Anti-thyroid peroxidase antibody, IA-2 antibody, and fasting C-peptide levels predict beta cell failure in patients with latent autoimmune diabetes in adults (LADA)--a 5-year follow-up of the Ehime study.

OBJECTIVE: To clarify the natural course and factors involved in beta cell failure in Japanese latent autoimmune diabetes in adults (LADA) patients. RESEARCH DESIGN AND METHODS: Insulin secretion in 57 LADA patients identified from among 4980 adult-onset diabetic patients in a hospital-based Ehime study were examined over a 5-year period. Postprandial serum C-peptide levels below 0.33 nmol/l were defined as beta cell failure. The involvement of clinical and immunological factors in the progression to beta cell failure were evaluated. RESULTS: Forty-two of the fifty-seven LADA patients completed the 5-year follow-up. Eleven (26.2%) required insulin treatment and five (11.9%) progressed to beta cell failure. A Cox regression analysis revealed that positive anti-thyroid peroxidase antibody (TPOAb) and insulinoma-associated protein 2 (IA-2Ab) were associated with the need for insulin treatment (p<0.05 and p<0.01, respectively). Positive TPOAb, anti-thyroglobulin antibody (TGAb), IA-2 antibody (p<0.01 for each), and lower serum fasting C-peptide levels (p<0.05) were contributors to the progression to beta cell failure. Involvement of type 1 diabetes susceptible HLA class II genes was not evident. CONCLUSIONS: Japanese LADA patients are a heterogeneous population. In addition to IA-2 antibody, presence of TPOAb and fasting C-peptide level could indicate an oncoming deterioration of beta cell function.

Initial experience with a new peroral electronic pancreatoscope with an accessory channel.

BACKGROUND: A peroral electronic pancreatoscope was previously developed to improve visualization of the pancreatic duct, but this instrument had no accessory channel. METHODS: A new peroral electronic pancreatoscope (2.6-mm external diameter) with an accessory channel (0.5 mm) was developed. Peroral pancreatoscopy or cholangioscopy was performed with this new instrument in 11 patients with various pancreatobiliary diseases. The clinical utility of the new peroral electronic pancreatoscope was assessed, and visualization with this new instrument was compared with that of the prototype. RESULTS: The resolution of the two instrument systems was nearly equal, with that provided by the new peroral electronic pancreatoscope being slightly better. The new peroral electronic pancreatoscope was inserted successfully into the pancreatic or bile duct in 9 of the 11 patients (82%). Observation of a predetermined target and juice collection with direct visualization was successful in 8 of the 9 patients (89%). CONCLUSIONS: The new peroral electronic pancreatoscope with an accessory channel was useful for clinical diagnosis of various pancreatobiliary diseases. Visualization is excellent. Pancreatic juice and other samples can be collected under direct visualization.

Limy bile syndrome complicated with primary hyperparathyroidism.

Limy bile is a rare condition characterized by excessive precipitation of calcium carbonate in the gallbladder. Cases of complicated hyperparathyroidism are extremely rare. There is only one reported case, where serum and urine calcium levels were high. On the other hand, the presence of limy bile in the common bile duct is also very rare, and has been reported in only 20 cases. We report a patient with obstructive jaundice in whom the initial abdominal radiography showed limy bile in the gallbladder and common bile duct, and laboratory values showed a high serum calcium level and highly sensitive PTH (HS-PTH) level.

A case of pseudotumorous pancreatitis that presented unique pancreatoscopic findings with the peroral electronic pancreatoscope.

A 49-year-old man was admitted to Hospital of Kyoto Prefectural University of Medicine complaining of epigastralgia and jaundice. There was a tumor (approximately 30 mm) in the pancreatic head on ultrasound, computed tomography and magnetic resonance imaging. Endoscopic retrograde cholangiopancreatography revealed a stenosis of the main pancreatic duct in the head of the pancreas. Pancreatoscopy with the peroral electronic pancreatoscope (PEPS) was performed to differentiate between pseudotumorous pancreatitis (PTP) and pancreatic carcinoma. The PEPS showed non-erosive erythematous mucosa around the stenosis and this unique finding was different from that of pancreatic carcinoma. Pylorus-preserving pancreatoduodenectomy was performed under the possible diagnosis of carcinoma. As a result, the diagnosis of PTP was confirmed histopathologically. At present, the diagnosis of PTP is difficult because of similar findings with carcinoma in various imaging procedures. However, we consider that detailed observation and accurate morphologic assessment of the main pancreatic duct with the PEPS has the possibility of differentiating PTP from pancreatic carcinoma.

Clinical, autoimmune, and genetic characteristics of adult-onset diabetic patients with GAD autoantibodies in Japan (Ehime Study).

OBJECTIVE: To characterize the clinical, autoimmune, and genetic features in Japanese adult-onset diabetic patients with GAD autoantibodies. RESEARCH DESIGN AND METHODS: GAD autoantibodies (GADab) were screened in 4,980 diabetic patients with age of onset >20 years in the hospital-based Ehime Study, and the GADab-positive (GADab(+)) patients were then divided into two groups according to their insulin secretion and compared with nondiabetic subjects. The insulin-deficient state was defined as <0.33 nmol/l serum C-peptide (CPR) at 2 h postprandial or 6 min after a 1-mg glucagon load. RESULTS: GADab was detected in 188 (3.8%) of the 4,980 diabetic patients tested. Of these patients, 72 (38.3%) were classified as insulin deficient, 97 (51.6%) were classified as non-insulin deficient, and 19 (10.1%) were unclassified. The GADab(+) insulin-deficient patients were characterized by young age at onset of diabetes, low BMI, low maximum BMI, and high levels of HbA(1c). The prevalence of IA-2 autoantibodies and thyrogastric autoantibodies in the GADab(+) insulin-deficient patients were significantly higher than those in the GADab(+) non-insulin-deficient patients (P < 0.05). GADab(+) patients with insulin deficiency had increased frequencies of HLA DRB1*0405-DQB1*0401, *0802-*0302, and *0901-*0303 haplotypes, whereas the frequency of only HLA DRB1*0405-DQB1*0401 was increased in the case of GADab(+) non-insulin-deficient patients. Of note is the fact that the GADab(+) non-insulin-deficient group did not differ from healthy control subjects with respect to type 1 diabetes protective haplotype HLA DRB1*1502-DQB1*0601. A total of 13% of the GADab(+) patients with diabetes had genotypes comprising the DRB1*1501-DQB1*0602 or *1502-*0601 and were characterized by old age at onset of diabetes, high BMI, resistance to the insulin-deficient state, low titer of GADab, and low frequency of other organ-specific autoantibodies. CONCLUSIONS: We conclude that GADab(+) non-insulin-deficient patients differ from GADab(+) patients with insulin deficiency with respect to clinical characteristics, humoral autoimmunity to other organ-specific autoantibodies, as well as HLA class II genes.

Electronic pancreatoscopy for the diagnosis of pancreatic diseases.

OBJECTIVES: Diagnostic pancreatoscopy was performed in 56 patients using the newly developed peroral electronic pancreatoscope (PEPS). The diagnostic value of the PEPS for pancreatic diseases was evaluated. METHODS: The PEPS (external diameter = 2.1 mm, bidirectional tip deflection) was developed with a minute 50,000-pixel interline charge-coupled device. Pancreatoscopy was performed by means of an endoscopic retrograde approach without sphincterotomy. The cases examined were normal (three), chronic pancreatitis (32), pancreatic cancer (eight), and intraductal papillary mucinous tumors (13). RESULTS: Of the 56 cases, 42 (75%) were adequately seen. In normal cases, fine capillary vessels were clearly visualized on the smooth whitish-pink mucosa. Findings in chronic pancreatitis included protein plugs, calcified stones, rough whitish mucosa, scar formation, edema, erythema, and indistinct capillary appearance. All the stenoses of chronic pancreatitis could be differentiated from those of pancreatic cancer with the PEPS. In the pancreatic cancer cases, all patients had stenoses or duct cutoffs; most cases had friable mucosa with erythema and erosive changes, and a single patient had a compressed pancreatic duct wall covered with normal epithelium. In the cases of intraductal papillary mucinous tumors, papillary tumors were visualized with extreme clarity. In the case of adenocarcinoma, the PEPS revealed oval-shaped tumors with spotty redness or villous tumors with dilation of capillary vessels. Moderate acute pancreatitis was recognized after pancreatoscopy in one of the 56 cases (1.8%). CONCLUSIONS: Electronic pancreatoscopy with the PEPS is feasible in most patients and technically safe, and improves diagnostic yield over conventional pancreatoscopy.