PubMed · 12527640
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Ranjeeta Sinvhal, Lorraine Tosiello, Greg Cable. 2003. Confounding issues in COPD risk study?. https://doi.org/10.1378/chest.123.1.307
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The obesity crisis in the United States has been associated with an alarming increase in the prevalence of the metabolic syndrome (MSX) disease cluster. Here we review evidence that the MSX reflects a failure of a system of intracellular lipid homeostasis that prevents lipotoxicity in the organs of overnourished individuals by confining the lipid overload to cells specifically designed to store large quantities of surplus calories, the white adipocytes. Normally, early in obesity, adipocytes increase leptin and adiponectin secretion, hormones that enhance oxidation of surplus liquids in nonadipose tissues by activating AMP-activated protein kinase and reducing the activity and expression of lipogenic enzymes. These events combine to lower malonyl coenzyme A. Deficiency of and/or unresponsiveness to leptin prevents these protective events and results in ectopic accumulation of lipids. Increased de novo ceramide formation is probably the most damaging lipid and is a cause of lipoapoptosis, abetted by a decline in tissue Bcl-2. Pancreatic beta-cells and myocardiocytes are cellular victims of the process, leading to non-insulin-dependent diabetes and lipotoxic cardiomyopathy. The MSX is particularly prevalent in visceral obesity, probably because visceral adipocytes make less leptin than sc adipocytes. Cushing's syndrome, the lipodystrophy associated with protease inhibitor therapy of AIDS, polycystic ovarian disease, as well as diet-induced visceral obesity, all have a high waist/hip ratio, and all exhibit MSX. Increased lipid content in the heart and skeletal muscle organs of such patients is now under study.
UNLABELLED: We report on a 16-month-old boy with congenital disorder of glycosylation type 1a (CDG-1a; OMIM 212065) showing an atypical phenotype. Whereas failure to thrive is known to be a prominent feature in this condition, our patient developed postnatal macrosomia with increase of weight, length and occipitofrontal circumference (OFC) above the 95th percentile within his 1st year of life. Thereafter, weight and length were close to the 90th and OFC at the 50th percentiles. In contrast to other CDG-1a patients, the child did not have abnormal fat pads or inverted nipples; but unusual eyebrows were present. CDG-1a was confirmed by isoelectric focusing of serum transferrin and measurement of phosphomannomutase activity in leucocytes and cultured fibroblasts (residual activity <5% of controls). Mutation analysis of the phosphomannomutase 2 gene (PMM2) revealed homozygosity for a 647A>T (N216I) mutation in our patient and heterozygosity in his consanguineous parents. CONCLUSION: This is the first report of macrosomia and of homozygosity for the 647A>T (N216I) mutation in a patient with congenital disorder of glycosylation type 1a which may allow further phenotype/genotype comparisons.
STUDY OBJECTIVES: This report describes clinical outcomes and threshold levels of respiratory disturbance index (RDI) associated with sleep-disordered breathing in children participating in the Tucson Children's Assessment of Sleep Apnea study. DESIGN: A community-based, prospective cohort study designed to assess the severity of sleep-related symptoms associated with sleep-disordered breathing in children aged 6 to 11 years. SETTING: Students attending elementary school in the Tucson Unified School District. PARTICIPANTS: Unattended home polysomnograms were completed on 239 children-55.2% boys, 51% Hispanic, and 55% between the ages of 6 and 8 years. MEASUREMENTS AND RESULTS: Based on full home polysomnography, levels of RDI that correspond to a higher prevalence of clinical symptoms of sleep-disordered breathing in children aged 6 to 11 were observed. An RDI of at least 5 was associated with frequent snoring (20.3% vs 9.1%, P<.01), excessive daytime sleepiness (22.9% vs 10.7%, P<.01), and learning problems (8.5% vs 2.5%, P<.04) when no oxygen desaturation accompanied the respiratory event. An RDI of at least 1 was associated with these symptoms when a 3% oxygen desaturation was required, snoring (24.0% vs 10.4%, P<.006), excessive daytime sleepiness (24.0% vs 13.4%, P<.04), and learning problems (10.7% vs 3.0%, P<.02). Hispanic or Caucasian ethnicity, sex, age category, obesity, insomnia, and witnessed apnea were not associated with RDI regardless of event definition. CONCLUSIONS: The Tucson Children's Assessment of Sleep Apnea study has shown that there are values of RDI based on polysomnography that correspond to an increased rate of clinical symptoms in children ages 6 to 11 years.