Elevated plasma immunoreactive neuropeptide Y concentrations and its increased urinary excretion in patients with advanced diabetic nephropathy.

Neuropeptide Y (NPY) is a potent vasoconstrictor peptide that is abundant in the brain and the peripheral sympathetic nervous system. In the present study we investigated possible changes in plasma immunoreactive (IR)-NPY concentrations and urinary IR-NPY excretion in patients with non-insulin dependent diabetes mellitus (NIDDM) and the relationship to diabetic complications, such as nephropathy and neuropathy. IR-NPY in plasma and urine was measured by radioimmunoassay in 69 patients with NIDDM. Plasma IR-NPY concentrations in patients with advanced nephropathy (creatinine clearance <30 ml/min) (100.5 +/- 10.3 pmol/l, n=9, mean +/- SEM) were higher than in the control subjects (55.0 +/- 6.8 pmol/l, n=15) (P<0.02). Urinary excretion of IR-NPY and fractional excretion of NPY were also increased in the patients with advanced nephropathy. Sephadex G-50 column chromatography of the urine extracts obtained from healthy subjects, diabetic patients with renal failure and non-diabetic patients with renal failure showed an immunoreactive peak eluting in the NPY position. On the other hand, neither plasma nor urinary IR-NPY was high in patients with retinopathy, or in patients with peripheral neuropathy. The present study has, for the first time, shown high plasma IR-NPY concentrations and urinary IR-NPY excretion in NIDDM patients with advanced nephropathy.

Effect of pravastatin on plasma ketone bodies in diabetics with hypercholesterolemia.

Hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) is a common intermediate metabolite of cholesterol synthesis and ketone formation in the liver. In order to study the effect of HMG-CoA reductase inhibitor (pravastatin) on ketone formation, changes in the plasma levels of ketone bodies by treatment with pravastatin were studied in 18 non-insulin dependent diabetics with hypercholesterolemia. Body mass index, diabetic control, and plasma free fatty acid levels were not changed during the study, and the plasma levels of cholesterol decreased significantly from 250 +/- 25 to 211 +/- 34 mg/100 ml after 6 months of pravastatin treatment. The plasma levels of acetoacetic acid also significantly decreased from 37.7 +/- 22.6 to 28.4 +/- 13.4 mumol/l, and those of 3-hydroxybutyric acid and total ketone bodies also tended to decrease after pravastatin treatment. These results suggest that pravastatin decreases ketone formation in hepatic mitochondria besides cholesterol synthesis in hepatic microsome.