Ahmet Corakci

Insulin Resistance in Nonobese Patients with Polycystic Ovary Syndrome

Objectives: Most patients with polycystic ovary syndrome (PCOS) are obese and known to have insulin resistance. Obesity per se is a cause of insulin resistance. This study was performed to determine whether insulin resistance occurs in patients with PCOS in the absence of obesity and acanthosis nigricans. Method: For this purpose, an euglycemic hyperinsulinemic clamp study was performed in 12 nonobese patients with PCOS and in 10 healthy control subjects matched for age and weight. Results: The mean serum testosterone and luteinizing hormone (LH) levels were significantly elevated (4.09 ± 1.32 vs. 1.18 ± 0.53 pg/ml, p < 0.001, and 11.63 ± 5.37 vs. 4.98 ± 2.73 mIU/ml, p < 0.001, respectively), and the serum sex hormone binding globulin level was significantly reduced (40.96 ± 14.94 vs. 73.98 ± 30.40 nmol/l, p < 0.001) in patients with PCOS as compared with the values in control subjects. The mean serum insulin level was also elevated in patients with PCOS as compared with control subjects (32.33 ± 4.98 vs. 19.56 ± 2.21 µU/ml, p < 0.05). The insulin sensitivity was lower in patients with PCOS as compared with the control subjects (200 ± 27.8 vs. 427.8 ± 88.9 µmol kg–1min–1, p < 0.001). In patients with PCOS, the serum levels of free testosterone (r = –0.89, p < 0.001) and LH were inversely correlated with the insulin sensitivity (r = –0.63, p < 0.05). Serum follicle-stimulating hormone, prolactin, and dehydroepiandrosterone sulfate levels were similar in both groups. Conclusions: These results indicate that a significant degree of insulin resistance exists in nonobese patients with PCOS and that this insulin resistance is significantly related to serum LH and free testosterone levels. Thus, measures to decrease insulin resistance may have to be considered earlier to decrease the potential risks of developing diabetes mellitus and coronary artery disease at later ages of life in these patients.

The effects of thyroid status on plasma leptin levels in women

Leptin, the product of the adipose specific ob gene, regulates food intake and energy expenditure. However, little is known about the effects of thyroid status on plasma leptin levels in women. We determined fasting plasma leptin levels before and 1 month after restoration of euthyroidism in 20 female patients with hypothyroidism, 20 female patients with hyperthyroidism and 20 age and BMI — matched female controls. To restore the normal thyroid function patients with hypothyroidism were treated with levothyroxine, whereas patients with hyperthyroidism were treated with propylthiouracil. Plasma leptin levels were measured by a RIA method with a sensitivity of 0.5 µg/l. Leptin levels were significantly lower in patients with hypothyroidism before treatment (4.17±2.58 µg/l) than in patients with hyperthyroidism (6.80±4.3 µg/l; z= −2.06, p=0.037). Leptin levels were significantly higher in hyperthyroid patients than in the control group (3.71±1.69 µ/l, z= −2.44, p=0.014) whereas leptin levels in the hypothyroid patients were not significantly different from those in control subjects (z= −0.16, p=0.87). Restoration of euthyroid state was not associated with a significant change in leptin levels either in the hypothyroid (from 4.17±2.58 to 5.22±3.4 µg/l; z= −1,74, p=0.08) or in the hyperthyroid group (from 6.80±4.37 µg/l to 7.93±6.25 µg/l z= −0.89, p=0.37), although a tendency for leptin to increase was observed in both groups. There was no correlation between plasma leptin and FT3, FT4, TSH, or BMI either before or after therapy in both groups. Leptin levels were significantly correlated with BMI in the control group (r= −0.53, p=0.018). We conclude that plasma leptin levels are increased in hyperthyroidism and unchanged in hypothyroidism. Furthermore, our study demonstrates that mean plasma leptin levels are not influenced by short term restoration of euthyroidism in both hypothyroidism and hyperthyroidism, although an effect of long-term treatment may not be excluded.

Adipose tissue 11-beta-Hydroxysteroid Dehydrogenase Type 1 and Hexose-6-Phosphate Dehydrogenase gene expressions are increased in patients with type 2 diabetes mellitus

AIMS We have determined 11-beta-Hydroxysteroid Dehydrogenase Type 1 (HSD11B1) and Hexose-6-Phosphate Dehydrogenase (H6PD) mRNA expression levels in adipose tissues from patients with type 2 diabetes mellitus. METHODS Six non-diabetic and seven diabetic male patients who undergo elective abdominal surgery were included in the study and visceral and subcutaneous adipose tissue samples were obtained. Fresh preadipocyte cultures were administered to low and high glucose medium (11M and 25M) in vitro for 24h and mRNA extractions were performed. HSD11B1 and H6PD gene mRNA expression levels were determined by real-time PCR and compared. Glyceraldehyde-3-phosphate Dehydrogenase (G3PD) mRNA level is used as housekeeping gene expression. RESULTS HSD11B1 mRNA levels were significantly higher in patient with T2DM than controls in both visceral and subcutaneous adipose tissues (3.35+/-0.7 vs. 0.37+/-0.1; P=0.01 and 2.07+/-0.8 vs. 0.11+/-0.05; P=0.01, respectively). H6PD mRNA levels were also significantly higher in patient with T2DM than controls in both visceral and subcutaneous adipose tissues (3.95+/-1.2 vs. 1.95+/-0.8; P=0.050 and 2.23+/-1.1 vs. 0.46+/-0.1; P=0.043, respectively). CONCLUSIONS Failure to down-regulate HSD11B1 activity in patients with type 2 diabetes may contribute to the pathogenesis of T2DM. Subcutaneous and visceral adipose tissues similarly exhibit the same variation in patients with type 2 diabetes mellitus.

Comparison of the effects of aminoguanidine and L-carnitine treatments on somatosensorial evoked potentials in alloxan-diabetic rats

The effects of aminoguanidine (AG) and L-carnitine (LC) on somatosensorial evoked potential (SEP) latency and neural levels of thiobarbituric acid reactive substances (TBARS), products of lipid peroxidation, were compared in alloxan-diabetic rats. AG and LC were given to diabetic rats starting from the 3rd week after the induction of diabetes and lasting for 4 weeks. SEP latency was measured by stimulating via caudal nerve and recording via cortex, once weekly during the treatments. Diabetes caused deficits in SEP (P < 0.05 vs non-diabetic control rats, respectively). AG and LC restored SEP latencies slightly but not significantly, with the exception of the prominent effect of AG at the first week and both treatments at the 4th week of the treatments (P < 0.05 vs untreated diabetic rats, respectively). Diabetes caused elevation in neural TBARS levels (P < 0.05 vs non-diabetic group), which was prevented by both AG and LC (P < 0.05 vs untreated diabetic rats, respectively). Weight and the glucose levels were not influenced by the treatments. Our results suggest that AG improves SEP latencies better than LC. Our results also suggest that the beneficial effects of both AG and LC on diabetic neuropathy are not associated with the regulation of glycemia, but these effects may be related in part with prevention of lipid peroxidation.

L-carnitine treatment improves brain stem auditory evoked potentials in diabetic rats

THE effect of L-carnitine (LC) on brain stem auditory evoked potentials (BAEP), was examined in alloxan-diabetic rats. LC (200 mg kg−1, i.p., once daily) was given to diabetic rats starting from the third week after the induction of diabetes, lasting for 4 weeks. Age-matched non-diabetic rats served as controls. The latency of wave I and interpeak latency I-IV were measured once weekly. Diabetes-induced deficits in BEAP latencies (p < 0.05, diabetics vs non-diabetic controls) were improved after LC treatment (p < 0.05, LC-treated diabetic rats vs non-diabetic controls). Weight and glucose levels were not influenced by LC treatment. Our results suggest that LC has beneficial effects on diabetic central neuropathy but these effects are not associated with the regulation of glycaemia in alloxan-diabetic rats.

Acute hypothyroidism leads to reversible alterations in central nervous system as revealed by somatosensory evoked potentials

Although functional alterations in the central nervous system (CNS) and peripheral nerves are well documented in overt hypothyroidism, little is known about alterations of CNS in acute hypothyroidism. Sixteen patients with differentiated thyroid carcinoma were studied when prepared for radioiodine scanning after stopping levothyroxine (L-T4) therapy for 6 weeks to determine whether acute hypothyroidism leads to alteration in somatosensory evoked potentials (SSEPs). Repeat SSEPs were performed on the same patients at 6 months following L-T4 therapy when patients were euthyroid. Neurophysiological findings were compared with a group of 20 normal controls with no history of thyroid disease. Peripheral and central conduction in the median and tibial nerve stimulated SSEPs studied. A significant prolongation of central conduction time in SSEPs was found in patients with acute hypothyroidism when compared to those in control subjects. Abnormal latencies were not correlated with thyroid hormone levels. These neurophysiologic abnormalities were completely restored to normal at 6 months after L-T4 therapy. We conclude that acute hypothyroidism leads to reversible alterations in CNS as determined by SSEP recordings. Our results also suggest that SSEPs could be useful tests to monitor functional alteration of the CNS in acute hypothyroidism.

EVENT-RELATED BRAIN POTENTIALS IN PATIENTS WITH HYPOTHYROIDISM

OBJECTIVE To evaluate the cognitive function of patients with hypothyroidism, based on long-latency auditory event-related potentials (ERPs). METHODS We investigated alterations of P300 latency in patients with hypothyroidism before treatment and after restoration of euthyroidism. ERPs were elicited in 14 untreated patients with hypothyroidism (mean age, 26.71 +/- 2.39 years) and in a group of 30 control subjects with comparable mean age, sex distribution, and educational level. ERP recordings were repeated at 1 and 6 months after attainment of euthyroidism. RESULTS Untreated patients with hypothyroidism had longer P300 and N1 wave latencies in comparison with those in the control subjects (P = 0.003 and P = 0.018, respectively). The mean P300 latencies did not change significantly 1 month after restoration of euthyroidism. At 6 months after attainment of euthyroidism, however, the mean P300 latencies returned to normal values, similar to those in the control subjects. CONCLUSION We conclude that P300 latencies are impaired in patients with hypothyroidism, which is indicative of cognitive dysfunction. These alterations, however, may be reversed 6 months after attainment of euthyroidism.

BIOCHEMICAL COMPOSITION OF BENIGN THYROID CYST FLUID

Although the availability of thyroid cyst fluid is easy by fineneedle aspiration, less is known about the biochemical composition of thyroid cyst fluid. The authors have, therefore, determined the biochemical composition of 18 benign thyroid cyst fluid specimens. They found that the activities of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and the concentrations of total protein, total bilirubin, and uric acid were highly increased in thyroid cyst fluid specimens when compared with normal human serum specimens. The concentrations of glucose, cholesterol, and triglycerides in cyst fluid were within normal serum limits. Selenium (Se) concentrations in most cyst fluids were low. Moreover, there was no correlation between Se and other biochemical parameters. Protein electrophoresis of cyst fluid specimens yielded high concentrations of α1 and especially α2 globulin fractions indicating an inflammation. The concentrations or activities of biochemical analytes were not significantly different in pure and mixed cysts. Those parameters were also not significantly different between cyst fluids of different colors. The gross appearance of the fluid and the presence of certain biochemical analytes were consistent with a hemorrhagic origin of most of the cyst fluid specimens. However, some biochemical markers indicate that autolysis or necrosis of thyroid tissue may also contribute the composition of thyroid cyst fluid. The reason for lower Se concentration in the thyroid cyst fluid may be the lower Se concentration in the Turkish population. These results also suggest that the fluid color or nature of cyst, e.g., pure or mixed cyst, is not a main determinant of biochemical composition of benign thyroid cyst fluid.

CENTRAL AND PERIPHERAL NEURAL RESPONSES IN ACROMEGALY

OBJECTIVE To assess the function of the central and peripheral nervous systems in patients with untreated acromegaly. METHODS We recorded the somatosensory evoked potentials (SSEPs) and brain stem auditory evoked potentials (BAEPs) in 10 patients with untreated acromegaly of brief duration and in 20 age- and sex-matched healthy control subjects to evaluate the function of the central nervous system and at least the median and tibial components of the peripheral nerves. Electrophysiologic studies were done at the time of diagnosis and before the initiation of any treatment for acromegaly. We also studied the distal motor latency, nerve conduction velocity, compound muscle action potentials, and F response in the peroneal nerve; the sensory nerve conduction velocity and sensory potential amplitude were measured in the sural nerve. RESULTS The mean duration of acromegaly (expressed as time elapsed since patients first recognized signs or symptoms) was 2.4 years. The N(9) and N(13) latencies in median SSEPs and the N(22) latency in tibial SSEPs were significantly prolonged in patients with acromegaly in comparison with the control group; however, central nervous system components of SSEPs and all components of BAEPs were normal. We also noted abnormalities in peroneal motor and sural sensory nerves. No correlation was found between the neurophysiologic data and the basal growth hormone level, the fasting blood glucose level, or the duration of disease. CONCLUSION Our results suggest that peripheral, but not central, nervous system involvement exists in patients with untreated acromegaly of short duration.