Effect of insulin treatment on plasma oxidized LDL/LDL-cholesterol ratio in type 2 diabetic patients.

OBJECTIVE: In type 2 diabetes mellitus, oxidized LDL/LDL-Cholesterol ratio, an accurate estimation of in vivo LDL oxidation, has been reported elevated and associated with macrovascular disease. Because insulin therapy induces significant modification of lipid metabolism, in type 2 diabetes, we evaluated the effect of insulin treatment on oxidized LDL/LDL-C ratio in type 2 diabetic patients and analyzed the results in comparison with the modifications induced by insulin on glycaemia, plasma lipids and LDL receptors. RESEARCH DESIGN AND METHODS: Plasma oxidized LDL concentrations were measured by sandwich ELISA in 21 type 2 diabetic patients before and 3 months after the introduction of insulin therapy, and in 27 age-matched controls. RESULTS: Type 2 diabetic patients had, compared to controls, significantly increased oxidized LDL/LDL-C ratio (P<0.0001). Three months after insulin treatment, oxidized LDL/LDL-C ratio was significantly reduced (21.1+/-4.7 vs. 24.0+/-5.8 U/mmol, P<0.01). This reduction was strongly associated, in multivariate analysis, with reduction of LDL(TG/cholesterol ratio) (P=0.008), and to a lesser extent with the decrease of LDL fructosamine (P=0.034), but not with the increase of the number of LDL receptors. CONCLUSIONS: In the present study we demonstrate for the first time a lowering effect of insulin therapy on oxidized LDL/LDL-C ratio in type 2 diabetic patients. This decrease is mainly associated with the reduction of LDL TG-enrichment, and to a lesser extent with the decrease of LDL glycation, but not with the insulin-induced increase in number of LDL receptors.

Potential influence of Type A personality on plasma C-reactive protein levels in people with diabetes.

AIM: Type A personality, although classically known as a factor linked to increased vascular risk, has recently been associated with increased survival in patients with diabetes. As low-grade inflammation predicts a poor outcome, the present study explored the potential associations between Type A and plasma levels of C-reactive protein (CRP) in diabetes. METHODS: Type A personality was assessed by the Bortner questionnaire in people with diabetes. The association between Type A and plasma CRP levels was examined by multivariable linear regression, and structural equation modelling (SEM) was performed to determine the impact of the major clinical, biological and psychological confounders. RESULTS: The study included 626 participants with type 1 and type 2 diabetes from the Diabetes and Psychological Profile study. Multivariable analyses showed an independent inverse association between Type A score and CRP levels. The structural model adjusted for age, gender, diabetes type and duration, body mass index (BMI), smoking status, alcohol abuse, oral antidiabetic and statin treatments, HbA1c levels, lipids, perceived stress, anxiety and depression revealed significant associations between CRP and Type A (ß=-0.135, 95% CI: -0.242, -0.028; P=0.014), BMI (ß=0.194, 95% CI: 0.038, 0.350; P=0.015) and HDL cholesterol (ß=-0.132, 95% CI: -0.245, -0.020; P=0.014). CONCLUSION: Our present study data indicate that Type A personality is independently associated with lower CRP levels. This lower level of inflammation might explain the better clinical outcomes associated with Type A personality in patients with diabetes.

Macrovascular disease is associated with increased plasma apolipoprotein A-IV levels in NIDDM.

Apolipoprotein A-IV (apoA-IV) might play an important role in lipoprotein metabolism, including modulation of triglyceride-rich lipoprotein catabolism, reverse cholesterol transport and cholesteryl ester transfer protein (CETP) activity. Increased apoA-IV levels have been reported in plasma from NIDDM patients. The aim of the present study was to look for a possible association between plasma apoA-IV level and prevalence of macrovascular disease in NIDDM. One hundred and thirty-six NIDDM patients were studied (71 men, 65 women). Macrovascular disease was assessed in each patient by a standardized questionnaire, physical examination, resting electrocardiogram (ECG), and laboratory evaluation (ankle/arm blood pressure ratio, continuous wave Doppler velocimetry). Moreover, patients without any history of coronary heart disease and showing a normal resting ECG underwent a bicycle exercise test or a dipyridamole thallium scintigraphy to detect possible silent myocardial ischemia. Among the 136 NIDDM patients, 56 had macrovascular disease. ApoA-IV levels were significantly higher in NIDDM patients with macrovascular disease than in NIDDM patients without macrovascular disease (20.9 +/- 8.6 vs. 13.3 +/- 5.3 mg/dl; P < 0.001). The influence of different factors, such as age, BMI, cigarette smoking, hypertension, total cholesterol, triglycerides, HDL cholesterol, apoA-IV level, apoA-IV phenotype, fasting glycemia, fasting C-peptide, and microalbuminuria, on the prevalence of macrovascular disease was analyzed using a logistic regression model. In the univariate analysis, apoA-IV level (P < 0.00001), age (P = 0.0087), hypertension (P = 0.012), microalbuminuria (P = 0.018), triglycerides (P = 0.02), and fasting C-peptide (P = 0.03) were positively associated with macrovascular disease. In the multivariate analysis, macrovascular disease was positively associated only with apoA-IV (P < 0.0001) and age (P = 0.003) and negatively associated with HDL cholesterol (P = 0.013). These results indicate that increased plasma apoA-IV level is associated with an increased prevalence of macrovascular disease in NIDDM. Moreover, apoA-IV, in NIDDM patients, appears to be a better marker for macrovascular disease than triglycerides.

A long-term follow-up of male alcohol abuse.

BACKGROUND: This study attempted to determine the course of male alcohol abuse from the age of 40 years to 60 or 70 years, to estimate the duration of abstinence required for stable remission and to study the hypothesis of progression of symptoms in chronic alcohol abuse. METHODS: The subjects were 268 former Harvard University (Cambridge, Mass) undergraduates (college sample) and 456 nondelinquent inner-city adolescents (core city sample) who had been repeatedly studied in multidisciplinary fashion since 1940. Since 47 years of age, these men have been followed up biennially by questionnaire and every 5 years by physical examination. At some point during their lives, 55 (21%) of the college and 150 (33%) of the core city men met DSM-III criteria for alcohol abuse. The college cohort has been followed until the age of 70 years, the core city cohort until age 60 years. The dependent variables were mortality and alcohol abuse status every 5 years. RESULTS: By 60 years of age, 18% of the college alcohol abusers had died, 11% were abstinent, 11% were controlled drinkers, and 59% were known to be still abusing alcohol. By 60 years of age, 28% of the core city alcohol abusers had died, 30% were abstinent, 11% were controlled drinkers, and only 28% were known to be still abusing alcohol. CONCLUSIONS: In three respects the two socially divergent samples resembled each other. After abstinence had been maintained for 5 years, relapse was rare. In contrast, return to controlled drinking without eventual relapse was unlikely. Alcohol abuse could continue for decades without remission or progression of symptoms. The samples differed in that the core city men began to abuse alcohol when younger and, although they were more likely than the college men to become alcohol dependent, the core city men were twice as likely to achieve stable abstinence.

Sociopathy as a human process. A viewpoint.

Case histories of narcotic addicts who also were imprisoned for felony were selected to illustrate some underlying dynamics of Cleckley's so-called psychopath and some principles useful in their management. Often in outpatient settings, such individuals seem to be without anxiety, unable to experience depression, and without motivation for recovery; but in inpatient settings, such deficits appear illusory. Once such chronically sociopathic individuals are prevented from 'running' their resemblance to individuals with severe but thoroughly 'human' and comprehensible personality disorders becomes evident. In treatment, external controls are important. It is vital both to appreciate the contagion of the psychopath's invisible anxiety and to provide such individuals with alternative defenses with which to mitagate their depression. Finally sociopaths must be realistically, but not puntively, confronted with consequences of their behavior.

Natural history of male psychological health. III. Empirical dimensions of mental health.

In a nonpatient polulation, the concept of mental health was operationally defined both in terms of behavior and of abstract psychological functioning. Ninety-five college sophomores, selected for psychological health, were prospectively followed up for 30 years. They were assessed by independent raters on a scale reflecting objectively defined healthy adult adjustment; on a scale of clinically defined psychiatric illness; and on a scale of maturity of ego defenses. These three scales were highly correlated. It seemed likely that relatively objective items like length of vacation, divorce, heavy use of mood-altering drugs, career dissatisfaction, and visits to medical physicians can--as a cluster--statistically identify the abstract concept of mental health.

Natural history of male psychological health. V. The relation of choice of ego mechanisms of defense to adult adjustment.

Ninety-five men, selected in college on the basis of health have been prospectively followed up for 30 years. Their adaptive styles have been isolated, labeled by the ego mechanisms of defense that their behavior reflects, and studied by semiquantitative techniques. A hierarchy of ego mechanisms was devised that ordered defenses along a continuum that reflected the following two dimensions: (1) immaturity-maturity and (2) psychopathology-mental health. The most important finding was that despite blind assessment, a scale reflecting the maturity of a subject's defenses correlated with scales measuring his objective psychopathology (r = -.35) and his objective adaptation to the external environment (r = .65). Highly significant shifts in defensive style occurred as individuals matured. In order to conceptualize the continuum that underlies mental health, identification of a person's dominant defensive styles may be superior to our current scheme of static unitary diagnoses.

Natural history of male alcoholism. IV. Paths to recovery.

Four hundred inner-city men were prospectively studied from age 14 until age 47. Of these men, 110 met our research criteria for alcohol abuse; 49 of them achieved at least a year of abstinence. Paradoxically, stable abstinence was associated with severity of alcohol abuse. Abstinence was also associated with finding substitute dependencies, new relationships, "behavior modification," and religious or Alcoholics Anonymous involvement. Clinic treatment and good premorbid adjustment were not predictive of abstinence. Eighteen men were able to return successfully to problem-free drinking. Such men had previously manifested only a few symptoms of alcohol abuse.

Maturity of ego defenses in relation to DSM-III axis II personality disorder.

Independent raters assessed a cohort of 307 inner-city men on three dimensions of psychosocial dysfunction: the Health-Sickness Rating Scale (HSRS), axis II of DSM-III, and dominant choice of ego mechanisms of defense. Two thirds of the 74 men with personality disorders and three fourths of the 55 men with the low scores (0 to 65) on the HSRS primarily used immature defense mechanisms (ie, projection, schizoid fantasy, passive aggression, dissociation, hypochondriasis, and acting out). Only 10% of men without personality disorders and only 10% of men with HSRS scores of over 70 were noted to favor such defenses.

What is a case? A 45-year study of psychiatric impairment within a college sample selected for mental health.

Six different models for assessing psychiatric impairment were applied to 188 men who had been studied prospectively for half a century. The six models were categorical DSM-III diagnosis by a senior psychiatrist; objective evidence of impairment in working and loving; relative maturity of ego mechanisms of defense; the Health Sickness Rating Scale; the Global Assessment Scale (Axis V of DSM-III-R); and a "research" scale designed to provide a consensual definition of "caseness." As a test of predictive validity of our impairment measures, assessments before the age of 50 years were used to predict psychosocial adjustment and physical health assessed 15 years later. All six models were highly intercorrelated and proved equally effective in predicting future impairment. Procedures to establish construct validity suggested that the presence of a DSM-III diagnosis was a valid categorical definition of case, and that Axis V of DSM-III-R was a valid dimensional measure of impairment.

An empirically validated hierarchy of defense mechanisms.

We empirically examined the validity of ego mechanisms of defense as an explanatory concept for psychological health in 307 middle-aged men who were prospectively followed up for 40 years. Assessed on the basis of a two-hour interview when the men were 47 years old, the maturity (health) of the men's defenses correlated highly with independently assessed outcome measures. Evidence is offered that defensive style provides an independent dimension of mental health. First, childhood variables significantly predicted midlife mental health but not midlife maturity of defenses. Second, the bleaker the childhood the stronger the association of maturity of defenses with adult mental health. Third, the Bond Defense Style Questionnaire, administered to 131 of the 307 men six to eight years after the interview, identified the same styles of defense that were identified earlier by clinical assessment.

An intriguing association between ancestral mortality and male affective disorder.

We examine the relationship between ancestral age at death and affective disorder. A cohort of 204 socioeconomically favored men was selected for mental and physical health 50 years ago and followed up until age 69 +/- 1 (+/- SD) years in an interdisciplinary study. During follow-up, 49 of these men were identified at some point as being psychosocially impaired. Of these 49 men, 25 were identified as having probable affective disorder based on family history of affective illness, clinical signs, subjective symptoms, clinical diagnosis, and choice of pharmacological treatment. Objective signs and symptoms distinguished these 25 men from the remaining 24 men, whose adjustment over the 50 years was equally psychosocially impaired, but who were never noted to be significantly depressed. The mean age at death of the maternal grandfathers for the 25 depressed men was 60.4 years, significantly younger than the mean age at death of maternal grandfathers for either the total sample (70.1 years) or the 25 psychosocially impaired but not depressed men (68.8 years). The mean age at death of the depressed men's other five first-degree ancestors was not significantly different from the age at death of the ancestors of the rest of the sample. If depressed alcohol abusers were excluded, the mean age at death of maternal grandfathers of alcohol abusers did not differ from that of the controls' maternal grandfathers. The evidence for possible X-chromosome linkage in male psychobiological vulnerability to affective spectrum disorder is discussed.

Vulnerability to schizophrenia. Prediction of adult schizophrenia using childhood information.

Forty years ago, Glueck and Glueck studied a group of Boston Inner city children to discover factors relating to delinquency. Detailed information was obtained on 1,000 boys aged 10 to 17 years, 500 "delinquents" and 500 "nondelinquent controls." In follow-up studies of this group, we have found that 24 have a diagnosis of adult schizophrenia. We matched these 24 with 48, who had a nonschizophrenic outcome, on the basis of IQ, ethnicity, age at interview, and original Glueck grouping (delinquent or control). The 72 childhood records were then examined on a blind basis by Independent raters looking for predetermined "indicators of vulnerability to schizophrenia." The total indicator scores were able to differentiate schizophrenic outcome from nonschizophrenic outcome at highly significant levels. A number of the individual indicators were likewise able to predict outcome. Prediction was improved when subjects with the lowest IQs (less than 85) were excluded from consideration.

Apolipoprotein A-IV levels and phenotype distribution in NIDDM.

OBJECTIVE: To determine plasma apolipoprotein A-IV (apoA-IV) levels and phenotype distribution in non-insulin-dependent diabetes mellitus (NIDDM) patients and to analyze the influence of apoA-IV phenotype on lipid profiles in NIDDM. RESEARCH DESIGN AND METHODS: Total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, HDL3 cholesterol, free fatty acid, and apoA-IV levels were measured in 83 NIDDM patients and 100 normal control subjects. The apoA-IV phenotype was determined in each individual. RESULTS: In both sexes, NIDDM patients had significantly higher levels of triglyceride and free fatty acid and significantly lower levels of HDL cholesterol and HDL2 cholesterol than control subjects. In men and women, apoA-IV levels were significantly higher in diabetic patients than in control subjects (men: 17.1 +/- 7.9 vs. 12.3 +/- 3.6 mg/dl, P < 0.001; women: 18.9 +/- 9.9 vs. 11.9 +/- 3.5 mg/dl, P < 0.001). The multiple regression analysis showed that the apoA-IV level in NIDDM patients was significantly and independently related to log triglyceride (P = 0.0001) and HDL cholesterol (P = 0.01) levels. The apoA-IV phenotype distribution was not significantly different between NIDDM patients and control subjects. In the control subjects, the apoA-IV-1-2 phenotype was associated with significantly higher levels of HDL cholesterol (69 +/- 12 vs. 56 +/- 11 mg/dl, P < 0.01) and of HDL2 cholesterol (36 +/- 15 vs. 25 +/- 12 mg/dl, P < 0.05) compared with the apoA-IV-1-1 phenotype; on the other hand, HDL cholesterol and HDL2 cholesterol levels were not different between the two apoA-IV phenotypes in NIDDM patients. CONCLUSIONS: Plasma apoA-IV levels are increased in NIDDM patients. This increase in apoA-IV is related mainly to hypertriglyceridemia and, to a lesser extent, to HDL cholesterol level. The apoA-IV phenotype distribution is not different between NIDDM patients and nondiabetic control subjects. The potential protective lipid profile (characterized by increased HDL and HDL2 cholesterol levels) linked with apoA-IV-1-2 phenotype in control subjects is no longer found in NIDDM patients. We suggest that the metabolic state of NIDDM has erased the potential protective lipid profile associated with the apoA-IV-1-2 phenotype.

Natural history of male psychological health: VIII. Antecedents of alcololism and "orality".

The author reports a prospective study of the mental health and alcohol use of 184 men first studied during their college years. When the men were 50 years old a rater blind to all other data classified the subjects' alcohol use as little (N = 48), social (N = 110), or abuse (N = 26). The warmth of the men's childhood environment and their personality stability in college were assessed by other raters blind to data on subjects' lives after college. Vignettes identifying "oral" adult behavior (pessimism, self-doubt, passivity, and dependence) were collected for each man by a rater blind to subjects' alcohol use and childhood ratings. Poor childhood, personality instability in college, and adult evidence of personality disorder were correlated with oral-dependent behavior but not with alcohol abuse. The 26 problem drinkers seem to have been depressed and unable to cope as a consequence--not a cause--of their inability to control their alcohol consumption.

Natural history of male psychological health, XIV: Relationship of mood disorder vulnerability to physical health.

OBJECTIVE: A 55-year prospective study attempted to determine the antecedents and consequences of positive mental and physical health in adult men. A substudy was conducted to look at the late-life physical health of men selected to be as unlike men with major depressive disorder as possible. METHOD: Of 237 men selected for health and followed since college, 64 undistressed men had never used mood-altering drugs or consulted a psychiatrist before the age of 50. The health at age 70 of these 64 men was compared with that of 20 men classified as depressed at age 70, 109 men classified as neither healthy nor depressed at age 70, and 44 men classified as having alcohol dependence or abuse at age 70. RESULTS: At age 70, the 64 undistressed men enjoyed significantly better health than the 109 men in the intermediate group. Only three (5%) of the 64 undistressed men were dead or disabled by age 70, compared with 30 (28%) of the 109 men in the intermediate group and nine (45%) of the 20 depressed men. The mean age of the subjects' maternal grandfathers at death also significantly differentiated the three groups. The differences in longevity among the three groups could not be explained by personality disorder, by cigarette, dietary, or alcohol abuse, or by longevity of the subjects' other first-degree ancestors. CONCLUSIONS: These findings lend support to the hypothesis that risk of affective disorder may lie along a continuum. At one extreme may be men with stable lifestyles, a lifelong resistance to mood disorder, and unusually good physical health in late life. At the other extreme of the continuum may be men with vulnerability to mood disorder and accelerated physical aging.

Natural history of male psychological health: VI. Correlates of successful marriage and fatherhood.

The author examines the relationship between quality of object relations and health on the basis of data from a prospective 35-year follow-up of 95 men selected for health. Judges blind to other data made independent ratings of physical health at 52, childhood environment, psychopathology, and maturity of defenses. These ratings were highly correlated with independent ratings of high school social adjustment, adult friendship patterns, marital satisfaction, and outcome of children. The author speculates that the capacity for object relations may be a relatively stable dimension of adult personality--a continous that stretches from mature, generative mental health to schizophrenia.

Natural history of male psychological health. XI: Escape from the underclass.

A long-term prospective study of 456 inner-city men tested the hypothesis that extreme poverty and chaotic family life produce a self-perpetuating underclass. Men from chronically dependent and multiproblem families were on average indistinguishable by midlife from the children of more stable working-class families in terms of mean income, years of employment, criminality, and mental health. Although attained social class was somewhat lower for the disadvantaged, given the opportunity for steady employment and occupational mobility, the children from multiproblem welfare families did not inevitably perpetuate their initial disadvantages.

Natural history of male psychological health, X: Work as a predictor of positive mental health.

A sample of 456 inner city men was prospectively followed from age 14 until age 47. Rates blind to adult outcome assessed the men's childhood success at tasks reflecting Erikson's fourth developmental stage, industry versus inferiority. Childhood assessments were made on the parenting the men received and other psychosocial variables, including social class and IQ, and were compared with independent judgments of these men's mental health and career success at age 47. Capacity to work in childhood predicted the success of these underprivileged men at work in adult life and surpassed social class, multiproblem-family membership, and all other childhood variables in predicting adult mental health and capacity for interpersonal relationships.

A validity study of axis II of DSM-III.

The authors examine DSM-III personality disorders in a longitudinally followed community sample of middle-aged inner city men. Eighty-six (23%) of the subjects received an axis II diagnosis of personality disorder. Although these men received relatively little psychiatric attention, they were severely impaired in terms of how they felt about themselves, how others saw their global mental health, and their ability to work and to love. When the strong overlap with alcoholism was controlled for, personality disorder was clearly related to adaptive problems that manifested by early adolescence. The evidence suggests that early deficiencies of biology, environmental support, and ego strength contribute to the development of personality disorder.