Impact of Sex and Gender on Clinical Management of Patients with Advanced Chronic Liver Disease and Type 2 Diabetes

Gender differences in the epidemiology, pathophysiological mechanisms and clinical features in chronic liver diseases that may be associated with type 2 diabetes (T2D) have been increasingly reported in recent years. This sexual dimorphism is due to a complex interaction between sex- and gender-related factors, including biological, hormonal, psychological and socio-cultural variables. However, the impact of sex and gender on the management of T2D subjects with liver disease is still unclear. In this regard, sex-related differences deserve careful consideration in pharmacology, aimed at improving drug safety and optimising medical therapy, both in men and women with T2D; moreover, low adherence to and persistence of long-term drug treatment is more common among women. A better understanding of sex- and gender-related differences in this field would provide an opportunity for a tailored diagnostic and therapeutic approach to the management of T2D subjects with chronic liver disease. In this narrative review, we summarized available data on sex- and gender-related differences in chronic liver disease, including metabolic, autoimmune, alcoholic and virus-related forms and their potential evolution towards cirrhosis and/or hepatocarcinoma in T2D subjects, to support their appropriate and personalized clinical management

Antihypertensive Treatment in Diabetic Kidney Disease: The Need for a Patient-Centered Approach

Diabetic kidney disease affects up to forty percent of patients with diabetes during their lifespan. Prevention and treatment of diabetic kidney disease is currently based on optimal glucose and blood pressure control. Renin-angiotensin aldosterone inhibitors are considered the mainstay treatment for hypertension in diabetic patients, especially in the presence of albuminuria. Whether strict blood pressure reduction entails a favorable renal outcome also in non-albuminuric patients is at present unclear. Results of several clinical trials suggest that an overly aggressive blood pressure reduction, especially in the context of profound pharmacologic inhibition of the renin-angiotensin-aldosterone system may result in a paradoxical worsening of renal function. On the basis of this evidence, it is proposed that blood pressure reduction should be tailored in each individual patient according to renal phenotype

Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fractures, resulting in disabilities and increased mortality. The pathophysiological mechanisms linking diabetes to osteoporosis have not been fully explained, but alterations in bone structure and quality are well described in diabetic subjects, likely due to a combination of different factors. Insulin deficiency and dysfunction, obesity and hyperinsulinemia, altered level of oestrogen, leptin, and adiponectin as well as diabetes-related complications, especially peripheral neuropathy, orthostatic hypotension, or reduced vision due to retinopathy may all be associated with an impairment in bone metabolism and with the increased risk of fractures. Finally, medications commonly used in the treatment of T2DM may have an impact on bone metabolism and on fracture risk, particularly in postmenopausal women. When considering the impact of hypoglycaemic drugs on bone, it is important to balance their potential direct effects on bone quality with the risk of falling-related fractures due to the associated hypoglycaemic risk. In this review, experimental and clinical evidence connecting bone metabolism and fracture risk to T2DM is discussed, with particular emphasis on hypoglycaemic treatments and gender-specific implications

The Burden of Structured Self-Monitoring of Blood Glucose on Diabetes-Specific Quality of Life and Locus of Control in Patients with Noninsulin-Treated Type 2 Diabetes: The PRISMA Study

Background: To evaluate whether structured self-monitoring of blood glucose (SMBG) is associated with changes in diabetes-specific quality of life (DSQoL) and locus of control (LOC) in patients with noninsulin-treated type 2 diabetes (T2DM). Study Design and Methods: In this analysis of the PRISMA (Prospective Randomized Trial on Intensive SMBG Management Added Value in Noninsulin-Treated T2DM Patients) Study psychosocial data, we evaluated the impact of 12 months of structured SMBG on the individual domains of DSQoL and LOC questionnaires, including the role of selected confounders. Results: The score for Satisfaction, Impact, and Worry domains (DSQoL) improved when compared with baseline, without significant differences between structured SMBG regimen (intervention group, n = 501) and active control group (n = 523). Scores for Internal, Chance, and Powerful Others domains (LOC) improved compared with baseline, with a significant between-group change in Chance (P = 0.0309). For DSQoL domain score, improvements were associated with higher number of SMBG measurements (P = 0.007), older age (P = 0.013), and male sex (P = 0.0133) for Satisfaction and with male sex (P < 0.0001) for Worry. Concerning LOC domain score, improvements were associated with longer diabetes duration (P = 0.0084) and younger age (P < 0.0001) for Chance and total number of SMBG measurements (P = 0.0036) for Internal, with the intervention group close to being significant (P = 0.06). Conclusions: Our analysis demonstrates that in patients with noninsulin-treated T2DM, structured SMBG is not associated with a deterioration of quality of life and LOC, which is strongly predicted by demographics and diabetes-related variables. These findings should be considered when tailoring educational support to SMBG for these patients

High Prevalence of Arcobacter Carriage in Older Subjects with Type 2 Diabetes

Arcobacters are potential pathogens related to diarrheic infections and, rarely, septicaemia. This study evaluated the prevalence of arcobacters in stool samples of subjects with (n = 38) and without (n = 61) type 2 diabetes by using cultural and molecular techniques. Three Arcobacter positive cultures were found, all among diabetic subjects, whereas molecular analysis showed a carriage rate of 79% and 26.2% in subjects with and without type 2 diabetes (P < .001), respectively. The multivariate analysis showed that type 2 diabetes (β = 1.913; 95%CI: 2.378–19.285; P < .0001) and age (β = 1.744; 95%CI: 2.077–15.766; P = .001) were the only factors independently associated with arcobacters colonization in this population. Our study demonstrated a high prevalence of arcobacters colonization in type 2 diabetic and older subjects. The clinical significance and the potential health risk associated with these emerging species remain to be determined

Diabetic kidney disease in the elderly: Prevalence and clinical correlates

Background: Diabetic kidney disease (DKD) is a major burden in elderly patients with type 2 diabetes (T2DM). Low estimated glomerular filtration rate (eGFR+, &lt; 60 mL/min/1.73 m2) and albuminuria (Alb+) are essential for the diagnosis of DKD, but their association with clinical variables and quality of care may be influenced by ageing. Methods: Here we investigated the association of clinical variables and quality of care measures with eGFR+ and Alb+ in 157,595 T2DM individuals participating to the Italian Association of Clinical Diabetologists (AMD) Annals Initiative, stratified by age. Results: The prevalence of eGFR+ and Alb+ increased with ageing, although this increment was more pronounced for low eGFR. Irrespective of age, both the eGFR+ and Alb + groups had the worst risk factors profile when compared to subjects without renal disease, showing a higher prevalence of out-of target values of HbA1c, BMI, triglycerides, HDL-C, blood pressure and more complex cardiovascular (CVD) and anti-diabetic therapies, including a larger use of insulin In all age groups, these associations differed according to the specific renal outcome examined: male sex and smoking were positively associated with Alb+ and negatively with eGFR+; age and anti-hypertensive therapies were more strongly associated with eGFR+, glucose control with Alb+, whereas BMI, and lipid-related variables with both abnormalities. All these associations were attenuated in the older (&gt; 75 years) as compared to the younger groups (&lt; 65 years; 65-75 years), and they were confirmed by multivariate analysis. Notably, Q-score values &lt; 15, indicating a low quality of care, were strongly associated with Alb+ (OR 8.54; P &lt; 0.001), but not with eGFR+. Conclusions: In T2DM patients, the prevalence of both eGFR and Albuminuria increase with age. DKD is associated with poor cardiovascular risk profile and a lower quality of care, although these associations are influenced by the type of renal abnormality and by ageing. These data indicate that clinical surveillance of DKD should not be unerestimated in old T2DM patients

Dual Routes from Social Identity to Collective Opposition against Criminal Organisations: Intracultural Appropriation Theory and the roles of Honour Codes and Social Change Beliefs

Italian criminal organisations (COs) are a serious global threat. Intracultural Appropriation Theory (ICAT) holds that such groups exploit cultural codes of masculinity and honour to legitimise and lower resistance to their actions. Such codes are an important feature of Southern Italian group membership. A large survey (N = 1173) investigated the role of two previously under-examined facets of honour cultures – personal concerns for reputation, and female honour ideology. In addition, drawing on social identity theory, and testing a dual route hypothesis, this research investigated the role of beliefs about the necessity of social change in the articulation between identification, honour, and collective action intentions. Consistent with ICAT, and with previous research, male-honour related values uniquely predicted collective action intentions against criminal organisations. In addition, consistent with the dual route hypothesis: a) regional identification positively predicted social change beliefs which in turn explained stronger intentions to oppose COs collectively, and, b) regional identification was also positively associated with masculine honour which in turn predicted weaker intentions to oppose COs. The evidence supports the idea that social identity can have opposing effects on collective action in the same context, depending on which beliefs are mobilised

Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes

Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter. AICAR is an intermediate in the purine de novo synthesis, and its tissue concentrations can be increased, in vivo, by low doses of methotrexate (MTX) through the inhibition of the enzyme AICAR transformylase. We report here the first evidence that, in experimental type 2 diabetes, chronic treatment with low doses of MTX increases skeletal muscle GLUT4 expression and improves metabolic control. MTX (0.5 mg/kg body weight) or vehicle was administered intraperitoneally, once a week for 4 weeks, to genetically diabetic female C57BL/KsJ-m+/+Leptdb mice (db+/db+) and their normoglycemic littermates (db+/+m). In the db+/db+ mice, MTX treatment was associated with a ∼2-fold increase in skeletal muscle GLUT4 protein concentration and a >4-fold increase in GLUT4 mRNA expression (P<0.01, all), as compared to vehicle-treated mice; no significant differences were noted in controls. MTX treatment was also associated with a significant reduction of glucose and insulin serum concentrations in diabetic mice (P<0.001), and glucose levels only (P<0.05) in controls. These data indicate a different route to increase skeletal muscle GLUT4 expression, through the potential inhibition of the enzyme AICAR transformylase