Elin S. Olafsdottir

Cognitive Impairment: An Increasingly Important Complication of Type 2 Diabetes The Age, Gene/Environment Susceptibility–Reykjavik Study

Persons with type 2 diabetes are at increased risk of cognitive dysfunction. Less is known about which cognitive abilities are affected and how undiagnosed diabetes and impaired fasting glucose relate to cognitive performance. The authors explored this question using data from 1,917 nondemented men and women (average age = 76 years) in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (2002-2006). Glycemic status groups included diagnosed diabetes (self-reported diabetes or diabetic medication use; n = 163 (8.5%)), undiagnosed diabetes (fasting blood glucose >or=7.0 mmol/L without diagnosed diabetes; n = 55 (2.9%)), and impaired fasting glucose (fasting blood glucose 5.6-6.9 mmol/L; n = 744 (38.8%)). Composites of memory, processing speed (PS), and executive function were constructed from a neuropsychological battery. Linear regression was used to investigate cross-sectional differences in cognitive performance between glycemic groups, adjusted for demographic and health factors. Persons with diagnosed diabetes had slower PS than normoglycemics (beta = -0.12; P < 0.05); diabetes duration of >or=15 years was associated with significantly poorer PS and executive function. Undiagnosed diabetics had slower PS (beta = -0.22; P < 0.01) and poorer memory performance (beta = -0.22; P < 0.05). Persons with type 2 diabetes have poorer cognitive performance than normoglycemics, particularly in PS. Those with undiagnosed diabetes have the lowest cognitive performance.

Biennial eye screening in patients with diabetes without retinopathy: 10-year experience

Aims: To evaluate the safety of every-other-year eye screening for patients with diabetes without retinopathy. Methods: Since 1994, patients with diabetes without retinopathy in Iceland have received eye screening every other year. 296 patients with diabetes who had no diabetic retinopathy in 1994/95 were followed with biennial eye examinations until they had developed retinopathy. The 10-year experience of this approach is reviewed. Results: Out of the 296 diabetic individuals, 172 did not develop diabetic retinopathy during the 10-year observation period. 96 patients developed mild non-proliferative retinopathy, six developed clinically significant diabetic macular oedema, 23 developed preproliferative retinopathy, and four developed proliferative diabetic retinopathy during the 10-year observation period. All the patients who developed macular oedema or proliferative retinopathy had already been diagnosed as having mild nonproliferative retinopathy and entered an annual screening protocol before the sight-threatening retinopathy developed. No patient had any undue delay in treatment. Conclusion: Every other year screening for diabetic eye disease seems to be safe and effective in diabetics without retinopathy. Such an approach will reduce the number of screening visits more than 25%. This reduces health costs and strain on resources considerably and relieves the patients with diabetes from unnecessary clinic visits and examinations.

Cyanohydrin glycosides of passifloraceae

Abstract Barterin, a classical cyclopentenoid cyanohydrin glucoside, was shown to be (1S,4S)-1-(β- d -glucopyranosyloxy)-4-hydroxy-2-cyclopentene-1-carbonitrile, being thus identical with tetraphyllin B, contrary to previous statements in the literature. Cyanohydrin glycosides from Adenia dinklagei, A. epigea, A. firingalavensis, A. frutescens, A. hastata, A. letouzeyi, A. spinosa, Passiflora coriacea, P. subpeltata, P. warmingii and Smeathmannia pubescens were isolated and identified. A summary of the present knowledge of distribution of cyanohydrin glycosides in Passifloraceae shows clear differences between the two chief genera, Adenia and Passiflora. Thus, the former genus appears to be dominated by β- d -glucopyranosides of 2-cyclopenten-1-one and 4-hydroxy-2-cyclopenten-1-one cyanohydrin; the glycosides generally occur as pairs having enantiomeric aglycones and the cyclopentene ring is usually trans-1,4-dioxygenated. By contrast, the pattern of cyanohydrin glycosides of Passiflora appears to be highly diversified, comprising valine or isoleucine-derived glycosides as well as cyclopentenoid glycosides, including more elaborate forms than those found in Adenia. The origin of epilotaustralin, possibly arising from the (3R)-epimer of l -isoleucine, is briefly discussed.

Glycemic Status and Brain Injury in Older Individuals The Age Gene/Environment Susceptibility–Reykjavik Study

OBJECTIVE To examine the association of glycemic status to magnetic resonance imaging indicators of brain pathological changes. RESEARCH DESIGN AND METHODS This was a cross-sectional, population-based study of 4,415 men and women without dementia (mean age 76 years) participating in the Age Gene/Environment Susceptibility–Reykjavik Study. Glycemic status groups included the following: type 2 diabetes (self-report of diabetes, use of diabetes medications, or fasting blood glucose ≥7.0 mmol/l [11.1%]); impaired fasting glucose (IFG) (fasting blood glucose 5.6–6.9 mmol/l [36.2%]); and normoglycemic (52.7%). Outcomes were total brain volume, white and gray matter volume, white matter lesion (WML) volume, and presence of cerebral infarcts. RESULTS After adjustment for demographic and cardiovascular risk factors, participants with type 2 diabetes had significantly lower total brain volume (72.2 vs. 71.5%; P < 0.001) and lower gray and white matter volumes (45.1 vs. 44.9%, P < 0.01 and 25.7 vs. 25.3%, P < 0.001, respectively) and were more likely to have single (odds ratio 1.45 [95% CI 1.14–1.85]) or multiple (2.27 [1.60–3.23]) cerebral infarcts compared with normoglycemic participants. Longer duration of type 2 diabetes was associated with lower total brain volume and gray and white matter volume, higher WML volume (all Ptrend < 0.05), and a greater likelihood of single and multiple cerebral infarcts (all Ptrend < 0.01). CONCLUSIONS Type 2 diabetic participants have more pronounced brain atrophy and are more likely to have cerebral infarcts. Duration of type 2 diabetes is associated with brain changes, suggesting that type 2 diabetes has a cumulative effect on the brain.

Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre.

The aim of this study was to investigate structures and acetylcholinesterase inhibitory activities of lycopodane-type alkaloids isolated from an Icelandic collection of Lycopodium annotinum ssp. alpestre. Ten alkaloids were isolated, including annotinine, annotine, lycodoline, lycoposerramine M, anhydrolycodoline, gnidioidine, lycofoline, lannotinidine D, and acrifoline, as well as a previously unknown N-oxide of annotine. 1H and 13C NMR data of several of the alkaloids were provided for the first time. Solvent-dependent equilibrium constants between ketone and hemiketal form of acrifoline were determined. Conformation of acrifoline was characterized using NOESY spectroscopy and molecular modelling. The isolated alkaloids were evaluated for their in vitro inhibitory activity against acetylcholinesterase and butyrylcholinesterase. Ligand docking studies based on mutated 3D structure of Torpedo californica acetylcholinesterase provided rationale for low inhibitory activity of the isolated alkaloids as compared to huperzine A or B, which are potent acetylcholinesterase inhibitors belonging to the lycodine class. Based on the modelling studies the lycopodane-type alkaloids seem to fit well into the active site gorge of the enzyme but the position of their functional groups is not compatible with establishing strong hydrogen bonding interactions with the amino acid residues that line the binding site. The docking studies indicate possibilities of additional functionalization of the lycopodane skeleton to render potentially more active analogues.

Immunologically active (1→3)-(1→4)-α-D-Glucan from Cetraria islandica

Summary A polysaccharide, Ci-3, resembling isolichenan except with a much higher degree of polymerization, has been isolated from the water extract, as well as from the alkali extract, of the lichen Cetraria islandica (L.) using ethanol fractionation, dialysis, ion-exchange chromatography and gel filtration. The mean Mr of Ci-3 was determined to be 2000 kD, compared to 6–8 kD reported for isolichenan. The structure of Ci-3 was elucidated and found to be composed of (1→3)- and (l→4)-α-D-glucopyranosyl units in the ratio of 2:1, using methanolysis, methylation analysis, optical rotation and NMR spectroscopy. The immunomodulating activity of Ci-3 was tested in an in vitro phagocytosis assay and anti-complementary, and proved to be active in both tests.

In vitro and in vivo immunomodulating effects of traditionally prepared extract and purified compounds from Cetraria islandica.

Cetraria islandica (Iceland moss) has been used for centuries in folk medicine in many countries against a number of conditions, including inflammatory conditions, mainly as an aqueous extract. C. islandica contains many compounds, such as polysaccharides and secondary metabolites, some of which have established biological activity. However, very little is known about their effect on the immune system. Human monocyte-derived immature dendritic cells were cultured with an aqueous extract from C. islandica quantified with regard to the polysaccharides lichenan and isolichenan and secondary metabolites protolichesterinic and fumarprotocetraric acids. The purified compounds were also tested individually. Their effect on the maturation of the dendritic cells was assessed by measuring secretion of IL-10 and IL-12p40 and expression of surface molecules. In addition, the effect of the aqueous extract on antigen-induced arthritis in rats was investigated. The aqueous extract caused upregulated secretion of both IL-10 and IL-12p40, with IL-10 secretion being more prominent. Lichenan had similar effects, whereas isolichenan and the secondary metabolites were inactive, suggesting that the effect observed by the aqueous extract was mainly mediated by lichenan. Significantly less arthritis was observed for rats treated by the aqueous extract, administered subcutaneously, compared with rats treated with saline alone. These results suggest that the aqueous extract of C. islandica has anti-inflammatory effect, possibly by changing the cytokine secretion bias from IL-12p40 towards IL-10.

Immunologically active O6-branched (1»3)-β-glucan from the lichen Thamnolia vermicularis var. subuliformis

A lentinan-type gel-forming beta-glucan, Ths-2, has been isolated in about 1.5% yield from the alkali extract of the lichen Thamnolia vermicularis var. subuliformis, using ethanol fractionation, dialysis and gel filtration. The mean Mr of Ths-2 was determined by GP-HPLC to be 67 kD, and the optical rotation was measured to be -14 degrees. The structure of Ths-2 was further elucidated by methylation analysis by GC-MS, 1H- and 13C-NMR spectroscopy and selective enzymatic hydrolysis with exo-(1 --> 3)-beta-D-glucanase followed by analysis of oligosaccharides by HPAEC-PAD. Ths-2 was found to be consisting of a (1 --> 3)-beta-D-glucopyranosyl main chain with branches of a (1 --> 6) linked glucopyranosyl unit on every third unit of the main chain. Similar polysaccharide structures have been described from fungi, but this is the first report of a lentinan-type (1 --> 3)-beta-D-glucan from a lichen species. The immunomodulating activity of Ths-2 was tested in an in vitro anti-complementary assay, and proved to be strongly active.

Effects of statin medication on mortality risk associated with type 2 diabetes in older persons: the population-based AGES-Reykjavik Study

Objective To examine if the beneficial effect of statin medication on mortality seen in randomised clinical trials of type 2 diabetes applies equally to observational studies in the general population of older people. Design A prospective, population-based cohort study. Setting Reykjavik, Iceland. Participants 5152 men and women from the Age, Gene/Environment Susceptibility-Reykjavik Study, mean age 77 years, range of 66–96 years. Main outcome measure Cardiovascular and all-cause mortalities and the RR of dying according to statin use and history of coronary heart disease (CHD) in persons with type 2 diabetes and those without diabetes with a median follow-up time of 5.3 years, until end of 2009. Results The prevalence of type 2 diabetes was 12.4% of which 35% used statins. Statin use was associated with a 50% (95% CI 8% to 72%) lower cardiovascular mortality and 53% (29% to 68%) lower all-cause mortalities in persons with diabetes. For those without diabetes, statin use was associated with a 16% (−24% to 43%) lower cardiovascular and 30% (11% to 46%) lower all-cause mortalities. Persons with diabetes using statins had a comparable risk of cardiovascular and all-cause mortality to that of the general population without diabetes. The effect was independent of the level of glycaemic control. Conclusion This observational study lends important support to existing data from randomised clinical trials. These data suggest that in the general population of older people with diabetes, statin medication markedly reduces the excess cardiovascular and all-cause mortality risk, irrespective of the presence or absence of coronary heart disease or glucose-lowering medication.

Chromatography and electrophoresis in separation and characterization of polysaccharides from lichens

1. Introduction 1632. Isolation and purification 1642.1. Ion-exchange chromatography 1642.2. Gel permeation chromatography (GPC) 1643. Determination of homogeneity and M