The effect of ubiquinone in diabetic polyneuropathy: a randomized double-blind placebo-controlled study

IntroductionDiabetic polyneuropathy aetiology is based on oxidative stress generation due to production of reactive oxygen species. Ubiquinone is reduced to ubiquinol and redistributed into lipoproteins, possibly to protect them from oxidation.AimsTo evaluate the impact of oral ubiquinone in diabetic polyneuropathy, and the role of lipid peroxidation (LPO) and nerve growth factor (NGF-β).MethodsWe conducted a double-blind, placebo-controlled clinical trial, patients were randomized to ubiquinone (400 mg) or placebo daily for 12 weeks. Main outcomes were clinical scores, nerve conduction studies, LPO, NGF-β and safety.ResultsTwenty four patients on experimental group and twenty five on control group met the inclusion criteria (mean age 56 years, 22% male and 78% female, mean evolution of type 2 diabetes mellitus 10.7 years). Significant improvement on experimental vs control group was found in neuropathy symptoms score (from 2.5 ± 0.7 to 1 ± 0.8, p < 0.001), neuropathy impairment score (5.5 ± 4 to 3.1 ± 2.6, p < 0.001), sural sensory nerve amplitude (13.0 ± 6.1 to 15.8 ± 5.1 μV, p = 0.049), peroneal motor nerve conduction velocity (39.7 ± 5.0 to 47.8 ± 4.9 m/s, p = 0.047), and ulnar motor nerve conduction velocity (48.8 ± 6.8 to 54.5 ± 6.1 m/s, p = 0.046). There was a significant reduction of LPO in subjects treated with ubiquinone vs placebo (16.7 ± 8.6 and 23.2 ± 15.8 nmol/mL, respectively) with p < 0.05, and NGF-β did not change (control 66.5 ± 26.7 vs. experimental 66.8 ± 28.4 pg/mL, p = 0.856). No drug-related adverse reactions were reported.ConclusionsTwelve weeks treatment with ubiquinone improves clinical outcomes and nerve conduction parameters of diabetic polyneuropathy; furthermore, it reduces oxidative stress without significant adverse events.     

Angiotensin-converting enzyme gene single polymorphism as a genetic biomarker of diabetic peripheral neuropathy: longitudinal prospective study

BackgroundIdentifying patients at risk of developing diabetic peripheral neuropathy (DPN) is of paramount importance in those with type 2 diabetes mellitus (T2DM) to provide and anticipate secondary prevention measures as well as intensify action on risk factors, particularly so in primary care. Noteworthy, the incidence of DPN remains unknown in our environment.Aims(i) To analyze a single angiotensin-converting enzyme (ACE) gene polymorphism (D/I) as a genetic marker of risk of developing DPN, and (ii) to determine the incidence of DPN in our environment.Research design and methodsLongitudinal study with annual follow-up for 3 years involving a group of T2DM (N = 283) randomly selected. ACE gene polymorphism distribution (I = insertion; D = deletion) was determined. DPN was diagnosed using clinical and neurophysiology evaluation.ResultsBaseline DPN prevalence was 28.97% (95% CI, 23.65–34.20). ACE polymorphism heterozygous genotype D/I presence was 60.77% (95% CI, 55.05–66.5) and was independently associated with a decreased risk of DPN (RR, 0.51; 95% CI, 0.30–0.86). DPN correlated with age (P < 0.001) but not with gender (P = 0.466) or time of evolution of T2DM (P = 0.555). Regarding end point, DPN prevalence was 36.4% (95% CI, 30.76–42.04), and accumulated incidence was 10.4% 3 years thereafter. In the final Poisson regression analysis, the presence of heterozygous genotype remained independently associated with a decreased risk of DPN (RR, 0.71; (95% CI, 0.53–0.96). DPN presence remained correlated with age (P = 0.002), but not with gender (P = 0.490) or time of evolution (P = 0.630).ConclusionsIn our series, heterozygous ACE polymorphism (D/I) stands as a protective factor for DPN development. Accumulated incidence of DPN was relevant. Further prospective studies are warranted.     

The diagnostic utility of Sudoscan for distal symmetric peripheral neuropathy

AimsDiagnosis of early distal symmetric polyneuropathy (DSP) is challenging. Nerve conduction studies (NCS) are often normal. Skin biopsy for intraepidermal nerve fiber density (IENFD) has better sensitivity, but is invasive. Sudoscan is a novel technology that measures electrochemical skin conductance (ESC; microSiemens, μS), which is thought to be proportionate to the number of functional sweat glands. This study evaluated Sudoscan’s diagnostic utility for DSP.Methods55 patients with suspected DSP (22 with diabetes, 2 prediabetes, 31 idiopathic) and 42 controls underwent the Utah Early Neuropathy Scale (UENS) and Sudoscan. Each was offered skin biopsy. DSP participants underwent quantitative sudomotor axon reflex testing (QSART) and NCS.ResultsFeet and hands ESCs were reduced among DSP participants compared to controls (64 ± 22 vs. 76 ± 14 μS p < 0.005, and 58 ± 19 vs. 66 ± 18 μS p < 0.04). There was no difference between diabetic and idiopathic DSP. Receiver operating characteristic curve analysis revealed feet ESC and IENFD had similar areas under the curve (0.761 and 0.752). ESC correlated with Sural amplitude (0.337, p < 0.02), UENS (− 0.388, p < 0.004), and MNSI (− 0.398, p < 0.005).ConclusionsSudoscan is a promising diagnostic test for diabetic and idiopathic DSP, with diagnostic performance similar to IENFD.     

Normalization of visceral adiposity is required to normalize plasma apolipoprotein B levels in response to a healthy eating/physical activity lifestyle modification program in viscerally obese men

ObjectiveLittle is known about how visceral adipose tissue (VAT) influences circulating apolipoprotein B (apoB) levels, which reflect atherogenic risk. We have examined the effects of a 1-year lifestyle modification program on plasma apoB levels in viscerally obese men and compared post-intervention levels to those of a reference group of lean healthy men.MethodsFasting plasma apoB levels were measured in 107 non-diabetic, viscerally obese men, before and after a 1-year lifestyle intervention program aiming at improving nutritional and physical activity/exercise habits.ResultsAfter the intervention, subjects significantly decreased their volume of VAT (Δ = ?26 ± 18%, p < 0.0001) measured by computed tomography and significantly, but modestly reduced their fasting apoB levels (Δ = ?3 ± 14%, p = 0.04). When compared to the reference group, men in the intervention group still had higher apoB levels suggesting that they did not “normalize” their apoB concentrations to the level of the healthy non-obese reference men. To further explore the relationship between VAT and apoB, men in the intervention group were stratified according to quartiles of VAT achieved after the intervention. Only men of the lowest quartile of VAT (corresponding to 844 ± 42 cm³, similar to the value of the reference group; 809 ± 52 cm³ of VAT) showed plasma apoB levels which were similar to those of the reference group (0.98 ± 0.21 vs. 0.99 ± 0.24 g/L, NS, for lowest VAT quartile and reference group, respectively).ConclusionThese results suggest that, in order to “normalize” apoB levels in response to a lifestyle modification program, viscerally obese dyslipidemic men need to achieve levels of VAT similar to healthy non-obese men.     

Exercise training enhances autonomic function after acute myocardial infarction: A randomized controlled study

IntroductionHeart rate recovery, defined as the fall in heart rate during the first minute after exercise, is an indicator of autonomic function, and has been found to be an independent predictor of mortality after acute myocardial infarction. Exercise training has several well-known benefits in terms of cardiorespiratory fitness, modifiable cardiovascular risk factors and prognosis after acute coronary events. However, there are no randomized controlled studies in the literature evaluating the effects of exercise training per se, controlling for changes in medication and diet, on heart rate recovery. Thus, this study aims to assess the effects of exercise training on autonomic function in coronary artery disease patients recovering from acute myocardial infarction.MethodsThirty-eight patients following a first acute myocardial infarction participated in this prospective randomized clinical trial. Patients were randomized into two groups: exercise training or control. The exercise group participated in an 8-week aerobic exercise program, while the control received standard medical care and follow-up. Changes in hemodynamics at rest and at peak exercise (heart rate, systolic and diastolic blood pressure, and rate pressure product), dietary intake, cardiorespiratory fitness, and heart rate recovery were assessed.ResultsMedication and diet remained unchanged in both groups during the study period. The exercise-training group improved resting hemodynamics, particularly resting heart rate (from 68.0 ± 9.2 to 62.6 ± 8.7 bpm, p = 0.030) and systolic blood pressure (from 135 ± 7.1 to 125.6 ± 11.3 mmHg, p = 0.012), cardiorespiratory fitness (from 30.8 ± 7.8 to 33.9 ± 8.3 ml/min/kg, p = 0.016), and heart rate recovery (from 20 ± 6 to 24 ±5 bpm, p = 0.007). No significant changes were observed in the control group.ConclusionsExercise training improved autonomic function, assessed by heart rate recovery, resting heart rate and systolic blood pressure, in the absence of changes in diet or medication.     

Circulating angiogenic cell populations, vascular function, and arterial stiffness

ObjectiveSeveral bone marrow-derived cell populations have been identified that may possess angiogenic activity and contribute to vascular homeostasis in experimental studies. We examined the extent to which lower quantities of these circulating angiogenic cell phenotypes may be related to impaired vascular function and greater arterial stiffness.MethodsWe studied 1948 Framingham Heart Study participants (mean age, 66 ± 9 years; 54% women) who were phenotyped for circulating angiogenic cells: CD34+, CD34+/KDR+, and early outgrowth colony forming units (CFU). Participants underwent non-invasive assessments of vascular function including peripheral arterial tone (PAT), arterial tonometry, and brachial reactivity testing.ResultsIn unadjusted analyses, higher CD34+ and CD34+/KDR+ concentrations were modestly associated with lower PAT ratio (β = ?0.052 ± 0.011, P < 0.001 and β = ?0.030 ± 0.011, P = 0.008, respectively) and with higher carotid-brachial pulse wave velocity (β = 0.144 ± 0.043, P = 0.001 and β = 0.112 ± 0.043, P = 0.009), but not with flow-mediated dilation; higher CD34+ was also associated with lower carotid-femoral pulse wave velocity (β = ?0.229 ± 0.094, P = 0.015). However, only the association of lower CD34+ concentration with higher PAT ratio persisted in multivariable analyses that adjusted for standard cardiovascular risk factors. In all analyses, CFU was not associated with measures of vascular function or arterial stiffness.ConclusionsIn our large, community-based sample of men and women, circulating angiogenic cell phenotypes largely were not associated with measures of vascular function or arterial stiffness in analyses adjusting for traditional risk factors.     

QT-interval dispersion in type 2 diabetic and non-diabetic patients with post-myocardial infarction

Background and aimsQT-interval dispersion (QTD), which reflects spatial ventricular repolarization inhomogeneity, has been reported to increase and to have a prognostic value in patients with either myocardial infarction or diabetes. Our aim was to compare increases in QTD in type 2 diabetic and non-diabetic patients following post-myocardial infarction (post-MI). We also compared QTD in type 2 diabetic patients with post-MI treated with insulin, sulfonylurea, or diet alone.Methods and resultsWe determined the rate corrected QT-interval (QTc) dispersion (QTcD) in 178 consecutive post-MI patients, including 48 type 2 diabetic and 130 non-diabetic patients. The QTcD, measured with software (QTD-1), was defined as the difference in the minimum and maximum QTc in any of the 12 standard electrocardiographic leads. There were no significant differences in age, gender, left ventricular end-diastolic diameter, ejection fraction, or minimum QTc between type 2 diabetic and non-diabetic patients with post-MI. Compared with post-MI patients without diabetes, those with type 2 diabetes had higher maximum QTc (481 ± 37 vs. 459 ± 43 ms, P < 0.05) and QTcD (67 ± 18 vs. 58 ± 16 ms, P < 0.05). Among type 2 diabetic patients with post-MI treated with insulin, sulfonylurea, or diet alone, the QTcD (81 ± 18 vs. 64 ± 16 vs. 62 ± 17 ms, P < 0.05, respectively) was significantly greater and the R-R interval was shorter in the insulin therapy group.ConclusionsType 2 diabetes is associated with an additional increase in the QTD in post-MI patients. This additional increase in spatial repolarization inhomogeneity might be implicated in the increased mortality risk in post-MI patients with type 2 diabetes. These findings were thought to be more striking in the insulin therapy group.     

Short term effects of physical exercise and low calorie diet on left ventricular function in obese subjects: a tissue Doppler study

Background and aimThe effects of combined physical exercise and a hypocaloric diet on left ventricular function in obese subjects without heart disease are not well defined and have never been studied with the tissue Doppler technique. The purpose of our study was to describe the modification of left ventricular systolic and diastolic functions after a short period of physical exercise and a hypocaloric diet in obese patients.Methods and resultsFifteen patients (10 females and 5 males) aged 29.7 ± 6.1 years with uncomplicated obesity (mean body mass index = 41.4 ± 5.5 kg/m²) were subjected to a low calorie diet and physical exercise. Systolic and diastolic functions were evaluated by Doppler and tissue Doppler echocardiography. After 3 weeks echocardiographic and conventional Doppler measurements were unchanged, while Sa increased (0.109 ± 0.019 vs 0.118 ± 0.016 m/s) and Ea decreased (0.162 ± 0.029 vs 0.147 ± 0.022 m/s, P = 0.044) resulting in a decrease in Ea/Aa (1.66 ± 0.53 vs 1.40 ± 0.28, P = 0.033) and an increase in E/Ea (5.65 ± 1.00 vs 6.35 ± 1.21, P = 0.038).ConclusionPhysical exercise and a hypocaloric diet in obese healthy subjects result in an improvement of a TDI index of systolic function and a slight reduction in early diastolic velocity of mitral annulus.     

Prevalence of gastroparesis-related symptoms in an unselected cohort of patients with Type 1 diabetes

BackgroundThe prevalence of diabetic gastroparesis is not well defined because of discrepancy between objective measurements, i.e. gastric emptying time, and symptoms experienced by patients. Furthermore most studies have been performed on small selected cohorts.ObjectiveTo determine the prevalence of clinical symptoms of diabetic gastroparesis in a large unselected cohort of out-patients with Type 1 diabetes.Methods1028 patients with Type 1 diabetes attending a specialized diabetes clinic were mailed a validated questionnaire; “patient assessment of upper gastrointestinal disorders-symptom severity index”, in which a subset of questions measures symptoms of gastroparesis (GCSI; Gastroparesis Cardinal Symptom Index). Response rate was 74.4% (n = 765). All patients were classified according to presence or absence of late diabetic complications and clinical and paraclinical data were obtained.ResultsA GCSI Total Score ≥ 1.90 signified definite symptoms of gastroparesis (n = 102) and patient charts were investigated for concomitant illness and/or medication influencing gastric emptying. In 30 patients an alternative etiology was revealed, leaving 72 (9.8%) patients with symptoms related to diabetic gastroparesis. Only 8 patients were previously diagnosed. HbA_1c levels were significantly higher in patients with diabetic gastroparesis (8.4 ± 1.3 vs. 8.2 ± 1.2 respectively, p = 0.02). Furthermore, patients with diabetic gastroparesis had more retinopathy (p = 0.006) and peripheral polyneuropathy (16.7% vs. 6.7%, p < 0.001) and there was a trend for diabetic nephropathy being more common (p = 0.08).ConclusionsSymptoms of diabetic gastroparesis affect approximately 10% of patients with Type 1 diabetes in a specialized diabetes clinic and are associated with poor glycemic control and other late diabetic complications.     

The effect of obesity on the assessment of diabetic peripheral neuropathy: A comparison of Michigan patient version test and Michigan physical assessment

ObjectiveNerve conduction studies (NCS) and Michigan Neuropathy Screening Instrument (MNSI) are commonly used to make the diagnosis of diabetic peripheral neuropathy. The objective of this study was to compare the diagnostic values of MNSI patient version test and physical test for the assessment of the diabetic peripheral neuropathy in obese vs. non-obese patients.MethodThis study was conducted on 70 type 2 diabetic patients. We carried out the MNSI patient version test and MNSI physical assessment test. Nerve conduction studies were performed for the diagnosis of the diabetic peripheral neuropathy.ResultsIn diabetic peripheral neuropathy (DPN) determined by NCS, the independent prediction of peripheral neuropathy was the score of Michigan physical assessment (odds 2.0; CI: 1.3–3.0). In BMI (body mass index) ≥30 diabetic patients who have peripheral neuropathy, Michigan patient version test is not significant. But the score of Michigan physical assessment is significantly increased in these patients compared to patients without peripheral neuropathy. In BMI < 30 diabetic patients who have peripheral neuropathy, scores of both Michigan patient version and physical assessment instruments are significantly increased.ConclusionTo screen diabetic peripheral neuropathy, Michigan physical assessment may be more useful instrument than Michigan patient version test in obese diabetic patients.     

Long-term cardiac rehabilitation and exercise training programs improve metabolic parameters in metabolic syndrome patients with and without coronary heart disease

Background and aimsThe effectiveness of long-term cardiac rehabilitation and exercise training programs on metabolic parameters was evaluated in metabolic syndrome subjects with and without coronary heart disease (CHD).Methods and resultsFifty-nine CHD and 81 non-coronary patients with metabolic syndrome (59 ± 8 vs 56 ± 9 years) were identified retrospectively at entry into identical cardiac rehabilitation and exercise-training programs. Metabolic syndrome was defined using modified Adult Treatment Panel III criteria. Exercise training occurred approximately twice per week. Metabolic and exercise testing data were collected at baseline and after 12 months during the course of the program. Mean duration of cardiac rehabilitation and exercise training programs was over one year in both coronary and non-coronary patients (366 ± 111 vs 414 ± 102 days for CHD and non-coronary CHD cohorts respectively, p < 0.01). Significant improvements in bodyweight, body mass index, blood lipids, triglyceride/HDL ratio and exercise tolerance were noted in both cohorts. At the end of follow-up, 31% of CHD and 20% of non-CHD subjects no longer possessed diagnostic criteria for metabolic syndrome (p < 0.0001 and p < 0.001 respectively).ConclusionsA long-term cardiac rehabilitation program reduces metabolic syndrome prevalence in CHD patients and results in a similar improvement in risk factor control for metabolic syndrome patients without CHD.     

The FTO gene modifies weight, fat mass and insulin sensitivity in women with polycystic ovary syndrome, where its role may be larger than in other phenotypes

AimGenome-wide association studies have shown that variation in the FTO gene predisposes to obesity and related traits that are common features of polycystic ovary syndrome (PCOS). The aim of the present study was to assess the effect of FTO variation on obesity, insulin sensitivity, and metabolic and hormonal profiles in PCOS.MethodsWe examined 136 PCOS women (mean body mass index [BMI]: 28.28 ± 6.95 kg/m², mean age: 25.36 ± 5.48 years). Anthropometric measurement, euglycaemic–hyperinsulinaemic clamp and oral glucose tolerance tests and sex hormone assessments were performed. The study group was genotyped for the FTO rs9939609 polymorphism.ResultsBMI (29.0 ± 6.9 kg/m² vs 26.1 ± 6.8 kg/m²; P = 0.023), body weight (80.1 ± 20.7 kg vs 72.6 ± 20.2 kg; P = 0.048), fat mass (29.7 ± 1 6.6 kg vs 24.6 ± 17.7 kg; P = 0.045) and waist circumference (89.8 ± 16.7 cm vs 83.2 ± 17.1 cm; P = 0.028) were higher in carriers of at least one copy of the A allele. Differences in these parameters were more significant when comparing AA and TT homozygotes. Women with the AA genotype also had decreased insulin sensitivity (P = 0.025) and follicle-stimulating hormone (P = 0.036). In logistic-regression analyses, the association of the FTO gene polymorphism with insulin sensitivity was no longer significant when BMI was included in the model.ConclusionVariation in the FTO gene modifies weight, adiposity and other measures of obesity and insulin sensitivity in PCOS. The examined FTO gene variant appears to have a greater impact on obesity and related traits in PCOS than in other phenotypes. The effect on insulin sensitivity appears to be secondary to its influence on obesity and body fat.     

Effect of 1, 25(OH)(2) vitamin D(3) on glucose homeostasis and DNA damage in type 2 diabetic mice

AimsThe purpose of the study was to examine the effect of 1, 25(OH)₂ VitaminD₃ supplementation on type 2 diabetic (T2DM) mice.Materials and MethodsA total of 24 mice were taken and divided into three groups of control; diabetic and diabetic + vitamin D supplemented ones. Serum calcium level, fasting blood glucose level (FBG), hexokinase activity, glucose-6-phosphatse and fructose 1,6 bisphosphatase activity were measured to establish a relevant correlation between vitamin D supplementation and hyperglycemia in T2DM.ResultsThere occurred an increase in FBG levels (250 ± 0.41 mg/dl) and a significant decrease in serum calcium levels in the diabetic group (8.63 ± 0.40 mg/ml) both of which reached near control levels on vitamin D₃ supplementation. The activity of the glucose metabolic enzymes was also assayed in diabetic group and was found to be deviated from control group; hexokinase (0.0241 ± 0.014 μg/mg/ml) FBPase (0.433 ± 0.002 μg/mg/ml) and G6Pase (0.918 ± 0.02 μg/mg/ml). However, the activity of these enzymes returned to near control values with hexokinase activity reaching 0.717 ± 0.003 μg/mg/ml on vitamin D₃ supplementation. The FBPase and G6Pase activities were decreased to 0.2733 ± 0.008 μg/mg/ml and G6Pase 0.71 ± 0.01 μg/mg/ml respectively. In addition to enzymatic analysis, the organs of all three groups of mice were subjected to comet assay. The diabetic group receiving vitamin D supplementation showed a marked recovery exhibiting shorter tail length both in liver (21.80 ± 2.40 μm) and pancreatic cells (19.25 ± 1.90 μm) as compared to the diabetic group exhibiting a tail length of 30.41 ± 2.50 μm and 32.45 ± 2.87 μm in liver and pancreatic cells respectively.ConclusionThe present study shows that vitamin D₃ supplementation is positively correlated with decrease in blood glucose level and serum calcium level in fasting condition. This suggests a positive influence of vitamin D on glucose homeostasis. Besides, the activity of various glucose metabolic enzymes (hexokinase, FBPase and G6Pase) as shown by our results and the remarkable shortening of DNA tail length in vitamin D supplemented diabetic group as compared to diabetic group without supplementation further support the idea that vitamin D supplementation might be an add-on therapy for patients with T2DM.     

Interaction between the uncoupling protein 2 -866G>A gene variant and cigarette smoking to increase oxidative stress in subjects with diabetes

Background and aimsIncreased oxidative stress is associated with coronary heart disease (CHD). The mitochondrial uncoupling protein-2 (UCP2) negatively regulates reactive oxygen species generation. We have observed that a common variant (−866G>A) in the promoter region of UCP2 is associated with increased CHD risk in healthy men and increased oxidative stress in diabetic men with CHD. The aim of the current study was to test the hypothesis that this variant might interact with smoking (an environmental stress) to influence plasma markers of oxidative stress.Methods and resultsAmongst 453 Caucasian diabetic men there was a significant interaction (p = 0.001) between genotype and smoking in determining plasma Total AntiOxidant Status (TAOS). Current smokers with the −866AA genotype had the lowest TAOS (indicating higher oxidative stress) of all subjects (AA vs. GG: 32.00 ± 17.4% vs. 45.8 ± 12.6%, p = 0.04). In a sub-sample of 20 subjects (10 GG, 10 AA) matched for baseline characteristics, plasma markers of oxidative stress in current smokers were significantly higher in AA compared to GG subjects (TAOS 36.8 ± 9.5% vs. 51.4 ± 9.5%, p = 0.04; F₂-isoprostanes 1133.6 ± 701.2 pg ml⁻¹vs. 500.8 ± 64.7 pg ml⁻¹, p = 0.04).ConclusionsThis study demonstrates an interaction between the UCP2 −866G>A variant and smoking to increase oxidative stress in vivo.     

Decreased fat oxidation during exercise in severe obstructive sleep apnoea syndrome

AimTo assess whether the severity of obstructive sleep apnoea syndrome (OSAS) is associated with altered fat oxidation (FO) during physical exercise in men with type 2 diabetes (T2DM) and/or the metabolic syndrome (MetS).MethodsA total of 105 consecutive overweight or/and T2DM male patients were hospitalized for metabolic check-ups including bioimpedancemetry to measure lean body mass (LBM), standardized exercise calorimetry to assess FO, maximum fat oxidation (MFO) and carbohydrate oxidation (CHO), and OSAS screening using respiratory polygraphy. Twenty patients were classified as having severe OSAS, according to the apnoea/hypopnoea index (AHI), with greater than 30 events/h (mean AHI: 45.2 ± 14.3 events/h). They were group-matched for age, BMI, and the presence of T2DM and/or MetS with two other OSAS groups: mild (AHI < 15 events/h [n = 20]; mean AHI: 8.8 ± 4.5 events/h); and moderate (AHI > 15 events/h and < 30 events/h [n = 20]; mean AHI: 23.7 ± 4.2 events/h).ResultsMFO adjusted for LBM was severely decreased in the severe OSAS group (1.6 ± 1.0 mg.min^?1.kgLM^?1) compared with the moderate (2.5 ± 0.9 mg.min^?1.kgLM^?1; P = 0.008) and mild (2.9 ± 0.8 mg.min^?1.kgLM^?1; P = 0.003) groups. All exercise-intensity levels (20%, 30%, 40% and 60% of the theoretical maximum aerobic power) showed reduced FO levels between the severe and mild-to-moderate OSAS groups. However, no differences in CHO were seen at any level of exercise between groups. Pearson's correlation analysis showed that AHI and the oxygen desaturation index were negatively associated with MFO corrected for LBM (r = 0.41 and r = 0.37, respectively; P < 0.005).ConclusionOSAS severity is associated with altered FO during exercise.     

Pulmonary function at peak exercise in patients with chronic heart failure

BackgroundVarious respiratory abnormalities are associated with chronic heart failure (CHF). However, changes in inspiratory capacity (IC) and breathing pattern from rest to exercise in patients with CHF have not been thoroughly investigated in these patients.Materials and methodsSeventy seven (66 male/11 female) patients with clinical stable CHF (age: 52 ± 11 years) were studied. All the patients underwent pulmonary function tests, including measurements of IC and maximal inspiratory pressure (Pimax) at rest and then a maximal cardiopulmonary exercise testing (CPET) on a treadmill. During the CPET, IC was measured every 2 min. Pimax was measured again after the end of CPET.ResultsPercent predicted forced expiratory volume in 1 s (FEV₁) was 91 ± 12, %predicted forced vital capacity (FVC) was 92 ± 13, %FEV₁/FVC was 81 ± 4, and %predicted IC was 85 ± 18. Peak exercise IC was lower than resting (2.4 ± 0.6 vs. 2.6 ± 0.6 l, p < 0.001). Analysis of variance between Weber's groups revealed statistically significant differences in peak exercise IC (p < 0.001), V_E/V_CO2slope (p < 0.001), resting Pimax (p = 0.005) and post-exercise Pimax(p < 0.001). At rest, there was a statistically significant difference in end-tidal CO₂ (P_etco2) (p = 0.002), in breathing frequency (p = 0.004), in inspiratory time (Ti) (p = 0.04) and in total respiratory time (T_Tot) (p = 0.004) among Weber's groups. At peak exercise there was a statistically significant decrease in minute ventilation (V_E) (p < 0.001), tidal volume (V_T) (p < 0.001), respiratory cycle (V_T/T_I) (p < 0.001) and P_etco2(p < 0.001).Peak IC was correlated with peak V_O2 (r = 0.72, p < 0.001), anaerobic threshold (r = 0.71, p < 0.001), V_O2/t slope (r = 0.54, p < 0.0001), and post-exercise Pimax (r = 0.62, p < 0.001).ConclusionsIn patients with CHF, peak exercise IC is reduced in parallel with disease severity, which is probably due to respiratory muscle dysfunction.     

Diabetes, comorbidities and increased long-term mortality in older patients admitted for geriatric inpatient care

AimsTo study the specific impact of diabetes on long-term mortality in very old subjects with multiple comorbidities and functional disabilities.MethodsThe prevalence of vascular disorders, global comorbidity load (cumulative illness rating scale [CIRS]) and functional disabilities (activities of daily living [ADL] and Lawton's instrumental ADL [IADL] scores) were determined according to diabetes status in a cohort of 444 patients (mean age 85.3 ± 6.7 years; 74.0% women) admitted to our geriatric service. Also, the specific impact of diabetes on 4-year mortality was analyzed using Cox proportional-hazards models.ResultsDiabetic patients had higher BMI scores (27.1 ± 4.9 vs. 23.4 ± 4.7 kg/m² in controls; P < 0.001), and higher prevalences of hypertension (81.9% vs. 65.1%, respectively; P = 0.003) and ischaemic heart disease (33.7% vs. 22.2%, respectively; P = 0.033), but not of stroke and renal insufficiency. They also had more comorbidities (CIRS score excluding diabetes: 15.1 ± 4.5 vs. 13.8 ± 4.8, respectively; P = 0.016) and functional disabilities. Diabetes was associated with mortality (HR: 1.42, 95% CI: 1.02–1.99; P = 0.041) after adjusting for age, gender and BMI, and this persisted after adjusting for individual vascular comorbidities, but disappeared after adjusting for CIRS, ADL or IADL scores.ConclusionDiabetes was associated with 4-year mortality after adjusting for the inverse relationship between mortality and BMI. This association was better accounted for by the global comorbidity load and functional disabilities than by the individual vascular comorbidities. These findings suggest that the active management of all – rather than selected – comorbidities is the key to improving the prognosis for older diabetic patients.     

Quarterly individual outpatients lifestyle counseling after initial inpatients education on type 2 diabetes: the REDIA Prev-2 randomized controlled trial in Reunion Island

AimsThis study aimed to describe the 1-year evolution of type 2 diabetes (T2D) patients who attended inpatients education, and to assess whether quarterly outpatients counseling visits by nurses and dietitians can improve metabolic control and health-related behaviours.MethodsFollowing in-hospital educational sessions, 398 adult T2D patients were randomized to either attend quarterly individual lifestyle counseling visits by a nurse and a dietitian (intervention group), or receive the usual care (control group). Primary (HbA_1c) and secondary endpoints (fasting blood glucose, lipids, body mass index, waist circumference, fat mass, blood pressure, diet, physical activity) were assessed at baseline and at 12 months.ResultsHbA_1c changes from baseline to 12 months were ? 1.74 ± 2.64% (P < 0.0001) for the intervention group and ? 2.02 ± 2.57% (P < 0.0001) for the control group. There was no statistically significant difference between the intervention group (n = 153) and the controls (n = 166) for any of the clinical and biological outcomes. In both groups, total energy and fat intakes decreased significantly from baseline levels. Also, no difference was found between the groups for any dietary outcome. A slight enhancement in sports activity was observed in the intervention group, but the difference between the two groups did not reach statistical significance, and no difference was found concerning any other physical activity scores.ConclusionIn this study of adults with T2D, patients significantly improved their metabolic control, and dietary and exercise habits, 1 year after receiving intensive inpatients education, whereas subsequent quarterly outpatients counseling visits with nurses and dietitians have not demonstrated any superiority compared with the usual care.     

C-reactive protein is directly related to plasminogen activator inhibitor type 1 (PAI-1) levels in diabetic subjects with the 4G allele at position -675 of the PAI-1 gene

Background and aimsC-reactive protein (CRP) has been identified as a possible factor able to promote atherosclerosis. “In vitro” studies have demonstrated that CRP induces plasminogen activator inhibitor type 1 (PAI-1) expression, suggesting a hypofibrinolytic role for CRP. As CRP and PAI-1 levels increase in type 2 diabetic subjects, we decided to study the relationship between CRP and PAI-1, and the role of the 4G/5G polymorphism of the PAI-1 gene on this relationship in a diabetic population without complications.Methods and resultsTwo hundred and ninety-five type 2 diabetic patients (age 60.9 ± 10.5 years) and 290 healthy controls (age 59.2 ± 11.5 years) were enrolled. A significant correlation between PAI-1 and CRP in diabetic subjects was found (r = 0.45, p < 0.001), whereas no relationship was evident in the control subjects between these inflammatory markers. Multiple regression analysis highlighted that CRP is the only one significant variable of PAI-1 antigen in diabetic subjects (partial r = 0.31, p < 0.01). Stratifying by genotype, a positive correlation between PAI-1 and CRP in 4G/4G (partial r = 0.64 p < 0.001) and 4G/5G (partial r = 0.47, p < 0.001) subjects was found, whereas no correlation in 5G/5G was present. Multiple regression analysis confirmed the presence of this correlation in 4G/4G (partial r = 0.45, p < 0.001) and in 4G/5G (partial r = 0.34, p = 0.007) diabetic patients.ConclusionsThese findings demonstrate that CRP plays an important role in the complex mechanism regulating PAI-1 antigen in 4G diabetic carriers.     

Does treatment affect the levels of serum Interleukin-6, Interleukin-8 and procalcitonin in diabetic foot infection? A pilot study

AimsTo investigate about serum PCT, IL-6 and IL-8 levels and how they are affected by the treatment in diabetic foot patients.MethodsFifty patients’ blood samples were taken to study ESR and CRP, IL-6, IL-8 and PCT before and at the 14th day of the treatment.ResultsThe pretreatment results of the 50 patients showed positive correlations between PCT and either ESH (r = 0.49, p < 0.001), or CRP (r = 0.56, p < 0.001). Similarly, there was a positive correlation between IL-6 and ESH (r = 0.46, p = 0.001), just like as it was between IL-6 and CRP (r = 0.54, p < 0.001). At the 14th day, the levels of ESR (70 ± 30.2 and 58.4 ± 26.2, p = 0.02), CRP (63.8 ± 73.1 and 18.1 ± 19.7, p < 0.001) and PCT (0.6 ± 2.1 and 0.05 ± 0.02, p = 0.007) were significantly decreased while IL-6 was decreased at a close range to statistical significancy at healing patients (97.5 ± 147.2 and 47.1 ± 77.6; p = 0.05), but they did not at nonhealing patients. IL-8 levels were not changed anyhow.ConclusionsPCT was significantly decreased such as ESR and CRP were in the early phase of healing; IL-6 and IL-8 levels were also decreased by the treatment, but not statistically significantly. IL-6 and PCT were affected in correlation with the other inflammatory parameters in the beginning, but IL-8 was not. PCT and IL-6 may be useful like CRP and ESR in the diagnosis and follow up of diabetic foot infection, but IL-8 is not. Further investigation is needed.