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Le système rénine-angiotensine-aldostérone est impliqué dans la physiopathologie de l’insuffisance cardiaque (IC). L’inhibition de l’aldostérone par les antagonistes du récepteur aux minéralocorticoïdes (ARM), la spironolactone et l’éplérénone, est associée à une réduction de morbidité et mortalité. Or, la spironolactone est un antagoniste non sélectif, avec des effets hors-cibles sur d’autres récepteurs stéroïdiens. Des données suggèrent qu’elle pourrait avoir un effet défavorable sur l’homéostasie du glucose, avec une augmentation en hémoglobine glyquée (HbA1c), un marqueur de contrôle du glucose à long terme. Au contraire, l’éplérénone semble exercer un effet neutre. Les objectifs de cette thèse de doctorat sont les suivants : 1) Assembler toutes les connaissances dans la littérature au sujet de l’effet glycémique des ARM; 2) Évaluer le risque de développement de diabète avec la spironolactone chez les patients IC; 3) Analyser si la spironolactone peut moduler l’effet glycémique d’autres médicaments utilisés en IC; 4) Comparer la spironolactone à l’éplérénone sur des marqueurs de glucose chez les patients IC avec dérèglements glycémiques. Quatre projets ont été effectués afin de répondre à ces questions. Premièrement, une revue systématique a permis d’identifier toutes les études publiées contenant de l’information sur l’effet glycémique des ARM. Les résultats étaient hétérogènes, mais ont suggéré que l’effet est dépendant de la pathologie et serait potentiellement néfaste dans les maladies à haut risque d’évènements cardiovasculaires. Une méta-analyse d’études en diabète indique que l’effet à long terme serait non significatif. Le deuxième projet utilise une cohorte de patients IC de bases de données administratives entre 1995 et 2009 (suivi jusqu’en 2010). Nous n’avons pas détecté d’association significative entre l’utilisation de la spironolactone et le risque de diabète. Par contre, l’étude a démontré qu’un âge plus jeune, la digoxine, et les corticostéroïdes augmentent le risque de diabète. Le troisième projet est une sous-étude d’une étude clinique CANDIID-II (Effect of ACE inhibitor alone versus ACE inhibitor plus high dose candesartan on BNP, immune markers, inflammatory status, and urinary kinins in patients with symptomatic left ventricular systolic dysfunction) chez des patients IC traités avec un inhibiteur de l’enzyme de conversion à l’angiotensine et le candésartan, antagoniste du récepteur à l’angiotensine II. Ces classes pharmacologiques ont des effets bénéfiques sur la glycémie. En comparant les patients traités aussi avec la spironolactone versus les patients sans ARM, nous n’avons pas trouvé que la spironolactone module l’effet bénéfique du candésartan sur le métabolisme du glucose. Le dernier projet consiste d’une étude prospective, multicentrique, randomisée, contrôlée à double-insu : SNOW (A comparison of the effects of selective and non selective mineralocorticoid antagonism on glucose homeostasis and lipid profile of heart failure patients with glucose intolerance or type 2 diabetes). Elle compare, pendant 16 semaines, la spironolactone à l’éplérénone sur des marqueurs glycémiques, notamment, l’HbA1c, chez 62 patients IC avec diabète de type II ou intolérance au glucose. Aucune différence significative n’a été observée entre les groupes. En résumé, les résultats de cette thèse indiquent que les ARM ne présentent pas de risque de détérioration du contrôle du glucose sur une durée modérée à longue en IC. / The renin-angiotensin-aldosterone system is involved in the pathophysiology of heart failure (HF). The inhibition of aldosterone by mineralocorticoid receptor antagonists (MRAs), spironolactone and eplerenone, is associated with a reduction in morbidity and mortality. However, spironolactone is a non selective antagonist, with off-target effects on other steroid receptors. There is some evidence suggesting that it may have an unfavorable effect on glucose homeostasis, with an increase in glycated hemoglobin (HbA1c), a marker of long-term glucose control. On the contrary, eplerenone seems to exert a neutral effect. The objectives of this doctoral thesis were the following: 1) Compile all current knowledge in the literature on the subject of MRAs’ glycemic effects; 2) Evaluate the risk of developing diabetes with spironolactone in HF patients; 3) Analyze if spironolactone may modulate the glycemic effects of other medications used in HF; 4) Compare spironolactone to eplerenone on markers of glucose control in HF patients with glycemic disorders. Four projects were conducted in order to meet these objectives. Firstly, a systematic review allowed us to identify all published studies containing information on MRAs’ glycemic effects. The literature search yielded heterogenous results; however, it suggested that the effect was disease-specific and would be potentially harmful in diseases with a high risk of cardiovascular events. A meta-analysis of studies in diabetes insinuated that the effect is non significant on a long-term basis. The second project uses a cohort of HF patients from administrative databases between 1995 and 2009 (follow-up till 2010). We did not detect a significant association between the use of spironolactone and the risk of diabetes. On the other hand, the study demonstrated that younger age, digoxin, and corticosteroids increase the risk of diabetes. The third project is a substudy of a clinical trial CANDIID-II (Effect of ACE inhibitor alone versus ACE inhibitor plus high dose candesartan on BNP, immune markers, inflammatory status, and urinary kinins in patients with symptomatic left ventricular systolic dysfunction) among HF patients treated with an angiotensin converting enzyme inhibitor and candesartan, an angiotensin II receptor blocker. These pharmacological classes have beneficial effects on glycemia. By comparing patients also treated with spironolactone versus patients without an MRA, we did not find that spironolactone alters the effect of candesartan on glucose metabolism. The last project consisted of a prospective, multicenter, randomized, controlled, double-blind trial: SNOW (A comparison of the effects of selective and non selective mineralocorticoid antagonism on glucose homeostasis and lipid profile of heart failure patients with glucose intolerance or type 2 diabetes). It compares, for 16 weeks, spironolactone to eplerenone on glycemic markers, notably, HbA1c, among 62 HF patients with type II diabetes or glucose intolerance. There was no significant difference between groups. In summary, the research results from this thesis reveal that, in HF, MRAs do not present additional risks of deterioration in glucose control over a moderate to long period.

<p>УВОД: Diabetes mellitus (DM) је водећа глобална епидемија 21. века, сложена болест коју карактерише поремећај метаболизма и хронична хипергликемија, која доводи до развоја микроваскуларних и макроваскуларних компликација. Повишене вредности гликемије у ДМT2 доводе до поремећаја ћелија крви и њихових параметара. Истраживања су показала да хема-толошки параметри имају допринос у настанку оштећења васкуларног ендотела и учествују у развоју дегенеративних промена и путем других механизама код пацијената са дијабетесом. Циљ истраживања је да се утврде могуће промене параметара комплетне крвне слике (ККС) у зависности од гликорегулације, дужине трајања болести и њихова повезаност са микро и макро ангиопатским комликацијама код пацијената са шећерном болести тип 2 (ДМT2). МЕТОДЕ: Студија је била проспективна у трајању од једне године, од 2016. до 2017. године. Истраживањем је обухваћено укупно 137 испитаника, од којих 90 болује од ДМТ2, а 47 је здравих, оба пола, старијих од 40 година, спроведена у Дому здравља &ldquo;Др Милорад Мика Павловић&rdquo;, Инђија, Србија. Да би се утврдила могућа корелација између параметара ККС, гликорегулације у ДМT2 и дегенеративних компликација, испитаници су подељени на више начина: на групу оболелих од ДМT2 и групу здравих; групе оболелих са вредностима HbA1c&le;7% и оне са вредностима HbA1c &gt;7%, као и на групе са и без дегенеративних компликација. Коришћењем стандардних биохемијских поступака анализирани су параметри ККС, параметри гликорегулације, липидни статус, а вршена су и антропометријска мерења. Подаци од пацијената прикупљени су путем упитника и електронског картона пацијента. РЕЗУЛТАТИ: Утврђена је статистички значајна разлика између група са и без шећерне болести за WBC, еозинофилне гранулоците, хемоглобин, MCH, MCHC, SE у 2016. год, неутрофилне гранулоците, моноците, RDW, PDW, SE у 2017. год. У групи чија је дужина трајања ДМT2 већа од 6 година утврђене су повишене вредности MCHC и PDW. У односу на гликорегулацију уочене су значајне разлике у PMDW, великим тромбоцитима и RDW у групи са HbA1c&gt;7%. У односу на дегенеративне микроваскуларне компликације постоје значајне разлике у броју лимфоцита и неутрофилних гранулоцита, а за макроваскуларне компликације у вредностима PDW-а. ЗАКЉУЧАК: На основу добијених резултата нашег истраживања може се закључити да постоји повезаност између појединих хематолошких параметара и гликорегулације, обољевања од шећерне болести као и повезаност са компликацијама код пацијената са ДМТ2.</p> / <p>UVOD: Diabetes mellitus (DM) je vodeća globalna epidemija 21. veka, složena bolest koju karakteriše poremećaj metabolizma i hronična hiperglikemija, koja dovodi do razvoja mikrovaskularnih i makrovaskularnih komplikacija. Povišene vrednosti glikemije u DMT2 dovode do poremećaja ćelija krvi i njihovih parametara. Istraživanja su pokazala da hema-tološki parametri imaju doprinos u nastanku oštećenja vaskularnog endotela i učestvuju u razvoju degenerativnih promena i putem drugih mehanizama kod pacijenata sa dijabetesom. Cilj istraživanja je da se utvrde moguće promene parametara kompletne krvne slike (KKS) u zavisnosti od glikoregulacije, dužine trajanja bolesti i njihova povezanost sa mikro i makro angiopatskim komlikacijama kod pacijenata sa šećernom bolesti tip 2 (DMT2). METODE: Studija je bila prospektivna u trajanju od jedne godine, od 2016. do 2017. godine. Istraživanjem je obuhvaćeno ukupno 137 ispitanika, od kojih 90 boluje od DMT2, a 47 je zdravih, oba pola, starijih od 40 godina, sprovedena u Domu zdravlja &ldquo;Dr Milorad Mika Pavlović&rdquo;, Inđija, Srbija. Da bi se utvrdila moguća korelacija između parametara KKS, glikoregulacije u DMT2 i degenerativnih komplikacija, ispitanici su podeljeni na više načina: na grupu obolelih od DMT2 i grupu zdravih; grupe obolelih sa vrednostima HbA1c&le;7% i one sa vrednostima HbA1c &gt;7%, kao i na grupe sa i bez degenerativnih komplikacija. Korišćenjem standardnih biohemijskih postupaka analizirani su parametri KKS, parametri glikoregulacije, lipidni status, a vršena su i antropometrijska merenja. Podaci od pacijenata prikupljeni su putem upitnika i elektronskog kartona pacijenta. REZULTATI: Utvrđena je statistički značajna razlika između grupa sa i bez šećerne bolesti za WBC, eozinofilne granulocite, hemoglobin, MCH, MCHC, SE u 2016. god, neutrofilne granulocite, monocite, RDW, PDW, SE u 2017. god. U grupi čija je dužina trajanja DMT2 veća od 6 godina utvrđene su povišene vrednosti MCHC i PDW. U odnosu na glikoregulaciju uočene su značajne razlike u PMDW, velikim trombocitima i RDW u grupi sa HbA1c&gt;7%. U odnosu na degenerativne mikrovaskularne komplikacije postoje značajne razlike u broju limfocita i neutrofilnih granulocita, a za makrovaskularne komplikacije u vrednostima PDW-a. ZAKLJUČAK: Na osnovu dobijenih rezultata našeg istraživanja može se zaključiti da postoji povezanost između pojedinih hematoloških parametara i glikoregulacije, oboljevanja od šećerne bolesti kao i povezanost sa komplikacijama kod pacijenata sa DMT2.</p> / <p>BACKGROUND: Diabetes mellitus (DM) is the leading global epidemic of the 21st century,a complex disease characterized by metabolism disorders and chronic hyperglycaemia, that leads to the development of microvascular and macrovascular complications. Elevated blood glucose level in T2DM lead to disturbance of blood cells and its parameters. Previous studies have reported that haematological parameters have contributed to the development of vascular endothelial damage and are involved in the development of degenerative changes through other mechanisms in patients with diabetes. The aim of the research is to determine possible changes in the complete blood count (CBC) parameters depending on glycemic control, the duration of the disease and their association with micro and macroangiopathic complications in patients with Type 2 diabetes mellitus (T2DM). METHODS: The study was prospective from 2016. to 2017. year. The study included a total of 137 subjects, 90 with T2DM and 47 healthy, of both gender over the age of 40 years, from the Health Care Center &quot;Dr Milorad Mika Pavlović&quot; Indjija, Serbia. The subjects were divided into several ways, in order to notice the possible correlation between the CBC parameters and glucose control in T2DM, with and without T2DM, two groups with HbA1c&le;7% and with HbA1c&gt;7%, and with and without complications. We analysed CBC parameters, parameters of glycoregulation, lipid status using standard biochemical methods, performed anthropometric measurements and collected patients data by questionnaire and electronic patient card. RESULTS: There were statistical difference between group with T2DM and healthy subjects for WBC, eos, Hgb, MCH, MCHC, ESR in 2016. and neutro, mono, RDW, PDW, ESR in 2017. In the group of T2DM patients with duration of disease longer than 6 years we found elevated value of MCHC, PDW. In relationship to glycoregulation, significant differences in PMDW, large platelets and RDW were found in the group HbA1c&gt;7%. According to degenerative complications significant differences were revealed in lympho, neutro in the group with microvascular complication, and PDW in the group with macrovascular complications. CONCLUSION: Based on the resuluts of our research, it can be concluded that there is an association between particular haematological parameters and glycoregulation, diabetes mellitus, as well as relationship with degenerative complications in patients with T2DM.</p>

Fundação de Amparo a Pesquisa do Estado de Minas Gerais / Doutor em Genética e Bioquímica / CHAPTER II: Purpose: We performed a meta-analysis of randomized trials to assess the effect of metformin on inflammatory markers and metabolic parameters in subjects with diabetes. Methods: We performed comprehensive searches on NCBI, Cochrane, Science Direct databases from 1966 to Jun of 2015. We included randomized trials of at least 4 weeks duration that compared groups with diabetes before and after the treatment with metformin or metformin plus other drugs, and evaluated body mass index, blood glucose, HbA1c and inflammatory parameters such as C-reactive protein, tumor necrosis factor and adiponectin. Results: Pooled results of the 26 trials, with 1760 participants at the end of treatment reduce BMI in 0.9% p=0,0043, as well as, decrease of blood glucose level [SMD -0,411 mg/dL, 95%CI -0,463 to -0,369, I2= 56.62%], HbA1c [SMD -0.479%, 95%CI -0,568 to -0,390, I2= 55.02%], CRP levels [SMD -0,274mg/dL, 95%CI -0,419 to -0,129, I2= 72.78%], TNFα concentration [SMD -0,103pg/ml, 95%CI -0,514 to 0,309, I2= 87.67%] and increase of adiponectin [SMD 0,171μg/ml, 95%CI 0,098 to 0,440, I2= 81.09%] compared with pretreatment. Conclusion: The long-treatment with metformin monotherapy or metformin plus other drugs improves metabolic parameters and induced changes in inflammatory markers in diabetic subject. CHAPTER III: Background: Metformin increases insulin sensitivity by decreasing hepatic glucose production and increasing glucose disposal in skeletal muscle. However, modulation of inflammatory response and CaMKKβ/AMPK/Myosin V activation in gastrocnemius muscle by metformin treatment has not been demonstrated in hypoinsulinemic diabetic rats. Objective: The present study investigated how the metformin improve insulin sensitivity in skeletal muscle of hypoinsulinemic diabetic rats. Methods: Diabetes was induced by streptozotocin (45 mg/kg, intraperitoneally) 10 days prior treatments. On 11th day, diabetic rats were treated with metformin (500 mg/kg, oral gavage), insulin (2U at 08:00 h and 4U at 17:00 h, subcutaneously) or untreated. After 20 days, glycemia was measured and insulin sensitivity was determined by KITT. Serum Insulin, GLUT4, IRSthr, inflammatory markers (NF-κB, IκB, TNF-α and p-JNK) and CAMKK, AMPK and Myosin V in gastrocnemius muscle were determined by ELISA. Results: As expected, insulin and metformin improved the insulin sensitivity. Besides, metformin treatment promoted reduction in inflammatory response mediated by NF-κB, IκB, TNF-α and p-JNK, and that was accompanied by increased CaMKKβ/AMPK/Myosin V/GLUT4 pathway activity in gastrocnemius muscle of diabetic rats. Conclusion: Our findings suggest that metformin induces significant reductions in several inflammatory markers in skeletal muscle of diabetic rats. Metformin-induced increase in CaMKKβ/AMPK/Myosin V/GLUT4 pathway activity was associated with higher insulin sensitivity. CHAPTER IV: Diabetes is characterized by a proinflammatory state which can activate TLR2 and TLR4, and these receptors could induce NF-κB and JNK activation in skeletal muscle. In this study, we investigated the inflammatory and apoptotic signaling pathways triggered by TLRs/NF-κB and JNK activation in skeletal muscle of diabetic rats treated with metformin before and after an insulin tolerance test. Metformin treatment decreased p-JNK and NF-κB, and increased IκB concentrations. This attenuation leads to a decrease of TNFα and CXCL1/KC, and an increase of p-AMPK, BAX and Bcl2 concentration. Furthermore, KITT revealed an improvement of the insulin sensitivity in the diabetic rats treated with metformin. In addition, metformin was not capable of attenuating the changes in the inflammatory pathway triggered by insulin injection as the increase of TNFα and TLR4 in metformin treated rats, and IκB, CXCL1/KC, TNFα and p-AMPK increase in the untreated group. Taken together, these results point out that metformin may attenuate the activation of the inflammatory pathway TLRs/NF-κB/TNFα/CXCL1/KC and the apoptotic signaling BAX/Bcl2/p-JNK, which could be accompanied by a reduction of the inflammatory damage caused by hyperglycemia and an improvement of insulin sensitivity in diabetic rats.

To address the challenge of accurate, low cost and robust biosensors for diabetes management and early detection of diabetes complications, we have developed novel, robust sensing chemistry (or receptors) for electrochemical POC biosensors. The biosensors have been developed for the bio-markers associated with diabetes management such as glycated haemoglobin (HbA1c), glycated albumin, glucose, biomarkers associated with diabetes complications such as microalbuminuria, urine creatinine and albumin-to-creatinine ratio (ACR) and biomarkers associated with anaemia and malnutrition conditions such as haemoglobin and serum albumin. For haemoglobin detection, a new POC bio sensing technique has been developed based on Aza-heterocyclic chemicals. The repeatability and accuracy of the biosensor have been tested on real pathology samples. The glycated form of haemoglobin, called glycated haemoglobin or HbA1c, is the gold standard test in diabetes management as it gives the 90-days average blood glucose value. We demonstrate a simple method for electrochemical detection of HbA1c by combining bosonic affinity principle along with aza-heterocyclic receptors. The technique has been verified on the real clinical patient samples. Albumin is the most abundant protein in the human blood. Human serum albumin (HSA) is either alone or an associative biomarker in several chronic diseases like necrosis, nephrosis, hepatitis, malnutrition, arthritis, immune disorders, cancer, diabetes and in some severe infections. In pathology laboratories, the serum albumin is usually tested on serum samples and not in whole blood samples. Since albumin is not a metalloproteinase, it is very difficult to develop electrochemical POC biosensor. We have developed a novel technique for the electrochemical detection of serum albumin in whole blood samples, by exploiting its binding property with redox active copper salts. The accuracy of technique has been verified on both real human blood plasma as well as whole blood samples. Glycated albumin, which is the glycated form of serum albumin, is emerging as a novel biomarker for diabetes management, as it gives the average blood glucose value of 15-20 days. It is also extremely useful in chronic kidney disease patients and patients with hemoglobinopathies where HbA1c can give the erroneous results. By combining the copper chemistry along with bosonic affinity principle, we present the first ever demonstration of glycated albumin sensing. Instant blood glucose monitoring is an integral part of diabetes management. Most of the glucometers available in the market are based on glucose oxidase enzyme. We have demonstrated a low cost non-enzymatic electrochemical technique for blood glucose detection using alkaline methylene blue chemistry. The accuracy of the technique has been verified on real human blood plasma samples. Glucometer is one of the most easily available POC biosensor and a useful tool for diabetes population. India has second largest diabetes population in the world. To analyse the accuracy of the POC glucometers which are available in Indian market, a comprehensive study was conducted. The results were compared with clinical accuracy guidelines using exhaustive statistical analysis techniques. The shortcomings of the commercial glucometers are elucidated, regarding different international standards. Diabetic nephropathy is one of the major diabetes complications and is the primary cause of chronic kidney disease (CKD). The presence of albumin in urine is a well-established biomarker for the early detection of diabetic nephropathy. We have developed a technique for electrochemical detection of microalbuminuria for point of care applications by exploring the binding property of human albumin with electrochemically active molecules like copper and hemin. Methylene blue mediated sensing technique has also been proposed. Urine Albumin-to creatinine ratio (ACR) is another variant of the microalbumuria test that can be done any time and does not suffer from the dilution factor of urine. Iron binding property of creatinine is exploited to develop creatinine biosensor, thus enabling POC ACR tests.

<p>Dijabetes melitus je metaboliĉki poremećaj koji karakteri&scaron;e hroniĉna hiperglikemija i predstavlja veoma ozbiljan javno-zdravstveni problem u celom svetu. Najveći potencijal za pobolj&scaron;anje zdravlja obolelih leţi u postizanju i odrţavanju optimalne glikoregulacije. Podaci iz literature pokazuju da se sprovođenjem strukturiranih edukativnih programa o tipu 2 dijabetesa postiţu pozitivni efekti na zdravstveno pona&scaron;anje i glikoregulaciju kod obolelih koji su pohađali edukaciju. Cilj ovog istraţivanja bio je da se proceni efekat strukturirane edukacije o tipu 2 dijabetesa u primarnoj zdravstvenoj za&scaron;titi na promenu nivoa znanja, zdravstveno pona&scaron;anje, antropometrijske i biohemijske parametre glikoregulacije pacijenata. Istraživanje je sprovedeno u vidu prospektivne studije od februara do avgusta 2018. godine u Savetovali&scaron;tu za dijabetes Doma zdravlja Subotica. Ispitivanje je obuhvatilo 91 pacijenta sa dijagnostikovanim tipom 2 dijabetesa. Ispitanici su pohađali strukturirani &scaron;estonedeljni grupni edukativni program, kreiran za potrebe ovog istraţivanja. U cilju procene efekata edukativnog programa, na poĉetku i ĉetiri meseca nakon edukacije, prikupljeni su podaci o: zdravstvenom pona&scaron;anju, nivou znanja o dijabetesu (Diabetes Knowledge Test), o aktivnostima samonege u prethodnih sedam dana (The Summary of Diabetes Self-Care Activities) i o aktivnostima samonege prethodnih osam nedelja (The Diabetes Self-Management Questionnaire), određeni su antropometrijski (telesna teţina, indeks telesne mase, obim struka i nivo arterijskog krvnog pritiska) i biohemijski parametri glikoregulacije (nivo &scaron;ećera u krvi na&scaron;te, dva sata nakon jela, nivo HbA1c) i lipidni status pacijenata. Na početku strukturirane edukacije 79% pacijenata imalo je nizak nivo znanja o dijabetesu, prosečna vrednost na DKT bila je 46,4%. Nivo samonege pacijenatna bio je nizak i prethodnih 7 dana (SDSCA 45,8%) i prethodnih 8 nedelja (DSMQ 6,75). Trećina (35%) pacijenata imala je prekomernu telesnu masu, a njih 45% bilo je gojazno (BMI 29,85&plusmn;5,47). Povi&scaron;ene vrednosti sistolnog krvnog pritiska imalo je 43%, a dijastolnog 54% pacijenata. Polovina (54,9%) pacijenata imala je idealnu glikoregulaciju (HbA1c 6,56&plusmn;0,96%). Trećina (35%) pacijenata imala je visokorizičan nivo holesterola, a 26% visokoriziĉan nivo triglicerida u krvi. Ispitivanja sprovedena ĉetiri meseca nakon strukturirane edukacije pokazuju značajno povi&scaron;en nivo znanja pacijenata o dijabetesu, tj. visok nivo sa prosečnom vredno&scaron;ću DKT 81,5%. Nivo aktivnosti samonege prethodnih 7 dana i prethodnih 8 nedelja dostigao je umeren nivo (SDSCA 57,7%; DSMQ 7,9). Utvrđeno je značajno smanjenje telesne mase pacijenata za 1,5 kg i indeksa telesne mase, BMI, za 0,58 kg/m2. Procenat gojaznih pacijenata smanjen je na 40%. Povi&scaron;ene vrednosti sistolnog krvnog pritiska imalo je 26,4% (uz proseĉno smanjenje od 4 mmHg), a dijastolnog krvnog pritiska kod 44% pacijenata (uz prosečno smanjenje od 3 mmHg). Utvrđeno je znaĉajno smanjenje nivoa HbA1c za 0,36%, idealnu glikoregulaciju postiglo je 68% pacijenata. Zabeleţeno je smanjenje nivoa ukupnog holesterola za 0,3 mmol/L i nivoa triglicerida u krvi pacijenata za 0,23 mmol/L. Broj pacijenata sa visokorizičnim nivoom holesterola smanjen je za 19,6%, a u visokoriziĉnoj kategoriji triglicerida za 12%. Rezultati studije ukazuju da su efekti strukturiranog edukativnog programa o tipu 2 dijabetesa u primarnoj zdravstvenoj za&scaron;titi značajni, povećani su nivoi znanja i aktivnosti samonege, znaĉajno je smanjena telesna masa, vrednosti arterijskog krvnog pritiska su smanjene a pobolj&scaron;ane su vrednosti pokazatelja glikoregulacije i lipidnog statusa pacijenata.</p> / <p>Diabetes Mellitus is a metabolic disorder characterised by chronic hyperglycaemia and is a very serious public health issue worldwide. Achieving and maintaining optimal glucoregulation represents major potential for the improvement of affected persons&rsquo; health. According to information available in relative literature, the implementation of restructured Type 2 diabetes education programmes, positive results on health behaviour and glucoregulation in persons who took part in the education. The objective of the research was to assess the effect of structured education on Type 2 diabetes in primary health care, on changes in the level of knowledge, health behaviour and the anthropometric and biochemical parameters of patients&rsquo; glucoregulation. The research was conducted in the form of a prospective study between February and August 2018 in the Diabetes Support Group of the Subotica Health Centre. The research included 91 patients who were diagnosed with Type 2 diabetes. Research subjects attended a structured six-week group educational programme, which was specifically developed for the purpose of this research. In order to assess the effects of this educational programme from its outset and four months following the education, data concerning the following were gathered: health behaviour, level of knowledge on diabetes (Diabetes Knowledge Test - DKT), self care activities in the past seven days (The Summary of Diabetes Self-Care Activities - SDSCA) and self care activities in the past eight weeks (The Diabetes Self-Management Questionnaire - DSMQ). These data were anthropomorphic measurements (weight, height, waist circumference and the level of arterial blood pressure) and biochemical glucoregulation parameters (blood sugar levels on an empty stomach, two hours after a meal, HbA1c levels) and patient lipid status. When the structured education first started, 79% patients had a low level of knowledge on diabetes, and the average score at the DKT was 46.4%. The level of patient self care was also low in the past seven days (SDSCA 45.8%) and past eight weeks (DSMQ 6.75%). One third (35%) of patients had excess body mass, of whom 45% were obese (Body Mass Index &ndash; BMI 29.85&plusmn;5.47). 43% of patients had higher systolic blood pressure values while 54% had higher diastolic blood pressure values. In one half of patients (54.9%), glucoregulation was ideal (HbA1c 6.56&plusmn;0.96%). One third of patients (35%) had highly elevated cholesterol levels, with 26% who had highly elevated triglyceride blood levels. Research conducted during the four-month structured education show a significantly higher level of patient knowledge of diabetes, i.e. high level with the average DKT score of 81.5%. The level of self care activities in the past seven days and eight weeks reached a moderate level (SDCA 57.7%; DSMQ 7.9). A significant reduction in body mass by 1.5 kg as well as Body Mass Index, BMI by 0.58 kg/m2 was determined. The percentage of obese patients was reduced to 40%. 26.4% of patients had increased values of systolic blood pressure (with an average reduction of 4 mmHg), diastolic blood pressure 44% of patients (with an average reduction of 3 mmHg). A significant reduction in HbA1c level by 36% was determined, while 68% of patients achieved ideal glucoregulation. The reduction of total cholesterol level by 0.3% mmol/L as well as triglycerides level by 0.23% mmol/L was recorded. The number of patients with a high-risk cholesterol level was reduced by 19.6%, and the number of patients in high-risk category of triglycerides by 12%. The results of the study indicate that the effects of a structured educational programme on Type 2 diabetes in primary health care are significant. Knowledge levels were increased along with self care activities, body mass was significantly reduced, arterial blood pressure values were reduced and glucoregulation and lipid status values improved.</p>

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