In this issue

Inflammation and the etiology of type 2 diabetes

In recent years, several studies have indicated that subclinical chronic inflammation is an important pathogenetic factor in the development of insulin resistance and type 2 diabetes. Existing antidiabetic agents such as the glitazones reduce inflammation, as do non-pharmacological actions that help prevent diabetes such as weight loss or stopping smoking. This review looks at epidemiological studies in which C-reactive protein serves as a independent risk factor for both diabetes and cardiovascular disease. The authors call for more specific and sensitive biomarkers to predict early disturbances in insulin sensitivity and cardiovascular risk. They review the results from trials of ACE inhibitors, angiotensin receptor antagonists and statins, focusing on effects on insulin resistance and inflammation. The authors believe that more detailed research on inflammatory signalling pathways may provide druggable targets that can be exploited to counter the epidemic of insulin resistance and atherosclerosis.

Energy well spent fighting the diabetes epidemic

This review focuses on the role of fat accumulation within skeletal muscle in the development of insulin resistance. The authors contend that short-term fat-induced insulin resistance in muscle underlies a coordinated physiological response that, for our ancestors, aided survival. This “hunter-gatherer” physiology predisposes to diabetes in a modern environment characterised by muscular inactivity, yet medical science continues to seek a molecular target in favour of the obvious “evolutionary medicine”. The suitability of current physical activity guidelines and the efficacy of physical activity interventions in the prevention of type-2 diabetes are discussed in relation to the expectations of our genes.

The psychological impact of screening for type 2 diabetes

The damage caused by undetected and therefore uncontrolled diabetes in terms of complications has resulted in calls for screening of general or high-risk populations. Until now, there has been little evidence regarding the impact of such screening on the mental health of people who receive a positive diagnosis. Some recent population-based studies on the psychological impact of such screening have been published. This review concludes that a positive diagnosis of type 2 diagnosis in patients who, despite exhibiting several risk factors, did not consider themselves to be at risk does not have an adverse effect on their perceived health status and well-being. The authors suggest more detailed research into the reasons underlying this lack of effect might be informative but generally this paper provides encouraging support for those trying to implement screening programmes.

The insulin sensitivity, glucose sensitivity, and acute insulin response to glucose load in adolescent type 2 diabetes in Taiwanese

Type 2 diabetes is becoming more prevalent in young people but few studies have been done on the pathological changes that occur during the development of diabetes in this age group. This study investigated insulin secretion, insulin sensitivity and the acute insulin response to glucose load in 40 Taiwanese patients aged up to 22 years. These were all impaired in the young diabetic patients, as is observed in older patients. The authors subdivided the group according to their BMI and found no differences in insulin or glucose sensitivity but a higher acute insulin response in the obese patients. Although small, this study provides some interesting data on the pathogenesis of diabetes in young people.

Increasing incidence of type 1 diabetes in population from Santiago of Chile: trends from 1986–2003

The incidence of type 1 diabetes varies around the world, according to both genetic and environmental factors. This population-based incidence study estimated the overall rate of type 1 diabetes in the Chilean capital as 4.02 cases per 100 000 children per year. This is considerably higher than the last estimate, which was 2.36 cases per 100 000 per year for the period 1986 to 1992, providing further evidence that the incidence of type 1 diabetes is increasing worldwide.

Antioxidants and an inhibitor of advanced glycation delay death of retinal microvascular cells in diabetic retinopathy

These Japanese authors have previously reported that the apoptosis of pericytes and endothelial cells in the eye, collectively known as retinal microvascular cells, was accelerated in diabetic patients and in two rat models that develop the early stages of retinopathy. In this study, they confirm that the Goto-Kakizaki rat, which spontaneously develops type 2 diabetes, also shows accelerated apoptosis of retinal microvascular cells. Thus retinal damage can occur in the presence of only mild hyperglycaemia. The authors treated these rats with a combination of Vitamin C and Vitamin E, or with an inhibitor of advanced glycation. Each treatment prevented most of the apoptosis in the retinas of the diabetic rats and thus holds promise for therapeutic application in patients with diabetic retinopathy.

Phenotypic and genetic clustering of diabetes and metabolic syndrome in Chinese families with type 2 diabetes mellitus

Prevention of type 2 diabetes may be achieved by screening to identify people at high risk of the disease but with a global epidemic of diabetes looming, whom should we screen? This report from the Hong Kong Family Diabetes Study demonstrates high recurrence risk ratios for diabetes, hypertension and central obesity in siblings of people with young-onset type 2 diabetes. The authors found high estimates of heritability for BMI, waist circumference, blood pressure, lipids, insulin resistance and β-cell function. They conclude that screening for both diabetes and the metabolic syndrome is important in relatives of young-onset type 2 diabetes patients. The families in this study should prove invaluable for further genetic studies of these disorders.

Clustering of β-cell autoimmunity within families

It is well established that type 1 diabetes is characterised by familial aggregation. This Finnish group studied whether β-cell autoimmunity preceding clinical disease also shows familial clustering. They tested 5836 children from 2283 families for their HLA DQB1 alleles and for islet cell autoantibodies. The proportion of families with a minimum of two children positive for at least the islet cell autoantibodies was almost five times higher than that expected. The frequency of multiple autoantibodies also showed familial aggregation. This study verifies that β-cell autoimmunity demonstrates familial clustering, although the antibodies did not appear in close temporal proximity or at an identical age within the same family.

Effect of antiretroviral agents on carbohydrate metabolism in HIV-1 infected pregnant women

Antiretroviral drugs are a very effective way of preventing vertical transmission of HIV but these drugs, particularly protease inhibitors, perturb carbohydrate metabolism. Although metabolic changes during gestation predispose to maternal and perinatal complications, there have been few studies of the effects of these drugs on pregnant women. El Beitune et al performed a prospective cohort study of 57 pregnant women attending their hospital in Sao Paolo, Brazil: 45 were infected with HIV and the remainder formed the control group. Glycaemia increased in the group receiving triple antiretroviral therapy (300 mg zidovudine, 150 mg lamivudine, and 1250 mg nelfinavir in two daily administrations) but not in those receiving zidovudine alone or the control group. Further studies are required to determine the safety of the use of these drugs for the mother-fetus pair.

Cyclic AMP/cAMP-GEF pathway amplifies insulin exocytosis induced by Ca2+ and ATP in rat islet ß cells

Incretins such as glucagon-like peptide-1 and gastric inhibitory polypeptide are secreted from gastrointestinal endocrine cells and provide a link between food intake and glucose homeostasis. These gut peptides bind to their cognate receptors on plasma membranes of pancreatic β-cells and have insulinotropic effects mediated mainly by increase of cytosolic cyclic AMP. The detailed mechanism, particularly the role of Ca2+, remains to be elucidated. The authors studied insulin exocytosis from permeabilized islet cells using two cyclic AMP messengers, namely a classical protein kinase A and a newly cloned cAMP-GEF. They found that cyclic AMP potentiates exocytosis induced by either Ca2+ or ATP to a similar extent, independent of Ca2+ concentrations. The process seemed to be mediated by cAMP-GEF, which acts downstream of ATP in the signalling pathway. The authors claim their results support the hypothesis that cyclic AMP replenishes the pool of readily releasable insulin granules.

Age-related anthropometric remodelling resulting in increased and redistributed adiposity is associated with increases in the prevalence of cardiovascular risk factors in Chinese subjects

Over half the population between 65 and 74 years in Hong Kong has hypertension and one-quarter have diabetes. The prevalence of obesity, as determined using Asian BMI guidelines, is 44% but Chinese subjects have a greater percentage of body fat at a given BMI than Caucasians. Central adiposity is regarded as a key component of the metabolic syndrome under some definitions. This study in almost 700 Han Chinese adults found that in men, while the BMI remained almost constant, waist size and percentage body fat both increased with age. In women, these two parameters also increased with age, as did BMI. In both sexes, the rise in the proportion of body fat, particularly centrally, was associated with worsening cardiovascular risk factors.

Elevated serum urate concentration independently predicts poor outcome following stroke in patients with diabetes

Type 2 diabetes is a risk factor for stroke and confers increased risk of poor outcome and further vascular events following stroke. Patients with type 2 diabetes commonly experience hyperuricaemia but its significance as a predictor of outcome following stroke is uncertain. This study assessed 140 patients with type 2 diabetes who presented to the Acute Stroke Unit in Glasgow. The main outcome event was time to myocardial infarction, recurrent stroke or vascular death, as defined in the CAPRIE trial. The study found that a high urate concentration is significantly and independently associated with increased risk of future vascular events in diabetic stroke patients. The authors suggest that urate should be routinely measured in diabetic patients with stroke, and aggressive risk factor modification should be instituted.