The impact of continuous subcutaneous infusion of octreotide on gallstone formation in acromegalic patients.

Treatment of acromegaly with intermittent sc injections of octreotide is associated with an increased incidence of cholelithiasis. We investigated the incidence of gallstone formation, the occurrence of gallbladder disease, and the response of gallstones to ursodeoxycholic acid in 30 acromegalic patients who were treated with a continuous sc infusion of octreotide at doses between 200 and 800 micrograms/day for 3-70 months. Of the 30 patients, 28 had pretretment ultrasonography of the biliary tree performed, and all had frequent follow-ups. Nine patients underwent pre- and posttreatment bile sampling. No patient treated for less than 6 months and 18.5% of patients treated for more than 6 months developed new gallstones. No patient developed symptomatic cholelithiasis while receiving octreotide therapy. Of six patients who developed gallstones, four were treated with ursodeoxycholic acid, which dissolved all gallstones. One patient with gallstones experienced an episode of biliary colic when octreotide was withdrawn; however, no cholecystitis was found at subsequent cholecystectomy. Bile sampling showed that 8 (75%) of the 12 patients who were assessed demonstrated microcrystals, whereas in 3 (50%) of 6 patients who were closely analyzed thereafter, microcrystals disappeared once octreotide therapy was stopped. Our results show that continuous sc infusion octreotide therapy increases the incidence of cholelithiasis over normal values, as is the case with intermittent sc injections. Although higher octreotide levels are sustained with continuous sc infusion, this is not associated with an increased risk of gallstone formation compared with intermittent sc octreotide therapy.

Changes in plasma catecholamine and neuropeptide Y levels after sympathetic activation in dogs.

1. Plasma levels of noradrenaline (NA) and neuropeptide Y (NPY) were evaluated in two experimental models associated with an increase in sympathetic tone: conscious dogs which were subject to either sinoaortic denervation or acute administration of the alpha 2-adrenoceptor antagonist yohimbine. 2. Dogs that had undergone sinoaortic denervation exhibited a two fold increase in plasma NA without any change in NPY levels. 3. Yohimbine (0.05 mg kg-1 i.v. as a bolus) produced similar effects. A higher dose of yohimbine (0.5 mg kg-1 i.v.) increased both plasma NA (7 fold) and NPY (6.5 fold) levels. 4. The present results indicate that changes in plasma catecholamines and NPY are not always concomitant. They suggest that the simultaneous release of NA and NPY is only observed under in vivo conditions for a marked increase in sympathetic tone.

Insulin therapy and GH-IGF-I axis disorders in diabetes: impact of glycaemic control and hepatic insulinization.

In Type 1 diabetes, high circulating growth hormone (GH) in conjunction with low plasma insulin-like growth factor-I (IGF-I) is indicative of a hepatic GH-resistance profile since the liver is the main source of circulating IGF-I. The reduction in specific growth hormone binding protein (GHBP), corresponding to the extracellular domain of the GH receptor, provides an indirect indication of the hepatic density of GH receptors, as does the reduction in IGFBP-3, the major IGF binding protein, which is GH-dependent. Type 1 diabetes is also associated with high levels of IGFBP-1, a binding protein down-regulated by insulin. Although most of these abnormalities have been described in situations of poor glycaemic control, hyperglycaemia does not seem to be the predominant factor in their pathogenesis. Even intensified subcutaneous insulin therapy does not normalize GH, IGF-I, GHBP and IGFBP-3 plasma levels. Some indirect evidence suggests that portal insulinopenia plays a role in the hepatic GH-resistance profile of Type 1 diabetes, i.e. discrepancies between the abnormalities reported in Type 1 and Type 2 diabetes, and the inverse relationship between residual insulin secretion in Type 1 diabetes and some of these abnormalities. Intraperitoneal insulin therapy administered to Type 1 diabetic patients by implantable pumps (without modification of glycaemic control) can improve GHBP activity, practically normalize plasma IGF-I and normalize IGFBP-3. The improvement in GH-IGF-I axis disorders obtained with intraperitoneal insulin therapy (which allows primary portal insulin absorption) provides direct evidence of the central role of portal insulin in the regulation of this system.

Multicenter randomized evaluation of a nutritional education software in obese patients.

OBJECTIVE: To study the efficacy of the nutritional education software, Nutri-Expert, in the management of obese adult patients. MATERIAL AND METHODS: Two groups of obese patients were followed up over one year in a randomized study: the first group received close traditional management (seven nutritional visits over the year, with physicians and dietitians conjointly) and the second one also used at home by Minitel the Nutri-Expert system. 557 patients were enrolled in the study by 16 French centers of diabetology and nutrition. Body mass index (BMI), tests of dietetic knowledge, dietary records and centralized biological measurements were assessed at inclusion, 6 and 12 months. 341 patients were evaluable at the end of the year. RESULTS: The group using Nutri-Expert scored significantly better in the tests of dietetic knowledge than the control group. For all patients, nutritional education led to a significant improvement in BMI, dietary records and biological measurements, without significant difference between the two groups. Five years after the end of the study, the weight of 148 patients was recorded; mean BMI was significantly lower than the initial value but there was no significant difference between the two groups. CONCLUSION: In the management of obese patients, Nutri-Expert system has a role to play in reinforcing nutritional knowledge; if regular follow-up is not possible, or if a large series of obese patients is to be treated, Nutri-Expert could partly replace traditional management, for example between visits.

Clonidine but not propranolol decreases plasma neuropeptide Y (NPY) levels.

The effects of acute administration of two antihypertensive drugs, clonidine and propranolol, on plasma NPY and catecholamine levels were compared in sinoaortic denervated (a model associated with a marked increase in sympathetic tone and a rise in blood pressure) and normal conscious dogs. Clonidine decreased plasma noradrenaline and NPY concentrations in both groups of animals. Propranolol failed to change plasma noradrenaline and NPY levels in sinoaortic denervated dogs but elicited a decrease in plasma noradrenaline with no change in NPY levels in normotensive animals. The present experiments show that changes in plasma noradrenaline and NPY concentrations are not always simultaneous. The decrease in plasma NPY concentrations could contribute to the sympatholytic effect of clonidine.

[Neuropeptide Y, orthosympathetic nervous system, hypertension and alpha-2 adrenergic receptors]. / Neuropeptide Y, système nerveux orthosympathique, hypertension arterielle et récepteurs alpha 2-adrénergiques.

Neuropeptide Y (NPY) is coreleased with noradrenaline (NA) from sympathetic nerve endings. In vitro data suggest that NPY is coreleased during high stimulation frequencies. The present study investigates plasma levels of catecholamines and neuropeptide Y (NPY) during changes in sympathetic nervous activity in conscious dogs. Increase in sympathetic tone: arterial hypertension elicited by sinoaortic denervation induced an increase (X 2) in plasma noradrenaline (NA) but no change in NPY levels. High (0.5 mg/kg i.v.) but not low (0.05 mg/kg i.v.) doses of yohimbine rose plasma NPY concentrations. Decrease in sympathetic tone: clonidine (10 micrograms/kg i.v.) but not beta-blocking agents (propranolol or atenolol: 1 mg/kg i.v.) reduced plasma NPY levels. These results show that NPY is correleased in vivo from sympathetic nerve endings during marked and rapid increases in sympathetic tone. They suggest a lack of relationship between NA and NPY release. Alpha 2-adrenoceptors are involved in the presynaptic control of NPY release from sympathetic tone. Finally, some antihypertensive drugs (clonidine but not beta-blocking agents) are able to decrease plasma NPY levels.

[Value of nocturnal blood pressure in treated non-insulin-dependent hypertensive patients]. / Valeur de la charge tensionnelle nocturne chez le diabétique non insulino-dépendant hypertendu traité.

The purpose of the study was to evaluate the loss of nocturnal (N) decline in blood pressure (BP) in type II treated hypertensive diabetics. The study concerned 36 hypertensive diabetics 59 +/- 10 years old, 20 men and 16 women, with poor metabolic control (HbA1C: 9.6 +/- 3%), without dysautonomia; 14 had macroproteinuria and/or microalbuminuria (mu alb) (< 30 micrograms/min). An ambulatory BP monitoring (Spacelabs 90207) was performed in all patients. Left ventricular mass index (LVMI) and E/A were determined by Doppler-echocardiography. Two groups (G) were individualized: G1 (n = 17), with a normal circadian rhythm (diurnal and N.BP significantly different); G2 (n = 19) with a loss of N decline in systolic (S) and diastolic (D) BP or both; and compared to non diabetic treated hypertensive controls (G3). There was no difference neither in LVMI (125 +/- 43 g/m2), E/A (0.7), 24 h-mean (M) BP in the three groups, nor in HbA1C levels and mu alb occurrence in G1 and G2. Mean N.SBP and mean N.DBP were more closely related to LVMI in G2 than in G1 and G3. [table: see text] Half of these hypertensive diabetics, with bad metabolic control, have an altered circadian BP pattern; the prognostic value of nocturnal BP, related to LVMI despite the antihypertensive treatment, is suggested.

Effect of intraperitoneal insulin delivery on growth hormone binding protein, insulin-like growth factor (IGF)-I, and IGF-binding protein-3 in IDDM.

Low plasma insulin-like growth factor (IGF)-I despite high circulating growth hormone (GH) in insulin-dependent diabetes mellitus (IDDM) indicate a hepatic GH resistance. This state may be reflected by the reduction of the circulating GH binding protein (GHBP), corresponding to the extracellular domain of the GH receptor, and the reduction of insulin-like growth factor binding protein (IGFBP)-3, major IGF-I binding protein, upregulated by GH. We carried out two studies. In the first, plasma GHBP activity was compared in patients with IDDM on continuous subcutaneous insulin infusion (CSII) or on conventional therapy and in healthy subjects. In the second study, the 18 patients on CSII at baseline were then treated by continuous intraperitoneal insulin infusion with an implantable pump (CPII) and prospectively studied for GH-IGF-I axis. Although HbA1c was lower in patients on CSII than in those on conventional therapy, GHBP was similarly reduced in both when compared to control subjects (10.2 +/- 0.8 and 11.6 +/- 0.9% vs 21.0 +/- 1.3, p < 0.01). CPII for 12 months resulted in: a slight and transient improvement in HbA1c (Time (T)0: 7.6 +/- 0.2%, T3: 7.1 +/- 0.2%, T12: 7.5 +/- 0.2%, p < 0.02), improvement in GHBP (T0: 10.2 +/- 0.8%, T12: 15.5 +/- 1.5, p < 0.0001), near-normalization of IGF-I (T0: 89.4 +/- 8.8 ng/ml, T12: 146.9 +/- 15.6, p < 0.002) and normalization of IGFBP-3 (T0: 1974 +/- 121 ng/ml, T12: 3534 +/- 305, p < 0.0001). The hepatic GH resistance profile in IDDM does not seem to be related to glycaemic control, but partly to insufficient portal insulinization. Intraperitoneal insulin delivery, allowing primary portal venous absorption, may influence GH sensitivity, and improve hepatic IGF-I and IGFBP-3 generation.