Controlling oxidative stress as a novel molecular approach to protecting the vascular wall in diabetes

PURPOSE OF REVIEW: In diabetes, oxidative stress plays a key role in the pathogenesis of vascular complications; therefore an antioxidant therapy would be of great interest in this disease. RECENT FINDINGS: Hyperglycemia directly promotes an endothelial dysfunction--inducing process of overproduction of superoxide at the mitochondrial level. This is the first and key event able to activate all the pathways involved in the development of vascular complications of diabetes. It has recently been shown that statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1 blockers, calcium channel blockers, and thiazolidinediones have a strong intracellular antioxidant activity. SUMMARY: Classic antioxidants, such as vitamin E, failed to show beneficial effects on diabetic complications probably because their action is only "symptomatic". The preventive activity against hyperglycemia-induced oxidative stress shown by statins, angiotensin-converting enzyme inhibitors, angiotensin II type 1 blockers, calcium channel blockers, and thiazolidinediones justifies use of these compounds for preventing complications in patients with diabetes, in whom antioxidant defences have been shown to be defective.     

Effects of gender and depression on oral medication adherence in persons with type 2 diabetes mellitus

Background: In a range of chronic conditions including diabetes, it has been observed that depressive symptoms may be associated with nonadherence to medications.Objective: The objective of the study was to determine the main effects, and interactive effect, of depression and gender on patients adherence to oral diabetes medications.Methods: A cross-sectional design was employed, in which persons with type 2 diabetes mellitus completed a questionnaire regarding medication use behaviors, depressive symptoms (measured by the 8-item Patient Health Questionnaire [PHQ-8]), health beliefs, and demographics. A 2 x 2 factorial analysis of variance was used to determine the effects of gender and depression on medication adherence after adjusting for age, education, self efficacy, social support, and number of doses of diabetes medications.Results: Of the 391 respondents who completed the questionnaire, 73 (18.7%) were categorized as having depression (ie, PHQ-8 score >10). Overall, women (n = 196) had a mean (SD) score of 6.10 (6.19) on the PHQ-8, and men (n = 195) had a lower score of 4.62 (5.28) (t = 2.75; P < 0.01). There was a significant main effect of depression, but not gender, on patients' adherence to diabetes medications in that those who were categorized as depressed had significantly worse adherence to diabetes medications (F = 4.82; P = 0.03).Additionally, there was a significant “gender x depression” interaction effect on adherence (F = 5.93; P = 0.01). Men with depression had mean adherence scores that indicated more nonadherence than did men without depression (9.44 [3.45] vs 7.47 [2.50], respectively), but adherence varied little between women with depression and women without depression (7.83 [2.69] vs 7.55 [2.58], respectively).Conclusions: The association between depression and medication adherence appears to be stronger in men than in women. Clinicians should be cognizant of the potential effect of depression on self-care for diabetes, particularly in men with depressive symptoms.     

No association between the angiotensin-converting-enzyme gene insertion/deletion polymorphism and the occurrence of macroangiopathy in patients with diabetes mellitus type 2.

Previous studies have reported an association between the ACE-I/D-polymorphism and coronary heart disease (CHD) in patients with diabetes mellitus. However, ACE inhibitor treatment, which could have compensated for negative effects of the D/D form of the ACE gene polymorphism, was not considered in the studies. We investigated the influence of the ACE-I/D polymorphism and the ACE inhibitor treatment in patients with diabetes mellitus on the occurrence of CHD by multiple-regression analysis. Distribution of the ACE gene I/D-polymorphism was investigated in 691 patients with diabetes mellitus prospectively characterised for the presence/absence of coronary heart disease. The distribution of DD; ID; II genotypes was 105 vs. 202 vs. 102 (25.7 % vs. 49.4 % vs. 24.9) in the CHD + group and 55 vs. 160 vs. 67 (19.5 % vs. 56.7 % vs. 23.8 %) in the CHD - group, respectively (p = 0.1). A multiple logistic regression analysis introducing the typical risk factors for CHD (age, gender, smoking, BMI > 26 kg/m 2, LDL elevation, HbA1c > 7 %) could not identify the ACE gene I/D-polymorphism as an independent risk factor for CHD (p = 0.87). Our data therefore suggest that the ACE gene I/D polymorphism is not associated with the occurrence of diabetic macroangiopathy in patients with or without treatment of ACE inhibitors.     

Gender differences in adiponectin and low-grade inflammation among individuals with normal glucose tolerance,prediabetes, and type 2 diabetes

Background: Women with prediabetes and type 2 diabetes mellitus have a higher relative risk of cardiovascular disease than do men. The reason for this is unknown.Objective: We studied the gender differences in adiponectin and in low-grade inflammation, measured by high-sensitivity C-reactive protein (hs-CRP) and interleukin-1 receptor antagonist (IL-1RA), in individuals with normal glucose tolerance, prediabetes, and type 2 diabetes.Methods: In this population-based, cross-sectional study, all individuals born in 1942, 1947, 1952, 1957, and 1962 in Pieksämäki, East Finland, were recruited for participation. A 75-g oral glucose tolerance test and lipid panel were performed, and concentrations of adiponectin, hs-CRP, and IL-1RA were measured. The World Health Organization diagnostic criteria for diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were used. Statistical comparisons between men and women were performed by a bootstrap-type ANCOVA.Results: The eligible population included 1294 middle-aged individuals, and of these, 904 (406 men and 498 women) had complete data and were included in the analyses. Absolute adiponectin concentrations were significantly higher in women at all levels of glucose tolerance (normal, prediabetes, and type 2 diabetes), but the gender ratio (women to men) for adiponectin concentrations decreased linearly (P = 0.011) from normal glucose tolerance (1.61; 95% CI, 1.48–1.75) to prediabetes (1.57; 95% CI, 1.36–1.83) and diabetes (1.16; 95% CI, 0.87–1.53). Among participants with normal glucose tolerance, no significant difference was found between the sexes in hs-CRP or IL-1RA. Among patients with prediabetes or diabetes, women had significantly higher concentrations than did men for hs-CRP (for prediabetes, 2.0 vs 1.5 mg/L; ratio, 1.39; 95% CI, 1.04–1.85) and IL-1RA (for prediabetes, 255 vs 178 pg/mL; ratio, 1.43; 95% CI, 1.121.83). The gender ratios (women to men) increased linearly from normal glucose tolerance to prediabetes and type 2 diabetes for both hs-CRP (P = 0.019) and IL-1RA (P = 0.013).Conclusions: Adiponectin concentrations in women decreased relatively more compared with men across individuals with normal glucose tolerance, prediabetes, and type 2 diabetes, whereas inflammatory markers increased relatively more in women. Higher inflammatory stress in women than in men with prediabetes and type 2 diabetes may explain their relatively higher cardiovascular disease risk.     

Diabetes mellitus and cardiac function

Cardiovascular complications are the most common causes of morbidity and mortality in diabetic patients. Coronary atherosclerosis is enhanced in diabetics, whereas myocardial infarction represents 20% of deaths of diabetic subjects. Furthermore, re-infarction and heart failure are more common in the diabetics. Diabetic cardiomyopathy is characterized by an early diastolic dysfunction and a later systolic one, with intracellular retention of calcium and sodium and loss of potassium. In addition, diabetes mellitus accelerates the development of left ventricular hypertrophy in hypertensive patients and increases cardiovascular mortality and morbidity. Treating the cardiovascular problems in diabetics must be undertaken with caution. Special consideration must be given with respect to the ionic and metabolic changes associated with diabetes. For example, although ACE inhibitors and calcium channel blockers are suitable agents, potassium channel openers cause myocardial preconditioning and decrease the infarct size in animal models, but they inhibit the insulin release after glucose administration in healthy subjects. Furthermore, potassium channel blockers abolish myocardial preconditioning and increase infarct size in animal models, but they protect the heart from the fatal arrhytmias induced by ischemia and reperfusion which may be important in diabetes. For example, diabetic peripheral neuropathy usually presents with silent ischemia and infarction. Mechanistically, parasympathetic cardiac nerve dysfunction, expressed as increased resting heart rate and decreased respiratory variation in heart rate, is more frequent than the sympathetic cardiac nerve dysfunction expressed as a decrease in the heart rate rise during standing.     

中国汉族人群ENPP1基因K121Q多态与2型糖尿病的关联及Meta分析

多个欧洲白人的Meta分析表明核苷酸焦磷酸酶1(Ectonucleotide pyrophosphatase/phosphodiesterase 1, ENPP1)基因K121Q多态与2型糖尿病相关联, 但在日本人、韩国人和中国台湾人的研究中没有发现相关性, 而在中国大陆人群中二者的关联研究结果不尽一致。文章调查了湖北地区539例2型糖尿病患者和404名正常人ENPP1基因K121Q多态性。基因型及等位基因频率在病例组和对照组间没有显著差异(P＞0.05), 但经性别、年龄和体重指数调整后的Logistic回归分析揭示XQ基因型与2型糖尿病显著相关(OR=1.5, 95%CI: 1.39~1.62, P<0.001)。对性别进行的亚组分析显示, 女性病例组Q等位基因和XQ基因型的频率显著高于对照组(Q: 12.4% vs. 6.1%, P=0.001; XQ: 23.7% vs. 11.7%, P=0.001)。结果表明ENPP1基因K121Q多态与湖北汉族人2型糖尿病的关联存在性别差异, 在女性中更明显。文章是对中国大陆人群进行的第一个Meta分析, 结果显示Q等位基因增加2型糖尿病的发病风险(OR=1.42, P=0.042)。     

Cardiac medication use in patients with suspected ischaemia without obstructive coronary arteries: sex differences and psychological distress

BackgroundIschaemia without obstructive coronary arteries (INOCA) is more prevalent in women and associated with psychological distress. Pharmacological treatment goals are angina relief and cardiovascular risk management. The present study aims to examine sex differences in cardiac and non-cardiac medication use, as well as medication and sex differences related to consistent psychological distress in patients with suspected INOCA.DesignA TweeSteden mild stenosis observational cohort study in patients with suspected INOCA as detected by ischaemic reason for referral and non-obstructive arteries based on coronary angiography or computed tomography.MethodsMedication documented in the hospital records of 488 patients (53% women) was coded as angina relief medication, blood-pressure-lowering medication, antithrombotics, statins, and non-cardiac medication, using the Anatomical Therapeutic Chemical code. Depressive symptoms and anxiety were recoded as ‘consistent distress’ (above the cut-off score for depression and anxiety on validated questionnaires), ‘inconsistent distress’ (above the cut-off for depression or anxiety) or ‘no distress’ (below the cut-off).ResultsNo sex differences were observed in cardiac medication use. Women used anxiolytic benzodiazepines more often (12% vs 4%, p = 0.002) compared to men. Consistent distress was more prevalent in women (22% vs 15%, p = 0.004) and was related to the use of more angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and diuretics in women and to calcium antagonist use as well as lower adherence levels in men. Women who reported chest pain more often received angina relief medication and blood-pressure-lowering medication than men.ConclusionNo sex differences were observed in cardiac medication use in patients with suspected INOCA. Psychological distress may reflect hypertension and subsequent medication use in women, and experiencing chest pain and subsequent medication use in men.     

Deletion/Deletion genotype of angiotensin-I converting enzyme gene is not associated with coronary artery disease in caucasians with type 2 diabetes

In this study we analyzed the contribution of genetic variability of the insertion/deletion (I/D) polymorphism of the angiotensin-I converting enzyme (ACE) gene to the predisposition for coronary artery disease (CAD) in a group of patients with type 2 diabetes. The I/D ACE gene polymorphism was tested in 366 Caucasians with type 2 diabetes: 148 cases with CAD and 218 subjects with no history of CAD. We failed to demonstrate that the ACE DD genotype was a risk factor for CAD in Caucasians with type 2 diabetes (OR 2.0, 95% CI 0.9-4.7; p = 0.1). In conclusion, we provide evidence that the ACE deletion/deletion genotype is not a risk factor for CAD in Caucasians with type 2 diabetes.     

Gender-modulated risk of coronary heart disease,diabetes and coronary mortality among Turks for three major risk factors,and residual adiposity risk

Background

We determined the proportion of the effects of body mass index (BMI) or its categories on cardiometabolic outcomes mediated through systolic blood pressure (SBP), total cholesterol and fasting glucose.

Methods

Cox regression analyses were performed for incident outcomes among Turkish Adult Risk Factor study participants in whom the three mediators had been determined (n?=?2158, age 48.5?±?11 years). Over a mean 10.2-years’ follow-up, new coronary heart disease (CHD) developed in 406, diabetes in 284 individuals, and 149 CHD deaths occurred.

Results

Hazard ratios (HR) of BMI for incident diabetes were no more than marginally attenuated by the 3 mediators including glucose, irrespective of gender. Compared to “normal-weight”, sex- and age-adjusted RRs for incident CHD of overweight and obesity were 1.40 and 2.24 (95 % CI 1.68; 2.99), respectively, in gender combined. Only three-tenths of the excess risk was retained by BMI in men, six-tenths in women. No mediation of glycemia was discerned in males, in contrast to greatest mediation in females. HR of age-adjusted continuous BMI was a significant but modest contributor to CHD mortality in each gender. While the BMI risk of CHD death was abolished by mediation of SBP in men, HR strengthened to over two-fold in women through mediation of fasting glucose.

Conclusions

Mediation of adiposity by 3 traditional factors exhibited among Turkish adults strong gender dependence regarding its magnitude for CHD risk and the mediation by individual risk factors. Retention of the large part of risk for diabetes in each sex and for CHD in women likely reflects underlying autoimmune activation.

     

Gender differences in presentation, management, and in-hospital outcomes for patients with AMI in a lower-middle income country: evidence from Egypt

Background

Many studies in high-income countries have investigated gender differences in the care and outcomes of patients hospitalized with acute myocardial infarction (AMI). However, little evidence exists on gender differences among patients with AMI in lower-middle-income countries, where the proportion deaths stemming from cardiovascular disease is projected to increase dramatically. This study examines gender differences in patients in the lower-middle-income country of Egypt to determine if female patients with AMI have a different presentation, management, or outcome compared with men.

Methods and Findings

Using registry data collected over 18 months from 5 Egyptian hospitals, we considered 1204 patients (253 females, 951 males) with a confirmed diagnosis of AMI. We examined gender differences in initial presentation, clinical management, and in-hospital outcomes using t-tests and χ² tests. Additionally, we explored gender differences in in-hospital death using multivariate logistic regression to adjust for age and other differences in initial presentation.We found that women were older than men, had higher BMI, and were more likely to have hypertension, diabetes mellitus, dyslipidemia, heart failure, and atrial fibrillation. Women were less likely to receive aspirin upon admission (p<0.01) or aspirin or statins at discharge (p = 0.001 and p<0.05, respectively), although the magnitude of these differences was small. While unadjusted in-hospital mortality was significantly higher for women (OR: 2.10; 95% CI: 1.54 to 2.87), this difference did not persist in the fully adjusted model (OR: 1.18; 95% CI: 0.55 to 2.55).

Conclusions

We found that female patients had a different profile than men at the time of presentation. Clinical management of men and women with AMI was similar, though there are small but significant differences in some areas. These gender differences did not translate into differences in in-hospital outcome, but highlight differences in quality of care and represent important opportunities for improvement.     

Women tolerate drug therapy for coronary artery disease as well as men do,but are treated less frequently with aspirin, β-blockers,or statins

Background: Women have worse morbidity, mortality, and health-related quality-of-life outcomes associated with coronary artery disease (CAD) compared with men. This may be related to underutilization of drug therapies, such as aspirin, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, or statins. No studies have sought to describe the relationship of gender with adverse reactions to drug therapy (ADRs) for CAD in clinical practice.Objective: The aim of this study was to determine the prevalence of ADRs associated with common CAD drug therapies in women and men in clinical practice.Methods: In a cohort of consecutive outpatients with CAD, detailed chart abstraction was performed to determine the use of aspirin, β-blocker, ACE inhibitor, and statin therapy, as well as the ADRs reported for these treatments. Baseline clinical characteristics were also determined to identify the independent association of gender with use of standard drug treatments for CAD.Results: Consecutive patients with CAD (153 men, 151 women) were included in the study. Women and men were observed to have a similar prevalence of cardiac risk factors and comorbidities, except that men had significantly higher prevalence of atrial fibrillation (30 [19.6%] men vs 15 [9.9%] women; P = 0.03) and significantly lower mean (SD) high-density lipoprotein cholesterol concentrations (45 [16] mg/dL for men vs 55 [19] mg/dL for women; P < 0.001). No significant differences were observed between the sexes in the prevalence of ADRs; however, significantly fewer women than men were treated with statins (118 [78.1%] vs 139 [90.8%], respectively; P = 0.003). After adjusting for clinical characteristics, women were also found to be less likely than men to receive aspirin (odds ratio [OR] = 0.164; 95% CI, 0.083–0.322; P = 0.001) and β-blockers (OR = 0.184; 95% CI, 0.096-0.351; P = 0.001).Conclusions: Women and men experienced a similar prevalence of ADRs in the treatment of CAD; however, women were significantly less likely to be treated with aspirin, β-blockers, and statins than were their male counterparts. To optimize care for women with CAD, further study is needed to identify the cause of this gender disparity in therapeutic drug use.     

Relationships between the amount of saliva and medications in elderly individuals

Gerodontology 2010; doi: 10.1111/j.1741‐2358.2009.00358.x
Relationships between the amount of saliva and medications in elderly individuals Objective: To investigate medications that are related to volume of saliva in the elderly. Background data: In the elderly, many cases of mouth dryness may represent side effects of medication. Materials and methods: The volume of unstimulated saliva was measured for 30 s (cotton roll test), and with stimulation for 3 min (gum test) in 368 subjects 79–80 years old (177 men, 191 women). Medications were investigated using subject’s medication notebooks. Results: Mean volumes of unstimulated and stimulated saliva were 0.14 ± 0.13 and 4.30 ± 2.54 ml respectively. Significant differences were seen between gender and mean volume of saliva. The volume of unstimulated saliva was 0.16 ± 0.15 ml for men and 0.11 ± 0.10 ml for women. The volume of stimulated saliva was 4.99 ± 2.67 ml for men and 3.67 ± 2.25 ml for women. The percentage of subjects taking medication was 64.7% (238/368). Mean number of medications was 2.08 ± 2.26, with no significant difference with gender (2.01 ± 2.37 for men, 2.16 ± 2.16 for women). In a stepwise multiple regression analysis with volume of saliva as the objective variable and number of drugs by category as explanatory variables, significant explanatory variables in addition to gender and number of medications were blood‐coagulating agents, Ca antagonists and peptic ulcer drugs for volume of unstimulated saliva, and diabetes medications and peptic ulcer drugs for volume of stimulated saliva. Conclusion: These findings suggest that differences exist between gender in volume of saliva for elderly individuals, and that the volume of saliva is affected by the number and type of medications.     

Cardiovascular and Renal Outcomes of Renin–Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses

Background

Medications aimed at inhibiting the renin–angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes.

Methods and Findings

Eligible trials were identified by electronic searches in PubMed/MEDLINE and the Cochrane Database of Systematic Reviews (1 January 2004 to 17 July 2014). Interventions of interest were angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and direct renin (DR) inhibitors. The primary endpoints were cardiovascular mortality, myocardial infarction, and stroke—singly and as a composite endpoint, major cardiovascular outcome—and end-stage renal disease [ESRD], doubling of serum creatinine, and all-cause mortality—singly and as a composite endpoint, progression of renal disease. Secondary endpoints were angina pectoris and hospitalization for heart failure. In all, 71 trials (103,120 participants), with a total of 14 different regimens, were pooled using network meta-analyses. When compared with ACE inhibitor, no other RAS blocker used in monotherapy and/or combination was associated with a significant reduction in major cardiovascular outcomes: ARB (odds ratio [OR] 1.02; 95% credible interval [CrI] 0.90–1.18), ACE inhibitor plus ARB (0.97; 95% CrI 0.79–1.19), DR inhibitor plus ACE inhibitor (1.32; 95% CrI 0.96–1.81), and DR inhibitor plus ARB (1.00; 95% CrI 0.73–1.38). For the risk of progression of renal disease, no significant differences were detected between ACE inhibitor and each of the remaining therapies: ARB (OR 1.10; 95% CrI 0.90–1.40), ACE inhibitor plus ARB (0.97; 95% CrI 0.72–1.29), DR inhibitor plus ACE inhibitor (0.99; 95% CrI 0.65–1.57), and DR inhibitor plus ARB (1.18; 95% CrI 0.78–1.84). No significant differences were showed between ACE inhibitors and ARBs with respect to all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, hospitalization for heart failure, ESRD, or doubling serum creatinine. Findings were limited by the clinical and methodological heterogeneity of the included studies. Potential inconsistency was identified in network meta-analyses of stroke and angina pectoris, limiting the conclusiveness of findings for these single endpoints.

Conclusions

In adults with diabetes, comparisons of different RAS blockers showed similar effects of ACE inhibitors and ARBs on major cardiovascular and renal outcomes. Compared with monotherapies, the combination of an ACE inhibitor and an ARB failed to provide significant benefits on major outcomes. Clinicians should discuss the balance between benefits, costs, and potential harms with individual diabetes patients before starting treatment.

Review registration

PROSPERO CRD42014014404     

Increased urinary angiotensin-converting enzyme 2 in renal transplant patients with diabetes

Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n?=?100) and healthy controls (age 45 yrs, 26% male, n?=?50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p?=?0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p?=?0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients.     

The Risk of Type 2 Diabetes in Men Is Synergistically Affected by Parental History of Diabetes and Overweight

Interactions between genetic- and lifestyle factors may be of specific importance for the development of type 2 diabetes. Only a few earlier studies have evaluated interaction effects for the combination of family history of diabetes and presence of risk factors related to lifestyle. We explored whether 60-year-old men and women from Stockholm with a parental history of diabetes are more susceptible than their counterparts without a parental history of diabetes to the negative influence from physical inactivity, overweight or smoking regarding risk of developing type 2 diabetes. The study comprised 4232 participants of which 205 men and 113 women had diabetes (the vast majority type 2 diabetes considering the age of study participants) and 224 men and 115 women had prediabetes (fasting glucose 6.1–6.9 mmol/l). Prevalence odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using logistic regression. Biologic interaction was analyzed using a Synergy index (S) score. The crude OR for type 2 diabetes associated with a parental history of diabetes was 2.4 (95% CI 1.7–3.5) in men and 1.4 (95% CI 0.9–2.3) in women. Adjustments for overweight, physical inactivity and current smoking had minimal effects on the association observed in men whereas in women it attenuated results. In men, but not in women, a significant interaction effect that synergistically increases the risk of developing type 2 diabetes was observed for the combination of BMI>30 and a parental history of diabetes, S 2.4 (95% CI 1.1–5.1). No signs of interactions were noted for a parental history of diabetes combined with physical inactivity and smoking, respectively. In conclusion, obesity in combination with presence of a parental history of diabetes may be particularly hazardous in men as these two factors were observed to synergistically increase the risk of developing type 2 diabetes in men.     

Serum Uric Acid Is More Strongly Associated with Impaired Fasting Glucose in Women than in Men from a Community-Dwelling Population

Serum uric acid (SUA) levels are associated with metabolic syndrome (MetS) and its components such as glucose intolerance and type 2 diabetes. It is unknown whether there are gender-specific differences regarding the relationship between SUA levels, impaired fasting glucose (IFG) and newly detected diabetes. We recruited 1,209 men aged 60±15 (range, 19–89) years and 1,636 women aged 63±12 (range, 19–89) years during their annual health examination from a single community. We investigated the association between SUA levels and six categories according to fasting plasma glucose (FPG) level {normal fasting glucose (NFG), <100 mg/dL; high NFG-WHO, 100 to 109 mg/dL; IFG-WHO, 110 to 125 mg/dL; IFG-ADA, 100 to 125 mg/dL; newly detected diabetes, ≥126 mg/dL; known diabetes} SUA levels were more strongly associated with the different FPG categories in women compared with men. In women, the associations remained significant for IFG-WHO (OR, 1.23, 95% CI, 1.00–1.50) and newly detected diabetes (OR, 1.33, 95% CI, 1.03–1.72) following multivariate adjustment. However, in men all the associations were not significant. Thus, there was a significant interaction between gender and SUA level for newly detected diabetes (P = 0.005). SUA levels are associated with different categories of impaired fasting glucose in participants from community-dwelling persons, particularly in women.     

Diabetic Polyneuropathy Relates to Bone Metabolism and Markers of Bone Turnover in Elderly Patients With Type 2 Diabetes: Greater Effects in Male Patients

BackgroundThere is evidence that diabetic polyneuropathy (PNP) is associated with reduced bone mineral density (BMD) in type 1 diabetes but little is known about the impact of diabetic PNP on bone metabolism in type 2 diabetes.ObjectivesThe aim of this study was to evaluate differences in bone metabolism by measuring markers of bone turnover and BMD in men and postmenopausal women with type 2 diabetes and diabetic PNP compared with those without PNP. Gender differences were analyzed for both groups of patients.MethodsOne hundred twenty patients with type 2 diabetes, 68 without PNP (43 men, 25 women, mean age 62 [8] years) and 52 with PNP (28 men, 24 women, mean age 64 [8] years) were studied. Clinical parameters with bone turnover biomarkers such as osteocalcin, bone alkaline phosphatase, procollagen type 1 amino-terminal propeptide, and carboxy-terminal telopeptide of type 1 collagen were measured in all patients. Dual energy x-ray absorptiometry to evaluate BMD was performed in a subgroup of patients.ResultsAfter controlling for age, body mass index, duration of diabetes, smoking, glycosylated hemoglobin, homeostasis model assessment index for insulin resistance, serum C-reactive protein, creatinine, calcium, gamma-glutamyltransferase, parathyroid and sex hormones levels, presence of micro/macrovascular complications, statin- as well as diabetes-related therapies, levels of carboxy-terminal telopeptide of type 1 collagen and procollagen type 1 amino-terminal propeptide were significantly higher among patients with PNP when compared with patients without PNP (P = 0.01 and P = 0.03, respectively). Differences in bone biomarkers were more pronounced among men with diabetes. BMD did not differ significantly between patients with and without PNP, independent of gender.ConclusionsMale patients with PNP exhibit a higher rate of bone turnover than men without PNP. High rate of bone turnover increases the susceptibility for developing osteoporosis. Prevention of diabetic PNP might also reduce the incidence of osteoporosis and fractures in patients with type 2 diabetes.