Type 2 diabetes mellitus (T2DM) is a chronic condition recognized as the inability to maintain glucose homeostasis, typically presenting with insulin resistance and systemic inflammation. With the prevalence of T2DM and major risk factors such as prediabetes and obesity increasing each year, there is a crucial need to identify strategies for the management and prevention of this condition. Addressing lifestyle-related risk factors through consumption of a well-balanced, nutritious diet and maintaining regular moderate- to high-intensity physical activity may provide a strategy for improving glycemic control, improving metrics of body composition, and decreasing the inflammatory response associated with metabolic dysregulation. Twenty-two overweight to obese adults with a medical diagnosis of T2DM, indicators of prediabetes, or who were metabolically healthy participated in Cal Poly’s Nutrition and Exercise in Type 2 Diabetes (CPNET) study. The study protocol included adherence to a Mediterranean-style diet, daily consumption of a high-quality whey protein supplement, and adherence to the Physical Activity Guidelines for Americans for 16 weeks. Body composition data, via dual-energy X-ray absorptiometry (DXA), and fasting blood samples were collected at baseline and following the intervention. Due to restrictions associated with the global COVID-19 pandemic, only 13 participants were able to return for the second data collection following the 16-week intervention. The prediabetic and T2DM groups exhibited reductions in fasting plasma glucose to that of normal and prediabetic levels, respectively, while the T2DM group also showed improvement in hemoglobin A1c to the prediabetic level. Additionally, the metabolically healthy, overweight group demonstrated significant improvements in adiposity, while the obese prediabetic and T2DM groups showed non-significant improvements in all measured metrics of body composition. No changes were observed in inflammatory biomarkers. Thus, our results suggest that adherence to a well-balanced nutritious diet and regular physical activity may improve parameters of glycemic control and provide benefits to body composition that help manage and prevent the development of T2DM.

Yes / The prevalence of Type 2 diabetes mellitus (T2DM) is escalating globally. Patients suffer from multiple complications including the development of chronic wounds that can lead to amputation. These wounds are characterised by an inflammatory environment including elevated tumour necrosis factor alpha (TNF-α). Dermal fibroblasts (DF) are critical for effective wound healing, so we sought to establish whether there were any differences in DF cultured from T2DM donors or those without diabetes (ND-DF). ND- and T2DM-DF when cultured similarly in vitro secreted comparable concentrations of TNF-α. Functionally, pre-treatment with TNF-α reduced the proliferation of ND-DF and transiently altered ND-DF morphology; however, T2DM-DF were resistant to these TNF-α induced changes. In contrast, TNF-α inhibited ND- and T2DM-DF migration and matrix metalloprotease expression to the same degree, although T2DM-DF expressed significantly higher levels of tissue inhibitor of metalloproteases (TIMP)-2. Finally, TNF-α significantly increased the secretion of pro-inflammatory cytokines (including CCL2, CXCL1 and SERPINE1) in ND-DF, whilst this effect in T2DM-DF was blunted, presumably due to the tendency to higher baseline pro-inflammatory cytokine expression observed in this cell type. Collectively, these data demonstrate that T2DM-DF exhibit a selective loss of responsiveness to TNF-α, particularly regarding proliferative and secretory functions. This highlights important phenotypic changes in T2DM-DF that may explain the susceptibility to chronic wounds in these patients. / This study was funded by an Iraqi government studentship to AHAA-R.

Type 2 diabetes mellitus (T2DM) disproportionality affects under-represented groups, specifically Asian Americans. Asian Americans are less likely to receive proper diabetes mellitus screening compared to other racial and ethnic groups, potentially due to improper screening guidelines by clinicians, and Asian Americans being unaware of their increased risk for diabetes mellitus. There are differences in the etiology of T2DM in Asian Americans compared to White Americans. Due to the increasing rates of T2DM among Asian Americans, new approaches in the screening of T2DM should be tailored based on race and ethnicity. The aging process is frequently associated with decreased muscle mass and increased adipose tissue, which can contribute to insulin resistance and lead to elevated hemoglobin A1c (HbA1c) percentages. Although sex has not been classified as an independent risk factor for T2DM, it is important to consider sex-specific conditions in the context of the disease. Body mass index (BMI) alone is insufficient to properly evaluate adiposity in Asian-American adults due to Asian Americans having a lower BMI with a higher body fat percentage. Waist circumference, waist-to-height ratio (WHtR), and visceral adiposity index (VAI) may be better for screening Asian Americans for T2DM. Multiple modifiable risk factors, such as sedentary behavior, and dietary intake (specifically dietary magnesium intake) can increase the risk for T2DM. Lack of physical activity can result in insulin resistance and impaired glucose metabolism as a result of muscle disuse and decreased lean body mass. Half of the Asian-American population is not consuming the recommended amounts of magnesium from foods, drinks, and dietary supplements. There is an inverse relationship between increased dietary magnesium intake and the risk of T2DM. In addition, the main language spoken in the household may influence lifestyle and risk of T2DM. The overarching goal of the present study was to establish which independent variables (age, sex, BMI, waist circumference, WHtR, VAI, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language) were the strongest predictors of HbA1c percentage (a measure of blood glucose control) in Asian-American adults using the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2020. The present study also evaluated the relationship among multiple predictors of HbA1c percentage, including age, sex, body composition, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language among Asian-American adults, 18 years of age and older, using the NHANES data from 2011 to 2020. / Doctor of Philosophy / Asian Americans have been disproportionately affected by type 2 diabetes mellitus (T2DM). Compared to other racial and ethnic groups, Asian Americans are less likely to receive proper diabetes mellitus screening. This may be due to inadequate screening guidelines and lack of awareness about their increased risk for diabetes mellitus. The cause of T2DM in Asian Americans differs from that in White Americans, which calls for tailored screening approaches based on race and ethnicity. The aging process is frequently associated with decreased muscle mass and increased adipose tissue, which can contribute to insulin resistance and lead to elevated hemoglobin A1c (HbA1c) percentages. Although sex has not been classified as an independent risk factor for T2DM, it is important to consider sex-specific conditions in the context of the disease. Body mass index (BMI) alone is not enough to accurately assess body fat in Asian-American adults, because they tend to have a lower BMI, but higher body fat percentage. Waist circumference, waist-to-height ratio (WHtR), and visceral adiposity index (VAI) might be more suitable for screening Asian Americans for T2DM. Several modifiable risk factors, such as a sedentary lifestyle and dietary intake (specifically, dietary magnesium intake), can increase the risk of T2DM. Lack of physical activity can lead to insulin resistance and impaired glucose metabolism due to muscle disuse and reduced lean body mass. Half of the Asian-American population does not consume the recommended amounts of magnesium from food, drinks, and dietary supplements. Researchers have shown that increased dietary magnesium intake is linked to a reduced risk of T2DM. In addition, the main language spoken in the household may influence lifestyle and risk of T2DM. The main goal of this study was to identify which factors (age, sex, BMI, waist circumference, WHtR, VAI, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language) were the strongest predictors of HbA1c percentage (a measure of blood glucose control) in Asian Americans. This was completed using the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2020. Additionally, the study aimed to establish the relationship among multiple predictors of HbA1c percentage, including age, sex, body composition, sedentary behavior time, dietary magnesium intake, self-reported healthy diet status, and language among Asian-American adults, 18 years of age and older, using the same NHANES data.

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Yes / To explore the perception of healthcare workers (HCWs) on diabetic foot ulcers (DFU) and foot care in Rotuma, Fiji. Using a qualitative study design, two focus group discussions (FGDs) were conducted among HCWs. A semistructured open-ended questionnaire was used to guide the discussion session. Each FGD was audiorecorded and was transcribed. The transcriptions were then manually analysed using thematic analysis. Rotuma hospital, Fiji. HCWs who were working in Rotuma hospital for at least a year and were involved in clinical foot care of type 2 diabetes mellitus patients were included. There were five main themes, namely, depth of knowledge, quality of care in practice, factors of influence on practice, lack of resources and capacity building. Participants had superficial knowledge that showed lack of in-depth scientific knowledge. A lack of staffing in the clinics affected the delivery of service. Additionally, patients defaulting clinics, late presentations with DFU and traditional medicine also affected the quality of healthcare service in clinics. There was also a need for a multidisciplinary team to prevent and manage DFU. HCWs mostly advised on glycaemic control and ignored offering foot care advice in clinics due mainly to the lack of sound knowledge on foot care. There was also a lack of resources, infrastructure, space and professional development opportunities, which negatively impacted how HCWs deliver foot care services to patients. HCWs lack significant in-depth knowledge on DFU and foot care. In addition, these are the availability of traditional medicine that delays presentations to hospital, further reducing the quality of services. HCWs need to keep their knowledge and skills updated through regular in-service training on foot care. Resources, infrastructure and supply chains need to be maintained by those in power to ensure HCWs deliver quality foot care services.

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Syfte: Att undersöka patienters upplevelser av livskvalitet vid nydiagnostiserad typ 2 Diabetes Mellitus. Metod: En empirisk studie med en kvalitativ ansats som innefattade tio deltagare med nydiagnostiserad typ 2 Diabetes Mellitus. Semistrukturerade intervjuer genomfördes utifrån en intervjuguide där insamlad data analyserades med kvalitativ manifest innehållsanalys. Resultat: Studien resulterade i fyra huvudkategorier och tio subkategorier. Upplevelsen av att få ett diagnosbesked varierade mellan deltagarna, för vissa deltagarna var beskedet inte förvånande medan andra upplevde känslor av chock och förnekelse. Deltagarna upplevde positiva förändringar, exempelvis viktnedgång och förbättrad hälsa men även negativa förändringar, exempelvis att vara beroende av läkemedel. Vissa upplevde ingen förändring alls. Typ 2 Diabetes Mellitus påverkade inte deltagarnas fysiska eller psykiska hälsa i de flesta fall. Deltagarna ansåg det som viktig att få stöd från både omgivningen och hälso- och sjukvården. Konklusion: Känslorna över ett diagnosbesked kunde variera men upplevelsen av livskvalitet påverkades inte av Typ 2 Diabetes Mellitus i de flesta fall i studien. Patientens inställning till att leva med Typ 2 Diabetes Mellitus inverkade på förmågan till att utföra egenvård, och distriktsköterskans stöd och engagemang ansågs vara betydelsefullt i sjukdomsprocessen. / Aim: To examine patients’ experiences of the quality of life in newly-diagnosed type 2 Diabetes Mellitus. Method: An empirical study with a qualitative approach that included ten participants with newly diagnosed type 2 Diabetes Mellitus. Semi-structured interviews were conducted on the basis of an interview-guide and the collected data was analyzed using qualitative manifest content analysis. Results: The study resulted in four main categories and ten subcategories. The experience of receiving a diagnosis varied between the participants, some participants did not experience the news as surprising, while others experienced feelings of shock and denial. The participants experienced positive changes, for example weight loss and improved health but also negative changes, such as being dependent of medicine. Some participants experienced no change at all. Type 2 Diabetes Mellitus did not affect the participants’ physical and mental health. The participants considered it important to get support from both surrounding people and health care. Conclusion: The feelings of a diagnosis could vary but the experience of quality of life is not affected by Type 2 Diabetes Mellitus in most cases in the study. The patient's attitude to living with Type 2 Diabetes Mellitus affects the ability to perform self-care, and the district nurse support and involvement is considered to be important in the process of the disease.

<p>A central aim in drug development is to ensure that the new drug is efficacious and safe in the intended patient population.</p><p>Mathematical models describing the pharmacokinetic-pharmacodynamic (PK-PD) properties of a drug are valuable to increase the knowledge about drug effects and disease and can be used to inform decisions. The aim of this thesis was to develop mechanism-based PK-PD-disease models for important safety and efficacy biomarkers used in anti-diabetic drug development. </p><p>Population PK, PK-PD and disease models were developed, based on data from clinical studies in subjects with varying degrees of renal function, non-diabetic subjects with insulin resistance and patients with type 2 diabetes mellitus (T2DM), receiving a peroxisome proliferator-activated receptor (PPAR) α/γ agonist, tesaglitazar.</p><p>The PK model showed that a decreased renal elimination of the metabolite in renally impaired subjects leads to increased levels of metabolite undergoing interconversion and subsequent accumulation of tesaglitazar. Tesaglitazar negatively affects the glomerular filtration rate (GFR), and since renal function affects tesaglitazar exposure, a PK-PD model was developed to simultaneously describe this interrelationship. The model and data showed that all patients had decreases in GFR, which were reversible when discontinuing treatment. </p><p>The PK-PD model described the interplay between fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c) and haemoglobin in T2DM patients. It provided a mechanistically plausible description of the release and aging of red blood cells (RBC), and the glucose dependent glycosylation of RBC to HbA1c. The PK-PD model for FPG and fasting insulin, incorporating components for β-cell mass, insulin sensitivity and impact of disease and drug treatment, realistically described the complex glucose homeostasis in the heterogeneous patient population. </p><p>The mechanism-based PK, PK-PD and disease models increase the understanding about T2DM and important biomarkers, and can be used to improve decision making in the development of future anti-diabetic drugs. </p>