Most European populations have a moderate to low prevalence of diabetes and IGR. Diabetes and IGR will be underestimated in Europe, particularly in women and in elderly men, if diagnoses are based on fasting glucose determination alone.

Amyloid deposits derived from the amylin peptide accumulate within pancreatic islet b-cells in most cases of type-2 diabetes mellitus (T2Dm). Human amylin 'oligomers' are toxic to these cells. Using two different experimental techniques, we found that H 2 O 2 was generated during the aggregation of human amylin into amyloid fibrils. This process was greatly stimulated by Cu(II) ions, and human amylin was retained on a copper affinity column. In contrast, rodent amylin, which is not toxic, failed to generate any H 2 O 2 and did not interact with copper. We conclude that the formation of H 2 O 2 from amylin could contribute to the progressive degeneration of islet cells in T2Dm.

OBJECTIVE -The aim of this study was to report the baseline and natural progression of diabetic peripheral neuropathy over 12 months in a large mild-to-moderate neuropathy population.RESEARCH DESIGN AND METHODS -Patients from a multicentered trial of zenarestat, an aldose reductase inhibitor, had serial measures of neurologic function, including nerve conduction studies (NCSs), quantitative sensory testing (QST), and clinical neuropathy rating scores at baseline and at 12 months. Baseline population descriptors and changes in neurologic function in placebo-treated patients were analyzed. CONCLUSIONS -The neurologic decline over 12 months is evident when measured by NCS and cool thermal QST. Other measures (vibration QST, neuropathy rating scores, monofilament examination) are insensitive to changes over 12 months in a mild-to-moderate affected population of this size. RESULTS Diabetes Care 27:1153-1159, 2004D iabetic peripheral neuropathy (DPN) is a debilitating condition affecting as many as one-half of all patients with diabetes during the course of their disease (1). The progressive, irreversible course of the disease ultimately leads to an increased incidence of ulceration and limb amputations (2).Currently, therapy is limited to intensive glycemic control and symptomatic treatments. It is critical to identify the appropriate study population within the broad continuum of the disease when evaluating potential therapies. For example, pancreatic islet transplantation work suggests that severe neuropathy is not amenable to therapy (3,4). Defining a mildto-moderate, perhaps more responsive, DPN population may be helpful in identifying new therapeutic modalities (5).Objective, yet clinically meaningful, data characterizing the natural progression of mild-to-moderate DPN are also lacking. One issue is the uncertain rate of disease progression (6,7). Another is lack of agreement regarding the clinical relevance of the available scientifically rigorous measures of DPN. The San Antonio neuropathy consensus called for study designs requiring multiple, often expensive electrophysiologic, sensory, and clinical tools to document disease progression and response to therapy (8,9). Only a fraction of these tools translate directly to patient outcomes. None are widely used in clinical practice or are accessible to primary care practitioners.Increased nerve sorbitol and fructose associated with hyperglycemia remain a hypothesized causal mechanism of DPN. Inhibition of aldose reductase, the enzyme responsible for converting glucose to sorbitol, demonstrates reduced nerve degeneration and improved nerve conduction in animal models and humans (10). Previous aldose reductase inhibitors (ARIs) have been plagued with problems, including occasional marginal efficacy, lack of tissue permeability, and a variety of toxicities lacking a common causal mechanism.Zenarestat, a highly potent ARI, was evaluated in a large phase 3 trial of mild distal symmetrical DPN, using guidelines provided by the consensus panels (8,9,11). This study was ...

Aims/hypothesis. We examined the association between plasma insulin and cardiovascular mortality in non-diabetic European men and women based on data from eleven prospective studies. Methods. The study population comprised 6156 men and 5351 women aged 30-89 years. Baseline measurements included oral glucose tolerance test, fasting and 2-h plasma insulin, and conventional risk factors. Cox models were used to calculate hazard ratios (HRs) and their 95% confidence intervals, and overall HRs were assessed by meta-analyses. Results. During the 8.8-year follow-up, 362 men and 70 women died from cardiovascular disease. The ageand smoking-adjusted overall HR of cardiovascular mortality for the highest vs the lower quartiles of fasting insulin was 1.58 (95% CI: 1.26-1.97) in men and 2.64 (1.54-4.51) in women. Adjusting for other risk factors in addition, the HR was 1.54 (1.16-2.03) in men and 2.66 (1.45-4.90) in women. For 2-h insulin these HRs were 1.28 (0.99-1.66), 1.87 (0.87-4.02), and 0.85 (0.60-1.21), 1.36 (0.53-3.45). The overall HRs for interquartile ranges for fasting and 2-h insulin, with full adjustment, were 1.13 (1.05-1.22) and 1.11 (1.01-1.23) in men, and 1.25 (1.08-1.45) and 1.11 (0.91-1.36) in women. Conclusions/interpretation. Hyperinsulinaemia, defined by the highest quartile cut-off for fasting insulin, was significantly associated with cardiovascular mortality in both men and women independently of other risk factors. Associations between high 2-h insulin and cardiovascular mortality were weaker and non-significant. Weak positive associations of fasting and 2-h insulin with cardiovascular mortality over interquartile ranges were, however, more similar. Diabetologia (2004) 47:1245-1256 DOI 10.1007/s00125-004-1433 Plasma insulin and cardiovascular mortality in non-diabetic European men and women: a meta-analysis of data from eleven prospective studies The DECODE Insulin Study Group IntroductionThe role of hyperinsulinaemia as an independent risk factor for cardiovascular disease (CVD) has previously been debated. An association between elevated plasma insulin, fasting or oral glucose load, and the risk of CHD or atherosclerotic CVD has been found in many [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16] but not in all [17,18,19,20,21] prospective studies. Among the studies showing the positive association between plasma insulin and CVD, the effect of adjustment for other risk factors has varied. In several studies the association remained statistically significant, although attenuated [1,2,3,5,6,7,9,10,12,13,15,16] , whereas in other studies it became non-significant [4,8,11,14]. The majority of the published Corresponding author of the DECODE Insulin Study Group: G. Hu, Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland, Phone: +358-9-19127366, Fax: +358-9-19127313, e-mail: hu.gang@ktl.fi Members of the DECODE Insulin Study Group are listed at the end of the paper studies were carried...

Conclusion In acute exacerbation of COPD there is no difference between 7-day and 14-day courses of treatment with oral prednisolone. The peak of FEV 1 and FVC in 7-day group on day-10 where corticosteroid was already stopped on day-7, (peak in 14-day group was on day-7) might be due to some other factor/factors responsible which would be cleared by further study. Clinical implications There was no difference between 7-day and 14-day courses of prednisolone treatment, so, 7-day might be the shortest effective course of steroid treatment in acute exacerbation of COPD to avoid the burden of cost and side effects.

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