Monozygotic twins concordant for Kleine-Levin syndrome

ABSTRACT: BACKGROUND: Kleine-Levin syndrome is a rare idiopathic form of episodic hypersomnia that typically occurs during adolescence. The cardinal clinical features are recurrent hypersomnia, accompanied by cognitive disturbances and behavioral abnormalities [1]. The most typical form of classical Kleine-Levin syndrome is associated with hyperphagia [2, 3], although hyperphagia is now optional after change of the criteria. Hypersexuality, behavioral disinhibition, delusions, autonomic alteration and hallucinations have also been described, but the patients show normal cognitive function and behavior between attacks. The pathogenesis of Kleine-Levin syndrome is not yet known. Although most cases of recurrent hypersomnia are sporadic, the occurrence of nine familial cases indicate that there may be a genetic predisposition to the syndrome [4-8] However, no cases of twins affected with Kleine-Levin syndrome have been reported [9]. In this case study we describe monozygotic twins suffering from the syndrome. This is the first case report describing twins affected with Kleine-Levin syndrome thereby supporting the theory that there is an underlying genetic predisposition to the syndrome.     

A Contribution to the Problem of Systematized Delusions in Adolescents

As we know, rigorously systematized delusions of long duration are very rarely seen in children and adolescents. Sander (1) held that "original paranoia" may begin in early childhood. Krafft-Ebing (2) believed that "hereditary primary insanity," as distinguished from its late form, is encountered only in predisposed children— weak-willed, hypochondriac, pathologically quick to take offense — and is manifested in delusions of grandeur and ideas of reference and of special significance. G. E. Sukhareva, (3) describing systematized delusions in schizophrenic adolescents, expresses the opinion that within the framework of schizophrenia, such delusions occur primarily in psychopathic adolescents with schizoid traits: dominating, suspicious and inclined to fantasy. Stable delusions and delusive ideas against the background of a schizophrenic process in adolescents have also been described by certain other authors. (4-8)     

Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe Chronic Central Post-Stroke Pain Patient: A Case Study

Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient’s left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20), in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions.     

La psychose hallucinatoire chronique doit-elle disparaître ? Une revue historique

At the beginning of the 19th century, while the semiology of hallucinations was being identified for the first time (Esquirol, 1817; Baillarger, 1856), a number of French alienists isolated partial delusions which are characterized by disorders of perception: “folie sensoriale” (Lélut, 1836), “monomanie sensoriale” (Aubanel, Calmeil, 1839), “délire des sensations” (Michéa, 1851). Others authors pointed that hallucinations were the main symptom of monomanias and mystic delusions (Brierre de Boismont, 1845; Baillarger, 1856). In 1882, Magnan introduces the concept of chronic delusion. But as most studies of the time were focused on degeneracy, it was not until the end of the century that persecutory delusions of a hallucinatory nature were distinguished from those of a “reasoning” or “combinatory” nature (Falret, 1878; Mendel, 1883; Sérieux, 1890). Between 1892 and 1900, J. Séglas, physician of the Salpêtrière hospital in Paris, was able to differentiate between hallucinatory patients with sensory and motor dysfunctions, in analogy with aphasias. The latter, also called “persécutés-possédés”, present delusions of being controlled and thought broadcasting (depersonalization). On the other hand, Chronic Hallucinatory Psychosis (CHP) was used initially to identify patients suffering from hallucinations without delusion or hallucinosis (Séglas and Cotard, 1908; Dide and Gassiot, 1910). In 1911 and then 1913, G. Ballet first used the term in its present French meaning to refer to Séglas’ patients with persecutory delusions of a hallucinatory nature. Séglas’ pupils then describe “influence psychosis” (Lévy-Darras, 1914; Ceillier, 1924), less famous nowadays than the “psychosis based on mental automatism” (G. de Clérambault, 1920-1926). In the 1930s, students of H. Claude at Sainte-Anne hospital criticize the concept of CHP (Ey, Nodet), because of the prevalence of delusional ideas on perceptive disorders. After 1945, most semiology of hallucinations is integrated into the “first rank symptoms” of schizophrenia by K. Schneider. Although it has not been retained by DSM-IV and ICD-10, French CHP could be integrated as a syndromic form into late-onset schizophrenia.     

Nuclear volume and total optical density in Down syndrome

OBJECTIVE: To estimate nuclear size and integrated optical density of parenchymal cells from various organs in patients with Down syndrome and a control group. STUDY DESIGN: During the years 1988-2000, 14 cases of Down syndrome were found (8 male and 6 female). Ten infants without congenital anomalies died of respiratory distress syndrome and were used as a control group. Five nuclear variables were estimated: area, equivalent diameter, volume of equivalent sphere, roundness and total optical density (TOD). RESULTS: Mean nuclear volume and TOD of thyroid follicular cells were significantly lower in patients with Down syndrome (43.82 +/- 8.95 and 173.81 +/- 32.85 microns 3, respectively) than in the control group (65.46 +/- 15.31 and 234.58 +/- 32.85 microns 3, respectively) (P < .01). Mean hepatocite nuclear volume and TOD were significantly higher in the control group (165.54 +/- 55.42 and 220.84 +/- 51.75 microns 3, respectively) than in trisomy 21 (110.39 +/- 32.97 and 176.58 +/- 28.53 microns 3, respectively) (P < .05). CONCLUSION: The present results suggest altered gene expression in excessive genetic material, especially in thyroid follicular cells.     

Phenomenological and neurocognitive perspectives on delusions: A critical overview

There is considerable overlap between phenomenological and neurocognitive perspectives on delusions. In this paper, we first review major phenomenological accounts of delusions, beginning with Jaspers’ ideas regarding incomprehensibility, delusional mood, and disturbed “cogito” (basic, minimal, or core self‐experience) in what he termed “delusion proper” in schizophrenia. Then we discuss later studies of decontextualization and delusional mood by Matussek, changes in self and world in delusion formation according to Conrad's notions of “apophany” and “anastrophe”, and the implications of ontological transformations in the felt sense of reality in some delusions. Next we consider consistencies between: a) phenomenological models stressing minimal‐self (ipseity) disturbance and hyperreflexivity in schizophrenia, and b) recent neurocognitive models of delusions emphasizing salience dysregulation and prediction error. We voice reservations about homogenizing tendencies in neurocognitive explanations of delusions (the “paranoia paradigm”), given experiential variations in states of delusion. In particular we consider shortcomings of assuming that delusions necessarily or always involve “mistaken beliefs” concerning objective facts about the world. Finally, we offer some suggestions regarding possible neurocognitive factors. Current models that stress hypersalience (banal stimuli experienced as strange) might benefit from considering the potential role of hyposalience in delusion formation. Hyposalience – associated with experiencing the strange as if it were banal, and perhaps with activation of the default mode network – may underlie a kind of delusional derealization and an “anything goes” attitude. Such an attitude would be conducive to delusion formation, yet differs significantly from the hypersalience emphasized in current neurocognitive theories.     

Symptoms of schizophrenia in Hispanic and Anglo veterans

This study explores cultural influences on symptoms and course of schizophrenic disorder. Hispanic veterans with schizophrenia are compared to a similar group of White non-Hispanic (Anglo) veterans. Symptoms were elicited with a structured diagnostic interview and a battery of rating instruments. Primary symptoms of schizophrenia (e.g., hallucinations, delusions, functional deterioration) were very similar for both groups. However, Hispanic patients reported a later age of onset, exhibited more somatization, and spent less time in the hospital than Anglo patients.This study was supported by a grant from the Veterans Administration Health Services Research and Development Service (Project 11R 81-633).     

The neural basis of hallucinations and delusions

Schizophrenia is a biologically based disorder characterised by false perceptions (hallucinations) and false beliefs (delusions). The underlying physiological cause of these mental abnormalities remains unknown. There is increasing evidence that one class of symptom, the 'made experiences' including delusions of alien control and thought insertion, is associated with abnormalities in the mechanism that predicts the outcome of intended actions (the forward model). For these patients active movements feel like passive movements. As a result these patients do not feel in control of their actions. However, comparison with various neurological disorders, such as those associated with parietal lobe lesions, suggest that this abnormal experience is not sufficient to explain the feeling that some other agent is controlling is one's actions. Preliminary evidence suggests that patients with schizophrenia have an exaggerated sense of agency. In combination with the feeling of not being in control, this exaggerated sense of agency could explain delusions of alien control in which the patient attributes his own actions to another agent. Little is yet know about the neural basis of the predictive mechanisms that create the feeling that we are in control of our movements. Such prediction requires integration of information about intended movements generated in frontal cortex with sensory processing in posterior regions of the brain. Measures of functional connectivity suggest that long-range interactions between frontal and posterior regions are abnormally reduced in patients with schizophrenia. Further research is needed to explore the precise involvement of long-range connections in the mechanisms of forward modelling.     

Adults with a history of child sexual abuse: evaluation of a pilot therapy service.

OBJECTIVE--To evaluate a pilot service offering therapy specifically to adults with a history of child sexual abuse. DESIGN--Questionnaire survey. SETTING--Specialised therapy unit, Breakfree, which offers care, therapy, and support. SUBJECTS--116 clients presenting to the service who were offered therapy. MAIN OUTCOME MEASURES--Scores from three psychological questionnaires--the social activities and distress scale, the general health questionnaire, and the delusions, symptoms, and states inventory--and from questionnaires about the clients'' abuse, previous use of health services, and opinion of the Breakfree service. RESULTS--Clients had received previous help from health services and other agencies without apparent effect; they were highly distressed according to their psychological scores; and they were very frequent users of the health services. The clients showed significant improvement in their psychological scores (Wilcoxon''s matched pairs signed ranks test): social activities and distress scale, z = -3.3, P = 0.001; general health questionnaire, z = -5.8, P < 0.00001; delusions, symptoms, and states inventory, z = -4.8, P < 0.00001). This was most pronounced for those who had completed therapy by the end of the study. Whereas 82/88 clients had a score for the general health questionnaire that indicated clinical distress at the start, only 28/58 did so at the end of the study (only 17/35 among those who had finished therapy). CONCLUSIONS--This group of adults with a history of child sexual abuse were highly disturbed and previous high users of the health service. The specialist service Breakfree was effective in the short term and, if the benefits are sustained, would yield a net cost saving to the health service.     

Persecutory delusions: reminiscence of ancestral hostile threats?

Recent studies suggest that both the form and the content of persecutory delusional beliefs may reflect pathological exaggerations of evolved psychological mechanisms for dealing with social threat recognition. Here, we tested the hypothesis first put forward by Walston et al. [Evolution and Human Behavior 19 (1998) 257–260] that sex differences in the content of persecutory delusions reflect divergent ancestral hostile social threats, in a prospective study of two samples of German and Russian patients with delusions of persecution. Deluded men and women differed significantly in their attributions of perceived threats. The majority of men felt persecuted by groups of hostile strange males, whereas women projected their paranoid fears onto familiar people of their social environment, largely irrespective of psychiatric diagnosis or cultural background. In contrast to our predictions, however, both men and women with persecutory delusions were most frightened of physical violence. Fear of sexual coercion was only present in a small number of patients. In sum, this study is largely supportive of the hypothesis that the content of persecutory delusions reflects ancestral hostile threats.     

Gender differences in psychotic bipolar mania

Objective: This study examined gender differences in the prevalence and types of psychotic symptoms in bipolar mania.Methods: Participants were drawn from consecutive admissions to the psychiatric clinic in Chemnitz, Germany, in 2005. The diagnosis of bipolar disorder, manic episode was made within 24 hours of admission, and the severity of mania was assessed using the Young Mania Rating Scale (YMRS) and the German version of the Altman Self-Rating Mania Scale. Data collected for each patient included age at the onset of bipolar illness, number of previous episodes, social functioning between episodes, and duration of hospitalization for the index episode. Based on the Task Force for Methods and Documentation in Psychiatry system, psychotic symptoms were classified as hallucinations (visual, auditory, olfactory, tactile, acousma, somatic); delusions (paranoid, reference, guilt, grandeur, religious, erotomania, hypochondriac, poverty, jealousy); and ego disorder (thought control, thought broadcasting).Results: One hundred thirty-seven women and 109 men met the criteria for an acute manic episode, of whom 93 women and 62 men had psychotic symptoms. Compared with psychotic men, psychotic women had more delusions and hallucinations, both overall and per patient, and more delusions of reference and paranoid delusions. Psychotic women had more mixed states compared with psychotic men. Psychotic women differed from both psychotic men and nonpsychotic women on a number of clinical and social variables: they had higher YMRS scores and more previous episodes of depression despite an earlier onset of illness.Conclusion: Women with bipolar mania exhibited a specific pattern of psychotic symptoms that appeared to be associated with greater severity of the acute episode, more mixed states, and a more severe course of illness.     

Metabolic Syndrome and Breast Cancer Risk: A Case-Cohort Study Nested in a Multicentre Italian Cohort

Background

Metabolic syndrome (defined as at least three among abdominal obesity, high blood triglycerides, low high-density lipoprotein cholesterol, high blood glucose, and high blood pressure) is emerging as a risk factor for breast cancer; however few studies – most confined to postmenopausal women – have investigated associations between breast cancer risk and metabolic syndrome. The purpose of this study was to examine the association between metabolic syndrome and its components, and risk of breast cancer in postmenopausal and premenopausal women.

Methods

We performed a case-cohort study on 22,494 women recruited in 1993-1998 to four Italian centres (Turin, Varese, Naples, Ragusa) of the European Prospective Investigation into Cancer and Nutrition (EPIC) and followed-up for up to 15 years. A random subcohort of 565 women was obtained and 593 breast cancer cases were diagnosed. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Prentice-weighted Cox proportional hazards models.

Results

Presence of metabolic syndrome was associated with significantly increased breast cancer risk in all women (HR 1.52, 95%CI 1.14-2.02). When the analyses were repeated separately for menopausal status, the association was limited to postmenopausal women (HR 1.80, 95%CI 1.22-2.65) and absent in premenopausal women (HR 0.71, 95%CI 0.43-1.16); P for interaction between metabolic syndrome and menopausal status was 0.001. Of metabolic syndrome components, only high blood glucose was significantly associated with increased breast cancer risk in all women (HR 1.47, 95%CI 1.13-1.91) and postmenopausal women (HR 1.89, 95%CI 1.29-2.77), but not premenopausal women (HR 0.80, 95%CI 0.52-1.22; P interaction=0.004).

Conclusions

These findings support previous data indicating that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women, but not in premenopausal women, and suggest that prevention of metabolic syndrome through lifestyle changes could confer protection against breast cancer.     

Work-Related Psychological Injury Is Associated with Metabolic Syndrome Components in Apparently Healthy Workers

Objective

The aim of this study was to evaluate the association between psychological damage caused by common occupational trauma and metabolic syndrome (MES).

Method

571 workers from 20 small Italian companies were invited to fill in the Psychological Injury Risk Indicator (PIRI) during their routine medical examination at the workplace.

Results

Compared to workers with no psychological injury, workers with a high PIRI score had a significantly increased risk of having at least one metabolic syndrome component (adjusted hazards ratio, 1.8; 95% confidence interval, 1.2 to 2.6). There was a significant increase in the risk of hypertriglyceridemia in male workers (OR 2.53 CI95% 1.03-6.22), and of hypertension in female workers (OR 2.45 CI95% 1.29-4.66).

Conclusion

Psychological injury related to common occupational trauma may be a modifiable risk factor for metabolic syndrome.     

Higher Gravidity and Parity Are Associated with Increased Prevalence of Metabolic Syndrome among Rural Bangladeshi Women

Background

Parity increases the risk for coronary heart disease; however, its association with metabolic syndrome among women in low-income countries is still unknown.

Objective

This study investigates the association between parity or gravidity and metabolic syndrome in rural Bangladeshi women.

Methods

A cross-sectional study was conducted in 1,219 women aged 15–75 years from rural Bangladesh. Metabolic syndrome was defined according to the standard NCEP-ATP III criteria. Logistic regression was used to estimate the association between parity and gravidity and metabolic syndrome, with adjustment of potential confounding variables.

Results

Subjects with the highest gravidity (> = 4) had 1.66 times higher odds of having metabolic syndrome compared to those in the lowest gravidity (0-1) (P _trend = 0.02). A similar association was found between parity and metabolic syndrome (P _trend = 0.04), i.e., subjects in the highest parity (> = 4) had 1.65 times higher odds of having metabolic syndrome compared to those in the lowest parity (0-1). This positive association of parity and gravidity with metabolic syndrome was confined to pre-menopausal women (P _trend <0.01). Among the components of metabolic syndrome only high blood pressure showed positive association with parity and gravidity (P _trend = 0.01 and <0.001). Neither Parity nor gravidity was appreciably associated with other components of metabolic syndrome.

Conclusions

Multi parity or gravidity may be a risk factor for metabolic syndrome.     

Reduced Apolipoprotein Glycosylation in Patients with the Metabolic Syndrome

Objective

The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls.

Methods

Very low density (VLDL), intermediate/low density (IDL/LDL, hereafter LDL), and high density lipoproteins (HDL) fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D) gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays.

Results

Metabolic syndrome patients differed from healthy controls in the following ways: (1) total plasma - apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2) VLDL - apoB, apoC3, and apoE were increased; (3) LDL - apoC3 was increased, (4) HDL -associated constitutive serum amyloid A protein (SAA4) was reduced (p<0.05 vs. controls for all). In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated) isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all). Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all). Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001).

Conclusions

Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.     

Alteration of mannose transport in fibroblasts from type I carbohydrate deficient glycoprotein syndrome patients

The aim of the present study was to explore how mannose enters fibroblasts derived from a panel of children suffering from different subtypes of type I carbohydrate deficient glycoprotein syndrome: seven carbohydrate deficient glycoprotein syndrome subtype Ia (phosphomannomutase deficiency), two carbohydrate deficient glycoprotein syndrome subtype Ib (phosphomannose isomerase deficiency) and two carbohydrate deficient glycoprotein syndrome subtype Ix (not identified deficiency). We showed that a specific mannose transport system exists in all the cells tested but has different characteristics with respect to carbohydrate deficient glycoprotein syndrome subtypes. Subtype Ia fibroblasts presented a mannose uptake equivalent or higher (maximum 1.6-fold) than control cells with a D-[2-3H]-mannose incorporation in nascent N-glycoproteins decreased up to 7-fold. Compared to control cells, the mannose uptake was greatly stimulated in subtype Ib (4.0-fold), due to lower Kuptake and higher Vmax values. Subtype Ib cells showed an increased incorporation of D-[2-3H]-mannose into nascent N-glycoproteins. Subtype Ix fibroblasts presented an intermediary status with mannose uptake equivalent to the control but with an increased incorporation of D-[2-3H]-mannose in nascent N-glycoproteins. All together, our results demonstrate quantitative and/or qualitative modifications in mannose transport of all carbohydrate deficient glycoprotein syndrome fibroblasts in comparison to control cells, with a relative homogeneity within a considered subtype of carbohydrate deficient glycoprotein syndrome. These results are consistent with the possible use of mannose as a therapeutic agent in carbohydrate deficient glycoprotein syndrome Ib and Ix.     

More Delusions May Be Observed in Low-Proficient Multilingual Alzheimer’s Disease Patients

Background

Language impairment and behavioral symptoms are both common phenomena in dementia patients. In this study, we investigated the behavioral symptoms in dementia patients with different language backgrounds. Through this, we aimed to propose a possible connection between language and delusion.

Methods

We recruited 21 patients with Alzheimer’s disease (AD), according to the DSM-IV and NINCDS-ADRDA criteria, from the memory clinic of the Cardinal Tien Hospital in Taipei, Taiwan. They were classified into two groups: 11 multilinguals who could speak Japanese, Taiwanese and Mandarin Chinese, and 10 bilinguals who only spoke Taiwanese and Mandarin Chinese. There were no differences between age, education, disease duration, disease severity, environment and medical care between these two groups. Comprehensive neuropsychological examinations, including Clinical Dementia Rating (CDR), Mini-Mental Status Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), Verbal fluency, Chinese version of the Boston naming test (BNT) and the Behavioral Pathology in Alzheimer’s Disease Rating Scale (BEHAVE-AD), were administered.

Results

The multilingual group showed worse results on the Boston naming test. Other neuropsychological tests, including the MMSE, CASI and Verbal fluency, were not significantly different. More delusions were noted in the multilingual group. Three pairs of subjects were identified for further examination of their differences. These three cases presented the typical scenario of how language misunderstanding may cause delusions in multilingual dementia patients. Consequently, more emotion and distorted ideas may be induced in the multilinguals compared with the MMSE-matched controls.

Conclusion

Inappropriate mixing of language or conflict between cognition and emotion may cause more delusions in these multilingual patients. This reminds us that delusion is not a pure biological outcome of brain degeneration. Although the cognitive performance was not significantly different between our groups, language may still affect their delusion.     

Reduced free IGF-I and increased IGFBP-3 proteolysis in Turner syndrome: modulation by female sex steroids

The bioactivity of the growth hormone-insulin-like growth factor (IGF) system is reduced in Turner syndrome and may explain the reduction seen in final height. We compared levels of free and total IGF-I, immunoreactive and Western ligand blot IGF-binding protein (IGFBP)-3, and IGFBP-3 proteolysis in women with Turner syndrome (n = 23) before (T(B)) and during 6 mo treatment with 17beta-estradiol and norethisterone. An age-matched group of controls (n = 24) was included. Total IGF-I and immunoreactive levels of IGFBP-3 were comparable in T(B) and controls, whereas free IGF-I (P = 0.02) in T(B) was less than in controls. Western ligand blotting (WLB)-IGFBP-3 was significantly lower in T(B) than in controls (P = 0.0005). Accordingly, IGFBP-3 proteolysis was greater in Turner syndrome (P = 0.001). Female sex steroid treatment increased WLB-IGFBP-3 (P = 0.0005), whereas immunoreactive IGFBP-3 and IGFBP-3 proteolysis were normalized (P = 0.004). Free IGF-I remained unchanged (P = 0.8), with a tendency toward a decrease in total IGF-I (P = 0.1). In conclusion, despite normal total IGF-I and immunoreactive IGFBP-3, free serum IGF-I is less and IGFBP-3 proteolysis is greater in Turner syndrome than in controls. During sex steroid treatment, IGFBP-3 proteolysis normalized, without any change in free IGF-I.     

Glycated Hemoglobin,Fasting Insulin and the Metabolic Syndrome in Males. Cross-Sectional Analyses of the Aragon Workers’ Health Study Baseline

Background and Aims

Glycated hemoglobin (HbA1c) is currently used to diagnose diabetes mellitus, while insulin has been relegated to research. Both, however, may help understanding the metabolic syndrome and profiling patients. We examined the association of HbA1c and fasting insulin with clustering of metabolic syndrome criteria and insulin resistance as two essential characteristics of the metabolic syndrome.

Methods

We used baseline data from 3200 non-diabetic male participants in the Aragon Workers'' Health Study. We conducted analysis to estimate age-adjusted odds ratios (ORs) across tertiles of HbA1c and insulin. Fasting glucose and Homeostatic model assessment - Insulin Resistance were used as reference. Here we report the uppermost-to-lowest tertile ORs (95%CI).

Results

Mean age (SD) was 48.5 (8.8) years and 23% of participants had metabolic syndrome. The ORs for metabolic syndrome criteria tended to be higher across HbA1c than across glucose, except for high blood pressure. Insulin was associated with the criteria more strongly than HbA1c and similarly to Homeostatic model assessment - Insulin Resistance (HOMA-IR). For metabolic syndrome, the OR of HbA1c was 2.68, of insulin, 11.36, of glucose, 7.03, and of HOMA-IR, 14.40. For the clustering of 2 or more non-glycemic criteria, the OR of HbA1c was 2.10, of insulin, 8.94, of glucose, 1.73, and of HOMA-IR, 7.83. All ORs were statistically significant. The areas under the receiver operating characteristics curves for metabolic syndrome were 0.670 (across HbA1c values) and 0.770 (across insulin values), and, for insulin resistance, 0.647 (HbA1c) and 0.995 (insulin). Among non-metabolic syndrome patients, a small insulin elevation identified risk factor clustering.

Conclusions

HbA1c and specially insulin levels were associated with metabolic syndrome criteria, their clustering, and insulin resistance. Insulin could provide early information in subjects prone to develop metabolic syndrome.     

Insulin resistance syndrome,body mass index and the risk of ischemic heart disease

Background

Many people who are not obese according to standard height and weight criteria may still display features of insulin resistance syndrome and thus be at high risk of ischemic heart disease. We sought to investigate the effect of cumulative features of insulin resistance syndrome on the risk of ischemic heart disease associated with variations in body mass index (BMI) among men who participated in the Québec Cardiovascular Study.

Methods

A cohort of 1824 nondiabetic men free of ischemic heart disease was evaluated at the 1985 baseline evaluation and followed for a period of 13 years, during which 284 first ischemic heart disease events were recorded. Relative hazards (RHs) of ischemic heart disease in 3 BMI groups (normal weight, overweight and obese) were estimated using Cox proportional hazards regression.

Results

Although obese men (BMI ≥ 30 kg/m²) were the most likely to accumulate features of insulin resistance syndrome, the univariate risk of ischemic heart disease in this group was not significantly increased compared with normal-weight men (BMI < 25 kg/m²) (RH 1.26, 95% confidence interval [CI] 0.88–1.80). However, obese men who accumulated more than 4 features of insulin resistance syndrome were at increased risk of ischemic heart disease (RH 1.81, 95% CI 1.02–3.19) compared with normal-weight men who had fewer than 3 features of the syndrome. Conversely, having more than 4 features of insulin resistance syndrome was associated with a 3-fold increase in the risk of ischemic heart disease among normal-weight men (RH 3.01, 95% CI 1.70–5.32).

Interpretation

Although obesity is an important risk factor for ischemic heart disease, variations in BMI alone poorly reflect the risk of ischemic heart disease associated with features of insulin resistance syndrome.In the late 1980s, Gerald Reaven proposed the concept of insulin resistance as the cornerstone of a plurimetabolic syndrome that included hypertriglyceridemia, low plasma high-density lipoprotein cholesterol concentrations, hypertension and hyperinsulinemia.¹ This syndrome has been referred to as syndrome X, insulin resistance syndrome and the metabolic syndrome.² Several other metabolic disturbances, such as an increase in the number of small, dense low-density lipoprotein particles, impaired fibrinolytic activity, a proinflammatory state, impaired postprandial lipoprotein metabolism and abdominal obesity, have been included as part of this syndrome over the years.^3,4Although obesity is an important component of insulin resistance syndrome, many people who are not obese according to standard height and weight criteria (i.e., body mass index [BMI]) may still display features of the syndrome. Indeed, studies have indicated that normal-weight subjects, whose BMI is less than 25 kg/m², may have as much as 40% fat in the abdominal area, a level that correlates closely with decreased insulin sensitivity⁵ and an atherogenic dyslipidemic state. In that context, the risk of ischemic heart disease among normal-weight people with insulin resistance syndrome and among obese people without insulin resistance syndrome represents a major gap in the existing literature. We therefore sought to investigate how features of insulin resistance syndrome affected the risk of ischemic heart disease associated with variations in BMI in a cohort of 1824 men who participated in the Québec Cardiovascular Study.