Cardiovascular autonomic function and vibration perception threshold in type 2 diabetes mellitus

ObjectiveThe aim of this study was to compare cardiovascular autonomic function tests (AFT) and vibration perception threshold (VPT) of patients with type 2 diabetes mellitus (T2DM) with controls.Research Design/MethodsThe study was conducted on 60 diabetic patients comparing with 30 controls. The cardiovascular AFT and VPT were assessed in both groups.ResultsAmong cardiovascular AFT, E:I ratio [1.24 (1.2–1.32) vs 1.3 (1.24–1.4), p = 0.001], and Valsalva ratio [1.28 (1.22–1.4) vs 1.6 (1.5–1.73), p = 0.001], the indicators of parasympathetic reactivity were reduced in T2DM. Rise in DBP during handgrip, an indicator of sympathetic reactivity was lower in T2DM [12 (10–14) vs 16 (14–18) mmHg, p = 0.001] whereas, fall in SBP during head up tilt [4 (4–8) vs 5 (4–8) mmHg] was comparable. VPT (somatic sensation) was comparable between T2DM and control.ConclusionAutonomic involvement is more marked than somatic, and parasympathetic involvement is more marked than the sympathetic, possibly reflecting severity and chronological pattern of their involvement.     

Heart rate-corrected QT interval prolongation is associated with decreased heart rate variability in patients with type 2 diabetes

We investigated the association between the heart rate-corrected QT interval (QTc interval) measured by standard electrocardiography and heart rate variability (HRV) in patients with type 2 diabetes mellitus (T2DM). From March 1, 2009, to December 12, 2009, 411 patients with T2DM who underwent resting 12-lead electrocardiography and cardiovascular autonomic function testing concurrently without the exclusion criteria were consecutively recruited in this cross-sectional study. Time- and frequency-domain HRV variables were assessed for 5 minutes by beat-to-beat HRV recording. The QT interval was corrected for the heart rate using Bazett’s formula. QTc interval measurements of >440 ms were considered abnormally prolonged. The mean age and diabetes duration were 56.3 ± 10.6 years and 9.6 ± 7.3 years, respectively. A total of 90 patients had QTc interval prolongation (21.9%). The participants with a prolonged QTc interval were older (59.4 ± 10.1 years vs 55.5 ± 10.6 years, P = .002), were more likely to be a woman (72.2% vs 51.7%, P = .001), had a higher prevalence of hypertension (46.7% vs 33.4%, P = .022), had a higher hemoglobin A1c level (8.8% ± 2.2% vs 8.2% ± 1.8%, P = .045), and had decreased values for the variables measuring HRV, except for the low frequency (LF)/high frequency (HF) ratio (total power [TP], 147.7 [74.1–335.9] ms vs 328.7 [185.7–721.7] ms, P = .002). After adjusting for multiple confounders, QTc interval prolongation was associated with the lowest quartile of the HRV parameters of TP (odds ratio [OR] = 3.99; 95% confidence interval [CI]: 2.29–6.96), HF (OR = 3.20; 95% CI: 1.84–5.58), LF (OR = 3.68; 95% CI: 2.10–6.43), standard deviation of the normal-to-normal interval (OR = 3.31; 95% CI: 1.89–5.77), and root-mean-square of the successive differences (OR = 1.98; 95% CI: 1.13–3.47) in patients with T2DM. Decreased values for the variables measuring HRV, except for the LF/HF ratio, might be associated with QTc interval prolongation in patients with T2DM.     

High frequency of osteoporosis and fractures in women with dermatomyositis/polymyositis

Bone mass was only previously studied in juvenile dermatomyositis/polymyositis (DM/PM) patients. Therefore, the objective this study was to evaluate the prevalence of osteoporosis and fractures in adult DM/PM. Forty female DM/PM and 78 age-, gender-, and BMI-matched healthy controls were studied. Medical charts and clinical interviews of all patients were evaluated for demographic and clinical data, including disease activity, cumulative doses of glucocorticoid, menarche and menopause age, and fractures. Bone mineral density (BMD) using dual X-ray absorptiometry (DXA) were measured at lumbar spine (L1–L4) and hip. A decreased BMD in lumbar spine [0.902 (0.136) vs. 0.965 (0.141) g/cm², P?=?0.022] and femoral neck [0.729 (0.12) vs. 0.784 (0.127) g/cm², P?=?0.027] was observed in patients compared to controls. In addition, osteoporosis was more frequent in patients than in controls in both lumbar spine (20 vs. 3.8%, P?=?0.007) and the femoral neck (27.5 vs. 10.3%, P?=?0.016). Moreover, a high prevalence of fractures was found in patients in comparison to healthy subjects (17.9 vs. 5.1%, P?=?0.040; OR?=?3.92; CI 95%:1.07–14.33). Comparing DM/PM patients with (n?=?17) and without (n?=?23) osteoporosis/fractures, significant differences were observed regarding age [56.8 (11.9) vs. 48.3 (13.2) years, P?=?0.042], weight [62.05 (13.56) vs. 71.51 (11.46) kg, P?=?0.022] and frequency of post menopausal women (94.1 vs. 65.2%, P?=?0.0002). No differences were observed concerning height, lean mass, total fat mass, disease activity, mean value of creatine kinase, cumulative glucocorticoid dose, or bisphosphonate use. Logistic regression analysis revealed a negative association between the presence of osteoporosis/fractures and weight (OR: 0.92, 95% CI: 0.85–0.98; P?=?0.016). This is the first study that analyzed bone mass in adult DM/PM patients and it demonstrated that about one quarter of these patients have osteoporosis/fracture.     

High-frequency modulation of heart rate variability during exercise in patients with COPD

STUDY OBJECTIVES: To evaluate cardiac autonomic modulation in patients with COPD during peak exercise. METHODS: Fifty-three patients with COPD (mean FEV(1), 35% predicted [SD, 11% predicted]; mean PaO(2), 68 mm Hg [SD, 11 mm Hg]; mean PaCO(2), 40 mm Hg [SD, 7 mm Hg]; mean age, 61 years [SD, 10 years]; 26 women and 27 men) and 14 healthy control subjects aged 60 years (SD, 8 years) [seven women and seven men] were studied at rest and during ramped bicycle ergometry to their volitional peak. Patients were not receiving autonomic medications other than inhaled beta-agonist agents and/or anticholinergic agents. Control subjects were not receiving any medications. Cardiac autonomic modulation was assessed via time-frequency analysis (Wigner-Ville) of ECG-derived heart rate variability as the power in the low-frequency (LF) band (ie, 0.04 to 0.15 Hz) and the high-frequency (HF) band (ie, > 0.15 to 0.4 Hz) averaged from > 3 min at rest and minutes 2 through 5 of their exercise period. RESULTS: Patients with COPD had a significantly increased mean, ln-transformed HF band from rest to peak exercise (9.9 ms(2) [SD, 1.4 ms(2)] vs 10.7 ms(2) [SD, 1.4 ms(2)], respectively; p < 0.01), while the HF band was unchanged for the control group (10.7 ms(2) [SD, 1.5 ms(2)] vs 10.4 ms(2) [1.3 ms(2)], respectively; difference not significant). The mean ln-transformed LF band was significantly increased from rest to peak exercise in patients with COPD (10.9 ms(2) [SD, 1.5 ms(2)] vs 11.5 ms(2) [SD, 1.4 ms(2)], respectively; p < 0.01) and in control subjects (10.9 ms(2) [SD, 1.5 ms(2)] vs 11.5 ms(2) [SD, 1.3 ms(2)], respectively; p < 0.01). The mean LF/HF ratio was significantly decreased from rest to peak exercise in patients with COPD (3.1 [SD, 1.5] vs 2.5 [SD, 1.0], respectively; p < 0.01) and was increased in control subjects (1.9 [SD, 0.8] vs 2.4 [1.0], respectively; p < 0.01). When expressed in normalized units ([absolute power of the components]/[total power - very low frequency power] x 100), the HF band was again significantly greater during peak exercise than at rest in the patients with COPD and was unchanged during peak exercise for the control group. Autonomic changes were not significantly correlated with age, gender, body mass index, spirometry, lung volumes, resting gas exchange, or oxygen saturation during exercise. CONCLUSION: These data suggest that, in contrast to control subjects, the balance of sympathetic to parasympathetic cardiac modulation decreases in patients with COPD during maximal volitional exercise.     

Transmission disequilibrium of rs4809957 in type 2 diabetes mellitus families and its association with vitamin D deficiency: A family-based case-control study

Aims

Association between T2DM and vitamin D was found in many epidemiologic reports. And 24-hydroxylase encoded by CYP24A1 is the very enzyme that degrades the active vitamin D metabolite. We aimed to investigate the association between rs4809957 in CYP24A1 and T2DM, as well as vitamin D level.

Modified orthostatic load for spectral analysis of short-term heart rate variability improves the sensitivity of autonomic dysfunction assessment

AimTo evaluate the impact of orthostatic load for sensitivity of short-term spectral analysis of heart rate variability (HRV) assessment of potential early autonomic dysfunction in diabetes mellitus.MethodsComparison of results of short-term time- and frequency-domain analysis of HRV during single positions and during modified orthostatic load (supine 1–standing–supine 2, each position 300 s) in diabetic subjects with good glycemic control (n=80, age 38±14, diabetes duration 16±10 years) and without autonomic neuropathy as assessed by a standard bedside reflex test battery, and in nondiabetic controls (n=150, age 40±13 years).ResultsNone of the short-term frequency-domain parameters [absolute and logarithmic (LN) values of spectral powers in total- (TF), low- (LF), and high-frequency (HF) bands and its centroid frequencies] as obtained in single positions “supine” or “standing” revealed a significant difference between well-controlled patients and healthy controls (P>.3). However, during modified orthostatic load, significant differences in ΔLN TF_{(supine 1–supine 2)} and in ΔLN LF_{(supine 1–supine 2)} as well as in ΔLN LF_{(standing–supine 2)} values between diabetic and healthy subjects were recorded [?0.2±0.5 vs. ?0.1±0.4 LN (ms²), P=.05; ?0.3±0.8 vs. 0.1±0.7 LN (ms²), P=.001 and 0.2±1.0 vs. 0.4±0.9 LN (ms²), P=.05, respectively] with insignificant intergroup differences in related centroid frequencies. This finding suggests a delayed recovery of LF spectral power in diabetic subjects after orthostatic challenge.ConclusionsWhen compared with single position measurements, the modified orthostatic load protocol improves the sensitivity of short-term HRV examination. In well-controlled diabetic subjects without cardiovascular autonomic neuropathy (as excluded by standard cardiovascular reflex testing), the delayed recovery of LF band spectral power after orthostatic load with standing up indicates diminished parasympathetic activation.     

Heart Rate Variability Declines with Increasing Age and CTG Repeat Length in Patients with Myotonic Dystrophy Type 1

Background: Cardiac myopathy manifesting as arrhythmias is common in the neurological disease, myotonic dystrophy type 1 (DM1). The purpose of the present study was to evaluate heart rate variability (HRV) in patients with DM1. Methods: In a multicenter study, history, ECG, and genetic testing were performed in DM1 patients. Results: In 289 patients in whom the diagnosis of DM1 was confirmed by a prolonged cytosine‐thymine‐guanine (CTG) repeat length the most common ambulatory ECG abnormality was frequent ventricular ectopy (16.3%). The 24‐hour time domain parameters of SDNN (SD of the NN interval) and SDANN (SD of the mean NN, 5‐minute interval) declined as age and CTG repeat length increased (SDNN: ?8.5 ms per decade, 95% confidence intervals [CI]?12.9, ?4.2, ?8.7 ms per 500 CTG repeats, CI ?15.7, ?1.8, r = 0.24, P < 0.001 ; SDANN: ?8.1 ms per decade, CI ?12.4, ?3.8, ?8.8 ms per 500 CTG repeats, CI ?15.7, ?1.9, r = 0.23, P < 0.001 ). Short‐term frequency domain parameters declined with age only (total power: ?658 ms² per decade, CI: ?984, ?331, r = 0.23, P < 0.001 ; low frequency (LF) power ?287 ms² per decade, CI: ?397, ?178, r = 0.30, P < 0.001 ; high frequency (HF) power: ?267 ms² per decade, CI: ?386, ?144, r = 0.25, P < 0.001 ). The LF/HF ratio increased as the patient aged (0.5 per decade, CI: 0.1, 0.9, r = 0.13, P = 0.03 ). Conclusions: In DM1 patients a decline in HRV is observed as the patient ages and CTG repeat length increases. A.N.E. 2003; 8(3):227‐232     

Gabapentin therapy improves heart rate variability in diabetic patients with peripheral neuropathy

PurposeDiabetic cardiac neuropathy, which is characterized by reduced heart rate variability (HRV), frequently coexists with peripheral neuropathy. Gabapentin has been used for the treatment of diabetic neuropathy. We aimed to evaluate the possible effect of gabapentin treatment on autonomic function in patients with type 2 diabetes via HRV.MethodsThirty patients with type 2 diabetes mellitus and peripheral neuropathy and 28 age- and sex-matched healthy controls were consecutively registered. Each patient underwent HRV measurements, and diabetic patients were administered gabapentin. After 3 months of gabapentin therapy, HRV parameters were measured again.ResultsBaseline HRV parameters were blunted in patients with diabetes mellitus according to the controls [standard deviation of all NN intervals (SDNN, ms): 106.3±29.9 vs. 148.8±36.5, P=.001; power spectrum of the high-frequency band (HF, ms²): 133.6±98.3 to 231.4±197.6, P=.02; power spectrum of the low-frequency band (LF, ms²): 341.8±247.8 to 511.5±409.4, P=.048; LF/HF ratio: 3.3±2.4 to 2.6±1.5, P=.33]. After 3 months of treatment with gabapentin, some HRV parameters showed some improvement. SDNN (106.2±29.8 to 119.4 ± 25, P=.016) and HF (133.6±98.3 to 167.6±118.3, P=.021) increased significantly. LF/HF ratio decreased (from 3.3±2.4 to 2.3±1.9, P=.039) and LF remained unchanged (341.8±247.8 to 352.3±228.9, P=.88).ConclusionsTherapeutic doses of gabapentin not only alleviate neuropathic symptoms but also improve cardiac autonomic function in diabetic patients with peripheral neuropathy.     

A randomized double-blind placebo-controlled trial showing rifaximin to improve constipation by reducing methane production and accelerating colon transit: A pilot study

Objective

Gut microbe-derived methane may slow colon transit causing chronic constipation (CC). Effect of rifaximin on breath methane and slow-transit CC was evaluated.

Method

Bristol stool form, frequency, colon transit time (CTT), and breath methane were evaluated in 23 patients with CC (10 patients with constipation-predominant irritable bowel syndrome [IBS-C], 13 functional constipation, Rome III) and m-ethane production compared with 68 non-constipating IBS. Methane-producing CC (basal ≥?10 PPM and/or post-lactulose rise by >?10 PPM) was randomized (double-blind) to rifaximin (400-mg thrice/day, 2-weeks) or placebo. Stool forms, frequency, breath methane, and CTT were recorded afterward.

Results

CC patients tended to be methane producer more often (13/23 [56.5%] vs. 25/68 [36.5%], p?=?0.07) and had greater area under curve (AUC) for methane (2415 [435–23,580] vs. 1335 [0–6562.5], p?=?0.02) than non-constipating IBS. Methane producers (8/13 [61.5%]) and 5/10 (50%) non-producers had abnormal CTT (marker retention: 36-h, 53 [0–60] vs. 19 [8–56], p?=?0.06; 60-h, 16 [0–57] vs. 13 [3–56], p?=?0.877). Six and 7/13 methane producers were randomized to rifaximin and placebo, respectively. Rifaximin reduced AUC for methane more (6697.5 [1777.5–23,580] vs. 2617.5 [562.5–19,867.5], p?=?0.005) than placebo (3945 [2415–12,952.5] vs. 3720 [502.5–9210], p?=?0.118) at 1 month. CTT normalized in 4/6 (66.7%) on rifaximin (36-h retention, 54 [44–57] vs. 36 [23–60], p?=?0.05; 60-h, 45 [3–57] vs. 14 [11–51], p?=?0.09) but none on placebo (p?=?0.02) (36-h, 31 [0–60] vs. 25 [0–45], p?=?0.078; 60-h, 6 [0–54] vs. 12 [0–28], p?=?0.2). Weekly stool frequency (3 [1–9] and 7 [1–14], p?=?0.05) and forms improved with rifaximin than placebo.

Conclusion

Rifaximin improves CC by altering methane production and colon transit.

Trial registration

Clinical Trial Registry, India: REF/2012/01/003216

Open image in new window

? ?

     

Beat‐to‐Beat QT Interval Variability Is Primarily Affected by the Autonomic Nervous System

Background : Beat‐to‐beat QT interval variability is associated with life‐threatening arrhythmias and sudden death, however, its precious mechanism and the autonomic modulation on it remains unclear. The purpose of this study was to determine the effect of drugs that modulate the autonomic nervous system on beat‐to‐beat QT interval. Method : RR and QT intervals were determined for 512 consecutive beats during fixed atrial pacing with and without propranolol and automatic blockade (propranolol plus atropine) in 11 patients without structural heart disease. Studied parameters included: RR, QTpeak (QRS onset to the peak of T wave), QTend (QRS onset to the end of T wave) interval, standard deviation (SD) of the RR, QTpeak, and QTend (RR‐SD, QTpeak‐SD, and QTend‐SD), coefficients of variation (RR‐ CV, QTpeak‐CV, and QTend‐CV) from time domain analysis, total power (TP; RR‐TP, QTpeak‐TP, and QTend‐TP), and power spectral density of the low‐frequency band (LF; RR‐LF, QTpeak‐LF, and QTend‐LF) and the high‐frequency band (HF; RR‐HF, QTpeak‐HF and QTend‐HF). Results : Administration of propranolol and infusion of atropine resulted in the reduction of SD, CV, TP, and HF of the QTend interval when compared to controlled atrial pacing (3.7 ± 0.6 and 3.5 ± 0.5 vs 4.8 ± 1.4 ms, 0.9 ± 0.1 and 0.9 ± 0.1 vs 1.2 ± 0.3%, 7.0 ± 2.2 and 7.0 ± 2.2 vs 13.4 ± 8.1 ms², 4.2 ± 1.4 and 4.2 ± 1.2 vs 8.4 ± 4.9 ms², respectively). Administration of propranolol and atropine did not affect RR interval or QTpeak interval indices during controlled atrial pacing. Conclusions : Beat‐to‐beat QT interval variability is affected by drugs that modulate the autonomic nervous system.     

Effect of percutaneous transluminal coronary angioplasty on QT dispersion and heart rate variability parameters

Background

The aim of the study was to analyse parameters reflecting the sympathovagal control of ventricular depolarisation and repolarisation [heart rate variability (HRV) and QT interval dispersion (QTd)] in patients undergoing elective percutaneous transluminal coronary angioplasty (PTCA), and determine whether HRV correlates with QT dispersion parameters.

Methods

The study consisted of 26 consecutive patients (16 men, 10 women) with single-vessel coronary artery disease (CAD) who underwent elective coronary angioplasty. HRV analyses of all subjects were obtained with the time- and frequency-domain methods. For frequency-domain analysis, low-frequency HRV (LF), high-frequency HRV (HF) and the LF:HF ratio were measured. For time-domain analysis, standard deviations of the normal-to-normal QRS intervals (SDNN) and square roots of the mean squared differences of successive N–N intervals (rMSSD) were obtained. QT intervals were also corrected for heart rate using the Bazett’s formula, and the corrected QT interval dispersion (QTcd) was then calculated. All measurements (HRV parameters and QTcd) were made before and immediately after PTCA.

Results

QTcd was significantly decreased after PTCA (52.2 ± 3.5 vs 42 ± 3.9 ms). SDNN (94.1 ± 22 vs 123.9 ± 35.2 ms), rMSSD (43.7 ± 20.1 vs 73.4 ± 14.5 ms) and HF (51.1 ± 48.8 vs 64.2 ± 28.6 ms²) were significantly higher after PTCA, whereas LF (142 ± 41.5 vs 157.2 ± 25.9 ms²) and the ratio of LF:HF (3.3 ± 1.9 vs 2.1 ± 1.2) were significantly decreased after PTCA. We observed a significant negative correlation after PTCA between QTcd and LF (r = −0.87, p = 0.01) and between QTcd and the ratio of LF:HF (r = −056, p < 0.05).

Conclusion

Among the patients with CAD undergoing PTCA, QTcd significantly decreased after PTCA, and negatively correlated with LF, the parameter reflecting the sympathetic system.     

Polymorphisms in Mn-SOD and EC-SOD gene and risk of nephropathy in Western Indian Type 2 diabetic patients

Single-nucleotide polymorphisms in genes related to oxidative stress are a risk factor for the development of diabetes and its complications. The allele and genotype frequencies of missense polymorphism Ala-9Val and Val16Ala in Mn-SOD and Arg213Gly in EC-SOD genes were studied in (a) patients with Type 2 diabetes mellitus (T2DM) without any complication (T2DM), (b) diabetic nephropathy (DN), (c) non-diabetic nephropathy (NDN) and (d) control healthy subjects from Western region of India. The PCR products were digested with BshTI, BsaWI and Eco52I restriction enzymes to detect Ala-9Val, Val16Ala and Arg213Gly polymorphisms respectively. The frequency of Val allele of Ala-9Val (P?=?0.568 and P?=?0.571) and Ala allele of Val16Ala (P?=?0.993 and P?=?0.152) polymorphisms of Mn-SOD gene did not show a significant difference in patient with T2DM and NDN compared to control subjects respectively. Frequency of Val allele of Ala-9Val (42.8 % vs. 61.5 %, P?<?0.001) and Ala allele of Val16Ala (39.0 % vs. 53.5 %, P?=?0.005) polymorphisms of Mn-SOD gene was significantly higher in patients with DN than that of patient with T2DM. For Arg213Gly polymorphism of EC-SOD gene, the Gly allele frequency in T2DM and NDN group did not significantly (P?=?0.993 and P?=?0.152 respectively) differ from control subjects as well as non-significantly higher in DN compared to T2DM. These results suggests that Ala-9Val and Val16Ala polymorphism in Mn-SOD is not involved in development of diabetes but may play a crucial role in determining genetic susceptibility to diabetic nephropathy in Western Indian Type 2 diabetic patients. Our data found a lack of association of EC-SOD (Arg213Gly) polymorphism with development of diabetes and diabetic nephropathy.     

Monocyte–Platelets Aggregates as Cellular Biomarker of Endothelium-Dependent Coronary Vasomotor Dysfunction in Patients with Coronary Artery Disease

Monocyte–platelet aggregates (MPA) are increased in patients with acute coronary syndrome. We investigated whether MPA are associated with the presence of functionally significant coronary stenoses or with coronary arterial endothelial dysfunction. One hundred forty five patients undergoing elective coronary angiography were prospectively enrolled. Functional significance of coronary stenosis was assessed by fractional flow reserve (FFR). Thirty randomly selected patients underwent pacing protocol to evaluate Coronary endothelium-dependent vasomotor function (CVF). Whole blood was drawn to evaluate MPA. In patients with FFR?≤?0.8 (FFR_pos, n?=?75), MPA did not significantly differ from FFR >0.8 patients (FFR_neg, n?=?70) (38.1 % [25.7–56.6] vs 34.0 % [20.5–49.9], p?=?0.08). CVF was similar in FFR_pos and FFR_neg patients (percent vessel diameter change, %VDC?=?7.19 % [6.01–10.9] vs 8.0 % [0.81–9.80], p?=?0.78). Yet, patients with abnormal CVF showed higher MPA as compared to patients with preserved CVF (28.3 % [28.8–53.4] vs 20.5 % [17.0–32.9], p?=?0.01). Moreover, MPA was inversely correlated with %VDC (R ²?=?0.26, p?<?0.01). MPA levels are significantly higher in patients with abnormal coronary vasomotor function regardless of the presence of functionally significant coronary stenosis.     

Effects of atorvastatin on apelin, visfatin (nampt), ghrelin and early carotid atherosclerosis in patients with type 2 diabetes

To investigate the influence of atrovastatin treatment on carotid intima-media thickness (CIMT) and serum levels of novel adipokines, like apelin, visfatin (nampt), and ghrelin, in patients with type 2 diabetes mellitus (T2DM). 87 statin-free patients (50 males) with T2DM, aged 55–70, but without carotid atherosclerotic plaques were initially enrolled. CIMT was assayed in all participants by ultrasound. Patients were then treated with atorvastatin (10–80?mg) to target LDL?<100?mg/dl. Anthropometric parameters, blood pressure, glycemic and lipid profile, high-sensitivity CRP (hsCRP), insulin resistance (HOMA-IR), apelin, visfatin and ghrelin were measured at baseline and after 12?months. Atorvastatin treatment significantly improved lipid profile across with increased apelin (from 0.307?±?0.130?pg/ml to 1.537?±?0.427?pg/ml; P?<?0.001) and suppressed visfatin (from 21.54?±?10.14?ng/ml to 15.13?±?7.61?ng/ml; P?=?0.002) serum levels in our diabetic patients. Standard multiple regression analysis showed that the atorvastatin-induced increment in apelin was independently associated with changes in total cholesterol (β?=?–0.510, P?=?0.030) and LDL-cholesterol (β?=?–0.590, P?<?0.001) (R ²?=?0.449, P?=?0.014), while the reduction of visfatin concentration was independently associated with the change in hsCRP (β?=?0.589, P?<?0.001; R ²?=?0.256, P?=?0.006), after adjustment for age, sex and BMI. CIMT and ghrelin did not alter significantly after 12?months of atorvastatin treatment (NS). Among participants, high-dose (80?mg) rather than low-dose (10?mg) of atorvastatin treatment yielded greater (P?<?0.05) changes in apelin, visfatin and CIMT levels despite the final equivalent levels of LDL. Atorvastatin administration increased apelin and decreased visfatin serum levels significantly, without change of CIMT, in patients with T2DM. However, high-dose of atorvastatin exerted more favourable impact on adipokines and CIMT than low-dose. Our results implicate another important link between adiposity and atherosclerosis.     

Body mass index and response to tocilizumab in rheumatoid arthritis: a real life study

Several studies have suggested that obesity could have a negative effect on response to anti-tumor necrosis factor α (anti-TNFα) in rheumatoid arthritis (RA). Little is known about the impact of body mass index (BMI) on other biologic agents. We aimed to evaluate the effect of BMI on response to tocilizumab (TCZ) in RA. RA patients treated with TCZ were included in this multicenter retrospective study. BMI was calculated at the initiation of treatment. After 6 months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, and tender and swollen joints were analyzed. The primary endpoint was decrease in DAS28 ≥ 1.2. Secondary outcomes were good response and remission by EULAR criteria. At baseline, among 115 RA patients included, the median (interquartile range) BMI was 25.4 (22.0–28.8)?kg/m². The number of patients with normal weight, overweight, and obesity was 53 (46 %), 37 (32 %), and 25 (22 %), respectively. Baseline characteristics did not differ between the three subgroups of BMI. The median BMI did not differ between responders and non-responders for DAS28 decrease ≥1.2 (25.7 [22.1–29.9] vs 24.9 [22.0–27.1], P?=?0.38), EULAR good response (25.9 [22.8–30.0] vs 25.4 [22.0–28.4], P?=?0.61), and remission (25.1 [22.5–28.6] vs 25.4 [22.0–28.9], P?=?0.76). BMI did not affect the response to TCZ in RA. If confirmed, these results could be helpful for the selection of a biologic agent in obese RA patients.     

Clinical and pathological characteristics of DKD patients with early-onset type 2 diabetes

AimsIn diabetic kidney disease (DKD) patients, early-onset T2DM effects on renal disease severity and outcomes remain uncertain. Herein, we aim to investigate the clinicopathological characteristics and renal outcomes in DKD patients with early-onset T2DM.Methods489 patients with T2DM and DKD were retrospectively recruited and classified as having early (age at onset of T2DM < 40 years) and late (age at onset of T2DM ≥ 40 years) T2DM onset, analyzing the clinical and histopathological data. The predictive value of early-onset T2DM to renal outcomes in DKD patients was analyzed by Cox's regression.ResultsAmong 489 DKD patients, 142 and 347 were classified as early and late T2DM onset, respectively. Early-onset T2DM patients exhibited worse glycaemic control (7.36 % ± 1.80 % vs. 6.86 % ± 1.57 %, P = 0.007) and more severe proteinuria (3.69 [1.55 to 7.03] vs. 1.81 [0.50 to 4.33] g/24 h, P < 0.001). Those with early-onset T2DM presented more severe glomerular lesions. In univariable Cox regression, early-onset T2DM showed a significant correlation with renal composite endpoint (HR [95%CI]: 0.56 [0.43 to 0.73], P < 0.001). However, after adjusting for potential confounders, early-onset T2DM was not independently correlated with renal composite endpoint (HR [95%CI]: 0.74 [0.46 to 1.21], P = 0.232).ConclusionsIn DKD patients with early-onset T2DM, renal clinicopathological manifestations were severe. Age at onset in T2DM was significantly correlated with eGFR slope (r = 0.211, P < 0.001).     

Diminishing prognostic role of preexisting diabetes mellitus for patients with diffuse large B-cell lymphoma in the rituximab era

Rituximab reforms the treatment of diffuse large B-cell lymphoma (DLBCL) and the prognostic significance of baseline patient features should be reevaluated. Few population-based studies have investigated the association of diabetes mellitus (DM) and outcomes of lymphoma; however, the results remain inconclusive. From January 1, 2000 to December 31, 2009, a total of 468 consecutive newly diagnosed DLBCL patients receiving first-line chemotherapy with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) or rituximab plus CHOP (R-CHOP) were enrolled. Pre-existing DM was defined according to medical history, use of antidiabetic medications, or any record of an abnormal hemoglobin A1c test. Progression-free survival (PFS) and overall survival (OS) were estimated and compared using the Kaplan–Meier method with a log-rank test. CHOP was administered in 194 patients, and 274 patients received R-CHOP. DM was identified in 16.2 % (76/468) of patients. Diabetic patients were older and more performance restricted, compared to the non-DM patients in both the CHOP and R-CHOP groups. In the CHOP group, 5-year PFS and OS were inferior in DM patients (PFS, 32.4 vs. 50.0 % (P?=?0.039); OS, 38.2 vs. 62.5 % (P?=?0.002)). However, outcomes were similar for both DM and non-DM patients in the context of R-CHOP treatment (PFS, 69.0 vs. 57.3 % (P?=?0.179); OS, 76.2 vs. 69.8 % (P?=?0.586)). The response rate of chemotherapy in DM patients was also improved to a level similar to non-DM patients with rituximab use. In conclusion, the prognostic significance of preexisting DM in DLBCL patients is changing in the rituximab era. The potentially additional benefit of rituximab in DM patients merits further investigation.     

Association of non-HDL-C/HDL-C ratio and its dynamic changes with incident type 2 diabetes mellitus: The Rural Chinese Cohort Study

BackgroundWe aimed to evaluate the association of the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (non-HDL-C/HDL-C) and its dynamic changes with incident type 2 diabetes mellitus (T2DM).MethodsA total of 11,487 nondiabetic participants ≥18 years old in rural China were recruited in 2007–2008 and followed up in 2013–2014. A Cox proportional-hazards model was used to assess the risk of incident T2DM by quartiles of baseline non-HDL-C/HDL-C ratio and dynamic absolute and relative changes in non-HDL-C/HDL-C ratio, estimating hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsRisk of incident T2DM was increased with quartiles 2, 3, and 4 versus quartile 1 of baseline non-HDL-C/HDL-C ratio (HR 1.46 [95% CI 1.08–1.98], 1.51 [1.12–2.03], and 2.16 [1.62–2.88], P_trend < 0.001). As compared with stable non-HDL-C/HDL-C ratio during follow-up, an absolute gain in non-HDL-C/HDL-C ratio was associated with increased risk of T2DM (HR 1.67 [95% CI 1.25–2.24] for quartile 3 and 2.00 [1.52–2.61] for quartile 4). A relative increase in non-HDL-C/HDL-C ratio was also associated with increased risk of T2DM (HR 1.56 [95% CI 1.19–2.04] for quartile 3 and 1.97 [1.49–2.60] for quartile 4). Subgroup analyses showed that the association of non-HDL-C/HDL-C ratio with T2DM risk remained consistent.ConclusionsIncreased non-HDL-C/HDL-C ratio is associated with increased risk of incident T2DM among rural Chinese adults, so the index may be an important indicator for identifying individuals at T2DM risk.     

Type 2 diabetes mellitus (T2DM) subjects of Bangladeshi origin with fast N-acetyltransferase 2 (NAT2) acetylator phenotype show lower insulin sensitivity than slow acetylator phenotype

Multiple genes may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). N-acetyltransferase 2 (NAT2) is a phase II drug detoxifying enzyme for which susceptibility to the development of T2DM has been linked with its genetic polymorphisms. The role of polymorphisms in NAT2 gene in the development of T2DM among Bangladeshi population is not yet known. In the present study, to investigate whether NAT2 gene polymorphisms play a role in the susceptibility to T2DM, three common polymorphisms 481C>T, 590G>A, and 857G>A were investigated by PCR-RFLP method in 93 T2DM patients and 145 healthy controls of Bangladeshi origin. Our results indicate that none of the markers were associated with the increased risk of T2DM development in the studied population (P?>?0.05). Although statistically insignificant (P?=?0.259), fast acetylator type was higher in T2DM subjects than in control subjects (53.3 % vs. 45.7 %). T2DM subjects with fast acetylator type had significantly higher absolute insulin level and lower insulin sensitivity than that of slow acetylator type (P?=?0.018 and P?=?0.038 respectively), the biochemical and molecular basis of this variation needs to be studied further.     

Monoclonal gammopathy in rheumatic diseases

To analyze the clinical spectrum, laboratory characteristics, and outcomes of monoclonal gammopathy (MG) in patients with rheumatic diseases. Screening for the presence of MG was performed in 872 inpatients with rheumatic diseases from January 2010 to July 2017. A total of 41 patients were enrolled. Their clinical and biological features in addition to outcomes were described. For each patient with primary Sjögren syndrome (pSS), 2 age- and sex-matched pSS patients without MG were selected as controls. Risk factors for the presence of MG and malignant hematological neoplasias were assessed. MG was observed in patients with SS, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, primary biliary cirrhosis, polymyositis, hypomyopathic dermatomyositis, psoriatic arthritis, ANCA-associated vasculitis, polyarteritis nodosa, and polymyalgia rheumatic, with SS the most frequent type. Serum M protein was detected in 37 patients. The monoclonal bands identified in serum were 16 IgG (5 κ, 11 λ), 11 IgA (6 κ, 5 λ), 6 IgM (5 κ, 1 λ), and 4 free λ chains. M components were observed in urine in the other 4 patients. High ESR, albumin/globulin inversion, rheumatoid factor positivity, hypergammaglobulinemia, and hypocomplementemia were common features, presented in more than half of the 41 patients. Patients with pSS, when complicated with MG, showed a higher rate of abnormal urine NAG (71.4 vs 15.8%, P?=?0.025), higher levels of ESR [55.0 (53.5) mm/h vs 21.0 (31.8) mm/h, P?=?0.001], ESSDAI [26.0 (25.0) vs 12.0 (9.0), P?=?0.006], and ClinESSDAI scores [24.0 (25.0) vs 10.5 (10.0), P?=?0.011]. Multivariate analysis revealed that the disease activity, assessed by either ESSDAI [adjusted OR 1.127 (95%CI 1.015–1.251), P?=?0.025] or ClinESSDAI [adjusted OR 1.121 (95%CI 1.011–1.242), P?=?0.030], was the only independent risk factor for the presence of MG. During the follow-up, 2 patients had transient serum M protein, 2 had isotype switch, 1 progressed to multiple myeloma (MM), and another 2 experienced renal injuries attributed by monoclonal or polyclonal plasma cell interstitial infiltration. Seven (17.1%) of the 41 MG patients presented hematological neoplasias, 4 with MM, 2 with smoldering multiple myeloma, and 1 with B cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The presence of light-chain MG was associated with the development of MM [OR 17.5 (95%CI 1.551–197.435), P?=?0.041], but not with an increased risk of lymphoma or SMM. MG was observed in patients with various rheumatic disorders, with SS being the most common type. The presence of MG might be associated with higher disease activity. The development of hematological neoplasias including MM and lymphoma was seen in this setting. Therefore, we recommend the screening for MG and close monitoring for potential malignant transformation in patients with rheumatic diseases as needed.