T-cadherin gene variants are associated with type 2 diabetes and the Fatty Liver Index in the French population

AimAdiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population.MethodsTwo polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n = 5212) and people with T2D in the DIABHYCAR study (n = 3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n = 230), and in controls who remained normoglycaemic (n = 226) throughout.ResultsIn a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04–1.18; P = 0.001) and 0.92 (95% CI: 0.87–0.98; P = 0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P = 0.03) and HbA_1c (P = 0.006), and lower plasma adiponectin levels (P = 0.03) in the D.E.S.I.R. participants. Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P = 0.03), HbA_1c (P = 0.02) and Fatty Liver Index (FLI; P ≤ 0.01), and higher plasma adiponectin levels (P = 0.002). Associations with HbA_1c, FLI and adiponectin levels persisted after adjusting for BMI.ConclusionCDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin.     

Effects of adipose tissue distribution on maximum lipid oxidation rate during exercise in normal-weight women

AimFat mass localization affects lipid metabolism differently at rest and during exercise in overweight and normal-weight subjects. The aim of this study was to investigate the impact of a low vs high ratio of abdominal to lower-body fat mass (index of adipose tissue distribution) on the exercise intensity (Lipox_max) that elicits the maximum lipid oxidation rate in normal-weight women.MethodsTwenty-one normal-weight women (22.0 ± 0.6 years, 22.3 ± 0.1 kg.m⁻²) were separated into two groups of either a low or high abdominal to lower-body fat mass ratio [L-A/LB (n = 11) or H-A/LB (n = 10), respectively]. Lipox_max and maximum lipid oxidation rate (MLOR) were determined during a submaximum incremental exercise test. Abdominal and lower-body fat mass were determined from DXA scans.ResultsThe two groups did not differ in aerobic fitness, total fat mass, or total and localized fat-free mass. Lipox_max and MLOR were significantly lower in H-A/LB vs L-A/LB women (43 ± 3% VO_2max vs 54 ± 4% VO_2max, and 4.8 ± 0.6 mg min⁻¹ kg FFM⁻¹ vs 8.4 ± 0.9 mg min⁻¹ kg FFM⁻¹, respectively; P < 0.001). Total and abdominal fat mass measurements were negatively associated with Lipox_max (r = –0.57 and r = –0.64, respectively; P < 0.01) and MLOR [r = –0.63 (P < 0.01) and r = –0.76 (P < 0.001), respectively].ConclusionThese findings indicate that, in normal-weight women, a predominantly abdominal fat mass distribution compared with a predominantly peripheral fat mass distribution is associated with a lower capacity to maximize lipid oxidation during exercise, as evidenced by their lower Lipoxmax and MLOR.     

Circulating PCSK9 levels in acute coronary syndrome: Results from the PC-SCA-9 prospective study

BackgroundSerum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations have been shown to be positively associated with LDL cholesterol (LDL-C), but the relationship between PCSK9 and coronary atherosclerosis lesions remains unclear.ObjectiveThis study aims to investigate the correlation between serum PCSK9 levels and coronary damage severity in patients hospitalized for acute coronary syndrome (ACS).MethodsIn this prospective proof-of-concept study, coronary lesions were assessed using SYNTAX scores. Serum PCSK9 concentrations were measured on admission (Day 0) for ACS by Elisa, and on every day of hospitalization. Spearman's correlations were used to determine the association between PCSK9 levels, SYNTAX score and metabolic parameters.ResultsA total of 174 patients (mean age: 59 ± 14 years, 79% male) with ACS (on Day 0, 119 patients were not taking statins, but 55 were) were included. After initiation of high-intensity statin therapy, serum PCSK9 concentrations increased significantly, reaching maximum levels on Day 2 (+31% vs. Day 0), and remained stable up to Day 4 (P < 0.001, by mixed model). Serum PCSK9 on Day 0 was associated with LDL-C (rho = 0.226, P = 0.017) and apolipoprotein B (rho = 0.282, P = 0.005) in the statin-naïve group only, and with triglycerides and non-HDL-C in all groups. More important, PCSK9 levels on Day 0 were positively associated with SYNTAX scores in the statin-naïve group (rho = 0.239, P = 0.009), but not in the statin-treated group (P = NS). This association was maintained after adjusting for LDL-C (P = 0.014) and major CV risk factors (P = 0.008).ConclusionSerum PCSK9 levels are positively associated with severity of coronary artery lesions independently of LDL-C concentrations in patients hospitalized for ACS. This reinforces the potential importance of PCSK9 inhibition in the management of ACS.     

Microalbuminuria,but not reduced eGFR,is associated with cardiovascular subclinical organ damage in type 2 diabetes

AimThis study explored the association between reduced estimated glomerular filtration rate (eGFR) and microalbuminuria vs. subclinical organ damage in patients with type 2 diabetes.MethodsData from middle-aged patients with type 2 diabetes (n = 706) treated in primary care were analyzed for microalbuminura, defined as a urinary albumin/creatinine ratio (uACR) ≥ 3.0 mmol/mol, and reduced eGFR, defined as < 60 mL/min/1.73 m², in relation to blood pressure, pulse wave velocity (PWV), left ventricular mass index (LVMI), and carotid intima–media thickness (IMT) and lumen diameter (LD).ResultsPatients with microalbuminuria had significantly higher 24-h ambulatory systolic blood pressure (ASBP) compared with subjects with uACR < 3 mg/mmol: 137 vs. 128 mmHg (P < 0.001). There were no differences in ASBP in patients with eGFR < 60 mL/min/1.73 m². However, patients with vs. without microalbuminuria had increased PWV (11.4 vs. 10.1 m/s; P < 0.001), LVMI (134.4 vs. 118.6 g/m²; P < 0.001), LD (7.01 ± 0.93 vs. 6.46 ± 0.74 mm; P < 0.001) and IMT (0.78 vs. 0.74 mm; P = 0.047), respectively. The associations between uACR vs. PWV and LVMI were more robust after adjusting for age, diabetes duration, ASBP, HbA_1c, LDL-cholesterol, and antihypertensive and lipid-lowering therapy compared with uACR vs. IMT. There were no statistically significant differences in PWV, LVMI or IMT between patients with reduced (< 60 mL/min/1.73 m²) vs. normal eGFR.ConclusionLevels of urinary albumin excretion, but not reduced eGFR, were associated with increased arterial stiffness, left ventricular mass and atherosclerosis in patients with type 2 diabetes.     

Telemedicine and type 1 diabetes: Is technology per se sufficient to improve glycaemic control?

AimIn the TELEDIAB-1 study, the Diabeo system (a smartphone coupled to a website) improved HbA_1c by 0.9% vs controls in patients with chronic, poorly controlled type 1 diabetes. The system provided two main functions: automated advice on the insulin doses required; and remote monitoring by teleconsultation. The question is: how much did each function contribute to the improvement in HbA_1c?MethodsEach patient received a smartphone with an insulin dose advisor (IDA) and with (G3 group) or without (G2 group) the telemonitoring/teleconsultation function. Patients were classified as “high users” if the proportion of “informed” meals using the IDA exceeded 67% (median) and as “low users” if not. Also analyzed was the respective impact of the IDA function and teleconsultations on the final HbA_1c levels.ResultsAmong the high users, the proportion of informed meals remained stable from baseline to the end of the study 6 months later (from 78.1 ± 21.5% to 73.8 ± 25.1%; P = 0.107), but decreased in the low users (from 36.6 ± 29.4% to 26.7 ± 28.4%; P = 0.005). As expected, HbA_1c improved in high users from 8.7% [range: 8.3–9.2%] to 8.2% [range: 7.8–8.7%] in patients with (n = 26) vs without (n = 30) the benefit of telemonitoring/teleconsultation (−0.49 ± 0.60% vs −0.52 ± 0.73%, respectively; P = 0.879). However, although HbA_1c also improved in low users from 9.0% [8.5–10.1] to 8.5% [7.9–9.6], those receiving support via teleconsultation tended to show greater improvement than the others (−0.93 ± 0.97 vs −0.46 ± 1.05, respectively; P = 0.084).ConclusionThe Diabeo system improved glycaemic control in both high and low users who avidly used the IDA function, while the greatest improvement was seen in the low users who had the motivational support of teleconsultations.     

Heart failure and chronic kidney disease in a registry of internal medicine wards

BackgroundThe aim of the present study was to evaluate the association between heart failure (HF) and chronic kidney disease (CKD) in tertiary care centers using the clinical records of patients enrolled in internal medicine departments.Patients and methodsWe used the clinical records of 1380 elderly patients to identify patients with a history of HF and CKD using admission ICD codes and glomerular filtration rate (GFR) formulas. Magnitude and strength of such associations were investigated by univariable and multivariable analysis.ResultsOf the 1380 patients enrolled, 27.9% had HF (age 80 ± 7, BMI 27 ± 6 kg/m²) and 17.4% CKD (age 81 ± 7, BMI 26.8 ± 6 kg/m²). Both groups were significantly older (P < 0.0001) with BMI higher than the patients without those diagnosis (P < 0.02). Patients with a history of CKD showed higher non-fasting glycaemia (140 ± 86 vs. 125 ± 63 mg/dL, P < 0.001). CKD was significantly associated with HF (P < 0.0001). Patients with HF had an estimated GFR lower than patients without HF (P < 0.0001). Comorbidity and severity indices were significantly higher in subjects with HF (P < 0.0001) and CKD (P < 0.0001) than in those without. Multivariable analysis showed a significant association between HF and age (for five years increase OR 1.13, P < 0.009), BMI (for each 3 kg/m² increase OR 1.15, P < 0.001), GFR (for each decrease of 10 mL/min increase OR 0.92, P < 0.002) and severity index (IS) (for each 0.25 units increase OR 1.43, P < 0.001).ConclusionHF on admission is strongly associated with CKD, older age, BMI, and SI. These data focus the value of epidemiological studies such REPOSI in identifying and monitoring multimorbidity in elderly.     

Interaction between vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D concentrations on metabolic and cardiovascular disease outcomes

Aim25-hydroxyvitamin D (25OHD) concentrations have been shown to be associated with major clinical outcomes, with a suggestion that individual risk may vary according to common genetic differences in the vitamin D receptor (VDR) gene. Hence, we tested for the interactions between two previously studied VDR polymorphisms and 25OHD on metabolic and cardiovascular disease-related outcomes in a large population-based study.MethodsInteractions between two previously studied VDR polymorphisms (rs7968585 and rs2239179) and 25OHD concentrations on metabolic and cardiovascular disease-related outcomes such as obesity- (body mass index, waist circumference, waist-hip ratio (WHR)), cardiovascular- (systolic and diastolic blood pressure), lipid- (high- and low-density lipoprotein, triglycerides, total cholesterol), inflammatory- (C-reactive protein, fibrinogen, insulin growth factor-1, tissue plasminogen activator) and diabetes- (glycated haemoglobin) related markers were examined in the 1958 British Birth cohort (n up to 5160). Interactions between each SNP and 25OHD concentrations were assessed using linear regression and the likelihood ratio test.ResultsAfter Bonferroni correction, none of the interactions reached statistical significance except for the interaction between the VDR SNP rs2239179 and 25OHD concentrations on waist-hip ratio (WHR) (P = 0.03). For every 1 nmol/L higher 25OHD concentrations, the association with WHR was stronger among those with two major alleles (−4.0%, P = 6.26e⁻²⁴) compared to those with either one or no major alleles (−2.3%, P ≤ 8.201e⁻⁰⁷, for both) of the VDR SNP rs2239179.ConclusionWe found no evidence for VDR polymorphisms acting as major modifiers of the association between 25OHD concentrations and cardio-metabolic risk. Interaction between VDR SNP rs2239179 and 25OHD on WHR warrants further confirmation.     

Usefulness of the plasma glucose concentration-to-HbA1c ratio in predicting clinical outcomes during acute illness with extreme hyperglycaemia

AimsTo evaluate the correlation between the plasma glucose-to-glycated haemoglobin ratio (GAR) and clinical outcome during acute illness.MethodsThis retrospective observational cohort study enrolled 661 patients who visited the emergency department of our hospital between 1 July 2008 and 30 September 2010 with plasma glucose concentrations > 500 mg/dL. Systolic blood pressure, heart rate, white blood cells, neutrophils, haematocrit, blood urea nitrogen, serum creatinine, liver function and plasma glucose concentration were recorded at the initial presentation to the emergency department. Data on glycated haemoglobin over the preceding 6 months were reviewed from our hospital database. The glucose-to-HbA_1c ratio (GAR) was calculated as the plasma glucose concentration divided by glycated haemoglobin.ResultsThe GAR of those who died was significantly higher than that of the survivors (81.0 ± 25.9 vs 67.6 ± 25.0; P < 0.001). There was a trend towards a higher 90-day mortality rate in patients with higher GARs (log-rank test P < 0.0001 for trend). On multivariate Cox regression analysis, the GAR was significantly related to 90-day mortality (hazard ratio [HR] for 1 standard deviation [SD] change: 1.41, 95% confidence interval [CI]: 1.22–1.63; P < 0.001), but not to plasma glucose (HR: 0.89, 95% CI: 0.70–1.13; P = 0.328). Rates of intensive care unit (ICU) admission and mechanical ventilator use were also higher in those with higher GARs.ConclusionGAR independently predicted 90-day mortality, ICU admission and use of mechanical ventilation. It was also a better predictor of patient outcomes than plasma glucose alone in patients with extremely high glucose levels.     

FGF21 deficiency is associated with childhood obesity,insulin resistance and hypoadiponectinaemia: The BCAMS Study

ObjectiveFibroblast growth factor 21 (FGF21) exerts beneficial effects on metabolic homoeostasis and has been reported to be regulated by adiponectin, leptin and resistin. However, while an association between increased circulating FGF21 and metabolic disorders has been reported in adults, paediatric-specific data are lacking.Design and methodsThis study investigated the relationship between FGF21 levels and obesity, insulin resistance (IR), the metabolic syndrome (MetS) and adipokines (adiponectin, leptin and resistin) in a cohort of 3231 Chinese youngsters aged 6–18.ResultsThere were gender- and puberty-related differences in FGF21 levels. Unexpectedly, FGF21 levels were decreased in children with obesity, and negatively correlated with insulin, HOMA-IR and leptin levels after adjusting for age, gender, puberty and lifestyle factors. Moreover, multiple regression analyses showed that serum FGF21 positively predicted adiponectin levels while resistin positively predicted FGF21 levels independent of BMI (P < 0.05). Children in the lowest FGF21 quintile were more likely to have IR (OR: 1.85, 95% CI: 1.41–2.42; P = 0.002) and MetS (OR: 1.62, 95% CI: 1.14–2.28; P = 0.007) than those in the highest quintile. Further adjusting for BMI and/or the three adipokines modified the association of FGF21 with MetS (P > 0.10) but not with IR (P < 0.01).ConclusionAlthough the associations between adiponectin, leptin, resistin and metabolic abnormalities in our paediatric population were similar to those in adults, correlations of FGF21 levels with obesity, IR and MetS were the inverse of those found in adults. Our present findings suggest that FGF21 deficiency, rather than resistance, contribute to IR and hypoadiponectinaemia independently of obesity in young people.     

Evolution of subcutaneous adipose tissue fibrosis after bariatric surgery

AimObesity is associated with the development of metabolic complications such as insulin resistance (IR). The mechanisms leading to IR remain unclear. This study aimed to investigate the relationship between adipose tissue fibrosis and IR in obese patients before and after bariatric surgery.MethodsThirty-five obese patients awaiting bariatric surgery (12 with type 2 diabetes) were included in the study. Non-diabetic patients were classified as either insulin-sensitive (n = 11) or insulin-resistant (n = 12), based on the Matsuda insulin sensitivity index (ISI_Matsuda). Homoeostasis model assessment (HOMA-IR) was used for longitudinal evaluation of insulin resistance. Fibrosis was quantified by Masson's trichrome staining on microscopy, and mRNA levels of fibrosis-related genes were examined in subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies collected during and 6 months after bariatric surgery (SAT only).ResultsDespite their similar age, body mass index and fat mass, SAT fibrosis was significantly higher in diabetic vs insulin-sensitive patients (P < 0.05), and associated with IR as assessed by both ISI_Matsuda (r = −0.417, P = 0.038) and HOMA-IR (r = 0.464, P = 0.007) at baseline, whereas VAT fibrosis was not. Six months after surgery and significant weight loss, fibrosis levels remained unchanged in SAT, although IR was significantly reduced in all groups (P < 0.0001). No correlation was found between SAT fibrosis and IR after surgery.ConclusionOverall, these results show a significant but, most likely, transient association between SAT fibrosis and IR in obese humans.     

Adipose tissue is influenced by hypoxia of obstructive sleep apnea syndrome independent of obesity

AimsObstructive sleep apnea syndrome (OSAS) is associated with increased cardiovascular risk and diabetes independent of obesity. We investigated whether adipose tissue dysfunction is exacerbated due to increased tissue hypoxia.MethodsAdipose tissue (AT) oxygenation was measured with a Clarke-type electrode (p_ATO₂) in 16 men with OSAS before and after 4 months of continuous positive airway pressure therapy (CPAP) and in BMI-matched controls. Oxygenation was simultaneously monitored in arterial blood by pulse oximetry (SaO₂); mixed blood in AT microcirculation by reflectance spectroscopy (S_ATO₂) along with blood flow. Markers of hypoxia, adipo- and angiogenesis, inflammation and fibrosis were analysed in AT and serum.ResultsOSAS subjects were more insulin resistant. Despite lower arterial SaO₂ (95.4 ± 1.3% vs. 97.1 ± 1.6%, P = 0.013) in subjects with OSAS, there was no difference in the oxygen content of AT microcirculation (61.6 ± 18.4 vs. 72.2 ± 7.0%, P = 0.07) or p_ATO₂ (49.2 ± 7.5 vs. 50.4 ± 14.7 mmHg, P = 0.83) between groups. Resting AT blood flow was higher in OSAS compared to controls (108.5 ± 22.7 vs. 78.9 ± 24.9 au, P < 0.005) and strongly associated with inflammation markers IL-6 and MCP-1. AT of OSAS subjects showed increased inflammation (TNFA P = 0.049) and fibrosis (COL3A1 P = 0.02), a trend of higher HIF1A expression (P = 0.06) and reduced adipogenesis (PPARG P = 0.006). After CPAP, only expression of the lipid deposition marker LPL increased (30%, P = 0.047).ConclusionsAdipose tissue of awake OSAS subjects appears no more hypoxic than adipose tissue of BMI-matched controls despite daytime hypoxaemia. Increased adipose tissue blood flow may be explained by an increased inflammatory response. We observe features of adipose dysfunction in subjects with OSAS, which attribute to increased cardiometabolic risk associated with this condition.     

Early changes in respiratory quotient and resting energy expenditure predict later weight changes in patients treated for poorly controlled type 2 diabetes

AimThis study looked at whether early changes in resting energy expenditure (REE) and respiratory quotient (RQ) are correlated with later weight changes in patients with type 2 diabetes (T2D) being treated with insulin or GLP-1 analogues, or diet.MethodsA total of 67 patients (age: 57 ± 9 years; BMI: 33.7 ± 5.0 kg/m²; HbA_1c: 9.9 ± 1.5%) began taking an insulin analogue at bedtime (INS, n = 28; initial dose: 0.2 IU/kg) or a GLP-1 analogue (GLP-1, n = 23), or only a dietary intervention (diet, n = 16; restricted carbohydrates and calories). Their respiratory exchanges were monitored on days 0, 1 and 2 before breakfast.ResultsTwo days after starting the bedtime insulin analogue, fasting glycaemia improved (INS: −65 ± 41 mg/dL; GLP-1: −29 ± 48 mg/dL; diet: −31 ± 46 mg/dL; P < 0.05), REE decreased (INS: −162 ± 241 kcal/24 h; GLP-1: 0 ± 141 kcal/24 h; diet: −41 ± 154 kcal/24 h; P < 0.05) and RQ increased (from 0.76 ± 0.04 to 0.80 ± 0.04; P < 0.01), whereas only RQ decreased with diet (from 0.79 ± 0.05 to 0.76 ± 0.04; P < 0.05) and remained unchanged with GLP-1 (P < 0.005 for ΔRQ across treatments). Only 33 patients attended the scheduled examination three months later. HbA_1c improved (INS, n = 16: −1.7 ± 1.4%; GLP-1, n = 12: −2.1 ± 1.4%; diet, n = 5: −1.7 ± 2.8%; NS), while weight changes differed (INS: +1.5 ± 4.3 kg; GLP-1: −2.8 ± 2.8 kg; diet: −2.2 ± 2.7 kg; P < 0.005). After three months, weight changes correlated with early changes in REE (r = −0.37, P < 0.05) and RQ (r = +0.43, P < 0.01), and remained correlated when both changes were included in a multivariate regression analysis (r = 0.58, P < 0.005).ConclusionIn poorly controlled patients with T2D and two days after the introduction of a bedtime insulin analogue, REE decreased by −9% while RQ increased by +5%, pointing to a reduction of lipid oxidation. These changes were predictive of later weight gain.     

Moderate intensity sports and exercise is associated with glycaemic control in women with gestational diabetes

AimTo assess the association of regular, unsupervised sports and exercise during pregnancy, by intensity level, with glycaemic control in women with gestational diabetes (GDM).MethodsProspective cohort study of 971 women who, shortly after being diagnosed with GDM, completed a Pregnancy Physical Activity Questionnaire assessing moderate and vigorous intensity sports and exercise in the past 3 months. Self-monitored capillary glucose values were obtained for the 6-week period following the questionnaire, with optimal glycaemic control defined ≥ 80% values meeting the targets < 5.3 mmol/L for fasting and < 7.8 mmol/L 1-hour after meals. Logistic regression estimated the odds of achieving optimal control; linear regression estimated activity level-specific least square mean glucose, as well as between-level mean glucose differences.ResultsFor volume of moderate intensity sports and exercise ([MET × hours]/week), the highest quartile, compared to the lowest, had significantly increased odds of optimal control (OR = 1.82 [95% CI: 1.06–3.14] P = 0.03). There were significant trends for decreasing mean 1-hour post breakfast, lunch and dinner glycaemia with increasing quartile of moderate activity (all P < 0.05). Any participation in vigorous intensity sports and exercise was associated with decreased mean 1-hour post breakfast and lunch glycaemia (both P < 0.05). No associations were observed for fasting.ConclusionHigher volumes of moderate intensity sports and exercise, reported shortly after GDM diagnosis, were significantly associated with increased odds of achieving glycaemic control. Clinicians should be aware that unsupervised moderate intensity sports and exercise performed in mid-pregnancy aids in subsequent glycaemic control among women with GDM.     

Serum sex steroids and steroidogenesis-related enzyme expression in skeletal muscle during experimental weight gain in men

ObjectivesLow-circulating testosterone is associated with development of type 2 diabetes in obese men. In this study, we examined the effects of experimental overfeeding and weight gain on serum levels of sex hormones and skeletal muscle expression of steroidogenic enzymes in healthy men with (FH+) and without (FH–) a family history of type 2 diabetes.MethodsFollowing a 3-day lead in energy balanced diet, FH+ (n = 9) and FH– men (n = 11) were overfed by 5200 kJ/day (45% fat) for 28 days. Body weight, fasting glucose, insulin, sex steroid, sex hormone binding globulin (SHBG) levels, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and body fat (DXA) were assessed in all individuals at baseline and day 28, and sex steroidogenesis-related enzyme expression in vastus lateralis biopsies was examined in a subset (n = 11).ResultsBody weight, fat mass and fasting insulin levels were increased by overfeeding (P < 0.01) and insulin was increased significantly more in FH+ men (P < 0.01). Serum sex hormone binding globulin (SHBG) and 5α-dihydrotestosterone (DHT) were reduced with overfeeding (P < 0.05), and serum testosterone and DHT were reduced to a greater extent in FH+ men (P < 0.05). Overfeeding reduced mRNA expression of 3β-hydroxysteroid dehydrogenase (HSD) and 17βHSD (P ≤ 0.007), independently of group. 5α-Reductase (SRD5A1) mRNA expression was not changed overall, but a time by group interaction was observed (P = 0.04).ConclusionOverfeeding reduced SHBG and muscle expression of enzymes involved in the formation of testosterone in skeletal muscle. Men with a family history of T2DM were more susceptible to deleterious outcomes of overfeeding with greater reductions in serum testosterone and DHT and greater increases in markers of insulin resistance, which may contribute to increased risk of developing type 2 diabetes.     

Dipeptidyl peptidase-4 inhibitors and risk of arthralgia: A systematic review and meta-analysis

BackgroundThe US Food and Drug Administration has warned that treatment with dipeptidyl peptidase (DPP)-4 inhibitors may promote serious arthralgia. However, the clinical evidence for this is relatively lacking.ObjectiveFor this reason, a systematic review and meta-analysis of randomized controlled trials (RCTs) were carried out to determine the relationship between DPP-4 inhibitors and risk of arthralgia, and also to investigate any potential risk factors.MethodsAn extensive electronic search for RCTs comparing DPP-4 inhibitors with any comparators was performed up to July 2016. Outcomes of interest were overall and serious arthralgia. Summary risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.ResultsA total of 67 RCTs (involving 79,110 patients) was ultimately included. Pooled results showed that DPP-4 inhibitors were associated with a slightly but significantly increased risk of overall arthralgia (RR: 1.13, 95% CI: 1.04–1.22; P = 0.003) and a non-significant increased risk of serious arthralgia (RR: 1.44, 95% CI: 0.83–2.51; P = 0.20). Also, subgroup analyses showed that add-on/combination therapy and longer diabetes duration (> 5 years) were possible factors associated with the increased risk of overall arthralgia.ConclusionThese findings suggest that DPP-4 inhibitors can increase the risk of arthralgia. Thus, the benefits of glycaemic control must be weighed against the risk of arthralgia when prescribing DPP-4 inhibitors. Further studies are now needed to identify and confirm these risk factors.     

Sex hormone levels are not associated with progression of renal disease in male patients with T2DM

BackgroundGreater renal function decline (RFD) in type 2 diabetes (T2DM) has been suggested in men compared with women, and imbalances in estrogen/androgen levels have been associated with cardiovascular disease mortality in elderly men, but it remains unclear whether sex hormone disequilibrium is related to diabetic nephropathy (DN) in men with T2DM.ObjectiveThis study examined the relationship between sex steroid concentrations and renal outcomes in male T2DM patients.Population and methodsTotal testosterone (T), total estradiol (E2), sex hormone-binding globulin (SHBG), and total and calculated free (cf) E2/T ratios were compared in 735 male T2DM patients with (n = 513) and without (n = 222) DN, using a cross-sectional approach. Also, in a pilot complementary prospective nested case-control cohort, total E2/total T and cfE2/cfT were evaluated according to a hard renal outcome (HRO): end-stage renal disease/doubling of baseline serum creatinine (36 HRO cases, 72 HRO controls) and rate of eGFR decline (68 rapid vs 68 slow RFD).ResultWith the cross-sectional approach, E2 and cfE2 were higher in DN cases vs DN controls (95.5 vs 86.8 pmol/L [P = 0.0246] and 2.59 vs 2.36 pmol/L [P = 0.005], respectively). The difference in E2 persisted on multivariate analysis. In the prospective approach, E2 and T concentrations, and total E2/total T and cfE2/cfT2 ratios did not differ in HRO cases vs controls or in patients with rapid vs slow RFD.ConclusionAlthough positively related to DN in the cross-sectional analysis, progression of renal disease in male patients with T2DM was not related to either sex hormone levels or aromatase index as reflected by E2/T ratio.     

Epicardial adipose tissue volume as a marker of coronary artery disease severity in patients with diabetes independent of coronary artery calcium: Findings from the CTRAD study

AimsThe association between epicardial adipose tissue (EAT) volume and coronary artery disease (CAD) severity was evaluated, independent of traditional risk factors and coronary artery calcium (CAC) scores, in patients with diabetes type 2 (DM-2) using cardiac computed tomography angiography (CTA).MethodsA multivariate analysis was utilized to assess for an independent association after calculating EAT volume, CAD severity, and calcium scores in 92 patients with DM-II from the CTRAD study. We graded CAD severity as none (normal coronaries), mild-moderate (<70% stenosis), and severe (70% or greater stenosis).ResultsA total of 39 (42.3%) asymptomatic patients with diabetes did not have CAD; 30.4% had mild/moderate CAD; and 27.1% had severe CAD. Mean EAT volume was highest in patients with severe CAD (143.14 cm³) as compared to mild/moderate CAD (112.7 cm³), and no CAD (107.5 cm³) (p = 0.003). After adjustment of clinical risk factors, notably, CAC score, multivariate regression analysis showed EAT volume was an independent predictor of CAD severity in this sample (odds ratio 11.2, 95% confidence interval 1.7–73.8, p = 0.01).ConclusionsIncreasing EAT volume in asymptomatic patients with DM-II is associated with presence of severe CAD, independent of BMI and CAC, as well as traditional risk factors.     

Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)

BackgroundA family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives.MethodsData from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age < 40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes.ResultsBoth FHD–T1D (OR: 5.8; 95% CI: 3.2–10.3) and FHD–T2D (OR: 1.9; 95% CI: 1.5–2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD–T2D (OR: 2.7; 95% CI: 2.2–3.3), but not FHD–T1D. In LADA patients, FHD–T1D vs FHD–T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P = 0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P = 0.0576).ConclusionThe risk of LADA is substantially increased with FHD–T1D but also, albeit significantly less so, with FHD–T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD–T1D had more T1D-like features, emphasizing the heterogeneity of LADA.     

Arritmias ventriculares en superrespondedores a la terapia de resincronización cardiaca

Introduction and objectivesCardiac resynchronization therapy is associated with improved quality of life and reduced morbidity and mortality in patients with severe ventricular dysfunction and wide QRS. However, its role in the reduction of ventricular arrhythmias is more controversial.MethodsWe compared the incidence of ventricular arrhythmias in patients who were undergoing cardiac resynchronization therapy with an implantable cardioverter-defibrillator in terms of the degree of echocardiographic response to resynchronization. Patients were classified in 3 subgroups; super-responders, responders, and nonresponders.ResultsWe included 196 patients who were followed up for a median 30.1 months [interquartile range, 18.0-55.1 months]. We recorded the presence of ventricular arrhythmias in 37 patients (18.8%); 3 patients (5.9%) in the super-responder group had ventricular arrhythmias vs 14 (22.2%) among the responders and 20 (24.4%) in the group of nonresponders (P = .025). In multivariate analysis, the only independent predictors of the appearance of ventricular arrhythmias were secondary–prevention device implantation (odds ratio = 4.04; 95% confidence interval, 1.52-10.75; P = .005), absence of echocardiographic super-response (odds ratio = 3.81; 95% confidence interval, 1.04-13.93; P = 043), QRS >160 ms (odds ratio = 2.39; 95% confidence interval, 1.00-1.35; P = .049) and treatment with amiodarone (odds ratio = 2.47; 95% confidence interval, 1.03-5.91; P = .041).ConclusionsThe patients classified as super-responders to cardiac resynchronization therapy had a significant reduction in incidence of ventricular arrhythmias by comparison with the other patients. Despite this, arrhythmic episodes do not completely disappear in this subgroup.Full English text available from: www.revespcardiol.org/en     

Relationship between olfactory dysfunction and cognitive impairment in elderly patients with type 2 diabetes mellitus

AimsRecent clinical studies identified the relation between olfactory dysfunction and cognitive impairment in the elderly without type 2 diabetes mellitus. The aim of the present study was to define the relation between olfactory function and cognition in elderly patients with type 2 diabetes mellitus.MethodsThe study participants comprised 250 elderly (age, 68–77, median 72) Japanese outpatient with type 2 diabetes mellitus free of clinically-evident cognitive impairment. Olfactory and cognitive functions were evaluated by the Open Essence (OE) test and Mini-mental State Examination (MMSE), respectively.ResultsBased on the MMSE score, 62.0%, 24.4%, and 13.6% of the participants were considered to have no impairment, possible cognitive impairment and probable dementia, respectively. The OE test score of the probable dementia group was significantly lower than other groups. Furthermore, age and serum uric acid were significantly higher in the probable dementia group than other groups. Simple correlation analysis showed positive correlation between the MMSE score and diastolic blood pressure, education, OE test score, total cholesterol, LDL cholesterol, folic acid, and negative correlation with age, HbA_1c, aspartate aminotransferase, serum adiponectin and urinary albumin excretion. Multivariate regression analysis showed that OE test score correlated significantly and independently with MMSE score (standardized coefficients β = 0.542, R² = 0.478, P < 0.01), in addition to education level, HbA1c and serum adiponectin.ConclusionsThe results suggested the association of olfactory dysfunction with cognitive impairment in elderly patients with type 2 diabetes mellitus.