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.

Made available in DSpace on 2015-07-22T20:49:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-06-29 / TEDE / BV UNIFESP: Teses e dissertações

Made available in DSpace on 2016-06-02T19:22:12Z (GMT). No. of bitstreams: 1 6350.pdf: 3538170 bytes, checksum: 7d36b58142cff837550ab8086a4637b7 (MD5) Previous issue date: 2014-11-07 / Universidade Federal de Sao Carlos / The Normal weight obesity (NWO) syndrome has been characterized on subjects with normal BMI and high body fat mass percentage (BF%>30 on with women) and is a risk factor for cardiometabolic dysregulation and cardiovascular mortality. The aim of this study was to evaluate whether circuit resistance training (CRT) improves body composition, heart size and functions, cardiometabolic parameters, and cardiorespiratory, cardiovascular and skeletal muscle fitness on women with NWO. Subjects/Methods: Data are mean [95%CI]. Twenty-nine white women participated in the study allocated to three groups: ten NWO-CRT (baseline: BMI=22.4 [21.4-23.3] kg/m2; BF%=44.5 [41.0-48.0]%) performed CRT during ten weeks; thirteen untrained NWO-control (baseline: BMI=21.7 [20.8-22.7] kg/m2; BF%=37.8 [34.6-41.1]%) and six non-obese (BMI=19.2 [17.9-20.6] kg/m2; BF%=23.6 [18.3-29.0]%). At baseline (all groups) and after ten weeks (NWO groups) performed: dualenergy- X-ray-absorptiometry, echocardiography, blood tests, arterial pressure, exercise testing, and total-overload-by-training-session (TOL) was calculated. Results: At baseline NWO-control showed almost double of body fat mass (BF) (22.41 [19.5-25.3] kg) than nonobese (11.88 [9.0-14.8] kg) (p=0.0001), and NWO-CRT had more BF than NWO-control (27.28 [23.9-30.6] kg) (p=0.0227). The NWO-CRT after training: reduced more than 8 kg of BF (p=0.000002); the BF% became lower than NWO-control (33.1 [30.1-36.0] < 37.0 [34.3- 39.6]%, p=0.0423) with 30% of NWO-CRT becoming non-obese; reduced 3 kg of trunk fat mass (p=0.000005); showed fasting glucose (72.8 [69.4-76.2] mg/dl) smaller than NWOcontrol (81.7 [78.6-84.8] mg/dl) (p=0.004) and non-obese (92.7 [86.6-98.8] mg/dl) (p=0.000003); increased TOL (5,087.5 [4,142.5-6,032.5] to 6 963.3 [6,226.4-7,700.2] rep.kg, p=0.0004); increased load at VO2peak (122.5 [106.8-138,2] to 137.5 [118.18-156.82] W, p=0.0051); reduced the double product/load at VO2peak ratio (277.4 [222.1-332.8] to 237.7 [194.2-281.2] mmHg.bpm/W, p=0.0015). The CRT increased left ventricular mass/body surface area ratio (84.29 [78.98-89.6] to 90.29 [81.45-99.12] g/m2, p=0.0215). Conclusions: CRT improves the body composition, cardiovascular and skeletal-muscle fitness and reduces fasting glucose without cardiorespiratory changes on normal weight obese women. / A síndrome de obesidade com peso normal tem sido caracterizada em indivíduos com índice de massa corporal normal e elevado percentual de massa gorda corporal (%MG), maior que 30% em mulheres, e é considerado um fator de risco para distúrbios metabólicos e mortalidade cardiovascular. Assim, o objetivo deste trabalho foi avaliar se um treinamento de circuito resistido melhora a composição corporal, parâmetros estruturais e funções cardíacas, parâmetros cardiometabólicos e capacidades cardiorrespiratória, cardiovascular e muscular esquelética em mulheres adultas sedentárias obesas de peso normal. Dados são mostrados em média [intervalo de confiança de 95%]. Vinte e nove mulheres participaram do estudo sendo alocadas em três grupos: dez mulheres inicialmente obesas de peso normal (IMC=22,4 [21,4-23,3] kg/m2; %MG=44,5 [41,0-48,0]%) que realizaram dez semanas de treinamento resistido em circuito (grupo MOPN-TRC); treze mulheres no grupo MOPN-controle (IMC=21,7 [20,8-22,7] kg/m2; %MG 37,8 [34,6-41,1]%) que permaneceram sedentárias nas dez semanas; e seis mulheres num grupo controle de nãoobesas sedentárias avaliadas (IMC=19,2 [17,9-20,6] kg/m2; %MG=23,6 [18,3-29,0]%) somente inicialmente como valores de referência geral. Inicialmente todos os grupos realizaram: avaliação a composição corporal por absortometria radiológica de dupla energia dual-energy-X-ray-absorptiometry (DXA), ecocardiografia com doppler, perfil lipídico glicemia de jejum, teste ergoespirométrico máximo em ciclo-ergômetro, pressão arterial e a sobrecarga total da sessão de treino foi calculada. Após dez semanas os dois grupos MOPN refizeram estas análises. Inicialmente o grupo MOPN-controle apresentava mais que o dobro de massa gorda corporal (MG) (22,41[19,5-25,3] kg) que as não-obesas (11,88 [9,0-14,8] kg) (p=0,0001), enquanto o grupo MOPN-TRC possuía MG (27,28 [23,9-30,6] kg) ainda maior MOPN-controle (p=0,0227). Após o treinamento as MOPN-TRC: reduziram mais de 8 kg de MG (p=0,000002); o %MG que era maior tornou-se menor que o das MOPN-controle (33,1 [30,1-36,0] < 37,0 [34,3-39,6]%, p=0,0423) e 30% das voluntárias tornaram-se não-obesas; reduziram 3 kg de massa gorda no tronco (p=0,000005); apresentaram glicemia de jejum (72,8 [69,4-76,2] mg/dl) menor que os grupos MOPN-controle (81,7 [78,6-84,8] mg/dl) (p=0,004) e não-obeso (92,7 [86,6-98,8] mg/dl) (p=0,000003); aumentou a sobrecarga total da sessão de treino (5.087,5 [4.142,5-6.032,5] para 6.963,3 [6.226,4-7.700,2] rep.kg, p=0,0004); aumentou a carga no VO2pico (122,5 [106,8-138,2] para 137,5 [118,18-156,82] W, p=0,0051); reduziu a taxa duplo produto/carga no VO2pico (277,4 [222,1-332,8] para 237,7 [194,2-281,2] mmHg.bpm/W, p=0,0015). Conclui-se que o treinamento resistido em circuito realizado melhora a composição corporal, as capacidades cardiovascular e muscular esquelética, enquanto reduz a glicemia de jejum sem alterar a capacidade cardiorrespiratória de mulheres obesas de peso normal.

Abstract Type 1 diabetes is considered to be a T cell-mediated autoimmune disease characterized by destruction of the pancreatic beta cells. Its prediction is currently based on diabetes-associated autoantibodies, giving a cumulative risk of 84% during 15 years of follow-up since seroconversion. Prediction of the timing of clinical onset has remained challenging, however. This thesis examines glucose metabolism in autoantibody-positive children with a high risk of developing type 1 diabetes. Out of a total of 14,876 children with an increased genetic risk followed up from birth in the Finnish DIPP study, 567 developed ≥2 autoantibodies during the follow-up and 255 of these (45%) were diagnosed with type 1 diabetes until the end of December 2011. The glucose parameters measured were HbA1c, OGTT and random plasma glucose with 3 to 12 months interval. Seven-day continuous glucose monitoring (CGM) was performed on an age and sex-matched cohort. We showed that rising HbA1c, impaired glucose tolerance in OGTT, random plasma glucose values of ≥7.8mmol/l and potentially CGM can predict type 1 diabetes with a median time to diagnosis of approximately one year. Our results suggest that especially HbA1c and random plasma glucose are cost-effective and improve the prediction of diabetes. These markers may be useful for monitoring the response to treatment in prevention studies. / Tiivistelmä Tyypin 1 diabetesta pidetään T-soluvälitteisenä autoimmuunitautina, joka johtaa haiman beetasolujen tuhoutumiseen. Tyypin 1 diabeteksen ennustaminen perustuu tällä hetkellä diabetekseen assosioituviin vasta-aineisiin, jotka antavat 84% kumulatiivisen riskin 15 vuoden seurannassa. Taudin puhkeamisen ajankohdan ennustaminen on kuitenkin edelleen vaikeaa. Tämä väitöskirja käsittelee glukoosiaineenvaihduntaa vasta-ainepositiivisilla lapsilla, joilla on suurentunut riski sairastua tyypin 1 diabetekseen. Suomalaisessa DIPP-tutkimuksessa vasta-aineiden kehittymistä on seurattu yhteensä 14876 lapselta. Seurannan aikana 567 lasta kehitti ≥2 autovasta-ainetta ja näistä 255 (45%) sairastui tyypin 1 diabetekseen joulukuun loppuun 2011 mennessä. Glukoosiaineenvaihduntaa seurattiin tutkimalla HbA1c, OGTT ja satunnaisia verensokeriarvoja 3-12 kuukauden välein. Ikä ja sukupuolivakioidussa kohortissa tehtiin jatkuvan sokeripitoisuuden seuranta (CGM). Tutkimuksessamme nouseva HbA1c, heikentynyt sokerin sieto OGTT-kokeessa, satunnainen verensokeri ≥7.8 mmol/l ja mahdollisesti CGM ennustavat tyypin 1 diabeteksen puhkeamista. Tulostemme perusteella erityisesti kustannustehokkaat HbA1c ja satunnainen verensokeri parantavat diabeteksen ennustamista. Nämä parametrit saattavat olla hyödyllisiä myös preventiotutkimuksissa hoitovasteen seurannassa.

<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>

<p>Since the late 1970s, biomedical researchers have heavily invested in the development of portable insulin pumps that allow people with Type 1 Diabetes (T1D) to carry several days-worth of insulin to be injected on an as-needed basis. That means fewer needles and syringes, making regular insulin injections less time consuming and troublesome. As insulin pump use has become more widespread over the past twenty years among people with T1D, the social and cultural effects of using these medical devices on their everyday experiences have become both increasingly apparent for individuals yet consistently absent from social and cultural studies of the disease.</p><p><br></p><p>In this dissertation, I explore the technological, medical, and cultural networks of insulin pump treatment to identify the role(s) these biomedicalized treatment acts play in the structuring of people, their bodies, and the cultural values constructed around various medical technologies. As I will show, insulin pump treatment alters people’s bodies and identities as devices become integrated as co-productive actors within patient-users’ biological and social systems. By analyzing personal interviews and digital media produced by people with T1D alongside archival materials, this study identifies compulsory patterns in the practices, structures, and narratives related to insulin pump use to center chapters around the productive (and sometimes stifling) relationship between people, bodies, technologies, and American culture.</p><p><br></p><p>By analyzing the layered and intersecting sites of insulin pump treatment together, this project reveals how medical technologies, health identities, bodies, and cultures are co-constructed and co-defined in ways that bind them together—mutually constitutive, medically compelled, cultural and social. New bodies and new systems, I argue, come with new (in)visibilities, and while this new technologically-produced legibility of the body provides unprecedented management of the symptoms and side-effects of the disease, it also brings with it unforeseen social consequences that require changes to people’s everyday lives and practices. </p>

Background The incidence of type 2 diabetes has increased dramatically, particularly among Latinos. While several studies suggest the beneficial effect of lowering glycemic index and glycemic load in patients with type 2 diabetes, no data exists regarding this issue in the Latino population. The purpose of this study was to determine the effect of lowering glycemic index and glycemic load on diabetes control, lipid profiles and anthropometrics among Latinos with type 2 diabetes. Methods Subjects participated in a 12 month randomized clinical trial. The intervention targeted diabetes knowledge, attitudes and behavioral capabilities related to diabetes self management with content including nutrition and physical activity. The nutrition protocol emphasized reduction in glycemic index, fat, salt and portion size and increase in fiber. The control group was given usual care. Measurements included Hba1c, fasting glucose, total cholesterol (TC), low density lipoproteins (LDL) and high density lipoproteins (HDL), HDL:LDL ratio, TC:HDL ratio, waist circumference and BMI and were collected at baseline, 4 and 12-months. Results Two hundred fifty two Latino adults with type 2 diabetes participated in the study. Baseline mean HbA1C was 8.98% (SD=1.87), BMI was 34.76 kg/cm (SD=6.94), age was 56 (SD=11.18) years and 76% were female. Reduction in glycemic index was positively associated with a reduction in logHbA1c (p=0.006), HDL:LDL ratio (p=0.037) and waist circumference (p=0.003) overtime, but not with fasting glucose, TC, LDL and HDL, TC:HDL ratio, body weight or BMI. No significant associations were found between glycemic load and any measures. Conclusion Results suggest that lowering glycemic index may have a positive effect on some markers of diabetes control, lipid profiles and anthropometrics among Latinos with type 2 diabetes, but not others. While statistically significant reductions in GI and GL were noted, the actual reduction was small. Thus, greater reduction in GI and GL may be needed for clinical significance and greater effect on metabolic outcomes. Future research should target populations with higher baseline GI and GL.

Preface - Biotechnology is generally accepted to be the next economical wave of the future. In order to attain the many benefits associated with this growing industry simulation modelling techniques have to be implemented successfully. One of the simulations that ne' ed to be performed is that of the human energy system. Pharmaceutical companies are currently pouring vast amounts of capital into research regarding simulation of bodily processes. Their aim is to develop cures, treatments, medication, etc. for major diseases. These diseases include epidemics like diabetes, cancer, cardiovascular diseases, obesity, stress, hypertension, etc. One of the most important driving forces behind these diseases is poor blood sugar control. The blood glucose system is one of the major subsystems of the complete human energy system. In this study a simulation model and procedure for simulating blood glucose response due to various external influences on the human body is presented. The study is presented in two parts. The first is the development of a novel concept for quantifying glucose energy flow into, within and out of the human energy system. The new quantification unit is called ets (equivalent teaspoons sugar). The second part of the study is the implementation of the ets concept in order to develop the simulation model. Development of the ets concept - In the first part of the study the ets concept, used for predicting glycaemic response, is developed and presented. The two current methods for predicting glycaemic response due to ingestion of food are discussed, namely carbohydrate counting and the glycaemic index. Furthermore, it is shown that it is currently incorrectly assumed that 100% of the chemical energy contained in food is available to the human energy system after consumption. The ets concept is derived to provide a better measure of available energy from food. In order to verify the ets concept, two links with ets are investigated. These are the links with insulin response prediction as well as with endurance energy expenditure. It is shown that with both these links linear relationships provide a good approximation of empirical data. It is also shown that individualised characterisation of different people is only dependent on a single measurable variable for each link. Lastly, two novel applications of the ets concept are considered. The first is a new method to use the ets values associated with food and energy expenditure in order to calculate both short-acting and long-acting insulin dosages for Type 1 diabetics. The second application entails a new quantification method for describing the effects of stress and illness in terms of ets. Development of the blood glucose simulation model - The second part of the study presents a literature study regarding human physiology, the development for the blood glucose simulation model as well as a verification study of the simulation model. Firstly, a brief overview is given for the need and motivation behind simulation is given. A discussion on the implementation of the techniques for construction of the model is also shown. The procedure for solving the model is then outlined. During the literature study regarding human physiology two detailed schematic layouts are presented and discussed. The first layout involves the complex flow pathways of energy through the human energy system. The second layout presents a detailed discussion on the control system involved with the glucose energy pathway. Following the literature review the model for predicting glycaemic response is proposed. The design of the component models used for the simulations of the internal processes are developed in detail as well as the control strategies implemented for the control system of the simulation model. Lastly, the simulation model is applied for glycaemic response prediction of actual test subjects and the quality of the predictions are evaluated. The verification of the model and the procedure is performed by comparing simulated results to measured data. Two evaluations were considered, namely long-term and short-term trials. The quality of both are determined according to certain evaluation criteria and it is found that the model is more than 70% accurate for long-term simulations and more than 80% accurate for short-term simulations. Conclusion - In conclusion, it is shown that simplified simulation of the human energy system is not only possible but also relatively accurate. However, in order to accomplish the simulations a simple quantification method is required and this is provided by the ets concept developed in the first part of this study. Some recommendations are also made for future research regarding both the ets concept and the simulation model. Finally, as an initial endeavour the simulation model and the ets concept proposed in this study may provide the necessary edge for groundbreaking biotechnological discoveries. / PhD (Mechanical Engineering) North-West University, Potchefstroom Campus, 2003

Preface - Biotechnology is generally accepted to be the next economical wave of the future. In order to attain the many benefits associated with this growing industry simulation modelling techniques have to be implemented successfully. One of the simulations that ne' ed to be performed is that of the human energy system. Pharmaceutical companies are currently pouring vast amounts of capital into research regarding simulation of bodily processes. Their aim is to develop cures, treatments, medication, etc. for major diseases. These diseases include epidemics like diabetes, cancer, cardiovascular diseases, obesity, stress, hypertension, etc. One of the most important driving forces behind these diseases is poor blood sugar control. The blood glucose system is one of the major subsystems of the complete human energy system. In this study a simulation model and procedure for simulating blood glucose response due to various external influences on the human body is presented. The study is presented in two parts. The first is the development of a novel concept for quantifying glucose energy flow into, within and out of the human energy system. The new quantification unit is called ets (equivalent teaspoons sugar). The second part of the study is the implementation of the ets concept in order to develop the simulation model. Development of the ets concept - In the first part of the study the ets concept, used for predicting glycaemic response, is developed and presented. The two current methods for predicting glycaemic response due to ingestion of food are discussed, namely carbohydrate counting and the glycaemic index. Furthermore, it is shown that it is currently incorrectly assumed that 100% of the chemical energy contained in food is available to the human energy system after consumption. The ets concept is derived to provide a better measure of available energy from food. In order to verify the ets concept, two links with ets are investigated. These are the links with insulin response prediction as well as with endurance energy expenditure. It is shown that with both these links linear relationships provide a good approximation of empirical data. It is also shown that individualised characterisation of different people is only dependent on a single measurable variable for each link. Lastly, two novel applications of the ets concept are considered. The first is a new method to use the ets values associated with food and energy expenditure in order to calculate both short-acting and long-acting insulin dosages for Type 1 diabetics. The second application entails a new quantification method for describing the effects of stress and illness in terms of ets. Development of the blood glucose simulation model - The second part of the study presents a literature study regarding human physiology, the development for the blood glucose simulation model as well as a verification study of the simulation model. Firstly, a brief overview is given for the need and motivation behind simulation is given. A discussion on the implementation of the techniques for construction of the model is also shown. The procedure for solving the model is then outlined. During the literature study regarding human physiology two detailed schematic layouts are presented and discussed. The first layout involves the complex flow pathways of energy through the human energy system. The second layout presents a detailed discussion on the control system involved with the glucose energy pathway. Following the literature review the model for predicting glycaemic response is proposed. The design of the component models used for the simulations of the internal processes are developed in detail as well as the control strategies implemented for the control system of the simulation model. Lastly, the simulation model is applied for glycaemic response prediction of actual test subjects and the quality of the predictions are evaluated. The verification of the model and the procedure is performed by comparing simulated results to measured data. Two evaluations were considered, namely long-term and short-term trials. The quality of both are determined according to certain evaluation criteria and it is found that the model is more than 70% accurate for long-term simulations and more than 80% accurate for short-term simulations. Conclusion - In conclusion, it is shown that simplified simulation of the human energy system is not only possible but also relatively accurate. However, in order to accomplish the simulations a simple quantification method is required and this is provided by the ets concept developed in the first part of this study. Some recommendations are also made for future research regarding both the ets concept and the simulation model. Finally, as an initial endeavour the simulation model and the ets concept proposed in this study may provide the necessary edge for groundbreaking biotechnological discoveries. / PhD (Mechanical Engineering) North-West University, Potchefstroom Campus, 2003