Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

Male gender differences in the thyroid ultrasound features, thyroid peroxidase antibodies and thyroid hormone levels: a large population-based study.

UNLABELLED: Anti-thyroid antibodies and thyroid ultrasound (US) are currently the methods for diagnosing autoimmune thyroid disease. Few data exist on their utility in males. The aim of the study was to investigate the gender-specific relationship between the Anti-TPO levels, thyroid ultrasound features, and thyroid function in a population with no known thyroid disorder. METHODS: We studied 1,887 subjects, 20-80 years, 953 females, 934 males. Anti-TPO antibodies, TSH and FT4 were measured and ultrasound of the thyroid was performed. The subjects were divided into antibody-positive and antibody-negative, and into four US pattern groups. The prevalence of subclinical (SHT) and overt (OHT) hypothyroidism was determined. RESULTS: Antibody positivity was found in 23 % of females and 10 % of males (p < 0.01), being highest in the hypoechoic/non-homogenous subgroups [68 % Ab-positive females versus 41 % Ab-positive males (p < 0.001)]. Hypothyroidism was most prevalent in the antibody-positive subjects with hypoechoic non-homogenous pattern (35 %, both genders). Odds ratios for hypothyroidism were similar in males and females with hypoechoic non-homogenous pattern (5.91, 95 %CI 2.50, 13.96 vs. 6.27, 95 % CI 2.64, 14.91), but higher in Ab-positive females than males. SHT was found in 4.5 % of females and 2 % of males, OHT in 3.2 % of females and 1.1 % of males. 65 % of the females with SHT, 81 % of those with OHT, 26 % of the males with SCH and 60 % with OHT were Anti-TPO positive. CONCLUSION: The prevalence and pattern of autoimmune-related changes differed in the two genders. Hypothyroidism prevalence was similar in both genders when both hypoechoic/non-homogenous pattern and anti-TPO positivity were present.

Multiple relapses of hyperthyroidism after thyroid surgeries in a patient with long term follow-up of sporadic non-autoimmune hyperthyroidism.

Constitutively activating thyrotropin receptor (TSHR) germline mutations have been identified as a molecular cause of congenital hyperthyroidism. Patients with relapsing hyperthyroidism were previously treated with surgery and radioiodine. We report on a 22-year-old male patient who was treated for his multiple relapses of hyperthyroidism by repeated subtotal thyroidectomies (STE). During the 22 years of follow-up, the patient developed several relapses of hyperthyroidism, four of them after thyroid surgeries. Sequencing of the TSHR gene revealed a gain-of-function mutation with an amino acid exchange of aspartate to tyrosine in codon 633 which is located in the sixth transmembrane domain of the TSH receptor. The absence of the mutation in all other family members identifies the patient's TSHR mutation as a sporadic germline mutation. In this patient, thyroid tissue growth and hyperthyroidism could repeatedly be controlled only for limited periods by near total thyroidectomy. Therefore, this case confirms that early combined treatment with near-total thyroidectomy plus radioiodine therapy seems to be the treatment of choice for patients with sporadic non-autoimmune hyperthyroidism.

Individual risk factors of the metabolic syndrome in adult patients with growth hormone deficiency--a cross-sectional case-control study.

OBJECTIVE: Growth hormone deficiency in adults (GHDA) is considered to be associated with increased cardiovascular risk, most commonly reflected by the prevalence of the metabolic syndrome (MS). However, there are still a limited number of studies comparing directly the MS prevalence in GHD patients to that in general population. The aim of this study was to investigate the individual risk factors of the MS in a cohort of GHD patients and to compare its prevalence with an age- and sex-matched control group. DESIGN: A cross-sectional case-control study. METHODS: In total, 54 adult patients with GHD (childhood onset GHD (COGHD): n=19, adult onset GHD (AOGHD): n=35) and 2 153 control subjects were studied. GHD was diagnosed according to the Endocrine Society Clinical Practice Guideline recommendations from 2011 and MS was scored by the NCEP-ATP III definition. RESULTS: The main metabolic abnormalities in GHD group were increased waist circumference (50.0%), low HDL-cholesterol (42.6%) and hypertriglyceridemia (40.7%) and their prevalence was significantly higher (p=0.013, p=0.019 and p=0.010, respectively) than in control group, where increased blood pressure prevailed (64.2%, p<0.0001). However, the difference in the MS prevalence between the 2 groups (29.6% vs. 24.9% in controls) failed to reach statistical significance (p=0.429). Patients with MS from both groups did not differ significantly in their metabolic profile (except for increased blood pressure), mean age and gender distribution. CONCLUSIONS: Although GHDA was associated with the development of visceral obesity and dyslipidemia, these adverse cardiovascular risk factors did not determine a higher prevalence of the MS in Bulgarian GHD patients compared to control subjects. Furthermore, the individual risk factors of the MS did not significantly differ between patients with MS from both groups.

Winter 25-hydroxyvitamin D levels in young urban adults are affected by smoking, body mass index and educational level.

BACKGROUND/OBJECTIVES: To study the relationship of winter 25-hydroxycholecalciferol (25-OHD) levels with age, education, place of residency, marital status and body mass index (BMI) as they may affect sun exposure, vitamin D synthesis and metabolism. SUBJECTS/METHODS: Subjects (1952) answered a structured questionnaire concerning education, marital status and smoking; and body weight/height, and parathyroid hormone and 25-OHD were measured. RESULTS: 25-OHD levels were higher in the males with elementary and secondary education compared with higher education (46.8±18.5 and 43.7±16 vs 39.9±15.3 nmol/l, P<0.01). Vitamin D deficiency was more prevalent (16.7%, (13.1-20.2) vs 10.8%, (8.4-13.2), P=0.08) and sufficiency was less prevalent (24.6% (20-29.2) vs 33.7%, (29.5-37.8), P=0.005) in those with higher than secondary education. No differences were found among the females. Male smokers had lower 25-OHD than nonsmokers (40.2±16.6 vs 43.6±15.7 nmol/l, P=0.004). Deficiency was more prevalent in the male smokers than nonsmokers with secondary and higher education (secondary 16.6%, (10.1-22.4) vs 8.2%, (5.1-11.3), P=0.006; higher 27.4%, (17.7-37.1) vs 13.2%, (9.0-17.5), P=0.003). 25-OHD was lower in the obese than in the normal-weight females (34.6±16.2 vs 38.2±17.8 nmol/l, analysis of variance, P=0.014), but not males. Marital status was not related to 25-OHD. Only in the urban residents, increasing BMI in the young females increased the risk for vitamin D deficiency by 1%, and smoking had an odds ratio of 1.99 (1.05-3.78) in the young and 2.5 (1.07-5.75) in the middle-aged males. CONCLUSIONS: Smoking and higher education in the males and obesity in the females were factors for vitamin D deficiency among Bulgarian urban population.

Insulin secretion, peripheral insulin sensitivity and insulin-receptor binding in subjects with different degrees of obesity.

OBJECTIVES: The aim of the present study was to investigate insulin secretion, insulin-receptor binding and peripheral insulin sensitivity in subjects with different degrees of obesity. METHODS: 36 obese subjects with normal glucose tolerance and different degrees of obesity and 40 healthy normal-weight subjects participated in the study. Peripheral insulin sensitivity was measured by using the euglycaemic hyperinsulinaemic clamp technique, and insulin-receptor binding-on circulating mononuclear blood cells. Insulin secretion was studied during intravenous tolbutamide test. RESULTS: The subjects with I degree of obesity demonstrated a significant decrease in the number of total (p<0.0001) and high-affinity (p<0.01) insulin receptors per cell, as well as significantly higher insulin receptor affinity (p<0.01) as compared to the normal-weight subjects. The subjects with II degree of obesity also demonstrated a significant decrease in the number of total (p<0.0001) and high-affinity receptors (p<0.001) per cell as well as an increase (p<0.001) in insulin-receptor affinity as compared to the controls. The significantly decreased receptor number in the subjects with I and II degree of obesity was accompanied by an increase in insulin receptor affinity; thus their insulin-receptor binding being maintained similar to the controls. The subjects with III degree obesity presented a significant decrease (p<0.0001) in the number of both the total and high-affinity insulin receptors as well as a reduction in insulin receptor affinity as compared to the controls. Therefore the percentage of specifically bound insulin was significantly lower (p<0.01) as compared to that of the control group. Insulin resistance in the obese subjects is associated with secondary hyperinsulinaemia, which is present in subjects with I and II degree of obesity; while in severely obese subjects exhaustion of beta-cell secretory capacity is observed. CONCLUSION: We consider that III degree of obesity appears to be a risk factor for type 2 diabetes mellitus as the alterations in insulin sensitivity, insulin-receptor binding and beta-cell secretion are quite similar to the reported in diabetic patients.

The effect of smoking on peripheral insulin sensitivity and plasma endothelin level.

OBJECTIVES: The aim of the present study was to investigate the effect of smoking on peripheral insulin effectiveness. METHODS: Seven healthy volunteers, nonsmokers, of mean age 39.6 +/- 7.1 Years and mean BMI 22.65 +/- 11.98 kg/m2, without family history of diabetes mellitus, with normal blood pressure participated in the study. All the parameters were studied twice - at baseline as well as after smoking (4 cigarettes per one hour). The study was performed in three days: at the first day we studied peripheral insulin effectiveness (M) in vivo by the artificial endocrine pancreas (Biostator), using the euglycaemic hyperinsulinaemic clamp technique, and insulin-receptor binding on circulating mononuclear blood cells; at the second day - the same parameters after one-hour smoking during the third hour of clamping; at the third day - plasma endothelin level, blood pressure and heart rate at baseline and after one-hour smoking. RESULTS: There was a significant decrease in glucose utilization during the second clamp test, when the volunteers smoked during the third hour as compared to the test at baseline (p=0.04). This was accompanied by a significant decrease in insulin receptor affinity (p=0.04). Systolic blood pressure and heart rate increased significantly after one-hour smoking (p=0.03 and p=0.001, respectively). Plasma endothelin level increased significantly after smoking (from 0.62 +/- 0.15 pg/ml to 2.05 +/- 1.67 pg/ml, p=0.03). CONCLUSION: Our results demonstrate that smoking decreases peripheral insulin sensitivity reducing insulin receptor affinity. We have confirmed that smoking increases plasma endothelin level, which probably by causing vasoconstriction and consequent tIssue hypoxaemia could decrease peripheral glucose utilization. We consider that smoking could also have a direct effect on insulin receptor affinity, thus leading to decreased peripheral insulin effectiveness.

A study of the psychological status and sexuality in middle-aged Bulgarian women: significance of the hormone replacement therapy (HRT).

OBJECTIVE: The psychoemotional and sexual status of Bulgarian urban postmenopausal women 10 years after the beginning of the period of extensive political, social, economic and cultural transitions was studied. SUBJECTS AND METHODS: Three hundred and thirty-two postmenopausal women (83.5% in natural menopause and 16.5% in surgical menopause) and 295 women with normal menstrual cycle in several Bulgarian cities and the capital were studied. A campaign for free-of-charge bone density measurement was announced and the examined subjects filled in an individual anonymous questionnaire. SPSS for Windows version 8.0 was used for the statistical processing of the results. The comparison was made between normally menstruating women (n=295), postmenopausal women on hormone replacement therapy (HRT) (n=36) and postmenopausal subjects without HRT (n=296). RESULTS: A significant correlation was observed between depression and sexual aversion, depression and pain with intercourse, depression and the change in the sexual life after menopause. The correlation between self-esteem and sexual thoughts, self-esteem and sexual desire, self-esteem and the arousal from the partner, self-esteem and orgasm also proved important. About 20% of the studied subjects reported depressive thoughts, 50% reported anxiety and the self-esteem was very low in 13%. These results can be explained in part with the economic stagnation in the country, the unemployment and uncertainty. However, 94% of Bulgarian women believe that they do well in life and rely on their professionalism and social positions. All parameters of sexual life are significantly lower in the postmenopausal group without HRT as compared both with menstruating women and postmenopausal women on HRT. Marital status influences them too. CONCLUSION: The change in the sexuality is related to the decline in the estrogen activity, the influence of the psychosocial factors, the lack of a permanent intimate partner, and the derogatory attitude of the society towards the sexuality of postmenopausal women.

L-carnitine consecutively administered to patients on hemodialysis improves beta-cell response.

Eight patients with end stage renal disease (ESRD) on chronic hemodialysis (CHD) treatment were supplemented with 1 g L-carnitine intravenously (i.v.) after each dialysis session for one month. A Tolbutamide test was done and blood sugar (BS), serum C-peptide (CP) were measured at 0, 20 and 60 minutes, as well as the plasma L-carnitine level before and after treatment. Delta CP and the area under CP curve were ascertained. After L-carnitine application delta CP was significantly increased (1.33 +/- 0.63 vs. 2.24 +/- 1.0 nmol/L; p<0.05) and also the area of the stimulated secretion under the CP curve (14.93 +/- 11.11 vs. 36.88 +/- 25.36 nmol/L x 60 min.; p<0.05). The fasting BS-level was significantly lower after the treatment--3.85 +/- 0.43 vs. 4.76 +/- 1.02 mmol/L; p<0.05 and plasma L-carnitine level significantly increased (72.8 +/- 43.2 vs. 35.2 +/- 18.3 mcmol/L; p<0.05) Improving the oxidative processes in peripheral tissues, L-carnitine increases the peripheral effectiveness of insulin and relieves the overstretched beta-cell apparatus.

Effects of perindopril treatment on plasma and urine of kallikrein activity and the stable metabolite of prostaglandin E2 in patients with essential hypertension.

Eleven male patients with essential hypertension were included in the study. They followed an unrestricted diet and received a single oral daily dose of 4 mg perindopril (ACE inhibitor) for 6 weeks. Plasma renin activity increased significantly and plasma aldosterone decreased significantly after perindopril treatment, suggesting that an effective blockade of angiotensin II formation was accomplished. Both systolic and diastolic blood pressure decreased. Urinary bicycloprostaglandin E2 (an inactive metabolite of prostaglandin E2) increased significantly, while plasma and urinary kallikrein activity decreased significantly after perindopril treatment. The results obtained demonstrated significant changes in prostaglandin E2 and kallikrein activity during ACE inhibition. The contributive role of these humoral factors in the hypotensive effect of perindopril are discussed.

Effect of amlodipine and hormone replacement therapy on blood pressure and bone markers in menopause.

The aim of this study was to observe the effect of an 8-week treatment with amlodipine, alone or in combination with hormone replacement therapy (HRT), on blood pressure (BP), serum osteocalcin, bone-specific alkaline phosphatase (B-ALP) and urine deoxypiridinoline in postmenopausal osteoporotic women with mild-to-moderate arterial hypertension. Both conventional clinical BP measurements and ambulatory blood pressure monitoring (ABPM) were used. Twenty hypertensive menopausal women with osteoporosis were randomly divided in two groups according to the treatment regimens: amlodipine and amlodipine + HRT. Neither treatment regimen significantly changed bone formation or bone resorption markers. There were no significant differences in levels of serum and urinary calcium and phosphorous or serum cholesterol and low-density lipoprotein (LDL)-cholesterol after treatment with amlodipine alone or in combination with HRT. Triglycerides were significantly decreased and high-density lipoprotein (HDL)-cholesterol was significantly increased after amlodipine treatment. Both treatment regimens significantly decreased conventionally measured BP to a similar extent. Amlodipine given alone lowered the midline estimating statistic of rhythm (MESOR; mean 24-level) of systolic BP and induced phase advances of the circadian rhythms of systolic, diastolic and mean BP. When combined with HRT, amlodipine lowered the MESOR and reduced the amplitude of systolic BP without any phase change. In conclusion, amlodipine is effective in reducing BP in postmenopausal women. The maintenance of a normal circadian BP pattern is also influenced by supplementation with 17beta-estradiol. The 8-week treatment with amlodipine alone and in combination with HRT is not associated with a marked influence on bone metabolism.

Vitamin D status in Bulgaria--winter data.

UNLABELLED: We assume that 25(OH)D level >50 nmol/l is necessary for adequate parathyroid hormone (PTH) suppression in our population. The epidemiology of vitamin D status in Bulgarian population shows deficiency in 21.3 %, insufficiency in 54.5 % and sufficiency in 24.2 %. The mean level of 25(ОН)D for the Bulgarian population is 38.75 nmol/l (95 % CI, 38.00-39.49). PURPOSE: The aim of the present study was to investigate the vitamin D levels in Bulgaria and the prevalence of vitamin D deficiency depending on gender and age, as well as to define population-specific 25(OH)D sufficiency thresholds through the relationship with PTH. MATERIAL AND METHOD: This cross-sectional study was conducted in January-February 2012 and included 2,032 subjects in 12 regions-1,076 women (53 %) and 956 men (47 %), mean age 49.30 ± 14.75 years (20-80 years), divided into three age groups: young (20-44 years, n = 894), middle-aged (45-59 years, n = 534), and elderly (≥60 years, n = 604). 25(OH)D and PTH were measured in all subjects. RESULTS: The mean level of 25(ОН)D was 38.75 nmol/l (95 % CI, 38.00-39.49). The men had significantly higher 25(ОН)D levels in comparison to women (41.51 nmol/l (95 % CI, 40.45-42.56) vs.36.29 nmol/l (95 % CI, 35.27-37.32), p < 0.05). We did not find significant differences in the 25(ОН)D levels between the three age groups. The prevalence of vitamin D deficiency was 21.3 %; insufficiency, 54.5 %; and sufficiency, 24.2 %. Deficiency was more prevalent in women (26.9 %) than in men (15.1 %), p < 0.001. PTH started to rise over the upper limit of the reference range at mean 25(OH)D 50 nmol/l. We assume that levels over 50 nmol/l are necessary for adequate PTH suppression. CONCLUSIONS: The status of vitamin D in our country is worrisome, and it is largely underestimated. The defining of a vitamin D sufficiency levels may help the devising of adequate strategies for prevention and treatment in clinical practice.

Gender-dependent effect of ageing on peripheral insulin action.

The aim of the present study was to investigate the effect of both gender and age on insulin secretion, peripheral insulin effectiveness and insulin-receptor binding. Eighty healthy volunteers, 40 females of mean age 38.47 +/- 11.37 years and mean BMI 21.99 +/- 2.06 kg/m(2) and 40 males of mean age 34.87 +/- 11.22 years and mean BMI 22.65 +/- 2.31 kg/m(2), with normal glucose tolerance participated in the study. Peripheral insulin effectiveness was measured by the artificial endocrine pancreas, using the euglycaemic hyperinsulinaemic clamp technique and insulin-receptor binding on circulating mononuclear blood cells. Peripheral insulin sensitivity was significantly higher in females as compared to males (p < 0.001), while males demonstrated higher total number of insulin receptors (p < 0.0001) and number of high-affinity receptors (p < 0.01). Peripheral insulin sensitivity decreased with ageing in both males and females, the reduction in females being more pronounced (p < 0.05). In the group under 40 years, the females demonstrated significantly higher insulin sensitivity as compared to males (p < 0.001) and lower insulin-receptor binding. Over 40 years, females presented higher peripheral insulin sensitivity and higher insulin-receptor binding. The percentage of specifically bound insulin increased significantly with ageing in females and decreased in males. We consider that probably the higher androgen level in males affects the post-receptor processes in insulin action and despite the higher insulin-receptor binding, males have lower insulin sensitivity. The androgen levels in females increase with ageing, which could probably affect peripheral insulin sensitivity at the post-receptor level. In conclusion, our results demonstrate that when analysing peripheral insulin effectiveness and insulin-receptor binding, one should always consider both gender and age.

Role of prostaglandin E2 (PGE2) in the growth hormone releasing hormone action on growth hormone, insulin and C-peptide in normal men.

Fourteen healthy men were placed in two treatment groups. 1. Seven men received growth releasing hormone (1 microgram/kg BW) intravenously during either saline or prostaglandin E2 (10 micrograms/min) infusion which were started 60 minutes before testing. Growth hormone response to growth releasing hormone was greater during prostaglandin E2 infusion compared to the control study. These data suggest that exogenous prostaglandin E2 positively modulates growth hormone response to growth releasing hormone. In the second group consisting also of 7 men a GRH test was performed before and after 3 days administration of meclofenamate. Meclofenamate significantly reduced plasma levels of stable metabolites of prostaglandin E2 as well as the growth hormone to growth releasing hormone, suggesting that the GRH effect on GH was at least partly under prostaglandin E2 control. GRH significantly reduced serum insulin in the two treatment groups. PGE2 infusion or meclofenamate did not change insulin response to GRH. Serum C-peptide and blood glucose did not change after GRH injection during saline or PGE2 infusions.

Increased somatostatin response to glucagon in insulin-dependent diabetes mellitus.

The dynamic study of somatostatin secretion was performed in patients with insulin-dependent diabetes mellitus and age- and sex matched volunteers. The basal levels of immunoreactive somatostatin, as well as its response to i.v. Glucagon (1 mg) at 10 and 20 min with consequent hyperglycemia were increased in most of diabetic patients as compared with the healthy controls. Our results suggest that the glucagon test could be used for estimating the somatostatin secretion in diabetes mellitus. This would reveal some impaired interactions between the endocrine function of the pancreas in diabetes mellitus.

Changes in sexual behavior in Bulgarian women after the menopause.

Sexual dysfunction is frequently observed in postmenopausal women but there are few epidemiological studies of the relationship between the menopause and sexual functioning. An epidemiological study of sexual function was performed among 619 Bulgarian women aged between 40 and 58 years. Two hundred and eighty-five (46%) had a normal menstrual cycle (group A) and 334 (54%) were postmenopausal. Of these, 302 (group C) did not use hormone replacement therapy (HRT) and 32 were on HRT (group B). Many women feel uneasy and are unwilling to talk about their sexual problems even with medical professionals. This fact warranted the implementation of an anonymous questionnaire. There were significant differences in all sexual function parameters reported between groups C and A (p < 0.001), as well as between groups C and B (p < 0.05). These results suggest that HRT restores the dynamics of sexual life in postmenopausal women and brings them closer to those of normally menstruating middle-aged women.

Role of prostaglandin E2 (PGE2) on the corticotropin-releasing hormone (CRH)-induced ACTH release in healthy men.

The effect of PGE2 on ACTH and cortisol responses to CRH was studied in 6 healthy men who received CRH i.v. during either saline or PGE2 infusions which were started 60 min. before testing. ACTH and cortisol responses to CRH were greater during PGE2 infusion compared to the control study. The results indicate that PGE2 positively modulates CRH-induced ACTH secretion.

Prostaglandin E2 affects both insulin secretion and peripheral insulin sensitivity.

The effect of prostaglandin E2 (PGE2) on plasma C-peptide (CP) level and peripheral insulin effectiveness was studied in twenty-five healthy volunteers. Plasma CP levels were studied in 14 volunteers (group C) during a three-hours PGE2 infusion. The same experiment was repeated a week later, with saline infusion. Plasma CP level were measured 15 minutes before the infusion, at the beginning of the experiment (0 min) as well as 15, 30, 60, 120 and 180 minutes after the start of the infusion. Peripheral insulin sensitivity was studied in vivo by means of the artificial endocrine pancreas (Biostator), using the euglycaemic hyperinsulinaemic clamp technique. The healthy volunteers underwent a three-hour experiment with saline (group A) or with saline and PGE2-10 micrograms/min during the third hour of clamping (group B). There was a significant decrease in plasma CP level at the 15 th and 30 th minute of PGE2 infusion in the subjects from group C (p less than 0.05). In the group A there was an increase of 14.2% in the amount of glucose infused during the third hour of clamping as compared to the second (2nd-9.673 +/- 1.680 mg/kg/min, 3rd-11.051 +/- 1.802 mg/kg/min). The amount of glucose infused in the subjects of group B remained the same in the course of clamping (2nd hour-7.938 +/- 2.180 mg/kg/min, 3rd hour-7.932 +/- 2.284 mg/kg/min). The difference in the dynamic changes of the amount of glucose infused between the two groups of volunteers (group A and group B) was significant (F = 5.68, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of nifedipine on renin-angiotensin-aldosterone system and renal prostaglandins in diabetic patients.

The present study investigated the short-term effect of calcium blocker nifedipine in 13 healthy subjects and in 13 patients with insulin-dependent diabetes mellitus. Nifedipine induced an increase in plasma renin activity in the control group, as well as in the diabetics. Plasma aldosterone did not change after nifedipine in either group. Urinary prostaglandin E2 and 6-keto prostaglandin F1 alpha increased significantly after nifedipine in the normal subjects. The diabetics showed a significant decrease of blood pressure without a concomitant change of the urinary prostaglandins. These findings suggest that the hypotensive effect of nifedipine in the diabetics is not mediated by prostaglandins.

The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients.

The aim of this study was to evaluate the effect of vitamin D3 supplementation on insulin secretion and insulin resistance. Ten females with type 2 diabetes being treated with oral hypoglycaemic agents and with normal serum and urine calcium levels were enrolled in the study. The study was conducted in March, when levels of vitamin D are lowest in our region. The level of plasma 25(OH)D was measured (normal range in winter 25-120 nmol/l). The first (FPIS) and second (SPIS) phases of insulin secretion were studied during IVGTT. Peripheral insulin resistance was measured. A group of 17 age- and BMI-matched females with normal glucose tolerance served as a control group. The diabetic patients were treated with cholecalciferol 1332 IU daily for one month. The mean plasma 25(OH)D level was 35.3 +/- 15.1 nmol/l at baseline, 70% of patients being vitamin D deficient. After one month of treatment with vitamin D3, the plasma 25(OH)D level increased by a mean of 75.8%; 70% of the patients achieved normal vitamin D levels. FPIS increased significantly by 34.3%, while the change in SPIS of 20.4% was not significant (p > 0.8). We found a significant correlation between the change in FPIS and the change in 25(OH)D level after vitamin D3 supplementation (p < 0.018). The results showed a decrease of 21.4% in insulin resistance after one month, but the change was not significant. Bearing in mind that the main defects in type 2 diabetes mellitus are reduced FPIS and insulin resistance, and the favourable effect vitamin D3 had on them, we suggest vitamin D3 deficiency may at least partly contribute to the impairment of insulin secretion and probably of insulin action. Our results suggest that vitamin D3 supplementation could be an element in the complex treatment of type 2 diabetes mellitus during the winter.