Plasma Adiponectin and Its Correlation with Carotid Intima-Media Thickness in Obesity and in Type 2 Diabetes and Nonalcoholic Fatty Liver Disease.

Methods and Results: The study included 200 Egyptian subjects. They were divided into four equal groups: group 1: obese patients with NAFLD and T2DM (O+/NAFLD+/DM+), group 2: nonobese patients with NAFLD and T2DM (O-/NAFLD+/DM+), group 3: obese nondiabetic patients with NAFLD (O+/NAFLD+/DM-), and group 4: nonobese healthy control subjects. Plasma adiponectin was measured using ELISA (enzyme-linked immunosorbent assay) technique. Ultrasonography was used to diagnose NAFLD. CIMT was assessed using Doppler ultrasonography. Plasma adiponectin was significantly lower and CIMT was significantly higher in O+/NAFLD+/DM+, as compared with O-/NAFLD+/DM+, O+/NAFLD+/DM-, and control subjects (p < 0.001 for all). A significant negative correlation was found between adiponectin and CIMT in obese patients with NAFLD (p < 0.05), but not in patients with NAFLD and T2DM. The significant independent predictors of CIMT were diabetes duration, BMI (body mass index), albumin/creatinine ratio, and cholesterol. Conclusion: Plasma adiponectin is inversely correlated with CIMT in obese patients with NAFLD, but not in patients with NAFLD and T2DM. Hypoadiponectinemia could be a good indicator of cardiovascular risk in obese patients with NAFLD, with or without T2DM, but not in nonobese patients with NAFLD.

The effect of vitamin K4 supplementation on insulin resistance in individuals with type 2 diabetes: a double-blind randomised placebo-controlled clinical trial.

PURPOSE: The purpose of this study was to assess the possible clinical effects of vitamin K4 supplementation in individuals with type 2 diabetes namely insulin resistance, glycaemic control, and lipid profile. METHODS: This was a prospective randomised double-blind placebo-controlled clinical trial. A total of 106 patients were randomised to receive either 1 mg of vitamin K4 (menadiol diacetate) or placebo for 24 weeks. RESULTS: Ninety patients (n = 45 in each study group) were included in the final analysis. After 24 weeks, homeostatic model assessment of insulin resistance (HOMA-IR) (16.54 ± 7.81 vs. 29.09 ± 36.56, P = 0.027) and fasting serum insulin (FSI) (6.86 ± 3.45 vs. 11.13 ± 12.66 µU/ml, P = 0.032) were significantly lower in the vitamin K group compared to placebo. Additionally, triglycerides (TG) (144.94 ± 50.7 vs. 172.8 ± 101.5 mg/dl, P = 0.031) and very low-density lipoproteins (VLDL) levels (28.9 ± 9.88 vs. 34.6 ± 20.30 mg/dl, P = 0.027) decreased significantly in the vitamin K group after 24 weeks compared to baseline. Moreover, more patients in the vitamin K group (35.6%) had their antidiabetic medication doses reduced after 24 weeks compared to placebo (13.3%, P = 0.029). CONCLUSION: Vitamin K4 supplementation for 24 weeks is capable of improving insulin resistance and TG levels in individuals with type 2 diabetes. In addition, the improvement in insulin resistance was reflected in the decrease in antidiabetic medication doses. However, it did not affect fasting plasma glucose (FPG) or glycated haemoglobin (HbA1c). TRIAL REGISTRATION: The study was registered on clinicaltrials.gov with ID: NCT04285450.

Assessment of early vascular changes in adult females with polycystic ovary syndrome: correlation with insulin resistance.

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in females in the reproductive period with estimated prevalence of 5% to 18% [1]. It contributes to the mortality and morbidity in patients with PCOS due to the increased risk of different metabolic and cardiovascular (CV) complications [2]. Despite the presence of obesity in 40-60% of cases [3], the disease may occur in non-obese women. The occurrence of metabolic disorders in non-obese PCOS patients, suggests that the syndrome itself may play a role in the development of metabolic and CV co-morbidities [4]. The identification of early stages of atherosclerosis in patients with PCOS might be useful in the development of new strategies to control modifiable CV risk factors [5]. Assessment of vascular endothelial function (ED) as an initial reversible step in atherosclerosis development, may serve as an integral index for CV risk factor burden [6]. In addition, carotid intima media thickness (CIMT) is a helpful marker for atherosclerosis and for the identification of increased risk of CV disease [7]. Our study assessed the early vascular changes in Egyptian women with PCOS both physically and functionally by looking at the CIMT using high resolution Doppler ultrasound and by measuring ED using brachial artery flow-mediated vasodilatation (FMD). Our results indicate that patients with PCOS have significant ED and premature atherosclerosis which is, to a great extent, independent of obesity and IR. This suggests that PCOS patients are at increased risk for premature CVD and may benefit from early detection and management.

The Impact of LEP rs7799039 Polymorphism and Obesity on the Severity of Coronavirus Disease-19.

Background and Aims: SARS-CoV-2 infection has been recorded in 230 countries to date. Obesity has a negative impact on one's quality of life and is one of the main causes of mortality globally. Obesity affects the immune system, making the host more susceptible to infectious infections. Also, obesity commonly provokes the severity of respiratory diseases so the correlation of LEP rs7799039 Polymorphism in corpulent patients with COVID-19 infection was clearly investigated in the current study. Methods: A total of 232 patients were recruited, 116 patients were obese with COVID-19 infection, and 116 patients were non obese COVID-19. Fasting blood glucose test (FBG), hemoglobin A1C (HbA1C), complete blood count (CBC), international normalized ratio (INR), urea, alanine transaminase (ALT), aspartate aminotransferase (AST), D dimer and C-reactive protein (CRP) were estimated. C.T. scan was performed for each patient, and C.T. severity score was calculated. Genotyping for the leptin rs7799039 SNPs was performed by TaqMan® (Applied Biosystems Step One TM Real-time PCR). Results: Regarding LEP polymorphism, all individuals of non-obese groups significantly had the homozygous allele GG (100%), whereas only 56% of obese groups had GG alleles (P = 0.001). The severity scores significantly (P = 0.001) varied regarding LEP polymorphism regarding Rs7799039, where the largest proportion of those with Grade IV had the homozygous allele AA (57.1%). Conclusion: There was a correlation between the leptin gene allelic discrimination and COVID-19 CT brutality in obese patients. The A allele was considered a risk factor for severity in COVID-19 patients while the G allele contributes to decreasing that risk.

The risk of micro and macrovascular disease in Egyptian patients with diabetes and peripheral arterial disease.

Aim: The aim of this study was to assess the prevalence of micro- and macrovascular disease in Egyptian patients with diabetes mellitus (DM) and peripheral arterial disease (PAD). Methods: The study included 161 Egyptian patients with DM and PAD (91.3% had type 2 DM and 67.1% were females). Mean diabetes duration was 14.2 ± 5.2 years. Full history, clinical and fundus examination as well as laboratory investigations were done. PAD was diagnosed through assessment of ankle/brachial index (ABI) by Doppler ultrasonography. Results: ABI was <0.9 in 33.5% and >1.3 in 66.5% of patients. A significant positive correlation was found between abnormal ABI and diabetes duration, ischemic heart disease (IHD), diabetic retinopathy and neuropathy, foot ulcers, elevated blood pressure (BP), creatinine, urine albumin/creatinine ratio (ACR) and triglycerides and a significant negative correlation with HDL. Multivariate regression analysis revealed that the independent predictors for PAD in patients with ABI< 0.9 were neuropathy, creatinine, triglyceride, LDL, urine ACR and low HDL, and in patients with ABI >1.3 were IHD, neuropathy, elevated diastolic BP and triglyceride. Conclusion: The risk of micro- and macrovascular disease is high in Egyptian patients with diabetes and PAD. Early diagnosis and good control of risk factors could reduce PAD progression.

Hypoadiponectinemia as a marker of increased cardiovascular risk in patients with non-alcoholic fatty liver disease: correlation with albumin/creatinine ratio

ABSTRACT Objective: We assessed plasma adiponectin and its correlation with carotid intima-media-thickness (CIMT), as a marker of atherosclerosis, and urine albumin/creatinine ratio (ACR) in patients with non-alcoholic fatty liver disease (NAFLD). Subjects and methods: The study included 100 Egyptian subjects (50 patients with NAFLD with no history of diabetes or hypertension and 50 age and sex-matched normal healthy control subjects). Urine albumin/creatinine ratio (ACR) was assessed in all participants and fasting plasma adiponectin was measured using ELISA technique. Ultrasonography was used to diagnose NAFLD. CIMT was assessed using high-resolution Doppler ultrasonography. Results: Mild albuminuria was detected in patients with NAFLD (mean urine ACR = 42 ± 30 mg/g). Plasma adiponectin was significantly lower and urine ACR and CIMT significantly higher in patients with NAFLD as compared with the control group (P < 0.001 for all). A significant negative correlation was found between plasma adiponectin and both urine ACR and CIMT in patients with NAFLD (P < 0.001 and < 0.05 respectively). A significant positive correlation was also found between CIMT and urine ACR in those patients (P < 0.05). Plasma adiponectin and urine ACR were independent determinants of CIMT in patients with NAFLD (P < 0.01 and < 0.05 respectively). Conclusion: Patients with NAFLD, without diabetes, have an increased risk of atherosclerosis and cardiovascular disease. Hypoadiponectinemia and low-grade albuminuria are important markers of that risk.

Hypoadiponectinemia as a marker of increased cardiovascular risk in patients with non-alcoholic fatty liver disease: correlation with albumin/creatinine ratio.

OBJECTIVE: We assessed plasma adiponectin and its correlation with carotid intima-media-thickness (CIMT), as a marker of atherosclerosis, and urine albumin/creatinine ratio (ACR) in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: The study included 100 Egyptian subjects (50 patients with NAFLD with no history of diabetes or hypertension and 50 age and sex-matched normal healthy control subjects). Urine albumin/creatinine ratio (ACR) was assessed in all participants and fasting plasma adiponectin was measured using ELISA technique. Ultrasonography was used to diagnose NAFLD. CIMT was assessed using high-resolution Doppler ultrasonography. RESULTS: Mild albuminuria was detected in patients with NAFLD (mean urine ACR = 42 ± 30 mg/g). Plasma adiponectin was significantly lower and urine ACR and CIMT significantly higher in patients with NAFLD as compared with the control group (P < 0.001 for all). A significant negative correlation was found between plasma adiponectin and both urine ACR and CIMT in patients with NAFLD (P < 0.001 and < 0.05 respectively). A significant positive correlation was also found between CIMT and urine ACR in those patients (P < 0.05). Plasma adiponectin and urine ACR were independent determinants of CIMT in patients with NAFLD (P < 0.01 and < 0.05 respectively). CONCLUSION: Patients with NAFLD, without diabetes, have an increased risk of atherosclerosis and cardiovascular disease. Hypoadiponectinemia and low-grade albuminuria are important markers of that risk.

Combined effect of high-dose vitamin A, vitamin E supplementation, and zinc on adult patients with diabetes: A randomized trial.

In type 2 diabetes mellitus (T2DM), hyperglycemia leads to oxidative insult. Vitamins A and E have antioxidant potentials and may help in managing diabetes. The combined effect of high-dose vitamin A plus E supplementation with and without zinc on T2DM, has never been examined. Thus, this study aimed to evaluate and compare the effect of high-dose vitamin A plus E supplementation (AE) versus high-dose vitamin A plus E with zinc (AEZ), on different diabetic parameters. Ninety-eight patients with T2DM were randomized to receive either: 50,000 IU vitamin A and 100 mg vitamin E (AE group, N = 36), an equivalent dose of vitamin A and E combined with 25 mg zinc (AEZ group, N = 35), or no supplements (control group, N = 27) for three months. Compared to control, AEZ group showed significant reductions in fasting blood glucose, 2 h postprandial blood glucose, and glycated hemoglobin (HbA1c) with significant increases in homeostasis model assessment of beta-cell function and difference value of fasting insulin. Two hair loss cases were recorded in both treated groups. Although vitamin A needs dose moderation, these results suggest that, high-dose vitamin A plus E supplementation combined with zinc may improve glycemic control, ß-cell function, and insulin secretion in adults with T2DM.

Assessment of thyroid functions and thyroid volume in normal pregnant Egyptian females.

The normal range of thyroid functions during pregnancy differs between ethnic groups. This study assessed the thyroid functions in normal pregnant Egyptian females. Thyroid peroxidase antibodies (TPO Abs) and thyroid volume were also assessed. The study included 150 normal pregnant Egyptian females, recruited from Cairo University Hospital Antenatal Care Clinic (50 in each trimester), with 40 age-matched non-pregnant females, as a control group. Serum thyroid stimulating hormone (TSH) and TPO Abs were measured. Thyroid volume was assessed by ultrasonography. TSH ranges were 0.21-1.7, 0.52-3.2 and 0.72-2.6 mIU/L during first, second and third trimesters, respectively. The mean TSH level in pregnant females was significantly lower than that of non-pregnant women (1.2 ± 0.7 vs 2.7 ± 0.9 mIU/L, p < .001). TPO Abs were significantly higher in the first trimester compared to both second and third trimesters (p < .001 for both). Thyroid volume of pregnant females was non-significantly higher than that of non-pregnant control subjects (p = .126). A significant positive correlation was found between thyroid volume and body mass index in pregnant females (p < 0.001). Our study established trimester-specific reference ranges for thyroid functions in normal pregnant Egyptian females. A larger population-based study would help to confirm those ranges. Thyroid volume was non-significantly higher than that of non-pregnant control subjects.

ARTERIAL WALL STIFFNESS AND THE RISK OF ATHEROSCLEROSIS IN EGYPTIAN PATIENTS WITH OVERT AND SUBCLINICAL HYPOTHYROIDISM.

Objective: Hypothyroidism is associated with an increased risk of atherosclerosis. Pulse wave velocity (PWV) is an index of arterial wall stiffness widely used for noninvasive assessment of early atherosclerosis. We assessed PWV in Egyptian patients with hypothyroidism. Methods: The study included 100 Egyptian females aged 18 to 55 years. They were classified into three groups: group I, 40 women with overt hypothyroidism; group II, 40 women with subclinical hypothyroidism; and group III, 20 euthyroid women as a control group. The three groups were age matched. Doppler ultrasonography was used to calculate the heart-femoral PWV. Results: PWV was significantly higher in women with overt and subclinical hypothyroidism as compared with the control group (9.55 ± 1.81 m/s and 9.30 ± 1.28 m/s, respectively vs. 7.82 ± 2.14 m/s; P<.001 and <.01, respectively). There was a positive correlation between thyroid-stimulating hormone (TSH) and PWV in women with overt hypothyroidism and in those with subclinical hypothyroidism (P<.05 for both). Multivariate regression analysis showed that age and diastolic blood pressure were independent determinants of PWV in women with overt and subclinical hypothyroidism (P<.01 for all). TSH was also an independent determinant of PWV in both groups (P<.05 for both). Conclusion: PWV is significantly higher in Egyptian women with overt and subclinical hypothyroidism as compared with normal control subjects. This denotes early increase in arterial wall stiffness in patients with hypothyroidism, even in the subclinical phase. The positive correlation between PWV and TSH in both groups of patients suggests that the risk of atherosclerosis is proportionate to the severity of hypothyroidism. Abbreviations: ABI = ankle/brachial index; baPWV = brachial-ankle pulse wave velocity; BP = blood pressure; CIMT = carotid intima-media thickness; ECG = electrocardiogram; FT4 = free thyroxine; HDL = high-density lipoprotein; hfPWV = heart-femoral pulse wave velocity; LDL = low-density lipoprotein; PTT = pulse transit time; PWV = pulse wave velocity; SCH = subclinical hypothyroidism; TSH = thyroid-stimulating hormone.

Endothelial dysfunction and the risk of atherosclerosis in overt and subclinical hypothyroidism.

Hypothyroidism is associated with increased risk of atherosclerosis. We assessed carotid intima-media thickness (CIMT), as a marker of atherosclerosis, and endothelial function in patients with hypothyroidism. We included 70 female patients with hypothyroidism in the study, 40 patients with overt and 30 patients with subclinical hypothyroidism. Forty, age- and sex-matched, subjects with normal thyroid functions were also included as a control group. CIMT was measured using high-resolution color-coded Doppler ultrasonography. Endothelial function was assessed by measuring the percent of change in blood flow following heat-mediated vasodilation using laser Doppler flowmetry. CIMT was significantly higher in patients with overt and subclinical hypothyroidism as compared with the control group (0.7 ± 0.2 and 0.6 ± 0.2 mm respectively vs 0.45 ± 0.07 mm, P < 0.001 for both). The percent of change in blood flow following heat-mediated vasodilation was significantly impaired in patients with overt and subclinical hypothyroidism as compared with the control group (328 ± 17 and 545 ± 406% respectively vs 898 ± 195%, P < 0.001 for both). The impairment was more significant in overt as compared with subclinical hypothyroidism (P = 0.014). CIMT negatively correlated with percent of change in blood flow following heat-mediated vasodilation in patients with overt and subclinical hypothyroidism (P < 0.001 for both). We concluded that CIMT is significantly higher in patients with overt and subclinical hypothyroidism compared with normal control subjects. Impairment of endothelial function is a contributing factor to the increased risk of atherosclerosis in both groups of patients.

Plasma adiponectin and carotid intima-media thickness in non-obese patients with type 2 diabetes.

AIM: We assessed the correlation between plasma adiponectin levels and carotid intima media thickness (IMT), as a marker of atherosclerosis, in non-obese patients with type 2 diabetes. METHODS: The study group included 112 (60 males and 52 females) non-obese Egyptian patients with type 2 diabetes. Fasting plasma adiponectin was measured using ELISA technique. Carotid IMT was assessed using high-resolution color- coded Doppler ultrasonography. Forty age, sex and weight matched normal Egyptian subjects were included in the study as a control group. RESULTS: A non-significant inverse correlation was found between plasma adiponectin levels and carotid IMT in the study group (p=0.054). Multiple regression analysis revealed that plasma adiponectin was not a determinant of carotid IMT in the study group (p=0.061). CONCLUSION: The inverse relation between plasma adiponectin and carotid IMT in type 2 diabetes could be explained, at least partially, by obesity.