Diabetes compromises tight junction protein claudin 14 in the urinary bladder.

Infections are common in patients with diabetes. Moreover, increasing incidence of antibiotic resistance impedes the complete bacterial clearance and calls for alternative treatment strategies. Along with antibacterial resistance, compromised host conditions create a favorable condition for the disease progression. In particular, cell junction proteins are of major importance as they contribute to a tight cell barrier, protecting against invading pathogens. However, the impact of high glucose on cell junction proteins has received little attention in the urinary bladder but merits closer investigation. Here, we report that during diabetes the expression of cell junction protein, claudin 14 is compromised in the human urine exfoliated cells and in the urinary bladder of type 2 diabetic mouse. Further in vitro analysis confirmed a direct correlation of lower intracellular calcium levels with claudin 14 expression in high glucose-treated human uroepithelial cells. Moreover, external calcium supplementation in high glucose-treated cells significantly affected the cell migration and restored the claudin 14 expression through focal adhesion and ß-1 integrins. Strengthening the epithelial barrier is essential, especially in individuals with diabetes where basal calcium levels could contribute.

Diabetes downregulates the antimicrobial peptide psoriasin and increases E. coli burden in the urinary bladder.

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.

HIF-1 mediated activation of antimicrobial peptide LL-37 in type 2 diabetic patients.

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.

Sexual dysfunction in Assyrian/Syrian immigrants and Swedish-born persons with type 2 diabetes.

BACKGROUND: Few studies have investigated sexual dysfunction in immigrant patients with type 2 diabetes in Sweden. The aim of this study was to examine the association between ethnicity and sexual dysfunction and to analyze if this association remains after adjusting for explanatory variables including age, marital status, HbA1c, triglycerides, and hypertension. This cross-sectional study was conducted at four primary health care centers in the Swedish town of Södertälje. A total of 354 persons with type 2 diabetes (173 Assyrians/Syrians and 181 Swedish-born patients) participated in the survey. The main outcome measure was the self-reported presence of sexual dysfunction based on two questions, one regarding loss of ability to have sexual intercourse and the other loss of sexual desire. Response rates were 78% and 86%, respectively. FINDINGS: The total prevalence of loss of ability to have intercourse was 29.5%. In the multivariate models, the odds of loss of ability to have intercourse was significantly higher in the oldest age group (OR = 5.80; 95% CI, 2.33-14.40), in men (OR = 3.33; 95% CI, 1.33-8.30), and in unmarried individuals (OR = 2.40; 95% CI, 1.02-5.70). The odds of reporting loss of sexual desire was higher in Assyrians/Syrians than in Swedish-born patients and increased from 2.00 in the age- and gender-adjusted model to 2.70 in the fully adjusted model when all confounders were taken into account. CONCLUSIONS: Sexual dysfunction appears to be more common in Assyrians/Syrians than in Swedish-born patients. Health care workers should actively ask about sexual function in their patients with type 2 diabetes.

Ethnic differences in dissatisfaction with sexual life in patients with type 2 diabetes in a Swedish town.

BACKGROUND: The first aim of this study was to analyze whether self-reported satisfaction with one's sexual life was associated with ethnicity (Swedish and Assyrian/Syrian) in patients with type 2 diabetes. The second was to study whether the association between satisfaction with one's sexual life and ethnicity remained after controlling for possible confounders such as marital status, HbA1c, medication, and presence of other diseases. METHODS: This cross-sectional, questionnaire-based study was conducted at four primary health care centers in the Swedish town of Södertälje. A total of 354 persons (173 ethnic Assyrians/Syrians and 181 ethnic Swedes) participated. RESULTS: The total prevalence of self-reported dissatisfaction with one's sexual life in both groups was 49%. No significant ethnic differences were found in the outcome. In the final model, regardless of ethnicity, the odds ratio (OR) for self-reported dissatisfaction with one's sexual life in those ≥ 70 years old was 2.52 (95% CI 1.33-4.80). Among those living alone or with children, the OR was more than three times higher than for married or cohabiting individuals (OR = 3.10, 95% CI 1.60-6.00). Those with other diseases had an OR 1.89 times (95% CI 1.10-3.40) higher than those without other diseases. CONCLUSIONS: The findings demonstrate that almost half of participants were dissatisfied with their sexual life and highlight the importance of sexual life to people with type 2 diabetes. This factor should not be ignored in clinical evaluations. Moreover, the findings demonstrate that it is possible to include questions on sexual life in investigations of patients with type 2 diabetes and even in other health-related, questionnaire studies, despite the sensitivity of the issue of sexuality.

Poor self-rated health in adult patients with type 2 diabetes in the town of Södertälje: A cross-sectional study.

OBJECTIVE: Several studies indicate that ethnicity may be a strong predictor of poor self-rated health (SRH). The aims of the present study were to investigate whether there was an association between ethnicity and poor SRH in subjects with type 2 diabetes and to determine if the association remained after adjusting for possible confounders such as age, gender employment, marital status, and education. DESIGN: A cross-sectional study based on a patient population in the town of Södertälje. An unconditional logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs). SETTING: Four primary health care centers. SUBJECTS: A total of 354 individuals were included: Assyrian/Syrian-born (n = 173) and Swedish-born (n = 181). RESULTS: The odds ratio for rating poor SRH for Assyrian/Syrian subjects with type 2 diabetes was 4.5 times higher (95% CI = 2.7-7.5) than for Swedish patients in a crude model. After adjusting for possible confounders, unemployed/retired people had 5.4 times higher odds for reporting poor SRH than employees (OR = 5.4; 95% CI = 2.3-12.5). Women had 1.8 times higher odds (95% CI = 1.0-3.0) for reporting poor SRH than men. In the final model poor SRH among Assyrians/Syrians decreased but still remained significant (OR=3.7; 95% CI = 2.5-6.6). CONCLUSIONS: The findings in this study are important for planning primary health care services. They highlight the crucial importance of being aware of the subjective health status of immigrants fleeing from war in the Middle East and resettling in Sweden.

Cardiovascular risk factors in Assyrians/Syrians and native Swedes with type 2 diabetes: a population-based epidemiological study.

BACKGROUND: A large number of people throughout the world have diabetes and the prevalence is increasing. Persons with diabetes have a twice higher risk of cardiovascular disease than those without diabetes. There is a lack of studies focusing on cardiovascular risk factors in Assyrians/Syrians with type 2 diabetes. The aim of this study is to estimate the prevalence of some cardiovascular risk factors among Assyrians/Syrians and native Swedes with type 2 diabetes and to study whether the association between ethnicity and cardio-vascular risk factors remains after adjustment for age, gender, employment status and housing tenure. METHODS: In the Swedish town of Södertälje 173 Assyrians/Syrians and 181 ethnic Swedes with type 2 diabetes participated in a study evaluating cardiovascular risk factors such as increased haemoglobin A1c (HbA1c), high blood lipids (total serum cholesterol and triglycerides), hypertension and high urinary albumin. The associations between the outcome variables and sociodemographic characteristics were estimated using unconditional logistic regression. RESULTS: The prevalence of increased triglycerides in Swedish-born subjects and Assyrian-Syrians was 61.5% and 39.7% respectively. Swedes had a prevalence of hypertension 76.8% compared to 57.8% in Assyrians/Syrians. In the final logistic models adjusted for gender, age, housing and employment the odds ratio (OR) for Swedish-born subjects for increased triglycerides was 2.80 (95% CI1.61-4.87) and for hypertension 2.32 (95% CI 1.35-4.00) compared to Assyrians-Syrians. CONCLUSION: Ethnic Swedes had higher prevalence of increased triglycerides and hypertension than Assyrians/Syrians. Total cholesterol, HbA1c and urinary albumin did not differ between the two ethnic groups.