M. Massi Benedetti

Low-grade inflammation, diet composition and health: current research evidence and its translation.

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institutes European Branch (ILSI Europe). It is co-authored by the speakers from a 2013 workshop led by the Obesity and Diabetes Task Force entitled ‘Low-grade inflammation, a high-grade challenge: biomarkers and modulation by dietary strategies’. The latest research in the areas of acute and chronic inflammation and cardiometabolic, gut and cognitive health is presented along with the cellular and molecular mechanisms underlying inflammation–health/disease associations. The evidence relating diet composition and early-life nutrition to inflammatory status is reviewed. Human epidemiological and intervention data are thus far heavily reliant on the measurement of inflammatory markers in the circulation, and in particular cytokines in the fasting state, which are recognised as an insensitive and highly variable index of tissue inflammation. Potential novel kinetic and integrated approaches to capture inflammatory status in humans are discussed. Such approaches are likely to provide a more discriminating means of quantifying inflammation–health/disease associations, and the ability of diet to positively modulate inflammation and provide the much needed evidence to develop research portfolios that will inform new product development and associated health claims.

A model of the endogenous glucose balance incorporating the characteristics of glucose transporters

This paper describes the development and preliminary test of a model of the endogenous glucose balance that incorporates the characteristics of the glucose transporters GLUT1, GLUT3 and GLUT4. In the modeling process the model is parameterized with nine parameters that are subsequently estimated from data in the literature on the hepatic- and endogenous- balances at various combinations of blood glucose and insulin levels. The ability of the resulting endogenous balance to fit blood glucose measured from patients was tested on 20 patients. The fit obtained with this model compared favorably with the fit obtained with the endogenous balance currently incorporated in the DIAS system.

The Artificial Pancreas

In type 1 diabetes an absolute deficiency of insulin secretion requires exogenous insulin supply to guarantee the patients life avoiding ketoacidotic coma and to prevent the chronic complications of diabetes. In order to obtain a more physiological replacement therapy different approaches have been pursued since the early 70s to create an artificial wearable pancreas able to deliver insulin according to the blood glucose values as determined by continuous monitoring. Four components are considered essential for the realisation of an artificial pancreas: the sampling system, the glucose sensor, the mathematical models and the related algorithms for the calculation of the insulin doses and the infusion system for the insulin delivery. At present the still unsolved issues are mainly represented by the availability of reliable continuous glucose monitor and control algorithms, while the new technologies allow for the miniaturisation of the system.

Prevalence of type 2 diabetes mellitus (T2DM) in the adult Russian population (NATION study).

AIM To estimate type 2 diabetes mellitus (T2DM) prevalence in Russian adults. METHODS NATION is a national, epidemiological, cross-sectional study, conducted in Russia. In adults (aged 20-79 years), recruitment was stratified by age, sex, geographic region and settlement type to obtain a representative sample. Recruitment was in public areas with high numbers of people. T2DM was diagnosed by glycated haemoglobin A1c (HbA1c) levels (diabetes: HbA1c ≥6.5% [≥48mmol/mol]; pre-diabetes: HbA1c ≥5.7 to <6.5% [≥39 to <48mmol/mol]). Socio-demographic and anthropometric data were collected. RESULTS Blood samples from 26,620 subjects were available. Overall, 5.4% were diagnosed with T2DM (previously diagnosed: 2.5%; previously undiagnosed: 2.9%); 19.3% were pre-diabetic. T2DM prevalence increased with age (up to 70 years) and was higher among females than males (6.1% vs. 4.7%, p<0.001). The estimated proportion of subjects with pre-diabetes and T2DM tended to increase with increasing body mass index. T2DM prevalence was higher in rural versus urban populations (6.7% vs. 5.0%, p<0.001). CONCLUSION In the Russian adult population, 19.3% had pre-diabetes, T2DM prevalence was 5.4%, and 54% of subjects with diabetes were previously undiagnosed. These results may help to develop a new T2DM predictive, preventative and management programme in Russia.

Correlates of psychological outcomes in people with diabetes: results from the second Diabetes Attitudes, Wishes and Needs (DAWN2(™) ) study.

To assess country‐ and individual‐level correlates of psychological outcomes, and differences among countries in the associations of individual characteristics with psychological outcomes among adults with diabetes.

Ketone bodies monitoring

Abstract Diabetic ketoacidosis (DK) is a serious acute complication in type 1 diabetic patients caused by insulin deficiency. The early detection of insulin deprivation represents therefore an important element in routine clinical practice, especially in ketone prone subjects such as CSII (continuous subcutaneous insulin infusion) treated subjects. Different methods have been developed for ketone bodies (KB) monitoring: urine dipsticks, laboratory readings, capillary β-hydroxybutirate (BOHB) meters. Urine dipsticks are not recommended for KB monitoring because they measure only acetoacetate and not BOBH the most prevalent ketone during DK. Laboratory methods are more reliable but not useful for self monitoring. Capillary BOHB represents the most suitable method for KB monitoring in home settings. Several experiences demonstrated the accuracy and reliability of this method at different degree of ketosis and their efficacy in detecting and managing the course of DKA. A recent experience, conducted by our group, investigated the efficacy of the dynamic evaluation of capillary BOBH levels, irrespectively of the absolute value, for early detection of insulin deprivation in CSII treated subjects. Results indicated that dynamic evaluation of capillary BOHB appears as a more rapid and accurate indicator of early insulin deprivation than blood glucose and could be used for targeting effectively insulin therapy in the restoration phase.

Impaired endothelial antithrombotic activity following short-term interruption of continuous subcutaneous insulin infusion in type1 diabetic patients

Review of literature has shown an increased rate of thrombotic complications in diabetic patients with frequent episodes of hyperketonemia. However, the mechanisms by which ketosis promotes vascular disease in diabetic patients are unclear. It was the aim of this study to investigate early changes in haemostatic parameters and oxidative stress markers during the hyperketonemic status which follows the interruption of continuous subcutaneous insulin infusion (CSII) in type I diabetic patients. Eight CSII-treated type I diabetic patients underwent a 4-hour pump arrest. Blood glucose, insulin and 3-hydroxybutirate were measured to verify the metabolic response. A vein-occlusive (VO) test was performed for the determination of tPA and PAI-1 activities and their antigen levels before and after the CSII arrest. Coagulation factor VII and VIII were evaluated by one-stage PT and PTT method, respectively. TF, vWF, tPA and PAI-1 antigens were determined by ELISA, whereas tPA and PAI-1 activities using chromogenic methods. Plasma malondialdehyde (MDA) and protein carbonyl groups (PCG) levels were determined by HPLC and spectrophotometry, respectively. After the insulin deprivation phase, post-VO tPA antigen level significantly decreased (P = 0.0391), whereas TF and post-VO PAI-1 activity and antigen levels significantly increased (P = 0.0156 and P = 0.0234, respectively). Plasma MDA and PCG levels were 1.88-fold and 1.74-fold higher than baseline values, respectively. In conclusion, the impairment of the fibrinolytic potential and the increases in TF, MDA and PCG levels may enhance the risk of both arterial and venous thrombosis during ketosis. Thus, early detection of hyperketonemia in DM patients could contribute to the prevention of life-threatening vascular events.

Discrimination and diabetes

The DAWN2 study has categorized a massive amount of information on different aspects of the needs of people with diabetes, and the findings on discrimination are amongst the most interesting. The history of the condition provides many examples of its unacceptable consequences. Diabetes has been known about for more than 5000 years and until the discovery of insulin in 1921, type 1 was a deadly condition giving no hope of survival, while type 2 was invariably associated with the occurrence of devastating complications, disability and premature mortality. Procreation was not usually an option for those with type 1 diabetes given the short timespan between onset and death, while type 2 diabetes or diabetes occurring during pregnancy was the cause of miscarriage, stillbirth, congenital malformations in the child and severe complications for the mother. Until relatively recent years, up to the 1970s, pregnancy was heavily discouraged, nearly forbidden, both in type 1 and type 2 diabetes, while male impotence and infertility were quite frequent. At the beginning of the ‘insulin era’ the main objective was the survival of people with type 1 diabetes striven for by rigid therapeutic regimes of rudimentary insulin, characterized by severe metabolic instability with frequent occurrence of hypoglycaemia and ketoacidosis resulting in very poor quality of life. The discovery of oral hypoglycaemic agents in the early 1950s resulted in a longer survival of people with type 2 diabetes although the concept of near-normoglycaemia was far from being contemplated, and insulin therapy in type 2 diabetes was considered as the last desperate chance before death. As a result, the longer survival and the poor quality of glucose control increased the number of people with longterm complications. Diabetes, both type 1 and type 2, was the leading cause of blindness, amputations and end stage renal disease, heavily affecting the lives of people with diabetes with respect to family life, work, sport and leisure activities, and in any other aspect of personal and social activities. Under these conditions it is not surprising that the low selfesteem of people with diabetes combined with the perception

The Umbria Diabetes Register

The project PROMODR (Progressive Model of Diabetes Register) funded by an Italian Ministry of Health grant, aimed at the realisation of a prototype regional registry for diabetes mellitus and its validation in a pilot experience. Primary data sources are the General Practitioners (GPs) and the Diabetes Centres (DCs) of the Umbria region already equipped with electronic medical records (EMR). A minimum registry data set was created consisting of personal data, metabolic indices, late diabetic complications and therapy. The GPs EMR system was modified in order to automatically identify, extract encrypt and send via e-mail to a central regional server the administrative and clinical data related to the diabetic patients. At this level the data are merged with the information derived by the DCs. The functionality of the prototype has been evaluated in a pilot experience consisting of two consecutive phases: the first collecting data from 7 GPs covering different areas of the region and a population of around 10680 inhabitants and the second one involving 13 DCs. Data from more than 12000 diabetic subjects were collected. Different examples indicators have been calculated. This pilot study showed an accurate functionality of the prototype without major errors in all the different phases of data collection and transmission.

Diabetes registers and prevention strategies: towards an active use of health information

Recent experiences in the use of diabetes registers show their ability to improve population health in a region. In the framework of the Umbria registry, we have defined general criteria for the development of a comprehensive model including new directions for active use of health information. General functions of the diabetes register have been designed for a range of stakeholders. Large scale data linkage is used to extract study cohorts and add information content to the register. Multidimensional/multilevel analysis is directly applied to define high risk strata on the basis of multiple individual, structural, contextual (ecological) and service-related components. Target subjects can be used to design specific interventions for the prevention of diabetic complications. The enhanced version of the Umbria Register involves a large group of institutional partners in a new program for clinical governance. Agreed routine health system evaluation now regards diabetes indicators as a high priority area. The data model supports information exchange across a network of national and international partners, contributing to the definition of a common benchmarking system. The present work shows that principles of evidence-based medicine can be used to underpin new ways of active use of health information. Involving policy makers and health professionals in the research and development of diabetes registers will be increasingly crucial to capture all opportunities arising from a wide application.