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Biomedical subjects

S Jacob

Publications and source records attributed to S Jacob.

At least 91 records · Page 5Linked to original sources
PubMed1999

Association of diabetes mellitus and chronic hepatitis C virus infection.

While patients with liver disease are known to have a higher prevalence of glucose intolerance, preliminary studies suggest that hepatitis C virus (HCV) infection may be an additional risk factor for the development of diabetes mellitus. To further study the correlation of HCV infection and diabetes, we performed a retrospective analysis of 1,117 patients with chronic viral hepatitis and analyzed whether age, sex, race, hepatitis B virus (HBV) infection, HCV infection, and cirrhosis were independently associated with diabetes. In addition, a case-control study was conducted to determine the seroprevalence of HCV infection in a cohort of 594 diabetics and 377 clinic patients assessed for thyroid disease. In the former study after the exclusion of patients with conditions predisposing to hyperglycemia, diabetes was observed in 21% of HCV-infected patients compared with 12% of HBV-infected subjects (P =.0004). Multivariate analysis revealed that HCV infection (P =.02) and age (P =.01) were independent predictors of diabetes. In the diabetes cohort, 4.2% of patients were found to be infected with HCV compared with 1.6% of control patients (P =.02). HCV genotype 2a was observed in 29% of HCV-RNA-positive diabetic patients versus 3% of local HCV-infected controls (P <.005). In conclusion, the data suggest a relatively strong association between HCV infection and diabetes, because diabetics have an increased frequency of HCV infection, particularly with genotype 2a. Furthermore, it is possible that HCV infection may serve as an additional risk factor for the development of diabetes, beyond that attributable to chronic liver disease alone.

Adult↗
PubMed1999

Lipolysis in skeletal muscle is rapidly regulated by low physiological doses of insulin.

AIMS/HYPOTHESIS: Both patients with Type II (non-insulin-dependent) diabetes mellitus and normoglycaemic, insulin resistant subjects were shown to have an increased lipid content in skeletal muscle, which correlates negatively with insulin sensitivity. Recently, it was shown that during a hyperinsulinaemic euglycaemic clamp interstitial glycerol was reduced not only in adipose tissue but also in skeletal muscle. To assess whether lipolysis of muscular lipids is also regulated by low physiological concentrations of insulin, we used the microdialysis technique in combination with a 3-step hyperinsulinaemic glucose clamp. METHODS: Nineteen lean, healthy subjects (12 m/7 f) underwent a glucose clamp with various doses of insulin (GC I = 0.1, GC II = 0.25 and GC III = 1.0 mU x kg(-1) x min(-1)). Two double lumen microdialysis catheters each were inserted in the paraumbilical subcutaneous adipose tissue and in skeletal muscle (tibialis anterior) to measure interstitial glycerol concentration (index of lipolysis) and ethanol outflow (index of tissue flow). RESULTS: During the different steps of the glucose clamp, glycerol in adipose tissue was reduced to 81 +/- 7 % (GC I), 55 +/- 8 % (GC II) and 25 +/- 5 % (GC III), respectively, of basal. In contrast, glycerol in skeletal muscle declined to 73 +/- 5 % (GC I) and to 57 +/- 6 % (GC II) but was not further reduced at GC III. Tissue flow was higher in the skeletal muscle and remained unchanged in both compartments throughout the experiment. CONCLUSION/INTERPRETATION: This study confirms the presence of glycerol release in skeletal muscle. Lipolysis in skeletal muscle and adipose tissue are suppressed similarly by minute and physiological increases in insulin but differently by supraphysiological increases. Inadequate suppression of intramuscular lipolysis resulting in increased availability of non-esterified fatty acids, could represent a potential mechanism involved in the pathogenesis of impaired glucose disposal, i. e. insulin resistance, in muscle. [Diabetologia (1999) 42: 1171-1174]

Adipose Tissue↗
PubMed1999

The beta2-adrenergic modulator celiprolol reduces insulin resistance in obese Zucker rats.

Essential hypertension is associated with an increased incidence of insulin resistance of skeletal muscle glucose transport. The present study determined if celiprolol, an antihypertensive agent with selective beta1-adrenoceptor antagonist and additional beta2-agonistic properties, administered by gavage either acutely (3 hr) or chronically (14 d), had a direct effect on improving glucose tolerance and insulin-stimulated glucose transport activity (using 2-deoxyglucose (2-DG) uptake) in isolated epitrochlearis muscles of the insulin-resistant obese Zucker rat. The effects of a selective beta1-blocker, metoprolol, were also assessed. Acute administration of celiprolol, but not metoprolol, increased insulin-stimulated 2-DG uptake in muscle by 22% (p<0.05). Chronic celiprolol treatment significantly lowered fasting plasma insulin (22%) and free fatty acids (40%) in comparison to obese control values. Moreover, chronic celiprolol administration decreased the glucose-insulin index (calculated as the product of the glucose and insulin areas under the curve during an oral glucose tolerance test), by 32% (p<0.05) compared to obese controls, indicating that peripheral insulin action was increased. Indeed, insulin-stimulated skeletal muscle 2-DG uptake was enhanced by 49% (p<0.05) in these celiprolol-treated obese animals. Metoprolol was without significant effect on any of these variables following chronic administration. These findings indicate that, in this animal model of insulin resistance, the beta1-antagonist/beta2-agonist celiprolol has a specific effect of improving insulin-stimulated skeletal muscle glucose transport that is independent of any hemodynamic alterations.

Adrenergic beta-Antagonists↗
PubMed1999

Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial.

Alpha-lipoic acid (ALA), a naturally occuring compound and a radical scavenger was shown to enhance glucose transport and utilization in different experimental and animal models. Clinical studies described an increase of insulin sensitivity after acute and short-term (10 d) parenteral administration of ALA. The effects of a 4-week oral treatment with alpha-lipoic acid were evaluated in a placebo-controlled, multicenter pilot study to determine see whether oral treatment also improves insulin sensitivity. Seventy-four patients with type-2 diabetes were randomized to either placebo (n = 19); or active treatment in various doses of 600 mg once daily (n = 19), twice daily (1200 mg; n = 18), or thrice daily (1800 mg; n = 18) alpha-lipoic acid. An isoglycemic glucose-clamp was done on days 0 (pre) and 29 (post). In this explorative study, analysis was done according to the number of subjects showing an improvement of insulin sensitivity after treatment. Furthermore, the effects of active vs. placebo treatment on insulin sensitivity was compared. All four groups were comparable and had a similar degree of hyperglycemia and insulin sensitivity at baseline. When compared to placebo, significantly more subjects had an increase in insulin-stimulated glucose disposal (MCR) after ALA treatment in each group. As there was no dose effect seen in the three different alpha-lipoic acid groups, all subjects receiving ALA were combined in the "active" group and then compared to placebo. This revealed significantly different changes in MCR after treatment (+27% vs. placebo; p < .01). This placebo-controlled explorative study confirms previous observations of an increase of insulin sensitivity in type-2 diabetes after acute and chronic intravenous administration of ALA. The results suggest that oral administration of alpha-lipoic acid can improve insulin sensitivity in patients with type-2 diabetes. The encouraging findings of this pilot trial need to be substantiated by further investigations.

Administration, Oral↗
PubMed1999

A dietary survey in Indian hemodialysis patients.

Malnutrition is a common problem in maintenance hemodialysis (MHD) patients, and compromised intake is an important cause. There is no information available about the nutrient intakes of MHD patients in India. The nutrient intakes of 106 MHD patients were studied cross-sectionally and on follow-up. A 24-hour recall was used on 4 consecutive days. After 2 months on dialysis, the mean energy intake was 29 +/- 6.6 kcal/kg ideal body weight (IBW) and the mean protein intake was.93 +/-.39 g/kg IBW (high biological value [HBV] protein 49% +/- 8.5%). Dietary deficiency of both protein and calories was present in 64.9%. Intake was better on nondialysis days compared with dialysis days, and in women and older patients. On follow-up there was no significant increase in food intake up to 6 months. After that, the total calorie intake increased significantly with a disproportionate drop in high biological value protein consumed and appeared to be derived predominantly from carbohydrate food (mean kcal/kg, 37 +/- 6.9; mean protein g/kg, 0.96 +/- 0.19; ratio of HBV protein to total protein consumed,.42 +/-.09). In summary this study showed suboptimal energy and protein intake in an MHD population. Intakes were further compromised on dialysis days, and with increasing time spent on dialysis, the quality of nutrient intake became poorer.

Adult↗
PubMed1999

Successful non-invasive ventilatory support in a patient with regimen-related toxicity during allogeneic bone marrow transplantation.

A 13-year-old patient with transfusion-dependent beta thalassemia major developed acute regimen-related lung toxicity after the conditioning regimen but before allogeneic bone marrow transplantation. He was successfully managed on non-invasive ventilatory support. Advances in non-invasive ventilatory support may drastically improve the outlook of this subset of patients who otherwise have a grim prognosis.

Adolescent↗
PubMed1999

Vascular surgical society of great britain and ireland: distal venous arterialization for non-reconstructable arterial disease

BACKGROUND: Despite advances in vascular surgical and interventional radiological techniques, 14-20 per cent of patients with critical lower limb ischaemia will not be suitable for distal arterial reconstruction owing to occlusion of crural and pedal vessels. Following investigation into the venous anatomy of the foot, the disease-free venous bed was used as an alternative conduit for perfusion of peripheral tissues. METHODS: For 22 months, venous arterialization was performed for all patients with non-reconstructable disease but potentially salvageable feet. There were 15 patients; 14 had surgery for chronic ischaemia and one for acute embolization from a popliteal aneurysm after unsuccessful thrombolysis. The inflow vessel was the common femoral artery in 12 and the popliteal artery in three patients. Reversed contralateral long saphenous vein was used in five, a composite graft in three and a polytetrafluoroethylene graft with vein patch in the remaining seven. The distal anastomosis was to the dorsal venous arch (13 cases) and in two to vena comitantes of the posterior tibial vein owing to extensive tissue loss. Various techniques were employed to destroy the valve. RESULTS: Three procedures failed immediately after operation and major amputation was required. The remaining 12 patent grafts were monitored by duplex scan; two required intervention to correct distal anastomotic stenosis by angioplasty and atherectomy (one patient each). The limb salvage rate at 2-22 months of follow-up was 80 per cent. CONCLUSION: Distal venous arterialization is a unique and promising operation which merits further evaluation.

Journal Article↗
PubMed1999

Vascular surgical society of great britain and ireland: review of out-of-hours vascular procedures in a tertiary vascular unit

BACKGROUND: The aim of this study was to review out-of-hours vascular procedures in a tertiary vascular unit. METHODS: The vascular emergencies that presented outside normal working hours (17. 00 to 08.00 hours) in a vascular unit between January and June 1998 were reviewed. Only cases considered to be life or limb threatening and requiring urgent surgical or radiological intervention were assessed. RESULTS: The Table shows that a significant number of vascular emergencies was performed out of hours in one unit. This was, in part, due to an increase in the number of tertiary referrals, which represented 57 per cent of all emergency procedures. Reasons for the tertiary referrals were: no consultant vascular surgeon on call (33 per cent), no consultant interventional radiologist on call (26 per cent), lack of intensive care beds (30 per cent) and complex procedure (11 per cent). The overall mortality rate of patients referred in this period was 15 per cent. The unit has three consultant vascular surgeons, two consultant interventional radio- logists and one vascular specialist registrar. CONCLUSION: The significant increase in out-of-hours vascular emergencies, both surgical and radiological, has placed an enormous demand on senior members of the team. In addition, it has had a significant impact on the unit's elective admissions and waiting lists, in particular those for routine general surgery. To support the growth in complex emergency referrals, senior vascular fellows in both vascular surgery and radiology have been appointed and proposals are underway to restructure local vascular services.

Journal Article↗
PubMed1999

Insulin action and secretion in healthy, glucose tolerant first degree relatives of patients with type 2 diabetes mellitus. Influence of body weight.

It is a matter of controversy, whether insulin action or secretion - or both - are disturbed in first degree relatives of patients with type 2 diabetes. We intended to assess both the compensatory and the obesity-related part of insulin secretion. In order to dissect out the latter, matching for insulin sensitivity was mandatory to normalize for the compensatory part of hyperinsulinemia. In 154 healthy, glucose tolerant first degree relatives of patients with type 2 diabetes we directly quantified both insulin sensitivity (by euglycemic-glucose-clamp technique) and insulin secretion (oral glucose load; stimulated serum c-peptide). Insulin sensitivity was scattered over a wide range with a considerable overlap of both first degree relatives of patients with type 2 diabetes and 97 controls without a family history of diabetes. Average insulin sensitivity was higher in controls (8.0+/-0.3 vs. 7.1 + 0.2 ml x kg-l x min-1, p < 0.05). Prevalence of insulin resistance (defined as controls, lowest tertile for insulin sensitivity) was 40% in first degree relatives of patients with type 2 diabetes. Insulin secretion after oral glucose was significantly increased in insulin resistant first degree relatives of patients with type 2 diabetes compared to insulin sensitive first degree relatives of patients with type 2 diabetes. Early phase relative insulin secretion (30 min) expressed as x-fold increase above basal was smaller in insulin resistant first degree relatives of patients with type 2 diabetes than in insulin sensitive counterparts (5.3+/-0.4 vs. 7.3+/-0.5; p < 0.01). Body mass index was distributed over the whole range in insulin resistant first degree relatives of patients with type 2 diabetes. In the insulin sensitive subgroup absolute and relative secretion did not differ in obese (Body mass index >25 kg/m2) and insulin sensitivity-matched lean. In obese insulin resistant first degree relatives of patients with type 2 diabetes absolute hyperinsulinemia was combined with reduced and delayed relative early insulin release. In summary, degree and prevalence of insulin resistance is higher in first degree relatives of patients with type 2 diabetes than in controls. However, both groups are of heterogenous metabolic composition and family history as major discriminator should not be overestimated. Our data suggest, that hyperinsulinemia cannot simply be explained as a compensatory event to balance insulin resistance. Hypersecretion is associated with insulin resistance predominantly in combination with obesity. It might be speculated that adipose tissue derived signals to the beta-cell might lead to hypersecretion only in the genetic background that also leads to insulin resistance.

Adolescent↗
PubMed1999

Beta-blocking agents in patients with insulin resistance: effects of vasodilating beta-blockers.

Essential hypertension is--at least in many subjects--associated with a decrease in insulin sensitivity, while glycaemic control is (still) normal. It seems that in hypertensive patients, two major functions of insulin are impaired: there is insulin resistance of peripheral glucose uptake (primarily skeletal muscle) and insulin resistance of insulin-stimulated vasodilation. In view of some retrospective data and meta-analyses, which showed a less than expected reduction in coronary events (coronary paradox), the metabolic side effects of the antihypertensive treatment have received more attention. Many groups have shown that conventional antihypertensive treatment, both with beta-blockers and/or diuretics, decreases insulin sensitivity by various mechanisms. While low-dose diuretics seem to be free of these metabolic effects, there is no evidence for this in the beta-adrenergic blockers. However, recent metabolic studies evaluated the effects of vasodilating beta-blockers, such as dilevalol, carvedilol and celiprolol, on insulin sensitivity and the atherogenic risk factors. None of them decreased insulin sensitivity, as has been described for the beta-blockers with and without beta1 selectivity. This supports the idea that peripheral vascular resistance and peripheral blood flow play a central role in mediating the metabolic side effects of the beta-blocking agents, as the vasodilating action (either via beta2 stimulation or alpha1-blockade) seems to more than offset the detrimental effects of the blockade of beta (or beta1) receptors. Further studies are needed to elucidate the relevance of the radical scavenging properties of these agents and their connection to their metabolic effects. Therefore, the beneficial characteristics of these newer beta-adrenoreceptor blockers suggest that the vasodilating beta-blocking agents could be advantageous for hypertensive patients with insulin resistance or type 2 diabetes.

Adrenergic beta-Antagonists↗
PubMed1999

Hepatic manifestations of familial patent ductus venosus in adults.

BACKGROUND: The ductus venosus connects the umbilical vein to the inferior vena cava during fetal life and subsequently closes rapidly after birth. It is known as patent ductus venosus when it remains patent in adulthood. PATIENTS: A 43 year old man with a history of panhypopituitarism presented with recurrent bouts of pedal oedema associated with fatigue, hypoalbuminaemia, and elevated prothrombin time. An ultrasound examination of his abdomen with Doppler revealed notable attenuation of the main portal vein with diminished intrahepatic branches; a computed tomography scan with angiography revealed a large collateral vein within the liver consistent with a patent ductus venosus. Sequential liver biopsies showed a considerable reduction in the calibre and number of the portal veins. His younger brother, who was diagnosed with alcohol related cirrhosis, suffered from intermittent bouts of encephalopathy and was found to have the same vascular lesion. A third brother was found to have a patent ductus venosus as well as two large hepatic masses consistent with focal nodular hyperplasia. CONCLUSION: The syndrome of familial patent ductus venosus has only previously been described in three infant brothers who presented with hepatic encephalopathy and fatty degeneration of the liver. This report documents three brothers with a patent ductus venosus presenting in adulthood with different manifestations of liver disease. The presence of the same vascular anomaly in three brothers is highly suggestive of a recessive genetic trait with an anatomical manifestation of patent ductus venosus.

Adult↗
PubMed1999

Regional alterations in SR Ca(2+)-ATPase, phospholamban, and HSP-70 expression in chronic hibernating myocardium.

We sought to identify mechanisms for chronic dysfunction in hibernating myocardium. Pigs were instrumented with a left anterior descending artery stenosis for 3 mo. Angiography demonstrated high-grade stenoses and hibernating myocardium with 1) severe anterior hypokinesis (P < 0.001 vs. shams), 2) reduced subendocardial perfusion [0.73 +/- 0.05 (SE) vs. 1.01 +/- 0.06 ml. min(-1). g(-1) in normal, P < 0.001], and 3) critically reduced adenosine flow (1.0 +/- 0.17 vs. 3.84 +/- 0.26 ml. min(-1). g(-1) in normal, P < 0.001). Histology did not reveal necrosis. Northern blot analysis of hibernating myocardium demonstrated regional downregulation in mRNAs for sarcoplasmic reticulum (SR) proteins phospholamban (0.76 +/- 0.08 vs. 1.07 +/- 0.06, P < 0.02) and SR Ca(2+)-ATPase (0.83 +/- 0.06 vs. 1.02 +/- 0.06, P < 0.05) with no change in calsequestrin (1.08 +/- 0.06 vs. 0.96 +/- 0.05, P = not significant). Heat shock protein (HSP)-70 mRNA was regionally induced in hibernating myocardium (2.4 +/- 0.3 vs. 1.0 +/- 0.11, P < 0.01). Directionally similar changes were confirmed by Western blot analysis of respective proteins. Our results indicate that hibernating myocardium exhibits a molecular phenotype that on a regional basis is similar to end-stage ischemic cardiomyopathy. This supports the hypothesis that SR dysfunction from reversible ischemia may be an early defect in the progression of left ventricular dysfunction.

Adenosine↗
PubMed1999

ACE inhibition and glucose transport in insulinresistant muscle: roles of bradykinin and nitric oxide.

Acute administration of the angiotensin-converting enzyme (ACE) inhibitor captopril enhances insulin-stimulated glucose transport activity in skeletal muscle of the insulin-resistant obese Zucker rat. The present study was designed to assess whether this effect is mediated by an increase in the nonapeptide bradykinin (BK), by a decrease in action of ANG II, or both. Obese Zucker rats (8-9 wk old) were treated for 2 h with either captopril (50 mg/kg orally), bradykinin (200 micrograms/kg ip), or the ANG II receptor (AT(1) subtype) antagonist eprosartan (20 mg/kg orally). Captopril treatment enhanced in vitro insulin-stimulated (2 mU/ml) 2-deoxyglucose uptake in the epitrochlearis muscle by 22% (251 +/- 7 vs. 205 +/- 9 pmol. mg(-1). 20 min(-1); P < 0.05), whereas BK treatment enhanced this variable by 18% (249 +/- 15 vs. 215 +/- 7 pmol. mg(-1). 20 min(-1); P < 0.05). Eprosartan did not significantly modify insulin action. The BK-mediated increase in insulin action was completely abolished by pretreatment with either the specific BK-B(2) receptor antagonist HOE 140 (200 micrograms/kg ip) or the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (50 mg/kg ip). Collectively, these results indicate that the modulation of insulin action by BK likely underlies the metabolic effects of ACE inhibitors in the insulin-resistant obese Zucker rat. Moreover, this modulation of insulin action by BK is likely mediated through B(2) receptors and by an increase in nitric oxide production and/or action in skeletal muscle tissue.

Acrylates↗
PubMed1999

Interactions of exercise training and ACE inhibition on insulin action in obese Zucker rats.

Exercise training or chronic treatment with angiotensin-converting enzyme (ACE) inhibitors can ameliorate glucose intolerance, insulin resistance of muscle glucose metabolism, and dyslipidemia associated with the obese Zucker rat. The purpose of the present study was to determine the interactions of exercise training and ACE inhibition (trandolapril) on these parameters in the obese Zucker rat. Animals were assigned to a sedentary control, a trandolapril-treated (1 mg. kg-1. day-1 for 6 wk), an exercise-trained (treadmill running for 6 wk), or a combined trandolapril-treated and exercise-trained group. Exercise training, alone or with trandolapril, significantly (P < 0. 05) increased peak O2 consumption by 31-34%. Similar decreases in fasting plasma insulin (34%) and free fatty acids (31%) occurred with exercise training alone or in combination with trandolapril. Compared with control, exercise training or trandolapril alone caused smaller areas under the curve (AUC) for glucose (12-14%) and insulin (28-33%) during an oral glucose tolerance test. The largest decreases in the glucose AUC (40%) and insulin AUC (53%) were observed in the combined group. Similarly, whereas exercise training or trandolapril alone improved maximally activated insulin-stimulated glucose transport in isolated epitrochlearis (26-34%) or soleus (39-41%) muscles, the greatest improvements in insulin action (67 and 107%, respectively) were seen in the combined group and were associated with similarly enhanced muscle GLUT-4 protein and total hexokinase levels. In conclusion, these results indicate combined exercise training and ACE inhibition improve oral glucose tolerance and insulin-stimulated muscle glucose transport to a greater extent than does either intervention alone.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects.

Insulin resistance plays an important role in the pathogenesis of type 2 diabetes; however, the multiple mechanisms causing insulin resistance are not yet fully understood. The aim of this study was to explore the possible contribution of intramyocellular lipid content in the pathogenesis of skeletal muscle insulin resistance. We compared insulin-resistant and insulin-sensitive subjects. To meet stringent matching criteria for other known confounders of insulin resistance, these individuals were selected from an extensively metabolically characterized group of 280 first-degree relatives of type 2 diabetic subjects. Some 13 lean insulin-resistant and 13 lean insulin-sensitive subjects were matched for sex, age, BMI, percent body fat, physical fitness, and waist-to-hip ratio. Insulin sensitivity was determined by the hyperinsulinemic-euglycemic clamp method (for insulin-resistant subjects, glucose metabolic clearance rate [MCR] was 5.77+/-0.28 ml x kg(-1) x min(-1) [mean +/- SE]; for insulin-sensitive subjects, MCR was 10.15+/-0.7 ml x kg(-1) x min(-1); P<0.002). Proton magnetic resonance spectroscopy (MRS) was used to measure intramyocellular lipid content (IMCL) in both groups. MRS studies demonstrated that in soleus muscle, IMCL was increased by 84% (11.8+/-1.6 vs. 6.4+/-0.59 arbitrary units; P = 0.008 ), and in tibialis anterior muscle, IMCL was increased by 57% (3.26+/-0.36 vs. 2.08+/-0.3 arbitrary units; P = 0.017) in the insulin-resistant offspring, whereas the extramyocellular lipid content and total muscle lipid content were not statistically different between the two groups. These data demonstrate that in these well-matched groups of lean subjects, IMCL is increased in insulin-resistant offspring of type 2 diabetic subjects when compared with an insulin-sensitive group matched for age, BMI, body fat distribution, percent body fat, and degree of physical fitness. These results indicate that increased IMCL represents an early abnormality in the pathogenesis of insulin resistance and suggest that increased IMCL may contribute to the defective glucose uptake in skeletal muscle in insulin-resistant subjects.

Adult↗