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.     

Blood pressure, erythrocyte sodium and potassium concentrations and Na+K+ATPase activity in children with hypertensive mothers

Fifty-four children aged 10-15 years were studied. Twenty-two children had mothers who had sustained hypertension after a hypertensive pregnancy (HT) and 17 had normotensive mothers who had previously had a hypertensive pregnancy (NT). A control group consisted of 15 children with normotensive mothers (C). Blood pressure was significantly higher in the HT group in comparison with the C group (P less than 0.01). Erythrocyte sodium (Na+) and potassium (K+) concentrations were similar in all groups and not related to blood pressure. The Na+K+ATPase activity in erythrocyte membranes was lower in the HT group than in the NT group (P less than 0.02), but not significantly different from the C group. There was no statistically significant correlation between Na+K+ATPase activity and blood pressure.     

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.     

Influence of treatment with acarbose or glibenclamide on insulin sensitivity in type 2 diabetic patients

Aim: The aim of our double-blind, placebo-controlled study was to compare the effect of acarbose and glibenclamide on the insulin sensitivity in type 2 diabetes.
Methods: We investigated 77 patients (mean age 58.7 years, mean BMI 27.3 kg/m²), treated by diet alone for at least 4 weeks. The subjects were randomized into three treatment groups for 16 weeks: 100 mg t.i.d. acarbose ( n  = 25) or 1 mg t.i.d. glibenclamide ( n  = 27) or one t.i.d. placebo ( n  = 25). Before and after therapy, the levels of fasting plasma glucose, glycosylated haemoglobin, fasting insulin, plasma glucose and insulin 1 h after a standardized breakfast were measured and insulin sensitivity determined by euglycaemic hyperinsulinaemic clamp test.
Results: After the treatment period, BMI in the acarbose and placebo group decreased significantly, whereas in the glibenclamide group a significant increase was observed. Fasting plasma glucose was only significant reduced under glibenclamide. The postprandial glucose decreased significantly after acarbose (13.8 vs. 11.4 mmol/l, p < 0.05) and glibenclamide treatment (14.6 vs. 11.4 mmol/l, p < 0.05) and was unchanged under placebo (13.8 vs. 13.7 mmol/l). The fasting insulin levels remained unchanged in all three groups, whereas postprandial insulin values increased significantly under glibenclamide. Neither acarbose nor glibenclamide significantly changed insulin sensitivity [acarbose: glucose disposal rate before treatment 2.3 mg/kg body weight/min/insulin, after treatment 3.2; glibenclamide 2.2 vs. 2.1; placebo 2.6 vs. 3.0].
Conclusions: Our results show a more substantial improvement of glucose control under glibenclamide than under acarbose which, however, was not associated with an increase of insulin sensitivity.     

Intrapulmonary administration of insulin to healthy volunteers

Objectives. To study the biological effects of nebulized insulin, administered intrapulmonary, to healthy volunteers.
Design. A double-blind, randomized, controlled intervention study.
Setting. The department of Internal Medicine, University Hospital, Linköping, Sweden.
Subjects. Eight healthy, non-smoking volunteers, with a mean age of 28 (range 22 to 56) years.
Interventions. Regular human insulin 100 U mL^-1 (Actrapid®) or 0.9% saline was given randomly as an oral inhalation. Insulin was given in three different doses (40, 80 and 160 U). Aerosol was generated by a new jet nebulizer.
Main outcome measures. Blood glucose, serum insulin, and serum C-peptide.
Results. After the 160 U insulin dose the blood glucose concentration (mean±SE) fell from 4.3±0.2 to 2.8±0.2 mmol L^-1 ( P <0.001), concomitant with an increase in mean serum insulin concentrations, rising from 9.5±1.5 to 26.1±2.5 mU L^-1 ( P <0.001). Serum C-peptide concentrations simultaneously decreased from 0.48±0.03 to 0.12±0.02 mmol L^-1 ( P <0.001). All changes were dose dependent. No adverse reactions were noted and no significant changes in lung function tests.
Conclusions. Intrapulmonary insulin administration to healthy subjects can induce a significant hypoglycaemia and cause a clinically relevant increase in serum insulin concentrations. If similar results can be obtained when administering insulin to diabetic subjects, this insulin administration route can be a future complement to certain groups of patients.     

Safety and immunogenicity of subcutaneous hepatitis A vaccine in children with Haemophilia

Individuals with Haemophilia are at risk from hepatitis A virus (HAV) infection through exposure to blood products. Havrix^®, an intramuscular hepatitis A vaccine, is currently recommended for the prevention of disease caused by hepatitis A virus. Because bleeding may complicate intramuscular injections in those with bleeding disorders, we conducted a randomized, Phase IV clinical trial to compare the safety and immunogenicity of Havrix^® given by the subcutaneous (s.c) vs. intramuscular (i.m.) route. A total of 45 children with Haemophilia were vaccinated subcutaneously, while their 41 nonhaemophlic siblings were vaccinated intramuscularly, at a dose of 720 Elisa units (EL.U.) at time 0 and 6 months. All children were anti-HAV and anti-HIV negative at baseline, and the haemophilic group did not differ from their siblings in alanine aminotransferase (ALT; 25 IU L⁻¹ vs. 22 IU L⁻¹), or in age; 8.5 years vs. 8.7 years. The vaccine was well tolerated, with minor adverse events being similar between groups; 21 (47%) vs. 24 (58%), P  > 0.05. Local symptoms included soreness in 39 (45%), erythema in 25 (29%), swelling in 21 (24%), and bruising in six (7%), with no differences between groups. The proportion seroconverting to anti-HAV IgG positive did not differ between groups; 98% vs. 97% at month 1; 82% vs. 93% at month 6; and 100% vs. 100% at month 8, respectively. The HAV geometric mean titre was lower in those with Haemophilia, 185 vs. 233 mIU mL⁻¹ at month 1; 68 vs. 94 mIU mL⁻¹ at month 6; and 584 vs. 1082 mIU mL⁻¹ at month 8, respectively. We conclude that Havrix^® is safe and immunogenic when administered s.c. in children with Haemophilia.     

Ethnic differences in C-peptide/insulin/glucose dynamics in young pregnant women

There are ethnic differences in insulin secretion and resistance in healthy nondiabetic adults, children, and adolescents. It is not known whether these ethnic differences are also detectable during normal pregnancy. The objective of this study was to examine whether ethnic differences in glucose homeostasis (C-peptide/insulin/glucose dynamics) are present in nondiabetic pregnant women. Fasting serum C-peptide, insulin, and plasma glucose were measured in the second and third trimesters in 773 pregnant women (343 African-Americans, 312 Hispanics, and 118 Caucasians), and a 50-g oral glucose challenge test was performed in the third trimester. Significantly reduced C-peptide levels and C-peptide to insulin ratio and elevated fasting insulin to glucose ratios were observed in African-American women compared with Caucasians and/or Hispanics. Similar results were found after a 50-g glucose load. In addition, African-Americans had greater insulin and lower glucose levels at glucose challenge test. There were ethnic differences in insulin production and resistance in both fasting and glucose-stimulated conditions in normal young nondiabetic pregnant women.     

PLASMA TUMOR NECROSIS FACTOR α LEVELS AND INSULIN SENSITIVITY IN HYPERTENSIVE SUBJECTS

Recent studies have shown that tumor necrosis factor-alpha (TNFα), secreted by macrophage, adipocyte and muscle cells, are associated with insulin resistance syndrome i.e., hyperinsulinemia, hypertriglyceridemia and decreased high density lipoprotein (HDL) cholesterol levels. However, it is unclear whether plasma TNFα levels relate to insulin resistance syndrome in subjects with essential hypertension who are also characterized by an insulin resistance state. We recruited 85 nondiabetic subjects (45 men and 40 women) with essential hypertension and 85 nondiabetic subjects who were matched for age, sex and body mass index (BMI) to determine their fasting plasma glucose, insulin and lipoprotein concentrations, their glucose and insulin responses to an oral glucose challenge, and their degrees of insulin resistance. Fasting plasma leptin and TNFα levels were measured by radioimmunoassay and chemiluminescent enzyme immunometric assay respectively. Total body fat mass was assessed by the bioelectrical impedance method. The results showed that fasting plasma leptin levels were similar between hypertensive and normotensive subjects (7.9±0.6 vs 7.4±0.7 ng/ml, p=0.190). Fasting plasma TNFα concentrations were not different between subjects with hypertension and normotension (10.5±0.5 vs 9.8±0.4 pg/ml, p=0.360). Fasting plasma TNFα concentrations were not different across three subgroups of the insulin resistance both in hypertensive patients (8.4±0.4 vs. 10.9±1.6 vs. 9.9±1.0 pg/ml, p=0.297) and normotensive subjects (9.2±0.7 vs. 9.3±0.9 vs. 9.7±0.9 pg/ml, p=0.875). Fasting plasma TNFα values showed significantly positive correlations with triglyceride concentrations (p<0.03) but negative correlation with HDL cholesterol concentrations (p<0.04) in normotensive but not in hypertensive individuals. These relations persisted even after adjustment for BMI and total fat mass. In conclusion, our data indicated that circulating levels of TNFα did not differ between hypertensive subjects and normotensive controls. Plasma TNFα concentrations correlated positively with fasting plasma triglyceride levels and negatively with HDL cholesterol concentrations in normotensive but not in hypertensive subjects. The influence of TNFα on carbohydrate and lipoprotein metabolism in hypertensive patients deserves further investigations.     

Insulin hypersecretion: a distinctive feature between essential and secondary hypertension.

Several studies have demonstrated that patients with hypertension have greater plasma insulin levels than normotensive subjects. The aim of the present study was to clarify if hyperinsulinemia in hypertension is a consequence of either increased pancreatic secretion or decreased hepatic clearance, and to determine whether abnormalities of glucose metabolism are equally present in essential and secondary hypertension. In an observational cross-sectional study, fasting blood glucose, plasma insulin, and plasma C-peptide levels were measured in five patient groups: 34 lean normotensive, 19 overweight normotensive, 25 lean essential hypertensive, 27 overweight essential hypertensive, and 20 secondary hypertensive subjects. The blood glucose/plasma insulin and plasma insulin/plasma C-peptide ratios were calculated as indexes of insulin sensitivity and hepatic insulin clearance, respectively. Subjects with essential hypertension and, to a greater extent, those who were overweight, exhibited significantly higher fasting insulin and C-peptide levels and significantly lower glucose/insulin ratios as compared with lean normotensive subjects. In contrast, no differences were observed between secondary hypertensive and control subjects. Mean blood pressure was significantly and independently correlated to body mass index, plasma insulin and plasma C-peptide levels, and the glucose/insulin ratio. In lean essential hypertensive and secondary hypertensive subjects, the insulin/C-peptide ratios were comparable to controls, indicating normal hepatic insulin clearance. In both overweight groups, a trend to increased insulin/C-peptide ratios was observed. This study shows that in essential hypertensive subjects, hyperinsulinemia is caused by insulin hypersecretion, whereas in overweight subjects, both increased insulin secretion and decreased hepatic insulin clearance might be involved.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Influence of exogenous insulin on C-peptide levels in subjects with type 2 diabetes

Aim:The aim of this study was to determine whether the influence of insulin therapy on fasting and stimulated C-peptide levels in type 2 diabetic subjects is due to plasma glucose reduction or a direct effect of exogenous insulin.Methods:Plasma glucose and serum C-peptide levels were determined before and after IV injection of 1 mg glucagon on three separate days in 21 type 2 diabetic subjects. Day 1: without pharmacological treatment and fasting plasma glucose >11.1 mmol/L; day 2: fasting plasma glucose 4.4–7.8 mmol/L, 1 h after withdrawing intravenous regular insulin infusion; day 3: fasting plasma glucose 4.4–7.8 mmol/L with bed-time NPH insulin.Results:Fasting and glucagon stimulated C-peptide levels were higher on day 1 than days 2 and 3. Fasting, but not stimulated C-peptide levels, were lower on day 3 than day 2. These differences were not appeared when the percentage of C-peptide increment or the C-peptide/glucose ratio were compared in the three days.Conclusions:Blood glucose reduction instead of exogenous insulin is responsible for the C-peptide decrease during insulin therapy in type 2 diabetic subjects.     

糖尿病并高血压患者高胰岛素血症初步探讨

对16例NIDDM合并高血压而无心、肾功能损害者与16例NIDDM血压正常者进行配对研究。同步检测空腹及馒头试验后血糖、胰岛素、C-肽等指标。NIDDM合并高血压组血清胰岛素水平、胰岛素/C-肽值明显高于NIDDM血压正常组,而胰岛素敏感指数则明显降低。结果表明,NIDDM合并高血压与高胰岛素血症有关,后者主要是由于肝脏对胰岛素清除率降低所致。     

Daily administration of the GIP-R antagonist (Pro3)GIP in streptozotocin-induced diabetes suggests that insulin-dependent mechanisms are critical to anti-obesity-diabetes actions of (Pro3)GIP

Aim:  Glucose-dependent insulinotropic polypeptide-receptor (GIP-R) antagonism using (Pro³)GIP improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure and function in a commonly used model of obesity-diabetes, namely ob/ob mice. The effect of GIP-R antagonism in a streptozotocin (STZ)-induced model of insulin deficiency has not been evaluated. The present study has investigated the effects of daily administration of (Pro³)GIP to STZ-treated mice.
Methods:  Swiss TO mice received once-daily injection of (Pro³)GIP (25 nmol/kg body weight) or saline 4 days prior to and 16 days after injection of STZ, and effects on metabolic parameters and islet architecture were assessed.
Results:  (Pro³)GIP treatment had no significant effect on hyperphagia or body weight loss. However, hyperglycaemia and glycated haemoglobin were worsened, glucose tolerance further decreased and insulin sensitivity was impaired by (Pro³)GIP. These effects were observed on an STZ-induced background characterized by severe reductions of circulating insulin, beta-cell mass and pancreatic insulin stores.
Conclusions:  These data indicate that the beneficial actions of the GIP-R antagonist, (Pro³)GIP, in obesity-diabetes appear to be largely mediated through insulin-dependent mechanisms that merit further investigation.     

Addition of rosiglitazone to metformin is most effective in obese,insulin-resistant patients with type 2 diabetes

Aim:   These analyses were undertaken to evaluate the efficacy of the insulin sensitizer rosiglitazone (RSG) when added to the therapy of obese type 2 diabetes mellitus patients (T2D M ) taking near-maximal doses (2.5 g/day) of metformin (MET). In obese, insulin-resistant patients with T2D M who are inadequately controlled on MET, the addition of an agent that reduces insulin resistance may be a more rational and innovative approach than the addition of an insulin secretagogue.
Methods:   Data were pooled from two double-blind studies of RSG added to 2.5 g/day MET, involving a total of 550 T2D M patients. Patients were categorized as non-overweight, overweight and obese according to their baseline BMI using WHO criteria (<25 kgm⁻², 25–30 kgm⁻², >30 kgm⁻² respectively).
Results:   RSG improved glycaemia (HbA1c) and fasting plasma glucose (FPG) to a clinically significant extent in all three subgroups but the effect was most pronounced in the obese patients. Improvements in HOMA estimates of insulin resistance and beta-cell function were also greatest in the obese patients (4 mg: −16% and +19%; 8 mg: −37% and + 33% respectively), as were reductions in fasting insulin. The profile of adverse events was not demonstrably different in obese patients from the non-obese.
Conclusions:   In obese type 2 diabetic patients inadequately controlled on MET alone, addition of rosiglitazone improves glycaemic control, insulin sensitivity and beta-cell function to a clinically important extent.     

Impaired glucose metabolism and obesity in Swedish patients with borderline isolated systolic hypertension: Skaraborg Hypertension and Diabetes Project

Summary
Aim   To assess the prevalence of borderline isolated systolic hypertension (borderline ISH), and to examine its association with other cardiovascular risk factors.
Methods   A cross-sectional community-based study was carried out in 1993–1994 in Skara, Sweden, including 1109 randomly chosen subjects ≥ 40 years old. Normotension (NT) was defined as systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg, borderline ISH as SBP 140–159 and DBP < 90 mmHg and hypertension (HT) as SBP ≥160 or DBP ≥ 90 mmHg or ongoing treatment.
Results   The prevalence of borderline ISH (n = 203) by age was 4% in ages 40–49 years, 15% in ages 50–59 years, 28% in ages 60–69 years and 25% in ages 70–79 years. With borderline ISH as reference, normotensive subjects less often had fasting blood glucose > 5.5 mmol/l (odds ratio (OR): 0.4, 95% CI: 0.26–0.75), BMI > 27 kg/m² (OR: 0.6, 95% confidence intervals (CI): 0.42–0.85) and known diabetes (OR: 0.4, 95% CI: 0.16–0.95). Hypertensive subjects more often had high density lipoprotein (HDL) cholesterol < 1.0 mmol/l (OR: 2.0, 95% CI: 1.35–2.99), a history of previous cardiovascular disease (CVD) (OR: 1.7, 95% CI: 1.01–2.72), known diabetes (OR: 2.4, 95% CI: 1.29–4.58) and microalbuminuria (men) (OR: 1.9, 95% CI: 1.15–3.11).
Conclusion   Borderline ISH is a common condition. It is associated with a more unfavourable risk factor profile than that of normotensive subjects concerning primarily glucose metabolism and obesity. The prevalence of known diabetes increased with the degree of hypertension.     

The assessment of hepatic and peripheral insulin sensitivity in hypertriglyceridemia

Peripheral insulin resistance is a common finding in hypertriglyceridemia. However, hepatic insulin sensitivity has rarely been investigated. We measured hepatic and peripheral insulin sensitivity in eight nondiabetic, nonobese hypertriglyceridemic subjects (HT) with raised triglyceride concentrations (4.3 +/- 0.6 mmol.L-1, mean +/- SEM) and eight age-, sex-, and weight-matched control subjects (C) with normal triglyceride concentrations (1.2 +/- 0.2 mmol.L-1). Insulin secretion was assessed during a 75-g oral glucose tolerance test (OGTT). Glucose turnover was determined using 3(3H) glucose in the postabsorptive state and during euglycemic glucose clamps at insulin infusion rates of 0.25 and 1.0 mU.kg-1.min-1. At identical fasting glucose concentrations (HT, 5.2 +/- 0.2; C, 5.2 +/- 0.2 mmol.L-1), the glucose responses to OGTT were similar in both groups. Fasting plasma insulin (HT, 8.3 +/- 1.2; C, 4.6 +/- 0.4 mU.L-1; P = .02), and C-peptide (HT, 1.7 +/- 0.2; C, 1.1 +/- 0.1 microgram.L-1; P = .006) concentrations were higher in hypertriglyceridemic subjects. The insulin and C-peptide responses to OGTT were greater in hypertriglyceridemic subjects (insulin, P = .005; C-peptide; P = .01). Hepatic glucose appearance in the postabsorptive state was similar (HT, 11.4 +/- 0.3; C, 10.9 +/- 0.7 mumol.kg-1.min-1; NS). At low insulin concentrations (HT, 20.7 +/- 1.4; C, 20.5 +/- 1.4 mU.L-1), hepatic glucose appearance was equally suppressed (HT, 9.6 +/- 0.9; C, 10.5 +/- 1.3 mumol.kg-1.min-1; NS).(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.     

Higher cholesterol and insulin levels in pregnancy are associated with increased risk for pregnancy-induced hypertension

Hyperinsulinemia and dyslipidemia are known to be associated with essential hypertension but their role in pregnancy-induced hypertension remains unclear. We performed a case-control study comparing cholesterol, insulin, and glucose levels in the early third trimester of pregnancy among 31 women who developed pregnancy-induced hypertension (PIH) (either preeclampsia [n = 6] or nonproteinuric gestational hypertension [n = 25]), with 31 women remaining normotensive through pregnancy. As compared with women remaining normotensive, women subsequently developing PIH had higher fasting cholesterol levels (279 v 247 mg/dL; P = .02) and higher fasting insulin levels (13.3 v 7.9 microU/mL; P = .03), although fasting glucose levels and levels of glucose and insulin after glucose load did not differ significantly between groups. In comparing hypertensive subgroups, fasting insulin levels were significantly higher among women who subsequently developed preeclampsia, but not among those subsequently developing nonproteinuric gestational hypertension. Although women developing PIH had higher pregravid body mass index (25.1 v 22.6 kg/m2, P = .06), fasting cholesterol and insulin levels were associated with risk for PIH even after adjustment for body mass index and age (relative risks for one unit increase, respectively: 1.02 (P = .03) and 1.12 (P = .03). Higher fasting cholesterol and insulin levels in mid- to late pregnancy are associated with increased risk for PIH. These observations support a role for insulin resistance in the development of this complication of pregnancy.     

Impaired Glucose Tolerance at Five-year Follow-up of Young Men with Borderline Hypertension

Wall U, Bergbrant A, Jern S. Impaired glucose tolerance at five-year, follow-up of young men with borderline. hypertension. Blood Pressure 1996; 5: 139-147.

Background: Recent studies suggest that patients with essential hypertension have impaired glucose tolerance and are hyperinsulinemic compared with normotensive subjects. The aims of the study were (I) to follow blood pressures of 56 young men with borderline hypertension for 5 years, (2) to investigate glucose tolerance in these subjects, and (3) to determine the relation of insulin/glucose metabolism to structural vascular changes and hemodynamic patterns in borderline hypertension. Methods: Thirty-nine young (age 22-34 years) male subjects with borderline hypertension (SBP 140-160 and/or DBP 85-95 mmHg initially) and 17 normotensive control subjects (SBP 110-130 and DBP 60-80mmHg) participated in the study. Blood pressure was measured, a standard oral glucose tolerance test (OGTT) was performed, and glucose, insulin and C-peptide were determined before and 30, 60, 90 and 120 minutes after a standard 75-g glucose load. Post-ischemic forearm vasodilatory responses were examined by plethysmography. Results: At follow-up, the borderline hypertensives had maintained significantly higher blood pressures than control subjects. Borderline hypertensives also had significantly impaired glucose tolerance compared to control subjects. The insulin response had a somewhat more sluggish descent, but did not differ significantly from the response of normotensives. The C-peptide response pattern resembled that of insulin, but C-peptide was significantly elevated after 120 min. On the whole group level, there were only weak relations of insulin to blood pressure. By contrast, fasting insulin and post-load insulin levels were strongly correlated with body mass index, the waist-hip circumference ratio, triglyceride, and both total and LDL cholesterol. Across the whole group, there were significant correlations between forearm minimal vascular resistance and fasting insulin (r = + 0.37 p = 0.007) and insulin area-under-the-curve (r = + 0.28 p = 0.044). However, R_min was even more strongly correlated with body mass index, suggesting that this relationship was related to degree of obesity. Conclusion: Borderline hypertension in young men is a persistent condition which is associated with impaired glucose tolerance without hyperinsulinemia. This finding suggests that impaired glucose tolerance might be a more primary phenomenon in early hypertension devoid of lipid metabolic aberrations.     

原发性高血压患者胰岛素抵抗与红细胞膜脂质成分及膜钙结合力之间的关系

目的探讨高血压（ＨＴ）时胰岛素抵抗（ＩＲ）与细胞膜脂质成分、膜内面Ｃａ２＋结合力之间的关系。方法３０例高血压伴ＩＲ（ＨＴ＋ＩＲ）及２５例单纯性高血压（ＨＴ）患者，及３２名正常人（ＮＴ）为研究对象。放免法测定血胰岛素（ＩＳ），氧化酶法测定血糖（Ｇ），比色法测定胆固醇（Ｃ）及磷脂（Ｐ），硫代巴比妥酸反应测定过氧化脂质（ＭＤＡ），原子吸收法测定膜结合Ｃａ２＋。结果（１）ＨＴ组胰岛素敏感性基本正常；与ＮＴ组比较无明显差别；ＨＴ＋ＩＲ组胰岛素敏感性低于ＮＴ组和ＨＴ组（Ｐ＜０．０１）；（２）ＨＴ组和ＨＴ＋ＩＲ组，膜脂Ｃ／Ｐ克分子比率及ＭＤＡ含量，高于ＮＴ组（Ｐ＜０．０５或０．００１）；（３）ＨＴ组和ＨＴ＋ＩＲ组红细胞膜内面Ｃａ２＋结合力皆显著低于ＮＴ组（Ｐ＜０．００１），而且ＨＴ＋ＩＲ组Ｃａ２＋结合力减低的程度甚于ＨＴ组（Ｐ＜０．０５）。结论高血压时ＩＲ对细胞膜Ｃａ２＋结合力具有减低之影响。