Nikolaos Papanas

Mean platelet volume in patients with type 2 diabetes mellitus

Aim of the study: To evaluate mean platelet volume (MPV) in type 2 diabetic versus non-diabetic patients, as well as to investigate the associations between MPV and diabetic complications. Materials and methods: This study included 416 patients divided into two groups. Group A comprised 265 type 2 diabetic patients (131 men) with a mean age of 67.4 ± 9.5 years and a mean diabetes duration of 14.5 ± 5.7 years. Group B comprised 151 non-diabetic patients (74 men) with a mean age of 68.6 ± 9.1 years. MPV (blood samples anticoagulated with sodium citrate) was measured in two blood cell counters (Sysmex SF 3000 and Cell-Dyn 3700). Results: MPV was significantly higher (P = 0.01) in group A (14.2 ± 2.2 fl) than in group B (7.1 ± 1.2 fl). In group A MPV was significantly higher (P = 0.043) in patients with retinopathy (15.8 ± 1.3 fl) than in patients without retinopathy (10.9 ± 1.1 fl) and also significantly higher (P = 0.044) in patients with microalbuminuria (15.6 ± 1.2 fl) than in patients without microalbuminuria (10.1 ± 1.2 fl). No association, however, was found in group A between MPV and age, gender, duration of diabetes, insulin dependency, BMI, HbA1c, coronary artery disease or dyslipidaemia. Conclusions: MPV is higher in type 2 diabetic patients than in non-diabetic patients. Among type 2 diabetic patients MPV is higher in those who have microvascular complications (retinopathy or microalbuminuria).

Macrolides: from in vitro anti-inflammatory and immunomodulatory properties to clinical practice in respiratory diseases

BackgroundMacrolides have long been recognised to exert immunomodulary and anti-inflammatory actions. They are able to suppress the “cytokine storm” of inflammation and to confer an additional clinical benefit through their immunomodulatory properties.MethodsA search of electronic journal articles was performed using combinations of the following keywords: macrolides, COPD, asthma, bronchitis, bronchiolitis obliterans, cystic fibrosis, immunomodulation, anti-inflammatory effect, diabetes, side effects and systemic diseases.ResultsMacrolide effects are time- and dose-dependent, and the mechanisms underlying these effects remain incompletely understood. Both in vitro and in vivo studies have provided ample evidence of their immunomodulary and anti-inflammatory actions. Importantly, this class of antibiotics is efficacious with respect to controlling exacerbations of underlying respiratory problems, such as cystic fibrosis, asthma, bronchiectasis, panbrochiolitis and cryptogenic organising pneumonia. Macrolides have also been reported to reduce airway hyper-responsiveness and improve pulmonary function.ConclusionThis review provides an overview on the properties of macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin), their efficacy in various respiratory diseases and their adverse effects.

Growth Factors in the Treatment of Diabetic Foot Ulcers: New Technologies, Any Promises?

Foot ulcers remain a common problem, leading to increased morbidity in patients with diabetes. Despite the progress that has been achieved in revascularization techniques as well as in off-loading to relieve high-pressure areas, diabetic foot wounds remain a clinical challenge. Growth factors are a major technological advance that promised to change the face of wound healing. The most important of growth factors are recombinant human platelet-derived growth factor-BB and granulocyte colony-stimulating factor. The former has been approved by the FDA for the treatment of neuropathic ulcers when there is adequate blood supply. The latter is less demonstrably useful. Advances include methods of delivering growth factors.

Epidemiology of polyneuropathy in diabetes and prediabetes

Diabetic distal symmetric sensorimotor polyneuropathy (DSPN) represents a major health problem, associated with excruciating neuropathic pain, increased morbidity and impaired quality of life. The understanding of its epidemiology is difficult due to methodological issues. Inconsistency in the selection of diagnostic procedures renders comparison between studies problematic. Further problems arise from selection bias due to the inclusion of hospital-based populations. DSPN affects approximately 30% of hospital-based populations, 20% of community-based samples, and 10% of the diabetic population identified by screening. Chronic painful DSPN is present in 13-26% of diabetic patients. Between 25% and 62% of patients with idiopathic peripheral neuropathy have prediabetes. Among pre-diabetic subjects, 11-25% exhibit peripheral neuropathy and 13-26% neuropathic pain. Evidence from population-based studies indicates that there is a gradient in the prevalence of neuropathy. Indeed, the highest frequency is found in patients with manifest diabetes mellitus, followed by individuals with impaired glucose tolerance, then impaired fasting glucose and, finally, those with normoglycemia. The most important etiologic factors are poor glycemic control, age, diabetes duration, visceral obesity, height, hypertension, age, smoking, hypoinsulinemia, and dyslipidemia. Clinic-based data suggest that DSPN is associated with increased mortality in diabetes, but confirmatory prospective population-based studies are required.

Mean Platelet Volume and Platelet Distribution Width in non-diabetic subjects with Obstructive Sleep Apnoea Syndrome: New indices of severity?

Aim of the study: To evaluate Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) in non-diabetic subjects, according to obstructive sleep apnoea syndrome (OSAS) severity and the associations of these indices with anthropometric characteristics and parameters of breathing function during sleep. Materials and methods: We included 610 non-diabetic subjects with suspected OSAS, evaluated by polysomnography. According to their apnoea-hypopnoea index (AHI), patients were divided into Group A (n = 148) with AHI < 5/h; Group B (n = 121) with AHI: 5–14.9/h; Group C (n = 85) with AHI: 15–29.9/h and Group D (n = 256) with AHI ≥ 30/h. MPV and PDW were measured using an automated blood cell counter. Results: MPV was significantly higher in group D (mean value 12.1 ± 1.3 fl) than in groups A (9.8 ± 1.1 fl), B (9.8 ± 1.6 fl), and C (11.5 ± 1.3 fl) (p < 0.001). The same pattern was observed in PDW values (15.9 ± 2.2 fl for group D and 13.2 ± 2.2 fl for group A, 14.1 ± 2.8 fl for group B, and 15 ± 2.2 fl for group C, p < 0.001). Significant correlations were seen between MPV and AHI (p < 0.001), average pulse oxygen saturation (SpO2) (p < 0.001), minimum SpO2 (p < 0.001) and percent of the total sleep time with SpO2 lower than 90% (t < 90%) (p < 0.001) during sleep, Arousal Index (p < 0.001) and Epworth sleepiness scale (ESS) (p = 0.028). Similarly, PDW was correlated with AHI (p < 0.001), average SpO2 (p = 0.001), minimum SpO2 (p < 0.001), t < 90% (p = 0.002), and Arousal Index (p < 0.001). Conclusions: MPV and PDW are higher in non-diabetic patients with severe OSAS and are correlated with different parameters of breathing function during sleep.

Markers of glycemic control and insulin resistance in non-diabetic patients with Obstructive Sleep Apnea Hypopnea Syndrome: Does adherence to CPAP treatment improve glycemic control?

BACKGROUND AND AIM Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) is associated with glucose dysmetabolism and insulin resistance, therefore the amelioration of breathing disturbances during sleep can allegedly modify the levels of markers of glucose regulation and insulin resistance, such as glycated hemoglobin, fasting glucose, insulin and HOMA(IR). The aim of this study was to explore the association between these parameters and sleep characteristics in non-diabetic OSAHS patients, as well as the effect of 6 months CPAP therapy on these markers, according to adherence to CPAP treatment. METHODS Euglycemic patients (n=56; mean age+/-SD: 46.07+/-10.67 years) with newly diagnosed OSAHS were included. Glycated hemoglobin, fasting glucose, insulin levels and HOMA(IR) were estimated at baseline and 6 months after CPAP application. According to CPAP adherence, patients were classified as follows: group 1 (mean CPAP use 4 h/night), group 2 (mean CPAP use < 4 h/night) and group 3 (refused CPAP treatment), and comparisons of levels of the examined parameters were performed. RESULTS At baseline, average SpO(2) during sleep was negatively correlated with insulin levels and HOMA(IR) while minimum SpO(2) during sleep was also negatively correlated with insulin levels. After 6 months, only group 1 patients demonstrated a significant decrease in glycated hemoglobin (p=0.004) accompanied by a decrease in hs-CRP levels (p=0.002). No other statistically significant change was observed. CONCLUSIONS Nighttime hypoxia can affect fasting insulin levels in non-diabetic OSAHS patients. Good adherence to long-term CPAP treatment can significantly reduce HbA(1C) levels, but has no effect on markers of insulin resistance.

Charcot osteoarthropathy in diabetes: A brief review with an emphasis on clinical practice

Charcot osteoarthropathy (COA) is a potentially limbthreatening condition that mainly affects diabetic patients with neuropathy. In everyday practice, it presents as a red, hot, swollen foot, usually painless, and is frequently triggered by trivial injury. Its etiology is traditionally attributed to impairment of either the autonomic nervous system, leading to increased blood flow and bone resorption, or of the peripheral nervous system, whereby loss of pain and protective sensation render the foot susceptible to repeated injury. More recently, excessive local inflammation is thought to play a decisive role. Diagnosis is based on clinical manifestation and imaging studies (plain X-rays, bone scan, Magnetic Resonance Imaging). The mainstay of management is immediate off-loading, while surgery is usually reserved for chronic cases with irreversible deformities and/or joint instability. The aim of this review is to provide an overview of COA in terms of pathogenesis, classification and clinical presentation, diagnosis and treatment, with an emphasis on the high suspicion required by clinicians for timely recognition to avoid further complications.

New diagnostic tests for diabetic distal symmetric polyneuropathy

Neuropathy needs to be diagnosed early to prevent complications, such as neuropathic pain or the diabetic foot. It is obvious that diagnosis of neuropathy needs to be improved. New peripheral nerve function tests that appear to facilitate diagnosis are now emerging. This review outlines the new tests that have been proposed for the diagnosis of diabetic distal symmetric polyneuropathy, the commonest form of neuropathy in diabetes. New tests are classified into those mainly assessing large-fiber function (tactile circumferential discriminator, steel ball-bearing, and automated nerve conduction study) and those mainly assessing small-fiber function (NeuroQuick and Neuropad). Emerging tests are promising but must be evaluated in prospective studies. Moreover, their cost-effectiveness needs more careful appraisal. The clinician should, therefore, still rely on established modalities to diagnose neuropathy, but wider use of the new tests is expected in the near future.

Benefit-Risk Assessment of Becaplermin in the Treatment of Diabetic Foot Ulcers

Becaplermin is a recombinant platelet-derived growth factor composed of two B chains that is approved for the treatment of neuropathic diabetic foot ulcers extending into or beyond the subcutaneous tissue in patients with adequate arterial perfusion. The aim of this review is to assess the benefits and risks associated with the use of this agent. Randomized controlled trials have provided evidence for the efficacy of becaplermin in increasing healing rates, and cost analyses have repeatedly shown a favourable cost-effectiveness ratio. However, clinical experience has not met these high expectations and becaplermin is not widely used. Moreover, this agent has not been compared with other additional treatment modalities, notably bioengineered skin substitutes and extracellular matrix proteins, and such comparisons are eagerly awaited. Of particular note, increased cancer risk has been reported in patients treated with more than three tubes of becaplermin; thus, this agent should be used only when the anticipated benefits outweigh the potential harm, and with extreme caution in patients with diagnosed malignancy. Finally, longer follow-up data are necessary to shed more light on the potential risk of malignancy in connection with becaplermin use.

HbA1c is associated with severity of obstructive sleep apnea hypopnea syndrome in nondiabetic men

The aim of this study was to examine the potential correlation of sleep characteristics with glucose metabolism in nondiabetic men with obstructive sleep apnea syndrome (OSAS). Included were 31 male patients (mean age 46.7 ±11 years), recently diagnosed with OSAS by full polysomnography. There was a significant correlation of fasting glucose and glycosylated hemoglobin (HbA1c) levels with arousal index (P = 0.047 and P =0.014, respectively). Moreover, HbA1c levels were correlated with apnea hypopnea index (P =0.009), a widely accepted marker of the severity of OSAS, and with percentage of sleep time with saturation of hemoglobin with oxygen as measured by pulse oximetry (SpO2) < 90% (t < 90%) ( P =0.010). Finally, glucose and HbA1c levels showed a significant negative correlation with average SpO2 (P =0.013 and P = 0.012, respectively) and, additionally, glucose levels with minimum SpO 2 (P =0.027) during sleep. In conclusion, severity of OSAS among nondiabetic men is associated with increased HbA1c levels and increased fasting glucose. Thus, severity of OSAS may be an additional marker of cardiovascular risk, as well as of future diabetes, in these subjects. However, further work is needed to confirm the clinical significance of these observations.