Preferred Treatment of Type 1.5 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Latent Autoimmune Diabetes in Adults
Study type: Interventional

Summary: 
      The purpose of this research was to test whether one treatment was superior over another in
      the management of type 1.5 diabetes. Specifically we tested recently diagnosed antibody
      positive type 2 diabetic patients to determine whether treatment with rosiglitazone results
      in greater preservation of beta cell function compared to treatment with glyburide.
    

Detailed description: 
      Type 1 diabetes and Type 2 diabetes have different underlying pathophysiologic processes. The
      disease process in classical Type 1 diabetes is an autoimmune destruction of the pancreatic
      beta cells. In contrast, the disease process in classical Type 2 diabetes is not autoimmune
      in nature, a decreased sensitivity to insulin action is central to the disease process, and a
      poorly understood but non-inflammatory beta cell lesion occurs which diminishes insulin
      secretion. In clinical practice, the diagnosis of Type 1 versus Type 2 diabetes is made
      phenotypically using variables such as age at onset, apparent abruptness of onset of
      hyperglycemia, presence of ketosis, degree of obesity (especially central and intra
      abdominal), prevalence of other autoimmune diseases, and apparent need for insulin
      replacement. This clinical distinction of Type 1 versus Type 2 diabetes is recognized to be
      imperfect.

      There is also a third group of individuals, who phenotypically are usually like classic Type
      2 diabetics but who are positive for one or more of the autoantibodies commonly seen in the
      Type 1 disease process, namely islet cell antibodies (ICA) and/or insulin autoantibodies
      (IAA) and/or autoantibodies to glutamic acid decarboxylase (GAD Ab) and/or autoantibodies to
      the tyrosine phosphatase islet cell autoantibody 512 (IA 2 Ab).

      These patients, autoantibody positive [Ab(+)] Type 2 or Type 1.5 diabetes, were the focus of
      our study. Compared to antibody negative Type 2 diabetics, patients with Type 1.5 diabetes
      have a more rapid decline in beta cell function, fail sulfonylurea therapy and require
      insulin therapy earlier (4-13).

      Hypothesis: Rosiglitazone treatment will ameliorate or slow the underlying disease process in
      antibody positive Type 2 diabetes.

      Patients meeting the inclusion criteria came in for a baseline visit. The nature of the study
      was explained and informed consent obtained. A fasting blood sample was obtained for
      autoantibodies, glucose, C peptide of proinsulin molecule (C-peptide), glycosylated
      hemoglobin (HbA1c), genetic typing, and T lymphocyte (T cell) responses to islet antigens.
      The beta cell function test was performed. Patients were then randomized to either
      rosiglitazone or glyburide.

      All patients were encouraged to perform self blood glucose monitoring twice per day, before
      breakfast and before dinner. The treatment goals for all patients was the same: before
      breakfast and before dinner blood sugar levels between 90-130 milligrams per deciliter
      (mg/dI) and HbA1c of less then 7% without severe hypoglycemia. Patients unable to reach goal
      with monotherapy had metformin (initially) or acarbose (secondarily) added, as there is no
      evidence to suggest that either affect beta-cell function.

      The rosiglitazone treatment group commenced therapy with 4 milligram (mg) once per day and
      increased to twice per day if adequate glycemic control was not achieved. For glyburide,
      therapy was initiated with 2.5 mg in the morning or the patient was maintained on the dose
      they had been receiving prior to starting the study. The starting dose was raised by 2.5 mg
      in the evening and further up to a maximum of 10 mg twice a day if necessary to achieve
      desired glycemic control.

      If adequate control, HbA1c less than 7%, was not achieved on glyburide or rosiglitazone
      monotherapy, metformin was added and the dose gradually increased as needed and tolerated to
      a maximum of 1000 mg twice daily. If necessary, acarbose was also used up to a maximum dose
      of 100 mg thrice daily as needed and tolerated.

      After initiation of the study, patients were seen at 1 month and then every 3 months for up
      to 3 years. Those patients randomized to rosiglitazone had the liver enzyme alanine
      transaminase (ALT) monitored every 2 months. In addition, telephone contact was utilized to
      achieve and maintain glycemic goals. Each participant was followed for up to 3 years. Drs.
      Chiu and Palmer coordinated the study. If the patient and his/her private physician prefer,
      the treatment protocol was implemented by the patient's private physician.
    

Intervention name(s): rosiglitazone; glyburide
Intervention type(s): Drug; Drug
Intervention description(s): Tablet taken orally at a dosage of 4 mg once per day and increase to twice per day if adequate glycemic control was not achieved. Study drug was taken up to 3 years.; Tablet taken orally, initially 2.5 mg in the morning or dose subject received prior to starting the study. Dosage was increased by 2.5 mg in the evening up to a maximum of 10 mg twice a day if necessary to achieve desired glycemic control. Study drug was taken up to 3 years.
Other intervention name(s): Avandia
Intervention MeSH terms: Rosiglitazone; Glyburide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: type 2 diabetes mellitus; autoantibodies; islet proteins; rosiglitazone; glyburide; c-peptide