RESUMEN

Diabetes mellitus type 3 refers to diabetes secondary to an existing disease or condition of the exocrine pancreas and is an uncommon cause of diabetes occurring due to pancreatogenic pathology. It accounts for 15-20% of diabetic patients in Indian and Southeast Asian continents. This is case report of a rare case of type 3 diabetes mellitus (T3DM) presenting with diabetic ketoacidosis (DKA). The patient was admitted for DKA along with complaint of hyperglycemia, blood glucose of 405 mg/dl with HbA1c level of 13.7%. Computed tomography evidence revealed chronic calcific pancreatitis with intraductal calculi and dilated pancreatic duct.

Asunto(s)

Calcinosis , Cálculos , Cetoacidosis Diabética , Conductos Pancreáticos , Pancreatitis Crónica , Humanos , Cetoacidosis Diabética/complicaciones , Cetoacidosis Diabética/diagnóstico , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/diagnóstico por imagen , Cálculos/complicaciones , Cálculos/diagnóstico por imagen , Cálculos/diagnóstico , Conductos Pancreáticos/patología , Conductos Pancreáticos/diagnóstico por imagen , Calcinosis/etiología , Calcinosis/diagnóstico , Calcinosis/complicaciones , Calcinosis/diagnóstico por imagen , Masculino , Adulto , Tomografía Computarizada por Rayos X

RESUMEN

Pancreatic surgery units undertake several complex operations, albeit with considerable morbidity and mortality, as is the case for the management of complicated acute pancreatitis or chronic pancreatitis. The centralisation of pancreatic surgery services, with the development of designated large-volume centres, has contributed to significantly improved outcomes. In this editorial, we discuss the complex associations between diabetes mellitus (DM) and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis, highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic services. Type 3c pancreatogenic DM, refers to DM developing in the setting of exocrine pancreatic disease, and its identification and management can be challenging, while the glycaemic control of such patients may affect their course of treatment and outcome. Adequate preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative period. The incidence of new onset diabetes after pancreatic resection is widely variable in the literature, and depends on the type and extent of pancreatic resection, as is the case with pancreatic parenchymal loss in the context of severe pancreatitis. Early involvement of a specialist diabetes team is essential to ensure a holistic management. In the current era, large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery, with inclusion of provisions for optimisation of the perioperative glycaemic control, to improve outcomes. While various guidelines are available to aid perioperative management of DM, auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required improvement. The need for perioperative support of diabetic patients by specialist diabetes teams is uniformly underlined, a fact that becomes clearly more prominent at all different stages in the setting of pancreatic surgery and the management of complex pancreatitis. Therefore, pancreatic surgery and tertiary pancreatitis services must be designed with a provision for support from specialist diabetes teams. With the ongoing accumulation of evidence, it would be reasonable to consider the design of specific guidelines for the glycaemic management of these patients.

RESUMEN

Post-acute pancreatitis diabetes (PAPD) is the second most common type of diabetes below type 2 diabetes mellitus. Due to the boom in research on this entity carried out during the last decade, its recognition has increased. However, much of the medical community still does not recognize it as a medium and long-term complication of acute pancreatitis (AP). Recent prospective cohort studies show that its incidence is about 23% globally and 34.5% in patients with severe AP. With the overall increase in the incidence of AP this complication will be certainly seen more frequently. Due to its high morbidity, mortality and difficult control, early detection and treatment are essential. However, its risk factors and pathophysiological mechanisms are not clearly defined. Its diagnosis should be made excluding pre-existing diabetes and applying the criteria of the American Diabetes Association after 90 d of resolution of one or more AP episodes. This review will show the evidence published so far on the incidence and prevalence, risk factors, possible pathophysiological mechanisms, clinical outcomes, clinical characteristics and preventive and corrective management of PAPD. Some important gaps needing to be clarified in forthcoming studies will also be discussed.

Asunto(s)

Diabetes Mellitus Tipo 2 , Pancreatitis , Humanos , Pancreatitis/complicaciones , Pancreatitis/diagnóstico , Pancreatitis/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Enfermedad Aguda , Factores de Riesgo

RESUMEN

Diabetes mellitus (DM) is a clinical syndrome that is manifested by hyperglycemia. Out of the numerous causes of diabetes, an uncommon cause is chronic pancreatic disease due to destruction of islet cells. Diabetic ketoacidosis is a rare entity in such cases as alpha cells are destroyed along with beta cells, which causes lack of glucagon that is responsible for ketogenesis. We hereby report a case of a 55-year-old woman with history of gall stone disease and who presented to the emergency department with multiple episodes of non-bilious, non-blood mixed vomiting along with increased frequency of micturition on background of malaise and anorexia along with significant weight loss. Her capillary blood glucose was 501 mg/dl, arterial blood gas showed high anion gap metabolic acidosis, and urine ketone were largely positive. Thus, she was diagnosed with diabetic ketoacidosis. She was admitted to the high dependency unit and her condition was treated along the lines of diabetic ketoacidosis. Further evaluation showed high HbA1c values without previous history of diabetes and computed tomography of the abdomen revealed presence of chronic pancreatitis. Though being a rare entity, this case outlines that DM3c can present with diabetic ketoacidosis (DKA); thus, early diagnosis and management are crucial to prevent mortality.

RESUMEN

Background/Objective: Total pancreatectomy is performed for pain relief in chronic pancreatitis. Concomitant autologous islet cell transplantation can be performed to improve glycemic control. We report the case of a patient with chronic pancreatitis who underwent a total pancreatectomy with autologous islet cell transplantation with increasing insulin requirements and its association with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder. Case Report: A 40-year-old woman presented with abdominal pain and had elevated levels of serum lipase. She was treated for acute pancreatitis. In the subsequent 2 years, she had 4 additional episodes of pancreatitis and eventually developed chronic abdominal pain. She underwent total pancreatectomy for pain relief with autologous intrahepatic islet cell transplantation. She experienced repeated episodes of pneumonia and underwent screening for cystic fibrosis, which showed a 7T/7T polymorphic variant at CFTR intron 8. The follow-up at 8 years after procedure showed increasing hemoglobin A1c levels despite increasing insulin use with multiple hospitalizations for hyperglycemia. The patient was transitioned to continuous subcutaneous insulin infusion with improvement in hemoglobin A1c levels. Discussion: Chronic pancreatitis can be a manifestation of an undiagnosed CFTR-related disorder, which in this case was followed by total pancreatectomy. Autologous islet cell transplantation was performed with declining postprocedural glycemic control. Interval failure of the transplanted islets is present in up to two thirds of the patients but is not affected by the presence of cystic fibrosis. Conclusion: A gradual decline in glycemic control may be expected in patients with autologous islet cell transplantation and can be improved with the use of continuous subcutaneous insulin infusion.

RESUMEN

Malnutrition in patients with chronic pancreatitis is common, but its evaluation is often missed in clinical practice. Pancreatic exocrine insufficiency is the single most important cause of malnutrition; therefore, it needs to be screened for and treated appropriately. Specific diet regimens in patients suffering from chronic pancreatitis are rarely reported in the literature. Patients suffering from chronic pancreatitis have a higher demand for energy but a lower caloric intake secondary to pancreatic exocrine insufficiency, combined with the malabsorption of liposoluble vitamin and micronutrients, which needs be corrected by appropriate dietary counselling. Diabetes is frequently observed in chronic pancreatitis and classified as type 3c, which is characterized by low levels of both serum insulin and glucagon; therefore, there is a tendency towards hypoglycaemia in patients treated with insulin. Diabetes contributes to malnutrition in chronic pancreatitis. Strategies to treat exocrine and endocrine insufficiency are important to achieve better control of the disease.

Asunto(s)

Diabetes Mellitus , Insuficiencia Pancreática Exocrina , Insulinas , Desnutrición , Pancreatitis Crónica , Humanos , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/terapia , Diabetes Mellitus/etiología , Diabetes Mellitus/terapia , Desnutrición/complicaciones , Insuficiencia Pancreática Exocrina/complicaciones , Insuficiencia Pancreática Exocrina/terapia , Apoyo Nutricional

RESUMEN

Acute pancreatitis (AP) is an acute inflammation of the pancreas associated with high morbidity and mortality. Endocrine pancreatic insufficiency secondary to AP has drawn increasing attention in recent years. The aim of this paper is to analyze the available clinical and experimental literature to determine the cause and effect relationship of diabetes type 3c (T3cDM; pancreatogenic diabetes) after acute pancreatitis. The clinico-pathological features and management challenges of pancreatogenic diabetes overlap with other secondary causes of diabetes. A complex pathogenesis involving pancreatic exocrine insufficiency, dysfunction of insulin secretion, and insulin resistance is likely the cause of T3cDM after AP. To obtain an improved understanding of the pathophysiology of diabetes after AP, more research is now needed to understand the risk of complications related to the pancreas and diabetes in these patients.

RESUMEN

Background: Total pancreatectomy (TP) has been increasingly performed in recent years. However, studies on diabetes management after TP during different postoperative periods are still limited. Objectives: This study aimed to evaluate the glycemic control and insulin therapy of patients undergoing TP during the perioperative and long-term follow-up period. Methods: Ninety-three patients undergoing TP for diffuse pancreatic tumors from a single center in China were included. Based on preoperative glycemic status, patients were divided into three groups: nondiabetic group (NDG, n = 41), short-duration diabetic group (SDG, preoperative diabetes duration ≤12 months, n = 22), and long-duration diabetic group (LDG, preoperative diabetes duration >12 months, n = 30). Perioperative and long-term follow-up data, including the survival rate, glycemic control, and insulin regimens, were evaluated. Comparative analysis with complete insulin-deficient type 1 diabetes mellitus (T1DM) was conducted. Results: During hospitalization after TP, glucose values within the target (4.4-10.0 mmol/L) accounted for 43.3% of the total data, and 45.2% of the patients experienced hypoglycemic events. Patients received continuous intravenous insulin infusion during parenteral nutrition at a daily insulin dose of 1.20 ± 0.47 units/kg/day. In the long-term follow-up period, glycosylated hemoglobin A1c levels of 7.43 ± 0.76% in patients following TP, as well as time in range and coefficient of variation assessed by continuous glucose monitoring, were similar to those in patients with T1DM. However, patients after TP had lower daily insulin dose (0.49 ± 0.19 vs 0.65 ± 0.19 units/kg/day, P < 0.001) and basal insulin percentage (39.4 ± 16.5 vs 43.9 ± 9.9%, P = 0.035) than patients with T1DM, so did those using insulin pump therapy. Whether in the perioperative or long-term follow-up period, daily insulin dose was significantly higher in LDG patients than in NDG and SDG patients. Conclusions: Insulin dose in patients undergoing TP varied according to different postoperative periods. During long-term follow-up, glycemic control and variability following TP were comparable to complete insulin-deficient T1DM but with fewer insulin needs. Preoperative glycemic status should be evaluated as it could guide insulin therapy after TP.

Asunto(s)

Diabetes Mellitus Tipo 1 , Humanos , Pancreatectomía , Automonitorización de la Glucosa Sanguínea , Estudios de Cohortes , Glucemia , Insulina/uso terapéutico , Glucosa

RESUMEN

INTRODUCTION: Diabetes of the exocrine pancreas (DEP; a.k.a. pancreatic diabetes or pancreatogenic diabetes or type 3c diabetes mellitus or T3cDM) refers to different diabetes types resulting from disorders of the exocrine pancreas. DEP is characterized by the structural and functional loss of glucose-normalizing insulin secretion in the context of exocrine pancreatic dysfunction. Among these forms, new-onset diabetes mellitus secondary to total pancreatectomy (TP) has unique pathophysiological and clinical features, for which we propose a new nomenclature such as post-total pancreatectomy diabetes mellitus (PTPDM). AREAS COVERED: TP results in the complete loss of pancreatic parenchyma, with subsequent absolute insulinopenia and lifelong need for exogenous insulin therapy. Patients with PTPDM also exhibit deficiency of glucagon, amylin and pancreatic polypeptide. These endocrine abnormalities, coupled with increased peripheral insulin sensitivity, deficiency of pancreatic enzymes and TP-related modifications of gastrointestinal anatomy, can lead to marked glucose variability and increased risk of iatrogenic (insulin-induced) severe hypoglycemic episodes ('brittle diabetes'). EXPERT OPINION: We believe that diabetes mellitus secondary to TP should not be included in the DEP spectrum in light of its peculiar pathophysiological and clinical features. Therefore, we propose a new classification for this entity, that would likely provide more accurate prognosis and treatment strategies.

Asunto(s)

Diabetes Mellitus , Páncreas Exocrino , Humanos , Pancreatectomía/efectos adversos , Pancreatectomía/métodos , Páncreas , Insulina/uso terapéutico , Glucosa , Diabetes Mellitus/terapia

RESUMEN

Diabetes mellitus type 3c (DM3c) is a diabetes caused by pancreatic pathology. It occurs due to the destruction of the endocrine islet cells. Diabetes diagnosed at the age of 20-30 years share a common dilemma in segregating between the type of diabetes the patient has, as its management varies depending on the type of diabetes the patient is harboring. However, insulin remains the treatment of choice in later decades as the pancreatic reserves of beta cells exhaust, although it takes decades to happen. We report a case of a woman who was diagnosed with diabetes mellitus at the age of 26, was on oral hypoglycemic agents (OHA), and was shifted to insulin therapy as she became non-responsive to OHA in a short span of six years, which was alarming. The patient presented to us with the chief complaints of recurrent abdominal pain that aggravated on taking meals and was associated with multiple episodes of vomiting for two months. Blood gas analysis on admission had no evidence of metabolic acidosis, urine ketones were negative, and a random blood sugar test (RBS:202) excluded the possibility of diabetic ketoacidosis. Serum amylase and serum lipase were within normal limits. Contrast-enhanced computed tomography (CECT) of the abdomen was suggestive of the atrophic pancreas with the non-dilated main pancreatic duct. Magnetic resonance cholangiopancreatography (MRCP) was done to rule out the congenital anomalies of the pancreas responsible for chronic pancreatitis, which showed no structural abnormalities. During our clinical workup, we postulated that the diabetes she was diagnosed with at the age of 26 was DM3c, i.e., pancreatogenic diabetes. The rapid shift of patients from OHA to subcutaneous insulin in a short span must be alarming to the physician managing diabetes and needs extensive workup to look upon the etiology of the same.

RESUMEN

BACKGROUND: Acute pancreatitis (AP) is known to result in endocrine dysfunction (prediabetes, diabetes). The objective of this study was to determine the temporal incidence of endocrine dysfunction after onset of AP and determine the risk factors in Indian patients. METHODS: In this prospective study, enrolled patients diagnosed with AP between February 2019 and May 2019 were followed at 3, 6, and 12 months until May 2020. Patients with recurrent AP, chronic pancreatitis, and pre-existing endocrine dysfunction were excluded. Demographic and disease severity (clinical, laboratory, and radiological) data were recorded. Mann-Whitney U and Chi-square tests were used to compare groups. Temporal trend for development of endocrine dysfunction was evaluated using the Extended Mantel Haenszel Chi-square test for trend. Logistic regression was used to identify independent risk factors. RESULTS: Eighty-six patients (males 66, median [IQR] age 33.0 [26.0-44.2] years) who fulfilled enrolment criteria were finally analyzed. The most common etiology was alcohol (n=31 [36%]) followed by gallstones (n=17 [19.8%]). The proportion of patients with moderately severe acute pancreatitis and severe AP were 59.3% and 15.1%, respectively. Overall, the frequency of prediabetes and diabetes increased temporally across the follow-up period. These were 2 (2.33%) and 1 (1.16%) at 3 months, 11 (12.8%) and 5 (5.81%) at 6 months, and 20 (23.2%) and 9 (10.5%) at 1 year, respectively. On multivariable logistic regression, intervention for walled-off necrosis (WON) emerged as the single independent risk factor for endocrine dysfunction (odds ratio 9.01 [2.3-35.5]; p=0.002). CONCLUSIONS: Endocrine dysfunction is frequent after an episode of AP. Intervention for WON is an independent risk factor for endocrine dysfunction.

Asunto(s)

Diabetes Mellitus , Pancreatitis , Estado Prediabético , Masculino , Humanos , Adulto , Pancreatitis/epidemiología , Pancreatitis/etiología , Pancreatitis/diagnóstico , Estado Prediabético/etiología , Estado Prediabético/complicaciones , Estudios Prospectivos , Enfermedad Aguda , Estudios de Seguimiento , Diabetes Mellitus/epidemiología , Factores de Riesgo

RESUMEN

BACKGROUND: Chronic pancreatitis (CP) is defined according to the recently proposed mechanistic definition as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. METHODS: The clinical practice guidelines for CP in Japan were revised in 2021 based on the 2019 Japanese clinical diagnostic criteria for CP, which incorporate the concept of a pathogenic fibro-inflammatory syndrome in the pancreas. In this third edition, clinical questions are reclassified into clinical questions, background questions, and future research questions. RESULTS: Based on analysis of newly accumulated evidence, the strength of evidence and recommendations for each clinical question is described in terms of treatment selection, lifestyle guidance, pain control, treatment of exocrine and endocrine insufficiency, and treatment of complications. A flowchart outlining indications, treatment selection, and policies for cases in which treatment is ineffective is provided. For pain control, pharmacological treatment and the indications and timing for endoscopic and surgical treatment have been updated in the revised edition. CONCLUSIONS: These updated guidelines provide clinicians with useful information to assist in the diagnosis and treatment of CP.

Asunto(s)

Pancreatitis Crónica , Endoscopía/efectos adversos , Humanos , Dolor , Páncreas/patología , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/etiología , Pancreatitis Crónica/terapia , Factores de Riesgo

RESUMEN

AIMS: The early distinction of pancreatic cancer associated diabetes (PaCDM) in patients with elderly diabetes is critical. However, PaCDM and type 2 diabetes mellitus (T2DM) remain indistinguishable. We aim to address the differences between the pancreatic and gut endocrine hormones of patients with PaCDM and T2DM. METHODS: A total of 44 participants underwent mixed meal tolerance test (MMTT). Fasting and postprandial concentrations of insulin, C-peptide, glucagon, pancreatic polypeptide (PP), glucagon-like peptide-1 (GLP-1), and gastric inhibitory peptide (GIP) were measured. Insulin sensitivity and secretion indices were calculated. One-way ANOVA with post-hoc analysis was used for statistical analysis. RESULTS: Insulin and C-peptide responses to MMTT were blunted in PaCDM patients compared with T2DM. Baseline concentrations and AUCs differed. PaCDM patients showed lower insulin secretion capacity but better insulin sensitivity than T2DM patients. The peak concentration and AUC of PP in T2DM group were higher than healthy controls, but in accordance with PaCDM. PaCDM patients presented lower baseline GLP-1 concentration than T2DM patients. No between-group differences were found for glucagon and GIP. CONCLUSIONS: PaCDM patients had a lower baseline and postprandial insulin and C-peptide secretion than T2DM patients. Reduced insulin secretion and improved peripheral sensitivity were found in PaCDM patients compared with T2DM.

Asunto(s)

Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Neoplasias Pancreáticas , Anciano , Glucemia , Péptido C , Diabetes Mellitus Tipo 2/complicaciones , Polipéptido Inhibidor Gástrico , Glucagón , Péptido 1 Similar al Glucagón , Humanos , Insulina , Neoplasias Pancreáticas

RESUMEN

BACKGROUND & AIMS: Elevations in fasting blood glucose are observed prior to the development of pancreatic ductal adenocarcinoma (PDAC). Our aim was to describe glycemic and weight changes that occur prior to PDAC diagnosis in a diverse population. METHODS: We conducted a case-control study comparing patients with PDAC with matched controls between January 2011 and November 2019 at a tertiary care institution. Normally distributed variables were compared using t tests, and the Wilcoxon rank sum test was used for non-normally distributed variables; logistic regression was used to estimate odds of PDAC based on changes over time in hemoglobin A1c (HbA1c) and body mass index (BMI), controlling for appropriate confounders. RESULTS: A total of 4626 patients met inclusion criteria: 1542 cases and 3084 controls; the median age was 69.3 years, and 2487 (53.8%) were male; 751 cases (48.7%) were non-Hispanic white. In the 3 years prior to diagnosis, HbA1c was higher in patients with PDAC compared with controls (P ≤ .02 for all); a similar trend was seen for glucose values. BMI was greater for patients with PDAC for all study periods, except 0 to 6 months prior to cancer diagnosis when BMI was lower (P < .01 for all). The change in BMI (ΔBMI) of cases at 1 year and 6 months before diagnosis was -0.59 and -1.21 when compared with -0.08 and 0.03 for controls (P < .01 for both). Multivariable logistic regression demonstrated that HbA1c slope (adjusted odds ratio, 1.33; 95% confidence interval, 1.01-1.76) and BMI slope (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87) were predictors of PDAC. CONCLUSION: Glycemic elevations and weight loss predate PDAC diagnosis. These metabolic changes may suggest an underlying PDAC.

Asunto(s)

Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Anciano , Glucemia/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/epidemiología , Estudios de Casos y Controles , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiología , Pérdida de Peso , Neoplasias Pancreáticas

RESUMEN

Nonalcoholic pancreatogenic diabetes mellitus (type 3c DM) is an often-misdiagnosed entity usually seen in young men of tropical countries. Although most of the patients present with abdominal pain and symptoms of exocrine pancreatic insufficiency, there is still a subset that does not present with these classical symptoms, which emphasizes the need for special diagnostic considerations. The significance of identifying this subset of diabetic lies not only in the change in management of the disease but also in early detection for pancreatic carcinoma that is more common among those patients. In our case, ultrasound with X-ray played a vital role in diagnosis, prompting us to consider it as an essential part of the investigation panel in all newly diagnosed nonobese diabetic individuals.

RESUMEN

Background: Type 3c diabetes mellitus (T3cDM) usually occurs because of a variety of exocrine pancreatic diseases with varying mechanisms, which eventually lead to secondary pancreatic endocrine insufficiency i.e. hyperglycemia. Phenomenology: A man suffering from previously undiagnosed T3cDM presenting with subacute onset hemifacial spasm. Educational value: This case emphasizes the importance of rapid bedside measurement of capillary blood glucose in patients presenting with acute to subacute onset movements disorders irrespective of their past glycemic status.

Asunto(s)

Diabetes Mellitus , Espasmo Hemifacial , Enfermedades Pancreáticas , Espasmo Hemifacial/diagnóstico por imagen , Espasmo Hemifacial/etiología , Humanos , Masculino

RESUMEN

The association of pancreatic cancer with type 2 diabetes mellitus was investigated by 1H NMR metabolomic analysis of blood plasma. Concentration data of 58 metabolites enabled discrimination of pancreatic cancer (PC) patients from healthy controls (HC) and long-term type 2 diabetes mellitus (T2DM) patients. A panel of eight metabolites was proposed and successfully tested for group discrimination. Furthermore, a prediction model for the identification of at-risk individuals for future development of pancreatic cancer was built and tested on recent-onset diabetes mellitus (RODM) patients. Six of 59 RODM samples were assessed as PC with an accuracy of more than 80%. The health condition of these individuals was re-examined, and in four cases, a correlation to the prediction was found. The current health condition can be retrospectively attributed to misdiagnosed pancreatogenic diabetes or to early-stage pancreatic cancer.

Asunto(s)

Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Neoplasias Pancreáticas , Diabetes Mellitus Tipo 2/diagnóstico , Detección Precoz del Cáncer , Humanos , Metabolómica , Neoplasias Pancreáticas/diagnóstico , Espectroscopía de Protones por Resonancia Magnética , Estudios Retrospectivos

RESUMEN

BACKGROUND: Studies evaluating endocrine and exocrine functions in fibrocalculous pancreatic diabetes (FCPD) are scarce. METHODS: Insulin, C-peptide, glucagon, incretin hormones (glucagon-like peptide 1 [GLP-1] and gastric inhibitory peptide [GIP]), and dipeptidyl peptidase IV (DPP-IV) were estimated in patients with FCPD (n = 20), type 2 diabetes mellitus (T2DM) (n = 20), and controls (n = 20) in fasting and 60 minutes after 75 g glucose. RESULTS: Fasting and post-glucose C-peptide and insulin in FCPD were lower than that of T2DM and controls. Plasma glucagon decreased after glucose load in controls (3.72, 2.29), but increased in T2DM (4.01, 5.73), and remained unchanged in FCPD (3.44, 3.44). Active GLP-1 (pmol/L) after glucose load increased in FCPD (6.14 to 9.72, P = <.001), in T2DM (2.87 to 4.62, P < .001), and in controls (3.91 to 6.13, P < .001). Median active GLP-1 in FCPD, both in fasting and post-glucose state (6.14, 9.72), was twice that of T2DM (2.87, 4.62) and 1.5 times that of controls (3.91, 6.13) (P < .001 for all). Post-glucose GIP (pmol/L) increased in all: FCPD (15.83 to 94.14), T2DM (21.85 to 88.29), and control (13.00 to 74.65) (P < .001 for all). GIP was not different between groups. DPP-IV concentration (ng/mL) increased in controls (1578.54, 3012.00) and FCPD (1609.95, 1995.42), but not in T2DM (1204.50, 1939.50) (P = .131). DPP-IV between the three groups was not different. Fecal elastase was low in FCPD compared with T2DM controls. CONCLUSIONS: In FCPD, basal C-peptide and glucagon are low, and glucagon does not increase after glucose load. GLP-1, but not GIP, in FCPD increases 1.5 to 2 times as compared with T2DM and controls (fasting and post glucose) without differences in DPP-IV.

Asunto(s)

Calcinosis/sangre , Diabetes Mellitus Tipo 2/sangre , Incretinas/sangre , Pancreatitis Crónica/sangre , Adolescente , Adulto , Biomarcadores/sangre , Glucemia/metabolismo , Péptido C/sangre , Calcinosis/diagnóstico , Calcinosis/tratamiento farmacológico , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipeptidil Peptidasa 4/sangre , Femenino , Fibrosis , Polipéptido Inhibidor Gástrico/sangre , Glucagón/sangre , Péptido 1 Similar al Glucagón/sangre , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Masculino , Persona de Mediana Edad , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/tratamiento farmacológico , Factores de Tiempo , Adulto Joven

RESUMEN

BACKGROUND/OBJECTIVES: Pancreatogenic diabetes mellitus has been assumed to result from non-immune beta cell destruction when the pancreas is replaced by fibrotic tissue secondary to acute and chronic pancreatitis. We hypothesize that recurrent episodes of pancreatic inflammation may increase the risk for developing ß-cell autoimmunity in susceptible individuals. METHODS: We describe 11 patients who had both recurrent acute and/or chronic pancreatitis and type 1 diabetes (T1D) requiring insulin therapy. RESULTS: All 11 patients had positive autoantibodies and 8 patients tested had minimal to undetectable (7/8) or moderate (1/8) stimulated C-peptide at 12 months after T1D onset. Three had biopsy confirmation of insulitis. CONCLUSIONS: These cases lend support to the theory that pancreatitis may increase risk for T1D. We postulate that the pro-inflammatory conditions of pancreatitis may increase posttranslational protein modifications of ß-cell antigens and neoepitope generation, which are potential initiating events for loss of ß-cell self-tolerance.

Asunto(s)

Diabetes Mellitus Tipo 1/complicaciones , Pancreatitis/complicaciones , Enfermedad Aguda , Adolescente , Adulto , Autoanticuerpos/sangre , Péptido C/sangre , Niño , Preescolar , Enfermedad Crónica , Diabetes Mellitus Tipo 1/sangre , Humanos , Lactante , Inflamación , Persona de Mediana Edad , Pancreatitis/sangre , Procesamiento Proteico-Postraduccional , Recurrencia , Factores de Riesgo , Adulto Joven

RESUMEN

Pancreatogenic diabetes mellitus (T3cDM) is a highly frequent complication of pancreatic disease, especially chronic pancreatitis, and it is often misdiagnosed as type 2 diabetes mellitus (T2DM). A correct diagnosis allows the appropriate treatment of these patients, improving their quality of life, and various technologies have been employed over recent years to search for specific biomarkers of each disease. The main aim of this metabolomic project was to find differential metabolites between T3cDM and T2DM. Reverse-phase liquid chromatography coupled to high-resolution mass spectrometry was performed in serum samples from patients with T3cDM and T2DM. Multivariate Principal Component and Partial Least Squares-Discriminant analyses were employed to evaluate between-group variations. Univariate and multivariate analyses were used to identify potential candidates and the area under the receiver-operating characteristic (ROC) curve was calculated to evaluate their diagnostic value. A panel of five differential metabolites obtained an area under the ROC curve of 0.946. In this study, we demonstrate the usefulness of untargeted metabolomics for the differential diagnosis between T3cDM and T2DM and propose a panel of five metabolites that appear altered in the comparison between patients with these diseases.