Haptoglobin genotype and its relation to asymptomatic cerebral small-vessel disease in type 1 diabetes.

AIM: Cerebral small-vessel disease (SVD) is prevalent in type 1 diabetes and has been associated with the haptoglobin variant allele Hp1. Contrarily, the Hp2-allele has been linked to cardiovascular disease and the role of haptoglobin-genotype in asymptomatic SVD is unknown. We, therefore, aimed to evaluate the alleles' association with SVD. METHODS: This cross-sectional study included 179 neurologically asymptomatic adults with type 1 diabetes (women 53%, mean age 39 ± 7 years, diabetes duration 23 ± 10 years, HbA1c 8.1 ± 3.2% [65 ± 12 mmol/mol]). Examinations included genotyping (genotypes Hp1-1, Hp2-1, Hp2-2) by polymerase chain reaction, clinical investigation, and magnetic resonance brain images assessed for SVD manifestations (white matter hyperintensities, cerebral microbleeds, and lacunar infarcts). RESULTS: SVD prevalence was 34.6%. Haptoglobin genotype frequencies were 15.6% (Hp1-1), 43.6% (Hp1-2), and 40.8% (Hp2-2). Only diastolic blood pressure differed between the genotypes Hp1-1, Hp1-2, and Hp2-2 (81 [74-83], 75 [70-80], and 75 [72-81] mmHg, p = 0.019). Haptoglobin genotype frequencies by presence versus absence of SVD were 16.1%; 46.8%; 37.1% versus 15.4%; 41.9%; 42.7% (p = 0.758). Minor allele frequencies were 39.5% versus 36.3% (p = 0.553). Hp1 homozygotes and Hp2 carriers displayed equal proportions of SVD (35.7% vs 34.4%, p > 0.999) and SVD manifestations (white matter hyperintensities 14.3% vs 17.9%, p = 0.790; microbleeds 25.0% vs 21.9%, p = 0.904; lacunar infarcts 0% vs 3.6%, p > 0.999). Hp1-1 was not associated with SVD (OR 1.19, 95% CI 0.46-2.94, p = 0.712) when adjusting for age, blood pressure, and diabetic retinopathy. CONCLUSIONS: Although the SVD prevalence was high, we detected no significant association between SVD and haptoglobin-genotype.

Urinary clusterin and cystatin B as biomarkers of tubular injury in dogs following envenomation by the European adder.

Diagnosing acute kidney injury remains a challenge since the established renal biomarkers, serum creatinine (sCr) and symmetric dimethylarginine (SDMA) reflect glomerular function and not tubular injury. Sensitive tubular markers such as urinary clusterin (uClust) and cystatin B (uCysB) have been proposed to detect AKI at an earlier stage. Since envenomation by the European adder (Vipera berus berus) could serve as a spontaneous disease model of AKI we investigated these new biomarkers in affected dogs. Concentrations of uClust and uCysB as well as sCr and SDMA were analyzed retrospectively in stored samples from 26 dogs with snake envenomation and 13 healthy controls. Higher concentrations of uClust (P < 0.012) and uCysB (P < 0.001) were observed in the snake-envenomed group. Normalization of uClust and uCysB to urinary creatinine did not alter the results. No differences were observed in sCr and SDMA between the snake-envenomed group and the healthy control group. Spearman rank correlation analysis revealed a strong association of uClust with uCysB in the snake-envenomed dogs (r = 0.75 P < 0.001) but not in the healthy controls. The high percentage of snake-envenomed dogs with increased uClust and uCysB concentrations in the absence of increased sCr and SDMA suggests renal tubular injury in the affected dogs. Larger prospective case-controlled studies are warranted to evaluate the clinical utility and prognostic value of these biomarkers.

Association between diet and measures of arterial stiffness in type 1 diabetes - Focus on dietary patterns and macronutrient substitutions.

BACKGROUND AND AIMS: Increased arterial stiffness contributes to diabetic vascular complications. We identified dietary factors related to arterial stiffness in individuals with type 1 diabetes, a population with high risk of cardiovascular disease. METHODS AND RESULTS: Altogether, 612 participants (40% men, mean ± standard deviation age 45 ± 13 years) completed a validated diet questionnaire and underwent measurements of arterial stiffness. Of these, 470 additionally completed a food record. Exploratory factor analysis was applied to identify dietary patterns from the diet questionnaires, and nutrient intakes were calculated from food record entries. Arterial stiffness was measured by applanation tonometry. Of the seven dietary factors formed, the factor scores of "Full-fat cheese and eggs" and "Sweet" patterns were negatively associated with measures of arterial stiffness. In the multivariable macronutrient substitution models, favouring carbohydrates over fats was associated with higher aortic mean arterial pressure and aortic pulse wave velocity. When carbohydrates were consumed in place of proteins, higher aortic pulse pressure, aortic mean arterial pressure, and augmentation index were recorded. Replacing energy from alcohol with proteins, was associated with lower aortic pulse pressure, aortic mean arterial pressure, and augmentation index. Relative distributions of dietary fatty acids were neutral with respect to the measures of arterial stiffness. CONCLUSION: The macronutrient distribution of the diet is likely to affect the resilience of the arteries. Our observations suggest that reducing energy intake from carbohydrates and alcohol may be beneficial. These observations, especially those dealing with dietary patterns, need to be confirmed in a longitudinal study.

Diabetes and intracerebral hemorrhage: baseline characteristics and mortality.

BACKGROUND AND PURPOSE: Acknowledging the conflicting evidence for diabetes as a predictor of short- and long-term mortality following an intracerebral hemorrhage (ICH), we compared baseline characteristics and 30-day and long-term mortality between patients with and without diabetes after an ICH, paying special attention to differences between type 1 (T1D) and type 2 (T2D) diabetes. METHODS: Patients with a first-ever ICH were followed for a median of 2.3 years. Adjusting for demographics, comorbidities and documented ICH characteristics increasing mortality after ICH, logistic regression analysis assessed factors associated with case fatality and 1-year survival among the 30-day survivors. Diabetes was compared with patients without diabetes in separate models as (i) any diabetes and (ii) T1D or T2D. RESULTS: Of our 969 patients, 813 (83.9%) had no diabetes, 41 (4.2%) had T1D and 115 (11.9%) had T2D. Compared with patients without diabetes, those with diabetes were younger, more often men and more frequently had hypertension, coronary heart disease and chronic kidney disease, with similar ICH characteristics. Patients with T1D were younger, more often had chronic kidney disease and brainstem ICH, and less often had atrial fibrillation and lobar ICH, than did patients with T2D. Diabetes had no impact on case fatality. Any diabetes (odds ratio, 2.57; 1.19-5.52), T1D (odds ratio, 7.04; 1.14-43.48) and T2D (odds ratio, 2.32; 1.04-5.17) were independently associated with 1-year mortality. CONCLUSIONS: Patients with ICH with diabetes exhibited a distinct pattern of comorbidities and disease characteristics with specific differences between T1D and T2D. Despite their younger age, T1D seems to carry a substantially higher likelihood of long-term mortality after an ICH than does T2D.

Intestinal alkaline phosphatase at the crossroad of intestinal health and disease - a putative role in type 1 diabetes.

BACKGROUND: Patients with type 1 diabetes have shown an increase in circulating cytokines, altered lipoprotein metabolism and signs of vascular dysfunction in response to high-fat meals. Intestinal alkaline phosphatase (IAP) regulates lipid transport and inflammatory responses in the gastrointestinal tract. We therefore hypothesized that changes in IAP activity could have profound effects on gut metabolic homeostasis in patients with type 1 diabetes. METHODS: Faecal samples of 41 nondiabetic controls and 46 patients with type 1 diabetes were analysed for IAP activity, calprotectin, immunoglobulins and short-chain fatty acids (SCFAs). The impact of oral IAP supplementation on intestinal immunoglobulin levels was evaluated in C57BL/6 mice exposed to high-fat diet for 11 weeks. RESULTS: Patients with type 1 diabetes exhibited signs of intestinal inflammation. Compared to controls, patients with diabetes had higher faecal calprotectin levels, lower faecal IAP activities accompanied by lower propionate and butyrate concentrations. Moreover, the amount of faecal IgA and the level of antibodies binding to oxidized LDL were decreased in patients with type 1 diabetes. In mice, oral IAP supplementation increased intestinal IgA levels markedly. CONCLUSION: Deprivation of protective intestinal factors may increase the risk of inflammation in the gut - a phenomenon that seems to be present already in patients with uncomplicated type 1 diabetes. Low levels of intestinal IgA and antibodies to oxidized lipid epitopes may predispose such patients to inflammation-driven complications such as cardiovascular disease and diabetic nephropathy. Importantly, oral IAP supplementation could have beneficial therapeutic effects on gut metabolic homeostasis, possibly through stimulation of intestinal IgA secretion.

Potentiality of the "Gum Metal" titanium-based alloy for biomedical applications.

In this study, the "Gum Metal" titanium-based alloy (Ti-23Nb-0.7Ta-2Zr-1.2O) was synthesized by melting and then characterized in order to evaluate its potential for biomedical applications. Thus, the mechanical properties, the corrosion resistance in simulated body fluid and the in vitro cell response were investigated. It was shown that this alloy presents a very high strength, a low Young's modulus and a high recoverable strain by comparison with the titanium alloys currently used in medicine. On the other hand, all electrochemical and corrosion parameters exhibited more favorable values showing a nobler behavior and negligible toxicity in comparison with the commercially pure Ti taken as reference. Furthermore, the biocompatibility tests showed that this alloy induced an excellent response of MC3T3-E1 pre-osteoblasts in terms of attachment, spreading, viability, proliferation and differentiation. Consequently, the "Gum Metal" titanium-based alloy processes useful characteristics for the manufacturing of highly biocompatible medical devices.

Design of a nitrogen-implanted titanium-based superelastic alloy with optimized properties for biomedical applications.

In this study, a superelastic Ni-free Ti-based biomedical alloy was treated in surface by the implantation of nitrogen ions for the first time. The N-implanted surface was characterized by X-ray diffraction, X-ray photoelectron spectroscopy, and secondary ion mass spectroscopy, and the superficial mechanical properties were evaluated by nano-indentation and by ball-on-disk tribological tests. To investigate the biocompatibility, the corrosion resistance of the N-implanted Ti alloy was evaluated in simulated body fluids (SBF) complemented by in-vitro cytocompatibility tests on human fetal osteoblasts. After implantation, surface analysis methods revealed the formation of a titanium-based nitride on the substrate surface. Consequently, an increase in superficial hardness and a significant reduction of friction coefficient were observed compared to the non-implanted sample. Also, a better corrosion resistance and a significant decrease in ion release rates have been obtained. Cell culture experiments indicated that the cytocompatibility of the N-implanted Ti alloy was superior to that of the corresponding non-treated sample. Thus, this new functional N-implanted titanium-based superelastic alloy presents the optimized properties that are required for various medical devices: superelasticity, high superficial mechanical properties, high corrosion resistance and excellent cytocompatibility.

Associations and interactions between lipid profiles, retinopathy and nephropathy in patients with type 1 diabetes: the FinnDiane Study.

OBJECTIVES: The aim of this study was to investigate the associations between lipid profiles and retinopathy in the large nationwide FinnDiane Study and to examine interactions and correlations between retinopathy, nephropathy and lipid variables. DESIGN AND SUBJECTS: A total of 1465 patients with type 1 diabetes, available lipid profiles, ophthalmic records and fundus photographs were included in the study. The Early Treatment of Diabetic Retinopathy Study scale was used to assess the severity of retinopathy. In an independent cohort of 1100 patients, laser treatment was used to define severe diabetic retinopathy. RESULTS: HDL cholesterol was associated with proliferative retinopathy (PDR), and triglycerides were associated with mild nonproliferative retinopathy (NPDR) independently of nephropathy and other conventional risk factors (P < 0.01). Significant interactions were seen between albumin excretion rate (AER), retinopathy status and lipid parameters (including triglycerides, non-HDL cholesterol and apolipoprotein B; P < 0.001). Highly different correlations between AER and lipid variables were observed in patients without retinopathy or with mild NPDR compared with patients with moderate to severe NPDR or PDR. Similar interactions and correlations were observed in an independent cohort stratified by laser treatment. In patients without retinopathy or with mild NPDR, AER was low despite HDL cholesterol in the lowest or triglycerides, total cholesterol or LDL cholesterol in the highest quartiles. CONCLUSIONS: Nephropathy had a strong effect on the associations between lipid variables and retinopathy, whilst dyslipidaemia was associated with nephropathy only in the presence of retinopathy. This finding suggests the existence of shared pathogenic mechanisms between retinopathy and nephropathy which could be targeted to prevent complications in patients with metabolic risk factors.

Surface characterization and biocompatibility of titanium alloys implanted with nitrogen by Hardion+ technology.

In this study, the new Hardion+ micro-implanter technology was used to modify surface properties of biomedical pure titanium (CP-Ti) and Ti-6Al-4V ELI alloy by implantation of nitrogen ions. This process is based on the use of an electron cyclotron resonance ion source to produce a multienergetic ion beam from multicharged ions. After implantation, surface analysis methods revealed the formation of titanium nitride (TiN) on the substrate surfaces. An increase in superficial hardness and a significant reduction of friction coefficient were observed for both materials when compared to non-implanted samples. Better corrosion resistance and a significant decrease in ion release rates were observed for N-implanted biomaterials due to the formation of the protective TiN layer on their surfaces. In vitro tests performed on human fetal osteoblasts indicated that the cytocompatibility of N-implanted CP-Ti and Ti-6Al-4V alloy was enhanced in comparison to that of the corresponding non treated samples. Consequently, Hardion+ implantation technique can provide titanium alloys with better qualities in terms of corrosion resistance, cell proliferation, adhesion and viability.

Diabetes mellitus and ischemic stroke in the young: clinical features and long-term prognosis.

OBJECTIVE: To compare risk factors, stroke characteristics, and long-term prognosis between nondiabetic young ischemic stroke patients and similar patients having either type 1 diabetes mellitus (T1D) or type 2 diabetes mellitus (T2D) to provide information for patient management, counseling, and future research in these patient groups. METHODS: Our database comprised 1,008 consecutive patients aged 15 to 49 with first-ever ischemic stroke from 1994 to 2007. Primary outcome measures were 1) nonfatal or fatal recurrent ischemic stroke and 2) composite vascular endpoint (myocardial infarction, any stroke, revascularization, or vascular death). RESULTS: Compared with nondiabetic stroke patients (n = 904), patients with T1D (44) or T2D (60) were more likely to have hypertension and stroke attributable to small-vessel disease (SVD). In addition, when compared with nondiabetic patients, those with T1D more frequently had coronary heart disease and peripheral arterial disease (PAD) and those with T2D more often had obesity, PAD, history of TIA, and stroke attributable to large-artery atherosclerosis, and T2D patients were also more likely to be older and male than were the nondiabetic patients. Mean follow-up in survivors was 9.0 (±3.8) years. Cumulative recurrent ischemic stroke rate at 10 years was 40.9% for T1D (14 events), 29.7% for T2D (15), and 12.0% for nondiabetic patients (94). Corresponding rates for the composite vascular endpoint were 65.1% for T1D (25), 46.9% for T2D (28), and 19.3% for nondiabetic patients (153). CONCLUSIONS: Our findings suggest that ischemic stroke patients with T1D or T2D exhibit a distinct risk-factor and etiologic profile and a worse vascular prognosis than do nondiabetic patients.

Serum adiponectin concentration is a positive predictor of all-cause and cardiovascular mortality in type 1 diabetes.

BACKGROUND: Adiponectin is widely regarded as an anti-atherogenic, antioxidant and anti-inflammatory molecule. However, adiponectin concentration is paradoxically increased in individuals with type 1 diabetes, in whom it is positively associated with adverse clinical outcomes. OBJECTIVE: To explore the association between serum adiponectin concentration and mortality outcomes in adults with type 1 diabetes. DESIGN: Multicentre prospective cohort study. SETTING: Primary and tertiary care. SUBJECTS: Finnish adults with type 1 diabetes (n= 2034). Main outcome measures. All-cause and cardiovascular mortality. Independent predictors of mortality were determined using the Cox and the Fine and Gray competing risks proportional hazards models. RESULTS: During a median of 11 years of follow-up, there were 173 deaths (8.5%, 1.0 per hundred person-years). Adiponectin was linearly associated with all-cause mortality [Cox model: hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.01-1.03, P<0.001] and cardiovascular mortality (Fine and Gray model: HR 1.02, 95% CI 1.00-1.04, P=0.035); patients with the highest adiponectin concentrations had the shortest survival. The mortality risk associated with adiponectin was independent of glycaemic and lipid control, pre-existing cardiovascular disease, markers of inflammation and the presence and severity of kidney disease. CONCLUSIONS: Although adiponectin is generally considered to be a protective molecule, increased concentrations of adiponectin in type 1 diabetes are independently associated with all-cause and cardiovascular mortality. Moreover, the fact that this association was observed for the first time in patients with normal urinary albumin levels, who have few comorbidities, suggests that adiponectin is specifically linked with vascular damage in type 1 diabetes.

Synthesis and characterisation of a new superelastic Ti-25Ta-25Nb biomedical alloy.

In this study, a new Ti-25Ta-25Nb (mass%) beta alloy was synthesised by cold crucible semi-levitation melting. This technique made it possible to obtain homogeneous ingots although the elements used have very different melting points. After melting, a thermo-mechanical treatment was applied in order to obtain a perfectly recrystallised beta microstructure. For this alloy composition, the tensile tests showed a very low Young's modulus associated with an important super-elastic behaviour, which contributes to decrease the elastic modulus under stress and to increase the recoverable strain. On the other hand, the corrosion tests, which were carried out in a neutral Ringer solution, indicated a corrosion resistance higher than that of the commercially pure CP Ti alloy. These results show that this new alloy possesses all the characteristics necessary for its long-term use in medical implants.

Lipid abnormalities predict progression of renal disease in patients with type 1 diabetes.

AIMS/HYPOTHESIS: We studied the impact of baseline lipid variables on the progression of renal disease in a large nationwide prospective cohort of patients with type 1 diabetes. METHODS: A total of 2,304 adult patients with type 1 diabetes and available lipid profiles participating in the Finnish Diabetic Nephropathy Study (FinnDiane) were evaluated. Data on progression of renal disease were verified from medical files and patients were followed for 5.4 +/- 2.0 (mean +/- SD) years. RESULTS: High triacylglycerol, apolipoprotein (Apo) B, ApoA-II and HDL(3)-cholesterol concentrations predicted incident microalbuminuria. Progression to macroalbuminuria was predicted by high triacylglycerol and ApoB. When AER was entered into the model, triacylglycerol was no longer an independent predictor, but when patients with normal AER and microalbuminuria at baseline were pooled, triacylglycerol, HbA(1c), male sex and AER were all independent predictors of renal disease. High total cholesterol, LDL-cholesterol, non-HDL-cholesterol and triacylglycerol as well as low HDL-cholesterol, HDL(2)-cholesterol, ApoA-I and ApoA-II concentrations were predictive of progression to end-stage renal disease. However, when estimated GFR was entered into the model, only total cholesterol remained an independent predictor of progression. CONCLUSIONS/INTERPRETATION: Lipid abnormalities, particularly high triacylglycerol concentrations, increase the risk of progression of renal disease.

Glucose variability, blood pressure and arterial stiffness in type 1 diabetes.

AIMS: Evidence suggests that chronic hyperglycaemia predicts not only microvascular disease but also macrovascular disease, however it is not known whether it is the glucose variability per se or the total glucose exposure that confers risk. The objective of this study was to investigate whether daily glucose variability influence blood pressure and arterial stiffness, an early sign of macrovascular disease, at baseline and during a hyperglycaemic clamp in patients with type 1 diabetes. METHODS: Twenty-two non-smoking male patients with type 1 diabetes without any diabetic complications, participated in the study. The patients were monitored for 72-h using a continuous glucose monitoring system. Before and during a 2-h hyperglycaemic clamp, blood pressure as well as pulse wave analysis and pulse wave velocity (PWV) were performed to assess arterial stiffness. RESULTS: No correlation was observed between mean amplitude of glycaemic excursions (MAGE) and arterial stiffness at baseline. There was a correlation between mean daily glucose and aortic PWV even after adjusting for BMI, HbA(1c), and duration of diabetes in a multiple regression analysis (r=0.48; P<0.01). MAGE (r=0.52; P<0.01) correlated independently with the change in aortic DBP during the clamp. CONCLUSIONS: This study suggests that high mean daily blood glucose but not glucose variability per se is associated with arterial stiffness in patients with T1D. Daily glucose variability is positively associated with the change in central blood pressure during a hyperglycaemic clamp.

Acute hyperglycaemia disturbs cardiac repolarization in Type 1 diabetes.

AIMS: Patients with Type 1 diabetes have an increased risk of cardiovascular mortality. Notably, a prolonged heart rate adjusted QT interval (QTc) is a predictor of sudden cardiovascular death. Therefore, the objectives of this study were to investigate whether acute hyperglycaemia affects the QTc duration and the QTc dispersion in patients with Type 1 diabetes and in healthy volunteers. METHODS: Acute hyperglycaemia (15 mmol/l) for 120 min was induced in 35 males (22 men with Type 1 diabetes and 13 age-matched non-diabetic volunteers). All participants were non-smokers without any diabetic complications. Electrocardiogram recordings were performed at normoglycaemia and at 0, 60 and 120 min of hyperglycaemia. RESULTS: Compared with normoglycaemia, acute hyperglycaemia increased the QTc interval in both patients with Type 1 diabetes (390 +/- 6 vs. 415 +/- 5 ms, P < 0.001) and in healthy volunteers (378 +/- 5 vs. 412 +/- 8 ms, P < 0.01). During hyperglycaemia, the QTc dispersion was prolonged in healthy volunteers (36 +/- 4 ms vs. 54 +/- 7 ms, P < 0.05) but not in patients with Type 1 diabetes (45 +/- 3 ms at baseline vs. 48 +/- 5 ms, NS). CONCLUSIONS: Acute hyperglycaemia alters myocardial ventricular repolarization in patients with Type 1 diabetes and in healthy volunteers and might consequently be an additional risk factor for cardiovascular events.

Microstructure, mechanical properties and cytocompatibility of stable beta Ti-Mo-Ta sintered alloys.

We have synthesized titanium-based alloys containing molybdenum and tantalum elements by powder metallurgy. The microstructure, the residual porosity and the mechanical properties of the sintered Ti-Mo and Ti-Ta-Mo alloys were investigated by using optical and electronic microscopy, X-ray diffraction, microhardness and compression tests. The cytocompatibility of the different alloys was evaluated by the assessment of bone cell density, migration and adhesion after 14 days incubation. All the alloys present a high ductility and an excellent cytocompatibility, which make these materials useful for medical implants.

Acute hyperglycaemia rapidly increases arterial stiffness in young patients with type 1 diabetes.

AIMS/HYPOTHESIS: Augmentation index (AIx) and pulse wave velocity (PWV), both measures of arterial stiffness, constitute risk factors for cardiovascular disease. Notably, hyperglycaemia during an acute cardiovascular event is associated with poor prognosis. The objective of this study was to investigate whether acute hyperglycaemia increases arterial stiffness in patients with type 1 diabetes and in healthy subjects. METHODS: Twenty-two male patients with type 1 diabetes and thirteen healthy men, who were age-matched non-smokers and without any diabetic complications, underwent a 120 min hyperglycaemic clamp (15 mmol/l). AIx was calculated to assess arterial stiffness. Before and during the clamp, carotid-radial (brachial) and carotid-femoral (aortic) PWV was measured. RESULTS: At baseline there was a difference in the AIx between patients with type 1 diabetes and healthy volunteers (-5 +/- 2.7 vs -20 +/- 2.8%, p < 0.05). Acute hyperglycaemia rapidly increased AIx in patients with type 1 diabetes (-5 +/- 2.7 vs 8 +/- 2.5%, p < 0.001) and healthy volunteers (-20 +/- 2.8 vs 6 +/- 8.8%, p < 0.001). Brachial PWV increased during acute hyperglycaemia in patients with type 1 diabetes (7.1 +/- 1.2 vs 8.0 +/- 1.0 m/s, p < 0.001), but not in healthy men (7.4 +/- 1.7 vs 7.3 +/- 1.4 m/s, NS). CONCLUSIONS/INTERPRETATION: Acute hyperglycaemia increases the stiffness of intermediate-sized arteries and resistance arteries in young patients with type 1 diabetes and consequently emphasises the importance of strict daily glycaemic control. No change was observed in aortic PWV during the clamp, indicating that acute hyperglycaemia does not affect the large vessels.

Pre-eclampsia but not pregnancy-induced hypertension is a risk factor for diabetic nephropathy in type 1 diabetic women.

AIMS/HYPOTHESIS: Our aim was to study whether pre-eclampsia and pregnancy-induced hypertension are predictors of diabetic nephropathy in type 1 diabetic women. MATERIALS AND METHODS: A total of 203 type 1 diabetic women, who were pregnant between 1988 and 1996 and followed at the Department of Obstetrics and Gynaecology in Helsinki, were re-assessed after an average of 11 years within the nationwide, multi-centre Finnish Diabetic Nephropathy Study. Diabetic nephropathy was defined as microalbuminuria, macroalbuminuria or end-stage renal disease. RESULTS: Patients with prior pre-eclampsia had diabetic nephropathy more often than patients with a normotensive pregnancy (diabetic nephropathy vs normal albumin excretion rate: 41.9% vs 8.9%; p<0.001), whereas patients with a history of pregnancy-induced hypertension did not (10.3% vs 8.9%; p=0.81). CHD was more prevalent in patients with a history of pre-eclampsia than in patients with a normotensive pregnancy (12.2% vs. 2.2%; p=0.03). Pre-eclampsia (odds ratio [OR] 7.7, 95% CI 1.6-36.1; p=0.01) and HbA(1c) (OR 2.0, 95% CI 1.1-3.8; p<0.05) were associated with incident diabetic nephropathy even when adjusted for follow-up time, BMI, smoking, diabetes duration and age. CONCLUSIONS/INTERPRETATION: These data suggest that a history of pre-eclamptic pregnancy but not pregnancy-induced hypertension is associated with an elevated risk of diabetic nephropathy.

Development of a beta-type Ti-12Mo-5Ta alloy for biomedical applications: cytocompatibility and metallurgical aspects.

Ti-based biocompatible alloys are especially used for replacing failed hard tissue. Some of the most actively investigated materials for medical implants are the beta-Ti alloys, as they have a low elastic modulus (to inhibit bone resorption). They are alloyed with elements such as Nb, Ta, Zr, Mo, and Fe. We have prepared a new beta-Ti alloy that combines Ti with the non-toxic elements Ta and Mo using a vacuum arc-melting furnace and then annealed at 950 degrees C for one hour. The alloy was finally quenched in water at room temperature. The Ti-12Mo-5Ta alloy was characterised by X-ray diffraction, optical microscopy, SEM and EDS and found to have a body-centred-cubic structure (beta-type). It had a lower Young's modulus (about 74 GPa) than the classical alpha/beta Ti-6Al-4V alloy (120 GPa), while its Vickers hardness remained very high (about 303 HV). This makes it a good compromise for a use as a bone substitute. The cytocompatibility of samples of Ti-12Mo-5Ta and Ti-6Al-4V titanium alloys with various surface roughnesses was assessed in vitro using organotypic cultures of bone tissue and quantitative analyses of cell migration, proliferation and adhesion. Mechanically polished surfaces were prepared to produce unorientated residual polished grooves and cells grew to a particularly high density on the smoother Ti-12Mo-5Ta surface tested.

Design of new titanium alloys for orthopaedic applications.

Parallel to the biofunctionalisation of existing materials, innovation in biomaterials engineering has led to the specific design of titanium alloys for medical applications. Studies of the biological behaviour of metallic elements have shown that the composition and structure of the material should be carefully tailored to minimise adverse body reactions and to enhance implant longevity, respectively. Consequently, interest has focused on a new family of titanium alloys: Ti-6Mo-3Fe-5Ta, Ti-4Mo-2Fe-5Ta and Ti-6Mo-3Fe-5Zr-5Hf alloys. The non-toxicity of the specially designed titanium alloys compared with osteoblastic cells has been ascertained using MTT and RN tests. In addition, phase transformations upon thermal processing have been investigated, with comparison with a well-defined beta titanium alloy. Optimum thermal processing windows (above 550 degrees C) have been designed to generate a stable and nanostructured alpha phase from the isothermal omega phase that precipitates in a low temperature range (150-350 degrees C). The generation of such nanostructured microstructures should provide a promising opportunity to investigate tissue-biomaterial interactions at the scale of biomolecules such as proteins.