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Introduction: The increasing burden of diabetes poses a great challenge to healthcare systems and economy worldwide. Although modern therapeutic strategies for diabetes are widely available, most patients still fail to achieve optimal clinical targets and well-being. The primary objective of this study was to assess and explore potential drivers and successful management of diabetes among people with diabetes, family members and healthcare professionals in Portugal, by applying the protocol of the multinational study "Diabetes, Attitudes, Wishes and Needs (DAWN2)"., Material and Methods: A total of 767 adults, including 417 people with diabetes, 123 family members and 227 healthcare professionals, participated in the study. Surveys assessed health-related quality of life, self-management, attitudes/beliefs, social support and priorities for improvement areas in diabetes care., Results: Diabetes has a negative impact on the physical health and emotional well-being of patients in Portugal and is also a psychological burden for family members. Earlier diagnosis and treatment of diabetes were mentioned as a major area of improvement. Healthcare professionals indicated the need for diabetes self-management education., Conclusion: We have used for the first time in Portugal the DAWN2 protocol to address the wishes, needs, and attitudes of Portuguese diabetes patients, their relatives, and healthcare professionals regarding the disease.

Aims/hypothesis: Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven., Methods: We dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet., Results: In individuals with normoglycaemia, DPP4 single-nucleotide variants governed glycaemic excursions (rs4664446, p=1.63x10 -7 ) and C-peptide release responses (rs2300757, p=6.86x10 -5 ) upon OGTT. Association with blood glucose levels was stronger at 30 min OGTT, but a higher association with the genetic control of insulin secretion was detected in later phases of the post-OGTT response, suggesting that the DPP4 gene directly senses glucose challenges. Accordingly, in mice fed a normal chow diet but not a high-fat diet, we found that, under OGTT, expression of Dpp4 is strongly downregulated at 30 min in the mouse liver. Strikingly, no genetic association was found in prediabetic individuals, indicating that post-OGTT control by DPP4 is abrogated in prediabetes. Furthermore, Dpp4 KO mice provided concordant evidence that Dpp4 modulates post-OGTT C-peptide release in normoglycaemic but not dysmetabolic states., Conclusions/interpretation: These results showed the DPP4 gene as a strong determinant of post-OGTT levels via glucose-sensing mechanisms that are abrogated in prediabetes. We propose that impairments in DPP4 control of post-OGTT insulin responses are part of molecular mechanisms underlying early metabolic disturbances associated with type 2 diabetes., (© 2021. The Author(s).)

Systemic insulin availability is determined by a balance between beta-cell secretion capacity and insulin clearance (IC). Insulin-degrading enzyme (IDE) is involved in the intracellular mechanisms underlying IC. The liver is a major player in IC control yet the role of hepatic IDE in glucose and lipid homeostasis remains unexplored. We hypothesized that IDE governs postprandial IC and hepatic IDE dysfunction amplifies dysmetabolic responses and prediabetes traits such as hepatic steatosis. In a European/Portuguese population-based cohort, IDE SNPs were strongly associated with postprandial IC in normoglycemic men but to a considerably lesser extent in women or in subjects with prediabetes. Liver-specific knockout-mice (LS-IDE KO) under normal chow diet (NCD), showed reduced postprandial IC with glucose intolerance and under high fat diet (HFD) were more susceptible to hepatic steatosis than control mice. This suggests that regulation of IC by IDE contributes to liver metabolic resilience. In agreement, LS-IDE KO hepatocytes revealed reduction of Glut2 expression levels with consequent impairment of glucose uptake and upregulation of CD36, a major hepatic free fatty acid transporter. Together these findings provide strong evidence that dysfunctional IC due to abnormal IDE regulation directly impairs postprandial hepatic glucose disposal and increases susceptibility to dysmetabolic conditions in the setting of Western diet/lifestyle., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this article were reported., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Diabetes Mellitus is a major public health threat worldwide and continues to increase in numbers and significance. Estimates of diabetes prevalence, awareness, treatment and control are essential to effectively monitor its trends, plan and evaluate interventions., Methods: We conducted a nationwide health examination survey in the population residing in Portugal aged between 25 and 74 years old in 2015. It consisted in a cross sectional prevalence study which included the measurement of HbA1c, a physical examination and a general health interview of a probabilistic sample of 4911 individuals (Authorization n°9348/2010 of the National Committee for Data Protection)., Results: The overall prevalence of diabetes was 9.9% (95%CI: 8.4; 11.5). It was higher in males than in females (12.1% vs 7.8%). Diabetes was more prevalent among individuals of lower education and without any professional activity. The majority of persons with diabetes was aware of their condition (87.1%) and was taking antidiabetic medication (79.7%). Of these, 63.2% had glycated hemoglobin levels lower than 7.0% (53 mmol/mol), but the majority failed to comply with the LDL and blood pressure recommended clinical targets (71.9% and 59.0%). Similarly, the prevalence of prediabetes was 16%, higher among women than men (17.5% vs 14.4%)., Conclusion: The prevalence of diabetes and prediabetes remains higher than the global and European estimates, although there is increasing awareness of this disorder., (Copyright © 2018. Published by Elsevier B.V.)

Background: Diabetes is known as a major cause of morbidity and mortality worldwide. Portugal is known as the European country with the highest prevalence of this disease. While diabetes prevalence data is updated annually in Portugal, the General Practitioner's (GP) Sentinel Network represents the only data source on diabetes incidence. This study describes the trends in Diabetes incidence, between 1992 and 2015, and estimate projections for the future incidence rates in Portugal until 2024., Methods: An ecological time-series study was conducted using data from GP Sentinel Network between 1992 and 2015. Family doctors reported all new cases of Diabetes in their patients' lists. Annual trends were estimated through Poisson regression models as well as the future incidence rates (until 2024), sex and age group stratified. Incidence rate projections were adjusted to the distribution of the resident Portuguese population given Statistics Portugal projections., Results: The average increase in Diabetes incidence rate was in total 4.29% (CI95% 3.80-4.80) per year under study. Until 1998-2000, the annual incidence rate was higher in women, and from 1998-2000 to 2013-2015 turn out to be higher in men. The incidence rate projected for 2022-2024 was 972.77/10(5) inhabitants in total, and 846.74/10(5) and 1114.42/10(5), respectively, in women and men., Conclusions: This is the first study in Portugal to estimate diabetes incidence rate projections. The disturbing reported projections seem realistic if things continue as in the past. Actually, effective public health policies will need to be undertaken to minimize this alarming future scenario., (Copyright © 2016 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to estimate the prevalence of diabetes mellitus (DM) in hospitalized patients with community-acquired pneumonia (CAP) and its impact on hospital length of stay and in-hospital mortality., Research Design and Methods: We carried out a retrospective, nationwide register analysis of CAP in adult patients admitted to Portuguese hospitals between 2009 and 2012. Anonymous data from 157 291 adult patients with CAP were extracted from the National Hospital Discharge Database and we performed a DM-conditioned analysis stratified by age, sex and year of hospitalization., Results: The 74 175 CAP episodes that matched the inclusion criteria showed a high burden of DM that tended to increase over time, from 23.7% in 2009 to 28.1% in 2012. Interestingly, patients with CAP had high DM prevalence in the context of the national DM prevalence. Episodes of CAP in patients with DM had on average 0.8 days longer hospital stay as compared to patients without DM (p<0.0001), totaling a surplus of 15 370 days of stay attributable to DM in 19 212 admissions. In-hospital mortality was also significantly higher in patients with CAP who have DM (15.2%) versus those who have DM (13.5%) (p=0.002)., Conclusions: Our analysis revealed that DM prevalence was significantly increased within CAP hospital admissions, reinforcing other studies' findings that suggest that DM is a risk factor for CAP. Since patients with CAP who have DM have longer hospitalization time and higher mortality rates, these results hold informative value for patient guidance and healthcare strategies.

Background: Data routinely collected in electronic health records (EHRs) offer a unique opportunity to monitor chronic health conditions in real-time. Geographic information systems (GIS) may be an important complement in the analysis of those data., Objective: The aim of this study was to explore the feasibility of using primary care EHRs and GIS for population care management and public health surveillance of chronic conditions, in Portugal. Specifically, type 2 diabetes was chosen as a case study, and we aimed to map its prevalence and the presence of comorbidities, as well as to identify possible populations at risk for cardiovascular complications., Methods: Cross-sectional study using individual-level data from 514 primary care centers, collected from three different types of EHRs. Data were obtained on adult patients with type 2 diabetes (identified by the International Classification of Primary Care [ICPC-2] code, T90, in the problems list). GISs were used for mapping the prevalence of diabetes and comorbidities (hypertension, dyslipidemia, and obesity) by parish, in the region of Lisbon and Tagus Valley. Descriptive statistics and multivariate logistic regression were used for data analysis., Results: We identified 205,068 individuals with the diagnosis of type 2 diabetes, corresponding to a prevalence of 5.6% (205,068/3,659,868) in the study population. The mean age of these patients was 67.5 years, and hypertension was present in 71% (144,938/205,068) of all individuals. There was considerable variation in diagnosed comorbidities across parishes. Diabetes patients with concomitant hypertension or dyslipidemia showed higher odds of having been diagnosed with cardiovascular complications, when adjusting for age and gender (hypertension odds ratio [OR] 2.16, confidence interval [CI] 2.10-2.22; dyslipidemia OR 1.57, CI 1.54-1.60)., Conclusions: Individual-level data from EHRs may play an important role in chronic disease surveillance, namely through the use of GIS. Promoting the quality and comprehensiveness of data, namely through patient involvement in their medical records, is crucial to enhance the feasibility and usefulness of this approach.

Introduction: Diabetes Mellitus is a public health problem that is on the increase throughout the world, including in Portugal. This paper aims to identify the changing geographic pattern of this cause of death in Portugal and its association with sociomaterial deprivation., Material and Methods: This is a transversal ecological study of the deaths by Diabetes Mellitus in Portuguese municipalities in three periods (1989-1993, 1999-2003 and 2006-2010). It uses a Bayesian hierarchical model in order to obtain a smooth standardized mortality ratio and the relative risk of death by Diabetes Mellitus associated to sociomaterial deprivation., Results: In 1989-1993, the highest smooth standardized mortality ratio values were found in coastal urban municipalities (80% of municipalities with smooth standardized mortality ratio ≥ 161, of which 60% are urban); in 2006-2010, the opposite was found, with the highest smooth standardized mortality ratio values occurring in rural areas in southern inland regions (76.9% of municipalities with smooth standardized mortality ratio ≥ 161, of which 69.2% are rural), particularly the Alentejo. The relative risk of death by Diabetes Mellitus increases with vulnerability associated to social and economic conditions in the area of residence, and is significant in the last two periods (relative risk: 1.00; IC95%: 0.98-1.02)., Discussion: Diabetes Mellitus presents a geographic pattern marked by coastal-inland and urban-rural asymmetry. However, this has been altering over the last twenty years. 48% of the population reside in municipalities where the smooth standardized mortality ratio has increased in the last twenty years, particularly in the rural areas of inland Portugal., Conclusion: The highest smooth standardized mortality ratio are currently found in rural municipalities with the highest index of sociomaterial deprivation.

Late complications of type 1 and type 2 diabetes can also be effectively avoided or delayed using active intervention and available therapies. Despite these facts, the percentage of people with diabetes following the therapy proposed by health care professionals is quite low. People with diabetes or any other chronic disease have to be involved in their own treatment. Basic knowledge is very important for the patient but the reinforcement of appropriate attitudes and a continuous process of motivation is fundamental in changing habits and behaviour. We need to educate patients, giving them the tools and skills to manage their disease, allowing them to become autonomous, empowering them. In the Therapeutic Patient Education model the patient is no longer the object but instead one of the actors in the process. He becomes part of the team and part of the solution. Goals are agreed as a result of input of the patient's desires, details of his daily life, his perceptions and the HCP's biomedical objectives. The patient takes care of himself and will, step by step, become aware of the consequences of his actions, in collaboration with his health team., (Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)

The dynamic response to insulin is highly potentiated after meal ingestion, and this meal-induced insulin sensitization (MIS) in healthy subjects is dependent on cholinergic mechanisms. The main objective of this study was to test the hypothesis that the reduced response to insulin observed in moderately overweight subjects, in comparison with control lean subjects, is due to MIS impairment and not to a reduction in the direct hypoglycemic action of insulin. Both lean and overweight male subjects were recruited. Insulin sensitivity (IS) was assessed by the rapid insulin sensitivity test (RIST) performed after a 24 h fast, as well as after a standardized meal. Fasting glucose disposal was similar between lean and overweight subjects. Following the meal, glucose disposal increased more extensively in lean than overweight subjects. The insulin profiles, in both fasted and fed states, were superimposable, suggesting that the absence of a factor other than insulin is responsible for the decreased postprandial insulin sensitivity observed in overweight subjects. Our data suggest that in overweight subjects, MIS contribution is decreased, which is responsible for the postprandial impaired IS observed and is suggested to be the cause, not effect, of mild adiposity.

Background/aims: Chronic kidney disease (CKD) is a growing public health problem. However, data on risk factors and prevalence of CKD exist only in a small number of countries. Portugal has the highest incidence of end-stage renal disease (ESRD) among European countries, but there are huge disparities among countries. Whether these disparities reflect differences in risk factors, prevalence of CKD or other factors is currently unknown., Methods: We analyzed data from a nationally representative sample of 5,167 subjects, and estimated the prevalence of CKD and associated risk factors, and combined these prevalence estimates with available data on ESRD., Results: The prevalence of risk factors such as diabetes (11.7%), obesity (33.7%), and metabolic syndrome (41.5%) was similar to that in the US, but greater than in most European countries. The prevalence of CKD stages 3-5 was 6.1%, which is similar to that in other Western countries. The risk of ESRD was greater than in other European countries, but lower than in the US., Conclusion: The high incidence of ESRD among the Portuguese population is not due to a greater prevalence of CKD. A higher rate of progression associated with the high prevalence of risk factors may account for the high incidence of ESRD. The role of unmeasured factors needs to be evaluated in further studies., (Copyright © 2011 S. Karger AG, Basel.)

Diabetes has been associated with depression since Thomas Willis' work in 1684 (Rubin and Peyrot in Diabetes Metab Rev 18:173-175, 2002). The aim of this study is to identify social and clinical factors independently associated with depression in individuals with type 1 diabetes. We carried out a descriptive transversal study with 110 type 1 diabetes patients, administered a questionnaire and obtained demographical and diabetes-related data (number of years from diagnosis, initial admission at diagnosis, glycated hemoglobin, number of complications, insulin dose, number of insulin injections per day, admission for ketoacidosis or hypoglycemia at diagnosis, and specific diabetes complications such as nephropathy, retinopathy, peripheral neuropathy, coronariopathy, and amputation). Depressive symptoms were quantified using the Hamilton Score. We used T tests to investigate potential relations between the covariates and depression (Hamilton score). We concluded the following: as few as 10% of our patients had glycated hemoglobin under 7%; women had more symptoms of depression, and there are four independent factors associated with depression in individuals with type 1 diabetes mellitus: age, Graffar score, admission for ketoacidosis, and insulin dose.

Aims: Diabetes is a growing worldwide problem. Ascertaining its prevalence is vital as a starting point to establish and measure the success of health interventions. This study aimed to determine the prevalence of Type 2 diabetes and 'pre-diabetes', defined as impaired fasting glucose and impaired glucose tolerance, in the Portuguese population aged between 20 and 79 years., Methods: Considering the number of inhabitants between 20 and 79 years old, statistical units were selected that were representative regionally and nationally. The total sample comprised 5167 subjects. National prevalence was calculated. Analyses were performed on all those without previously known diabetes using World Health Organization reference diagnostic criteria., Results: We found a diabetes prevalence of 11.7% (95% confidence interval 10.8-12.6%), with a significant difference between men (14.2%; 95% confidence interval 12.5-15.5%) and women (9.5%; 95% confidence interval 8.5-10.6%). While 6.6% of the subjects had previously been diagnosed with diabetes, 5.1% were undiagnosed. By age groups, 2.4% of the population between 20 and 39 years, 12.6% of people from 40 to 59 years old and 26.3% of those aged between 60 and 79 years had diabetes. Prevalence of 'pre-diabetes' (impaired fasting glucose, impaired glucose tolerance or both) in the population was 23.3%., Conclusions: Diabetes has a high prevalence in Portugal. If 'pre-diabetes' is also considered, about one-third (34.9%) of the population aged 20-79 years is affected. A greater number of males were found to have diabetes. We detected a high percentage of people with undiagnosed diabetes (43.6%).

Background: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide., Aims: This guideline provides evidence-based recommendations for preventing T2DM., Methods: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria., Results: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective., Conclusions: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication., (Georg Thieme Verlag KG Stuttgart-New York.)

When we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: prevention is better than cure. Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20-79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe. The good news is that diabetes is preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society. A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play. Small changes in lifestyle will bring big changes in health. Through joint efforts, more people will be reached. The time to act is now., (Georg Thieme Verlag KG Stuttgart-New York.)

Background: The marked increase of type 2 diabetes necessitates active development and implementation of efficient prevention programs. A European level action has been taken by launching the IMAGE project to unify and improve the various prevention management concepts, which currently exist within the EU. This report describes the background and the methods used in the development of the IMAGE project quality indicators for diabetes primary prevention programs. It is targeted to the persons responsible for diabetes prevention at different levels of the health care systems., Methods: Development of the quality indicators was conducted by a group of specialists representing different professional groups from several European countries. Indicators and measurement recommendations were produced by the expert group in consensus meetings and further developed by combining evidence and expert opinion., Results: The quality indicators were developed for different prevention strategies: population level prevention strategy, screening for high risk, and high risk prevention strategy. Totally, 22 quality indicators were generated. They constitute the minimum level of quality assurance recommended for diabetes prevention programs. In addition, 20 scientific evaluation indicators with measurement standards were produced. These micro level indicators describe measurements, which should be used if evaluation, reporting, and scientific analysis are planned., Conclusions: We hope that these quality tools together with the IMAGE guidelines will provide a useful tool for improving the quality of diabetes prevention in Europe and make different prevention approaches comparable., (Georg Thieme Verlag KG Stuttgart-New York.)

Objectives: To evaluate the effect of etonogestrel implant on the control of the carbohydrate and lipid metabolism and on the progression of vascular complications in diabetic women treated with insulin, and to assess the acceptability of this modality of contraception in these patients., Methods: Prospective-observational study of 23 women with insulin-treated diabetes. Clinical and metabolic evaluation was performed before and at 3, 6, 12, and 24 months after implant insertion. Changes from baseline were compared using the mixed effects models or Wilcoxon matched-pairs signed-rank tests., Results: There were no significant changes in BMI, in daily insulin requirement and in mean HbA1c. There was a significant reduction of total serum cholesterol (TC) at 6 and 12 months, of triglyceride levels at 6, 12 and 24 months, and of high-density lipoprotein cholesterol (HDL-C) at 6, 12 and 24 months. Neither the low-density lipoprotein (LDL) levels nor the HDL/TC ratio changed. Albuminuria decreased significantly at 12 and 24 months. No deterioration of the retina was observed over the study period. Amenorrhoea and infrequent bleeding were the most common menstrual bleeding patterns. One woman discontinued the method due to frequent bleeding., Conclusion: We found no evidence of impaired control of the carbohydrate and lipid metabolism or aggravation of vascular lesions during the two years an etonogestrel implant was used by diabetic women.

In animal studies, the whole-body glucose disposal effect of insulin is low in the fasted state or after atropine infusion, but doubles after a meal, consistent with the hepatic insulin-sensitizing substance (HISS) hypothesis. We tested how a standardized test meal and atropine affected the dynamic response to insulin in humans. Insulin sensitivity was assessed in healthy male subjects (aged 28.9 +/- 1.9 years, body mass index 23.3 +/- 0.8 kg.m-2) by using the rapid insulin sensitivity test (RIST), which is a transient euglycemic clamp. After a 24-hour fasting period, dynamic insulin sensitivity was assessed and then repeated 100 min after the test meal. In a second protocol, the volunteers were fed the standardized test meal and intravenous atropine (0.5 mg) or saline (control group) was administered 50 min before insulin sensitivity assessment. Insulin sensitivity increased in the fed state (232.1% +/- 46.3%, n = 7) in comparison with the 24-hour fasted state. In the atropine protocol, the drug partially blocked (56.5% +/- 11.6%, n = 6) insulin sensitivity. In humans, feeding resulted in increased insulin sensitivity. The low dose of atropine in humans lead to a partial HISS-dependent decrease in insulin sensitivity. Meal-induced insulin sensitization occured in humans by a similar mechanism as that reported in other species. The sensitization process was regulated by a cholinergic 'feeding signal.'

The objective of this study was to develop a Rapid Insulin Sensitivity Test (RIST) in humans, a test already used in animal studies. Insulin sensitivity was assessed using a rapid modified euglycemic clamp, the RIST. In this test, glucose disposition was determined after an intravenous (i.v.) bolus (50mU/kg bw administered over 30 seconds) of insulin, before and after feeding a standardized test meal, in healthy male subjects (aged 27.8 +/- 2.4 years, BMI 23.5 +/- 1.2 kg/m2). The RIST uses as the index of insulin sensitivity, the total amount of glucose required to be infused to maintain euglycemia during insulin action following an i.v. bolus of insulin. During the RIST, glucose levels are determined at 2-min intervals in order to clamp the glycemia at baseline values. Following a 24 hr fasting period, the RIST index was 225.6 +/- 25.1 mg glucose/kg bw. The volunteers were then fed a standardized test meal, a new stable glucose level was obtained 100 min after the meal, and a second RIST was performed. The glucose requirement (RIST index) increased to 647.9 +/- 73.5 mg glucose/kg bw following the standardized test meal (n = 5, p < 0.001). This report describes a new technique to evaluate insulin sensitivity in healthy humans. The RIST is a powerful research tool to assess the glucose utilization action of an insulin bolus in fasted and fed states both evaluated in the same day.

At the present time, there are markers which we can use to identify individuals with a high susceptibility of developing insulin-dependent diabetes mellitus (IDDM) years before the onset of the disease. Insulin-dependent diabetes mellitus is an autoimmune disease strongly associated with HLA antigens DR3 and DR4. In this manuscript, we discuss the usefulness of several markers, such as islet cell antibodies, insulin autoantibodies and glutamic acid decarboxylase antibodies, to identify individuals with a high susceptibility to IDDM before the disease is clinically evident. Monitoring first phase insulin release during intravenous glucose administration is a useful index of residual beta cell function that can be used to detect individuals who are close to insulin dependence. Several drugs have been used to prevent the development of IDDM. These include immunodepressors, anti-inflammatory agents, non-specific immunomodulators and free radical scavengers. Due to their toxicity, studies employing aziothioprine and cyclosporin were discontinued. Other agents, such as tetrandrin and lymphotoxin, are now restricted to non-human trials. Currently, two large-scale multicentric human trials, one in Europe using nicotinamide (European Nicotinamide Diabetes Intervention Trial, ENDIT) and the other in the USA using insulin (Diabetes Prevention Trial), are now in full activity and will test the benefits of these drugs in the prophylaxis of IDDM in highly susceptible individuals.