Metabolic Syndrome and Autoimmune Diabetes: Action LADA 3
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OBJECTIVE—The purpose of this study was to estimate whether prevalence of metabolic syndrome in adult European diabetic patients is associated with type of diabetes. RESEARCH DESIGN AND METHODS—A consecutive series of patients attending hospital-based diabetes clinics were assessed for the frequency of metabolic syndrome and compared with population-based control subjects as part of the Action LADA study. In total, 2,011 subjects (aged 30–70 years) were studied, including 1,247 patients with recent-onset type 2 diabetes without glutamic acid decarboxylase autoantibodies (GADAs), 117 non–insulin-requiring patients with GADAs who had not received insulin therapy for at least 6 months after diagnosis (designated latent autoimmune diabetes of adults [LADA]), 288 type 1 diabetic patients, and 359 normal subjects. RESULTS—Frequency of metabolic syndrome was significantly different in patients with type 1 diabetes (31.9%) and LADA (41.9%) (P = 0.015) and in both conditions was less frequent than in type 2 diabetic patients (88.8%) (P < 0.0001 for each). Eliminating glucose as a variable, the prevalence of metabolic syndrome was similar in patients with autoimmune diabetes (type 1 diabetes and/or LADA) (17.3%) and control subjects (23.7%) but remained more common in type 2 diabetic patients (47.8%) (P = 0.001 for all groups). In both type 1 diabetic patients and those with LADA, individual components of metabolic syndrome were similar but less common than in type 2 diabetic patients (P < 0.0001 for each). CONCLUSIONS—The prevalence of metabolic syndrome is significantly higher in type 2 diabetic patients than in patients with LADA or adults with type 1 diabetes. Excluding glucose as a variable, metabolic syndrome is not more prevalent in patients with autoimmune diabetes than in control subjects. Metabolic syndrome is not a characteristic of autoimmune diabetes. Type 1 diabetes is an autoimmune disease in which insulin deficiency results from immune-mediated destruction of insulin-secreting islet cells. The majority of patients with type 1 diabetes have autoantibodies in their peripheral blood, and these autoantibodies can predict the disease. Autoimmune diabetes, as characterized by these autoantibodies, such as glutamic acid decarboxylase autoantibodies (GADAs), is the most prevalent form of diabetes in children and also occurs in a proportion of patients who initially present with adult-onset non–insulin-requiring diabetes, also called latent adult-onset autoimmune diabetes (LADA) (1). Because glucose disposal and blood glucose are determined by both insulin secretion and insulin action, it follows that insulin sensitivity could be important in the pathogenesis of autoimmune diabetes. Insulin sensitivity has not been studied in detail in autoimmune diabetes, although studies suggest that its loss may occur in established disease as well as in the pre-diabetic phase (2–5). Loss of insulin sensitivity is difficult to assess epidemiologically but is reflected in the cluster of metabolically related cardiovascular risk factors that together comprise the metabolic syndrome and include altered glucose levels, central obesity, dyslipidemia, and hypertension. Several groups, including the International Diabetes Federation (IDF) and the National Cholesterol Education Program (NCEP), with Adult Treatment Panel III (6), have proposed their own definitions for the metabolic syndrome. LADA is clearly distinct from type 2 diabetes, in that LADA is associated with histocompatability (HLA) genes, diabetes-associated autoantibodies, reduced insulin secretion, no need for insulin therapy initially after diagnosis, and less prevalence of metabolic syndrome (7–9). The key question is whether LADA is distinct from type 1 diabetes (1,10,11), that is, whether LADA is one end of a rainbow of pathophysiological variations encompassing autoimmune diabetes with a frequency of metabolic syndrome similar to that of childhood-onset type 1 diabetes or whether LADA is a distinct form of autoimmune diabetes that resembles type 2 diabetes, showing evidence of insulin resistance with a high frequency of metabolic syndrome (1). Therefore, the aim of this study was to test whether individuals with type 2 diabetes and autoimmune diabetes (incorporating type 1 diabetes and LADA) have a higher frequency of metabolic syndrome than normal subjects, and our hypothesis was that they would.
AuthorsHawa, MI; Thivolet, C; Mauricio, D; Alemanno, I; Cipponeri, E; Collier, D; Hunter, S; Buzzetti, R; de Leiva, A; Pozzilli, P; Leslie, RDG; Action LADA Grp
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