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Beta Cell Function as a Baseline Predictor of Weight Loss After Bariatric Surgery.
Borges-Canha, M, Neves, JS, Mendonça, F, Silva, MM, Costa, C, M Cabral, P, Guerreiro, V, Lourenço, R, Meira, P, Salazar, D, et al
Frontiers in endocrinology. 2021;:714173
Abstract
BACKGROUND Obesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain. AIM: To evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity. METHODS Retrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery). RESULTS There were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (β = -1.04 [-1.82 to -0.26], p<0.01; β = -1.16 [-2.13 to -0.19], p=0.02; β = -1.29 [-2.64 to 0.06], p=0.061, respectively). This was not observed in the first year post-surgery nor for the other indexes. Glycemia at baseline was positively associated to EWL% at second and third years post-surgery. CONCLUSION β-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice.
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Changes in adiposity mediate the associations of diet quality with insulin sensitivity and beta-cell function.
Lai, KZH, Semnani-Azad, Z, Retnakaran, R, Harris, SB, Hanley, AJ
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(11):3054-3063
Abstract
BACKGROUND AND AIMS To examine the mediating role of adiposity on the associations of diet quality with longitudinal changes in insulin sensitivity and beta-cell function. METHODS AND RESULTS Adults at-risk for type 2 diabetes (T2D) in the PROMISE cohort had 4 assessments over 9 years (n = 442). Alternate Healthy Eating Index (AHEI) scores were used to assess diet quality. Generalized Estimating Equations (GEE) evaluated the associations between the AHEI and longitudinal changes in insulin sensitivity (HOMA2-%S and ISI) and beta-cell function (IGI/HOMA-IR and ISSI-2). The proportion of the mediating effect of waist circumference changes was estimated using the difference method. In the primary longitudinal analysis, AHEI was positively associated with insulin sensitivity and beta-cell function over time (% difference per standard deviation increase of AHEI for HOMA2-%S (β = 11.0, 95%CI 5.43-17.0), ISI (β = 10.4, 95%CI 4.35-16.8), IGI/HOMA-IR (β = 7.12, 95%CI 0.98-13.6) and ISSI-2 (β = 4.38, 95%CI 1.05-7.80), all p < 0.05). There was no significant association between AHEI and dysglycemia incidence (OR = 0.95, 95%CI 0.77-1.17). Adjustments for longitudinal changes in waist circumference substantially attenuated all associations of AHEI with insulin sensitivity and beta-cell function. Mediation analysis indicated that waist circumference mediated 73%, 70%, 83% and 81% of the association between AHEI and HOMA2-%S, ISI, IGI/HOMA-IR, and ISSI-2, respectively (all p < 0.01). CONCLUSION In a Canadian population at-risk for T2D, AHEI score was positively associated with changes in insulin sensitivity and beta-cell function. These associations were substantially mediated by waist circumference, suggesting that changes in adiposity may represent an important pathway linking diet quality with risk phenotypes for T2D.
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Virus Elimination by Direct-Acting Antiviral Agents Impacts Glucose Homeostasis in Chronic Hepatitis C Patients.
Cheng, CH, Chu, CY, Chen, HL, Lin, IT, Wu, CH, Lee, YK, Bair, MJ
Frontiers in endocrinology. 2021;:799382
Abstract
BACKGROUND AND AIMS Chronic hepatitis C virus (HCV) infection is associated with dysregulation of glucose homeostasis, including insulin resistance (IR) and type 2 diabetes. However, independent risk factors associated with IR in chronic HCV-infected patients have not been detailly elucidated. Previous data regarding the impact of HCV elimination by direct-acting antiviral agents (DAAs) on glucose homeostasis is insufficient and controversial. This study aimed to analyze the independent factors associated with IR and to evaluate the changes in glucose homeostasis in chronic HCV-infected patients treated with DAAs therapies. METHODS We screened 704 patients with chronic HCV infection who underwent treatment with interferon-free DAAs. Patients' baseline characteristics, biochemical and virological data were collected. The outcome measurements were their IR and β-cell function assessed by the homeostasis model assessment (HOMA) method at baseline and 12-weeks post-treatment. RESULTS High IR (HOMA-IR ≥ 2.5) was observed in 35.1% of the patients. Multivariable logistic regression analysis revealed that body mass index (BMI) >25 kg/m2, treatment experience, elevated baseline levels of alanine aminotransferase (ALT) and triglyceride, as well as Fibrosis-4 score >3.25 were independently associated with high IR. In patients who achieved sustained virological response (SVR), no significant change in mean HOMA-IR was observed from baseline to 12-weeks post-treatment (2.74 ± 2.78 to 2.54 ± 2.20, p = 0.128). We observed a significant improvement in β-cell secretion stress from 121.0 ± 110.1 to 107.6 ± 93.0 (p = 0.015). Subgroup analysis revealed that SVR was associated with a significant reduction in mean HOMA-IR in patients with baseline HOMA-IR ≥ 2.5 (5.31 ± 3.39 to 3.68 ± 2.57, p < 0.001), HCV genotype 1 (3.05 ± 3.11 to 2.62 ± 2.05, p = 0.027), and treatment experience (4.00 ± 3.37 to 3.01 ± 2.49, p = 0.039). CONCLUSIONS There were several independent factors associated with IR in patients with chronic HCV infection, including obesity, treatment experience, high serum ALT and triglyceride levels, as well as advanced hepatic fibrosis. After viral elimination by DAAs, we observed a significant reduction in mean HOMA-IR in patients with baseline high IR, HCV genotype 1, and treatment experience.
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Multiple risk factors for diabetes mellitus in patients with chronic pancreatitis: A multicentre study of 1117 cases.
Olesen, SS, Poulsen, JL, Novovic, S, Nøjgaard, C, Kalaitzakis, E, Jensen, NM, Engjom, T, Tjora, E, Waage, A, Hauge, T, et al
United European gastroenterology journal. 2020;(4):453-461
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Abstract
BACKGROUND Diabetes mellitus is a common complication of chronic pancreatitis. It is traditionally considered to develop as a consequence of beta cell loss, but there might be additional factors. Recent studies have highlighted the importance of type 2 diabetes-related risk factors in this context and population-based studies show increased risk of diabetes following acute pancreatitis. The aim of this study was to explore multiple risk factors for diabetes in patients with chronic pancreatitis. METHODS We conducted a multicentre, cross-sectional study of patients with definitive chronic pancreatitis according to the M-ANNHEIM criteria. We used multivariable logistic regression models to determine risk factors independently associated with diabetes. RESULTS The study included 1117 patients of whom 457 (40.9 %) had diabetes. The mean age was 52.8 ± 14.2 years and 67% were men. On multivariate analysis, parameters indicative of beta cell loss (pancreatic calcification, exocrine insufficiency, pancreatic resection) were confirmed as independent risk factors for diabetes (all p ≤ 0.02). In addition, type 2 diabetes-related risk factors (dyslipidaemia and overweight/obesity) were associated with the presence of diabetes (all p ≤ 0.002). Patients with a history of pancreatic fluid collections (indicative of previous attacks of acute pancreatitis) had a marginally increased risk of diabetes (p = 0.07). CONCLUSION In patients with chronic pancreatitis the presence of diabetes is associated with multiple risk factors including type 2 diabetes-related factors. Our observations attest to the understanding of this entity and may have implications for treatment.
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Disruption of fasting and post-load glucose homeostasis are largely independent and sustained by distinct and early major beta-cell function defects: a cross-sectional and longitudinal analysis of the Relationship between Insulin Sensitivity and Cardiovascular risk (RISC) study cohort.
Mengozzi, A, Tricò, D, Nesti, L, Petrie, J, Højlund, K, Mitrakou, A, Krebs, M, Mari, A, Natali, A, ,
Metabolism: clinical and experimental. 2020;:154185
Abstract
BACKGROUND/AIMS: Uncertainty still exists on the earliest beta-cell defects at the bases of the type 2 diabetes. We assume that this depends on the inaccurate distinction between fasting and post-load glucose homeostasis and aim at providing a description of major beta-cell functions across the full physiologic spectrum of each condition. METHODS In 1320 non-diabetic individuals we performed an OGTT with insulin secretion modeling and a euglycemic insulin clamp, coupled in subgroups to glucose tracers and IVGTT; 1038 subjects underwent another OGTT after 3.5 years. Post-load glucose homeostasis was defined as mean plasma glucose above fasting levels (δOGTT). The analysis was performed by two-way ANCOVA. RESULTS Fasting plasma glucose (FPG) and δOGTT were weakly related variables (stβ = 0.12) as were their changes over time (r = -0.08). Disruption of FPG control was associated with an isolated and progressive decline (approaching 60%) of the sensitivity of the beta-cell to glucose values within the normal fasting range. Disruption of post-load glucose control was characterized by a progressive decline (approaching 60%) of the slope of the full beta-cell vs glucose dose-response curve and an early minor (30%) decline of potentiation. The acute dynamic beta-cell responses, neither per se nor in relation to the degree of insulin resistance appeared to play a relevant role in disruption of fasting or post-load homeostasis. Follow-up data qualitatively and quantitatively confirmed the results of the cross-sectional analysis. CONCLUSION In normal subjects fasting and post-load glucose homeostasis are largely independent, and their disruption is sustained by different and specific beta-cell defects.
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Cross-Sectional and Longitudinal Examination of Insulin Sensitivity and Secretion across Puberty among Non-Hispanic Black and White Children.
Marwitz, SE, Gaines, MV, Brady, SM, Mi, SJ, Broadney, MM, Yanovski, SZ, Hubbard, VS, Yanovski, JA
Endocrinology and metabolism (Seoul, Korea). 2020;(4):847-857
Abstract
BACKGROUND Few studies using criterion measures of insulin sensitivity (SI) and insulin secretory capacity (ISC) have been conducted across puberty to adulthood. We examined how SI and ISC change from pre-puberty through adulthood. METHODS Hyperglycemic clamp studies were performed in a convenience sample of non-Hispanic Black (NHB) and White children evaluated at age 6 to 12 years and at approximately 5-year intervals into adulthood (maximum age 27 years). SI and ISC (first-phase and steady-state insulin secretion) were determined cross-sectionally in 133 unique participants across puberty and in adulthood. Additionally, longitudinal changes in SI and ISC were compared at two timepoints among three groups defined by changes in pubertal development: pre-pubertal at baseline and late-pubertal at follow-up (n=27), early-pubertal at baseline and late-pubertal at follow-up (n=27), and late-pubertal at baseline and adult at follow-up (n=24). RESULTS Cross-sectionally, SI was highest in pre-puberty and early puberty and lowest in mid-puberty (analysis of covariance [ANCOVA] P=0.001). Longitudinally, SI decreased from pre-puberty to late puberty (P<0.001), then increased somewhat from late puberty to adulthood. Cross-sectionally, first-phase and steady-state ISC increased during puberty and decreased in adulthood (ANCOVA P<0.02). Longitudinally, steady-state and first-phase ISC increased from pre-puberty to late puberty (P<0.007), and steady-state ISC decreased from late puberty to adulthood. The NHB group had lower SI (P=0.003) and greater first-phase and steady-state ISC (P≤0.001), independent of pubertal development. CONCLUSION This study confirms that SI decreases and ISC increases transiently during puberty and shows that these changes largely resolve in adulthood.
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Decreased beta-cell function in breastfeeding obese and non-obese women: A prospective observational study.
Harreiter, J, Vila, G, Leitner, K, Wattar, L, Leutner, M, Worda, C, Bancher-Todesca, D, Kautzky-Willer, A
Clinical nutrition (Edinburgh, Scotland). 2019;(6):2790-2798
Abstract
BACKGROUND & AIMS Obesity is associated with lower breastfeeding rates. The underlying pathophysiological mechanisms are not well-understood, but there is increasing evidence on an association between parameters of maternal glucose metabolism and prolactin concentrations. In this cross-sectional observational study we investigate the relationship between breastfeeding, maternal obesity, and maternal glucose metabolism postpartum with beta cell function as a primary outcome measure. METHODS We investigated 106 women (44% obese) prospectively recruited during the pregnancy, who underwent a 75 g - 2 h oral glucose tolerance test (OGTT) between the 3rd and 5th months postpartum. At this time point, we tested the relationship between breastfeeding status, maternal prolactin concentrations, maternal obesity, and fasting and dynamic indices of glucose metabolism using multivariate logistic regression in a post hoc analysis of prospective observational data. RESULTS During the study visit at a mean of 122 (SE 9.3) days after delivery, 47% of obese women and 68% of non-obese women were breastfeeding (p < 0.05). Lactation and higher prolactin concentrations were associated with lower prepregnancy weight and lower postpartum insulin concentrations. Prehepatic beta-cell function was decreased in both obese (mean (SD); 0.16 (0.04) vs. 0.19 (0.05), p < 0.05) and non-obese (0.12 (0.05) vs. 0.16 (0.06), p < 0.01), lactating women. Obese lactating women have significantly lower first (1135.1 (306.7) pmol/L vs. 1517.3 (475.8) pmol/L, p < 0.01) and second phase insulin secretion (mean (SD), 300.2 (70.7) pmol/L vs. 393.1 (115.5) pmol/L, p < 0.01) as shown by Stumvoll indices when comparing to obese non-lactating women. Prehepatic beta-cell function and Stumvoll 1st phase insulin secretion index, but not BMI, were independently and negatively associated with breastfeeding and circulating prolactin concentrations. CONCLUSIONS Beta-cell function during lactation relates to breastfeeding and circulating prolactin concentrations independently of obesity. The well-known positive effects of lactation on maternal and offspring outcomes might reflect a causative relationship of higher breastfeeding rates in metabolically healthier women.
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Changes Over Time in Hepatic Markers Predict Changes in Insulin Sensitivity, β-Cell Function, and Glycemia.
Pinnaduwage, L, Ye, C, Hanley, AJ, Connelly, PW, Sermer, M, Zinman, B, Retnakaran, R
The Journal of clinical endocrinology and metabolism. 2018;(7):2651-2659
Abstract
CONTEXT Serum concentrations of liver enzymes and the hepatokine fetuin-A have been linked to the risk of type 2 diabetes, but their longitudinal impact on insulin resistance and β-cell dysfunction is unclear. OBJECTIVE To evaluate the impact of changes over 2 years in fetuin-A and the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyltransferase (GGT) on changes in insulin sensitivity, β-cell function, and glycemia in women with varying degrees of previous gestational dysglycemia, reflecting a range of future diabetic risk. DESIGN/SETTING/PARTICIPANTS In total, 336 women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT and measurement of ALT/AST/GGT/fetuin-A at both 1 year and 3 years postpartum. The antepartum GCT/OGTT identified four gestational glucose tolerance groups: gestational diabetes (n = 104), gestational impaired glucose tolerance (n = 59), abnormal GCT with normal OGTT (n = 98), and normal GCT/OGTT (n = 75). RESULTS At 1 and 3 years postpartum, ALT, AST, GGT, and fetuin-A did not differ across the four groups, but the intervening change in ALT/AST ratio was greater in the gestational dysglycemia groups (P = 0.05). Higher baseline ALT/AST (t = -1.99, P = 0.05) and fetuin-A (t = -3.17, P = 0.002) predicted lower insulin sensitivity (Matsuda) at 3 years, as did their respective changes from 1 to 3 years (ALT/AST: t = -5.47, P < 0.0001; fetuin-A: t = -3.56, P = 0.0004). Change in ALT/AST predicted lower β-cell function (t = -2.33, P = 0.02) and higher fasting glucose at 3 years (t = 2.55, P = 0.01). Moreover, baseline fetuin-A predicted prediabetes/diabetes at 3 years (OR, 1.38; 95% CI, 1.01 to 1.88). CONCLUSION Circulating hepatic markers, particularly ALT/AST ratio and fetuin-A, track with changes in insulin sensitivity and β-cell function, supporting a pathophysiologic basis in their prediction of diabetic risk.
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Pancreatic beta cell function is preserved in the short term in patients with type 2 diabetes undergoing non-urgent surgery.
Hernanz-Rodriguez, G, Pedrianes-Martin, P, de Pablos-Velasco, P, Rodriguez-Perez, A
Minerva endocrinologica. 2018;(2):109-116
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a progressive condition influenced by many factors. Surgery usually produces hyperglycemia in the postoperative period, which leads to adverse clinical outcomes. Possible consequences of surgery on beta cell reserve have not been explored. The aim of this study was to assess the effect of surgery on the beta cell function of patients with T2DM undergoing non-urgent surgery. METHODS We performed a prospective observational study on the population of patients with T2DM scheduled for surgery in a tertiary level hospital. After adequate wash-out periods for antidiabetic medications, two blood samples were collected: one fasting and the other one six minutes after an intravenous stimulation with glucagon. Glucose, insulin and C-peptide concentrations were measured. This determination was repeated about a month after surgery. RESULTS We included 42 patients with the following characteristics: 47.6% males, average HbA1c 7%, average time from T2DM diagnosis 7.3 years and average age 62.1 years. Intravenous glucagon produced a significant increase in C-peptide after six minutes in both the presurgical (C-peptide values: basal 2.97 ng/mL; after glucagon 5.53 ng/mL) and the postsurgical (C-peptide values: basal 3.12 ng/mL; after glucagon 5.67 ng/mL) periods (mean difference 2.56 ng/mL and 2.55 ng/mL respectively, P<0.001). However, C-peptide increase after glucagon was not different between the presurgical and the postsurgical periods (2.56 ng/mL vs. 2.55 ng/mL, P>0.05). CONCLUSIONS The pancreatic beta reserve of patients with T2DM was not affected a month after the non-urgent surgery. The direct measurement of pancreatic function by dynamic assessment with glucagon did not change, nor did we find alterations in the indirect calculation of insulin secretion using the HOMA-B. None of these parameters reached statistical significance. Non-urgent surgical procedures included in our study are safe for patients with short lasting, properly controlled T2DM, from the point of view of glucose metabolism assessed by pancreatic insulin secretion. We can consider non-urgent surgical procedures safe from the point of view of the preservation of the pancreatic reserve in patients with T2DM. A sharp deterioration of metabolic control is not expectable in the short term for these patients, which represent a large proportion of the population undergoing surgery in modern hospitals.
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Fetal overnutrition and offspring insulin resistance and β-cell function: the Exploring Perinatal Outcomes among Children (EPOCH) study.
Sauder, KA, Hockett, CW, Ringham, BM, Glueck, DH, Dabelea, D
Diabetic medicine : a journal of the British Diabetic Association. 2017;(10):1392-1399
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Abstract
AIMS: To examine the associations of intrauterine exposure to maternal diabetes and obesity with offspring insulin resistance, β-cell function and oral disposition index in a longitudinal observational study of ethnically diverse offspring. METHODS A total of 445 offspring who were exposed (n=81) or not exposed (n=364) to maternal diabetes in utero completed two fasting blood measurements at mean (sd) ages of 10.5 (1.5) and 16.5 (1.2) years, respectively, and an oral glucose tolerance test at the second visit. We used linear mixed models and general linear univariate models to evaluate the associations of maternal diabetes and pre-pregnancy BMI with offspring outcomes. RESULTS Maternal diabetes in utero predicted increased insulin resistance [18% higher updated homeostatic model assessment of insulin resistance (HOMA2-IR), P=0.01; 19% lower Matsuda index, P=0.01 and 9% greater updated homeostatic model assessment of β-cell function (HOMA2-β), P=0.04]. Each 5-kg/m2 increase in pre-pregnancy BMI predicted increased insulin resistance (11% greater HOMA2-IR, P<0.001; 10% lower Matsuda index, P<0.001; 6% greater HOMA2-β, P<0.001). Similar results were obtained in a combined model with both exposures. After adjustment for offspring BMI, only maternal diabetes was associated with higher HOMA2-IR (β=1.12, P=0.03) and lower Matsuda index (β=0.83, P=0.01). Neither exposure was associated with early insulin response or oral disposition index. CONCLUSIONS Intrauterine exposure to diabetes or obesity is associated with greater offspring insulin resistance than non-exposure, supporting the hypothesis that fetal overnutrition results in metabolic abnormalities during childhood and adolescence.