Iatrogenic Rhabdomyolisis and Guillain-Barre’ Syndrome: a Dangerous Association.

Guillan-Barré Syndrome (GBS) is an acute, symmetrical polyneuropathy with a clinical manifestation of flaccid paralysis with areflexia and variable sensory disturbance. GBS has an incidence of 1-2 cases/100.000 inhabitants for year. The pathological spectrum of GBS includes Acute Inflammatory Demyelinating Polyneuropathy (AIDP), Acute Motor Axonal Neuropathy (AMAN) and Acute Motor Sensory Axonal Neuropathy (AMSAN). We report a case of an 81-year-old man with GBS (subtype AMSAN), secondary to a previous Micoplasma Pneumoniae infection, who presented with an elevation of Creatin Kinase (CK) serum levels, and worsened by a co-administration of statins and clarithromycin. By our knowledge there are few cases in the literature in which the association of these drugs contributed to worsening GBS

Future Perspectives on GLP-1 Receptor Agonists and GLP-1/glucagon Receptor Co-agonists in the Treatment of NAFLD

Along the obesity pandemic, the prevalence of non-alcoholic fatty liver disease (NAFLD), often regarded as the hepatic manifestation of the metabolic syndrome, increases worldwide representing now the prevalent liver disease in western countries. No pharmacotherapy is approved for the treatment of NAFLD and, currently, the cornerstone treatment is lifestyle modifications focusing on bodyweight loss, notoriously difficult to obtain and even more difficult to maintain. Thus, novel therapeutic approaches are highly demanded. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are approved for the treatment of type 2 diabetes and obesity. They exert their body weight-lowering effect by reducing satiety and food intake. GLP-1RAs have also been shown to reduce liver inflammation and fibrosis. Furthermore, glucagon receptor agonism is being investigated for the treatment of NAFLD due to its appetite and food intake-reducing effects, as well as its ability to increase lipid oxidation and thermogenesis. Recent studies suggest that glucagon receptor signaling is disrupted in NAFLD, indicating that supra-physiological glucagon receptor agonism might represent a new NAFLD treatment target. The present review provides (1) an overview in the pathophysiology of NAFLD, including the potential involvement of GLP-1 and glucagon, (2) an introduction to the currently available GLP-1RAs and (3) outlines the potential of emerging GLP-1RAs and GLP-1/glucagon receptor co-agonists in the treatment of NAFLD

Dapagliflozin acutely improves endothelial dysfunction, reduces aortic stiffness and renal resistive index in type 2 diabetic patients: A pilot study

Background: Sodium-glucose cotransporter-2 inhibitors reduce blood pressure (BP) and renal and cardiovascular events in patients with type 2 diabetes through not fully elucidated mechanisms. Aim of this study was to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function, as well as putative mechanisms. Methods: Neuro-hormonal and vascular variables, together with 24 h diuresis, urinary sodium, glucose, isoprostanes and free-water clearance were assessed before and after a 2-day treatment with dapagliflozin 10 mg QD in sixteen type 2 diabetic patients; data were compared with those obtained in ten patients treated with hydrochlorothiazide 12.5 mg QD. Brachial artery endothelium-dependent and independent vasodilation (by flow-mediated dilation) and pulse wave velocity were assessed. Renal resistive index was obtained at rest and after glyceryl trinitrate administration. Differences were analysed by repeated measures ANOVA, considering treatment as between factor and time as within factor; Bonferroni post hoc comparison test was also used. Results: Dapagliflozin decreased systolic BP and induced an increase in 24 h diuresis to a similar extent of hydrochlorothiazide; 24 h urinary glucose and serum magnesium were also increased. 24 h urinary sodium and fasting blood glucose were unchanged. Oxidative stress was reduced, as by a decline in urinary isoprostanes. Flow-mediated dilation was significantly increased (2.8 ± 2.2 to 4.0 ± 2.1%, p < 0.05), and pulse-wave-velocity was reduced (10.1 ± 1.6 to 8.9 ± 1.6 m/s, p < 0.05), even after correction for mean BP. Renal resistive index was reduced (0.62 ± 0.04 to 0.59 ± 0.05, p < 0.05). These vascular modifications were not observed in hydrochlorothiazide-treated individuals. Conclusions: An acute treatment with dapagliflozin significantly improves systemic endothelial function, arterial stiffness and renal resistive index; this effect is independent of changes in BP and occurs in the presence of stable natriuresis, suggesting a fast, direct beneficial effect on the vasculature, possibly mediated by oxidative stress reduction

Effetto della riduzione acuta della glicemia sulla funzione β-cellulare in soggetti sani ed affetti da diabete tipo 2

Studi effettuati su preparati autoptici hanno evidenziato una riduzione della massa β-cellulare (BCM) in pazienti affetti da diabete tipo 2. Non essendo ad oggi disponibile una misurazione in vivo affidabile della BCM, la valutazione della funzione β-cellulare, in certe precise condizioni sperimentali, costituisce l’unica modalità alternativa per averne una valida stima. In particolare, la risposta insulinica ad un bolo e.v. di arginina in condizioni di iperglicemia (AIRmax) è ritenuta espressione della riserva funzionale massimale β-cellulare e quindi una buona stima della BCM. Dati preliminari suggeriscono tuttavia che questo parametro in realtà possa essere modulato dalla precedente esposizione a variazioni anche modeste di glicemia plasmatica. Per verificare questa ipotesi, abbiamo valutato l’AIRmax in tredici soggetti sani (NGT) e dieci affetti da diabete tipo 2 (T2D) due volte a distanza di una settimana: il test veniva eseguito una volta senza alterare la glicemia basale (Test iso) mentre nell’altra la glicemia prima del test veniva ridotta del 20-25% per 100 min (test Sub). Gli indici di funzione β-cellulare, derivati dalla deconvoluzione del C-peptide hanno mostrato nel test Sub una riduzione della stessa sia in risposta alla iperglicemia che alla arginina nei soggetti NGT ed un’assenza di variazioni nel gruppo T2D; in merito alla valutazione della sensibilità insulinica, la riduzione della glicemia comportava un incremento della sensibilità insulinica nei soggetti NGT, mentre nessuna modifica era osservata nel gruppo T2D. Possiamo concludere che il test nei soggetti normali, risultando sensibile al valore di glicemia precedente l’esame, non costituisca una valida modalità per la stima della BMC. Inoltre abbiamo descritto una nuova anomalia della beta cellula del soggetto con diabete la quale risulta non più in grado di adattarsi rapidamente alle glicemie prevalenti

Should low birth-weight be considered a relevant risk factor for rise in pulse pressure among adult overweight-obese subjects?

Low birth-weight (BW) is related to rise in blood pressure (BP) later in life. Aim of this study is investigating whether presence of overweight-obesity modifies this relationship, independently from any additional correlate of metabolic syndrome. We studied 535 (216 M/319 F) otherwise healthy overweight-obese people (body mass index≥25 kg/m2), recording systolic, diastolic and pulse BP as well as plasma glucose and lipids, additionally interviewing them about BW and weight-change after age of 18 years. The reciprocal of BW was related only to pulse pressure (PP, r=0.14; P=0.04), uniquely in men and individuals with BW≤2500 g had a higher relative risk of having PP above upper quartile (>60 mmHg), independently of sex. After adjusting for confounders each 1 kg rise in BW was associated with 2.84±0.88 (standard error) mmHg decrease in PP; P=0.0042. Moreover, again only among males, the lower BW the higher was the risk of a PP>60 mmHg [odds ratio (95% confidence interval): 2.43 (1.39-4.24); P=0.0018]. In conclusion BW was inversely related only with PP in overweight-obese subjects, uniquely in men, being such effect independent from other correlates of metabolic syndrome. Since elevated PP can be considered a proxy of vascular damage, these findings further stress the importance of inquiring about BW to better stratify the risk of vascular damage, in adult overweight-obese individuals

Short Course of Insulin Treatment versus Metformin in Newly Diagnosed Patients with Type 2 Diabetes

The ß-cell dysfunction of type 2 diabetes is partly reversible. The optimal time window to induce glycemic remission is uncertain; short courses of insulin treatment have been tested as a strategy to induce remission. In a pilot study in 38 newly-diagnosed patients, we assessed the time-course of insulin sensitivity and ß-cell function (by repeat oral glucose tolerance tests) following a 6-week basal insulin treatment compared to metformin monotherapy in equipoised glycemic control. At 6 weeks, insulin secretion and sensitivity were increased in both groups whilst ß-cell glucose sensitivity was unchanged. From this time onwards, in the insulin group glycemia started to rise at 3 months, and was no longer different from baseline at 1 year. The initial improvement in insulin secretion and sensitivity dissipated. In the metformin group, fasting plasma glucose and HbA1c levels reached a nadir at 8 months, at which time insulin secretion, glucose and insulin sensitivity were significantly better than at baseline and higher than in the insulin group. A short course of basal insulin in newly-diagnosed patients does not appear to offer clinical advantage over recommended initiation with metformin

Determinants of glomerular filtration rate following bariatric surgery in individuals with severe, otherwise uncomplicated, obesity: an observational, prospective study

Aims: Obesity-induced nephropathy is an established clinical entity arising from a “maladaptive” response to lipid accumulation at the nephron level. Bariatric surgery positively affects renal function, reducing or increasing glomerular filtration rate (GFR) in subjects with hyperfiltration and renal impairment, respectively. The effect of this surgery in patients with normal estimated GFR (eGFR) is less clear. Methods: A complete clinical and biochemical assessment of 135 severely obese, otherwise healthy subjects, was obtained before Roux-en-Y gastric bypass (RYGB). All subjects underwent an OGTT with plasma glucose and insulin determinations. Follow-up data were recorded at 6, 12, 24 and 48 months after intervention. Results: Baseline eGFR was 98.2 ± 13.6 ml/min/1.73 m2; hyperfiltration (>120 ml/min/1.73 m2) was present in 7% of the cohort. No eGFR variation over the follow-up emerged, except at the last visit (−3.6 ± 1.4 ml/min/1.73 m2 at month 48, p = 0.01 vs baseline). In the univariate analysis, the renal performance at 48 months was inversely related to baseline eGFR (r = −0.17, p = 0.04) and plasma triglycerides (r = −0.04, p = 0.05). Fasting and OGTT-derived variables did not impact eGFR. By multiple regression analysis, eGFR time course was independently predicted only by baseline eGFR (p = 0.03). Interestingly, patients having a baseline eGFR >100 ml/min/1.73 m2 (median value) showed, after 48 months, an average loss of −8.3 ± 2.2 ml/min/1.73 m2, while those with eGFR <100 exhibited a slight increase (+1.8 ± 2.3 ml/min/1.73 m2, p < 0.01). Conclusions: Long-term data confirm the safety of RYGB on renal function. Interestingly, a subtle hyperfiltration, i.e., occurring in high-normal range of eGFR, is attenuated by surgical procedure. Lastly, high serum triglycerides may track an unfavorable renal outcome