A higher-carbohydrate, lower-fat diet reduces fasting glucose concentration and improves β-cell function in individuals with impaired fasting glucose

Abstract Background In people with obesity, β-cell function may adapt to insulin resistance. We describe β-cell function in people with severe obesity and normal fasting glucose (NFG), impaired fasting glucose (IFG), and type 2 diabetes (T2DM), as assessed before, 3 to 6 months after, and 2 years after medical weight loss to describe its effects on insulin sensitivity, insulin secretion, and β-cell function. Methods Fifty-eight participants with body mass index (BMI) ≥ 35 kg/m2 (14 with NFG, 24 with IFG, and 20 with T2DM) and 13 normal weight participants with NFG underwent mixed meal tolerance tests to estimate insulin sensitivity (S[I]), insulin secretion (Φ), and β-cell function assessed as model-based Φ adjusted for S(I). All 58 obese participants were restudied at 3 to 6 months and 27 were restudied at 2 years. Results At 3 to 6 months, after a 20-kg weight loss and a decrease in BMI of 6 kg/m2, S(I) improved in all obese participants, Φ decreased in obese participants with NFG and IFG and tended to decrease in obese participants with T2DM, and β-cell function improved in obese participants with NFG and tended to improve in obese participants with IFG. At 2 years, β-cell function deteriorated in participants with NFG and T2DM but remained significantly better in participants with IFG compared to baseline. Conclusions Short-term weight loss improves β-cell function in participants with NFG and IFG, but β-cell function tends to deteriorate over 2 years. In participants with IFG, weight loss improves longer-term β-cell function relative to baseline and likely relative to no intervention, suggesting that obese people with IFG are a subpopulation whose β-cell function is most likely to benefit from weight loss.

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Inhibition of Renal Sodium–Glucose Cotransport With Empagliflozin Lowers Fasting Plasma Glucose and Improves β-Cell Function in Subjects With Impaired Fasting Glucose

Diabetes ◽

10.2337/db17-0055 ◽

2017 ◽

Vol 66 (9) ◽

pp. 2495-2502 ◽

Cited By ~ 8

Author(s):

Muhammad Abdul-Ghani ◽

Hussein Al Jobori ◽

Giuseppe Daniele ◽

John Adams ◽

Eugenio Cersosimo ◽

...

Keyword(s):

Impaired Fasting Glucose ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Cell Function ◽

Fasting Glucose ◽

Β Cell ◽

Fasting Plasma ◽

Β Cell Function ◽

Sodium Glucose Cotransport

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Impact of lack of suppression of glucagon on glucose tolerance in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1999.277.2.e283 ◽

1999 ◽

Vol 277 (2) ◽

pp. E283-E290 ◽

Cited By ~ 23

Author(s):

Pankaj Shah ◽

Ananda Basu ◽

Rita Basu ◽

Robert Rizza

Keyword(s):

Insulin Secretion ◽

Glucose Concentration ◽

Cell Function ◽

Hormone Secretion ◽

Glucose Production ◽

Glucagon Secretion ◽

Β Cell ◽

Β Cell Function ◽

Glucagon Suppression

People with type 2 diabetes have defects in both α- and β-cell function. To determine whether lack of suppression of glucagon causes hyperglycemia when insulin secretion is impaired but not when insulin secretion is intact, twenty nondiabetic subjects were studied on two occasions. On both occasions, a “prandial” glucose infusion was given over 5 h while endogenous hormone secretion was inhibited. Insulin was infused so as to mimic either a nondiabetic ( n = 10) or diabetic ( n = 10) postprandial profile. Glucagon was infused at a rate of 1.25 ng ⋅ kg−1 ⋅ min−1, beginning either at time zero to prevent a fall in glucagon (nonsuppressed study day) or at 2 h to create a transient fall in glucagon (suppressed study day). During the “diabetic” insulin profile, lack of glucagon suppression resulted in a marked increase ( P < 0.002) in both the peak glucose concentration (11.9 ± 0.4 vs. 8.9 ± 0.4 mmol/l) and the area above basal of glucose (927 ± 77 vs. 546 ± 112 mmol ⋅ l−1 ⋅ 6 h) because of impaired ( P < 0.001) suppression of glucose production. In contrast, during the “nondiabetic” insulin profile, lack of suppression of glucagon resulted in only a slight increase ( P< 0.02) in the peak glucose concentration (9.1 ± 0.4 vs. 8.4 ± 0.3 mmol/l) and the area above basal of glucose (654 ± 146 vs. 488 ± 118 mmol ⋅ l−1 ⋅ 6 h). Of interest, when glucagon was suppressed, glucose concentrations differed only minimally during the nondiabetic and diabetic insulin profiles. These data indicate that lack of suppression of glucagon can cause substantial hyperglycemia when insulin availability is limited, therefore implying that inhibitors of glucagon secretion and/or glucagon action are likely to be useful therapeutic agents in such individuals.

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Maternal Gestational Glucose Concentration Is Associated with Offspring Insulin Sensitivity and β-Cell Function in Children Aged 5-10 Years.

10.1210/endo-meetings.2010.part3.or2.or30-2 ◽

2010 ◽

pp. OR30-2-OR30-2

Author(s):

NC Bush ◽

PC Chandler-Laney ◽

WM Granger ◽

DJ Rouse ◽

BA Gower

Keyword(s):

Insulin Sensitivity ◽

Glucose Concentration ◽

Cell Function ◽

Β Cell ◽

Β Cell Function

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Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose

Clinical Science ◽

10.1042/cs20110284 ◽

2011 ◽

Vol 122 (4) ◽

pp. 193-202 ◽

Cited By ~ 19

Author(s):

Todd S. Perlstein ◽

Robert R. Henry ◽

Kieren J. Mather ◽

Michael R. Rickels ◽

Nicola I. Abate ◽

...

Keyword(s):

Insulin Sensitivity ◽

Endothelial Function ◽

Impaired Fasting Glucose ◽

Cell Function ◽

Fasting Glucose ◽

Post Treatment ◽

P Value ◽

Markers Of Inflammation ◽

Β Cell Function ◽

Pre Treatment

AngII (angiotensin II) may contribute to cardiovascular risk in obesity via adverse effects on insulin sensitivity and endothelial function. In the present study, we examined the effects of ARB (angiotensin receptor blocker) therapy (losartan, 100 mg/day) on insulin sensitivity and endothelial function in 53 subjects with stage I hypertension, abdominal obesity and impaired fasting glucose. The study design was a randomized double-blinded parallel design placebo-controlled multi-centre trial of 8 weeks duration. We used the hyperinsulinaemic–euglycaemic clamp technique to measure insulin sensitivity (expressed as the ‘M/I’ value) and RH-PAT (reactive hyperaemia-peripheral arterial tonometry) to measure endothelial function. Additional measures included HOMA (homoeostasis model assessment)-B, an index of pancreatic β-cell function, and markers of inflammation [e.g. CRP (C-reactive protein)] and oxidative stress (e.g. F2-isoprostanes). ARB therapy did not alter insulin sensitivity [5.2 (2.7) pre-treatment and 4.6 (1.6) post-treatment] compared with placebo therapy [6.1 (2.9) pre-treatment and 5.3 (2.7) post-treatment; P value not significant], but did improve the HOMA-B compared with placebo therapy (P=0.05). ARB therapy also did not change endothelial function [RH-PAT, 2.15 (0.7) pre-treatment and 2.11 (0.7) post-treatment] compared with placebo therapy [RH-PAT, 1.81 (0.5) pre-treatment and 1.76 (0.7) post-treatment; P value not significant]. Markers of inflammation and oxidative stress were not significantly changed by ARB therapy. In conclusion, ARB therapy did not alter peripheral insulin sensitivity or endothelial function in this cohort of patients with essential hypertension, abdominal obesity and impaired fasting glucose, but did improve pancreatic β-cell function.

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The Influence of the Levonorgestrel-Releassing Intrauterine System (Lng Ius) on Metabolic Markers in Women with Normal Body Mass and Overweight Women

Acta Chirurgica Latviensis ◽

10.2478/chilat-2014-0006 ◽

2013 ◽

Vol 13 (2) ◽

pp. 27-32

Author(s):

Ineta Vasaraudze ◽

Dace Rezeberga ◽

Renars Erts ◽

Aivars Lejnieks

Keyword(s):

Insulin Sensitivity ◽

Body Mass ◽

Cell Function ◽

Fasting Glucose ◽

Density Lipoprotein ◽

Β Cell ◽

C Peptide ◽

Overweight Women ◽

Normal Body ◽

Β Cell Function

Abstract Introduction. In Latvia, the number of overweight women is increasing, while the rate of cardio vascular disease (CVD) is one of the highest in the European Union. The influence of hormonal contraception on the development of CVD has not been studied in Latvia so far. Aim of the study. A nonrandomized open-label prospective trial of healthy reproductive-age women desiring to use the LNG IUS. Materials and methods. Before starting the use of contraception and six months after starting the use of contraception, the homeostasis model assessment insulin resistant (HOMA-IR) score, insulin sensitivity (HOMA-%S) and β-cell function (HOMA-%B) were calculated using fasting glucose (FG) and C peptide values. There were also determined other cardio-metabolic parameters: total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride level, systolic and diastolic blood pressure, and abdominal circumference. Results. Thirty women were involved in the study: seventeen women with a normal body-mass index (BMI) (BMI below 25) and thirteen overweight women (BMI above 25). When using the LNG IUS, the fasting glucose level increased in women with normal body mass, the level of insulin sensitivity decreased in both study groups; C peptide level, β-cell function and insulin resistance increased in both groups, but the changes were not statistically reliable (p>0.05). Conclusion. Although during the study there were determined changes in the FG level, insulin sensitivity, C peptide, β-cell function and insulin resistance parameters, these changes are not clinically significant, and the LNG IUS may be safely used clinically both by women with normal body mass and overweight women.

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PANCREATIC β-CELL FUNCTION IN THE FETAL FOAL AND MARE

Journal of Endocrinology ◽

10.1677/joe.0.0870293 ◽

1980 ◽

Vol 87 (2) ◽

pp. 293-301 ◽

Cited By ~ 26

Author(s):

ABIGAIL L. FOWDEN ◽

R. J. BARNES ◽

R. S. COMLINE ◽

MARIAN SILVER

Keyword(s):

Gestational Age ◽

Glucose Concentration ◽

Cell Function ◽

Insulin Concentration ◽

Β Cell ◽

Exogenous Glucose ◽

Β Cell Function ◽

The Mean ◽

Mean Glucose ◽

Mean Concentration

Insulin secretion and the factors influencing β-cell function were investigated in the chronically catheterized fetal foal and mare during the second half of gestation. The response of the fetal β cells to exogenous glucose was also examined. The mean concentration of insulin in the fetal foal was 7·5 ± 0·5 (s.e.m.) μu./ml (n = 20) which was significantly less than the corresponding maternal value of 49·0 ± 5·0μu./ml (n = 20, P<0·01). The insulin concentration in non-pregnant horses was 24·5 ± 1·5 μu./ml (n = 5) which was significantly less than the value in the pregnant animals (P<0·01). However, there was no significant difference in the mean glucose concentration between the groups of adult animals. The insulin concentration was related to the endogenous glucose level in both adult and fetal horses. Wide variation in the maternal insulin concentration was observed above a glucose concentration of about 5·0 mmol/l. The mean concentration of insulin in pregnant mares decreased with increasing gestational age while the mean glucose concentration remained unaltered throughout the second half of gestation. There was no change in the basal concentrations of insulin or glucose in the fetus with gestational age although the fetal β-cell response to exogenous glucose appeared to increase with increasing fetal age after 270 days of gestation (term 330 days). There was a significant arterio-venous difference in the concentration of insulin across the gravid uterus in the mare when the arterial insulin level was greater than 30 μu./ml. Below this value, there was no consistent uptake of insulin by the uterus. The observations are discussed in relation to the regulation of insulin release in utero and the effects of pregnancy on maternal β-cell function.

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