Aim:The study aim was to evaluate the efficacy and safety of initial combination therapy with saxagliptin þ metformin vs. saxagliptin or metformin monotherapy in treatment-naïve patients with type 2 diabetes (T2D) and inadequate glycaemic control. Methods: In this multicentre, randomized, double-blind, active-controlled phase 3 trial, 1306 treatment-naïve patients with T2D !18 to 77 years, glycosylated haemoglobin (HbA1c) !8 to 12%, fasting C-peptide concentration !1.0 ng/ml, body mass index 40 kg/m 2 were randomized to receive saxagliptin 5 mg þ metformin 500 mg, saxagliptin 10 mg þ metformin 500 mg, saxagliptin 10 mg þ placebo or metformin 500 mg þ placebo for 24 weeks. From weeks 1-5, metformin was uptitrated in 500-mg/day increments to 2000 mg/day maximum in the saxagliptin 5 mg þ metformin, saxagliptin 10 mg þ metformin and metformin þ placebo treatment groups. The main outcome measure was HbA1c change from baseline to week 24. Selected secondary outcomes included change from baseline to week 24 in fasting plasma glucose (FPG), proportion of patients achieving HbA1c <7% and postprandial glucose area under the curve (PPG-AUC).Results: At 24 weeks, saxagliptin 5 mg þ metformin and saxagliptin 10 mg þ metformin demonstrated statistically significant adjusted mean decreases vs. saxagliptin 10 mg and metformin monotherapies in HbA1c (À2.5 and À2.5% vs. À1.7 and À2.0%, all p < 0.0001 vs. monotherapy) and FPG (À60 and À62 mg/dl vs. À31 and À47 mg/dl, both p < 0.0001 vs. saxagliptin 10 mg; p ¼ 0.0002 saxagliptin 5 mg þ metformin vs. metformin; p < 0.0001 saxagliptin 10 mg þ metformin vs. metformin). Proportion of patients achieving an HbA1c <7% was 60.3 and 59.7%, respectively, for saxagliptin 5 mg þ metformin and saxagliptin 10 mg þ metformin (all p < 0.0001 vs. monotherapy). PPG-AUC was significantly reduced [À21 080 mgÁmin/dl (saxagliptin 5 mg þ metformin) and À21 336 mgÁmin/dl (saxagliptin 10 mg þ metformin) vs. À16 054 mgÁmin/dl (saxagliptin 10 mg) and À15 005 mgÁmin/dl (metformin), all p < 0.0001 vs. monotherapy]. Adverse event occurrence was similar across all groups. Hypoglycaemic events were infrequent. Conclusion: Saxagliptin þ metformin as initial therapy led to statistically significant improvements compared with either treatment alone across key glycaemic parameters with a tolerability profile similar to the monotherapy components.

Waist circumference is a predictor of insulin resistance syndrome in children and adolescents and could be included in clinical practice as a simple tool to help identify children at risk.

OBJECTIVE -In the 5-10% of diabetic men with type 1 diabetes, erectile dysfunction (ED) may be a particularly common and unwanted complication. This is the first study focusing exclusively on the effects of sildenafil in men with type 1 diabetes and ED.RESEARCH DESIGN AND METHODS -A total of 188 patients were entered into a double-blind, placebo-controlled, parallel-group, flexible-dose study and were randomized to receive sildenafil (25-100 mg; n ϭ 95) or placebo (n ϭ 93) for 12 weeks. Efficacy was evaluated using questions three (Q3; achieving an erection) and four (Q4; maintaining an erection) from the International Index of Erectile Function (IIEF), a global efficacy question (GEQ; "Did treatment improve your erections?"), and a patient event log of sexual activity.RESULTS -Improvements in mean scores from baseline to end-of-treatment for IIEF Q3 (35.7 vs. 19.9%) and Q4 (68.4 vs. 26.5%) were significant in patients receiving sildenafil compared with those receiving placebo (P ϭ 0.0001). Moreover, the percent of improved erections (GEQ, 66.6 vs. 28.6%) and successful intercourse attempts (63 vs. 33%) was significantly increased with sildenafil compared with placebo. Improvements in sexual function were seen irrespective of the degree of ED severity. Adverse events were generally mild to moderate in severity, with headache (20 vs. 8%), flushing (18 vs. 3%), and dyspepsia (8 vs. 1%) reported more often in the sildenafil than in placebo-treated patients.CONCLUSIONS -Treatment with sildenafil for ED was effective, resulting in an increased percentage of successful attempts at intercourse, and was well tolerated among men with type 1 diabetes. Diabetes Care 26:279 -284, 2003A ccording to the World Health Organization, the number of adults with diabetes was ϳ135 million in 1995, which corresponds to a worldwide prevalence of 4% (1). It is estimated that 5-10% of diagnosed cases are type 1 diabetes (2).A common complication of diabetes is erectile dysfunction (ED), with an estimated prevalence of 20 -85% (ranging from mild to complete ED) (3), which occurs at an earlier age than in nondiabetic men. In the Massachusetts Male Aging Study (4), men with treated diabetes had a 28% age-adjusted prevalence of complete ED (no erections), almost three times higher than the prevalence of complete ED observed in the entire sample of men (10%). Several studies have shown an increased risk of ED in men with diabetes; however, most information refers to the total male diabetic population, and few studies have presented data specifically for type 1 diabetes (5-8). Although the prevalence of ED in the total diabetic population increases with age, smoking, and poor metabolic control, one study reported that men with elevated BMI and type 1 diabetes showed a significantly higher risk of ED than men with elevated BMI and type 2 diabetes (7). The same study also showed that the age-adjusted prevalence of ED was higher in men with type 1 diabetes (51%) than with type 2 diabetes (37%).Although the etiology of ED in patients with diabetes...

The present report concerns investigation of bladder disturbances in 31 juvenile diabetics. It was shown that: 1. The predominant lesion is one of neuropathy.-2. Vesical involvement such as increased capacity and atony was demonstrated by cystometry in 27 out of the 31 cases (87%).-3. 4 cases had neck hypertrophy.-4. The most striking symptom was a large volume of first morning urine. This information was elicited from the patients. They had no urological complaints.-5. A high incidence of impotence was seen in diabetics with neurogenic bladder.-6. The possible causes of such lesions and the value of certain therapeutic measures was discussed. Vessie neurog~ne asymptomatique ehez des diabdtigue~ ]eunes Rdsumd. Le prdsent travail coneerne une investigation sur les troubles de la vessie chez 31 diabdtiques jeunes. I1 a @t6 dgmontrd que: 1. La 16sion pr6dominante est une 16sion de neuropathie.-2. Des signes v@sicaux tels que la capacitd accrue et l'atonie mesur6es par cystom@trie, ont 6t4 d6montr6s darts 27 cas sur les 31 (87%).-3. 4 cas avaient une hypertrophie du col.-4. Le symptome le plus frappant 6tait l'important volume de la premiere urine du matin. Ceci a 6t6 indiqu6 par los patients. Ils ne se plaignaient d'aucun trouble urologiquc.-5. On trouve une haute frdquence d'impuissance chez les diab@tiques ayant une vessie neurog6ne.-6. Les causes possibles de telles 16sions et la valeur de eertaines mesures th@rapeutiques sont diseutges. Asymptomatische neurogene BlasenstSrung bei jugendlichen Diabetilcern Zusammenfassung. Es wird fiber Blasenst6rungen bei 31 jugendliehen Diabetikern berichtet. Es konnte gezeigt werden, dal3: 1. die Neuropathie die vorherrschende StSrung darstellt ; 2. bei 27 yon 31 F~llen (87%) eine Blasenbeteiligung (gesteigerte Kapazit~t und zytometrisch nachweisbare Atonie) vorlag;-3. bei 4 F~llen eine Blasenhalshypertrophie bestand;-4. hervorstechendes Syruptom war die grol]e Harnmenge bei der ersten morgcndlichen Blasenentleerung, fiber das die Patienten auf Anfrage beriehteten. Sic iiul~erten keine urologischen Beschwerden;-5. Bei vielen Diabetikern mit einer neurogenen Blasenst6rung ist eine Impotenz festzustellen;-6. Die fiir diese Lfisionen in Frage kommenden Ursachen und der Weft einiger therapeutiseher Ma2nahmen werden diskutiert.

Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions.

Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile.

LA enlargement is present in childhood and is related to abdominal OB and insulin resistance, suggesting that children with central OB are at increased risk for cardiovascular disease.

Reports on the histologic aspects of the autonomic nerves in diabetics are infrequent. This investigation was carried out to study histologically and histochemically the autonomic nerve fibers of the urinary bladder wall in ten diabetic patients. Of the five subjects examined by biopsy, four showed damage of nerve fibers; absence of cholinesterase activity was the only finding in the fifth patient who had chemical diabetes.In four autopsies we found alterations in all the cases. The lesions appeared as beaded or spindle-shaped fibers or small vacuolated or uniformly thickened fibers. The most severe cases exhibited fragmentation of the fibers.Histochemical analysis demonstrated absence of cholinesterase activity in the muscle, in all cases, and absence or decrease of such activity in the nerves in all but one case.Similar studies performed on eight nondiabetic subjects revealed no anatomic or histochemical lesions.The findings lead to the hypothesis that diabetic neuropathy injures the biochemical phase of the myelin sheath in the first stage and the nerve fibers later. No previous reports on the subject here studied could be found in the literature. DIABETES 22:225-37, April, 1973.