Metformin improves insulin sensitivity and hyperandrogenemia in Egyptian hirsute patients with polycystic ovary syndrome

PCOS is a heterogeneous clinical syndrome characterized by a spectrum of symptomatology, pathology and laboratory findings. It is now accepted that polycystic ovary syndrome has important long-term health implications, including metabolic disorders and increased risk factors for cardiovascular disease like insulin resistance, abdominal obesity, dyslipidemia, hypertension and markers of abnormal vascular function. The aim of this work was to study the effect of metformin on the clinical, metabolic and endocrine parameters in hirsute women secondary to polycystic ovary syndrome. The study was conducted on 30 Egyptian hirsute patients suffering from polycystic ovary syndrome. Clinical examination included anthropometric measurements [BMI and WHR] and Ferriman and Gallwey scoring for hirsutism. Fasting serum insulin and fasting blood glucose were measured from which insulin resistance [IR] was assessed by HOMA. The glucose to insulin ratio [GIR] was calculated. Lipid profile was estimated. Serum luteinizing hormone [LH] and follicle stimulating hormone [FSH] were estimated in the early follicular phase. Total serum testosterone and sex hormone-binding globulin [SHBG] were measured. Ultrasonographgy was done on the pelvis for examination of the ovaries. The patients were instructed to do diet and physical exercise. They received metformin 1500 mg/day for 6 successive months. Clinical, metabolic and endocrine parameters were reevaluated after the medication. A significant 31% improvement in the frequency of the menstrual cycle was observed. Hirsutism improved by 19%. BMI was reduced by 8%. WHR decreased by 2.3%. Insulin resistance decreased by 54%. Total serum cholesterol, LDL-cholesterol, serum triglyceride and total cholesterol/H DL-cholesterol ratio showed slight decrease [3%, 6%, 9% and 9%, respectively], while HDL-cholesterol showed a slight increase by 7%. Total serum testosterone decreased by 32% and LH/FSH ratio improved by 28%. SHBG levels increased by 9%. There was a positive correlation between BMI and HOMA-IR, serum cholesterol and serum TG. There was a highly significant positive correlation between BMI and FBG as well as fasting serum insulin and HOMA-IR. On the other hand, there was a significant negative correlation between BMI and GIR. A highly significant positive correlation was found between BMI and total cholesterol and TG. Also, there was a significant positive correlation between BMI and total cholesterol/HDL-cholesterol ratio. Again, BMI showed a highly significant positive correlation with LH/FSH ratio. There was a highly significant positive correlation between WHR and the frequency of the menstrual cycle and fasting serum insulin. There was a significant positive correlation between WHR and HOMA-IR, serum total cholesterol and TG. There was a significant negative correlation between WHR and SHBG. HOMA-IR showed a significant positive correlation with GIR. Metformin improves insulin sensitivity and hyperandrogenemia in Egyptian hirsute women with polycystic ovary syndrome. This is associated with improvement in menstrual abnormalities. Metformin has additional benefit in reducing hair growth in Egyptian hirsute young women with polycystic ovary syndrome

Transferrinuria in type 2 diabetes mellitus: An early marker of diabetic nephropathy

Diabetic nephropathy is the commonest cause of end-stage renal failure in the Western world. The incidence of DN rises rapidly over the first 15 to 20 years of diabetes to decline sharply afterwards. The stages of DN progress from normoalbuminuria to microalbuminuria to clinical proteinuria and finally to end-stage renal failure. Several studies proved the applicability of urinary albumin quantification in the early diagnosis of diabetic nephropathy. Several studies of different urinary proteins demonstrated the increased excretion of other high and low molecular mass proteins in different stages of diabetic nephropathy: macromolecular, e.g. transferrin and micromolecular proteins like alpha 1-microalbumin. Elevated urinary transferrin excretion rates have been reported in patients with type 2 diabetes and its complications. Therefore, the aim of the present study was to evaluate the role of transferrin as an early marker for the detection of nephropathy in Egyptian type 2 diabetic patients. Sixty Egyptian type 2 diabetic patients grouped according to the presence or absence of albumin in urine into three groups: group I consisted of 20 normoalbuminuric Egyptian type 2 diabetic patients, group II included 20 microalbuminuric Egyptian type 2 diabetic patients, and group Ill comprised 20 macroalbuminuric Egyptian type 2 diabetic patients. Twenty healthy subjects of matched age and sex were included as a control group. Laboratory investigations included FBG and 2 hours PPBG, HbA[1C] serum albumin, ALT, AST, prothrombin activity, blood urea, serum creatinine and creatinine clearance, and complete urine analysis. Determination of microalbuminuria in fresh urine samples was done using immunoturbidimetry. Estimation of urinary transferrin was done by immuno-nephelometry. Results: Type 2 diabetic patients who had frank proteinuria had a significantly longer duration of diabetes mellitus as compared to micro and norrnoalbuminuric patients. Type 2 diabetic patients with frank proteinuria had significantly higher FBG, PPBG and HbA[1C] levels as compared to normoalbuminuric type 2 diabetic patients and controls. Type 2 diabetic patients with frank proteinuria had significantly higher blood urea and serum creatinine and a significantly lower creatinine clearance as compared to norrnoalbuminuric type 2 diabetic patients and controls. Type 2 diabetic patients with frank proteinuria showed significantly higher urinary albumin and transferrin excretion as compared to normo-and microalbuminuric type 2 diabetic patients and controls. Also, microalbuminuric type 2 diabetic patients had significantly higher urinary albumin and transferrin excretion as compared to normoalbuminuric type 2 diabetic patients and controls. In normoalbuminuric type 2 diabetic patients, a negative correlation was observed between creatinine clearance and transferrinuria. In microalbuminuric type 2 diabetic patients, a strong positive correlation was found between albuminuria and transferrinuria. In type 2 diabetic patients with frank proteinuria, strong positive correlations were obtained between blood urea and serum creatinine and transferrinuria, while a strong negative correlation was observed between creatinine clearance and transferrinuria. However, no significant correlations were found in any of the type 2 diabetic groups between duration of the disease, blood pressure, FBG, PPBG, or HbA[1C] and transferrinuria. Urinary transferrin is a convenient diagnostic parameter of renal impairment in Egyptian type 2 diabetic patients. Transferrinuria could be considered as an early marker of diabetic nephropathy as compared to microalbuminuria

Insulin sensitivity from meal tolerance tests: a computer program

Recently, a new approach was introduced that allows estimation of insulin sensitivity [S[l]] from orally ingested glucose during an OGTT, or a meal glucose tolerance test [MGTT]. S1 from the MGTT was strongly correlated to the S[l] values obtained from an insulin-modified, frequently sampled intravenous glucose test [FSIGT], which is considered as one of the gold standards. This new method makes use of MGTT/OGTT data, which are relatively much easier to obtain. This makes this method of value in the assessment of insulin sensitivity in various circumstances in which the use of clamps or the minimal model is impractical. For epidemiological studies, screening of high-risk populations, and large-scale intervention trials, S[l] calculations would be rather tedious and time-consuming. Therefore, it was thought to develop a computer program to carry out the calculations quickly and accurately. Ten healthy subjects [4 men and 6 women; age 47 +/- 2.6 years; body mass index 25.9 +/- 1.2 kg/m[2]], with normal glucose tolerance. The studied subjects received, on different occasions, a meal tolerance test [MGTT]. The meal was eaten within 10 mm. Blood samples were collected at - 30, - 1, 10, 20, 30, 40, 50, 60, 75, 90, 120, 150, 180, 210, and 240 mm. Plasma glucose and serum insulin were determined in the blood samples. A computer program, COBELLBAS, was developed. It computes the insulin sensitivity SI[oral] from MGTT/OGTT data. Use is made of function AREA to calculate the areas under the curves, and function FUN1 for interpolation. The computer program was tested, and results comparable with the published ones were obtained. The computer program was tested, and satisfactory results were obtained

Angiotensin converting polymorphism in obese patients

Obesity is a complex disorder caused by the interaction of environmental and genetic susceptibility associated with increased risk of morbidity from a variety of disorders. The aim of the present study was to investigate the association between ACE I/D polymorphism and obesity and its contribution to the different risk factors among obese patients which may constitute the basis for strategies to manage this serious problem. Fifty-four male obese patients with BMI >/= 30 kg/m[2] were recruited. Twenty-six healthy men with BMI < 25 kg/m[2] of comparable age were selected as a control group. All patients and controls were subjected to thorough history taking, anthropometric measurements [weight, height, BMI, waist and hip circumference and WHR] and BP measurement. ECG was done. Laboratory investigations included FPG, PPPG, HbA[1c], OGTT, lipid profile and fasting serum insulin. IR was determined by the computer updated 1996 version of HOMA2. ACE I/D polymorphism was determined by PCR. Eighteen and a half percent of obese patients had a family history of CHD and 31.5% were smokers. Nineteen patients were categorized as prehypertensives while 20 had stage 1 or stage 2 hypertension. IHD was diagnosed in five obese patients. Hyperlipidemia, IGT and DM were detected in 61.1%, 50% and 22.2% of obese patients, respectively; 29.6% of patients had grade I obesity, 29.6% had grade II and 40.7% had grade III obesity. Sixty-three percent of patients had a waist circumference> 102 cm and 38.9% had a WHR> 1.0. Obese patients had significantly higher FPG, PPPG, HbA[1c], fasting serum insulin, HOMA2-IR and HOMA2-%B as compared to controls. On the other hand, HOMA2-% S was significantly lower in obese patients. All studied lipid parameters were significantly higher in obese patients except HDL-cholesterol which was significantly lower in obese patients. The distribution of the ACE genotype for obese patients was 38.9%, 46.3% and 14.8%, for the DD, ID and II, respectively. In controls, 34.6% were DD, 46.2% were ID and 19.2% were II genotype. There was no statistically significant difference between obese patients and controls as regards the genotype frequency [Pearson X[2]=0.296; P=0.862]. Relative allele frequencies in both groups were D allele: 0.620 in obese versus 0.577 in controls and I allele: 0.380 versus 0.423, respectively with no statistically significant difference as well. There was a statistically significant difference between the three ACE I/D genotypes of obese patients as regards BMI, waist circumference and WHR. The DD genotype was associated with higher values of these obesity markers. No such differences were observed for control participants. There were no significant differences in age, SBP and DBP among the three ACE genotypes of obese patients. However, there was a tendency towards DD genotype in the older age group and in patients with higher BP. There was no significant difference between DD, ID and II ACE genotypes of obese patients as regards any of the studied metabolic parameters. However, numerically higher values of FPG, PPPG, HbA[1c], fasting serum insulin, HOMA2-IR, serum triglycerides, total cholesterol and LDL-C and lower values of HOMA2-%S and HDL-cholesterol were observed among DD genotypic obese patients. Overall, DD homozygote obese patients showed a tendency for family history of CHD, smoking, abdominal adiposity, hypertension, hyperlipidemia and DM. ACE I/D polymorphism was significantly associated with abdominal adiposity, hyperlipidemia and DM in obese patients when compared with patients having no such risk factors [P=0.021, P=0.049, P=0.045, respectively]. Nine obese patients showed a maximum of five associated risk factors that were added to obesity, while only two obese patients presented with no such associated risk factors at all. Seven of those nine obese patients were DD homozygotes. It was found that the more the number of studied risk factors added to obesity, the more the prevalence of the DD homozygote genotype [LLR=27.153; P=0.002]. The results of the present study could indirectly suggest that the DD genotype contributes a genetic factor for the development of abdominal obesity and that this would predispose obese patients to further risk for development of CHD. ACE inhibitor therapy can induce improvements in atherosclerosis and IR and therefore they are ideal drugs to be used in obese hypertensive patients

Thyroid function and ultrasonographic features in male Egyptian diabetic patients

To study thyroid function and Ultrasonographic features in male Egyptian diabetic patients, and, to compare them with normal healthy male control subjects. Subjects and Fifteen male Egyptian type 1 diabetic patients, 15 male Egyptian type 2 diabetic patients, 10 young male controls and 13 old male controls. TT4, FT4, TT3, FT3 and TSH were determined, as well as HbA1C. Thyroid ultrasonography was carried out to determine thyroid volume and morphology. No statistically significant difference was found between the four studied groups as regards serum TSH, TT4, FT4 or FT3. In both type 1 and type 2 diabetic patients, TT3 was significantly lower than that of young and old controls, respectively. Subclinical hypothyroidism was found in 6.7% of type 1 diabetic patients, but in none of type 2 diabetic patients. In type 2 diabetic patients, the mean right and left thyroid lobe volumes were significantly larger than those of type 1 diabetic patients, as well as those of old controls. The right thyroid lobe was homogeneously echogenic in all type 1 diabetic patients, but was nodular in 8 out of 15 type 2 diabetic patients. The left thyroid lobe was nodular in only 1 out of 15 type 1 diabetic patients, while it was nodular in 7 out of 15 type 2 diabetic patients. The mean total thyroid gland volume of type 2 diabetic patients was significantly larger than that of old controls. The total thyroid gland was homogeneously echogenic in 26.7% of patients and nodular in 73.3% of patients. No Doppler flow was detected over the thyroid gland of any of the studied patients. In both type 1 and type 2 diabetic patients, no significant correlation was found between age, duration of illness, BMI, body surface area or metabolic control. Also, there was no significant correlation between these parameters and serum level of TSH, TT4, FT4, TT3 and FT3. No significant correlation was found between thyroid nodularity and age, duration of illness, degree of metabolic control, BMI or type of treatment used among type 2 diabetic patients. Conclusions: Community-based biochemical screening for thyroid disease may be justified in diabetic patients, in view of the likelihood of symptoms of thyroid disease being masked by the diabetic state, high-resolution ultrasonography was found to be a sensitive tool capable of detecting many small, nonpalpable thyroid nodules

Body composition and serum leptin level in Egyptian growth hormone deficient short children

Aim: This work was designed to evaluate the effect of growth hormone [GH]- deficiency on body composition and serum leptin level in Egyptian GH-deficient [GHD] short children. In addition, the relationship between serum leptin level, gender and anthropometric variables was also determined. Subjects and This study was conducted on 28 GHD children [19 boys and 9 girts] and 12 healthy controls [6 boys and 6 girls]. All children were prepubertal. Except for GH deficiency, the children were otherwise healthy with no evidence of organic diseases, chromosomal abnormalities, skeletal dysplasia or any other endocrinological disturbances. In all studied subjects, anthropometric parameters [weight, height, body mass index [BMI], waist/hip ratio [WHR] and subcutaneous skinfold thickness] were measured. To determine body composition, body fat percent [BF%] was calculated from subcutaneous skinfold thickness by specific equations from which the amount of total body fat mass [FM] and fat free mass [FFM] were calculated. Serum GH levels were estimated, using IRMA, under basal conditions and after applying two provocation tests [after exercise and after clonidine stimulation]. GH peak and GH area under the curve [GH AUC] were determined following clonidine stimulation. Baseline values of insulin-like growth factor-l [IGF-I] and leptin were also estimated in serum samples by ELISA. FFM was significantly lower in GHD children than controls. GHD children had a significantly higher BF% as compared to controls. Although FM showed a tendency to be higher in the GHD than the control group, the difference was statistically insignificant. Serum leptin level and leptin values, expressed per unit fat mass [ng/ml/kg], were significantly higher in GHD cases compared with controls. Significant positive correlations were detected between serum leptin and indices of adiposity [BMI, WHR, BF% and FM] in cases and controls. Multiple linear regression analysis with serum leptin considered as the dependent variable revealed that 52.6% of the variability of serum leptin level in GHD cases was significantly attributed to BF%,GH peak, GH AUC and IGF-I level [F= 8.480*, P= 0.000]. Healthy and GHD girls had a significantly higher BF%, FM and serum leptin levels than the boys of the corresponding group. However, leptin levels adjusted for fat mass did not differ significantly between boys and girls in each group. Conclusions: GH deficiency resulted in a significant increase of BF%. Serum leptin and leptin per unit fat mass were significantly higher in GHD cases. These findings suggest that GH could have an additional direct effect on leptin production from adipose tissue independent of its influence on body composition. Gender difference in serum leptin level is not obvious before puberty when the total body fat mass is taken into consideration

Osteoporotic changes in Egyptian cirrhotic patients

Aim: Hepatic osteodystrophy occurs in most patients with chronic liver disease. Subjects and In this study, bone density, measured by dual energy X-ray absorptiometry [DEXA], and some biochemical markers of bone turnover were studied in 30 Egyptian schistosomal patients classified equally into 3 groups according to the Child-Pugh score of severity of liver disease. Patients showed significant reduction of BMD in both lumbar spine and femoral neck [LS: -2.87 +/- 1.39; FN: -0.54 +/- 1.13, p< 0.001]. Osteoporosis was found in 56.7% of patients. Urinary D-Pyr/cr, as a marker of bone resorption, showed marked significant increase in Child B and C patients [p<0.001], while serum B-AP and serum PICP, as markers of bone formation, showed less changes. Serum B-AP was significantly increased in the patient group [p<0.05], while serum PICP was insignificantly decreased in patients as compared to controls. The rate of bone loss, determined by the ratio of urinary D-Pyr/cr to PICP, was increased in Child A, B, and C patients. Serum testosterone was significantly decreased in both Child B and C patients and was markedly decreased in the whole patient group [p<0.001]. Conclusions: These results suggest that increased bone resorption is the predominant cause of hepatic osteodystrophy and its risk increases with the severity of liver disease. It also provides bone biomarkers as useful alternatives to bone biopsy in evaluating hepatic bone changes

Non invasive evaluation of patients with ventricular septal defect after surgical correction

The present work is planned to study the cause of any residual cardiac murmur after surgical closure of ventricular septal defect and to evaluate cardiac function using Doppler echocardiography. Twenty cases of isolated VSD who underwent trans-atrial surgical closure of VSD were studied. They were 14 males and 6 females. Their age ranged between 3 and 20 years with a mean of 8. 5 +/- 4 years. Preoperative data were collected from patients files as cardiac catheterization data. Operative details were recorded during operation. Post operative study was also conducted and included clinical examination for any residual cardiac murmur. ECG, chest X-ray and Doppler echocardiography were performed to assess closure of the defect. Patients were classified into two groups. Group I included 8 patients with RV pressure < 50 mm Hg. Group 2: included 12 patients with RV pressure > 50 mm Hg. Doppler examination revealed 14 cases of 20 [70%] proved to have no residual shunt. 4 cases had mild shunt [20%], 2 cases had moderate shunt [10%] and no case showed large shunt. The shunt occurred along the suture line. Left ventricular function was assessed by the EF% which ranged between 47% and 63%. RV pressure decreased significantly in both groups postoperatively, post operative echo evaluation has also showed that 9 patients had TR 45%, 1 patient had pericardial effusion [5%], 1 showed vegetation on the patch [5%] and I patient had right atrial thrombus [5%]. We conclude that Doppler echocardiography is highly sensitive in the early post operative detection of VSD shunt, as well as other postoperative complications as pericardial effusion, vegetation on the patch and myocardial dysfunction. Results showed also that RV pressure decreased significantly after closure of the defect in both groups, however, in patients with VSD and at least moderate pulmonary hypertension, pulmonary artery pressure was not returning to normal therefore, it is advisable to operate on individuals with VSD and moderate pulmonary hypertension before there is the any increase of pulmonary vascular resistance