Growth hormone treatment for sustained pain reduction and improvement in quality of life in severe fibromyalgia.

Functional defects in growth hormone (GH) secretion and its efficacy as a complementary treatment have been suggested for fibromyalgia. This study investigated the efficacy and safety of low-dose GH as an add-on therapy in patients with both severe FM and low insulin-like growth factor 1 levels. A total of 120 patients were enrolled in a multicenter, placebo-controlled study for 18 months. They were randomly assigned to receive either 0.006 mg/kg/day of GH subcutaneously (group A, n=60) or placebo (group B, n=60) for 6 months (blind phase). The placebo arm was switched to GH treatment from month 6 to month 12 (open phase), and a follow-up period after GH discontinuation was performed until month 18. Standard treatment for fibromyalgia (selective serotonin re-uptake inhibitors, opioids, and amitriptyline) was maintained throughout the study. Number and intensity of tender points, Fibromyalgia Impact Questionnaire (FIQ) with its subscales, and EuroQol 5 dimensions test (EQ5D) with visual analogue scale (VAS) were assessed at different time points. At the end of the study, 53% of group A patients obtained fewer than 11 positive tender points, vs 33% of group B patients (P<.05). 39.1% vs 22.4% reached more than 50% improvement in VAS (P<.05). Group A patients showed significantly improved FIQ scores (P=.01) compared with group B. Although GH discontinuation worsened all scores in both groups during follow-up, impairment in pain perception was less pronounced in the GH-treated group (P=.05). In this largest and longest placebo-controlled trial performed in FM (NCT00933686), addition of GH to the standard treatment is effective in reducing pain, showing sustained action over time.

Proof-of-concept trial on the efficacy of sodium tungstate in human obesity.

AIM: Considering the poor long-term success of current dietary and pharmacological interventions, we aimed to evaluate the potential effect of sodium tungstate in the treatment of grade I and II obesity (ClinicalTrials.gov identifier: NCT00555074). METHODS: Prospective, randomized, placebo-controlled, double-blind, proof-of-concept study was carried out. Following a 2-week lead-in period, 30 obese (body mass index, BMI 30.0-39.9 kg/m(2)), non-diabetic subjects were randomized to receive either sodium tungstate (100 mg bid) or placebo for 6 weeks. The primary study endpoint was the absolute change in body weight relative to the time of randomization. RESULTS: Treatment with sodium tungstate [-0.135 ± 0.268 kg (95% CI -0.686 to +0.416 kg)] was not associated with a significant weight loss compared to placebo [-0.063 ± 0.277 kg (95% CI -0.632 to +0.507 kg)] (p = 0.854). Likewise, treatment with sodium tungstate was not associated with significant changes in fat mass (DEXA), resting energy expenditure (indirect calorimetry) or caloric consumption (3-day food records). CONCLUSION: Our data do not support sodium tungstate as a pharmacological agent in the treatment of human obesity.

Effects of isradipine and nifedipine retard in hypertensive patients with type II diabetes mellitus.

Twenty patients were randomized to receive either 2.5 mg isradipine twice daily or 20 mg nifedipine retard once daily for 6 months. After 2 weeks of placebo wash-out, evaluations were carried out every 4 weeks. These evaluations included assessment of blood pressure, lipid profile, hemoglobin A1 sigma glucagon, C peptide, and insulin requirements. Both isradipine and nifedipine retard lowered systolic and diastolic blood pressures to normal values (P < .001). However, isradipine was accompanied by a decrease in heart rate (P < .005). Neither drug modified hemoglobin A1c or the glycemic profile. The endogenous insulin-secretion response decreased in both treatment groups (P < .05). In conclusion, isradipine and nifedipine retard are efficacious in the treatment of hypertension in patients with type II diabetes mellitus, and neither treatment produces modification of metabolic control.

Effect of treatment with an inhibitor of platelet aggregation on the evolution of background retinopathy: 2 years of follow-up.

Ophthalmic evolution was studied for 2 years in 17 patients with insulin-dependent diabetes mellitus and background diabetic retinopathy. Nine patients were treated with triflusal, a new platelet antiaggregant drug, and the eight remaining patients, with similar clinical and biological characteristics, were considered the control group. At the end of the study the ophthalmic evolution was different in the two groups. In the control group the degree of fluorescein leakage and the number of microaneurysms increased, while in the triflusal-treated group both parameters were reduced. There were no differences in visual acuity and computerised perimetry between the groups. Our results suggest that platelet antiaggregant therapy can be useful in the treatment of background diabetic retinopathy.

Suppression by insulin treatment of glucose-induced inhibition of insulin release in non-insulin-dependent diabetics.

Although restoration of normoglycemia in non-insulin-dependent diabetic subjects improves insulin release evoked by several secretagogues, conflicting data were reported concerning the effect of intensive insulin therapy on the first-phase response of the B-cell to an intravenous glucose challenge. In the present study, 14 non-insulin-dependent diabetics underwent an intravenous glucose test performed before and after 20 h of glycemic normalization. Before insulin treatment, glucose failed, as a rule, to provoke an early positive secretory response. On the contrary, a paradoxical inhibition of insulin release was observed in most patients. This phenomenon was reproducible when a second test was performed 120 min after the first one. The paradoxical inhibition was not observed any more after glycemic normalization. As judged from the paired difference (delta) between the early increment in insulin release before and after insulin treatment, normoglycemia resulted in an improved secretory response (delta greater than 5.0 microU/ml) in seven patients, whilst the first-phase response remained little affected (delta less than 3.0 microU/ml) in the other seven subjects. These findings suggest that an impaired first-phase response to glucose does not always represent an irreversible primary defect of the pancreatic B-cell in diabetic subjects.

Antihypertensive therapy with guanfacine induces elevated plasma growth hormone levels in diabetic patients.

Guanfacine, a central alpha-adrenoreceptor agonist, may increase growth hormone (GH) secretion. We have investigated the effect of guanfacine upon plasma GH levels in 16 hypertensive non-insulin-dependent diabetic (NIDD) patients. Guanfacine (1 to 2 mg/day/os) was administered for six months, and GH measured in basal plasma samples before and after treatment with this drug. Our results show an increase in GH plasma levels after guanfacine administration (2.88 +/- 2.05 ng/ml (X +/-SD) before, and 4.37 +/- 1.80 ng/ml (X +/- SD) after treatment). Since it is believed that GH levels plays a role in the course of diabetic retinopathy, caution should be taken with guanfacine antihypertensive treatment in patients affected with diabetes mellitus.

The effect of hypoglycemic sulfonylureas on human red blood cell transglutaminase activity.

We have examined the effect of glipizide, a hypoglycemic sulfonylurea, upon transglutaminase activity in human red blood cells. In a first series of experiments the in vitro effect of the drug was assessed. The results obtained showed that glipizide inhibits transglutaminase activity in human red blood cells. In a second approach, glipizide was administered orally to six type 2 diabetic patients during 3 months, in order to evaluate the long-term effect upon transglutaminase activity. Again, glipizide induced a significant decrease in the enzyme activity in blood red cells (P less than 0.01). We suggest that treatment of type 2 diabetes mellitus with hypoglycemic sulfonylureas could improve insulin effects by inhibiting cellular transglutaminase activity.

[Effect of tolbutamide on the activity of transglutaminase]. / Efecto de la tolbutamida sobre la actividad transglutaminasa.

Five obese patients were studied during 7 days, 750 mg of tolbutamide, per os, was given. Blood samples were drawn at basal state and at 3, 5, 7 days during the treatment and 6 days after it. The values of transglutaminase activity (that in the basal state were similar to that in the controls) decreased significantly at the seventh day of treatment (72.3%). This decrease was transient and rapidly returned to the basal values when the drug was suspended. The results suggest that sulfonylureas exert in part their hypoglucemic effect by modificating the insulin receptor binding through the inhibition of transglutaminase activity.

Acute effect of glibenclamide upon red cell transglutaminase activity in diabetic patients.

The acute effect of glibenclamide, a hypoglycemic sulfonylurea, upon transglutaminase activity was investigated in 6 type II diabetic patients by perfusing 1 mg glibenclamide during 1 h. Blood samples were drawn 0, 10, 20, 30, 60 min during and 30 and 60 min after perfusion to determine insulin, glucose and transglutaminase activity. No significant modifications in plasma insulin, plasma glucose and transglutaminase activity in red cells was induced by glibenclamide perfusion. Nevertheless, glibenclamide induced a significant decrease (p less than 0.005) in transglutaminase activity after 20 min of perfusion (629.83 +/- 53.08 and 521.18 +/- 43.92, mean +/- SE, at 0 and 20 min). No correlation was observed between glucose or insulin plasma levels and transglutaminase activity.