Glutamic acid decarboxylase and ICA512/IA-2 autoantibodies as disease markers and relationship to residual beta-cell function and glycemic control in young type 1 diabetic patients.

Circulating autoantibodies (Ab) to islet autoantigens, glutamic acid decarboxylase (GAD(65)), and tyrosine phosphatase ICA512/IA-2 have been proposed as predictive markers of type 1 diabetes mellitus. To ascertain residual beta-cell function and the clinical relevance for monitoring autoimmunity after clinical manifestation of disease, we studied 63 children at diagnosis of type 1 diabetes (mean SD age 7.5 +/- 4 years) and 91 adolescent patients with type 1 diabetes (age 14.7 +/- 1.6 years) with a mean duration of disease of 7 +/- 3.5) years. Forty-two normal adolescent subjects (age 14.6 +/- 1.8 years) without a family history of diabetes were the control group. Anti-GAD(65) and ICA512/IA-2 Ab were assessed by a quantitative radioimmunoprecipitation assay. The relationship between humoral autoimmunity and clinical parameters was explored. GAD(65) and ICA512/IA-2 Ab were detected in 56% and 63% of newly diagnosed children and the prevalence was not different in relationship to clinical characteristics. Levels of GAD(65) Ab positively correlated with diagnosis age (P <.05). Both Ab were associated with islet cell antibodies (ICA) (P <.05), but one fifth of patients had at least 1 of the 2 Ab and absent ICA. At onset, only age showed a significant relationship to residual C-peptide secretion. Among the cohort of patients with diabetes of short-mid duration, GAD(65) and ICA512/IA-2 Ab were present in 44% and 45% of cases (P >.05 and P <.05 v newly diagnosed children, respectively) and more patients were identified by these Ab (68%) than by ICA alone (34%) (P <.05). In this cohort, levels of ICA512/IA-2 Ab negatively correlated with levels of glycosylated hemoglobin (HbA(1c)) (P <.005) and with daily insulin requirement (P <.05). Moreover, the presence of some residual C-peptide secretion was significantly associated with the presence of ICA512/IA-2 Ab (P <.05). Our findings confirm that positivity for either GAD(65) or ICA512/IA-2 Ab is a highly sensitive marker of type 1 diabetes in the pediatric age group, identifying a group of patients with absent ICA immunofluorescence. The persistence of Ab to islet tyrosine phosphatase possibly represents a marker of better glycemic control and less insulin requirement, indicating residual beta-cell function, thus conferring clinical and prognostic relevance to these Ab, as well as potential usefulness in intervention strategies.

Helicobacter pylori infection in type 2 diabetic patients.

BACKGROUND AND AIM: A high prevalence of Helicobacter pylori (Hp) infection in diabetic patients has been described in recent years. This study investigates its prevalence in type 2 diabetics and its correlation with the degree of metabolic control and the presence of chronic complications. METHODS AND RESULTS: Forty-one consecutive type 2 diabetics (21 males, 20 females aged 46-78, mean 62) and 31 age-matched controls participated. Hp infection was assessed by means of the 13C-urea breath test. Fasting glucose and glycated haemoglobin (HbA1c) levels were measured to evaluate metabolic control. Chronic complications were assessed by means of albumin excretion rate (AER), fundoscopy, vibratory perception threshold (VPT), ECG, clinical history of coronary, cerebral or peripheral arteriopathy, foot examination and cardiovascular autonomic function tests. A higher prevalence of Hp infection was found in diabetic than in control women (80% vs 37.5%; p < 0.05), whereas there was no difference between males. A higher prevalence correlated with macroangiopathy and neuropathy and higher BMI, blood pressure, fasting glucose and HbA1c values. By contrast, microangiopathy was significantly more prevalent (p < 0.05) in Hp negative (85%) than in Hp positive patients (48%). CONCLUSIONS: There is a high prevalence of Hp infection in type 2 diabetic women. The absence of microangiopathy may be a predisposing factor: microvascular changes in the gastric mucosa may create an unfavourable environment for the establishment or survival of Hp.