Massive synchronous B-cell necrosis causing Type 1 (insulin-dependent) diabetes — a unique histopathological case report

Diabetologia, Jan 1988

A 22-year-old Chinese male died in hyperglycaemic coma following a 36-h illness. The only significant pathological findings were in the pancreas where there was a heavy diffuse infiltrate of lymphocytes admixed with numerous eosinophils, macrophages and polymorphs. There appeared to have been massive, recent, synchronous necrosis of insulin-secreting B cells with no destruction of any other pancreatic parenchymal cells. The biochemical findings of severe hyperglycaemia, insulinopoenia, but a normal glycosylated HbA1 were compatible with an acute onset to the patient's diabetes. These features contrast with the very much slower destruction of B cells associated with insulitis seen in “classical” Type 1 (insulin-dependent) diabetes.

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Massive synchronous B-cell necrosis causing Type 1 (insulin-dependent) diabetes — a unique histopathological case report

M a s s i v e synchronous B-cell necrosis causing Type 1 (insulin-dependent) diabetes -- a unique histopathological case report A. K. Foulis 0 N. D. Francis 0 M. A. F a r q u h a r s o n 0 a n d A. Boylston 0 0 Departments of Pathology, i Royal Infirmary , Glasgow and 2St. Mary's Hospital , London , UK Summary. A 22-year-old Chinese male died in hyperglycaemic coma following a 36-h illness. The only significant pathological findings were in the pancreas where there was a heavy diffuse infiltrate of lymphocytes admixed with numerous eosinophils, macrophages and polymorphs. There appeared to have been massive, recent, synchronous necrosis of insulin-secreting B cells with no destruction of any other pancreatic parenchymal cells. The biochemical findings of severe hyperglycaemia, insulinopoenia, but a normal glycosylated HbA1 were compatible with an acute onset to the patient's diabetes. These features contrast with the very much slower destruction of B cells associated with insulitis seen in "classical" Type 1 (insulin-dependent) diabetes. Type 1 (insulin-dependent) diabetes; pancreas; histopathology - 9 Springer-Verlag1988 It has long b e e n held possible that viruses m a y be involved in the aetiology o f s o m e cases o f Type I (insulin-dependent) diabetes. A C o x s a c k i e B4 virus was isolated f r o m the p a n c r e a s o f a 10-year-old b o y w h o p r e s e n t e d in h y p e r g l y c a e m i c ketoacidosis a n d w h o died 8 days later [ 1 ]. The virus which was cultured was later s h o w n to cause diabetes w h e n injected into certain strains o f mice. I n a second case report a 5-yearold girl d e v e l o p e d diabetes 19 days after heart surgery [ 2 ]. She died in c o m a a n d there was i m m u n o h i s t o l o g i cal evidence o f C o x s a c k i e B virus in the p a n c r e a t i c islets. Serological studies h a v e also b e e n d o n e on patients with newly d i a g n o s e d Type 1 diabetes a n d these h a v e s h o w n raised titres to C o x s a c k i e B viruses in a p r o p o r t i o n o f cases [ 3-5 ]. Initially it was t h o u g h t that viral-induced diabetes w o u l d cause a massive simultan e o u s destruction o f insulin-secreting B cells a n d that the seasonality o f p r e s e n t a t i o n o f Type I diabetes m i g h t b e related to the seasonality o f viral infections a situation akin to poliomyelitis. H o w e v e r , with the d e m o n s t r a t i o n that islet cell antibodies m a y be present for years before p r e s e n t a t i o n o f the disease [ 6 ] a n d the finding o f residual C - p e p t i d e secretion in the m a j o r i t y o f patients 2 years after p r e s e n t a t i o n [ 7 ], it has b e c o m e a c c e p t e d that B-cell killing in the p a n c r e a s takes place o v e r m a n y years in the vast m a j o r i t y o f patients with Type 1 diabetes. It has m o r e recently b e e n p r o p o s e d that C o x s a c k i e B viruses m a y not be involved in a direct c y t o p a t h i c effect on B cells but m a y stimulate an a u t o i m m u n e reaction to B cells [ 8 ]. We report the histological findings in the p a n c r e a s o f a patient w h o died o f i n s u l i n - d e p e n d e n t diabetes in w h o m there a p p e a r e d to h a v e b e e n a total a n d a l m o s t simultaneous destruction o f B cells. The histological features were suggestive o f a viral aetiology. Case report The patient was a 22-year-old Chinese male who gave a 36-h history of abdominal discomfort and vomiting. Prodromal diabetic symptoms such as polyuria, polydypsia and weight loss were lacking. There was no significant past medical history and no familiy history of diabetes. He had not knowingly taken any drugs or toxins. On admission to St.Mary's Hospital, London, he was hypotensive and dehydrated. His blood biochemical findings were as follows: Na,111 mmol/1; 14,,7.7retool/l; glucose, 92 mmol/1; amylase, 148 Somogyi units/100 ml (Normal less than 180); arterial blood: pH, 7.1; pCO2, 16 mm Hg; pO2,70 mm Hg; bicarbonate, 3.5 mmol/1; Base excess - 22.9. He had a cardio-respiratory arrest 1 h after admission and resuscitation was unsuccessful. Other investigations which were done on blood taken prior to death included the following: plasma insulin, less than 2 mU/l (normal range 3-30) and a test for islet cell antibodies which proved negative. Unfortunately, no serum was sent for viral serological studies. A post mortem examination was performed 34 h after death. Blood taken at that time showed a glycosylated HbA1 of 7.1% (normal less than 8%). Pathological findings at autopsy included pulmonary congestion, small erosions in the stomach associated with the presence of some altered blood, and approximately 200 ml of slightly blood-stained fluid in the peritoneal cavity. All other organs, including the pancreas, were thought to be macrosopically normal. Liver, spleen, prostate, adrenal, aorta, thyroid, heart, lung, pancreas, kidney, testis, pituitary, sto (...truncated)


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A. K. Foulis, N. D. Francis, M. A. Farquharson, A. Boylston. Massive synchronous B-cell necrosis causing Type 1 (insulin-dependent) diabetes — a unique histopathological case report, Diabetologia, 1988, pp. 46-50, Volume 31, Issue 1, DOI: 10.1007/BF00279132