Capillary Permeability and Blood Flow in Skeletal Muscle of Patients with Diabetes Mellitus and Genetic Prediabetes

Alpert, Joseph S.; Coffman, Jay D.; Balodimos, Marios C.; Koncz, Lajos; Soeldner, J S

doi:10.1056/nejm197203022860903

Cited by 78 publications

(34 citation statements)

References 27 publications

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“…I ncreased microvascular permeability has been demonstrated in type I (insulin-dependent) and type II (noninsulin-dependent) diabetic patients and has been implicated in the pathogenesis of diabetic microangiopathic complications (1)(2)(3)(4)(5)(6). An increased transcapillary escape rate (TER) of albumin has been demonstrated in type I diabetic patients who have microalbuminuria or clinical nephropathy (2).…”

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confidence: 99%

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Increased Transcapillary Escape Rate of Albumin in Nondiabetic Men in Response to Hyperinsulinemia

et al. 1990

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Diabetic patients manifest increased vascular permeability. To determine whether insulin per se might increase vascular permeability, five nondiabetic men were studied by the hyperinsulinemic-euglycemic clamp technique. Each subject received a 0.72-nmol/kg body wt i.v. insulin bolus, followed by a 72-pmol.kg-1.min-1 insulin infusion for 4 h. Euglycemia was maintained by the Biostator glucose controller. At 7 h of study, 10 microCi i.v. 125I-labeled albumin was injected as bolus dose. Frequent blood samples were drawn during the next 70 min for determination of the transcapillary escape rate (TER) of albumin. Subjects returned 1-2 wk later for a control study, during which 0.45% saline was infused at a rate identical to the dextrose and insulin infusion rates during the hyperinsulinemic clamp. The mean +/- SE serum insulin levels during the hyperinsulinemic clamp and saline infusion were 9786 +/- 126 and 46 +/- 4 pM, respectively, whereas serum glucose during the two sessions was similar (5.0 +/- 0.2 vs. 4.8 +/- 0.1 mM, NS). Identical fluid volumes were infused during the two sessions (1767 +/- 197 ml/7 h), and urine outputs did not differ significantly (1615 +/- 309 vs. 1035 +/- 248 ml/7 h). The TER of albumin was greater in all five men after hyperinsulinemia than after saline infusion (18.3 +/- 2.7 vs. -2.8 +/- 2.3%/h, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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“…An increased transcapillary escape rate (TER) of albumin has been demonstrated in type I diabetic patients who have microalbuminuria or clinical nephropathy (2). In these studies, the magnitude of the permeability defect seems to be related to the severity of clinical microangiopathy, particularly nephropathy (1,2,4,5).…”

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confidence: 99%

Increased Transcapillary Escape Rate of Albumin in Nondiabetic Men in Response to Hyperinsulinemia

et al. 1990

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“…A functional and structural alteration of diabetic capillaries should be considered for this intervening pathologic alteration because (i) a generalized basement membrane abnormality is characteristic of diabetes (25)(26)(27); (ii) such an abnormality has also been described for diabetic nerve (28-31); (iii) increased permeability has been described for capillaries of several tissues (32)(33)(34); (iv) the complications of retinopathy, nephropathy, and neuropathy are correlated in the same patient (5,35) and, since capillary dysfunction is involved in retinopathy and nephropathy, it may also be involved in neuropathy; (v) reduced nerve blood flow and oxygen tension have recently been described in streptozotocin diabetes (36); and (vi) the nerve conduction abnormality of streptozotocin diabetes can be partially prevented by oxygen supplementation (37). For nerve, however, capillaries have not been systematically studied and severity of capillary derangement has not yet been critically related to neuropathic deficit.…”

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confidence: 99%

Capillary number and percentage closed in human diabetic sural nerve.

Dyck¹,

Hansen²,

Karnes³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

189

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The number of capillaries per mm2, minimum intercapillary distance, number of endothelial nuclei per capillary section, and percentage of capillaries closed were evaluated in transverse sections of fascicles of 45 control and 36 diabetic sural nerves. All controls and patients were prospectively studied to ascertain their diabetic and neuropathic status. An index of pathology was introduced and it was found to provide a sensitive and reliable measurement of the presence and severity of neuropathy. The number of capillaries and minimum intercapillary distance of diabetic nerves were not significantly different from those of controls (P > 0.05). Diabetic nerves exhibited a small but statistically significant increase in the number of endothelial nuclei per capillary that was positively correlated with the severity of neuropathy. The most striking abnormality was the statistically significant increase in the percentage of capillaries closed in patients with neuropathy as compared to those without neuropathy and controls. Among diabetics, this percentage increased with the severity of neuropathy (P = 0.008). The two capillary abnormalities that have been demonstrated may play a role in the development of diabetic polyneuropathy.Diabetic polyneuropathy, a common complication of diabetes mellitus, is typically expressed as sensory loss, pain, and autonomic dysfunction in the feet and legs (1). Although the mechanisms underlying diabetic neuropathy remain unknown, chronic hyperglycemia may lead to metabolic derangement that directly affects neurons (axons) or Schwann cells or indirectly affects them by first altering another tissue-e.g., vessels. Since a higher rate of atherosclerotic heart disease and peripheral vascular disease occurs among diabetics (2, 3) and since arteriosclerosis with vessel occlusion is reported for vasa nervorum of nerve (4-6), arteriosclerosis has been postulated as a cause of diabetic neuropathy. This hypothesis, however, may not explain the common occurrence of an abnormality of nerve conduction and development of a diffuse neuropathy among diabetic patients who do not manifest peripheral vascular disease (7-10). Attention, therefore, has been focused on metabolic derangements that might affect neurons (or their peripheral axons) or Schwann cells. Among the metabolic mechanisms that have been considered are the following: (i) lipid alterations (11-13); (ii) accumulation of sorbitol and fructose (14, 15); (iii) decreased nerve myo-inositol (16); (iv) increased nonenzymatic glycosylation of protein (17, 18); (v) decrease of Na+,K+-ATPase (19); (vi) increased intraaxonal sodium (20); (vii) alterations in axonal flow (21) and axonal attenuation (22); and (viii) tissue dehydration (23). Since the nerve conduction abnormality is not readily reversed after near normalization of blood glucose for periods of up to 8 months, an irreversible nerve alteration or an intervening pathologic alteration interposed between metabolic derangement and neuropathic dysfunction is inferred (24).A functional...

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“…These basement membrane changes appear to be similar to those associated with an increase in capillary permeability [1,27], Transcapillary exchange has not been inves tigated in any peripheral organ from a subject in congestive HF.…”

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confidence: 96%

Transcapillary Exchange in the Hindlimb and Intestine of Dogs with Right Heart Failure

Mh¹,

Jn²

1986

Cardiology

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The effects of chronic right ventricular volume overload, congestive heart failure (HF) on transcapillary exchange of lipid-insoluble solutes in the hindlimb and small intestine were studied in anesthetized dogs. Using the single injection indicator diffusion method, extractions (E), capillary clearances (C), and capillary permeability surface area products (PS) of urea, sucrose, and inulin were measured in the hindlimb and small intestine of 16 control and 14 HF dogs. Right HF was caused by surgically produced tricuspid insufficiency. The HF dogs exhibited increased central venous pressures, right ventricular end diastolic pressure, and heart rates as well as gross ascites and pleural effusion. The small intestine of the HF dogs demonstrated increased E, C and PS values for all three solutes, while no changes were seen in the hindlimb. These changes in the capillary bed of the small intestine could be due to an increase in capillary permeability, and/or capillary surface area.

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Capillary Permeability and Blood Flow in Skeletal Muscle of Patients with Diabetes Mellitus and Genetic Prediabetes

Cited by 78 publications

References 27 publications

Increased Transcapillary Escape Rate of Albumin in Nondiabetic Men in Response to Hyperinsulinemia

Increased Transcapillary Escape Rate of Albumin in Nondiabetic Men in Response to Hyperinsulinemia

Capillary number and percentage closed in human diabetic sural nerve.

Transcapillary Exchange in the Hindlimb and Intestine of Dogs with Right Heart Failure

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