Utility of C-peptide for a reliable estimate of insulin secretion in children with growth hormone deficiency.

OBJECTIVE: GH treatment (GHT) can lead to glucose metabolism impairment through decreased insulin sensitivity and impaired pancreatic β-cell function, which are the two key components of the pathogenesis of diabetes. Therefore, in addition to insulin sensitivity, during GHT it is very important to perform a reliable evaluation of insulin secretion. However, conflicting data exist regarding the insulin secretion in children during GHT. C-peptide provides a more reliable estimate of β-cell function than insulin, but few studies evaluated it during GHT. Our aim was to assess the usefulness of C-peptide in the evaluation of insulin secretion in GH deficiency (GHD) children. DESIGN: In 48 GHD children, at baseline and after 12 and 24months of GHT, and in 56 healthy subjects we evaluated fasting and glucagon-stimulated (AUCCpep) C-peptide levels in addition to other commonly used secretion indexes, such as fasting and oral glucose tolerance test-stimulated insulin levels (AUCINS), Homa-β, and insulinogenic index. The main outcomes were the change in C-peptide during GHT and its correlation with the auxological and hormonal parameters. RESULTS: At baseline GHD children showed a significant lower AUCCpep (p=0.006), while no difference was found for the other indexes. Both fasting C-peptide (beta 0.307, p=0.016) and AUCCpep (beta 0.379, p=0.002) were independently correlated with IGF-I SDS, while no correlation was found for all other indexes. After 12months an increase in Homa-β (p<0.001), fasting C-peptide (p=0.002) and AUCCpep (p<0.001) was found. At multivariate analysis, only fasting C-peptide (beta 0.783, p=0.001) and AUCCpep (beta 0.880, p<0.001) were independently correlated with IGF-I SDS. CONCLUSIONS: C-peptide, rather than the insulin-derived indexes, has proved to be the most useful marker of insulin secretion correlated to IGF-I levels in GHD children. Therefore, we suggest the use of glucagon test both as diagnostic test for the GH assessment and as a useful tool for the evaluation of insulin secretion during GHT in children

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency

The visceral adiposity index, based on anthropometric and metabolic parameters, has been shown to be related to adipose tissue function and insulin sensitivity. We aimed to evaluate the performance of the visceral adiposity index in adult patients with growth hormone deficiency. We enrolled 52 patients(mean age 51\u2009\ub1\u200913 years) with newly diagnosed growth hormone deficiency and 50 matched healthy subjects as controls at baseline. At baseline and after 12 and 24 months of treatment we evaluated anthropometric measures, lipid profile, glucose and insulin during an oral glucose tolerance test, hemoglobin A1c, homeostasis model assessment estimate of insulin resistance, quantitative insulin sensitivity check index, insulin sensitivity index Matsuda, insulin-like growth factor-I and visceral adiposity index. At baseline growth hormone deficiency patients showed higher waist circumference (p\u2009<\u20090.001), low-density lipoprotein cholesterol (p\u2009<\u20090.001) and visceral adiposity index (p\u2009=\u20090.003) with lower insulin sensitivity index (p\u2009=\u20090.007) and high-density lipoprotein cholesterol (p\u2009=\u20090.001) than controls. During growth hormone treatment we observed a significant increase in insulin-like growth factor-I (p\u2009<\u20090.001), high-density lipoprotein (p\u2009<\u20090.001) with a trend toward increase in insulin sensitivity index (p\u2009=\u20090.055) and a significant decrease in total cholesterol (p\u2009<\u20090.001) and visceral adiposity index (p\u2009<\u20090.001), while no significant changes were observed in other clinical and metabolic parameters. The visceral adiposity index was the only parameter that significantly correlated with growth hormone peak at diagnosis (p\u2009<\u20090.001) and with insulin-like growth factor-I and insulin sensitivity index both at diagnosis (p\u2009=\u20090.009 and p\u2009<\u20090.001) and after 12 (p\u2009=\u20090.026 and p\u2009=\u20090.001) and 24 months (p\u2009<\u20090.001 and p\u2009=\u20090.001) of treatment. The visceral adiposity index, which has shown to be associated with both insulin-like growth factor-I and insulin sensitivity, proved to be the most reliable index of metabolic perturbation, among the most common indexes of adiposity assessment and a marker of benefit during treatment in adult growth hormone deficiency patients

Corneal thickness in children with growth hormone deficiency: The effect of GH treatment.

Abstract OBJECTIVE: The eye represents a target site for GH action, although few data are available in patients with GH deficiency (GHD). Our aim was to evaluate central corneal thickness (CCT) and intraocular pressure (IOP) values in GHD children to assess the role played by GHD or GH treatment on these parameters. DESIGN: In 74 prepubertal GHD children (51M, 23F, aged 10.4\ub12.4years) we measured CCT and IOP before and after 12months of treatment. A baseline evaluation was also made in 50 healthy children matched for age, gender and body mass index. The study outcome considered CCT and IOP during treatment and their correlations with biochemical and auxological data. RESULTS: No difference in CCT and IOP between GHD children at baseline and controls was found (all p>0.005). GHD children after 12months of therapy showed greater CCT (564.7\ub113.1\u3bcm) than both baseline values (535.7\ub117\u3bcm; p<0.001) and control subjects (536.2\ub112.5\u3bcm; p<0.001), with a concomitantly higher corrected mean IOP (15.6\ub10.7mmHg; p<0.001) than both baseline (12.5\ub10.8mmHg; p<0.001) and controls (12.3\ub10.5mmHg; p<0.001), without correlation with auxological and biochemical parameters. CONCLUSIONS: 12months of GH treatment in children with GHD, regardless of auxological and biochemical data, affect CCT and IOP. Our findings suggest careful ocular evaluation in these patients to prevent undesirable side effects during the follow-up

Liraglutide Improves Cardiovascular Risk as an Add-on to Metformin and Not to Insulin Secretagogues in Type 2 Diabetic Patients: A Real-life 48-Month Retrospective Study.

INTRODUCTION: Although liraglutide is widely recognized to have glycemic and extra-glycemic effects, few studies have compared these effects in relation to hypoglycemic treatment starting from the diagnosis of diabetes. We evaluated the effectiveness of liraglutide in reducing the Framingham risk score (FRS) and visceral adiposity index (VAI) in relation to first-line hypoglycemic treatment from diagnosis of type 2 diabetes, continued without any changes. METHODS: We selected 105 diabetic outpatients who were treated with liraglutide for at least 48 months as an add-on therapy to metformin alone (group A, n = 52) or insulin secretagogues (group B, n = 53) from diagnosis time. RESULTS: Although both groups showed a reduction in BMI, waist circumference, blood pressure, HbA1c and triglycerides, only group A showed a significant reduction in FRS (p &lt; 0.001) and VAI (p = 0.012) after 48 months. No significant intergroup difference was found for any parameters at either baseline or 48 months, with the exception of FRS at 48 months, lower in group A (p = 0.002), regardless of duration of disease, improvement in glycemic control and VAI. CONCLUSION: Our data show that during a 48-month follow-up liraglutide was more efficacious in reducing cardiovascular risk than when it was used as add-on therapy to the first-line therapy from diagnosis with metformin and not with insulin secretagogues

One Year of Dapaglifozin Add-On Therapy Ameliorates Surrogate Indexes of Insulin Resistance and Adiposity in Patients with Type 2 Diabetes Mellitus

Introduction: This study investigates the effects of dapagliflozin on the visceral adiposity index (VAI), lipid accumulation product (LAP), product of triglycerides and glucose (TyG) and triglycerides to HDL-cholesterol ratio (TG/HDL-C) in patients with type 2 diabetes mellitus (T2D). Methods: In this real-life study, dapaglifozin was added to metformin alone (group 1, no. 42) or insulin plus metformin (group 2, no. 58) in 100 T2D patients. Results: In group 1, after 6 months of dapaglifozin addition, a significant decrease in BMI (p &lt; 0.001), waist circumference (WC) (p &lt; 0.001), systolic blood pressure (SBP) (p = 0.009), diastolic blood pressure (DBP) (p = 0.012), mean fasting blood glucose (FBG), post-breakfast glucose (PBG), post-lunch glucose (PLG) and post-dinner glucose (PDG) (all p &lt; 0.001), HbA1c (p &lt; 0.001), VAI (p = 0.020), LAP (p = 0.028), Tyg (p &lt; 0.001), TG/HDL-C (p = 0.020) and glutamate pyruvate transaminase (GPT) (p &lt; 0.001) was observed compared to baseline. After 12 months a significant decrease in BMI (p &lt; 0.001), WC (p = 0.006), SBP (p = 0.023), DBP (p = 0.005), mean FPG, PBG, PLG and PDG (all p &lt; 0.001), HbA1c (p &lt; 0.001), total cholesterol (p = 0.038), triglycerides (p = 0.026), VAI (p = 0.013), GPT (p &lt; 0.001), LAP index (p = 0.024), Tyg index (p &lt; 0.001) and TG/HDL-c ratio (p = 0.016) was observed compared to baseline. In group 2, after 6 months of dapaglifozin addition, a significant decrease in BMI (p &lt; 0.001), WC (p &lt; 0.001), SBP (p = 0.015), DBP (p = 0.007), mean FPG, PBG, PLG and PDG (all p &lt; 0.001), HbA1c (p &lt; 0.001), VAI (p = 0.040), LAP (p = 0.047), Tyg (p &lt; 0.001), TG/HDL-C (p = 0.048) and GPT (p &lt; 0.001) was observed compared to baseline. By contrast, after 12 months a significant decrease in BMI (p &lt; 0.001), WC (p &lt; 0.001), SBP (p = 0.001), DBP (p = 0.002), mean FPG, PBG, PLG and PDG (all p &lt; 0.001), HbA1c (p &lt; 0.001), GPT (p &lt; 0.001) and Tyg index (p = 0.003) was observed compared to baseline. Conclusions: Dapagliflozin treatment significantly reduced surrogate indexes of insulin resistance and adiposity in patients with T2D

More favorable metabolic impact of three-times-weekly versus daily growth hormone (GH) treatment in na\uefve GH-deficient children

OBJECTIVE: Growth hormone treatment (GHT) is commonly administered daily, although pulsatile GH secretion is unlikely to be achieved. The auxological effect of a three-injections-per-week (TIW) regimen is controversial, while the metabolic effects have been never evaluated in children. The objective was to evaluate whether two different regimens of weekly injections could lead to similar auxological and metabolic effects in children with GH deficiency (GHD). DESIGN: 32 GHD children (25 males, mean age 10.5 \ub1 2.2 yr) were randomly assigned to receive daily (group A, No 16) or TIW (group B, No 16) GHT for 12 months. METHODS: Auxological parameters, insulin-like growth factor-I (IGF-I), glucose and insulin during OGTT, glycosylated hemoglobin (HbA1c), lipid profile, the oral disposition index (DIo), the homeostasis model assessment estimate of insulin resistance (Homa-IR) and the insulin sensitivity index (ISI). RESULTS: After 12 months, both groups showed a significant and comparable improvement in height (p<0.001) and IGF-I (p<0.001). As regards the metabolic parameters, in both groups we found a significant increase in fasting insulin (p<0.001 and p=0.026) and Homa-IR (p<0.001 and p=0.019). A significant increase in fasting glucose (p=0.001) and a decrease in ISI (p<0.001) and DIo (p=0.002) were only found in group A. CONCLUSIONS: The TIW regimen is effective and comparable with the daily regimen in improving auxological parameters and has a more favorable metabolic impact in GHD children (www.ClinicalTrials.gov. NCT03033121)

Dual-release hydrocortisone improves hepatic steatosis in patients with secondary adrenal insufficiency: A real-life study

Background: Conventional glucocorticoid treatment has a significant impact on liver in patients with adrenal insufficiency. Dual-release hydrocortisone (DR-HC) provides physiological cortisol exposure, leading to an improvement in anthropometric and metabolic parameters. We aimed to evaluate the effects of 12-month DR-HC treatment on the hepatic steatosis index (HSI), a validated surrogate index of hepatic steatosis, in patients with secondary adrenal insufficiency (SAI). Methods: A total of 45 patients with hypopituitarism, 22 with hypogonadism, hypothyroidism, ACTH, and GH deficiencies, and 23 with hypogonadism, hypothyroidism, and ACTH deficiency, on replacement therapy for all the pituitary deficiencies, were switched from conventional hydrocortisone to DR-HC. At baseline and after 12 months, glucose and insulin levels, surrogate estimates of insulin sensitivity, and hepatic steatosis were evaluated through ultrasonography and HSI. Results: At diagnosis, ultrasonography documented steatosis in 31 patients (68.8%) while 33 (73.3%) showed high HSI. Hydrocortisone (HC) dose (beta = 1.231, p = 0.010), insulin resistance index (HOMA-IR) (beta = 1.431, p = 0.002), and insulin sensitivity index (ISI)-Matsuda (beta = -1.389, p = 0.034) were predictors of HSI at baseline. After 12 months of DR-HC, a significant decrease in body mass index (BMI) (p = 0.008), waist circumference (WC) (p = 0.010), fasting insulin (p = 0.041), HOMA-IR (p = 0.047), HSI (p &lt; 0.001) and number of patients with HSI &gt; 36 (p = 0.003), and a significant increase in sodium (p &lt; 0.001) and ISI-Matsuda (p = 0.031) were observed. HOMA-IR (beta = 1.431, p = 0.002) and ISI-Matsuda (beta = -9.489, p &lt; 0.001) were identified as independent predictors of HSI at 12 months. Conclusions: In adults with SAI, DR-HC is associated with an improvement in HSI, regardless of the dose used, mainly related to an improvement in insulin sensitivity

Correlation between adrenal function, growth hormone secretion, and insulin sensitivity in children with idiopathic growth hormone deficiency

Purpose Patients with growth hormone deficiency (GHD) demonstrate an increased cortisol/cortisone ratio which could potentially explain the metabolic features of GHD, while GH treatment (GHT) could increase the cortisol metabolism. Methods In 35 children (27 M, mean age 10.1 years) with idiopathic GHD at baseline and after 12 months of GHT and in 25 controls, in addition to metabolic parameters, we assessed adrenal function by morning serum cortisol, its peak, and its area under the curve (AUCCOR) during insulin tolerance test (ITT). Results A cortisol peak <18 \ub5g/dl was shown in 22 and 31% of GHD children at baseline and after GHT, respectively. At baseline, GHD children had lower fasting glucose (p < 0.001) and ISI-Matsuda (p = 0.042), with concomitant higher Homa-IR (p = 0.006) and morning cortisol (p = 0.012) than controls. Morning cortisol was negatively correlated with GH (p < 0.001), fasting glucose (p < 0.001) and ISI-Matsuda (p < 0.001) and positively with Homa-IR (p = 0.010). Both cortisol peak and AUCCOR were negatively correlated with GH (all p < 0.001) and ISI-Matsuda (p = 0.016 and p = 0.001, respectively). After 12 months of GHT, a significant increase in fasting glucose (p < 0.001), and Homa-IR (p = 0.011) was documented, with a concomitant decrease in morning cortisol (p = 0.002), AUCCOR (p = 0.038), total (p = 0.003) and LDL-cholesterol (p = 0.016). No significant correlations were found among cortisol levels and all parameters were investigated. Conclusions Cortisol levels correlate with GH secretion and with many metabolic parameters in GHD children, while the metabolic effects during GHT are mainly due to GHT per se and less to cortisol reduction

Diabetic foot ulcers: Retrospective comparative analysis from Sicily between two eras

Aim: The aim of this study was to analyze changes in the incidence, management and mortality of DFU in Sicilian Type 2 diabetic patients hospitalized between two eras, i.e. 2008-2013 and 2014-2019. Methods: We compared the two eras, era1: 2008-13, era2: 2014-19. In era 1, n = 149, and in era 2, n = 181 patients were retrospectively enrolled. Results: In the population hospitalized for DFU in 2008-2013, 59.1% of males and 40.9% of females died, whilst in 2014-2019 65.9% of males and 34.1% of females died. Moderate chronic kidney disease (CKD) was significantly higher in patients that had died than in ones that were alive (33% vs. 43%, p &lt; 0.001), just as CKD was severe (14.5% vs. 4%, p &lt; 0.001). Considering all together the risk factors associated with mortality, at Cox regression multivariate analysis only moderate-severe CKD (OR 1.61, 95% CI 1.07-2.42, p 0.021), age of onset greater than 69 years (OR 2.01, 95% CI 1.37-2.95, p &lt;0.001) and eGFR less than 92 ml/min (OR 2.84, 95% CI 1.51-5.34, p 0.001) were independently associated with risk of death. Conclusions: Patients with DFU have high mortality and reduced life expectancy. Age at onset of diabetic foot ulcer, eGFR values and CKD are the principal risk factors for mortality