A Clinical Trial to Prevent New Onset Diabetes After Transplantation

Phase 4

Completed

Conditions: Prevention of New Onset Diabetes Among Kidney Transplant Patients

Brief Summary: Specific Aim 1: To determine the clinical efficacy of early initiation of insulin therapy in decreasing the incidence of NODAT among de novo kidney transplant patients with manifested post-transplant hyperglycemia during the first week after transplantation.

Hypothesis 1: Early initiation of insulin therapy protects beta-cell from early stress related to the surgery and use of higher doses of immunosuppressive medications, and leads to lower incidence of NODAT at 1 and 2 years.

Specific Aim 2: To determine the improvement in overall glycemic control with the early initiation of insulin therapy.

Hypothesis 2: Early initiation of insulin therapy results in greater overall control of glycemia compared to standard care of dietary counseling, life-style modification, oral hypoglycemic agents and/or insulin as needed at 1 year.

Specific Aim 3: To determine the improvement in beta-cell function among patients assigned to the early initiation of insulin therapy at one year post-transplantation.

Hypothesis 3: Early initiation of insulin therapy protects beta-cell from glucotoxicity of post-transplant hyperglycemia and preserves better beta-cell function at 1 year.

Recruitment & Eligibility

Inclusion Criteria

Adult patients (> 18 years) with end stage renal disease (ESRD) undergoing kidney transplantation;
Standard triple immunosuppressive medications following kidney transplantation including tacrolimus, mycophenolate mofetil and corticosteroids;
Capable to understand the study protocol and to give informed consent;

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
Insulin treatment for hyperglycemia	Insulin treatment for hyperglycemia	Neutral Protamine Hagedorn (NPH) Insulin Titration Regimen, based on pre-dinner capillary blood glucose measurements (CPG) expressed in mg/dl; All NPH initiation doses and dose adjustments are presented in IU/day For pts. with CPG \> 240, NPH initiation: 14, dose increases by 4; For pts. with CPG \> 180 mg/dl, NPH initiation: 12, dose increases by 4; For pts. with CPG \> 140 mg/dl, NPH initiation: 10, dose increases by 4; For pts. with CPG \> 120 mg/dl, NPH initiation: 0, dose increases by 2; For pts. with CPG 100-119 mg/dl, NPH initiation: 0, maintain dose; For pts. with CPG 80-\<100 mg/dl, NPH initiation: 0, dose decrease by 4; For pts. with CPG 60-\<80 mg/dl, NPH initiation: 0, decrease by 8; For pts. with CPG \<60 mg/dl, NPH initiation: 0, ½ of previous dose.

Primary Outcome Measures

Name	Time	Method
The Incidence of New Onset of Diabetes After Transplant (NODAT) 12 Months After Kidney Transplantation	12 months	NODAT will be defined according to American Diabetes Association definition: 1. Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or 2. 2 hours Oral Glucose Tolerance Test (OGTT) values equal or greater than 200 mg/dl; and/or 3. Glycosylated hemoglobin A1c equal or greater than 6.5; and/or 4. On oral hypoglycemic agents and/or insulin therapy; Incidence is measured in terms of number of participants who meet any of these 4 criteria.

Secondary Outcome Measures

Name	Time	Method
The Incidence of New Onset of Diabetes After Transplant (NODAT) 24 Months After Kidney Transplantation	24 months	NODAT will be defined according to American Diabetes Association definition: 1. Fasting glucose level equal or greater than 126 mg/dl on two separate blood testings; and/or 2. 2 hours OGTT values equal or greater than 200 mg/dl; and/or 3. Glycosylated hemoglobin A1c equal or greater than 6.5; and/or 4. On oral hypoglycemic agents and/or insulin therapy;