Anna Gotzamani-Psarrakou

Effect of various treatments on leptin, adiponectin, ghrelin and neuropeptide Y in patients with type 2 diabetes mellitus

Introduction: Several peptides are involved in the regulation of food intake and energy expenditure, among which are leptin, adiponectin, ghrelin and neuropeptide Y (NPY). These peptides may be implicated in the obesity seen in the majority of patients with type 2 diabetes mellitus (T2DM). Areas covered: The present review considers: i) the role of leptin, adiponectin, ghrelin and NPY in patients with T2DM, and, ii) the effect of insulin as well as oral hypoglycemic, antihypertensive, hypolipidemic, antiobesity and antiplatelet agents on these peptides in patients with T2DM. Expert opinion: Patients with T2DM have either lower or similar leptin levels, decreased adiponectin and ghrelin levels, and increased NPY circulating levels compared with nondiabetic controls. Treatment with insulin, oral hypoglycemic, antihypertensive, hypolipidemic, antiobesity and antiplatelet drugs may influence the levels of these peptides. It is not widely appreciated that several drugs commonly administered to patients with T2DM can influence adipokine levels. The clinical relevance of these effects needs to be evaluated.

Evaluation of Dopaminergic Function in Frontotemporal Dementia Using 123I-FP-CIT Single Photon Emission Computed Tomography

Extrapyramidal symptoms are observed in frontotemporal dementia (FTD). 123I-FP-CIT (DaT scan) single photon emission computed tomography (SPECT) can detect loss of presynaptic dopamine transporters in the striatum. We aimed to evaluate the dopaminergic status of the striatum in patients with FTD using DaT scan. Seven patients (age range 65–76 years), who fulfilled the Neary criteria and in whom the diagnosis of FTD was confirmed by hexamethylpropyleneamine oxime SPECT, were included in the study. The severity of the extrapyramidal symptoms was evaluated by the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS). SPECT using 123I-FP-CIT was done. A (region – occipital)/occipital ratio was calculated for the striatum, putamen and caudate nucleus. The results were compared with those of the 7 age-matched normal controls. The uptake of the radiotracer in the right and left striatum was reduced to 62% (p = 0.000) and 68% (p = 0.000), respectively, compared to controls. The motor UPDRS score of the patients with FTD showed a negative correlation to the uptake of the radiotracer. The presynaptic dopamine transporter in FTD is impaired, related to the severity of the extrapyramidal symptoms. Since an effective treatment for FTD is still to be established, there is a need for evaluating the efficacy of dopaminergic drugs.

Response of biochemical markers of bone turnover to oral glucose load in diseases that affect bone metabolism

OBJECTIVE Postprandial suppression of bone resorption is considered one of the main contributors in the circadian rhythm of bone turnover markers. The aim of this study was to investigate this physiological response of bone tissue in diseases that affect bone metabolism. PATIENTS AND METHODS In this study, 118 patients (45 hypothyroid, 40 hyperthyroid, and 33 β-thalassemic patients) and 78 healthy individuals matched for age and body mass index were included. An oral glucose test (75 g glucose) was performed after overnight fasting. Serum levels of procollagen type-I N-terminal propeptide (P1NP), β-C-terminal telopeptide of type I collagen (β-CTX), and osteocalcin were assayed at 0, 60, and 120 min. RESULTS Baseline values of bone turnover markers were significantly elevated in hyperthyroid and β-thalassemic patients but not in hypothyroid patients compared with the control group. After oral glucose, the levels of β-CTX but not P1NP or osteocalcin were significantly suppressed in all groups (mean change from baseline is 46.9% for β-CTX, 7.9% for P1NP, and 8% for osteocalcin). The percentage change from baseline for β-CTX was significantly augmented in hypothyroidism (52 vs 42%, P=0.009). CONCLUSION The preservation or even augmentation of postprandial suppression of bone resorption in diseases that affect bone metabolism through distinct pathogenetic mechanisms suggests the importance of this physiological response to nutrients for the general homeostasis and functional integrity of the skeleton.

Effects of Improving Glycemic Control with Insulin on Leptin, Adiponectin, Ghrelin and Neuropeptidey Levels in Patients with Type 2 Diabetes Mellitus: a Pilot Study

Objective: Insulin therapy is associated with weight gain in patients with type 2 diabetes mellitus (T2DM). Several peptides are implicated in appetite control. We evaluated the effects of insulin-induced improved glycaemic control on leptin, adiponectin, ghrelin, neuropeptide Y (NPY) levels and patient characteristics. Method: Consecutive T2DM patients (n = 90) were divided into 2 groups: Group A: 45 insulin-naïve uncontrolled (glycosylated haemoglobin A1c; HbA1c >7%) patients on oral hypoglycaemic agents (OHAs) who converted to insulin monotherapy. Group B: 45 well-controlled (HbA1c <7%) patients on OHAs. Both groups were monitored at baseline, 3 and 6 months. Males and females were analyzed separately because some hormone levels differ between genders. Results: In both genders, insulin therapy (Group A) was associated with significant (p = 0.003 to <0.001) increases in weight, body mass index and leptin levels and significant decreases in glucose, HbA1c and NPY levels. In male insulin-treated patients a significant increase in adiponectin levels (p = 0.008) was observed. There were significant correlations (p = 0.016 to <0.001) between leptin levels, waist circumference and body fat in all patient groups, except group B males. Conclusion: Changes in leptin, adiponectin and NPY levels may occur after insulin-induced improved glycaemic control. These changes may be influenced by gender, weight, body fat and HbA1c.

Pupillometry and 123I-DaTSCAN imaging in Parkinson's Disease: A Comparison Study

ABSTRACT The purpose of this study was the evaluation of pupil light reflex (PLR) in patients with Parkinsons disease (PD) by using a modern pupillometry system and the investigation of its potential relationship with dopamine transporter imaging (DaTSCAN), which is an objective method for the evaluation of presynaptic dopaminergic system. PLR was evaluated using pupillometry in 35 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited using a fully automated pupillometry system and six parameters were measured. Dopamine transporter imaging was performed using radioactive ioflupane 123I-FP-CIT [123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane]. A significant increase in latency and a significant decrease in amplitude, maximum constriction velocity, as well as maximum acceleration were observed in PD patients. There was no significant difference in initial radius and minimum radius values. Investigating the relationship between pupillometry parameters and 123I-FP-CIT binding values, we correlated values from the semiquantitative analysis of radioligand uptake with pupillometry parameters, but we found no significant correlation. This study demonstrates PLR impairment in patients with PD without overt autonomic dysfunction. This impairment does not seem to correspond to the reduction of radioligand binding in the striatum as the result of presynaptic dopaminergic dysfunction, suggesting a different deterioration rate of these systems.

Imaging beyond the striatonigral dopaminergic system in Parkinson's disease.

Parkinson s disease (PD) is characterized by progressive loss of dopaminergic neurons in the nigrostriatal pathway, but this seems to constitute only part of the whole pathological process of the disease. Accumulating data have documented the concomitant degeneration of other dopaminergic pathways and of the serotonergic, cholinergic and noradrenergic neurotransmitter systems. In addition, pathologic process is not only restricted in the brain, since the spinal cord and the peripheral autonomic nervous system are also affected. The pathogenesis of PD remains unclear. The use of positron emission tomography and single photon emission tomography may contribute to the understanding of these aspects of the disease. This review will discuss the role of PET and SPET in imaging the extrastriatal dopaminergic system and other neurotransmitter systems as well as the imaging of microglial activation and cardiac sympathetic denervation in PD. In conclusion, several PET and SPET ligands can detect changes in extrastriatal dopaminergic system as well as in the serotonergic, cholinergic and noradrenergic systems in PD and also explore its possible correlation with motor and non motor symptoms. The use of PET scintigraphy allows the detection of microglial activation in PD, while (123)I-MIBG scintigraphy depicts cardiac sympathetic denervation in PD and is a useful imaging tool for differentiating PD from other types of parkinsonism.

Adipokines and vascular risk in type 2 diabetes mellitus.

In this issue of Angiology, El-Mesallamy et al report the levels of adipokines (ie, adiponectin and monocyte chemoattractant protein 1 [MCP-1]), as well as inflammatory (high-sensitivity C-reactive protein [hsCRP], interleukin 1b [IL-1b], and soluble E-selectin) and oxidative stress markers (malondialdehyde [MDA] and nitric oxide [NO]) in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease ([CHD] group III), T2DM patients without CHD (group II), and controls (group I). All participants were obese. Monocyte chemoattractant protein 1, hsCRP, IL-1b, E-selectin, and MDA levels were significantly higher, and the adiponectin levels significantly lower in the diabetic groups compared with controls. These findings represent the low-grade inflammation and endothelial dysfunction that characterize T2DM, even in the absence of CHD. Monocyte chemoattractant protein 1, hsCRP, and E-selectin concentrations differed significantly between patients groups, suggesting that the inflammatory atherosclerotic process is more severe in T2DM patients with CHD than in T2DM patients without CHD. However, IL-1b levels were similar in both patient groups, whereas adiponectin and MDA were nonsignificantly lower in group III. In the T2DM population of the El-Mesallamy et al study (ie, groups II and III), significant inverse associations were observed between adiponectin and body mass index (BMI), glycosylated hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), MDA, IL-1b, MCP-1, and E-selectin. Furthermore, adiponectin correlated significantly with HDL-C and NO. These associations are in agreement with the previous studies and suggest that adiponectin participates in several biological processes. Indeed, adiponectin has been shown to exert beneficial ‘‘pleiotropic effects’’ (ie, anti-inflammatory, antioxidant, insulin sensitizing, and antiatherosclerotic). In obese patients and patients with T2DM or cardiovascular disease ([CVD] ie, CHD, carotid atherosclerosis, and peripheral artery disease [PAD]), the adiponectin levels are decreased. As a result, adiponectin-induced protection on the vasculature is lost and thus hypoadiponectinemia leads to increased CVD risk. Low circulating adiponectin levels have also been linked with diabetic nephropathy, retinopathy, and diabetic foot complications. Although high adiponectin levels are considered beneficial for the cardiovascular system, Dekker et al reported a significant association between elevated adiponectin levels and CVD mortality in patients with prevalent CVD. It was suggested that in those patients the adiponectin increase is compensatory and, therefore, indicative of a high mortality risk. Furthermore, in patients with clinical evidence of vascular disease, low adiponectin concentrations were related to low risk for future cardiovascular events. The authors concluded that ‘‘the potential antiatherosclerotic properties of adiponectin do not apply for patients with already established vascular disease.’’ Monocyte chemoattractant protein 1 levels are elevated in patients with T2DM; hyperglycemia was shown to increase MCP-1 concentration in diabetic endothelial cells. Furthermore, endothelial cells obtained from the aorta of T2DM patients were characterized by MCP-1 overexpression. Upregulation of MCP-1 synthesis has also been associated with an increased risk of CVD and mortality in T2DM patients. Of note, the MCP-1-2518 AG þ GG polymorphism was an independent predictor of carotid intima-media thickness (cIMT) in patients with T2DM. Regarding diabetic microvascular complications, the aqueous MCP-1 levels are elevated in patients with severe diabetic retinopathy. Furthermore, there is evidence that MCP-1 contributes to the development of diabetic nephropathy. Apart from adiponectin and MCP-1, several other adipokines (ie, leptin, resistin, tumor necrosis factor-a [TNF-a], IL-6, and plasminogen activator inhibitor 1 [PAI-1]) may affect vascular risk in patients with T2DM. Briefly, plasma leptin levels were associated with CHD in diabetic patients, a correlation that remained significant even after adjustment for BMI

Hypertrophic osteoarthropathy manifested with isolated calcaneal periostitis in bone scintigraphy

Hypertrophic osteoarthropathy (HOA) is an incompletely understood syndrome characterized by digital clubbing and periosteal proliferation of long bones and it is commonly associated with primary lung tumors. Bone scintigraphy is a sensitive method in detecting HOA and characteristic findings have been reported. We present the case of a man with newly diagnosed non-small cell lung cancer, unremarkable clinical examination and blood tests and no digital clubbing. During disease staging, however, bone scintigraphy showed intense calcaneal cortical proliferation bilaterally without involvement of other parts of the skeleton. Cortical reaction of both calcanei resolved significantly after chemotherapy. This case indicates that HOA may manifest with isolated calcaneal periostitis bilaterally, which is a new addition to the literature.

Tc-99m depreotide imaging of I-131-negative recurrent metastatic papillary thyroid carcinoma

The detection of radioiodine (I‐131)‐negative metastases of differentiated thyroid carcinoma (DTC) has been hitherto successfully tried by the well‐known synthetic somatostatin analogue indium‐111‐labeled DTPA‐octreotide (In‐111 pentetreotide). The objective of this study was to evaluate the usefulness of scintiscan with the newer synthetic somatostatin analogue Tc‐99m depreotide, in the restaging of papillary thyroid carcinoma (PTC) with detectable serum thyroglobulin (Tg) levels and negative I‐131 whole‐body scan (WBS). Whole‐body planar and cervico‐thoracic tomographic scintigraphy (single‐photon emission tomography—SPET) with Tc‐99m depreotide was performed in a 68‐year‐old male patient suffering from PTC stage III, with a mild increase in serum Tg levels coupled with a recent negative I‐131 WBS. The findings were compared with those of neck ultrasonography (US) and computerized tomography (CT). Nodal neck dissection and histopathology provided the definitive diagnosis. Tc‐99m depreotide scanning revealed foci of cervical lymph node metastases, which did not accumulate I‐131. The findings were in accordance with neck US and CT. Histopathology established the diagnosis of metastatic cervical lymph node PTC. Lymph node immunoreactivity was positive for the somatostatin receptor subtypes 2, 5 and 3. Scintigraphy with Tc‐99m depreotide could prove a useful adjunct to the armamentarium for the follow‐up of PTC, especially in the setting of detectable serum Tg and negative I‐131 WBS.

Thyroid Autoimmunity in the Context of Type 2 Diabetes Mellitus: Implications for Vitamin D

Vitamin D deficiency has been associated with both type 2 diabetes mellitus (T2DM) and autoimmune disorders. The association of vitamin D with T2DM and thyroid autoimmunity (TAI) has not been investigated. Thus, we aimed to explore the putative association between T2DM and thyroid autoimmunity (TAI) focusing on the role of 25-hydroxy-vitamin D (25(OH)D). Study population included 264 T2DM patients and 234 controls. To explore the potential association between 25(OH)D and thyroid autoimmunity while controlling for potential confounders—namely, age, gender, body mass index, and presence of T2DM—multivariate logistic regression analyses were undertaken. Patients with T2DM were younger (P < 0.001) and had significantly lower 25(OH)D levels (P < 0.001) and higher anti-TPO titers (P = 0.005). Multivariable logistic regression analyses suggested that T2DM and 25(OH)D levels were significantly associated with the presence of thyroid autoimmunity. In an elderly population of diabetic patients and controls with a high prevalence of vitamin D deficiency/insufficiency, a patient with T2DM was found to be 2.5 times more likely to have thyroid autoimmunity compared to a nondiabetic individual and the higher the serum 25(OH)D levels were, the higher this chance was.