In this issue
Insulin glargine and receptor-mediated signalling: clinical implications in treating type 2 diabetes
With the introduction of insulin analogues for improving treatment of type 1 and type 2 diabetes, concerns have been raised about the altered interaction of these insulins with the insulin and insulin-like growth factor-1 receptors (IGF-1R). A change in the binding or activation of the IGF-1R could be reflected in a mitogenic effect. Most in vitro binding-affinity and cell-culture studies have demonstrated that insulin glargine is comparable to regular human insulin for both metabolic and mitogenic potential. Furthermore, insulin glargine is not associated with clinically apparent carcinogenesis or progression of diabetic retinopathy.
Circulating adiponectin and adiponectin receptor expression in skeletal muscle: effects of exercise
Circulating levels of adiponectin, particularly the high molecular weight (HMW) form, are decreased in obesity. Adiponectin exerts insulin-like and sensitizing actions to promote glucose uptake into skeletal muscle and increase fat oxidation. This is akin to exercise and effectively improves metabolic abnormalities associated with obesity and diabetes. In this review, the authors examine the relationship between exercise and adiponecin action or circulating levels. They summarize key findings from a variety of exercise protocols, which largely suggest that changes in the expression of adiponectin receptor isoforms in skeletal muscle, rather than circulating total adiponectin levels, may be of physiological importance.
Glycemic control is related to the severity of impaired thermal sensations in type 2 diabetes
Sensory neuropathy is associated with ominous consequences of diabetes, such as foot ulcer and amputation, but there is a lack of systematic studies on its occurrence in large cohorts. With quantitative sensory testing, we investigated (1) patterns of sensory deficits, (2) impact of glycemic control on thermal thresholds, and (3) contribution of these abnormalities to neuropathic symptoms. Impaired thermal sensation was the most frequent sensory deficit in diabetes and thermal thresholds linearly correlated with HbA1C. Elevated thermal threshold was an independent risk factor of neuropathic symptoms. These results provide rationales for quantitative sensory testing as a screening procedure of diabetic neuropathy.
The relationship of the methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish type 2 diabetic patients with and without nephropathy
In this paper Turkish type 2 diabetic patients with/without diabetic nephropathy and healthy control subjects were examined as to the contribution of the MTHFR (methylenetetrahydrofolate reductase) gene polymorphism to the development of diabetic nephropathy. Genotyping of the MTHFR C677T polymorphism for all individuals was performed by melting curve analysis of the generated amplicons after real-time online PCR. Results of the study showed that the MTHFR genotype and allele frequencies were not different between diabetic patients with and without nephropathy (χ2 = 3, 386, p > 0.005; χ2 = 2.320, p > 0.005, respectively). The authors conclude that the MTHFR gene polymorphism is not associated with the development of diabetic nephropathy in type 2 diabetic patients.
Prognostic value of serum liver enzymes levels in type 2 diabetic patients
Elevated liver enzymes are associated with cardiovascular disease, although their relationship with cancer-related mortality has yet to be assessed in diabetic patients. An observational cohort study was performed on a consecutive series of 1,952 type 2 diabetic patients to assess whether γ-GT and ALT levels were associated with cardiovascular and cancer-related mortality. A total of 362 deaths were recorded, corresponding to a yearly mortality rate of 4.2%. Both cardiovascular and cancer-related mortality were increased in patients with elevated γ-GT (15.3% vs. 10.8%, p < 0.05), even after adjusting for diabetes duration and control.
CYP2R1 (vitamin D 25-hydroxylase) gene is associated with susceptibility to type 1 diabetes and vitamin D levels in Germans
So far, CYP2R1 has been investigated in patients with vitamin D-dependent rickets (3) but not in association with type 1 diabetes, where low vitamin D serum levels have been associated with a higher risk. In the present study, the authors analyzed the role of two polymorphisms within the CYP2R1 gene and their influence on the 25(OH)D3 levels and on the CYP2R1 mRNA in the susceptibility to type 1 diabetes in Germans. In this population, the allele “G” of the rs10741657 polymorphism was more frequently transmitted from the parents to their affected offspring. Based on this result, this allele “G” is associated with susceptibility to type 1 diabetes in the German population, while the allele “A” might confer protection. Thus, the findings reveal a novel association of CYP2R1 polymorphisms in patients with type 1 diabetes and with their circulating levels of 25(OH)D3.
The age at diagnosis of type 1 diabetes continues to decrease in Belgian boys but not in girls: a 15-year survey
The age at onset of type 1 diabetes is decreasing in much of the world. Preliminary Belgian data suggested that this anticipation (earlier age of onset) occurred preferentially in boys. These authors investigated whether this gender-specific anticipation could be confirmed by studying incidence trends in 746 type 1 diabetic patients under age 40 from Antwerp. Analyses revealed that the incidence of type 1 diabetes under age 15 increased over time. The rising incidence in children was restricted to boys under age 10, in whom the incidence more than doubled during the 15-year period. The authors conclude that, over a 15-year observation period, a selective anticipation of clinical onset of type 1 diabetes was found in boys but not in girls.
C-fos expression at the spinal dorsal horn of streptozotocin- induced diabetic rats
The activation of the c-fos protooncogene was used to study the activity of spinal dorsal horn neurons in streptozotocin (STZ)-induced diabetic rats, with 4 weeks of disease, in the absence of stimulation or in response to innocuous or noxious stimuli. In the absence of stimulation STZ-injected rats presented significantly higher numbers of Fos-immunoreactive neurons than controls both in the superficial and deep dorsal horn. Noxious stimuli increased the numbers of Fos-immunoreactive neurons both in control and STZ-rats. Our study shows that the responses of spinal neurons are strongly affected during diabetes, probably underlying the spontaneous pain detected during the disease.
Tissue factor activities of streptozotocin induced diabetic rat tissues and the effect of peanut consumption
Tissue factor activity (TFA) of streptozotocin induced diabetic rat tissues and the effect of peanut consumption for 12 weeks were investigated in this study. TFA of liver, kidney and spleen increased whereas TFA of brain decreased in diabetic group. Peanut consumption decreased TFA of spleen and aorta in diabetic group. Haemostatic parameters did not change significantly in groups. Elevated TFA in diabetic rats, may contribute to the increased risk of atherothrombotic disease whereas the decreased brain TFA may be due to a different hemostatic mechanism. Decreased TFA in peanut given diabetic rats might protect tissues from the risk of thrombosis.
