INTRODUCTION/OBJECTIVES: Current screening guidelines for pre-diabetes and type 2 diabetes mellitus note that there are discrepancies in diagnosing the disease using the fasting plasma glucose test, oral glucose tolerance test, and HbA1c in high-risk populations. The objective of this study is to compare the effectiveness of screening methods for type 2 diabetes mellitus (T2DM) and pre-diabetes by race/ethnicity and gender. METHODS: Secondary analyses of the National Health and Nutrition Examination Survey (NHANES, 2005-2008) were performed using SPSS 19.0. Screening outcomes were assessed and compared for a sample of n=10,566, NHW, NHB, MA, and Multiracial/other men and women. Analyses included cross tabulations, ANOVA and partial correlations to establish disease prevalence, effectiveness of screenings, and statistical significance. RESULTS: It was found that the HbA1c test is comparable in precision, and is correlated with the FPG for racial and ethnic minorities. The specificities for detecting pre-diabetes using the HbA1c were higher (64-66%) for these groups than by using the standard, FPG screening method (42-49%). There were no strong, significant differences for screening effectiveness for men versus women. DISCUSSION: This study revealed that the HbA1c test might be an effective method for screening for pre-diabetes in racial and ethnic minorities instead of the FPG test alone. Screening in high-risk populations will help delay the onset of T2DM, with increased prevention during the pre-clinical phase.

Magister Public Health - MPH (Public Health) / The prevalence of diabetes in Africa has been on the increase. A prevalence of 1%- 10% has been reported by different authors in different regions in Nigeria. The International Diabetes Federation estimates that 1.9% of Nigerians are diabetic and most of them have complications at the time of diagnosis. Laboratory measurement of Glycosylated hemoglobin (HbA1c) is the method of choice for monitoring glycaemic control but due to its cost and limited availability, most developing countries use fasting plasma glucose (FPG) measurement (which is less reliable) to assess glycaemic control. Most diabetic patients in Nigeria have poor glycaemic control and several factors have been implicated especially socio-economic, behavioral and treatment-related factors. Understanding the reasons for poor glycaemic control is essential in order to reduce the rate of diabetes complications.

Aim/Objectives: There were two aims; improving type II diabetes glycaemic control; and enhancing the role of community pharmacists by engaging them in type II diabetes medicine management. Methods: This quantitative study collected data from both community pharmacists and patients. In a premises survey, 426 self-administered questionnaires were distributed to community pharmacies. In a knowledge survey, 125 questionnaires were distributed to community pharmacists. In a clinical trial, 40 community pharmacies were randomly assigned to be control (18) and intervention (22) premises. Each pharmacy recruited 4 or 5 patients with type II diabetes. 225 patients were recruited and assigned to receive usual pharmacist care (n=100) or a pre-defined pharmacist intervention (n=125). Results: Community pharmacists had good knowledge of diabetes with average scores 21/29 (±3.18). The differences between control and intervention groups in patients' HbA1c and FPG changes were not significant. In the intervention group patients' diabetes knowledge was significantly improved (p=0.031). In the intervention group HbA1c and FPG improved significantly and in the control group FPG improved significantly and HbA1c did not. Patients' self-reported self-management activities improved significantly around blood glucose measurements (p < 0.001) and physical exercising (p=0.001). Attitudes around the value of tight control of diabetes improved (p < 0.001). Conclusion: The findings suggest that community pharmacists in Libya may have the ability to improve type II diabetes care. The primary outcomes were not improved in intervention versus control. The before/after analysis showed significant improvement in primary outcomes in the intervention group and also in one of the primary outcomes in the control group. Patients' self-reported self-care activities and attitudes improved significantly in the intervention group.

Type 2 diabetes mellitus (T2DM) is a global health concern affecting six to ten percent of adults worldwide, with the number of diagnosed individuals projected to double in the next 25 years. However, effective public health strategies can help mitigate its impact on quality of life, morbidity, mortality and the associated social and economic burden. In Sweden, screening programs classify individuals with Impaired fasting glucose (IFG) as high-risk individuals, however scholars argue that preventative measures should also include those at lower fasting plasma glucose (FPG) concentrations as some evidence suggests that the disease begins developing several years before the current threshold. A systematic review and meta-analysis of cohort and case-control studies was conducted with the purpose of exploring the IFG threshold from a longitudinal perspective. Eleven studies on the incidence rates of T2DM in normoglycemic individuals and seven studies on pre-diagnostic trajectories of FPG concentrations were analyzed. Incidence rates increased progressively across the normoglycemic range, with a twelve-fold difference between the low and high end. FPG concentrations in eventual progressors and non-diabetic controls were significantly different twelve years prior to diagnosis. Mildly increasing FPG concentrations were observed in eventual progressors until three years before diagnosis, at which a larger increase followed. In the last year before diagnosis, FPG concentrations rose dramatically in this group. The findings imply that a lowering of the threshold would extend the time spent in the IFG state, allowing for earlier identification of at-risk individuals. In addition, further stratification of normoglycemic range may enhance the accuracy of T2DM risk assessment.

Background Type 2 diabetes mellitus (T2DM) is a globally prevalent disease anticipated to double from 500 million diagnosed cases in 2021 to more than one billion by 2050. The investigation of the potentially protective effects of skeletal muscle mass on glucose intolerance may lead to the development of more precise screening protocols. Purpose This thesis aimed to address the lack of clear consensus in existing literature by exploring the relationship between skeletal muscle mass and glucose intolerance. Methods Fifteen healthy young adults were recruited to partake in a prospective correlational study. The participants underwent anthropometric measurements and an oral glucose tolerance test (OGTT). Anthropometric data was collected using an bioelectrical impedance analysis (BIA) scale. Blood glucose levels were measured using capillary sampling before and after ingestion of a 75 g/200 mL glucose solution. Statistical analysis included Spearman’s rank correlation test and Pearson’s correlation coefficient test. Results All associations between skeletal muscle mass and glucose intolerance were of moderate strength. Skeletal muscle mass (SMM) correlated significantly with glucose concentrations two hours (2hPG) following ingestion of the glucose solution and an adjusted measure of SMM was significantly associated with glucose area under the curve (AUC). Statistical significance was also found between Sex and incremental glucose area under the curve (iAUC). Conclusion This thesis suggests an inverse relationship between skeletal muscle mass and glucose intolerance in a group of healthy young adults. The results imply the potential usefulness of incorporating muscle mass when determining the glucose load during an OGTT, especially in preventive contexts. Nevertheless, further research with larger samples is crucial to establish precise cutoff levels for clinical applications. / Bakgrund Typ 2 diabetes mellitus (T2DM) är en global sjukdom och antalet diagnostiserade individer förväntas fördubblas från 500 miljoner fall 2021 till över en miljard år 2050. En undersökning av muskelmassans potentiellt skyddande effekt på glukostolerans kan leda till utvecklandet av noggrannare screeningmetoder. Syfte Syftet med denna uppsats var att bemöta den bristfälliga konsensus som råder bland befintlig forskning genom att undersöka sambandet mellan muskelmassa och glukosintolerans. Metod Femton friska yngre vuxna rekryterades för att delta i en prospektiv korrelationsstudie. Deltagarna genomgick antropometriska mätningar samt ett oralt glukostoleranstest (OGTT). Antropometriska värden mättes med hjälp av en bioelektrisk impedansanalysvåg. Blodglukosnivåer mättes kapillärt före och efter intag av en 75 g/200 mL glukoslösning. Statistisk analys inkluderade Spearmans rangkorrelationstest och Pearsons korrelationskoefficientstest. Resultat Alla samband mellan muskelmassa och glukosintolerans var av måttlig styrka. Muskelmassa (SMM) korrelerade signifikant med blodglukos två timmar (2hPG) efter intag av glukoslösningen och ett justerat SMM-mått (adjSMM) var signifikant associerat med arean under glukoskurvan (AUC). Statistisk signifikans hittades även mellan kön och den inkrementella arean under glukoskurvan (iAUC). Slutsats Resultaten från denna uppsats antyder att ett omvänt samband existerar mellan muskelmassa och glukosintolerans hos en grupp friska yngre vuxna. Resultatet innebär en potentiell möjlighet att använda muskelmassan vid bestämmandet av mängden glukos som administreras vid ett OGTT, särskilt i preventiva syften. Ytterligare forskning med fler studiedeltagare är avgörande för att fastställa exakta gränsvärden för klinisk tillämpning.

Current screening tests for type 2 diabetes mellitus (T2DM) identify less than 50% of undiagnosed T2DM patients and provide no information about how the disease will develop in prediabetic patients. Here, twenty-nine protein glycation sites were quantified after tryptic digestion of plasma samples at the peptide level using tandem mass spectrometry and isotope-labelled peptides as internal standard. The glycation degrees were determined in three groups, i.e., 48 patients with a duration of T2DM exceeding ten years, 48 non-diabetic individuals matched for gender, BMI, and age, and 20 prediabetic men. In long-term controlled diabetic patients, 27 glycated peptides were detected at significantly higher levels, providing moderate diagnostic accuracies (ACCs) from 61 to 79%, allowing a subgrouping of patients in three distinct clusters. Moreover, a feature set of one glycated peptides and six established clinical parameters provided an ACC of 95%. The same number of clusters was identified in prediabetic males (ACC of 95%) using a set of eight glycation sites (mostly from serum albumin). All patients present in one cluster showed progression of prediabetic state or advanced towards diabetes in the following five years. Overall, the studied glycation sites appear to be promising biomarkers for subgrouping prediabetic patients to estimate their risk for the development of T2DM.

Aim/Objectives: There were two aims; improving type II diabetes glycaemic control; and enhancing the role of community pharmacists by engaging them in type II diabetes medicine management. Methods: This quantitative study collected data from both community pharmacists and patients. In a premises survey, 426 self-administered questionnaires were distributed to community pharmacies. In a knowledge survey, 125 questionnaires were distributed to community pharmacists. In a clinical trial, 40 community pharmacies were randomly assigned to be control (18) and intervention (22) premises. Each pharmacy recruited 4 or 5 patients with type II diabetes. 225 patients were recruited and assigned to receive usual pharmacist care (n=100) or a pre-defined pharmacist intervention (n=125). Results: Community pharmacists had good knowledge of diabetes with average scores 21/29 (±3.18). The differences between control and intervention groups in patients' HbA1c and FPG changes were not significant. In the intervention group patients' diabetes knowledge was significantly improved (p=0.031). In the intervention group HbA1c and FPG improved significantly and in the control group FPG improved significantly and HbA1c did not. Patients' self-reported self-management activities improved significantly around blood glucose measurements (p<0.001) and physical exercising (p=0.001). Attitudes around the value of tight control of diabetes improved (p<0.001). Conclusion: The findings suggest that community pharmacists in Libya may have the ability to improve type II diabetes care. The primary outcomes were not improved in intervention versus control. The before/after analysis showed significant improvement in primary outcomes in the intervention group and also in one of the primary outcomes in the control group. Patients' self-reported self-care activities and attitudes improved significantly in the intervention group.

La prévalence du diabète ne cesse d’augmenter et la détection de sujets à risque de développer cette maladie reste une préoccupation importante afin qu’un programme de prévention leur soit proposé. Le dosage de l’HbA1c est utilisé pour l’évaluation de l’efficacité du traitement pris par les diabétiques. Il n’était pas utilisé pour le diagnostic des dysglycémies car les méthodes de ce dosage n’étaient pas standardisées. Actuellement l’IFCC (International Federation of Clinical Chemistry) propose une nouvelle méthode de référence pour cette mesure, et l’OMS (Organisation Mondiale de la Santé) a intégré ce paramètre dans les critères diagnostiques du diabète. but Evaluer la capacité de l’HbA1c à prédire un diabète incident, chercher des seuils, d’HbA1c, de GAJ et de glycémie deux heures (G2H) après un test d’hyperglycémie provoquée par voie orale (HGPO), au delà desquels les sujets sont plus à risque de développer un diabète incident et, enfin, étudier l’influence du tabac sur les variations de ces mesures. Méthodes Pour l’évaluation de la prédiction du diabète et la recherche de seuils, nous avons utilisé les données de l’étude australienne AusDiab, de l’étude danoise Inter99 et de l’étude française D.E.S.I.R. avec plus de 5500, 4500 et 3550 sujets, respectivement. Dans la troisième partie, nous avons utilisé les données du projet DETECT-2 (12 études, 26 000 sujets), ainsi que celles des études françaises D.E.S.I.R. et TELECOM (3700 sujets). Les distributions de l’HbA1c dans les trois premières études étaient différentes, nous avons donc, dans les deux premières parties d’analyses, ajusté les moyennes d’HbA1c à l’inclusion et après le suivi. Nous avons utilisé un modèle logistique pour la comparaison du pouvoir prédictif de l’HbA1c et de GAJ ; l’intervalle de confiance des Odds Ratios (ORs) à été obtenu par bootstrap. Pour rechercher les seuils de prédiction du diabète, nous avons comparé le modèle logistique (avec la variable glycémique) sans seuil au modèle avec seuil. Enfin, nous avons utilisé un modèle linéaire mixte pour évaluer la différence entre les moyennes d’HbA1c, de GAJ et de G2H en fonction du tabagisme, en attribuant un effet aléatoire à la variable ‘centre’. Résultats Avant ajustement des moyennes d’HbA1c, l’incidence du diabète (défini par la prise de traitement antidiabétique, une HbA1c≥6.5% ou une GAJ≥7mmol/l) était de 3.1% dans AusDiab, 2.7% dans Inter99 et 2.5% dans D.E.S.I.R. Les sujets dépistés comme étant diabétiques par l’HbA1c et par la GAJ n’étaient pas toujours les mêmes. L’incidence estimée du diabète augmente bien avec l’augmentation du taux de l’HbA1c et de la GAJ à l’inclusion. Pour chaque critère, l’aire sous la courbe de ROC (Receiver Operating Characteristic) était supérieure à 0.80 témoignant d’une bonne discrimination des deux tests entre les diabétiques incidents et les non diabétiques et le test de Hosmer-Lemeshow témoigne d’une bonne adéquation des modèles utilisés (p>0.05). Dans les trois populations, les ORs qui mesurent l’association entre les taux d’HbA1c et de GAJ et la survenue du diabète étaient presque toujours supérieurs pour l’HbA1c. Les seuils d’HbA1c et de GAJ au-delà desquels les sujets étaient plus à risque de développer un diabète variaient en fonction de la définition du diabète incident sauf pour l’HbA1c dans l’étude D.E.S.I.R. (5.3%) et la GAJ dans l’étude AusDiab (5.5mmol/l). Enfin, la moyenne d’HbA1c chez les fumeurs actuels était 0.10%(0.08,0.12) plus élevée que chez ceux qui n’ont jamais fumé ; la moyenne de G2H était -0.44(-0.51,-0.36) moins élevée chez les fumeurs actuels que chez ceux qui n’ont jamais fumé.Conclusion Ces résultats soulignent : 1) l’importance de l’utilisation de l’HbA1c comme critère diagnostique de dysglycémies, 2) la nécessité de mieux explorer les limites inférieures des stades intermédiaires qui précèdent la survenue du diabète, 3) l’importance de prendre en considération les facteurs qui peuvent influencer les taux d’HbA1c / The increasing prevalence of diabetes worldwide makes the detection of people at risk of developing diabetes a major concern, so that they can benefit from diabetes prevention programs. HbA1c is used to evaluate the effectiveness of treatment taken by diabetic patients. HbA1c had not been used to diagnose dysglycemia because the assay methods were not standardized. The International Federation of Clinical Chemistry has proposed a reference method, and in 2011 the World Health Organization included HbA1c as one of the criteria for the diagnosis of diabetes. aims: 1) To evaluate the ability of HbA1c to predict incident diabetes compared with fasting plasma glucose (FPG); 2) to find thresholds for HbA1c, FPG and two hour plasma glucose (G2H) after an oral glucose tolerance test (OGTT) beyond which subjects are more at risk for developing incident diabetes and finally; 3) to study the influence of smoking on HbA1c, FPG and G2H.Methods: Several populations were studied. To evaluate the prediction of diabetes and the search for thresholds, we used data from the Australian study (AusDiab), a Danish study (Inter99) and a French study (D.E.S.I.R.) with respectively more then 5500, 4500 and 3550 participants. In the third part, we used data from the DETECT-2 consortium (12 studies with more than 26 000 men and women) and from two French studies: D.E.S.I.R. and TELECOM (with more than 3700 participants). The distribution of HbA1c in AusDiab, Inter99 and D.E.S.I.R. differed, so in the first two parts of this thesis, we adjusted HbA1c so that all three studies had the same mean HbA1c at baseline and the same mean HbA1c at follow-up. We used a logistic model to quantify the predictive ability of HbA1c and FPG for diabetes, and then derived confidence intervals for the difference in Odds Ratios (ORs) by bootstrap. To search for thresholds to predict incident diabetes, based on HbA1c, FPG and G2H at inclusion, we compared logistic regression models that were linear in the glycaemic variable, without a threshold, with a spline model with a threshold. Linear mixed models with ‘centre’ as a random variable, were used to assess the difference between the means of HbA1c, FPG and G2H in current-, ex- and never-smokers.Results: With unadjusted HbA1c data, the incidence of diabetes (defined by treatment, HbA1c≥6.5% or FPG≥7 mmol/l) was 3.1% in AusDiab, 2.7% in Inter99 and 2.5% in D.E.S.I.R.. Subjects detected as having diabetes by HbA1c and FPG were not always the same. The incidence of diabetes increased with increasing HbA1c and FPG at baseline. For each test, the area under the Receiver Operating Characteristic curve was greater than 0.80, indicating good discrimination for these two measures between those with and without incident diabetes, and the Hosmer-Lemeshow test indicated that the models fitted well (p>0.05). In all three populations, the ORs measuring the association between HbA1c and FPG and the development of diabetes were almost always higher for HbA1c than for FPG. The thresholds of HbA1c and FPG above which the incidence of diabetes were higher, varied according to the definition of incident diabetes - except for HbA1c in D.E.S.I.R. (always 5.3%) and for FPG in AusDiab (always 5.5mmol/l). Finally, in current-smokers, the mean HbA1c was 0.10%(0.08,0.12) higher than in never-smokers; the mean G2H was 0.44( 0.51,-0.36) lower in current-smokers than in never-smokers. Conclusion: The results that we found emphasize: 1) the importance of using HbA1c as a diagnostic criterion for dysglycemia, as those diagnosed diabetic by HbA1c did not have always an FPG ≥ 7 mmol/l, 2) the need to better explore the lower limits of the “pre-diabetic” stage as the thresholds of HbA1c, FPG and 2H-PG that we found were lower than those used in clinical practice, 3) the importance to consider factors that may influence HbA1c and G2H, such as smoking.

Background: African-Americans are a vulnerable population group with disproportionately elevated rates of type 2 Diabetes Mellitus (DM). Resistant starch is a promising food ingredient that has the potential to reduce the risk factors involved in the development of type 2 DM. To date, there is a dearth of published research studies on the effect of resistant starch on African-Americans who are at increased risk for type 2 DM. Objective: The major objective of this study was to determine if daily consumption of approximately twelve grams of high-maize™ 260 resistant starch (RS) added to bread improved glucose homeostasis by monitoring changes in fasting plasma glucose, fructosamine, hemoglobin A1c, insulin, glucagon-like peptide-1, C-reactive protein, homeostasis model assessment insulin resistant (HOMA- IR) and beta-cell function (HOMA-Beta), serum acetate, propionate, and butyrate levels. Design: A fourteen-week, randomized, double-blind, within-subject crossover design feeding study was carried out in African-American males (n=8) and females (n=7) at increased risk for type 2 DM who resided in Southwest Virginia. All participants consumed bread containing added RS or control bread (no added RS) for six-weeks. RS and control bread feedings were separated by a two-week washout period. Results: Fasting Plasma Glucose (FPG) levels were significantly lower (P = 0.0179) after six-week control bread feedings compared to baseline. FPG levels were also significantly lower (P < 0.0001) after two-week washout period than at baseline. FPG levels were significantly higher (P < 0.0001) after six-week resistant starch bread feeding than at washout. FPG levels due to consumption of resistant starch versus control bread approached significance (P = 0.0574). Fructosamine levels were significantly lower (P = 0.0054) after control bread and resistant starch bread (P < 0.0012) consumption compared to baseline. No significant differences were found in fructosamine levels due to resistant bread intake versus control (P = 0.9692). Mean baseline HbA1c levels were 6.9% (n=15). This value was slightly lowered to 6.79% (n=14) at the end of the fourteen-week study, although statistical significance was not found. Mean ± standard errors for HbA1c values were 6.9% ± 0.18% and 6.9% ± 0.14% at baseline for the sequence groups, resistant starch first (n=7) and control treatment first (n=8) groups, respectively. Mean± standard error HbA1c values were 6.7%± 0.27% and 6.9% ± 0.27% at the conclusion of fourteen-week study for sequence groups, resistant starch first group (n=7) and control treatment first group, respectively. Baseline mean and standard errors C-reactive Protein (CRP) levels for male and female combined results were 0.62 ± 0.16 mg/dL (n=15). Mean CRP levels were 0.53 ± 0.12 mg/dL for resistant starch bread and 0.64 ± 0.21 mg/dL for control bread feeding periods. No significant differences were found for treatment, gender, or sequence effects for C-reactive protein levels during the fourteen-week study (P > 0.05). Mean HOMA-IR levels following six-week resistant starch and control bread consumption decreased to normal values (> 2.5), although no significant differences were found for treatment (P = 0.5923). Conclusions: Eighty-seven grams of Hi- maize™ 260 Resistant Starch added to baked loaves of bread consumed by a free-living African-American population at increased risk for type 2 diabetes did not consistently show significance in all clinical indicators and biochemical markers assessed. On the basis of the evidence in this study we do not have evidence that this amount of resistant starch in this population's diet will prevent the onset of diabetes. However, results are suggestive that higher levels of resistant starch in a more controlled experiment could reduce clinical risk factors for type 2 diabetes. / Ph. D.