scholarly journals Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome: effects on beta-cell function and post-load glucose tolerance

2004 ◽  
pp. 39-45 ◽  
Author(s):  
K Yuen ◽  
N Wareham ◽  
J Frystyk ◽  
S Hennings ◽  
J Mitchell ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Low Dose ◽  
Cell Function ◽  
Oral Glucose ◽  
Fasting Insulin ◽  
Short Term ◽  
The Metabolic Syndrome ◽  
Igf I

OBJECTIVE: Modest elevations in circulating IGF-I levels have been suggested to protect against the development of glucose intolerance in insulin-resistant subjects. To further understand the interactions of GH and IGF-I on beta-cell function and post-load glucose tolerance in glucose-intolerant subjects predisposed to diabetes, we performed a pilot study in 12 subjects with impaired glucose tolerance and the metabolic syndrome using a low GH dose (1.7 microg/kg per day) known to increase endogenous IGF-I production. DESIGN: Fourteen daily GH or placebo injections in a double-blind cross-over study. METHODS: Baseline and post-treatment oral glucose tolerance tests were performed. The homeostasis model assessment and the insulinogenic index was used to estimate fasting insulin sensitivity (S(I)) and beta-cell function respectively, whereas changes in the incremental area under the curve were used to estimate post-load glucose tolerance (DeltaAUC(glu)) and post-load insulin levels (DeltaAUC(ins)). RESULTS: GH increased total IGF-I (P<0.02), free IGF-I (P<0.04) and fasting insulin (P<0.04) levels, but did not modify plasma IGF-binding proteins (IGFBPs)-1 and -3, fasting glucose, non-esterified fatty acid and C-peptide levels, and fasting S(I). After oral glucose intake, glucose tolerance improved (P<0.03), but post-load insulin levels and beta-cell function remained unchanged. CONCLUSION: Short-term low-dose GH administration induced fasting hyperinsulinaemia possibly by reducing insulin clearance but improved post-load glucose tolerance, suggesting that increased bioavailable IGF-I enhanced post-load S(I) without altering beta-cell function. Longer-term studies are required to ascertain whether these positive effects on post-load glucose tolerance and the preservation of beta-cell function can be sustained by this GH dose in these high-risk subjects.

scholarly journals Advancing Dinner Timing Is an Effective Strategy in Improving Glucose Tolerance in Free-Living Adults: A Randomized Cross-Over Trial

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 585-585
Author(s):  
Hassan Dashti ◽  
Jesus Lopez ◽  
Céline Vetter ◽  
Millán Pérez-Ayala ◽  
Juan Carlos Baraza ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Disease Risk ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Effective Strategy ◽  
Free Living

Abstract Objectives Eating at times that conflict with our physiology and coincide with the biological evening has been associated with increased disease risk. In free-living adults from the ONTIME-MT study (#NCT03036592) study, we tested the hypothesis that advancing the timing of dinner relative to bedtime, simulated by advancing an evening oral glucose tolerance test (OGTT), will result in improved glucose control. Methods In a randomized, cross-over study design, following an 8h fast, each participant underwent two evening 2-hour 75-gram oral OGTT: early and late (4h vs. 1h prior to habitual bedtime), simulating early and late dinner timing. Habitual bedtime was determined using one-week of electronic sleep logs via smartphone application. The OGTT order was randomized and separated by 1-week washout period. Light intensity was kept bright (≥450 lux) and dim (0–25 lux) in the early and late conditions, respectively. Melatonin was assessed at the start and end of each OGTT by radioimmunoassay. Postprandial glucose and insulin were determined using incremental area under the curve (AUC). Insulin sensitivity and beta-cell function were evaluated using standard metrices: insulin sensitivity index (ISI), corrected insulin response (CIR), and disposition index (DI). Values were compared using paired t-tests and differences were considered significant at P &lt; 0.05. Results A total of 750 participants (mean age = 37 ± 14; 70% female; mean BMI = 26.12 ± 5.66) underwent OGTTs in two evening timing conditions. As expected, melatonin levels were higher in the late vs. early condition (4.49 ± 4.15-fold lower in the early vs. late meal condition. In the early condition, there was an 8.68% lower AUC for glucose (P = .0001) and 4.4% higher insulin AUC (P = 0.059), relative to the late condition. In addition, the CIR was 16% (P = .0001) higher and the DI was higher by 20% (P = .014) in the early compared to the late condition. The ISI was similar in both conditions (P = 0.66). Conclusions In this large study, glucose tolerance was better during early vs. late evening OGTT. Better glucose tolerance was primarily attributed to improved insulin secretion and beta-cell function. These results indicate that for the general population, advancing dinner relative to bedtime may be a novel and an effective strategy to improve glucose tolerance. Funding Sources ONTIME-MT was funded by the NIH R01 grant R01DK105072.

scholarly journals The impact of low dose gliclazide on the incretin effect and indices of beta cell function

2021 ◽  
Author(s):  
Ruth L M Cordiner ◽  
Andrea Mari ◽  
Andrea Tura ◽  
Ewan R Pearson
Keyword(s):  
Beta Cell ◽  
Beta Cell Function ◽  
Low Dose ◽  
Cell Function ◽  
Late Phase ◽  
Oral Glucose ◽  
Incretin Effect ◽  
Lower Blood ◽  
Glucose Sensitivity ◽  
The Impact

Abstract Aims/Hypothesis Studies in permanent neonatal diabetes suggest that sulphonylureas lower blood glucose without causing hypoglycaemia, in part by augmenting the incretin effect. This mechanism has not previously been attributed to sulphonylureas in patients with type 2 diabetes (T2DM). We therefore aimed to evaluate the impact of low dose gliclazide on beta-cell function and incretin action in patients with T2DM. Methods Paired oral glucose tolerance tests and isoglycaemic infusions were performed to evaluate the difference in the classical incretin effect in the presence and absence of low dose gliclazide in 16 subjects with T2DM (HbA1c &lt;64mmol/mol, 8.0%) treated with diet or metformin monotherapy. Beta-cell function modelling was undertaken to describe the relationship between insulin secretion and glucose concentration. Results A single dose of 20mg gliclazide reduced mean glucose during the OGTT from 12.01 ± 0.56 to 10.82 ± 0.5 mmol/l (p=0.0006) (mean ± SEM). The classical incretin effect was augmented by 20mg gliclazide, from 35.5% (LQ 27.3, UQ 61.2) to 54.99% (34.8, 72.8) (p=0.049). Gliclazide increased beta-cell glucose sensitivity by 46% (Control 22.61 ± 3.94, Gliclazide 33.11 ± 7.83 (p=0.01)) as well as late-phase incretin potentiation (Control 0.92 ± 0.05, Gliclazide 1.285 ± 0.14 (p=0.038). Conclusions/Interpretation Low dose gliclazide reduces plasma glucose in response to oral glucose load, with concomitant augmentation of the classical incretin effect. Beta-cell modelling shows that low plasma concentrations of gliclazide potentiate late phase insulin secretion and increase glucose sensitivity by 50%. Further studies are merited to explore whether low dose gliclazide, by enhancing incretin action, could effectively lower blood glucose without risk of hypoglycaemia.

scholarly journals Metabolic characteristics of Africans with normal glucose tolerance and elevated 1-hour glucose: insight from the Africans in America study

2020 ◽  
Vol 8 (1) ◽  
pp. e000837 ◽  
Author(s):  
Sara M Briker ◽  
Thomas Hormenu ◽  
Christopher W DuBose ◽  
Lilian S Mabundo ◽  
Stephanie T Chung ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Normal Glucose Tolerance ◽  
Lipid Profiles ◽  
Oral Glucose ◽  
Normal Glucose ◽  
Glucose Threshold

IntroductionRisk of insulin resistance, dyslipidemia, diabetes and cardiac death is increased in Asians and Europeans with normal glucose tolerance (NGT) and 1-hour glucose ≥8.6 mmol/L. As African descent populations often have insulin resistance but a normal lipid profile, the implications for Africans with NGT and glucose ≥8.6 mmol/L (NGT-1-hour-high) are unknown.ObjectiveWe performed oral glucose tolerance tests (OGTTs) in 434 African born-blacks living in Washington, DC (male: 66%, age 38±10 years (mean±SD)) and determined in the NGT group if either glucometabolic or lipid profiles varied according to a 1-hour-glucose threshold of 8.6 mmol/L.MethodsGlucose tolerance category was defined by OGTT criteria. NGT was subdivided into NGT-1-hour-high (glucose ≥8.6 mmol/L) and NGT-1-hour-normal (glucose <8.6 mmol/L). Second OGTT were performed in 27% (119/434) of participants 10±7 days after the first. Matsuda Index and Oral Disposition Index measured insulin resistance and beta-cell function, respectively. Lipid profiles were obtained. Comparisons were by one-way analysis of variance with Bonferonni corrections for multiple comparisons. Duplicate tests were assessed by к-statistic.ResultsOne-hour-glucose ≥8.6 mmol/L occurred in 17% (47/272) with NGT, 72% (97/134) with pre-diabetes and in 96% (27/28) with diabetes. Both insulin resistance and beta-cell function were worse in NGT-1-hour-high than in NGT-1-hour-normal. Dyslipidemia occurred in both the diabetes and pre-diabetes groups but not in either NGT group. One-hour glucose concentration ≥8.6 mmol/L showed substantial agreement for the two OGTTs (к=0.628).ConclusionsAlthough dyslipidemia did not occur in either NGT group, insulin resistance and beta-cell compromise were worse in NGT-1 hour-high. Subdividing the NGT group at a 1-hour glucose threshold of 8.6 mmol/L may stratify risk for diabetes in Africans.

Oral Glucose Tolerance Test with Insulin Assay and the evaluation of Insulin Resistance and Impaired Beta-cell function in primary prevention for Type 2 Diabetes

2020 ◽  
pp. 1-7
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Glucose Tolerance Test ◽  
Cell Function ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance

Background: Insulin resistance and impaired beta-cell function are associated with type 2 diabetes mellitus (T2DM). Many insulin resistance and beta-cell function indices have been developed using the data from an oral glucose tolerance test (OGTT) with insulin assay. However, insulin assays are not widely used along with the OGTT in primary prevention outpatient clinics. We aimed to evaluate the association of having impaired fasting glucose (IFG), impaired glucose tolerance (IGT), isolated or combined, with insulin resistance and impaired beta-cell function in subjects at risk for T2DM. Methods: This is a cross-sectional study that included 376 subjects who underwent an OGTT who had at least two risk factors for T2DM without any chronic disease. Results: Participants were 51.6±8.2 years old, 71.8% were women, had a mean body mass index (BMI) of 30.1±6.5 kg/m2, 42.4% had obesity and 26.7% hypertension. A HOMA-IR ≥2.5 was independently associated with male sex, BMI>25kg/m2, and with isolatedIFG, isolated-IGT, or combined (p<0.05 for all). On the other hand, only overweight, but not obesity, was independently associated with impaired beta-cell function (disposition index <1.24). Additionally, combined IFG and IGT had 29.7 higher odds to have impaired beta-cell function compared with those that had a normal OGTT. Conclusions: IFG alone, IGT alone, or the presence of both, are associated with higher odds to have insulin resistance and impaired beta-cell function in asymptomatic subjects at risk for T2DM without any chronic disease. Further studies are needed to evaluate this associations with the risk to develop T2DM, cardiovascular events and mortality.

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