Early insulin sensitivity after restrictive bariatric surgery, inconsistency between HOMA-IR and steady-state plasma glucose levels

Glucose is the primary fuel for brain function, and determining the kinetics of cerebral glucose transport and utilization is critical for quantifying cerebral energy metabolism. The kinetic parameters of cerebral glucose transport, K M t and Vmax t, in humans have so far been obtained by measuring steady-state brain glucose levels by proton (1H) NMR as a function of plasma glucose levels and fitting steady-state models to these data. Extraction of the kinetic parameters for cerebral glucose transport necessitated assuming a constant cerebral metabolic rate of glucose ( CMR glc) obtained from other tracer studies, such as 13C NMR. Here we present new methodology to simultaneously obtain kinetic parameters for glucose transport and utilization in the human brain by fitting both dynamic and steady-state 1H NMR data with a reversible, non-steady-state Michaelis-Menten model. Dynamic data were obtained by measuring brain and plasma glucose time courses during glucose infusions to raise and maintain plasma concentration at ∼17 mmol/l for ∼2 h in five healthy volunteers. Steady-state brain vs. plasma glucose concentrations were taken from literature and the steady-state portions of data from the five volunteers. In addition to providing simultaneous measurements of glucose transport and utilization and obviating assumptions for constant CMR glc, this methodology does not necessitate infusions of expensive or radioactive tracers. Using this new methodology, we found that the maximum transport capacity for glucose through the blood-brain barrier was nearly twofold higher than maximum cerebral glucose utilization. The glucose transport and utilization parameters were consistent with previously published values for human brain.

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A defect in insulin release in women at risk of future non-insulin-dependent diabetes

Clinical Science ◽

10.1042/cs0810195 ◽

1991 ◽

Vol 81 (2) ◽

pp. 195-199 ◽

Cited By ~ 18

Author(s):

Anne Dornhorst ◽

Simon G. M. Edwards ◽

Jonathan S. D. Nicholls ◽

Victor Anyaoku ◽

Duncan Mclaren ◽

...

Keyword(s):

Insulin Sensitivity ◽

Gestational Diabetes ◽

Plasma Glucose ◽

Fasting Glucose ◽

Glucose Production ◽

Tolerance Test ◽

Oral Glucose ◽

Glucose Levels ◽

Control Subjects ◽

Previous Gestational Diabetes

1. A study on seven Caucasian glucose-tolerant women with previous gestational diabetes and seven matched control subjects is presented. The insulin response to oral glucose, insulin sensitivity and fasting glucose production rates were measured by using a 75 g oral glucose tolerance test, an insulin tolerance test and a non-radioactive tracer, [6,6-2H]glucose, respectively. 2. Fasting plasma glucose levels were similar between the women with previous gestational diabetes and the control subjects (4.8 ± 0.3 versus 4.7 ± 0.2 mmol/l), as were fasting plasma insulin levels (median 4 m-units/l, range 1–13 m-units/l versus median 4 m-units/l, range 1–24 m-units/l). After oral glucose the 60 min plasma glucose levels in the women with previous gestational diabetes were significantly higher (8.5 ± 0.6 versus 6.7 ± 0.8 mmol/l, P < 0.05), whereas the plasma insulin level was significantly lower at both 30 min (median 23 m-units/l, range 4–47 m-units/l versus median 55 m-units/l, range 23–100 m-units/l, P < 0.02) and at 60 min (median 23 m-units/l, range 4–43 m-units/l versus median 60 m-units/l, range 16–126 m-units/l, P< 0.02). 3. Insulin sensitivity, expressed as the slope of the regression line of plasma glucose level against time after intravenous infusion of insulin (0.05 unit/kg), was similar in the women with previous gestational diabetes and the control subjects (mean slope, −0.17 ± 0.01 versus −0.17 ± 0.01). 4. Fasting glucose production rates were similar in the women with previous gestational diabetes and the control subjects (2.2 ± 0.3 versus 1.9 ± 0.1 mg min−1 kg−1). 5. Women with previous gestational diabetes, a group at risk of future non-insulin-dependent diabetes, have abnormalities of insulin release at a time when insulin sensitivity and fasting glucose production are normal.

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Counterregulatory hormones oscillate during steady-state hypoglycemia

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1998.275.5.e821 ◽

1998 ◽

Vol 275 (5) ◽

pp. E821-E829 ◽

Cited By ~ 2

Author(s):

Pauline Genter ◽

Nancy Berman ◽

Mary Jacob ◽

Eli Ipp

Keyword(s):

Steady State ◽

Plasma Glucose ◽

Cardiovascular Responses ◽

Large Magnitude ◽

Counterregulatory Hormones ◽

Glucose Levels ◽

Clinical Observations ◽

Serial Blood Sampling ◽

The Mean ◽

Glucose Reduction

During hypoglycemia, the magnitude of the counterregulatory response depends on the extent of plasma glucose reduction. However, our clinical observations during steady-state hypoglycemia indicate that symptom severity can change independently of plasma glucose concentrations, i.e., symptoms appeared to fluctuate despite stable glucose levels. This study was therefore designed to test the hypothesis that hormonal and symptomatic responses to hypoglycemia are pulsatile. Seven healthy subjects had serial blood sampling at 3-min intervals during 90 min of insulin-induced hypoglycemia. Mean ± SE plasma glucose levels plateaued at 62 ± 3 mg/dl. Counterregulatory hormones were significantly elevated ( P < 0.05–0.01, except norepinephrine) and strikingly pulsatile. Cluster analysis revealed pulses of large magnitude in plasma glucagon, epinephrine, and norepinephrine concentrations. Amplitudes were, respectively, 72 ± 4, 64 ± 8, and 48 ± 3% of the mean. Interpeak intervals were 27 ± 7, 19 ± 4, and 25 ± 5 min, respectively. Symptom score and cardiovascular responses were also pulsatile; their peaks were found to coincide with epinephrine peaks. We conclude that hormonal and symptomatic counterregulation in hypoglycemia, while critically driven by plasma glucose levels, is also influenced by an endogenous pulsatility that exists despite steady-state glucose concentrations.

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Design of FitFor2 study: the effects of an exercise program on insulin sensitivity and plasma glucose levels in pregnant women at high risk for gestational diabetes

BMC Pregnancy and Childbirth ◽

10.1186/1471-2393-9-1 ◽

2009 ◽

Vol 9 (1) ◽

Cited By ~ 54

Author(s):

Nicolette Oostdam ◽

Mireille NM van Poppel ◽

Elisabeth MW Eekhoff ◽

Maurice GAJ Wouters ◽

Willem van Mechelen

Keyword(s):

Insulin Sensitivity ◽

High Risk ◽

Gestational Diabetes ◽

Pregnant Women ◽

Plasma Glucose ◽

Exercise Program ◽

Glucose Levels

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NMR Determination of Intracerebral Glucose Concentration and Transport Kinetics in Rat Brain

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1992.62 ◽

1992 ◽

Vol 12 (3) ◽

pp. 448-455 ◽

Cited By ~ 82

Author(s):

Graeme F. Mason ◽

Kevin L. Behar ◽

Douglas L. Rothman ◽

Robert G. Shulman

Keyword(s):

Steady State ◽

Plasma Glucose ◽

Glucose Concentration ◽

Goodness Of Fit ◽

Glucose Consumption ◽

Plasma Glucose Concentration ◽

Transport Parameters ◽

Glucose Levels ◽

Normal Glucose ◽

Wet Weight

The concentration of intracerebral glucose as a function of plasma glucose concentration was measured in rats by 13C NMR spectroscopy. Measurements were made in 20–60 min periods during the infusion of [1-13C]d-glucose, when intracerebral and plasma glucose levels were at steady state. Intracerebral glucose was found to vary from 0.7 to 19 μmol g−1 wet weight as the steady-state plasma glucose concentration was varied from 3 to 62 m M. A symmetric Michaelis–Menten model was fit to the brain and plasma glucose data with and without an unsaturable component, yielding the transport parameters Km, Vmax, and Kd. If it is assumed that all transport is saturable ( Kd = 0), then Km = 13.9 ± 2.7 m M and Vmax/ Vgly = 5.8 ± 0.8, where Vgly is the rate of brain glucose consumption. If an unsaturable component of transport is included, the transport parameters are Km = 9.2 ± 4.7 m M, Vmax/ Vgly = 5.3 ± 1.5, and Kd/ Vgly = 0.0088 ± 0.0075 ml μmol−1. It was not possible to distinguish between the cases of Kd = 0 and Kd > 0, because the goodness of fit was similar for both. However, the results in both cases indicate that the unidirectional rate of glucose influx exceeds the glycolytic rate in the basal state by 2.4-fold and as a result should not be rate limiting for normal glucose utilization.

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Weight Reduction Increases Plasma Levels of an Adipose-Derived Anti-Inflammatory Protein, Adiponectin

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.8.7741 ◽

2001 ◽

Vol 86 (8) ◽

pp. 3815-3819 ◽

Cited By ~ 488

Author(s):

Wei-Shiung Yang ◽

Wei-Jei Lee ◽

Tohru Funahashi ◽

Sachiyo Tanaka ◽

Yuji Matsuzawa ◽

...

Keyword(s):

Body Mass Index ◽

Body Weight ◽

Steady State ◽

Body Mass ◽

Plasma Glucose ◽

Weight Reduction ◽

Plasma Levels ◽

Plasma Adiponectin ◽

Body Weight Reduction ◽

Glucose Levels

Adiponectin, an adipose tissue-specific plasma protein, was recently revealed to have anti-inflammatory effects on the cellular components of vascular wall. Its plasma levels were significantly lower in men than in women and lower in human subjects with obesity, type 2 diabetes mellitus, or coronary artery disease. Therefore, it may provide a biological link between obesity and obesity-related disorders such as atherosclerosis, against which it may confer protection. In this study, we observed the changes of plasma adiponectin levels with body weight reduction among 22 obese patients who received gastric partition surgery. A 46% increase of mean plasma adiponectin level was accompanied by a 21% reduction in mean body mass index. The change in plasma adiponectin levels was significantly correlated with the changes in body mass index (r = −0.5, P = 0.01), waist (r = −0.4, P = 0.04) and hip (r =− 0.6, P = 0.0007) circumferences, and steady state plasma glucose levels (r = −0.5, P = 0.04). In multivariate linear regression models, the increase in adiponectin as a dependent variable was significantly related to the decrease in hip circumference (β = −0.16, P = 0.028), after adjusting body mass index and waist circumference. The change in steady state plasma glucose levels as a dependent variable was related to the increase of adiponectin with a marginal significance (β =− 0.92, P = 0.053), after adjusting body mass index and waist and hip circumferences. In conclusion, body weight reduction increased the plasma levels of a protective adipocytokine, adiponectin. In addition, the increase in plasma adiponectin despite the reduction of the only tissue of its own synthesis suggests that the expression of adiponectin is under feedback inhibition in obesity.

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C-Peptide Suppression During Insulin Infusion in the Extremely Preterm Infant Is Associated With Insulin Sensitivity

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-02681 ◽

2019 ◽

Vol 104 (9) ◽

pp. 3902-3910

Author(s):

William Hellström ◽

Ingrid Hansen-Pupp ◽

Gunnel Hellgren ◽

Eva Engström ◽

Lennart Stigson ◽

...

Keyword(s):

Insulin Sensitivity ◽

Preterm Infants ◽

Plasma Glucose ◽

Insulin Infusion ◽

Exogenous Insulin ◽

Serum Concentrations ◽

C Peptide ◽

Glucose Levels ◽

Extremely Preterm ◽

Extremely Preterm Infants

Abstract Context Little is known about the individual response of glucose-regulating factors to administration of exogenous insulin infusion in extremely preterm infants. Objective To evaluate longitudinal serum concentrations of insulin, C-peptide, and plasma glucose levels in a high-frequency sampling regimen in extremely preterm infants treated with insulin because of hyperglycemia. Design Prospective longitudinal cohort study. Setting Two university hospitals in Sweden between December 2015 and September 2016. Patients and Intervention Serum samples were obtained from nine extremely preterm infants, gestational age between 22 (+3) and 26 (+5) weeks (+ days), with hyperglycemia (plasma-glucose >10 mmol/L) at the start of insulin infusion, at 12, 24, and every 24 hours thereafter during ongoing infusion, and 12, 24, and 72 hours after the end of insulin infusion. Main outcome measures Longitudinal serum concentrations of insulin and C-peptide and plasma glucose levels. Results During insulin infusion, the serum C-peptide concentrations decreased compared with at start of infusion (P = 0.036), and then increased after ending the infusion. Individual insulin sensitivity based on the nonfasting plasma glucose/insulin ratio at the start of insulin infusion correlated with the initial decrease in serum ΔC-peptide[after 12h] (P = 0.007) and the degree of lasting decrease in serum ΔC-peptide[after end of infusion] (P = 0.015). Conclusion Exogenous insulin infusion suppressed the C-peptide concentration to individually different degrees. In addition, the effect of insulin infusion on β cells may be linked to individual insulin sensitivity, where a low insulin sensitivity resulted in a more pronounced decrease in C-peptide during insulin infusion.

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