Hypoxia of diabetic feet with abnormal arterial blood flow.

Necrotic ulcers of the feet are a dangerous complication of the diabetic foot syndrome. Besides peripheral vascular disease (PVD) peripheral neuropathy is an important factor in the pathogenesis of necroses. We examined whether the reserve of circulation during reactive hyperemia at the feet of patients with type I diabetes mellitus with abnormal blood flow (n = 17) is decreased compared with diabetic (n = 14) and nondiabetic (n = 20) controls. Further we analyzed whether there is a correlation with the oxygen supply of the foot. PVD was excluded by clinical check-up, oscillography, and Doppler ultrasound. The reserve of circulation of the foot was measured during reactive hyperemia and oxygen supply of the foot by oximetry. Abnormal blood flow of the foot was diagnosed by the pulsation index. On examination it was found that the reserve of circulation of diabetic feet with abnormal blood flow is about 52% less than in diabetic and about 50% less than in nondiabetic controls (P < or = 0.005). The decreased reserve of circulation correlates with the oxygen supply of the feet; this is about 21% less compared to diabetic feet with normal blood flow and about 16% less in comparison to nondiabetic feet. The present study shows that diabetic feet suffer from disturbed circulation although there is no evidence of PVD. This disturbed circulation is correlated with a decreased oxygen supply of the feet. Hypoxia during strain could be of great importance in the pathogenesis and treatment of necrotic ulcers of diabetic feet.

Decrease of macrovascular hyperemic response of blood flow in diabetics with arterial neuropathy.

Doppler sonographic examination of 51 diabetic subjects showed that the macrovascular hyperemic response of the pedal blood flow was negatively correlated to the duration of the disease (p less than 0.01). In comparison with non-diabetic controls (n = 20), the response was increased by more than 210% in newly detected diabetics, but decreased by more than 20% in long-term diabetics. Vascular response was correlated also not only to the duration of the diabetes, but to peripheral neuropathy (p less than 0.001). The hyperemic response was reduced in patients with reduced nerve conduction time, or somatic neuropathy (142 + 152%, p less than 0.005), and in patients with reduced arterial pulsation, or autonomic neuropathy (152 + 88, p less than 0.005), both in comparison with non-diabetic controls (293 +/- 108%). The frequency of decreased macrovascular hyperemic response was in agreement with somatic neuropathy in 69.7% and with autonomic neuropathy in 75.8% of all patients. The results demonstrate that the macrovascular hyperemic response of blood flow in diabetic feet is already reduced at an early stage of peripheral neuropathy without peripheral vascular occlusive disease. The functional reduction of pedal blood flow may be important for the development of diabetic foot gangrene.

Measurement of Doppler velocity in diagnosis of peripheral vascular disease in diabetics with peripheral pulse deficit.

Forty-nine diabetics (aged 50-69 yr, with a pulse deficit in 54 legs) were examined for peripheral vascular disease (PVD). In relation to pulse deficits PVD was proved by oscillography in 24 (44%), by qualitative Doppler velocity measurements in 19 (51%) and by quantitative Doppler in 28 (35%) cases. The overall rate of the agreement in the diagnosis between the two Doppler techniques and oscillography was 76.8% and 73.5% respectively. The differences in the PVD frequency detected by Doppler sonography were not significant. However, a comparison of Doppler deficits and pulse deficits showed that PVD was more frequently found by the qualitative Doppler technique (76.0% vs 35.2%, p less than 0.0005). Also in 94.7% of all cases PVD could be detected by the qualitative examination of only one artery. The quantitative Doppler results were directly correlated to localized findings in the foot in PVD. Thus, it can be concluded that in comparison to oscillography the qualitative Doppler velocity measurements are simpler and more time-saving for a screening diagnosis of PVD, while the quantitative technique is useful for evaluating the severity of evident PVD.

[Doppler sonographic criteria of reactive hyperemia in the diagnosis of peripheral arterial occlusive diseases in diabetes mellitus]. / Dopplersonographische Kriterien der reaktiven Hyperämie in der Diagnostik peripherer arterieller Verschlusskrankheiten bei Diabetes mellitus.

The doppler-sonographic measurement of reactive hyperemia is a simple method to make a functional diagnosis of PVD. In contrast to Doppler pressure measurements the new method does not only allow a screening-diagnosis of PVD, it also fit to inform about the localisation and severity of vascular occlusions. Thus the method assist to make sure whether PVD is occlusive and whether angiographic or surgical intervention is necessary.

Doppler sonographic examination of reactive hyperemia in the diagnosis of peripheral vascular disease.

Fifty-four patients with angiographically confirmed peripheral vascular disease (PVD) were examined in order to find out whether the occlusive form of this disease can be better diagnosed by measuring the reappearance time and mean velocity of the blood flow during reactive hyperemia than by determining the peripheral systolic blood pressure, using Doppler ultrasound for both measurements. It was shown that the Doppler pressure was only reliable for a screening diagnosis of PVD. However, using the reappearance time of reactive hyperemia, it was possible to distinguish specific localization types of sclerosis; while reactive hyperemia already reached its half maximum in controls in 4.6 s this occurred in the stenosis type of PVD after 6.9 s, in the upper leg occlusion type after 21.6 s, in the lower leg occlusion type after 46.6 s, and in the multilevel disease after 70.1 s. The delay in the half-maximum reappearance time was significantly different, not only in comparison with controls (P less than 0.001) but also in the specific types of occlusive PVD as compared with one another (P less than 0.01). Regarding the intensity of velocity it could also be shown that the mean velocity of blood flow during reactive hyperemia was lower in all patients with PVD than in controls. Again this alteration during reactive hyperemia was significant, not only in comparison with controls (P less than 0.001), but also when the specific stages of severity according to Fontaine were compared with one another (P less than 0.05).2+n the basis of these findings it can be stated that in

Apo E 2 phenotypes in type II diabetics with and without insulin therapy.

In 106 type II diabetics with persisting hyperlipidemia (i.e. persistently increased triglycerides greater than 200 mg/dl during intensive diabetes therapy) the Apo E polymorphism was examined in relation to IDDM (n = 68) and NIDDM (n = 38). It was shown that Apo E2 phenotypes are more (22.6% vs. 14.5%, p less than 0.05) and Apo E3 phenotypes less frequent in type II diabetics than in non-diabetic controls (86.8% vs. 94.7%, p less than 0.001). Looking at the increase in Apo E2 phenotypes it could be proved that the phenotype composition was distinctly different between diabetics with and in those without insulin therapy. While in NIDDM the increase was consequent to a higher concentration of Apo E2 homozygotes (p less than 0.005) it was caused by Apo E2 heterozygotes in IDDM (p less than 0.025) accompanied by a simultaneous decrease in Apo E3 homozygotes (p less than 0.025). Regarding blood lipids there was an increase in total cholesterol due only to VLDL cholesterol in IDDM as well as in NIDDM. It is concluded that in spite of similar hyperlipidemias in type II diabetics the increase in Apo E2 phenotypes is different; it is induced by heterozygotes in IDDM and by homozygotes in NIDDM.

[Sonographic studies during drug treatment of diabetic gastroparesis]. / Sonographische Untersuchungen bei der medikamentösen Behandlung der diabetischen Gastroparese.

Ultrasound examination of ten insulin-dependent diabetics with neuropathic gastroparesis demonstrated that gastric motility can be increased by intravenous injection of both cisapride and metoclopramide (Paspertin) (P less than 0.05 to less than 0.0005). During a one-hour period of observation stimulation lasted longer after cisapride than metoclopramide, but there were no qualitative differences between them. Compared with healthy subjects the frequency of antral contractions was increased after both drugs (P less than 0.05 and less than 0.025, respectively). Intensity and speed of contraction was less in patients than in the control subjects, but this effect was significant only for speed of contraction 20 min after injection of the drugs (P less than 0.05). The results indicate that ultrasonography makes it possible to monitor drug treatment of abnormal gastric emptying in diabetics by measurement of both frequency and degree of antral contraction.

Measurement of pulse reappearance time in diagnosis of peripheral vascular disease in diabetes.

Forty-eight patients (20 diabetic, 28 nondiabetic) with angiographically confirmed peripheral vascular disease (PVD) were examined to discover whether the measurement of pulse reappearance time (PRT) during reactive hyperemia is a more useful method than the measurement of peripheral systolic blood pressure (ankle pressure index; API) for making a specific diagnosis of PVD. Specific diagnosis refers to the degree and localization of occlusive atherosclerosis determined by Doppler ultrasound techniques for both measurements. We found that PRT and API both provided accurate qualitative proof of a peripheral blood flow deficit in diabetic and nondiabetic subjects. However, in relation to the angiographically defined degree and localization of sclerotic lesions, there were significant differences. The sclerotic degree of occlusive PVD in diabetic subjects was correlated with the results of the PRT (P less than .001), whereas the API was not (P greater than .05). The occlusion localization could only be distinguished by PRT measurements in both diabetic and nondiabetic subjects. Compared with control subjects (4.1 s) the half-maximum PRT of blood flow velocity was delayed in stenotic PVD to 5.7 s, in occlusive PVD of the upper leg to 14.3 s, in occlusive PVD of the lower leg to 29.6 s, and in multilevel disease to 45.0 s (P less than .0005 vs. control). The results show that Doppler sonographic measurement of the peripheral systolic blood pressure is only useful for an overall diagnosis of PVD in diabetic subjects, whereas PRT measurement, by quantifying the degree and localization of sclerotic lesions, can be used additionally either to confirm or to specify this diagnosis.

[Doppler ultrasound determination of maximal blood flow velocity in the diagnosis of peripheral arterial occlusive diseases in diabetes mellitus]. / Die dopplersonographische Bestimmung der maximalen Blutströmungsgeschwindigkeit in der Diagnostik peripherer arterieller Verschlusskrankheiten bei Diabetes mellitus.

Seventy-five diabetic and 40 nondiabetic subjects who were suffering from peripheral vascular disease were studied in order to determine whether the degree of the severity of their disease can be better calculated by Doppler ultrasound examinations of the peak velocity than by the systolic pressure of the peripheral bloodstream. In 46 examinations of normal controls the mean value of the peak velocity was 13.3 +/- 3.3 cm/s with a standard deviation of 15.4% +/- 13.2% on one day and 16.1% +/- 15.9% on different days. Considering patients with or without diabetes mellitus the velocity was significantly decreased in correlation to an increasing degree of severity of the vascular disease (P less than 0.001); however, the decrease was lower in diabetic than in nondiabetic subjects (6.9 +/- 2.8 vs 4.6 +/- 6.2, P less than 0.05). The systolic pressure hardly decreased, but remained higher in all stages of peripheral vascular disease of diabetics than in the nondiabetic subject (P less than 0.05 to P less than 0.005). There was a significant decrease of the systolic pressure only in diabetic subjects with the most advanced degree of the disease, i.e. stage IV (P less than 0.05). It is concluded from this study that Doppler ultrasound measurements of the peak velocity of the peripheral bloodstream are a useful parameter to calculate the degree of severity of the peripheral vascular disease. In addition, it is concluded than peak velocity is an even better prognostic indicator of peripheral vascular disease than is measurement of the systolic blood pressure at the feet.

Sonographic examination of gastric motility in diabetics with autonomic neuropathy.

The frequency, intensity and velocity of antral contractions were measured by ultrasonography in 32 patients with insulin-dependent diabetes mellitus and in 12 controls before and up to 60 min after a test breakfast. The examination showed that motility was lower in the diabetics with autonomic neuropathy than in those without and in the non-diabetic controls. The frequency of contractions was determined in the 3 groups as follows: 3.6 +/- 2.0 vs. 4.8 +/- 1.7 vs. 4.8 +/- 1.6 contractions per 2 min (p less than 0.0025); the intensity of contractions was 30.9 +/- 8.2 vs. 41.4 +/- 5.2 vs. 57.5 +/- 8.8 delta % of antral area (p less than 0.025, resp. p less than 0.0005); the velocity of contractions was 4.8 +/- 1.5 vs. 8.2 +/- 1.2 vs. 9.95 + 2.8 delta % of antral area/sec (p less than 0.0125 resp. p less than 0.005). There was a significant difference in the intensity and velocity of contractions between the patients without autonomic neuropathy and the non-diabetic controls (p less than 0.0025 resp. p less than 0.025). 10 min after the test breakfast the motility indices reached a maximum and then decreased continuously towards the end of the test period (p less than 0.01). 20 min after the test meal this decrease was significantly faster in the patients with autonomic neuropathy than in those without and in controls. In all the diabetics the velocity was positively correlated to the coefficient of the variation from beat to beat of the heart, and also positively correlated to the increase of blood glucose concentrations (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Sonographic criteria for studying gastric motility in diabetics with autonomic neuropathy]. / Sonographische Kriterien zur Untersuchung der Magenmotilität bei Diabetikern mit autonomer Neuropathie.

Antral contraction after a test meal was measured by ultrasonography in 32 insulin-dependent diabetics with and without autonomic neuropathy and in 12 control subjects. In sequence of the three groups studied the results were: frequency of contractions 3.6 +/- 2.0, 4.8 +/- 1.6, and 4.8 +/- 1.6, respectively, per two minutes; intensity of contraction 30.9 +/- 8.2, 41.4 +/- 5.2 and 57.5 +/- 8.8% of maximal antral surface decrease; and contraction velocity per sec 4.8 +/- 1.5, 8.2 +/- 1.2 and 9.95 +/- 2.8% of maximal antral surface decrease. Different from the frequency, intensity and velocity of antral contraction were reduced in diabetics (compared with normal controls) even without an autonomic neuropathy. In all diabetics, contraction velocity was positively correlated to variations in heart rate and to the postprandial blood-glucose rise. The results indicate that disorders of motility in diabetics with autonomic neuropathy can be visualized by ultrasonography and can be diagnosed early from a reduction in contraction velocity.

[Persisting hyperlipidemias as risk factors of diabetic macroangiopathy]. / Persistierende Hyperlipidämien als Risikofaktoren der diabetischen Makroangiopathie.

Severe forms of arterial occlusive diseases occurred more frequently in 11 insulin-treated diabetics with persisting hyperlipidemia than in 10 control subjects who were 11 years older. Triglycerides and cholesterol of total serum and of VLDL were 2-7 times higher (P less than 0.01); however, LDL-cholesterol was 2 times lower than in control subjects (P less than 0.025). HDL-cholesterol was not significantly different in either group. After insulin administration (81 U/die vs 37 U/die, P less than 0.00251), the increased lipids were only insignificantly reduced, while LDL-cholesterol and the ratio of LDL-/HDL-cholesterol was even increased (P less than 0.0025 and P less than 0.05). In contrast to control subjects, VLDL-cholesterol was positively correlated to the tolbutamide-induced insulin reserve (before insulin administration) and to the diurnal insulin dosage (after insulin administration) (P less than 0.01 and P less than 0.001). The results show that the atherosclerotic risk in diabetics with persisting hyperlipidemia is higher than in control subjects and that the risk is distinguished by increased VLDL-cholesterol in correlation with increased insulin concentrations. Since the atherosclerotic risk is even more accentuated by the fact that insulin administration increases LDL-cholesterol, insulin therapy must be observed carefully in these patients.

[Gastric emptying and blood glucose in insulin-dependent diabetes mellitus with autonomic neuropathy]. / Magenentleerung und Blutglucose bei insulinpflichtigem Diabetes mellitus mit autonomer Neuropathie.

Gastric emptying following the ingestion of 200 ml orange juice was investigated sonographically in 24 insulin-dependent diabetics with and without autonomic neuropathy and in 11 control subjects. Furthermore, the relationship between emptying and blood glucose was determined. The duration of gastric emptying in all patients was negatively correlated with the heart rate variation (P less than 0.01) and was longer in patients with autonomic neuropathy than in control subjects or patients without autonomic neuropathy (t1/2 48 +/- 12 min vs. 20 +/- 9 min and 24 +/- 5 min, respectively, P less than 0.0005). The rise in blood glucose was positively correlated with the heart rate variation in all patients (P less than 0.01) and was slower in autonomic neuropathy (1.2 vs. 2.9 mg/dl X min, P less than 0.0005). The delayed carbohydrate absorption in autonomic neuropathy with slower gastric emptying could be important in the management of diabetic patients in whom metabolic control is difficult.

Hypertriglyceridemia in insulin dependent diabetes mellitus with peripheral vascular disease.

Hypertriglyceridemias are the most frequent lipid disorders in diabetes mellitus with peripheral vascular disease. In spite of increasing knowledges the arteriosclerotic risk of hypertriglyceridemias is still controversial. In 77 insulin dependent diabetes (IDDM) (23 m, 54 f, age: 52 +/- 18 y. body weight: 119 +/- 21% to Brocal) with hypertriglyceridemia (TG greater than or equal to 200 mg/dl) and 97 IDDM (39 m, 68 f, age: 47 +/- 18 y, body weight: 116 +/- 22% to Broca) without lipid disorders (TG less than 200 mg/dl, CH less than 260 mg/dl) we investigated whether measurement of lipoprotein-lipids is better indicator of arteriosclerotic risk than total triglycerides. Peripheral vascular diseases (PVD) were present in 45% of patients with HTG and in 32% of patients without lipid disorders. In both groups patients with PVD had lower HDL-cholesterol (p less than 0.05 resp. p less than 0.0005) and higher VLDL-cholesterol (p less than 0.025 resp. p less than 0.005). A negative relationship between VLDL-cholesterol and HDL-cholesterol was only significant in IDDM without lipid disorders (p less than 0.001). Considering a ratio of VLDL/HDL-cholesterol of greater than or equal to 1.0 resp. less than 1.0 to be discriminating for patients with or without PVD 65.1% of all PVD (specifity) and 60.7% of all Non-PVD (sensitivity) could be correctly characterized. It is concluded, that in IDDM the ratio of VLDL/HDL-cholesterol is a better indicator for the arteriosclerotic risk than total triglycerides or total cholesterol.

[Gallbladder contractility, cholelithiasis and autonomic neuropathy in diabetes mellitus]. / Gallenblasenkontraktilität, Cholelithiasis und autonome Neuropathie bei Diabetes mellitus.

Decrease in gall-bladder surface area, as obtained by ultrasound, was measured in 52 patients with insulin-dependent diabetes (27 with and 25 without autonomic neuropathy) 60 minutes after administration of the bile stimulant Biloptin. The post-stimulation area was 33 +/- 6% of initial value in patients with autonomic neuropathy, and 67 +/- 8% (P less than 0.0005) in those without autonomic neuropathy. Comparison with insulin-dependent chronic diabetics matched for sex, age and duration of illness, demonstrated that heart-rate variability in cholelithiasis was less than in the control subjects (P less than 0.05). It is concluded that autonomic neuropathy, measured by the occurrence of spontaneous vagotomy, in insulin-dependent diabetics is an important risk factor in the overall pathogenesis of cholelithiasis.

[The somatostatin infusion test for the evaluation of glucose utilization in bezafibrate medication]. / Der Somatostatin-Infusionstest zur Beurteilung der Glukose-Utilisation unter Bezafibrat-Medikation.

The utilisation of blood glucose may be used for definition of insulin resistance in type II diabetes mellitus. To evaluate this possibility we adapted an infusion test of somatostatin in 10 normal persons (age 26 +/- 3 years, relative body weight 26 +/- 10% according to Broca) in a randomized cross-over therapy with bezafibrate (3 X 200 mg/die). As the coefficient of variation (VC) of measured blood glucose continuously increased the best time of a steady state was between 90 and 130 min after beginning the infusion (mean VC 8.9%). While insulin remained nearly constant (41 (45; 38) microU/ml) blood glucose dropped by about 14% and reached a steady state of 89 (134; 45) mg/dl. During the therapy of bezafibrate blood glucose was significantly decreased by 36% 130 min after beginning the infusion. Although the effect was not significant during the whole time of the steady state it became evident by a negative correlation with lactate (r = -0.687) and pyruvate (r = -0.843). A correlation with a concomitant decrease of triglyceride and cholesterol also induced by bezafibrate could not be proven. The results show that the infusion test of somatostatin is fitted to measure a steady state of blood glucose and insulin and that it is possible by this technique to quantify a changed utilisation of blood glucose induced by specific therapy.