Cardiac Autoimmunity as a Novel Biomarker, Mediator, and Therapeutic Target of Heart Disease in Type 1 Diabetes

Patients with type 1 diabetes (T1D) suffer excess mortality from cardiovascular disease (CVD) that has persisted despite substantial reductions in microvascular complications. Although T1D and type 2 diabetes (T2D) are etiologically distinct, it has generally been assumed that CVD in T1D is “the same disease” as that found in T2D. Here, we review the most recent epidemiological and clinical studies on heart disease in T1D, highlighting differences between CVD in T1D and T2D. In addition, we discuss experimental and clinical evidence for a post-myocardial infarction (MI) autoimmune heart syndrome in T1D, including the development of diagnostic assays which we believe can, for the first time, differentiate between heart disease in T1D and T2D. We postulate that a clinically unrecognized form of chronic myocardial inflammation (“myocarditis”) triggered by MI contributes to the poor CVD outcomes in T1D. These findings provide a conceptual shift in our understanding of CVD in T1D and have important diagnostic and therapeutic implications

Pramlintide but Not Liraglutide Suppresses Meal-Stimulated Glucagon Responses in Type 1 Diabetes

Postprandial hyperglycemia remains a challenge in type 1 diabetes (T1D) due, in part, to dysregulated increases in plasma glucagon levels after meals

The one-hour post-load plasma glucose predicts progression to prediabetes in a multiethnic cohort of obese youths

One-hour post-load hyperglycemia has been proposed as an independent predictor of type 2 diabetes in adults. We examined whether 1-hour plasma glucose (1hPG) during an oral glucose tolerance test (OGTT) can predict changes in the glucose tolerance status in a multiethnic cohort of youths with normal glucose tolerance (NGT)

Long-term continuous monitoring of the preterm brain with diffuse optical tomography and electroencephalography: A technical note on cap manufacturing

open12noDiffuse optical tomography (DOT) has recently proved useful for detecting whole-brain oxygenation changes in preterm and term newborns' brains. The data recording phase in prior explorations was limited up to a maximum of a couple of hours, a time dictated by the need to minimize skin damage caused by the protracted contact with optode holders and interference with concomitant clinical/nursing procedures. In an attempt to extend the data recording phase, we developed a new custom-made cap for multimodal DOT and electroencephalography acquisitions for the neonatal population. The cap was tested on a preterm neonate (28 weeks gestation) for a 7-day continuous monitoring period. The cap was well tolerated by the neonate, who did not suffer any evident discomfort and/or skin damage. Montage and data acquisition using our cap was operated by an attending nurse with no difficulty. DOT data quality was remarkable, with an average of 92% of reliable channels, characterized by the clear presence of the heartbeat in most of them.openopenAlfonso Galderisi; Sabrina Brigadoi; Simone Cutini; Sara Basso Moro; Elisabetta Lolli; Federica Meconi; Silvia Benavides-Varela; Eugenio Baraldi; Piero Amodio; Claudio Cobelli; Daniele Trevisanuto; Roberto Dell'AcquaGalderisi, Alfonso; Brigadoi, Sabrina; Cutini, Simone; BASSO MORO, Sara; Lolli, Elisabetta; Meconi, Federica; Silvia, Benavides-Varela; Baraldi, Eugenio; Amodio, Piero; Cobelli, Claudio; Trevisanuto, Daniele; Dell'Acqua, Robert

Quantifying beta cell function in the preclinical stages of type 1 diabetes

Clinically symptomatic type 1 diabetes (stage 3 type 1 diabetes) is preceded by a pre-symptomatic phase, characterised by progressive loss of functional beta cell mass after the onset of islet autoimmunity, with (stage 2) or without (stage 1) measurable changes in glucose profile during an OGTT. Identifying metabolic tests that can longitudinally track changes in beta cell function is of pivotal importance to track disease progression and measure the effect of disease-modifying interventions. In this review we describe the metabolic changes that occur in the early pre-symptomatic stages of type 1 diabetes with respect to both insulin secretion and insulin sensitivity, as well as the measurable outcomes that can be derived from the available tests. We also discuss the use of metabolic modelling to identify insulin secretion and sensitivity, and the measurable changes during dynamic tests such as the OGTT. Finally, we review the role of risk indices and minimally invasive measures such as those derived from the use of continuous glucose monitoring

Diabete Tipo 1, Tipo 2 e Tipo X

Il muro concettuale secondo il quale il diabete in età pediatrica ha preferibilmente una patogenesi autoimmune sta ormai definitivamente crollando. Il diabete in età infantile e adolescenziale è molto più eterogeneo dal punto di vista eziopatogenetico di quanto si pensasse. In presenza di una qualsiasi iperglicemia è ormai diventato importantissimo chiedersi la patogenesi di questo sintomo utilizzando tutti gli strumenti che abbiamo oggi a disposizione

Mitochondrial Diabetes in Children: Seek and You Will Find It

Maternally Inherited Diabetes and Deafness (MIDD) is a rare form of diabetes due to defects in mitochondrial DNA (mtDNA). 3243 A>G is the mutation most frequently associated with this condition, but other mtDNA variants have been linked with a diabetic phenotype suggestive of MIDD. From 1989 to 2009, we clinically diagnosed mitochondrial diabetes in 11 diabetic children. Diagnosis was based on the presence of one or more of the following criteria: 1) maculopathy; 2) hearing impairment; 3) maternal heritability of diabetes/impaired fasting glucose and/or hearing impairment and/or maculopathy in three consecutive generations (or in two generations if 2 or 3 members of a family were affected). We sequenced the mtDNA in the 11 probands, in their mothers and in 80 controls. We identified 33 diabetes-suspected mutations, 1/33 was 3243A>G. Most patients (91%) and their mothers had mutations in complex I and/or IV of the respiratory chain. We measured the activity of these two enzymes and found that they were less active in mutated patients and their mothers than in the healthy control pool. The prevalence of hearing loss (36% vs 75–98%) and macular dystrophy (54% vs 86%) was lower in our mitochondrial diabetic adolescents than reported in adults. Moreover, we found a hitherto unknown association between mitochondrial diabetes and celiac disease. In conclusion, mitochondrial diabetes should be considered a complex syndrome with several phenotypic variants. Moreover, deafness is not an essential component of the disease in children. The whole mtDNA should be screened because the 3243A>G variant is not as frequent in children as in adults. In fact, 91% of our patients were mutated in the complex I and/or IV genes. The enzymatic assay may be a useful tool with which to confirm the pathogenic significance of detected variants