Paolo Caradonna

Circadian rhythm of immunoreactive insulin under glycemic stimulus

Abstract Five diabetic non‐obese males, non‐insulin dependent, and five healthy subjects were given three constant glucose loads (50 g per os) at the same intervals (08.00 hr; 16.00 hr; 00.00 hr). Blood glucose and plasma immunoreactive insulin (IRI) were measured before and 1 hr after the glucose loads. The test was repeated three days later, with varied glucose loads sequence: the 1st glucose load was given at 16.00 hr. In the controls the net increase of blood glucose was less in the morning than in the afternoon and at night. The insulin response to oral glucose exhibits a cyclic pattern with a peak in the morning, which was unaltered by prolonging the period of caloric deprivation. In the diabetics both basal values and the net increases of blood glucose (AG) were higher in the morning, decreasing in the afternoon and reaching the trough during the night. No clear pattern of cyclicity could be demonstrated in respect of insulin response to glucose.

Analysis of the globins from fast human haemoglobins by isoelectrofocusing on polyacrylamide gel rods

The globins from all fast haemoglobin (Hb) components obtainable by Bio-Rex 70 cation-exchange chromatography were examined by isoelectrofocusing on polyacrylamide gel rods with 8.0 mol/l urea. From this analysis HbA1a1 and HbA1a2 seem to be very heterogeneous components. HbA1b is separable into two components, one of which is varied in both the beta chains. Between HbA1b2 and the well-known HbA1c components two chromatographic peaks are separated, one with a noticeable percentage of glucosylated beta chain and one that probably contains HbF. HbA1c has both beta chains glucosylated, while HbA1x seems to be a beta monoglucosylated Hb form. Finally, the early part of the HbAo peak has a large amount of glucosylation on both alpha and beta chains.

Determination of the non-enzymatic glycation of hemoglobin by isoelectrofocusing of its globin chains

Micro cation exchange chromatography determination of HbA1c does not provide a complete picture of Hb glycation, for it does not determine all the glycated forms of hemoglobin. For the determination of total glycation, we describe here a rod IEF method, which allows the simultaneous quantitation of glycation on alpha and beta globin chains. The method exhibits good sensitivity; it is not affected by artifacts deriving from temperature, hypertriglyceridemia, Hb variants or labile HbA1 (aldiminic Hb). The results obtained indicate that in a normal population approximately 18% of the beta chain and 8% of the alpha chain are glycated. These mean percentages increase in the diabetic to 28% and 12%, respectively. The beta chain is glycated on both valine and lysine residues, while the alpha chain is glycated only on the latter. HbA1 values from micro cation exchange chromatography are significantly related to both alpha and beta glycation. Thus, valinic or lysinic glycation have roughly the same clinical significance.

Ketoalkalosis as a result of triple derangement of acid-base equilibrium in a diabetic patient

SummaryA diabetic patient presented with weight loss, ketosis, and hyperventilation, thus mimicking the clinical picture of diabetic ketoacidosis. Laboratory investigations revealed alkalemia and a pattern consistent with a triple derangement of acid-base equilibrium: respiratory alkalosis, metabolic acidosis and metabolic alkalosis. High cortisol level suggested a genesis of ketosis different from diabetes mellitus. The patient died suddenly from acute gastrointestinal bleeding. Autopsy showed a carcinoma of the head of the pancreas with secondary portal hypertension and rupture of varices. Pulmonary micrometastases were demonstrated. It is suggested that stress hormones were the main cause of the ‘ketoalkalotic’ pattern observed.

Decreased bone mineral density in Costello syndrome

INTRODUCTION Costello syndrome (CS) is a multisystemic disorder characterized by postnatal reduced growth, facial dysmorphism, cardiac defects, cognitive impairment, skin and musculo-skeletal anomalies, and predisposition to certain cancers. CS is caused by activating germline mutations in the HRAS proto-oncogene. Similar to what is observed in other RASopathies, CS causative HRAS mutations promote enhanced signal flow through the RAF-MEK-ERK and PI3K-AKT signaling cascades. While decreased bone mineralization has been documented in other RASopathies, such as neurofibromatosis type 1 and Noonan syndrome, systematic studies investigating bone mineral density (BMD) are lacking in CS. MATERIALS AND METHODS Dual-energy X-ray absorptiometry (DXA) was utilized to assess BMD and body composition (fat and fat-free mass) in a cohort of subjects with molecularly confirmed diagnosis of CS (n = 9) and age-matched control individuals (n = 29). Using general linear regression, subtotal body (total body less head), lumbar, femoral neck and femur BMD parameters were compared considering age, sex, body mass index (BMI) and Tanner stage. Blood and urine biomarkers of bone metabolism were also assessed. RESULTS All individuals with CS showed significantly lower mean values of subtotal, lumbar and femoral neck BMD compared to the control group (p ≤ 0.01). Similarly, mean total body mass and fat-free mass parameters were lower among the CS patients than in controls (p < 0.01). Low 25-OH vitamin D concentration was documented in all individuals with CS, with values below the reference range in two patients. No significant correlation between vitamin D levels and BMD parameters was observed. DISCUSSION CS belongs to a family of developmental disorders, the RASopathies, that share skeletal defects as a common feature. The present data provide evidence that, similar to what is recently seen in NF1 and NS, bone homeostasis is impaired in CS. The significant decrease in BMD and low levels of vitamin D documented in the present cohort, along with the risk for pathologic fractures reported in adult individuals with CS, testifies the requirement for a preventive treatment to alleviate evolutive complications resulting from dysregulated bone metabolism.