Glucokinase gene polymorphisms: a genetic marker for glucose intolerance in a cohort of elderly Finnish men

Although mutations in the glucokinase gene are implicated in the pathogenesis of glucose intolerance in pedigrees with maturity-onset diabetes of the young, the role of such mutations in typical Type 2 diabetes is poorly characterized. We studied a cohort of elderly men born (between 1900 and 1919) in two Finnish communities and exhibiting a continuous spectrum of glucose tolerance at assessments made in 1984 and 1989. Individuals were typed at two polymorphic microsatellites straddling the glucokinase gene, GCK(3') (n = 169) and GCK(5') (n = 166): these two markers were in linkage equilibrium in this cohort. Significant associations between alleles at the GCK(3') marker and glucose tolerance were evident (p = 0.002), the frequency of the (z + 2) allele rising from zero in control subjects (n = 88 chromosomes) to 6.5% (n = 62) in subjects with impaired tolerance and 12.2% (n = 188) in subjects with diabetes. Mean 2-h glucose levels were 10.5 (9.6-11.4, 95% confidence interval) mmol l-1 in individuals with the (z + 2) allele and 8.1 (7.6-8.7) mmol l-1 in those without (p = 0.01, corrected for multiple comparisons). No association was evident between GCK(5') alleles and glucose tolerance. The GCK(3') microsatellite is a marker for abnormal glucose tolerance in this cohort of elderly Finnish men.     

Body iron stores are associated with serum insulin and blood glucose concentrations. Population study in 1,013 eastern Finnish men

OBJECTIVE: To study if there is an association between mildly elevated body iron and glucose homeostasis indexes. RESEARCH DESIGN AND METHODS: A cross-sectional population study was conducted in 1,013 middle-aged men, and an association of serum ferritin with concentrations of serum insulin, blood glucose, and serum fructosamine was tested. RESULTS: The mean concentration of fasting serum insulin was 21.6% higher (95% CI 7.3-37.9%, P < 0.001) in the 5th quintile of serum ferritin compared with the 1st quintile. The elevation in blood glucose was 6.1% (95% CI 2.3-9.9%, P < 0.001) and in serum fructosamine 3.9% (1.5-6.9%, P < 0.01). CONCLUSIONS: Mildly elevated body iron stores are associated with statistically significant elevations in glucose homeostasis indexes.     

Whole blood viscosity and haematocrit are associated with internal carotid atherosclerosis in men

BACKGROUND: Alterations in blood viscosity and haematocrit have been described in patients with coronary and cerebrovascular diseases. The results have not been conclusive, as modifications of these parameters are often associated with the presence of coronary heart disease (CHD) risk factors. The aim of this study was to verify whether blood viscosity and haematocrit are increased in patients with carotid atherosclerosis, independently of the presence of CHD risk factors. METHODS: Male patients with internal carotid atherosclerosis (ICA+, n = 28) were selected from participants in a cardiovascular disease prevention campaign. Controls (ICA-, n = 28), also participating in the prevention campaign, were matched for age and all the classical CHD risk factors. Plasma lipids, glucose and fibrinogen were determined by routine methods. Cigarette smoking and current drug therapy was established by questionnaire. Whole blood viscosity was measured at shear rates of 450 and 225/s, using a cone-plate viscometer. Echo-Doppler of carotid arteries was performed with an ATL Ultramark 9 HDI using a 5-10 MHz multifrequency probe. RESULTS: Blood pressure, plasma lipids, glucose, body mass index, fibrinogen and plasma viscosity were similar in the two groups. ICA+ patients, compared with the ICA- group, had significantly greater values of blood viscosity (4.52 +/- 0.37 cP compared with 4.18 +/- 0.45 cP, P < 0.005 respectively; shear rate 450/s) and haematocrit (48.57 +/- 3.19% compared with 45.57 +/- 4.81%, P < 0.008 respectively). CONCLUSIONS: Our findings demonstrate that blood viscosity and haematocrit are increased in men with internal carotid atherosclerosis, independently of the presence of risk factors for atherosclerosis.     

Chromium, glucose intolerance and diabetes

Myopathies, regardless of their varied etiologies, are associated with muscle damage and, often, other organ system involvement causing physical impairment. The resultant adverse impact on mobility, activities of daily living, communication, and cardiorespiratory fitness results in disability, handicap, and reduced quality of life. The extent of the functional impact depends on the type of myopathy and the extent of clinical involvement caused by it, duration of the disease, time to diagnosis and treatment, and rate of progression and response to medical management. The usefulness of rehabilitation in maintaining function in muscular dystrophy has been addressed in the literature for several decades. However, the need for and efficacy of specific rehabilitation interventions and assessment tools to measure function in inflammatory myopathy have just recently emerged this decade. Although studies are few in number, they are useful. More research is needed and should be encouraged. The overall goal of rehabilitation is to enhance function and quality of life.     

Relationships between maternal glucose intolerance and neonatal blood glucose

Blood glucose changes in 63 infants during the first three hours of life were related to indices of glucose tolerance of their mothers. Of the mothers, 34 had insulin-dependent diabetes, 16 had gestational diabetes, and 11 had minor abnormalities of glucose tolerance. The fasting blood glucose level of the mother and the umbilical cord blood glucose level were both proportional to the rate of glucose decline in the infant after birth which, in turn, was inversely related to the lowest glucose level attained within three hours. Hypoglycemia occurred in 77% of the infants of diabetic mothers, 25% of the infants of mothers with gestational diabetes, and one of 12 (8%) of infants of mothers with minor degrees of glucose intolerance. The blood glucose level at two hours during an oral glucose tolerance test in the mother can be used to predict the probability of her infant having neonatal hypoglycemia.     

Relationship between fasting plasma glucose, atherosclerosis risk factors and carotid intima media thickness in non-diabetic individuals

We analysed the relationship between fasting plasma glucose, carotid intima media thickness and some atherosclerosis risk factors in 307 non-diabetic individuals. Male (n = 120) and female subjects (n = 187) with a familial history of Type II diabetes mellitus and/or obesity and hyperlipoproteinaemia were examined in the age group 40-70 years. Plasma triglycerides, total and high-density-lipoprotein cholesterol, plasminogen activator inhibitor were measured by conventional methods. Specific insulin, pro-insulin and C-peptide were measured by specific enzyme immunoassay. Intima media thickness increased in quintiles for fasting plasma glucose in men, but not in women. There was a rise of triglycerides, body mass index, waist to hip ratio, plasminogen activator inhibitor, true insulin, proinsulin, C-peptide and a decrease of high-density-lipoprotein cholesterol in quintiles for fasting plasma glucose. Fasting plasma glucose was found to be significantly positively correlated to intima media thickness, body mass index, waist to hip ratio, haemoglobin A1c, insulin, C-peptide, triglycerides, plasminogen activator inhibitor and significantly negatively correlated to high density lipoprotein cholesterol. However, the correlation of fasting plasma glucose to intima media thickness was no longer significant after adjustment for age and sex. After adjustment for age and sex intima media thickness was significantly correlated to body mass index, total cholesterol, triglycerides, albuminuria and inversely correlated to high-density-lipoprotein cholesterol. In multivariate analysis age, male sex, high-density-lipoprotein cholesterol and total cholesterol were significant determinants of intima media thickness. Our data suggest that a weak association exists between fasting plasma glucose and intima media thickness, which may be mediated by a clustering of risk factors in the upper range of non-diabetic fasting plasma glucose level with a central role for dyslipidaemia.     

Prevalence and causes of proteinuria in 20-year-old Finnish men

The prevalence and causes of proteinuria were studied in a cohort of 36147 men aged 20 (born in 1956). Proteinuria was found in 139 men (0.4%) at the initial screening or examination. Further investigations reduced the number of proteinuria cases to 72 (0.2%). Persistent proteinuria was demonstrated in 46 men (0.13% of the series) and orthostatic proteinuria in 26 (0.07%). Urography revealed anomalies in 18 of 104 cases. Elevated blood pressure and reduced glomerular filtration rate were observed in a few men, mainly from the group with persistent proteinuria. Renal biopsy was performed in 61 cases--38 with persistent proteinuria, 12 with orthostatic proteinuria and 11 without proteinuria at the time of examination. Light microscopy gave normal findings or showed only slight mesangial or focal glomerulonephritis in the great majority of cases. Membranous, mesangiocapillary or chronic proliferative glomerulonephritis was present in one-fourth of the men with persistent proteinuria. This was the only group with such lesions.     

Hostility and the progression of carotid atherosclerosis

We studied prospectively the association of hostility and anger suppression by the use of ultrasonographically assessed 2-year progression of carotid atherosclerosis (PCA) in a sample of 119 middle-aged men from eastern Finland. Based on measures of cynical distrust, impatience-irritability, anger-in, and anger-control, four variants of hostility-by-anger suppression model were tested with multiple regression analysis. In addition to the previously established risk factors (i.e., serum low-density lipoprotein cholesterol concentration, smoking, and old age), cynical distrust and anger-control significantly predicted PCA. There was about a two-fold accelerated PCA in the group with high cynical distrust and high anger-control even after we controlled for the established biological risk factors and possible confounding background variables. The impact of the independent variables on PCA seemed to be additive rather than synergistic. These results, based on a relatively small, but nonselected population sample, extend previous results of angiographic studies.     

Multimodal approach to carotid bifurcation in atherosclerosis

The cost of treatment of ischemic stroke (second cause of death for elderly patients) is increasing. carotid bifurcation surgery can change the prognosis (as proven by NASCET and ECST studies) for symptomatic patients with over 70% of carotid narrowing. Exploration of the carotid bifurcation is an important step in the diagnosis and must assess the degree of stenosis, the smoothness of the plaque and describe the collateral vessels. Duplex sonography is used to analyze the plaque and to measure the hemodynamic consequences beyond the stenosis. Transcranial Doppler is used to study the hemodynamic consequences at the circle of Willis. 3D TOF MR Angiography visualizes vessels using MIP but with a risk of overestimation of the degree of stenosis. A good morphological study of the circle of Willis can be achieved. With spiral CT, 3D data bases can be acquired with a single injection of contrast medium. Analysis is based on native, reformatted and MIP images. The image quality is generally good, but decreases in the case of huge calcifications. Brain examination can be performed in the same session, looking for rupture of the blood-brain barrier. Angiography remains the gold standard with a high complication rate. It allows excellent analysis from the aortic arch to distal cortical vessels. Isotope studies are only performed in difficult cases (vertebro-basilar lesions, differential diagnosis). Duplex ultrasound is performed first in all protocols. Until recently, angiography was performed before surgery, but the current tendency is to use a less invasive examination (MR angiography or CT angiography) and angiography is then only performed when necessary. A knowledge of the respective advantages of each technique is essential in order to adapt the protocols to each local team.     

Prevalence and determinants of carotid atherosclerosis in healthy postmenopausal women

Fecal incontinence is an under-reported complication of scleroderma. Ten incontinent patients with scleroderma were evaluated through anorectal manometry and compared with 20 incontinent patients without scleroderma who were matched for age and sex as controls. The scleroderma patients had a higher voluntary external anal squeeze pressure, whereas the resting internal anal sphincter pressure was similar to that of the control group. The threshold for rectal sensation in the scleroderma group was significantly less than that in controls. Episodes of fecal incontinence, anal canal length, and maximal tolerable volume were not significantly different between the study groups. The rectoanal inhibitory response was abnormal in 80% of patients with systemic sclerosis but was normal in 70% of the controls. Stool consistency was significantly looser in the scleroderma patients. Treatment of fecal incontinence in scleroderma patients may be successful in many patients using a combination of dietary and pharmacologic manipulation because diarrhea is an important etiologic cofactor superimposed on reduced internal anal sphincter pressure.     

Ophthalmologic manifestations of internal carotid artery dissection

PURPOSE: To report the ophthalmologic symptoms and signs associated with extracranial internal carotid artery dissection. METHODS: One hundred forty-six consecutive patients with extracranial internal carotid artery dissection were evaluted; 29 were studied retrospectively from 1972 to 1984 and 117 prospectively from 1985 to 1997. RESULTS: Sixty-two percent of patients (91/146) with extracranial internal carotid artery dissection had ophthalmologic symptoms or signs that were the presenting symptoms or signs of dissection in 52% (76/146). Forty-four percent (65/146) had painful Horner syndrome, which remained isolated in half the cases (32/65). Twenty-eight percent (41/146) had transient monocular visual loss, which was painful in 31 cases, associated with Horner syndrome in 13 cases, and described as "scintillations" or "flashing lights"-often related to postural changes or exposure to bright lights-suggesting acute choroidal hypoperfusion in 23 cases. Four patients had ischemic optic neuropathy; one had diplopia. Among the 76 patients with ophthalmologic symptoms or signs as the presenting features of carotid dissection, a nonreversible ocular or hemispheric stroke later occurred in 27, within a mean of 6.2 days (range, 1 hour to 31 days). Eighteen patients had a stroke within the first week after the onset of neuro-ophthalmic symptoms and signs, and 24 had a stroke within the first 2 weeks. CONCLUSION: Ophthalmologic symptoms or signs are frequently associated with and are often the presenting features in internal carotid artery dissection. Painful Horner syndrome or transient monocular visual loss should prompt investigations to diagnose carotid artery dissection and begin early treatment to prevent a devastating ocular or hemispheric stroke.     

颈动脉粥样硬化与脑梗死关系探讨

目的 研究颈动脉粥样硬化病变特点和颈动脉内膜中层厚度(IMT)与脑梗死的关系.方法 对观察组100例急性脑梗死患者和对照组100例同期体检的健康者进行颈动脉彩色多普勒超声检查,检测双侧颈总动脉、颈动脉分叉和颈内动脉IMT和颈动脉粥样硬化斑块情况.结果 观察组颈动脉粥样硬化检出率为76.1%,以软斑、溃疡斑和混合斑为主;对照组颈动脉粥样硬化检出率为37.8%,以硬斑和扁平斑为主,两组差异有统计学意义(P<0.05).观察组颈总动脉、颈动脉分叉和颈内动脉IMT均显著大于对照组(P<0.05).结论 颈动脉粥样硬化斑块的形成是造成脑梗死的主要原因,颈动脉超声检查能准确显示斑块的形态、大小、位置及管腔狭窄程度,对脑梗死的早期预防和治疗具有重要的临床价值.     

Glucose concentration in parotid saliva after glucose/food intake in individuals with glucose intolerance and diabetes mellitus

[125I]beta-endorphin bound to high affinity (Kd = 0.25 nM) receptors in the caudal dorsomedial medulla of rats with a Bmax of 97 fmol/mg protein. The relative potency for displacement of [125I]beta-endorphin binding was: beta-endorphin(1-31) > beta-endorphin(1-27) > DAMGO > naloxone > N-acetyl-beta-endorphin(1-31) > U50488 > DPDPE. The Bmax for [3H]DAMGO binding was 81 fmol/mg protein, indicating that most [125I]beta-endorphin binding corresponds to mu-opioid receptors. [3H]DAMGO binding was not influenced by lesioning noradrenergic nerve terminals in the caudal dorsomedial medulla. Our findings indicate that beta-endorphin interacts primarily with mu-opioid receptors in the caudal dorsomedial medulla. These receptors are not affected by noradrenergic denervation.     

Clinical and electronystagmographic manifestations in the elderly with vertigo

The goal of the present work is to realize a review over the difference aspects of the alterations of the equilibrium and the vestibular system in the elderly patient. We also present a statistics about the symptomatology, the results of the vestibular tests and the diagnose, in a range of patients complaining of vertigo, aged over 65, studied in our ENT-Department.     

Hyperinsulinemia and clustering of cardiovascular risk factors in middle-aged hypertensive Finnish men and women

OBJECTIVE: To examine the relationship between hyperinsulinemia and clusters of cardiovascular risk factors in middle-aged hypertensive patients. DESIGN: A population-based study. SETTING: Pieks?m?ki District Health Center, and the Community health Center of the city of Tampere, in central Finland. SUBJECTS: Hypertensive men and women aged 36, 41, 46, and 51 years (n = 18) in the town of Pieks?m?ki, and a normotensive control population of 177 subjects aged 40 and 45 years in the city of Tampere. MAIN OUTCOME MEASURES: Clusters of obesity (body mass index > 30.0 kg/m2), abdominal adiposity (waist:hip ratio > 1.00 for men and > 0.88 for women), hypertriglyceridemia (> 1.70 mmol/l), a low level of high-density lipoprotein cholesterol (< 1.0 mmol/l in men and < 1.20 mmol/l in women) and abnormal glucose metabolism (impaired glucose tolerance or noninsulin-dependent diabetes as defined by World Health Organization criteria) according to statistical quartiles of the fasting plasma insulin concentration. RESULTS: Among the hypertensives, there was a 2.0- to 3.6-fold higher risk of having a clustering of the insulin-resistance associated cardiovascular risk factors compared with that of the normotensives. Among the hypertensive subjects in the highest quartile of fasting plasma insulin there was a six- to 12-fold increase in risk associated with having two or more insulin resistance-associated cardiovascular risk factors compared with the subjects in the lowest quartile. There was a positive correlation between a high number of ascertained risk factors and high levels of fasting plasma insulin. CONCLUSION: In clinical practice, knowledge of the close relationship between risk-factor cluster status and fasting plasma insulin levels offers a tool to evaluate the occurrence of hyperinsulinemia in middle-aged hypertensive men and women.     

Declining gonadal function in elderly men

Ageing in men is accompanied by a progressive decline of gonadal function with, in particular, a decline of total and free testosterone (T) plasma levels resulting in a significant proportion of elderly men over age 60 years presenting with subnormal T levels compared with the levels in young adults. A great interindividual variation in T levels is observed in elderly men, a variability explained in part by physiological variables and differences in life style, while associated acute or chronic diseases may accentuate the age-related decline of T levels. The progressive decrease of plasma T levels has been shown to result from both primary testicular changes and altered neuroendocrine regulation of Leydig cell function. At present, little is known about the clinical relevance of the relative hypoandrogenism of elderly men and there is an urgent need for more longitudinal studies, which may clarify a possible role of decreased T levels in the modulation of the clinical consequences of ageing in men. In view of the lack of relevant controlled clinical trials having careful assessment of the risks and benefits of androgen replacement therapy in elderly men, this treatment should be reserved for selected patients with clinically and biochemically manifest hypogonadism, after careful screening for contraindications.     

LDL-unbound apolipoprotein(a) and carotid atherosclerosis in hemodialysis patients

High lipoprotein(a) [Lp(a)] plasma concentrations, which are genetically determined by apo(a) size polymorphism, are directly associated with an increased risk for atherosclerosis. Patients with end-stage renal disease (ESRD), who show an enormous prevalence of cardiovascular disease, have elevated plasma concentrations of Lp(a). In recent studies we were able to show that apo(a) size polymorphism is a better predictor for carotid atherosclerosis and coronary artery disease in hemodialysis patients than concentrations of Lp(a) and other lipoproteins. Less than 5% of apo(a) in plasma exists in a low-density lipoprotein (LDL)-unbound form. This "free" apo(a) consists mainly of disintegrated apo(a) molecules of different molecular weight, ranging from about 125 to 360 kDa. LDL-unbound apo(a) molecules are elevated in patients with ESRD. The aim of this study was therefore to investigate whether the LDL-unbound form of apo(a) contributes to the prediction of carotid atherosclerosis in a group of 153 hemodialysis patients. The absolute amount of LDL-unbound apo(a) showed a trend to increasing values with the degree of carotid atherosclerosis, but the correlation of Lp(a) plasma concentrations with atherosclerosis was more pronounced. In multivariate analysis the two variables were related to neither the presence nor the degree of atherosclerosis. Instead, the apo(a) phenotype took the place of Lp(a) and LDL-unbound apo(a). After adjustment for other variables, the odds ratio for carotid atherosclerosis in patients with a low molecular weight apo(a) phenotype was about 5 (p<0.01). This indicates a strong association between the apo(a) phenotype and the prevalence of carotid atherosclerosis. Finally, multivariate regression analysis revealed age, angina pectoris and the apo(a) phenotype as the only significant predictors of the degree of atherosclerosis in these patients. In summary, it seems that LDL-unbound apo(a) levels do not contribute to the prediction of carotid atherosclerosis in hemodialysis patients. However, this does not mean that "free", mainly disintegrated, apo(a) has no atherogenic potential.