Distinct Inflammatory Changes of the Pancreas of Slowly Progressive Insulin-dependent (Type 1) Diabetes

Aida, Kaoru; Fukui, Tetsuya; Jimbo, Erika; Yagihashi, Soroku; Shimada, Akira; Oikawa, Yoichi; Mori, Yusaku; Fujii, Takeshi; Nishida, Yoriko; Koyama, Rikako; Kobayashi, Tetsuro

doi:10.1097/mpa.0000000000001144

Cited by 17 publications

(25 citation statements)

References 39 publications

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“…We should mention that the pancreatic neuroendocrine dead organ donors with and without T1D is reproduced, assuring that this finding is not an artifact consequent on high doses glucocorticoids given prior to organ procurement. Also, the finding of prominent exocrine changes of immune inflammation, acinar to ductal metaplasia and acinar atrophy in the pre-T1D phase are supportive of studies that implied that exocrine inflammation may contribute to development of islet inflammation eventually leading to T1D [3,9,[12][13][14]. e present case supports those findings of low grade islet immune cell infiltration but more prominent changes in exocrine pancreas extended here to pre-T1D consistent with loss of pancreas volume in pre-T1D [11].…”

Section: Discussionsupporting

confidence: 89%

“…e small pancreatic size has recently been found to be already present in individuals with pre-T1D [10,11]. e exocrine pancreas in both slowly progressive and fulminant forms of T1D have increased in ammatory cells that are comparable in subtypes to those observed in islets in the same individuals [12][13][14] as well as activation of the pancreatic duct compartment (PDG) [15], a regenerative compartment that is activated by pancreatitis. Taken together these studies have raised the possibility that in ammation originating in the exocrine pancreas may play a role in the pathophysiology of insulitis.…”

Section: Introductionmentioning

confidence: 99%

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Low Grade Islet but Marked Exocrine Pancreas Inflammation in an Adult with Autoimmune Pre-Diabetes

Nishimura¹,

Gurlo²,

Rosenberger³

et al. 2019

Case Reports in Endocrinology

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There is unexplained deficit in size and function of the exocrine pancreas in type 1 diabetes (T1D). We obtained pancreas from an individual with pre-T1D obtained at surgery and addressed the question, what is the relative inflammation in the exocrine and endocrine pancreas in pre-T1D in the absence of the potential confounding changes at autopsy or in brain dead organ donors. Pancreas was removed surgically from a 36 year woman for benign neuroendocrine tumors (NET). The patient had gestational diabetes at age 29 and has a 23 year old sister with T1D. Pre-operative fasting glucose of 109 mg/dl and HbA1C 5.8% revealed prediabetes with an anti-GAD 1,144 (5–250 U/ml) together with family history implying pre-T1D. There was patchy low grade immune infiltration in some, but not all, islets that met criteria for autoimmune insulitis. The exocrine pancreas showed more abundant inflammation with areas of chronic pancreatitis and acinar to ductal metaplasia, and with other areas of atrophy and fatty infiltration. In pre-T1D inflammation may be more prominent in the exocrine than the endocrine pancreas, calling into question the sequence of events and assumed islet centric basis of autoimmunity leading to T1D.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Low Grade Islet but Marked Exocrine Pancreas Inflammation in an Adult with Autoimmune Pre-Diabetes

Nishimura¹,

Gurlo²,

Rosenberger³

et al. 2019

Case Reports in Endocrinology

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“…The pancreatic ducts of cases with SPIDDM showed marked pancreatic intraepithelial neoplasia (PanIN lesions) (Figure 1A). 20,21 PanIN lesions are precancerous pancreatic ductal changes with Kras mutations, which are characterized by tall columnar cells and significant mucinous secretions. Secreted mucin-rich content sometimes builds up around pancreatic ducts and blocks the secretion of pancreatic digestive enzymes.…”

Section: Pathogenesis and Immunologic Findings Of The Pancreas In Patmentioning

confidence: 99%

<p>Slowly Progressive Type 1 Diabetes Mellitus: Current Knowledge And Future Perspectives</p>

Nishimura¹,

Matsumura²,

Kikuno³

et al. 2019

DMSO

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Slowly progressive type 1 insulin-dependent diabetes mellitus (SPIDDM), sometimes referred to as latent autoimmune diabetes in adults (LADA), is a heterogeneous disease that is often confused with type 1 and type 2 diabetes. As a result, there were few diagnostic criteria for this disorder until 2012, when the Japan Diabetes Society established criteria that could be used in clinical practice. A primary question is whether pathologic markers for type 1 or type 2 diabetes are present in the pancreas of patients with SPIDDM, because the phenotype of SPIDDM is similar to both type 1 and type 2 diabetes. Recent studies clarified pathologic findings in the pancreas of patients with SPIDDM, which included T-cell-mediated insulitis, a marker of type 1 diabetes; pseudoatrophic islets (islets specifically devoid of beta cells), another hallmark of type 1 diabetes; and a lack of amylin (ie, islet amyloid polypeptide) deposition to the islet cells, a pathologic marker of type 2 diabetes. In terms of preventing the loss of beta-cell function in patients with SPIDDM, several studies have shown that some drugs, including dipeptidyl peptidase-4 inhibitors, are effective. There is an increased need for early diagnosis of SPIDDM to preserve beta-cell function. This review presents updated findings on the pathogenesis and immunologic findings of the affected pancreas, diagnostic markers, risk factors for progression of beta-cell dysfunction, epidemiology, clinical features, diagnostic strategies, prevention strategies, and clinical options for patients with SPIDDM.

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“…They include the prevention of progressive beta cell failure by DPP4 inhibitors, GLP-1 analogs, metformin, and insulin [39]. Furthermore, there was an investigation of islet cells and exocrine pancreatic tissues in the pancreas for LADA which were positive for GADAs and ICAs [40].…”

Section: Discussionmentioning

confidence: 99%

Glucose variability for a short period of low carbohydrate diet in diabetic patients with possible latent autoimmune diabetes in adults

Bando¹,

Ebe²,

Muneta³

et al. 2019

Int Med

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Background: Authors have continued research for meal tolerance test (MTT) by calorie restriction diet (CRD) and low carbohydrate diet (LCD), besides M value and glucose variability. Methods: Subjects were 38 patients of two groups. Group-1 has 19 patients (57.6±12.9 years) with type 2 diabetes mellitus (T2DM) and positive glutamic acid decarboxylase antibody (GADA), which is possible to latent autoimmune diabetes in adults (LADA). Group-2 has recruited 19 cases with T2DM and negative GADA, who showed age, sex, glucose variability-matched subjects. They were given CRD on day 1-2, and LCD day 3-14, and biomarkers were compared between Group-1 and Group-2. Results: Average values of the daily profile of blood glucose on day2(CRD)/day4(LCD) in Group-1 vs 2 were studied. Obtained data were 202/148 mg/dL vs 205/143 mg/dL, respectively with similarity. However, M value showed 174/58 vs 179/22, respectively with difference. There were significant correlations of M value between day2 and day4 in Group-1 vs Group-2. Further, both showed contrast tendency, associated with wide distribution vs narrow distribution, respectively. Conclusions: These results suggested that Group-1 with positive GADA may have insufficient pancreas secretion compared with that of Group-2, and these data may become a basal reference for future study of LADA.

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Distinct Inflammatory Changes of the Pancreas of Slowly Progressive Insulin-dependent (Type 1) Diabetes

Abstract: Supplemental digital content is available in the text.

Cited by 17 publications

References 39 publications

Low Grade Islet but Marked Exocrine Pancreas Inflammation in an Adult with Autoimmune Pre-Diabetes

Low Grade Islet but Marked Exocrine Pancreas Inflammation in an Adult with Autoimmune Pre-Diabetes

<p>Slowly Progressive Type 1 Diabetes Mellitus: Current Knowledge And Future Perspectives</p>

Glucose variability for a short period of low carbohydrate diet in diabetic patients with possible latent autoimmune diabetes in adults

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