Human morbid genetics revisited: relevance of epigenetics

Identification of genes predisposing their carrier to complex diseases is a much more complicated task than finding genes involved in simple mendelian diseases. The slow progress in the genetic research of complex diseases could be due to limitations in the basic research strategy, which is almost exclusively orientated to the detection of disease-related DNA mutations or polymorphisms. I argue in this article that epigenetic misregulation of genes is more consistent with the features of complex diseases than is DNA sequence variation, and therefore that epigenetic factors could be important in understanding the origins of complex diseases.     

Part I: Cardiopulmonary consequences of morbid obesity

Markedly obese patients represent a unique subset of the population. The condition of obesity is related to physiological derangements of the cardiovascular system, deleterious effects of the mechanical and gas exchange function of the lung, severe biochemical derangements in the liver, and changes in normal endocrine functions. Therapy for and research efforts in obesity require a thorough understanding of the definition, measurement, and classification of obesity. The ability to assess pertinent physiological and biochemical alternations is a prerequisite for studying and caring for these patients. A subsequent review will address the biochemical derangements of morbid obesity. The present communication will focus on the physiologic derangements of the cardiopulmonary system unique to marked obesity.     

Plasma levels of neurotensin in gastroplasty for morbid obesity

Fasting and postprandial plasma levels of the tridecapeptide neurotensin were determined in ten women before and three months after gastroplasty for morbid obesity. Measurements were by radioimmunoassay in unextracted plasma with two antisera recognizing intact neurotensin (NT1-13) or intact neurotensin together with small C-terminal fragments, which may circulate as metabolites of neurotensin. Levels of both intact neurotensin and C-terminal immunoreactivity in obese women were in the same order of magnitude as those found previously in lean persons. Fasting levels measured with both antisera were significantly reduced following gastroplasty (P less than 0.01). Meal-stimulated levels and increments were unchanged. The cause of this prolonged reduction is at present unknown, but may be a reduced luminal stimulation of the small intestine or an altered vagal tonus following gastroplasty.     

Wernicke's encephalopathy after vertical banded gastroplasty for morbid obesity.

Thiamine deficiency is known to lead to certain neurological sequelae including Wernicke- Korsakoff encephalopathy. Signs attributable to this condition include ataxia, ophthalmoplegia, nystagmus, and mental confusion. Recognised predisposing conditions include alcoholism gastric carcinoma, pyloric obstruction, hyperemesis gravidarum, and prolonged intravenous feeding. We have recently encountered two cases of Wernicke''s encephalopathy after vertical banded gastroplasty for morbid obesity . Other neurological sequelae are recognised after vertical banded gastroplasty, including Guillain-Barre syndrome, psychosis, and pseudoathetosis, but the causes are multifactorial.     

Minireview: Part II: Biochemical considerations of morbid obesity

Whereas the cardiorespiratory derangements of severe obesity have received careful scrutiny, the biochemical alterations unique to that state are not well known. This review will examine in morbidly obese patients the hepatic abnormalities related to morphology, function, and lipid metabolism. Altered xenobiotic biotransformation will then be discussed. Available studies in man will emphasize what is known about the biochemical aberrations exemplified by this abnormal biologic state.     

Particular characteristics of the metabolic syndrome in patients with morbid obesity

BackgroundCriteria for the diagnosis of the metabolic syndrome are currently being reconsidered, as their usefulness is not the same for all phenotypes in relation to the risk of cardiovascular disease.AimWe analyzed the changes in metabolic parameters after a fat overload in different groups of patients.Materials and methodsThe study included 20 healthy persons, 30 metabolic syndrome patients without morbid obesity, 80 metabolic syndrome patients with morbid obesity and 16 patients with morbid obesity without the metabolic syndrome. All the participants received a fat overload of 60 g. Measurements were made before the overload and 3 h afterwards of triglycerides, free fatty acids, insulin and uric acid.ResultsMetabolic syndrome patients with morbid obesity had a lower waist-to-hip ratio, and lower plasma free fatty acid and triglycerides levels at baseline and after the overload than patients without morbid obesity. Plasma uric acid levels rose after the fat overload in the metabolic syndrome patients who had morbid obesity but not in the patients without morbid obesity. A positive relation was found between plasma triglycerides and free fatty acid levels in all the patients but not in the controls after the fat overload. A positive relation was also found between uric acid and insulin levels in the metabolic syndrome patients with morbid obesity.ConclusionsMetabolic syndrome patients with and without morbid obesity presented different metabolic characteristics. This suggests that there are 2 different clinical phenotypes, both grouped under the metabolic syndrome umbrella.