The metabolic syndrome in type 1 diabetes: does it exist and does it matter?

The significance of the metabolic syndrome in type 1 diabetes is not well understood. This study aimed to estimate its prevalence and attendant complications. Four hundred twenty-seven type 1 diabetic subjects were grouped according to the presence or absence of metabolic syndrome (WHO criteria). Macro- and microvascular complications were compared between the groups as individual and as composite endpoints. Data were analyzed for the total cohort and in subgroups according to duration of diabetes quartiles (<6.9, 7-12.9, 13-19.9, and >20 years) and year of presentation. Fifteen percent of individuals fulfilled the WHO criteria for metabolic syndrome, and of these, 26.9% were insulin resistant, as compared with 3.4% of those without metabolic syndrome [odds ratio (OR)=8.9, P=.001]. Both BMI and metabolic syndrome showed an increasing trend from 1992 to 2003. Those with metabolic syndrome required significantly higher insulin dosage [0.9 (0.7-1.2) vs. 0.6 (0.5-0.9) units/kg, P=.03], were older [35.0 (26.2-47.3) vs. 29.7 (23.4-36.4) years, P=.002], and had longer duration of diabetes [19.7 (10.7-25.6) vs. 12.1 (6.3-17.9) years, P=.0001]. They also had a significantly higher macrovascular composite endpoint (OR=3.3, P=.02) as well as higher macrovascular and microvascular composite endpoint (OR=3.1, P=.0001). The prevalence of stroke (OR=22.8, P=.008), peripheral vascular disease (OR=7.3, P=.05), and severe retinopathy (OR=3.7, P=.01) is higher in subjects with metabolic syndrome in the >or=20-year quartile group; in addition, these subjects have higher macrovascular composite endpoint (OR=3.9, P=.03) and macrovascular and microvascular composite endpoint (OR=2.9, P=.03). This remained so even when subjects with albuminuria were excluded. Some individuals with type 1 diabetes can also have metabolic syndrome. They are more prone to complications and require even more intensive glycemic control and reduction of macrovascular risk factors.     

Aspirin resistance: does it exist?

Aspirin irreversibly inhibits platelet cyclooxygenase-1 (COX-1). Aspirin sensitivity can be measured easily by its inhibition of arachidonic acid (AA) -induced platelet aggregation. Aspirin resistance has to be defined by its inability to inhibit COX-1. By using this definition, aspirin resistance very likely does not exist. A specific rapid laboratory test using either AA-induced platelet aggregation or AA-induced malondialdehyde production in platelet-rich plasma is needed to test aspirin sensitivity. The reports on so-called aspirin resistance are usually due to noncompliance of aspirin intake or consumption of inadequate doses of aspirin. In addition, data generated from using nonspecific platelet function tests have added confusion to this observed phenomenon of aspirin resistance.     

Reperfusion injury: does it exist?

It is well established that reperfusion of the heart is the optimal method of salvaging previously ischemic myocardium. However, the idea of reperfusion injury, i.e. injury caused by the process of reperfusion per se, still remains a controversial issue. In this review, we present mounting evidence supporting the concept that reperfusion injury exists, based on work conducted with adenosine and opioid receptor ligands, and the discovery of two new concepts regarding reperfusion injury: 'postconditioning' (POC) and the reperfusion injury salvage kinase (RISK) signaling pathway.     

Asthma remission: does it exist?

Subjects believed to have grown out of asthma often develop symptoms again later in life. Ongoing airway inflammation may determine the risk of relapse, although the mechanisms involved are still misunderstood. Additionally, patients with asthma during childhood may develop irreversible airflow obstruction ( airway remodeling) as a result of chronic airway inflammation. Recently, airway inflammation and remodeling could be demonstrated in bronchial biopsy specimens from young adults who considered themselves grown out of asthma. It is also shown that evidence of airway inflammation and remodeling can be obtained noninvasively, thereby providing the opportunity to monitor disease activity. If chronic airway inflammation and/or remodeling are consistent findings in asymptomatic subjects with a history of atopic asthma, the question arises whether natural history can be positively altered with prolonged antiinflammatory therapy. Benefits of long-term prognosis are, however, not yet shown. Since epidemiologic work has demonstrated that a certain percentage of subjects with apparently outgrown atopic asthma remains asymptomatic without needing therapy for the rest of their lives, it can be argued that "asthma remission does exist." The question is whether this percentage can be increased with prolonged antiinflammatory therapy and regular control.     

Spontaneous tension pneumothorax: what is it and does it exist?

Tension pneumothorax is variously defined but is generally thought of as a pneumothorax in which the pressure of intrapleural gas exceeds atmospheric pressure, producing adverse effects, including mediastinal shift associated with cardiovascular collapse, often attributed to reduced venous return and kinking of the great vessels. The mechanism of tension pneumothorax is said to be a valvular defect in the visceral pleura such that air enters the pleural space in inspiration but cannot exit in expiration, leading to a progressive increase in pressure. However, as the driving pressure forcing air into the pleura in inspiration is atmospheric pressure, the pleural pressure can never exceed 1 atm during inspiration in a spontaneously breathing subject. Furthermore, all pneumothoraces must have pressures greater than atmospheric during expiration, or conventional treatment with intercostal tube drainage would not work. Pilot experiments have failed to show any re‐entry of pleural gas into the lung in patients with persistent air leaks but no evidence of tension, suggesting these behave as valvular pneumothoraces. Case reports of tension pneumothorax in spontaneously breathing patients are rare, and most patients have other explanations for clinical deterioration. Although a large and rapidly expanding pneumothorax may require urgent intervention, it is unlikely that the effects are mediated by high intrapleural pressures. The term tension pneumothorax in spontaneously breathing patients should be reconsidered.     

The metabolic syndrome in type 2 diabetes: When does it matter?

AIMS: Young adults with type 2 diabetes (T2Dm) present the clinician with the problem of when to start therapies for the primary prevention of vascular disease and how to identify those at most vascular risk. We examine whether the metabolic syndrome (MetS) can be a useful clinical tool to stratify vascular risk in this context. METHODS: Data were collected from 5928 subjects with T2Dm, and subjects were categorized as having MetS by World Health Organization criteria (body mass index criteria modified for Asians using >23 kg/m2). The prevalence of macrovascular disease was examined by MetS status and age. RESULTS: The overall MetS prevalence was 72.3%. MetS was associated with an increased prevalence of ischaemic heart disease (IHD) (17.2% MetS vs. 11.6% no MetS, p < 0.0001), coronary artery bypass graft (7.6 vs. 4.7%, p < 0.0003), peripheral vascular disease (PVD) (4.7 vs. 3.7%, p = 0.08) and stroke (6 vs. 3.9%, p = 0.002) across all age groups. MetS subjects had an IHD prevalence equivalent to that seen in subjects who were one decade older without MetS. The most significant impact of MetS was for the age group of 40-49 years with much lesser impact seen with progressively increasing age [odds ratio (OR) = 2.1 for IHD in MetS compared with no MetS at age 40-50 years, p < 0.05; falling progressively to OR = 1.5 at age >70 years, p > 0.05]. Similar trends were seen for coronary artery by-pass graft (CABG) and PVD. There was a strong relationship between the number of MetS risk factors and IHD prevalence (r = 0.99, p = 0.0001). CONCLUSIONS: These data suggest that MetS is particularly useful in stratifying vascular risk in younger T2Dm patients and in those with a high number of MetS components. For patients with MetS, especially those with a full house of MetS risk factors, commencing risk-lowering interventions 10 years earlier than their MetS-free counterparts could be considered.     

Acute idiopathic pancreatitis: does it really exist or is it a myth?

BACKGROUND: Acute pancreatitis is a severe disease with considerable morbidity and mortality. Gallstones and alcohol abuse are the most frequent causes (75% of patients). Other well-known causes are: hyperlipidemia, hypercalcaemia, abdominal surgery and drugs. In 10%-40% of patients however, no cause is identified after initial diagnostic evaluation: acute idiopathic pancreatitis. Identifying a cause in these patients is important, since the recurrence rate is high. METHODS: A systematic review of the current literature was performed to identify possible causes, diagnoses and treatment options of acute idiopathic pancreatitis. Relevant literature was found via Pubmed. RESULTS: The presence of microlithiasis or biliary sludge is an important cause of acute 'idiopathic' pancreatitis (up to 80% of patients). Microlithiasis and sludge can be detected by transabdominal/endoscopic ultrasonography, ERCP or polarizing light microscopy of bile. Cholecystectomy is the treatment of choice, whereas endoscopic sphincterotomy and ursodeoxycholic acid maintenance therapy are effective alternatives. Sphincter of Oddi dysfunction can be identified as the cause of acute 'idiopathic' pancreatitis in up to 30% of patients. Manometry of Oddi's sphincter is the gold standard for its diagnosis. Endoscopic sphincterotomy prevents recurrence in most patients. Anatomic abnormalities such as major papilla stenosis, pancreas divisum, pancreatic duct strictures and tumours may also cause acute 'idiopathic' pancreatitis. Endoscopic sphincterotomy and surgery are effective treatments. Finally, genetic screening may reveal gene mutations as the cause of acute 'idiopathic' pancreatitis. CONCLUSIONS: Acute 'idiopathic' pancreatitis is a severe disease with a high recurrence rate. Extensive diagnostic investigations may lead to a cause in >90% of patients.     

What is lifespan regulation and why does it exist?

The development of a unified conceptual framework for the field of biogerontology has been impeded by confusing and misleading terminology. Thus, distinctions and definitions are provided for key terms (and their concepts) used in the paper: senescence, lifespan, potential lifespan, essential lifespan, and lifespan regulation. An organismal perspective is then used to examine the relationships between reproduction, lifespan regulation and senescence. The principal conclusions drawn from this examination are: (1) the inevitability of death makes physiological investments in reproduction a higher priority than somatic maintenance, (2) the race between reproduction and death creates a probabilistic window of time (essential lifespan) within which reproduction must occur, (3) the integrated network of genetic processes responsible for achieving essential lifespan (lifespan regulation) must be evolutionarily conserved and extensively regulated, (4) senescence is a stochastic byproduct of these regulated processes rather than a direct target of natural selection, and (5) genomic instability (an important stochastic component of senescence) plays no active role in lifespan regulation.