The Effects of Thiazolidinedione on the Diabetic Retinopathy and Nephropathy
The effects of thiazolidinedione on the diabetic retinopathy and nephropathy:
Overall Goal and Specific Aims
The overall goal of this study is to examine the effects of thiazolidinediones on the
diabetic retinopathy and nephropathy.
The specific aims are:
1. To investigate the short-term effects of thiazolidinediones on the macular thickness
measured by optical coherence tomography and the long-term effects of
thiazolidinediones on the clinically significant macular edema and diabetic retinopathy
documented by color photography and fluoroscein angiography.
2. Short-term effects of thiazolidinediones on the change of urine albumin excretion and
serum cardiovascular risk profiles and long-term effects of thiazolidinediones on the
estimated GFR change and progression to overt diabetic nephropathy.
Thiazolidinediones (TZDs) are insulin sensitizers that decrease plasma glucose in type 2
diabetic patients. Thiazolidinediones can cause fluid retention and peripheral edema in
diabetic patients, and the systematic fluid retention can be manifested as diabetic macular
edema (DME). The overall goal of this study is to examine the effects of thiazolidinediones
on the diabetic retinopathy and nephropathy.
This is a prospective, randomized, open-labeled, controlled design to assess the effects
thiozolidinediones on the diabetic retinopathy and nephropathy. The investigators will
recruit 300 type 2 diabetic patients without significant retinopathy, nephropathy and
cardiovascular disease. Inclusion criteria are type 2 diabetes, age between 30-80 years
old, with microabluminuria, no significant retinopathy, on submaximal dose of sulphonylureas
and metformin treatment, and A1C between 7-9%. Exclusion criteria are on insulin treatment,
significant retinopathy and significant nephropathy. Patients with cardiovascular diseases,
malignancy, pregnancy, in acute intercurrent illness, congestive heart failure, myocardial
infarction, received PCI or CABG. All subjects will receive EKG and CXR before
These subjects will be randomized equally to 3 groups: acarbose, rosiglitazone and
pioglitazone. The investigators will follow up for 6 months to investigate the short-term
effects and 5 years to evaluate the long-term outcomes. The primary study end point of
short-term study will be the macular thickness changes measured by optical coherence
tomography, the changes in the level of urinary albumin-to-creatinine ratio, circulating
metabolic parameters and adipocytokines during thiozolidinediones treatment. Secondary end
point will be fasting blood glucose, A1C levels, development of clinically significant
macular edema, serum creatinine change in patients with no history of diabetic retinopathy
and nephropathy at baseline.
The primary study end point of long-term study will be the development of clinically
significant macular edema and the time from the base-line visit to the first detection of
overt nephropathy. Secondary end points include the development of greater than moderate
NPDR, the time to the first event of the time from the base-line visit to a doubling of the
serum creatinine concentration, end-stage renal disease, or death.
The investigators also monitor the long-term safety issue, such as congestive heart failure,
myocardial infarction, any cardiovascular event, and fracture.
TZDs can decrease plasma glucose in type 2 diabetic patients, but the major side effects are
able to cause fluid retention. This prospective study will be able to test whether
thiozolidinediones causes macular edema and to evaluate whether thiozolidinediones delays
onset of diabetic retinopathy. The investigators also will be able to find the changes in
the level of urinary albumin-to-creatinine ratio, circulating metabolic parameters and
adipocytokines between the treatment of TZDs and Acrbose. The investigators can compare the
time from the base-line visit to the first detection of overt nephropathy, the time to the
first event of the composite end point of the time from the base-line visit to a doubling of
the serum creatinine concentration, end-stage renal disease, or death.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
The macular thickness changes
Harn-Shen Chen, MD, PhD
Taipei Veterans General Hospital,Taiwan
Taiwan: Department of Health