Arvo Haenni

Treatment with a β-blocker with β2-agonism improves glucose and lipid metabolism in essential hypertension

Abstract In a randomized double-blind crossover study in 42 patients with essential hypertension, the metabolic effects of a β-adrenergic blocker with a pronounced β 2 -agonistic effect, dilevalol 400 mg × 1, were compared with those of metoprolol succinate 200 mg × 1. The effects on glucose metabolism were evaluated by the hyperinsulinemic euglycemic clamp technique and an intravenous glucose tolerance test (IVGTT). Insulin-mediated glucose disposal (M) and the insulin sensitivity index (M/I) increased by 19% ( P = .011) and 10% ( P = .27), respectively, during dilevalol treatment, but decreased by 10% ( P = .15) and 22% ( P = .0025), respectively, during metoprolol treatment, giving rise to significant differences between the two treatment regimens. Compared with dilevalol-treated patients, those treated with metoprolol showed increased plasma insulin values at the end of the IVGTT, but there was no difference in plasma glucose concentrations or glucose tolerance. Hemoglobin A 1c (HbA 1c ) levels increased by 5.4% ( P = .04) in the metoprolol group. Serum cholesterol, total serum and very-low-density lipoprotein (VLDL) triglycerides, and serum urate levels decreased significantly (by 6%, 22%, 29%, and 14%, respectively) during dilevalol treatment, and there was a significant difference between the effects of the two drugs on total, VLDL, and low-density lipoprotein (LDL) triglyceride and serum urate levels. These data demonstrate that a β-blocker with a partial β 2 -agonist action differs in its metabolic effect profile from a selective β 1 -blocker and may offer advantages by improving glucose and lipid metabolism.

Induction of insulin resistance by beta-blockade but not ACE-inhibition: long-term treatment with atenolol or trandolapril

The effects on glucose metabolism by the beta-blocker atenolol and the angiotensin-converting enzyme (ACE)-inhibitor trandolapril were investigated in a randomised double-blind parallel group study of patients with primary hypertension. Twenty-six patients were treated with 50–100 mg atenolol and 27 patients with 2–4 mg trandolapril o.d. Intravenous glucose tolerance tests, euglycaemic hyperinsulinaemic clamps and serum lipid measurements were performed after 8 and 48 weeks of active treatment. After 48 weeks insulin sensitivity was reduced by 23% by atenolol while it remained unchanged during trandolapril treatment (+0.5%, P = 0.0010 for difference between treatments, ANCOVA). The effect on triglycerides (+22% vs −8.5%) and high-density lipoprotein cholesterol (−13% vs +0.7%) also differed significantly between atenolol and trandolapril. Results after 8 weeks were similar. Glucose tolerance was not affected by either drug. Atenolol reduced diastolic blood pressure (DBP) better than trandolapril (−15.3 mm Hg vs −6.6 mm Hg for supine DBP after 48 weeks, P = 0.012). The difference in effect on insulin sensitivity between the drugs corresponded to 25% of the baseline values of insulin sensitivity, and persisted over 48 weeks of treatment. The choice of antihypertensive treatment could influence the risk of diabetes associated with treated hypertension.

Effect of fat emulsion (Fabuless) on orocecal transit time in healthy men

Background. Given the growing prevalence of overweight and related health consequences, there is increased interest in the search for novel dietary strategies for weight control. A food ingredient, an emulsion based on palm and oat oil (Fabuless, previously known as Olibra), has been associated with short-term reductions of food intake, induction of satiety, alternation in the satiety hormones, as well as long-term effects on weight control. The mechanism by which it can exert these effects is so far unclear, though it has been suggested that the “ileal break” may play a role in increasing gastrointestinal transit time. The aim of this study was to investigate the effects of this stable fat emulsion on orocecal transit time in healthy men. Material and methods. In a controlled, double-blind, cross-over-designed study, 15 healthy men (aged 20–59 years, body mass index (BMI) 22–28), randomly allocated to two treatments, consumed the stable fat emulsion or a milk fat in yoghurt during two days of investigation, with an interval of 1 week. Orocecal transit time was determined by following blood sulfapyridine levels, which is a metabolite of salazopyrine in the colon. Results. A statistically significant delay in the appearance of sulfapyridine in serum was obtained after active treatment versus control treatment, corresponding to a 45-min longer orocecal transit time due to fat emulsion consumption. Conclusions. This study provides the first evidence to suggest that this stable fat emulsion may affect the ileal brake mechanism by slowing down the gastrointestinal transit time, which might explain the weight control and appetite suppression previously observed in association with this emulsion.

The alterations in insulin sensitivity during angiotensin converting enzyme inhibitor treatment are related to changes in the calcium/magnesium balance

The present analysis was undertaken to investigate the relations between alterations in mineral factors, especially the balance between serum calcium and magnesium concentrations (S-Ca and S-Mg, respectively), and variables reflecting glucose and lipid metabolism during angiotensin converting enzyme (ACE) inhibitor treatment. A total of 96 patients with essential hypertension, participating in four double-blind studies with four different ACE inhibitors and similar protocols, were included. At the end of the initial placebo period and at the end of the period of active drug treatment, a hyperinsulinemic euglycemic clamp test was carried out, lipoprotein status was assessed, and the concentrations of serum electrolytes were measured. The serum ACE activity was determined in the group treated with fosinopril. Changes in insulin sensitivity index (M/I) were directly correlated to alterations in S-Mg (r = 0.24, P < .02), and inversely correlated to changes in S-Ca (r = -0.19, P = .07) and the ratio between serum calcium and magnesium concentrations (Ca/Mg) (r = -0.27, P < .008). The change in total serum triglycerides (S-Tg) was inversely correlated to the change in S-Mg (r = -0.35, P < .0005), and directly correlated to the change in Ca/Mg ratio (r = 0.36, P < .0004). The reduction in serum ACE activity correlated to a more pronounced increase in S-Mg r = -0.62, P < .002), and decrease in the Ca/Mg ratio (r = 0.73, P = .0002). We conclude that the changes in the studied metabolic variables and serum ACE activity during ACE inhibitor treatment are related to alterations in mineral status and the balance between calcium and magnesium concentrations in serum.

Urapidil treatment decreases plasma fibrinogen concentration in essential hypertension.

The effects of antihypertensive drugs on cardiovascular metabolic risk factors were monitored in 42 patients with essential hypertension (diastolic blood pressure [DBP] >95 mm Hg). In a double-blind randomized parallel-group study, they were treated with atenolol 50 mg once per day (n = 25) or urapidil 60 mg twice per day (n = 17), a peripheral alpha1-receptor blocker with an additional central serotonin 1A (5HT1A) receptor agonistic effect, for 12 weeks. Plasma fibrinogen concentration decreased by 24% (P < .0001) during urapidil treatment and by 9% (P = .05) during atenolol treatment, with the effects of the two drugs differing significantly. Plasminogen activator inhibitor (PAI) activity tended to increase by 17% (nonsignificant [NS]) in the atenolol-treated group and to decrease by 4% (NS) in the urapidil group. Differences between the effects of the two drugs on very-low-density lipoprotein (VLDL) triglycerides (TG) and on total TG were significant. During urapidil medication, these two parameters were reduced by 22% and 13%, respectively, but the changes were nonsignificant (P = .11 and P = .14, respectively). In contrast, atenolol treatment caused a significant increase in both VLDL TG and total TG of 31% and 21%, respectively. Hemoglobin A1c (HbA1c) increased by 4% (P = .06) during atenolol treatment, but was unaffected by urapidil. There were no significant changes within or between atenolol- and urapidil-treated groups regarding glucose disposal on an oral glucose tolerance test (OGTT) or the insulin sensitivity index on a hyperinsulinemic-euglycemic clamp test. In conclusion, urapidil treatment was characterized by neutral or favorable effects on several variables associated with the metabolic syndrome. Atenolol treatment had neutral properties in some metabolic aspects, but deleterious effects on lipid status.

Magnesium infusion improves endothelium-dependent vasodilation in the human forearm

The effect of intra-arterial magnesium infusion on endothelium-dependent vasodilation (EDV) in the forearm was studied in nine young healthy students (four men and five women). The EDV was assessed as forearm blood flow (FBF), measured by venous occlusion plethysmography, during infusion of methacholine (MCh). Endothelium-independent vasodilation (EIDV) was defined as FBF during infusion of sodium nitroprusside (SNP). During magnesium infusion in the brachial artery, 0.066 mmol/min, the concentration of ionized magnesium in venous plasma in the infused arm increased by 114%, from 0.59 (SD 0.04) to 1.26 (0.34) mmol/L (P = .0002). The FBF at baseline (ie, before administration of MCh or SNP) increased from 3.5 (1.1) to 7.3 (3.4) mL/min/100 mL tissue during magnesium infusion (P = .002). During low-dose MCh administration (2 microg/min), FBF increased by 24%, from 15.4 (5.5) to 19.1 (6.8) mL/min/100 mL tissue (P = .04), and during high-dose MCh administration (4 microg/min) FBF increased by 18%, from 20.3 (6.4) to 24.0 (7.2) mL/min/100 mL tissue (P = .04). The EIDV did not change significantly. Systemic blood pressure was not significantly altered by magnesium infusion. No change in FBF either at rest or during infusion of MCh or SNP was observed during the time-control protocol. In conclusion, this in vivo study showed that intraarterial magnesium infusion increased EDV in the infused human forearm, which is in accordance with findings in previous in vitro and animal experiments.

Serum aldosterone changes during hyperinsulinemia are correlated to body mass index and insulin sensitivity in patients with essential hypertension.

Objective To measure the effects of hyperinsulinemia on serum electrolyte status and associated hormones, and on serum free fatty acid (FFA) concentrations, in patients with essential hypertension. Design and methods The serum electrolyte status (Na, K, Ca, ionized Ca, Mg, P, pH) and associated hormones [plasma renin activity (PRA), serum parathyroid hormone (PTH) and aldosterone concentrations], and FFA were measured during an euglycemic hyperinsulinemic clamp test in 49 patients with untreated essential hypertension. Results Serum potassium, phosphate, PTH, and FFA concentrations decreased during hyperinsulinemia, while serum ionized calcium concentration, pH, and PRA increased significantly (P < 0.05). The changes in serum potassium and magnesium were both inversely related to the insulin-mediated glucose uptake (r = −0.62, P < 0.0001;r = −0.31, P < 0.05, respectively). Both body mass index (BMI) and insulin-mediated glucose disposal were significantly correlated to the changes in serum aldosterone concentration during hyperinsulinemia (r = 0.41, P< 0.01;r = −0.40, P < 0.01, respectively). The change in serum aldosterone during the clamp test was not significantly related to the change in PRA, but tended to correlate to the change in potassium concentration (r = 0.25, P = 0.10). A less pronounced reduction in FFA during induced hyperinsulinemia was associated with low insulin sensitivity (r = −0.35, P < 0.05). Conclusion Hypertensive patients with normal BMI and a more pronounced glucose uptake showed a larger serum potassium decline and lowered aldosterone concentrations during induced euglycemic hyperinsulinemia. Insulin-resistant patients showed a less pronounced reduction in FFA during hyperinsulinemia. The observations in the present study may indicate that alterations in aldosterone and FFA metabolism might be linked to the insulin resistance metabolic syndrome.

C3 and C4 are strongly related to adipose tissue variables and cardiovascular risk factors

In several reports, C3 and C4 have been linked to diabetes and cardiovascular disease (CVD). Here, we investigate this link and the degree of C3 activation in elderly individuals.

Metabolic effects of long-term angiotensin-converting enzyme inhibition with fosinopril in patients with essential hypertension: relationship to angiotensin-converting enzyme inhibition

Fifty patients with mild to moderate essential hypertension were randomized to receive either 20 mg fosinopril daily for 16 weeks or placebo for 4 weeks followed by 12 weeks of 50 mg atenolol daily. Prior to these 16 weeks there was a placebo wash-out period of 2–6 weeks. Blood pressure measurements, euglycaemic, hyperinsulinaemic glucose clamps, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and after 4 and 16 weeks. Blood lipid status was evaluated at baseline and 16 weeks.The insulin sensitivity index (M/I) increased by 12% during the prolonged placebo period, and subsequently decreased by 12% during treatment with atenolol in that group. A post-hoc analysis of covariance indicated that the increase in insulin sensitivity during the initial 4 weeks may have been due to carry over effects from previous anti-hypertensive treatment. Fosinopril increased glucose disappearance during IVGTT at 4 and 16 weeks (k values 1.46 and 1.33 vs 1.10 at baseline) but had no effect on insulin sensitivity. The change in insulin sensitivity and serum triglycerides during treatment with fosinopril was related to angiotensin-converting enzyme inhibition in serum.In conclusion, carry-over effects from previous anti-hypertensive medication were indicated in this study, probably because of an insufficient wash-out period in many patients. Therefore, 4 weeks of placebo wash-out in all patients is advisable in this kind of investigation.

Changes in liver volume and body composition during 4 weeks of low calorie diet before laparoscopic gastric bypass.

BACKGROUND Weight loss before laparoscopic Roux-en-Y gastric bypass (LRYGB) is desirable, because it can reduce liver volume and thereby facilitate the procedure. The optimal duration of a low-calorie diet (LCD) has not been established. The objective of this study was to assess changes in liver volume and body composition during 4 weeks of LCD. METHODS Ten women (aged 43±8.9 years, 114±12.1 kg, and body mass index 42±2.6 kg/m(2)) were examined on days 0, 3, 7, 14, and 28 after commencing the LCD. At each evaluation, body composition was assessed through bioelectric impedance analysis, and liver volume and intrahepatic fat content were assessed by magnetic resonance imaging. Serum and urine samples were obtained. Questionnaires regarding quality of life and LCD-related symptoms were administered. RESULTS In total, mean weight decreased by 7.4±1.2 kg (range 5.7-9.1 kg), and 71% of the weight loss consisted of fat mass according to bioelectric impedance analysis. From day 0 to day 3, the weight loss (2.0 kg) consisted mainly of water. Liver volume decreased by 18%±6.2%, from 2.1 to 1.7 liters (P<.01), during the first 2 weeks with no further change thereafter. A continuous 51%±16% decrease was seen in intrahepatic fat content. Systolic blood pressure, insulin, and lipids improved, while liver enzymes, glucose levels, and quality of life were unaffected. CONCLUSION A significant decrease in liver volume (18%) occurred during the first 2 weeks of LCD treatment, and intrahepatic fat gradually decreased throughout the study period. A preoperative 2-week LCD treatment seems sufficient in similar patients.