BackgroundIt is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. MethodsIn this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. ResultsThe cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P = 0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P = 0.85). ConclusionsAmong patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.)Copyright © 2010 Massachusetts Medical Society. All rights reserved.Downloaded from www.nejm.org by JEAN-CHRISTOPHE PHILIPS on May 3, 2010 .T h e ne w e ngl a nd jou r na l o f m e dic i ne n engl j med 362;16 nejm.org april 22, 2010 1478 P atients with impaired glucose tolerance have an increased risk of type 2 diabetes mellitus and cardiovascular disease. [1][2][3] Interventions that might reduce the incidence of diabetes and associated rates of death and complications from cardiovascular causes in such patients are therefore of importance. 3 Several trials have shown that lifestyle modification, including increased physical activity and weight loss, reduces the risk of diabetes, although these trials did not evaluate cardiovascular outcomes. [3][4][5][6][7][8] Certain drugs, including metformin, acarbose, and rosiglitazone, also reduce the incidence of diabetes, although their effect on cardiovascular events is uncertain. 6,9,10 Another pharmacologic approach to reducing the risk of diabetes and cardiovascular disease is inhibition of the renin-angiotensin system. Some studies have shown that angiotensin-convertingenzyme (ACE) inhibitors and ang...

BackgroundThe ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown. MethodsIn a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization. ResultsAfter adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P = 0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P = 0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P = 0.16). Nateglinide did, however, increase the risk of hypoglycemia. ConclusionsAmong persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.)

The occurrence of oral leukoplakia and lichen planus in 1600 patients with diabetes mellitus (815 type 1: insulin-dependent, 761 type 2: non-insulin-dependent)-under care at the International Medicine Department-was studied. Precancerous lesions and conditions were diagnosed and grouped according to internationally accepted criteria. The prevalence of oral leukoplakia in diabetic patients was 6.2%, as compared to 2.2% in the healthy controls, that of oral lichen was 1.0% in the test-, and 0.0% in the control group. Leukoplakia and lichen both showed the highest occurrence in the second year of established diabetes, and their prevalence was higher among insulin-treated diabetics. Smokers were more often affected, by both kind of lesions, oral lichen showed a more frequent association with candidiasis. The prevalence of oral leukoplakia and lichen in diabetes mellitus patients was higher, than average ratios in population samples from the same country.

Dental and oral examinations of 1360 patients with diabetes mellitus showed higher DMFT mean values with fewer carious teeth and more filled and extracted teeth than the controls. PI mean values were higher in diabetics than in the controls, the difference being statistically significant, and showed a positive correlation with age, but no correlation with the length of time since the disease was established. No correlation was found between the severity of gingivitis and changes in blood glucose levels. The sucrose-free diet of diabetics does not seem to reduce caries prevalence. The increased DMFT index is explained by the fact that, due to periodontitis, diabetics lose more teeth sooner than do healthy people.

OBJECTIVE -In the U.S., both primary care and specialist physicians share in the care of type 1 diabetic patients, often in an informal collaboration. In Hungary, however, type 1 diabetic patients are generally managed in special centralized diabetes units. These different treatment settings may lead to different health care practices and outcomes. To determine if this is true, diabetes care indicators and complications were compared across representative study populations from the 2 countries. RESEARCH DESIGN AND METHODS -The Pittsburgh Epidemiology of DiabetesComplications Study (EDC) is a prospective cohort of childhood-onset type 1 diabetic patients. DiabCare Hungary, a multicenter cross-sectional study, was developed for quality control purposes and provides a nationwide data set of diabetic patients. We identified 2 comparable populations (EDC, n = 416; DiabCare, n = 405) in terms of age (Ն14 years) and age at onset (Ͻ17 years).RESULTS -EDC patients were less likely to receive diabetes education (P Ͻ 0.0001), see an ophthalmologist (P Ͻ 0.0001), be treated by diabetologists (P Ͻ 0.0001), or perform selfmonitoring of blood glucose (P Ͻ 0.0001). They were more likely to use conservative insulin regimens (i.e., 1-2 injections/day, P Ͻ 0.0001) and have a higher glycated hemoglobin (P Ͻ 0.0001). DiabCare patients more often experienced severe hypoglycemia (P Ͻ 0.01) and had a lower prevalence of proliferative retinopathy (P Ͻ 0.0001), legal blindness (P Ͻ 0.05), and albuminuria (Ն30 mg/day, P Ͻ 0.01). No significant differences in macrovascular complications were seen, although rates were generally low.CONCLUSIONS -These data suggest that the 2 populations differ by their diabetes care practices, degree of glycemic control, and microvascular complication status.