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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreas and kidney transplantation is performed in uremic IDDM patients to cure end-stage renal failure and diabetes. Seventy-two simultaneous kidney-pancreas transplantations were performed at our Institution between July 1985 and November 1994. All transplants were performed using heart-beating cadaver donors. The first 25 patients received 26 segmental pancreas according to Dubernard (KPS), whereas the last 46 patients received a whole, bladder-drained pancrea according to Sollinger (KPW). Mean pancreas cold and warm ischemia times were 294 +/- 14 and 44 +/- 2 minutes, respectively, in the KPS group and 660 +/- 37 and 40 +/- 8 minutes, respectively, in the KPW group. Twelve (48%) KPS patients and 19 (41%) KPW patients had postoperative pancreas surgical complications: vascular thrombosis led to graft failure in 5 KPS patients (20%) and 2 KPW patients (4%) (p = 0.01). Pancreatic fistula, hemorrhagic complications, and duodenum-bladder leakage were the surgical complications observed more frequently. Six KPS patients (24%) and 8 KPW patients (17%) underwent reintervention as a consequence of surgical complications. Fifteen KPS patients (60%) and 30 KPW patients (65%) experienced an acute kidney rejection episode, which was steroid-resistant in 14 KPW and 2 KPS patients. The actuarial survival rates for simultaneous kidney-pancreas recipients at one and 4 years were 92% and 84%, respectively, for KPS recipients, and 95% and 88%, respectively, for KPW patients. Kidney actuarial survival rates at one and 4 years were 96% and 76% respectively, for group KPS, and 93% and 89%, respectively, for KPW patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Simultaneous kidney and pancreas transplantation at the San Raffaele Scientific Institute: clinical experience and results. 754 47

The mechanism of beta-cell destruction leading to insulin dependent diabetes is probably a cell mediated auto-immune process occurring in genetically susceptible individuals. Since 50-70% of monozygotic twins will not get the disease non-genetic risk factors must play an important role in the etiology of the disease. During the past decade population based epidemiological studies have identified several risk determinants for insulin dependent diabetes. Based on these studies a multifactorial hypothesis of causation is proposed. Some risk determinants (maternal child blood group incompatibility, fetal viral infections, early exposure to cow's milk proteins, a high exposure level of nitrosamines) may independently initiate the autoimmune process by causing the initial damage of the beta-cell, leading to antigen release. Other risk determinants may promote an already ongoing autoimmune destructive process through induction of lymphokine release or by causing an increased work load on the beta-cell. Risk factors that may increase the peripheral need for insulin (infectious diseases, cold environment, a high growth rate and stressful life events) may act as promoters of the beta-cell destruction but also disclose the beta-cell impairment and make the disease clinically overt. Possibilities of different risk profiles in different age groups and of synergism between different risk factors are also discussed.
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PMID:Etiological aspects of insulin-dependent diabetes mellitus: an epidemiological perspective. 821 32

The vascular reactivity of forearm arterioles was measured in 16 control subjects (C) and 30 insulin-dependent diabetic (IDDM) subjects, 16 of whom were shown to have microvascular and/or neuropathic complications (DC) including 8 with autonomic neuropathy (DCa) and 14 were shown to be free of complications (DNC). Forearm blood flow was measured by strain gauge plethysmography basally, following a cold pressor stress and following a period of arterial occlusion (reactive hyperaemia). The tests were repeated 24 h later following aspirin treatment. Both C and DNC showed a significant reduction in blood flow in the cold pressor test (C 0.64 +/- 0.12, DNC 0.89 +/- 0.22 ml/100 ml forearm tissue/min reduction in flow P < 0.005), while DC showed no significant response. Reactive hyperaemia was significantly greater in C than in DNC or DC (8.37 +/- 1.14, 5.51 +/- 1.27 and 4.95 +/- 0.75 ml/100 ml tissue/min, respectively, P < 0.02). In the DC group, DCa had significantly less response than those without autonomic neuropathy. Aspirin treatment restored the response of DNC but not DC to normal, suggesting that the abnormality in the former group may have been due to overproduction of a vasoconstrictive cyclooxygenase product (such as thromboxane A2). It is concluded that the abnormalities of vasomotor responses in diabetic subjects are complex and are apparently dependent on autonomic neuropathy, humoral and perhaps structural changes.
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PMID:Forearm arterial vascular responsiveness in insulin-dependent diabetic subjects. 826 13

Nerve conduction studies, tests of autonomic function and terminal nerve branches, and soleus muscle H reflexes were applied to 60 patients with insulin dependent diabetes mellitus who had no clinical symptoms but abnormal vibratory or temperature perception thresholds indicating subclinical neuropathy. In most patients neurophysiological examination yielded a broad spectrum of neural dysfunction. The perception threshold for cold stimuli was sometimes selectively impaired and abnormal pupillometry results were common, suggesting that small fibres are vulnerable in the early stage of diabetic neuropathy. The arms were less frequently and less severely affected than the legs, an effect that may be related to nerve length. The neurophysiological test results did not change in 30 patients followed up for one year.
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PMID:Subclinical diabetic polyneuropathy: early detection of involvement of different nerve fibre types. 838 97

Studies of heart-rate variability have demonstrated that abnormal cardiac parasympathetic activity in individuals with IDDM precedes the development of other signs or symptoms of diabetic autonomic neuropathy. To determine whether IDDM patients have impaired sympathetic activity compared with normal control subjects before the onset of overt neuropathy, we directly recorded MSNA. We also examined the effects of changes in plasma glucose and insulin on sympathetic function in each group. MSNA was recorded by using microneurographic techniques in 10 IDDM patients without clinically evident diabetic complications and 10 control subjects. MSNA was compared during a 15-min fasting baseline period and during insulin infusion (120 mU.m-2.min-1) with 30 min of euglycemia. A cold pressor test was performed at the end of euglycemia. Power spectral analysis of 24-h RR variability was used to assess cardiac autonomic function. IDDM patients had lower MSNA than control subjects at baseline (8 +/- 1 vs. 18 +/- 3 burst/min, P < 0.02). MSNA increased in both groups with insulin infusion (P < 0.01) but remained lower in IDDM patients (20 +/- 3 vs. 28 +/- 3 burst/min, P < 0.01). In the IDDM group, we found no relationships between MSNA and plasma glucose, insulin, or HbA1c concentrations. BP levels did not differ at rest or during insulin. Heart-rate variability and the MSNA response to cold pressor testing in IDDM patients did not differ from those in healthy control subjects. IDDM patients had reduced MSNA at rest and in response to insulin. The lower MSNA is not attributable to differences in plasma glucose or insulin, but, rather, is most likely an early manifestation of diabetic autonomic neuropathy that precedes impaired cardiac parasympathetic control.
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PMID:Muscle sympathetic nerve activity is reduced in IDDM before overt autonomic neuropathy. 834 48

1. Insulin-dependent diabetes mellitus is a known risk factor for congestive heart failure and an early diastolic dysfunction has been described. In order to see if diabetes itself and not complications like hypertension, nephropathy or ischaemic heart disease can be considered responsible for the abnormal diastolic function of the left ventricle, 17 young patients with uncomplicated insulin-dependent diabetes mellitus and 12 control subjects were exposed to a cold pressor test. 2. Blinded echo-Doppler examination was performed before and during the test. During basal conditions, left ventricular dimensions and volumes were smaller in diabetes and atrial contributions to left ventricular filling were increased. 3. During the cold pressor test, isovolumic relaxation time increased, peak early filling velocity (E) decreased, E deceleration time decreased and atrial contribution (A) increased significantly in diabetes, while only A increased in the control group. A marked increase in left atrial ejection force was seen in diabetes only (P < 0.002). This difference was seen in spite of comparable reductions in mitral area and atrioventricular compliance in the two groups. 4. The hyperfunction of the left atrium in diabetes is hypothesized to be due to reduce size of the left ventricle combined with incipient autonomic neuropathy.
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PMID:Abnormal left ventricular diastolic function during cold pressor test in uncomplicated insulin-dependent diabetes mellitus. 854 59

Environmental factors appear to be nongenetic risks of importance in the progression of insulin-dependent diabetes mellitus (IDDM) or type 1 diabetes, whose mechanisms are not yet well understood. Stressful life events, in particular, have been linked to the expression of overt diabetes in humans. However, in rodent models of IDDM, contradictory data exist concerning the effects of stress on the disease. Here, we show that a stressor, such as long-term repeated injections of vehicle (0.9% saline), was able to delay the appearance and/or decrease the incidence of diabetes in both sexes of NOD mice. Short-term chronic stress applied from the 6th to the 8th week of age by a combination of multiple stressors (overcrowding + immobilization + cold exposure + anesthesia) protected NOD mice from diabetes, particularly males. In contrast, prenatal stress, induced by immobilization of the mothers during the third part of pregnancy, accelerated the onset and increased the prevalence of diabetes at 30 weeks of age in NOD females, while it had no effect in males. Finally, adrenalectomy appears to aggravate the development of diabetes in NOD mice, particularly in males. In conclusion, these data demonstrate that the appearance of diabetes in NOD mice is extremely sensitive to various experimental and environmental conditions. These results are discussed in the context of the complex neuroendocrine-immune interactions which occur during the progression of IDDM, with a particular focus on glucocorticoids and cytokines.
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PMID:Environmental and experimental procedures leading to variations in the incidence of diabetes in the nonobese diabetic (NOD) mouse. 898 23

Like most cytokines, IL-1 transduces its signals for growth, differentiation and diverse cellular functions after binding to specific receptors on the cell surface. Up to now two IL-1 receptors have been reported, type I which induces signal transduction and type II which binds IL-1 but does not transduce signalling. By using the rat insulinoma RIN-5AH cell line that expresses both types of receptor mRNA, and computer-assisted binding analysis, we show that interleukin-1 beta (IL-1 beta) binds to a single class of high affinity receptors with a Kd of 155 pmol/l. The average number of receptors on adherent cell layer is calculated to be 7300 per cell. 125I-IL-1 beta binding can be competed out by unlabelled IL-1 beta. 125I-IL-1 alpha binding can be also obtained and is subject to competition by cold IL-1 alpha. Its saturation curve, however, varies within experiments due to differential receptor up-regulation. These results have also been confirmed by FACS analysis using specific antibodies to type I and II IL-1 receptors, where type I receptor antibody binds strongly to RIN-5AH cells, and type II receptor antibody shows weak staining, also due to inadequate receptor up-regulation. In order to determine whether functional signal transduction occurs via the receptors detected, it is shown that IL-1 beta is able to induce MHC class II antigen expression on the surface of the RIN cells, whereas IL-1 alpha is unable to do so, indicating different signal reception by the cells. IL-1 beta-induced class II upregulation shows moderate signs of p21ras or/and PKC dependency, whereas IL-1 alpha strongly activates both pathways that probably regulate different functions. Finally, both IL-1 alpha and beta induce nitric oxide (NO) production in a time-dependent fashion which appears to be unrelated to the signals and pathways described, but may be involved in the onset of autoimmune type 1 diabetes.
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PMID:IL-1 beta transduces different signals than IL-1 alpha leading to class II antigen expression on beta-insulinoma RIN-5AH cells through specific receptors. 902 92

Sardinia and Finland have the highest incidence of IDDM in the world. Thus, both regions represent ideal observatories for investigating the environmental, genetic and immunological factors, which have led to this dramatic increase. We have concentrated our efforts in Sardinia. Among several projects, there is the mapping of the Island for hot and cold spots for overt IDDM. In order to map the Island for pre-IDDM, we have collected and bled around 10,000 school children (age 6-14 years) and we are now in the process to enroll around 30,000 newborn. We report here our initial results, which show that progression to IDDM is accompanied in both cohorts by the presence of a combination of ICA with either GAD and IA-2 antibodies or both. This approach should lead to design reliable models of IDDM prediction in the general population, which will benefit an early insulin treatment and, hopefully, an effective prevention of the disease.
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PMID:The "Sardinia-IDDM study": an attempt to unravel the cause of insulin-dependent diabetes mellitus in one of the countries with the highest incidence of the disease in the world. 954 74

Islet allografts in insulin-dependent diabetic (IDDM) patients exhibit variable survival lengths and low rates of insulin-independence despite treatment with anti-T-cell antibodies and maintenance immunosuppression. Use of poorly characterized freshly isolated preparations makes it difficult to determine whether failures are caused by variations in donor tissue. This study assesses survival of standardized beta-cell allografts in C-peptide negative IDDM patients on maintenance immunosuppression following kidney transplantation and without receiving anti-T-cell antibodies or additional immunosuppression. Human islets were isolated from pancreatic segments after maximal 20 h cold-preservation. During culture, preparations were selected according to quality control tests and combined with grafts with standardized cell composition (> or = 50% beta cells), viability (> or = 90%), total beta-cell number (1 to 2 x 10(6)/kg body weight) and insulin-producing capacity (2 to 4 nmol x graft(-1) x h(-1)). Grafts were injected in a liver segment through the repermeabilized umbilical vein. After 2 weeks C-peptide positivity, four out of seven recipients became C-peptide negative; two of them were initially GAD65-antibody positive and exhibited a rise in titre during graft destruction. The other three patients remained C-peptide positive for more than 1 year, two of them becoming insulin-independent with near-normal fasting glycaemia and HbA1c; they remained GAD65- and islet cell antibody negative. The three patients with surviving grafts presented a history of anti-thymocyte globulin therapy at kidney transplantation. Long-term surviving grafts increased C-peptide release following intravenous glucagon or oral glucose but not following intravenous glucose. Thus, cultured human beta-cells can survive for more than 1 year in IDDM patients on maintenance anti-rejection therapy for a prior kidney graft and without the need for an increased immunosuppression at the time of implantation. The use of functionally standardized beta-cell grafts helps to identify recipient and graft factors which influence their survival and metabolic effects. Insulin-independence can be achieved by injection of 1.5 million beta-cells per kg body weight in a liver segment. These beta-cell implants respond well to adenylcyclase activators but poorly to glucose.
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PMID:Implantation of standardized beta-cell grafts in a liver segment of IDDM patients: graft and recipients characteristics in two cases of insulin-independence under maintenance immunosuppression for prior kidney graft. 956 50


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