Diabetes mellitus as a specific etiological type of disease is a relatively frequent complication of chronic pancreatitis and is found always after total pancreatectomy. It is not clear whether in the frequently profound hypoglycaemias of these patients also increased insulin sensitivity may participate. Data in the literature are not uniform. The objective of the submitted work was to assess the insulin sensitivity in 10 patients with chronic pancreatitis (confirmed by ERCP) and diabetes and to compare them with 10 controls and 10 diabetics type 2 treated by diet matched for age and body mass index. The effect of insulin was assessed by the method of the 3-hour hyperinsulin euglycaemic clamp (insulin level 75 microU/ml, blood sugar level 5 mmol/l) acording to glucose consumption as glucose Mglu, glucose clearance MCRglu and insulin sensitivity index SI. Patients with pancreatic diabetes did not differ from controls and type 2 diabetics resp. as regards fasting insulin, C peptide level and lipid parameters. The groups did not differ as regards the glucagon level. Patients with chronic pancreatitis and diabetes had a lower insulin sensitivity than healthy controls.

The aim of the study was the comparison of a simple standardized noninvasive examination of neuropathy and angiopathy with routine diagnostic practice in community diabetes clinics for the identification of patients at risk of foot ulceration. Consecutive patients (n=322), aged 30 years and more, with a diabetes duration of more than 5 years, were examined by trained podiatric nurses in six diabetes clinics over a 1-year period; 44 of these patients had active or previous foot ulcerations. We evaluated the differences between the routine diagnostic practice (based on the patient's medical history and a physical examination) and noninvasive testing of peripheral neuropathy [vibration perception threshold (VPT) and the Semmes-Weinstein 10-g monofilament wire system] and angiopathy [Doppler ankle/brachial index (ABI)]. Using receiver operating characteristic (ROC) analysis, we evaluated the sensitivity and specificity of noninvasive testing methods for identifying patients at risk and selecting the optimal diagnostic cutoff points. Patients with severe neuropathy, as determined by noninvasive testing (VPT ≥30 V and/or insensitivity to 10 g monofilament), had been diagnosed to have neuropathy in diabetes clinics in 54% of cases. Patients with angiopathy at risk of developing diabetic foot ulcers (ABI ≤0.8) had been diagnosed, in diabetes clinics, to have peripheral arterial disease in 50% (they reported claudications in 41%, had femoral artery bruits detected in 29% and nonpalpable peripheral pulsations in 12%). Our findings stress the importance of using standardized simple noninvasive testing methods to increase the accuracy of identifying patients at risk for the diabetic foot at the community level.

In pancreas recipients with advanced diabetic eye disease, conflicting ophthalmologic results over different follow-up periods have been reported. In the present prospective study we performed ophthalmologic evaluation groups of type I diabetic patients: 1) normoglycemic recipients of pancreas and kidney grafts (group SPK, n = 43, follow-up 44.9 ± 35.1 months), 2) pancreas and kidney graft recipients with nonfunctioning pancreatic graft, and recipients of isolated kidney graft (group K, n = 45, follow-up 60.3 ± 34.2 months). The examinations were performed before transplantation, at the end of follow-up (at least 1 year), and in 63 recipients also at 3 years posttransplant. Visual acuity results at baseline and at the end of follow-up were 0.48 ± 0.39 vs. 0.50 ± 0.39 in the SPK group, and 0.46 ± 0.38 vs. 0.40 ± 0.39 in the K group. While intragroup changes were not significant, the changes were significantly different between the groups (p < 0.05). Fundoscopic findings at the end of follow-up were improved, stabilized, or deteriorated in the SPK group in 21.3%, 61.7%, and 17.0%, respectively. The respective figures for the K group were 6.1%, 48.8%, and 45.1% (p < 0.001). Similar results were obtained when evaluating findings at 3 years posttransplant. Before transplantation, 78% of the SPK group and 81% of the K group had been treated by laser. The need for additional posttransplant laser therapy was significantly lower in the SPK (31%) than in the K group (58%; p < 0.001). In conclusion, pancreas transplant exerts a beneficial effect on the course of diabetic retinopathy even in its late stage.

As part of screening focused on the incidence and risk of the diabetic foot syndrome in patients in a model area the authors compared values of different parameters of non-invasive examination methods of angiopathy and neuropathy in patients with diabetic foot and in diabetic patients without diabetic foot. They compared the data with normal clinical diagnosis and used them to assess the degree of risk of diabetic foot. Patients with diabetic foot had when examined for the threshold of vibration perception (VPT) by a biothesiometer, as compared with patients without diabetic foot, significantly higher VPT levels 361 +/- 16 vs. 25 +/- 12 V, p < 0.001. For assessment of a high risk of diabetc foot in this age group of diabetics it proved useful to use as a critical VPT level, values above 30 V. During the non-invasive diagnosis of angiopathy in the group with diabetic foot a significantly lower ratio of systolic pressures ankle/arm (0.82 +/- 0.43 vs. 0.92 +/- 0.26, p < 0.05) was found. The critical value for high risk of diabetic foot is the ratio 0.8. Both non-invasive methods make current clinical diagnosis markedly more accurate when assessing the risk of diabetic foot. Patients with diabetic foot had, as compared with other diabetics, a poorer compensation of diabetes (HbA1c 8.6 +/- 2 vs. 8.0 +/- 1.5%, p < 0.05) and poorer renal functions (creatinine 114 +/- 57 vs. 94 +/- 25 umol/l, p < 0.01), the cholesterol and triacyglycerol levels were higher in both groups, however they did not differ significantly.

The risk of tissue damage of the foot in diabetic subjects is due to a combination of arterial insufficiency and peripheral neuropathy. The probable development of diabetic foot with possible subsequent amputation is greater in uraemic diabetics. The objective of the presented work was to assess the incidence and risk of diabetic foot in diabetic patients where on account of renal failure transplantation of the kidney was performed.In a retrospective study in 1983-1992 for a period of 6 months to 7 years a group of 64 diabetics was investigated (37 men and 27 women), mean age 42.8 years, range 29-58 years where on account of diabetic nephropathy renal (n = 49, 76.6%) or renal and pancreatic transplantation (n = 15, 23.4%) was performed. At the time of transplantation 53 patients (82.8%) suffered from peripheral neuropathy, 24 (37.5%) from angiopathy of the lower extremities. During the follow up period 22 patients (34.4%) developed ulcerations of the skin of the lower extremities, incl. 15 patients (23.4%) with a local and 4 (6.3%) with a phlegmonous infection. In 10 patients (15.6%) amputation had to be performed.Ulceration of the foot in diabetics cannot be prevented by transplantation of the kidney or transplantation of the kidney and pancreas. Ulceration of the foot is at present an important contraindication for transplantation.

BACKGROUND:By transplantation of the pancreas in diabetics type 1 long-term-term independence on exogenous insulin can be achieved. The extent of normalization of the carbohydrate metabolism can depend on the applied surgical technique. The objective of the submitted work was to compare indicators of compensation of diabetes one year after combined transplantation of the kidney and pancreas, using the method of transplantation of a segment of the pancreas with obliteration of the pancreatic duct by a polymer and the method of transplantation of the whole pancreas with drainage of the pancreatic duct into the urinary bladder.METHODS AND RESULTS:The authors examined two groups of recipients, 13 subjects each with full function of the pancreatic graft one year after transplantation where a combined transplantation of the kidney and pancreatic segment (group SP) had been performed or of the kidney and whole pancreas (group CP). The authors investigated the blood sugar level, glycated haemoglobin, intravenous glucose tolerance test, free insulin level and C-peptide as well as some indicators of the lipid metabolism and acid base balance. In both groups normal blood sugar levels were achieved, though the mean values in the course of the day were higher in group SP than in group CP (mean +/- SE 5.48 +/- 0.11 as compared with 4.98 +/- 0.09; p < 0.01). Glycated haemoglobin declined in group SP from the pretransplantation value of 9.31 +/- 0.09 to 6.40 +/- 0.10% and in group CP from 9.49 +/- 0.15 to 4.92 +/- 0.08%. In group CP the glycated haemoglobin after transplantation was significantly lower (p < 0.01), similarly as the coefficient of glucose assimilation (1.83 +/- 0.03 as compared with 1.25 +/- 0.15; p < 0.05). Indicators of the acid base balance did not differ. Recipients in group CP were however permanently treated with bicarbonate.CONCLUSIONS:With both transplantation method it is possible to achieve compensation of diabetes close to normal. The carbohydrate tolerance is however better after transplantation of the whole pancreas.

BACKGROUND:Successful transplantation of the pancreas is at present the only way how to ensure on a long-term basis an almost physiological regulation of the carbohydrate metabolism in type 1 diabetics. So far it is, however, indicated mainly in patients with already advanced microangiopathy where at the same time also renal transplantation is planned and long-term experience is so far limited. The objective of the submitted paper is to report on the development of metabolic compensation and its impact on the development of microangiopathic changes in type 1 diabetics where the complete function of both grafts persisted more han five years.METHODS AND RESULTS:From a group of 34 combined transplantations of a pancreatic segment with an obliterated duct and a kidney, implemented in 1983-1988 in the Institute of Clinical and Experimental Medicine, a group of nine type 1 diabetics was followed up where the independence on exogenous insulin and haemodialyzation treatment persisted for or still persists for 5-8 years. After annual intervals the blood sugar level was examined, the intravenous glucose to tolerance test, free insulin levels, glycosylated haemoglobin, an ophthalmological and neurological examination was made, incl. the peripheral and autonomous system, and by means of a standard questionnaire the quality of life before and after transplantation was assessed. In all examined subjects normal blood sugar levels were recorded. The fasting insulin levels in transplant recipients were higher than in healthy subjects (22 vs. 10.2 microU/ml, p < 0.01) while in the course of the blood sugar curve corresponding levels were recorded. Glycosylated haemoglobin remained after 5 years quite or almost normal (4.2-7.2%). The coefficient of glucose assimilation after 5 years varied in the range from 0.7 to 1.9% min. Hypoglycaemic states were not recorded. In none of the recipients in the course of the investigation deterioration of the ophthalmological finding was observed and in three patients improvement was recorded. Symptoms of somatic polyneuropathy improved in all patients but signs of vegetative neuropathy remained unchanged. In all recipients psychic, physical and social rehabilitation as well as the general quality of life improved markedly.CONCLUSIONS:Although the group of investigated patients is so far small, the authors provided evidence that combined transplantation of the pancreas and kidney can influence in a very favourable way the quality of life and development of microangiopathic complications. As the success rate of transplantations of the pancreas in increasing and the risk of surgical complications is declining due to improving surgical techniques, the authors conclude that combined transplantation of the pancreas and kidney is at present the optimal therapeutic procedure in type 1 diabetics with chronic renal insufficiency and that indication for transplantation of the pancreas could be moved to earlier stages of diabetes when it would be possible to influence the development of diabetic microangiopathy more favourably.

Insulin resistance is present in pancreatic graft recipients treated with immunosuppressive therapy. To investigate quantitatively the impact of insulin resistance on glucose tolerance, both hyperglycemic insulin clamp (12 mmol/l for 120 min) and hyperinsulinemic isoglycemic clamp studies were performed in 53 subjects divided into 4 groups. Group 1 consisted of 10 normoglycemic pancreas and kidney recipients, group 2 of 16 non-diabetic kidney recipients on the same immunosuppressive regimen, group 3 of 10 Type II diabetic patients satisfactorily treated with diet only, and group 4 of 17 matched healthy controls. Using the hyperinsulinemic isoglycemic clamp technique insulin resistance was found to manifest as 39% (p<0.05), 44% (p<0.01) and 42% (p<0.01) decreases in metabolic clearance rates of glucose at an insulin level of approx. 100 mU/l in groups 1, 2 and 3, respectively, and as 34% and 25 % decreases of metabolic clearance rates at insulin concentrations of approx. 2000 mU/l in groups 1 and 2 (p<0.05). During the last 20 min of the hyperglycemic clamp, glucose utilization rates in groups 1, 2 and 3 were reduced by 53%, 47% and 73%, respectively, compared to healthy subjects (p<0.01). Both early and late insulin responses were normal in groups 1 and 2 but impaired in Type II diabetic subject. Glucose tolerance, insulin action and insulin concentrations did not differ between both groups of transplant recipients (p>0.05). We conclude that glucose tolerance after pancreas transplantation is impaired because of the inability of beta-cells to increase insulin secretion enough to overcome the immunosuppression-induced insulin resistance.