Postprandial impairment of resistance vessel function in insulin treated patients with diabetes mellitus type-2.

Reduced postischaemic reactive hyperaemia, is considered a marker of impaired resistance vessel function. Acute postprandial hyperlipidaemia has been shown to induce vascular dysfunction. In the present study, the impact of postprandial hyperglycaemia on resistance vessel reactivity was investigated in insulin treated type-2 diabetic patients. The study was performed in 16 insulin treated type-2 diabetics (eight male/eight female, age 47 +/- 3 years, HbA1c 7.2 +/- 0.2) and 16 controls. Reactive hyperaemia was measured in the forearm by venous occlusion plethysmography after 5 min of ischaemia in the fasting state and 90 min after a test meal. In diabetics, blood glucose increased from 8.7 +/- 1.1 to 15.3 +/- 1.0 mmol l-1 (P<0.001) postprandially. This resulted in (i) a significant increase of resting blood flow (3.4 +/- 0.3 to 4.8 +/- 0.4 ml min-1 100 ml-1, P<0.01) and (ii) in a reduced peak reactive hyperaemia (52.3 +/- 7.4 to 36.8 +/- 4.3 ml min-1 100 ml-1, P<0.005). In controls, a similar effect of the meal on resting flow was observed but reactive hyperaemia was unaltered. In the absence of a test meal, basal flow as well as peak reactive hyperaemia remained unchanged in diabetic as well as in non-diabetic subjects. Our data provide evidence that in the postprandial state resistance vessel reactivity becomes reduced in insulin treated type-2 diabetic patients.     

Determinants of post-ischaemic reactive hyperaemia in patients with diabetes mellitus type II

Dysfunction of resistance arteries is thought to be an early reversible stage in the development of atherosclerosis. Dynamics of post-ischaemic reactive hyperaemia are believed to constitute a useful tool for monitoring resistance vessel function. Patient characteristics influencing reactive hyperaemia, however, need to be defined more precisely. Since reactive hyperaemia is a dynamic process, yielding submaximal peak values after 5 min of ischaemia, this period was chosen to investigate the determinants of reactive hyperaemia in 100 type II diabetic patients as well as in 61 control subjects. Reactive hyperaemia was measured by venous-occlusion plethysmography; clinical and laboratory data were acquired by routine methods. Statistical comparison was performed with SYSTAT 5·0 for Apple Macintosh. Overall, no significant differences between diabetic patients and controls were observed by group comparison. In control subjects, only gender showed an influence on peak reactive hyperaemia (females 40·5 ± 15·3; males 51·8 ± 17·7 ml min^–1 100 ml^–1, P<0·01). In diabetic patients, in addition to gender, actual blood glucose (r=0·377, P<0·05) and meal intake (non-fasting 42·8 ± 19·2; fasting 51·2 ± 19·5 ml min^–1 100 ml^–1, P<0·05) were found to influence reactive hyperaemia. Further investigation revealed a loss of the correlation between peak reactive hyperaemia and actual blood glucose observed in the fasting state (P<0·001) in non-fasting diabetic patients, indicating an influence of meal intake on resistance vessel reactivity. Our results suggest that, in diabetic subjects, in addition to gender actual blood glucose and the postprandial situation impacts on peak reactive hyperaemia.     

Resistance to activated protein C (APC): mutation at ARG506 of coagulation factor V and vascular access thrombosis in haemodialysis patients

BACKGROUND.: Vascular access thrombosis represents a serious problem in haemodialysispatients. Therefore identification of relevant thrombotic riskfactors is clinically valuable. Resistance to activated proteinC (APC) was recently identified as a new thrombophilic defectwhich is caused by a single point mutation in the factor V gene.Whether this mutation predisposes to vascular access thrombosisis unknown. METHODS.: The presence of factor V Leiden (mutation at nucleotide position1691 of the factor V gene) was determined by polymerase chainreaction (PCR) analysis in 152 haemodialysis patients from allthree haemodialysis units of the University Hospital of Vienna.In 61 patients (54 without mutation, 7 with heterozygous mutation)resistance to APC was evaluated. Onehundredseven individualswithout renal failure (57 negative for factor V Leiden, 50 heterozygoussubjects) served as controls. Haemodialysis patients with heterozygousfactor V Leiden mutation were carefully investigated for thromboticcomplications of vascular access, other thromboembolic eventsand additional putative thromboembolic risk factors. RESULTS.: Seven of 152 (4.6%) patients were heterozygous carriers of factorV Leiden. The mean APC resistance ratio in heterozygous dialysispatients was 2.31; in the 50 heterozygous controls the ratiowas 2.02. The mean APC ratio in haemodialysis patients withoutmutation was 3.53 in contrast to 2.95 in the control group.Not one of the seven heterozygous haemodialysis patients sufferedfrom vascular access thrombosis of inexplicable origin. Threepatients remained totally free of access thrombosis from onsetof haemodialysis treatment. In four of seven patients nine eventsof thrombosis of the vascular access occurred, but were dueto anatomical stenosis in each case. In six permanent centralvenous catheters no episode of occlusion or reduced blood flowrequiring thrombolytic therapy was observed. Family historywith regard to thrombotic events was negative in all seven patients.No thromboembolic complication occurred during 13 periods ofimmobilization, in the course of six pregnancies and duringoral contraception. CONCLUSIONS.: The heterozygous carrier status for factor V Leiden does notappear to represent a risk factor for vascular access thrombosisin haemodialysis patients. This is possibly due to the factthat the functional APC activity is high and in heterozygoushaemodialysis patients APC resistance ratios are very closeto the normal range. However, it cannot be excluded that a homozygousfactor V mutation represents an increased risk for shunt thrombosis.Therefore patients suffering from repeated and/or inexplicableshunt thrombosis should be tested for the factor V mutationto evaluate the effect of a homozygous mutation.     

Postprandial impairment of resistance vessel function in insulin treated patients with diabetes mellitus type‐2

Reduced postischaemic reactive hyperaemia, is considered a marker of impaired resistance vessel function. Acute postprandial hyperlipidaemia has been shown to induce vascular dysfunction. In the present study, the impact of postprandial hyperglycaemia on resistance vessel reactivity was investigated in insulin treated type‐2 diabetic patients. The study was performed in 16 insulin treated type‐2 diabetics (eight male/eight female, age 47 ± 3 years, HbA1c 7·2 ± 0·2) and 16 controls. Reactive hyperaemia was measured in the forearm by venous occlusion plethysmography after 5 min of ischaemia in the fasting state and 90 min after a test meal. In diabetics, blood glucose increased from 8·7 ± 1·1 to 15·3 ± 1·0 mmol l^?1 (P<0·001) postprandially. This resulted in (i) a significant increase of resting blood flow (3·4 ± 0·3 to 4·8 ± 0·4 ml min^?1 100 ml^?1, P<0·01) and (ii) in a reduced peak reactive hyperaemia (52·3 ± 7·4 to 36·8 ± 4·3 ml min^?1 100 ml^?1, P<0·005). In controls, a similar effect of the meal on resting flow was observed but reactive hyperaemia was unaltered. In the absence of a test meal, basal flow as well as peak reactive hyperaemia remained unchanged in diabetic as well as in non‐diabetic subjects. Our data provide evidence that in the postprandial state resistance vessel reactivity becomes reduced in insulin treated type‐2 diabetic patients.     

Determinants of post-ischaemic reactive hyperaemia in patients with diabetes mellitus type II.

Dysfunction of resistance arteries is thought to be an early reversible stage in the development of atherosclerosis. Dynamics of post-ischaemic reactive hyperaemia are believed to constitute a useful tool for monitoring resistance vessel function. Patient characteristics influencing reactive hyperaemia, however, need to be defined more precisely. Since reactive hyperaemia is a dynamic process, yielding submaximal peak values after 5 min of ischaemia, this period was chosen to investigate the determinants of reactive hyperaemia in 100 type II diabetic patients as well as in 61 control subjects. Reactive hyperaemia was measured by venous-occlusion plethysmography; clinical and laboratory data were acquired by routine methods. Statistical comparison was performed with SYSTAT 5.0 for Apple Macintosh. Overall, no significant differences between diabetic patients and controls were observed by group comparison. In control subjects, only gender showed an influence on peak reactive hyperaemia (females 40.5 +/- 15.3; males 51.8 +/- 17.7 ml min-1 100 ml-1, P < 0.01). In diabetic patients, in addition to gender, actual blood glucose (r = 0.377, P < 0.05) and meal intake (non-fasting 42.8 +/- 19.2; fasting 51.2 +/- 19.5 ml min-1 100 ml-1, P < 0.05) were found to influence reactive hyperaemia. Further investigation revealed a loss of the correlation between peak reactive hyperaemia and actual blood glucose observed in the fasting state (P < 0.001) in non-fasting diabetic patients, indicating an influence of meal intake on resistance vessel reactivity. Our results suggest that, in diabetic subjects, in addition to gender actual blood glucose and the postprandial situation impacts on peak reactive hyperaemia.     

K-ras mutations as pathogenetic and diagnostic markers in pancreatic cancer

Conclusions K-ras codon 12 mutations are an early event in pancreatic carcinogenesis. However more than 1 in 1000 cells have to be mutated and other (additional?) mutations may be necessary for the development of pancreatic neoplasia. Only long term studies will provide insight into the clinical significance of K-ras gene mutations in chronic pancreatitis.