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Background: One of the most frequently adopted strategies to counterbalance the risk of exercise-induced hypoglycemia in patients with type 1 diabetes is carbohydrates supplement. Nevertheless, the estimation of its amount is still challenging. We investigated the efficacy of the personalized Exercise Carbohydrate Requirement Estimation System (ECRES) method compared to a tabular approach to estimate the glucose supplement needed for the prevention of exercise-related glycemic imbalances., Method: Twenty-six patients performed two one-hour constant intensity exercises one week apart; the amount of extra carbohydrates was estimated, in random order, by the personalized ECRES method or through the tabular approach; glycemia was determined every 30 minutes. Continuous glucose monitoring (CGM) metrics were calculated over the 48 hours preceding, and the afternoon and night following the trials., Results: Applying the personalized ECRES method, a significantly lower amount of carbohydrates was administered to the active patients compared to the tabular approach, median (interquartile range): 9.0 (0.5-21.0) g vs 23.0 (21.0-25.0) g; P < .01; the two methods were similar for the sedentary patients, 18 (13.5-36.0) g vs 23.0 (21.0-27.0) g; P = NS. After overlapping CGM metrics before the exercises, both methods avoided hypoglycemia and resulted in similar glucose levels throughout them. The ECRES method led to CGM metrics within the guidelines for either the afternoon and the night just following the trials, whereas the tabular approach resulted in a significantly greater time below range in the afternoon (11.8% ± 18.2%; P < .05) and time above range during the night (39.3% ± 29.8%; P < .05)., Conclusions: The results support the validity of the personalized ECRES method: although the estimated amounts of carbohydrates were lower, patients' glycemia was maintained within safe clinical limits.

Background: Charcot neuroarthropathy is a serious complication associated with diabetic neuropathy. This complication probably is most serious when the ankle is involved because of the instability and progressive deformity, which often leads to ulceration, osteomyelitis, and amputation. Arthrodesis before the ulcerated lesion appears is considered a limb salvage treatment. One of the most effective techniques for an unstable ankle in Charcot neuroarthropathy is retrograde transcalcaneal nailing., Methods: Eighteen diabetic patients, without a history of ulceration, were treated from July, 2003, to November, 2005, with panarthrodesis of the ankle using intramedullary retrograde transcalcaneal nailing. The average follow up was 14 +/- 10.1 months. All patients completed the unloaded postoperative period with a fiberglass cast (3 months nonweightbearing and 3 months partial weightbearing) and commenced walking in shoes with a stiff rocker sole and a molded insole., Results: During the followup period there were no major complications. In three patients, removal of one of the proximal screws used for anchoring the nail to the tibia was done because of protrusion causing skin breakdown. Fourteen patients had a stable fusion and four patients had fibrous union. The percentage of limb salvage was 100% in the followup period., Conclusions: Our study confirms that this operative technique is effective and safe.

Background and Aims: A single high-fat meal may induce endothelial activation and dysfunction in both normal subjects and in patients with type 2 diabetes. The aim of this study was to assess the effect of a high-fat meal on endothelial function in patients with the metabolic syndrome., Methods and Results: Twenty-five patients with the metabolic syndrome (ATP III criteria) were matched for sex, age and body mass index with 25 subjects without the metabolic syndrome. All subjects ate under supervision a high fat meal (760 calories) with 59% energy from fat, 12% energy from protein and 29% energy from carbohydrates. Compared with the control group, subjects with the metabolic syndrome had reduced endothelial function, as assessed with the l-arginine test, and higher circulating levels of TNF-alpha. Following the high-fat meal, both triglyceride and TNF-alpha levels increased more in subjects with the metabolic syndrome than in subjects without, while endothelial function decreased more in subjects with the metabolic syndrome. There was a significant relation between increases in TNF-alpha levels and decreases in endothelial function score in subjects with the metabolic syndrome (r=-0.39, P=0.03)., Conclusion: TNF-alpha levels are increased in subjects with the metabolic syndrome; moreover, a high-fat meal produces further increase in its levels associated with endothelial dysfunction.

There is increasing evidence that the postprandial state is an important contributing factor to the development of atherosclerosis. In diabetes, the postprandial phase is characterized by a rapid and large increase in blood glucose levels, and the possibility that the postprandial hyperglycemic spikes may be relevant to the pathophysiology of late diabetic complications has received recently much more attention. The oral glucose tolerance test, although non-physiological, has been used highly as model of the postprandial state. Epidemiological studies have shown that, when impaired, oral glucose tolerance is associated with an increased risk of cardiovascular disease, being the glycemia after two hours of the glucose challenge a direct and independent risk factor. Moreover, the possibility that postprandial hyperglycemia is a risk factor for cardiovascular disease also in diabetic patients has been reported. Most of the cardiovascular risk factors are modified in the postprandial phase in diabetic subjects and directly affected by an acute increase of glycemia. The mechanisms through which acute hyperglycaemia exerts its effects may be identified in labile non-enzymatic glycation and in production of free radicals. It is likely that the two mechanisms co-operate in causing the disorders induced by acute hyperglycemia. Correction of the postprandial hyperglycemia can be part of the strategy for the prevention and management of cardiovascular diseases in diabetes.

In diabetes, oxidative stress plays a key role in the pathogenesis of vascular complications, and an early step of such damage is considered to be the development of an endothelial dysfunction. Hyperglycemia directly promotes an endothelial dysfunction inducing process of overproduction of superoxide and consequently peroxynitrite, that damages DNA and activates the nuclear enzyme poly(ADP-ribose) polymerase. This process, depleting NAD+, slowing glycolsis, ATP formation and electron transport, results in acute endothelial dysfunction in diabetic blood vessels and contributes to the development of diabetic complications. These new findings may explain why classical antioxidants, like vitamin E, that work scavenging already formed toxic oxidation products, have failed to show beneficial effects on diabetic complications, and suggest new and attractive "causal" antioxidant therapy. New, low molecular mass compounds that act as SOD or catalase mimetics or L-propionyl-carnitine and lipoic acid, that work as intracellular superoxide scavengers, improving mitochondrial function and reducing DNA damage, may be good candidates for such strategy, and preliminary studies support this hypothesis. This "causal" therapy would also be associated with other promising tools such as LY 333531, PJ34 and FP15, which block protein kinase beta isoform, poly(ADP-ribose) polymerase and peroxynitrite, respectively. It is now evident that, statins, ACE inhibitors, AT-1 blockers, calcium channel blockers and thiazolidinediones have a strong intracellular antioxidant activity, and it has been suggested that many of their beneficial ancillary effects are due to this property. This preventive activity against oxidative stress generation can justify a large utilization and association of this compounds for preventing complications in diabetic patients where antioxidant defences have been shown to be defective.

In diabetes oxidative stress plays a key role in the pathogenesis of vascular complications, and an early step of such damage is considered the development of an endothelial dysfunction. Hyperglycemia directly promotes an endothelial dysfunction inducing process of overproduction of superoxide and consequently peroxynitrite that damages DNA and activates the nuclear enzyme poly(ADP-ribose) polymerase. This process, depleting NAD+, slowing glycolysis, ATP formation and electron transport, results in acute endothelial dysfunction in diabetic blood vessels and contributes to the development of diabetic complications. Classic antioxidants, like vitamin E, failed to show beneficial effects on diabetic complications probably due to their only "symptomatic" action. It is now evident that, statins, ACE inhibitors, AT-1 blockers, calcium channel blockers and thiazolinediones have a strong intracellular antioxidant activity, and it has been suggested that many of their beneficial ancillary effects are due to this property. Statins increase NO bioavailability and decrease superoxide production, probably interfering with NAD(P)H activity and modulating eNOS expression. ACE inhibitors and AT-1 blockers prevent hyperglycemia-derived oxidative stress modulating angiotensin action and production. This effect is of particular interest because hyperglycemia is able to directly modulate cellular angiotensin generation. Calcium channel blockers inhibit the peroxidation of cell membrane lipids and their subsequent intracellular translocation. Thiazolinediones bind and activate the nuclear peroxisome proliferator-activated receptor gamma, a nuclear receptor of ligand-dependent transcription factors. The inhibition of this receptors lead to inhibition of the inducible nitric oxide synthase and consequently reduction of peroxynitrite generation. This preventive activity against oxidative stress generation can justify a large utilization and association of this compound for preventing complications in diabetic patients, where antioxidant defences have been shown to be defective.