. Results: Compared with control subjects, the subgroup of patients with Hamilton depression scores of 22 or greater demonstrated decreased absolute rCMRglu in right prefrontal cortex and paralimbic/amygdala regions as well as bilaterally in the insula and temporoparietal cortex (right > left); they also exhibited increased normalized metabolic activity bilaterally in the cerebellum, lingula/cuneus, and brain stem. Severity of depression negatively correlated with absolute rCMRglu in almost the entire extent of the right cingulate cortex as well as bilaterally in prefrontal cortex, insula, basal ganglia, and temporoparietal cortex (right > left). Conclusions: Areas of frontal, cingulate, insula, and temporal cortex appear hypometabolic in association with different components of the severity and course of illness in treatment-resistant unipolar depression.

Relationship between visceral fat accumulation and anti-lipolytic action of insulin in patients with type 2 diabetes mellitus.

Insulin resistance is closely related to developing type 2 diabetes mellitus. Visceral fat accumulation is associated with insulin resistance, which affects the free fatty acid (FFA) metabolism. We investigated the interactions among visceral fat accumulation, FFA metabolism and insulin resistance in 20 patients with type 2 diabetes mellitus, including 11 obese and 9 non-obese subjects. Body fat distribution was estimated by measuring the areas of both subcutaneous and visceral fat mass on abdominal computed tomography at the umbilical level. Glucose infusion rate (GIR) and plasma FFA responses to insulin were determined as an index of insulin resistance and anti-lipolytic action, respectively, in a euglycemic hyperinsulinemic clamp study. There was an inverse correlation between GIR and insulin-induced decrease in plasma FFA in all diabetic patients (r = -0.652, P < 0.01). Visceral fat mass area was well correlated with GIR (r = -0.583, P < 0.01) and insulin-induced decrease in plasma FFA (r = 0.724, P < 0.001), whereas subcutaneous fat mass area was not correlated either with GIR or plasma FFA decrease. These findings suggest that visceral fat accumulation results in increasing the resistance against the anti-lipolytic action of insulin, and that FFA metabolism is closely related with glucose utilization in patients with type 2 diabetes mellitus.

Septal glucose utilization in patients with left bundle-branch block depends on severity of left anterior descending artery disease

Septal glucose utilization in patients with left bundle-branch block depends on severity of left anterior descending artery disease

Prostacyclin improves glucose utilization in patients with sepsis

Purpose: In patients with sepsis, impaired glucose metabolism and altered microcirculatory blood flow are common findings. Prostacyclin (PGI 2) improves tissue oxygenation, indicated by enhanced oxygen delivery (Do 2) and oxygen uptake (Vo2). The purpose of this study was to explore whether these effects are associated with improved glucose utilization. Methods: In 7 patients with sepsis, glucose metabolism was analyzed using dideuterated and 13C-labeled glucose and isotope dilution mass spectrometry. All patients received total parenteral nutrition with glucose covering 60% to 70% of the predicted energy expenditure and needed continuous intravenous insulin (40 μU · kg −1 · min −1) to keep blood glucose concentrations below 10 mmol · l −1. Vo2 and carbon dioxide production (Vco2) were continuously measured directly from the respiratory gases via indirect calorimetry. After equilibration of the infused labeled glucose with body glucose pool, baseline variables of glucose metabolism were assessed: glucose oxidation rate was determined from the enrichment of 13CO 2 in the expired gas during primed constant infusion of [U- 13C]glucose, glucose turnover rate (R a) from the plasma enrichment of simultaneously infused [6,6 2H 2]glucose. Endogenous glucose production rate was calculated as the difference between R a and glucose infusion rate. Then, we examined the effect of PGI 2 infusion (5 to 12.5 ng · kg −1 · min −1) on glucose metabolism and gaseous exchange. Results: The PGI 2-induced increase in DO 2 (from 15.8 to 17.7 ml · kg −1 - min −1; P < .05) resulted in an increase in directly measured Vo 2 from 5.0 to 5.3 ml · kg −1 min −1 ( P < .01) whereas Vco 2 remained unchanged. Although glucose turnover and production rates remained constant, glucose oxidation rate increased significantly from 1.21 to 1.38 mg · kg −1 · min −1 ( P < .02). Conclusions: Improving tissue perfusion and oxygenation with PGI 2 may also modify the impaired glucose metabolism by increasing glucose oxidation rate in patients with sepsis, suggesting enhanced adenosine triphosphate production.

Resting baseline topography of local cerebral glucose utilization in patients with schizophrenia

Resting baseline topography of local cerebral glucose utilization in patients with schizophrenia

Regional blood flow, oxidative metabolism, and glucose utilization in patients with recent myocardial infarction.

Metabolic imaging with positron emission tomography (PET) can detect tissue viability in clinical infarct regions. With appropriate tracer kinetic models and serial PET imaging, regional myocardial blood flow and rates of metabolism can now be quantified in patients with recent myocardial infarctions. Serial PET imaging with [13N]ammonia, [11C]acetate, and 18F-deoxyglucose was performed in 22 patients with recent infarctions to measure regional blood flow (in milliliters per gram per minute), glucose metabolism (in micromoles per gram per minute), and oxidative metabolism (in clearance rate per minute). Hypoperfused clinical infarct regions were classified as "PET mismatch" if 18F was increased relative to 13N activity or "PET match" if 13N and 18F activities were reduced concordantly. Blood flows differed significantly between normal, mismatch, and match segments (0.83 +/- 0.20, 0.57 +/- 0.20, and 0.32 +/- 0.12 mL.g-1.min-1, respectively). The relation between oxidative metabolism and blood flow was piecewise linear and differed significantly between PET mismatch and PET match. Oxidative metabolism was less severely reduced than blood flow in mismatch regions but but reduced in proportion to blood flow in match regions. There was considerable overlap of blood flows between both types of PET segments. Quantification of regional blood flow and substrate metabolism in postinfarction patients revealed alterations in the relation between substrate delivery and consumption demonstrated previously only in invasive animal experiments. The preserved oxidative metabolism in myocardium with PET mismatches may be ascribed to a regional increase in oxygen extraction. Such increase together with preserved glucose utilization may be the prerequisite for survival of ischemically injured myocardium.

Defective glucose utilization in patients with functioning beta-cell tumors persists after tumor excision.

Glucose utilization was assessed before and after operation in five patients with insulin-secreting tumors using the euglycemic clamp. Two groups of age, sex, and weight-matched controls were studied under conditions of either acute (3 h, N = 7) or chronic (48-72 h, N = 6) hyperinsulinemia (46 +/- 4 microU/mL). The rate of glucose infusion (M = mg/kg/min) required to maintain steady-state euglycemia was taken as index of glucose utilization. M was higher both in postoperative patients and in chronic controls than in preoperative patients (2.1 +/- 0.1 and 1.8 +/- 0.2 vs. 1.0 +/- 0.2, p less than 0.01), yet never achieved levels seen in acute controls (3.3 +/- 0.3, p less than 0.01). Also reported is one subject who had a predominantly proinsulin-producing tumor with little insulin secretion, who also manifested a similar defect in glucose utilization. Excision of this tumor resulted in partial reversal of the peripheral defect in glucose metabolism. In conclusion, chronic endogenous hyperinsulinemia (and hyperproinsulinemia) in humans is associated with a defect in peripheral glucose utilization that is only partially resolved 2 years after tumor removal.

Myocardial glutamate and alanine exchanges related to carbohydrate metabolism in patients with normal and stenotic coronary arteries.

Myocardial exchanges of glutamate, alanine, glucose, lactate, free fatty acids (FFA) and oxygen in resting state were determined in nine subjects (controls) without and in 28 patients with coronary artery disease (CAD). Patients with CAD showed increased myocardial glutamate uptake (2.51 +/- 0.60 mumol/min) and alanine release (1.25 +/- 0.60 mumol/min) compared to controls (glutamate uptake: 1.66 +/- 0.79 mumol/min; alanine release: 0.63 +/- 0.41 mumol/min). Myocardial glucose and lactate uptake was augmented in CAD patients, whereas FFA arteriovenous differences were decreased in patients with three-vessel-disease. The amount of glutamate taken up by the heart correlated positively to lactate uptake in all subjects (r = 0.84) and to external glucose utilization in patients with CAD (r = 0.72). Myocardial alanine release was positively related to glucose and lactate uptake in controls and in patients with only moderate CAD (one-vessel-disease). Glucose and FFA uptake correlated inversely in controls (r = 0.84), but not in CAD patients. A tight relation between exchanges of glutamate/alanine and carbohydrate metabolism in human heart is demonstrated. The data suggest altered myocardial substrate exchange towards augmented carbohydrate utilization in CAD patients in resting state. The results agree with in vitro and animal studies suggesting extraction of glutamate from the circulation to be of importance for maintaining carbohydrate consumption in chronic ischaemic heart disease.