Olcay Gedik

Effects of vitamin D deficiency and repletion on insulin and glucagon secretion in man

SummaryWe have studied the effects of vitamin D deficiency on pancreatic A- and B-cell function. Four subjects with vitamin D deficiency and 10 healthy subjects were studied. Pancreatic B-cell function was assessed by the insulin response to an oral glucose tolerance test. An insulin tolerance test was used to evaluate pancreatic A-cell function. The patients were then treated with 2000 U/day of vitamin D3 for 6 months, after which the clinical, metabolic, biochemical and radiological features of vitamin D deficiency resolved, and pancreatic A-and B-cell function was repeated. In the vitamin D-deficient subjects pre-treatment and post-treatment serum calcium levels (mean±SEM) were 2.22±0.01 mmol/l and 2.24±0.01 mmol/1 respectively, and 2.27 ± 0.02 mmol/l in healthy subjects (NS). The pre-treatment level of 1,25-dihydroxy vitamin D (1,25-(OH)2D) of 29.7 ± 3.3 pg/ml in the vitamin D deficient subjects rose to 70.3±10.3pg/ml after treatment (p < 0.05). The 1,25-(OH)2D level in the healthy subjects was 50.0 ± 13.7 pg/ml (p < 0.05 versus pre- and post-treatment values in the patients). Insulin secretion, calculated by the area under the insulin curve, was significantly lower before vitamin D3 treatment in the patients (9.09±0.7 mU × min,p<0.05) compared with the healthy subjects (11.9±0.5 mU × min) and post-treatment values of the patients with vitamin D deficiency (13.7 ± 0.5 mU x min). Similar changes were seen in the insulogenic indicesΔ I/ΔG). WhileΔI/ΔG was 1.71±0.4 (mean ± SEM) during vitamin D deficiency, it increased to 2.48±0.3 with vitamin D repletion. The insulogenic index in the healthy subjects was 2.68±0.3. The glucose areas were not significantly different. Insulin-induced glucagon secretion was similar in all instances. The results of this study suggest that vitamin D deficiency reduces pancreatic insulin secretion but it does not affect pancreatic A-cell function.

Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study

Abstract We compared the efficacy of treatment protocols with an angiotensin converting enzyme (ACE) inhibitor alone (enalapril, 5 mg) or angiotensin II (ATII) receptor blocker (losartan, 50 mg) or both enalapril plus losartan in patients with microalbuminuria in a prospective, randomized clinical trial. Normotensive type 2 diabetic patients with microalbuminuria documented by at least 3 consecutive urinary albumin excretion analyses were recruited for the study. Patients were grouped randomly into one of the protocols which consisted of treatment with 5 mg enalapril daily (group 1; n=12), 50 losartan daily (group 2; n=12) or both drugs (group 3; n=10). They were reevaluated with regard to HbA1c levels, lipid profiles, blood pressure and urinary albumin excretion rates (UAER) at 3-month intervals for 12 months. Mean age, duration of diabetes, body mass index, plasma lipid profiles and blood pressure levels were similar at the initial visit. In group 1, UAER returned to normal levels in 10 patients. Normalization of UAER occurred in 8 and 7 patients in groups 2 and 3, respectively. Percentage of reduction in UAERs at the end of 12 months were 58%, 59% and 60% (p=0.0001; p=0.0002; p=0.0003, respectively). The amount of reduction in UAER did not differ significantly among the three groups (p=0.346). ACE inhibitors and angiotensin II receptor blockers have similar efficacy in treating diabetic microalbuminuria, and the combination of the two drugs does not add any further benefit.

Adrenal incidentaloma: report of 33 cases.

The aim of our study was to review the imaging characteristics, endocrinologic screening and histologic diagnoses of adrenal incidentaloma cases encountered in our institute.

Endogenous sex steroid, GH and IGF-I levels in normal elderly men : Relationships with bone mineral density and markers of bone turnover

There are studies concerning the association among endogenous sex steroids, growth hormone (GH), insulin-like growth factor-I (IGF-I) and bone mineral density (BMD) in both men and women. However, little is known concerning the association of these parameters with markers of bone turnover in healthy elderly men. We studied the association of BMD (dual energy X-ray absorptiometry of spine, hip and forearm) and markers of bone turnover (bone-specific alkaline phosphatase, serum C-terminal propeptide of type I collagen, and serum osteocalcin reflecting formation, urine deoxypyridinoline and calcium excretion in relation to creatinine excretion reflecting resorption) with endogenous sex steroids, GH and IGF-I in 14 elderly normal men (age range 60–79 years). There was a negative correlation between age and dehydroepiandrosterone sulphate (DHEAS) (r=−0.60, p=0.022) and a positive correlation between GH and IGF-I (r=0.53, p=0.048). Serum estradiol concentrations correlated with BMD at distal 1/3 radius (r=0.41, p=0.1) and mid-radius (r=0.47, p=0.08), and negatively correlated with age (r=−0.45, p= 0.09). There was no correlation of estradiol with bone turnover markers, testosterone, free testosterone, DHEAS, GH and IGF-I. Serum GH and IGF-I levels showed no correlation with BMD (all sites) and bone turnover markers. Serum total testosterone concentrations positively correlated with BMD at distal 1/3 radius (r=0.47, p=0.09), femoral neck (r=0.56, p=0.037) and Ward’s triangle (r=0.49, p=0.07). These data suggest that serum estradiol and testosterone levels are associated with BMD in elderly men, possibly indicating their contribution to skeletal maintenance in old age. However, correlations of IGF-I, GH and DHEAS with BMD and bone turnover markers are lacking in the group studied.

Effects of combination of insulin and acarbose compared with insulin and gliclazide in type 2 diabetic patients.

Abstract In this prospective study we aimed to compare insulin plus acarbose with insulin plus gliclazide with respect to their effect on insulin requirement, lipid profiles and body mass index (BMI) while achieving good glycemic control. Forty patients with type 2 diabetes mellitus who were on conventional insulin therapy (subcutaneous insulin therapy consisting of regular and NPH insulin, two times a day) were included in the study. They were randomized to double blind treatment with insulin in combination with gliclazide or acarbose for 6 months. For both groups, acceptable glycemic control was achieved at the end of study period. The mean HbA1c levels decreased from 8.32±0.26 to 7.13±0.18% in acarbose group and 8.6±0.15 to 7.48±0.21% in the gliclazide group. The difference between groups was not significant (P 0.29). In the acarbose group, total cholesterol and LDL concentration decreased significantly while other parameters did not change. In the gliclazide group, HDL levels decreased significantly from 46.6±2.48 mg/dl to 41.3±2.09 mg/dl (P 0.001) BMI increased significantly from 27.60±1.21 kg/m2 to 28.69±1.26 kg/m2. (P 0.003) Total daily insulin dose was not changed in the acarbose group significantly, but increased from 42.6±2.73 to 49.27±3.58 U/day, which was significant in gliclazide group of (P 0.016). In the acarbose group, there were no significant differences between responders and nonresponders with respect to fasting and stimulated C-peptide, HbA1c levels and baseline BMI values. But in the gliclazide group, baseline BMI values were significantly higher in the nonresponding group compared to responders (P 0.02). In conclusion, combination of insulin with acarbose can be a good alternative for type 2 diabetic patients on insulin therapy; seems more beneficial than combination with gliclazide; may have advantage of achieving good glycemic control without increasing insulin dose and BMI; also may have the advantage of providing a decrease in LDL level, which are all important to prevent atherosclerosis.

Insulin resistance in polycystic ovary syndrome: hyperandrogenemia versus normoandrogenemia

OBJECTIVE The goal of this study was to evaluate the insulin resistance and glucose tolerance in hyperandrogenemic and normoandrogenemic groups of patients with polycystic ovary syndrome (PCOS). STUDY DESIGN In this cross-sectional study, 17 hyperandrogenemic and 14 normoandrogenemic, age and weight-matched non-obese women with PCOS were studied. All patients had clinical hyperandrogenism and chronic anovulation with polycystic ovaries on ultrasound. Insulin resistance and glucose tolerance were determined by measuring insulin and glucose concentrations following a 75 g oral glucose tolerance test (OGTT). Fasting glucose to insulin ratio (FG:I ratio), insulin area under the curve (AUC(insulin)) during OGTT, and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. RESULTS Hyperandrogenemic group of patients had fasting hyperinsulinemia, lower FG:I ratio, higher AUC(insulin), and HOMA-IR compared with normoandrogenemic group. The differences between two groups were statistically significant. CONCLUSION PCOS has variable biochemical features. Hyperandrogenemia associated with insulin resistance differs from normoandrogenemia in this syndrome. Fasting insulin concentrations, FG:I ratio, AUC(insulin), and HOMA-IR are convenient markers for determining insulin resistance in PCOS.

Comparison of Calcitriol Treatment with Etidronate–Calcitriol and Calcitonin–Calcitriol Combinations in Turkish Women with Postmenopausal Osteoporosis: A Prospective Study

Abstract. Calcitriol has been widely used in the management of osteoporosis, but its efficiency is a matter of controversy. It is not known whether combinations of calcitriol and antiresorptive agents such as etidronate and calcitonin are superior to calcitriol alone in the treatment of postmenopausal osteoporosis. To make this determination, 30 Turkish women with postmenopausal osteoporosis between 45 and 68 years of age were randomized to receive either intermittent cyclical etidronate (400 mg/day, for 14 days) followed by 60 days of cyclical calcitriol therapy 0.25 μg twice daily (group 1; n= 10), or calcitriol 0.25 μg twice daily (group 2; n= 10), or calcitriol 0.25 μg/day in combination with 100 IU intranasal salmon calcitonin taken every other day (group 3; n= 10) through a 1-year period. Bone mineral density (BMD) of lumbar spine (L2 to L4) was determined for each patient by dual-photon absorptiometry (153Gd) at baseline, after 6 months, and at the end of the study. There was no significant difference among groups with respect to mean spinal BMD at baseline, after 6, and after 12 months. No significant spinal BMD changes occurred in any group from baseline, after 6 months, and after 12 months. Four patients in groups 1 and 2 and five patients in group 3 developed hypercalcemia at least once during therapy. Hypercalciuria occurred at least once in 9, 10, and 7 patients in groups 1, 2, and 3, respectively. One patient in group 2 developed a renal stone at the end of the study. Mean urine hydroxyproline levels did not change significantly in any group with respect to baseline. The data suggest that one-year treatment with calcitriol, given either alone or in combination with antiresorptive agents, does not improve spinal BMD in Turkish women with postmenopausal osteoporosis, and is associated with a high rate of adverse events.

Effects of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and their combination on microalbuminuria in normotensive patients with type 2 diabetes

The goal of this study was to compare the effects of lisinopril, losartan, and their combination on microalbuminuria in normotensive patients with type 2 diabetes mellitus. Patients were randomly assigned to 3 groups: group 1 (n=9), group 2 (n=9), and group 3 (n=8) received 10 mg lisinopril, 50 mg losartan, and 10 mg lisinopril plus 50 mg losartan, respectively, each day. For 12 mo, the 24-h urine albumin excretion rate was assessed at 3-mo intervals. At study completion, the urine albumin excretion rate had been reduced significantly in each group (P=.001); however, no significant differences were noted among groups (P=.587). Investigators in the present study have concluded that lisinopril, losartan, and their combination have similar effects on microalbuminuria in normotensive patients with type 2 diabetes mellitus, and that combination therapy does not provide additional benefit.

Isolated adrenocorticotropic hormone deficiency, thyroid autoimmunity, and transient hyperprolactinemia.

OBJECTIVE To describe a case of isolated adrenocorticotropic hormone (ACTH) deficiency associated with thyroid autoimmunity, subclinical hypothyroidism, and transient hyperprolactinemia. METHODS We present a detailed case report, including results of laboratory studies and magnetic resonance imaging, and discuss potential contributing factors in this setting. RESULTS In a 23-year-old woman with isolated ACTH deficiency accompanied by thyroid autoimmunity (Hashimotos thyroiditis), subclinical primary hypothyroidism, and hyperprolactinemia, magnetic resonance imaging of the pituitary showed normal findings but dynamic stimulation testing of the pituitary gland indicated an isolated ACTH deficiency with intact growth hormone and gonadotropin secretory reserves. The cortisol response to the short ACTH stimulation test was subnormal. Therapy with prednisolone (5 mg/day) and levothyroxine (100 microg/day) was initiated. Results of thyroid function tests were normalized after 1 month, the prolactin level decreased to normal after 1 year, and titers of thyroid autoantibodies decreased substantially after 1.5 years of treatment. CONCLUSION The correction of the related glucocorticoid deficiency resulted in resolution of the hyperprolactinemia and a decrease in titers of thyroid autoantibodies.

Effects of alendronate and risedronate on bone mineral density and bone turnover markers in late postmenopausal women with osteoporosis.

This study was undertaken to compare the effects of alendronate and risedronate on bone mineral density (BMD) and bone turnover markers (BTMs) in late postmenopausal women with osteoporosis. Thirty women older than 60 y of age were randomly assigned to receive alendronate 10 mg (n=16) or risedronate 5 mg (n=14) on a daily basis. The patients were followed every 3 mo for 12 mo. BMD measurements were taken at baseline and at the end of the study, and BTMs were measured at 3-mo intervals. By the end of the study, there were statistically significant increases in BMD in both groups at all sites at which they were measured (P < .001). However, these differences were not statistically significant between groups. By the end of the study, all BTMs had decreased significantly and to a similar extent in both groups. The most significant change was observed in the third month of the study. A negative correlation was noted between percentage change in bonespecific alkaline phosphatase and femoral neck BMD (r=-0.467). This study reported no difference between the 2 drugs in their effects on BMD and BTMs.