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2.
Scand J Prim Health Care ; 42(1): 170-177, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38214672

ABSTRACT

OBJECTIVE: Describe a method in a real-world setting to identify persons with undiagnosed prediabetes and type 2 diabetes through an interprofessional collaboration between Public Dental Services and Primary Health Care in Regions Stockholm. DESIGN: A descriptive observational study. SETTING: The study was conducted at seven sites in the region of Stockholm, Sweden. Each collaborating site consisted of a primary health clinic and dental clinic. SUBJECTS: Study participants included adults over 18 years of age who visited the Public Dental Services and did not have a medical history of prediabetes or type 2 diabetes. MAIN OUTCOME MEASURES: Selective screening is conducted in accordance with a risk assessment protocol at the Public Dental Services. In the investigated method, DentDi (Dental and Diabetes), adults diagnosed with caries and/or periodontitis over a cut-off value are referred to the Primary Health Care clinic for screening of prediabetes and type 2 diabetes. RESULTS: DentDi, introduced at seven sites, between the years 2017 and 2020, all of which continue to use the method today. A total of 863 participants from the Public Dental Services were referred to the Primary Health Care. Of those 396 accepted the invitation to undergo screening at the primary health care centre. Twenty-four individuals did not meet the inclusion criteria, resulting in a total of 372 persons being included in the study. Among the 372 participants, 27% (101) had elevated glucose levels, of which 12 were diagnosed with type 2 diabetes and 89 with prediabetes according to the study classification. CONCLUSIONS: DentDi is a feasible method of interprofessional collaboration where each profession contributes with the competence included in everyday clinical practice for early identification of persons with prediabetes and type 2 diabetes with a complete chain of care. The goal is to disseminate this method throughout Stockholm County and even other regions in Sweden.


Type 2 diabetes and poor oral health have a bidirectional association. The number of persons with undetected prediabetes and type 2 diabetes is high and rising globally.Through collaboration between Public Dental Services and Primary Health Care we have developed a feasible and novel method of selectively screening for prediabetes and type 2 diabetes in a real-world setting.By utilizing everyday practice within each discipline, this method has been implemented at seven sites in Region Stockholm.From the original number of 863 participants referred from the Public Dental Services to Primary Health Care 396 attended the medical screening. After excluding 24 participants, a total of 372 participants underwent screening for prediabetes and type 2 diabetes.The results of this study showed that almost 30% who were screened for prediabetes and type 2 diabetes had elevated blood glucose levels.


Subject(s)
Diabetes Mellitus, Type 2 , Prediabetic State , Adult , Humans , Adolescent , Sweden , Mass Screening/methods , Ambulatory Care Facilities , Primary Health Care , Dental Care
3.
Sci Rep ; 14(1): 594, 2024 01 05.
Article in English | MEDLINE | ID: mdl-38182624

ABSTRACT

The present study investigated primary care patients and compared self-reported sexual health in Swedes and Middle Easterners; analysed differences within and between the groups and analysed differences in 25-hydroxyvitamin D [25(OH)D] levels between the groups. 522 patients responded to a health questionnaire that included items on sexual health: 225 Middle Easterners from Iran, Iraq, and Turkey and 297 Swedes. Logistic regression was used to calculate the odds ratio (OR). Middle Easterners reported less sexual dysfunction than Swedes, and 75.8% of them and 18.9% of Swedes presented a 25(OH)D of < 50 nmol/L. The crude OR for reporting sexual dysfunction was 70% higher in Swedes compared to Middle Easterners (OR 1.70, 95% CI 1.15-2.50). This OR remained significant after adjustment for age, gender, waist circumference, and reported sexual desire. However, the significance disappeared after additional adjustment for 25(OH)D. In both groups, more females than males reported insufficient sexual desire. More female Middle Easterners reported sex life dissatisfaction. More female Swedes reported sexual dysfunction. Vitamin D could explain an association between gender and sex life dissatisfaction in Middle Easterners, and age could explain an association between gender and sexual dysfunction in Swedes. Age, waist circumference, and 25(OH)D levels were significant covariates in the logistic regression models. Results from the present study suggest that 25(OH)D variation partly explains differences in sexual dysfunction between the groups and between genders within the groups. Vitamin D therapy should be investigated to determine if these results are clinically useful.


Subject(s)
Sexual Dysfunction, Physiological , Vitamin D , Vitamins , Female , Humans , Male , Primary Health Care , Sweden , Vitamin D/blood , Middle Eastern People , Sexual Dysfunction, Physiological/epidemiology
4.
J Diabetes Metab Disord ; : 1-7, 2023 May 22.
Article in English | MEDLINE | ID: mdl-37363201

ABSTRACT

Purpose: To determine fasting plasma glucose and serum 25-hydroxyvitamin D (s-25(OH)D) levels and associations between abnormal fasting plasma glucose levels and inadequate s-25(OH)D levels in individuals of Middle Eastern and Swedish descent. Methods: Observational study with individuals without a diabetes diagnosis, 54.5% of Swedish descent and 45.5% of Middle Eastern descent. In total, 830 participants from two primary healthcare centres in Flemingsberg and Jakobsberg, which are southern and northern suburbs, respectively, of Stockholm, Sweden were included in the study. Results: Prevalence of inadequate s-25(OH)D levels (at or below 50 nmol/L) was 67.2% among those of Middle Eastern descent and 20.5% among those of Swedish descent (P < 0.001). S-25(OH)D levels correlated weakly positively with fasting plasma glucose levels (ρ = 0.20, P = 0.002) in individuals of Middle Eastern descent. Being of Middle Eastern descent (OR 6.7, 95% CI 4.3-10.4) and having abnormal fasting plasma glucose (OR 1.8, 95% CI 1.2-2.9) were independent predictors of having inadequate s-25(OH)D levels. Conclusions: Healthcare in Sweden should consider testing fasting plasma glucose and s-25(OH)D levels, particularly in individuals of Middle Eastern descent. The unclear relationship between vitamin D and glucose levels warrants investigation. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01226-0.

5.
BMC Public Health ; 23(1): 543, 2023 03 22.
Article in English | MEDLINE | ID: mdl-36949436

ABSTRACT

BACKGROUND: The prevalence of cardiovascular disease around the world varies by ethnicity and region of birth. Immigrants living in Sweden may have a higher prevalence of cardiovascular diseases than native-born Swedes, but little is known about their actual cardiovascular risk. This study aimed to examine the relationship in Sweden between 10-year cardiovascular risk and birthplace. METHOD: This cross-sectional study was based on cardiovascular risk factor data obtained from the 4D Diabetes Project, a Programme 4D subproject in Sweden. Participants were recruited from two primary healthcare centres in Stockholm without a history of diabetes or pre-diabetes. The outcome variable was 10-year cardiovascular risk based on the calculation of a Framingham Risk Score with six risk factors: age, sex, LDL, HDL, BP, diabetes and smoking for each participant. Multiple linear regression was performed to generate ß-coefficients for the outcome. RESULTS: There was an average of 8.86% cardiovascular risk over 10 years in Sweden-born participants and a 5.45% 10-year risk in foreign-born, (P < 0.0001). Foreign-born participants were about 10 years younger (mean age 46 years vs. 56 years, P < 0.001), with a significantly higher proportion of smokers (23.9% vs. 13.7%; P = 0.001). To be born in Sweden (with parents born in Sweden) was significantly associated with a 10-year cardiovascular risk in the crude model (ß- coefficient = 3.40, 95% CI 2.59-4.22; P < 0.0001) and when adjusted for education and alcohol consumption (ß- coefficient = 2.70 95% CI 1.86-3.54; P < 0.0001). Regardless of the birthplace, 10-year cardiovascular risk was lower for those with higher education compared to those with less than 10 years of education. CONCLUSION: This study found a relationship between 10-year calculated cardiovascular risk and place of birth. Sweden-born participants had a higher association with 10-year cardiovascular risk than foreign-born participants. These results contradict previous reports of higher rates of CVD in residents of Middle-Eastern countries and Middle-Eastern immigrants living in Sweden.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus , Emigrants and Immigrants , Female , Humans , Middle Aged , Sweden/epidemiology , Risk Factors , Cardiovascular Diseases/epidemiology , Cross-Sectional Studies , Heart Disease Risk Factors , Primary Health Care
6.
Eur Clin Respir J ; 10(1): 2181291, 2023.
Article in English | MEDLINE | ID: mdl-36861117

ABSTRACT

Purpose: Co-morbidities are common in chronic obstructive pulmonary disease (COPD) and are associated with increased morbidity and mortality. The aim of the present study was to explore the prevalence of several comorbid conditions in severe COPD, and to investigate and compare their associations with long-term mortality. Methods: In May 2011 to March 2012, 241 patients with COPD stage 3 or 4 were included in the study. Information was collected on sex, age, smoking history, weight and height, current pharmacological treatment, number of exacerbations the recent year and comorbid conditions. At December 31st, 2019, mortality data (all-cause and cause specific) were collected from the National Cause of Death Register. Data were analyzed using Cox-regression analysis with gender, age, previously established predictors of mortality and comorbid conditions as independent variables, and all-cause mortality and cardiac and respiratory mortality, respectively, as dependent variables. Results: Out of 241 patients, 155 (64%) were deceased at the end of the study period; 103 patients (66%) died of respiratory disease and 25 (16%) of cardiovascular disease. Impaired kidney function was the only comorbid condition independently associated with increased all-cause mortality (HR (95% CI) 3.41 (1.47-7.93) p=0.004) and respiratory mortality (HR (95%CI) 4.63 (1.61 to 13.4), p = 0.005). In addition, age ≥70, BMI <22 and lower FEV1 expressed as %predicted were significantly associated with increased all-cause and respiratory mortality. Conclusion: In addition to the risk factors high age, low BMI and poor lung function; impaired kidney function appears to be an important risk factor for mortality in the long term, which should be taken into account in the medical care of patients with severe COPD.

8.
J Dent ; : 104382, 2022 Nov 26.
Article in English | MEDLINE | ID: mdl-36574596

ABSTRACT

OBJECTIVE: The aim of the present study was to evaluate, after 5 years, the efficacy of proximal microinvasive sealing of permanent teeth on the risk for caries lesion development. METHODS: Children aged 8 to 10 y at baseline, at high caries risk, were studied. In the preventive (P) group the children had caries lesions on the distal surface of primary second molars (05d) but sound mesial surfaces of the approximating permanent first molars (6m). In the therapeutic (T) group the children had initial caries lesions on 6m that abutted lesions on 05d. Each child in the two groups had one 05d/6m pair. Using a split-mouth design, one 6m surface in each pair was randomly assigned to receive sealing while the other pair served as an unsealed control. RESULTS: Of the 61 children at baseline 42 could be blindly examined clinically and radiographically both at baseline and after 5 years. In the P group, 8 of 28 (28.6%) sealed and 15 of 28 (53.6 %) unsealed sound 6m surfaces had developed caries lesions (p = 0.04). In the T group, the progression of the carious lesions on 6m was observed in 4 of 14 sealed (28.6%) and 8 of 14 (57.1%) unsealed caries control surfaces (p = 0.29). Pooling the data from the two groups, the difference between sealed and non-sealed surfaces was significant (p = 0.013). CONCLUSION: Both preventive and therapeutic sealant to 6m adjacent to a lesion on 05d has effectiveness in caries reduction in high caries risk children CLINICAL SIGNIFICANCE: The beneficial effect of sealing is observed for at least 5 years after a single sealant treatment.

9.
BMC Med ; 20(1): 356, 2022 10 18.
Article in English | MEDLINE | ID: mdl-36253773

ABSTRACT

BACKGROUND: The prevention of type 2 diabetes is challenging due to the variable effects of risk factors at an individual level. Data-driven methods could be useful to detect more homogeneous groups based on risk factor variability. The aim of this study was to derive characteristic phenotypes using cluster analysis of common risk factors and to assess their utility to stratify the risk of type 2 diabetes. METHODS: Data on 7317 diabetes-free adults from Sweden were used in the main analysis and on 2332 diabetes-free adults from Mexico for external validation. Clusters were based on sex, family history of diabetes, educational attainment, fasting blood glucose and insulin levels, estimated insulin resistance and ß-cell function, systolic and diastolic blood pressure, and BMI. The risk of type 2 diabetes was assessed using Cox proportional hazards models. The predictive accuracy and long-term stability of the clusters were then compared to different definitions of prediabetes. RESULTS: Six risk phenotypes were identified independently in both cohorts: very low-risk (VLR), low-risk low ß-cell function (LRLB), low-risk high ß-cell function (LRHB), high-risk high blood pressure (HRHBP), high-risk ß-cell failure (HRBF), and high-risk insulin-resistant (HRIR). Compared to the LRHB cluster, the VLR and LRLB clusters showed a lower risk, while the HRHBP, HRBF, and HRIR clusters showed a higher risk of developing type 2 diabetes. The high-risk clusters, as a group, had a better predictive accuracy than prediabetes and adequate stability after 20 years. CONCLUSIONS: Phenotypes derived using cluster analysis were useful in stratifying the risk of type 2 diabetes among diabetes-free adults in two independent cohorts. These results could be used to develop more precise public health interventions.


Subject(s)
Diabetes Mellitus, Type 2 , Prediabetic State , Blood Glucose , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Humans , Insulin , Risk Assessment , Risk Factors
10.
Article in English | MEDLINE | ID: mdl-36162865

ABSTRACT

INTRODUCTION: Type 2 diabetes (T2D) and its complications are increasing rapidly. Support for healthy lifestyle and self-management is paramount, but not adequately implemented in health systems. Process evaluations facilitate understanding why and how interventions work through analyzing the interaction between intervention theory, implementation and context. The Self-Management and Reciprocal Learning for Type 2 Diabetes project implemented and evaluated community-based interventions (peer support program; care companion; and link between facility care and community support) for persons at high risk of or having T2D in a rural community in Uganda, an urban township in South Africa, and socioeconomically disadvantaged urban communities in Sweden. RESEARCH DESIGN AND METHODS: This paper reports implementation process outcomes across the three sites, guided by the Medical Research Council framework for complex intervention process evaluations. Data were collected through observations of peer support group meetings using a structured guide, and semistructured interviews with project managers, implementers, and participants. RESULTS: The countries aligned implementation in accordance with the feasibility and relevance in the local context. In Uganda and Sweden, the implementation focused on peer support; in South Africa, it focused on the care companion part. The community-facility link received the least attention. Continuous capacity building received a lot of attention, but intervention reach, dose delivered, and fidelity varied substantially. Intervention-related and context-related barriers affected participation. CONCLUSIONS: Identification of the key uncertainties and conditions facilitates focus and efficient use of resources in process evaluations, and context relevant findings. The use of an overarching framework allows to collect cross-contextual evidence and flexibility in evaluation design to adapt to the complex nature of the intervention. When designing interventions, it is crucial to consider aspects of the implementing organization or structure, its absorptive capacity, and to thoroughly assess and discuss implementation feasibility, capacity and organizational context with the implementation team and recipients. These recommendations are important for implementation and scale-up of complex interventions. TRIAL REGISTRATION NUMBER: ISRCTN11913581.


Subject(s)
Diabetes Mellitus, Type 2 , Self-Management , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/prevention & control , Humans , South Africa , Sweden/epidemiology , Uganda/epidemiology
11.
Nat Commun ; 13(1): 4983, 2022 09 20.
Article in English | MEDLINE | ID: mdl-36127330

ABSTRACT

Diabetes is known to increase susceptibility to infections, partly due to impaired granulocyte function and changes in the innate immunity. Here, we investigate the effect of diabetes, and high glucose on the expression of the antimicrobial peptide, psoriasin and the putative consequences for E. coli urinary tract infection. Blood, urine, and urine exfoliated cells from patients are studied. The influence of glucose and insulin is examined during hyperglycemic clamps in individuals with prediabetes and in euglycemic hyperinsulinemic clamped patients with type 1 diabetes. Important findings are confirmed in vivo in type 2 diabetic mice and verified in human uroepithelial cell lines. High glucose concentrations induce lower psoriasin levels and impair epithelial barrier function together with altering cell membrane proteins and cytoskeletal elements, resulting in increasing bacterial burden. Estradiol treatment restores the cellular function with increasing psoriasin and bacterial killing in uroepithelial cells, confirming its importance during urinary tract infection in hyperglycemia. In conclusion, our findings present the effects and underlying mechanisms of high glucose compromising innate immunity.


Subject(s)
Diabetes Mellitus, Experimental , Escherichia coli Infections , Urinary Tract Infections , Animals , Antimicrobial Peptides , Escherichia coli/metabolism , Escherichia coli Infections/drug therapy , Estradiol/metabolism , Glucose/metabolism , Humans , Insulin/metabolism , Membrane Proteins/metabolism , Mice , S100 Calcium Binding Protein A7/metabolism , Urinary Bladder/metabolism
12.
J Innate Immun ; : 1-16, 2022 Aug 23.
Article in English | MEDLINE | ID: mdl-35998572

ABSTRACT

Contrasting the antigen-presenting dendritic cells (DCs) in the conducting airways, the alveolar DC populations in human lungs have remained poorly investigated. Consequently, little is known about how alveolar DCs are altered in diseases such as chronic obstructive pulmonary disease (COPD). This study maps multiple tissue DC categories in the distal lung across COPD severities. Specifically, single-multiplex immunohistochemistry was applied to quantify langerin/CD207+, CD1a+, BDCA2+, and CD11c+ subsets in distal lung compartments from patients with COPD (GOLD stage I-IV) and never-smoking and smoking controls. In the alveolar parenchyma, increased numbers of CD1a+langerin- (p < 0.05) and BDCA-2+ DCs (p < 0.001) were observed in advanced COPD compared with controls. Alveolar CD11c+ DCs also increased in advanced COPD (p < 0.01). In small airways, langerin+ and BDCA-2+ DCs were also significantly increased. Contrasting the small airway DCs, most alveolar DC subsets frequently extended luminal protrusions. Importantly, alveolar and small airway langerin+ DCs in COPD lungs displayed site-specific marker profiles. Further, multiplex immunohistochemistry with single-cell quantification was used to specifically profile langerin DCs and reveal site-specific expression patterns of the maturation and activation markers S100, fascin, MHC2, and B7. Taken together, our results show that clinically advanced COPD is associated with increased levels of multiple alveolar DC populations exhibiting features of both adaptive and innate immunity phenotypes. This expansion is likely to contribute to the distal lung immunopathology in COPD patients.

14.
Int J Mol Sci ; 23(11)2022 May 29.
Article in English | MEDLINE | ID: mdl-35682776

ABSTRACT

BMP signaling is crucial for differentiation of secretory ameloblasts, the cells that secrete enamel matrix. However, whether BMP signaling is required for differentiation of maturation-stage ameloblasts (MA), which are instrumental for enamel maturation into hard tissue, is hitherto unknown. To address this, we used an in vivo genetic approach which revealed that combined deactivation of the Bmp2 and Bmp4 genes in the murine dental epithelium causes development of dysmorphic and dysfunctional MA. These fail to exhibit a ruffled apical plasma membrane and to reabsorb enamel matrix proteins, leading to enamel defects mimicking hypomaturation amelogenesis imperfecta. Furthermore, subsets of mutant MA underwent pathological single or collective cell migration away from the ameloblast layer, forming cysts and/or exuberant tumor-like and gland-like structures. Massive apoptosis in the adjacent stratum intermedium and the abnormal cell-cell contacts and cell-matrix adhesion of MA may contribute to this aberrant behavior. The mutant MA also exhibited severely diminished tissue non-specific alkaline phosphatase activity, revealing that this enzyme's activity in MA crucially depends on BMP2 and BMP4 inputs. Our findings show that combined BMP2 and BMP4 signaling is crucial for survival of the stratum intermedium and for proper development and function of MA to ensure normal enamel maturation.


Subject(s)
Ameloblasts , Amelogenesis , Amelogenesis/genetics , Animals , Bone Morphogenetic Protein 2/genetics , Bone Morphogenetic Protein 2/metabolism , Bone Morphogenetic Protein 4/genetics , Bone Morphogenetic Protein 4/metabolism , Cell Differentiation , Epithelium , Mice , Signal Transduction
15.
Sci Rep ; 12(1): 3031, 2022 Feb 22.
Article in English | MEDLINE | ID: mdl-35194105

ABSTRACT

Optimisation and reproducibility of beams of protons accelerated from laser-solid interactions require accurate control of a wide set of variables, concerning both the laser pulse and the target. Among the former ones, the chirp and temporal shape of the pulse reaching the experimental area may vary because of spectral phase modulations acquired along the laser system and beam transport. Here, we present an experimental study where we investigate the influence of the laser pulse chirp on proton acceleration from ultrathin flat foils (10 and 100 nm thickness), while minimising any asymmetry in the pulse temporal shape. The results show a [Formula: see text] change in the maximum proton energy depending on the sign of the chirp. This effect is most noticeable from 10 nm-thick target foils, suggesting a chirp-dependent influence of relativistic transparency.

16.
PLOS Glob Public Health ; 2(5): e0000425, 2022.
Article in English | MEDLINE | ID: mdl-36962331

ABSTRACT

Health systems in many low- and middle-income countries are struggling to manage type 2 diabetes (T2D). Management of glycaemia via well-organized care can reduce T2D incidence, and associated morbidity and mortality. The primary aim of this study was to evaluate the effectiveness of facility plus community care interventions (integrated care), compared to facility only care interventions (facility care) towards improvement of T2D outcomes in Uganda and South Africa. A pragmatic cluster randomized trial design was used to compare outcomes among participants with T2D and those at high risk. The trial had two study arms; the integrated care arm, and the facility care arm; and in Uganda only, an additional usual care arm. Participants were enrolled at nine primary health facilities in Uganda, and two in South Africa. Participants were adults aged 30 to 75 years, and followed for up to 12 months. Primary outcomes were glycaemic control among participants with T2D, and reduction in HbA1c > = 3 mmol/mol among participants at high risk. Secondary outcomes were retention into care and incident T2D. Adjusted analysis revealed significantly higher retention into care comparing integrated care and facility care versus usual care in Uganda and integrated care versus facility care in South Africa. The effect was particularly high among participants at high risk in Uganda with an incident rate ratio of 2.46 [1.33-4.53] for the facility care arm and 3.52 [2.13-5.80] for the integrated care arm. No improvement in glycaemic control or reduction in HbA1c was found in either country. However, considerable and unbalanced loss to follow-up compromised assessment of the intervention effect on HbA1c. Study interventions significantly improved retention into care, especially compared to usual care in Uganda. This highlights the need for adequate primary care for T2D and suggest a role for the community in T2D prevention. Trial registration number: ISRCTN11913581.

17.
Pharmacology ; 107(3-4): 160-166, 2022.
Article in English | MEDLINE | ID: mdl-34929688

ABSTRACT

INTRODUCTION: Sunitinib, a multi-targeted tyrosine kinase receptor inhibitor used to treat renal-cell carcinoma and gastrointestinal stromal tumor, was recently shown to have a beneficial effect on metabolism in type 2 diabetes (T2D). Endothelial dysfunction is a key factor behind macro- and microvascular complications in T2D. The effect of sunitinib on endothelial function in T2D remains, however, unclear. We therefore tested the hypothesis that sunitinib ameliorates endothelial dysfunction in T2D. METHODS: Sunitinib (2 mg/kg/day, by gavage) was administered to T2D Goto-Kakizaki (GK) rats for 6 weeks, while water was given to GK and Wistar rats as controls. Hemodynamic, inflammatory, and metabolic parameters as well as endothelial function were measured. RESULTS: Systolic, mean arterial blood pressures, plasma tumor necrosis factor α levels, kidney weight to body weight (BW) ratio, and glucose levels were higher, while BW was lower in GK rats than in Wistar rats. Six-week treatment with sunitinib in GK rats did not affect these parameters but suppressed the increase in glucose levels. Endothelium-dependent relaxations were reduced in both aortas and mesenteric arteries isolated from GK as compared to Wistar rats, which was markedly reversed in both types of arteries from GK rats treated with sunitinib. CONCLUSIONS: This study demonstrates that sunitinib has a glucose-lowering effect and ameliorates endothelial dysfunction in both conduit and resistance arteries of GK rats.


Subject(s)
Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Animals , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/metabolism , Endothelium, Vascular , Rats , Rats, Wistar , Sunitinib/metabolism , Sunitinib/pharmacology , Sunitinib/therapeutic use
18.
J Mol Med (Berl) ; 100(1): 101-113, 2022 01.
Article in English | MEDLINE | ID: mdl-34651203

ABSTRACT

Infections are common in patients with diabetes, but increasing antibiotic resistance hampers successful bacterial clearance and calls for alternative treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is known to influence the innate immune defense and could therefore serve as a possible target. However, the impact of high glucose on HIF-1 has received little attention and merits closer investigation. Here, we show that higher levels of proinflammatory cytokines and CAMP, encoding for the antimicrobial peptide cathelicidin, LL-37, correlate with HIF-1 in type 2 diabetic patients. Chemical activation of HIF-1 further enhanced LL-37, IL-1ß, and IL-8 in human uroepithelial cells exposed to high glucose. Moreover, HIF-1 activation of transurethrally infected diabetic mice resulted in lower bacterial load. Drugs activating HIF-1 could therefore in the future potentially have a therapeutic role in clearing bacteria in diabetic patients with infections where antibiotic treatment failed. KEY MESSAGES: • Mohanty et al. "HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients." • Our study highlights induction of the antimicrobial peptide, LL-37, and strengthening of the innate immunity through hypoxia-inducible factor 1 (HIF-1) in diabetes. • Our key observations are: 1. HIF-1 activation increased LL-37 expression in human urothelial cells treated with high glucose. In line with that, we demonstrated that patients with type 2 diabetes living at high altitude had increased levels of the LL-37. 2. HIF-1 activation increased IL-1ß and IL-8 in human uroepithelial cells treated with high glucose concentration. 3. Pharmacological activation of HIF-1 decreased bacterial load in the urinary bladder of mice with hereditary diabetes. • We conclude that enhancing HIF-1 may along with antibiotics in the future contribute to the treatment in selected patient groups where traditional therapy is not possible.


Subject(s)
Antimicrobial Cationic Peptides/immunology , Diabetes Mellitus, Experimental/immunology , Diabetes Mellitus, Type 2/immunology , Escherichia coli Infections/immunology , Hypoxia-Inducible Factor 1/immunology , Urinary Tract Infections/immunology , Adult , Aged , Aged, 80 and over , Animals , Cytokines/genetics , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Type 2/genetics , Escherichia coli Infections/genetics , Female , Humans , Hypoxia-Inducible Factor 1/genetics , Male , Mice , Middle Aged , Urinary Tract Infections/genetics , Urothelium/cytology , Cathelicidins
19.
Front Endocrinol (Lausanne) ; 13: 1092307, 2022.
Article in English | MEDLINE | ID: mdl-36686443

ABSTRACT

Objective: Adiponectin and insulin-like growth factor (IGF) binding proteins IGFBP-1 and IGFBP-2 are biomarkers of insulin sensitivity. IGFBP-1 reflects insulin sensitivity in the liver, adiponectin in adipose tissue and IGFBP-2 in both tissues. Here, we study the power of the biomarkers adiponectin, IGFBP-1, IGFBP-2, and also included IGF-I and IGF-II, in predicting prediabetes and type 2 diabetes (T2D) in men and women with normal oral glucose tolerance (NGT). Design: Subjects with NGT (35-56 years) recruited during 1992-1998 were re-investigated 8-10 years later. In a nested case control study, subjects progressing to prediabetes (133 women, 164 men) or to T2D (55 women, 98 men) were compared with age and sex matched NGT controls (200 women and 277 men). Methods: The evaluation included questionnaires, health status, anthropometry, biochemistry and oral glucose tolerance test. Results: After adjustment, the lowest quartile of adiponectin, IGFBP-1 and IGFBP-2 associated independently with future abnormal glucose tolerance (AGT) in both genders in multivariate analyses. High IGFs predicted weakly AGT in women. In women, low IGFBP-2 was the strongest predictor for prediabetes (OR:7.5), and low adiponectin for T2D (OR:29.4). In men, low IGFBP-1 was the strongest predictor for both prediabetes (OR:13.4) and T2D (OR:14.9). When adiponectin, IGFBP-1 and IGFBP-2 were combined, the ROC-AUC reached 0.87 for women and 0.79 for men, higher than for BMI alone. Conclusion: Differences were observed comparing adipocyte- and hepatocyte-derived biomarkers in forecasting AGT in NGT subjects. In women the strongest predictor for T2D was adiponectin and in men IGFBP-1, and for prediabetes IGFBP-2 in women and IGFBP-1 in men.


Subject(s)
Diabetes Mellitus, Type 2 , Glucose Intolerance , Insulin Resistance , Prediabetic State , Humans , Male , Female , Prediabetic State/diagnosis , Prediabetic State/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/metabolism , Insulin-Like Growth Factor Binding Protein 1/metabolism , Insulin-Like Growth Factor Binding Protein 2 , Adiponectin/metabolism , Case-Control Studies , Biomarkers
20.
BMC Palliat Care ; 20(1): 130, 2021 Aug 24.
Article in English | MEDLINE | ID: mdl-34429078

ABSTRACT

BACKGROUND: In early stage chronic obstructive pulmonary disease (COPD), dyspnea has been reported as the main symptom; but at the end of life, patients dying from COPD have a heavy symptom burden. Still, specialist palliative care is seldom offered to patients with COPD; they more often receive end of life care in hospitals. Furthermore, symptoms, symptom relief and care activities in the last week of life for COPD patients are rarely studied. The aim of this study was to compare patient and care characteristics in late stage COPD patients treated in specialized palliative care (SPC) versus hospital. METHODS: Two nationwide registers were merged, the Swedish National Airway Register (SNAR) and the Swedish Register of Palliative Care (SRPC). Patients with COPD and < 50% of predicted forced expiratory volume in 1 s (FEV1), who had died in inpatient or outpatient SPC (n = 159) or in hospital (n = 439), were identified. Clinical COPD characteristics were extracted from the SNAR, and end of life (EOL) care characteristics from the SRPC. Descriptive statistics were used to describe the sample and the registered care and treatments. Independent samples t-test, Mantel-Haenszel chi-square test and Fisher's exact test was used to compare variables. To examine predictors of place of death, bivariate and multivariate logistic regression analyses were performed with a dependent variable with demographic and clinical variables used as independent variables. RESULTS: The patients in hospitals were older and more likely to have heart failure or hypertension. Pain was more frequently reported and relieved in SPC than in hospitals (p = 0.001). Rattle, anxiety, delirium and nausea were reported at similar frequencies between the settings; but rattle, anxiety, delirium, and dyspnea were more frequently relieved in SPC (all p < 0.001). Compared to hospital, SPC was more often the preferred place of care (p < 0.001). In SPC, EOL discussions with patients and families were more frequently held than in hospital (p < 0.001). Heart failure increased the probability of dying in hospital while lung cancer increased the probability of dying in SPC. CONCLUSION: This study provides evidence for referring more COPD patients to SPC, which is more focused on symptom management and psychosocial and existential support.


Subject(s)
Pulmonary Disease, Chronic Obstructive , Terminal Care , Hospitals , Humans , Palliative Care , Pulmonary Disease, Chronic Obstructive/therapy , Registries
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