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.

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 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.

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.

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.

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.

Premature ovarian failure could be an alarming sign of polyglandular autoimmune dysfunction.

A 31-year-old lady, diagnosed to have premature ovarian failure in the gynecology clinic, was referred for endocrine assessment because of an abnormal thyroid function test. Clinical examination revealed hypotension, and fungal skin infection under her atrophic breasts. Thyroid stimulating hormone (TSH) level was very high. Assessment of the suprarenal function revealed evidence of Addison's disease. Polyglandular autoimmune dysfunction was diagnosed. She was treated with prednisone, fludrocortisone, and levothyroxine with significant improvement of her general condition and blood pressure.

Toll-like receptors-2 and -9 (TLR2 and TLR9) gene polymorphism in patients with type 2 diabetes and diabetic foot.

Toll-like receptors (TLRs) are innate immune receptors that mediate the inflammatory response in diabetes mellitus (DM). The aim of this study is to evaluate the association of TLR2 and TLR9 gene polymorphism in patients with type 2 DM (T2DM) and diabetic foot (DF).The study included 90 subjects divided into group I (30 patients with T2DM and DF), group II (30 patients with T2DM and no evidence of DF), and group III (normal control subjects). TLR2 (1350 T/C, rs3804100) and TLR9 (1237 T/C, rs5743836) genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for all subjects.There was a statistically significant difference in the distribution of TLR9-1237 T/C genotypes between groups I and II (P < .029) as well as between groups I and III (P < .001). Calculated risk estimation revealed that TLR9-1237 polymorphism conferred almost 20 times increased risk of DF disorders in T2DM (OR = 20, 95% CI = 5.38-74.30). There was no statistical difference in the distribution of TLR2-1350T/C genotypes between the 3 groups.TLR9-1237 T/C gene polymorphism may be considered as a molecular risk for DF among patients with T2DM.

Urinary α1 -microglobulin and albumin excretion in children and adolescents with type 1 diabetes.

BACKGROUND: The present study investigated the correlation between urinary α1 -microglobulin as a marker of tubular dysfunction and albumin excretion in children and adolescents with type 1 diabetes (T1D). METHODS: Ninety-two Egyptian patients with T1D were included in the study (mean [± SD] age 14.14 ± 5.13 years). The duration of diabetes in all patients was >5 years (mean [± SD] duration 8.28 ± 2.62 years) and all had normal renal function. Forty healthy subjects were also included as a control group. Urinary albumin excretion was assessed in all patients and urinary α1 -microglobulin was measured in both patients and control in the morning urine specimen. RESULTS: Analysis of the results showed that patients had significantly higher levels of urinary α1 -microglobulin than the controls (P < 0.01). Among the patients, there was a strong positive correlation between urinary α1 -microglobulin and urinary albumin excretion (P < 0.01). Positive correlations were also found between urinary α1 -microglobulin and duration of diabetes (P < 0.01), HbA1c (P < 0.05), and fasting and postprandial blood glucose (P < 0.05 for both). CONCLUSION: The present study shows that urinary α1 -microglobulin is strongly correlated with urinary albumin excretion in children and adolescents with T1D. In addition, it demonstrates the importance of tubular dysfunction as an early and integral component of diabetic nephropathy syndrome in these patients. The results of the present study emphasize the value of tight glycemic control in slowing the progression of tubular dysfunction, especially in patients with a longer duration of diabetes.

Primary hyperparathyroidism presenting with acute pancreatitis and asymptomatic bone involvement.

A 15-year-old female patient presented to the emergency room with vomiting and abdominal pain. She had two similar attacks in the previous three months both of them were diagnosed as pancreatitis in two different hospitals. On admission, her serum calcium and parathyroid hormone levels were very high. CT scan revealed left inferior parathyroid adenoma. Investigations to rule out possible multiple endocrine neoplasia were all negative. The patient was managed by intravenous fluids and furosemide to lower her serum calcium level. Then, left inferior parathyroidectomy was done. Postoperatively, the patient had hungry bone syndrome with severe hypocalcaemia and was managed by intravenous calcium infusion for five days in the intensive care unit. Later, she was kept on oral calcium and vitamin D supplementation. She became symptom-free and her serum calcium improved gradually.

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.

Doppler assessment of renal hemodynamic alterations in homozygous sickle cell disease and sickle Beta-thalassemia.

We evaluated the renal vascular indices in children and adolescents with sickle cell disease (SCD) using Doppler ultrasonography. We also assessed the renal hemodynamics alterations in patients with homozygous SCD and sickle beta-thalassemia (sickle ß-thalassemia). We studied 75 patients (age range = 3-20 years; M = 9.95 ± 4.15) with SCD: 42 patients suffering from homozygous SCD and 33 patients diagnosed with sickle ß-thalassemia. Thirty, age- and sex-matched, normal subjects were also included as a control group. Both patients and control groups had Doppler assessment of pulsatility (PI) and resistivity (RI) indices of main renal, segmental, interlobar, and arcuate arteries. Both PIs and RIs were significantly higher in SCD patients, compared with the control group. Among patients, PIs and RIs in the main renal, segmental, interlobar, and arcuate arteries were significantly higher in patients with homozygous SCD as compared with those with sickle ß-thalassemia (p values <0.01, <0.001, <0.001, and <0.001 for PIs and <0.001, <0.001, <0.001, and <0.01 for RIs, respectively). We concluded that renal vascular resistance is raised in children and adolescents with SCD. This is more pronounced in patients with homozygous SCD as compared with those with sickle ß-thalassemia.

Retinopathy is a Strong Determinant of Atherosclerosis in Type 2 Diabetes: Correlation with Carotid Intima Media Thickness.

OBJECTIVE: We investigated the correlation between the severity of diabetic retinopathy (DR) and carotid intima media thickness (IMT) as a marker of atherosclerosis in patients with type 2 diabetes. METHODS: The study group consisted of 140 normotensive Egyptian patients (68 males and 72 females) with type 2 diabetes and DR. Carotid IMT was evaluated using high-resolution B-mode ultrasonography. DR was assessed and graded using colored fundus photography and fundus fluorescein angiography, as either nonproliferative DR (NPDR) or proliferative DR (PDR). RESULTS: Carotid IMT was greater in patients with PDR compared to those with NPDR (1.094 ± 0.142 mm vs. 0.842 ± 0.134 mm; P<.001). Carotid IMT showed positive correlation with diabetes duration (P<.01), systolic blood pressure (P<.001), diastolic blood pressure (P<.01), fasting blood glucose (P<.01), postprandial blood glucose (PPBG) (P<.001), glycated hemoglobin (P<.01), total cholesterol (P<.01), triglycerides (TGs) (P<.001), and DR (P<.0001). No significant difference was found between males and females in any of the studied parameters. Multiple regression analysis revealed that the determinants of carotid IMT in the studied group were age (P<.01), PPBG (P<.01), TGs (P<.001), and DR (P<.0001). CONCLUSION: Our study proves that both NPDR and PDR are strong determinants of carotid IMT and atherosclerosis in patients with type 2 diabetes.

Primary anti-phospholipid antibody syndrome causing recurrent venous thrombosis and thrombocytopenia in a patient with Addison's disease.

We report a case of Addison's disease presenting with recurrent deep venous thrombosis and thrombocytopenia and proved to have primary anti-phospholipid antibody syndrome. The case report highlights the shared autoimmune nature of both diseases.

Early evaluation of renal hemodynamic alterations in type I diabetes mellitus with duplex ultrasound.

To evaluate the role of renal duplex ultrasonography in the detection of early alteration of renal blood flow in type I diabetic patients, we studied with duplex ultrasound 32 patients with type I diabetes mellitus (19 males, 13 females, age range 8-19 years) and 35 age and sex-matched controls. The resistivity indices (RIs) and pulsatility indices (PIs) of the main renal as well as intra-renal arteries were calculated. Compared with the healthy control subjects, diabetic patients had significantly higher resistivity indices (RIs) in the intrarenal (segmental, arcuate and interlobar) arteries (P= 0.001). The study, also revealed a significantly positive correlation between the RIs in the intrarenal arteries in diabetics and the albumin/creatinine ratio (r= 0.54, 0.52 and 0.51 respectively), glycated hemoglobin (r= 0.61, 0.59 and 0.63 respectively), as well as the estimated GFR (e-GFR) (r= 0.53, 0.51 and 0.57 respectively). We conclude that the current study documented early intra-renal hemodynamic alterations in the form of pathologically elevated intrarenal RIs. This denotes the potential usefulness of duplex evaluation of the intrarenal arteries, as a noninvasive procedure, for monitoring type 1 diabetic patients to predict those at risk of diabetic nephropathy.

Renal duplex doppler ultrasonography in patients with recurrent urinary tract infection.

Renal hemodynamics were studied using duplex Doppler ultrasonography in forty (33 females and 7 males; mean age: 12.1 +/- 5.3 years) normotensive patients with recurrent urinary tract infection and with no evidence of obstructive uropathy and age matched control group of 24 healthy children and adolescents. Resistivity index (RI) and pulsatility index (PI) in both arcuate (AA) and interlobar (IA) arteries were significantly higher in patients as compared to controls (P= 0.001, 0.01 respectively). Diastolic/systolic ratio (D/S) at the same levels of renal vasculature (AA and IA) was significantly lower in study patients as compared to their controls (P= 0.01, 0.001 respectively). Moreover, scarred renal units had higher RI and PI values as well as lower D/S ratio as compared to non scarred units (p= 0.01, 0.001, 0.001 respectively).). In conclusion, intra renal vascular resistivity is significantly increased in recurrent UTI patients particularly in those sustaining renal scarring. Further follow up studies are recommended to determine if duplex assessment of intrarenal vasculature could be useful as an ancillary diagnostic and/or prognostic technique in the evaluation and follow up of recurrent UTI.