No association of psoriasis with autoimmune thyroiditis.

BACKGROUND: Common autoimmune diseases tend to coexist in the same patients. Few studies have examined the possible association between autoimmune thyroiditis and psoriasis or psoriatic arthritis (PsA), with inconsistent results. OBJECTIVE: To investigate the prevalence of autoimmune thyroiditis in psoriatic patients with or without PsA, living in an iodine-sufficient area. METHODS: We studied prospectively, 114 psoriatic patients with disease duration of 5-38 years, 30 of them with PsA, and 286 age- and body mass index (BMI)-matched subjects without psoriasis or known thyroid disease or autoimmune disease. A detailed medical history was obtained from all participants and clinical examination and laboratory evaluation was performed. Psoriasis severity was assessed with Psoriasis Area and Severity Index (PASI). Autoimmune thyroiditis was defined by the presence of positive autoantibodies to thyroid peroxidase and/or thyroglobulin. RESULTS: There was no difference in the prevalence of autoimmune thyroiditis between psoriatic patients and controls (20.2% vs. 19.6%). The prevalence of autoimmune thyroiditis in male and female psoriatic patients was similar (9.6% and 10.5% respectively), in contrast to the increased, as expected, prevalence in female vs. male controls (14.7% vs. 4.9%, P < 0.01). Detected cases with hypothyroidism due to autoimmune thyroiditis were similar in psoriatic patients and controls (7.9% and 7.0% respectively). Autoimmune thyroiditis in psoriatic patients was not related with age of psoriasis onset, psoriasis duration, PASI score, PsA and obesity. CONCLUSION: These data support that psoriatic patients with or without PsA do not have an increased risk for autoimmune thyroiditis.

Increased prevalence of polycystic ovary syndrome in premenopausal women with nonalcoholic fatty liver disease.

OBJECTIVE: Limited data exist concerning the presence of polycystic ovary syndrome (PCOS) in premenopausal women with nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prevalence of PCOS in overweight and obese premenopausal women with NAFLD. DESIGN: Prospective, observational, and cross-sectional study. METHODS: We studied 110 apparently healthy, overweight, and obese (BMI: 25.1-49.1 kg/m(2)) premenopausal women (age: 18-45 years) reporting no or minimal alcohol consumption for NAFLD with abdominal ultrasonography after excluding causes of secondary liver disease and for PCOS (Rotterdam criteria) with clinical examination, biochemical evaluation, and pelvic ultrasonography. Insulin resistance (IR) was assessed by homeostasis model assessment of IR (HOMA-IR), and free androgen index was calculated. RESULTS: NAFLD was detected in 71/110 women (64.5%). Women with NAFLD compared to women without NAFLD were more commonly diagnosed with PCOS (43.7% vs 23.1%, respectively, P=0.04), metabolic syndrome (30.2% vs 5.3%, respectively, P=0.003), and abnormal lipid profile (81.1% vs 51.3%, P=0.002). All women with abnormal glucose metabolism had NAFLD (P=0.01). Although PCOS was associated with NAFLD (OR 2.6, 95% CI: 1.1-6.2, P=0.04), in a multivariate analysis higher HOMA-IR values (OR 2.2, 95% CI: 1.1-4.4, P=0.02) and triglyceride levels (OR 1.01, 95% CI: 1.00-1.02, P=0.04) independently predicted NAFLD, after adjusting for age, BMI, and waist-to-hip ratio. CONCLUSIONS: These findings indicate an increased prevalence of PCOS in overweight and obese premenopausal women with NAFLD, although it is not supported that the syndrome is primarily involved in NAFLD. Evaluation for PCOS may be considered in these women.

Two different corticosteroid-binding globulin variants that lack cortisol-binding activity in a greek woman.

BACKGROUND: Corticosteroid-binding globulin (CBG), encoded by SERPINA6, is the principal plasma binding protein for cortisol. Most nonsynonymous single-nucleotide polymorphisms that alter the production or function of CBG occur rarely, and their clinical significance remains obscure. METHODS: Serum and DNA were obtained from a Greek woman with low morning cortisol levels and from family members. SERPINA6 exons were sequenced, and serum CBG was measured by ELISA and cortisol-binding capacity assay. Recombinant CBG variants were produced for detailed functional studies. RESULTS: A novel heterozygous c.1282G>C transversion in exon 5 of SERPINA6, resulting in a p.Trp393Ser (W371S) substitution, was identified in the proband, who was also heterozygous for single-nucleotide polymorphisms encoding the CBG Lyon (D367N) and CBG A224S variants. The proband had no measurable plasma cortisol-binding activity despite a CBG level of 273 nm by ELISA. She inherited CBG W371S from her mother whose plasma cortisol-binding capacity was approximately 50% lower than the CBG measurements by ELISA (314 nm). The proband's father and four children were heterozygous for CBG D367N; their CBG levels by ELISA were normal, but corresponding cortisol-binding capacity measurements were 50% lower. Pedigree analysis revealed that W371S segregates with A224 and that D367N and W371S segregate separately. Recombinant CBG D367N and CBG W371S had no measureable cortisol-binding activity. CONCLUSION: A new CBG Athens (W371S) variant that lacks cortisol-binding activity has been identified in a carrier of the cortisol-binding deficient CBG Lyon (D367N) variant. Analyses of CBG levels in this pedigree illustrate how immunoassays fail to accurately reflect cortisol-binding activity.

Clinical and biochemical impact of BCL1 polymorphic genotype of the glucocorticoid receptor gene in patients with adrenal incidentalomas.

BACKGROUND: Adrenal incidentaloma (AI) is a common clinical problem. Subtle hormonal abnormalities are present in a substantial proportion of patients. BCL1 gene polymorphism of the glucocorticoid receptor (GR) is associated with increased sensitivity to glucocorticoid action. The genotype- phenotype associations of this polymomorphism in patients presenting with AI has not been extensively investigated. AIM: A cross-sectional study in secondary/tertiary care centers. SUBJECTS/METHODS: Ninety-five subjects with AI were genotyped for the BCL1 GR gene polymorphism. Patients underwent an oral glucose tolerance test and a dexamethasone suppression test (DST). The presence of subclinical hypercortisolism, features of metabolic syndrome, and osteoporosis/ osteopenia were also assessed. RESULTS: No significant differences in markers of adrenal function between BCL1 carriers and non-carriers were revealed. Also, no difference was found in the features of metabolic syndrome, as well as in bone metabolism and density between these 2 groups. However, DST suppressor patients belonged more frequently to the BCL1 carriers group (41 out of 69 patients, 59.4% vs 9 out of 26 patients, 34.6%, p=0.0039), had smaller total adenoma size (2.4±0.2 cm vs 3.5±0.4 cm, p=0.04), and lower incidence of bilateral adrenal masses (18.8% vs 46.2%, p=0.01). CONCLUSIONS: AI patients who also carry the polymorphic BCL1 variant exhibit smaller size adrenal nodules. Those AI patients with complete DST suppression had a higher incidence of the polymorphic BCL1 variant. However, this study failed to demonstrate any significant impact of BCL1 GR polymorphism on the frequency of cortisol-dependent co-morbidities in patients with AI.

Diabetes in postmenopause: different influence on bone mass according to age and disease duration.

OBJECTIVE: Studies addressing the influence of diabetes mellitus on bone metabolism have yielded conflicting results. The aim of the present study is to investigate the bone mineral density (BMD) status of postmenopausal diabetic women with different ages or diabetes duration. METHODS: Two hundred postmenopausal women with type 2 diabetes (DM) and 800 postmenopausal healthy women (PMP), serving as control subjects, were studied. Subjects were divided into either 6 groups according to 5 year age segments, or 6 groups according to 5 year segments of diabetes duration. BMD was measured at the femoral neck and at the trochanter major with dual energy X-ray absorptiometry. RESULTS: Diabetic women studied as a whole, exhibited significantly higher BMD values compared to healthy postmenopausal women at both femoral neck and trochanter. Diabetic women of 48-53, 53-58, 58-63 and 63-68 age groups had significantly higher BMD values than the respective control groups, whereas BMD values of DM 73-78 were significantly lower compared to the PMP 73-78 group at both anatomic sites. When the same diabetic women were divided according to diabetes duration (DUR), groups DUR 6-10 and DUR 11-15 exhibited significantly higher BMD values at both anatomic sites compared to control groups. In contrast, BMD values of group DUR 21-25 were significantly lower only at the femoral neck. CONCLUSIONS: Type 2 diabetes mellitus' influence on bone metabolism seems to depend on the patient's disease duration and age. The initial positive effect on bone mass appears to be ameliorated as age or disease duration advance. Studies concerning type 2 diabetes and bone mass should take these parameters into account.

Comparison of T- and Z-score in identifying risk factors of osteoporosis in inflammatory bowel disease patients.

OBJECTIVE: Most studies have shown contradictory results regarding predictive factors of osteoporosis in inflammatory bowel disease (IBD). Since in these studies either T- or Z-scores has been used, our aim was to compare T- and Z-score in identifying risk factors of osteoporosis in IBD patients. MATERIALS AND METHODS: Bone density was measured by dual X-ray absorptiometry (DXA) at L2-L4 of the spine and femoral neck in 122 patients. Twenty-two clinical parameters were recorded prior to DXA and evaluated by univariate and multivariate analysis. RESULTS: On multivariate analysis, cumulative steroid dose was a predictive factor of femoral neck T-score (p<0.001) and Z-score (p=0.001). Age was a predictive factor of femoral neck T-score (p<0.001). BMI was a predictive factor of femoral neck Z-score (p=0.03). None of the other 19 variables tested had any predictive value for bone density. Age >or=55 years was a risk factor of low femoral neck T-score (OR 5.08, 95% CI 1.90-13.57, p=0.001), as was cumulative dose of prednisolone >or=5 g (OR 3.41, 95% CI 1.50-7.73, p=0.004). CONCLUSIONS: There is a discordance of results depending on whether T- or Z-scores are used in analysis. Among 22 parameters, cumulative steroid dose and age proved to be the most important factors.

Discrepancies between vertebral bone density values: the least dense vertebra.

Vertebral bone mineral density (BMD) measurements by DXA are considered reliable indicators of local fracture risk in the absence of radiographic deformities. The clinical evaluation of one individual vertebra presenting a BMD value significantly less than the others is attempted in this study. For a period of 30 months, BMD measurements of L1-L4 vertebrae and femoral neck (FN) were performed by DXA in 817 postmenopausal women, aged under 65 years, with a BMI less than 33 kg/m(2). In 204 (25%) of these women (group A), the least dense vertebra (LDV) presented a BMD value lower than 92.4% from the immediate denser vertebra. The remaining 613 women comprised group B. Women with X-ray proven vertebral degenerative lesions or deformities were excluded from the study. Among the four measured vertebrae, L1 was the most frequent LDV (47%), whilst L3 was the most rare (2%). Absolute and age-adjusted BMD values of L1-L4 and FN, as well as the proportions of osteopenic or osteoporotic women, did not differ significantly between the two groups. A significant positive correlation was observed between either L1-L4 or LDV and FN BMD values in both groups, but stepwise multiple regression analysis revealed that in group A the LDV did not participate in the model explaining the variability of the FN BMD values. In group B, the least dense vertebra was the only variable participating in the respective model (adjusted-R(2) = 37.7%). It is concluded that in a significant proportion of relatively young postmenopausal women, a wide variance of BMD values exists between individual vertebral BMD values without radiographic background. L1 was the most frequent LDV and L3 the most rare. In such cases, the evaluation of the least dense vertebra seems to offer an alternative estimation of vertebral bone mass, instead of mean L1-L4.

Diabetes and premature menopause: is their co-existence detrimental to the skeleton?

OBJECTIVE: Premature menopause is a known risk factor for osteoporosis, whilst the influence of type 2 diabetes on bone mineral density (BMD) is still controversial. DESIGN AND METHODS: BMD values assessed by dual-energy X-ray absorptiometry (DXA) in L2-L4 vertebrae and the femoral neck (FN) of 40 diabetic women with premature menopause (D-EMP) were compared with those of 60 non-diabetic, prematurely menopausal women (EMP) and 60 diabetic women with normal menopause (D-NMP) who had been matched by age and body mass index (BMI). In all women, the time elapsed since menopause ranged between 10 and 25 years and the duration of diabetes exceeded 75% of the postmenopausal time period. The age of D-EMP women was 58.7+/-5 years (mean+/-1 s.d.), age at menopause 39.5+/-2.7, years since menopause 18.6+/-4.9, BMI 27.8+/-4.3 kg/m(2) and duration of diabetes 13.9+/-3.9 years. RESULTS: Vertebral BMD values of D-EMP women were significantly higher than those of EMP women (0.908+/-0.135 vs. 0.817+/-0.14 g/cm(2), P = 0.002), although there was no significant difference between D-EMP and D-NMP women (0.886+/-0.15 g/cm(2)). No significant differences were observed in FN BMD values between all groups. Age-adjusted BMD values (Z scores) of D-EMP women were higher than EMP women in both anatomic sites (P < 0.01), but did not differ from D-NMP women. In contrast to the other two groups, no statistically significant correlation was observed in D-EMP women between the BMD values of either anatomic area and the time elapsed since menopause. HbA(1c) values were positively correlated only to vertebral BMD values of the D-EMP group (P < 0.05). No correlation was observed between the BMD values and the duration of diabetes either in D-EMP or in D-NMP women. CONCLUSIONS: Type 2 diabetes seems to positively affect the mineral density of the trabecular bone in women with premature menopause. The duration of diabetes does not appear to influence bone mass.

Does subclinical hypercortisolism adversely affect the bone mineral density of patients with adrenal incidentalomas?

OBJECTIVE: Subclinical hypercortisolism (SH) is detected increasingly in a substantial proportion of patients with incidentally discovered adrenal adenomas. The clinical implications of SH are currently unclear. Osteoporosis is a well-known complication of glucocorticoid excess. So far, the impact of SH on bone mineral density (BMD) has been studied in a limited number of reports with discordant results. In the present study we evaluated the BMD in a large cohort of post-menopausal women with adrenal incidentalomas. : patients and measurements Forty-two post-menopausal women with incidentally discovered adrenal masses and radiological features highly suggestive of benign adrenal adenomas were investigated. All patients underwent a standard low-dose dexamethasone suppression test (LDDST; 0.5 mg 6-hourly for 2 days). The diagnosis of subclinical hypercortisolism (SH) was based on post-LDDST cortisol concentrations of > 70 nmol/l. According to this criterion patients were subdivided into two groups: with (n = 18; group A) or without (n = 24; group B) SH. There was no significant difference in age, years since menopause and body mass index between these groups. BMD was measured at L2-L4 vertebrae and three sites of the proximal femur by the dual energy X-ray absorptiometry (DEXA) method. RESULTS: Post-menopausal women with SH (group A) exhibited slightly but significantly lower absolute and age-adjusted BMD values compared to group B patients in the femoral neck (BMD g/cm2: 0.72 +/- 0.08 vs. 0.79 +/- 0.09; Z-score: -0.20 +/- 0.82 vs. +0.43 +/- 0.94, P < 0.05) and trochanter (BMD g/cm2: 0.60 +/- 0.09 vs. 0.69 +/- 0.10; Z-score: -0.32 +/- 1.0 vs. +0.30 +/- 1.05, P < 0.01). BMD measurements of the Ward's triangle were also lower in group A patients but the difference did not reach statistical significance (BMD g/cm2: 0.60 +/- 0.10 vs. 0.68 +/- 0.13, P = 0.06). There was no difference in the lumbar vertebrae between the two groups (BMD g/cm2: 0.888 +/- 0.13 vs. 0.90 +/- 0.16, P = 0.78; z-score: +0.50 +/- 1.16 vs. +0.11 +/- 1.5, P = 0.36). The number of patients in the osteoporotic range was minimal with no significant difference between the two groups. However, the frequency of osteopenia in group A was significantly greater than in group B patients in the trochanter and Ward's triangle areas. Serum osteocalcin (BGP) levels were significantly lower in group A compared to group B patients (18.6 +/- 8.6 vs. 26.2 +/- 8.1 ng/ml, P < 0.01); no difference existed regarding parathyroid hormone (PTH) concentrations (43 +/- 15.6 vs. 41.2 +/- 14.8 pg/ml, P = 0.72). CONCLUSIONS: In this series, post-menopausal women with subclinical hypercortisolism had lower absolute and age-adjusted BMD values and a higher rate of osteopaenia in the trabecular loaded and mixed cortical-trabecular bone of proximal femur. These data demonstrate that the subtle hypercortisolism of patients with adrenal incidentalomas may have an adverse effect on the bone mass of these patients.

Correlation of bone mineral density with the histological findings of renal osteodystrophy in patients on hemodialysis.

AIMS: To examine the distribution of bone mineral density (BMD) in different histological groups of renal osteodystrophy. PATIENTS: We prospectively studied 62 patients, 41 men and 21 women, aged 57+/-11.5 years, who had been on hemodialysis for 60+/-55 months. The women had been amenorrheic for 13+/-4 years and 7 patients (11%) had a positive fracture history. METHODS: A bone biopsy was taken after tetracycline labelling and BMD of the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry (DEXA); serum intact parathyroid hormone (iPTH), bone Gla protein (BGP), phosphorus, calcium and alkaline phosphatase (ALP) were also determined. RESULTS: Histologically, 40 patients showed secondary hyperparathyroidism (sHPT), 6 mixed bone disease, 14 adynamic bone disease (A) and 2 osteomalacia. BMD of the lumbar spine was decreased in 43 patients (69%) and in 9 (14.5%) it was lower than -2 Z score units. BMD of the femoral neck was low in 55 patients (89%) and in 22 (35.5%) it was lower than -2 Z scores. BMD was lower in patients with sHPT than in those with adynamic bone disease (p<0.05) in which it was close to normal. BMD in both these sites correlated inversely with the biochemical markers (serum iPTH, BGP and ALP) and the histomorphometric indices of bone turnover. CONCLUSIONS: Osteopenia is frequent in patients on hemodialysis, especially those with biochemical and histological findings of sHPT.

The type and time of menopause as decisive factors for bone mass changes.

BACKGROUND: Early menopause, whether it be natural or surgical, is one of the established risk factors for osteoporosis. Surgical menopause, however, differs from natural menopause owing to the abrupt cessation of estrogen secretion. This study attempts to investigate the influence of menopause type on bone mineral density (BMD) changes. METHODS: Four groups, each consisting of 30 women, were compared: early menopause (EMP), surgical menopause (SUMP) and two groups of natural menopause. The two groups share a similar number of years since menopause (YSM) but have a different chronological age (NMPO), or share a similar age but different YSM (NMPY) to the EMP and SUMP. BMD was measured by the DXA method at L2-L4 vertebrae and proximal femur. RESULTS: Mean vertebral BMD of EMP was lower than that of SUMP (P < 0.05) and of NMPY (P < 0.001) women. Femoral neck BMD did not differ between SUMP and EMP women but both exhibited significantly lower BMD than either natural menopause groups. BMD of SUMP and vertebral BMD of NMPY women was inversely correlated to chronological age and to number of YSM. Pertaining to T-score values according to the osteoporotic range, NMPO, EMP and SUMP women being homogeneous exhibited significantly lower values than NMPY in the vertebrae (F-ratio = 7.84, P < 0.001). Whereas, in the femoral neck and the trochanter major, EMP and SUMP categories presented significantly lower T-score values than the NMPO and NMPY (F = 3.61, P < 0.01 and 2.8, P < 0.05 respectively). CONCLUSION: Women with early menopause exhibit lower vertebral BMD than women of similar age after either surgical or natural menopause. In women of similar age, surgical menopause results in lower vertebral and femoral neck densities compared to natural menopause. Chronological age and the interval after menopause negatively affects bone density in women with similar age whether in surgical or natural menopause.

Bone mineral density of vertebrae, proximal femur and os calcis in normal Greek subjects as assessed by dual-energy X-ray absorptiometry: comparison with other populations.

Dual energy X-ray absorptiometry (DXA) is an established method for the detection of even small changes in bone mineral density (BMD). It thus allows the earliest possible diagnosis of osteopenia, with consequent prompt estimation of fracture risk. However, for proper evaluation of densitometry results it is essential that a comparison with reference BMD values of normal age- and sex-matched persons from the same population be performed. For this purpose we determined bone density of the L2-L4 vertebrae, the L3 vertebra in the lateral projection, the proximal femur and the os calcis in a cross-sectional study of 168 men and 244 women from the Greek population. The age range of the subjects was 20-80 years. Peak bone mass for both sexes was attained in the 30-35 year age group for the vertebrae and in the 25-30 year age group for the proximal femur and os calcis. Mean annual vertebral bone loss calculated on cross-sectional data ranged from 0.1% to 0.22% for women < 50 years and from 1.3% to 1.6% for those > 50 years, whereas in men the range was from 0.36% to 0.64% for the whole age spectrum. Regarding femoral neck, the values wer 0.3% (women < 50 years), 1.2-1.5% (> 50 years) and 0.6-0.8% for men. Total bone loss between ages 20 and 70 was 29.5% for the vertebrae and 32% for the femoral neck in women, whereas the values for men were 19.5% and 29% respectively. A positive correlation was observed between bone density, body weight and body height in both sexes. Body mass index correlated significantly with density only in postmenopausal women. Compared with North American, Finnish and German populations, Greek men presented with lower BMD values in the decades above 40 years. Greek women exhibited lower vertebral BMD values than those from the USA. Germany and Japan (50-60 age group), whereas they did not differ from those of Finnish women. However, femoral neck BMD in Greek women was higher than in Japanese women in all age groups.

Bone loss in experimental diabetes. Comparison with the model of inflammation mediated osteopenia.

Osteopenia occurs in diabetes mellitus. Since bone status is altered in Inflammation Mediated Osteopenia (IMO), it was appropriate to study its course in diabetic animals in order to investigate the mechanism of diabetic osteopenia. To this end, we compared the bone loss in streptozotocin (STZ) diabetes with that of IMO. Female rats were studied in total of 8 groups: Control, IMO, Diabetes, IMO with Diabetes (IMO-DIA) on the 3rd and similar groups on the 6th week after induction of IMO with 8 s.c. injections of talcum suspension. Femoral mineral content as reflected by ash weight per femoral volume after 3 weeks was lower in IMO compared to control rats (p < 0.05) while after 6 weeks this difference was not significant. The femur ash weight per volume of diabetic rats was lower than the one of intact rats with and without IMO both after 3 and 6 weeks. Diabetic rats with and without IMO exhibited no difference in this respect. Spleen weight as a measure of the extent of inflammation per body weight was increased only in the IMO group. The diabetic rats with and without IMO did not differ significantly with regard to spleen weight. Similar changes were observed 6 weeks after the induction of IMO. However the difference between IMO and diabetes rats was of borderline significance and no difference existed between the IMO and IMO-diabetic group. The serum calcium levels of intact, IMO and diabetic rats showed no change during both experimental periods. Those of diabetic rats with IMO were higher than those of the diabetic and IMO animals after 6 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Proinsulin as a possible therapeutic agent.

Gene technology has made significant amounts of biosynthetic human proinsulin (BHP) for biological and clinical studies available. It has been shown both in vitro and in vivo that BHP is about 10% as active as biosynthetic human insulin. More specifically it is 8% as potent regarding its action in stimulating peripheral glucose disposal and 12% as potent in suppressing hepatic glucose output. Its hypoglycemic effect is rather produced by the intact molecule or its intermediates and not by conversion to insulin or C-peptide. BHP appears to exert a more prolonged action when administered subcutaneously compared to NPH insulin. Furthermore because of its weaker effect on peripheral glucose utilization it is expected to create less profound hypoglycemia. Under conditions of equipotency BHP may stimulate triglyceride synthesis in a lower degree and in that way be less lipogenic. On longterm basis BHP proved to have a low immunogenic potential. We investigated the efficacy of BHP in split doses in type II diabetics with relative insulin resistance. Glucose levels at 1600 and 2000 and 0400 hrs as well as integrated glycemia over the 24 h period were lower under BHP. The potency of BHP in this and other studies has been demonstrated after application of greater quantities from it in terms of equimolarity. Nevertheless there are certain features such as the protracted action, the stronger effect on hepatic glucose production and the lower suppression of endogenous insulin secretion which make proinsulin a promising agent in the future management of type II diabetes.

Comparative study of the therapeutic effects of glibenclamide or the fixed combination of glibenclamide-phenformin with those of gliclazide or chlorpropamide.

This study was designed to compare the therapeutic effects of glibenclamide or the fixed combination of glibenclamide-phenformin with those of gliclazide, chlorpropamide or biguanides in non-insulin-dependent diabetes. It is divided into two parts: a) in the retrospective study (473 subjects), glucose control of patients who were transferred from chlorpropamide, gliclazide, glibenclamide, glibenclamide + biguanide or metformin to the fixed combination glibenclamide-phenformin in the same tablet (2.5 mg and 25 mg, respectively) was monitored. A statistically significant decrease of blood glucose and glycosylated hemoglobin values was found under the combination of glibenclamide-phenformin contained in the same tablet in contrast to the values obtained with the treatment with glibenclamide, gliclazide, chlorpropamide, combination of glibenclamide and biguanides, metformin, and insulin. b) In the prospective study (57 subjects), the patients were transferred from chlorpropamide or gliclazide to glibenclamide for 3 months and then reallocated to the previous treatment for 3 additional months. It was found that under glibenclamide, glucose control was significantly better than under chlorpropamide or gliclazide. In conclusion, glibenclamide, a second generation sulfonylurea, and the fixed combination glibenclamide-phenformin in the same tablet are more effective compared to the other antidiabetic agents here studied and lead to a better control of type II diabetic patients. There was no increase in plasma lactic acid concentration in all patients studied before and after having received the fixed combination of glibenclamide-phenformin in the single tablet form.

Efficacy of a new needleless insulin delivery system monitoring of blood glucose fluctuations and free insulin levels.

A new insulin delivery system Vitajet has been invented which involves a high-pressure spring and obviates the use of needle injections. To study its efficacy we compared blood glucose fluctuations, integrated glycemia, free insulin and total free insulin concentrations in six insulin-dependent diabetics. After obtaining a steady state of carbohydrate metabolism overnight by feedback control through the artificial endocrine pancreas (AEP) Biostator, the patients received their usual morning and evening doses of insulin by either conventional injection or Vitajet in random order. Blood glucose levels were significantly lower after Vitajet than conventional injections (p less than 0.04) between 10 a.m. and 4 p.m., but the difference disappeared from 4 p.m. onwards. The areas under the curve (AUCs) of glucose fluctuations were lower after Vitajet (28036 +/- 4655 vs 31086 +/- 2310 mg. min% mean +/- SEM, p less than 0.01). AUCs for free insulin concentrations (microU.min/ml) were close: 39286 +/- 4510 (Vitajet) vs 30597 +/- 3575 (conventional). It is concluded that Vitajet constitutes an efficient needleless route for administering insulin pulses.

The effects of the somatostatin analogue SMS 201-995 on carbohydrate homeostasis of insulin-dependent diabetics as assessed by the artificial endocrine pancreas.

On the basis of the inhibitory actions of the somatostatin analogue SMS 201-995 on growth hormone (GH) and glucagon (IRG) secretion we investigated its effects on carbohydrate metabolism of insulin-dependent diabetics. Six patients with no residual insulin secretion were connected to the artificial endocrine pancreas (AEP) and after the establishment of a steady state overnight they were injected either normal saline or 50 micrograms of SMS 201-995 s.c., t.i.d., or 100 micrograms of the same compound b.i.d. Insulin requirements were assessed by the AEP and compared during the 24 h and after the main meals. The inhibition of GH and IRG secretion was evaluated as well. 50 micrograms of SMS analogue t.i.d. induced a significant reduction of insulin requirement (mean +/- SEM) while no significant difference was observed between control and 100 micrograms s.c., b.i.d., nor between 50 micrograms and 100 micrograms. The curve of glucose fluctuations was smoother after 50 micrograms than after 100 micrograms and control. Postprandial IRG secretion was inhibited by both regimens of SMS after lunch and dinner. GH secretion was significantly inhibited after all meals during the days of analogue administration. SMS 201-995 analogue appears to have a remarkable antidiabetic activity as shown by the sparing of administered amount of insulin, suppression of counter-insulin hormones and smoothing of blood glucose curve. It may constitute a safe and effective adjunctive measure in the management of insulin-dependent diabetics.

The antidiabetic action of somatostatin-28 as assessed by the artificial endocrine pancreas: greater potency than somatostatin-14.

In order to investigate the action of somatostatin-28 (SS-28) on the metabolic homeostasis of insulin-dependent diabetics, we compared its effects to those of somatostatin-14 (SS-14) in terms of insulin sparing, changes in dextrose demands, glucose fluctuations and behavior of growth hormone and glucagon secretion. Eight insulin-dependent subjects were connected to Artificial Endocrine Pancreas (Biostator) for 84 hours during which they received intravenous infusions of either SS-14, SS-28 or isotonic saline in a randomized order, after a steady state of metabolism had been achieved. Five of the patients received SS-28 100 micrograms/h and SS-14 250 micrograms/h for 10 hours and three of them SS-28, 50 micrograms/h and SS-14 250 micrograms/h for 12 hours. Identical doses of both peptides were administered as bolus infusions prior to the continuous ones. Under SS-28 100 micrograms/h and SS-14 250 micrograms/h patients required 13.5 +/- 2.3 and 14.5 +/- 1.9 U of insulin respectively vs 40 +/- 5.6 U under isotonic saline infusion (mean +/- SEM, P less than 0.005 and P less than 0.01). At the same period the apparatus delivered 15 times more dextrose under SS-28 and 20 times more under SS-14. The magnitude of glucose fluctuations diminished from 64.6 +/- 2.47 mg% without to 41.4 +/- 2 mg% under SS-14 (P less than 0.01) and 46 +/- 3.8 mg% under SS-28 (P less than 0.02). Similar changes were observed in the remaining three patients who received SS-28 in the dose of 50 micrograms/h.(ABSTRACT TRUNCATED AT 250 WORDS)

24-h blood glucose pattern in type I and type II diabetics after oral treatment with pentoxifylline as assessed by artificial endocrine pancreas.

Based on the known action of xanthine derivatives on the insulin secretion, the effect of pentoxifylline on carbohydrate homeostasis of type I (IDDM) and type II (NIDDM) diabetics was investigated. Pentoxifylline is known to exert a favorable influence on hemorheological disturbances in such patients. Twenty-four hour blood glucose pattern and insulin requirements were evaluated in type I and type II diabetics by the use of the artificial pancreas before and after a 14-day treatment with pentoxifylline 400 mg p.o. (Trental 400) t.i.d. During the stabilization period before treatment with pentoxifylline, NIDDM patients required 10.1 +/- 3.8 U of insulin and the IDDM 35 +/- 13.7 U. After 2 weeks on pentoxifylline, NIDDM required only 6.3 +/- 2.8 U (p less than 0.05) and IDDM 28.5 +/- 9.7 U (n.s.). Average blood glucose during the 24h decreased by 15.8 +/- 3.5% in NIDDM and by 10.3 +/- 2.5% in IDDM. Moreover, a significant smoothing of glucose fluctuations during the 24h was noted in both groups. It is concluded that pentoxifylline administered concurrently to any antidiabetic type of treatment leads to better blood glucose control as well as to prevention or delay of vascular complications.

Differences between somatostatin-28 and somatostatin-14 with respect to their biological effects in healthy humans and acromegalics.

In order to compare the effects of somatostatin-28 (SS-28) with those of somatostatin-14 (SS-14) in humans, we administered both compounds randomly in 5 healthy persons and 3 patients with active acromegaly. Blood glucose, growth hormone, insulin, glucagon, TSH, FSH, LH and prolactin were estimated after arginine, TRH and LHRH stimulation in the normals and without stimulation in the acromegalics. Both substances were administered in doses of 25, 50, 200 and 250 micrograms. Our results indicate that SS-28 is at least 5 times more potent in man than SS-14 as far as inhibition of growth hormone, insulin, glucagon and prolactin secretion is concerned. On the other hand SS-28 is at least 2 times more potent than SS-14 in the inhibition of TSH, FSH and LH. If this difference in potency is calculated on the basis of equimolarity, the action of SS-28 becomes even much greater. According to these findings, SS-28 appears to be either the main hormone and SS-14 a fragment of it with a lesser degree of biologic activity, or the prohormone with special properties.