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- Zethelius, Björn, 1962-
(författare)
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Proinsulin and Insulin Sensitivity as Predictors of Type 2 Diabetes Mellitus and Coronary Heart Disease : Clinical Epidemiological Studies with up to 27 Years of Follow-Up
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Defects in insulin secretion and insulin action are the major abnormalities in the development of Type 2 diabetes. Hyperinsulinemia is a risk marker for Type 2 diabetes and according to some, but not in all studies also for coronary heart disease (CHD). Conventional insulin assays measure immunoreactive insulin including proinsulin-like molecules. Proinsulin and insulin measured by specific methods, insulin sensitivity measured by the euglycemic insulin clamp and early insulin response after a glucose challenge give more detailed information and may be better estimates of true risk for Type 2 diabetes and CHD. This study examined relationships between proinsulin, insulin, insulin secretion and insulin sensitivity for the development of Type 2 diabetes and CHD. The investigation of the prognostic significance of proinsulin and insulin for the development of Type 2 diabetes and CHD was performed in prospective studies of 50-year and 70-year-old men in a population-based cohort. The results indicated, that increased proinsulin concentrations, was a marker of increased risk for Type 2 diabetes independent of measurements of insulin secretion and insulin sensitivity whereas insulin was not. Proinsulin was shown to be a predictor for CHD mortality and morbidity, respectively, independent of conventional risk factors, whereas insulin was not. Insulin sensitivity measured by the gold standard euglycemic insulin clamp at age 70 was a predictor of CHD morbidity, independently of established risk factors.In summary, these data provide evidence that an increased concentration of proinsulin and not an elevated plasma insulin level per se, that constitutes the association with Type 2 diabetes and CHD and that insulin resistance per se, is associated with CHD risk.
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| 2. |
- Ärnlöv, Johan, 1970-
(författare)
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Left Ventricular Function in Elderly Men : Metabolic, Hormonal, Genetic and Prognostic Implications
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Heart failure and left ventricular dysfunction are major causes of morbidity and mortality. In this thesis, metabolic, hormonal, genetic and prognostic aspects of echocardiographically determined left ventricular function were investigated in a fairly large longitudinal population-based study of men. The participants were examined both at age 50 and 70 years and were followed for mortality using the national cause-of-death registry.Several factors associated with the insulin resistance syndrome predicted left ventricular systolic dysfunction independent of myocardial infarction, hypertension, diabetes and the use of cardiovascular medication after twenty years follow-up. Plasma levels of N-terminal atrial natriuretic peptide (N-ANP) were significantly increased in men with left ventricular dysfunction in comparison to healthy men. However, the diagnostic accuracy was poor due to the extensive overlapping between the groups. Relations between a haplotype of the novel hUNC-93B1 gene and the E/A-ratio were found and validated in separate samples of the cohort. Myocardial performance index (a Doppler derived index of combined left ventricular systolic and diastolic function) and left ventricular ejection fraction were found to be predictors for cardiovascular mortality independent of traditional cardiovascular risk factors in a longitudinal analysis with a mean follow-up of seven years.In conclusion, this thesis showed that left ventricular function is influenced by metabolic, hormonal and genetic factors and that echocardiographic measurements of left ventricular function, such as the myocardial performance index, are strong independent risk factors for cardiovascular mortality in elderly men.
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| 6. |
- Risberg, Jarl, et al.
(författare)
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A new tomographic technique for absolute measurements of white and gray matter blood flow
- 2004
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Ingår i: Proceedings of the 8th Nordic Meeting in Neuropsychology, Turku, Finland, August 26–29, 2004, 85.
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Konferensbidrag (refereegranskat)abstract
- Objective. Most methods for measurements of the regional cerebral blood flow are unable to provide absolute blood flow values. Until now interest has been focused on measurement of the gray matter blood flow, while the white matter blood flow has been rather neglected. The aim of the present project was to develop and evaluate an improved method for reliable tomographic measurements of absolute white and gray matter blood flow Method. The new tomographic method (modified Xe-SPECT) is based on an extension of the period of 133Xe inhalation from one to eight minutes followed by 22 instead of four minutes of breathing of ambient air. This gives a markedly enhanced signal from the white matter and better basis for correct quantification of the blood flow. The arrival and clearance of the tracer are recorded by a three head gamma camera system that provides flow maps with a spatial resolution of about one cm. Results The new method has been evaluated in 33 healthy younger and older (around 70 years) subjects as well as in a group of elderly patients with organic dementia. Our preliminary findings indicate that new and clinically valuable information is obtained by the improved Xe-SPECT method.
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| 7. |
- Risberg, Jarl, et al.
(författare)
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A new tomographic technique for absolute measurements of white and gray matter blood flow
- 2003
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Ingår i: Journal of the International Neuropsychological Society. - 1355-6177. ; 9, s. 323-323
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Konferensbidrag (refereegranskat)abstract
- The integrity of the white matter is as important as that of the gray matter and white matter pathology has commonly been reported in elderly subjects and in patients with organic dementia. The aim of the present study is to develop and evaluate an improved method for reliable tomographic measurements of absolute white and gray matter blood flow. The new tomographic method (modified Xe-SPECT) is based on an extension of the period of 133Xe inhalation from one to eight minutes followed by 22 instead of four minutes of breathing of ambient air. This gives a markedly enhanced signal from the white matter and better basis for correct quantification pf the blood flow. The arrival and clearance of the tracer are recorded by a three head gamma camera system that provides flow maps with a spatial resolution of about one cm. The new method has been evaluated in healthy younger and older (around 70 years) subjects as well as in a group of elderly patients with organic dementia. Our preliminary findings indicate that new and clinically valuable information is obtained by the improved Xe-SPECT method
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| 8. |
- Sjöbeck, Martin, et al.
(författare)
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Alzheimer's disease and the cerebellum: a morphologic study on neuronal and glial changes
- 2001
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:3, s. 211-218
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Tidskriftsartikel (refereegranskat)abstract
- Structural manifestations of Alzheimer's disease (AD) including neuronal loss were investigated in 12 cases of AD and in 10 healthy age-matched controls, with focus on the cerebellum. Linear Purkinje cell (PC) density was measured in the vermis and cerebellar hemispheres. Neurons were also counted in the inferior olivary nucleus. In vermis of the AD cases, the mean PC number was significantly lower (p = 0.019) than in the controls. The neurons in the inferior olive were similarly fewer, though not significantly (p = 0.13). Molecular layer gliosis and atrophy in the vermis was clearly severer in AD than in the controls. Features typical of cerebral Alzheimer encephalopathy (plaques, tangles and microvacuolization) were inconspicious. The structural cerebellar changes in the AD cases were thus neuronal loss, atrophy and gliosis, judged to represent the disease process, and with a main involvement in the vermis. This may be reflected in some of the symptoms and signs seen in AD, signs that are generally overlooked or judged to be of noncerebellar origin.
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| 9. |
- McCaddon, Andrew, et al.
(författare)
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Transcobalamin polymorphism and serum holo-transcobalamin in relation to Alzheimer's disease
- 2004
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 17:3, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Isoforms of the vitamin B<sub>12</sub> carrier protein transcobalamin (TC) might influence its cellular availability and contribute to the association between disrupted single-carbon metabolism and Alzheimer’s disease (AD). We therefore investigated the relationships between the TC 776C>G (Pro259Arg) genetic polymorphism, total serum cobalamin and holo-TC levels, and disease onset in 70 patients with clinically diagnosed AD and 74 healthy elderly controls. TC 776C>G polymorphism was also determined for 94 histopathologically confirmed AD patients and 107 controls. Serum holo-TC levels were significantly higher in TC 776C homozygotes (p = 0.04). Kaplan-Meier survival functions differed between homozygous genotypes (Cox’s F-Test F(42, 46) = 2.1; p = 0.008) and between 776C homozygotes and heterozygotes (Cox’s F test F(46, 108) = 1.7; p = 0.02). Proportionately fewer TC 776C homozygotes appear to develop AD at any given age, but this will require confirmation in a longitudinal study.
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| 10. |
- Wallin, Åsa, et al.
(författare)
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Five-year outcome of cholinergic treatment of Alzheimer's disease: Early response predicts prolonged time until nursing home placement, but does not alter life expectancy
- 2004
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 18:2, s. 197-206
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Tidskriftsartikel (refereegranskat)abstract
- Fifty consecutive outpatients with Alzheimer’s disease (AD) received treatment with the cholinesterase inhibitor tacrine in an open longitudinal study. Assessments using Mini-Mental State Examination, Alzheimer’s Disease Assessment Scale – cognitive subscale, and a global rating were made at baseline and at 6, 12, 24, 36, 48 and 60 months. Three outcome groups were characterized: responders, unchanged and deteriorated. Additional outcome measures were time until nursing home placement, and mortality rate. At 6 months –75%, at 12 months –42%, at 24 months –20%, and after that 10% of the patients still on medication had improved or remained stable. The mortality rate did not differ between the outcome groups. Response to tacrine treatment at 6 or 12 months was found to predict a prolonged time until nursing home placement. No predictors for a positive treatment response could be identified at baseline.
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