Hyperinsulinaemia, dyslipaemia and cardiovascular risk in girls with a history of premature pubarche

Girls with a history of premature pubarche, i.e. appearance of pubic hair before 8 years of age, show hyperinsulinism in response to an oral glucose tolerance test. As hyperinsulinaemia has a major role in dyslipaemia, and is considered an independent risk factor for cardiovascular disease, we assessed the patterns of plasma insulin concentration after a standard oral glucose tolerance test as well as fasting serum lipid, lipoprotein, and sex hormone-binding globulin concentrations in girls (n = 81) with premature pubarche compared with girls (n = 55) matched with them for stage and bone age to ascertain their metabolic states to identify those potentially at risk for the development of premature cardiovascular disease. Mean serum insulin concentrations were higher in patients at all pubertal stages, and associated with elevated serum triglyceride, very low density cholesterol and very low density triglyceride concentrations (p value range 0.04 to < 0.0001) but reduced sex hormone-binding globulin. Premature pubarche patients also displayed higher low density to high density lipoprotein cholesterol ratios compared with control subjects (p = 0.004 to 0.008). In conclusion, hyperinsulinaemia, decreased sex hormone-binding globulin concentrations and an unfavourable lipid pattern are common features in premature pubarche girls supporting the contention that atherogenic abnormalities composing the metabolic syndrome could start in childhood. To determine the clinical sequelae of such clustering of metabolic deviations, girls who were identified need to be followed up for the potential development of premature cardiovascular disease.     

Chemical respiratory allergy, IgE and the relevance of predictive test methods: a commentary

Polycystic ovary syndrome is a diagnosis made in 5%-10% of women between late adolescence and the menopause. Patients may present with oligomenorrhoea or amenorrhoea, anovulation or infertility, hirsutism or acne. Women with the syndrome have at least seven times the risk of myocardial infarction and ischaemic heart disease of other women, and by the age of 40 years up to 40% will have type 2 diabetes or impaired glucose tolerance. Polycystic ovary syndrome is associated with insulin resistance, with consequent hyperinsulinaemia and (frequently) hyperlipidaemia and obesity. Recent research has shown that the application of diabetes management techniques aimed at reducing insulin resistance and hyperinsulinaemia (such as weight reduction and the administration of oral hypoglycaemic agents) can not only reverse testosterone and luteinising hormone abnormalities and infertility, but can also improve glucose, insulin and lipid profiles. The management of polycystic ovary syndrome should now include patient education and attention to diabetes and cardiovascular risk factors such as hyperlipidaemia, obesity, physical exercise, glucose intolerance, hypertension and cigarette smoking.     

A case of congenital infantile fibrosarcoma of the right hand

BACKGROUND AND AIMS: In recent years it has been proposed that hypertension is part of a cluster of metabolic risk factors (syndrome X) involving hyperlipidaemia and hyperglycaemia, with hyperinsulinaemia as the common link. This study has investigated: (1) the prevalence of the metabolic syndrome and its component variables and their relationship to body mass index (BMI) and non-fasting insulin levels in a general population; and (2) the distribution and clustering of metabolic variables in normotensives and hypertensives. METHODS: Cross-sectional study of 5222 men aged 40-59 years with no history of coronary heart disease (CHD), diabetes mellitus or stroke drawn from general practices in 18 British towns. The men were a subgroup of the 7735 men in the British Regional Heart Study (BRHS) cohort whose baseline non-fasting serum was analysed for insulin, using a specific ELISA method. MAIN OUTCOME MEASURES: Hyperinsulinaemia, hyperglycaemia, high serum total cholesterol, high triglyceride and hyperuricaemia were defined as the top 20% of the distribution in the 5222 men. Low HDL-cholesterol was defined as the bottom 20%. RESULTS: BMI and non-fasting insulin were both significantly and strongly associated with non-diabetic hyperglycaemia, lipid abnormalities (HDL-cholesterol, triglyceride and total cholesterol) and hyperuricaemia. BMI was strongly associated with hypertension whereas non-fasting insulin showed a much weaker relationship which was abolished after adjustment for BMI. However, only 2.9% of men showed the 'full metabolic syndrome' (hypertension, hyperglycaemia and dyslipidaemia) and a large proportion of these men were hyperinsulinaemic (65%) or obese (47%). Dyslipidaemia (any one of low-HDL-cholesterol, high triglyceride or high cholesterol) was common in both normotensives and hypertensives (40.5% vs 46.4%). Hypertensives showed significantly higher levels of total cholesterol, triglyceride, blood glucose, urate and more clustering of hyperglycaemia and dyslipidaemia than normotensives even after adjustment for BMI. CONCLUSION: Hypertensives were more likely to have lipid abnormalities and clustering of risk factors than normotensives even after adjustment for BMI. The metabolic syndrome is more strongly associated with hyperinsulinaemia than with obesity but it is relatively uncommon in men with no history of cardiovascular disease or diabetes. Given the weak relationship between hypertension and hyperinsulinaemia, the latter is unlikely to explain the higher levels of lipid abnormalities and clustering seen in hypertensives. Overweight/obesity may be primarily involved in the pathways to hypertension and lipid abnormalities but the unravelling of these relationships require more specific measures of adipose tissue distribution, composition and function.     

Syndrome X and mortality: a population-based study. Risk Factor and Life Expectancy Research Group

The present report analyzes the prevalence of the cluster of metabolic abnormalities defined as syndrome X (high blood glucose, high blood pressure, low high density lipoprotein (HDL) cholesterol, and high triglycerides) and its impact on cardiovascular disease mortality in a large cohort of men and women (22,561 men and 18,495 women). These individuals were participants in a series of epidemiologic investigations of cardiovascular disease conducted in Italy between 1978 and 1987. They were followed for an average of 7 years, during which time a total of 1,218 deaths occurred (1,003 in men and 215 in women). Deaths were coded according to the International Classification of Diseases, 9th Revision (ICD-9). The prevalence of the full cluster of metabolic abnormalities (syndrome X) was low in the population as a whole, with only 3.0 percent of men and 3.4 percent of women exhibiting the full cluster of abnormalities that comprise syndrome X. The risk of death from all causes and cardiovascular disease increased with increased numbers of metabolic abnormalities in both men and women. Mortality from cancer was significantly increased in women (but not in men) with syndrome X, compared with women with no metabolic abnormalities. Population attributable risks for all cause mortality and cardiovascular disease mortality were 0.06 and 0.09 in men and 0.04 and 0.48 in women when assessed by population cutpoints. These data from a large population-based epidemiologic investigation indicate that the presence of a full cluster of metabolic abnormalities from syndrome X is an important risk factor for cardiovascular disease and all-cause mortality in both men and women, but that the low prevalence of such a cluster in the population reduces the public health impact of syndrome X. The majority of individuals who die from cardiovascular disease present elevations in any one, two, or three of the metabolic abnormalities. The notion of the cluster of metabolic abnormalities (syndrome X) should not distract our attention from established individual risk factors that have been proven to be major causes of cardiovascular disease death and disability in our society.     

Obesity and insulin resistance syndrome

Obesity is commonly associated with insulin resistance. The etiology of insulin resistance syndrome such as syndrome X or deadly quartet is not clear. We have proposed visceral fat syndrome, in which fat accumulation is predominant in the intra-abdominal cavity, frequently accompanied by disorders of glucose and lipid metabolism, and also hypertension. Excess free fatty acid of the portal circulation may cause the enhancement of lipid synthesis and gluconeogenesis as well as insulin resistance, resulting in hyperlipidemia, glucose intolerance and hypertension and finally atherosclerosis. Enhanced production of PAI-1 by increased visceral fat may be partly responsible for the development of cardiovascular disease in patient with visceral fat assmulation.     

Inadequate vitamin D status: does it contribute to the disorders comprising syndrome 'X'?

Environmental factors are important in the aetiology of glucose intolerance, type II diabetes and IHD. The lack of vitamin D, which is necessary for adequate insulin secretion, relates demographically to increased risk of myocardial infarction. These disorders are connected, degenerative vascular disease increasing with glucose intolerance and diabetes and, with its risk factors, comprising syndrome 'X'. Evidence is presented suggesting that vitamin D deficiency may be an avoidable risk factor for syndrome 'X', adding another preventative measure to current recommendations which are aimed at reducing the worldwide epidemic of these disorders. Experimentally, vitamin D deficiency progressively reduces insulin secretion; glucose intolerance follows and becomes irreversible. Relationships between vitamin D status, glucose tolerance and 30 min insulin secretion during oral glucose tolerance tests are reported in British Asians; insulin secretion, but not glycaemia, improving with short-term supplementation. Studies showing reduction in blood pressure and in risk of heart attack and diabetes with exercise (usually outdoor), rarely consider the role of vitamin D status. Glycaemia and insulin secretion in elderly European men, however, relate to vitamin D status, independent of season or physical activity. Prolonged supplementation can improve glycaemia. Hypertension improves with vitamin D treatment with or without initial deficiency. Vitamin D status and climate are reviewed as risk factors for myocardial infarction; the risk reducing with altitude despite increasing cold. Glycaemia and fibrinogenaemia improve with insulin secretion increases in summer. Variation in vitamin D requirements could arise from genetic differences in vitamin D processing since bone density can vary with vitamin D-receptor genotype. Vitamin D receptors are present in islet beta cells and we report insulin secretion in healthy Asians differing profoundly with the Apa I genotype, being independent of vitamin D status. Those at risk of vitamin D deficiency include the elderly, those living indoors or having a covered-up style of dress, especially dark-skinned immigrants, and pregnant women, and these are groups recognized as being at increased risk of diabetes.     

Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma

The occurrence of neuro-endocrine deficiencies following craniospinal irradiation for medulloblastoma is well known, but data concerning the spectrum and prevalence of endocrine abnormalities in adulthood are scarce. We studied endocrine function in 20 (median age 25 years) adult subjects, 8-25 years (median 16 years) after therapy. The radiation dose to the whole cranium and spinal axis was 35 +/- 2.6 Gray (mean +/- standard deviation) with a boost to the posterior fossa of 18 +/- 3.7 Gray. 13 subjects had received additional chemotherapy. In 15 of 20 (75%) subjects, endocrine abnormalities were observed. In 14 (70%), growth hormone (GH) secretion was impaired; 7 (35%) subjects had an absolute GH deficiency, while 7 (35%) showed subnormal responses to insulin-induced hypoglycaemia. In contrast, only 20% (4) of these subjects showed impairment of the hypothalamus-pituitary-thyroid (HPT) axis, while 15% (3) showed central impairment of hypothalamus-pituitary-gonadal (HPG) function. Central impairment of the HPG axis was associated with impaired GH secretion in all cases. Central adrenal insufficiency was not observed. Basal levels of prolactin were normal in all subjects. Young age at treatment was a determinant of GH deficiency in adulthood (P = 0.014). Neither post-treatment interval, nor the use of chemotherapy were determinants of central endocrine impairment in adulthood. In long-term survivors of medulloblastoma, GH deficiency has a high prevalence. In contrast, impairment of the HPG and HPT axis is less common, while central adrenal insufficiency was not observed.     

Current concepts of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) may be loosely defined as unexplained hyperandrogenism, with variable degrees of cutaneous symptoms, anovulatory symptoms, and obesity. The vast majority of patients with the full-blown Stein-Leventhal syndrome have functional ovarian hyperandrogenism (FOH). However, FOH often occurs without the LH excess or polycystic ovaries of classic PCOS. Functional adrenal hyperandrogenism (FAH) is often found in the syndrome, but it is less closely associated with anovulatory symptoms than is FOH. The vast majority of FOH seems to arise from abnormal regulation (dysregulation) of ovarian androgen secretion. This typically is due to escape from desensitization to luteinizing hormone (LH); this appears to occur because of a breakdown in the processes that normally coordinate ovarian androgen and oestrogen secretion so as to prevent hyperoestrogenism. Similar dysregulation of adrenal androgen secretion in response to ACTH seems to account for most FAH. Dysregulation of androgen secretion may affect the ovary alone (isolated FOH), the adrenal alone (isolated FAH), or both together. Modest insulin resistance is common in PCOS/FOH, and the resultant hyperinsulinaemia is a major candidate as the cause of the dysregulation. The hyperinsulinaemia may arise from either 'nature' (genetic defects) or 'nurture' (exogenous obesity). Although hyperinsulinaemia alone does not have an obvious effect on steroidogenesis, it may act in genetically predisposed women as a 'second hit' to unmask latent abnormalities in steroidogenesis. The ovary, the adrenal cortex, and several other organs paradoxically function as if responding to the hyperinsulinaemic state in spite of resistance to the effects of insulin on glucose metabolism. PCOS should be viewed as an early manifestation of a hyperinsulinaemic condition that will predispose to cardiovascular and metabolic complications later in life. A subset of PCOS patients appear to have not only insulin resistance but also beta-cell secretory dysfunction, which may indicate a relationship of the disorder to NIDDM. The fundamental genetic defects remain to be elucidated.     

Influence of delayed staging laparotomy after laparoscopic removal of ovarian masses later found malignant

OBJECTIVE: To study the prevalence of cardiovascular risk factors in native urban Asian Indians and to look for the occurrence of clustering of these factors. RESEARCH DESIGN AND METHODS: The study included 953 subjects (532 men and 421 women), aged > or = 40 years, selected from a population survey for diabetes, which was conducted in 1994 in Madras, Tamil Nadu, India. Measurements of anthropometry, blood pressure, plasma lipid profile, glucose tolerance, plasma insulin response, and electrocardiogram were made. Based on the normal ranges derived from the population study, abnormalities in anthropometric values, plasma lipids, and insulin values were determined. Age-adjusted prevalences of the abnormalities were calculated using data from a 1991 urban census in Madras. The expected prevalences of the abnormalities in isolation and in combinations were calculated and compared with the corresponding observed figures. RESULTS: The prevalences of risk factors were in the order of central adiposity > dyslipidemia > hyperinsulinemia (2-h) > glucose intolerance > obesity > hypertension. The age-adjusted prevalence of coronary heart disease (CHD) was 3.9% (3.5% in men and 4.5% in women, NS), and T wave inversion was seen in an additional 10.3%. Isolated prevalences of all factors, except hypertension, were in lower frequency than expected. Combinations of each risk factor with one or two more risk factors occurred more frequently (1.3-4 times) than expected by chance. Impaired glucose tolerance and dyslipidemia showed association with hyperinsulinemia, whereas hypertension did not show such an association. CONCLUSIONS: Clustering of the cardiovascular risk factors or the components of insulin resistance syndrome occurs in the native Asian Indian population. This finding under-scores the need for preventive aspects of metabolic disorders and CHD.     

Ulnar ray deficiency

Benfluorex is a clinical lipid-lowering agent with antihyperglycemic properties. The effect of long-term oral treatment (10 mg/kg/day for 7.5 months) on carbohydrate and lipid metabolism and aortic morphology was investigated in 24 insulin-resistant sand rats receiving a standard laboratory diet supplemented with cholesterol (2%). Untreated controls (n=34) developed impaired glucose tolerance, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia and elevated plasma LDL- and VLDL-cholesterol, positively correlated with the proportion of the thoracic aorta displaying oil red O-positive atherosclerosis; ultrastructural examination showed intimal lipid deposits, foam cells, polymorph infiltrates and fibrosis. Benfluorex-treated animals showed significant decreases in glucose intolerance, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and plasma LDL- and VLDL-cholesterol, with no evidence of aortic atheroma. The metabolic benefits of benfluorex may protect against the long-term development of atherosclerosis in the insulin-resistant dyslipidemic syndrome.     

Experimental benefit of moxonidine on glucose metabolism and insulin secretion in the fructose-fed rat

OBJECTIVE: Non-insulin-dependent diabetes mellitus (NIDDM) is often associated with hypertension leading to a specifically high cardiovascular risk in these patients. However, there is evidence that insulin resistance and hyperinsulinaemia are not only characteristic for diabetic patients but also for some non-diabetic populations in which a cluster of cardiovascular risk factors is observed (hypertension, hypertriglyceridaemia, obesity). Therefore, hyperinsulinaemia and insulin resistance have been suggested to be of major pathophysiological importance for the development of this syndrome (syndrome X). Since imidazoline receptors are currently considered to be a specific pharmacological target for blood pressure reduction, it is important to know whether and in which way these compounds affect the glucose homoeostasis and insulin release. DESIGN: The influence of moxonidine on glucose tolerance in vivo was determined in healthy control rats, in rats receiving a high fructose diet for 6 weeks to induce insulin resistance, hyperinsulinaemia and hypertension, and in rats receiving in addition to a high fructose diet moxonidine (1.5 mg/kg body weight daily). In vitro, using isolated pancreatic islets of mice, long-lasting effects (chronic) and immediate (acute) effects of moxonidine on beta-cell function were determined by basal and glucose stimulated insulin release in two different experimental systems: (1) islets were exposed for 24 h (37 degrees C) to various concentrations of moxonidine ranging from 1 nmol/l to 1 mmol/l, followed by a washing procedure to remove excess of moxonidine and then used for the beta-cell function test; (2) islet cultures were incubated again with moxonidine for 24 h (37 degrees C) with either 1 nmol/l or 1 micromol/l. In contrast to the first experiments, however, after the washing procedure moxonidine was added at the same concentration as used for preincubation to test its direct effect on beta-cell function. RESULTS: In healthy control rats acute administration of moxonidine in vivo impaired the glucose tolerance in high dosages, which effectively reduced the blood pressure (>1 mg/kg body weight). This effect was, however, smaller that that observed by clonidine. In fructose-fed rats, moxonidine completely prevented the development of insulin resistance, hyperinsulinaemia and hypertension. In vitro, pancreatic islets preincubated with moxonidine exhibited dose-dependently both stimulatory and inhibitory chronic effects on beta-cell function compared with that in controls. Preincubation of islet cultures with moxonidine at concentrations between 1 nmol/l and 1 mmol/l resulted in a reduction of basal insulin release which was very pronounced at concentrations higher than 100 nmol/l. The results obtained for glucose-stimulated insulin release opposed in part those for basal insulin release, since the preincubation with moxonidine up to 10 micromol/l gave rise to an increased insulin release. An additional direct effect of moxonidine with a marked reduction of glucose-stimulated insulin release was observed, however, when moxonidine was present during the preincubation (24 h) and the functional test at a concentration of 1 nmol/l or 1 micromol/l. CONCLUSIONS: Our data suggest that a causal linkage exist between the development of hypertension and insulin resistance/hyperinsulinaemia in the high fructose diet rat model. Since central activation of imidazoline receptors by moxonidine can prevent this syndrome, it follows that an overactivity of the sympathetic nervous system is of major importance. Suppression of this sympathetic overactivity might be an effective approach to reduce hypertension and the concomitant metabolic defect. Therefore, such an interventional strategy could contribute to reduce the cardiovascular risk of NIDDM patients and patients with other forms of insulin resistance/hyperinsulinaemia such as metabolic cardiovascular syndrome.     

Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidaemia and atherosclerosis

Insulin resistance syndrome (IRS) has the potential to explain a large group of common metabolic and cardiovascular disorders [e.g., obesity, non-insulin-dependent diabetes mellitus (NIDDM), hypertension, hyperlipidaemia, hypercoagulability] which are all in themselves cardiovascular risk factors. This contribution firstly reviews the convincing evidence from glucose-clamp studies that all of these conditions are characterised by the presence of combined insulin resistance and hyperinsulinaemia, and secondly examines the relationships of the components of this syndrome to coronary artery disease and to the rational choice of antihypertensive therapy.     

Spontaneous glucose intolerance in the progeny of low dose streptozotocin-induced diabetic mice

Multiple low doses of streptozotocin (LDS) induce low-incidence diabetes mellitus in Balb/cHan and high-incidence diabetes in CD-1 mice. We studied offspring of diabetic parents in both strains. Group 1 consisted of litters from control mice with no streptozotocin treatment. Group 2 litters had an LDS diabetic mother and a control father, group 3 litters had control mother with LDS diabetic father, and group 4 litters had both, LDS diabetic mother and father. Diabetes was induced by 5 x 40 mg streptozotocin per kg on five consecutive days. Progeny of diabetic mothers showed a state of reduced glucose tolerance associated with reduced glucose disappearance during intravenous glucose tolerance test and increased insulin secretion of isolated islets of Langerhans. These metabolic abnormalities predominated in the male litters of both strains of mice. Amniotic insulin was increased in diabetic mothers during pregnancy. No histologic abnormalities were observed in group 2 progeny. Pancreases in male offspring of LDS diabetic CD-1 fathers (group 3) were studied for insulitis. Insulitis was found in 40% of mice with normal glucose tolerance. A single subdiabetogenic dose of streptozotocin (40 mg/kg) induced insulitis in 90% of pancreases accompanied by reduced insulin release of isolated islets. By contrast, male Balb/cHan progeny of diabetic fathers failed to develop insulitis. In conclusion, we found (1) parental LDS diabetes was transmitted more often to male offspring, (2) maternal LDS diabetes was associated with hyperinsulin secretion and glucose intolerance in the offspring and (3) paternal LDS diabetes was accompanied by insulitis and insulin secretion deficiency in CD-1 progeny.     

Cardiovascular causes of exercise intolerance

Exercise intolerance, due to cardiovascular disease in horses, may be caused by cardiac arrhythmias, valvular regurgitation, congenital abnormalities, myocardial dysfunction, pericardial disease, and vascular thrombosis. The most common cardiovascular cause of exercise intolerance in horses is atrial fibrillation. Cardiovascular abnormalities such as cardiac arrhythmias or murmurs, however, are common in athletic horses and are not always associated with exercise intolerance. Use of an electrocardiography (during rest and exercise) and echocardiography may be necessary to better determine the significance of the cardiovascular abnormality.     

Insulin resistance, high prevalence of diabetes, and cardiovascular risk in immigrant Asians. Genetic or environmental effect?

OBJECTIVES: To compare the prevalence of diabetes, hyperinsulinaemia, and associated metabolic abnormalities in immigrant Asians, Asians in India, and native white British men. DESIGN: Case control study. SETTING: Wythenshawe Hospital, Manchester, United Kingdom, and Maulana Azad Medical School, New Delhi, India. SUBJECTS: Men with angiographically proved coronary artery disease; 83 British Asians, 87 white men, and 30 Indian Asians with age matched controls. INTERVENTIONS: Fasting lipid concentrations, serum glucose, and total insulin concentrations were measured in the fasting state and one and two hours after a 75 g glucose load by mouth. All subjects had a physical examination by the same observer. RESULTS: Asians in the United Kingdom and in India had a higher prevalence of diabetes and impaired glucose tolerance than the white British men. Patients in all three ethnic groups had higher total insulin concentrations than their controls in the fasting state and after the glucose load. British Asian and Indian Asian patients and controls had higher total insulin concentrations than the white men in the fasting state and after the glucose load. Total insulin concentrations were similar in British and Indian Asians, though fasting concentrations were higher in British Asians than Indian Asians. White men had similar cholesterol, lower triglyceride, and higher high density lipoprotein cholesterol concentrations than Asians in the United Kingdom and in India. British Asian patients had higher cholesterol concentrations and British Asian controls had higher triglyceride concentrations than the Indian Asian groups. Asian patients and controls were more active. British and Indian Asian patients had higher waist to hip ratios than controls. The waist to hip ratio was positively correlated with insulin and triglyceride concentrations and negatively correlated with the high density lipoprotein cholesterol concentration. Fasting insulin and high density lipoprotein concentrations were independent predictors of coronary artery disease in white men, whereas in British Asians the waist to hip ratio was the strongest independent predictor. In Indian Asians the waist to hip ratio and high density lipoprotein concentration were independent predictors of coronary artery disease. CONCLUSIONS: Central obesity in the subgroups of Asians studied showed a close association with hyperinsulinaemia and the risk of coronary artery disease. A predisposition to insulin resistance and its metabolic abnormalities in this group of Asians seems to be genetically determined, environmental changes after migration having only a small additional effect.     

Does insulin resistance unite the separate components of the insulin resistance syndrome? Evidence from the Miami Community Health Study

A number of coronary heart disease risk factors have been identified that often cluster together to increase the risk of macrovascular disease. This cluster is referred to as the insulin resistance syndrome, and the risk factors commonly include dyslipidemia, elevated blood pressure, an android pattern of body fat distribution, and glucose intolerance. Whether hyperinsulinemia or insulin resistance per se provides a common pathway for these metabolic abnormalities is unclear. The authors studied 50 nondiabetic persons who had completed a euglycemic hyperinsulinemic clamp protocol in addition to a 75-g oral glucose tolerance test and other measures of the coronary risk profile. Using principal-component analysis, we reduced nine coronary risk factors to two uncorrelated factors that explained 54.5% of the variance. Factor 1 consisted of positive loadings for uric acid, systolic and diastolic blood pressure, triglyceride concentration, and waist girth and negative loadings for HDL cholesterol and the rate of insulin-mediated glucose disposal (M, in milligrams per kilogram of body weight per minute). M also loaded on factor 2, along with fasting insulin and glucose concentrations, diastolic blood pressure, and waist girth. The observation that M loaded on both factors suggests that a resistance to insulin action may provide the mechanism uniting the features of the insulin resistance syndrome. Hyperinsulinemia with concomitant insulin resistance may be necessary to produce this metabolic derangement, as well as the increased risk of macrovascular complications.     

Mapping of a serine-rich domain essential for the transcriptional, antiapoptotic, and transforming activities of the v-Rel oncoprotein

Patients with adult GH deficiency are often dyslipidemic and may have an increased risk of cardiovascular disease. The secretion and clearance of very low density lipoprotein apolipoprotein B 100 (VLDL apoB) are important determinants of plasma lipid concentrations. This study examined the effect of GH replacement therapy on VLDL apoB metabolism using a stable isotope turnover technique. VLDL apoB kinetics were determined in 14 adult patients with GH deficiency before and after 3 months GH or placebo treatment in a randomized double blind, placebo-controlled study using a primed constant [1-(13)C]leucine infusion. VLDL apoB enrichment was determined by gas chromatography-mass spectrometry. GH replacement therapy increased plasma insulin-like growth factor I concentrations 2.9 +/- 0.5-fold (P < 0.001), fasting insulin concentrations 1.8 +/- 0.6-fold (P < 0.04), and hemoglobin A1C from 5.0 +/- 0.2% to 5.3 +/- 0.2% (mean +/- SEM; P < 0.001). It decreased fat mass by 3.4 +/- 1.3 kg (P < 0.05) and increased lean body mass by 3.5 +/- 0.8 kg (P < 0.01). The total cholesterol concentration (P < 0.02), the low density lipoprotein cholesterol concentration (P < 0.02), and the VLDL cholesterol/VLDL apoB ratio (P < 0.005) decreased. GH therapy did not significantly change the VLDL apoB pool size, but increased the VLDL apoB secretion rate from 9.2 +/- 2.0 to 25.9 +/- 10.3 mg/kg x day (P < 0.01) and the MCR from 11.5 +/- 2.7 to 20.3 +/- 3.2 mL/min (P < 0.03). No significant changes were observed in the placebo group. This study suggests that GH replacement therapy improves lipid profile by increasing the removal of VLDL apoB. Although GH therapy stimulates VLDL apoB secretion, this is offset by the increase in the VLDL apoB clearance rate, which we postulate is due to its effects in up-regulating low density lipoprotein receptors and modifying VLDL composition.     

Objective echocardiographic evaluation of the cardiovascular system: state of the art

In recent years it has been demonstrated that both GH deficiency and excess include in their advanced clinical manifestations an impaired cardiovascular function, which may reduce life expectancy. This observation has allowed the investigation of the role played by the GH/IGF-I axis on cardiac structure and function. In particular, several recent experimental and clinical studies support the evidence implicating GH and/or IGF-I in the regulation of heart development. Acromegalic cardiomyopathy is characterized by myocardial hypertrophy with interstitial fibrosis, lymphomononuclear infiltration and areas of monocyte necrosis which often result in increased right and left ventricular mass and concentric hypertrophy. Conversely, patients with childhood or adulthood-onset GH deficiency (GHD) have a reduced left ventricular mass and ejection fraction and the indexes of left ventricular systolic function remained markedly depressed during exercise. In addition, a significant increase in the thickness of the vascular intima-media wall and a higher number of atheromatous plaques have been reported. These abnormalities of the cardiovascular system are partially reversed after normalization of GH and IGF-I levels, by octreotide in acromegaly or after GH replacement therapy in GHD patients. The evidence that GH is able to increase cardiac mass suggested its use in the treatment of idiopathic dilated cardiomyopathy. In a recent study on such patients, the administration of rhGH was demonstrated to increase myocardial mass and to reduce the size of the left ventricular chamber, resulting in an improvement in hemodynamics, myocardial energy metabolism and clinical status. These promising results might open a new field for GH treatment.     

The value of certain parameters in the diagnosis and detection of metabolic X syndrome

Authors summarise their 5-year long experiences on 343 patients about diagnostic methods of metabolic syndrome X and offer a simple possibility for screening of the jeopardized individuals. In a group of patients with hypertension and central obesity (group I: with 2 insulin resistant condition), 229 (89%) out of 255 cases met the basic criteria of the syndrome X which were hypertension, central obesity and high insulin levels for the corresponding blood sugar levels during oral glucose tolerance test (probable insulin resistance). Dyslipidemia was missing in 20% of these people. Hyperinsulinism occurred in 85%, glucose intolerance in 53%, presumable insulin resistance in 90% of cases. Insulin resistance was characterised by late hyperinsulinism (90 and 120 min.) during oral glucose tolerance test. This was the case in people with "diabetoid" glucose responses too, suggesting an early failure of glucose tolerance and/or insulin secretion. Components of syndrome X were present with a lower frequency in 24 patients with obesity (group II), in 35 patients with hypertension (group III) and in 29 patients without obesity or hypertension (group IV), as well. According to central obesity and hypertension, syndrome X could be screened by a probability of 90%. This can be helpful in prevention of NIDDM and coronary heart disease.     

Dental abnormalities in children treated for acute lymphoblastic leukemia

The purpose of this study was to define the therapy-associated dental abnormalities in survivors of acute lymphoblastic leukemia (ALL). We reviewed the clinical records and panoramic radiographs of 423 survivors of ALL who were treated on one of four consecutive protocols (1975-1991). Dental abnormalities included root stunting, microdontia, hypodontia, taurodontia (enlarged pulp chambers), and over-retention of primary teeth. The frequency of these factors was determined in relation to age at initiation of treatment (< or = 8 years vs > 8 years), addition of cranial irradiation, and chemotherapeutic protocol. A total of 423 patients met the study criteria. The abnormalities comprised root stunting in 24.4% (n = 103), microdontia in 18.9% (n = 80), hypodontia in 8.5% (n = 36), taurodontia in 5.9% (n = 25), and over-retention of primary dentition in 4.0% (n = 17). Patients who were < or = 8 years old at diagnosis or who received cranial irradiation therapy developed more dental abnormalities than did those > 8 years and those who did not receive cranial irradiation (42 vs 32%). Survivors of childhood ALL often have dental abnormalities that may affect their quality of life. Dental evaluation at diagnosis and frequent follow-up may help to ensure appropriate preventive measures and minimize dental and periodontal disease.