Coronary heart disease is the single greatest contributor to mortality within developed countries in our time. Type 2 diabetes mellitus and obesity, both of which are potent risk factors for coronary heart disease, are common conditions with rapidly rising rates of prevalence both globally and in Australia. Within Australia, Indigenous Australians suffer from disproportionately high rates of diabetes, obesity and coronary heart disease, the reason for which lies, in part, with changes in dietary intake and decreased levels of physical activity over the past 200 years. These disease trends have led to a substantially reduced life expectancy from an increase in excess cardiovascular deaths in Indigenous Australians. Assessment of cardiovascular risk in Indigenous Australians is complicated by ethnic differences in cardiovascular risk factors and their prevalence. There is also evidence that Indigenous Australians are genetically predisposed to diabetes. Current cardiovascular risk stratification algorithms are suboptimal, significantly underestimating risk in Indigenous Australians. This thesis aimed to address these issues. Firstly, to evaluate the efficacy of a lifestyle intervention programme to sustainably improve markers of health outcome in a cohort of Indigenous Australians who were overweight or had type 2 diabetes mellitus by improving diet and physical activity levels. Secondly, to evaluate the utility of anthropometric markers of obesity, ultrasound markers of atherosclerotic burden and serum C-reactive protein as additional cardiovascular risk stratification tools. The Healthy Lifestyle Programme (HELP) was a two year prospective intervention study designed and implemented with substantial input from the Indigenous community. The primary intervention consisted of a series of educational workshops delivered predominantly by Indigenous health workers advocating improving diet and increasing physical activity. To complement these workshops, facilities were established within the community to support dietary improvement and increased physical activity. Sustainable changes to markers of cardiovascular outcome, including significant reductions in central obesity and blood pressure were demonstrated over time. A slowing in the deterioration of renal function as marked by albuminuria was also detected. These beneficial changes were accompanied by increased physical activity and improved dietary intake. In a substudy, individuals with the apolipoprotein E4 genotype, who were dyslipidaemic at baseline, benefited from lipid profiles that improved significantly during the course of the study. Changes in blood pressure and central obesity detected during the course of the project are likely to have significant clinical impact on health outcomes considering their sustained nature. Evaluating ultrasound imaging based markers of cardiovascular risk, carotid artery intimal medial thickness was a more reliable measure of risk based on its firm correlation with established cardiovascular risk factors compared to brachial artery flow mediated vasodilatation. Carotid artery intimal medial thickness may be the better surrogate marker to improve cardiovascular risk stratification in the Indigenous population. Examining anthropometric markers of obesity, body mass index and waist circumference but not waist hip ratio correlated well with traditional cardiovascular risk factors. Furthermore, both body mass index and waist circumference predicted insulin resistance fairly well using threshold values derived from receiver operating characteristics curve analyses. Both body mass index and waist circumference were simple to perform with a high degree of reproducibility between observers and will likely be valuable additional cardiovascular risk stratification tools. Raised inflammatory stress, as marked by elevated serum C-reactive protein levels, was found in individuals with diabetes or obesity. C-reactive protein levels did not correlate with carotid artery intimal medial thickness, suggesting that C-reactive protein raises cardiovascular risk by means other than increasing atherosclerotic burden. Genotyping a small random sample of our the C-reactive protein gene promoter region. This SNP was found to independently increase serum C-reactive protein in the Framingham cohort. A genetic basis for increased inflammatory stress may contribute to coronary heart disease in Indigenous Australians. In summary, a community centred lifestyle intervention programme was efficacious in producing sustainable improvement in markers of health outcome. Examination of additional cardiovascular risk markers in the Indigenous community have provided evidence for using carotid artery intimal medial thickness, waist circumference, body mass index and serum C-reactive protein levels to improve cardiovascular risk stratification. These additional tools would allow for more specific resource allocation to target individuals at highest cardiovascular risk for preventative management. C-reactive protein gene polymorphisms, their contribution to circulating C-reactive protein levels and cardiovascular outcomes warrants further investigation in the Indigenous population. A more proactive risk management plan, which includes a lifestyle intervention component, may yield the greatest improvement in long term health outcomes if targeted at younger members of the Indigenous community.

BACKGROUND Quality improvement literature usually conceptualises two principal dimensions of quality, technical and service. Technical quality is what the customers receive relative to what is known to be effective and largely reflects issues related to the health care providers. Service quality is how the customers receive the services and reflects the way and the environment in which health services are provided. This thesis proposes and tests a third principal dimension, Customer Quality, which is the characteristics that customers need for effective involvement in health care processes, decision making and action to improve the quality of care delivered and received. This model is applied in the context of care for people with Type 2 diabetes as an example of the high priority common chronic diseases and one of the most important public health problems in Australia and worldwide. The study also examines the feasibility of using patient reports of received care as a way of measuring service and technical quality on a population basis. OBJECTIVE The present study aims to assess the quality of delivered care as perceived by people with Type 2 diabetes. Specifically it aims to measure service quality, technical quality, customer quality; and finally an overall quality index by combining all three dimensions. METHODS A community based cross-sectional survey of 603 people with Type 2 diabetes was carried out in Queensland, Australia in 2005/06 using a self-administered questionnaire. The eligible participants were Diabetes Australia-Queensland members over 25 years old with diagnosed Type 2 diabetes at least one year prior to the study. Adherence to the eleven clinical, lifestyle and management indicators, derived from standard Diabetes Australia Guidelines, were measured from the patients’ reports as a representative of technical quality to explore the likely gap between received services and what should have been received in the 12-month period. Focus Group Discussions were used to determine the elements of service quality that were important from the patients’ perspective. Twelve service quality indicators, derived from the review of the literature and the focus groups, were assessed to calculate service quality as perceived by people with Type 2 diabetes. The validated, reliable and practical 13- item Patient Activation Measure was used to evaluate customer quality in terms of customers’ knowledge, skills and confidence. Demographic and disease related information was obtained using a self-reported questionnaire. Two types of outcome variables were used in this study: participantreported binary variables (having complications, continuity of care and diabetes control status) and calculated continuous variables (technical quality rating, service quality and customer quality scores and, finally, the overall quality index). RESULTS The response rate from the 1500 mailed out questionnaires was 40%. Nonrespondents were a little younger (P<0.001) than study participants and matched on gender (P> 0.05). Participants were mostly over 65 years old, over 50% were male, almost half of them were obese and a quarter were studying or had completed tertiary level of education. Almost two-thirds reported well controlled diabetes and 60% had diabetes for more than five years. Most of them were not treated by specialists and maintained continuity of care for their diabetes management. The majority of participants were treated with insulin or oral agents (72%) and 37% reported diabetes complications. Overall adherence rate for top 5 clinical and top 3 management and lifestyle indicators were 49.7% and 18.8% respectively. Over 90% of participants reported an appropriate level of checks of HbA1c, blood pressure and serum cholesterol. For lifestyle and management indicators, reported adherence rates to guidelines were lower than for clinical indicators. Participants who reported care as recommended for blood pressure measurements; feet examinations; self-management, diabetes knowledge and nutritional consultation reviews were more likely to report their diabetes as being well controlled. Participants maintaining continuity of care also reported fewer complications and well controlled diabetes. Of the twelve service quality indicators, the highest service quality score were for support group, basic amenities, dignity and confidentiality. Inadequate quality was identified for overall service quality (86.2), choice of care provider, continuity, timeliness, safety, prevention and accessibility. Younger participants reported lower service quality scores (P=0.001) and participants with good control of their diabetes had higher scores (P<0.001). Overall reported Customer Quality score was 64.5. Ten percent of participants did not achieve the Customer Quality score for the confidence stage and 26% did not reach the actual action stage. Nearly three quarters of respondent reported the capacity to take action for self-management but only 38% reported the highest Customer Quality score equating to perceived ability to change the action by changing health and environment. Participants with a higher level of education and those who maintain continuity of care reported a higher Customer Quality score. Participants with a higher Customer Quality score were also more likely to report well controlled diabetes status. An overall imperfect Quality Index score (70) reflects significant room for overall quality improvement of diabetes care services. The younger participants reported lower Quality Index scores than older ones. Higher Quality Index scores were highly significantly associated with reporting better diabetes control status and continuity of care. There were no significant differences in the Quality Index scores in terms of gender, participants’ education level and diabetes complications. CONCLUSION Customer quality appears to be a useful third dimension in conceptualising quality in health care, particularly in the context of chronic disease where good selfmanagement can improve the outcomes of care. A substantial proportion of Queensland adults with Type 2 diabetes reported receiving suboptimal care. From the perspective of people with Type 2 diabetes there is a notable gap between their expectations and what they have actually received in most aspects of provided care. The overall service quality and choice of care provider, accessibility, prevention, continuity, timeliness and safety were identified to be of inadequate quality. Participants also reported relatively low customer quality scores based on the personal knowledge, skills and confidence as well as low overall quality score for delivered diabetes care. Thus, there was a significant opportunity to improve the quality of diabetes care on all three dimensions. The study demonstrated that a patient selfadministered survey is a potentially useful way of measuring all three dimensions of quality of care for diabetes.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Thesis (Ph. D.)--West Virginia University, 2004. / Title from document title page. Document formatted into pages; contains xiv, 287 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 261-282).

<p>Typ 2 diabetes är den vanligaste diabetesformen i Sverige och har samband med vår vällevnad. Tidigare studier visar att sjukdomen är mer vanlig bland fysiskt inaktiva och bland människor med ett ökat energiintag. Syftet med studien var att kartlägga sjuksköterskans hälsofrämjande arbete i primärvården vid typ 2 diabetes. En kvalitativ intervjustudie användes för att samla data. Fem sjuksköterskor från olika vårdcentraler i gamla Skaraborgs län deltog. Analysen av intervjuerna resulterade i ett huvudtema och fem underteman. Resultatet visar på att sjuksköterskorna aktivt arbetar med att motivera patienterna till att ändra kostvanor och öka den fysiska aktiviteten i den icke- farmakologiska behandlingen. Sjuksköterskorna använde information, patientrelation, konkret arbete, patientens villkor och mål som verktyg för att få patienterna motiverade. Att förespråka kost och fysisk aktivitet anses vara mycket viktig uppgift för sjuksköterskorna och utgör en central del i deras arbete.</p> / <p>Type 2 diabetes is the most common form of diabetes in Sweden today and is related to our lifestyle. Previous studies indicate that the disease is more common among physical inactive people and in people with increased energy intake. The aim of this study was to survey how nurses´ in primary health care promote lifestyle change in patients with type 2 diabetes. A qualitative interview study was used for data collection. Five nurses from different primary health care settings in old Skaraborgs county participated. The analyses of the interviews resulted in one major theme and five sub themes. The result shows that nurses work actively to motivate patients to change dietary habits and start with daily physical activity as a part of non-drug therapy. The nurses´ used information, nurse- patient relationship, concrete work, goals and the patient terms as tools to get patients motivated. Promoting diet and physical activity is a central part of the nurses’ daily work.</p>

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Objetivo: Avaliar o efeito da intervenção dietética individualizada sobre o diagnóstico nutricional e controle metabólico em diabéticos tipo 2 sedentários Casuística e Métodos: Trata-se de um ensaio clínico controlado e prospectivo com 80 adultos, de ambos dos sexos, com Diabetes Mellitus tipo 2 divididos em GI (grupo intervenção: 40 indivíduos submetidos à intervenção dietética e a utilização de hipoglicemiante) e GC (grupo controle: 40 indivíduos submetidos à medicação hipoglicemiante). Foi realizada intervenção dietética individualizada por três meses baseando-se nas recomendações da American Diabetes Association (2002). Foram analisadas as variáveis antropométricas: massa corporal total (MCT), estatura com determinação do Índice de Massa Corporal (IMC) e perímetro da cintura (PC); as variáveis bioquímicas glicemia, colesterol total, LDL-colesterol, HDL-colesterol, triglicerídeos (TG) e hemoglobina glicada (HbA1c) e as variáveis dietéticas energia, proteínas, carboidratos, lipídeos, colesterol e fibras alimentares. Para estatística inferencial foi utilizado o Anova two-way com nível de significância de 95%. Resultados: Na análise intergrupos, o GC apresentou aumento nas variáveis: MCT (&#916;%=0,78; p=0,014), IMC (&#916;%=0,76; p=0,012), PC (&#916;%=0,75; p=0,019) enquanto que o GI apresentou redução nas variáveis: MCT (&#916;%=-3,71; p<0,001), IMC (&#916;%=-3,77; p<0,001), PC (&#916;%=-3,98; p<0,001). Na comparação da média do IR intergrupos, observou-se diferença nas variáveis: energia (p<0,001), lipídeos (p=0,012), gorduras saturadas (p<0,001); colesterol dietético (p=0,006); fibras alimentares (p=0,001); glicemia (p<0,001), colesterol total (p<0,001), LDL-colesterol (p<0,001) e HbA1c (p<0,001).Conclusão: A intervenção dietética foi eficiente em melhorar o perfil antropométrico e o controle metabólico dos diabéticos tipo 2 sedentários. / Objective: To evaluate the effect of individualized dietary intervention on nutritional diagnosis and metabolic control in sedentary subjects with type 2 diabetes. Materials and methods: This controlled clinical trial, investigated 80 adults, of both sexes, with type 2 diabetes. Patients were divided into intervention group (IG: 40 individuals subjected to intervention and hypoglycemic drug) and control group (CG: 40 individuals subjected only hypoglycemic drug). Individualized dietary intervention was conducted, for three months, based on the American Diabetes Association (2002). The anthropometric variables evaluated included: total body mass (TBM) and height to calculate body mass index (BMI), and waist circumference (WC): biochemical variables assessed were: blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides (TG), and glycated hemoglobin (HbA1c): In addition, the intake of energy, protein, carbohydrate, lipid, cholesterol, and dietary fibers. For inferential statistics two-way ANOVA was used with significant level of 95%.Results: In the intergroup analysis, the CG showed increase in TBM (&#916;%=0.78; p=0.014), BMI (&#916;%=0.76; p=0.012), WC (&#916;%=0.75; p=0.019); whereas IG decreased TBM (&#916;%=-3.71; p<0.001), BMI (&#916;%=-3.77; p<0.001), WC (&#916;%=-3.98; p<0.001). In comparing the mean RI intergroups, there was difference in the variables: energy/day (p<0.001), lipids (p=0.012), saturated fats (p<0.001), cholesterol (p=0.006), dietary fibers (p=0.001); blood glucose (p<0.001), total cholesterol (p<0.001), LDL-cholesterol (p<0.001), and HbA1c (p<0.001). Conclusions: The dietary intervention was efficiently the improvement the anthropometric and metabolic control of type 2 sedentary diabetics.

Over the past decade, there has been unprecedented increase in the number of genetic loci associating with type 2 diabetes (T2D) risk and related glycemic traits, thanks to advances in sequencing technologies and access to large sample sizes. Identification of associated genetic variants across the frequency spectrum can provide valuable insight into disease pathophysiology. However, the translation into biological insights has been slow often due to uncertainties over the underlying effector transcripts. G6PC2/ABCB11 is one locus characterised by common non-coding variants that are strongly associated with fasting plasma glucose (FG) levels in healthy adults. The work presented in this thesis aims to understand how protein-coding variants in glycemic trait loci such as G6PC2 contribute to the variability of glycemic traits and in addition gain further insight into the physiological role of G6PC2. To evaluate the role of coding variants in glycemic trait variation, an exome array genotyping study of non-diabetic European individuals (n=33,407) reported multiple coding variants in G6PC2 that were independently associated with FG. I designed and conducted in vitro assays to functionally assess these variants and showed that they result in loss of function (LOF) due to reduced protein stability. This established G6PC2 as the effector transcript influencing FG and highlighted a critical role for G6PC2 (encoding the islet-specific glucose-6-phosphatase catalytic subunit) in glucose homeostasis. To investigate the role of low frequency (MAF=1-5%) and rare (MAF&LT;1%) coding variants in influencing glycemic traits, recent large-scale exome array meta-analyses and whole exome sequencing were carried out as part of MAGIC (n=144,060) and the T2D-GENES/GoT2D consortia (n=12,940) respectively. G6PC1, a gene homolog of G6PC2 that primarily acts through the liver, was uncovered as a novel glycemic locus. My functional follow-up studies demonstrated that rare coding variants in G6PC1 exhibited LOF to influence both FG and FI levels. As rare variation in G6PC2 not previously identified could also affect G6PC2 function and modulate glycemic traits, I also functionally characterised a suite of rare non-synonymous G6PC2 variants. Most of the variants tested exhibited markedly reduced protein levels and/or loss of glycosylation. Several variants were also found to impact on enzymatic activity through inactivating or activating mechanisms to influence FG levels. Finally, to gain better understanding of the function of G6PC2 I performed gene knockdown studies in the EndoC-&beta;H1 human beta cell model followed by insulin secretion analyses. G6PC2 knockdown resulted in increased insulin secretion at sub-threshold glucose stimulation levels, consistent with studies in knockout mouse models. In addition, expression of LOF G6PC2 variants were found to upregulate ER stress responses. These results warrant further studies of the precise roles that G6PC2, an ER-resident protein, plays in regulating insulin secretory function and ER homeostasis in the beta cell. Overall, my work described multiple rare coding variants in both G6PC1 and G6PC2 that alter protein function to regulate glucose metabolism through diverse mechanisms in different tissues. Improved understanding of these effector transcripts will open up opportunities for the exploration of new therapeutic targets for glucose regulation and T2D.

Sur l’île de La Réunion, la prévalence du diabète de type 2 est 3,5 fois plus élevée que celle de la France hexagonale. Parmi les diverses complications qu’engendre le diabète, les AVC qui en résultent sont responsables d’une forte mortalité faisant des maladies cardiovasculaires un problème de santé publique majeur sur l’île. Les AVC ischémiques proviennent de l’occlusion d’une artère cérébrale par un thrombus généré localement ou qui s’est détaché d’une plaque d’athérothrombose généralement localisée au niveau des bifurcations carotidiennes. Les plaques compliquées sont souvent caractérisées par des hémorragies intraplaques, responsables de l’extravasation des cellules sanguines. Différents marqueurs moléculaires, protéiques et physiques peuvent refléter ces processus et renseigner le médecin sur l’instabilité de la plaque du patient. Il est donc important d’étudier ces marqueurs de risque de rupture de plaques carotidiennes chez les patients diabétiques, afin d’en prévenir les complications et la mortalité associée. L’hémorragie intraplaque, notamment pourvoyeuse d’érythrocytes et de neutrophiles libérant leurs contenus cytoplasmiques, participe activement à la déstabilisation de la plaque d’athérothrombose chez le diabétique. Cette thèse a permis l’étude de l’influence de ces marqueurs à travers une étude clinique et de proposer un nouveau concept de phagocytose des érythrocytes glyqués par les cellules endothéliales in vitro. Ainsi, les résultats préliminaires de l’étude clinique nous permettent de supposer que la clairance des globules rouges des patients diabétiques est altérée, ce qui leurs permettraient de résider sur une période plus longue dans les plaques de ces patients. De cette manière, les globules rouges pourraient y être pris en charge par d’autres types cellulaires comme les cellules endothéliales. Nous avons tout d’abord mis au point un modèle de glycation des érythrocytes in vitro reflétant un diabète mal équilibré. Nous avons ensuite mis en évidence que les globules rouges glyqués pouvaient être phagocytés par les cellules endothéliales humaines, conduisant à une prolifération limitée et à la surexpression de l’HO-1. Ces données suggèrent qu’une ingestion des érythrocytes glyqués par les cellules endothéliales pourrait amplifier la déstabilisation des plaques d’athérothrombose carotidiennes des diabétiques. / Type 2 diabetes prevalence in Reunion Island, a French overseas department, is 3.5 higher than in France mainland. Among the various diseases caused by diabetes, stroke induces high mortality making cardiovascular diseases a major public health problem on the island. Ischemic stroke results from a cerebral artery occlusion by a thrombus that is locally produced or has detached from an atherothrombotic plaque usually located at the carotid bifurcations. Complicated plaques can are often characterized by intraplaque hemorrhages, responsible for blood cell extravasation. Several molecular and physical markers can reflect these processes and inform the physician about the instability of the patient's plaque. It is therefore of major importance to study the markers of carotid plaque rupture in diabetic patients in order to prevent complications and associated mortality. Intraplaque hemorrhage, providing erythrocytes and neutrophils releasing their cytoplasmic contents, plays an active role in destabilizing atherothrombotic plaque in diabetic subjects. The objectives of the present thesis were to study these markers in a clinical study and to suggest a new concept of red blood cell phagocytosis by endothelial cells in vitro. According to the first results of the clinical study, we can suggest that in diabetic patients, the clearance of red blood cells is impaired. This prolonged residence of red blood cells in atherosclerotic plaques from diabetic patients. In this way, red blood cells could be phagocytosed by othercell types such as endothelial cells. In this work, we have also set up an in vitro model of erythrocyte glycation that reflects a clinical situation of poorly controlled diabetes. We have demonstrated that glycated red blood cell phagocytosed by human endothelial cells, leading to their limited proliferation and to HO-1 overexpression. These data suggest an ingestion of glycated erythrocytes by endothelial cells may amplify the destabilization of carotid atherothrombotic plaques in diabetics.

ABSTRACT Lifestyle factors related to overweight, obesity, and Type 2 diabetes are currently in the forefront of health issues affecting children and adolescents. Schools have been considered important venues for disseminating health education and promotion programs. Some investigators, however, contend that school-based programs have only seen modest success over the last two decades. Typically short-term, school-based interventions do not address program sustainability or larger social issues such as socioeconomic status (SES). A growing body of literature suggests there is value in collaborative efforts between university researchers and communities as these relationships can help build the capacity of the school and community. The Coordinated School Health Program (CSHP) model was developed as a mechanism to build the organizational capacity of schools to facilitate, integrate and sustain health education and promotion efforts to improve the health of youth in our nation. The purpose of the current study was to assess a mid-western middle school's capacity to sustain a previously implemented Type 2 diabetes prevention program. An instrumental case study design was utilized. A total of 19 interviews were conducted. Additionally, observations and documents related to school policies and procedures were reviewed. The four infrastructures of the CSHP framework were used as predetermined categories into which data were coded. This study found that there was potential for the school to sustain the Type 2 diabetes program within the framework of the CSHP Model. The school already had in place five of the eight CSHP components. The three remaining components could be implemented if several issues were addressed. First, there were many myths and misconceptions regarding the purpose and costs of a CSHP. Education for district administrators, school faculty and staff, as well as the community, would be vital. Concerns regarding personnel to implement a CSHP were expressed. A dedicated health course would also need to be implemented. When planning health related interventions that will be implemented in school-based settings researchers should seriously consider implementing a CSHP prior to employing their short-term programs. If programs can be planned with sustainability in mind, there is potential for greater health outcomes for school-aged children and adolescents.

A nefropatia diabética (ND) é uma complicação microvascular freqüente, que acomete cerca de 40% dos indivíduos com diabete melito (DM). A ND associa-se a significativo aumento de morte por doença cardiovascular. É a principal causa de insuficiência renal terminal em países desenvolvidos e em desenvolvimento, representando, dessa forma, um custo elevado para o sistema de saúde. Os fatores de risco para o desenvolvimento e a progressão da ND mais definidos na literatura são a hiperglicemia e a hipertensão arterial sistêmica. Outros fatores descritos são o fumo, a dislipidemia, o tipo e a quantidade de proteína ingerida na dieta e a presença da retinopatia diabética. Alguns parâmetros de função renal também têm sido estudados como fatores de risco, tais como a excreção urinária de albumina (EUA) normal-alta e a taxa de filtração glomerular excessivamente elevada ou reduzida. Alguns genes candidatos têm sido postulados como risco, mas sem um marcador definitivo. O diagnóstico da ND é estabelecido pela presença de microalbuminúria (nefropatia incipiente: EUA 20-199 μg/min) e macroalbuminúria (nefropatia clínica: EUA ≥ 200 μg/min). À medida que progride a ND, aumenta mais a chance de o paciente morrer de cardiopatia isquêmica. Quando o paciente evolui com perda de função renal, há necessidade de terapia de substituição renal e, em diálise, a mortalidade dos pacientes com DM é muito mais significativa do que nos não-diabéticos, com predomínio das causas cardiovasculares. A progressão nos diferentes estágios da ND não é, no entanto, inexorável. Há estudos de intervenção que demonstram a possibilidade de prevenção e de retardo na evolução da ND principalmente com o uso dos inibidores da enzima conversora da angiotensina, dos bloqueadores da angiotensina II e do tratamento intensivo da hipertensão arterial. Os pacientes podem entrar em remissão, ou até mesmo regredir de estágio. A importância da detecção precoce e da compreensão do curso clínico da ND tem ganhado cada vez mais ênfase, porque a doença renal do DM é a principal causa de diálise no mundo e está associada ao progressivo aumento de morte por causas cardiovasculares. / Diabetic nephropathy (DN) is a frequent microvascular complication, which affects about 40% of diabetes mellitus (DM) patients. DN is associated with an increased cardiovascular death rate. DN is the major cause of kidney failure in developing as well as in developed countries, and it is, therefore, associated with increased health system costs. The more defined risk factors for the development and progression of DN are sustained hyperglycemia and hypertension. Other putative risk factors are smoking, dyslipidemia, the amount and source of protein in the diet, and the presence of diabetic retinopathy. Some renal function parameters have also been studied as risk factors, such as high normal urinary albumin excretion (UAE) and extremely high or low glomerular filtration rate levels. Some candidate genes have been analyzed as risk factors, but without any definitive marker. DN diagnosis is established by the presence of microalbuminuria (incipient nephropathy: UAE 20-199 μg/min), and macroalbuminuria (overt nephropathy: UAE ≥200 μg/min). As DN progress, the chance of death from coronary artery disease increases. When patients progress to kidney failure with uremia, renal replacement therapy becomes necessary, and when on dialysis, diabetic patients have higher mortality rates in comparison to non-diabetic ones, primarily from cardiovascular causes. DN progression through stages is not always the rule. Intervention studies demonstrate that DN prevention and remission are possible, mainly with angiotensinconverting enzyme inhibitors, angiotensin-II receptor blockers, and intensive hypertension treatment. The importance of the earlier detection, and the understanding of clinical course of DN, have progressively grown, because it is the leading cause of dialysis in the world, and is associated with increased cardiovascular mortality.