scholarly journals SUN-621 Body Weight and Body Composition in Patients with Chronic Pancreatitis Are Associated with Islet Function After Total Pancreatectomy and Islet Cell Transplantation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Tasma Harindhanavudhi ◽  
Yi Yang ◽  
Jim Hodges ◽  
Melena Dawn Bellin

Abstract Background: Total pancreatectomy with islet autotransplant (TPIAT) is done in patients with chronic pancreatitis to treat intractable pain. In TPIAT, islets are isolated after pancreatectomy and infused into the liver via the portal vein to mitigate post-operative diabetes. Outcomes vary, with ≥60% needing exogenous insulin supplementation to maintain normoglycemia. The current study’s aim was to determine if pre-surgical body composition is associated with islet function and insulin sensitivity after TPIAT. Methods: We characterized body weight and composition as related to insulin sensitivity and dependence and diabetes outcome in 88 adults who underwent TPIAT for chronic pancreatitis at the University of Minnesota. At baseline, 12 and 18 months after TPIAT, insulin independence was assessed; metabolic testing used mixed meal tolerance testing and frequent sample intravenous glucose tolerance testing. Body composition was measured by Dual X-ray absorptiometry (DXA). Statistical analyses used linear and logistic regression. Results: At baseline, mean age was 39.9 (SD 11.1) years. 9.1% were underweight (BMI<18.5 kg/m2), 45.5% normal weight (BMI=18.5–24.9), 22.7% overweight (BMI=25–29.9) and 22.7% obese (BMI≥30). Islet equivalent per kg did not differ between body weight categories (p=0.17). Overweight/obese patients had higher peak and AUC c-peptide and lower insulin sensitivity index, as expected. Compared to baseline, android to gynoid fat ratio was lower at 12 (0.80 vs 0.88; p=0.012) and 18 months (0.81 vs 0.88; p=0.041), and lean mass was lower at 18 months (38848 vs 42338 kg; p=0.029). Baseline body weight was positively associated with acute insulin response to glucose (AIRg) at 12 months (effect size 38.5, SE 17.1 mU/L/min; p=0.029) and 18 months (38.3, SE 18.5 mU/L/min; p=0.045), while baseline lean mass was inversely associated with AIRg at 12 (p=0.01) and 18 months (p=0.033). Baseline body weight was positively associated, and fat mass inversely associated with disposition index (Di; islets’ ability to secrete insulin normalized to insulin resistance) at 18 months (p=0.019 for both). Percent body fat and percent gynoid fat predicted Sg (glucose effectiveness index, i.e., ability of glucose to promote its own disposal and inhibit hepatic glucose production absent an incremental insulin effect) at 18 months (p=0.042 and p=0.019, respectively). Insulin independence at 12 and 18 months was not significantly associated with baseline body weight or body composition. Conclusions: Overweight/obesity is common in patients with chronic pancreatitis. After TPIAT, patients had lower muscle mass and A/G ratio. Preoperative body weight and composition were associated with islet function but not insulin independence after TPIAT surgery.

Author(s):  
Tasma Harindhanavudhi ◽  
Yi Yang ◽  
James S Hodges ◽  
Timothy L Pruett ◽  
Varvara Kirchner ◽  
...  

Abstract Context Body composition in total pancreatectomy with islet autotransplantation (TPIAT) has never been studied. Objective Determine whether presurgical body composition is associated with islet function and insulin sensitivity after TPIAT. Methods In 88 adults undergoing TPIAT (median age 41.0 years, IQR 32.8-48.0), beta-cell function and insulin sensitivity were assessed using mixed meal tolerance test and frequent sample intravenous glucose tolerance test before surgery and 12 and 18 months afterward. Body composition was measured by dual x-ray absorptiometry. Analyses used linear and logistic regression. Results Before surgery, 8 individuals (9.1%) were underweight, 40 (45.5%) normal weight, 20 (22.7%) overweight, and 20 (22.7%) obese. Overweight/obese patients had higher area under the curve C-peptide and lower insulin sensitivity index. Baseline body weight was positively associated with first-phase insulin secretion (AIRg) at 12 months (average 38.5 [SE 17.1] mU/L/min higher per extra kg; P = 0.03) and 18 months (38.3 [18.5]; P = 0.04), while baseline lean mass was inversely associated with AIRg at 12 months (−0.05 [0.02] per extra kg; P = 0.01) and 18 months (−0.05 [0.02]; P = 0.03). Percent gynoid fat was inversely associated with disposition index at 18 months (−206.0 [97.2] per extra percent; P = 0.04). Percent body fat and percent gynoid fat were associated with glucose effectiveness index at 18 months (1.9 × 10-3 [0.9 × 10-3] per extra percent; P = 0.04 and −1.96 × 10-3 [0.8 × 10-3]; P = 0.02, respectively). Insulin independence was not significantly associated with body weight or composition. Conclusions Half of these chronic pancreatitis patients were overweight/obese; underweight was uncommon. Preoperative body weight and composition were associated with islet function but not insulin independence after TPIAT.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Kelsey Smith ◽  
Sarah Francisco ◽  
Ying Zhu ◽  
Kathryn Barger ◽  
Donald E Smith ◽  
...  

Abstract Objectives We sought to identify the role of gut microbiota in the previously discovered relationship between a high glycemic diet and the development of retinal damage and metabolic health outcomes in aged mice. Methods Male C57Bl6/J mice aged 12 months were fed equal amounts of a high glycemic (HG) or low glycemic (LG) diet for 12 months. The compositions of the diets were identical apart from the starch, which was 100% amylopectin in the HG diet and 30% amylopectin/70% amylose in the LG diet. Within each diet, mice were assigned to one of three treatment conditions: antibiotic ablation of gut microbiota (HGabx or LGabx), weekly fecal microbiota transplants (FMT) from donor control mice fed the alternate diet (HG[tLG] or LG[tHG]), or a control group. Mice were weighed weekly and feces and urine were collected at regular intervals for microbiome and metabolome analysis respectively. Mice underwent MRIs to determine body composition, intraperitoneal glucose tolerance tests to determine glycemic responses, and eye fundus imaging and fluorescein angiography to evaluate the health of the retina and retinal vasculature. Results Compared with LG-fed controls, the HG-fed controls had significantly increased body fat mass, decreased insulin sensitivity, and an increased prevalence of retinal damage including hypopigmentation and vascular tortuosity. There was no significant difference in body weight between the HGabx and LGabx group throughout the study. The LGabx group had a significantly higher body weight and the HGAbx had significantly lower body weight than their respective control groups throughout the study. The LGabx group had the highest prevalence of abnormal retinal findings. Survival was significantly decreased in the HGabx mice compared with mice of all other groups of mice, and most died suddenly and presented with an enlarged and hemorrhagic cecum. There was no significant effect of the FMT on body weight or body composition compared with the control mice. The HG[tLG] group had improved insulin sensitivity relative to the HG controls. Conclusions Gut microbiota mediate the relationship between the glycemic response to the diet and health outcomes such as obesity, insulin sensitivity, eye health, and survival. Funding Sources BrightFocus Foundation, USDA/NIFA AFRI grant 2015-05470, USDA contract 1950-510000-060-03A from ARS, Stanley N. Gershoff Scholarship.


1991 ◽  
Vol 71 (6) ◽  
pp. 2402-2411 ◽  
Author(s):  
K. R. Segal ◽  
A. Edano ◽  
A. Abalos ◽  
J. Albu ◽  
L. Blando ◽  
...  

To clarify the impact of vigorous physical training on in vivo insulin action and glucose metabolism independent of the intervening effects of concomitant changes in body weight and composition and residual effects of an acute exercise session, 10 lean, 10 obese, and 6 diet-controlled type II diabetic men trained for 12 wk on a cycle ergometer 4 h/wk at approximately 70% of maximal O2 uptake (VO2max) while body composition and weight were maintained by refeeding the energy expended in each training session. Before and 4–5 days after the last training session, euglycemic hyperinsulinemic (40 mU.m2.min-1) clamps were performed at a plasma glucose of 90 mg/dl, combined with indirect calorimetry. Total insulin-stimulated glucose disposal (M) was corrected for residual hepatic glucose output. Body weight, fat, and fat-free mass (FFM) did not change with training, but cardiorespiratory fitness increased by 27% in all groups. Before and after training, M was lower for the obese (5.33 +/- 0.39 mg.kg FFM-1.min-1 pretraining; 5.33 +/- 0.46 posttraining) than for the lean men (9.07 +/- 0.49 and 8.91 +/- 0.60 mg.kg FFM-1.min-1 for pretraining and posttraining, respectively) and lower for the diabetic (3.86 +/- 0.44 and 3.49 +/- 0.21) than for the obese men (P less than 0.001). Insulin sensitivity was not significantly altered by training in any group, but basal hepatic glucose production was reduced by 22% in the diabetic men. Thus, when intervening effects of the last exercise bout or body composition changes were controlled, exercise training per se leading to increased cardiorespiratory fitness had no independent impact on insulin action and did not improve the insulin resistance in obese or diabetic men.


2019 ◽  
Vol 28 (1_suppl) ◽  
pp. 25S-36S
Author(s):  
Hongjun Wang ◽  
Wenyu Gou ◽  
Charlie Strange ◽  
Jingjing Wang ◽  
Paul J. Nietert ◽  
...  

Stresses encountered during human islet isolation lead to unavoidable β-cell death after transplantation. This reduces the chance of insulin independence in chronic pancreatitis patients undergoing total pancreatectomy and islet autotransplantation. We tested whether harvesting islets in carbon monoxide-saturated solutions is safe and can enhance islet survival and insulin independence after total pancreatectomy and islet autotransplantation. Chronic pancreatitis patients who consented to the study were randomized into carbon monoxide (islets harvested in a carbon monoxide-saturated medium) or control (islets harvested in a normal medium) groups. Islet yield, viability, oxygen consumption rate, β-cell death (measured by unmethylated insulin DNA), and serum cytokine levels were measured during the peri-transplantation period. Adverse events, metabolic phenotypes, and islet function were measured prior and at 6 months post-transplantation. No adverse events directly related to the infusion of carbon monoxide islets were observed. Carbon monoxide islets showed significantly higher viability before transplantation. Subjects receiving carbon monoxide islets had less β-cell death, decreased CCL23, and increased CXCL12 levels at 1 or 3 days post transplantation compared with controls. Three in 10 (30%) of the carbon monoxide subjects and none of the control subjects were insulin independent. This pilot trial showed for the first time that harvesting human islets in carbon monoxide-saturated solutions is safe for total pancreatectomy and islet autotransplantation patients.


2011 ◽  
Vol 301 (5) ◽  
pp. E825-E835 ◽  
Author(s):  
Lucy S. Jun ◽  
C. Parker Siddall ◽  
Evan D. Rosen

Adipose tissue controls energy homeostasis and systemic insulin sensitivity through the elaboration of a series of cytokines and hormones, collectively termed “adipokines.” We and others have identified Lcn2 as a novel adipokine, but its exact role in obesity-induced insulin resistance remains controversial. The aim of this study was to examine the metabolic phenotype of Lcn2−/− mice to clarify the role of Lcn2 in metabolism. Male and female Lcn2−/− and wild-type (WT) littermates were placed on either chow or high-fat diet (HFD) to characterize their metabolic phenotype. Studies included body weight and body composition, glucose and insulin tolerance tests, and adipokine expression studies in serum and in white adipose tissue (WAT). Neither chow nor HFD cohorts showed any differences in body weight or body composition. Chow-fed Lcn2−/− mice did not exhibit any difference in glucose homeostasis compared with WT mice. Fasting serum glucose levels were lower in the chow-fed Lcn2−/− mice, but this finding was not seen in the HFD cohort. Serum adiponectin, leptin, resistin, and RBP4 levels were not different between WT and Lcn2−/− on chow diet. HFD-fed male Lcn2−/− mice did display a small improvement in glucose tolerance, but no difference in insulin sensitivity was seen in either male or female Lcn2−/− mice on HFD. We conclude that the global ablation of Lcn2 has a minimal effect on obesity-associated glucose intolerance but does not appear to affect either age- or obesity-mediated insulin resistance in vivo.


Diabetes Care ◽  
2022 ◽  
Author(s):  
Sarah E. Swauger ◽  
Lindsey N. Hornung ◽  
Deborah A. Elder ◽  
Appakalai N. Balamurugan ◽  
David S. Vitale ◽  
...  

OBJECTIVE Total pancreatectomy with islet autotransplantation (TPIAT) is indicated to alleviate debilitating pancreas-related pain and mitigate diabetes in patients with acute recurrent and chronic pancreatitis when medical/endoscopic therapies fail. Our aim was to evaluate predictors of insulin requirement at 1 year following TPIAT in a cohort of children. RESEARCH DESIGN AND METHODS This was a review of 43 pediatric patients followed after TPIAT for 1 year or longer. Primary outcome was insulin use at 1 year, categorized as follows: insulin independent, low insulin requirement (<0.5 units/kg/day), or high insulin requirement (≥0.5 units/kg/day). RESULTS At 1 year after TPIAT, 12 of 41 (29%) patients were insulin independent and 21 of 41 (51%) had low and 8 of 41 (20%) had high insulin requirement. Insulin-independent patients were younger than those with low and high insulin requirement (median age 8.2 vs. 14.6 vs. 13.1 years, respectively; P = 0.03). Patients with insulin independence had a higher number of transplanted islet equivalents (IEQ) per kilogram body weight (P = 0.03) and smaller body surface area (P = 0.02), compared with those with insulin dependence. Preoperative exocrine insufficiency was associated with high insulin requirement (P = 0.03). Higher peak C-peptide measured by stimulated mixed-meal tolerance testing (MMTT) at 3 and 6 months post-TPIAT was predictive of lower insulin requirement at 1 year (P = 0.006 and 0.03, respectively). CONCLUSIONS We conclude that insulin independence following pediatric TPIAT is multifactorial and associated with younger age, higher IEQ per kilogram body weight transplanted, and smaller body surface area at time of operation. Higher peak C-peptide measured by MMTT following TPIAT confers a higher likelihood of low insulin requirement.


Author(s):  
Fernanda L Alvarado ◽  
Perrie O’Tierney-Ginn ◽  
Patrick Catalano

Abstract Context Efforts to decrease the risk of developing metabolic complications of pregnancy such as gestational diabetes (GDM) through lifestyle intervention (decreasing excessive gestational weight gain (GWG)) during pregnancy have met with limited success. Objective The purpose of this study was to determine the relationship between the longitudinal changes in weight/body composition and insulin sensitivity and response in women with normal glucose tolerance (NGT) and those who developed GDM. Design We conducted a secondary analysis of a prospective cohort developed before conception and again at 34-36 weeks gestation. Twenty-nine NGT and seventeen GDM women were evaluated for longitudinal changes in insulin sensitivity/response using the hyperinsulinemic-euglycemic clamp and an IV-glucose tolerance test. Body composition was estimated using hydrodensitometry. Both absolute (Δ) and relative change (%Δ) between these two time points were calculated. We performed simple and multiple linear regression analysis to assess the relationship between GWG and measures of glucose metabolism, i.e. insulin sensitivity and response. Results Based on the primary study design there was no significant difference in clinical characteristics between women with NGT and those developing GDM. Prior to pregnancy, women who developed GDM had lower insulin sensitivity levels (p=0.01) compared to NGT women. Absolute change and %Δ in insulin sensitivity/insulin response and body weight/body composition was not significantly different between NGT and GDM women. Changes in body weight contributed to only 9% of the Δ insulin sensitivity both in women developing GDM and NGT women. Conclusions These data suggest that other factors – such as maternal pre-pregnancy insulin sensitivity and placental derived factors affecting insulin sensitivity rather than maternal GWG account for the changes in glucose metabolism during human pregnancy.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2917
Author(s):  
Hana Kahleova ◽  
Emilie Rembert ◽  
Jihad Alwarith ◽  
Willy N. Yonas ◽  
Andrea Tura ◽  
...  

Diet modulates gut microbiota and plays an important role in human health. The aim of this study was to test the effect of a low-fat vegan diet on gut microbiota and its association with weight, body composition, and insulin resistance in overweight men and women. We enrolled 168 participants and randomly assigned them to a vegan (n = 84) or a control group (n = 84) for 16 weeks. Of these, 115 returned all gut microbiome samples. Gut microbiota composition was assessed using uBiome Explorer™ kits. Body composition was measured using dual energy X-ray absorptiometry. Insulin sensitivity was quantified with the predicted clamp-derived insulin sensitivity index from a standard meal test. Repeated measure ANOVA was used for statistical analysis. Body weight decreased in the vegan group (treatment effect −5.9 kg [95% CI, −7.0 to −4.9 kg]; p < 0.001), mainly due to a reduction in fat mass (−3.9 kg [95% CI, −4.6 to −3.1 kg]; p < 0.001) and in visceral fat (−240 cm3 [95% CI, −345 to −135 kg]; p < 0.001). PREDIcted M, insulin sensitivity index (PREDIM) increased in the vegan group (treatment effect +0.83 [95% CI, +0.48 to +1.2]; p < 0.001). The relative abundance of Faecalibacterium prausnitzii increased in the vegan group (+5.1% [95% CI, +2.4 to +7.9%]; p < 0.001) and correlated negatively with changes in weight (r = −0.24; p = 0.01), fat mass (r = −0.22; p = 0.02), and visceral fat (r = −0.20; p = 0.03). The relative abundance of Bacteroides fragilis decreased in both groups, but less in the vegan group, making the treatment effect positive (+18.9% [95% CI, +14.2 to +23.7%]; p < 0.001), which correlated negatively with changes in weight (r = −0.44; p < 0.001), fat mass (r = −0.43; p < 0.001), and visceral fat (r = −0.28; p = 0.003) and positively with PREDIM (r = 0.36; p < 0.001), so a smaller reduction in Bacteroides fragilis was associated with a greater loss of body weight, fat mass, visceral fat, and a greater increase in insulin sensitivity. A low-fat vegan diet induced significant changes in gut microbiota, which were related to changes in weight, body composition, and insulin sensitivity in overweight adults, suggesting a potential use in clinical practice.


Sign in / Sign up

Export Citation Format

Share Document