Olfactory and gustatory functions in patients with non-complicated type 1 diabetes mellitus.

The aim of this study was to evaluate any possible relationship between diabetic state and olfactory and gustatory functions in patients with non-complicated diabetes mellitus type 1 (T1D), and also to present evidence of the association between olfactory and gustatory scores and HbA1c values and disease durations. The study included 39 patients with non-complicated T1D and 31 healthy controls. Clinical characteristics such as age, gender, duration of disease, education levels and biochemical analyses (fasting blood glucose, urea, creatinine, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein (HDL-C), triglyceride, HbA1c, C-peptide, postprandial blood glucose) were measured. Subjective olfactory and gustatory tests were performed for all participants. There were no significant differences in olfactory tests between the two groups (odor thresholds 8.63 ± 0.91 vs. 8.55 ± 0.57, p = 0.66; odor discrimination 12.97 ± 0.80 vs. 12.74 ± 0.79, p = 0.24; odor identification 13.81 ± 0.98 vs. 13.72 ± 0.89, p = 0.69; TDI score 35.34 ± 1.94 vs. 34.97 ± 1.4, p = 0.37). There were also no significant differences in gustatory tests between the two groups (bitter 3.45 ± 0.51 vs. 3.44 ± 0.50, p = 0.90; sweet 3.32 ± 0.48 vs. 3.38 ± 0.49, p = 0.60; salty 3.13 ± 0.72 vs. 3.10 ± 0.72, p = 0.88; total score of taste 13.16 ± 1.61 vs. 13.13 ± 1.22, p = 0.92). Comparison of gustatory and olfactory scores according to disease duration of type 1 diabetes mellitus patients revealed that there were no differences between groups (all p > 0.05). T1D without complications may not be associated with olfactory and gustatory dysfunction according to subjective testing. We also found that gustatory and olfactory functions may not be related with HbA1c values and disease duration in non-complicated T1D.

The relationship between severity of coronary artery disease and plasma level of vascular endothelial growth factor.

OBJECTIVE: It has been known that ischemia or occlusion of coronary arteries in animal models increases the production of vascular endothelial growth factor (VEGF); however, little is known about the relationship between coronary artery disease and VEGF in humans. In this study, our aim was to evaluate the relationships between the degree of coronary occlusion and plasma VEGF level as well as other risk factors, including age, weight, arterial blood pressure, cholesterol, triglyceride, blood glucose, and high-sensitive C-reactive protein (hsCRP) in patients with established coronary artery disease. MATERIALS AND METHODS: Our study group consisted of 77 patients. Of these, 38 patients had normal coronary angiography (control group; group C) and 39 had abnormal angiography (17 critical lesion; group CL, 22 noncritical lesion; non-CL group). RESULTS: Plasma VEGF level was 116.95+/-30.12 pg/ml in the control group, 212.47+/-75.28 pg/ml in group CL, and 138.89+/-45.18 pg/ml in the non-CL group. Plasma VEGF level of group C was found to be lower than that of group CL (P<.05), but the difference between groups C and non-CL was insignificant (P>.05). However, logistic regression analysis showed that VEGF level of group CL was significantly higher (P<.001). There was a negative correlation between VEGF and haemoglobin (r=-0.58, P<.01), and positive correlation between VEGF and age (r=0.29, P<.04). There was no relationship between plasma VEGF level and other cardiac risk parameters. Group CL had a higher level of total and LDL-cholesterol levels. CONCLUSION: Increased plasma VEGF levels in patients with coronary artery disease may point that the coronary lesion is critical, and VEGF increase in patients with established coronary artery disease may be used as an indicator of the need for revascularization.

Retro- and orthonasal olfactory function in relation to olfactory bulb volume in patients with hypogonadotrophic hypogonadism.

INTRODUCTION: Idiopathic hypogonadotrophic hypogonadism with an olfactory deficit is defined as Kallmann syndrome and is distinct from normosmic idiopathic hypogonadotrophic hypogonadism. OBJECTIVE: Because olfactory perception not only consists of orthonasally gained impressions but also involves retronasal olfactory function, in this study we decided to comprehensively evaluate both retronasal and orthonasal olfaction in patients with idiopathic hypogonadotrophic hypogonadism. METHODS: This case-control study included 31 controls and 45 idiopathic hypogonadotrophic hypogonadism patients. All participants whose olfactory and taste functions were evaluated with orthonasal olfaction (discrimination, identification and threshold), retronasal olfaction, taste function and olfactory bulb volume measurement. The patients were separated into three groups according to orthonasal olfaction: anosmic idiopathic hypogonadotrophic hypogonadism, hyposmic idiopathic hypogonadotrophic hypogonadism and normosmic idiopathic hypogonadotrophic hypogonadism. RESULTS: Discrimination, identification and threshold scores of patients with Kallmann syndrome were significantly lower than controls. Threshold scores of patients with normosmic idiopathic hypogonadotrophic hypogonadism. were significantly lower than those of controls, but discrimination and identification scores were not significantly different. Retronasal olfaction was reduced only in the anosmic idiopathic hypogonadotrophic hypogonadism group compared to controls. Identification of bitter, sweet, sour, and salty tastes was not significantly different when compared between the anosmic, hyposmic, and normosmic idiopathic hypogonadotrophic hypogonadism groups and controls. Olfactory bulb volume was lower bilaterally in all patient groups when compared with controls. The olfactory bulb volume of both sides was found to be significantly correlated with threshold, discrimination and identification scores in idiopathic hypogonadotrophic hypogonadism patients. CONCLUSION: 1) There were no significant differences in gustatory function between controls and idiopathic hypogonadotrophic hypogonadism patients; 2) retronasal olfaction was reduced only in anosmic patients but not in orthonasally hyposmic participants, possibly indicating presence of effective compensatory mechanisms; 3) olfactory bulb volumes were highly correlated with olfaction scores in the hypogonadotrophic hypogonadism group. The current results indicate a continuum from anosmia to normosmia in idiopathic hypogonadotrophic hypogonadism patients.

Is There Any Effect on Smell and Taste Functions with Levothyroxine Treatment in Subclinical Hypothyroidism?

Subclinical hypothyroidism has been accused for coronary heart disease, lipid metabolism disorders, neuropsychiatric disorders, infertility or pregnancy related problems with various strength of evidence. Currently there is insufficient knowledge about olfaction and taste functions in subclinical hypothyroidism. Aim of the present study is to investigate the degree of smell and taste dysfunction in patients with subclinical hypothyroidism. 28 subclinical hypothyroid patients, and 31 controls enrolled in the prospective study in Istanbul, Turkey. Subclinical hypothyroid patients were treated with L-thyroxine for 3 months. Psychophysiological olfactory testing was performed using odor dispensers similar to felt-tip pens ("Sniffin' Sticks", Burghart, Wedel, Germany). Taste function tests were made using "Taste Strips" (Burghart, Wedel, Germany) which are basically tastant adsorbed filter paper strip. Patients scored lower on psychophysical olfactory tests than controls (odor thresholds:8.1±1.0 vs 8.9±1.1, p = 0.007; odor discrimination:12.4±1.3 vs 13.1±0.9, p = 0.016; odor identification:13.1±0.9 vs 14.0±1.1, p = 0.001; TDI score: 33.8±2.4 vs 36.9±2.1, p = 0.001). In contrast, results from psychophysical gustatory tests showed only a decreased score for "bitter" in patients, but not for other tastes (5.9±1.8 vs 6.6±1.0, p = 0.045). Three month after onset of treatment olfactory test scores already indicated improvement (odor thresholds:8.1±1.0 vs 8.6±0.6, p<0.001; odor discrimination:12.4±1.31 vs 12.9±0.8, p = 0.011; odor identification:13.1±0.9 vs 13.9±0.8, p<0.001; TDI scores:33.8±2.4 vs 35.5±1.7, p<0.001) respectively. Taste functions did not differ between groups for sweet, salty and, sour tastes but bitter taste was improved after 3 months of thyroxin substitution (patients:5.9±1.8 vs 6.6±1.2, p = 0.045). Correlation of changes in smell and taste, with thyroid function test were also evaluated. TSH, fT4 were found have no correlation with smell and taste changes with treatment. However bitter taste found positively correlated with T3 with treatment(r: 0.445, p: 0.018). Subclinical hypothyroid patients exhibited a significantly decreased olfactory sensitivity; in addition, bitter taste was significantly affected. Most importantly, these deficits can be remedied on average within 3 months with adequate treatment.

Identification of a Novel Deletion in AVP-NPII Gene in a Patient with Central Diabetes Insipidus.

Central Diabetes Insipidus (CDI) is caused by a deficiency of antidiuretic hormone and characterized by polyuria, polydipsia and inability to concentrate urine. Our objective was to present the results of the molecular analyses of AVP-neurophysin II (AVP-NPII) gene in a large familial neurohypophyseal (central) DI pedigree. A male patient and his family members were analyzed and the prospective clinical data were collected. The proband applied to hospital for eligibility to be a recruit in Armed Forces. The patient had severe polyuria (20 L/day), polydipsia (20.5 L/day), fatique, and deep thirstiness. CDI was confirmed with the water deprivation-desmopressin test according to an increase in urine osmolality from 162 mOsm/kg to 432 mOsm/kg after desmopressin acetate injection. To evaluate the coding regions of AVP-NPII gene, polymerase chain reactions were performed and amplified regions were submitted to direct sequence analysis. We detected a heterozygous three base pair deletion at codon 69-70 (207_209delGGC) in exon 2, which lead to a deletion of the amino acid alanine. A three-dimensional protein structure prediction was shown for the deleted AVP-NPII and compared with the wild type. The three base pair deletion may yield an abnormal AVP precursor in neurophysin moiety, but further functional analyses are needed to understand the function of the deleted protein.

Evaluation of electrocardiographic parameters in patients with diabetes insipidus.

BACKGROUND: There is limited data regarding the effect of altered serum osmolality on cardiac electrical activity. The aim of the present study is to evaluate the electrocardiographic (ECG) effects of diabetes insipidus (DI) and any related hyperosmolality in a population of young patients with DI and without any known cardiovascular disease or risk factors. METHODS: Twelve-lead ECG's of 44 consecutive untreated young male patients (age: 21.8 ± 2.9 years) who had been referred to endocrinology clinic and diagnosed as DI based on water deprivation test were retrospectively evaluated. A total of 30 age-matched (21.9 ± 2.4 years) healthy males were selected as control group and ECG's of these controls were obtained for comparison with ECG's of DI patients. All ECG parameters were measured and compared. RESULTS: Duration of QRS complex was significantly shorter in patients with DI compared with controls (85.2 ± 12.0 vs. 94.0 ± 10.6 ms, p: 0.001). P wave dispersion (PWD) of patients with DI was significantly higher compared with controls (31.9 ± 9.9 vs. 26.5 ± 10.6 ms, p: 0.03) and it was significantly correlated with serum osmolality and serum sodium level (r = - 0.36, p: 0.02 and r: - 0.35, p: 0.02, respectively). CONCLUSIONS: DI patients without any cardiovascular disease or risk factors displayed significantly shorter QRS duration and increased p wave dispersion compared with controls.

A large deletion of the AVPR2 gene causing severe nephrogenic diabetes insipidus in a Turkish family.

X-linked nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by mutations in arginine vasopressin type 2 receptor (AVPR2) and characterized by the production of large amounts of urine and an inability to concentrate urine in response to the antidiuretic hormone vasopressin. We have identified a novel 388 bp deletion starting in intron 1 and ending in exon 2 in the AVPR2 gene in a patient with NDI and in his family. We have revealed that this mutation is a de novo mutation for the mother of the proband patient. Prospective clinical data were collected for all family members. The water deprivation test confirmed the diagnosis of diabetes insipidus. The patient has severe symptoms like deep polyuria nocturia, polydipsia, and fatigue. He was given arginine vasopressin treatment while he was a child. However, he could not get well due to his nephrogenic type of illness. Both of his nephews have the same complains in addition to failure to grow. We have sequenced all exons and intron-exon boundaries of the AVPR2 gene of all family members. The analyses of bioinformatics and comparative genomics of the deletion were done via considering the DNA level damage. AVPR2 gene mutation results in the absence of the three transmembrane domains, two extracellular domains, and one cytoplasmic domain. Three-dimensional protein structure prediction was shown. We concluded that X-linked NDI and severity of illness in this family is caused by a novel 388 bp deletion in the AVPR2 gene that is predicted to truncate the receptor protein, and also this deletion may lead to dysfunctioning in protein activity and inefficient or inadequate binding abilities.

Retro-and orthonasal olfactory function in relation to olfactory bulb volume in patients with hypogonadotrophic hypogonadism / Função olfativa retro e ortonasal em relação ao volume do bulbo olfatório em pacientes com hipogonadismo hipogonadotrófico

Abstract Introduction: Idiopathic hypogonadotrophic hypogonadism with an olfactory deficit is defined as Kallmann syndrome and is distinct from normosmic idiopathic hypogonadotrophic hypogonadism. Objective: Because olfactory perception not only consists of orthonasally gained impressions but also involves retronasal olfactory function, in this study we decided to comprehensively evaluate both retronasal and orthonasal olfaction in patients with idiopathic hypogonadotrophic hypogonadism. Methods: This case-control study included 31 controls and 45 idiopathic hypogonadotrophic hypogonadism patients. All participants whose olfactory and taste functions were evaluated with orthonasal olfaction (discrimination, identification and threshold), retronasal olfaction, taste function and olfactory bulb volume measurement. The patients were separated into three groups according to orthonasal olfaction: anosmic idiopathic hypogonadotrophic hypogonadism, hyposmic idiopathic hypogonadotrophic hypogonadism and normosmic idiopathic hypogonadotrophic hypogonadism. Results: Discrimination, identification and threshold scores of patients with Kallmann syndrome were significantly lower than controls. Threshold scores of patients with normosmic idiopathic hypogonadotrophic hypogonadism. were significantly lower than those of controls, but discrimination and identification scores were not significantly different. Retronasal olfaction was reduced only in the anosmic idiopathic hypogonadotrophic hypogonadism group compared to controls. Identification of bitter, sweet, sour, and salty tastes was not significantly different when compared between the anosmic, hyposmic, and normosmic idiopathic hypogonadotrophic hypogonadism groups and controls. Olfactory bulb volume was lower bilaterally in all patient groups when compared with controls. The olfactory bulb volume of both sides was found to be significantly correlated with threshold, discrimination and identification scores in idiopathic hypogonadotrophic hypogonadism patients. Conclusion: 1) There were no significant differences in gustatory function between controls and idiopathic hypogonadotrophic hypogonadism patients; 2) retronasal olfaction was reduced only in anosmic patients but not in orthonasally hyposmic participants, possibly indicating presence of effective compensatory mechanisms; 3) olfactory bulb volumes were highly correlated with olfaction scores in the hypogonadotrophic hypogonadism group. The current results indicate a continuum from anosmia to normosmia in idiopathic hypogonadotrophic hypogonadism patients.

Resumo Introdução: O hipogonadismo hipogonadotrófico idiopático com déficit olfatório é definido como síndrome de Kallmann e é distinto de hipogonadismo hipogonadotrófico idiopático normósmico. Objetivo: Pelo fato de a percepção olfativa não apenas consistir em impressões obtidas ortonasalmente, mas também envolver a função olfativa retronasal, neste estudo decidimos avaliar de maneira abrangente o olfato retronasal e ortonasal em pacientes com hipogonadismo hipogonadotrófico idiopático. Método: Este estudo caso-controle incluiu 31 controles e 45 pacientes com hipogonadismo hipogonadotrófico idiopático. Todos os participantes tiveram as funções olfativas e de paladar avaliadas com olfação ortonasal (discriminação, identificação e limiar), olfação retronasal, função do paladar e medida do volume do bulbo olfatório. Os pacientes foram separados em três grupos de acordo com a olfação ortonasal: hipogonadismo hipogonadotrófico idiopático anósmico, hipogonadismo hipogonadotrófico idiopático hipósmico e hipogonadismo hipogonadotrófico idiopático normósmico. Resultados: Os escores de discriminação, identificação e limiar de pacientes com síndrome de Kallmann foram significativamente menores do que os controles. Os escores dos limiares de pacientes com hipogonadismo hipogonadotrófico idiopático normósmico foram significativamente menores do que os dos controles, mas os escores de discriminação e identificação não foram significativamente diferentes. A olfação retronasal foi reduzida apenas no grupo hipogonadismo hipogonadotrófico idiopático anósmico em comparação com os controles. A identificação de gostos amargos, doces, azedos e salgados não foi significativamente diferente quando comparada entre os grupos e controles de hipogonadismo hipogonadotrófico idiopático anósmicos, hipósmicos e normósmicos. O volume do bulbo olfatório foi menor bilateralmente em todos os grupos de pacientes quando comparado com os controles. O volume do bulbo olfatório de ambos os lados foi significativamente correlacionado com os escores de limiar, discriminação, identificação em pacientes com hipogonadismo hipogonadotrófico idiopático. Conclusão: 1) Não houve diferenças significativas na função gustativa entre controles e pacientes com hipogonadismo hipogonadotrófico idiopático; 2) A olfação retronasal foi reduzida apenas em pacientes anosmáticos, mas não em participantes ortonasalmente hipósmicos, possivelmente indicou presença de mecanismos compensatórios efetivos; 3) Os volumes do bulbo olfatório foram altamente correlacionados com os escores de olfação no grupo hipogonadismo hipogonadotrófico. Os resultados atuais indicam um contínuo da anosmia à normosmia em pacientes com hipogonadismo hipogonadotrófico idiopático.

Plasma apelin and asymmetric dimethylarginine levels in type 2 diabetic patients with diabetic retinopathy.

Oxidative stress is thought to be one of the underlying mechanisms of diabetic microvascular complications such as diabetic nephropathy and diabetic retinopathy (DRP). Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthase inhibitor and increased by oxidative stress. Apelin is an endogenous ligand for human orphan G-protein-coupled receptor, APJ and increases NO generation. In this study, our aim was to evaluate ADMA and apelin levels in diabetic patients with or without retinopathy and their relationships between retinopathy stages and metabolic parameters. Seventy-nine diabetic patients were included into the study and classified into three groups. Group 1 consisted of 41 patients with no DRP (NDRP), group 2 consisted of 23 patients with nonproliferative DRP (NPDRP), and group 3 consisted of 15 patients with proliferative DRP (PDRP). Plasma ADMA and apelin levels were found to be similar in all groups. But, there was a positive correlation between apelin levels and urinary albumin/creatinine ratio. Further studies involving larger patients populations and healthy controls should be done to clarify the pathogenetic significance of ADMA and apelin in diabetic microvascular complications.

Plasma ghrelin levels in males with idiopathic hypogonadotropic hypogonadism.

It has recently been shown that ghrelin is a pleitropic modulator with effects on diverse biological functions, such as energy homeostasis and reproduction. In this study, ghrelin levels and its relationship between metabolic and biochemical parameters were investigated in male subjects with idiopathic hypogonadotropic hypogonadism (IHH). Patients in the study were composed of 33 men with IHH, and controls were composed of 36 healthy age-matched men. The patients' group had significantly higher waist/hip ratio (WHR), and lower testis volume, luteinizing hormone (LH), follicle stimuling hormone (FSH) and total testosterone (TT) levels when compared with controls. Plasma total ghrelin levels were significantly lower in patients than in controls (96.4 +/- 29.1 ng/ml vs. 146.1 +/- 28.9 ng/ml, P < 0.001, respectively). No correlation of ghrelin was found with body mass index, waist/hip ratio, homeostasis model assessment insulin resistance index, testis volume, LH, FSH and TT levels in both patients and controls. The present study showed that ghrelin levels were significantly lower in men with IHH than in controls. However, further studies are needed to better understand the relationships between ghrelin, and metabolic and reproductive systems.

Plasma soluble intercellular adhesion molecule 1 levels are increased in type 2 diabetic patients with nephropathy.

BACKGROUND/AIM: Intercellular adhesion molecule 1 (ICAM-1) is a mediator in the recruitment of leukocytes in the glomerular cells. The role of ICAM-1 in diabetic complications is still a matter of debate. This study was performed to investigate the relation of plasma soluble ICAM-1 (sICAM-1) to nephropathy in patients with type 2 diabetes mellitus. METHODS: Ninety-three patients (24 males and 69 females) with type 2 diabetes mellitus were included into the study. Fifty patients had nephropathy, and 43 were free from nephropathy. Fifty healthy subjects (14 males and 36 females) served as the control group (group 1). Twenty-five of the diabetic patients had microalbuminuria (group 2), 25 had macroalbuminuria (group 3), and 43 had neither micro- nor macroalbuminuria (group 4). The plasma sICAM-1 levels were measured in blood samples drawn after fasting. RESULTS: The mean plasma sICAM-1 levels were not different in the 93 diabetic patients as compared with the healthy controls (392.7 +/- 119.5 vs. 350.1 +/- 90.2 ng/ml, p > 0.05). The mean sICAM-1 level was significantly higher in the diabetic patients with nephropathy than in those without nephropathy (430.3 +/- 78.2 vs. 368.2 +/- 122.5 ng/ml, p = 0.03) and in the controls (430.3 +/- 78.2 vs. 350.1 +/- 90.2 ng/ml, p = 0.016). The difference in sICAM-1 levels between groups 2 and 3 was not significant (p > 0.05). The plasma sICAM-1 levels were significantly higher in both groups 2 and 3 than in both groups 1 and 4 (434.5 +/- 129.2 vs. 427.2 +/- 113.7 ng/ml and 368.2 +/- 122.5 vs. 350.1 +/- 90.2 ng/ml, respectively). CONCLUSIONS: The plasma sICAM-1 levels in patients with type 2 diabetes mellitus are not significantly different from those in nondiabetic subjects. High levels of sICAM-1 suggest that sICAM-1 may play a role in the development of nephropathy in patients with type 2 diabetes mellitus.