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- Fhärm, Eva, 1955-
(författare)
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Treatment of cardiovascular risk factors in type 2 diabetes : time trends and clinical practice
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives Patients with type 2 diabetes are at much greater risk of developing cardiovascular diseases (CVD), including coronary heart disease (CHD), compared to non-diabetics. The lowering of glucose, blood pressure, and plasma lipid levels has been shown to reduce CHD risk, and treatment goals for these risk factors are now part of clinical practice guidelines. However, the incidence and outcome of CHD in diabetic patients does not show the same favourable trend as in the general population. Thus, the overall aim of the thesis was to investigate how the treatment goals for CVD risk factors contained in the national guidelines for diabetes care were reflected in clinical practice, and to explore factors that might influence the remaining high incidence of CHD in the type 2 diabetes population. Research designs and results I. The effectiveness of the introduction of treatment goals for dyslipidaemia was evaluated in a retrospective observational population-based cross-sectional study of 971 diabetic patients participating in the Västerbotten Intervention Programme (VIP) 1995–2004. There was a stronger trend of decrease in cholesterol levels among patients with diabetes compared to the non-diabetic population in 2000–2004. Increased use of lipid-lowering agents influenced the trend in diabetic patients, even though only 25.3% received lipid-lowering treatment after the introduction of the new guidelines. II. The experiences of general practitioners relating to treatment practice for type 2 diabetes with specific focus on the prevention of cardiovascular disease were explored in a focus group study. The overall theme was ‘dilemmas’ in GPs’ treatment practice for patients with type 2 diabetes. Five main dilemma categories were identified. First, GPs were hesitant about labelling a person who feels healthy as ill. Second, as regards communicating a diabetes diagnosis and its consequences, GPs were unsure as to whether patients should be frightened or comforted. Third, GPs experienced uncertainty in their role: should they take responsibility for the care or not? Fourth, GPs expressed concern over a conflict between lifestyle changes and drug treatment. Fifth, the GPs described difficulties when attempting to translate science into reality. III. Screening for microvascular and coronary heart disease according to national guidelines was evaluated in a cross-sectional study of 201 screening-detected patients with type 2 diabetes 1.5±0.7 years after diagnosis. A larger proportion of diabetic patients was screened for nephropathy and retinopathy than for CHD. Twenty-three percent of the patients had minor or major ECG abnormalities, but ECG findings seemed to have little or no impact on CHD prevention using lipid-lowering medication and ASA. A clinical history of CHD correlated with a larger proportion of patients receiving secondary prevention. IV. Time trends relating to the achievement of treatment goals and 10-year CHD risk at three years of diabetes duration were studied in 19,382 patients with type 2 diabetes without CHD, who were reported by primary health care sources in the National Diabetes Register in 2003–2008. National treatment goals for glycaemia, blood pressure, total cholesterol, and LDL cholesterol were achieved in 78.4%, 65.5%, 55.6%, and 61.0%, respectively, of the diabetic patients in 2008 following a trend of improved results in 2003–2008. Absolute 10-year risk of CHD increased between year of diagnosis and follow up in a studied subgroup while modifiable risk decreased. Conclusions The introduction of treatment goals for dyslipidemia in Swedish national guidelines in 1999 were reflected in lowered cholesterol levels in people with type 2 diabetes. Since the introduction of the guidelines, an increasing number of diabetic patients are treated in accordance with guidelines. A remaining microvascular focus on the patients together with the revealed dilemmas within the GP’s consultation with diabetic patients might negatively influence the remaining high incidence of CHD in the type 2 diabetes population. Lipid levels, blood pressure and smoking are targets for further improvements.
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| 2. |
- Husdal, Rebecka
(författare)
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Key Features for Successful Swedish Primary Diabetes Care – Reality or Fiction? : Nationwide studies of longitudinal follow-up, HbA1c levels and all-cause mortality in an organizational context
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims To extend knowledge about the changes in Swedish primary diabetes care from 2006 to 2013 and investigate associations of personnel resources, organizational features and quality-of-work conditions of primary health-care centres (PHCCs) with individual HbA1c levels and all-cause mortality in people with type 2 diabetes mellitus (T2DM).Methods Information about organizational features, personnel resources and quality-of-work conditions were collected from responses of PHCC managers to the Swedish National Survey of the Quality and Organisation of Diabetes Care in Primary HealthCare (Swed-QOP) questionnaire. The longitudinal cross-sectional study included 74.3% and 76.4% of PHCCs in 2006 and 2013, respectively. Individual clinical data for 230,958 people with T2DM obtained from the Swedish National Diabetes Register were linked to the data from the Swed-QOP questionnaire. Individual data were linked to socio-economic and comorbidity data. All-cause mortality was followed up for a median of 4.2 years for 187,570 people with T2DM.Results The longitudinal follow-up study showed a decreased median PHCC list size but an increased median number of people with T2DM. The mean European Credit Transfer and Accumulation System (ECTS) credits in diabetes-specific education for registered nurses (RNs) increased. The number of PHCCs providing group education programs and involving the patient in goal setting remained low (I). PHCCs having diabetes teams and group education programs were associated with decreased HbA1c levels. Using call-recall system to general practitioners (GPs) was associated with increased HbA1c levels (II). Seven quality-of-work features were identified, of which Individualized treatment was associated with decreased HbA1c levels in people with controlled (≤ 52 mmol/mol), intermediate (53–69 mmol/mol) and uncontrolled (≥ 70 mmol/mol) HbA1c (III). GP staffing was associated with a decreased risk of early death and the mean ECTS credits in diabetes-specific and pedagogical education of RNs was associated with a decreased risk of early death in people aged ≥ 55 years and in men, respectively (IV).Conclusion This thesis adds to previous work on significant but less pronounced key features for successful organization of primary diabetes care, and indicates that the complexity of diabetes disease makes it difficult to identify success factors applicable to all people living with T2DM.
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| 3. |
- Lilja, Mikael
(författare)
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Trends in obesity and type 2 diabetes : ethnic aspects and links to adipokines
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 4. |
- Pourhamidi, Kaveh, 1985-
(författare)
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Peripheral nerve function : metabolic features, clinical assessment, and heat shock protein 27
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peripheral neuropathy is a common complication among patients with diabetes mellitus, but whether peripheral neuropathy is present in individuals with impaired glucose tolerance (IGT) is debatable. In order to identify and diagnose peripheral neuropathy correctly, it is important to evaluate diagnostic tools that can be implemented in routine health care to assess both large and small nerve fibre function. There is currently limited knowledge about neuroprotective factors that could be useful for measuring peripheral nerve function in individuals at risk of developing neuropathy such as those with diabetes mellitus. Thus, studies are needed to investigate potential neuroprotective factors in relation to peripheral nerve function in humans.Objectives: The overall goal of this thesis was to study the metabolic features and clinical assessment of peripheral nerve function and the potential relationship between the neuroprotective factor heat shock protein 27 (HSP27) and peripheral nerve function.Methods: Thirty-nine participants with normal glucose tolerance (NGT) and 29 participants with IGT were recruited from the population-based Västerbotten Intervention Programme in 2003–2004. Patients with type 2 diabetes mellitus (T2DM, n = 51) were recruited from primary health care centres. NGT and IGT individuals underwent two separate oral glucose tolerance tests to verify their glucose status. The peripheral nerve function in the lower limb was assessed by nerve conduction studies, neuropathy disability scoring, quantitative sensory tests, and skin biopsies with subsequent quantification of intraepidermal nerve fibre density (IENFD). The concentrations of HSP27 in serum were determined in the NGT, IGT, and T2DM individuals. Patients with type 1 diabetes mellitus (T1DM) were recruited from the Diabetes Clinic, Skåne University Hospital in Malmö, Sweden (n = 27) in 1992 and were followed-up in 2005. Baseline and follow-up concentrations of HSP27 were determined in T1DM patients as well as in healthy non-diabetic controls (n = 397). The T1DM patients underwent nerve conduction studies and thermal and vibration perception threshold tests at baseline and at follow-up. Delta changes in HSP27 concentrations and small and large nerve fibre function were calculated.Results: There was no difference between IGT and NGT in sural nerve conduction, intraepidermal nerve fibre density, or thermal thresholds. The biothesiometer had a sensitivity of 82% and a specificity of 72% in identifying peripheral neuropathy with a cut-off value of ≥24.5 V at the medial malleolus. Adding the quantification of IENFD to the combination of the tuning fork and biothesiometer increased the diagnostic sensitivity from 81% to 95%, the negative predictive value from 87% to 94%, and the positive likelihood ratio from 1.8 to 1.9 when identifying small nerve fibre dysfunction. T2DM patients had lower HSP27 concentrations (mean HSP27 = 412 pg/mL, 95% CI 284–598 pg/mL) than NGT (mean HSP27 = 722 pg/mL, 95% CI 564–922 pg/mL) and IGT (mean HSP27 = 1010 pg/mL, 95% CI 638–1300 pg/mL) individuals (p <0.05 for both comparisons). T1DM patients had lower HSP27 concentrations at baseline (mean HSP27 = 547 pg/mL, 95% CI 421–711 pg/mL) and at follow-up (mean HSP27 = 538 pg/mL, 95% CI 417–693 pg/mL) compared to healthy controls (mean HSP27 = 785 pg/mL, 95% CI 732–842 pg/mL), p <0.05 for both comparisons). High concentrations of HSP27 were associated with better large nerve fibre function (Odds ratio = 2.51, 95% CI 1.25–5.05, p <0.05). Deteriorating large nerve fibre function correlated with decreasing HSP27 concentrations over time in T1DM patients (r = 0.50, p = 0.01).Conclusions: Measures of large and small nerve fibre function in IGT individuals do not differ significantly from NGT individuals. The existence of peripheral neuropathy as a consequence of IGT is not likely, and extensive control of neuropathy in IGT individuals is not advocated by this thesis. The biothesiometer is a useful clinical tool to identify peripheral neuropathy in routine health care. Quantification of IENFD using skin biopsies in combination with methods measuring vibrotactile sense, such as the biothesiometer and the tuning fork, increase the diagnostic usefulness of identifying small nerve fibre dysfunction. High HSP27 concentrations are associated with better peripheral large nerve fibre function. Patients with diabetes mellitus have lower HSP27 concentrations than healthy non-diabetic controls, and deterioration of large nerve fibre function correlates with a decrease in HSP27 concentrations over time in T1DM. This could be indicative of insufficient neuroprotection in patients with diabetes mellitus.
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