Silvia Manfrini

No protective effect of calcitriol on β-cell function in recent-onset type 1 diabetes the IMDIAB XIII trial.

OBJECTIVE We investigated whether supplementation of the active form of vitamin D (calcitriol) in recent-onset type 1 diabetes can protect β-cell function evaluated by C-peptide and improve glycemic control assessed by A1C and insulin requirement. RESEARCH DESIGN AND METHODS Thirty-four subjects (aged 11–35 years, median 18 years) with recent-onset type 1 diabetes and high basal C-peptide >0.25 nmol/l were randomized in a double-blind trial to 0.25 μg/day calcitriol or placebo and followed-up for 2 years. RESULTS At 6, 12, and 24 months follow-up, A1C and insulin requirement in the calcitriol group did not differ from the placebo group. C-peptide dropped significantly (P < 0.001) but similarly in both groups, with no significant differences at each time point. CONCLUSIONS At the doses used, calcitriol is ineffective in protecting β-cell function in subjects (including children) with recent-onset type 1 diabetes and high C-peptide at diagnosis.

Environmental risk factors for type 1 diabetes in Rome and province

Background: In subjects genetically susceptible to type 1 diabetes, exposure to environmental factors during the gestational period, the neonatal period, and the first years of life is thought to play an important role in triggering the immune process leading to β cell destruction. Aims: To investigate risk factors for inhabitants of continental Italy. Methods: A case-control study of 150 type 1 diabetes cases and 750 control subjects (age range 6–18 years) was carried out in Rome and its province, measuring the exposure to environmental risk factors. Results: Three environmental factors were found to occur significantly more in the diabetic group than in the controls. During the mothers’ pregnancies, the one risk factor which proved to be higher in diabetics than in controls was maternal infectious disease. During the neonatal period, no risk factors associated with the disease were detected. During early life, eczema and a short duration of breast feeding (less than three months), occurred significantly more in diabetic cases than controls. Conclusion: Eczema and breast feeding for less than three months are risk factors for type 1 diabetes in a southern European population. The type, duration, and mode of treatment for infectious diseases during pregnancy need additional investigation as risk factors for type 1 diabetes.

Residual insulin secretion at diagnosis of type 1 diabetes is independently associated with both, age of onset and HLA genotype.

We investigated whether residual insulin secretion and metabolic derangement at diagnosis of type 1 diabetes (T1DM) are influenced by human leukocyte antigens (HLA) class II genes.

TNF-α and growth hormone resistance in patients with chronic liver disease

Liver cirrhosis is characterized by a severe impairment of the growth hormone/insulin-like growth factor-1 (GH-IGF-1) axis, that is, acquired GH resistance. The condition of the GH-IGF-1 axis in the phase of chronic liver disease (CLD) preceding cirrhosis, however, remains uncertain. The origin of GH resistance during CLD is multifactorial, and to date, the liver functional mass is considered to play a major role. Although proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, were found to be elevated in patients with CLD and were shown to induce a state of GH resistance in other disease models, their involvement in the pathogenesis of GH resistance during CLD has never been investigated. We characterized the GH-IGF-1 axis by analyzing the individual components of the axis (GH, IGF-1, IGF-binding protein-3 [IGFBP-3], acid-labile subunit [ALS]) and the corresponding ratios (GH/IGF-1, GH/IGFBP-3, and GH/ALS) and verified the links with circulating proinflammatory cytok...

Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity.

Although there is an evidence of correlation between irisin and osteoporotic fractures, previous studies have not elucidated the relationship between irisin and either lean or fat mass. The main aim of this study is to investigate the relationship between irisin and body composition in postmenopausal women with osteoporosis and the impact of irisin levels on fragility vertebral fractures.

A 2-Year Pilot Trial of Continuous Subcutaneous Insulin Infusion Versus Intensive Insulin Therapy in Patients with Newly Diagnosed Type 1 Diabetes (IMDIAB 8)

In a pilot study, the metabolic effects of continuous subcutaneous insulin infusion (CSII) versus intensive subcutaneous insulin therapy (ISIT) started at diagnosis in patients with Type 1 diabetes and continued for a 2-year period were evaluated and compared. Twenty-three patients (between 12 and 35 years old, mean +/- SD 18.4 +/- 9 years) were randomized into two treatment groups (CSII vs. ISIT), and both received supplemental nicotinamide (NA), 25 mg/kg of body weight. CSII was started immediately after admission to the hospital. Parameters of metabolic control [insulin dose, hemoglobin A1c (HbA1c), and C-peptide] were evaluated for a 2-year follow-up period. Data are presented for a total of 19 patients who remained in the study for its duration. Two years after diagnosis, mean +/- SD HbA1c was 6.3 +/- 0.5% and 6.2 +/- 0.3% for the CSII and ISIT groups, respectively (p=not significant). Compared with baseline values, an increase of baseline C-peptide of 38% for the CSII group and 27% for the ISIT group was observed; however, the difference between the groups was not significant. The insulin requirement for the entire duration of the study, but not at entry and 3 months, was significantly higher in CSII compared with ISIT patients (0.62 +/- 0.4 IU/kg/day vs. 0.3 +/- 0.4 IU/kg/day, respectively; p<0.01). After trial completion patients on CSII continued with this mode of therapy. Implementation of CSII as well as ISIT at diagnosis of Type 1 diabetes and continuation for 2 years thereafter achieved similar and optimal metabolic control, but more insulin was required with the CSII group. Both types of intensive insulin therapy combined with NA are able to preserve C-peptide secretion or even increase baseline levels for up to 2 years after diagnosis.

BMI and BMD: The Potential Interplay between Obesity and Bone Fragility

Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specifically, Visceral Adipose Tissue (VAT) may potentially prove detrimental. It is widely acknowledged that obesity is positively associated to many chronic disorders such as metabolic syndrome, dyslipidemia and type 2 diabetes, conditions that could themselves affect bone health. Although aging is largely known to decrease bone strength, little is yet known on the mechanisms via which obesity and its comorbidities may contribute to such damage. Given the exponentially growing obesity rate in recent years and the increased life expectancy of western countries it appears of utmost importance to timely focus on this topic.

Detection of insulitis by pancreatic scintigraphy with 99mTc-labeled IL-2 and MRI in patients with LADA (Action LADA 10)

OBJECTIVE Pancreatic scintigraphy with interleukin-2 radiolabeled with 99mTc (99mTc-IL-2) is a technique used to image chronic inflammatory-mediated disorders. We used this method to detect a signal consistent with the presence of insulitis in patients with autoimmune diabetes. Positive and negative controls (patients with pancreatic carcinoma and type 2 diabetes, respectively) also were studied. RESEARCH DESIGN AND METHODS We examined 25 patients with autoimmune diabetes (16 with recently diagnosed type 1 diabetes, 9 with latent autoimmune diabetes in adults [LADA]), 6 with type 2 diabetes, and 7 with pancreatic carcinoma (the latter two groups were used as negative and positive controls, respectively). All patients underwent 99mTc-IL-2 scintigraphy and contrast-enhanced MRI of the pancreas. To validate positive controls, samples were taken from patients with pancreatic carcinoma during surgery for histological and immunohistochemical investigations. RESULTS Pancreatic accumulation of 99mTc-IL-2 was detected in patients with autoimmune diabetes (61% positive) and, notably, in 6 of 9 patients with LADA; semiquantitative evaluation of pancreatic uptake of 99mTc-IL-2 showed higher values in patients with autoimmune diabetes (both childhood and LADA) and pancreatic carcinoma than in those with type 2 diabetes (4.45 ± 1.99, 4.79 ± 1.1, and 4.54 ± 1.62 vs. 2.81 ± 0.63; P = 0.06, P = 0.01, and P = 0.04, respectively). In patients with pancreatic carcinoma, pancreatic interleukin-2 receptor expression correlated with pancreatic 99mTc-IL-2 uptake (r = 0.8; P = 0.01). In patients with LADA, 99mTc-IL-2 uptake inversely correlated with duration of disease (r = 0.7; P = 0.03). CONCLUSIONS Autoimmune diabetes in adults is associated with increased pancreatic 99mTc-IL-2 uptake, indicating the presence of insulitis, particularly within 1 year of the beginning of insulin therapy, similar to type 1 diabetes at diagnosis.

PTH(1-34) for Surgical Hypoparathyroidism: A Prospective, Open-Label Investigation of Efficacy and Quality of Life.

CONTEXT Conventional therapy for hypoparathyroidism consists of calcium and calcitriol, but sometimes normal serum calcium cannot be maintained, and/or this approach might lead to nephrocalcinosis, nephrolithiasis, or renal insufficiency. OBJECTIVE The objective of the study was to investigate the effects of 6 months of PTH(1-34) treatment in adult subjects with postoperative hypoparathyroidism and to evaluate quality-of-life changes. DESIGN This was a 2-year prospective, open-label study. At baseline and after 6 months of PTH(1-34) treatment, calcium and vitamin D supplementation requirements, serum calcium, phosphate, creatinine, alkaline phosphatase, uric acid, and 24-hour urinary calcium excretion were evaluated. Quality of life was evaluated by the Rand 36-Item Short Form Health Survey covering eight domains of physical and mental health. SETTING This was an Italian multicentric study. PARTICIPANTS Participants included 42 subjects with surgical hypoparathyroidism (90% females, age range 34-77 y). INTERVENTION The intervention included a twice-daily PTH(1-34) 20 μg sc injection. RESULTS The mean serum calcium levels significantly increased from baseline to 15 days (7.6 ± 0.6 vs 9.1 ± 0.9 mg/dL, P < .001) and remained stable until the end of the observational period, despite a significant reduction in calcium and vitamin D supplementation. Phosphate levels gradually decreased from baseline to the sixth month (P = .005 for the trend), whereas the alkaline phosphatase increased (P < .001). Data from the Rand 36-Item Short Form Health Survey showed a significant improvement in the mean scores of all eight domains (P < .001). CONCLUSION This is the largest study that demonstrates the effectiveness of PTH(1-34) in the treatment of adult patients with postsurgical hypoparathyroidism, and it shows that PTH(1-34) may improve the mental and physical health in hypoparathyroid subjects.

A Novel Insulin Unit Calculator for the Management of Type 1 Diabetes

BACKGROUND Intensive insulin therapy is the gold standard therapy for type 1 diabetes (T1D) patients. To achieve optimal glycemic control, adjustments of insulin dose at mealtimes must be made taking into account several parameters: blood glucose levels, insulin/carbohydrate ratio, carbohydrate intake, and physical activity. Calsulin (Thorpe Products Ltd., Cambridge, UK) is a new tool for the administration of insulin dose before each meal. The aim of this study was to evaluate the efficacy of Calsulin on metabolic control in T1D patients undergoing intensive insulin therapy. SUBJECTS AND METHODS Forty consecutive patients affected by T1D, 18-65 years old, with disease duration of >1 year, were randomized to Calsulin or to the control group. Hemoglobin A1c (HbA1c) was evaluated at entry into the study and at 3- and 6-month follow-ups. Paired t test (two tailed) and analysis of variance were used to evaluate differences in HbA1c at 3 and 6 months in the two groups. RESULTS HbA1c at entry was 7.9 ± 1.0% (SD) in the Calsulin-treated group and 7.8 ± 1.6% (SD) in control patients (P not significant). Data showed a slight improvement in HbA1c levels at 3 months in the Calsulin-treated group (-0.61% vs. -0.14% difference, respectively; P not significant). At the 6-month follow-up, a significant reduction in HbA1c levels was observed in the Calsulin-treated group versus the control group (-0.85% vs. -0.07% difference, respectively; P < 0.05). CONCLUSIONS Calsulin is an acceptable and practical tool that makes the process of calculating insulin doses easy to use, and, most importantly, it improves metabolic control as shown by a significant reduction of HbA1c levels.