The posttreatment basal GH concentration less than 2.5 microg/liter in acromegalic patients is associated with a normal lifespan. Excess mortality is confined to poorly controlled patients and possibly those who have received conventional radiotherapy.

Disturbances of coronary circulation have been reported in diabetic patients with microvascular complications but without obstructive coronary atherosclerosis. The aim of the present study was to investigate coronary flow reserve in young adult patients with IDDM but without microalbuminuria and diabetic autonomic neuropathy. Coronary flow reserve was determined in 12 nonsmoking male patients with IDDM (age 30.0 +/- 6.6 years) and 12 healthy matched volunteers. Groups were similar with respect to blood pressure and serum lipid concentrations, and no subject had a positive family history of coronary heart disease. The patients with IDDM had normal exercise echocardiography and autonomic nervous function tests. Five patients had minimal background retinopathy, and none had microalbuminuria. Positron emission tomography and [15O]H2O were used to measure myocardial blood flow at rest and after dipyridamole administration. The studies were performed during euglycemic hyperinsulinemia (serum insulin approximately 70 mU/l). The baseline myocardial blood flow was similar in patients with IDDM and in control subjects (0.84 +/- 0.18 vs. 0.88 +/- 0.25 ml x g(-1) x min(-1), NS). The myocardial blood flow during hyperemia was 29% lower in patients with IDDM (3.17 +/- 1.57) compared with the control subjects (4.45 +/- 1.37 ml x g(-1) x min(-1), P < 0.05). Consequently, coronary flow reserve (the ratio of flow during hyperemia and at rest) was lower in diabetic patients than in control subjects (3.76 +/- 1.69 vs. 5.31 +/- 1.86, P < 0.05) and the total coronary resistance during hyperemia was higher in diabetic patients (53.7 +/- 31.5) compared with the control subjects (31.4 +/- 11.6 mmHg x min x g x ml(-1), P < 0.05). The coronary flow reserve was similar in diabetic patients with and without mild background retinopathy. No association was found between the coronary flow reserve and serum lipid or HbA1c values in either group. Coronary flow reserve is impaired in young adult males with IDDM and no or minimal microvascular complications and without any evidence of coronary heart disease. This abnormality cannot be explained by standard coronary heart disease risk factors. The results imply early impairment of coronary vascular reactivity in IDDM patients, which may represent an early precursor of future coronary heart disease or may contribute to the pathogenesis of diabetic cardiomyopathy.

Defects in insulin stimulation of blood flow have been suggested to contribute to insulin resistance. To directly test whether glucose uptake can be altered by changing blood flow, we infused bradykinin (27 g over 100 min), an endothelium-dependent vasodilator, into the femoral artery of 12 normal subjects (age 25 Ϯ 1 yr, body mass index 22 Ϯ 1 kg ր m 2 ) after an overnight fast ( n ϭ 5) and during normoglycemic hyperinsulinemic ( n ϭ 7) conditions (serum insulin 465 Ϯ 11 pmol ր liter, 0-100 min). Blood flow was measured simultaneously in both femoral regions using and PET. During hyperinsulinemia, muscle blood flow was 58% higher in the bradykinin-infused (38 Ϯ 9 ml ր kg muscle и min) than in the control leg (24 Ϯ 5, P Ͻ 0.01). Femoral muscle glucose uptake was identical in both legs (60.6 Ϯ 9.5 vs. 58.7 Ϯ 9.0 mol ր kg и min, bradykinin-infused vs. control leg, NS). Glucose extraction by skeletal muscle was 44% higher in the control (2.6 Ϯ 0.2 mmol ր liter) than the bradykinin-infused leg (1.8 Ϯ 0.2 mmol ր liter, P Ͻ 0.01). When bradykinin was infused in the basal state, flow was 98% higher in the bradykinin-infused (58 Ϯ 12 ml ր kg muscle и min) than the control leg (28 Ϯ 6 ml ր kg muscle и min, P Ͻ 0.01) but rates of muscle glucose uptake were identical in both legs (10.1 Ϯ 0.9 vs. 10.6 Ϯ 0.8 mol ր kg и min). We conclude that bradykinin increases skeletal muscle blood flow but not muscle glucose uptake in vivo. These data provide direct evidence against the hypothesis that blood flow is an independent regulator of insulin-stimulated glucose uptake in humans. ( J. Clin. Invest . 1996. 97:1741-1747.)

Detection of early vascular changes indicated by lowered coronary flow reserve (CFR) would allow early treatment and prevention of atherosclerosis. The purpose of this study was to test whether it is possible to reproducibly measure CFR with transthoracic Doppler echocardiography (TTE) in healthy volunteers. We measured CFR using dipyridamole infusion in ten healthy male volunteers with two methods: TTE and positron emission tomography (PET) with oxygen-15-labelled water (group A). However, CFR was assessed twice with TTE in eight healthy male volunteers (group B) to study the reproducibility of this method. We compared CFRs obtained using TTE flow measurements in the left anterior descending coronary artery (LAD) and PET flow measurements in the corresponding myocardial area. Coronary flow in LAD could be measured in all subjects using TTE. By TTE, an average CFR based on peak diastolic flow velocity (PDV) was 2.72 +/- 1.16, mean diastolic flow velocity (MDV) 2.56 +/- 1.06 and velocity time integral (VTI) 1.87 +/- 0.49. The results were reproducible in two repeated TTE studies (coefficient of variation in MDV 6.1 +/- 4.3%, n=8). By PET, CFR was 2.52 +/- 0.84. CFR assessed by TTE correlated closely with that measured by PET (MDV r=0.942, P<0.001; PDV r=0.912, P<0.002 and VTI r=0.888, P<0.006) and intraclass correlation was 0.929 (MDV) and tolerance limits for differences of CFRs was -0.78 to 0.72. We show that CFR measured by TTE has an excellent correlation with CFR measured by PET. We also found that TTE measurements of CFR were highly reproducible.