Original Data

The Impact of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Severe Hypoglycemia in Type 2 Diabetes

Rachel M. Freathy, Kathryn F. Lonnen, Anna M. Steele, Jayne A. L. Minton, Timothy M. Frayling, Andrew T. Hattersley, Kenneth M. MacLeod

Abstract

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) is associated with altered serum ACE activity. Raised ACE levels and the ACE DD genotype are associated with a 3.2 to 6.8-fold increased risk of severe hypoglycemia in type 1 diabetes. This relationship has not been assessed in type 2 diabetes. We aimed to test for association of the ACE I/D polymorphism with severe hypoglycemia in type 2 diabetes. Patients with type 2 diabetes (n = 308), treated with insulin (n = 124) or sulphonylureas (n = 184), were classified according to whether or not they had previously experienced severe hypoglycemia. Samples of DNA were genotyped for the ACE I/D polymorphism using two alternative polymerase chain reactions to prevent mistyping due to preferential amplification of the D allele. Overall, 12% of patients had previously experienced one or more episodes of severe hypoglycemia. This proportion did not differ between genotype groups (odds ratio (95% confidence limits) for carriers of D allele relative to II homozygotes: 0.79 (0.35-1.78)). This study found no evidence for association of the ACE I/D polymorphism with severe hypoglycemia frequency in patients with type 2 diabetes. However, we cannot rule out a smaller effect (odds ratio ≤ 1.78). Our results suggest that any effect of ACE genotype on severe hypoglycemia risk in type 2 patients is likely to be smaller than that seen in type 1 diabetes. We recommend future larger-scale studies.

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Prevalence of Type 2 Diabetic Patients Within the Targets of Care Guidelines in Daily Clinical Practice: A Multi-Center Study in Brazil

Marilia de Brito Gomes¹, Daniel Gianella², Manuel Faria³, Marcos Tambascia⁴, Reine Marie Fonseca⁵, Rosangela Réa⁶, Geísa Macedo⁷, João Modesto Filho⁸, Helena Schmid⁹, Alcina Vinhaes Bittencourt¹⁰, Saulo Cavalcanti¹¹, Nelson Rassi^12,13, Hermelinda Pedrosa¹³, Sérgio Atala Dib¹⁴

Abstract

Major clinical studies have shown that the targets for blood glucose, lipid profile and blood pressure in type 2 diabetic patients are difficult to maintain in clinical practice. However, there are few data concerning South American populations. Using guidelines represented by the Brazilian Diabetes Society, we evaluated cardiovascular (CV) risk factors, glycemic control and the availability of screening for diabetes complications in 2233 (60% females) outpatients with type 2 diabetes aged 59.2 ± 11.3 yr and with a known duration of diabetes of 9.2 ± 7.2 yr, collected from 8 Brazilian cities. The outcome showed that less intensive clinical care available for diabetic patients in Brazil compared to western industrialized countries leads to widespread poor metabolic control and health status. Less than 30% of the patients reached the target for systolic (28.5%, < 130 mmHg) and diastolic (19.3%, < 80 mmHg) blood pressure, BMI (24.6%, < 25 kg/m2), LDL cholesterol (20.6%, < 2.6 mmol/l) and only 46% reached the goal for HbA1c (one % point above the upper limits of normality for the method used). Only 0.2% of patients reached all the targets. A lower number of women reached the targets for HbA1c, LDL and HDL cholesterol than men (p < 0.001). Women were less likely than men to have funduscopy examinations and urine albumin testing (p < 0.001). We conclude that the national goals for glycemic control, blood pressure and lipid levels are rarely achieved in clinical practice, and that the availability for diabetic complication screening is low. The quality of diabetes care, in particular for women, is poor and should be further reviewed in developing countries.

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