Weight Loss Improves β-Cell Function in People With Severe Obesity and Impaired Fasting Glucose: A Window of Opportunity

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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The increase in serum 25-hydroxyvitamin D following weight loss does not contribute to the improvement in insulin sensitivity, insulin secretion and β-cell function

British Journal Of Nutrition ◽

10.1017/s0007114515001610 ◽

2015 ◽

Vol 114 (2) ◽

pp. 161-168 ◽

Cited By ~ 3

Author(s):

Véronique Thibault ◽

Anne-Sophie Morisset ◽

Christine Brown ◽

André C. Carpentier ◽

Jean-Patrice Baillargeon ◽

...

Keyword(s):

Weight Loss ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Cell Function ◽

Disposition Index ◽

Model Assessment ◽

Β Cell ◽

Hydroxyvitamin D ◽

Β Cell Function ◽

25 Hydroxyvitamin D

Serum 25-hydroxyvitamin D (25(OH)D) concentrations have been reported to increase following weight loss. Moreover, both weight loss and higher serum 25(OH)D concentrations have been associated with a lower risk of developing type 2 diabetes. The objective of the present study was to determine whether the increase in serum 25(OH)D concentration following weight loss is associated with improved insulin sensitivity, insulin secretion and disposition index (β-cell function). Data from two prospective lifestyle modification studies had been combined. Following a lifestyle-modifying weight loss intervention for 1 year, eighty-four men and women with prediabetes and a BMI ≥ 27 kg/m2 were divided based on weight loss at 1 year: < 5 % (non-responders, n 56) and ≥ 5 % (responders, n 28). The association between the change in serum 25(OH)D concentration and changes in insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA%S) and Matsuda), insulin secretion (AUC of C-peptide) and disposition index after adjustment for weight loss was examined. Participants in the responders' group lost on average 9·5 % of their weight when compared with non-responders who lost only 0·8 % of weight. Weight loss in responders resulted in improved insulin sensitivity (HOMA%S, P= 0·0003) and disposition index (P= 0·02); however, insulin secretion remained unchanged. The rise in serum 25(OH)D concentration following weight loss in responders was significantly higher than that in non-responders (8·9 (sd 12·5) v. 3·6 (sd 10·7) nmol/l, P= 0·05). However, it had not been associated with amelioration of insulin sensitivity and β-cell function, even after adjustment for weight loss and several confounders. In conclusion, the increase in serum 25(OH)D concentration following weight loss does not contribute to the improvement in insulin sensitivity or 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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Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00506.2014 ◽

2015 ◽

Vol 308 (6) ◽

pp. E535-E544 ◽

Cited By ~ 37

Author(s):

Christoffer Martinussen ◽

Kirstine N. Bojsen-Møller ◽

Carsten Dirksen ◽

Siv H. Jacobsen ◽

Nils B. Jørgensen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cell Function ◽

Β Cell ◽

Glucose Effectiveness ◽

Β Cell Function ◽

First Phase Insulin Secretion

Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study.

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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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Glucose metabolic disorder in Klinefelter syndrome: a retrospective analysis in a single Chinese hospital and literature review

BMC Endocrine Disorders ◽

10.1186/s12902-021-00893-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shixuan Liu ◽

Tao Yuan ◽

Shuoning Song ◽

Shi Chen ◽

Linjie Wang ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Literature Review ◽

Glucose Tolerance ◽

Cell Function ◽

Klinefelter Syndrome ◽

Oral Glucose ◽

Model Assessment ◽

Β Cell ◽

Β Cell Function

Abstract Background We aimed to investigate the clinical characteristics and islet β-cell function in patients with Klinefelter syndrome (KS) and hyperglycemia. Methods This is a retrospective study. In total, 22 patients diagnosed with KS were identified from the electronic medical record system, including 9 patients with hyperglycemia (total patients with hyperglycemia, THG-KS group) and 5 hyperglycemic KS patients with oral glucose tolerance test (OGTT) results (HG-KS group). An additional 5 subjects with hyperglycemia and 5 normal glucose tolerance (NGT) subjects matched based on body mass index were included as the HG group and NGT group, respectively. Data from clinical and laboratory examinations were collected. We further performed a literature review of KS and hyperglycemia. Results We found that KS patients developed abnormal glucose metabolism earlier in life than those without KS, and the median age was 17 years, ranging from 10 years to 19 years. Six of 17 (35.3%) patients were diagnosed with diabetes mellitus and 3 of 17 (17.6%) patients were diagnosed with prediabetes. Among 10 patients with both fasting blood glucose and insulin results recorded, there were 8 out of 17 (47.1%) KS patients had insulin resistance. The prevalence of hypertension and dyslipidemia was higher in patients with hyperglycemia and KS than in patients with NGT KS. Compared with the HG group, insulin sensitivity levels were lower in HG-KS group, whereas homeostasis model assessment of β-cell function levels (p = 0.047) were significantly, indicating higher insulin secretion levels in the HG-KS group. Conclusions KS patients develop hyperglycemia earlier in life than those without KS and show lower insulin sensitivity and higher insulin secretion. These patients also have a higher prevalence of other metabolic diseases and may have different frequencies of developing KS-related symptoms.

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Role of the Gut in the Temporal Changes of β-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission

10.2337/figshare.16989505 ◽

2021 ◽

Author(s):

Malini Prasad ◽

Victoria Mark ◽

Chanel Ligon ◽

Roxanne Dutia ◽

Nandini Nair ◽

...

Keyword(s):

Weight Loss ◽

Gastric Bypass ◽

Insulin Sensitivity ◽

Cell Function ◽

Diabetes Remission ◽

Oral Glucose ◽

Β Cell ◽

Remission Status ◽

Β Cell Function

Objective: The role of the gut in diabetes remission after gastric bypass (RYGB) is incompletely understood. We therefore assessed the temporal change in insulin secretory capacity after RYGB, using oral and intravenous (IV) glucose, in individuals with type 2 diabetes. Research Design and Methods: Longitudinal, prospective measures of β-cell function after oral glucose and IV graded glucose infusion in individuals with severe obesity and diabetes studied at 0, 3 (n=29), 12 (n=24) and 24 (n=20) months after RYGB. Data were collected between 2015 and 2019 in an academic clinical research center. Results: The decreases in body weight, fat mass, waist circumference and insulin resistance after surgery (all p<0.001 at 12 and 24 months), did not differ according to diabetes remission status. In contrast, both the magnitude and temporal changes in β-cell glucose sensitivity after oral glucose differed by remission status (p=0.04): greater (6.5 fold, p<0.01) and sustained in full remitters, moderate and not sustained past 12 months in partial remitters (3.3 fold, p<0.001), minimal in non-remitters (2.7 fold, p=ns). The improvement in β-cell function after IV glucose was not apparent until 12 months, significant only in full remitters, and only ~1/3 of that observed after oral glucose. Pre-intervention β-cell function and its change after surgery predicted remission; weight loss and insulin sensitivity did not. Conclusion: Our data show the time course of changes in β-cell function after RYGB. The improvement in β-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.

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The effects of aging on male mouse pancreatic β-cell function involve multiple events in the regulation of secretion: influence of insulin sensitivity

The Journals of Gerontology Series A ◽

10.1093/gerona/glab276 ◽

2021 ◽

Author(s):

Eva Tudurí ◽

Sergi Soriano ◽

Lucía Almagro ◽

Anabel García-Heredia ◽

Alex Rafacho ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Cell Function ◽

Aged Mouse ◽

Β Cells ◽

Β Cell ◽

Peripheral Insulin Sensitivity ◽

Increased Risk ◽

Β Cell Function ◽

Effects Of Aging

Abstract Aging is associated with a decline in peripheral insulin sensitivity and an increased risk of impaired glucose tolerance and type 2 diabetes. During conditions of reduced insulin sensitivity, pancreatic β-cells undergo adaptive responses to increase insulin secretion and maintain euglycemia. However, the existence and nature of β-cell adaptations and/or alterations during aging are still a matter of debate. In this study, we investigated the effects of aging on β-cell function from control (3-month-old) and aged (20-month-old) mice. Aged animals were further categorized in two groups: high insulin sensitive (aged-HIS) and low insulin sensitive (aged-LIS). Aged-LIS mice were hyperinsulinemic, glucose intolerant and displayed impaired glucose-stimulated insulin and C-peptide secretion, whereas aged-HIS animals showed characteristics in glucose homeostasis similar to controls. In isolated β-cells, we observed that glucose-induced inhibition of KATP channel activity was reduced with aging, particularly in the aged-LIS group. Glucose-induced islet NAD(P)H production was decreased in aged mice, suggesting impaired mitochondrial function. In contrast, voltage-gated Ca 2+ currents were higher in aged-LIS β-cells, and pancreatic islets of both aged groups displayed increased glucose-induced Ca 2+ signaling and augmented insulin secretion compared with controls. Morphological analysis of pancreas sections also revealed augmented β-cell mass with aging, especially in the aged-LIS group, as well as ultrastructural β-cell changes. Altogether, these findings indicate that aged mouse β-cells compensate for the aging-induced alterations in the stimulus-secretion coupling, particularly by adjusting their Ca 2+ influx to ensure insulin secretion. These results also suggest that decreased peripheral insulin sensitivity exacerbates the effects of aging on β-cells.

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