Epicardial adipose tissue is a predictor of decreased kidney function and coronary artery calcification in youth- and early adult onset type 2 diabetes mellitus.

PURPOSE: To examine the association of epicardial and pericardial fat volume (EFV, PFV) with cardiovascular risk factors and kidney function in Native Americans of southwestern heritage with youth and early adult onset type 2 diabetes mellitus (T2DM) versus healthy controls. METHODS: Using computed tomography, we quantified EFV and PFV in 149 Native Americans (92 women, 57 men), 95 of which had T2DM (38 diagnosed prior to age 20 years). Duration of T2DM, mean carotid arterial mass (AM), coronary artery calcification (CAC), IL-6, and estimated glomerular filtration rate eGFRcr(CKD-EPI) were measured. RESULTS: EFV and PFV were associated with BMI (r = 0.37, p < 0.0001; r = 0.26, p = 0.001) and did not differ between onset age-groups and controls (p > 0.05). EFV was associated with AM only in controls (r = 0.51, p < 0.0001). After adjustment for BMI, T2DM duration, HbA1C, age, and sex, EFV was a predictor of CAC and IL-6 concentrations in early adult onset T2DM (ß = 0.05 ± 0.02 cm3, p = 0.03; ß = 0.05 ± 0.01 pg/ml/cm3, p = 0.002). EFV and PFV were independent predictors of reduced eGFRcr(CKD-EPI) in the youth onset T2DM group (ß = -0.3 ± 0.08 ml/min/cm3, p = 0.001; ß = -0.25 ± 0.05 ml/min/cm3, p < 0.0001). CONCLUSIONS: Epicardial fat volume may be a risk factor for heart disease in individuals with early adult onset T2DM and a predictor of decreased kidney function in individuals with youth onset T2DM.

Changes in glycemia, insulin and gut hormone responses to a slowly ingested solid low-carbohydrate mixed meal after laparoscopic gastric bypass or band surgery.

OBJECTIVE: To evaluate early changes in glycemia, insulin physiology and gut hormone responses to an easily tolerated and slowly ingested solid, low-carbohydrate mixed meal test (MMT) following laparoscopic adjustable gastric banding (LAGB) or Roux-en-Y gastric bypass (RYGB) surgery. SUBJECTS/METHODS: This was a prospective non-randomized study. Plasma glucose, insulin and c-peptide (to estimate hepatic insulin extraction; %HIE), incretins (GIP, aGLP-1) and pancreatic polypeptide (PP) responses to the MMT were measured at 4-8 weeks before and after surgery in obese, metabolically healthy patients (RYGB=10F or LAGB =7F/1M). Supplementary clamp data on basal endogenous glucose production (EGP) and peripheral insulin action (Rd=rate of glucose disposal) and metabolic clearance rates of insulin (MCR-INS) were available in five of the RYGB patients. Repeated measures were appropriately accounted for in the analyses. RESULTS: Following LAGB surgery, C-peptide and insulin MMT profiles (P=0.004 and P=0.0005, respectively) were lower with no change in %HIE (P=0.98). In contrast, in RYGB subjects, both fasting glucose and insulin (Δ=-0.66 mmol l-1, P⩽0.05 and Δ=-44.4 pmol l-1, P⩽0.05, respectively) decreased, and MMT glucose (P<0.0001) and insulin (P=0.001) but not c-peptide (P= 0.69) decreased. Estimated %HIE increased at fasting (Δ=8.4%, P⩽0.05) and during MMT (P=0.0005). Early (0-20 min) prandial glucose (0.27±0.26 versus 0.006±0.21 mmol l-1, P⩽0.05) and insulin (63(48, 66) versus 18(12, 24) pmol l-1, P⩽0.05) responses increased after RYGB. RYGB altered the trajectory of prandial aGLP-1 responses (treatment × trajectory P=0.02), and PP was lower (P<0.0001). Clamp data in a subset of RYGB patients showed early improvement in basal EGP (P=0.001), and MCR-INS (P=0.015). CONCLUSION: RYGB results in distinctly different changes in plasma glucose, insulin and gut hormone response patterns to a solid, slowly ingested low-carbohydrate MMT versus LAGB. Altered nutrient delivery, along with indirect evidence for changes in hepatic and peripheral insulin physiology, are consistent with the greater early improvement in glycemia observed after RYGB versus LAGB surgery.

The impact of genetic variants on BMI increase during childhood versus adulthood.

BACKGROUND: Genetic variants that predispose individuals to obesity may have differing influences during childhood versus adulthood, and additive effects of such variants are likely to occur. Our ongoing studies to identify genetic determinants of obesity in American Indians have identified 67 single-nucleotide polymorphisms (SNPs) that reproducibly associate with maximum lifetime non-diabetic body mass index (BMI). This study aimed to identify when, during the lifetime, these variants have their greatest impact on BMI increase. SUBJECTS/METHODS: A total of 5906 Native Americans of predominantly Pima Indian heritage with repeated measures of BMI between the ages of 5 and 45 years were included in this study. The association between each SNP with the rates of BMI increase during childhood (5-19 years) and adulthood (20-45 years) were assessed separately. The significant SNPs were used to calculate a cumulative allelic risk score (ARS) for childhood and adulthood, respectively, to assess the additive effect of these variants within each period of life. RESULTS: The majority of these SNPs (36 of 67) were associated with rate of BMI increase during childhood (P-value range: 0.00004-0.05), whereas only nine SNPs were associated with rate of BMI change during adulthood (P-value range: 0.002-0.02). These 36 SNPs associated with childhood BMI gain likely had a cumulative effect as a higher childhood-ARS associated with rate of BMI change (ß=0.032 kg m(-2) per year per risk allele, 95% confidence interval: 0.027-0.036, P<0.0001), such that at age 19 years, individuals with the highest number of risk alleles had a BMI of 10.2 kg m(-2) greater than subjects with the lowest number of risk alleles. CONCLUSIONS: Overall, our data indicates that genetic polymorphisms associated with lifetime BMI may influence the rate of BMI increase during different periods in the life course. The majority of these polymorphisms have a larger impact on BMI during childhood, providing further evidence that prevention of obesity will need to begin early in life.

Lower core body temperature and greater body fat are components of a human thrifty phenotype.

BACKGROUND/OBJECTIVES: In small studies, a thrifty human phenotype, defined by a greater 24-hour energy expenditure (EE) decrease with fasting, is associated with less weight loss during caloric restriction. In rodents, models of diet-induced obesity often have a phenotype including a reduced EE and decreased core body temperature. We assessed whether a thrifty human phenotype associates with differences in core body temperature or body composition. SUBJECTS/METHODS: Data for this cross-sectional analysis were obtained from 77 individuals participating in one of two normal physiology studies while housed on our clinical research unit. Twenty-four-hour EE using a whole-room indirect calorimeter and 24-h core body temperature were measured during 24 h each of fasting and 200% overfeeding with a diet consisting of 50% carbohydrates, 20% protein and 30% fat. Body composition was measured by dual X-ray absorptiometry. To account for the effects of body size on EE, changes in EE were expressed as a percentage change from 24-hour EE (%EE) during energy balance. RESULTS: A greater %EE decrease with fasting correlated with a smaller %EE increase with overfeeding (r=0.27, P=0.02). The %EE decrease with fasting was associated with both fat mass and abdominal fat mass, even after accounting for covariates (ß=-0.16 (95% CI: -0.26, -0.06) %EE per kg fat mass, P=0.003; ß=-0.0004 (-0.0007, -0.00004) %EE kg(-1) abdominal fat mass, P=0.03). In men, a greater %EE decrease in response to fasting was associated with a lower 24- h core body temperature, even after adjusting for covariates (ß=1.43 (0.72, 2.15) %EE per 0.1 °C, P=0.0003). CONCLUSIONS: Thrifty individuals, as defined by a larger EE decrease with fasting, were more likely to have greater overall and abdominal adiposity as well as lower core body temperature consistent with a more efficient metabolism.

Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants.

BACKGROUND: In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. OBJECTIVE: The objective of this study is to compare BDNF concentrations of subjects with loss-of-function (LOF) and gain-of-function (GOF) MC4R variants with those of controls with common sequence MC4R. METHODS: Circulating BDNF was measured in two cohorts with known MC4R sequence: 148 subjects of Pima Indian heritage ((mean±s.d.): age, 15.7±6.5 years; body mass index z-scores (BMI-Z), 1.63±1.03) and 69 subjects of Hispanic heritage (10.8±3.6 years; BMI-Z, 1.57±1.07). MC4R variants were characterized in vitro by cell surface expression, receptor binding and cyclic AMP response after agonist administration. BDNF single-nucleotide polymorphisms (SNPs) rs12291186, rs6265 and rs7124442 were also genotyped. RESULTS: In the Pima cohort, no significant differences in serum BDNF was observed for 43 LOF subjects versus 65 LOF-matched controls (age, sex and BMI matched; P=0.29) or 20 GOF subjects versus 20 GOF-matched controls (P=0.40). Serum BDNF was significantly associated with genotype for BDNF rs12291186 (P=0.006) and rs6265 (P=0.009), but not rs7124442 (P=0.99); BDNF SNPs did not interact with MC4R status to predict serum BDNF. In the Hispanic cohort, plasma BDNF was not significantly different among 21 LOF subjects, 20 GOF subjects and 28 controls (P=0.79); plasma BDNF was not predicted by BDNF genotype or BDNF-x-MC4R genotype interaction. CONCLUSIONS: Circulating BDNF concentrations were not significantly associated with MC4R functional status, suggesting that peripheral BDNF does not directly reflect hypothalamic BDNF secretion and/or that MC4R signaling is not a significant regulator of the bulk of BDNF expression in humans.

Couple distress after sudden infant or perinatal death: a 30-month follow up.

OBJECTIVE: To examine, using a 30-month prospective study, patterns of anxiety, depression and alcohol use in couples following stillbirth, neonatal death or sudden infant death syndrome. METHODOLOGY: One hundred and thirty-eight bereaved and 156 non-bereaved couples completed standardized interviews at 2, 8, 15 and 30 months post-loss. RESULTS: At all interviews, bereaved couples were significantly more likely than non-bereaved couples to have at least one distressed partner. Rarely were both partners distressed in either group. For bereaved couples, 'mother only' distress declined from 21% to 10% during the study. 'Father only' distress ranged from 7% to 15%, peaking at 30 months. Bereaved mothers who were distressed at 2 months reported significantly lower marital satisfaction at 30 months. CONCLUSIONS: At the couple level, the experience of a baby's death is multifaceted. Gender differences are common and partners' needs may change over time. Early recognition of these differences may facilitate longer-term adjustment for both partners.

Effects of leptin deficiency and short-term repletion on hepatic gene expression in genetically obese mice.

By supplying most organs of the body with metabolic substrates, the liver plays a central role in maintaining energy balance. Hepatic metabolism of glucose, fatty acids, and lipoproteins is disrupted in the leptin-deficient obese (Lep(ob)/Lep(ob)) mouse, leading to hyperglycemia, steatosis, and hypercholesterolemia. Microarray expression profiles were used to identify transcriptional perturbations that underlie the altered hepatic physiology of Lep(ob)/Lep(ob) mice. A wide variety of genes involved in fatty acid metabolism are altered in expression, which suggests that both fatty acid synthesis and oxidation programs are activated in obese mice. The expression of a small subset of genes is upregulated by leptin deficiency, not modulated by caloric restriction, and markedly suppressed by short-term leptin treatment. Among these leptin-regulated genes, apolipoprotein A-IV is a strong candidate for mediating the atherogenic-resistant phenotype of Lep(ob)/Lep(ob) mice.

Osteoporosis: an unusual presentation of childhood Crohn's disease.

Osteoporosis is known to be associated with Crohn's disease. We report a 12-yr-old boy without a history of steroid use, in whom severe osteoporosis and multiple collapsed vertebrae were the presenting manifestations of Crohn's disease. After treatment of the Crohn's disease, he resumed normal growth and progressed through puberty. Concomitantly, he demonstrated a substantial recovery of vertebral bone mineral density and structure. Possible pathophysiological mechanisms underlying the osteoporosis and the subsequent improvement in bone density are discussed.

'My beloved chloroform'. Attitudes to childbearing in colonial Queensland: a case study.

In 1847 the anaesthetic and analgesic properties of chloroform were discovered. This technology generated a new era for midwifery: mothers could be relieved of pain in childbirth. The introduction of chloroform for childbirth saw increasing medical dominance in obstetrics, traditionally in the hands of the midwife. At the same time the use of chloroform sparked a medical and moral controversy which lasted for several decades. On the one hand women were destined by the 'curse of Eve' to experience pain during childbirth; on the other, medical humanitarians and practitioners believed that there were technical and moral reasons for alleviating pain in childbirth. In concentrating on the debate historians have largely ignored the reactions of mothers to the introduction of the technology. This paper explores changing attitudes to childbearing within the context of colonial Queensland society, 1860-90, by examining the correspondence of an upper-class mother. Her education and liberal outlook, and a certain ambivalence towards motherhood, all influenced her attitude to the use of chloroform and the process of childbirth.

The mental health impact of stillbirth, neonatal death or SIDS: prevalence and patterns of distress among mothers.

Although stressful events have long been implicated in the onset of psychological disorder, available data suggest that the majority of individuals appear to escape serious impairment even following highly traumatic events. Related to this is the question of chronicity and whether those who do become impaired develop mental health problems of an ongoing nature. This paper documents the psychological adjustment of 194 women following a highly stressful event-the death of an infant due to stillbirth, neonatal death or SIDS. Anxiety and depression were measured on four occasions-at 2, 8, 15 and 30 months post-loss--using the Delusions Symptoms States Inventory (DSSI/sAD). For comparative purposes, the mental health of 203 mothers of a surviving infant was similarly assessed. The results demonstrate that bereaved mothers, as a group, manifest significantly higher rates of psychological distress than mothers of living infants for at least 30 months after their loss. Their impairment may be either acute or chronic in form. The majority of bereaved mothers appear not be develop serious mental health problems in response to the loss or experience psychological impairment that is usually self-limiting. For a smaller group of women, the death of a baby may herald serious and ongoing distress. Bereaved mothers who were not distressed soon (2 months) after the loss were unlikely to become so later, but those who were still distressed at 8 months were likely to remain so subsequently.

Estimating nonparticipation bias in a longitudinal study of bereavement.

Nonparticipants in epidemiological studies may differ in important respects from participants but the magnitude of this potential bias is rarely quantified. This study estimates the effect of nonparticipation on estimates of mental health problems following stillbirth, neonatal death or sudden infant death syndrome. Of 805 families approached, 512 (64 per cent) were recruited, of whom 77 per cent of mothers and 71 per cent of fathers completed four study interviews. Younger, unmarried, unemployed parents without private health insurance were less often recruited, and even if recruited, were less likely to complete the interview. By evaluating several possible scenarios, we estimated that had mothers lost to follow-up remained in the study, anxiety rates would have varied by no more than +/-4 per cent. Relative risks associated with bereaved-control comparisons would have differed little from the observed estimate of 2.33. Estimating the effects of initial nonresponse is more difficult but the adoption of a worst-case scenario produced a relative risk of 3.47. Despite systematic nonparticipation suggestive of social disadvantage, attrition-related bias may have had only a modest effect on anxiety and depression rate estimates. However, this may not be the case when sample loss is high, when associations between attrition and outcome are strong, and when attrition-related behaviour differs across comparison groups.

Gender differences in parental psychological distress following perinatal death or sudden infant death syndrome.

BACKGROUND: Stress responses of bereaved parents (mothers 194, fathers 143) who experienced infant loss were compared with parents (mothers 203, fathers 157) with a live born child. METHOD: Psychological distress using scales of anxiety, depression and alcohol use was compared at 2, 8, 15 and 30 months post-loss. RESULTS: Bereaved mothers showed significantly more anxiety/depression than controls at all four interviews. For bereaved fathers, anxiety/depression differed significantly from controls only at two months. Heavy alcohol use was significantly more prevalent at 2 and 30 months. Relative risks showed significant gender differences between bereaved parents at all four interviews for anxiety/depression. When this outcome was extended to include heavy drinking in addition to anxiety/depression, these differences diminished and were significant only at 2 and 8 months. CONCLUSION. Female responses are longer lasting and reflected by elevated levels of anxiety/depression. Male responses equally involve anxiety, depression and heavy alcohol consumption.

Psychological changes in parents eight months after the loss of an infant from stillbirth, neonatal death, or sudden infant death syndrome--a longitudinal study.

OBJECTIVE: We proposed to measure part of the natural history of grief by determining the changes in the psychological symptoms experienced by bereaved parents over the 8 months after the loss of an infant from sudden infant death syndrome (SIDS), neonatal death (NND), or stillbirth (SB). Parents were interviewed twice, at 2 and 8 months after the loss. METHODOLOGY: A total of 220 bereaved families (45 SIDS, 93 NND, and 82 SB) were compared with 226 control families who had a live born child. Comparison was based on responses to a standardized measure of anxiety and depression (Delusions-Symptoms-States Inventory). RESULTS: For separate cross-sectional comparison at both 2 and 8 months, significant differences were noted in the frequency of maternal symptoms of anxiety and depression between bereaved and control groups (P < .001). Such differences were present for paternal anxiety and depression at 2 months, but not 8 months. A second series of analysis examined longitudinal changes in symptom frequency between 2 and 8 months for each bereaved group. For mothers, the changes were significant for anxiety and depression: SIDS and NND (P < .001), SB (P < .01). For fathers, the changes for anxiety and depression in SIDS were P < .01; NND, P < .05 for anxiety and P < .01 per depression; changes were not significant for SB. At 2 months, relative risks for symptoms of maternal anxiety were significant for all three bereaved groups: SIDS, 22.4; NND, 5.4; and SB, 5.1. Comparable significant figures at 8 months were: SIDS, 5.5; NND, 3.9; and SB, 3.0, respectively. For depression the results for 2 months were: SIDS, 8.6; NND, 5.9; and SB, 6.7 (all significant) while at 8 months the results were: SIDS, 5.1; NND, 3.8; and SB, 2.4 (SB group not significant). For fathers the relevant risks were generally lower. At 2 months, anxiety levels were higher than controls in all three groups, and for depression in the SIDS and SB groups. At 8 months, significant results persisted only in the SB group. CONCLUSION: These data indicate that bereaved parents have a marked reduction in the symptoms of mental illness over the first 8 months after the loss. Although the changes over time are significant for both mothers and fathers, mothers at 8 months still demonstrated higher levels of anxiety and depression when compared with controls. These levels of symptoms are far less evident for fathers at 8 months.

Alcohol and drug usage in parents soon after stillbirth, neonatal death or SIDS.

The behaviour of bereaved parents with respect to their drug and alcohol ingestion was examined 2 months following the loss of an infant from stillbirth (SB) neonatal death (NND) or sudden infant death syndrome (SIDS). Responses from bereaved families (99 SB, 109 NND, 52 SIDS) were compared with 252 control families (who had a liveborn infant). There was no difference in self-medication using aspirin as the example. The use of sedative drugs was significantly higher in all bereaved mothers (but especially the SIDS group). Use of sedatives by fathers was significantly higher only in the SIDS group. There was also a greater frequency of heavy drinking of mothers in all the bereaved groups and fathers in the SIDS group. These results have implications for the understanding and care of families following infant loss.

The rise and fall of phrenology in Australia.

In the first half of the nineteenth century phrenology, which was claimed to be the first science of the mind, experienced enormous popularity in the western world. It gave rise to a widespread movement attracting the attention of the professional and lay members of society. In Australia, as elsewhere, it had influence in penology and criminology, psychiatry, notions of racial inferiority, education, anthropology and popular application. By the second half of the nineteenth century, following advances in the knowledge of neuro-anatomy, it became relegated to the status of a pseudo-science. As such, it remained popular with charlatans and the public well into the twentieth century.

Evolution of bereavement counselling in sudden infant death syndrome, neonatal death and stillbirth.

There have been changing attitudes to death and grief in Western society in recent centuries. During the twentieth century complex medical and social changes have resulted in changing attitudes to and experiences with death. Specifically, the impact of death in childhood is reviewed. In recent decades sudden and unexpected death associated with stillbirth, the newborn and infants appears to have a more profound affect on the bereaved parents than in the past when the overall death rates in childhood were higher. The evolution of parent support groups developed since the 1960s to alleviate the psychological trauma of unexpected and sudden death in childhood has been traced. These groups were founded initially for support with sudden infant death syndrome and later extended to include families with stillbirth and neonatal death.

Early parental responses to sudden infant death, stillbirth or neonatal death.

OBJECTIVE: To examine the mental health of parents after stillbirth (SB), neonatal death (NND) or sudden infant death syndrome (SIDS). DESIGN: The sampling frame from southeast Queensland was observed over 2.5 years. Control families were matched for birth date, sex of child, hospital and health insurance status. SETTING: Home interviews, by specially trained social workers, took place two months after the death of the infant. PARTICIPANTS: Results were based on 918 responses from 260 bereaved families (99 SB, 109 NND, 52 SIDS) and 252 control families, with a 63.6% overall participation rate. MAIN OUTCOME MEASURES: Questionnaires included standardised measures of anxiety, depression, biographic and demographic data. It was hypothesised that subject families would show more symptoms of anxiety and depression than control families, with mothers and parents affected by SIDS having the highest levels. RESULTS: Affected parents report significantly more psychological symptoms than controls, mothers more than fathers (P less than 0.001). Parents affected by SIDS showed more symptoms than other affected parents. High levels of anxiety were 14 times more likely in mothers affected by SIDS than controls (95% confidence interval, 5.4-36.6), with depression 12 times more likely (95% confidence interval, 3.8-43.5). Anxiety for groups affected by SB and NND were respectively 3.9 (2.1-10.5) and 6.5 (2.6-16.3) times more likely than for controls, and depression 6.9 (2.1-22.5) and 8.5 (2.7-26.7) times more likely. Differences were less marked for fathers, except for fathers affected by SIDS. CONCLUSIONS: Parents affected by stillbirth, neonatal death or sudden infant death syndrome manifest high levels of anxiety and depression two months after the death. Mothers have more symptoms than fathers, and parents affected by SIDS have the most symptoms of anxiety and depression.