Is Pancreatic Diabetes (Type 3c Diabetes) Underdiagnosed and Misdiagnosed?

Hardt, Philip D.; Brendel, Mathias D.; Kloer, H. U.; Bretzel, Reinhard G.

doi:10.2337/dc08-s244

Cited by 172 publications

(133 citation statements)

References 41 publications

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“…Among the 43 participating patients who underwent this surgery in our department in 2010, 32 were non-diabetic, 5 were affected by type 2 diabetes and 6 had type 3c diabetes. These data agree with previous studies pointing to impaired glucose metabolism and diabetes in a sizeable fraction of patients suffering from pancreatic cancer or chronic pancreatitis 6 . We considered diabetes to be of primary origin if it was diagnosed at least one year prior to the onset of symptoms leading to pancreatic surgery 7 .…”

Section: Discussionsupporting

confidence: 93%

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Isolation of Human Islets from Partially Pancreatectomized Patients

Bötticher

Sturm

Ehehalt

et al. 2011

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Investigations into the pathogenesis of type 2 diabetes and islets of Langerhans malfunction 1 have been hampered by the limited availability of type 2 diabetic islets from organ donors 2 . Here we share our protocol for isolating islets from human pancreatic tissue obtained from type 2 diabetic and non-diabetic patients who have undergone partial pancreatectomy due to different pancreatic diseases (benign or malignant pancreatic tumors, chronic pancreatitis, and common bile duct or duodenal tumors). All patients involved gave their consent to this study, which had also been approved by the local ethics committee. The surgical specimens were immediately delivered to the pathologist who selected soft and healthy appearing pancreatic tissue for islet isolation, retaining the damaged tissue for diagnostic purposes. We found that to isolate more than 1,000 islets, we had to begin with at least 2 g of pancreatic tissue. Also essential to our protocol was to visibly distend the tissue when injecting the enzyme-containing media and subsequently mince it to aid digestion by increasing the surface area.To extend the applicability of our protocol to include the occasional case in which a large amount (>15g) of human pancreatic tissue is available , we used a Ricordi chamber (50 ml) to digest the tissue. During digestion, we manually shook the Ricordi chamber 3 at an intensity that varied by specimen according to its level of tissue fibrosis. A discontinous Ficoll gradient was then used to separate the islets from acinar tissue. We noted that the tissue pellet should be small enough to be homogenously resuspended in Ficoll medium with a density of 1.125 g/ml. After isolation, we cultured the islets under stress free conditions (no shaking or rotation) with 5% CO 2 at 37 °C for at least 48 h in order to facilitate their functional recovery. Widespread application of our protocol and its future improvement could enable the timely harvesting of large quantities of human islets from diabetic and clinically matched non-diabetic subjects, greatly advancing type 2 diabetes research. Video LinkThe video component of this article can be found at https://www.jove.com/video/2962/ Protocol 1. Pancreatic tissue collection in the operating room 1. The surgeon performs a partial resection of the pancreas. 2. After placing the pancreatic specimen in a box on ice, deliver it immediately to the pathologist. Tissue selection for islet isolation1. The pathologist selects tissue that appears soft and healthy, retaining the damaged tissue for diagnostic purposes. Fibrotic tissue and specimens offering less than 2 g of usable tissue are excluded from islet isolation. 2. Immerse the pancreatic tissue in Euro Collins Solution and deliver on ice to the laboratory. Isolation of human islets1. Weigh the pancreatic tissue, then place it into a 10 cm dish. 2. Put 150 ml RPMI media in a 500 ml flask. 3. In a 250 ml flask, prepare the digestive enzyme solution by combining 130 ml RPMI media with 100 mg/ml DNase and 20 ml of 5mg/ml Liberase RI. Dr...

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Section: Discussionsupporting

confidence: 93%

“…A partially pancreatectomized patient could be affected by type 3c diabetes, i.e. diabetes secondary to the pancreatic disorder leading to surgery 6 . Among the 43 participating patients who underwent this surgery in our department in 2010, 32 were non-diabetic, 5 were affected by type 2 diabetes and 6 had type 3c diabetes.…”

Section: Discussionmentioning

confidence: 99%

Isolation of Human Islets from Partially Pancreatectomized Patients

Bötticher

Sturm

Ehehalt

et al. 2011

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“…T3cDM had been estimated to account for only 1-2% of all diabetic patients in North America (Ganda 2005) but is known to affect as many as 15-20% of diabetic patients in the Indian and Southeast Asian continents, where tropical or fibrocalcific pancreatitis is endemic (Abu-Bakare et al 1986). In a careful evaluation of almost 2000 diabetic patients referred to an academic medical center in Germany, Hardt et al (2008) discovered that 8% of all diabetic patients harbored T3cDM (Fig. 9).…”

Section: Prevalence Of T3cdmmentioning

confidence: 99%

Diabetes and pancreatic cancer

Cui¹,

Andersen²

2012

Endocrine-Related Cancer

131

102

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Epidemiological studies clearly indicate that the risk of pancreatic cancer (PC) is increased in diabetic patients, but most studies focus on overall diabetes or type 2 diabetes mellitus (T2DM), and there are few studies on the risks of type 1 and type 3c (secondary) diabetes. Possible mechanisms for increased cancer risk in diabetes include cellular proliferative effects of hyperglycemia, hyperinsulinemia, and abnormalities in insulin/IGF receptor pathways. Recently, insulin and insulin secretagogues have been observed to increase the PC risk, while metformin treatment reduces the cancer risk in diabetic subjects. In addition, anticancer drugs used to treat PC may either cause diabetes or worsen coexisting diabetes. T3cDM has emerged as a major subset of diabetes and may have the highest risk of pancreatic carcinoma especially in patients with chronic pancreatitis. T3cDM is also a consequence of PC in at least 30% of patients. Distinguishing T3cDM from the more prevalent T2DM among new-onset diabetic patients can be aided by an assessment of clinical features and confirmed by finding a deficiency in postprandial pancreatic polypeptide release. In conclusion, diabetes and PC have a complex relationship that requires more clinical attention. The risk of developing PC can be reduced by aggressive prevention and treatment of T2DM and obesity and the prompt diagnosis of T3cDM may allow detection of a tumor at a potentially curable stage.

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“…In Western countries, 8-9% of all patients with diabetes have type 3c disease and 2-3% developed diabetes after pancreatectomy [2,3]. Accordingly, the importance of also maintaining endocrine pancreatic function after pancreatectomy has been emphasized.…”

Section: Introductionmentioning

confidence: 99%

The Evaluation of the Early and Late Postoperative Pancreatic Function and Nutritional Status: Central Pancreatectomy Versus Distal Pancreatectomy

Izumo¹

2017

Int J Surg Res Pract

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Is Pancreatic Diabetes (Type 3c Diabetes) Underdiagnosed and Misdiagnosed?

Cited by 172 publications

References 41 publications

Isolation of Human Islets from Partially Pancreatectomized Patients

Isolation of Human Islets from Partially Pancreatectomized Patients

Diabetes and pancreatic cancer

The Evaluation of the Early and Late Postoperative Pancreatic Function and Nutritional Status: Central Pancreatectomy Versus Distal Pancreatectomy

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