Association between plasma renin activity and metabolic cardiovascular risk factors in essential hypertension

Objectives. To study the relationships between plasma renin activity and metabolic cardiovascular risk factors in patients with essential hypertension.
Subjects and design. Patients with uncomplicated essential hypertension ( n =36) with a diastolic blood pressure of 95–115 mmHg were studied. Assessment of plasma renin activity (PRA) related to urinary sodium excretion was used to define subgroups with high ( n =12), medium ( n =16) and low renin profiles ( n =8).
Main outcome measures. Fasting plasma lipid levels were determined. Glucose, insulin and C-peptide responses to standard oral glucose tolerance test (OGTT) were measured.
Results. Patients with high PRA had higher levels of plasma cholesterol (6.13±0.81 versus 4.67±0.7 mmol L^-1, P <0.05) and triglycerides (2.14±0.18 versus 0.98±0.13 mmol L^-1, P <0.05), than the low PRA group. HDL-cholesterol levels were lower in the high renin group than in the low renin group (1.05±0.04 versus 1.26±0.09 mmol L^-1, P <0.05). Insulin and C-peptide sums were higher in high PRA group (33.8±1.2 versus 25.1±0.9 and 2.6±0.3 versus 1.9±0.4 ng L^-1, P <0.05), than in the low PRA group.
Conclusions. Essential hypertensive patients with a high renin profile display more pronounced dyslipidaemia and higher levels of plasma insulin than patients with a low renin profile. This may be one explanation for higher incidence of cardiovascular disease previously reported in high PRA group.     

Glucose and insulin levels in young subjects with different maternal histories of hypertension: The Hypertension in Pregnancy Offspring Study

Objective: To analyse whether hypertension during pregnancy is associated with early signs of impaired glucose metabolism in the offspring.
Design: Longitudinal study with a 5-year follow-up.
Setting: University Hospital, Göteborg, Sweden.
Main outcome measures: Fasting levels of glucose, insulin and C-peptide.
Subjects: Thirty-six children were born to mothers with hypertension in pregnancy. The children were divided into two groups according to their mothers' blood pressure at follow-up 7–12 years after pregnancy. Nineteen children had hypertensive mothers (HT), while 17 children had normotensive mothers at follow-up (NT). A control group (C) comprised 16 children, who were born after normotensive pregnancies to mothers who remained normotensive.
Results: Fasting plasma glucose was significantly higher in HT than in NT (5.2 vs. 4.9 mmol L⁻¹; P < 0.05). In C fasting glucose was 5.1 mmol L⁻¹. The same trend was seen for fasting insulin in HT, NT and C, respectively (6.7 vs. 4.7 vs. 5.3 μU mL⁻¹). The C-peptide level was 1.61, 155 and 1.64 ng mL⁻¹, respectively. Calculated insulin resistance was 1.5 in HT, 1.0 in NT and 1.2 in C.
Conclusions: It is suggested that hypertension during pregnancy may be associated with impaired glucose metabolism and elevated fasting glucose levels in the offspring during adolescence.     

Relationships between vitamin D, parathyroid hormone and bone mineral density in inflammatory bowel disease

Objectives. To explore the relationships between vitamin D intake, serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (250HD) concentrations, and bone mineral density (BMD) in inflammatory bowel disease (IBD).
Setting. A university hospital clinic in Finland.
Subjects. One hundred and fifty randomly selected patients with IBD from the hospital register and 73 healthy controls.
Measurements. BMD of the lumbar spine and the proximal femur was measured with dual energy X-ray absorptiometry. Vitamin D intake and serum levels of 250HD and PTH were determined.
Results. The IBD patients had a lower serum 250HD concentration (28.4 [SD 12.0] nmol L^-1) than the controls (36.1 [16.7] nmol L^-1; P =0.001), whereas no differences in the vitamin D intake or the serum PTH levels were found. The serum 250HD concentrations and the vitamin D intake of the patients with ulcerative colitis ( n =67) were similar to those of the Crohn's disease patients ( n =76). The patients with Crohn's disease of the small bowel had slightly, but not significantly, lower serum 250HD concentrations (25.6 [11.0] nmol L^-1) than the other Crohn's disease patients (31.4 [14.3] nmol L^-1; P =0.061). In the IBD patients, the vitamin D intake and the serum 250HD and PTH concentrations were not associated with BMD.
Conclusions. Patients with IBD have lower serum levels of 250HD than healthy controls, but similar serum PTH concentrations and vitamin D intake. Vitamin D intake, and the serum levels of 250HD and PTH are not associated with BMD, and malabsorption is unlikely to be a major factor in the aetiology of bone loss in unselected IBD patients.     

Application of the intravenous glucose tolerance test and the minimal model to patients with insulinoma: insulin sensitivity (Si) and glucose effectiveness (Sg) before and after surgical excision

Background  The unmodified frequently sampled intravenous glucose tolerance test (FSIGT) has not previously been used to assess insulin/glucose kinetics in patients with insulinoma.
Objective  To measure insulin sensitivity (Si) and glucose effectiveness (Sg) by means of the FSIGT in patients with insulinoma, before and after surgical removal of the tumour.
Subjects and methods  FSIGTs were performed in five patients, before and approximately 3 months post-surgery, and in 11 controls. Si and Sg were estimated using Minimal Model computer analysis of dynamic glucose and insulin data.
Results  Si was lower in insulinoma patients before, compared with after surgery (3·37 ± 0·62 vs. 6·24 ± 1·09 SE [×10⁻⁴] min⁻¹µU⁻¹ ml, P  < 0·05). Sg was similar in patients pre- and post-surgery (3·0 ± 0·67 vs. 2·4 ± 0·6 [×10⁻²] min⁻¹, NS).
Conclusions  Insulin sensitivity improves after excision of an insulinoma. Glucose effectiveness is not influenced by chronic hyperinsulinaemia and hypoglycaemia.     

Dissociation between urinary albumin excretion and variables associated with insulin resistance in a healthy population

Objectives. To see if the cluster of metabolic and haemodynamic variables defined as comprising Syndrome X varied as a function of urinary albumin excretion (UAE) rate in a healthy population.
Design. A cross-sectional, population-based study.
Setting. A factory in Italy.
Subjects. Two hundred and twenty-five healthy volunteers, 115 men and 110 women.
Outcome measures. Measurements were made of the plasma glucose and insulin responses to oral glucose, fasting triglyceride (TG) and high density lipoprotein (HDL)-cholesterol concentrations, blood pressure, and UAE rates.
Results. Only five of the 225 volunteers had microalbuminuria, defined as a UAE rate >2 μg min^-1, and the UAE rate was <5 μg min^-1 in 80% of the volunteers. Significant variations in the metabolic and haemodynamic variables measured were not associated with any differences in UAE. Finally, significant relationships were found between various measures of plasma insulin concentration and plasma glucose response to oral glucose, plasma TG and HDL-cholesterol concentrations, and mean arterial blood pressure, independent of variations in age, body mass index, ratio of waist-to-hip girth, and UAE rates.
Conclusion. The widespread variability in plasma glucose and insulin responses, plasma TG and HDL-cholesterol concentrations, and blood pressure that are seen in the population at large cannot be attributed to variations in UAE rate.     

Influence of meals on variations of ST segment elevation in patients with Brugada syndrome

Background: Glucose-induced insulin secretion is one of the contributing factors to fluctuation of ST segment elevation in Brugada syndrome.
Objectives: The purpose of this study was to explore the influence of meals on variations of ST elevation in Brugada syndrome.
Methods: We assessed changes of ST segment elevation in lead V1-3 on ECG before and after taking meals, at midnight, and at 3:00 a.m. in 20 patients with Brugada syndrome. Plasma glucose, insulin, and K⁺ concentrations were measured. Variations of ST elevation were defined as morphological changes and/or augmentation of ST segment level by >1.0 mm.
Result: Variations of ST segment morphology or elevation level after meals were observed in 15 of 20 patients (75%). ST elevation was augmented most markedly after dinner (3.3 ± 1.7 mm) and decreased both at midnight (2.6 ± 1.3 mm: P < 0.01 vs after dinner) and at 3:00 a.m. (2.4 ± 1.2 mm: P < 0.01 vs after dinner). Morphologic changes and elevation levels of ST segment were associated with changes in glucose-induced insulin levels after meals, being highest after dinner (47 ± 33 μU/mL) and decreasing significantly at midnight (7 ± 4 μU/mL) and at 3:00 a.m. (5 ± 2 μU/mL). There were no correlations between ST elevation and changes in serum K⁺ level or heart rate.
Conclusions: The present findings suggest that variations of ST elevation are frequently associated with meals. Aggravation of ST elevation is most prominent in the evening to night after dinner rather than the period between midnight and early morning. This information may help to predict event times at high risk for life-threatening arrhythmias in Brugada syndrome.     

Insulin detemir causes increased symptom awareness during hypoglycaemia compared to human insulin

Aim: The long-acting insulin analogue detemir (Levemir^®) has structural and physicochemical properties which differ from human insulin. The aim of the present study was to test whether this leads to altered hormone and symptom response during hypoglycaemia.
Methods: 12 healthy subjects [6f/6m, age 32 ± 6 years (mean ± s.d.), body mass index (BMI) 24.2 ± 2.5 kg/m²] underwent a 200-min stepwise hypoglycaemic clamp (45 min steps of 4.4, 3.7, 3.0 and 2.3 mmol/l) with either detemir or human insulin in random order. A bolus of detemir (660 mU/kg) or human insulin (60 mU/kg) was given before insulin was infused at a rate of 5 (detemir) or 2 (human insulin) mU/kg/min. Blood was drawn and a semi-quantitative symptom questionnaire was administered before and after each plateau of the hypoglycaemic clamp. Cognitive function was assessed during each step.
Results: Blood glucose levels and glucose infusion rates were comparable with detemir and human insulin. The total symptom score was higher with detemir during the 3 and 2.3 mmol glucose step compared to human insulin (p = 0.048). Especially sweating was increased with detemir (p = 0.02) with an earlier and faster increase during the clamp (interaction insulin × time: p = 0.04). No significant differences between detemir and human insulin in cortisol, norepinephrine, epinephrine, glucagon, growth hormone, lactate or free fatty acid (FFA) levels during hypoglycaemia were observed, and there were no significant differences in cognitive function tests.
Conclusions: Insulin detemir increased symptom awareness during hypoglycaemia compared to human insulin in healthy individuals, whereas counter-regulatory hormone response and cognitive function were unaltered.     

The effect of acarbose on insulin resistance in obese hypertensive subjects with normal glucose tolerance: a randomized controlled study

Aim:  Acarbose, a glucose oxidase inhibitor, delays the absorption of glucose thus reducing post-prandial blood glucose level, haemoglobin A1c (HbA1c) and insulin resistance in patients with diabetes mellitus and in subjects with impaired glucose tolerance. The effect of acarbose in subjects with normal glucose tolerance (NGT) has hitherto not been examined. The aim of the present study was to examine the effect of acarbose in obese hypertensive subjects with NGT.
Methods:  A double-blinded, parallel group study was performed on 56 male subjects with hypertension, body mass index (BMI) 27–35 kg/m², fasting blood glucose ≤ 6 mmol/l and a normal oral glucose tolerance test. Blood pressure, HbA1c, lipid profile and insulin resistance [homeostasis model assessment (HOMA) index] were determined initially and following 24 weeks of acarbose, 150 mg/day or placebo. The primary end point was the change in insulin resistance. Anti-hypertensive treatment and diet were kept constant during the study.
Results:  Insulin resistance decreased in acarbose users but not on placebo. HOMA index declined from 5.36 ± 1.7 to 4.10 ± 1.6 (p = 0.001) on acarbose, the corresponding values on placebo were 5.44 ± 1.9 and 5.53 ± 1.7. A decrease in serum triglyceride values (2.16 ± 0.16 mmol/l to 1.76 ± 0.15 mmol/l, p = 0.02) took place on acarbose with no change on placebo. There was no change in BMI, low-density lipoprotein or high-density lipoprotein values in either group. Blood pressure declined equally in both the groups, probably due to better patient compliance.
Conclusions:  Acarbose may reduce insulin resistance and triglycerides also in obese hypertensive subjects with normal glucose tolerance.     

A placebo-controlled crossover study comparing the effects of nateglinide and glibenclamide on postprandial hyperglycaemia and hyperinsulinaemia in patients with type 2 diabetes

Aim:  This was a randomized, double blind, three period crossover study. The objective was to compare glucose, insulin and C-peptide 24 h profiles in patients with type 2 diabetes mellitus after dosing with nateglinide (given preprandially before three test meals), glibenclamide (administered once before breakfast) or placebo (given before three test meals).
Methods:  Fourteen patients underwent screening followed within 3 weeks by three treatment periods of 1 day, each separated by 7 days. Dosing followed a six-sequence balanced, two 3 × 3-replicated Latin square.
Results:  Mean peak serum insulin levels were lower after nateglinide (115 mU/l) than after glibenclamide (145 mU/l.h; p = 0.017) but higher than after placebo (79 mU/l; p = 0.001). However, peak insulin levels were reached earlier after nateglinide [mean time to peak ( t _max) 1.7 h] compared to glibenclamide (mean t _max 2.1 h, p = 0.06). Total insulin exposure over the day was higher after glibenclamide compared with that following nateglinide (1216 vs. 1067 mU/l.h; p = 0.009). Similar findings were seen with serum C-peptide. Despite this, mean peak plasma glucose concentrations were lower following nateglinide (11.4 mmol/l from a baseline of 8.3 mmol/l) compared with glibenclamide (13.2 mmol/l from a baseline of 8.5 mmol/l; p = 0.001) and placebo (14.0 mmol/l from a baseline of 8.0 mmol/L; p < 0.001).
Conclusions:  Nateglinide improves early prandial measures of insulin and glucose response to a standard meal, more so than glibenclamide, in people with type 2 diabetes.     

Ethnic differences in the clinical and laboratory associations with retinopathy in adult onset diabetes: studies in patients of African, European and Indian origins

Objective. To evaluate the prevalence of diabetic retinopathy (DR) and its associations in adult onset diabetic patients of African, European and Indian origins.
Design. The prevalence of retinopathy was determined by 60° retinal photography in 507 consecutive out-patients. Clinical and laboratory associations were evaluated.
Setting. Diabetes clinic in a large community hospital.
Main outcome measures. The associations between clinical and laboratory measurements with retinopathy.
Results. African patients (A) had shorter duration of diabetes ( P < 0.001), higher HbA1 levels ( P < 0.01) compared to those of Europeans (E) and Indian (I) extraction. A also had lower C-peptide levels (median 0.57 nmol L⁻¹; vs. E, 0.81 nmol L⁻¹ and I, 0.93 nmol L⁻¹) ( P < 0.001). The prevalences of retinopathy at diagnosis (21–25%) and overall were similar (A 37%, E 41%, I 37%). Severe DR was more frequent in the Africans (52%, P < 0.0001) and Indians (41%, P = 0.03) compared to the Europeans (26%). In Africans DR was significantly associated only with duration of diabetes ( P < 0.0001) and macro-albuminuria ( P = 0.01); in I it was also associated with systolic BP ( P = 0.03); in E also with lower C-peptide levels ( P = 0.0002), worse glycaemic control and greater use of insulin ( P < 0.0001). In patients with DR insulin was used less frequently in A (35%) than in E patients (62%) ( P = 0.001).
Conclusions. In South Africa, the African population with adult onset diabetes has the highest prevalence of severe retinopathy, probably the result of very poor glycaemic control attributable to more severe insulinopenia and infrequent insulin treatment. Visual loss from diabetic retinopathy is likely to be considerable in Africans.     

TISSUE CHARACTERIZATION TO DIFFERENTIATE PATHOLOGICAL FROM PHYSIOLOGICAL HYPERTROPHY IN PATIENTS WITH HYPERTENSION AND ATHLETES

Precedents: In pathological left ventricular (LV) hypertrophy (H) of hypertensive patients (P) there is a deposition of collagen. Myocardial fibrosis is one of the factors responsible for systolic and diastolic dysfunction. Athletes increase their ventricular mass as physiological ventricular H. Integrated backscatter (IB) demonstrates changes in myocardial acoustic properties, depending upon their composition and function.
Objectives: (1).Assess the capability of IB to differentiate physiological from pathological H. (2).Correlate IB with overall and regional systolic and diastolic functions.
Methods: Group I(GI):13 hypertensive P with an LV mass index (LVMI)>124 gr/m², Group II(G2):11 athletes, Group III(G3): 8 volunteers. We determined overall systolic and diastolic functions and regional function of the basal septum, IB and cyclic variation of the IB (CVIB) of the posterior wall.
Results: Age (years): G1:52 ± 15, G2:28 ± 8 G3:35 ± 8 p = 0.000; Sex: G1:m/f 12/1, G2: m/f 9/2, G3: m/f 4/4, LVMI: G1: 180.1 ± 58 gr/m², G2:130.2 ± 20 gr/m² G3: 90.2 ± 16 gr/m² p = 0.000. Left atrial area (LAA): G1: 22 ± 4 cm², G2: 18.8 ± 1.8 cm², G3: 15.8 cm² p = 0.001, mid-wall shortening fraction (MWSF): G1:26.9 ± 3.5, G2:27.5 ± 4 G3:25 ± 3 p = NS; CVIB: G1:5,3 ± 2,5 G2:7.6 ± 2,1 G3:6.4 ± 1.1 P = 0.048.Correlation of IB and MWSF, p = NS; IB and MWSF p = NS, IB and CVIB:-0.56 p = 0.005.  

  TABLE     

12.

Thrombin generation in vitro in the presence of by-passing agents in siblings with severe haemophilia A     

J. KLINTMAN  E. BERNTORP  J. ASTERMARK  ON BEHALF OF THE MIBS STUDY GROUP 《Haemophilia》2010,16(1):e210-e215

Summary.  Previous data have shown an inter-individual difference in the thrombin generating capacity in vitro as well as phenotypic bleeding pattern among patients with severe haemophilia A (FVIII:C activity below 1%). The reason for this is not known. In addition, there are no reports on how thrombin generation may correlate between siblings. In this study, we evaluated and compared thrombin generation in vitro using plasma samples in the presence of by-passing agents (FEIBA^® and NovoSeven^®) in 21 unrelated brother pairs with and without inhibitors enrolled in the Malmö International Brother Study (MIBS). Mean maximum thrombin formation in patients with a current inhibitor titer was 182.0 ± 52.8 mmol mL⁻¹ (FEIBA^®) and 130.7 ± 54.9 mmol mL⁻¹ (rFVIIa), respectively, and somewhat higher in those without inhibitors, 222.7 ±85.5 mmol mL⁻¹ (FEIBA^®) and 142.8 ±53.6mmol mL⁻¹ (rFVIIa) ( P  = 0.16 and 0.29). The variance regarding the maximum thrombin production within a family was significantly lower compared with the thrombin production between families ( P  < 0.001 for both FEIBA^® and NovoSeven^®). Our data indicate that genetically determined factors, other than the FVIII:C activity seems to influence the phenotypic variation in thrombin formation in the presence of by-passing agents. The nature of these determinants remains to be identified.     

13.

Chronic consumers of boiled coffee have elevated serum levels of lipoprotein(a)     

R. URGERT  M. P. M. E. WEUSTEN-VAN DER WOUW  R. HOVENIER  P. G. LUND-LARSEN  & M. B. KATAN 《Journal of internal medicine》1996,240(6):367-371

Objectives. Lipoprotein(a) consists of an LDL-particle attached to apolipoprotein(a), which is made by the liver. Diterpenes present in boiled coffee raise serum levels of LDL cholesterol and of the liver enzyme alanine aminotransferase in man. We investigated the association between intake of boiled coffee and serum levels of lipoprotein(a).
Design, setting and subjects. Healthy Norwegians 40–42 years of age, who habitually consumed five or more cups of boiled coffee per day ( n =150) were compared with matched filter coffee consumers ( n =159) in a cross-sectional study, as part of the Norwegian National Health Screening in 1992.
Results. The median lipoprotein(a) level was 13.0 mg  dL⁻¹ (10th and 90th percentile: 2.5 and 75.0 mg  dL⁻¹, respectively) on boiled and 7.9 mg dL^-1 (10th and 90th percentile: 1.9 and 62.5 mg dL⁻¹, respectively) on filter coffee ( P =0.048). Means±SE were 25.8±2.4 mg dL⁻¹ and 19.6±2.0 mg dL⁻¹, respectively ( P =0.04). Although not statistically significant, subjects consuming nine or more cups of coffee per day had higher lipoprotein(a) levels than those drinking five to eight cups per day in both coffee groups.
Conclusion. Chronic consumers of unfiltered, boiled coffee have higher serum levels of lipoprotein(a) than filter coffee drinkers.     

14.

Dissociated incretin response to oral glucose at 1 year after restrictive vs. malabsorptive bariatric surgery     

M. Guldstrand  B. Ahrén  E. Näslund  J. J. Holst  U. Adamson 《Diabetes, obesity & metabolism》2009,11(11):1027-1033

Aim: Compare the response to oral glucose of the two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) at 1 year after restrictive vs. malabsorptive bariatric surgery.
Methods: Vertical banded gastroplasty (VBG, n = 7) or jejunoileal bypass (JIB, n = 5) was performed in 12 women, aged 26–39 years, with severe obesity [body mass index (BMI) 46.6 ± 2.3 kg/m²]. After 1 year, 75 g glucose was administered and plasma levels of glucose, insulin, GIP and GLP-1 were determined regularly during the following 2 h.
Results: At 1 year after operation, reduction in body weight, actual body weight, fasting glucose or insulin, or the glucose and insulin responses to oral glucose did not differ significantly between the groups. Similarly, fasting GIP and GLP-1 levels did not differ significantly between the groups. In contrast, the GIP and GLP-1 responses to oral glucose were different between the groups in a dissociated pattern. Thus, AUC_GIP was significantly higher after VBG than after JIB (53 ± 8 vs. 26 ± 6 pmol/l/min, p = 0.003). In contrast, AUC_GLP−1 was significantly higher after JIB than after VBG (49 ± 5 vs. 20 ± 3 pmol/l/min, p = 0.007).
Conclusions: We conclude that at 1 year after bariatric surgery, the two incretins show dissociated responses in that the GIP secretion is higher after VBG whereas GLP-1 secretion is higher after JIB. This dissociated incretin response is independent from reduction in body weight, glucose tolerance or insulin secretion.     

15.

Plasma glutathione concentration in patients with chronic hepatitis C virus infection     

H. L. Lim  B. M. Myers  B. A. Hamilton  G. L. Davis  J. Y. N. Lau 《Journal of viral hepatitis》1995,2(4):211-214

Summary. It has recently been proposed that a depletion of glutathione (GSH) may be a contributing factor to viral persistence and resistance to interferon-α (IFN-α) therapy in chronic hepatitis C virus (HCV) infection. The aim of this study was: (1) to compare plasma GSH levels in patients with chronic HCV infection and normal healthy controls; and (2) to correlate GSH levels with liver histology and serum HCV RNA levels. Twenty-four patients with compensated chronic hepatitis C and 2 7 healthy subjects were studied. Serum and heparinized plasma were prospectively prepared and frozen within 1 h of collection. Plasma glutathione and glutathione peroxidase (GP) levels were measured spectrophotometrically. The serum HCV RNA level was quantitated by the branched chain DNA signal-amplification assay. Plasma GSH levels were not decreased in patients with chronic HCV infection but were actually greater than in controls (control 1.2 7 ± 0.12 μg ml^-1, HCV 1.62 ± 0.11 μg ml^-1, P < 0.05). There was also no difference in plasma GP activity between these two groups (control 0.233 ± 0.007 U ml^-1, HCV 0.230 ± 0.007 U ml^-1). Among the patients with chronic HCV infection, there was no correlation between either plasma GSH or GP levels and the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), serum HCV RNA level, or liver histology. This study demonstrates that chronic HCV infection does not decrease the plasma GSH and GP levels.     

16.

The metabolic syndrome as a link between smoking and cardiovascular disease     

Dzien A  Dzien-Bischinger C  Hoppichler F  Lechleitner M 《Diabetes, obesity & metabolism》2004,6(2):127-132

Objective:  Smoking is associated with a significant increase in the cardiovascular risk. The possible relationship of smoking with insulin resistance might further enhance the cardiovascular risk of the patients and is therefore of great clinical interest.
Design, Setting and Subjects:  We have retrospectively evaluated data of 3804 non-diabetic men attending a medical outdoor clinic. Clinical [body mass index (BMI), percentage of body fat, waist-to-hip ratio] and laboratory results were compared between smokers (n = 124) and non-smokers (n = 1915) without cardiovascular disease, as well as between smokers (n = 759) and non-smokers (n = 1006) with cardiovascular disease.
Results:  Smokers without clinically manifest cardiovascular disease revealed significantly higher fasting glucose (5.8 ± 0.6 mmol/l) and triglyceride levels (1.8 ± 0.9 mmol/l) than non-smokers (fasting glucose: 5.1 ± 0.7 mmol/l, p < 0.010; triglycerides: 1.5 ± 0.8 mmol/l, p < 0.030). The adverse metabolic profile of smokers was even more pronounced in patients with cardiovascular disease. An age-matched analysis of smokers could demonstrate that cardiovascular patients revealed higher BMI values (27.3 ± 2.4 kg/m²) and a higher percentage of body fat (25.5 ± 5.5%) than those without cardiovascular disease (BMI: 25.7 ± 2.2 kg/m², p < 0.010; percentage of body fat: 23.0 ± 5.5%, p < 0.030).
Conclusion:  In men with and without clinically manifest cardiovasular disease, smoking was associated with a metabolic profile indicating a higher degree of insulin resistance.     

17.

Insulin glulisine, insulin lispro and regular human insulin show comparable end-organ metabolic effects: an exploratory study     

Horvath K  Bock G  Regittnig W  Bodenlenz M  Wutte A  Plank J  Magnes C  Sinner F  Fürst-Recktenwald S  Theobald K  Pieber TR 《Diabetes, obesity & metabolism》2008,10(6):484-491

Aims:  To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro (lispro) and regular human insulin (RHI) in patients with type 1 diabetes mellitus.
Methods:  Eighteen patients with type 1 diabetes mellitus (mean age 36.9 ± 8.6 years, BMI 23.6 ± 2.8 kg/m², haemoglobin A_1c 7.4 ± 0.9%) were randomized in this single-centre, double-blind, three-period cross-over, standard Latin-square, euglycaemic glucose clamp trial. Patients received sequential, primed stepwise intravenous infusions of glulisine, lispro or RHI (infusion rates were increased in a stepwise manner from an initial rate of 0.33 [180 min] to 0.66 [180 min] and 1.00 [180 min] mU/kg/min). The primary variables were the suppression of endogenous glucose production ( S _EGP) and glucose uptake (GU).
Results:  Mean basal endogenous glucose production (EGP) was 1.88, 2.12 and 2.12 mg/kg/min for glulisine, lispro and RHI respectively. Mean (±s.e.) maximum absolute S _EGP (adjusted for basal EGP) was −1.64 ± 0.06, −1.72 ± 0.05 and −1.56 ± 0.05 mg/kg/min respectively. Mean (±s.e.) maximum absolute increase in GU (adjusted for basal GU) was 6.46 ± 0.26, 6.23 ± 0.24 and 6.72 ± 0.24 mg/kg/min respectively. There were no clinically relevant differences between the three insulin treatments with respect to serum insulin, free fatty acid (FFA), glycerol or lactate levels. No serious adverse events and no episodes of severe hypoglycaemia were reported.
Conclusions:  This study shows that glulisine, lispro and RHI have similar effects on S _EGP, GU, FFA, glycerol and lactate levels, providing evidence for similar end-organ metabolic effects.     

18.

Rosiglitazone (PPARgamma-agonist) attenuates atherogenesis with no effect on hyperglycaemia in a combined diabetes-atherosclerosis mouse model     

Levi Z  Shaish A  Yacov N  Levkovitz H  Trestman S  Gerber Y  Cohen H  Dvir A  Rhachmani R  Ravid M  Harats D 《Diabetes, obesity & metabolism》2003,5(1):45-50

Background: The administration of peroxisome proliferator-activated receptor γ (PPARγ) agonists to low-density lipoprotein (LDL)-receptor-deficient mice resulted in a reduction in the atherosclerotic lesion area in male mice, but not in female mice. The male mice also exhibited reduction in insulin resistance while the female mice did not. To further examine the relationship between PPARγ agonists, insulin resistance and atherosclerosis, we used the model of accelerated atherosclerosis in male apolipoprotein E (apoE)-deficient mice rendered diabetic by low-dose streptozotocin (STZ).
Methods: Male, apoE-deficient mice ( n  = 48) were randomly divided into four groups. To induce diabetes, two groups received low-dose STZ and two groups served as controls. After diabetes induction, rosiglitazone (a PPARγ agonist) was administered by oral gavage to one of the diabetic and one of the non-diabetic groups.
Results: Rosiglitazone reduced significantly the atherosclerotic aortic plaque area in both diabetic and non-diabetic apoE-deficient mice: 340 ± 54 vs. 201 ± 27 μmol² (p = 0.001) in diabetic mice; 243 ± 22 vs. 158 ± 27 μmol² (p = 0.001) in non-diabetic mice. Also, rosiglitazone reduced the correlation coefficient between plasma glucose and the degree of atherosclerosis (p < 0.0025) without affecting plasma glucose levels. The rosiglitazone-treated mice, both diabetic and non-diabetic, had higher lipid levels.
Conclusions: Rosiglitazone-treated animals showed less atherosclerosis despite higher lipid levels and similar glucose levels. These data suggest a direct anti-atherogenic effect of rosiglitazone on the arterial wall.     

19.

Drug Delivery at the Aortic Valve Tissues of Healthy Domestic Pigs with a Paclitaxel-Eluting Valvuloplasty Balloon     

KONSTANTINOS SPARGIAS  M.D.    KRZYSTOF MILEWSKI  M.D.    MARCIN DEBINSKI  M.D.    PIOTR P BUSZMAN  M.D.    DENNIS V. COKKINOS  M.D.    REMBERT POGGE  Ph  .D.  PAWEL BUSZMAN  M.D. 《Journal of interventional cardiology》2009,22(3):291-298

Background: Restenosis occurs invariably within 1 year following balloon valvulopasty in aortic valve stenosis. The mechanism of restenosis seems to involve a dynamic cellular component that could be a target for drug inhibition. We investigated the feasibility of local drug delivery at the aortic valve tissues of healthy pigs with a paclitaxel-eluting balloon.
Methods: Aortic valvuloplasty was performed in eight anesthetized domestic pigs using paclitaxel-eluting balloons (3 μg/mm² balloon surface area). They were assigned to two or four times 15-second balloon inflations and were sacrificed 30 minutes after final balloon inflation.
Results: The aortic annulus to balloon diameter ratio was 1.15 ± 0.07. The mean paclitaxel concentration in the aortic valve leaflets was 0.91 ± 1.36 μg/mL (0.34 ± 0.05 μg/mL in the two-inflation group, 1.48 ± 1.86 μg/mL in the four-inflation group, P = 0.23). The percentage of the total paclitaxel dose recovered in the aortic valve leaflets was 18 ± 11⁻⁶% (13 ± 6⁻⁶% and 25 ± 14⁻⁶% in the two- and four-inflation group, P = 0.16).
Conclusion: Local drug delivery at the aortic valve leaflets of healthy pigs with a paclitaxel-eluting balloon is feasible and concentrations within the therapeutic window are detected 30 minutes after the procedure. The antirestenotic potential of this treatment should be studied.     

20.

Insulin and C-peptide responses to 75 g oral glucose load in the healthy man     

E Bonora  I Zavaroni  O Alpi  A Pezzarossa  F Bruschi  L Guerra  E Dall'Aglio  C Coscelli  U Butturini 《Diabète & métabolisme》1986,12(3):143-148

Plasma insulin and C-peptide levels in the fasting state and after a 2-h 75 g oral glucose tolerance test (OGTT) in a large number of healthy subjects are reported. 247 volunteers (134 males, 113 females), aged 13-69 years, who had a negative history of diabetes, no history of significant disease, normal physical examination, normal body weight, normal glucose tolerance, normal blood tests, and who were taking no drugs were studied. Results, mean +/- SEM (range): fasting glucose concentration = 4.64 +/- 0.03 mmol/l (3.10 - 6.10), 1-h glucose concentration = 5.23 +/- 0.10 mmol/l (2.20 - 9.90), 2-h glucose concentration = 4.11 +/- 0.06 mmol/l (2.00 - 6.80); fasting insulin level = 0.088 +/- 0.002 nmol/l (0.03 - 0.28), 1-h insulin level = 0.45 +/- 0.01 nmol/l (0.06 - 1.63), 2-h insulin level = 0.24 +/- 0.01 nmol/l (0.05 - 1.12); fasting C-peptide concentration = 0.60 +/- 0.01 nmol/l (0.14 - 1.34), 1-h C-peptide concentration = 2.17 +/- 0.05 (0.63 - 8.56), 2-h C-peptide concentration = 1.77 +/- 0.04 nmol/(0.35 - 5.74). Fasting insulin and fasting C-peptide concentrations correlated to post-glucose insulin and C-peptide concentrations, respectively. At each sampling-point insulin concentration correlated to C-peptide concentration. After glucose ingestion, both insulin and C-peptide plasma levels correlated significantly with the corresponding glucose levels. During fasting, C-peptide but no insulin level correlated to glucose level.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thrombin generation in vitro in the presence of by-passing agents in siblings with severe haemophilia A

Summary.  Previous data have shown an inter-individual difference in the thrombin generating capacity in vitro as well as phenotypic bleeding pattern among patients with severe haemophilia A (FVIII:C activity below 1%). The reason for this is not known. In addition, there are no reports on how thrombin generation may correlate between siblings. In this study, we evaluated and compared thrombin generation in vitro using plasma samples in the presence of by-passing agents (FEIBA^® and NovoSeven^®) in 21 unrelated brother pairs with and without inhibitors enrolled in the Malmö International Brother Study (MIBS). Mean maximum thrombin formation in patients with a current inhibitor titer was 182.0 ± 52.8 mmol mL⁻¹ (FEIBA^®) and 130.7 ± 54.9 mmol mL⁻¹ (rFVIIa), respectively, and somewhat higher in those without inhibitors, 222.7 ±85.5 mmol mL⁻¹ (FEIBA^®) and 142.8 ±53.6mmol mL⁻¹ (rFVIIa) ( P  = 0.16 and 0.29). The variance regarding the maximum thrombin production within a family was significantly lower compared with the thrombin production between families ( P  < 0.001 for both FEIBA^® and NovoSeven^®). Our data indicate that genetically determined factors, other than the FVIII:C activity seems to influence the phenotypic variation in thrombin formation in the presence of by-passing agents. The nature of these determinants remains to be identified.     

Chronic consumers of boiled coffee have elevated serum levels of lipoprotein(a)

Objectives. Lipoprotein(a) consists of an LDL-particle attached to apolipoprotein(a), which is made by the liver. Diterpenes present in boiled coffee raise serum levels of LDL cholesterol and of the liver enzyme alanine aminotransferase in man. We investigated the association between intake of boiled coffee and serum levels of lipoprotein(a).
Design, setting and subjects. Healthy Norwegians 40–42 years of age, who habitually consumed five or more cups of boiled coffee per day ( n =150) were compared with matched filter coffee consumers ( n =159) in a cross-sectional study, as part of the Norwegian National Health Screening in 1992.
Results. The median lipoprotein(a) level was 13.0 mg  dL⁻¹ (10th and 90th percentile: 2.5 and 75.0 mg  dL⁻¹, respectively) on boiled and 7.9 mg dL^-1 (10th and 90th percentile: 1.9 and 62.5 mg dL⁻¹, respectively) on filter coffee ( P =0.048). Means±SE were 25.8±2.4 mg dL⁻¹ and 19.6±2.0 mg dL⁻¹, respectively ( P =0.04). Although not statistically significant, subjects consuming nine or more cups of coffee per day had higher lipoprotein(a) levels than those drinking five to eight cups per day in both coffee groups.
Conclusion. Chronic consumers of unfiltered, boiled coffee have higher serum levels of lipoprotein(a) than filter coffee drinkers.     

Dissociated incretin response to oral glucose at 1 year after restrictive vs. malabsorptive bariatric surgery

Aim: Compare the response to oral glucose of the two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) at 1 year after restrictive vs. malabsorptive bariatric surgery.
Methods: Vertical banded gastroplasty (VBG, n = 7) or jejunoileal bypass (JIB, n = 5) was performed in 12 women, aged 26–39 years, with severe obesity [body mass index (BMI) 46.6 ± 2.3 kg/m²]. After 1 year, 75 g glucose was administered and plasma levels of glucose, insulin, GIP and GLP-1 were determined regularly during the following 2 h.
Results: At 1 year after operation, reduction in body weight, actual body weight, fasting glucose or insulin, or the glucose and insulin responses to oral glucose did not differ significantly between the groups. Similarly, fasting GIP and GLP-1 levels did not differ significantly between the groups. In contrast, the GIP and GLP-1 responses to oral glucose were different between the groups in a dissociated pattern. Thus, AUC_GIP was significantly higher after VBG than after JIB (53 ± 8 vs. 26 ± 6 pmol/l/min, p = 0.003). In contrast, AUC_GLP−1 was significantly higher after JIB than after VBG (49 ± 5 vs. 20 ± 3 pmol/l/min, p = 0.007).
Conclusions: We conclude that at 1 year after bariatric surgery, the two incretins show dissociated responses in that the GIP secretion is higher after VBG whereas GLP-1 secretion is higher after JIB. This dissociated incretin response is independent from reduction in body weight, glucose tolerance or insulin secretion.     

Plasma glutathione concentration in patients with chronic hepatitis C virus infection

Summary. It has recently been proposed that a depletion of glutathione (GSH) may be a contributing factor to viral persistence and resistance to interferon-α (IFN-α) therapy in chronic hepatitis C virus (HCV) infection. The aim of this study was: (1) to compare plasma GSH levels in patients with chronic HCV infection and normal healthy controls; and (2) to correlate GSH levels with liver histology and serum HCV RNA levels. Twenty-four patients with compensated chronic hepatitis C and 2 7 healthy subjects were studied. Serum and heparinized plasma were prospectively prepared and frozen within 1 h of collection. Plasma glutathione and glutathione peroxidase (GP) levels were measured spectrophotometrically. The serum HCV RNA level was quantitated by the branched chain DNA signal-amplification assay. Plasma GSH levels were not decreased in patients with chronic HCV infection but were actually greater than in controls (control 1.2 7 ± 0.12 μg ml^-1, HCV 1.62 ± 0.11 μg ml^-1, P < 0.05). There was also no difference in plasma GP activity between these two groups (control 0.233 ± 0.007 U ml^-1, HCV 0.230 ± 0.007 U ml^-1). Among the patients with chronic HCV infection, there was no correlation between either plasma GSH or GP levels and the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), serum HCV RNA level, or liver histology. This study demonstrates that chronic HCV infection does not decrease the plasma GSH and GP levels.     

The metabolic syndrome as a link between smoking and cardiovascular disease

Objective:  Smoking is associated with a significant increase in the cardiovascular risk. The possible relationship of smoking with insulin resistance might further enhance the cardiovascular risk of the patients and is therefore of great clinical interest.
Design, Setting and Subjects:  We have retrospectively evaluated data of 3804 non-diabetic men attending a medical outdoor clinic. Clinical [body mass index (BMI), percentage of body fat, waist-to-hip ratio] and laboratory results were compared between smokers (n = 124) and non-smokers (n = 1915) without cardiovascular disease, as well as between smokers (n = 759) and non-smokers (n = 1006) with cardiovascular disease.
Results:  Smokers without clinically manifest cardiovascular disease revealed significantly higher fasting glucose (5.8 ± 0.6 mmol/l) and triglyceride levels (1.8 ± 0.9 mmol/l) than non-smokers (fasting glucose: 5.1 ± 0.7 mmol/l, p < 0.010; triglycerides: 1.5 ± 0.8 mmol/l, p < 0.030). The adverse metabolic profile of smokers was even more pronounced in patients with cardiovascular disease. An age-matched analysis of smokers could demonstrate that cardiovascular patients revealed higher BMI values (27.3 ± 2.4 kg/m²) and a higher percentage of body fat (25.5 ± 5.5%) than those without cardiovascular disease (BMI: 25.7 ± 2.2 kg/m², p < 0.010; percentage of body fat: 23.0 ± 5.5%, p < 0.030).
Conclusion:  In men with and without clinically manifest cardiovasular disease, smoking was associated with a metabolic profile indicating a higher degree of insulin resistance.     

Insulin glulisine, insulin lispro and regular human insulin show comparable end-organ metabolic effects: an exploratory study

Aims:  To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro (lispro) and regular human insulin (RHI) in patients with type 1 diabetes mellitus.
Methods:  Eighteen patients with type 1 diabetes mellitus (mean age 36.9 ± 8.6 years, BMI 23.6 ± 2.8 kg/m², haemoglobin A_1c 7.4 ± 0.9%) were randomized in this single-centre, double-blind, three-period cross-over, standard Latin-square, euglycaemic glucose clamp trial. Patients received sequential, primed stepwise intravenous infusions of glulisine, lispro or RHI (infusion rates were increased in a stepwise manner from an initial rate of 0.33 [180 min] to 0.66 [180 min] and 1.00 [180 min] mU/kg/min). The primary variables were the suppression of endogenous glucose production ( S _EGP) and glucose uptake (GU).
Results:  Mean basal endogenous glucose production (EGP) was 1.88, 2.12 and 2.12 mg/kg/min for glulisine, lispro and RHI respectively. Mean (±s.e.) maximum absolute S _EGP (adjusted for basal EGP) was −1.64 ± 0.06, −1.72 ± 0.05 and −1.56 ± 0.05 mg/kg/min respectively. Mean (±s.e.) maximum absolute increase in GU (adjusted for basal GU) was 6.46 ± 0.26, 6.23 ± 0.24 and 6.72 ± 0.24 mg/kg/min respectively. There were no clinically relevant differences between the three insulin treatments with respect to serum insulin, free fatty acid (FFA), glycerol or lactate levels. No serious adverse events and no episodes of severe hypoglycaemia were reported.
Conclusions:  This study shows that glulisine, lispro and RHI have similar effects on S _EGP, GU, FFA, glycerol and lactate levels, providing evidence for similar end-organ metabolic effects.     

Rosiglitazone (PPARgamma-agonist) attenuates atherogenesis with no effect on hyperglycaemia in a combined diabetes-atherosclerosis mouse model

Background: The administration of peroxisome proliferator-activated receptor γ (PPARγ) agonists to low-density lipoprotein (LDL)-receptor-deficient mice resulted in a reduction in the atherosclerotic lesion area in male mice, but not in female mice. The male mice also exhibited reduction in insulin resistance while the female mice did not. To further examine the relationship between PPARγ agonists, insulin resistance and atherosclerosis, we used the model of accelerated atherosclerosis in male apolipoprotein E (apoE)-deficient mice rendered diabetic by low-dose streptozotocin (STZ).
Methods: Male, apoE-deficient mice ( n  = 48) were randomly divided into four groups. To induce diabetes, two groups received low-dose STZ and two groups served as controls. After diabetes induction, rosiglitazone (a PPARγ agonist) was administered by oral gavage to one of the diabetic and one of the non-diabetic groups.
Results: Rosiglitazone reduced significantly the atherosclerotic aortic plaque area in both diabetic and non-diabetic apoE-deficient mice: 340 ± 54 vs. 201 ± 27 μmol² (p = 0.001) in diabetic mice; 243 ± 22 vs. 158 ± 27 μmol² (p = 0.001) in non-diabetic mice. Also, rosiglitazone reduced the correlation coefficient between plasma glucose and the degree of atherosclerosis (p < 0.0025) without affecting plasma glucose levels. The rosiglitazone-treated mice, both diabetic and non-diabetic, had higher lipid levels.
Conclusions: Rosiglitazone-treated animals showed less atherosclerosis despite higher lipid levels and similar glucose levels. These data suggest a direct anti-atherogenic effect of rosiglitazone on the arterial wall.     

Drug Delivery at the Aortic Valve Tissues of Healthy Domestic Pigs with a Paclitaxel-Eluting Valvuloplasty Balloon

Background: Restenosis occurs invariably within 1 year following balloon valvulopasty in aortic valve stenosis. The mechanism of restenosis seems to involve a dynamic cellular component that could be a target for drug inhibition. We investigated the feasibility of local drug delivery at the aortic valve tissues of healthy pigs with a paclitaxel-eluting balloon.
Methods: Aortic valvuloplasty was performed in eight anesthetized domestic pigs using paclitaxel-eluting balloons (3 μg/mm² balloon surface area). They were assigned to two or four times 15-second balloon inflations and were sacrificed 30 minutes after final balloon inflation.
Results: The aortic annulus to balloon diameter ratio was 1.15 ± 0.07. The mean paclitaxel concentration in the aortic valve leaflets was 0.91 ± 1.36 μg/mL (0.34 ± 0.05 μg/mL in the two-inflation group, 1.48 ± 1.86 μg/mL in the four-inflation group, P = 0.23). The percentage of the total paclitaxel dose recovered in the aortic valve leaflets was 18 ± 11⁻⁶% (13 ± 6⁻⁶% and 25 ± 14⁻⁶% in the two- and four-inflation group, P = 0.16).
Conclusion: Local drug delivery at the aortic valve leaflets of healthy pigs with a paclitaxel-eluting balloon is feasible and concentrations within the therapeutic window are detected 30 minutes after the procedure. The antirestenotic potential of this treatment should be studied.     

Insulin and C-peptide responses to 75 g oral glucose load in the healthy man

Plasma insulin and C-peptide levels in the fasting state and after a 2-h 75 g oral glucose tolerance test (OGTT) in a large number of healthy subjects are reported. 247 volunteers (134 males, 113 females), aged 13-69 years, who had a negative history of diabetes, no history of significant disease, normal physical examination, normal body weight, normal glucose tolerance, normal blood tests, and who were taking no drugs were studied. Results, mean +/- SEM (range): fasting glucose concentration = 4.64 +/- 0.03 mmol/l (3.10 - 6.10), 1-h glucose concentration = 5.23 +/- 0.10 mmol/l (2.20 - 9.90), 2-h glucose concentration = 4.11 +/- 0.06 mmol/l (2.00 - 6.80); fasting insulin level = 0.088 +/- 0.002 nmol/l (0.03 - 0.28), 1-h insulin level = 0.45 +/- 0.01 nmol/l (0.06 - 1.63), 2-h insulin level = 0.24 +/- 0.01 nmol/l (0.05 - 1.12); fasting C-peptide concentration = 0.60 +/- 0.01 nmol/l (0.14 - 1.34), 1-h C-peptide concentration = 2.17 +/- 0.05 (0.63 - 8.56), 2-h C-peptide concentration = 1.77 +/- 0.04 nmol/(0.35 - 5.74). Fasting insulin and fasting C-peptide concentrations correlated to post-glucose insulin and C-peptide concentrations, respectively. At each sampling-point insulin concentration correlated to C-peptide concentration. After glucose ingestion, both insulin and C-peptide plasma levels correlated significantly with the corresponding glucose levels. During fasting, C-peptide but no insulin level correlated to glucose level.(ABSTRACT TRUNCATED AT 250 WORDS)