Urinary excretion patterns of various endogenously produced alcohols, such as ethanol, propanol, isobutanol, butanol, and isopentanol, were evaluated in 17 type 1 (IDDM) and 15 type 2 (NIDDM) diabetic patients, and in two different groups of healthy control subjects (n = 12, n = 8, respectively) matched for sex, age and weight. In addition to the urinary alcohol excretion determined by gas-chromatography and mass-spectrometry, four cardiovascular reflex tests were performed, and the motor and sensory conduction velocities of three different peripheral nerves were measured. In the type 1 diabetic patients, urinary excretions of ethanol and propanol were significantly higher than in the control subjects (P less than 0.0001, P less than 0.00001, respectively), whereas the control subjects exhibited significantly higher urinary excretion rates of the other three alcohols (P less than 0.007, P less than 0.02 and P less than 0.002, respectively) compared with the type 1 diabetic patients. In the type 2 diabetic patients, only the urinary excretion of propanol was significantly elevated (P less than 0.002) compared with the control subjects, while the urinary excretion rates of butanol and isopentanol were significantly lower (P less than 0.02, P less than 0.05, respectively) than in the controls. Urinary alcohol excretions were not related to diabetic peripheral neuropathy in both groups studied. The clinical meaning of the urinary excretion patterns of different endogenously produced alcohols in diabetes mellitus has to be further evaluated.

Cardiovascular reflex tests are used to assess cardiac autonomic neuropathy in diabetes mellitus. Cardiovascular diseases (CVD) are known to alter baroreflex mechanisms. Diabetic patients are at a high risk for cardiovascular complications. In order to prove whether cardiovascular diseases reduce the diagnostic value of the cardiovascular reflex tests in diabetic autonomic neuropathy unselected groups of 274 nondiabetic and 103 diabetic patients were studied: E/I, 30/15, and Valsalva ratios, sustained handgrip test and blood pressure response to standing. Both groups were subdivided into young (≤45 years) and older (>45 years) patients and into subjects with and without CVD. In young nondiabetic patients with CVD, E/I and Valsalva ratios were significantly lower than in those without CVD. In young diabetic patients with CVD, only E/I ratios were significantly reduced compared to those without CVD. The tests reflecting sympathetic nerve function did not differ between patients with and without CVD, neither in the nondiabetic nor in the diabetic subjects. In the older nondiabetic and diabetic patients, cardiovascular reflexes were generally impaired, but did not show any difference between subjects with and without CVD. In young diabetic patients suffering from CVD, the diagnostic value of cardiovascular reflex tests is reduced as far as cardiac autonomic neuropathy is concerned. In older patients, the tests are not suitable for the diagnosis of diabetic autonomic neuropathy. More specific methods are required.

Increased platelet reactivity and enhanced platelet turnover have been found by several authors in diabetes mellitus. Since activated platelets can release mitogens like PDGF that cause the proliferation of vascular smooth muscle cells it seems possible that hyperreactive platelets can accelerate the development of vascu­ lar complications in diabetes (for review refer to 1). In platelets of diabetic patients enhanced sensitivity to and increased formation of thromboxane A2 (TXA2) have been found (2,3). The increased formation of TXA2 was attributed to an enhanced availability of arachidonic acid upon the addition of appropriate stimuli (4). This could be the result of an altered composition of membrane phospholipids (5). On the other hand, the occupation of specific TXA2/PGH2 receptors causes a positive feedback amplification of the TXA2 generation by the formation of the Ca2+ ionophore inositoltrisphosphate (IP3) (6) and presumably also via the activation of receptor-operated Ca2+ channels (7). Therefore, it seems conceivable that an enhanced surface expression of TXA2/ PGH2 receptors or alterations in the signal transduction process could contribute to an enhanced sensitivity to and an increased formation of TXA2 in diabetes. Such alterations for instance could result from changes in the membrane lipid microenviron-

Gallbladder motor function was studied in nine diabetic patients and nine control subjects matched for sex, age, and weight. None of the subjects had gallstones. Two different techniques were employed: real-time ultrasonography and cholescintigraphy using 99mTc-HIDA as imaging agent. Gallbladder volumes were determined sonographically by using three dimensions: length, lateral, and anterior-posterior diameters. Gallbladder emptying was stimulated by a standard test drink (Biloptin®). Ejection fraction was computed and the results obtained by both techniques were compared. Fasting and residual gallbladder volumes after contraction were significantly larger in the diabetic patients than in the control subjects (15.9 ± 7.6 cm3 vs. 2.3 ± 1.3 cm3, p < .0007; and 9.2 ± 9.8 cm3 vs. 0.7 ± 0.7 cm3, p < .0007). Ejection fractions (ultrasonography/cholescintigraphy) were lower in the diabetic patients compared with the control subjects (59.9 ± 26.6% and 63.1 ± 23.2% vs. 73.2± 23.8% and 75.3 ± 24.8%), however, this difference was not statistically significant. Sonographically and scintigraphically determined ejection fractions were closely correlated (r = 0.90, p < .00005).

In order to assess hemodynamic changes in early phases of insulin-dependent diabetes mellitus, muscle tissue oxygen tensions were determined in 7 newly diagnosed insulin-dependent diabetic patients and in 6 healthy control subjects matched for sex, age and weight. Muscle tissue oxygen tension was measured by polarrographic needle probes while breathing ambient air and oxygen enriched air with an oxygen concentration of 40 per cent as well. Three times during the experiment, heart rates, blood pressures, blood glucose concentrations, and capillary oxygen tensions were obtained. Heart rate, blood pressure, peripheral and autonomic nerve functions did not differ between the 2 groups studied. While breathing ambient air, muscle tissue oxygen tensions were significantly (p = 0.025) higher in the diabetic patients than in the control subjects. In contrast to the control subjects, diabetic patients did not increase muscle tissue oxygen tensions after inhalation of oxygen enriched air despite of an equal increase in capillary oxygen tensions (2p less than 0.05). Local tissue hypoxia does not seem to be a leading cause of hemodynamic abnormalities in the early phases of diabetes.

For evaluation of 2 simple methods gastric emptying was studied simultaneously by ultrasound and scintigraphy. In 12 patients (25-76 years-old) gastric emptying was quantified by scintigraphy after ingestion of 300 ml Tc-99m-labelled orange juice; simultaneously, the region of the gastric antrum was measured in 5-minute intervals in the aortic longitudinal section. In the following day gastric emptying was studied after ingestion of the identical volume of orange juice by planimetry of the maximal gastric area in an anatomical long-axis section in dextro-decline position. By linear regression analysis a significant correlation coefficient (r = 0.83, p less than 0.001) was obtained between the results of the sonographic antrum method and scintigraphy and between scintigraphy and the sonographic dextro-decline method (r = 0.83, p less than 0.001). These results imply that gastric emptying of fluids can be quantified by both simple sonographic methods. The sonographic dextro-decline method is less influenced by air and hence easier to perform.

The objective of this study was to determine whether a favorable effect of short term continuous sc insulin infusion (CSII) therapy on the peripheral and autonomic nervous system could be maintained by subsequent intensified conventional treatment (ICT). Nine type I diabetic patients, aged 18-32 yr, who had been diabetic for 4-23 yr and had reduced nerve conduction velocities received CSII for 4 weeks and subsequently ICT for up to 26 weeks. Motor and sensory nerve conduction velocities (MNCV and SNCV) and heart rate variations during deep breathing (E/I ratio), during lying and standing (30/15 ratio), and during the Valsalva maneuver (Valsalva ratio) were measured before CSII and at intervals of 1, 2, 4, 6, 10, and 26 weeks. During CSII, MNCV and SNCV increased significantly (P less than 0.01), the E/I ratio improved in seven patients (P less than 0.05), the Valsalva ratio increased in eight patients (P less than 0.01), and the 30/15 ratio increased in five patients. The E/I ratio increased significantly earlier than the Valsalva ratio (P less than 0.025). During ICT, nerve conduction velocity slightly, though not significantly, decreased, and the results of the cardiovascular reflex tests also gradually declined. The hemoglobin A1 concentration before initiation of CSII and the diminution of the hemoglobin A1 concentration during CSII therapy were inversely correlated to the increase in MNCV (P less than 0.01 and P less than 0.05, respectively). In conclusion, CSII improved peripheral and autonomic nervous system function, but the improvement diminished somewhat during ICT.

The particular questions asked in our study were: 1. does the individual reproducibility of the cardiovascular reflex tests differ between healthy controls and patients suffering from type I diabetes mellitus and 2. if there is a difference, do the different cardiovascular reflexes vary in this regard? Nine healthy controls (4 women, 5 men, age 31±2.1 years) and 11 type I diabetics (4 women, 7 men, age 30.9±5.6 years, duration of diabetes 3–23 years) underwent the following tests 6 times in a 12-h period (0700 to 1900): variation of heart rate during deep breathing (E/I ratio). variation of heart rate during lying and standing (tachycardia/bradycardia or 30/15 ratio), Valsalva maneuver (Valsalva ratio), response of diastolic blood pressure to sustained hand grip, and response of systolic blood pressure to posture. The test results did not indicate a diurnal fluctuation nor were they systematically influenced by antecedent insulin injections or meals, either in diabetic patients or in healthy, controls. The 11 diabetics had significantly lower intraindividual variations of E/I and Valsalva ratios than the controls (p<0.05, p<0.001, respectively). In the diabetics with parasympathetic failure the intraindividual variabilities of all cardiovascular reflex responses were lower than those of the patients with an intact autonomic nervous system as well as those of the control subjects. On the contrary, in the diabetic patients without autonomic neuropathy, only the intraindividual variability of the Valsalva maneuver was significantly attenuated (p<0.025), compared with the healthy volunteers. To conclude, the more pathological the single test result, the greater is its reproducibility and its clinical significance.

Damages of the sensory, motor, and autonomic nervous systems probably are the most common complications of diabetes mellitus. In this overview diagnostic procedures, including anamnestic criteria, symptoms and signs, are proposed, which may be easily performed in outpatients. Up to now the treatment of symptomatic neuropathy is disappointing. Some major complaints (i.e. pain, orthostatic hypotension, gastric atony) can be treated effectively. Possibly therapeutic interventions must be initiated much earlier in asymptomatic stages.