Hypertension, but not body mass index, is predictive of increased pancreatic lipid content and islet dysfunction

Tremmel, Daniel M.; Feeney, Austin K.; Mitchell, Samantha A.; Chlebeck, Peter J.; Raglin, Sierra A.; Fernández, Luis A.; Odorico, Jon S.; Sackett, Sara Dutton

doi:10.1111/ajt.15698

Cited by 7 publications

(6 citation statements)

References 70 publications

(204 reference statements)

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“…Some studies from newly diagnosed T2DM patients and non-diabetic individuals demonstrated that higher systolic blood pressure (SBP) was associated with improved beta-cell function 10,11 . In contrast, other studies found that hypertension or elevated SBP was a risk factor for betacell function [12][13][14] . Notably, there are no study to exam whether the optimal range of SBP needed for better islet beta-cell function is different in T2DM patients with different glycemic status.…”

mentioning

confidence: 75%

Higher systolic blood pressure is specifically associated with better islet beta-cell function in T2DM patients with high glycemic level

Xia

Song²,

Fang³

et al. 2022

Preprint

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Background Patients with type 2 diabetes mellitus (T2DM) usually have high blood viscosity, which could decrease blood supply to the pancreas. Increased blood pressure (BP) has been reported as a potentially compensatory response to the maintenance of islet blood perfusion. However, the influence of BP on beta-cell function in people with diabetes remains inconsistent. This study aimed to examine the relationship between BP and beta-cell function in patients with T2DM under different HbA1c levels. Methods This cross-sectional study included 615 T2DM patients. Clinical data were extracted from hospital medical records. Beta-cell function was assessed with insulin secretion-sensitivity index-2 (ISSI2). Multivariable linear regression analysis and restricted cubic splines (RCS) analysis were performed to identify the association between systolic blood pressure (SBP) and ISSI2. Mediation analysis was performed to determine whether higher SBP could reduce blood glucose by enhancing beta-cell function. Results After adjustment of age, sex, duration of diabetes, blood lipids, Matsuda index, and drug treatment, in participants with HbA1c ≥10%, SBP was positively associated with log ISSI2 (b = 0.044, 95%CI: 0.011, 0.078), and the SBP between 140 to150 mmHg had the highest log ISSI2 (b = 0.306, 95%CI: 0.126, 0.485). RCS analyses further demonstrated an inverted U-shaped association between SBP and ISSI2 with the SBP at 146 mmHg corresponding to the best beta-cell function. Additionally, higher SBP was “paradoxically” associated with lower 2h postprandial blood glucose (PBG) when SBP < 150mmHg, which was almost exclusively mediated by ISSI2 (mediating effect=-0.057, 95%CI: -0.085, -0.029). However, SBP was not associated with ISSI2 and 2h PBG in participants with HbA1c < 10%. Conclusions A certain degree of elevated SBP (140–150 mmHg) was associated with better beta-cell function and reduced 2h PBG in T2DM patients with HbA1c ≥10% but not in those with HbA1c < 10%. T2DM patients with unfavorable glycemic control may benefit from higher SBP through enhanced islet beta-cell function.

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mentioning

confidence: 75%

Higher systolic blood pressure is specifically associated with better islet beta-cell function in T2DM patients with high glycemic level

Xia

Song²,

Fang³

et al. 2022

Preprint

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“…Furthermore, a recent study reported that donors with a history of HBP exhibited increased pancreatic lipid content and islet lipid content, irrespective of gender. This association was correlated with poorer islet performance after isolation ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Donor- and isolation-related predictive factors of in vitro secretory function of cultured human islets

Buemi,

Mourad,

Ambroise

et al. 2024

Front. Endocrinol.

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Background and aimsHuman islet preparations designated for research exhibit diverse insulin-secretory profiles. This study aims to assess the impact of donor- and isolation-related factors on in vitro islet secretory function.MethodsA retrospective analysis of 46 isolations from 23 pancreata discarded for clinical transplantation was conducted. In vitro islet secretory function tests were performed on Day 1 and Day 7 of culture. Linear mixed-effects models (LMMs) were employed to investigate the relationships between various predictors characterizing the patient and donor characteristics as well as the isolation effectiveness and two functional outcomes including the islet stimulation index (SI) and area under the insulin curve (AUC). Fixed effects were introduced to represent the main effects of each predictor, and backward elimination was utilized to select the most significant fixed effects for the final model. Interaction effects between the timepoint (Day 7 vs. Day 1) and the predictors were also evaluated to assess whether predictors were associated with the temporal evolution of SI and AUC. Fold-change (Fc) values associated with each predictor were obtained by exponentiating the corresponding coefficients of the models, which were built on log-transformed outcomes.ResultsAnalysis using LMMs revealed that donor body mass index (BMI) (Fc = 0.961, 95% CI = 0.927–0.996, p = 0.05), donor gender (female vs. male, Fc = 0.702, 95% CI = 0.524–0.942, p = 0.04), and donor hypertension (Fc = 0.623, 95% CI = 0.466–0.832, p= <0.01) were significantly and independently associated with SI. Moreover, donor gender (Fc = 0.512, 95% CI = 0.302–0.864, p = 0.02), donor cause of death (cerebrovascular accident vs. cardiac arrest, Fc = 2.129, 95% CI = 0.915–4.946, p = 0.09; trauma vs. cardiac arrest, Fc = 2.129, 95% CI = 1.112–7.106, p = 0.04), pancreas weight (Fc = 1.01, 95% CI = 1.001–1.019, p = 0.03), and islet equivalent (IEQ)/mg (Fc = 1.277, 95% CI = 1.088–1.510, p ≤ 0.01) were significantly and independently associated with AUC. There was no predictor significantly associated with the temporal evolution between Day 1 and Day 7 for both SI and AUC outcomes.ConclusionThis study identified donor- and isolation-related factors influencing in vitro islet secretory function. Further investigations are essential to validate the applicability of these results in clinical practice.

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“…Lyophilized material was weighed to record the tissue dry weight. Lipids were extracted from each sample using a modified Folch method as previously described 26 , 67 . The lipid phase was dried and weighed to measure the lipid content as a percentage of the initial dry weight.…”

Section: Methodsmentioning

confidence: 99%

A human pancreatic ECM hydrogel optimized for 3-D modeling of the islet microenvironment

Tremmel

Sackett

Feeney

et al. 2022

Sci Rep

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Extracellular matrix (ECM) plays a multitude of roles, including supporting cells through structural and biochemical interactions. ECM is damaged in the process of isolating human islets for clinical transplantation and basic research. A platform in which islets can be cultured in contact with natural pancreatic ECM is desirable to better understand and support islet health, and to recapitulate the native islet environment. Our study demonstrates the derivation of a practical and durable hydrogel from decellularized human pancreas that supports human islet survival and function. Islets embedded in this hydrogel show increased glucose- and KCl-stimulated insulin secretion, and improved mitochondrial function compared to islets cultured without pancreatic matrix. In extended culture, hydrogel co-culture significantly reduced levels of apoptosis compared to suspension culture and preserved controlled glucose-responsive function. Isolated islets displayed altered endocrine and non-endocrine cell arrangement compared to in situ islets; hydrogel preserved an islet architecture more similar to that observed in situ. RNA sequencing confirmed that gene expression differences between islets cultured in suspension and hydrogel largely fell within gene ontology terms related to extracellular signaling and adhesion. Natural pancreatic ECM improves the survival and physiology of isolated human islets.

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Hypertension, but not body mass index, is predictive of increased pancreatic lipid content and islet dysfunction

Cited by 7 publications

References 70 publications

Higher systolic blood pressure is specifically associated with better islet beta-cell function in T2DM patients with high glycemic level

Higher systolic blood pressure is specifically associated with better islet beta-cell function in T2DM patients with high glycemic level

Donor- and isolation-related predictive factors of in vitro secretory function of cultured human islets

A human pancreatic ECM hydrogel optimized for 3-D modeling of the islet microenvironment

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