Efficacy and safety of a biosimilar recombinant human growth hormone (r-hGH Cristalia) compared with reference r-hGH in children with growth hormone deficiency (CERES study): A randomized, multicentric, investigator-blind, phase 3 trial.

OBJECTIVE: The CERES study was a randomized, multicenter, investigator-blind trial aimed to evaluate the efficacy and safety of a recombinant human growth hormone (r-hGH) developed by Cristalia, as a biosimilar product, with analytical, functional and pharmacokinetics similarities comparable to Genotropin™, in children with growth hormone deficiency (GHD). DESIGN: A total of 135 naïve prepubertal children with GHD were recruited, of whom 97 were randomized in 14 Brazilian sites to received either r-hGH Cristalia (n = 49) or Genotropin™ (n = 48). Efficacy was evaluated considering the height standard deviation score (SDS) and growth velocity as auxological parameters, IGF-1 and IGFBP-3 were measured as pharmacodynamic parameters during 12 months treatment time. Safety was assessed by monitoring adverse events, immunogenicity, blood count with platelets, biochemical profile and hormonal levels particularly fasting glucose, insulin and HbA1C. RESULTS: The auxological parameters and IGF-1 and IGFBP-3 levels were comparable between both groups of patients. At end of study or the 12th month treatment, the means growth velocity was 9.7 cm/year and 9.5 cm/year, for r-hGH Cristalia and Genotropin™, respectively. The ANCOVA mean difference between the groups was 0.16 cm/year to Cristalia group (CI 95% = -0.72 to 1.03 cm/year). There was no difference in adherence among the treatment groups. The safety profile was comparable between groups. CONCLUSIONS: The clinical similarity between r-hGH and Genotropin™ was demonstrated within 12 month of treatment. On the basis of comparability of quality, safety, and efficacy to the reference product, r-hGH from Cristalia can be considered a cost-effective therapeutic option for patients with growth disorders.

Mini-fasting tests diagnosing endogenous hyperinsulinism: a follow-up of 26 cases.

CONTEXT: The supervised 72-h fast remains the gold standard test for the diagnosis of endogenous hyperinsulinism and has recently been suggested to be shortened or even avoided. OBJECTIVE: This study aimed to evaluate whether measurement of blood glucose, insulin and C-peptide levels after a 12 h overnight fast (mini-fasting test), in at least 3 consecutive days, could allow making or ruling out diagnosis of endogenous hyperinsulinism, according to the Endocrine Society's recent guidelines. PATIENTS AND METHODS: We performed 12 h mini-fasting test in at least 3 consecutive days, dosing blood glucose, insulin and C-peptide levels in 26 inpatient patients with pathologically proven endogenous hyperinsulinism. RESULTS: In our series, 100% of patients showed insulin levels of at least 3 µU/ml and C-peptide levels of at least 0.6 ng/ml concomitant with symptomatic hypoglycemia (≤ 55 mg/dl). CONCLUSION: It leads to the conclusion that mini-fasting test might avoid, in most cases, prolonged fasting test for the diagnosis of hypoglycemia due to endogenous hyperinsulinism.

A study comparing insulin lispro mix 25 with glargine plus lispro therapy in patients with Type 2 diabetes who have inadequate glycaemic control on oral anti-hyperglycaemic medication: results of the PARADIGM study.

AIMS: To test the hypothesis that initiation and intensification with 25% insulin lispro, 75% insulin lispro protamine suspension (LM25), is non-inferior to initiation and intensification with glargine + insulin lispro therapy on change from baseline in HbA(1c). METHODS: In this randomized, non-inferiority (margin of 0.4%), parallel, prospective, multi-country, 48-week, open-label study, patients (n = 426) with Type 2 diabetes inadequately controlled with oral anti-hyperglycaemic medications were assigned to either initiating therapy with one daily LM25 injection, progressing up to three daily injections (full analysis set n = 211; per protocol set n = 177) or initiating therapy with one daily glargine injection and progressing up to three daily insulin lispro injections (full analysis set n = 212; per protocol set n = 184). RESULTS: LM25 therapy was found to be non-inferior to glargine + insulin lispro therapy by study end (upper limit of 95% CI < 0.4), with a least-squares mean difference (95% CI) in HbA(1c) (LM25 minus glargine + insulin lispro) of -0.4 mmol/mol (95% CI -2.7 to 1.9); -0.04% (95% CI -0.25 to 0.17). No statistically significant differences between treatment groups were found in the percentage of patients achieving HbA(1c) targets or postprandial blood glucose levels. The increase in insulin dose, number of injections and weight change during the course of the study were similar in both groups. Patients in both groups experienced similar hypoglycaemia rates and safety profile. CONCLUSIONS: For patients with Type 2 diabetes inadequately controlled with oral anti-hyperglycaemic medications, glycaemic control when initiating and intensifying with LM25 therapy was found to be non-inferior to treatment with glargine + insulin lispro therapy.

Glucagon test in insulinoma: Is it useful?

Diagnosis of endogenous hyperinsulinism caused by insulinoma is based on confirmation of hypoglycemia during the symptoms associated to elevated insulin levels. Patients with insulinoma may demonstrate an excessive insulin response and subsequent hypoglycemia after 1 mg of glucagon iv injection. Glucagon test was performed in 11 patients with insulinoma before therapy and in 4 after therapy. Our study suggests that the presence of plasma glucose levels less than 55 mg/dl and below baseline at time 120 min of glucagon test strongly reinforce the diagnosis of insulinoma.

Effect of blood glucose on left ventricular mass in patients with hypertension and type 2 diabetes mellitus.

The aim of our prospective study was to evaluate the influence of blood glucose (BG) on left ventricular mass and diastolic function in patients with hypertension and type 2 diabetes mellitus (DM). Fifty-six hypertensive patients with type 2 DM and 26 healthy controls were investigated. They were submitted to echocardiography (ECHO) with Doppler and we calculated the mean of their fasting BG values, office blood pressure (OBP), cholesterol and fractions, and triglycerides during the previous 4 years. The diabetic patients were then followed-up for 1 year with OBP, fasting BG, and lipids measured every 2 months. After this period, the patients were again submitted to ECHO and in 22 patients (group I [GI]), reductions greater than 10% in left ventricular mass index (LVMI) were observed (122 +/- 35 v 89 +/- 23 g/m2, P < .01), whereas increases greater than 10% (group II [GII], n = 17) (94 +/- 18 v 115 +/- 27 g/m2, P < .01) or no changes (group III [GIII], n = 17) (98 +/- 16 v 99 +/- 18 g/m2, NS) in LVMI were detected in the remaining patients. The OBP values did not change during the follow-up. In GI the reduction of LVMI was associated with a BG fall from 178 +/- 36 to 147 +/- 30 mg/dL (P < .01) and a correlation was observed between BG and LVMI percent variations (delta) (r = 0.48, P < .01). No important changes in left ventricular diastolic function were observed during the follow-up. We concluded that the improvement in glycemic control may contribute to LVH regression in hypertensive patients with type 2 DM.