"I have got diabetes!" - interviews of patients newly diagnosed with type 2 diabetes.

BACKGROUND: To be diagnosed with type 2 diabetes is a challenge for every patient. There are previous studies on patients' experience in general but not addressing the increased cardiovascular risk and multifactorial treatment. The aim of this study was to explore the thoughts, experiences and reactions of newly diagnosed patients with diabetes to this diagnosis and to the risk of developing complications. METHODS: Ten adults (7 men/3 women, aged 50-79) diagnosed with type 2 diabetes within the last 12 months were interviewed at a primary health care center in Sweden. An interview guide was used in the semi-structured interviews that were transcribed verbatim. The analysis was qualitative and inspired by systematic text condensation (Malterud). The text was read several times and meaning units were identified. Related meaning units were sorted into codes and related codes into categories during several meetings between the authors. Finally, the categories were merged and formed themes. RESULTS: We defined three main themes: Reaction to diagnosis, Life changes and Concerns about the future. Most patients reacted to the diagnosis without intensive feelings. Lifestyle changes were mainly accepted but hard to achieve. The patients' major concerns for the future were the consequences for daily life (being able to drive and read) and concerns for relatives rather than anxieties regarding medical issues such as laboratory tests. There were considerable differences in how much patients wanted to know about their future risks. CONCLUSIONS: The results of this study might help to focus doctor-patient communication on issues highlighted by the patients and on the importance of individualizing information and recommendations for each patient.

Association between copeptin and declining glomerular filtration rate in people with newly diagnosed diabetes. The Skaraborg Diabetes Register.

AIMS: Copeptin has shown association with development of chronic kidney disease (CKD) in people with diabetes. Early detection of individuals having the highest risk could help avoid this complication. Therefore we decided to study copeptin concentrations and estimated glomerular filtration rate (eGFR) retrospectively in people with newly diagnosed diabetes. METHODS: People with newly diagnosed type 2 diabetes in 1996-1998 from Skaraborg Diabetes Register (SDR) were reinvestigated in 2008-2010. Copeptin concentration at the time of diagnosis was determined. Creatinine and cystatin C were used for determination of eGFR at baseline and at reinvestigation (n=161). Data on cardiovascular complications were extracted from national registers. Analyzes were done with logistic regression. RESULTS: From baseline to follow up eGFR decreased with 33ml. Twenty-nine individuals (18.1%) developed CKD stage 3. There was a significant association between elevated copeptin concentrations and development of CKD stage 3 (OR=1.78, 95% CI=1.01-3.16). When adjusting for GFR at baseline the association between copeptin and GFR decline was borderline significant (OR=1.79, 95% CI=0.99-3.25, p=0.055). CONCLUSIONS: Determination of copeptin may early identify people with diabetes and high risk for CKD. To prevent complications for these individuals aggressive treatment should be discussed.

C-peptide concentration, mortality and vascular complications in people with Type 2 diabetes. The Skaraborg Diabetes Register.

AIM: To study the prognosis of patients with newly diagnosed Type 2 diabetes in primary care in relation to their baseline C-peptide concentration. METHODS: C-peptide concentrations were determined in 399 patients aged < 65 years with newly diagnosed Type 2 diabetes using the Skaraborg Diabetes Register, Sweden. Data on cardiovascular complications and death were extracted from national registers and a local study of retinopathy. Statistical analyses were performed using Cox regression. RESULTS: An analysis of C-peptide concentrations in quartiles, after adjusting for confounders, showed that patients in the highest quartile had a 2.75-fold higher risk of death from all causes compared with those in the lowest quartile (CI 1.17-6.47). By contrast, C-peptide concentration was not associated with the incidence of cardiovascular events or the development of retinopathy. CONCLUSIONS: Measurement of C-peptide concentration at diagnosis could help identify patients who are at high risk and who presumably would benefit from more intensive treatment.

Antihypertensive treatment and control according to gender, education, country of birth and psychiatric disorder: the Swedish Primary Care Cardiovascular Database (SPCCD).

The reasons why women and men are treated with different antihypertensive drugs are not clear. Whether socioeconomic factors influence prescription patterns and blood pressure control differently in women and men has not been investigated. This cross-sectional study performed in a cohort of hypertensive patients from the Swedish Primary Care Cardiovascular Database (SPCCD) examined the influence of educational level, country of birth, gender and concomitant psychiatric disorder on prescription pattern and blood pressure control in 40,825 hypertensive patients. Men were more often than women treated with calcium channel blocker and angiotensin-converting enzyme inhibitor (ACEI), irrespective of education, country of birth and psychiatric disorder. Educational level influenced the prescription pattern to some extent, where the gender differences were reduced in patients with a higher educational level. In women, but not in men, high educational level and concomitant psychiatric disorder were associated with a higher proportion reaching target blood pressure. The predominant use of ACEI and calcium channel blockers in men is not influenced by educational level, country of birth or psychiatric disorder. Thus other explanations must be considered such as gender differences in side effects. Educational level seems to have a greater impact on reaching target blood pressure in women compared with men.

Does it look like melanoma? A pilot study of the effect of sunless tanning on dermoscopy of pigmented skin lesions.

BACKGROUND: Dermoscopy has led to an improvement in diagnosing malignant melanoma (MM). Sunless tanning agents containing dihydroxyacetone (DHA) could lead to a decrease in ultraviolet exposure, decreasing the risk of MM. Importantly, DHA has been reported to change dermoscopic features and could thus endanger diagnostic improvement in dermoscopy. OBJECTIVES: To investigate whether the use of DHA can lead to changes that simulate a real, clinically relevant dermoscopic change, suggesting malignant transformation either in facial solar lentigo/initial seborrhoeic keratosis (SL/ISK) or in naevi on the body. METHODS: Seven patients with 25 pigmented skin lesions (PSLs) were photographed, resulting in 38 dermoscopic images. Photographs were taken before, 1 week after and 1-2 months after the use of DHA. Two dermatologists separately evaluated the PSLs and their dermoscopic features. For lesions on the body Menzies' method was used, and for facial lesions the criteria defined by Stolz et al. were used. RESULTS: In facial PSLs equivocal lesions were registered by both evaluators significantly more often after DHA use than before (42% vs. 12%, P=0·021 and 69% vs. 19%, P=0·001). Furthermore, follicular pigmentation that partly mimics that of lentigo maligna was also seen significantly more often after DHA use than before (81% vs. 12%, P<0·001 and 69% vs. 15%, P<0·001) and in these instances the evaluators recommended a biopsy. Equivocal lesions in naevi on the body were not significantly increased after DHA use. CONCLUSIONS: Dermoscopists that come across unclear dermoscopic findings, especially in facial PSL, should ask patients about the use of DHA.

Group treatment of obesity in primary care practice: a qualitative study of patients' perspectives.

AIMS: To explore patients' experiences of very low calorie diet (VLCD) and subsequent corset treatment of obesity in a primary care setting, and to explore their perceptions of factors influencing weight control. METHODS: In western Sweden, five focus group sessions were carried out. The main themes for the discussions were the informants' perceptions of the treatment they had received and their experiences of living with obesity. The analysis was based on the Grounded Theory methodology. RESULTS: The outcomes reflect obese individuals' struggle to handle the demands of their life situation and to recognize their own resources. The core category generated was labelled ''Achieving a balance in life and adjusting one's identity''. Three categories related to the process of weight reduction were identified: living with obesity, reducing weight and developing self-management. The group treatment with VLCD was positively perceived by the participants, but the corset treatment was considered to be of less value. CONCLUSIONS: Maintenance after weight reduction was demanding and the findings indicate a need for extended support. For some individuals the corset treatment could be a psychological support. Follow-up after weight reduction programmes should focus on long-term self-help strategies.

Global patterns of diversity and community structure in marine bacterioplankton.

Because of their small size, great abundance and easy dispersal, it is often assumed that marine planktonic microorganisms have a ubiquitous distribution that prevents any structured assembly into local communities. To challenge this view, marine bacterioplankton communities from coastal waters at nine locations distributed world-wide were examined through the use of comprehensive clone libraries of 16S ribosomal RNA genes, used as operational taxonomic units (OTU). Our survey and analyses show that there were marked differences in the composition and richness of OTUs between locations. Remarkably, the global marine bacterioplankton community showed a high degree of endemism, and conversely included few cosmopolitan OTUs. Our data were consistent with a latitudinal gradient of OTU richness. We observed a positive relationship between the relative OTU abundances and their range of occupation, i.e. cosmopolitans had the largest population sizes. Although OTU richness differed among locations, the distributions of the major taxonomic groups represented in the communities were analogous, and all local communities were similarly structured and dominated by a few OTUs showing variable taxonomic affiliations. The observed patterns of OTU richness indicate that similar evolutionary and ecological processes structured the communities. We conclude that marine bacterioplankton share many of the biogeographical and macroecological features of macroscopic organisms. The general processes behind those patterns are likely to be comparable across taxa and major global biomes.

Hypertension prevalence in obstructive sleep apnoea and sex: a population-based case-control study.

Obstructive sleep apnoea (OSA) is a recognised risk factor for hypertension (HT). The current authors investigated confounders of this association in a sex-balanced community-based sample of patients with HT (n=161) from the Skaraborg Hypertension and Diabetes Project (n=1,149) and normotensive controls (n=183) from an age and sex stratified community-based population sample (n=1,109). All participants underwent ambulatory home polysomnography. Severe OSA (apnoea-plus-hypopnoea index (AHI)>or=30 events.h-1) was found in 47 and 25% of hypertensive and normotensive males, respectively. The corresponding numbers in females were 26 and 24%, respectively. The odds ratio (OR) for HT increased across AHI tertiles from 1.0 to 2.1 (95% confidence interval: 0.9-4.5) and 1.0 to 3.7 (95% CI: 1.7-8.2) in males, but not in females where the OR increased from 1.0 to 1.8 (95% CI: 0.8-3.9) and 1.0 to 1.6 (95% CI: 0.7-3.5). Regression analysis correcting for age, body mass index (or waist-hip ratio) and smoking did not eliminate the association between OSA and HT in males. The present data suggest that obstructive sleep apnoea is highly prevalent in both the general population and in patients with known hypertension. The contribution of obstructive sleep apnoea to hypertension risk may be sex dependent and higher in males than in females.

Placental calcification: a metastatic process?

Placental calcification commonly increases with gestational age. The mechanism of apatite mineralization probably involves one of three known mechanisms of tissue calcification: physiological (like bone), dystrophic (ischaemia-related) or metastatic (mineralization in a supersaturated environment). This study was designed to determine the mechanism of calcification by examining (1) the mineral content of placental calcifications in comparison to other physiological and pathological apatites, and (2) the expression of bone morphogenetic proteins (BMPs), which are important in physiological calcification, across gestational age. By energy-dispersive x-ray analysis (EDXA), the Ca/P weight ratio for apatitic mineral from mature calcifications was 2.00+/-0.05 (s.e.), which is similar to that for stones formed in a metastatic, supersaturated environment and lower than that observed in physiological calcification. Biologically active BMP, which was determined by bioassay, was demonstrated in mature and postmature placentae. The BMPs PLAB, PDF and related protein INSL-4 were identified by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), but their mRNA expression was independent of gestational age (7-41 weeks of gestation). We conclude that (1) the identified BMPs were not related directly to placental calcification, which argues against physiological calcification, and (2) the chemical composition of the apatitic mineral was suggestive of rapid formation in a supersaturated environment, which is consistent with a metastatic mechanism of calcification.

Insights into the mechanism of vascular calcification.

Vascular calcification is common and clinically significant in atherosclerosis and heart failure. It was long believed to be an end-stage process of "passive" mineral precipitation. However, there is now a growing awareness that vascular calcification is a biologically regulated phenomenon. It has many similarities to bone formation, and ectopic bone is a well-documented part of vascular calcification. This implies that alterations in vascular cell differentiation, extensive or localized, are an integral part of vascular calcification. Matrix gamma-carboxylated glutamate (GLA) protein (MGP)-deficient mice develop extensive vascular calcification with replacement of the media by progressively calcifying cartilage. A potential mechanism that explains these findings is MGP interference with bone morphogenetic proteins-potent inducers of cartilage and bone.

Matrix GLA protein modulates differentiation induced by bone morphogenetic protein-2 in C3H10T1/2 cells.

Matrix GLA protein (MGP) is ubiquitously expressed with high accumulation in bone and cartilage, where it was found to associate with bone morphogenetic proteins (BMP) during protein purification. To test whether MGP affects BMP-induced differentiation, three sets of experiments were performed. First, pluripotent C3H10T1/2 cells transfected with human MPG (hMGP) or antisense to hMGP (AS-hMGP) were treated with BMP-2. In cells overexpressing hMGP, osteogenic and chondrogenic differentiation was inhibited indicating decreased BMP-2 activity. Conversely, in cells overexpressing AS-hMGP, BMP-2 activity was enhanced. Second, cells were prepared from homozygous and heterozygous MPG-deficient mice aortas. When treated with BMP-2, these cells underwent chondrogenic and osteogenic differentiation, respectively, whereas controls did not. Third, FLAG-tagged hMGP with the same biological effect as native hMGP inhibited BMP-induced differentiation, when exogenously added to culture media. Together, these results suggest that MGP modulates BMP activity. To test whether hMGP fragments would retain the effect of full-length hMGP, three subdomains were overexpressed in C3H10T1/2 cells. In cells expressing the mid-region, alone (amino acids (aa) 35-54) or in combination with the N terminus (aa 1-54) but not the C terminus (aa 35-84), osteogenic differentiation was enhanced and occurred even without added BMP-2. Thus, two subdomains had the opposite effect of full-length hMGP, possibly due to different expression levels or domain characteristics.

HOXB7 overexpression promotes differentiation of C3H10T1/2 cells to smooth muscle cells.

The presence of immature smooth muscle cells and ectopic tissues such as fully-formed bone in atherosclerotic lesions, may result from recapitulation of embryonic mechanisms in the artery wall. We hypothesized that expression of homeobox genes is triggered in atherogenesis and that these regulate proliferation and differentiation of multipotential progenitor cells along one or more specific lineages. We identified expression of the homeobox gene HOXB7 in clones of bovine aortic medial cells previously shown to be multipotent. HOXB7 was subsequently detected in human atherosclerotic plaques by RT-PCR and in situ hybridization. Expression was localized to areas adjacent to calcification and scattered in media and neointima, which may be reflective of a role in either osteoblastic or smooth muscle cell differentiation. To differentiate between these possibilities, we overexpressed HOXB7 in C3H10T1/2 cells, a multipotent cell line able to differentiate into vascular smooth muscle cells (SMC), as well as osteogenic and chondrogenic lineages. Results showed that overexpression of HOXB7 increased proliferation 3.5-fold, and induced an SMC-like cell morphology. In addition, expression of the early SMC markers calponin and SM22alpha increased 4-fold and 3-fold respectively by semi-quantitative RT-PCR. Expression of the intermediate SMC marker smooth muscle myosin heavy chain (SM-MHC) did not change. No increase in osteogenic or chondrogenic differentiation was detected, neither in the C3H10T1/2 cells nor in M2 cells, a bone marrow stromal cell line used to confirm this result. These findings suggest that HOXB7 plays a role in expansion of immature cell populations or dedifferentiation of mature cells.

Cell differentiation in vascular calcification.

Ectopic tissue formation is commonly found in calcified atherosclerotic plaques. This suggests that cell differentiation plays an important role in vascular calcification, even though the origin of the cells involved is unclear. Calcifying vascular cells (CVCs), derived from bovine aortic media, have been used as an in vitro model for vascular calcification. CVCs have many characteristics in common with bone cells, but there are also differences suggesting mechanisms that may be applicable to the problem of osteoporosis in the setting of vascular calcification. Matrix GLA protein (MGP) deficient mice develop severe vascular calcification and die prematurely from heart failure and/or aortic rupture. The molecular mechanism of MGP is unknown. It has been hypothesized that MGP acts as a calcification inhibitor by binding calcium, preventing mineral deposition in extracellular fluids near the saturation point for calcium and phosphate. Alternatively, MGP expression may be an attempt to regulate cell differentiation in the vascular wall, possibly by acting as an inhibitor to a factor able to induce cartilage and bone such as bone morphogenetic proteins (BMPs).

Regulatory mechanisms in vascular calcification.

Vascular calcification is increasingly recognized as a significant contributor to cardiovascular morbidity and mortality as well as a biologically regulated process potentially subject to prevention and reversal. Both coronary and aortic calcification are common and influence plaque rupture, angioplasty and surgical complications, and compensatory enlargement. Aortic calcification increases aortic rigidity and contributes to cadiac ischemia, left ventricular hypertrophy, heart failure, and stroke. Calcification is also common in aortic valve leaflets further compounding adverse hemodynamic effects. Vascular calcification has often been attributed to "passive" crystallization. However, functional similarities between atherosclerotic lesions and bone contradict this view and indicate that it is no more "passive" than in embryonic bone formation or bone repair. Similarities include presence of all the major components of bone osteoid, bone regulatory factors, and subpopulations of artery wall cells that retain osteoblastic lineage potential. Several animal models for vascular calcification are available. Spontaneous vascular calcification occurs in null mice for matrix GLA protein (MGP), a small matrix protein of unknown function, and osteoprotegerin (OPG), known to modulate osteoclast differentiation. Vascular calcification may also be induced by feeding vitamin D and calcium or warfarin to normal animals, or by fat-feeding mice null for apoE or the LDL-receptor. Overall, regulation of vascular calcification is a growing field with surprising mechanisms and connections to other fields of biology.

Neuronal survival using a resorbable synthetic conduit as an alternative to primary nerve repair.

Clinically optimal situations for primary nerve repair are rarely observed. Crushed nerve ends result in either suboptimal repair or a need for nerve grafting. Functional results after nerve surgery are relatively poor, including major sensory deficits, which may be due to the death of primary sensory neurons that follows the nerve injury. The aim of this study was to determine if using polyhydroxybutyrate (PHB), a resorbable nerve conduit, could be an alternative to primary nerve repair in reducing loss of neurons. The superficial radial nerves in 20 cats were sectioned bilaterally and primarily repaired microsurgically by the use of two different strategies; either wrapping the nerve ends in sheets of PHB or epineurally suturing of the nerve. After 6 or 12 months, the surviving neurons within the dorsal root ganglia [C5-T1] were counted. No statistically significant differences were found between the two methods. This may imply a future possibility of using PHB as a synthetic nerve graft in situations where suboptimal primary repair or nerve grafts are the alternatives.

A new resorbable wrap-around implant as an alternative nerve repair technique.

Poly-3-hydroxybutyrate (PHB), a bacterial storage product, is available as bioabsorbable sheets and has been used in this study for primary nerve repair. The aim was to assess axonal regeneration following such repair and determine the inflammatory response to PHB. In 20 adult cats, the transected superficial radial nerve was wrapped in PHB sheets, while primary epineural repair was carried out in the contralateral limb. At 6 and 12 months, the repair sites were assessed immunohistochemically for macrophage infiltration and myelinated axons were counted in the distal nerve. Mean macrophage counts across the whole width of the nerve in both groups at 6 and 12 months showed no statistically significant difference. Nor was there any significant difference between the two groups at both time-points in axon counts, axon diameter, myelin thickness and g-ratio. There was a statistically significant increase in fibre diameters at 12 months, indicating that fibres were undergoing continuous maturation.

Expression of the GM1-species, [NeuN]-GM1, in a case of human glioma.

Altered glycosylation is a common feature in tumors of various kind and particular interest has been focused on the expression of tumor-associated gangliosides. We have previously identified some human glioma-associated gangliosides and in this study yet another, not previously described, ganglioside has been isolated. The ganglioside was prepared from human glioma tissue taken at autopsy. The new ganglioside bound cholera-toxin B-subunit and its structure was confirmed by fast atom bombardment-mass spectrometry to be NeuN-GM1 (II3NeuNH2-GgOse4Cer). In the dissected tumor specimen, the concentration of NeuN-GM1 was 0.1 micromol/g wet weight and accounted for approximately 20% of the monosialoganglioside fraction. Normal human brain tissue specimens (n = 10) did not contain detectable (>0.5 nmol/g wet weight of tissue) amounts of NeuN-GM1, indicating that this ganglioside might be associated with human glioma. However, none of the 17 other tumour specimens reveal any detectable amounts of this ganglioside. In conclusion, NeuN GM1 is a glioma-associated ganglioside but its exceptional expression limits its relevance as a molecule involved in general tumor biology.

cAMP stimulates osteoblast-like differentiation of calcifying vascular cells. Potential signaling pathway for vascular calcification.

The role of the cAMP signaling pathway in vascular calcification was investigated using calcifying vascular cells (CVC) derived from primary aortic medial cell cultures. We previously showed that CVC have fibroblastic morphology and express several osteoblastic differentiation markers. After confluency, they aggregate into cellular condensations, which later mature into nodules where mineralization is localized. Here, we investigated the effects of cAMP on CVC differentiation because it plays a role in both osteoblastic differentiation and vascular disease. Dibutyryl-cAMP or forskolin treatment of CVC for 3 days induced osteoblast-like "cuboidal" morphology, inhibited proliferation, and enhanced alkaline phosphatase activity, all early markers of osteoblastic differentiation. Isobutylmethylxanthine and cholera toxin had the same effects. Treatment of CVC with pertussis toxin, however, did not induce the morphological change or increase alkaline phosphatase activity, although it inhibited CVC proliferation to a similar extent. cAMP also increased type I procollagen production and gene expression of matrix gamma-carboxyglutamic acid protein, recently shown to play a role in in vivo vascular calcification. cAMP inhibited the expression of osteopontin but did not affect the expression of osteocalcin and core binding factor. Prolonged cAMP treatment enhanced matrix calcium-mineral incorporation but inhibited the condensations resulting in diffuse mineralization throughout the monolayer of cells. Treatment of CVC with a protein kinase A-specific inhibitor, KT5720, inhibited alkaline phosphatase activity and mineralization during spontaneous CVC differentiation. These results suggest that the cAMP pathway promotes in vitro vascular calcification by enhancing osteoblast-like differentiation of CVC.

Changes in weight and compositions of major membrane components of human brain during the span of adult human life of Swedes.

Brain weight, total solids, protein, and major lipids have been determined in 83 female and 101 male brains from subjects 20-100 years of age. The brain weight began to diminish at 20 years of age. The brain weight at 20 years for females: 1,368 +/- 26 and for males 1,632 +/- 27 g diminished at 100 years for females to 1,100 +/- 25 and for males to 1,266 +/- 25 g, a decrease of 20% for female and 22% for male brains. The decrease in dry solids was larger during the same period, 36% for females and males. Proteins decreased by 39% in females and 37% in males. Phospholipids decreased by 42% in females and 43% in males, cholesterol by 47% and 53%, cerebroside by 46% and 58%, sulfatide by 46% and 49% and gangliosides by 28% and 30%, respectively. There is, thus, a significantly larger loss of myelin lipids than of gangliosides-the biochemical marker for neuronal membranes. The loss of myelin lipids was particularly large in female brain after 70 years of age, while the loss in male brain was linear as early as from 20 years of age.