ABSTRACT
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.
ABSTRACT
BACKGROUND: Adolescence is a period of psychological and neural development in which harms associated with cannabis use may be heightened. We hypothesised that adolescent who use cannabis (adolescentsWUC) would have steeper delay discounting (preference for immediate over future rewards) and greater demand (relative valuation) for cannabis than adults who use cannabis (adultsWUC). METHODS: This cross-sectional study, part of the 'CannTeen' project, compared adultsWUC (n = 71, 26-29 years old) and adolescentsWUC (n = 76, 16-17 years old), and gender- and age-matched adolescent (n = 63) and adult (n = 64) controls. AdolescentsWUC and adultsWUC used cannabis 1-7 days/week and were matched on cannabis use frequency (4 days/week). The Monetary Choice Questionnaire assessed delay discounting. A modified Marijuana Purchase Task (MPT) assessed cannabis demand in adolescentsWUC and adultsWUC. The MPT yielded five indices: intensity (amount of cannabis used at zero cost), Omax (total peak expenditure), Pmax (price at peak expenditure), breakpoint (cost at which cannabis demand is suppressed to zero) and elasticity (degree to which cannabis use decreases with increasing price). Analyses were adjusted for covariates of gender, socioeconomic status, other illicit drug use. RESULTS: Both adolescentsWUC and adultsWUC had steeper delay discounting than controls (F, (1,254)= 9.13, p = 0.003, ηp2= 0.04), with no significant age effect or interaction. AdolescentsWUC showed higher intensity (F, (1,138)= 9.76, p = 0.002, ηp2= 0.07) and lower elasticity (F, (1,138)= 15.25, p < 0.001, ηp2= 0.10) than adultsWUC. There were no significant differences in Pmax, Omax or breakpoint. CONCLUSION: Individuals who use cannabis prefer immediate rewards more than controls. AdolescentsWUC, compared to adultsWUC, may be in a high-risk category with diminished sensitivity to cannabis price increases and a greater consumption of cannabis when it is free.
Subject(s)
Cannabis , Delay Discounting , Marijuana Smoking , Adolescent , Adult , Analgesics , Cross-Sectional Studies , Economics, Behavioral , Humans , Marijuana Smoking/psychology , RewardABSTRACT
BACKGROUND: Preclinical and human studies suggest that adolescent cannabis use may be associated with worse cognitive outcomes than adult cannabis use. We investigated the associations between chronic cannabis use and cognitive function in adolescent and adult cannabis users and controls. We hypothesised user-status would be negatively associated with cognitive function and this relationship would be stronger in adolescents than adults. METHODS: As part of the 'CannTeen' project, this cross-sectional study assessed cognitive performance in adolescent cannabis users (n = 76; 16-17-year-olds), adolescent controls (n = 63), adult cannabis users (n = 71; 26-29-year-olds) and adult controls (n = 64). Users used cannabis 1-7 days/week. Adolescent and adult cannabis users were matched on cannabis use frequency (4 days/week) and time since last use (2.5 days). Verbal episodic memory (VEM) was assessed using the prose recall task, spatial working memory (SWM) was assessed using the spatial n-back task, and response inhibition was assessed with the stop-signal task. Primary outcome variables were: delayed recall, 3-back discriminability, and stop signal reaction time, respectively. RESULTS: Users had worse VEM than controls (F(1,268) = 7.423, p = 0.007). There were no significant differences between user-groups on SWM or response inhibition. Null differences were supported by Bayesian analyses. No significant interactions between age-group and user-group were found for VEM, SWM, or response inhibition. CONCLUSIONS: Consistent with previous research, there was an association between chronic cannabis use and poorer VEM, but chronic cannabis use was not associated with SWM or response inhibition. We did not find evidence for heightened adolescent vulnerability to cannabis-related cognitive impairment.
Subject(s)
Cannabis , Memory, Episodic , Adolescent , Adult , Bayes Theorem , Cognition , Cross-Sectional Studies , Humans , Memory, Short-Term/physiology , Neuropsychological TestsABSTRACT
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.
Subject(s)
Blood Pressure , Human Growth Hormone/deficiency , Metabolic Syndrome/blood , Metabolic Syndrome/pathology , Adult , Age of Onset , Aged , Aged, 80 and over , Case-Control Studies , Cholesterol, HDL/blood , Cross-Sectional Studies , Female , Humans , Male , Metabolic Syndrome/etiology , Middle Aged , Obesity/blood , Prevalence , Risk FactorsABSTRACT
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.
Subject(s)
Body Mass Index , Educational Status , Obesity/complications , Seasons , Smoking/adverse effects , Vitamin D Deficiency/etiology , Vitamin D/analogs & derivatives , Adult , Bulgaria/epidemiology , Calcifediol/blood , Female , Humans , Male , Middle Aged , Obesity/blood , Odds Ratio , Parathyroid Hormone/blood , Prevalence , Risk Factors , Sex Factors , Smoking/blood , Urban Population , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/epidemiologyABSTRACT
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.
Subject(s)
Autoantibodies/blood , Hypothyroidism/diagnostic imaging , Hypothyroidism/epidemiology , Iodide Peroxidase/immunology , Thyroid Gland/diagnostic imaging , Thyroid Hormones/blood , Adult , Aged , Aged, 80 and over , Bulgaria/epidemiology , Female , Follow-Up Studies , Humans , Hypothyroidism/blood , Male , Middle Aged , Prevalence , Prognosis , Thyroid Function Tests , Thyroid Gland/pathology , Ultrasonography , Young AdultABSTRACT
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(ÐÐ)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(ÐÐ)D was 38.75 nmol/l (95 % CI, 38.00-39.49). The men had significantly higher 25(ÐÐ)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(ÐÐ)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.
Subject(s)
Parathyroid Hormone/blood , Vitamin D Deficiency/epidemiology , Vitamin D/blood , Adult , Aged , Aged, 80 and over , Bulgaria/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Young AdultABSTRACT
The structure and spectral signatures of the protonated homodimer of pyridine in its complex with a poorly coordinating anion have been studied in solution in CDF(3)/CDClF(2) down to 120 K and in a single crystal. In both phases, the hydrogen bond is asymmetric. In the solution, the proton is involved in a fast reversible transfer that determines the multiplicity of NMR signals and the sign of the primary H/D isotope effect of --0.95 ppm. The proton resonates at 21.73 ppm that is above any value reported in the past and is indicative of a very short hydrogen bond. By combining X-ray diffraction analysis with model computations, the position of the proton in the crystal has been defined as d(N-H) = 1.123 Å and d(H···N) = 1.532 Å. The same distances have been estimated using a (15)N NMR correlation. The frequency of the protonic out-of-plane bending mode is 822 cm(-1) in agreement with Novak's correlation.
Subject(s)
Dimerization , Pyridines/chemistry , Spectrum Analysis/methods , Magnetic Resonance Spectroscopy , Molecular Structure , Neutron Diffraction , Protons , X-Ray DiffractionABSTRACT
Crystallization of calcium oxalate monohydrate in a section of a single kidney nephron (distal convoluted tubule) is simulated using a model adapted from industrial crystallization. The nephron fluid dynamics is represented as a crystallizer/separator series with changing volume to allow for water removal along the tubule. The model integrates crystallization kinetics and crystal size distribution and allows the prediction of the calcium oxalate concentration profile and the nucleation and growth rates. The critical supersaturation ratio for the nucleation of calcium oxalate crystals has been estimated as 2 and the mean crystal size as 1 mum. The crystal growth order, determined as 2.2, indicates a surface integration mechanism of crystal growth and crystal growth dispersion. The model allows the exploration of the effect of varying the input calcium oxalate concentration and the rate of water extraction, simulating real life stressors for stone formation such as dietary loading and dehydration.
Subject(s)
Calcium Oxalate/urine , Kidney Calculi/metabolism , Kidney Tubules, Distal/metabolism , Models, Biological , Algorithms , Chemical Engineering/methods , Crystallization , Humans , HydrodynamicsABSTRACT
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.
Subject(s)
Hyperthyroidism/surgery , Adult , Amino Acid Substitution , DNA/blood , DNA/genetics , DNA/isolation & purification , Follow-Up Studies , Gene Amplification , Humans , Hyperthyroidism/genetics , Male , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Receptors, Thyrotropin/genetics , Recurrence , ThyroidectomyABSTRACT
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.
Subject(s)
Aging/metabolism , Insulin/metabolism , Sex Characteristics , Adult , Analysis of Variance , Blood Glucose/metabolism , Body Mass Index , C-Peptide/metabolism , Female , Glucose Tolerance Test , Humans , Insulin/physiology , Insulin Secretion , Male , Receptor, Insulin/metabolismABSTRACT
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.
Subject(s)
Blood Glucose/metabolism , Insulin/metabolism , Receptor, Insulin/metabolism , Smoking/blood , Adult , Body Mass Index , Female , Glucose Clamp Technique , Glycolysis , Humans , Hyperinsulinism , Insulin Secretion , Male , Middle Aged , Reference ValuesABSTRACT
The aim of this study was to follow up the effect of an 8-week treatment with amlodipine given alone or in combination with hormone replacement therapy (HRT) on blood pressure and active renin in postmenopausal women with mild to moderate arterial hypertension using both conventional clinical blood pressure measurements and ambulatory blood pressure monitoring. Twenty-nine hypertensive menopausal women were divided randomly into two groups according to the treatment regimens: amlodipine and amlodipine plus HRT. The combination with HRT led to normalization of 24-h and daytime systolic and diastolic blood pressure. In contrast to the group treated with amlodipine alone, where a significant fall only of systolic night-time blood pressure was observed, in the group treated with amlodipine plus HRT both systolic and diastolic night-time blood pressure decreased significantly. Active renin did not change significantly after treatment in both groups. Triglycerides decreased significantly and high-density lipoprotein-cholesterol increased significantly only after amlodipine treatment. There were no significant differences in serum total cholesterol and low-density lipoprotein-cholesterol after HRT plus amlodipine. In conclusion, amlodipine is effective in reducing blood pressure in postmenopausal women. The maintenance of a normal circadian blood pressure pattern was influenced by HRT.
Subject(s)
Amlodipine/therapeutic use , Antihypertensive Agents/therapeutic use , Estrogen Replacement Therapy , Hypertension/drug therapy , Menopause , Renin/blood , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Cholesterol, HDL/blood , Female , Heart Rate , Humans , Hypertension/blood , Middle Aged , Triglycerides/bloodABSTRACT
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.
Subject(s)
Blood Glucose/metabolism , Insulin Resistance , Insulin/metabolism , Obesity/physiopathology , Receptor, Insulin/metabolism , Area Under Curve , Body Weight , Glucose Tolerance Test , Humans , Hyperinsulinism/blood , Insulin/blood , Insulin/pharmacology , Insulin Secretion , Obesity/blood , Obesity/classification , Reference ValuesABSTRACT
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.
Subject(s)
Calcifediol/blood , Cholecalciferol/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Insulin/metabolism , Vitamin D Deficiency/complications , Adult , Aged , Analysis of Variance , Blood Glucose/metabolism , Calcifediol/physiology , Case-Control Studies , Cholecalciferol/pharmacology , Diabetes Mellitus, Type 2/physiopathology , Female , Glucose Tolerance Test , Humans , Insulin Resistance/physiology , Insulin Secretion , Middle Aged , SeasonsABSTRACT
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.
Subject(s)
Amlodipine/therapeutic use , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Estrogen Replacement Therapy , Hypertension/drug therapy , Osteoporosis, Postmenopausal/complications , Female , Heart Rate/drug effects , Humans , Hypertension/complications , Middle Aged , Osteocalcin/bloodABSTRACT
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.
Subject(s)
Carbohydrate Metabolism , Carnitine/pharmacology , Carnitine/therapeutic use , Insulin Resistance/physiology , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Renal Dialysis/adverse effects , Adult , Blood Glucose/analysis , Blood Glucose/drug effects , C-Peptide/blood , C-Peptide/drug effects , Carnitine/administration & dosage , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Hypoglycemic Agents/pharmacology , Kidney Failure, Chronic/metabolism , Male , Middle Aged , Time Factors , Tolbutamide/pharmacologyABSTRACT
The aim of the present study was to evaluate the effect of three different combinations of hormone replacement therapy (HRT) on insulin secretion, peripheral insulin sensitivity, serum lipid levels and parameters of oxidative stress. Seven type II diabetic women of mean age 55.4 +/- 4.7 years, who had been menopausal for an average of 5 years, were enrolled in the study. Phases of insulin secretion--first (FPIS) and second (SPIS)--and the area under the curve (AUC) for insulin secretion were studied during an intravenous glucose tolerance test (IVGTT). Insulin sensitivity was determined using the manual euglycemic-hyperinsulinemic clamp technique. Three different HRT combinations were applied consecutively for 3-month periods: estradiol valerate plus cyproterone acetate (Climen); transdermal 17 beta-estradiol (System TTS 50) plus dydrogesterone (Duphaston) 10 mg daily for 10 days a month; oral 17 beta-estradiol plus dydrogesterone (Femoston) for 14 days a month. A group of nine women with normal glucose tolerance (according to World Health Organization criteria during a 75-g oral glucose tolerance test (OGTT)), of mean age 50.1 +/- 8.2 years and mean body mass index 24.60 +/- 2.01 kg/m2, were also studied, and served as a control group. Insulin secretion improved significantly after Climen: FPIS increased by 16% and SPIS by 44%. Insulin sensitivity increased by 50% after Systen TTS 50 + Duphaston; fasting hyperinsulinemia was normalized and total antioxidant capacity of the serum (TAOCS) was significantly raised (p < 0.01). Femoston led to an increase in insulin sensitivity (by 23%) and in TAOCS (p < 0.05), while fasting hyperinsulinemia remained unchanged. HRT should be prescribed in type II diabetic postmenopausal women because of its favorable effect on existing pathophysiological defects. Cyproterone acetate should be preferred in cases with a predominant beta-cell insulin secretion defect, while dydrogesterone in combination with a transdermal estrogen should be recommended in cases with leading insulin resistance.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Estradiol/analogs & derivatives , Estrogen Replacement Therapy , Insulin Resistance , Insulin/metabolism , Postmenopause , Administration, Cutaneous , Antioxidants/metabolism , Body Mass Index , Cyproterone Acetate/administration & dosage , Dydrogesterone/administration & dosage , Estradiol/administration & dosage , Fasting , Female , Glucose Clamp Technique , Glucose Tolerance Test , Glycated Hemoglobin/analysis , Humans , Insulin/blood , Insulin Secretion , Middle Aged , Oxidative Stress , Superoxide Dismutase/bloodABSTRACT
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.