Girls are born lighter than boys. The consistency of this observation across different populations is striking, suggesting that it may have fundamental significance for those conditions linked with lower birth weight, such as diabetes. Previous hypotheses relating low birth weight to subsequent diabetes have addressed differences in insulin resistance within the sexes, not between them. Here, we propose that gender-specific genes affecting insulin sensitivity are responsible for the gender difference in birth weight -the genetically more insulin resistant female fetus is less responsive to the trophic effects of insulin and is therefore smaller. These genes also render female subjects more susceptible to diabetes, explaining why reports of type 2 diabetes (T2D) in younger populations show a female preponderance. Consistent with our proposal, concentrations of insulin and/or its propeptides are higher at birth in female populations and they are intrinsically more insulin resistant throughout life, with attendant impact on their metabolism, and the regressions describing the relationship between insulin resistance and adiposity in female and male subjects have similar gradients, but different constants. These gender-specific genes have a demonstrable impact on fetal growth and insulin resistance. Diabetes and cardiovascular disease are thought to be driven by insulin resistance, and the observations reported here may help to focus the search for genes that control it.
This report describes a rare case of a patient with increased urinary dopamine excretion in association with bilateral carotid body tumours. Excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and 4-hydroxy-3-methoxymandelic acid (HMMA) were within the reference ranges, and an 123 I-meta-iodobenzylguanidine (MIBG) scan showed uptake in the neck masses, with no other abnormal uptake anywhere else in the body. The patient is being managed conservatively as the tumours are not amenable to resection on account of their size and vascularity. There are only four previous case reports of dopamine-secreting tumours of the carotid body described in the literature, all of whom were women. The tumours were unilateral in three cases and bilateral in the fourth case. Familial cases of carotid body tumours have a higher prevalence of bilateral tumours than nonfamilial cases. Recent reports in the literature have suggested that a significant number of patients with extra-adrenal catecholamine-secreting paragangliomas have a genetic mutation in one of the identified susceptibility genes for catecholamine-secreting tumours, despite having no other affected family members, and a mutation has been found in the succinate dehydrogenase gene for this patient. 2006; 43: 156-160 Case report Ann Clin BiochemA 61-year-old gentleman with a long-standing history of hypertension presented with syncopal episodes to the casualty department in December 1999. The initial diagnosis was thought to be recurrent transient ischaemic attacks in association with bilateral carotid bruits. Following a neck ultrasound scan, carotid angiography revealed bilateral large carotid body tumours encircling each common carotid artery with splaying of the internal and external carotid arteries; a characteristic benign tumour blush was seen (Figure1). The masses in the neck (Figure 2) were ¢rst commented on by an Ear, Nose and Throat (ENT) surgeon when the patient underwent a tonsillectomy 20 years ago to alleviate sleep apnoea. Due to recurrence of this problem, a trachaeostomy was carried out, and due to episodes of collapse ascribed to asystole as a result of carotid sinus baroreceptor hypersensitivity secondary to his carotid body tumours, a permanent pacemaker was inserted. 1 Although these interventions brought about signi¢-cant improvement in the clinical condition of the patient, his blood pressure and heart rate showed large variations on 24 h monitoring (70/41--219/102 mmHg, 14--98 bpm). The patient is not currently receiving any medical management for his labile hypertension.Baseline laboratory investigations were normal (urea. As his blood pressure remained labile, urinary catecholamines were requested. Dopamine excretion was signi¢cantly elevated at 20,679 nmol/24 h (upper limit of reference range 4440 nmol/24 h); excretion of the dopamine metabolite homovanillic acid (HVA) was also increased at 13.1mmol/mol creatinine (upper limit of reference range 5 mmol/mol creatinine). Excretion of noradrenaline, adrenaline, normetadrenalin...
1 The efficacy of labetalol in the treatment of severe hypertension (diastolic > 115 mm Hg) was studied retrospectively. Ten patients were followed for more than 6 months. At 6 months, eight were well controlled and the mean dose in those was 975 mg daily. Four of these were receiving labetalol alone; two were on labetalol and diuretic only. 2 Three patients were resistant to doses to 1600, 1800 and 2400 mg daily respectively; two of these were controlled with increased doses of vasodilator drugs. In two cases labetalol had produced large falls in the standing BP while not influencing the supine BP. 3 Three other resistant patients were seen, of whom one merely required an increase in dose to 2200 mg daily and the addition of a diuretic. Both the others were elderly, had severe vascular disease, and suffered disabling postural hypotension on a dose of labetalol which did not influence the supine BP. 4 Labetalol can control severe hypertension. There remain patients whose supine BP is not influenced by a dose of labetalol which produces marked postural hypotension.
Background Concentrations of cholesterol, triglycerides and glucose are higher in young men with a paternal history of premature myocardial infarction than in ageand sex-matched controls.
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