Band 43, Heft 3

Objectives Several metabolic disturbances are seen in acromegaly however, data regarding the contribution of irisin to these disturbances is currently insufficient. In a cohort of patients with acromegaly, we measured serum irisin levels in active and controlled cases and determined independent factors that effect serum irisin including fibronectin type III domain-containing protein 5 (FNDC5) genotyping. Methods A cross-sectional case-control study including 46 patients with acromegaly (28 F/18 M, age: 50.3 ± 12.1 year, BMI: 30.7 ± 5.1 kg/m 2 ) and 81 age-, gender-, body mass index- and body composition-matched healthy controls was conducted. 15 acromegalic patients (33%) had active disease. Irisin levels were measured by enzyme-linked immunosorbent assay. Three different regions (rs3480, rs1746661, and rs16835198) of FNDC5 were subjected to polymorphism analyses. Results Both groups were overweight and had similar body composition. Irisin levels were lower in patients with acromegaly than controls (median [IQR]: 44.8 [41.7–46.7] ng/mL vs. 51.7 [45.5–60.1] ng/mL, p≤0.001, respectively). Active and controlled patients had similar irisin levels. Irisin was not correlated with growth hormone (GH), insulin-like growth factor 1 (IGF-1), and IGF-1 index. In multiple linear regression model, somatostatin receptor ligand use ( β =−20.30, 95% CI [−34]–[−6], p=0.006) was determined as the only independent factor that affect serum irisin. Conclusions Serum irisin levels are low in patients with acromegaly who are on somatostatin receptor ligand therapy. Single nucleotide polymorphisms (SNPs) of FNDC5 have no independent effects on circulating irisin levels under somatostatin ligand action. Endocrine muscle functions also seem to be regulated by somatostatin action, which requires further studies.

Objectives We aimed to evaluate the levels of serum lipoprotein a, LP (a), in Jordanian patients with type 2 diabetes mellitus (DM); and to examine its relation to glycemic control, metabolic syndrome (MS) and duration of DM. The LP (a) is considered one of the independent risk factors for coronary artery disease (CAD) in the general population. Methods Fasting blood samples were drawn from 51 diabetic patients with type 2 DM and 31 non-diabetic age and sex control subjects. Serum LP (a) was measured along with other parameters, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and glycosylated haemoglobin (HbA 1c ). Correlation analyses were performed between LP (a) and the various variables measured. Results LP (a) measurement showed a skewed distribution towards the lower levels in both groups. Mean LP (a) levels showed a statistically insignificant difference between the two groups. No correlations of LP (a) were observed with age, sex or body mass index (BMI). No correlations of LP (a) with LDL-c, HDL-c, TG, TC, MS, DM duration or HbA 1c were observed. The LP (a) serum levels were significantly higher in type 2 diabetic patients with retinopathy. Conclusions LP (a) serum levels are not increased in type 2 diabetic patients; so, LP (a) may not be a reliable marker for early therapeutic interventions in DM patients, even in high-risk for thrombosis groups.

Background Type 2 diabetes mellitus (T2DM) and obesity are prevalent in Kuwait. Vitamin D (VD) deficiency and leptin resistance are risk factors for both disorders. A correlation between the two risk factors has been suggested albeit inconsistently reported. Our objective was to determine the effect and association of VD and leptin levels and their related common variants with T2DM. Methods This case-control study included 203 Kuwaiti T2DM patients and 162 healthy Kuwaiti controls. Leptin and VD levels were measured using enzyme linked immunosorbent assays. Genotyping of LEP rs7799039, LEPR rs1137101, VDR rs2228570 and rs731236 was performed using Taqman genotyping assays. Results Leptin levels were higher in T2DM patients than controls, but vitamin D levels did not differ. No correlation was found between the levels of the two hormones. VDR rs731236G associated with T2DM risk (Odds ratio 1.66, p=0.0008). VDR haplotype analysis revealed GG/AA, GA/AA or GG/AG to associate with T2DM risk (p=0.01) and increased risk of diabetic neuropathy (p=0.002). VDR rs2228570GG associated with leptin levels in T2DM (p=0.01). Effect of LEP rs7799039 on leptin (p=0.01) and VD levels (p=0.02) was only evident in healthy controls. Conclusions VDR rs731236G is associated with T2DM risk in Kuwait, and a VDR haplotype of a less active, low expressing VDR is associated with T2DM and diabetic neuropathy risk. Common variants in leptin and VD related genes appear to mediate the suggested positive correlation of both hormones however their influence is disrupted in T2DM.

Objectives Vitamin D is an important regulator of the immune system, and it has been shown that deficiency of vitamin D is significant environmental factor in some immune-mediated diseases such as Multiple Sclerosis (MS). In this study, we have compared serum 25 hydroxyvitamin (OH) D levels in Relapsing-Remitting Multiple Sclerosis (RRMS), clinically isolated syndrome (CIS), and control groups. Methods Forty patients with CIS and 60 patients who have been diagnosed RRMS between age 18–45, respectively, and followed up at Pamukkale University Faculty of Medicine, Department of Neurology, and 60 healthy individuals have been included in this study. Serum 25(OH) vitamin D, calcium, phosphorus, alkaline phosphatase, parathormone, insulin, and fasting blood glucose levels were studied for all three groups. Results A statistically significant difference was determined in the comparison of three groups for mean 25(OH) vitamin D levels. In the intergroup comparison of mean 25(OH) vitamin D; mean 25(OH) vitamin D level was determined to be statistically significantly lower in both RRMS and CIS groups compared to control group (p<0.05). Conclusions Since vitamin D deficiency poses a problem from the early stage of disease spectrum in both CIS patients and MS patients, 25(OH) vitamin D level should be routinely controlled, and replacement should be administered upon any deficiency state.

Objectives Alpinia officinarum Hance, commonly known as lesser galangal, is a member of the ginger family (Zingiberaceae) traditionally used for many decades to treat inflammation, pain, stomach ache and cold. In the present study, the antidiabetic and hypolipidemic potentials of the hydroalcoholic extract of A. officinarum (AO) were investigated in the nicotinamide/streptozotocin induced type II diabetic rats. Methods Male Wistar rats were divided into following six groups: Group I was normal control rats. Group II: normal diabetic control, Group III: Diabetic rats treated with glibenclamide (0.25 mg/kg), IV, V and VI: Diabetic rats treated with 100, 200 and 500 mg/kg AO hydroalcoholic extract by daily gavage for 28 days, respectively. At the end of treatment, biochemical analysis, histological study, phytochemical analysis and acute toxicity tests were carried out. Results The results show significant reduction in blood glucose, serum lipid profiles, and liver enzyme levels in diabetic rats compared with diabetic control in AO treated group. Conclusions In conclusion, the present study demonstrated that AO extract had significant (p<0.05) antidiabetic and anti-hyperlipidemia effects in addition to hepatoprotective effect in type II diabetic rats.

Background Although obesity and T2DM comorbidity is too frequent, the molecular basis of diabetic obesity is largely unexplained and barely investigated. Materials Cross-sectional studies were conducted in Kingdom of Saudi Arabia (KSA) in 2013 and Kuwait in 2019. Fasting blood samples were obtained from a total of 216 T2DM patients (104 from KSA) and 193 nondiabetic subjects (93 from KSA) after their consents. Eight SNPs in 5 genes known to be associated with both obesity and T2DM, ghrelin ( GHRL ) and growth hormone secretagogue receptor - GHSR (KSA) and telomeres maintenance genes (Kuwait) were genotyped by rtPCR. Both patients and controls were grouped into obese and non-obese and sub-grouped into 4-BMI- grades: normal, overweight (OW), obese (OBS) and severely obese (SOBS). Results Showed that the only SNP which was distinguished between all groups/subgroups in all study subjects was the ACYP2 rs6713088G/C, where the common CC genotype was under-expressed in the obese compared to non-obese diabetics (17.8% vs. 40.4%, p 0.01) and between the 4-BMI-grade (p 0.025). Interestingly the same genotype was over-expressed in obese compared to non-obese non-diabetics (50% vs. 27.6%, p 0.04 ). Furthermore, the GHRL (rs27647C/T), GHSR (rs509030G/C) and TERC (rs12696304G/C) MAFs were significantly low in normal BMI patients; p=0.034, 0.008 and 0.011, respectively. Conclusions This is the first report about the molecular distinction between the obese and non-obese diabetics, it showed the association of rs6713088G/C mutant allele with diabetic obesity, while the GHRL , GHSR and TERC SNPs were differentially expressed based on the BMI-grades.

Objectives Diet is the major modifiable risk factor for the onset of insulin resistance and its progression into diabetes. In the present study the effect of various dietary fats on inflammatory homeostasis and glucose tolerance is investigated in high fat and high fructose fed mice model. Methods C57/BL6J mice were divided into four groups and fed a casein-based diet containing high fructose (45%) and high fat (24%) (clarified butter oil [CBO]; safflower oil [SFFO] and lard oil [LO]) for 120 days; oral glucose tolerance (OGTT), plasma lipid profile and plasma & adipose tissue cytokines levels were compared with the control diet (10% groundnut oil and 59.5% starch) fed animals. Results The total cholesterol and triglycerides were higher in CBO and LO fed animals with glucose intolerance and increased body weights; liver and white adipose tissue weights were higher in CBO and LO fed animals respectively. CBO feeding increased the plasma (IFN-γ) and adipose tissue cytokines (IFN-γ, IL-10, IL-6 & TNF-α). LO feeding increased plasma IFN-γ, TNF-α and IL-1β and adipose tissue IL-6. SFFO feeding decreased body weight and tissue cytokines and increased plasma IFN-γ levels without causing impairment in the glucose tolerance. Conclusions Consumption of a high fructose and high fat diet which mimic the present-day dietary pattern resulted in altered inflammatory homeostasis and impairment in glucose tolerance in 24% CBO and LO fed animals. The deleterious effects of high fructose feeding were reversed in SFFO fed mice possibly due to the presence of oleic and linoleic acids.

Objectives There is a need to develop reference interval of NO in health and disease. Methods Subjects aged between 25 and 55 years were drawn from a random sample of the north Indian population, based on defined inclusion and exclusion criteria. Measurement of NO was done based on principle of greiss reaction. Results Reference interval of NO in healthy individual of age group 25–55 years was 21 ± 13.3 μM/L (n=350), Premenopausal women of age group 25–35 years was 12.7 ± 4.9 μM/L (n=180), Postmenopausal women of age group 40–55 years was 10.3 ± 3.84 μM/L (n=100) and healthy pregnant females of age group 25–35 years was 70.9 ± 15.95 μM/L (n=330). In pathological state group, reference interval of NO in metabolic syndrome cases of age group 25–55 years was 19.4 ± 15.3 μM/L (n=100), coronary artery disease patient of age group more than 35 years was 17.6 ± 10.8 μM/L (n=160), pregnancy induced hypertension (PIH) of age group 25–30 years was 45.7 ± 7.2 μM/L (n=330), pre-eclampsia patient of age group 25–35 years was 39.8 ± 14.7 μM/L (n=200) and diabetic individuals of age group of more than 30 years was 15.5 ± 1.4 μM/L (n=50). Conclusions The reference intervals presented may be used for various research purposes. Based upon our study, reference interval for NO levels of various disease states like MetS, CAD, diabetes, PIH showed lower levels of NO compared to their respective healthy group due to shared etiopathologies with decreased NO levels.

Objectives Pregnancy is a critical period keenly regulated by both maternal and foetal factors and a shift in these factors could result in severe complications manifesting in foetal and adult life. However, maternal hypothyroidism before and/or during pregnancy is a critical factor. This study investigated the effect of maternal hypothyroidism on glucose tolerance and thyroid function in male and female offspring. Methods Fifteen adult female Wistar rats were divided into three groups: Group 1 (sham-control), Group 2 (thyrodectomized) and Group 3 (thyroidectomised + L-thyroxine treated). Blood thyroxine (T4) level was measured on the day 10 after thyroidectomy in Groups 1 and 2, and day 35 in Group 3. Males were introduced to the female rats after T4 measurement. At PND-112, T4 levels of their offspring were measured. Oral Glucose Tolerance Test (OGTT) was measured in offspring at PND-133. Results Thyroxine reduced significantly in Group 2 and their offspring (male and female) compared to Group 3 while gestation period was prolonged significantly in Group 2 compared to Group 1. Hypothyroid male offspring showed depressed glucose tolerance, however, no effect was observed in female offspring. Conclusions This study suggests that maternal hypothyroidism prolonged gestation period, induced foetal hypothyroidism in both genders and depressed glucose tolerance in male offspring.

Objectives Hypothyroidism is the most common endocrine disorder worldwide. Hypothyroisim increases cardiovascular risk, thus the study focuses on the assessment of cardiovascular risk factors such as serum Homocysteine, serum Oxidized LDL and Lipid profile and their correlation with TSH levels. Timely evaluation of these risk predictors would help in reducing cardiovascular disease morbidity and mortality in hypothyroidism. Methods This was a hospital based cross-sectional study consisting of Forty newly diagnosed patients with overt hypothyroidism in the age group of 20–60 years attending Medicine OPD were included as cases and Fifty healthy age and gender matched healthy controls participated as controls in the study. A written and informed consent to all the participants of both the groups was taken after explaining the purpose and details of the study. The Thyroid profile was assessed by CLIA-based MAGLUMI- 1000 analyzer and Serum total cholesterol, triglycerides and high-density lipoproteins were analyzed in Fully automated clinical chemistry analyzer EM-200 by using commercially available kits. LDL was calculated indirectly using Friedwalds equation. Commercially available ELISA-based kits were used for analysis of serum Homocysteine and serum oxidized-LDL. Results Elevated levels of serum homocysteine (p<0.0001), Oxidized LDL (p<0.0001) were found in newly diagnosed overt hypothyroid patients as compared to controls whereas significant elevated levelsof TC, TG, LDL, and VLDL (p<0.0001) and decrease in HDLcholesterol (p<0.0001) were reported in newly diagnosed newly diagnosed overt hypothyroid patients. Conclusions We concluded that the association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state and thyroid hormone failed to completely normalize Hcy levels. Thus, elevated plasma homocysteine levels may be an independent risk factor for the accelerated atherosclerosis seen in hypothyroidism. In addition, we found that the circulating ox-LDL levels were elevated in untreated hypothyroidism and they tend to be higher in thyroid dysfunction.

Objectives The cut off values for serum high sensitivity C-reactive protein (hsCRP), ferritin, interleukin 6 (IL-6) and plasma D-dimer could be of profound help in detecting COVID-19 patients at risk of adverse outcomes. Therefore, the aim of the present study is to determine the cut off values of the serum hsCRP, ferritin, IL-6 and plasma D-dimer in predicting mortality in COVID-19 patients. Methods Four hundred RT-PCR confirmed cases of COVID-19 were sub divided into two groups based on their outcome during hospitalisation. Group I consisted of survivors and Group II consisted of non-survivors. The survivors were further divided into three sub-groups: mild, moderate and severe based on the severity of infection. The laboratory data of serum hsCRP, ferritin, IL-6 and plasma D-dimer for all these patients was retrieved from the Medical Record Section of the Hospital. Results Mean serum hsCRP, ferritin, IL-6 and plasma D-dimer levels were significantly higher in non-survivors as compared to survivors of COVID-19. The levels of these biomarkers correlated with the severity of COVID-19 illness. ROC curve analysis revealed that plasma D-dimer is having a better predictive value as compared to other parameters in predicting mortality in COVID-19. Conclusions The serum hsCRP, ferritin, IL-6 and plasma D-dimer levels could be used in risk stratification of COVID-19 patients. The optimum cut off given by the current study could be considered in predicting adverse outcome in these patients. Amongst the many studied biomarkers, plasma D-dimer might be the best early biomarker to predict mortality in COVID-19 patients.

Objectives In this study, we investigated the beneficial effects of swimming exercise on the SIRT1, NF-κB, IL-1β protein levels, and pancreatic tissue damage in an ovariectomized diabetic rat model based on the anti-inflammatory effect of exercise. Methods Forty mature female Wistar rats were purchased and divided into sham (n=10) and OVX (bilateral ovariectomy) (n=30) groups. The ovariectomized rats were divided into 1-OVX, 2-ovariectomized diabetic (OVX.D), 3-OVX.D + exercise (OVX.D. E). After surgical recovery, animals in the diabetic group received a high-fat diet for one month. Swimming exercise (1 h/day) was performed concurrently with the start of the HFD diet for eight weeks. At the end of the high-fat diet, streptozotocin (30 mg/kg) was injected intraperitoneally. At the end of the second month, pancreatic tissue was collected from the animals after deep anesthesia for molecular evaluation and histology by Western blotting and hematoxylin-eosin, respectively. Results Swimming exercise significantly decreased inflammatory cytokines and tissue damage, and this decrease in cytokine expression appears to be associated with SIRT1 expression. The increase in SIRT1 by training was associated with decreased NF-κB-p65 and IL–1β expression and preventing tissue damage. Induction of diabetes in the ovariectomized group (OVX.D) resulted in a significant increase in NF-κB-p65 and IL–1β proteins and a decrease in the expression of SIRT1 compared with the sham group. However, swimming training significantly reversed these effects compared with the OVX.D group. Conclusions Increased inflammation of β-cells impairs insulin secretion in estrogen insufficiency. Swimming exercise eliminates inflammation in post-menopausal diabetes and supports the potential to prevent pancreatic activity after menopause. Highlights Combined effects of type 2 diabetes mellitus and estrogen deficiency increased the pancreatic expression of Nf-kB and IL-1B and subsequently decreased SIRT1 and finally lead to tissue injury in the pancreas compared to sham or OVX groups. – The exercise pretreatment significantly decreased destructive effect removing ovary as well as injection of STZ. – The exercise effectively decreased the pancreatic expression of Nf-κB and IL-1B and subsequently increased the pancreatic expression of SIRT1 and led to tissue damage in the pancreas of ovariectomized diabetic rat. – Lipid profile and Blood levels of insulin, glucose and HbA 1c in the exercise group was lower than the OVX and OVX-diabetic groups. In conclusion, increased β-cell inflammation led to reduced insulin secretion and glucose deregulation in estrogen insufficiency and menopause. Swimming exercise reduced the inflammation of contracting diabetes in the postmenopausal state. The results of this study support the potential preventing effect of exercise from pancreatic injury after surgical menopause.

Objectives To evaluate the potential relationship between COVID-19 pandemic and mucormycosis outbreak. Methods PubMed, Embase, Cochrane Library and Google Scholar were searched for the term “COVID-19 and mucormycosis” up to May 31, 2021. Results After the second wave of COVID-19, the mucormycosis outbreak complicates the natural course of COVID-19. COVID-19 patients with uncontrolled diabetes mellitus with diabetic ketoacidosis, excessive glucocorticoid use, prolonged neutropenia, malnutrition and any underlying immunocompromised conditions are at risk of developing mucormycosis. Conclusions Hyperglycaemia impairs the motility of phagocytes and also decreases the oxidative and non-oxidative mechanism of killing the causative pathogen. Chronic hyperglycemia also leads to the formation of advanced glycation end-products (AGE), which leads to cross-linking between key proteins of inflammation and connective tissue such as collagen which makes tissue susceptible to immunological dysregulation. The receptor for AGE (RAGE) is expressed on various inflammatory cells including neutrophils and its activation by AGEs leads to activation of many down signaling pathways which ultimately leads to impairment of the inflammatory response. Hyperglycemia also increases serum Nitric Oxide (NO), which decreases neutrophil motility and reduces the synthesis and release of various inflammatory mediators such as TNF-α and IL-1β, IL-6. It also decreases the expression of adhesion molecules such as LFA-1 and ICAM-2, on neutrophils. Steroids cause immunosuppression majorly by inhibiting the NF-κB pathway which is a transcription factor involved in the synthesis of many immunological mediators such as Interleukins, cytokines, chemokines, etc., and various adhesion molecules.

Objectives PCOS is the most common endocrinological disorder amongst women of reproductive age. The consequences of PCOS extend beyond the reproductive axis and may lead to the development of metabolic syndrome leading to a high risk for hypertension and cardiovascular disease. Therefore, a more comprehensive evaluation of biochemical markers that reflect the cardiovascular risk is required for further understanding of pathophysiologic mechanisms, diagnosis and management. Methods In this case-control study, women diagnosed with PCOS (n=100) in the age group (18–35 years) years were taken as cases and age matched healthy controls (n=100) were enrolled. Estimations of fasting plasma Glucose, serum total cholesterol (TC), triglycerides (TG) and High-density lipoprotein (HDL) concentrations were assayed while Low-density lipoprotein (LDL) was calculated by using Fredrickson Friedwald’s formula. Serum Lipoprotein-a (Lp-a) was estimated using ELISA (Enzyme Linked Immunosorbent Assay). The quantitative data were expressed as Mean ± Standard Deviation (SD). Unpaired Student’s t-test was used to compare the values (PCOS vs Controls) and Pearson’s correlation coefficient was used to elucidate the relationship between the variables. Results FBS and all lipid parameters were significantly increased in PCOS patients compared to control subjects. On the other hand, HDL-C was significantly decreased as compared to the control subjects. The hormones TSH, LH, FSH, PRL and LH/FSH ratio were significantly increased in PCOS patients compared to control subjects. Lipoprotein-a and PAI-1 was significantly increased in PCOS patients compared to the control subjects. Upon bivariate correlation analysis, Lp(a) had significant correlations with PAI-1 (r=0.35, p=0.000), WHR (r=0.25, p=0.000), LDL (r=0.52, p=0.000) and TSH (r=0.24, p=0.000). While the correlations with FBS (r=−0.008, p=0.91) and LH/FSH ratio (r=−0.004, p=0.95) were statistically insignificant. Conclusions The evaluation of serum biomarkers such as Lp-a, PAI-1 and lipid profile routinely in PCOS patients may have diagnostic role in the early detection of metabolic abnormalities and endocrine derangements and timely management of comorbid Diabetes and Cardiovascular disease in PCOS females.

Objectives In this hypothesis paper we explore the underlying mechanisms for long-COVID and how the oxytocinergic neurones could be infected by SARS-CoV-2 leading to a reduction in plasma oxytocin (OXT). Furthermore, we aim to review the relevance of OXT and hypothalamic function in recovery from long-COVID symptoms and pathology, through exploring the pro-health effects of the OXT neuropeptide. Methods A review of published literature was surveyed using Google Scholar and PubMed. Results Numerous experimental data can be shown to correlate with OXT and long-COVID symptoms and conditions, thus providing strong circumstantial evidence to support our hypothesis. It is postulated that the reduction in plasma OXT due to acute and post-viral damage to the hypothalamus and oxytocinergic neurones contributes to the variable multi-system, remitting and relapsing nature of long-COVID. The intranasal route of OXT application was determined to be most appropriate and clinically relevant for the restoration of oxytocinergic function post COVID-19 infection. Conclusions We believe it is imperative to further investigate whether OXT alleviates the prolonged suffering of patients with long-COVID. Succinctly, OXT may be the much-needed post-pandemic panacea. Highlights – A comparison of long-COVID pathology with OXT therapeutic mechanisms was performed – Following advances in neuroendocrinology and proposed use of OXT as an acute antiviral for COVID-19; we elaborate OXT mechanisms in treating long-COVID, via therapeutic relevance and methods of administration. – Further demonstration of OXT levels for different demographic and susceptibility groups, acute levels in COVID-19 patients and periodic monitoring of OXT levels is warranted.

The world has been coping up with the grave pandemic of COVID-19 since its inception into the human race in December, 2019. By entering the host through the spike (S) glycoprotein, it paves way for its own survival and multiplication. Respiratory tract being the point of entry causes pulmonary compromise and leads to development of ARDS. Having non-specific clinical features that resemble flu makes the clinical diagnosis much more difficult. Pregnancy being an immunocompromised and a hypercoagulable state is prone to be a high-risk group for COVID-19. This study is an attempt to understand the maternal and fetal outcomes in COVID-19 and the vertical transmissibility of the virus. Evidence suggests that the contribution of COVID-19 is not very significant in maternal morbidity and mortality. However, due to some factors such as the immunological response in the mother, certain complications may arise in the neonate in the post-natal period. No vertical transmission of the virus has been reported yet. However, the management remains crucial as two lives are at stake. Some of the precautionary measures that can be implemented to prevent COVID-19 can be segregation of medical services from that of the general population in settings of outpatient care, inpatient care and labor room care. Also, triaging the patients into low risk, moderate risk and high risk can aid in faster delivery of health-care facilities to the pregnant and the newborn.