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.

The purpose of this study was to assess the epidemiology of preventable risk factors for NCDs among the adult population in Tigray, Northern Ethiopia. A quantitative descriptive cross-sectional design was employed to describe the distribution of behavioural and biological risk factors for NCDs, assess the status of knowledge, perceptions, attitude and behaviour of the study participants for NCDs and their risk factors, and a matched case-control study to identify the determinants of hypertension. The data was collected using a structured questionnaire for the interview, physical measurements including weight and height scales, non-elastic measuring tape for waist and hip circumferences, Omron digital BP apparatus for blood pressure and heart rate; Accutrend Plus for measuring fasting blood glucose, cholesterol and triglycerides. For the descriptive cross-sectional study a total of 2347 participants were included, and for the matched case control study a total of 117 cases and 235 controls participated. Behavioural and biological risk factors were assessed. Only 0.8% of the study participants used optimal fruit serving per day. The prevalence of low level physical activity (<600 MET-minutes/week) was 44.8%. The magnitude of ever alcohol consumption was 66.8%. However, the magnitude of khat chewing and tobacco smoking among the study participants was not as high as the other risk factors i.e. 3.3% and 2.3% respectively. The magnitude of hypertension, central obesity, hyperglycaemia, hypercholesterolemia and hypertriglyceridemia was 9.9%, 22.2%, 3.5%, 30.3% and 32.2% respectively. Factors associated with the risks aforementioned were gender, age, place of residence, education, knowledge status on NCDs, mental stress and others. The status of knowledge on CVDs, breast and cervical cancers, diabetes and their potential risk factors was low and not comprehensive. Misconceptions on NCDs and body size and shape were pervasive. Risky behaviours underlying NCDs were rampant in the study population. Factors related to poor knowledge on NCDs were gender, age, place of residence, education and misconceptions on NCDs. The determinants of hypertension were physical inactivity, duration of alcohol intake, central obesity and mental stress. Awareness raising interventions on NCDs and their risk factors; improving socio-economic status and accessibility to health care settings have to be in place to curb these formidable problems. / Health Studies / D. Litt. et Phil. (Health Studies)

The purpose of this study was to assess the epidemiology of preventable risk factors for NCDs among the adult population in Tigray, Northern Ethiopia. A quantitative descriptive cross-sectional design was employed to describe the distribution of behavioural and biological risk factors for NCDs, assess the status of knowledge, perceptions, attitude and behaviour of the study participants for NCDs and their risk factors, and a matched case-control study to identify the determinants of hypertension. The data was collected using a structured questionnaire for the interview, physical measurements including weight and height scales, non-elastic measuring tape for waist and hip circumferences, Omron digital BP apparatus for blood pressure and heart rate; Accutrend Plus for measuring fasting blood glucose, cholesterol and triglycerides. For the descriptive cross-sectional study a total of 2347 participants were included, and for the matched case control study a total of 117 cases and 235 controls participated. Behavioural and biological risk factors were assessed. Only 0.8% of the study participants used optimal fruit serving per day. The prevalence of low level physical activity (<600 MET-minutes/week) was 44.8%. The magnitude of ever alcohol consumption was 66.8%. However, the magnitude of khat chewing and tobacco smoking among the study participants was not as high as the other risk factors i.e. 3.3% and 2.3% respectively. The magnitude of hypertension, central obesity, hyperglycaemia, hypercholesterolemia and hypertriglyceridemia was 9.9%, 22.2%, 3.5%, 30.3% and 32.2% respectively. Factors associated with the risks aforementioned were gender, age, place of residence, education, knowledge status on NCDs, mental stress and others. The status of knowledge on CVDs, breast and cervical cancers, diabetes and their potential risk factors was low and not comprehensive. Misconceptions on NCDs and body size and shape were pervasive. Risky behaviours underlying NCDs were rampant in the study population. Factors related to poor knowledge on NCDs were gender, age, place of residence, education and misconceptions on NCDs. The determinants of hypertension were physical inactivity, duration of alcohol intake, central obesity and mental stress. Awareness raising interventions on NCDs and their risk factors; improving socio-economic status and accessibility to health care settings have to be in place to curb these formidable problems. / Health Studies / D. Litt. et Phil. (Health Studies)