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Intensive Therapy for Type 2 Diabetes Reverses Large and Small Vessel Disease

In patients with diabetic nephropathy, atherosclerotic changes can be stabilized, and decreased microcirculation in the skin can be reversed with the use of nephroprotective therapies….

Researchers in the Department of Metabolic Diseases, Nephrology, and Internal Medicine at University Hospital Krakow of Jagiellonian University in Poland, studied a cohort of 70 patients with Type 2 diabetes. The study consisted of 48 patients with nephropathy and a control group of 22 patients without vascular complications.

Those with nephropathy were found to have advanced atherosclerotic changes and decreased microcirculatory flow in the skin, compared with patients without nephropathy. A third group of 25 patients with nephropathy was examined after 36 months of intensive nephroprotective therapy, mainly with angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) and statins.

The study group, control group, and 36-month study group were well matched for age (64.6 ± 12.3, 60.1 ± 10.3, and 64.8 ± 13.2 years, respectively) and fairly well matched for diabetes duration (13.5, 10.5, and 14.2 years, respectively). Drug treatments are shown in the table.

Treatments by Study Group:

Treatments

Study group (with nephropathy),
n = 48

Control group (no vascular complications),
n = 22

36-month study group (with nephropathy),
n = 25

Insulin/oral hypoglycemic drugs

24/24
15/7
0/25

ACE inhibitor/ARB

40/5
22/1
22/1
Statins
42
20
23


As vessel changes progress in diabetes, the vessels become stiffer, more so than in people without diabetes. To follow these changes, the investigators used pulse wave velocity. The stiffer the vessel, the faster the pulse wave was. Intima-media thickness was assessed with ultrasonography, using an 8 MHz ultrasonograph. Laser Doppler flowmetry was used to assess forearm skin microcirculation under various conditions.

The group with nephropathy had significantly higher pulse wave velocities and greater intima-media thicknesses in their cervical arteries than the control group (< .010). They also had slower flow in the microcirculation at rest (< .010), and lower peak flow during reactive hyperemia after occlusion (= .05).

After 36 months of treatments, these patients exhibited improvements in their microcirculation over their initial values (= .05). They also had significant increases in microvascular blood flow when exposed to temperatures of 44°C. No substantial changes were noted in their aortic pulse wave velocity or intima-media thickness, meaning that their macrovascular disease was stable.

Dr. Cyganek said the researchers concluded that patients with Type 2 diabetes and nephropathy have more advanced atherosclerotic changes and decreased microcirculation in the skin than diabetic patients who do not have nephropathy. Intensive nephroprotective therapy for 36 months stabilized macrovascular circulation and was associated with regression of skin microcirculatory abnormalities.

Per-Henrik Groop, MD, DMSc, professor of nephrology at the University of Helsinki in Finland, asked Dr. Cyganek if vascular parameters correlated to changes in glycated hemoglobin (HbA1c). She answered that HbA1c was quite stable throughout the study — 7.1% at baseline and 7.2% at 36 months — and therefore was not a factor in influencing outcomes.

Dr. Groop suggested that the researchers investigate the effect of changes in blood pressure, because “we know that blood pressure is a major driver of vascular damage.”

European Association for the Study of Diabetes (EASD) 46th Annual Meeting: Abstract 1198. Presented September 22, 2010.