Chiara Guglielmi

Double or hybrid diabetes associated with an increase in type 1 and type 2 diabetes in children and youths

Abstract:  The increase in the incidence of type 1 diabetes (T1D), especially in children <5 yr of age, reported over the past decade can be attributed to changes in environmental factors (either quantitative or qualitative) rather than to an effect of genetic factors operating in such a short period of time. The notable increase in the incidence of type 2 diabetes (T2D) in children and adolescents is very likely the consequence of an increasing sedentary lifestyle and an increase in obesity, which has been occurring in developed countries. An increase in the number of children and adolescents with a mixture of the two types of diabetes has recently come to light (i.e., subjects who are obese and/or with signs of insulin resistance as well as positive for markers of autoimmunity to β cells), although the epidemiological data supporting such a conclusion are sparse. Under the current classification, it is difficult to define the type of diabetes affecting these young subjects, who might be classified as T2D because they are obese and insulin resistant but also as T1D because of the presence of autoantibodies to β cells. These subjects show an overlapping diabetes phenotype typical of both T1D and T2D, suggesting that the current classification of diabetes should be revised to take into account this new form of diabetes, which has been called ‘double diabetes’ or ‘hybrid diabetes’. In this review, we report recent findings on the increasing rates of all forms of diabetes in the young population, including unpublished data collected in Russia.

Obesity, Autoimmunity, and Double Diabetes in Youth

A few obese youth with type 2 diabetes have evidence of islet cell autoimmunity with autoantibodies toward β-cells typical of type 1 diabetes defining what is called “double diabetes” (DD). The increasingly “obesogenic” environment that favors insulin resistance could account for the development of islet cell autoimmunity through different mechanisms. Therefore, a rising obesity trend seems to have a role (in association with other environmental factors) in the increasing incidence and the changing phenotype of type 1 diabetes in youth. Over the past decade, it has become apparent that more cases of type 1 diabetes are diagnosed in children and adolescents who were overweight or even obese before hyperglycemia developed. Accordingly, diagnosis of type 1 diabetes is not easy to place because of the phenotypic features typically associated with type 2 diabetes. In addition, the increase of obesity observed in children may contribute to the escalation of β-cell destruction, as suggested by the accelerator hypothesis in subjects genetically susceptible to type 1 diabetes. Lifestyle modifications, including diet and exercise, which are relevant for the prevention of type 2 diabetes, may be important modifiable environmental factors also for type 1 diabetes prevention in subjects with DD. A few years ago, the terms “type 1 diabetes” and “type 2 diabetes” replaced “insulin-dependent diabetes” and “non-insulin-dependent diabetes,” respectively. This new nomenclature reflected two distinct forms of the disease in terms of pathogenesis (1). The classification is still maintained, although other subtypes have been included in the latest classification (2). An increase in blood glucose results either from failure of the β-cells to secrete insulin (type 1 diabetes) or reduction in insulin secretion combined with insulin resistance of peripheral tissues (type 2 diabetes), or a combination of both (3). The prevalence of both types of diabetes is rapidly increasing in industrialized countries, and although …

Double diabetes: a mixture of type 1 and type 2 diabetes in youth.

The increase in the incidence of type 1 diabetes (T1D), especially in children <5 years of age reported over the past decade can be attributed to changes in environmental factors, either quantitative or qualitative, rather than to an effect of genetic factors operating in such a short period of time. The notable increase in the incidence of type 2 diabetes (T2D) in children and adolescents is very likely the consequence of the increase in obesity and sedentary life style occurring in developed countries. The increase in the number of children and adolescents with a mixture of the two types of diabetes has recently come to light (i.e. subjects who are obese and/or with signs of insulin resistance as well as positive for markers of autoimmunity to beta cells). Under the current classification, it is difficult to define the type of diabetes affecting these young subjects, being classified as T2D because they are obese and insulin resistant, but also as T1D because of the presence of auto-antibodies to beta cells. There is no doubt that these subjects show an overlapping diabetes phenotype typical of both T1D and T2D suggesting that the current classification of diabetes should be revised taking into account this new form of diabetes which has called double diabetes or hybrid diabetes.

Menarche in type 1 diabetes is still delayed despite good metabolic control

OBJECTIVE To analyze the age at menarche of girls with type 1 diabetes (T1D) who were diagnosed with the disease before puberty and compare it with that of an age-matched group of normal girls. Previous studies on the appearance of menarche showed that the mean age of onset of menarche is delayed in girls affected by T1D compared with normal girls. DESIGN Case-control study. SETTING Patients and controls in an academic research environment. PATIENT(S) We studied, retrospectively, the charts of 162 consecutive girls with T1D born in a geographically defined region between 1984 and 1994 with a mean disease duration of 3-5 years, all of whom were on intensive insulin therapy since diagnosis of T1D. The control group consisted of 214 normal girls born between 1984 and 1994, who agreed to fill in an anonymous questionnaire regarding age at menarche and other clinical information. INTERVENTION(S) There was no intervention per se in the study. Age at menarche appears as a dependent variable of body mass index (BMI), HbA1c, and so on. MAIN OUTCOME MEASURE(S) BMI, HbA1c, and duration of T1D at menarche were considered among the potential factors affecting the age of menarche. RESULT(S) Age at menarche in girls with T1D was significantly delayed compared with control girls (12.6 +/- 1.5 years vs. 12.25 +/- 1.4 years, respectively). HbA1c levels and BMI did not influence the age at menarche. CONCLUSION(S) Despite intensive insulin therapy and good metabolic control since diagnosis of T1D, the age at menarche is still delayed in girls who develop T1D before puberty.

Latent autoimmune diabetes in the adults (LADA) in Asia: from pathogenesis and epidemiology to therapy

Diabetes mellitus is a metabolic disorder resulting from a defect in insulin secretion, insulin action or both. An effect of this process is chronic hyperglycaemia with disorder of carbohydrate, fat and protein metabolism and with long‐term complications of diabetes including retinopathy, nephropathy and neuropathy. Latent autoimmune diabetes in adults (LADA) is a type of autoimmune diabetes that resembles Type 1 diabetes (T1D), however, it shows a later onset and slower progression towards insulin necessity. Epidemiological studies suggest that LADA may account for 2–12% of all cases of diabetes in adult population. The epidemiology and phenotypic characteristics of LADA may vary between Caucasian and Asian diabetic patients as lifestyle, food habits and body mass index differ between these two populations. Data on LADA from population‐based studies in Asia are sparse and only few studies have looked at it.

Raised C-reactive protein levels in patients with recent onset type 1 diabetes

To investigate serum concentrations of high‐sensitive C‐reactive protein (CRP) and alpha(1)‐acid glycoprotein (AGP) in patients with T1DM, at diagnosis and after 12 months of intensive insulin therapy (T12).

Circulating Reg1α proteins and autoantibodies to Reg1α proteins as biomarkers of β-cell regeneration and damage in type 1 diabetes.

Type 1 diabetes is an autoimmune disease where β-cells are in a constant process of death and renewal. Reg genes play a role in β-cells regeneration. Reg proteins may be target of an autoimmune response in type 1 diabetes with consequent production of autoantibodies and failure of regeneration. The objective of this work was to characterize the role of Reg1α proteins and anti-Reg1α antibodies as biomarkers of β-cell regeneration and damage. Serum levels of Reg1α protein were investigated in 87 type 1 diabetic subjects (31 newly diagnosed and 56 long standing), 63 type 2 diabetic subjects, 39 subjects with systemic lupus erythematosus (SLE), a nonpancreatic autoimmune disorder, and 64 healthy subjects. The presence of anti-Reg1α antibodies and correlation with metabolic, immune, and genetic parameters were analyzed in diabetic subjects. Increased levels of Reg1α protein were observed in newly diagnosed (p=0.002), and long standing (p=0.001) type 1 diabetes patients and type 2 diabetic subjects (p<0.001). Anti-Reg1α antibodies were found in 47% of patients with type 1 diabetes. No correlation was found with metabolic, immune, and genetic parameters. Patients with SLE showed no increase in Reg1α protein. We report here for the first time raised serum Reg1α protein in type 1 and type 2 diabetes and anti-Reg1α antibodies in type 1 diabetes. Reg1α levels appear not to be influenced by genetic or metabolic control. These findings allow considering future studies on Reg1α protein and autoantibody as new tools in the evaluation and monitoring of β-cells regeneration and autoimmunity.

Westernization of the Filipino population resident in Rome: obesity, diabetes and hypertension

Aims of the present study were to examine the anthropometrical and metabolic characteristics of the Filipino population migrant to the Southern European city of Rome, Italy.

Prevention of Type 1 Diabetes Mellitus

Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing beta cells in the pancreas. Genetic, metabolic, and environmental factors act together to precipitate the onset of the disease. The excess mortality associated with complications of T1D and the increasing incidence of childhood T1D emphasize the importance of therapeutic strategies to prevent this chronic metabolic disorder.

Efficacy and safety of otelixizumab use in new-onset type 1 diabetes mellitus

ABSTRACT Introduction: Type 1 diabetes (T1DM) is an immune-mediated disease induced by antigen-specific T cells infiltrating pancreatic beta cells leading to the progressive loss of endogenous insulin secretion. Areas covered: The identification of specific components of the autoimmune response favoured the implementation of several immunomodulatory therapies including antiCD3 monoclonal antibody (mAb) called otelixizumab. Otelixizumab is a chimeric monoclonal antibody that targets the ε-chain of the CD3T-lymphocyte surface receptor that has been developed with the aim of short therapeutic courses capable of inducing a remission of T1DM. Clinical trials have been carried out with otelixizumab to evaluate its safety and efficacy, but despite positive results of Phase I and II studies, the results of Phase III studies have been contradictory. Expert opinion: High doses of otelixizumab have shown beneficial effects on beta cell function whereas a lower dose, which was tested to avoid the adverse effects associated with higher doses, was not effective on beta cells preservation. We believe that otelixizumab is a drug of potential interest for treating new onset T1DM patients and its use in combination with other immunomodulatory agents should be considered as a solution to circumvent adverse effects while maintaining efficacy.