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Insulin dependent diabetes mellitus is a disease of ubiquitous distribution. The basic
character of the disease causing widespread damage to all the end organs demands for a permanent cure for the disease. Till three decades back treatment for diabetes was depressing life-long insulin therapy which causes poor patient compliance.
Treatment of diabetes has been revolutionised by advent of pancreatic transplantation.
First pancreatic transplantation was performed by Kelly in 1966.
Aims of pancreatic transplantation
1. To maintain euglycemia in patient and abolish further requirement of insulin.
2. To arrest further end organ damage.
Types of pancreatic transplantation
1. Whole pancreatic transplantation.
2. Islet cell transplantation.
Whole pancreatic transplantation
Indication
1. In non uraemic patients at any time.
2. In uraemic patients along with renal transplantation with end stage diabetic
nephropathy.
3. After successful renal transplantation with end stage diabetic nephropathy.
Advantages : Whole pancreatic transplantation is a highly successful surgery with more
than 90% cases having more than one year survival after combined pancreatic and renal transplantation (1,2). Success rate of surgery is improving with better techniques arid immunosuppresion.
Contraindication of pancreatic transplantation
i. Malignancy
II. Acute infection
III. Major amputions due to diabetes
IV. Advanced CAD
V. Blindness secondary to diabetes
Surgical complications (3)
I. Post transplant pancreatitis.
II. Transplant related vascular thrombosis.
III. Haemorrhage.
IV. Sepsis.
V. Fungal infections.
Islet cell transplantation
Theoritically this is the ideal procedure in which separated pancreatic B cell are
transplanted and they secrete insulin.
Advantages
1. Decreased antigenicity due to avoidance of transplantation of exocrine part of pancreas.
2. Islets from a single donor can be transplanted to multiple recipients.
But the basic problem which hinders the success of islet cell transplantation is separation
of islets from human pancreas and keeping them viable for transplantation. Islet cell though supposed to be less immunogenic but still often requires strong immunosuppresion, immunomodulation and immunoisolation.
Till 31st Dec. 1993 there were only four patients without requiring insulin injections out of
study of 215 patients (4). There is another mode of pancreatic tranplantation i.e. fetal pancreatic transplantation. But due to some ethical problems this had been banned (5). Yet another method for islet cell transplantation which is under trial is Xenotransplantation. In this porcine fetal islet were used but it did not prove to be significantly advantageous (6).
Metabolic control after pancreatic transplantation (7,8)
After pancreatic transplantation there is near normal restoration of glucose tolerance test.
There is mild hyperglycemia and mild hyperketonemia with normal plasma lactate and glycogen levels. These minor metabolic derangements are supposed to be due to reduced islet cell mass, denervation, disturbance in peripheral hormonal delivery system and immunosuppression.
There is lack of feedback inhibition of insulin secretion due to denervation of pancreas.
This causes mild hypherinsulinimia in between meals and at night. In a recent study it was found that after intravenous glucose infusion there was absolutely normal GTT in about 44% of cases. But about 52% could tolerate glucose well with mild degree of hypherinsulinimia. There was increase rate of hypoglycemia but it was soon corrected by catacholamine release. Thus there was near normalization of glucose metabolism.
Effect of pancreatic transplantation on lipoprotein levels
There is significant lowering of VLDL cholesterol, VLDL triglycerides, apo-B in cases of
combined renal-pancreatic transplantation as compared to renal transplantation. But in comparison with nondiabetic group there is persistence of increased VLDL, and increased triglycerides content in LDL and HDL. The cause of persistence of these abnormalitites is supposed to be due to insulin resistance (Secondary to steroid therapy and associated high peripheral and low hepatic insulin levels.
Renal function after successful pancreatic and renal transplantation
After successful renal and pancreatic transplantation sequential kidney biopsy samples
were studied. Initial samples showed normal or moderately increased mesengial volume and moderately increased thickening of basement membrane. But subsequent samples showed no progress in lesions thus there is significant decrease in progression of diabetic glomrulonephritis by maintaining euglycemia.
Effect of pancreatic transplantation on diabetic retinopathy
There is no significant alteration in progress of ophthatmological complications after
successful pancreatic transplantation.
Effect of pancreatic transplantation on diabetic neuropathy Strict normalisaton of blood
sugar after pancreatic transplantation causes subjective improvement in neuropathic symptoms but there is no decrease in conduction velocities. But there is stabilization of progress of peripheral neuropathy. Pancreatic transplantation offers a new hope for cases of type 1 diabetes with multiple complication especially nephropathy a successful renal pancreatic transplantation offers a significantly improved life-style to the patient. But there is still much to be done regarding islet cell transplantation, fetal pancreatic transplantation and Xeno transplantation. Improved surgical techniques and better immunosuppresion have reduced post surgical complications and graft rejection. So Pancreatic transplantation is a new ray of light in treatment modalities for Type 1 diabetes mellitus.
REFERENCES
1. Suther land Der. Report from the. International Pancreas Transplant Registry.
Diabetologia 1991; 34 (suppl 1): 28-39.
2. Suther land DER. Greussner A. et. al. Tabulation of cases from International
Pancreas Transplant Registry Data according to multiple variables. Transplant Proc.
1993; 25:1707 -1709.
3. Sabiston's Text book of Surgery~14th Ed.
4. International Islet cell Transplant Registry 1994; 4
5. Lafferty KJ, Hae L. Fetal Pancreas Transplantation for Treatment of IDDM patient.
Diabetics care 1993;16:383-386.
6. Groth CG, AndersonA, et al. Transplantation of porcine fetal islet like cell cluster into
eight diabetic patients. Transplant Proc. 1993;25:970.
7. Corttrella DA. Normalisation of insulin sensitivity and glucose homeostasis in Type 1
deabetic pancreas Transplant recipients: a 48 months cross sectional study a clinical
research centre study. J. Clin. Endocrinal Metab. 1996 Oct;'81 (10): 3513- 9.
8. Pozza G, Bosi E, et al. Metabolic control of Typel diabetics after pancreas
transplantation. Br. Med. j. (clinical res, Ed) 1985. Aug. 24;291 (6494) 510-3.
9. La Racca E. Secchi A, et. al. Lipo protein profile after combined kidney pancreas
transplantation in insulin dependent diabetes mellitus. Transplant Int. 1995;3: (190-5)
10. Fiorett OP, Mauer SM, et. al. Effect of pancreatic transplantation on glomerular
structure in insulin dependent diabetic patients with their own kidney. Lancet 1993,
Nov. 13th; 342(8881):1193-6
11. Bilous RW, mauer SM, et. al. The effet of pancreas transplantation on the glomerular
structure of renal allograft in patients with IDDM. N. Engl. J- Med. 1989, July 13th;
321(2):80-5.
12. Ramsay R.C, Goetz FC et. al. Progression of diabetic retinopathy after pancreas
transplantation for IDDM. N. Engl. ]. Med. 1988 Jan 28th; 818{4):208-14.
13. Muller Felber W, Wagner S. et. al. Follow up study of sensory motor polyneuropathy
in Type 1 diabetic subjects after simultaneous pancreas and kidney transplantation
and after graft rejection. Diabetologia 1991 Aug; 34 suppl l;S113-7.,
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