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.     

Impact of flexible insulin therapy on blood glucose variability,oxidative stress and inflammation in type 1 diabetic patients: The VARIAFIT study

AimsHbA_1c only partially predicts vascular risk in patients with type 1 diabetes (T1D), and a role for blood glucose variability (BGV) is a matter of debate. For this reason, this study investigated the impact of an educational programme of flexible insulin therapy (FIT) on BGV and oxidative stress.MethodsTests were conducted on 30 adult T1D patients in a prospective, single-centre trial at baseline (M0), and at 3 and 6 months (M3 and M6, respectively) of the FIT programme to determine BGV, as reflected by mean amplitude of glycaemic excursions (MAGE), low blood glucose index (LBGI), lability index (LI), average daily risk range (ADRR), glycaemic lability (scored by two diabetologists), urinary leukotriene E₄ (LTE4), 11-dehydro-thromboxane B₂ (TXB2) and 8-iso-prostaglandin F2α (PGF2).ResultsHbA_1c (7.7 ± 0.9%), ADRR, MAGE, LBGI and LI did not change from M0 to M3 and M6, although ADRR and LBGI significantly improved at M3 and M6 in patients with the highest baseline indices (≥ 40 and ≥ 5, respectively). TXB2 declined at M6 (832 ± 625 vs. 633 ± 972 pg/mg; P = 0.048), whereas LTE4 and PGF2 remained stable. ADRR showed the strongest correlation with glycaemic lability scores at all visits (r ≥ 0.84, P < 0.0001).ConclusionA FIT educational programme improved BGV only in patients with the highest baseline variability, and led to no changes in HbA_1c, while ADRR closely correlated with glycaemic lability score. Our data do not support a relationship between BGV and oxidative stress in T1D patients, although the impact of variability on TXB2 deserves further investigation (ClinicalTrials.gov NCT00973492).     

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.     

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.     

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.     

Early age at menarche and gestational diabetes mellitus risk: Results from the Healthy Baby Cohort study

AimEarly age at menarche has been reported to increase type 2 diabetes risk, but little is known of its impact on gestational diabetes mellitus (GDM) risk. The aim of this study was to examine the association between age at menarche and plasma glucose levels as well as GDM risk.MethodsA total of 6900 pregnant women from the Healthy Baby Cohort Study were included in our analysis. Age at menarche was self-reported and categorized into five groups (9–11, 12, 13, 14 and 15–18 years of age). GDM was diagnosed using the International Association of Diabetes and Pregnancy Study Groups criteria. Comparisons of plasma glucose levels according to age at menarche categories were performed using analysis of covariance. Logistic regression models were used to estimate the association between age at menarche and GDM risk.ResultsOf our 6900 participants, 1015 (14.7%) were diagnosed with GDM. Mean age at menarche was 13.1 ± 1.2 years. Early age at menarche (9–11 years) was associated with higher fasting, 1-h and 2-h plasma glucose levels (all P < 0.05) compared with menarche at age 13 years. Furthermore, early age at menarche was linked to increased GDM risk after adjusting for potential confounders (OR: 1.41, 95% CI: 1.06–1.87).ConclusionEarly age at menarche is an independent risk factor for GDM and, as such, may help to identify women at higher GDM risk who would benefit from early preventative strategies.     

Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations

AimWe hypothesised that some of the genetic risk for gestational diabetes (GDM) is due to the fetal genome affecting maternal glucose concentrations. Previously, we found associations between fetal IGF2 gene variants and maternal glucose concentrations in late pregnancy.MethodsIn the present study, we tested associations between SNP alleles from 15 fetal imprinted genes and maternal glucose concentrations in late pregnancy in the Cambridge Baby Growth and Wellbeing cohorts (1160 DNA trios).ResultsFour fetal SNP alleles with the strongest univariate associations: paternally-transmitted IGF2 rs10770125 (P-value = 2 × 10^–4) and INS rs2585 (P-value = 7 × 10^–4), and maternally-transmitted KCNQ1(OT1) rs231841 (P-value = 1 × 10^–3) and KCNQ1(OT1) rs7929804 (P-value = 4 × 10^–3), were used to construct a composite fetal imprinted gene allele score which was associated with maternal glucose concentrations (P-value = 4.3 × 10^–6, n = 981, r² = 2.0%) and GDM prevalence (odds ratio per allele 1.44 (1.15, 1.80), P-value = 1 × 10^–3, n = 89 cases and 899 controls). Meta-analysis of the associations including data from 1367 Hyperglycaemia and Adverse Pregnancy Outcome Study participants confirmed the paternally-transmitted fetal IGF2/INS SNP associations (rs10770125, P-value = 3.2 × 10^–8, rs2585, P-value = 3.6 × 10^–5) and the composite fetal imprinted gene allele score association (P-value = 1.3 × 10^–8), but not the maternally-transmitted fetal KCNQ1(OT1) associations (rs231841, P-value = 0.4; rs7929804, P-value = 0.2).ConclusionThis study suggests that polymorphic variation in fetal imprinted genes, particularly in the IGF2/INS region, contribute a small but significant part to the risk of raised late pregnancy maternal glucose concentrations.     

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.     

Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL versus insulin glargine 100 U/mL in insulin-naïve people with type 2 diabetes: 12-month results from the EDITION 3 trial

AimTo explore if efficacy and safety findings for insulin glargine 300 U/mL (Gla-300) versus insulin glargine 100 U/mL (Gla-100), observed over 6 months in insulin-naïve people with type 2 diabetes, are maintained after 12 months.MethodsEDITION 3 was a phase 3a, randomized, multicentre, open-label, parallel-group, treat-to-target study of once-daily Gla-300 versus Gla-100 (target fasting self-monitored plasma glucose, 4.4–5.6 mmol/L [80–100 mg/dL]). Participants completing the initial 6-month treatment phase continued their previously allocated basal insulin.ResultsOf 878 participants randomized, 337/439 (77%) and 314/439 (72%) assigned to Gla-300 and Gla-100, respectively, completed 12 months of treatment. Improved glycaemic control was sustained until 12 months in both treatment groups, with similar reductions in HbA_1c from baseline to month 12 (difference: −0.08 [95% confidence interval (CI): −0.23 to 0.07] % or −0.9 [−2.5 to 0.8] mmol/mol). Relative risk of experiencing ≥ 1 confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycaemic event with Gla-300 versus Gla-100 was 0.86 (95% CI: 0.69 to 1.07) at night and 0.92 (0.82 to 1.03) at any time of day. For events with a glycaemic threshold of < 3.0 mmol/L (< 54 mg/dL) these numbers were 0.76 (0.49 to 1.19) and 0.66 (0.50 to 0.88). A similar pattern was seen for documented symptomatic events. No between-group differences in adverse events were identified.ConclusionOver 12 months, Gla-300 treatment was as effective as Gla-100 in reducing HbA_1c in insulin-naïve people with type 2 diabetes, with lower overall risk of hypoglycaemia at the < 3.0 mmol/L threshold.     

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.     

Study of the impact of viral load of hepatitis C on patients with concomitant psoriasis vulgaris

Background and study aimConcomitant hepatitis C virus (HCV) infection and psoriasis vulgaris (PV) are not uncommon coexisting diseases, especially in areas with high viral hepatitis endemicity. To date, data about the interaction between both diseases are scarce. Therefore, we aimed to describe the possible interplay between the HCV viral load and psoriatic activity in concomitant Egyptian diseased patients.Patients and methodsBetween December 2011 and August 2013, all psoriatic patients attending Assiut University Hospital outpatient clinics were tested for HCV serologic assay. Patients with positively coexisting diseases were further reevaluated for psoriasis area severity index (PASI) score assessment, liver function tests, HCV-RNA-polymerase chain reaction (PCR) assays, and sonographic examination of the liver. For comparative purposes, another matched group (n = 26) with psoriasis only (HCV-negative group) was enrolled as a control.ResultsDuring the period of the study, 20 patients with concomitant PV and HCV infection (HCV-positive group; 50% males, mean age of 44.15 ± 10.66 years) were recruited. The mean PASI score was 44.75 ± 10.38 and clinical signs of liver dysfunction were observed in 40% (n = 8), 100% had abnormal liver function tests (n = 20), and 75% had sonographic findings of cirrhosis (n = 15). The PASI score was significantly higher in the HCV-positive psoriatic group compared to the HCV-negative control (p < 0.001). Significant correlations were detected between the PASI score and the viral loads, and also with alanine aminotransferase (ALT).ConclusionWhen HCV was found concomitantly with PV, a high possibility of severe disease pattern will be expected that entails special precautions in the treatment process.     

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.     

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.     

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.     

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.     

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.     

Skin autofluorescence is associated with past glycaemic control and complications in type 1 diabetes mellitus

As skin autofluorescence (AF) can assess subcutaneous accumulation of fluorescent advanced glycation end-products (AGEs), this study aimed to investigate whether it was linked to glycaemic control and complications in patients with type 1 diabetes mellitus (T1DM). Using the AGE Reader™, AF was measured in T1DM patients referred to Haut-Levêque Hospital (Bordeaux, France); data on their HbA_1c levels measured every 6 months as far back as the last 5 years were also collected. The association of AF with the patients’ past glucose control, based on their latest HbA_1c values, and the means of the last five and 10 HbA_1c values, and with diabetic complications was also examined by linear regression analysis. The sample included 300 patients: 58% were male; the mean age was 49 (SD 17) years and the mean diabetes duration was 21 (SD 13) years. The median skin AF measurement was 2.0 [25th–75th percentiles: 1.7–2.4] arbitrary units (AU), and this was associated with age (β = 0.15 per 10 years, P < 0.001) and diabetes duration (β = 0.17 per 10 years, P < 0.001). After adjusting for age and estimated glomerular filtration rate (eGFR), the skin AF measurement was also related to the means of the last five and 10 HbA_1c values (β = 0.10 per 1% of HbA_1c, P = 0.005, and β = 0.13 per 1% of HbA_1c, P = 0.001, respectively). In addition, the skin AF was associated with retinopathy (P < 0.001), albuminuria (P < 0.001) and decreased eGFR (P < 0.001). In conclusion, the skin AF is related to the long-term glucose control and diabetic complications.     

Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL compared with glargine 100 U/mL in Japanese adults with type 2 diabetes using basal insulin plus oral anti-hyperglycaemic drugs (EDITION JP 2 randomised 12-month trial including 6-month extension)

AimsTo compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months.MethodsEDITION JP 2 was a randomised, open-label, phase 3 study. Following a 6-month treatment period, participants continued receiving previously assigned once daily Gla-300 or Gla-100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period. Glycaemic control, hypoglycaemia and adverse events were assessed.ResultsThe 12-month completion rate was 88% for Gla-300 and 96% for Gla-100, with comparable reasons for discontinuation. Mean HbA_1c decrease from baseline to month 12 was 0.3% in both groups. Annualised rates of confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycaemia were lower with Gla-300 than Gla-100 (nocturnal [00:00–05:59 h]: rate ratio 0.41; 95% confidence interval: 0.18 to 0.92; anytime [24 h]: rate ratio 0.64; 95% confidence interval: 0.44 to 0.94). Cumulative number of hypoglycaemic events was lower with Gla-300 than Gla-100. Adverse event profiles were comparable between treatments.ConclusionOver 12 months, Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results.     

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.