Predictive and Comparative Study Between Clinic Consensus Document for Pancreas Acceptance and Predictive Value of Preprocurement Pancreas Allocation Suitability Score (P-PASS).

The strict selection of pancreas for transplant has forced the development of different documents to select the suitable organ in order to minimize the risks and complications of the transplant. In 2008, Eurotransplant published the Preprocurement Pancreas Allocation Suitability Score (P-PASS) for pretransplant selection. In 2001 the Hospital Clinic of Barcelona developed a Clinical Consensus Document (CCD). OBJECTIVES: We aimed to analyze the predictive decision of the pancreas acceptance to offers received in the hospital, according to the CCD criteria and compare it with the recommended value of suitability for accepting the pancreas according to the P-PASS value. MATERIAL AND METHODS: We performed a retrospective comparative study between the criteria of selection of the CCD for pancreas from 2016-2017 in comparison with the values obtained if the P-PASS had been used: ≤ 17, acceptance criteria and P-PASS; > 17, risk criteria. We defined the organ reported as rejected or accepted. The accepted organ could be procured and transplanted or discarded. RESULTS: With the CCD criteria, 7 more organs were transplanted than if we only applied the potential P-PASS criteria. In contrast, P-PASS would have ruled out an additional 9% of pancreases in relation to CCD criteria. CONCLUSIONS: According our experience, it is difficult to find an adequate prediction model to select pancreas for transplantation. The application of the DCC criteria increases the number of organs valid for transplantation. At present, new criteria should be re-evaluated within multicenter studies.

Relatives' Perception After Tissue Donation Experience: Results of a Postdonation Phone Survey.

INTRODUCTION: Postmortem tissue donation (TD) requires the establishment of strategies for family approach to clearly explain the characteristics of multi-tissue donation. In a tertiary university hospital with a long tradition of tissue generation, we designed a survey to be applied to tissue donor families to evaluate global hospital care, care from Transplant Coordinators (TC), quality and content of information given about TD, experience, and motivations after TD process. METHODOLOGY: A prospective phone survey of 10 multiple-choice items was conducted to all TD relatives that agreed to donate one or more tissues. RESULTS: From the 166 calls made to TD relatives, 75 (45%) were answered: 50 were cornea donors and 25 were multiple-tissues donors. None of the relatives denied participating, the rest were not found. No statistical differences in demographical variables were found between both types of TD. The hospital and TC care perception, the quality of the given information about the processes of TD, the postdonation experiences in terms of procedures, and the impression about body appearance for relatives regardless of the type of donation, corneas or multiple tissues, were evaluated as good or very good for most of the TD relatives. Our study showed that 83% of the family members would agree to donate again; 40% of the relatives were surprised to be offered the option to donate; 10% did not know if they would donate again. Solidarity was the leading reason for TD. CONCLUSION: The relatives' perception of care is a critical component of the quality evaluation of the TD process. The global evaluation results support our strategies for family approach.

Quality Assessment of Postmortem Tissue Donors in a University Hospital: Detection and Generation Tissue Indicators.

BACKGROUND: Defining quality assessment and measurement tools in the area of tissue donation should be considered to be one of the most important strategies for developing health centers. The aim of this project was to identify, define, and analyze a set of indicators to assess the most important steps in the tissue donor detection and generation processes. METHODS: A prospective, descriptive, and comparative study of all potential tissue donors (TDs) detected and generated in a university hospital was performed. All deceased patients after cardiocirculatory death were evaluated in 2015 by the transplant coordinators (TCs). We defined as detection indicators: total deaths, percentage of detection and evaluation, percentage of clinical contraindications, tissue donor potentiality (TDP; corneal or multitissue potentiality), and the functional detection time (FDT); and as generation indicators: generation rate (corneal or multitissue generation), family request time, number of interviewed relatives, and TC experience (y). RESULTS: The detection and evaluation rate was 100% (n = 1,235); tissue clinical contraindications were 57%, and TDP was 43% (n = 528; corneal, 80%; multitissue, 20%). The FDT was 24 ± 30 minutes. The generation rate was 53.4% (n = 282): corneal, 57% (n = 241); and multitissue, 40% (n = 41). Family request time was 10 ± 17 minutes, average number of interviewed relatives was 2.2 ± 1.6, and 35% of TCs had experience in the field for >5 years. CONCLUSIONS: Obtaining indicators for quality assessment in the area of tissue donation is useful in predicting the outcome of the TD process as well as promoting the approach of continuous improvement.

Does the Pulsatile Preservation Machine Have Any Impact in the Discard Rate of Kidneys From Older Donors After Brain Death?

BACKGROUND: Donors after brain death (DBD) older than 60 years have become 46.8% of our current activity, with higher risk of renal discard rate (RDR). Assessment of kidney suitability requires complementary strategies: macroscopic evaluation, kidney biopsy score (KBS), and renal hemodynamic evaluation with the Pulsatile Perfusion Machine (PPM). METHODS: Descriptive, cross-sectional, comparative study of kidneys procured and RDR, comparing 3 time periods: 2000 to June 2004, when only KBS were used; July 2004 to 2008 (introduction of PPM and learning period); and 2009 to 2013 (experienced use of PPM). Transplantation criteria were KBS <3 and PPM renal resistance <0.4 mm Hg/mL/min and arterial renal flow >70 mL/min. RESULTS: Between 2000 and 2013, a 59.2% reduction in DBD kidneys was observed. However, older kidneys had an increase from 33.5% to 46.8%. The RDR had increased, comparing the first to the third period from 25.4% to 38.3%. However, the RDR was lower when kidneys were evaluated with PPM than those evaluated only with KBS and preserved in cold storage (CS) (21.4% versus 43.7%). There was a significant difference in cold ischemia time, because CS kidney was grafted before PPM. During the third period, more kidneys with KBS ≥4 were assigned to PPM. CONCLUSIONS: Notwithstanding the decrease in DBD-procured kidneys and the increase in older kidneys during last period, the use of PPM allowed low DR compared with CS. A bias in the results of PPM could be generated when kidneys with higher KBS were excluded from PPM. The use of KBS only to decide acceptance could preclude the use of an additional tool to evaluate suitability.

Successful Pancreas Transplantation From a Deceased Donor Intoxicated With Oral Antidiabetic Agent: A Case Report.

Simultaneous kidney pancreas transplantation (SKP) is a common procedure for the patient with long-term type 1 diabetes mellitus (DM) with terminal renal failure. It is unusual to consider the pancreas from a deceased donor who died after an acute intoxication with oral antidiabetic agent (OAA), which would suggest an abnormal functionality of the organ and preclude the potential use of the graft. We present a case of a successful pancreatic transplantation from a donor who died of acute cerebral edema secondary to severe hypoglycemia induced by OAA acute intoxication.

O-linked N-acetylglucosamine (O-GlcNAc) protein modification is increased in the cartilage of patients with knee osteoarthritis.

OBJECTIVE: There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. In chondrocytes, accumulation of O-GlcNAc-modified proteins induces hypertrophic differentiation. Osteoarthritis (OA) is characterized by cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes. However, the mechanisms responsible for these changes have not been described. Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC). DESIGN: Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. HOC were cultured and stimulated with the catabolic cytokine IL-1α. Global protein O-GlcNAcylation and the synthesis of the key enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot. RESULTS: OA was associated with a 4-fold increase in the global O-GlcNAcylation in the cartilage. OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. In HOC, IL-1α stimulation rapidly increased O-GlcNAcylation and OGT and OGA synthesis. CONCLUSIONS: Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification. The increase in O-GlcNAcylation could be responsible, at least partially, for the re-expression of hypertrophic differentiation markers that have been observed in OA.

Perception of transplant coordinator regarding relatives' attitude toward tissue donation request.

INTRODUCTION: Family denials for tissue donation are higher than denials obtained after organ donation. OBJECTIVES: To find out families' perception toward tissue request as well as its relation with the degree of acceptance or denial. MATERIALS AND METHODS: Following the request for tissue donation (corneas or different tissues), a five closed-question survey was designed and immediately answered by the Transplant Coordinator. The main aim was to find out whether the request determined surprise, disapproval, understanding, knowledge, and immediacy in the decision-making process, as well as its relation with the decision to donate. RESULTS: Of 1751 surveys, 991 were answered and collected from 2009 to 2011, which represents a 56% from the total. Data collected relate to families 510 who donated and 481 who did not (P = NS). The fact of requesting corneas only or different tissues did not influence the answers. Surprise and disapproval variables significantly predicted refusal to donation (P = .000). CONCLUSIONS: Regardless the request type (corneas or multitissue) variables influencing the decision making when approaching families are expression of surprise and disapproval. Neither understanding the application nor existence of a prior approach to donation has any influence whatsoever in the decision-making process.

Attitude of health professionals toward cadaveric tissue donation.

INTRODUCTION: A positive attitude toward organ donation would be expected among health professionals from transplant centers with active donor activities. However, acceptance and knowledge about cadaveric tissue donation has been insufficiently studied. OBJECTIVE: The objective of this study was to analyze the knowledge and attitude of health professionals toward cadaveric tissue donation. METHODS: An anonymous survey composed of 23 questions was given to health professionals from 2 university hospitals with donation experience. Sociodemographic and professional characteristics were described to analyze knowledge and acceptance of cadaveric tissue donation. RESULTS: Among 600 distributed questionnaires we collected 514 completely answered surveys. Gender distribution was 399 females/115 males of ages ranging from 18-65 years, namely 18-28 years, 27%; 29-39 years, 31%; 40-50 years, 32%; and 51-65 years, 10%. Among the sample, 31% of health professionals had never been in contact with a transplant recipient. In this study 99.4% had knowledge about cadaveric organ donation compare with 89.7% about tissue donation. The knowledge about various types of tissue donation was as follows: eye, 96%; musculoskeletal, 87%; skin, 72%, and cardiovascular, 67%. In the sample, 93% and 92% accepted the opportunity to receive an organ or tissue transplantation, respectively. The acceptance of a tissue varied according to the type: cardiovascular, 93%; ocular, 94%; skin, 89%; and musculoskeletal, 87%. Participant acceptance of a relative's tissue donation was 74%, refusal was 22%, and with doubts was 4%. CONCLUSIONS: Insufficient knowledge about cadaveric tissue was demonstrated among health professionals more exposed to the donation process. These results highlighted the importance of health professional's education to facilitate public information about organ and tissue donation.

Telephone consent in tissue donation: effectiveness and efficiency in postmortem tissue generation.

UNLABELLED: One reason for the loss of donors is the impossibility to contact family members for an interview. We sought to determine the effectiveness [(donors/total deaths) x 100] and efficiency [(donors/potential donors) x 100] of the telephone interview to obtain tissue for transplant purposes. METHODS: A prospective, comparative cross-sectional study was performed on the personal and telephone interviews with family members during the tissue donation application process from January 1, 2004 to December 31, 2005. RESULTS: Of the 3625 deaths hospital registered, we obtained 770 potential donors (21%). On 65% of occasions (503/770), the interview was held personally; on 29% (222/770), it had to be held over the telephone; and on 6% (45/770), family members could not be located. The refusals by family members over the telephone represented 48% (106/222), and the refusals during personal interviews were 37% (188/503). A positive family answer was obtained over the telephone on 116/431 donations (27%), and in the physical presence of the coordinator for 315/431 donors (73%). The donations obtained over the telephone were only for corneas in 83% (96/116) of cases, and for multiple tissues in 17% (20/116). The donor-generation effectiveness reached 9% in personal interviews and 12% if the telephone interviews were included. The donor generation efficiency reached 43% for personal interviews and 59% when telephone interviews were included. The use of the telephone enabled a 16% increase in tissue generation with a year-on-year increase of 4%. CONCLUSIONS: The telephone has shown itself to be a useful tool for obtaining tissues postmortem.

Comparison of a high-carbohydrate and a high-monounsaturated fat, olive oil-rich diet on the susceptibility of LDL to oxidative modification in subjects with Type 2 diabetes mellitus.

AIMS: To compare the effects of a high-carbohydrate (CHO) diet and a high-monounsaturated fatty acid (MUFA) diet on LDL oxidative resistance in free-living individuals with Type 2 diabetes mellitus. METHODS: Twenty-two men and women out-patients with Type 2 diabetes, with mean age 61 years and in fair metabolic control (HbA1c<8.0%), were enrolled at a university hospital lipid clinic in a randomized, crossover feeding trial comparing two isocaloric diets for 6 weeks each: CHO (fat, 28% energy) and MUFA (fat, 40% energy) based on virgin olive oil. Outcome measurements were changes in LDL susceptibility to oxidation, body weight, glycaemic control, and lipoprotein profiles. RESULTS: Planned and observed diets were well matched. Participants preferred the MUFA diet over the CHO diet. The lag time of conjugated diene formation during Cu2+-induced LDL oxidation was similar after the CHO and MUFA diets (36.4 +/- 12.2 min and 36.0 +/- 13.7 min, respectively). Body weight, glycaemic control, total triglycerides, and total, LDL- and HDL-cholesterol levels also were similar after the two diets. Compared with the CHO diet, the MUFA diet lowered VLDL-cholesterol by 35% (P=0.023) and VLDL triglyceride by 16% (P=0.016). CONCLUSIONS: Natural food-based high-CHO and high-MUFA diets have similar effects on LDL oxidative resistance and metabolic control in subjects with Type 2 diabetes. A MUFA diet is a good alternative to high-CHO diets for nutrition therapy of diabetes because it also has a beneficial effect on the lipid profile and superior patient acceptance.

The living kidney donation process: the donor perspective.

OBJECTIVE: To evaluate the living kidney donation (LKD) process using donors' opinions on the impact on social, emotional, and financial aspects affecting donor quality of life. MATERIALS AND METHODS: From May 2000 to December 2002, we studied 22 donors of living kidneys at the Hospital Clinic, Barcelona, Spain, who completed an anonymous survey 6 months after donation. RESULTS: Most donors (86%) had themselves informed the recipient about their wish to donate, the other 14% were asked by family members. Eighty-eight percent stated that the information provided to the donor about the evaluation process was well explained and understood whereas 12% disagreed with the statement. At the time of thin decision, 90.5% of donors understood the vital risk. For 95%, the explanations about the process corresponded with the actual experience. One hundred percent of donors stated after donation that they would again favor it. Mean hospital stay was 6 days (range, 3-9 days). Those donors with a labor contract have been out of work for an average of 57.8 days (range, 18 days to 6 months). Twenty-five percent of donors admitted financial effects as a result of donation. All but 1 felt completely recovered with the same quality of life after donation. DISCUSSION: LKD is a good therapeutic alternative. Some aspects should be developed, such as more information about living donation and the need to considering donors as healthy persons without loss of earnings. Recognition of the benefits of living donation requires more wide participation of all citizens nationally.

The process of adult living liver donation.

OBJECTIVE: To evaluate both the opinion that living liver donors have of the process and the psychological, economic, and social consequences of donation. MATERIAL AND METHODS: Six months after the donation, an anonymous survey was sent to 22 donors of the right liver lobe between March 2000 and December 2002. RESULTS: 15 surveys were returned with all of the questions answered. Almost all the donors had no prior knowledge of living donation. When they were considered to be suitable donors, all of them felt happy, 21% were scared and 15% felt joy and insecurity. The information provided was well understood and accurately described the experiences of 93% of donors. All donors understood the vital risk, and 93% understood that transplantation is not always completely successful. All donors would repeat the experience. Mean hospital stay was 12.6 days. Mean convalescence was 50.6 days. Salaried donors were on sick leave for a mean of 96.4 days (21-150 days), causing financial problems in six cases (36%), due to no financial compensation and compulsory redundancy in one case. All donors had completely recovered at six months after donation. DISCUSSION: Adult living donation of the right liver lobe is an accepted therapeutic alternative. In order to regulate medical and economic protection to avoid additional disturbances after donation, the public, patients, and physicians require more complete information about living donation.

Impairment of insulin secretion. A long way to go from islets to clinical research

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High-monounsaturated fat, olive oil-rich diet has effects similar to a high-carbohydrate diet on fasting and postprandial state and metabolic profiles of patients with type 2 diabetes.

Whether metabolic control in type 2 diabetes mellitus (DM) is best achieved with the traditional high-carbohydrate (CHO), low-fat diet or a low-CHO, high-fat diet is still controversial. In a randomized crossover study, we compared the effects of a low-fat (30% of daily energy) diet and a high-fat (40% of daily energy), high-monounsaturated-fat diet for 6 weeks each on fasting and postprandial glucose, insulin, and lipoprotein concentrations in 12 patients with well-controlled type 2 DM (fasting blood glucose, 176 +/- 54 mg/dL; hemoglobin A1c, 6.4% +/- 0.7%) and no overt dyslipidemia (serum total cholesterol, 235 +/- 43 mg/dL; triglycerides, 180 +/- 63 mg/dL). Home-prepared foods were used and olive oil was the main edible fat, accounting for 8% and 25% of daily energy requirements in the low-fat and high-fat diets, respectively. For postprandial studies, the same mixed meal containing 36% fat was used in both dietary periods. Body weight and fasting and 6-hour postprandial blood glucose, insulin, and lipoprotein levels were similar after the two diets. The mean incremental area under the curve of serum triglycerides 0 to 6 hours after the challenge meal, adjusted for baseline levels, did not change significantly after the high-fat diet compared with the low-fat diet (1,484 +/- 546 v 1,714 +/- 709 mg x 6 h/dL, respectively, P = .099). Mean postprandial triglyceride levels at 6 hours were increased about 2 times over fasting levels and were still greater than 300 mg/dL after either diet. A diet high in total and monounsaturated fat at the expense of olive oil is a good alternative diet to the traditional low-fat diet for patients with type 2 DM. However, ongoing postprandial hypertriglyceridemia with either diet points to the need for other therapies to decrease triglyceride-rich lipoproteins (TRL) and the inherent atherogenic risk in type 2 diabetics.

Effects of insulin administration in a group of high-risk, non-diabetic, first-degree relatives of Type 1 diabetic patients: an open pilot trial.

AIMS: To elucidate the effect of prophylactic insulin, in a treatment schedule previously demonstrated to achieve beta-cell rest, in a group of high-risk, non-diabetic first-degree relatives of Type 1 diabetic patients. METHODS: Ten high risk subjects for Type 1 diabetes mellitus (DM) (seven male/three female, aged 19.8+/-9.6 years) defined as: first-degree relatives of Type 1 DM patients, islet cell autoantibodies (ICA) > or =20 Juvenile Diabetes Foundation (JDF) units twice, first phase insulin response (FPIR) to glucose in an intravenous glucose tolerance test < or =10th percentile of a control group were included in an open pilot trial. Five were treated with subcutaneous insulin: 0.1 IU/kg body weight/day of neutral protamine hagedorn (NPH) insulin once a day. Five declined treatment and were used as controls. Control and treatment groups did not differ in terms of age, ICA, insulin autoantibodies (IAA), glutamic acid dehydrogenase (GAD) and FPIR. RESULTS: Three out of five subjects in both groups developed Type 1 DM during follow-up: after 21, and 32-57 months in the insulin-treated group and after 4, and 18-60 months in the untreated group. Three out of six subjects who developed overt diabetes had a FPIR below the 2nd percentile of the control value at the onset of the study. All subjects who developed diabetes were positive for antibodies to GAD and expressed the HLA-DR3 or DR4 alleles, whereas only one of the non-progressors had these parameters (P < 0.05). During follow-up, a decrease in ICA titres was observed in the group which received prophylactic insulin in contrast with the untreated group. GAD, as well as insulin secretory capacity, remained unchanged in both groups. CONCLUSION: The subcutaneous administration of insulin (0.1 IU/kg body weight/day of NPH insulin once a day) in our group of high-risk subjects for Type 1 DM produced only a minor effect in some immunological markers (ICA), without preventing the development of overt disease. The efficacy and safety of insulin used at either a different dose or by a different route, as well as its potential effect in the early phases of prediabetes, warrants further investigation.

Randomized crossover study of gemfibrozil versus lovastatin in familial combined hyperlipidemia: additive effects of combination treatment on lipid regulation.

The most appropriate therapy for combined hyperlipidemia remains to be determined. We compared the lipid-regulating effects of gemfibrozil and lovastatin in 30 patients with familial combined hyperlipidemia (FCHL) in a randomized, double-blind, placebo-controlled crossover study including 8-week courses of one drug followed by a washout period and a crossover phase to the alternate drug. After completion of the trial, open-label combination therapy was given for up to 12 months. Lovastatin was more efficacious than gemfibrozil in the reduction of total cholesterol (23% v. 9%, P<.001) and low-density lipoprotein (LDL) cholesterol (28% v. 2%, P<.001), whereas gemfibrozil surpassed lovastatin in the reduction of triglycerides (48% v. 0%, P<.001) and very-low-density lipoprotein (VLDL) cholesterol (50% v. 19%, P = .005) and the increase of high-density lipoprotein (HDL) cholesterol (18% v. 4%, P = .005). Lovastatin caused a greater decline in total apolipoprotein B (apo B) and LDL apo B than gemfibrozil, whereas VLDL apo B decreased only after gemfibrozil therapy. Drug-induced changes in lipoprotein composition indicated that gemfibrozil reduced both the number and size of VLDL particles and lovastatin decreased the number of LDL particles. Combined treatment was safe and had additive effects on lipids, causing significant (P<.001) reductions in total cholesterol (32%), triglycerides (51%), LDL cholesterol (34%), and apo B (26%) and an increase in HDL cholesterol (19%). Target LDL cholesterol levels were achieved only in 11% of patients given gemfibrozil alone and triglycerides decreased to target levels in 22% after lovastatin alone, whereas combined therapy normalized both lipid fractions in 96% of patients. Thus, in FCHL, gemfibrozil has no effect on LDL cholesterol levels but favorably influences the putative atherogenic alterations of lipoprotein composition that are related to hypertriglyceridemia. Conversely, lovastatin markedly decreases LDL cholesterol but has little effect on triglyceride-rich lipoproteins. Combination treatment safely corrects all of the lipid abnormalities in most patients.

Recurrence of immunological markers for type 1 (insulin-dependent) diabetes mellitus in immunosuppressed patients after pancreas transplantation.

BACKGROUND: Type 1 (insulin dependent) diabetes mellitus (IDDM) is an autoimmune disease in which autoantibodies against islet cells develop concomitantly with or even preceding diagnosis. Because the recurrence of diabetes can be the cause of graft failure in patients with pancreas transplantation, we studied the possible recurrence of IDDM immunomarkers after transplantation. METHODS: The following determinations were performed every 1-2 years after transplantation in 50 immunosuppressed IDDM patients with simultaneous kidney and pancreas transplantation (bladder drainage of exocrine secretion): islet cell antibodies (ICA) by direct immunofluorescence, antibodies against glutamic acid decarboxylase (GADab) by radiobinding assay, and the oral glucose tolerance test. The mean follow-up was 4.1+/-6.3 (range 1 to 9 years). RESULTS: GADab were detected in 11 patients after transplantation, 10 of whom had been positive beforehand. ICA reappearance after transplantation was detected in seven patients (14%). The presence of ICA was related to GADab positivity (P=0.001) and HLA DR3 patients (P=0.04), but not with pancreatitis and rejection episodes, immunosuppression induction therapy, or donor HLA haplotype. During follow-up, an abnormal oral glucose tolerance test was more frequent in ICA-positive patients (P=0.02), with no differences in metabolic control or insulin secretion. CONCLUSION: We conclude that GADab persist and ICA reappear despite immunosuppressive therapy in patients with functioning pancreas transplants. The relevance and the risk that this implies for IDDM development should be determined.

Lack of interaction of apolipoprotein E phenotype with the lipoprotein response to lovastatin or gemfibrozil in patients with primary hypercholesterolemia.

The magnitude of serum lipid changes in response to hypolipidemic drugs varies considerably between individuals. These differences may be due to interactions between genetic and environmental factors that effect drug bioavailability or the capacity of the lipid-regulating enzyme and receptor targets to be affected. The apolipoprotein E (apoE) gene locus has been examined in this regard, but reports are conflicting on the effect of its variability on the response to hypolipidemic drugs. We investigated the effect of apoE polymorphism on the serum lipid response to the hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase inhibitor lovastatin and the fibric acid derivative gemfibrozil. Lipoprotein changes were assessed after 12 weeks of therapy in 106 patients with primary hypercholesterolemia and combined hyperlipidemia treated with lovastastin and in 63 given gemfibrozil therapy. No significant effect of the apoE phenotypes E3/2, E3/3, or E4/3 on the heterogeneity of lipid responses to either drug was found.

High proinsulin levels in late PRE-IDDM stage.

AIM: To analyse the fasting proinsulin levels in first degree relatives of patients with insulin-dependent diabetes mellitus (IDDM) with different risk for developing the disease. PATIENTS AND METHODS: Non siblings first degree relatives, 33, of IDDM patients were separated into three groups with different risk for developing IDDM: Group 1, 14 first degree relatives (eight male/six female), aged from 18 to 57 years, normal first phase insulin release (FPIR) in the intravenous glucose tolerance test, negative ICA; Group 2, 11 first degree relatives (six male/five female), aged from 16 to 62 years, normal FPIR and ICA < 20 JDF U; Group 3, eight first degree (six male/two female), from 16 to 52 years, FPIR diminished and ICA > 20 JDF U. All patients had normal oral glucose tolerance test at the initiation of the study. We tested fasting proinsulin (PRO) and insulin (IRI) levels by radioimmunoassay (RIA) and the PRO/IRI ratio. RESULTS: Four first degree from the group 3 developed IDDM after 2-32 months. No differences were observed in-fasting PRO levels and PRO/IRI ratio between the groups. However, the PRO (21.7 +/- 5.8 pmol/l) and PRO/IRI ratio (0.29 +/- 0.10) levels of the subjects who developed IDDM were significantly higher (P < 0.05) than those values obtained in subjects who did not developed the disease. CONCLUSION: these data indicate that fasting PRO levels and the PRO/IRI ratio may be an additional marker in post-puberty first-degree relatives of IDDM patients with immunological and metabolic evidence of high risk for developing the disease.

[Presence of markers predictive of type I pre-diabetes mellitus status in relatives of patients with type I diabetes mellitus]. / Presencia de marcadores predictivos del estado de prediabetes mellitus tipo I en familiares de pacientes con diabetes mellitus tipo I.

BACKGROUND: The aim of this study was to analyze the predictive factors of IDDM in first degree relatives of IDDM patients. SUBJECTS AND METHODS: From 1992 to 1994, 1,053 first degree relatives were screened for measuring islet cell antibodies (ICA) by indirect immunofluorescence (iFl). In all ICA positive subjects, beta cell function was analyzed by intravenous glucose tolerance test (IVGTT) and other immunologic parameters were also studied: anti-insulin antibodies (IAA) by radiobinding and antibodies to glutamic acid decarboxylase (GADAb) by ELISA methods. RESULTS: ICA were found in 3.1% of the first degree relatives. IVGTT showed a significant decrease in acute first phase of insulin response to glucose (IRI 1 minute + 3 minute) in those with ICA > or = 20 JDF units. In patients with ICA > or = 20 JDF units, 20% were found to be positive for IAA and 40% were positive for GAdAb. Thirty-one percent (10/32) of ICA positive first degree relatives fulfilled prediabetes criteria. During follow-up, 40% (4/10) of these prediabetic patients developed IDDM. CONCLUSION: This study confirms the possibility of identifying among first degree relatives of IDDM patients the subgroup with high risk of developing IDDM thus allowing the initiation of therapy for preventing or delaying IDDM onset.