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1.
Cardiovasc Diabetol ; 19(1): 122, 2020 08 05.
Article in English | MEDLINE | ID: mdl-32758235

ABSTRACT

BACKGROUND: Studies suggest that cardio-vascular risk factors could foster the development of type 2 diabetes (T2D). This could partly be mediated by pancreatic atherosclerosis resulting in pancreatic ischemia. We hypothesized that patients with T2D present with more severe atherosclerosis of pancreas-bound arteries than control patients without T2D. METHODS: We performed a retrospective study comparing the abdominal computed tomography of patients with T2D and of control subjects matched for gender and for age. We performed a multivariate logistic regression with adjustment for age, gender, BMI and the presence or absence of hypertension. RESULTS: Forty-eight patients with T2D and 48 control subjects were included. A calcification score of the splenic artery was defined (from 0: no calcification to 3: continuous linear calcifications). Seventeen percent of the patients with T2D presented with a high calcification score (i.e. 2 or 3), versus only 2% of the control subjects (p = 0.04). The mean number of pancreas-bound branches among the greater pancreatic artery, dorsal pancreatic artery and inferior pancreatic artery (from 0 to 3) was lower in patients with T2D than in control subjects (1.1 vs 1.7, p = 0.003). The mean number of visible intrapancreatic arterial subdivisions (from 0 to 2) was lower in patients with T2D than in control subjects (0.7 vs 1.3, p = 0.0017). All these differences hold true using multivariate logistic regression. None of these differences correlated with the duration of diabetes. The relationship between pancreas volume and BMI seen in control subjects was not confirmed in patients with T2D. Conversely, in patients with T2D but not in control subjects, the splenic artery diameter correlated with the pancreas volume. CONCLUSIONS: Patients with T2D present with more calcifications of the splenic artery and with a less dense pancreatic arterial tree than control subjects.


Subject(s)
Arteries/diagnostic imaging , Computed Tomography Angiography , Diabetes Mellitus, Type 2/complications , Pancreas/blood supply , Vascular Malformations/diagnostic imaging , Aged , Arteries/abnormalities , Atherosclerosis/complications , Atherosclerosis/diagnostic imaging , Diabetes Mellitus, Type 2/diagnosis , Female , Humans , Male , Middle Aged , Plaque, Atherosclerotic , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Risk Factors , Splenic Artery/diagnostic imaging , Vascular Calcification/complications , Vascular Calcification/diagnostic imaging , Vascular Malformations/complications
2.
Pancreatology ; 20(1): 60-67, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31708473

ABSTRACT

BACKGROUND: Tobacco smoking and alcohol consumption are established risk factors for diseases of the pancreas. With the recent advances in imaging modalities (such as magnetic resonance (MR) imaging), opportunities have arisen to study pancreas size, in both health and disease. Studies investigating the relationship between tobacco smoking, alcohol consumption, and total pancreas volume (TPV) - a holistic measure of pancreatic exocrine reserve - are lacking. The aim of the present study was to investigate the associations between MR-derived TPV and tobacco smoking/alcohol consumption. METHODS: This cross-sectional study recruited individuals with a history of pancreatitis and healthy controls. A validated questionnaire was used to ascertain current and lifetime tobacco smoking and alcohol consumption. TPV was quantified using MR images by two independent raters. Generalized additive models and linear regression analyses were conducted and adjusted for demographic, metabolic, and pancreatitis-related factors. RESULTS: A total of 107 individuals following pancreatitis and 38 healthy controls were included. There was no statistically significant difference in TPV between any of the tobacco smoking/alcohol consumption categories of individuals following pancreatitis and healthy controls, in both unadjusted and adjusted analyses. In individuals following pancreatitis, multivariate linear regression found no association between TPV and 7 smoking- and alcohol-related variables. Sensitivity analyses constrained to individuals who did not abstain from either smoking or drinking following their first attack of pancreatitis did not yield statistical significance with TPV. In post-hoc analysis, age was significantly inversely associated with TPV in the most adjusted model (p = 0.016). CONCLUSIONS: This is the first study to investigate the association between tobacco smoking, alcohol consumption, and MR-derived TPV following pancreatitis. It appears that age, but not tobacco smoking or alcohol consumption, is associated with a significantly reduced TPV.


Subject(s)
Alcohol Drinking/adverse effects , Pancreas/pathology , Pancreatitis/pathology , Tobacco Smoking/adverse effects , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Risk Factors
3.
Clin Transplant ; 34(8): e14008, 2020 08.
Article in English | MEDLINE | ID: mdl-32530540

ABSTRACT

Islet yield is an important predictor of acceptable glucose control after total pancreatectomy with islet autotransplantation (TP-IAT). We assessed if pancreas volume calculated with preoperative MRI could assess islet yield and postoperative outcomes. We reviewed dynamic MRI studies from 154 adult TP-IAT patients (2009-2016), and associations between calculated volumes and digest islet equivalents (IEQs) were tested. In multivariate regression analysis, pancreas volume (P < .001) and preoperative HbA1c levels (P = .009) were independently associated with digest IEQs. The IEQ prediction formula was calculated according to each preoperative HbA1c level, (a) pancreas volume × 5800 for HbA1c ≥ 6.5, (b) pancreas volume × 10 000 for HbA1c ≥5.7/<6.5 and (iii) pancreas volume × 11 400 for HbA1c < 5.7. The formula was internally validated with 28 TP-IAT patients between 2017 and 2018 (r2  = .657 and r2  = .710 when restricted to 24 patients without prior pancreatectomy). An estimated IEQs/Body Weight (kg) ≥3700 predicted HbA1c ≤6.5 and insulin independence at 1 year after TP-IAT with 77% and 88% sensitivity and 55% and 43% specificity, respectively. The combination of pancreas volume and preoperative HbA1c levels may be useful to estimate islet yield. Estimated IEQs were reasonably sensitive to predict acceptable glucose control at 1 year.


Subject(s)
Islets of Langerhans Transplantation , Pancreatitis, Chronic , Adult , Glycated Hemoglobin , Humans , Pancreas/diagnostic imaging , Pancreas/surgery , Pancreatectomy , Pancreatitis, Chronic/surgery , Transplantation, Autologous , Treatment Outcome
4.
J Pak Med Assoc ; 70(8): 1408-1412, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32794496

ABSTRACT

OBJECTIVE: To investigate whether measuring pancreas volume with abdominal tomography in patients with severe abdominal pain can predict acute pancreatitis. METHODS: The case-control study was conducted at Adnan Menderes University from January 1, 2015, to January 1, 2017, and comprised patients who were diagnosed with acute pancreatitis. Pancreas volume measurements of patients and control group were made with Telemed Ekinoks software using freehand technique. Presence of a correlation between pancreas volume and pancreatitis was found in patients aged <57 years and a cut-off value was calculated for pancreatitis in this particular patient group. RESULTS: Of the 183 subjects, 132(72%) were patients with a mean age of 59.6±16.5 years, and 51(28%) were controls with a mean age of 55.8±18.6 years (p=0.170). The difference between the groups in terms of pancreas volume was significant (p<0.001). There was a negative correlation between age and pancreas volume among the patients (p<0.001), the correlation was not significant among the controls (p=0.898). Among the subjects aged <57 years, the cut-off value was calculated at 95.055, and sensitivity to pancreas volume was 70.91% while specificity was 82.14%. Positive predictive value was 88.6%. CONCLUSIONS: High pancreas volume with pancreatitis was observed in patients aged <57 years.


Subject(s)
Pancreatitis , Abdominal Pain , Acute Disease , Adult , Aged , Case-Control Studies , Humans , Middle Aged , Pancreas/diagnostic imaging , Pancreatitis/diagnostic imaging
5.
Endocr J ; 64(5): 487-498, 2017 May 30.
Article in English | MEDLINE | ID: mdl-28321030

ABSTRACT

This study aimed to assess the relationship between the metabolic effect after laparoscopic sleeve gastrectomy (LSG) in morbidly obese Japanese patients, with or without type 2 diabetes mellitus (T2DM), and improved pancreatic steatosis (PS). The study enrolled 27 morbidly obese Japanese patients who were undergoing LSG. Their clinical and metabolic effects were evaluated at baseline and six months after LSG. Pancreas volume (PV), pancreatic attenuation (PA), and splenic attenuation (SA) were measured using a 64-row computed tomography (CT). Changes in PV, PA-SA, and PA/SA were evaluated. The mean body-weight loss, body mass index loss, and percentage of excess weight loss (%EWL) were -34.4 kg (p < 0.001), -11.0 kg/m2 (p < 0.001), and 43.7%, respectively. The mean PV was 96.7 mL at baseline, and it decreased six months after LSG (-16.3mL, p < 0.001). The mean PA significantly increased six months after LSG (9.5 HU, p < 0.001). PA-SA (-23.2 HU vs. -13.3 HU, p = 0.003), and PA/SA (0.54 vs. 0.73, p < 0.001) also significantly increased six months after LSG. In T2DM patients, decreased PV correlated with decreased fasting blood sugar, decreased insulin, and reduced liver volume. In conclusion, PV significantly decreased after LSG in morbidly obese Japanese patients, and that decrease correlated with improvements in PS. In addition, PS plays an important role of development and progression of insulin resistance and T2DM.


Subject(s)
Gastrectomy/methods , Insulin Resistance/physiology , Obesity, Morbid/surgery , Pancreas/pathology , Adiponectin/blood , Adult , Blood Glucose , Body Mass Index , Female , Humans , Insulin/blood , Japan , Leptin/blood , Lipids/blood , Male , Middle Aged , Obesity, Morbid/diagnostic imaging , Obesity, Morbid/metabolism , Obesity, Morbid/pathology , Organ Size/physiology , Pancreas/diagnostic imaging , Retrospective Studies , Spleen/diagnostic imaging , Spleen/pathology , Tomography, X-Ray Computed , Treatment Outcome , Weight Loss/physiology
6.
Acta Endocrinol (Buchar) ; 13(2): 168-173, 2017.
Article in English | MEDLINE | ID: mdl-31149169

ABSTRACT

PURPOSE: We aimed to assess the relationship between the regional body fat distribution and insulin resistance and pancreas volume (PV) in type-2 diabetes (DM) patients. METHODS: Fifty-three consecutive type-2 diabetic and 51 non-diabetic patients matched by age, gender and body mass index (BMI) were enrolled. Subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), waist circumference, and PV were measured with computed tomography. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Patients with type-2 DM had significantly lower PV than non-diabetic individuals. HOMA-IR ranged from 0.74 to 6.24; and from 0.37 to 3.26, in type-2 DM patients and non-diabetics, respectively. VAT was positively correlated with HOMA-IR in two groups. There were inverse correlations between PV and VAT and VAT/SAT but only in diabetics. CONCLUSIONS: The VAT/SAT ratio may reflect the possible role of VAT to better understand the pathogenesis of obesity-related disorders in patients with type-2 DM.

7.
Diabetes Metab Res Rev ; 32(7): 675-684, 2016 10.
Article in English | MEDLINE | ID: mdl-26991675

ABSTRACT

BACKGROUND: Gluten-free (GF) diet alleviates type 1 diabetes in animal models and possibly in humans. We recently showed that fatty acid-induced insulin secretion is enhanced by enzymatically digested gluten (gliadin) stimulation in INS-1E insulinoma cells. We therefore hypothesized that GF diet would induce beta-cell rest and ameliorate type 2 diabetes. METHODS: C57BL/6JBomTac (B6) mice were fed a high-fat (HF), gluten-free high-fat (GF-HF), standard (STD) or gluten-free (GF) diet for 42 weeks. RESULTS: Short-term (6-24 weeks) GF-HF versus HF feeding impaired glucose tolerance and increased fasting glucose. Long-term (36-42 weeks) GF-HF versus HF feeding improved glucose tolerance and decreased fasting leptin. Mice fed a GF-HF versus HF diet for 42 weeks showed higher volumes of beta cells, islets and pancreas. The beta-cell volume correlated with the islet- and pancreas volume as well as body weight. GF-HF versus HF diet did not influence toll-like receptor 4 (Tlr4), interleukin 1 (IL-1), interleukin 6 (IL-6) or tumour necrosis factor-alpha (TNF-alpha) mRNA expression in intestine. STD versus GF feeding did not affect any parameter studied. CONCLUSIONS: Long-term feeding with GF-HF versus HF increases beta-cell volume and improves glucose tolerance in B6 mice. The mechanism may include beta-cell rest, but is unlikely to include TLR4 and proinflammatory cytokines in the intestine. Beta-cell volume correlates with pancreas volume and body weight, indicating that insulin secretion capacity controls pancreas volume. Thus, long-term GF diets may be beneficial for obese type 2 diabetes patients and trials should be performed. Copyright © 2016 John Wiley & Sons, Ltd.


Subject(s)
Diabetes Mellitus, Type 2/diet therapy , Diet, Gluten-Free , Disease Models, Animal , Glucose Intolerance/prevention & control , Insulin-Secreting Cells/cytology , Animals , Cell Size , Diabetes Mellitus, Type 2/metabolism , Glucose Tolerance Test , Insulin Resistance , Insulin-Secreting Cells/metabolism , Male , Mice , Mice, Inbred C57BL
8.
Pancreatology ; 14(4): 268-74, 2014.
Article in English | MEDLINE | ID: mdl-25062875

ABSTRACT

BACKGROUND/OBJECTIVES: To compare pancreas volume (PV) measurement using MRI-based planimetry in patients with Type 2 diabetes mellitus (DM) to PV in normoglycemic individuals. METHODS: Our institutional review board granted approval of this retrospective study with waiver of informed consent. We searched 2296 consecutive abdominal MRI studies performed at our hospital on patients with no pancreas pathology between September 1, 2010 and February 28, 2013, for those who also had a fasting plasma glucose and/or hemoglobin A1C within six months of the MRI examination. For those patients who met biochemical criteria for DM, we used medication and clinical records to confirm that 32 of these patients had Type 2 DM. The pancreas contours of 32 Type 2 diabetics and 50 normoglycemic individuals were then traced on non-gadolinium T1-weighted 3D fat suppressed gradient echo images by a radiologist trained in abdominal MRI to calculate PV. PV index (PVI) was calculated as PV/weight to adjust PV for each patient's weight. PVs and PVIs in both cohorts were compared using t-tests and regression models correcting for weight, age and gender. RESULTS: Patients with Type 2 DM had significantly lower PVs than normoglycemic individuals (72.7 ± 20.7 cm(3) versus 89.6 ± 22.7 cm(3), p < 0.001), and significantly lower PVIs (1.0 ± 0.3 cm(3)/kg versus 1.3 ± 0.3 cm(3)/kg, p < 0.001). Using regression models, we found that given the same age, weight and gender, the PV in a patient with Type 2 DM was 17.9 mL (20%) lower compared to a normoglycemic individual (p < 0.001). CONCLUSION: PV is reduced in Type 2 DM compared to normoglycemic individuals and can be measured using MRI without contrast injection.


Subject(s)
Diabetes Mellitus, Type 2/pathology , Magnetic Resonance Imaging/methods , Pancreas/pathology , Adult , Aged , Anatomy, Cross-Sectional , Blood Glucose/metabolism , Cohort Studies , Female , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Phantoms, Imaging , Retrospective Studies
9.
Obes Res Clin Pract ; 18(1): 56-63, 2024.
Article in English | MEDLINE | ID: mdl-38278667

ABSTRACT

OBJECTIVE: To comprehensively investigate the associations of pancreas fat content and size with circulating markers of iron metabolism. METHODS: A total of 116 individuals underwent magnetic resonance imaging and spectroscopy on a 3.0 Tesla scanner, exclusively for the purpose of the COSMOS research programme. Intra-pancreatic fat deposition, total pancreas volume, liver fat content, visceral and subcutaneous fat volumes were quantified. Plasma levels of hepcidin and ferritin were measured. Multiple linear regression analysis was conducted, adjusting for body mass index, age, and sex. RESULTS: Total intra-pancreatic fat deposition was inversely associated with hepcidin (ß = -0.54, 95 % confidence interval -1.02 to -0.07) whereas total pancreas volume was not associated with hepcidin (ß = 0.36, 95 % confidence interval -7.12 to 7.84) in the most adjusted model. Neither total intra-pancreatic fat deposition (ß = -0.03, 95 % confidence interval -0.39 to 0.33) nor total pancreas volume (ß = -1.02, 95 % confidence interval -6.67 to 4.63) was associated with ferritin in the most adjusted model. Subcutaneous fat, visceral fat, and liver fat were not associated with hepcidin. Subcutaneous fat was inversely associated with ferritin (ß = -0.06, 95 % CI -0.11 to -0.01) whereas visceral fat (ß = 0.05, 95 % CI -0.01 to 0.14) and liver fat (ß = 0.09, 95 % CI -0.04 to 0.34) were not associated with ferritin in the most adjusted model. CONCLUSIONS: Increased intra-pancreatic fat deposition, but not other fat depots, is associated with reduced circulating levels of hepcidin. Deranged iron metabolism may play a role in the pathogenesis of fatty change of the pancreas.


Subject(s)
Hepcidins , Pancreas , Humans , Pancreas/diagnostic imaging , Liver/diagnostic imaging , Ferritins , Iron
10.
Biomedicines ; 12(8)2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39200119

ABSTRACT

BACKGROUND: New-onset diabetes (NOD) has been identified as a high-risk factor for the early detection of pancreatic ductal adenocarcinoma (PDAC). The role of tumor volume and remnant pancreas volume (RPV) in the progression from normal to NOD in PDAC patients is not fully illustrated yet. METHODS: In this cross-sectional study, glycemic metabolism traits of 95 PDAC patients before pancreatic surgery were described and compared with chronic pancreatitis and type 2 diabetes mellitus patients based on the oral glucose tolerance test. The remnant RPV and tumor volume, calculated by three-dimensional reconstruction of radiological images, were included in the ordinal logistic regression models. RESULTS: The prevalence of NOD was high among PDAC patients (38.9%). However, normal glucose tolerance (NGT) or prediabetes mellitus status were present as more than half (24/44) of advanced tumor stage patients. Indexes reflecting beta-cell function but not insulin sensitivity gradually worsened from NGT to NOD patients (all p < 0.05). The remnant pancreas volume (RPV) was identified as a potential protective factor for diabetes secondary to PDAC (odds ratio 0.95, 95% CI [0.92, 0.97], p < 0.001). CONCLUSIONS: Reduced RPV causing beta-cell dysfunction might be one of the mechanisms of NOD secondary to PDAC. Subjects with sufficient pancreas volume could not be detected earlier when regarding patients with NOD as the population at risk for PDAC.

11.
Metabol Open ; 19: 100250, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37396402

ABSTRACT

Aims/introduction: There have been few reports about the longitudinal changes in pancreas volume (PV) or pancreatic steatosis (PS) in response to obesity. In this longitudinal analysis using health check-up data, we explored changes in PV, PS and glucose metabolic indices that occurred after weight gain in Japanese without diabetes. Materials/methods: Clinical data on 37 Japanese subjects with a ≥1 kg/m2 increase in body mass index between two health check-ups and without diabetes were collected. PV, pancreas attenuation (PA) and splenic attenuation (SA) were evaluated using computed tomography (CT) images. The pancreas area was outlined by hand in multiple images with slice thickness of 2 mm, and the PV was computed by summing these areas. PS was defined as the difference between SA and PA (SA-PA). Medical records were collected, including findings on immunoreactive insulin (IRI), homeostasis model assessment of insulin resistance (HOMA-R) and beta cell function (HOMA-ß). Paired t-test and Spearman's correlation coefficient were used in the analyses. Results: The median follow-up period was 21.1 months and the mean BMI was increased from 25.5 ± 3.3 kg/m2 to 27.0 ± 3.3 kg/m2. PV (53.5 ± 15.9 cm3 vs. 56.2 ± 16.4 cm3) and SA-PA (8.7 ± 9.1 HU vs. 13.6 ± 10.9 HU) increased significantly after weight gain (both, P < 0.001). There were significant increases of IRI and HOMA-R with the weight gain (both, P < 0.05), whereas HOMA-ß exhibited only a nonsignificant trend of increase (55.4% (41.5-65.5) vs. 56.8% (46.2-83.7), P = 0.07). Conclusions: Both PV and PS were increased longitudinally with weight gain in Japanese without diabetes.

12.
J Clin Endocrinol Metab ; 108(10): 2699-2707, 2023 09 18.
Article in English | MEDLINE | ID: mdl-36938587

ABSTRACT

CONTEXT: Individuals with type 1 diabetes (T1D) have a smaller pancreas, but longitudinal changes in pancreas size and shape are unclear. OBJECTIVE: We monitored changes in pancreas size and shape after diagnosis with T1D. DESIGN: We conducted a prospective cohort study at an academic medical center between 2014 and 2022. PATIENTS AND HEALTHY CONTROLS: Individuals with T1D (n = 91) or controls (n = 90) underwent magnetic resonance imaging (MRI) of the pancreas, including longitudinal MRI in 53 individuals with new-onset T1D. INTERVENTION: Interventions included MRI and continuous glucose monitoring (CGM). MAIN OUTCOME MEASURES: Pancreas size and shape were measured from MRI. For participants who used CGM, measures of glycemic variability were calculated. RESULTS: On longitudinal imaging, pancreas volume and pancreas volume index normalized for body weight declined during the first year after diagnosis. Pancreas volume index continued to decline through the fifth year after diagnosis. A cross-sectional study of individuals with diabetes duration up to 60 years demonstrated that pancreas size in adults negatively correlated with age and disease duration, whereas pancreas volume and pancreas volume index remained stable in controls. Pancreas volume index correlated inversely with low blood glucose index, a measure of risk for hypoglycemia. Pancreas shape was altered in individuals with T1D and further diverged from controls over the first 5 years after diagnosis. Pancreas size and shape are altered in nondiabetic individuals at genetic risk for T1D. Combined pancreas size and shape analysis better distinguished the pancreas of individuals with T1D from controls than size alone. CONCLUSIONS: Pancreas size declines most rapidly near the clinical diagnosis of T1D and continues to decline throughout adulthood. Declines in pancreas size are accompanied by changes in pancreas shape.


Subject(s)
Diabetes Mellitus, Type 1 , Adult , Humans , Blood Glucose , Blood Glucose Self-Monitoring/methods , Cross-Sectional Studies , Prospective Studies , Pancreas/diagnostic imaging , Magnetic Resonance Imaging
13.
Obes Facts ; 15(1): 70-82, 2022.
Article in English | MEDLINE | ID: mdl-34753126

ABSTRACT

INTRODUCTION: Ectopic fat deposition in the pancreas is involved in the pathogenesis of metabolic sequelae following an attack of pancreatitis. However, its relationship with the exocrine pancreas has never been explored in this setting. The aim was to investigate the associations between intra-pancreatic fat deposition (IPFD), pancreas size, and pancreatic enzymes. METHODS: This cross-sectional study recruited individuals with a history of acute pancreatitis and healthy controls. All participants underwent 3T magnetic resonance imaging, from which IPFD, total pancreas volume (TPV), and pancreas diameters (across the head, body, and tail) were measured independently by 2 raters in a blinded fashion. Circulating levels of pancreatic amylase, pancreatic lipase, and chymotrypsin were measured in a fasted state. A series of linear regression analyses was conducted, accounting for possible confounders. RESULTS: A total of 108 individuals with pancreatitis and 60 healthy controls were studied. There was a statistically significant difference in IPFD (p < 0.001), but not in TPV (p = 0.389), between the groups. In the post-pancreatitis group, IPFD was significantly inversely associated with pancreas tail diameter (ß = -0.736, p = 0.036 in the most adjusted model). In the control group, IPFD was significantly inversely associated with TPV (ß = -3.557, p = 0.026 in the most adjusted model). Levels of pancreatic amylase were significantly directly associated with pancreas tail diameter in the post-pancreatitis group (ß = 3.891, p = 0.042 in the most adjusted model), whereas levels of pancreatic lipase were significantly inversely associated with TPV in the control group (ß = -10.533, p = 0.024 in the most adjusted model). CONCLUSION: Increased IPFD in individuals after an attack of pancreatitis is associated with reduced pancreas tail diameter, which is in turn associated with reduced circulating levels of pancreatic amylase. The relationship between IPFD and the exocrine pancreas warrants further investigations.


Subject(s)
Pancreatitis , Acute Disease , Cross-Sectional Studies , Humans , Magnetic Resonance Imaging/methods , Pancreas/diagnostic imaging , Pancreas/metabolism , Pancreas/pathology , Pancreatitis/complications , Pancreatitis/diagnostic imaging
14.
Acta Diabetol ; 56(12): 1239-1245, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31423559

ABSTRACT

Immune checkpoint inhibitors (CPI) are increasingly being used in oncology, and many autoimmune side effects have been described. Diabetes mellitus (DM) has been reported in approximately 1% of subjects treated with programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors, alone or in association with CTLA-4 inhibitors. In the present mini-review, we aimed to describe different clinical pictures and pathophysiology associated with these forms of diabetes. Data on CPI-related DM was gathered from the largest case series in the literature and from our centre dedicated to immunotherapy complications (ImmuCare-Hospices Civils de Lyon). Most cases are acute autoimmune insulin-dependent diabetes which are similar to fulminant diabetes (extremely acute onset with concomitant near-normal HbA1c levels). Other cases, however, have a phenotype close to type 2 diabetes or appear as a decompensation of previously known type 2 diabetes. The occurrence of diabetes can also be a complication of autoimmune pancreatitis induced by CPI use. Finally, two cases of diabetes in a context of autoimmune lipoatrophy have recently been described. Regarding the wide variety of CPI-induced diabetes, the discovery of a glucose disorder under CPI should motivate specialised care for aetiological diagnosis and appropriate treatment.


Subject(s)
Cell Cycle Checkpoints , Diabetes Mellitus, Type 2/chemically induced , Immunotherapy/adverse effects , Protein Kinase Inhibitors/adverse effects , Autoimmune Diseases/chemically induced , Autoimmune Diseases/epidemiology , Autoimmune Diseases/etiology , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/immunology , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/immunology , Diabetes Mellitus, Lipoatrophic/chemically induced , Diabetes Mellitus, Lipoatrophic/epidemiology , Diabetes Mellitus, Lipoatrophic/immunology , Diabetes Mellitus, Type 1/chemically induced , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/immunology , Humans , Protein Kinase Inhibitors/therapeutic use
15.
Acta Diabetol ; 56(4): 441-448, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30284618

ABSTRACT

AIMS: Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors restore antitumor immunity, but many autoimmune side-effects have been described. Diabetes mellitus is a rare complication, and little data concerning its pathophysiology and phenotype have been published. This study aimed to describe both pancreatic endocrine and exocrine functions, immunological features and change in pancreas volume in subjects with diabetes mellitus induced by PD-1 and PD-L1 inhibitors. METHODS: We analyzed the data of six subjects treated with immunotherapy who presented acute diabetes. RESULTS: There were five men and one woman. Median age was 67 years (range 55-83). Three subjects were treated with nivolumab, two with pembrolizumab and one with durvalumab. Median time to diabetes onset after immunotherapy initiation was 4 months (range 2-13). Four patients presented fulminant diabetes (FD); none of these had type 1 diabetes (T1D)-related autoantibodies, none of them had T1D or FD-very high-risk HLA class II profiles. The bi-hormonal endocrine and exocrine pancreatic failure previously reported for one FD patient was not found in other FD subjects, but glucagon response was blunted in another FD patient. Pancreas volume was decreased at diabetes onset in 2 FD patients, and all patients presented a subsequent decrease of pancreas volume during follow-up. CONCLUSIONS: In the patients presented herein, immunotherapy-induced diabetes was not associated with T1D-related autoantibodies. The hormonal and morphological analysis of the pancreatic glands of these six cases contributes to the understanding of the underlying and probably heterogeneous mechanisms. There is a need to find biomarkers to identify patients at risk to develop these new forms of diabetes at early stages of the process to prevent ketoacidosis and to evaluate preventive strategies.


Subject(s)
B7-H1 Antigen/immunology , Diabetes Mellitus/chemically induced , Immunotherapy/adverse effects , Islets of Langerhans/drug effects , Pancreas, Exocrine/drug effects , Programmed Cell Death 1 Receptor/immunology , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Autoantibodies/blood , B7-H1 Antigen/antagonists & inhibitors , Diabetes Mellitus/pathology , Female , Humans , Islets of Langerhans/metabolism , Islets of Langerhans/pathology , Male , Middle Aged , Nivolumab/adverse effects , Pancreas, Exocrine/metabolism , Pancreas, Exocrine/pathology , Phenotype , Programmed Cell Death 1 Receptor/antagonists & inhibitors
16.
Expert Rev Gastroenterol Hepatol ; 12(8): 757-766, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29972077

ABSTRACT

INTRODUCTION: The pancreas plays a central role in metabolism and is involved in the pathogenesis of several diseases. Pancreas volume is a holistic quantitative measure of pancreas size but the clinical relevance of pancreas volumetry is poorly understood. Areas covered: The aim was to systematically review studies in adults that used computed tomography or magnetic resonance imaging to measure pancreas volume in health and disease, to determine normal pancreas volume range, and to quantify changes in pancreas volume that are associated with disease. Expert commentary: The normal pancreas volume range in adults is 71-83 cm3, with no statistically significant difference between men and women. Type 2 diabetes and type 1 diabetes are associated with a progressively reduced pancreas volume. Overweight and obesity are associated with a progressively increased pancreas volume. There is a paucity of studies on pancreas volume in the setting of diseases of the exocrine pancreas, which should become a research priority in the future.


Subject(s)
Pancreas/anatomy & histology , Pancreas/pathology , Pancreatic Diseases/diagnostic imaging , Diabetes Complications/complications , Healthy Volunteers , Humans , Magnetic Resonance Imaging , Organ Size , Overweight/complications , Pancreas/diagnostic imaging , Pancreatic Diseases/etiology , Pancreatic Diseases/pathology , Reference Values , Tomography, X-Ray Computed
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