Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

A resistência à insulina é um problema cada vez mais presente na rotina clínica dos veterinários que trabalham com equídeos. A hiperinsulinemia resultante da resistência à insulina está associada a diversas alterações fisiológicas e podem levar a enfermidades graves como a Síndrome Metabólica Equina ou a Laminite que podem culminar na invalidez ou até morte do animal. O diagnóstico da resistência à insulina em equinos é baseado em modelos dos mesmos testes realizados em humanos. Até a presente data não há testes práticos, acessíveis e com sensibilidade e especificidade suficientemente capazes de diagnosticar a resistência à insulina em equinos. Em humanos e outros modelos animais a frutosamina é um biomarcados utilizado no diagnostico da resistência a insulina. A dosagem de frutosamina sérica é simples e barata, porém, seu uso no diagnostico da resistência à insulina em equinos ainda não foi testado. O presente estudo tem como objetivo avaliar a frutosamina em cavalos estabulados e sedentários diagnosticados com resistência à insulina por três diferentes métodos descritos em literatura sendo estes: Teste Combinado de Glicose e Insulina, Reciproco da Raiz Quadrada da Insulina (RRQI) e Relação Glicose-Insulina Modificada (RGIM). Além disso avaliamos a incidência de resistência à insulina em cavalos estabulados e sedentários. Todos os testes foram capazes de identificar grupos resistentes e não resistentes a insulina, porém com baixo concordância entre si. Apesar disso a dosagem de frutosamina sérica não diferiu entre os grupos formados a partir de qualquer um dos métodos diagnósticos de resistência à insulina. / Insulin resistance is an increasing problem in the clinical routine of equine veterinarians. The hyperinsulinemia resulting from insulin resistance is associated with several physiologic alterations and can lead to serious diseases like equine metabolic syndrome or laminitis which can to early retirement or animal death. Equine insulin resistance diagnosis is based in human tests. Until now, there is no practical, accessible, sensible and specificity test capable of diagnosing equine insulin resistance. In human and other animals model, frutosamine is simple and cheap biomarker use in this diagnosis, however its use for equine insulin resistence diagnosis never had been tested. The aim of the present study was to evaluate the fructosamine in stable and sedentary horses diagnosed with or without insulin resistance by three different methods described in the literature (Combined Glucose and Insulin Test - TCGI, Reciprocal of the Square Root of Insulin (RISQI) and Modified Insulin-to-Glucose Ratio (MIRG). For this, 17 adult male horses were evaluated. All tests were able to identify resistant and not resistant to insulin animals, but with low concordance between them. Regardless of the test used, the serum fructosamine dosage did not differ between the resistant and non-insulin resistant groups and could not be used as an early marker for insulin resistance in horses.

O Diabetes Mellitus (DM) é uma doença metabólica que implica em altas incidências de mortalidade e morbidade. A hiperglicemia crônica é responsável pelo surgimento de inúmeras complicações em longo prazo nestes pacientes. Atualmente, é recomendado por diretrizes internacionais que pacientes com DM sejam monitorados e manejados em seu tratamento a partir dos níveis de hemoglobina glicada (A1C). A A1C é formada por reações não enzimáticas de glicação na hemoglobina, refletindo a glicemia dos últimos 120 dias. A A1C possui forte associação com os desfechos clínicos no DM e apresenta uma excelente padronização de seus métodos analíticos. Contudo, diversas situações clínicas podem interferir falsamente em seus níveis e prejudicar a interpretação de seus resultados, como em anemias (carenciais ou hemolíticas), hemoglobinopatias, gravidez, doença renal crônica, etc. Por outro lado, a albumina glicada (AG) é uma frutosamina formada por glicações na albumina e reflete uma glicemia média de cerca de 2 a 3 semanas. A AG não é influenciada pela concentração de outras proteínas no plasma e também não sofre interferência pelas condições que afetam a A1C. Este marcador tem sido fortemente avaliado como uma ferramenta alternativa para a A1C, a partir da análise de seus níveis por um novo método enzimático descrito em 2002. Estudos tem demonstrado uma forte associação entre estes dois marcadores e grande semelhança em predizer as complicações do DM. Entretanto, a AG se mostra melhor para avaliar flutuações nos níveis de glicose e a resposta ao tratamento terapêutico. Neste trabalho, foi avaliado o desempenho analítico de dois kits enzimáticos de AG e realizado uma comparação entre os métodos, encontrando excelentes resultados. Ainda, foi determinado o intervalo de referência para os níveis de AG em brasileiros saudáveis. A forte correlação encontrada entre AG e A1C demonstra que a AG pode ser um teste útil para o controle glicêmico no DM, principalmente quando a A1C não é recomendada. / Diabetes Mellitus is a metabolic disease with high incidence rates of mortality and morbidity. Chronic hyperglycemia is responsible for several long-term complications in these patients. Currently, international guidelines recommend that glycemic monitoring in DM should be performed by glycated hemoglobin (A1C) levels, to provide a correct clinical conduction. A1C is relative to non-enzymatic glycation reactions in hemoglobin and reflects the glucose levels from the last 120 days. It is well established the great association between A1C and clinical outcomes in DM, besides, its analytical methods present an excellent standardization. However, some conditions may influence and imply misinterpretation in A1C results, such as anemia, hemoglobinophaties, pregnancy, chronic renal disease, etc. On the other hand, glycated albumin (GA) is a fructosamine produced by glycation reactions in albumin and it reflects a mean glycemia at around 2 to 3 weeks. GA is not influenced by the concentrations of other plasma proteins, as well as by those conditions that interfere in A1C. GA has been strongly evaluated as an alternative marker to A1C, through its quantitative measurement by an enzymatic methodology described in 2002. Recent studies have demonstrated a high association between GA and A1C and a great similarity between these tests in predicting DM future complications. Nevertheless, GA has showed be better to assess the glucose fluctuations in blood and the response to treatment. This study evaluated the analytical performance of two GA enzymatic kits and also executed a methods comparison, and found excellent results. Also, we established the reference range for GA levels in healthy Brazilians. The high correlation found between GA and A1C indicates that GA could be a useful test for glycemic control in DM, especially when A1C is unreliable.

O Diabetes Mellitus (DM) é uma doença metabólica que implica em altas incidências de mortalidade e morbidade. A hiperglicemia crônica é responsável pelo surgimento de inúmeras complicações em longo prazo nestes pacientes. Atualmente, é recomendado por diretrizes internacionais que pacientes com DM sejam monitorados e manejados em seu tratamento a partir dos níveis de hemoglobina glicada (A1C). A A1C é formada por reações não enzimáticas de glicação na hemoglobina, refletindo a glicemia dos últimos 120 dias. A A1C possui forte associação com os desfechos clínicos no DM e apresenta uma excelente padronização de seus métodos analíticos. Contudo, diversas situações clínicas podem interferir falsamente em seus níveis e prejudicar a interpretação de seus resultados, como em anemias (carenciais ou hemolíticas), hemoglobinopatias, gravidez, doença renal crônica, etc. Por outro lado, a albumina glicada (AG) é uma frutosamina formada por glicações na albumina e reflete uma glicemia média de cerca de 2 a 3 semanas. A AG não é influenciada pela concentração de outras proteínas no plasma e também não sofre interferência pelas condições que afetam a A1C. Este marcador tem sido fortemente avaliado como uma ferramenta alternativa para a A1C, a partir da análise de seus níveis por um novo método enzimático descrito em 2002. Estudos tem demonstrado uma forte associação entre estes dois marcadores e grande semelhança em predizer as complicações do DM. Entretanto, a AG se mostra melhor para avaliar flutuações nos níveis de glicose e a resposta ao tratamento terapêutico. Neste trabalho, foi avaliado o desempenho analítico de dois kits enzimáticos de AG e realizado uma comparação entre os métodos, encontrando excelentes resultados. Ainda, foi determinado o intervalo de referência para os níveis de AG em brasileiros saudáveis. A forte correlação encontrada entre AG e A1C demonstra que a AG pode ser um teste útil para o controle glicêmico no DM, principalmente quando a A1C não é recomendada. / Diabetes Mellitus is a metabolic disease with high incidence rates of mortality and morbidity. Chronic hyperglycemia is responsible for several long-term complications in these patients. Currently, international guidelines recommend that glycemic monitoring in DM should be performed by glycated hemoglobin (A1C) levels, to provide a correct clinical conduction. A1C is relative to non-enzymatic glycation reactions in hemoglobin and reflects the glucose levels from the last 120 days. It is well established the great association between A1C and clinical outcomes in DM, besides, its analytical methods present an excellent standardization. However, some conditions may influence and imply misinterpretation in A1C results, such as anemia, hemoglobinophaties, pregnancy, chronic renal disease, etc. On the other hand, glycated albumin (GA) is a fructosamine produced by glycation reactions in albumin and it reflects a mean glycemia at around 2 to 3 weeks. GA is not influenced by the concentrations of other plasma proteins, as well as by those conditions that interfere in A1C. GA has been strongly evaluated as an alternative marker to A1C, through its quantitative measurement by an enzymatic methodology described in 2002. Recent studies have demonstrated a high association between GA and A1C and a great similarity between these tests in predicting DM future complications. Nevertheless, GA has showed be better to assess the glucose fluctuations in blood and the response to treatment. This study evaluated the analytical performance of two GA enzymatic kits and also executed a methods comparison, and found excellent results. Also, we established the reference range for GA levels in healthy Brazilians. The high correlation found between GA and A1C indicates that GA could be a useful test for glycemic control in DM, especially when A1C is unreliable.

O Diabetes Mellitus (DM) é uma doença metabólica que implica em altas incidências de mortalidade e morbidade. A hiperglicemia crônica é responsável pelo surgimento de inúmeras complicações em longo prazo nestes pacientes. Atualmente, é recomendado por diretrizes internacionais que pacientes com DM sejam monitorados e manejados em seu tratamento a partir dos níveis de hemoglobina glicada (A1C). A A1C é formada por reações não enzimáticas de glicação na hemoglobina, refletindo a glicemia dos últimos 120 dias. A A1C possui forte associação com os desfechos clínicos no DM e apresenta uma excelente padronização de seus métodos analíticos. Contudo, diversas situações clínicas podem interferir falsamente em seus níveis e prejudicar a interpretação de seus resultados, como em anemias (carenciais ou hemolíticas), hemoglobinopatias, gravidez, doença renal crônica, etc. Por outro lado, a albumina glicada (AG) é uma frutosamina formada por glicações na albumina e reflete uma glicemia média de cerca de 2 a 3 semanas. A AG não é influenciada pela concentração de outras proteínas no plasma e também não sofre interferência pelas condições que afetam a A1C. Este marcador tem sido fortemente avaliado como uma ferramenta alternativa para a A1C, a partir da análise de seus níveis por um novo método enzimático descrito em 2002. Estudos tem demonstrado uma forte associação entre estes dois marcadores e grande semelhança em predizer as complicações do DM. Entretanto, a AG se mostra melhor para avaliar flutuações nos níveis de glicose e a resposta ao tratamento terapêutico. Neste trabalho, foi avaliado o desempenho analítico de dois kits enzimáticos de AG e realizado uma comparação entre os métodos, encontrando excelentes resultados. Ainda, foi determinado o intervalo de referência para os níveis de AG em brasileiros saudáveis. A forte correlação encontrada entre AG e A1C demonstra que a AG pode ser um teste útil para o controle glicêmico no DM, principalmente quando a A1C não é recomendada. / Diabetes Mellitus is a metabolic disease with high incidence rates of mortality and morbidity. Chronic hyperglycemia is responsible for several long-term complications in these patients. Currently, international guidelines recommend that glycemic monitoring in DM should be performed by glycated hemoglobin (A1C) levels, to provide a correct clinical conduction. A1C is relative to non-enzymatic glycation reactions in hemoglobin and reflects the glucose levels from the last 120 days. It is well established the great association between A1C and clinical outcomes in DM, besides, its analytical methods present an excellent standardization. However, some conditions may influence and imply misinterpretation in A1C results, such as anemia, hemoglobinophaties, pregnancy, chronic renal disease, etc. On the other hand, glycated albumin (GA) is a fructosamine produced by glycation reactions in albumin and it reflects a mean glycemia at around 2 to 3 weeks. GA is not influenced by the concentrations of other plasma proteins, as well as by those conditions that interfere in A1C. GA has been strongly evaluated as an alternative marker to A1C, through its quantitative measurement by an enzymatic methodology described in 2002. Recent studies have demonstrated a high association between GA and A1C and a great similarity between these tests in predicting DM future complications. Nevertheless, GA has showed be better to assess the glucose fluctuations in blood and the response to treatment. This study evaluated the analytical performance of two GA enzymatic kits and also executed a methods comparison, and found excellent results. Also, we established the reference range for GA levels in healthy Brazilians. The high correlation found between GA and A1C indicates that GA could be a useful test for glycemic control in DM, especially when A1C is unreliable.

A resistência à insulina é um problema cada vez mais presente na rotina clínica dos veterinários que trabalham com equídeos. A hiperinsulinemia resultante da resistência à insulina está associada a diversas alterações fisiológicas e podem levar a enfermidades graves como a Síndrome Metabólica Equina ou a Laminite que podem culminar na invalidez ou até morte do animal. O diagnóstico da resistência à insulina em equinos é baseado em modelos dos mesmos testes realizados em humanos. Até a presente data não há testes práticos, acessíveis e com sensibilidade e especificidade suficientemente capazes de diagnosticar a resistência à insulina em equinos. Em humanos e outros modelos animais a frutosamina é um biomarcados utilizado no diagnostico da resistência a insulina. A dosagem de frutosamina sérica é simples e barata, porém, seu uso no diagnostico da resistência à insulina em equinos ainda não foi testado. O presente estudo tem como objetivo avaliar a frutosamina em cavalos estabulados e sedentários diagnosticados com resistência à insulina por três diferentes métodos descritos em literatura sendo estes: Teste Combinado de Glicose e Insulina, Reciproco da Raiz Quadrada da Insulina (RRQI) e Relação Glicose-Insulina Modificada (RGIM). Além disso avaliamos a incidência de resistência à insulina em cavalos estabulados e sedentários. Todos os testes foram capazes de identificar grupos resistentes e não resistentes a insulina, porém com baixo concordância entre si. Apesar disso a dosagem de frutosamina sérica não diferiu entre os grupos formados a partir de qualquer um dos métodos diagnósticos de resistência à insulina. / Insulin resistance is an increasing problem in the clinical routine of equine veterinarians. The hyperinsulinemia resulting from insulin resistance is associated with several physiologic alterations and can lead to serious diseases like equine metabolic syndrome or laminitis which can to early retirement or animal death. Equine insulin resistance diagnosis is based in human tests. Until now, there is no practical, accessible, sensible and specificity test capable of diagnosing equine insulin resistance. In human and other animals model, frutosamine is simple and cheap biomarker use in this diagnosis, however its use for equine insulin resistence diagnosis never had been tested. The aim of the present study was to evaluate the fructosamine in stable and sedentary horses diagnosed with or without insulin resistance by three different methods described in the literature (Combined Glucose and Insulin Test - TCGI, Reciprocal of the Square Root of Insulin (RISQI) and Modified Insulin-to-Glucose Ratio (MIRG). For this, 17 adult male horses were evaluated. All tests were able to identify resistant and not resistant to insulin animals, but with low concordance between them. Regardless of the test used, the serum fructosamine dosage did not differ between the resistant and non-insulin resistant groups and could not be used as an early marker for insulin resistance in horses.

Approximately half of all reported laminitis cases are the result of “grass founder” (laminitis associated with long-term over consumption of lush, early spring pastures). Elevated body weights (BW), body condition scores (BCS), and blood glucose concentrations have all been associated with the onset of grass founder. Plasma fructosamine concentrations (PFC) have recently been used as an indicator of long-term (14–21 d), mean blood glucose concentrations in horses and numerous authors have reported that elevated PFC were observed in laminitic horses (Murphy et al., 1997; Keen et al., 2004; Knowles et al., 2012). This study was conducted to evaluate the long-term effects of transitioning from an ad-libitum tall fescue hay diet in late winter to an adlibitum tall fescue pasture diet in early spring on parameters associated with grass founder in horses. Five mature stock horse mares were given free choice access to good quality tall fescue hay for 18 weeks before initiation of data collection. Each horse acted as their own control. PFC were determined on day 1, day 128, and then monitored at 14 d intervals for the following 84 d (February 26th through May 21st). Three trained lab technicians evaluated BW and BCS on day 1, 128, 170 and 212 of the trial. The horses were placed in a 20 acre field where their diets consisted of free choice access to hay only for 156 days (DTP1) followed by free choice access to tall fescue hay with minimal access to some early emerging tall fescue pasture for 14 days (DTP2), and finally to free choice access to lush spring tall fescue pasture only for the final 42 days (DTP 3) when the animals refused to eat offered hay. Mean PFC were highest (P < 0.01) for DTP1 and decreased with each successive transition to DTP2 and DTP3. This may have been due to increased insulin secretion associated with the pasture only diet. Mean BCS at the beginning of the trial was 5.7 and increased throughout the trial (P < 0.001) to a value of 7.8. BCS associated with the pasture only diet were higher (P < 0.001) than those associated with the free choice hay and hay plus pasture diets. Mean BW increased (P < 0.05) from 1199 lbs. to 1268.3 lbs. during the 12-week trial. Mean weight gain was 113 lbs. with an average daily gain of 1.35 lbs./day. No incidence of laminitis was observed.

Recent statistics show that approximately 415 million people worldwide have diabetes. Glycated haemoglobin (HbA1c) measurements were introduced many years ago as the gold standard tool for detecting and monitoring treatment as well as making management decisions for diabetic patients. Glycated haemoglobins are formed by the non-enzymatic glycation of haemoglobin molecules. This non-enzymatic glycation process has been strongly related to pathogenesis of chronic complications associated to diabetes. It was suggested that this glycation process may be moderated by an enzymatic deglycation process thought to involve a deglycating enzyme known as Fructosamine-3-kinase (FN3K), an enzyme that deglycates the glycated haemoglobin in erythrocytes and other glycated proteins in other tissues. FN3K acts through phosphorylation of fructosamines on the third carbon of their sugar moiety, making them unstable and consequently causing them to detach from the protein. The degree of deglycation is thought to depend on the activity of the FN3K enzyme. Moreover, variation in the activity of FN3K between individuals is hypothesised to lead to apparent differences in glycated haemoglobin levels: some individuals have high rates of deglycation so that they tend to have lower average glycaemia than actually the case, while others with low rates of deglycation appear to have higher than actual glycaemia (known as the glycation gap, G-gap). The G-gap has been reported to be associated with alteration of diabetic complications risk. The G-gap reflects the discrepancy between average glycaemia as determined from glycated haemoglobin (measured as HbA1c) and that from the determination of fructosamine. The positive G-gap is defined as a higher level of glycation of proteins than expected whereas a negative G-gap means a lower level of glycation than expected. To explore the role of FN3K in diabetes and other associated morbidities, we decided to divide our research into 3 studies. Each study was categorised according to the type and the source of samples involved. The first study explored the correlation between FN3K activity and protein level with G-gap data; it involved 148 diabetic patients who were recruited at New Cross Hospital, Wolverhampton, selected as having a consistent positive G-gap > +0.5 and a consistent negative G-gap > -0.5 over a minimum of 2 estimations. Age, gender, race and BMI were collected from patients in this study. Blood samples were also 3 collected to measure FN3K activity, protein levels, and markers of CVD in relation to G-gap. The second study involved 23 AECOPD patients who were recruited from St George’s Hospital (London) and were treated with either metformin or a placebo. Serum samples were collected from these patients for a larger study: we assayed those 23 serum samples for FN3K protein levels to explore any possible correlation between FN3K with metformin therapy in COPD patients. The third study utilised 36 human peripheral lung samples from healthy individuals, asymptomatic smokers and stable COPD patients (GOLD 2) who were recruited at The Section of Respiratory Medicine, University Hospital of Ferrara, Italy. Those samples were assessed for FN3K expression by means of immunohistochemistry to explore the difference in FN3K activity between those three categories. It was found that the intracellular activity and protein expression of the FN3K enzyme in diabetic patients negatively correlated with the values of G-gaps where FN3K activity was high in patients with negative G-gap. FN3K serum protein levels were shown to be enhanced with metformin administration in COPD diabetic patients, suggesting a protective role for FN3K enzyme against protein damaged caused by the non-enzymatic glycation of proteins. Therefore, patients with positive G-gap have lower FN3K activity than those with negative G-gap, and in turn they are more susceptible to diabetes related complications. Our data also indicate that metformin has a beneficial effect in reducing damage caused by carbonyl stress from cigarette smoking in COPD patients by the action of FN3K. Our research has demonstrated that FN3K contributes to the protein repair system which protects against damage caused by non-enzymatic glycation. The high activity for the FN3K enzyme was associated with low levels of AGEs and low carbonyl stress levels in observed among patients with diabetes and COPD. In contrast, COPD patients tend to have low FN3K-mediated protection against protein damage in comparison to the normal population. These patients tend to be at risk for developing more complications, particularly CVD complications, than normal, healthy individuals. Treatment with metformin enhances FN3K action in COPD diabetic patients, possibly as a protective enzyme against the damaged caused by the non-enzymatic glycation.

Motivation: The prevalence of non-communicable diseases such as diabetes mellitus (DM) and cardiovascular disease (CVD) is rapidly increasing in industrialized societies. Experts believe that lifestyle, and in particular its nutritional aspects, plays a decisive role in increasing the burden of these chronic conditions. Dietary habits would, therefore, be modified to exert a positive impact on the prevention and treatment of chronic diseases of lifestyle. It is believed that the state of hyperglycaemia that is observed following food intake under certain dietary regimes contributes to the development of various metabolic conditions. This is not only true for individuals with poor glycaemic control such as some diabetics, but could also be true for healthy individuals. It would, therefore, be helpful to be able to reduce the amplitude and duration of postprandial hyperglycaemia. Selecting the correct type of carbohydrate (CHO) foods may produce less postprandial hyperglycaemia, representing a possible strategy in the prevention and treatment of chronic metabolic diseases. At the same time, a key focus of sport nutrition is the optimal amount of CHO that an athlete should consume and the optimal timing of consumption. The most important nutritional goals of the athlete are to prepare body CHO stores pre-exercise, provide energy during prolonged exercise and restore glycogen stores during the recovery period. The ultimate aim of these strategies is to maintain CHO availability to the muscle and central nervous system during prolonged moderate to high intensity exercise, since these are important factors in exercise capacity and performance. However, the type of CHO has been studied less often and with less attention to practical concerns than the amount of CHO. The glycaemic index (GI) refers to the blood glucose raising potential of CHO foods and, therefore, influences secretion of insulin. In several metabolic disorders, secretion of insulin is inadequate or impossible, leading to poor glycaemic control. It has been suggested that low GI diets could potentially contribute to a significant improvement of the conditions associated with poor glycaemic control. Insulin secretion is also important to athletes since the rate of glycogen synthesis depends on insulin due to it stimulatory effect on the activity of glycogen synthase. Objectives: Three main objectives were identified for this study. The first was to conduct a meta-analysis of the effects of the GI on markers for CHO and lipid metabolism with the emphasis on randomised controlled trials (RCT's). Secondly, a systematic review was performed to determine the strength of the body of scientific evidence from epidemiological studies combined with RCT's to encourage dieticians to incorporate the GI concept in meal planning. Finally, a systematic review of the effect of the GI in sport performance was conducted on all available literature up to date to investigate whether the application of the GI in an athlete's diet can enhance physical performance. Methodology: For the meta-analysis, the search was for randomised controlled trials with a cross-over or parallel design published in English between 1981 and 2003, investigating the effect of low GI vs high GI diets on markers of carbohydrate and lipid metabolism. The main outcomes were serum fructosamine, glycosylated haemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC) and triacylglycerols (TG). For the systematic review, epidemiological studies as well as RCT's investigating the effect of LGI vs HGI diets on markers for carbohydrate and lipid metabolism were used. For the systematic review on the effect of the GI on sport performance, RCT's with either a cross-over or parallel design that were published in English between January 1981 and September 2004 were used. All relevant manuscripts for the systematic reviews as well as meta-analysis were obtained through a literature search on relevant databases such as the Cochrane Central Register of Controlled Trials, MEDLINE (1981 to present), EMBASE, LILACS, SPORTDiscus, ScienceDirect and PubMed. This thesis is presented in the article format. Results and conclusions of the individual manuscripts: For the meta-analysis, literature searches identified 16 studies that met the strict inclusion criteria. Low GI diets significantly reduced fructosamine (p<0.05), HbA1c, (p<0.03), TC(p<0.0001) and tended to reduce LDL-c (p=0.06) compared to high GI diets. No changes were observed in HDL-c and TG concentrations. Results from this meta analysis, therefore, support the use of the GI concept in choosing CHO-containing foods to reduce TC and improve blood glucose control in diabetics. The systematic review combined the results of the preceding meta-analysis and results from epidemiological studies. Prospective epidemiological studies showed improvements in HDL-c concentrations over longer time periods with low GI diets vs. high GI diets, while the RCT's failed to show an improvement in HDL-c over the short-term. This could be attributed to the short intervention period during which the RCT's were conducted. Furthermore, epidemiological studies failed to show positive relationships between LDL-c and TC and low GI diets, while RCT's reported positive results on both these lipids with low GI diets. However, the epidemiological studies, as well as the RCT's showed positive results with low GI diets on markers of CHO metabolism. Taken together, convincing evidence from RCT's as well as epidemiological studies exists to recommend the use of low GI diets to improve markers of CHO as well as of lipid metabolism. 3 From the systematic review regarding the GI and sport performance it does not seem that low GI pre-exercise meals provide any advantages over high GI pre-exercise meals. Although low GI pre-exercise meals may better maintain CHO availability during exercise, low GI pre-exercise meals offer no added advantage over high GI meals regarding performance. Furthermore, the exaggerated metabolic responses from high GI compared to low GI CHO seems not be detrimental to exercise performance. However, athletes who experience hypoglycaemia when consuming CHO-rich feedings in the hour prior to exercise are advised to rather consume low GI pre-exercise meals. No studies have been reported on the GI during exercise. Current evidence suggests a combination of CHO with differing Gl's such as glucose (high GI), sucrose (moderate GI) and fructose (low GI) will deliver the best results in terms of exogenous CHO oxidation due to different transport mechanisms. Although no studies are conducted on the effect of the GI on short-term recovery it is speculated that high GI CHO is most effective when the recovery period is between 0-8 hours, however, evidence suggests that when the recovery period is longer (20-24 hours), the total amount of CHO is more important than the type of CHO. Conclusion: There is an important body of evidence in support of a therapeutic and preventative potential of low GI diets to improve markers for CHO and lipid metabolism. By substituting high GI CHO-rich with low GI CHO-rich foods improved overall metabolic control. In addition, these diets reduced TC, tended to improve LDL-c and might have a positive effect over the long term on HDL-c. This confirms the place for low GI diets in disease prevention and management, particularly in populations characterised by already high incidences of insulin resistance, glucose intolerance and abnormal lipid levels. For athletes it seems that low GI pre-exercise meals do not provide any advantage regarding performance over high GI pre-exercise meals. However, low GI meals can be recommended to athletes who are prone to develop hypoglycaemia after a CHO-rich meal in the hour prior to exercise. No studies have been reported on the effect of the GI during exercise. However, it has been speculated that a combination of CHO with varying Gl's deliver the best results in terms of exogenous CHO oxidation. No studies exist investigating the effect of the GI on short-term recovery, however, it is speculated that high GI CHO-rich foods are suitable when the recovery period is short (0-8 h), while the total amount rather than the type of CHO is important when the recovery period is longer (20-24 h). Therefore, the GI is a scientifically based tool to enable the selection of CHO-containing foods to improve markers for CHO and lipid metabolism as well as to help athletes to prepare optimally for competitions. Recommendations: Although a step nearer has been taken to confirm a place for the GI in human health, additional randomised, controlled, medium and long-term studies as well as more epidemiological studies are needed to investigate further the effect of low GI diets on LDL-c. HDL-c and TG. These studies are essential to investigate the effect of low GI diets on endpoints such as CVD and DM. This will also show whether low GI diets can reduce the risk of diabetic complications such as neuropathy and nephropathy. Furthermore, the public at large must be educated about the usefulness and application of the GI in meal planning. For sport nutrition, randomised controlled trials should be performed to investigate the role of the GI during exercise as well as in sports of longer duration such as cricket and tennis. More studies are needed to elucidate the short-term effect of the GI post-exercise as well as to determine the mechanism of lower glycogen storage with LGI meals post-exercise. / Thesis (Ph.D. (Dietetics))--North-West University, Potchefstroom Campus, 2005.

Motivation: The prevalence of non-communicable diseases such as diabetes mellitus (DM) and cardiovascular disease (CVD) is rapidly increasing in industrialized societies. Experts believe that lifestyle, and in particular its nutritional aspects, plays a decisive role in increasing the burden of these chronic conditions. Dietary habits would, therefore, be modified to exert a positive impact on the prevention and treatment of chronic diseases of lifestyle. It is believed that the state of hyperglycaemia that is observed following food intake under certain dietary regimes contributes to the development of various metabolic conditions. This is not only true for individuals with poor glycaemic control such as some diabetics, but could also be true for healthy individuals. It would, therefore, be helpful to be able to reduce the amplitude and duration of postprandial hyperglycaemia. Selecting the correct type of carbohydrate (CHO) foods may produce less postprandial hyperglycaemia, representing a possible strategy in the prevention and treatment of chronic metabolic diseases. At the same time, a key focus of sport nutrition is the optimal amount of CHO that an athlete should consume and the optimal timing of consumption. The most important nutritional goals of the athlete are to prepare body CHO stores pre-exercise, provide energy during prolonged exercise and restore glycogen stores during the recovery period. The ultimate aim of these strategies is to maintain CHO availability to the muscle and central nervous system during prolonged moderate to high intensity exercise, since these are important factors in exercise capacity and performance. However, the type of CHO has been studied less often and with less attention to practical concerns than the amount of CHO. The glycaemic index (GI) refers to the blood glucose raising potential of CHO foods and, therefore, influences secretion of insulin. In several metabolic disorders, secretion of insulin is inadequate or impossible, leading to poor glycaemic control. It has been suggested that low GI diets could potentially contribute to a significant improvement of the conditions associated with poor glycaemic control. Insulin secretion is also important to athletes since the rate of glycogen synthesis depends on insulin due to it stimulatory effect on the activity of glycogen synthase. Objectives: Three main objectives were identified for this study. The first was to conduct a meta-analysis of the effects of the GI on markers for CHO and lipid metabolism with the emphasis on randomised controlled trials (RCT's). Secondly, a systematic review was performed to determine the strength of the body of scientific evidence from epidemiological studies combined with RCT's to encourage dieticians to incorporate the GI concept in meal planning. Finally, a systematic review of the effect of the GI in sport performance was conducted on all available literature up to date to investigate whether the application of the GI in an athlete's diet can enhance physical performance. Methodology: For the meta-analysis, the search was for randomised controlled trials with a cross-over or parallel design published in English between 1981 and 2003, investigating the effect of low GI vs high GI diets on markers of carbohydrate and lipid metabolism. The main outcomes were serum fructosamine, glycosylated haemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), total cholesterol (TC) and triacylglycerols (TG). For the systematic review, epidemiological studies as well as RCT's investigating the effect of LGI vs HGI diets on markers for carbohydrate and lipid metabolism were used. For the systematic review on the effect of the GI on sport performance, RCT's with either a cross-over or parallel design that were published in English between January 1981 and September 2004 were used. All relevant manuscripts for the systematic reviews as well as meta-analysis were obtained through a literature search on relevant databases such as the Cochrane Central Register of Controlled Trials, MEDLINE (1981 to present), EMBASE, LILACS, SPORTDiscus, ScienceDirect and PubMed. This thesis is presented in the article format. Results and conclusions of the individual manuscripts: For the meta-analysis, literature searches identified 16 studies that met the strict inclusion criteria. Low GI diets significantly reduced fructosamine (p<0.05), HbA1c, (p<0.03), TC(p<0.0001) and tended to reduce LDL-c (p=0.06) compared to high GI diets. No changes were observed in HDL-c and TG concentrations. Results from this meta analysis, therefore, support the use of the GI concept in choosing CHO-containing foods to reduce TC and improve blood glucose control in diabetics. The systematic review combined the results of the preceding meta-analysis and results from epidemiological studies. Prospective epidemiological studies showed improvements in HDL-c concentrations over longer time periods with low GI diets vs. high GI diets, while the RCT's failed to show an improvement in HDL-c over the short-term. This could be attributed to the short intervention period during which the RCT's were conducted. Furthermore, epidemiological studies failed to show positive relationships between LDL-c and TC and low GI diets, while RCT's reported positive results on both these lipids with low GI diets. However, the epidemiological studies, as well as the RCT's showed positive results with low GI diets on markers of CHO metabolism. Taken together, convincing evidence from RCT's as well as epidemiological studies exists to recommend the use of low GI diets to improve markers of CHO as well as of lipid metabolism. 3 From the systematic review regarding the GI and sport performance it does not seem that low GI pre-exercise meals provide any advantages over high GI pre-exercise meals. Although low GI pre-exercise meals may better maintain CHO availability during exercise, low GI pre-exercise meals offer no added advantage over high GI meals regarding performance. Furthermore, the exaggerated metabolic responses from high GI compared to low GI CHO seems not be detrimental to exercise performance. However, athletes who experience hypoglycaemia when consuming CHO-rich feedings in the hour prior to exercise are advised to rather consume low GI pre-exercise meals. No studies have been reported on the GI during exercise. Current evidence suggests a combination of CHO with differing Gl's such as glucose (high GI), sucrose (moderate GI) and fructose (low GI) will deliver the best results in terms of exogenous CHO oxidation due to different transport mechanisms. Although no studies are conducted on the effect of the GI on short-term recovery it is speculated that high GI CHO is most effective when the recovery period is between 0-8 hours, however, evidence suggests that when the recovery period is longer (20-24 hours), the total amount of CHO is more important than the type of CHO. Conclusion: There is an important body of evidence in support of a therapeutic and preventative potential of low GI diets to improve markers for CHO and lipid metabolism. By substituting high GI CHO-rich with low GI CHO-rich foods improved overall metabolic control. In addition, these diets reduced TC, tended to improve LDL-c and might have a positive effect over the long term on HDL-c. This confirms the place for low GI diets in disease prevention and management, particularly in populations characterised by already high incidences of insulin resistance, glucose intolerance and abnormal lipid levels. For athletes it seems that low GI pre-exercise meals do not provide any advantage regarding performance over high GI pre-exercise meals. However, low GI meals can be recommended to athletes who are prone to develop hypoglycaemia after a CHO-rich meal in the hour prior to exercise. No studies have been reported on the effect of the GI during exercise. However, it has been speculated that a combination of CHO with varying Gl's deliver the best results in terms of exogenous CHO oxidation. No studies exist investigating the effect of the GI on short-term recovery, however, it is speculated that high GI CHO-rich foods are suitable when the recovery period is short (0-8 h), while the total amount rather than the type of CHO is important when the recovery period is longer (20-24 h). Therefore, the GI is a scientifically based tool to enable the selection of CHO-containing foods to improve markers for CHO and lipid metabolism as well as to help athletes to prepare optimally for competitions. Recommendations: Although a step nearer has been taken to confirm a place for the GI in human health, additional randomised, controlled, medium and long-term studies as well as more epidemiological studies are needed to investigate further the effect of low GI diets on LDL-c. HDL-c and TG. These studies are essential to investigate the effect of low GI diets on endpoints such as CVD and DM. This will also show whether low GI diets can reduce the risk of diabetic complications such as neuropathy and nephropathy. Furthermore, the public at large must be educated about the usefulness and application of the GI in meal planning. For sport nutrition, randomised controlled trials should be performed to investigate the role of the GI during exercise as well as in sports of longer duration such as cricket and tennis. More studies are needed to elucidate the short-term effect of the GI post-exercise as well as to determine the mechanism of lower glycogen storage with LGI meals post-exercise. / Thesis (Ph.D. (Dietetics))--North-West University, Potchefstroom Campus, 2005.