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Biomedical subjects

F W LoGerfo

Publications and source records attributed to F W LoGerfo.

At least 19 recordsLinked to original sources
PubMed2001

Combined iliac angioplasty and infrainguinal revascularization surgery are effective in diabetic patients with multilevel arterial disease.

The success of percutaneous transluminal angioplasty (PTA) in the treatment of common and external iliac atherosclerotic lesions has been established for the general population. However, several studies have suggested that the presence of diabetes may reduce the effectiveness of iliac angioplasty, particularly in the setting of limb-threatening ischemia requiring concomitant lower extremity revascularization. This study compared the results of iliac artery PTA performed in conjunction with infrainguinal bypass for limb-threatening ischemia for diabetic (DM) and nondiabetic (non-DM) patients. Between 1991 and 2000, 159 PTA were performed in 126 patients (DM = 99/79%, non-DM = 27/21%) in conjunction with subsequent infrainguinal bypass for limb-threatening ischemia (gangrene = 42%, ulcer = 36%, rest pain = 22%). These patients were followed prospectively using a computerized vascular registry. Stents were placed in 34 (21.4%) cases for suboptimal angioplasty results. In this study the combined use of standard surgical and endoluminal modalities for the treatment of multilevel arterial occlusive disease resulted in excellent cumulative patency and limb salvage rates. The presence of diabetes did not alter these favorable results. Multimodal vascular therapy may be used effectively in diabetic patients with limb-threatening ischemia due to multiple levels of arterial occlusion.

Aged↗
PubMed2001

The impact of diabetes on arterial reconstructions for multilevel arterial occlusive disease.

PURPOSE: Critical limb ischemia due to multilevel arterial occlusive disease often may be treated with an inflow procedure alone; however, a subset patients require a subsequent infrainguinal revascularization for persistence of their symptoms. As diabetic patients typically exhibit a pattern of extensive distal arterial disease, we sought to determine if the presence of diabetes mellitus altered the need for an outflow procedure after inflow bypass. METHODS: A total of 504 patients undergoing inflow bypass for occlusive disease and lower extremity ischemia between 1990 and 1998 were entered prospectively into a computerized vascular registry. Inflow bypass procedures performed were as follows: aortofemoral (370; 73%), axillofemoral (56; 11%), femorofemoral (81; 16%). Of these patients, 79 required subsequent outflow bypass for unresolved ischemic symptoms. Multiple logistic regression analysis was used to analyze the effects of diabetes and multiple other risk factors on the need for an additional outflow procedure. RESULTS: The indications for surgery were limb salvage (78%) and disabling claudication (22%). Overall morbidity was 17.7% (hematoma, 3.8%; wound infection, 2.5%; graft occlusion, 1.3%; myocardial infarction, 2.5%; acute renal failure,1.3%; pulmonary failure, 2.5%; pneumonia, 3.8%). Overall mortality was 0%. Diabetic patients comprised a greater proportion of the total number of patients requiring inflow bypass (301 of 504) as well as a greater proportion of patients requiring inflow and outflow procedures (47 of 79). Diabetes was determined not to be an independent risk factor for the need for multiple revascularization procedures by multiple logistic regression analysis (P >0.10). CONCLUSION: Although patients with diabetes are predisposed to the development of distal arterial occlusive disease, in this study the subgroup of diabetic patients who present with aortoiliac occlusive disease were no more likely than patients without diabetes to require multiple levels of revascularization. These findings provide little rationale for simultaneous inflow and outflow procedures based on the presence of diabetes alone.

Arterial Occlusive Diseases↗
PubMed2001

Coating of Dacron vascular grafts with an ionic polyurethane: a novel sealant with protein binding properties.

The purpose of this study was to develop a novel sealant that would seal prosthetic vascular graft interstices and be accessible for protein binding. Crimped knitted Dacron vascular grafts were cleaned (CNTRL) and hydrolyzed in boiling sodium hydroxide (HYD). These HYD grafts were sealed using an 11% solids solution of a polyether-based urethane with carboxylic acid groups (PEU-D) via a novel technique that employs both trans-wall and luminal perfusion. Carboxylic acid content, determined via methylene blue dye uptake, was 2.3- and 4.2-fold greater in PEU-D segments (1.0+/-0.27 nmol/mg) as compared to HYD and CNTRL segments, respectively. Water permeation through PEU-D graft (1.1+/-2 ml/cm2 min(-1)) was comparable to collagen-impregnated Dacron (9.8+/-10 ml/cm2 min(-1)). Non-specific 125I-albumin (125I-Alb) binding to PEU-D segments (18+/-3 ng/mg) was significantly lower than HYD and CNTRL segments. 125I-Alb linkage to PEU-D using the crosslinker EDC resulted in 5.7-fold greater binding (103+/-2 ng/mg) than non-specific PEU-D controls. However, covalent linkage of 125I-Alb to PEU-D was 4.9- and 5.9-fold less than CNTRL and HYD segments with EDC, respectively. Thus, ionic polyurethane can be applied to a pre-formed vascular graft, seal the interstices and create "anchor" sites for protein attachment.

Biocompatible Materials↗
PubMed2001

Apolipoprotein J inhibits the migration and adhesion of endothelial cells.

BACKGROUND: Apolipoprotein J (ApoJ) is expressed after vascular injury and remodeling and may inhibit endothelial cell activation in the vascular wall. Recently, ApoJ was identified as upregulated in hyperplastic lesions after prosthetic arterial grafting. This study analyzed the effect of ApoJ on human umbilical vein endothelial cell (HUVEC) migration, adhesion, and proliferation. METHODS: Cell migration towards ApoJ + fetal bovine serum (FBS) or vascular endothelial growth factor (VEGF) was evaluated with the use of a microchemotaxis chamber with or without a fibronectin-coated membrane. For migration that involved fibronectin, cells were exposed to ApoJ before or after placement on the membrane. Cell adhesion to fibronectin was studied similarly but without stimulant. The vital dye alamar blue assessed proliferation of ApoJ + FBS- or VEGF-stimulated HUVECs. RESULTS: ApoJ alone did not cause migration or proliferation of HUVECs. Without fibronectin, ApoJ decreased the migration of HUVECs towards FBS or VEGF. When fibronectin was introduced, ApoJ decreased cell migration toward FBS or VEGF and decreased adhesion only when HUVECs in solution were exposed to ApoJ before the placement on fibronectin. ApoJ had no effect on FBS- or VEGF-induced proliferation. CONCLUSIONS: ApoJ inhibits HUVEC migration and adhesion. By altering endothelial function during vascular injury, ApoJ appears to regulate, in part, the early development of intimal hyperplasia after prosthetic arterial grafting.

Cell Adhesion↗
PubMed2001

Altered ubiquitin/proteasome expression in anastomotic intimal hyperplasia.

OBJECTIVE: Anastomotic intimal hyperplasia remains a leading mechanism of prosthetic arterial graft failure. Recent studies using messenger RNA differential display have demonstrated altered proteasome gene expression at the anastomoses in an expanded polytetrafluoroethylene canine carotid model. However, this technique is technically limited because of a paucity of available hyperplastic tissue at early time periods after arterial injury. Microarray gene chip technology offers a new and sensitive technique to assay early gene expression, requiring far less tissue for analysis. The purpose of this study was to screen for altered proteasome gene expression at 48 hours and 14 days after prosthetic arterial grafting. METHODS: Expanded polytetrafluoroethylene grafts (6-mm diameter, n = 9) were implanted into 25-kg mongrel dogs. The normal intervening carotid artery was used as control. At 48 hours and 14 days, RNA was extracted from the perianastomotic tissue and compared with RNA from the control carotid. Messenger RNA was then hybridized to microarray genomes screening for differential gene expression. RESULTS: Two 26S proteasome genes and five ubiquitin pathway genes were significantly underexpressed at 48 hours, among several hundred significantly expressed clones. The two 26S proteasome genes were 26S proteasomal subunit p55 (0.26), and 26S proteasomal subunit p40.5 (0.13). The underexpressed ubiquitin genes included ubiquitin (0.31), Nedd-4-like ubiquitin-protein ligase (0.30), ubiquitin conjugating enzyme UbcH2 (0.25), putative ubiquitin C-terminal hydrolase UHX1 (0.11), and ubiquitin-conjugating enzyme UbcH7 (0.12). At 14 days, six ubiquitin genes were underexpressed, and 17 26S proteasome genes were significantly downregulated. CONCLUSIONS: This study shows decreased expression of the ubiquitin/proteasome pathway 48 hours after graft implantation and similar diminished expression patterns after 14 days. This early and sustained underexpression after arterial bypass may lead to altered cell cycle control and matrix protein signaling, contributing to the unregulated proliferation of smooth muscle cells and extracellular matrix in anastomotic intimal hyperplasia after prosthetic arterial grafting.

Anastomosis, Surgical↗
PubMed2001

Contribution of nerve-axon reflex-related vasodilation to the total skin vasodilation in diabetic patients with and without neuropathy.

OBJECTIVE: To examine the contribution of nerve-axon reflex-related vasodilation to total acetylcholine-induced vasodilation in the skin of normal and diabetic subjects. RESEARCH DESIGN AND METHODS: The skin microcirculation was evaluated at the forearm level in 69 healthy subjects and 42 nonneuropathic diabetic patients and at the foot level in 27 healthy subjects and 101 diabetic patients (33 with neuropathy, 23 with Charcot arthropathy, 32 with peripheral vascular disease and neuropathy, and 13 without complications). Two single-point laser probes were used to measure total and neurovascular vasodilation response to the iontophoresis of 1% acetylcholine, 1% sodium nitroprusside, and deionized water. RESULTS: The neurovascular response to acetylcholine was significantly higher than the response to sodium nitroprusside and deionized water (P < 0.01). At the forearm level, the contribution of neurovascular response to the total response to acetylcholine was 35% in diabetic patients and 31% in control subjects. At the foot level, the contribution was 29% in diabetic patients without neuropathy and 36% in control subjects, while it was significantly diminished in the three neuropathic groups. A significantly lower nonspecific nerve-axon-related vasodilation was observed during the iontophoresis of sodium nitroprusside, which does not specifically stimulate the C nociceptive fibers. CONCLUSIONS: Neurovascular vasodilation accounts for approximately one-third of the total acetylcholine-induced vasodilation at both the forearm and foot levels. The presence of diabetic neuropathy results in reduction of both the total vasodilatory response to acetylcholine and the percentage contribution of neurovascular vasodilation to the total response. Acetylcholine and sodium nitroprusside cause vasodilation in the skin microcirculation through different pathways.

Acetylcholine↗
PubMed2000

Lower extremity revascularization in diabetes: late observations.

HYPOTHESIS: Despite the success of infrainguinal arterial bypass in diabetic limb and foot salvage, optimism remains guarded because of purported high late mortality and limb loss in patients with diabetes. DESIGN: Inception cohort, with minimum 5-year follow-up. SETTING: Tertiary referral center. PATIENTS: Eight hundred forty-three consecutive patients undergoing lower extremity arterial reconstruction from July 1, 1990, through July 31, 1993. INTERVENTION: Infrainguinal arterial bypass with vein graft. MAIN OUTCOME MEASURES: Graft patency, limb salvage, and survival. RESULTS: A total of 962 vein grafts (843 patients) were performed; 795 grafts (82.6%) were performed in patients with diabetes (DM group) and 167 (17.4%) in nondiabetic patients (NDM group). Average age was 68.4 years, and was lower in the DM group (66.2 [range, 27-92 years] vs. 70.5 years [range, 37-96 years]) (P = .005). Inhospital 30-day perioperative mortality was 1.4%, lower in the DM group (0.9% vs. 4.2%) (P = .005). The target vessel was more frequently infrageniculate in the DM group (87% vs. 77%; P = .002). Five-year primary and secondary graft patencies were 74.7% (DM group, 75.6%; NDM group, 71.9%; P = .80) and 76.2% (DM group, 77.0%; NDM group, 73.6%; P = .90), respectively. The 5-year overall limb salvage rate was 87.1%, also unaffected by diabetes (DM group, 87.3%; NDM group, 85.4%; P = .80). Survival at 5 years was 58.1% overall and virtually identical in the DM (58.2%) and NDM groups (58.0%). CONCLUSIONS: Diabetes mellitus does not influence late mortality, graft patency, or limb salvage rates after lower extremity arterial reconstruction. Concern for longterm mortality and limb loss in diabetic patients is unwarranted and should not prevent aggressive attempts at limb salvage.

Adult↗
PubMed2000

The use of gastric tonometry in the assessment of celiac artery compression syndrome.

This report describes the use of gastric tonometry to measure gastric mucosal ischemia/intestinal mucosa pH (pHi) in a patient treated for celiac artery compression syndrome. Significant gastric mucosal ischemia was demonstrated prior to celiac artery decompression as indicated by a pHi of 7.29. The ischemia was relieved by celiac artery decompression, with an increase in the pHi to 7.48. The patient experienced complete relief of his symptoms after surgical decompression and remains asymptomatic 14 months after surgery. Gastric tonometry provides an objective measurement of intestinal perfusion and ischemia in the treatment of celiac artery compression syndrome.

Adult↗
PubMed2000

The use of arm vein in lower-extremity revascularization: results of 520 procedures performed in eight years.

PURPOSE: The absence of an adequate ipsilateral saphenous vein in patients requiring lower-extremity revascularization poses a difficult clinical dilemma. This study examined the results of the use of autogenous arm vein bypass grafts in these patients. METHODS: Five hundred twenty lower-extremity revascularization procedures performed between 1990 and 1998 were followed prospectively with a computerized vascular registry. The arm vein conduit was prepared by using intraoperative angioscopy for valve lysis and identification of luminal abnormalities in 44.8% of cases. RESULTS: Seventy-two (13. 8%) femoropopliteal, 174 (33.5%) femorotibial, 29 (5.6%) femoropedal, 101 (19.4%) popliteo-tibial/pedal, and 144 (27.7%) extension "jump" graft bypass procedures were performed for limb salvage (98.2%) or disabling claudication (1.8%). The average age of patients was 68.5 years (range, 32 to 91 years); 63.1% of patients were men, and 36.9% of patients were women. Eighty-five percent of patients had diabetes mellitus, and 77% of patients had a recent history of smoking. The grafts were composed of a single arm vein segment in 363 cases (69. 8%) and of spliced composite vein with venovenostomy in 157 cases (30.2%). The mean follow-up period was 24.9 months (range, 1 month to 7.4 years). Overall patency and limb salvage rates for all graft types were: primary patency, 30-day = 97.0% +/- 0.7%, 1-year = 80.2% +/- 2.1%, 3-year = 68.9% +/- 3.6%, 5-year = 54.5% +/- 6.6%; secondary patency, 30-day = 97.0% +/- 0.7%, 1-year = 80.7% +/- 2.1%, 3-year = 70.3% +/- 3.4%, 5-year = 57.5% +/- 6.2%; limb salvage, 30-day = 97.6% +/- 0.7%, 1-year = 89.8% +/- 1.7%, 3-year = 82.1% +/- 3.3%, 5-year = 71.5% +/- 6.9%. Secondary patency and limb salvage rates were greatest at 5 years for femoropopliteal grafts (69.8% +/- 12.8%, 80.7% +/- 11.8%), as compared with femorotibial (59.6% +/- 10. 3%, 72.7% +/- 10.5%), femoropedal (54.9% +/- 25.7%, 56.8% +/- 26.9%, ) and popliteo-tibial/pedal grafts (39.0% +/- 7.3%, 47.6% +/- 15.4%). The patency rate of composite vein grafts was equal to that of single-vein conduits. The overall survival rate was 54% at 4 years. CONCLUSION: Autogenous arm vein has been used successfully in a wide variety of lower-extremity revascularization procedures and has achieved excellent long- and short-term patency and limb salvage rates, higher than those generally reported for prosthetic or cryopreserved grafts. Its durability and easy accessibility make it an alternative conduit of choice when an adequate saphenous vein is not available.

Adult↗
PubMed1999

Perioperative strokes after 1001 consecutive carotid endarterectomy procedures without an electroencephalogram: incidence, mechanism, and recovery.

HYPOTHESIS: That alternative methods of cerebral protection, especially routine shunting of all patients undergoing general anesthesia or shunting on the basis of neurologic assessment with the patient awake under cervical plexus block, result in outcomes of carotid endarterectomy comparable with those reported using electroencephalographic monitoring. DESIGN: Retrospective review of cases from a vascular registry established in 1990. SETTING: Tertiary care center. PATIENTS: Consecutive sample of 1001 patients who underwent carotid endarterectomy. INTERVENTIONS: Carotid endarterectomy procedures were performed without electroencephalographic monitoring, using general anesthesia with routine shunting or using regional anesthesia. MAIN OUTCOME MEASURES: Overall stroke and mortality rates and cause and consequence of the postoperative strokes. RESULTS: There were 14 nonfatal strokes (1.4%) and 2 deaths (0.2%), for a combined stroke and death rate of 1.6%. Nine (64%) of the 14 strokes appeared to result from a technical error during the endarterectomy. Mild deficits were noted after 7 strokes (50%), with the remainder resulting in deficits that required inpatient rehabilitation. Twelve patients with strokes (86%) eventually returned home without need for assistance. CONCLUSIONS: Most postoperative strokes in this series were due to technical errors. Overall, even in patients with strokes initially requiring inpatient rehabilitation, there was good recovery of function. Low stroke and mortality rates can be achieved in carotid endarterectomy without the use of electroencephalographic monitoring.

Adult↗
PubMed1999

Efficacy of dorsal pedal artery bypass in limb salvage for ischemic heel ulcers.

PURPOSE: Although pedal artery bypass has been established as an effective and durable limb salvage procedure, the utility of these bypass grafts in limb salvage, specifically for the difficult problem of heel ulceration, remains undefined. METHODS: We retrospectively reviewed 432 pedal bypass grafts placed for indications of ischemic gangrene or ulceration isolated to either the forefoot (n = 336) or heel (n = 96). Lesion-healing rates and life-table analysis of survival, patency, and limb salvage were compared for forefoot versus heel lesions. Preoperative angiograms were reviewed to evaluate the influence of an intact pedal arch on heel lesion healing. RESULTS: Complete healing rates for forefoot and heel lesions were similar (90.5% vs 86.5%, P =.26), with comparable rates of major lower extremity amputation (9.8% vs 9.3%, P =.87). Time to complete healing in the heel lesion group ranged from 13 to 716 days, with a mean of 139 days. Preoperative angiography demonstrated an intact pedal arch in 48.8% of the patients with heel lesions. Healing and graft patency rates in these patients with heel lesions were independent of the presence of an intact arch, with healing rates of 90.2% and 83.7% (P =.38) and 2-year patency rates of 73.4% and 67.0% in complete and incomplete pedal arches, respectively. Comparison of 5-year primary and secondary patency rates between the forefoot and heel lesion groups were essentially identical, with primary rates of 56.9% versus 62.1% (P =.57) and secondary rates of 67.2% versus 60.3% (P =.50), respectively. CONCLUSION: Bypass grafts to the dorsalis pedis artery provide substantial perfusion to the posterior foot such that the resulting limb salvage and healing rates for revascularized heel lesions is excellent and comparable with those observed for ischemic forefoot pathology.

Aged↗
PubMed1999

Renal insufficiency and altered postoperative risk in carotid endarterectomy.

PURPOSE: Higher complication rates have been reported in patients with renal insufficiency (RI) undergoing peripheral vascular surgery. Little attention has been paid specifically to carotid endarterectomy (CEA) in patients with RI where the risk/benefit considerations are very sensitive to small increases in postoperative complications. METHODS: One thousand one consecutive CEAs performed since 1990 were reviewed from our vascular registry, and 73 CEAs on patients with RI were identified. For comparison, two groups were established: group I (n = 928), normal renal function (creatinine level, <1.5 mg/dL); and group II (n = 73), RI (creatinine level, >/=1.5 mg/dL). RESULTS: Differences in the nonfatal stroke rates and combined stroke and death rates were statistically significant (P <.02) between the groups: group I (1. 08% and 1.18%) and group II (5.56% and 6.94%) respectively. Both groups were similar in regard to operative indications. In addition with the comparison of group I to group II, there was a statistically significant increase in hematoma rate, 1.61% versus 12. 5% ( P <.001), total cardiac morbidity, 1.72% versus 6.94% (P =.003), and total complications, 6.24% versus 36.1% (P =.001). Multivariate analysis demonstrated pre-existing RI to be the only significant predictor for perioperative stroke and hematoma. CONCLUSION: Patients with preoperative RI are at a higher, but not prohibitive, risk for stroke and death after CEA than patients with normal renal function. They are also at risk for hematoma formation, cardiac morbidity, and overall complications. Care in selection of these patients for CEA must be emphasized.

Aged↗
PubMed1999

Interferon gamma up-regulates a novel protein in vascular smooth muscle cells.

PURPOSE: By means of the technique of messenger RNA (mRNA) differential display, we previously isolated a partial DNA clone found to be down-regulated at the polytetrafluoroethylene (PTFE) hyperplastic arterial anastomosis compared with the normal artery. The partial DNA gene sequence was found to be homologous with interferon gamma up-regulated protein (IGUP) first found in human psoriatic keratinocytes. We cloned the entire IGUP gene from human vascular smooth muscle cells (VSMCs) to determine its regulation by gamma interferon (gamma-IFN) and other cytokines in cultured human VSMCs. METHODS: By means of polymerase chain reaction, the IGUP gene was amplified from a QUICK-Clone complementary DNA human aorta kit using 5' and 3' oligonucleotide primers to the known IGUP sequence. Immunohistocytochemistry studies compared normal artery and distal anastomotic IH. Human VSMCs were stimulated with 1000 U/mL of gamma-IFN, 5 ng/mL of platelet-derived growth factor BB (PDGF-BB), 3. 2 ng/mL basic fibroblast growth factor, 3.3 ng/mL transforming growth factor beta(TGF-beta), 10 ng/mL of vascular endothelial growth factor, and 10% fetal bovine serum (FBS) for zero, 24, 48 and 72 hours. Western blot analysis of lysates of the stimulated VSMCs was performed to determine up-regulation of IGUP. RESULTS: DNA sequencing confirmed the cloning of the entire coding region of the IGUP gene with 100% homology to the known IGUP DNA sequence. There was strong expression of IGUP in quiescent VSMCs and marked reduction of expression of IGUP in proliferating smooth muscle cells. gamma-IFN was the only cytokine, of the cytokines evaluated, to up-regulate production of IGUP in VSMCs. CONCLUSION: IGUP is a novel protein in VSMCs found to be down-regulated in areas of anastomotic IH, as compared with a normal artery. We have now shown IGUP to be up-regulated only by gamma-IFN in human VSMCs. IGUP may, therefore, be the intermediary for the known gamma-IFN inhibition of human VSMC proliferation.

Base Sequence↗
PubMed1999

Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes.

Abnormalities in vascular reactivity in the micro- and macrocirculation are well established in type 2 diabetes. However, little is known about changes in vascular reactivity in those at risk for developing type 2 diabetes. To address this situation, the vascular reactivity in both the micro- and macrocirculation was studied in four age and sex comparable groups: 30 healthy normoglycemic subjects with no history of type 2 diabetes in a first-degree relative (controls), 39 healthy normoglycemic subjects with a history of type 2 diabetes in one or both parents (relatives), 32 subjects with impaired glucose tolerance (IGT), and 42 patients with type 2 diabetes without vascular complications (diabetes). Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent) and 1% sodium nitroprusside (SNP) (endothelium-independent), whereas high-resolution ultrasound images were used to measure brachial artery diameter changes during reactive hyperemia. Plasma concentrations of endothelin-1 (ET-1), von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The vasodilatory responses to Ach, expressed as percent increase of blood flow over baseline, were reduced in relatives (98 +/- 48, mean +/- SD), IGT (94 +/- 52), and diabetes (74 +/- 45) compared with controls (126 +/- 67) (P < 0.001 controls versus relatives, IGT, and diabetes). The responses to SNP were similarly reduced: controls (123 +/- 46), relatives (85 +/- 46), IGT (83 +/- 48), and diabetes (65 +/- 31) (P < 0.001 controls versus relatives, IGT, and diabetes) as were the responses in the brachial artery diameter during reactive hyperemia: controls (13.7 +/- 6.1), relatives (10.5 +/- 6.7), IGT (9.8 +/- 4.5), and diabetes (8.4 +/- 5.0) (P < 0.01 controls versus relatives, IGT, and diabetes). Women had greater responses than men in both the micro- and macrovascular circulatory tests, but a similar progressive reduction was observed in both sexes with increasing degrees of glucose intolerance. A significant inverse correlation was found between microvascular reactivity and systolic blood pressure, fasting plasma glucose, HDL cholesterol, fasting plasma insulin, and homeostasis model assessment (HOMA) values, an index of insulin resistance. BMI and diastolic blood pressure had a significant inverse correlation only with endothelium-dependent vasodilation. In the macrocirculation, systolic blood pressure, HbA1c, HDL cholesterol, and HOMA had significant correlation with brachial artery diameter changes. Compared with control subjects, ET-1 was significantly higher in all groups, vWF was higher only in the diabetic group, sICAM levels were higher in the IGT and diabetic groups, while sVCAM concentrations were higher in the relatives and those with diabetes (P < 0.05). On stepwise multivariate analysis, age, sex, fasting plasma glucose, and BMI were the most important contributing factors to the variation of vascular reactivity. Addition of all clinical and biochemical measures explained only 32-37% of the variation in vascular reactivity. These results suggest that abnormalities in vascular reactivity and biochemical markers of endothelial cell activation are present early in individuals at risk of developing type 2 diabetes, even at a stage when normal glucose tolerance exists, and that factors in addition to insulin resistance may be operative.

Acetylcholine↗
PubMed1999

Soluble intercellular adhesion molecule, vascular cell adhesion molecule, and impaired microvascular reactivity are early markers of vasculopathy in type 2 diabetic individuals without microalbuminuria.

OBJECTIVE: Using von Willebrand Factor (vWF) as a marker of endothelial function, previous studies have shown that the development of microalbuminuria is associated with the onset of endothelial dysfunction in individuals with type 2 diabetes. We tested the hypothesis that endothelial dysfunction is already evident in normoalbuminuric individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: We used laser Doppler imaging scanning to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent). Multiple indicators of endothelial function--soluble intercellular adhesion molecule (sICAM), soluble vascular cell adhesion molecule (sVCAM), vWF, and microvascular reactivity--were measured in 20 healthy control subjects, 45 normoalbuminuric (urinary albumin/creatinine ratio < 30 micrograms/mg) individuals with type 2 diabetes, and 14 microalbuminuric (urinary albumin/creatinine ratio between 30 and 300 micrograms/mg) individuals with type 2 diabetes. RESULTS: Serum sICAM and sVCAM levels were elevated in the normoalbuminuric (305 +/- 120, 851 +/- 284 ng/ml) and microalbuminuric (300 +/- 89, 845 +/- 252 ng/ml) individuals with diabetes when compared with the healthy control subjects (213 +/- 58, 661 +/- 176 ng/ml) (P < 0.01). Furthermore, the microvascular endothelium-dependent and -independent vasodilation was reduced in the normoalbuminuric (76 +/- 44, 70 +/- 33) (percent increase in perfusion over baseline) and microalbuminuric (74 +/- 41, 73 +/- 28) individuals with diabetes compared with healthy control subjects (126 +/- 67, 120 +/- 47) (P < 0.05). In contrast, plasma vWF was elevated only in the microalbuminuric individuals with diabetes (129 +/- 35%) compared with the normoalbuminuric individuals with diabetes (110 +/- 34) and healthy control subjects (111.3 +/- 39) (P < 0.05). On stepwise multivariate analysis, fasting blood glucose was the most important contributing factor to the variation in microvascular reactivity and sVCAM, whereas insulin resistance (by homeostasis model assessment) was the most important contributing factor to the variation in sICAM. Addition of all clinical and biochemical measures explained only 15-22% of the variation in sICAM, sVCAM, and microvascular reactivity. CONCLUSIONS: Multiple markers of endothelial dysfunction were evident in normoalbuminuric individuals with type 2 diabetes. The pathogenic process of vasculopathy in type 2 diabetes occurs early and may be operative before the development of microalbuminuria.

Adult↗