Showing papers by "Francesco Rubino published in 2009"

How Do We Define Cure of Diabetes

Abstract: The mission of the American Diabetes Association is “to prevent and cure diabetes and to improve the lives of all people affected by diabetes.” Increasingly, scientific and medical articles (1) and commentaries (2) about diabetes interventions use the terms “remission” and “cure” as possible outcomes. Several approved or experimental treatments for type 1 and type 2 diabetes (e.g., pancreas or islet transplants, immunomodulation, bariatric/metabolic surgery) are of curative intent or have been portrayed in the media as a possible cure. However, defining remission or cure of diabetes is not as straightforward as it may seem. Unlike “dichotomous” diseases such as many malignancies, diabetes is defined by hyperglycemia, which exists on a continuum and may be impacted over a short time frame by everyday treatment or events (medications, diet, activity, intercurrent illness). The distinction between successful treatment and cure is blurred in the case of diabetes. Presumably improved or normalized glycemia must be part of the definition of remission or cure. Glycemic measures below diagnostic cut points for diabetes can occur with ongoing medications (e.g., antihyperglycemic drugs, immunosuppressive medications after a transplant), major efforts at lifestyle change, a history of bariatric/metabolic surgery, or ongoing procedures (such as repeated replacements of endoluminal devices). Do we use the terms remission or cure for all patients with normal glycemic measures, regardless of how this is achieved? A consensus group comprised of experts in pediatric and adult endocrinology, diabetes education, transplantation, metabolism, bariatric/metabolic surgery, and (for another perspective) hematology-oncology met in June 2009 to discuss these issues. The group considered a wide variety of questions, including whether it is ever accurate to say that a chronic illness is cured; what the definitions of management, remission, or cure might be; whether goals of managing comorbid conditions revert to those of patients without diabetes if someone is …

The effect of bilio-pancreatic diversion on type 2 diabetes in patients with BMI <35 kg/m2

Abstract: Aims/hypothesis To aim of the study was to investigate the effect of bilio-pancreatic diversion (BPD) on type 2 diabetes in patients with BMI <35 kg/m2.

Diabetes Surgery: A New Approach to an Old Disease

Abstract: Since its earliest description several thousand years ago, diabetes has remained a chronic progressive disease (1). The disease now affects ∼200 million people worldwide, and diabetes-related death is expected to increase by >50% in the next 10 years (2). The situation is only getting worse. The prevalence of diabetes among the elderly has increased 63% in the 10 years 1994–2004 (3). This increasing prevalence is a testament to improvement in managing diabetes-related complications, as well as our global “modernization” and the accompanying metabolic derangements. Diabetes is now ranked as the sixth leading cause of death by disease in the U.S. (4). In many places, it ranks far higher. The economic burden in 2007 alone exceeded $174 billion (5). Diet modification and oral hypoglycemic medications have proven inadequate, whereas insulin therapy only solves the problem temporarily. In the U.K. Prospective Diabetes Study, diabetic patients were treated with diet modification, metformin, sulfonylurea, or insulin. Consistent with the progressive nature of diabetes, monotherapy was abandoned in 75% of the patients studied in a follow-up of 9 years (6). Even with the newest pharmaco-therapies, patients continue to develop macro- and microvascular complications. Diabetes is associated with increased cardiac- and stroke-related deaths, kidney failure, blindness, and 60% of nontrauma lower-limb amputations (4). In cardiac surgery, diabetes as a preoperative risk factor confers greater morbidity than a previous myocardial infarction (7,8). While these numbers show that diabetes will be the global health crisis of the next generation, its true pathophysiology has yet to be delineated. Alternative treatments targeting different models of this disease require careful and responsible examination. A large body of evidence now demonstrates surgery for type 2 diabetes can achieve up to complete disease remission, a goal almost unheard of in current diabetes care. Evidence collected over decades of bariatric …

Access to bariatric surgery and patients with diabetes.

Abstract: scribed the association between tamsulosin and adverse events following cataract surgery. The authors theorized that tamsulosin may demonstrate greater receptor affinity and selectivity compared with other antagonists studied, thereby resulting in the observed selective toxicity. However, a hypothesis that tamsulosin is bound to receptors in a manner resulting in protracted selective and specific ocular toxicity is problematic. Descriptionsof receptoraffinitydevelopedasa resultof formal receptor-ligand assays should not be interpreted as indicating intrinsic (agonist or antagonistic) properties of drug action. Rather than receptor affinity alone, it is the pharmacodynamic consequence of drug exposure described in terms of dose-responserelationships thatmoreaccuratelypredictsdrug effect. The 1 antagonists examined in the study by Bell et al demonstratecompetitiveantagonismof 1receptoractivity,with relative similarity in the agonist-concentration effect (E/[A]) curve shift with increasing agonist concentration. Although relativedifferencesarenotedamong 1 antagonists in termsof dose-response relationships, the toxicity associated only with tamsulosin is in marked contrast with the general commonality of findings describing dose-response relationships typical of 1 antagonist action. Drug compounds are chemical ligands that are attracted to anyphysicochemicalentitybyvirtueofcharacteristicdispersal patterns of charge and polarity. For example, heterocyclic basic compounds such as tamsulosin as well as chlorpromazine andchloroquinedemonstrateapronouncedaffinity for 1 acid glycoproteinand, inthecaseof the latter2compounds,aphysicochemical interactionwiththe indolequinonepolymer,melanin. Whether tamsulosindemonstratesanyparticularaffinity for melanin is speculative. However, attributing tamsulosinrelated ocular toxicity to a heightened receptor affinity is inconsistent with dose-response relationships of 1 antagonist activity. Indeed,analysisof themydriaticagonisteffectofphenylephrine in the setting of preexisting systemic -antagonist exposure isoneexampleof thedose-responserelationship that describes antagonistic drug action.

"METAbOlIC" SuRgER y fOR TREATMENT Of TyPE 2 DIAbETES MEllITuS

Abstract: Objective:� Todiscussthepotentialcontributionof� "metabolic"�surgeryinprovidingoptimalmanagementof� patientswithtype�2�diabetesmellitus�(T2DM). � Methods:�Aliteraturesearchwasperformedwithuse� ofPubMed,�andtheclinicalexperienceoftheauthorswas� alsoconsidered. � Results:� Bariatric—or,� moreappropriately,� meta- bolic—surgicalprocedureshavebeenshowntoprovide� dramaticimprovementinbloodglucoselevels,� blood� pressure,�andlipidcontrolinobesepatientswithT2DM.� Inthesepatients,�metabolicsurgeryinvolvesalowriskof� short-termmortalityandasignificantlong-termsurvival� advantage,�whereasthediagnosisofdiabetesisassociated� withsignificantlong-termmortality.�Experimentalstudies� inanimalsandclinicaltrialssuggestthatgastrointestinal� bypassprocedurescancontroldiabetesandassociatedmet- abolicalterationsbymechanismsindependentofweight� loss.�Asaresult,�theuseofbariatricsurgeryandexperi- mentalgastrointestinalmanipulationstotreatT2DMis� increasing,�evenamonglessobesepatients.�Althoughbody� massindex�(BMI)�currentlyisthemostimportantfactor� foridentifyingcandidatesforbariatricsurgery,�evidence� showsthataspecificcutoffBMIvaluecannotaccurately� predictsuccessfulsurgicaloutcomes.�Furthermore,�BMI� appearslimitedindefiningtheriskprofileforpatientswith� T2DM. � Conclusion:� CurrentBMI-basedcriteriaforper- formanceofbariatricsurgeryarenotadequatefordeter- miningeligibilityforoperativetreatmentinpatientswith� diabetes.�Largeclinicaltrials,�comparingbariatricsurgery� versusoptimalmedicalcareofpatientswithT2DM,�should� begivenpriorityinordertodefinetheroleofsurgeryin� themanagementofdiabetes.�Recognizingtheneedtowork� asamultidisciplinaryteamthatincludesendocrinologists� andsurgeonsisaninitialstepinaddressingtheissues� andopportunitiesthatsurgeryofferstodiabetescareand� research.�(Endocr Pract. 2009;15:624-631)