Type 2 diabetes mellitus (T2DM) is now increasingly diagnosed in children and adolescents at an alarming rate, especially in youth from diverse ethnic backgrounds. Youth diagnosed with T2DM and their families face many challenges associated with the illness and its complications. Given that the prevalence of T2DM in youth is a recent trend, most of the studies examining T2DM have been conducted with adults. The current study expands the literature base of youth with T2DM by collecting demographic and clinical data of youth with T2DM and their families. Regression analyses were used to investigate the relationship among youth's executive function, their body mass index (BMI) and glycosylated hemoglobin (HbA1c) level. Furthermore, the study analyzed the relationship among depressive symptoms and health related quality of life (HRQOL) in youth, and the role of family members in sharing of tasks related to T2DM care and the youth's HRQOL. Results of this study demonstrated that executive function does not predict a youth's HbA1c, nor their BMI. Interestingly, one of the more significant findings to emerge from this study is that youth's rating of their ability to adjust to changes in routine or task demands and their ability to modulate emotions significantly correlated with their BMI. Results also demonstrated that HbA1c does not mediate the relationship between depressive symptoms and HRQOL, nor the relationship between the family sharing of responsibilities related to T2DM tasks and HRQOL. Future research examining the relationship among psychological and family characteristics can aid the development of diabetes prevention and treatment management.

Objective The prevalence of obesity and related diseases such as type 2 diabetes mellitus (T2DM) is increasing worldwide, and the Asian Indian population seems to be particularly susceptible to developing T2DM, even at a low body mass index (BMI). In Sweden, the age-adjusted prevalence of diabetes has not increased despite increasing self-reported obesity. However, modern data on the prevalence of obesity and T2DM in Scandinavia are absent.The biochemical links between obesity and subsequent T2DM are unknown, but the adipocyte-derived hormones leptin and adiponectin (adipokines) have been suggested as potential links because they both are related to insulin and glucose physiology. Some studies have found leptin to be an independent predictor of T2DM in men but not in women, although these results are inconsistent. In contrast, adiponectin has more consistently been linked to development of T2DM in both men and women. Furthermore, the leptin–adiponectin ratio may predict incident T2DM better than either of the two hormones separately.The aims of this thesis were to describe time trends in obesity and T2DM in northern Sweden, to evaluate leptin and adiponectin as predictors of deterioration in glucose metabolism including T2DM, and to evaluate leptin as a risk marker regarding ethnic differences, circ-annual variation, and intra-individual stability. Materials and methods Three large population surveys were used, the Northern Sweden MONICA (MONitoring of Trends and Determinants in CArdiovascular Disease) study, the Västerbotten Intervention Programme (VIP), and the Mauritius Non-Communicable Disease Study. Within the MONICA study, six cross-sectional surveys were performed in Sweden’s two northernmost counties, Norrbotten and Västerbotten, between 1986 and 2009. A total of 1000 men and 1000 women ages 25–64 years, also including from 1994 250 men and 250 women ages 65–74 years, were independently chosen for each survey. The overall participation rate was 75%. In 1999, a reinvestigation was performed in 74% of all participants from the three first surveys. Data from the MONICA surveys were used in papers I and IV and data from the reinvestigation survey in paper II. VIP is an ongoing population intervention program that started in the mid-eighties targeting cardiovascular risk factors and has covered the whole county of Västerbotten since 1991. Inhabitants are invited the years they turn 40, 50, and 60 years old, and the annual participation rate has varied between 48% and 67%. A subset (n=1780) from VIP was used in paper II for the circ-annual leptin analysis, and VIP data linked to the diabetes register in Västerbotten (DiabNorr) were used in a case referent study (640 patients with T2DM) in paper III. The Mauritius Non-Communicable Disease Study was performed in 1987 in 10 randomly selected (with probability proportional to size) population clusters. All eligible adults ages 25–74 years were invited, and the participation rate was 86% (n=5083). In 1992, a follow-up survey was performed in 49% of the initial participants. The Mauritius survey data were used in paper II. Results I. BMI increased in men ages 25–74 years and in women ages 25–44 years in northern Sweden between 1986 and 2004. The prevalence of obesity (BMI 30) increased in men ages 25–44 and 55–74 years and in women ages 25–44 years. The prevalence of obesity increased from 10.4% to 19.1% in men and from 12.9% to 17.9% in women ages 25–64 years. Waist circumference (WC) decreased in women of all ages and in men ages 55–64 years between 1986 and 1990. After 1990, WC increased again, and the prevalence of abdominal obesity rose markedly in women ages 25–64 years. II. Differences in circulating levels of leptin, leptin per BMI unit (leptin/BMI), and leptin per cm in WC (leptin/waist) were tested in men and women of Asian Indian, Creole (African), and Caucasian ethnicity. Asian Indian men and women had the highest leptin concentrations and Caucasian men and women the lowest while Creole men and women had intermediate values for leptin, leptin/BMI, and leptin/waist. No circ-annual variation in leptin concentrations was seen in Caucasians. The intra-individual test– retest stability for leptin was equal in men and women of different ethnicities, over 5–13 years, with an intra-class correlation of 0.65–0.82. III. High adiponectin concentrations predicted decreased risk of T2DM in both insulin-sensitive and insulin-resistant men and women, whereas high leptin levels predicted increased risk for T2DM only in insulinsensitive men. A high leptin–adiponectin ratio predicted T2DM in both men and women, and men with a high ratio had a shorter time to diagnosis than those with a low ratio. IV. In northern Sweden, fasting and post-load glucose increased in women ages 24–65 years with 0.2 mmol/l and 0.7 mmol/l, respectively, between 1990 and 2009. Consequently, the prevalence of impaired fasting glucose and impaired glucose tolerance (IGT) rose from 4.5% to 7.7%, and from 7.8% to 14.5%, respectively. In men, post-load glucose increased at 0.5 mmol/l, and the prevalence of IGT rose from 3.5% to 10.1%. The prevalence of diabetes did not increase. An independent relationship between leptin and changes in fasting and post-load glucose was seen in men but not in women. Conclusion An increasing obesity and concomitant deterioration in glucose metabolism was seen in northern Sweden in the period studied. High adiponectin concentrations predicted a decreased risk of T2DM in both men and women, whereas high leptin concentrations predicted an increase in fasting and post-load glucose as well as an increased risk of T2DM in men but not in women. Individual insulin resistance status modified the association between leptin and T2DM, and the leptin–adiponectin ratio may add further predictive information beyond the measures of the separate hormones. In relation to traditional anthropometric measures of obesity, Asian Indian men and women had the highest and Caucasians the lowest concentrations of leptin while Creole (African) men and women had intermediate levels. As a risk marker, leptin has a high intra-individual stability, equal in men and women and among different ethnicities over 5–13 years with no circ-annual variation.

Type 2 diabetes is a common chronic disease, which has a negative health impact and results in enormous economic burden. The prevalence of type 2 diabetes is increasing dramatically and it affects older people disproportionately. The healthcare system in China is faced with an overwhelming burden due to a large ageing population, high prevalence of diabetes and limited healthcare resources. Self-management has been widely accepted as the cornerstone of the clinical management of type 2 diabetes. Since self-management usually involves complex behaviour change and can be emotionally challenging, effective education is essential to facilitate this transition. However, there has been no existing program of type 2 diabetes self-management for older patients in China until now. Furthermore, the generalisation of any health education programs is often hampered due to limited healthcare resources in China. The primary purpose of this study was to develop a socially and culturally suitable self-management program, which addressed self-efficacy and social support to facilitate behaviour change and subsequent health improvement, for older people with type 2 diabetes living in the community in China. The secondary purpose was to test a feasible delivery model of the program through involvement of peer leaders and existing community networks. This study was conducted in three phases. Phase one gathered information about barriers related to self-management behaviours and help needed to address them, from the perspective of older people with type 2 diabetes and community health professionals, through focus group discussion. Data from Phase One, together with guidelines of the selected theoretical frame work, results from an extensive literature review, and experiences of previous relevant studies provided the basis for development of a peer-led type 2 diabetes self-management program (Phase Two). Phase Three involved a pre-test, post-test non-equivalent control group design to test the effectiveness of the self-management program on older people with type 2 diabetes in the community. The impact of the program on peer leaders was examined using a one group pre-test, post-test design. In addition, evaluation of the program from peer leaders’ and older people’s perceptions was conducted through a post-test questionnaire. Older people with type 2 diabetes and health professionals expressed broadly the same concerns, which were: social support; confidence to practice self-management behaviours; self-management behaviours; barriers to self-management behaviours; and advice for ongoing health education. However, their points of view were not always identical and different emphases were identified. The peer-led program produced significant improvement in social support, self-efficacy, self-management behaviours and depressive status in the experimental group, as compared to the non-equivalent control group. However, there was no significant effect on quality of life nor health care utilisation. Therefore, the effectiveness of the program among older people with type 2 diabetes was partially confirmed. In addition, the participants were supportive, giving positive feedback about the program. Suggestions for future improvement were provided as well. After receiving specific peer leader training and assisting in most of the delivery process of the program, the peer leaders improved, significantly, in overall self-management behaviours and in specific areas of social support and self-efficacy, though they did not improve in depressive status, quality of life and health care utlisation. In addition, these peer leaders enjoyed being peer leaders, and gave very positive feedback about the whole program. In conclusion, this study has implications for understanding and facilitating self-management behaviours for older people with type 2 diabetes in China. The peer-led self-management program was effective in improving levels of self-efficacy, social support, self-management behaviours and depressive status among older people with type 2 diabetes living in the community in China. The delivery process involving peer leaders was deemed feasible to implement within the health care system in China. The program is suitable to be used by community health professionals in their practice in China. The study also has potential wider benefit to nursing practice and global health practice.

Beta-cell failure is a key step in the progression from metabolic disorder to overt type 2 diabetes (T2D). This failure is characterised by both secretory defects and loss of beta-cell mass, the latter most likely through increases in the rate of apoptosis. Although the mechanisms underlying these beta-cell defects are unclear, evidence suggests that chronic exposure of beta-cells to elevated fatty acid (FA) plays a role in disease development in genetically susceptible individuals. Furthermore, it has been postulated that endoplasmic reticulum (ER) stress signalling pathways (the unfolded protein response; UPR) play a role in FA-induced beta-cell dysfunction. The broad aim of this thesis was to explore the nature of these relationships. Experiments detailed in this thesis demonstrate that MIN6 beta-cells mount a comprehensive ER stress response with exposure to elevated saturated fatty acid palmitate, but not the unsaturated fatty acid, oleate, within the low elevated physiological range. This response was time-dependent and involved both transcriptional and translational changes in UPR transducers and targets. The differential activation of ER stress in MIN6 beta-cells by saturated, but not unsaturated FA species may represent a mechanism of differential beta-cell death described in many studies with these FA. Furthermore, these experiments describe defects in ER to Golgi trafficking with chronic palmitate treatment, but not oleate or thapsigagin treatment, identifying this as a potential mechanism by which palmitate treatment induces ER stress. Moreover, these studies have shown the relevance to ER stress to a whole body model of T2D by demonstrating UPR activation in the islets of the db/db mouse. In conclusion, studies detailed in this thesis have demonstrated that ER stress occurs in in vitro and in vivo models of beta-cell lipotoxicity and apoptosis. In addition, these studies have identified defects in ER to Golgi trafficking as a mechanism by which palmitate treatment induces ER stress. These studies highlight the importance of ER stress in the development of T2D.

Obesity and type 2 diabetes (T2D) are associated with insulin resistance and increased levels of inflammation markers, suggesting activation of the immune system. However, the link between this so called ??low-grade inflammation?? and insulin resistance is poorly understood. In this thesis we aimed to investigate the direct effects of insulin on immune cells, and if these effects are changed in the setting of insulin resistance. We showed that insulin has anti-inflammatory effects by shifting T cell differentiation into a T helper type 2 phenotype. This effect was lost in insulin resistant subjects, which resulted in a more pro-inflammatory T helper type 1 cell hyperpolarisation. We also demonstrated that the Th1/2 balance is related to the degree of insulin resistance, and varies accordingly in clinical models of increasing or decreasing insulin resistance. Furthermore, we demonstrated that in a very early stage of pre-diabetes, where normal glucose tolerance and insulin sensitivity are still preserved, we cannot detect any immune activation, but we see a blunted food response of the appetite suppressant hormone PYY. Whilst this could put subjects at risk for further weight gain and development of obesity and T2D, we also demonstrated for the first time that PYY itself has strong anti-inflammatory properties, and that a deficiency in PYY could result in promoting a pro-inflammatory environment. In summary, we could demonstrate strong evidence that both, insulin and PYY are potent anti-inflammatory hormones which modulate immune function, and the observed deficiency in these hormones could contribute to further increase in inflammation and disease progression. Further work is indicated in this area to better understand the sequence and mechanism of immune activation, which may open up new therapeutic avenues for prevention and treatment of T2D.

Adult Oral Health Programme: The Effect of Periodontal Treatment and the Use of a Triclosan Containing Toothpaste on Glycaemic Control in Diabetics Abstract Aim: The aim of the research study is to establish an adult oral health programme for diabetics in Majuro, Republic of the Marshall Islands in order to determine the impact of non-surgical periodontal treatment followed by the use of a triclosan containing dentifrice on the maintenance of periodontal health and glycaemic control in type 2 diabetic patients. Hypothesis: Non-surgical periodontal treatment results in improved periodontal health and better glycaemic control in diabetics and use of a triclosan containing toothpaste is effective in maintaining this improvement in diabetics. Methods: An adult oral health programme was created, within which was conducted a two-group randomised clinical trial to address the hypothesis that non-surgical periodontal treatment results in improved periodontal health and better glycaemic control in type 2 diabetics and that the use of a triclosan containing toothpaste is effective in maintaining this improvement in diabetics. In this double blind controlled trial, sixty adult patients (aged 35 to 65 years) with type 2 diabetes mellitus having a minimum of 16 teeth received non-surgical periodontal treatment. Half of the patients were randomly assigned to use a triclosan containing toothpaste, Colgate Total, and the other group a non-triclosan toothpaste, Colgate Fluoriguard. The study evaluated the improvement in periodontal health by recording Probing Pocket Depth (PPD) on 6 sites of each tooth, and the number of sites bleeding on probing (BOP) at baseline, and at 6 months and 12 months after treatment. The second part of the study evaluated the impact of improvement of periodontal health on glycaemic control in type 2 diabetics by measuring HbA1c and RBS, and also assessing the levels of C-Peptides and CRP at baseline, and at 6 months and 12 months after treatment. The study also evaluated the effectiveness of a triclosan containing toothpaste in maintaining the improvement in periodontal health after non-surgical periodontal treatment. Results: The results showed that it was feasible to establish an oral health programme for the diabetics and could improve their periodontal health, and that toothpaste containing triclosan is effective in maintaining the improved periodontal heath in type 2 diabetics. Mean PPD dropped from 2.35mm to 1.95mm in the triclosan group and from 2.49mm to 2.24 mm in the non-triclosan group and the mean number of BOP sites dropped from 4.9 to 2.8 in the triclosan group and from 4.7 to 3.2 in the fluoriguard at 12 month visits. However, the results did not show improvement of HbA1c nor RBS levels in either group. C-Peptide levels increased and C-Reactive Protein levels decreased in both groups, however, not to significant levels at 12 month visits. Conclusion: The results of this research study lead to the conclusion that treating periodontal infection has effect of periodontal health of type 2 diabetic patients and following-up with simple personal oral hygiene of regular tooth-brushing helps maintain their periodontal health. This programme also proved that this type of oral health programme is feasible and valuable for diabetics in isolated places like the Marshall Islands, where infrastructure, personnel and resources are limited to treat microvascular and macrovascular complications of diabetes. As for the effectiveness of treating periodontal infections on glycaemic control of diabetics, this study failed to support the hypothesis that non-surgical treatment plus triclosan containing toothpaste would lead to better glycaemic management through improved periodontal health.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 1995. / Vita. Includes bibliographical references (leaves [188]-209).

Includes bibliographical references and index.