Influence of preprandial vs. postprandial insulin glulisine on weight and glycaemic control in patients initiating basal-bolus regimen for type 2 diabetes: a multicenter, randomized, parallel, open-label study (NCT00135096).

AIM: Insulin therapy is commonly associated with weight gain. The timing of prandial insulin administration may enhance its efficacy/safety and maintain effective weight control. This study examined the effect of postprandial vs. preprandial insulin glulisine on weight gain and glycaemic control in type 2 diabetes patients taking basal insulin. METHODS: This was a multicenter, randomized, open-label trial conducted in 45 centres in the USA. A total of 716 patients with type 2 diabetes and glycated haemoglobin A(1c) (HbA(1c) ) ≥ 7.5% and ≤10.0% were screened; 345 were randomized and 322 comprised the intent-to-treat group (premeal, 163; postmeal, 159). Insulin glargine once daily, ±metformin and subcutaneous injections of premeal or postmeal insulin glulisine were given for 52 weeks. Main outcome measures included changes in HbA(1c) , fasting plasma glucose and weight from study baseline to endpoint (week 52). RESULTS: At study end, insulin glulisine achieved similar glycaemic control whether it was administered before or after meals (HbA(1c) : 7.04% premeal vs. 7.16% postmeal, p = NS). Overall hypoglycaemia incidence and severe hypoglycaemia rates were not significantly different between premeal and postmeal groups; however, symptomatic and nocturnal hypoglycaemia rates were higher in the postprandial group. Mean body weight was lower in the postmeal group, with the difference between postmeal and premeal weight change from baseline to week 52 of -0.87 kg (p = 0.243). CONCLUSION: Postprandial glulisine administration provided similar glycaemic control and was non-inferior to preprandial administration on weight gain, without additional risk of severe hypoglycaemia, showing dosing flexibility and the feasibility of such approach when clinically indicated.

Efficacy and safety of an extended-release niacin (Niaspan): a long-term study.

Crystalline nicotinic acid (immediate-release niacin) is effective therapy for lipoprotein regulation and cardiovascular risk reduction. However, inconvenient regimens and unpleasant side effects decrease compliance. Sustained-release formulations designed to circumvent these difficulties increase hepatotoxicity. Niaspan, a new US Food and Drug Administration (FDA)-approved, once-daily, extended-release form, has been found effective and safe in short-term trials. The long-term efficacy and safety of Niaspan lipid monotherapy was studied in 517 patients (aged 21-75 years) for < or =96 weeks in dosages < or =3,000 mg/day. Primary efficacy endpoints were low-density lipoprotein (LDL) cholesterol and apolipoprotein B (apo B) changes from baseline; secondary efficacy endpoints were changes in total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, lipoprotein(a), and total cholesterol/HDL-cholesterol ratio; safety data included adverse events and laboratory values over the 2-year study period. LDL-cholesterol levels decreased significantly: 18% at week 48 and 20% at week 96; apo B reduction was similar (16% decrease at week 48 and 19% at week 96). Large elevations in HDL cholesterol (26%, week 48; 28%, week 96) allowed only modest decreases in total cholesterol (12% and 13%, respectively), whereas total cholesterol/HDL-cholesterol ratio decreased by almost one third. Triglyceride and lipoprotein(a) levels were decreased by 27% and 30%, respectively (week 48), and by 28% and 40%, respectively (week 96). All changes from baseline were significant (p <0.001). Niaspan was generally well tolerated, although flushing was common (75%); however, there was a progressive decrease in flushing with time from 3.3 episodes in the first month to < or = 1 episode by week 48. Aspirin was used by one third of patients before Niaspan dosing to minimize flushing episodes. Although serious adverse events occurred in about 10% of patients, none were considered probably or definitely related to Niaspan. Adverse events in general varied widely, but their true relation to the study drug is difficult to ascertain without a placebo (control) group. No deaths occurred. There were statistically significant changes in hepatic transaminases, alkaline phosphatase, direct bilirubin, phosphorus, glucose, amylase, and uric acid. However, these changes were mostly small and are not likely to be biologically or clinically significant (the decrease in phosphorus is a new finding in niacin therapy). No myopathy was observed. Thus, this long-term study confirms the earlier short-term findings that Niaspan is safe and effective as monotherapy in plasma lipoprotein regulation.

[Lovastatin: short-term treatment of hypercholesterolemia; multicenter clinical trial]. / Lovastatin: tratamiento a corto plazo de la hipercolesterolemia. Ensayo clínico multicéntrico.

Two hundred and ten patients (119 men and 91 women, mean age 54) with primary hypercholesterolemia (97% with total serum cholesterol greater than 240 mg/dl) were treated with lovastatin during 12 weeks in a placebo-controlled multicenter trial (10 cities and 21 investigators). All patients remained under an isocaloric low-fat, low-cholesterol diet throughout the study, and received placebo on a single-blind basis for the first 4 weeks (pretreatment period). Serum total cholesterol (TC), triglycerides (TG) and HDL-cholesterol (HDL-C) were measured at the beginning (week-4) and again at week 12. TC was also measured at weeks 0, 4, 8 and 12, while LDL-cholesterol (LDL-C) was calculated by a modification of Friedewald's formula. At the 5 clinic visits vital signs and body weight were recorded, and patients were questioned about adverse experiences. Safety laboratory tests (complete blood count, serum creatinine and creatinine phosphokinase, fasting plasma glucose, serum bilirubin, transaminases and alkaline phosphatase) plus a resting electrocardiogram (EG) and a complete (slit lamp) ophthalmologic examination were also carried out at weeks-4 and 12. During the treatment period lovastatin dosage was adjusted from 20 mg/day to 40 or 80 mg/day, if the TC value was greater than 200 mg/dL, with the resulting mean daily increasing doses of 28 mg (weeks 0-4), 37 mg (weeks 4-8), and 55 mg (weeks 8-12).(ABSTRACT TRUNCATED AT 250 WORDS)

Neuromodulators of the lingual von Ebner gland: an immunocytochemical study.

The serous lingual glands of von Ebner secrete lingual lipase, an enzyme that begins fat digestion in the stomach. The objective of this study was to characterize the neuromodulators in the rat tongue and von Ebner glands using immunocytochemical techniques. Rat lingual tissues were fixed in formalin, embedded in paraffin and sectioned at 4 microns for light microscopic studies. Immunocytochemical localization of neuromodulators was performed with monospecific anti-rat neuromodulator IgG or control (preimmune) IgG as the primary antibody, using the peroxidase-antiperoxidase (PAP) technique. No staining was seen with control anti-rat IgG. Immunospecific staining for vasoactive intestinal peptide (VIP), tyrosine hydroxylase and choline acetyltransferase (CHAT) was observed in nerves in the tongue, and cells containing immunospecific staining for serotonin (5-hydroxytryptamine) were seen in the stroma between the lingual glands. Selected cells in the serous glands stained positively for the presence of substance P and somatostatin. Adrenergic, VIP-containing and cholinergic nerves appear to innervate the tongue and serous glands. Substance P and somatostatin were identified in cells of the lingual serous glands and may be additional local modulators regulating lingual lipase release.

Niacin dosing: relationship to benefits and adverse effects.

Because of the original observation by Altschul et al., that nicotinic acid (niacin), not nicotinamide, in pharmacologic doses lowered human serum cholesterol levels, an avalanche of reports have been published over the past 45 years on the plasma lipid-regulating properties of this drug and its beneficial cardiovascular effects. A myriad of studies that have examined efficacy, safety, adverse effects, and pharmacologic properties of niacin rendered convincing evidence that niacin, used alone or combined with other agents, has favorable effects on serum lipoprotein regulation and on containment of atherothrombotic cardiovascular diseases. However, because of the unusual side effect profile of niacin and the availability of various formulations of this drug, niacin must be used prudently and with careful instruction and monitoring of patients. This review summarizes the pertinent and recent literature on niacin that impacts its therapeutic use. We also discuss some controversial issues and personal clinical experience and opinions on this topic.

Lovastatin: tratamiento a corto plazo de la hipercolesterolemia; ensayo clínico multicéntrico / Lovastatin: short-term treatment of hypercholesterolemia; multicenter clinical trial

El lovastatin, nuevo medicamento hiopocolesterolemiante, que inhibe la síntesis intracelular de colesterol por bloqueo de la enzima hidroxi-metil-glutaril-CoA reductasa e induce un aumento del número de receptores-LDL, fue administrado durante 12 semanas a 210 pacientes de ambos sexos con hipercolesterolemia primaria, en el primer ensayo clínico multicéntrico argentino. De los 205 pacientes que finalizaron el estudio, 48% recibió una dosis máxima de 40 mg/día, 39% 80 mg/día y 12% 20 mg/día. En la semana 12 de tratamiento se observaron las siguientes modificaciones lipídicas medias, todas ellas altamente significativas (p < 0,0001): colesterol -34%, triglicéridos -15%, colesterol-HDL + 11%, colestero-LDL -43% y relación colesterol total/colesterol-HDL -41%. El medicamento fue bien tolerado y 84% de los pacientes completó el estudio sin ninguna clase de efectos adversos. El estudio fue interrumpido en 3 pacientes (1,4%) por efectos adversos de laboratorio y clínicos moderados, mientras que completaron el mismo con efectos adversos de laboratorio leves el 3,4% y con efectos adversos clínicos, también leves, el 6,8% de los pacientes. No se observaron manifestaciones clínicas o bioquímicas de miositis, ni tampoco se registraron alteraciones del cristalino. Se concluye que el lovastatin es un medicamento hipocolesterolemiante muy eficaz, que reduce especificamente la concentración de LDL circulante y que tiene un importante efecto normolipemiante (triglicéridos, colesterol-HDL) adicional...

Lipidemia en 150 cordones umbilicales para detectar un factor de riesgo coronario. / Lipidemia in 150 umbilical cords to detect a coronary risk factor

Se establecen las concentraciones de colesterol, trigliceridos, fosfolipidos, acidos grasos libres y lipoproteinas en un primer grupo de 100 recien nacidos (55 varones, 45 mujeres) considerados clinicamente normales, no habiendose podido demostrar la existencia de diferencias en los valores entre ambos sexos. Por medio del estudio lipidico determinado en un segundo grupo de 50 cordones ubilicales se pudo confirmar, mediante el metodo de las "rectas de alerta" y "rectas de accion" la validez estadistica de la cifra del colesterol asi como de los trigliceridos plasmaticos. En este segundo grupo se determinaron, ademas, el colesterol transportado por la alfa-lipoproteina (HDL) y beta-lipoproteina (LDL). Los valores hallados en la sangre del cordon umbilical de ambos grupos son muy inferiores a los que se encuentran en etapas mas avanzadas de la vida. Debido al hecho de que la frecuencia de las alteraciones del transporte lipidico caracteristica de la hiperlipoproteinemia de tipo IIa alcanzo una cifra del 4%, se concluye que seria conveniente estudiar la lipidemia del cordon umbilical en los recien nacidos, especialmente en aquellos de "alto riesgo" que presenten historia familiar positiva para aterosclerosis precoz o muerte subita y/o evidencias de alteraciones del transporte lipidico en uno o ambos progenitores