Associations between persistent organic pollutants and metabolic syndrome in morbidly obese individuals.

BACKGROUND AND AIMS: Persons with "metabolically healthy" obesity may develop cardiometabolic complications at a lower rate than equally obese persons with evident metabolic syndrome. Even morbidly obese individuals vary in risk profile. Persistent organic pollutants (POPs) are widespread environmental chemicals that impair metabolic homeostasis. We explored whether prevalence of metabolic syndrome in morbidly obese individuals is associated with serum concentrations of POPs. METHODS AND RESULTS: A cross-sectional study among 161 men and 270 women with BMI >35 kg/m2 and comorbidity, or >40 kg/m2. Circulating concentrations of 15 POPs were stratified by number of metabolic syndrome components. In multiple logistic regression analysis odds ratios between top quartile POPs and metabolic risk factors versus POPs below the top quartile were calculated adjusting for age, gender, body mass index, smoking status, alcohol consumption and cholesterol concentrations. Age-adjusted concentrations of trans-nonachlor and dioxin-like and non-dioxin-like polychlorinated biphenyls (PCBs) increased with number of metabolic syndrome components in both genders (p < 0.001), while the organochlorine pesticides HCB, ß-HCH and p,p'DDE increased only in women (p < 0.008). Organochlorine pesticides in the top quartile were associated with metabolic syndrome as were dioxin-like and non-dioxin-like PCBs (OR 2.3 [95% CI 1.3-4.0]; OR 2.5 [95% CI 1.3-4.8] and 2.0 [95% CI 1.1-3.8], respectively). Organochlorine pesticides were associated with HDL cholesterol and glucose (OR = 2.0 [95% CI = 1.1-3.4]; 2.4 [95% CI = 1.4-4.0], respectively). Dioxin-like PCBs were associated with diastolic blood pressure, glucose and homeostatic model assessment-insulin resistance index (OR = 2.0 [95% CI = 1.1-3.6], 2.1 [95% CI = 1.2-3.6] and 2.1 [95% CI = 1.0-4.3], respectively). CONCLUSION: In subjects with morbid obesity, metabolic syndrome was related to circulating levels of organochlorine pesticides and PCBs suggesting that these compounds aggravate clinically relevant complications of obesity.

Whole-exome sequencing for diagnosis of hereditary ichthyosis.

BACKGROUND: Hereditary ichthyosis constitutes a diverse group of cornification disorders. Identification of the molecular cause facilitates optimal patient care. OBJECTIVE: We wanted to estimate the diagnostic yield of applying whole-exome sequencing (WES) in the routine genetic workup of inherited ichthyosis. METHODS: During a 3-year-period, all ichthyosis patients, except X-linked and mild vulgar ichthyosis, consecutively admitted to a university hospital clinic were offered WES with subsequent analysis of ichthyosis-related genes as a first-line genetic investigation. Clinical and molecular data have been collected retrospectively. RESULTS: Genetic variants causative for the ichthyosis were identified in 27 of 34 investigated patients (79.4%). In all, 31 causative mutations across 13 genes were disclosed, including 12 novel variants. TGM1 was the most frequently mutated gene, accounting for 43.7% of patients suffering from autosomal recessive congenital ichthyosis (ARCI). CONCLUSION: Whole-exome sequencing appears an effective tool in disclosing the molecular cause of patients with hereditary ichthyosis seen in clinical practice and should be considered a first-tier genetic test in these patients.

FTO genotype and weight gain in obese and normal weight adults from a Norwegian population based cohort (the HUNT study).

The fat mass and obesity associated gene ( FTO) is associated with bodyweight and obesity. The aim of this study was to investigate if FTO genotype affects weight gain in adulthood. We investigated the weight development over a period of 11 years in a case-control study, consisting of 1,632 cases (BMI≥35 kg/m (2)) and 3,379 normal weight controls (BMI 20-24.9 kg/m (2)) from a Norwegian population based cohort, the HUNT study. Subjects were aged 20-80 at baseline, 25% men and 75% women. FTO genotype was assessed by genotyping of the SNP rs1421085. A strong association between FTO and obesity was found, consistent with an additive gene effect. Cases had an average weight gain of 11.1 kg, whereas controls had an average weight gain of 1.4 kg. Genotype was neither associated with weight gain in obese, nor controls. Cases had an average weight gain of 10.7 kg for individuals with zero risk alleles, 11.3 for one risk allele and 11.1 kg for two risk alleles. Controls had an average weight gain of 1.4 kg, 1.4 and 1.3 for the respective genotypes. In conclusion, FTO was associated with obesity, but not with weight gain in adults during 11 years of follow-up.

Mutations in the melanocortin 4 receptor (MC4R) gene in obese patients in Norway.

BACKGROUND: Mutations in the melanocortin 4 receptor ( MC4R) gene are the most frequent cause of monogenic forms of obesity, but the reported prevalences of mutations in obese individuals diverge, varying from 0.2 to 5.8%. OBJECTIVE: The aim of this study was to assess the prevalence of MC4R mutations in obese children and adults residing in Norway. SUBJECTS AND METHODS: We sequenced the coding region of MC4R in 1 027 obese patients. Among these, were 644 adults with a BMI >35 kg/m(2) and 383 children with a body weight >97.5 percentile for height. Identified mutations were analyzed by family studies and a bioinformatic approach including comparative sequence analysis and prediction of impact on transmembrane helix and three dimensional structure. RESULTS: Nine mutations were identified, of which four were novel and five previously described. The prevalence of MC4R mutations was 1.6% in pediatric and 0.8% in adult patients. All four novel mutations, I69R, M79I, I195S, and M200del were identified among pediatric patients. M79I was found in an ethnic Norwegian patient, while the rest were identified in second generation immigrants. The previously described mutations Y35X/D37V, V95I, T150I, R236C and V253I were identified in one pediatric and five adult patients. None of the adult patients reported childhood onset of obesity. The M200del mutation was found in a homozygous state, while the rest were heterozygous. CONCLUSION: MC4R mutations are not a common cause of obesity in Norway and screening of obese patients does not appear to be warranted. The results are consistent with results from previous studies.

Plasma total homocysteine levels and prognosis in patients with previous premature myocardial infarction: a 10-year follow-up study.

OBJECTIVES: To explore plasma total homocysteine (tHcy) as a predictor of long-term prognosis after premature myocardial infarction (MI). DESIGN: Prospective cohort study. SETTINGS: Akershus University Hospital. SUBJECTS: A total of 247 patients (193 men and 54 women) in stable clinical phase after premature MI (males: first MI at age < or =55; females < or =60). MAIN OUTCOME MEASURES: The primary end-point was total mortality and the secondary end-point was cardiac death. The third end-point was major cardiac events: a combination of cardiac death, MI and cardiac arrest. RESULTS: After 10 years, 44 patients had died, 36 from cardiac causes. Major cardiac event occurred in 70 patients. The relative risk for death of all causes increased 1.43 (95% CI, 1.08-1.88) per tHcy quartile (P for trend = 0.01), and was only modestly reduced after adjustment for age, ejection fraction, total cholesterol, C-reactive protein, fibrinogen, smoking and hypertension to 1.37 (95% CI, 1.04-1.80) (P for trend = 0.03). Similar results were observed when cardiac death was used as the end-point, but we observed no association between tHcy and the end-point major cardiac event. CONCLUSIONS: Total homocysteine was an independent predictor of total and cardiac mortality in stable patients following premature MI. tHcy had no effect on major cardiac event in contrast to most other risk factors in this study. Thus, the mechanism(s) underlying the effects of homocysteine on coronary heart disease may differ from other risk factors.

Abstention from filtered coffee reduces the concentrations of plasma homocysteine and serum cholesterol--a randomized controlled trial.

BACKGROUND: Elevated concentrations of plasma total homocysteine (tHcy) and serum total cholesterol are risk factors for ischemic heart disease (IHD). Previous studies showed that the consumption of very high doses of unfiltered coffee increases tHcy and total cholesterol. OBJECTIVE: A prospective intervention study was performed to assess the effects of coffee consumption on the concentrations of tHcy and total cholesterol by using doses and brewing methods common in southeastern Norway. DESIGN: The study was an unblinded, controlled trial with 191 healthy, nonsmoking, coffee-drinking volunteers aged 24-69 y randomly assigned to 3 groups who were asked to consume for 6 consecutive weeks no coffee, 1-3 cups (approximately 175-525 mL)/d, or > or =4 cups (approximately 700 mL)/d prepared in the manner to which they were accustomed. Blood samples were drawn when the subjects were randomly assigned and at 3 and 6 wk of the trial. Dietary data were collected by questionnaire. RESULTS: Ninety-seven percent of the participants reported being regular consumers of caffeinated filtered coffee. Abstention from coffee for 6 wk was associated with a decrease in the tHcy concentration of 1.08 micromol/L and a decrease in the total cholesterol concentration of 0.28 mmol/L in participants who had been drinking on average 4 cups of filtered coffee daily for the past year. Adjustments for several possible confounders did not alter the results. CONCLUSION: Abstention from filtered coffee in doses that are commonly consumed was associated with lower concentrations of tHcy and total cholesterol.

Plasma fibrinogen level and long-term prognosis in Norwegian middle-aged patients with previous myocardial infarction. A 10 year follow-up study.

OBJECTIVES: To investigate the prognostic value of plasma fibrinogen level amongst middle-aged survivors of myocardial infarction (MI). DESIGN: Prospective cohort study. SETTINGS: Determination of fibrinogen and other prognostic variables in MI patients recruited in a presumably stable phase of coronary heart disease (CHD). SUBJECTS: A total of 247 middle-aged CHD patients (54 women and 193 men) who had their first MI at age < or = 60 (women) or < or = 55 (men) were recruited at least 3 months after (mean 2.1 years) the most recent MI. MAIN OUTCOME MEASURES: The primary endpoint was total mortality, and the secondary endpoint was cardiac deaths. The tertiary endpoint was major cardiac events (cardiac death, MI and cardiac arrest). RESULTS: During a follow-up period of 10 years a total of 44 patients had died, 36 from cardiac causes. Major cardiac event occurred in 70 patients. After adjusting for age, ejection fraction (EF), total serum cholesterol (TC), smoking and hypertension, patients in the top quartile of fibrinogen (> or = 4.0 g L-1) had a relative risk (RR) of 1.8 (95% CI 1.0-3.6) (P = 0.07) for death of all causes. The top quartile of fibrinogen was a stronger predictor of cardiac death; RR = 2.2 (95% CI 1.1-4.4) (P = 0.03), whilst the effect on the endpoint major cardiac event was not significant; RR=1.1 (95% CI 0.6-1.9) (P = 0.69). CONCLUSIONS: A plasma fibrinogen level in the top quartile predicted cardiac death in middle-aged patients who had suffered MI.

Plasma N-terminal pro-atrial natriuretic peptide predicts death after premature myocardial infarction, but not as well as radionuclide ejection fraction. A ten-year follow-up study.

OBJECTIVE: To assess N-terminal pro-atrial peptide (N-ANP) as a predictor of total and cardiac death in patients with previous premature myocardial infarction (MI). DESIGN: In this prospective cohort study, we measured plasma N-ANP by ELIZA assays and ejection fraction (EF) by radionuclide ventriculography in a cohort of 247 patients (193 men and 54 women) who had had MI at a relatively young age (males: first MI at age < or =55; females <60). RESULTS: After 10 years 44 patients had died, 36 from cardiac causes. After using a stepwise procedure to adjust for other prognostic factors (i.e. plasma total homocysteine (tHcy), C-reactive protein and age), the relative risk (RR) was 2.00 (95% confidence interval (CI) 1.05-3.80) (p = 0.03) for death of all causes and 2.32 (95% CI 1.19-4.55) (p=0.01) for cardiac death when the top quartile was compared to the three lower quartiles of N-ANP. When radionuclide EF entered the Cox model, N-ANP became insignificant as a predictor of mortality. CONCLUSION: N-ANP was a significant predictor of total death and cardiac death in young survivors of MI, but radionuclide EF was a more independent prognostic variable.

Whole blood folate, homocysteine in serum, and risk of first acute myocardial infarction.

High level of total homocysteine (tHcy) is a risk factor for coronary artery disease (CAD), but the mechanism is not known. The serum concentration of tHcy, total cholesterol, high density lipoprotein cholesterol (HDL-C), and apolipoprotein A-I (apo A-I) and the concentration of folate in whole blood were measured in 107 patients with first acute myocardial infarction (MI) and 103 controls. The level of whole blood folate was lower and that of tHcy higher in cases than in controls. An increase of 50 nmol/l whole blood folate was associated with an OR for MI of 0.75, and an increase of 5 micromol/l tHcy with an OR for MI of 1.57. Correlations were observed between the levels of whole blood folate and tHcy and between whole blood folate and alcohol intake, and in MI cases, between tHcy, HDL-C, and apo A-I as well as between HDL-C and alcohol intake. The number of cigarette smokers was higher among cases than controls. In smokers, the level of tHcy was higher and that of whole blood folate lower than in non-smokers. After adjustment for smoking, the whole blood folate and tHcy-associated risks of MI became non-significant. We conclude that smoking may affect folate status and tHcy level adversely. The risk of MI in smokers may at least partly be attributed to hyperhomocysteinemia or low folate.

[Acute psychosis--an unusual clinical manifestation of primary hyperparathyroidism]. / Akutt psykose--en uvanlig klinisk debut ved primaer hyperparatyreoidisme.

In 1942, the Norwegian psychiatrist Eitinger drew attention to the fact that acute psychosis may be the presenting and major symptom of primary hyperparathyroidism. A case of this variety is reported. In the course of two months a 77-year old woman developed an acute psychosis characterized by apathy, amnesia, somatic delusions and hallucinations. Initially, the case was misinterpreted as senile dementia. The serum calcium level was 4.3 mmol/l. After parathyroidectomy her mental symptoms were completely relieved.