Obesity in Prediabetic Patients: Management of Metabolic Complications and Strategies for Prevention of Overt Diabetes.

Obesity and prediabetes affect a substantial part of the general population, but are largely underdiagnosed, underestimated, and undertreated. Prediabetes differs from diabetes only in the degree of hyperglycaemia consequent to the progressive decline in residual beta-cell function. Both prediabetes and diabetes occur as a consequence of insulin resistance that starts several years before the clinical onset of overt diabetes. Macrovascular complications in patients with diabetes are mainly caused by insulin resistance. This is why in prediabetes, the overall cardiovascular risk is, by all means, similar to that in patients with diabetes. It is important, therefore, to identify prediabetes and treat patients not only to prevent or delay the onset of diabetes, but to reduce the cardiovascular risk associated with prediabetes. This review provides an overview of the pathophysiology of prediabetes in patients with obesity and the progression toward overt diabetes. We have reviewed nutritional and pharmacological approaches to the management of obesity and reduced glucose tolerance, and the treatment of the major comorbidities in these patients, including hypertension, dyslipidaemia, and Metabolic dysfunction-associated Steatotic Liver Disease (MASLD), has also been reviewed. In patients with obesity and prediabetes, the nutritional approach is similar to that adopted for patients with obesity and diabetes; treatments of dyslipidaemia and hypertension also have the same targets compared to patients with diabetes. MASLD is a critical issue in these patients; in the prediabetic state, MASLD rarely progresses into fibrosis. This highlights the importance of the early recognition of this pathological condition before patients become diabetic when the risk of fibrosis is much higher. It is necessary to raise awareness of the clinical relevance of this pathological condition in order to prompt early intervention before complications occur. The single most important therapeutic goal is weight loss, which must be early and persistent.

Older Adults with Type 2 Diabetes Treated with Metformin: AME-MET Study - A Multicentric Real-world Study in Italy.

AIMS: Metformin is the most widely used drug for the first-line treatment of type 2 diabetes mellitus (T2DM), but its use and schedule have been poorly investigated in elderly patients. METHODS: We conducted an observational, cross-sectional, multicentric study on metformin in T2DM outpatients older than 65 years who were taking the drug for at least 6 months and referred to Italian Endocrinology and Diabetology Services. The primary endpoint was daily metformin dose, and secondary endpoints were the correlations between metformin dose and age, comorbidities, and concomitant use of other drugs. The study was open to all members of AME (Associazione Medici Endocrinologi). RESULTS: Fifteen Italian centers recruited 751 consecutive participants (42.9% older than 75 years, 48.6% females). T2DM duration was 12.9 ± 9.7 years (longer than 10 years in 53.8%). Metformin had been used for 10.3 ± 6.8 years (longer than 10 years in 52.4%). Metformin dose was 1.6 ± 0.9 g/day (>1.5 g/day in 63.4%). As compared to the youngest, participants older than 75 years did not differ for metformin daily dose or number of administrations. Metformin dose was significantly directly correlated to eGFR, diabetes duration, and metformin treatment duration. CONCLUSION: In this real-world study, the minimum daily effective dose of metformin was prescribed in more than half of older T2DM outpatients.

Complete remission of recurrent multiple insulin-producing neuroendocrine tumors of the pancreas with somatostatin analogs: a case report and literature review.

Hyperinsulinemic hypoglycemia is most commonly caused by a single, sporadic insulinoma. Multicentric insulinoma disease (insulinomatosis) as well as metachronous neuroendocrine tumors of the pancreas, known also as neuroendocrine adenomatosis, represent a very rare condition, if not associated with multiple endocrine neoplasia type 1 syndrome (MEN1) or Von Hippel Lindau disease. We report a 9-year follow-up of a 41-year-old woman, initially presenting with hypoglycemic syndrome caused by two insulin-producing tumors, who underwent subtotal pancreasectomy in 2012, with histology compatible with multiple small neuroendocrine tumors. An approximately 1-cm insulin-producing tumor recurred at subsequent biochemical and radiological follow-up, and was cured with the somatostatin analog octreotide as a single treatment, until remission of symptoms and complete regression of the pancreatic lesion achieved after only 16 months of treatment. The possible mechanisms for these findings are discussed and the literature is briefly reviewed.

Hepatosplenic Cat Scratch Disease: Description of Two Cases Undergoing Contrast-Enhanced Ultrasound for Diagnosis and Follow-Up and Systematic Literature Review.

Cat scratch disease (CSD) is a disease usually characterized by self-limited lymphadenopathy of the young man. Rarely CSD, however, can manifest itself as an unusual hepatosplenic form (HS-CSD) in immunocompetent patients. HS-CSD diagnosis is generally based on clinical features, imaging, and serologies, but sensitivity of serologies is very variable, like that of other diagnostic methods, as Warthin-Starry silver stain and isthology. Also there are no specific markers for the follow-up. The use of the CEUS (abdominal contrast-enhanced ultrasound) in HS-CSD is not previously described in literature examined, but we think that CEUS can be of help to diagnosis and follow-up of these patients, even after an initial CT scan, because it is a sensitive method, as seen in other diseases associated with granulomas, such as sarcoidosis. We describe 2 new cases of HS-CSD, and we performed a systematic review of the clinical cases reported in the past 10 years in the literature associated to an analysis of clinical, diagnostic, and therapeutic aspects of the disease.

Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas.

Temozolomide is effective in some patients with progressive pituitary adenoma or carcinoma. We report a survey study of Italian patients treated with Temozolomide because of aggressive pituitary adenoma or carcinoma resistant to standard therapies. Italian endocrinologists were surveyed and asked to participate into the study. A questionnaire was sent to all those who agreed and had used Temozolomide in at least one patient with pituitary tumor. Database was closed in December 2013. A literature review was also performed. Thirty-one patients were included into the analysis. Mean age at start of Temozolomide treatment was 58.3 ± 1.9 years (± standard error). Six of the 31 (19.4%) Italian patients had a pituitary carcinoma. Twenty-five patients (80.6%) had disease control during Temozolomide treatment, while 6 patients (19.4%) had disease progression. Median follow-up after beginning Temozolomide was 43 months. Thirteen patients had tumor growth after stopping Temozolomide. The 2-year progression-free survival was 47.7% (95% CI 29.5-65.9%), while the 2-year disease control duration was 59.1% (95% CI 39.1-79.1%). Eleven patients died of progressive disease and other two patients of unrelated causes. The 2-year and 4-year overall survival rates were 83.9% (95% CI 70.7-97.1%) and 59.6% (95% CI 40.0-79.2%), respectively. Temozolomide is an additional effective therapeutic option for the treatment of aggressive pituitary tumors. The drug is well tolerated and causes few severe adverse effects. Recurrence of the tumor can occur after an initial positive response and usually portends a grim outcome.

Paraneoplastic hypocalcemia-induced heart failure in advanced breast cancer: A case report and literature review.

Hypocalcemia is an uncommon clinical symptom of patients with malignant tumors, and a number of factors may be involved in its development. The present study describes the case of a 67-year-old Caucasian female, presenting with severe refractory hypocalcemia and heart failure. The patient was subsequently diagnosed with breast cancer and bone metastases. The paraneoplastic origin of the syndrome was confirmed by its complete resolution once the tumor responded to specific antineoplastic treatments, comprising weekly paclitaxel and aromatase inhibitor administration. The present case report suggested the need for greater awareness of the possibility of paraneoplastic hypocalcemia in breast cancer patients, and suggested that this condition may also contribute to the occurrence of heart failure. The mechanisms potentially responsible for this event were discussed and a brief review of the literature presented.

A New Case of DRESS Syndrome Induced by Sulfasalazine and Triggered by Amoxicillin.

Drug Rash Eosinophilia Systemic Symptoms (DRESS) syndrome is a systemic hypersensitivity reaction characterized by exfoliative dermatitis and maculopapular rash, lymphadenopathy, fever, eosinophilia, leukocytosis, and involvement of internal organs as liver, lung, heart, and kidney; the disorder starts within 2-6 weeks after taking a drug with an incidence that ranges from 1/1000 to 1/10000 exposures. Fatal cases are reported. The exact pathogenesis of DRESS syndrome is not completely understood, while it is reported that amoxicillin could trigger it in patients who are taking allopurinol, sulfasalazine, NSAIDs, carbamazepine, strontium ranelate, lisinopril, lansoprazole, and minocycline. Amoxicillin could act directly, inducing the reactivation of a viral infection (HHV 6 and EBV) with symptoms similar to DRESS syndrome or by reducing the patients' ability to detoxify the body from substances chronically taken. We describe a case of a patient admitted to our hospital for a DRESS syndrome flared after amoxicilline intake during treatment with sulfasalazine; this combination can activate severe reactions often with an insidious onset that can mimic an infectious disease.

Efficacy of Corticosteroids Alone in the Eradication of Factor VIII Inhibitor in an Old Female with Idiopathic Acquired Haemophilia A: Description of a Case.

Acquired haemophilia A (AHA) is a rare and serious disorder mainly affecting elderly patients. It is caused by the production of autoantibodies directed against coagulation factors; patients present with spontaneous bleeding, potentially fatal, in the absence of familial or personal history. Autoimmune disorders, infections, solid and hematologic tumors, and drugs are predisposing factors, but up to 50 percent of cases remain unexplained. The diagnosis of AHA is confirmed by specific laboratory tests; and the therapy is a clinical challenge, due to the fact that older patients are often affected by comorbidities. By passing agents may be used when persistent bleeding or haemodynamic instability is observed; corticosteroids, alone or with immunosuppressive therapy, are necessary to inhibit the production of the autoantibodies. We describe a case in which steroids in monotherapy successfully, safely, and persistently inhibited the production of anti-Factor VIII antibodies, in an old patient admitted after rheumatologic consult.