Steroids, sex hormone-binding globulin, homocysteine, selected hormones and markers of lipid and carbohydrate metabolism in patients with severe hypothyroidism and their changes following thyroid hormone supplementation.

Laboratory markers of thyroid function, selected steroid hormones, sex hormone-binding globulin (SHBG), homocysteine, prolactin, major markers of lipid- and glucose metabolism and of insular-growth hormone axes were investigated in fasting sera from 16 female patients with severe hypothyroidism after thyroidectomy because of thyroid cancer. The results obtained in severe hypothyroidism within 5-6 weeks after withdrawal of thyroid substitution therapy before control scintigraphy were compared with those obtained after correction of thyroid function. Elevated levels of homocysteine and prolactin in hypothyroidism significantly decreased after correction, while SHBG concentration increased. Correction of thyroid function led to significant changes of growth hormone and immunoglobulin F1 (decrease and increase, respectively), while insulin and proinsulin increased only insignificantly. Elevated levels of total cholesterol and triglycerides in hypothyroidism were normalized, along with a significant increase in high density lipoprotein (HDL)-cholesterol. As revealed by correlation and factor analyses, different relationships characterizing both states were found in hypothyroidism and after correction of thyroid function. A strong inverse relationship between homocysteine and free thyroid hormones confirms the effect of thyroid hormones on homocysteine metabolism. No such inverse relation was found in euthyroid state, however. Similarly, in hypothyroidism only, dehydroepiandrosterone sulfate correlated positively with immunoglobulin F1 and homocysteine and negatively with thyroid hormones and SHBG.     

Influence of thyroid hormone status on mevalonate metabolism in rats.

Mevalonate, an essential intermediate in cholesterol synthesis, is metabolized either to cholesterol or, by the shunt pathway, to CO2. Previous investigations have demonstrated that the kidneys are the chief site of circulating mevalonate metabolism and that sex hormones as well as insulin markedly influence circulating mevalonate metabolism. The present study examined in rats the influence of thyroid hormone status on mevalonate metabolism in vivo and in vitro. L-thyroxine administration increased renal conversion of circulating mevalonate to cholesterol, 41% in the females and 22% in the males. Conversely, hypothyroidism induced by 6 N propyl-2-thiouracil reduced renal conversion of circulatng mevalonate to cholesterol by 45% in females and 27% in males; thyroid hormone replacement in these animals returned cholesterogenesis in the kidneys to supranormal levels. Neither L-thyroxine nor hypothyroidism altered circulating mevalonate conversion to cholesterol in the liver or carcass. In vitro studies confirmed the in vivo observations. Changes in thyroid hormone produced only minor changes in the shunt pathway of mevalonate metabolism. This study demonstrates that the major effect of the thyroid hormone on the metabolism of circulating mevalonate is to alter the conversion of mevalonate to cholesterol, an effect localized solely to the kidneys.     

Dimethylglycine supplementation does not affect plasma homocysteine concentrations in pre-dialysis chronic renal failure patients

OBJECTIVE: To determine whether daily dimethylglycine supplementation affects plasma homocysteine concentrations. DESIGN AND METHODS: A randomized, blinded, crossover design was used. Seven pre-dialysis chronic renal failure patients consumed 400 mg of dimethylglycine or placebo daily for 28 days. Fasting blood samples and 12-h urine samples were collected at baseline and at the end of each treatment period for analysis. RESULTS: No significant differences were observed in plasma homocysteine (P = 0.624), glycine betaine (P = 0.452) and methionine (P = 0.457) concentrations between dimethylglycine and placebo treatments. CONCLUSION: Daily supplementation with dimethylglycine does not affect plasma homocysteine.     

Plasma and urine betaine and dimethylglycine variation in healthy young male subjects

ObjectivesWe aimed to compare the individuality (within subject consistency) of plasma and urine betaine and N,N-dimethylglycine.Design and methodsIn two separate groups of 8 males (ages 19 to 40), plasma (10) and urine (6) samples were collected either over a single day or over an 8 week period. The individuality of the betaine and N,N-dimethylglycine plasma concentrations and excretions were estimated by one-way repeated measures analysis of variance. The reliability coefficients and indices of individuality were calculated. The between-subject variation in the study population was compared with that in a normal population (n = 192 for plasma, 205 for urine).ResultsPlasma betaine concentrations were significantly different between subjects over 24 h and 8 weeks (p < 0.00001). Plasma dimethylglycine concentrations were different over 24 h. Urine betaine and dimethylglycine excretions were different in both (p < 0.0001). Betaine was more individual than dimethylglycine in both plasma and urine. Compared with a normal healthy population, the between-subject variation in plasma betaine was less (p < 0.001) in the study group, but similar for dimethylglycine and for urine betaine.ConclusionsPlasma betaine and urinary betaine excretions are more individual than dimethylglycine. Plasma and urine betaine are highly individual in the general population.     

Association of thyroid dysfunction with vitamin B12, folate and plasma homocysteine levels in the elderly: a population-based study in Sicily.

BACKGROUND: Association of thyroid dysfunction with plasma homocysteine levels and vitamin B(12) has previously been reported. We evaluated these associations in the elderly in San Teodoro, a mountainous village of Sicily. METHODS: Subjects (n=279) aged 60-85 years (119 males and 160 females) were examined using self-reported signs, clinical examination and laboratory tests. RESULTS: Hypothyroidism and/or goiter were two characteristics that were not associated with a significant change in homocysteine when compared with euthyroidism and the absence of goiter. Vitamin B(12) was significantly higher in subjects in the first quartile of the thyroid-stimulating hormone distribution, compared with those in the fourth quartile (371+/-207 vs. 297+/-196 pmol/L, p=0.0121). Homocysteine was significantly higher in the first quartile of the free tri-iodothyronine distribution compared to the third quartile (18.0+/-5.7 vs. 16.0+/-6.2 micromol/L, p=0.0130) and was correlated with log tri-iodothyronine in euthyroid subjects (p=0.0254). In multivariate analysis, homocysteine was associated with vitamin B(12) (p=0.0014), folate (p<0.0001), creatinine (p<0.0001) and age (p<0.0001), but not with either free tri-iodothyronine (p=0.7680), tetra-iodothyronine (p=0.5706) or thyroid-stimulating hormone (p=0.2294). CONCLUSIONS: Our results suggest that the influence of thyroid hormones on homocysteine is much weaker in elderly subjects than in selected patients with hypothyroidism.     

Betaine: a key modulator of one-carbon metabolism and homocysteine status.

Betaine serves as a methyl donor in a reaction converting homocysteine to methionine, catalysed by the enzyme betaine-homocysteine methyltransferase. It has been used for years to lower the concentration of plasma total homocysteine (tHcy) in patients with homocystinuria, and has recently been shown to reduce fasting and in particular post-methionine load (PML) tHcy in healthy subjects. Betaine exists in plasma at concentrations of about 30 micromol/L; it varies 10-fold (from 9 to 90 micromol/L) between individuals, but the intra-individual variability is small. Major determinants are choline, dimethylglycine and folate in plasma, folic acid intake and gender. Recent studies have demonstrated that plasma betaine is a stronger determinant of PML tHcy than are vitamin B6 and folate. The betaine-PML tHcy relationship is attenuated after supplementation with B-vitamins, and is most pronounced in subjects with low folate. Betaine shows a weaker association with fasting tHcy (than with PML tHcy), and also this association is most pronounced in subjects with low folate. In pregnancy, plasma betaine declines until gestational week 20, and thereafter remains constant. From gestational week 20 onwards, fasting tHcy shows a strong inverse association with plasma betaine, and betaine becomes a stronger predictor than folate of fasting tHcy. To conclude, betaine status is a component of an individual's biochemical make-up with ramifications to one-carbon metabolism. Betaine status should be investigated in pathologies related to altered metabolism of homocysteine and folate, including cardiovascular disease, cancer and neural tube defects.     

Short and long-term variation of plasma glycine betaine concentrations in humans

BACKGROUND: Glycine betaine is important in cell volume regulation and in remethylating homocysteine, a vascular risk factor. OBJECTIVE: We investigated changes in circulating glycine betaine concentrations in human volunteers both under acute osmotic stress and over longer time scales. DESIGN: Plasma glycine betaine concentrations were measured in normal human volunteers in three studies: (1) during acute diuresis and antidiuresis; (2) during prolonged diuresis for 5 days, and antidiuresis for 5 days followed by further diuresis for the final 5 days; (3) repeated samples taken 3 years apart. RESULTS: Circulating glycine betaine concentrations remained almost unchanged for several hours after acute diuretic or antidiuretic stresses. There was more (3-10-fold) interindividual variation than intraindividual variation. A similar pattern was found on day 15 of the study. In a 3-year follow-up, plasma glycine betaine concentrations on the two occasions were highly correlated with no systematic change, showing that individual set points remain stable for years. In contrast, there was no relationship among plasma proline betaine concentrations at these times. Urinary glycine betaine excretions measured 3 years apart were also found to correlate once the perturbing effect of dietary proline betaine excretion was allowed for. CONCLUSIONS: Human circulating glycine betaine is homeostatically controlled with a distinct control value for each individual. In contrast, peripheral blood concentrations of proline betaine, which is present in the diet (and has no known metabolic or physiological role in mammals), is not controlled.     

Plasma betaine concentrations correlate with plasma cortisol but not with C-reactive protein in an elderly population

Abstract Background: Low plasma betaine concentrations are a feature of seriously ill patients. Increased dietary betaine intake has been associated with lowered systemic inflammation. We aimed to compare plasma cortisol (a stress marker) and C-reactive protein (an inflammation marker) as statistical predictors of plasma betaine concentrations. Methods: Plasma carnitine, cortisol and C-reactive protein concentrations, other biochemical measures and urine betaine excretion, were compared with plasma betaine concentration by correlation and in multiple regression models, using morning blood and urine samples from 64 ambulant elderly subjects and from 55 patients admitted to hospital with hip fractures. Results: In the ambulant elderly without acute trauma, plasma cortisol (with negative coefficients) and carnitine (with positive coefficients) statistically predicted plasma betaine concentrations. C-reactive protein was not a predictor. In the patients, the significant predictors were plasma carnitine (positive coefficient) and plasma homocysteine (negative coefficient) and C-reactive protein again was not a predictor. In regression models using combined patient and control data there were large ranges of both cortisol and especially C-reactive protein; cortisol and homocysteine (negative coefficients) and carnitine (positive coefficient) were significant predictors but C-reactive protein was not significant. Conclusions: Stress rather than inflammation may affect plasma betaine concentrations.     

Pitfalls in the radioactive method of galactose-1-phosphate uridyltransferase activity measurement

Serum and urine zinc were measured by atomic absorption spectrophotometry. The drift in base-line was continuously registered and corrections for the drift were made in the calculations of zinc measurements to avoid any adjustment in the instrument settings. Food intake was shown to lower the serum zinc concentration by 19% on average (p < 0.001). A diurnal variation of serum zinc was observed with a minimum at 7 p.m. Venous stasis elevated the mean serum zinc concentration by 13% (p < 0.001) and the mean serum protein level by 14% (p < 0.001). Weak correlations between serum zinc and both the serum concentration of proteins and of albumin were found in 104 normal subjects. There was no correlation between serum concentrations of zinc and α₂-macroglobulin. The concentration of serum zinc was 9% higher in males than in females (p < 0.005) which was not explained by sex differences in serum protein concentrations. Furthermore, males had a higher excretion rate of zinc in urine than females, when expressed as μmol Zn/24 hour (p < 0.01). This difference disappeared when urine zinc was corrected to urinary excretion rate of creatinine. Our results show that blood samples for serum zinc measurement should be taken in the morning in fasting state. The urinary zinc excretion rate should be related to the creatinine excretion rate to avoid sex differences.     

Serum levels of leptin and homocysteine in women with polycystic ovary syndrome and its relationship to endocrine, clinical and metabolic parameters

We examined the relationship between endocrine, clinical and metabolic parameters in 35 women (mean age 27.3 years) with polycystic ovary syndrome (PCOS) and 30 age- and body mass index-matched normal ovulatory women. In PCOS women, serum leptin, homocysteine, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein-3 levels and the insulin resistance index (HOMA-IR) were significantly higher, while sex hormone-binding globulin and high-density lipoprotein cholesterol levels were lower compared with healthy women. Serum luteinizing hormone (LH), estradiol (E(2)), androstenedione, testosterone and dehydroepiandrosterone sulphate levels were found to be significantly higher in PCOS women compared with healthy women. The levels of E(2), LH and testosterone were positively correlated with leptin levels in PCOS women. Similarly, androstenedione levels and HOMA-IR were positively correlated with homocysteine levels and insulin levels were positively correlated with LH. We conclude that increased homocysteine levels, hyperandrogenaemia, insulin resistance and impaired lipid metabolism contribute to the risk of premature atherosclerosis in PCOS women.     

Insulin resistance is associated with larger thyroid volume in adults with type 1 diabetes independently from presence of thyroid autoimmunity

To investigate the effect of insulin resistance (IR) on thyroid function, thyroid autoimmunity (AIT) and thyroid volume in type 1 diabetes (T1DM). 100 consecutive patients with T1DM aged 29 (±6) years with diabetes duration 13 (±6) years were included. Exclusion criteria were: history of thyroid disease, current treatment with L-thyroxin or anti-thyroid drugs. Evaluation of thyroid stimulating hormone (TSH), free thyroid hormones and anti-thyroid antibodies was performed. Thyroid volume was measured by ultrasonography. IR was assessed using the estimated glucose disposal rate (eGDR) formula. In the study group 22% of subjects had insulin resistance defined as eGDR lower or equal to 7.5 mg/kg/min. The prevalence of thyroid autoimmunity (positivity for ATPO or ATg or TRAb) in the study group was 37%. There were no significant differences in the concentration of TSH, FT3, FT4, the prevalence of AIT and hypothyroidism between IR and insulin sensitive (IS) group. Mean (±SD) thyroid volume was 15.6 (±6.2) mL in patients with IR and 11.7 (±4.7) mL in IS subjects (p?=?.002). Thyroid volume correlated inversely with eGDR (r?=?–0.35, p?p?=?.012). Insulin resisance is associated with larger thyroid volume in patients with type 1 diabetes independently of sex, body mass index, TSH value and presence of autoimmune thyroid disease.     

Betaine:homocysteine methyltransferase--a new assay for the liver enzyme and its absence from human skin fibroblasts and peripheral blood lymphocytes

Chronic elevation of plasma homocysteine is associated with increased atherogenesis and thrombosis, and can be lowered by betaine (N,N,N-trimethylglycine) treatment which is thought to stimulate activity of the enzyme betaine:homocysteine methyltransferase. We have developed a new assay for this enzyme, in which the products of the enzyme-catalysed reaction between betaine and homocysteine are oxidised by performic acid before being separated and quantified by amino acid analysis. This assay confirmed that human liver contains abundant betaine:homocysteine methyltransferase (33.4 nmol/h/mg protein at 37 degrees C, pH 7.4). Chicken and lamb livers also contain the enzyme, with respective activities of 50.4 and 6.2 nmol/h/mg protein. However, phytohaemagglutinin-stimulated human peripheral blood lymphocytes and cultured human skin fibroblasts contained no detectable betaine:homocysteine methyltransferase (less than 1.4 nmol/h/mg protein), even after cells were pre-cultured in media designed to stimulate production of the enzyme. The results emphasize the importance of the liver in mediating the lowering of elevated circulating homocysteine by betaine.     

Comparison of aortic calcium and contractility in male, female and lactating female rats.

Catecholamine-induced vascular smooth muscle contration is enhanced in female animals and in presence of emale sex hormones in vitro. Androgens appear to depress these responses. Sex steroids may also alter calcium ion (Ca++) binding and metabolism. We compared contractility as well as quantity and relative lability of tissue calcium pools in male and female rat isolated aortic strips bathed in Ca++-free solution. We also studied aortic strips from 21-day postpartum lactating female rats to determine the effects of previous high circulating levels of female sex steroids (present during pregnancy) and prolactin (present during lactation). Rat aortic strips were found to contain loosely and more tightly held calcium stores. Strips from males were unresponsive in Ca++-free solution unless previously exposed to a Ca++-rich bathing medium. They accumulated more tissue calcium when bathed in Ca++-rich solution than did strips from females. This extra calcium appears to reside in the loosely-held fraction. Tissues from males first incubated in Ca++-rich solution to enhance the loosely held fraction respond more readily in Ca++-free solution to a high potassium (K+) concentration than to epinephrine. Strips from females respond about equally to high K+ or epinephrine whereas aorta from lactating female rats are much more responsive to epinephrine in Ca++-free solution and gain less calcium in Ca++-rich medium than those of the other rats. These data suggest that in the presence of high circulating levels of female sex hormones or other female factors (e.g., prolactin) enhanced binding or sequestration of potential activator ions occurs which increases the responsiveness of the tissue to catecholamines. Male sex hormones and/or factors promote the capacity of the rat aorta to gain a more loosely held calcium fraction which is readily used for contraction by K+ depolarization.     

Weight control practices and disordered eating behaviors among adolescent females and males with type 1 diabetes: associations with sociodemographics,weight concerns,familial factors,and metabolic outcomes

OBJECTIVE: This study examines the prevalence of specific weight control practices/disordered eating behaviors and associations with sociodemographic characteristics, BMI and weight perceptions, family functioning, and metabolic control among adolescent females and males with type 1 diabetes. RESEARCH DESIGN AND METHODS: The study population included 70 adolescent females and 73 adolescent males with type 1 diabetes who completed the AHEAD (Assessing Health and Eating among Adolescents with Diabetes) survey. Data on BMI and glycosylated hemoglobin (HbA(1c)) were drawn from medical records. RESULTS: Unhealthy weight control practices were reported by 37.9% of the females and by 15.9% of the males. Among the females, 10.3% reported skipping insulin and 7.4% reported taking less insulin to control their weight. Only one male reported doing either of these behaviors. Weight control/disordered eating behaviors were not associated with age, parental level of education, family structure, or race/ethnicity. Higher levels of weight dissatisfaction tended to be associated with unhealthy weight control/disordered eating; associations with BMI were inconsistent. Family cohesion was negatively associated with disordered eating among females (r = -0.52; P < 0.001) and males (r = -0.41; P < 0.001), but correlations with other measures of family environment (control, independence, and responsibility for diabetes management) were not significant. Correlations between disordered eating and HbA(1c) levels were significant among females (r = 0.33; P < 0.01) and males (r = 0.26; P < 0.05). CONCLUSIONS: Special attention is needed for youth with weight concerns and those from less cohesive families to assist in the development of healthy diabetes management behaviors.     

Increased insulin sensitivity and responsiveness of glucose metabolism in adipocytes from female versus male rats.

This study was undertaken to examine whether there were sex-associated differences in the action of insulin on glucose metabolism in adipocytes. Insulin binding and the dose-response curves for glucose transport (assessed by measuring the cell-associated radioactivity after 15-s incubation with 50 microM [6-14C]glucose) and [U-14C]glucose (5 mM) metabolism into CO2 and lipids were compared in retroperitoneal adipocytes from age-matched (84 d) male and female rats. In addition, the activity of fatty acid synthetase, one of the key lipogenic enzymes, was determined. Fat cell size was not significantly larger in females than in males (0.238 vs. 0.209 microgram lipid per cell). At insulin concentrations less than or equal to 1.6 nM, adipocytes from females bound significantly more insulin than did adipocytes from males, due to an increased apparent affinity of the receptors for insulin. Accordingly, the sensitivity of glucose transport to insulin was greater in females than in males: insulin concentration eliciting half-maximal stimulation (ED50) = 0.19 nM vs. 0.41 nM. At maximal insulin stimulation the rates of glucose transport (12 times the basal values) were similar in the two sexes. In contrast, the maximal effect of insulin on glucose conversion to CO2 plus lipids was much greater in the adipocytes from females than males (increment over basal: 472 vs. 249 nmol/10(6) cells per 2 h). Fatty acid synthesis contributed approximately 40% of the incremental difference between the two types of adipocytes, while glyceride-glycerol synthesis contributed less than 10%. The insulin dose-response curves for adipocytes from females were shifted to the left for all the metabolic pathways investigated. The mean ED50 for total glucose metabolism in females was 50% of that in males (0.07 nM vs. 0.15 nM). Marked sex-associated differences in the action of insulin on glucose metabolism were also observed in subcutaneous inguinal adipocytes (increment over basal: 137 and 56 nmol/10(6) cells per 2 h, ED50 = 0.13 nM and 0.30 nM in females and males, respectively). The intracellular capacity to metabolize glucose through the fatty acid synthesis pathway, as assessed by FAS activity, was higher in adipocytes from females than in those from males and was greater in retroperitoneal than in inguinal adipocytes. Furthermore, by plotting the individual data, a highly significant correlation (r = 0.92, P less than 0.001) was found between the absolute effect of insulin on glucose metabolism at maximal stimulation and the fatty acid synthetase activity of the cells. These results indicate that the response of glucose metabolism to insulin in adipocytes from female as compared with male rats is characterized by two main features: (a) an increased sensitivity primarily due to an increase in insulin binding, and (b) an increased responsiveness closely associated with a postreceptor increase in the lipogenic capacity of the cell. These findings might be relevant to the differential disposition of male and female rats to develop fatness.     

The clinical significance of betaine,an osmolyte with a key role in methyl group metabolism

Betaine is an essential osmolyte and source of methyl groups and comes from either the diet or by the oxidation of choline. Its metabolism methylates homocysteine to methionine, also producing N,N-dimethylglycine. Betaine insufficiency is associated with the metabolic syndrome, lipid disorders and diabetes, and may have a role in vascular and other diseases. Betaine is important in development, from the pre-implantation embryo to infancy. Betaine supplementation improves animal and poultry health, but the effect of long-term supplementation on humans is not known, though reports that it improves athletic performance will stimulate further studies. Subsets of the population that may benefit from betaine supplementation could be identified by the laboratory, in particular those who excessively lose betaine through the urine.Plasma betaine is highly individual, in women typically 20–60 μmol/L and in men 25–75 μmol/L. Plasma dimethylglycine is typically < 10 μmol/L. Urine betaine excretion is minimal, even following a large betaine dose. It is constant, highly individual and normally < 35 mmol/mole creatinine. The preferred method of betaine measurement is by LC-MS/MS, which is rapid and capable of automation. Slower HPLC methods give comparable results. Proton NMR spectrometry is another option but caution is needed to avoid confusion with trimethylamine-N-oxide.     

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.     

调查来宾市人口甲状腺功能性疾病的患病情况

目的 研究来宾市人口不同性别、年龄甲状腺功能性患病情况.方法 采用横断面研究方法,回顾性分析本院甲状腺检查的38 798例患者的资料.结果 女性在年龄的11～20、21～30、31～40、41～50岁中甲状腺功能亢进所占的比例分别为:70%、71%、57%、67%;女性在年龄为11～20、21～30、31～40、41～50岁中甲状腺功能减退所占的比例分别为:76%、77%、56%、71%;男女比例差异有统计学意义.结论 女性和男性激素分泌的差异导致男女在甲状腺疾病方面发病率的差异.     

Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy.

We examined insulin sensitivity and secretion, together with the levels of selected glucoregulatory hormones, in 15 female patients with severe hypothyroidism (H) and during subsequent thyroid hormone replacement therapy (HRT) using the euglycaemic hyperinsulinaemic clamp technique. Insulin action, as evaluated by glucose disposal, the insulin sensitivity index, and fasting post-hepatic insulin delivery rate were established. The basal levels of insulin, C-peptide and counter-regulatory hormones were measured in basal condition. In H, glucose disposal (p<0.01), the insulin sensitivity index (p<0.01) and post-hepatic insulin delivery rate (p<0.05) were significantly lower than during HRT. No significant changes in the levels of fasting insulin and C-peptide were observed. The levels of counter-regulatory hormones in patients with H were significantly higher than during HRT (glucagon, p<0.05; epinephrine, p<0.01; cortisol, p<0.05; growth hormone, p<0.05). In H, an inverse correlation between insulin sensitivity and insulin secretion was observed (p<0.05). Cortisol was the most important factor affecting the variability of insulin sensitivity values, regardless of thyroid function (p=0.0012). In conclusion, H altered both insulin sensitivity and the levels of selected counter-regulatory hormones. The situation was restored by HRT, as manifested not only by normalisation of insulin sensitivity, secretion and levels of glucoregulatory hormones, but also by improvement of their relationships.     

Racial differences in metabolic control of children and adolescents with type I diabetes mellitus

OBJECTIVE: This study evaluated racial differences in the metabolic control of children and adolescents with insulin-dependent (type I) diabetes mellitus and examined the interactive effects of race with age and sex. RESEARCH DESIGN AND METHODS: Data on several demographic and clinical variables were obtained for 102 black and 108 white children, including the percentage of total HbA1, age, age at diagnosis, duration of diabetes, pubertal status, insulin dose (U.kg-1.day-1), body mass index, number of clinic visits kept and missed, number of hospitalizations for diabetic ketoacidosis (DKA) for the year, and socioeconomic status (SES). RESULTS: Black children had higher insulin dosages (P less than 0.05) and lower SESs (P less than 0.001) than white children. HbA1 was higher in black than white children (P less than 0.01) after statistically adjusting for the effects of insulin dose, diabetes duration, and SES. With HbA1-based criteria, more black than white children were in poor and fewer in good metabolic control (P less than 0.001). Older children (greater than or equal to 13 yr) had higher HbA1 levels than younger (less than 13 yr) children (P less than 0.002), but there were no differences in HbA1 between males and females nor were there interactive effects of race, sex, and age-group. Black children were hospitalized for DKA more frequently than white children (P less than 0.04). More black than white children missed clinic visits (P less than 0.01), but they did not differ in number of visits kept. CONCLUSIONS: Black youths with type I diabetes mellitus are in poorer metabolic control than white youths.