Diabetes mellitus, a microRNA-related disease?

Diabetes mellitus is a complex disease resulting in altered glucose homeostasis. In both type 1 and type 2 diabetes mellitus, pancreatic β cells cannot secrete appropriate amounts of insulin to regulate blood glucose level. Moreover, in type 2 diabetes mellitus, altered insulin secretion is combined with a resistance of insulin-target tissues, mainly liver, adipose tissue, and skeletal muscle. Both environmental and genetic factors are known to contribute to the development of the disease. Growing evidence indicates that microRNAs (miRNAs), a class of small noncoding RNA molecules, are involved in the pathogenesis of diabetes. miRNAs function as translational repressors and are emerging as important regulators of key biological processes. Here, we review recent studies reporting changes in miRNA expression in tissues isolated from different diabetic animal models. We also describe the role of several miRNAs in pancreatic β cells and insulin-target tissues. Finally, we discuss the possible use of miRNAs as blood biomarkers to prevent diabetes development and as tools for gene-based therapy to treat both type 1 and type 2 diabetes mellitus.

Relationship between the users' contact time in educational programs on diabetes mellitus and self-care skills and knowledge

Abstract OBJECTIVE Check the relationship between the users' contact time in educational programs and self-care and knowledge variables in diabetes mellitus. METHOD A longitudinal study with a quantitative approach with the participation, in the initial phase, of 263 users linked to Basic Health Units in Belo Horizonte, Brazil during the years 2012 and 2013. The data were collected with respect to the total contact time of the users' participation in the educational program as regards knowledge and self-care in acquired diabetes mellitus. The data were analyzed using the Student t-test for comparison of means, considering a 0.05 significance level. RESULTS The final sample included 151 users. The analysis showed that the improvement in self-care scores was statistically higher during an educational intervention of eight hours or more (p-value <0.05). In relation to the scores for knowledge, there was a statistically significant improvement at the end of the educational program. It was not possible to identify a value for the contact time from which there was an increase in mean scores for the ability of knowledge. CONCLUSION To improve the effectiveness of the promotion of skills related to knowledge and self-care in diabetes mellitus, it is necessary to consider the contact time as a relevant factor of the educational program.

Diabetes mellitus and cancer risk in a network of case-control studies.

Diabetes has been associated to the risk of a few cancer sites, though quantification of this association in various populations remains open to discussion. We analyzed the relation between diabetes and the risk of various cancers in an integrated series of case-control studies conducted in Italy and Switzerland between 1991 and 2009. The studies included 1,468 oral and pharyngeal, 505 esophageal, 230 gastric, 2,390 colorectal, 185 liver, 326 pancreatic, 852 laryngeal, 3,034 breast, 607 endometrial, 1,031 ovarian, 1,294 prostate, and 767 renal cell cancer cases and 12,060 hospital controls. The multivariate odds ratios (OR) for subjects with diabetes as compared to those without-adjusted for major identified confounding factors for the cancers considered through logistic regression models-were significantly elevated for cancers of the oral cavity/pharynx (OR = 1.58), esophagus (OR = 2.52), colorectum (OR = 1.23), liver (OR = 3.52), pancreas (OR = 3.32), postmenopausal breast (OR = 1.76), and endometrium (OR = 1.70). For cancers of the oral cavity, esophagus, colorectum, liver, and postmenopausal breast, the excess risk persisted over 10 yr since diagnosis of diabetes. Our data confirm and further quantify the association of diabetes with colorectal, liver, pancreatic, postmenopausal breast, and endometrial cancer and suggest forthe first time that diabetes may also increase the risk of oral/pharyngeal and esophageal cancer. [Table: see text] [Table: see text].

Polimorfismos Genéticos do Vegf, Rage, Pon1 e Pon2 na Retinopatia Diabética em Indivíduos com Diabetes Tipo 2

A diabetes mellitus tipo 2 (DM2) é responsável por uma elevada morbilidade e mortalidade em todo o Mundo, essencialmente devido às suas complicações, entre as quais a retinopatia diabética (RD), considerada uma das mais graves, e responsável por 4,8% dos casos de cegueira. Estudos sugerem uma componente genética como um dos principais factores para o desenvolvimento da RD. O gene do VEGF (vascular endothelial growth factor) é um dos mais estudados, por promover a angiogénese e a neovascularização. Outro importante gene candidato é o RAGE (receptor for advanced glycation end products), e, mais recentemente, os genes da paraoxonase, PON1 e PON2. Objectivou-se avaliar a influência dos polimorfismos VEGF -634C/G, RAGE -374T/A, PON1Gln192Arg e PON2Cys310Ser no aparecimento e progressão da RD em indivíduos com DM2 e a sua influência no aparecimento da DM2. Analisaram-se 129 indivíduos, 86 com DM2 e 43 indivíduos saudáveis. Os polimorfismos foram avaliados em todos os indivíduos por PCR-FRLP. A caracterização clínica e a determinação da actividade enzimática da PON1 foram avaliadas em 47 diabéticos. Não se obtiveram diferenças para o polimorfismo do VEGF-634 G/C. O alelo A do polimorfismo RAGE -374A/T mostrou-se mais frequente em indivíduos sem RD ou EMD quando comparados com indivíduos com RD ou EMD. O alelo Q (Gln) e o alelo S (Ser) dos polimorfismos PON1Gln192Arg e PON2Cys310Ser, respectivamente, mostraram-se mais frequentes em indivíduos com DM2 quando comparados com indivíduos saudáveis. Não houve quaisquer diferenças relativamente à actividade enzimática da PON1, nem em relação ao polimorfismo da PON1 nem em relação à presença ou ausência de RD ou EMD. Conclui-se que o alelo A do polimorfismo RAGE -374A/T é factor protector para o aparecimento da RD e do EMD, enquanto os alelos Q e S dos polimorfismos PON1Gln192Arg e PON2Cys310Ser, respectivamente, são factores de risco para o aparecimento da DM2

Traitements des facteurs de risque cardiovasculaire et dépistage de la maladie coronarienne dans le diabète de type 2 [Treatments for cardiovascular risk factors and screening for coronary artery disease in type 2 diabetes mellitus]

The recent ACCORD and DIAD studies revealed results which could modify treatments and the screening of diabetes vascular complications. Indeed, ACCORD shows no benefit on the prevention of diabetes vascular complications by aggressive treatment of hypertension or the combined treatment of the dyslipidemia. The intensive treatment of the blood glucose, if associated with severe hypoglycemias, increases mortality. DIAD revealed 20% of silent myocardial ischaemia in diabetic patients but no beneficial effect on the cardiovascular mortality. A careful reading of these studies in the light of long term studies such as UKPDS and STENO reveals that these negative results are generated by a too short follow-up and too aggressive objectives. The long term studies reveal that more realistic objectives remain beneficial.

Mortality associated with diabetes mellitus in comparison with history of cardiovascular disease in older women.

BACKGROUND: Women with diabetes mellitus have an increased risk of cardiovascular disease (CVD) mortality and current treatment guidelines consider diabetes to be equivalent to existing CVD, but few data exist about the relative importance of these risk factors for total and cause-specific mortality in older women. METHODS: We studied 9704 women aged ≥65 years enrolled in a prospective cohort study (Study of Osteoporotic Fractures) during a mean follow-up of 13 years and compared all-cause, CVD and coronary heart disease (CHD) mortality among non-diabetic women without and with a prior history of CVD at baseline and diabetic women without and with a prior history of CVD. Diabetes mellitus and prior CVD (history of angina, myocardial infarction or stroke) were defined as self-report of physician diagnoses. Cause of death was adjudicated from death certificates and medical records when available (>95% deaths confirmed). Ascertainment of vital status was 99% complete. Log-rank tests for the rates of death and multivariate Cox hazard models adjusted for age, smoking, physical activity, systolic blood pressure, waist girth and education were used to compare mortality among the four groups with non-diabetic women without CVD as the referent group. Results are reported as adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: At baseline mean age was 71.7±5.3 years, 7.0% reported diabetes mellitus and 14.5% reported prior CVD. 4257 women died during follow-up, 36.6% were attributed to CVD. The incidence of CVD death per 1000 person-years was 9.9 and 21.6 among non-diabetic women without and with CVD, respectively, and 23.8 and 33.3 among diabetic women without and with CVD, respectively. Compared to nondiabetic women without prior CVD, the risk of CVD mortality was elevated among both non-diabetic women with CVD (HR=1.82, CI: 1.60-2.07, P<0.001) and diabetic women without prior CVD (HR=2.24, CI: 1.87-2.69, P<0.001). CVD mortality was highest among diabetic women with CVD (HR=3.41, CI: 2.61-4.45, P<0.001). Compared to non-diabetic women with CVD, diabetic women without prior CVD had a significantly higher adjusted HR for total and CVD mortality (P<0.001 and P<0.05 respectively). CHD mortality did not differ significantly between non-diabetic women with CVD and diabetic women without prior CVD. CONCLUSION: Older diabetic women without prior CVD have a higher risk of all-cause and CVD mortality and a similar risk of CHD mortality compared to non-diabetic women with pre-existing CVD. For older women, these data support the equivalence of prior CVD and diabetes mellitus in current guidelines for the prevention of CVD.

Diabetes mellitus and vascular lesions.

Cardiovascular complications represent by far the most severe manifestations of diabetes mellitus. Treatment aimed at stopping progression of vascular lesions may fall short if initiated when the disease becomes clinically evident. Therefore, identification of the earliest vascular disfunctions may offer the best opportunity to interfere with pathogenic mechanisms and avoid progression of diabetic vasculopathy. In this report, we present a few mechanisms that alter hemodynamic and metabolic homeostasis in the course of diabetes mellitus. Endothelial function with special emphasis on nitric oxide and oxidative stress, advanced glycation end products, and the renin angiotensin system are briefly discussed. New pharmacological agents that may favorably influence these parameters are presently undergoing clinical trials. However, tight control of plasma glucose and cardiovascular risk factors represent the cornerstone of the treatment in diabetes to slow progression of vascular disease.

Gestational diabetes mellitus and the risk of metabolic syndrome: a population-based study in Lausanne, Switzerland.

AIMS: To investigate the relationships between gestational diabetes mellitus (GDM) and the metabolic syndrome (MS), as it was suggested that insulin resistance was the hallmark of both conditions. To analyse post-partum screening in order to identify risk factors for the subsequent development of type 2 diabetes mellitus (DM). METHODS: A retrospective analysis of all singleton pregnancies diagnosed with GDM at the Lausanne University Hospital for 3 consecutive years. Pre-pregnancy obesity, hypertension and dyslipidaemia were recorded as constituents of the MS. RESULTS: For 5788 deliveries, 159 women (2.7%) with GDM were identified. Constituents of the MS were present before GDM pregnancy in 26% (n = 37/144): 84% (n = 31/37) were obese, 38% (n = 14/37) had hypertension and 22% (n = 8/37) had dyslipidaemia. Gestational hypertension was associated with obesity (OR = 3.2, P = 0.02) and dyslipidaemia (OR = 5.4, P=0.002). Seventy-four women (47%) returned for post-partum OGTT, which was abnormal in 20 women (27%): 11% (n = 8) had type 2 diabetes and 16% (n = 12) had impaired glucose tolerance. Independent predictors of abnormal glucose tolerance in the post-partum were: having > 2 abnormal values on the diagnostic OGTT during pregnancy and presenting MS constituents (OR = 5.2, CI 1.8-23.2 and OR = 5.3, CI 1.3-22.2). CONCLUSIONS: In one fourth of GDM pregnancies, metabolic abnormalities precede the appearance of glucose intolerance. These women have a high risk of developing the MS and type 2 diabetes in later years. Where GDM screening is not universal, practitioners should be aware of those metabolic risks in every pregnant woman presenting with obesity, hypertension or dyslipidaemia, in order to achieve better diagnosis and especially better post-partum follow-up and treatment.

Gestational diabetes mellitus and the risk of metabolic syndrome: a population-based study in Lausanne, Switzerland

RESUME EN FRANÇAIS BUTS. Étudier les relations entre le diabète gestationnel (GDM) et le syndrome métabolique (MS), comme la résistance à l'insuline est une des caractéristiques des 'deux conditions. Analyser le dépistage du diabète dans le post-partum pour identifier les facteurs de risque associés au développement d'un diabète de type 2 ultérieur. MÉTHODES. Étude rétrospective de toutes les grossesses uniques diagnostiquées avec un diabète gestationnel à l'hôpital universitaire de Lausanne, pendant une durée de trois ans. La présence d'une obésité, d'une hypertension ou d'une dyslipidémie avant la grossesse définissent les composants du syndrome métabolique. RÉSULTATS. Sur 5788 grossesses, 159 patientes (2.7%) présentaient un diabète gestationnel. Des composants du syndrome métabolique étaient présents avant la grossesse chez 26% des patientes (n=37/144) : 84% (n=31/37) étaient obèses, 38% (n=14/37) présentaient une hypertension et 22% (n=8/37) une dyslipidémie. Le développement d'une hypertension gravidique était associé à l'obésité (OR=3.2, p=0.02) et à la dyslipidémie (OR=5.4, p=0.002). Septante-quatre patientes (47%) sont revenues pour l'HGPO dans le post-partum. Celle-ci était anormale chez 20 femmes (27%): 11 % (n=8) présentaient un diabète de type 2 et 16% (n=12) avaient une intolérance au glucose. Les facteurs de risque indépendants associés à une anomalie de la tolérance au glucose dans le post-partum étaient d'avoir plus de 2 valeurs anormales au test diagnostique durant la grossesse et présenter des composants du syndrome métabolique (OR=5.2, CI 1.8-23.2 et OR=5.3, CI 1.3-22.2). CONCLUSIONS. Dans un quart des grossesses avec un diabète gestationnel, des anomalies métaboliques précèdent l'apparition de l'intolérance au glucose. Ces patientes présentent un haut risque de développer un syndrome métabolique et un diabète de type 2 ultérieurement. Là où le dépistage du diabète gestationnel n'est pas systématique, les praticiens devraient être avertis de ces risques métaboliques chez les patiente se présentant avec une obésité, une hypertension ou une dyslipidémie, afin de mieux les diagnostiquer et surtout de mieux les suivre et traiter après leur grossesse.

Prevalence, awareness and treatment of type 2 diabetes mellitus in Switzerland : the COLAUS study

Le diabète de type 2 (DT2) a une prévalence élevée dans les pays industrialisés, et on s'attend à une augmentation dans les années à venir en raison du vieillissement de la population ainsi que des modifications du mode de vie. Il existe malheureusement peu de données épidémiologiques sur la prévalence et la prise en charge du diabète en Suisse. Les objectifs de cette étude étaient donc 1) évaluer la prévalence du DT2 dans une cohorte lausannoise ; 2) caractériser la prise en charge des patients atteints de DT2, et 3) identifier les facteurs associés à la prévalence, la connaissance par les patients de leur maladie et le traitement du DT2. Pour ce faire, 6181 sujets (3246 femmes), âgés de 35 à 75 ans et vivant à Lausanne ont été inclus dans l'étude. La prévalence totale du DT2 était de 6.3% (intervalle de confiance à 95%: 5.7-7.0%), une valeur comparable à celle des pays avoisinants. La prévalence était plus élevée chez les hommes que chez les femmes (9.1% contre 3.8%, p<0.001), et augmentait avec l'âge. Deux tiers des patients avec DT2 (65.3% ; 60.4-70.0%) avaient connaissance de leur situation, et plus de trois-quarts d'entre eux étaient traités. Les hommes étaient plus fréquemment traités que les femmes (91.3% contre 75.9%, p<0.001). La plupart des patients suivait une monothérapie (majoritairement par biguanides). Parmi les sujets avec une thérapie multiple, une prévalence plus élevée de glycémie à jeun >7 mmol/1 était présente. L'analyse multivariée a montré que le sexe masculin, l'âge croissant et un indice de masse corporelle élevé étaient associés à une plus grande prévalence du DT2, alors qu'aucune association n'a été trouvée pour l'activité physique et la consommation d'alcool. Parmi les sujets atteints de DT2, l'âge croissant était positivement associé à la connaissance du diabète, de même que l'âge croissant et le sexe masculin étaient associés à une plus grande prévalence du traitement. Le faible taux de connaissance de diabète pourrait être dû à un manque de dépistage par les médecins de premier recours. La présence d'autres facteurs de risque cardiovasculaire devrait inciter les médecins à un dépistage du diabète pour obtenir un meilleur profil de risque. Cette étude a des limitations. D'abord, aucune mesure de l'hémoglobine glyquée n'a été mesurée, et par conséquent la détermination de la prise en charge uniquement par la glycémie à jeun peut être difficile. Ensuite, le taux de participation était bas et pourrait limiter l'interprétation des résultats ; néanmoins, il est comparable à celui d'autres études effectuées dans les pays occidentaux. Il existe peu de données épidémiologiques du DT2 en Suisse, cette étude permet donc d'évaluer la situation actuelle et de déterminer la prévalence et la prise en charge du diabète à Lausanne à travers la cohorte CoLaus. Une telle étude a par conséquent son importance dans le contexte actuel, au vu du vieillissement de la population et de l'augmentation des facteurs de risque cardio-vasculaires.

Phenotypic and molecular characterization of the onset of neuropathy in rodent models of diabetes mellitus

Abstract : The principal focus of this work was to study the molecular changes leading to the development of diabetic peripheral neuropathy (DPN). DPN is the most common complication associated with both type I and II diabetes mellitus (DM). This pathology is the leading cause of non-traumatic amputations. Even though the pathological and morphological changes underlying DPN are relatively well described, the implicated molecular mechanisms remain poorly understood. The following two approaches were developed to study the development of DPN in a rodent model of DM type I. As a first approach, we studied the implication of lipid metabolism in DPN phenotype, concentrating on Sterol Response Element Binding Protein (SREBP)-lc which is the key regulator of storage lipid metabolism. We showed that SREBP-1c was expressed in peripheral nerves and that its expression profile followed the expression of genes involved in storage lipid metabolism. In addition, the expression of SREBP-1c in the endoneurium of peripheral nerves was dependant upon nutritional status and this expression was also perturbed in type I diabetes. In line with this, we showed that insulin elevated the expression of SREBP-1c in primary cultured Schwann cells by activating the SREBP-1c promoter. Taken together, these findings reveal that SREBP-1c expression in Schwann cells responds to metabolic stimuli including insulin and that this response is affected in type I diabetes mellitus. This suggests that disturbed SREBP-1c regulated lipid metabolism may contribute to the pathophysiology of DPN. As a second approach, we performed a comprehensive analysis of the molecular changes associated with DPN in the Akital~1~+ mouse which is a model of spontaneous early-onset type I diabetes mellitus. This mouse expresses a mutated non-functional isoform of insulin, leading to hypoinsulinemia and hyperglycaemia. To determine the onset of DPN, weight, blood glucose and motor nerve conduction velocity (MNCV) were measured in Akital+/+ mice during the first three months of life. A decrease in MNCV was evident akeady one week after the onset of hyperglycemia. To explore the molecular changes associated with the development of DPN in these mice, we performed gene expression profiling using sciatic nerve endoneurium and dorsal root ganglia (DRG) isolated from early diabetic male Akita+/+ mice and sex-matched littermate controls. No major transcriptional changes were detected either in the DRG or in the sciatic nerve endoneurium. This experiment indicates that the phenotypic changes observed during the development of DPN are not correlated with major transcriptional alterations, but mainly with alterations at the protein level. Résumé Lors ce travail, nous nous sommes intéressés aux changements moléculaires aboutissant aux neuropathies périphériques dues au diabète (NPD). Les NPD sont la complication la plus commune du diabète de type I et de type II. Cette pathologie est une cause majeure d'amputations. Même si les changements pathologiques et morphologiques associés aux NPD sont relativement bien décrits, les mécanismes moléculaires provoquant cette pathologie sont mal connus. Deux approches ont principalement été utilisées pour étudier le développement des NPD dans des modèles murins du diabète de type I. Nous avons d'abord étudié l'impact du métabolisme des lipides sur le développement des NPD en nous concentrant sur Sterol Response Element Binding Protein (SREBP)-1 c qui est un régulateur clé des lipides de stockage. Nous avons montré que SREBP-1 c est exprimé dans les nerfs périphériques et que son profil d'expression suit celui de gènes impliqués dans le métabolisme des lipides de stockage. De plus, l'expression de SREBP-1c dans l'endoneurium des nerfs périphériques est dépendante du statut nutritionnel et est dérégulée lors de diabète de type I. Nous avons également pu montrer que l'insuline augmente l'expression de SREBP-1c dans des cultures primaires de cellules de Schwann en activant le promoteur de SREBP-1c. Ses résultats démontrent que l'expression de SREBP-1c dans les cellules de Schwann est contrôlée par des stimuli métaboliques comme l'insuline et que cette réponse est affectée dans le cas d'un diabète de type I. Ces données suggèrent que la dérégulation de l'expression de SREBP-1c lors du diabète pourrait affecter le métabolisme des lipides et ainsi contribuer à la pathophysiologie des NPD. Comme seconde approche, nous avons réalisé une analyse globale des changements moléculaires associés au développement des NPD chez les souris Akita+/+, un modèle de diabète de type I. Cette souris exprime une forme mutée et non fonctionnelle de l'insuline provoquant une hypoinsulinémie et une hyperglycémie. Afin de déterminer le début du développement de la NPD, le poids, le niveau de glucose sanguin et la vitesse de conduction nerveuse (VCN) ont été mesurés durant les 3 premiers mois de vie. Une diminution de la VCN a été détectée une semaine seulement après le développement de l'hyperglycémie. Pour explorer les changements moléculaires associés avec le développement des NPD, nous avons réalisé un profil d'expression de l'endoneurium du nerf sciatique et des ganglions spinaux isolés à partir de souris Akital+/+ et de souris contrôles Akita+/+. Aucune altération transcriptionnelle majeure n'a été détectée dans nos échantillons. Cette expérience suggère que les changements phénotypiques observés durant le développement des NPD ne sont pas corrélés avec des changements importants au niveau transcriptionnel, mais plutôt avec des altérations au niveau protéique. Résumé : Lors ce travail, nous nous sommes intéressés aux changements moléculaires aboutissant aux neuropathies périphériques dues au diabète (NPD). Les NPD sont la complication la plus commune du diabète de type I et de type II. Cette pathologie est une cause majeure d'amputations. Même si les changements pathologiques et morphologiques associés aux NPD sont relativement bien décrits, les mécanismes moléculaires provoquant cette pathologie sont mal connus. Deux approches ont principalement été utilisées pour étudier le développement des NPD dans des modèles murins du diabète de type I. Nous avons d'abord étudié l'impact du métabolisme des lipides sur le développement des NPD en nous concentrant sur Sterol Response Element Binding Protein (SREBP)-1c qui est un régulateur clé des lipides de stockage. Nous avons montré que SREBP-1 c est exprimé dans les nerfs périphériques et que son profil d'expression suit celui de gènes impliqués dans le métabolisme des lipides de stockage. De plus, l'expression de SREBP-1c dans l'endoneurium des nerfs périphériques est dépendante du statut nutritionnel et est dérégulée lors de diabète de type I. Nous avons également pu montrer que l'insuline augmente l'expression de SREBP-1c dans des cultures primaires de cellules de Schwann en activant le promoteur de SREBP-1c. Ses résultats démontrent que l'expression de SREBP-1c dans les cellules de Schwann est contrôlée par des stimuli métaboliques comme l'insuline et que cette réponse est affectée dans le cas d'un diabète de type I. Ces données suggèrent que la dérégulation de l'expression de SREBP-1c lors du diabète pourrait affecter le métabolisme des lipides et ainsi contribuer à la pathophysiologie des NPD. Comme seconde approche, nous avons réalisé une analyse globale des changements moléculaires associés au développement des NPD chez les souris Akita~~Z~+, un modèle de diabète de type I. Cette souris exprime une forme mutée et non fonctionnelle de l'insuline provoquant une hypoinsulinémie et une hyperglycémie. Afin de déterminer le début du développement de la NPD, le poids, le niveau de glucose sanguin et la vitesse de conduction nerveuse (VCN) ont été mesurés durant les 3 premiers mois de vie. Une diminution de la VCN a été détectée une semaine seulement après le développement de l'hyperglycémie. Pour explorer les changements moléculaires associés avec le développement des NPD, nous avons réalisé un profil d'expression de l'endoneurium du nerf sciatique et des ganglions spinaux isolés à partir de souris Akital+/+ et de souris contrôles Akita+/+. Aucune altération transcriptionnelle majeure n'a été détectée dans nos échantillons. Cette expérience suggère que les changements phénotypiques observés durant le développement des NPD ne sont pas corrélés avec des changements importants au niveau transcriptionnel, mais plutôt avec des altérations au niveau protéique.

Prevalence, awareness and treatment of type 2 diabetes mellitus in Switzerland: the CoLaus study.

ABSTRACT: Aims To assess the prevalence, awareness and treatment levels of Type 2 diabetes in a Swiss city. Methods Population-based cross-sectional study of 6181 subjects (3246 women) aged 35-75 years living in Lausanne, Switzerland. Type 2 diabetes was defined as fasting plasma glucose >/= 7 mmol/l and/or oral hypoglycaemic treatment and/or insulin. Results Total prevalence of Type 2 diabetes was 6.3% (95% confidence interval: 5.7-7.0%), higher in men (9.1%) than in women (3.8%, P < 0.001) and increased with age. Two-thirds (65.3%; 60.4-70.0%) of participants with Type 2 diabetes were aware of their status and among those aware 86.0% (81.5-90.3%) were treated. Treatment was more frequent in men (91.3%) than in women (75.9%, P < 0.001). Two-thirds of those treated for Type 2 diabetes were on monotherapy. Biguanides were prescribed in 65.0% of Type 2 diabetes patients and represented 48% of all antidiabetic drugs. Multivariable analysis showed male gender, increasing age, waist or BMI to be positively associated with prevalence of Type 2 diabetes, while leisure-time physical activity and alcohol consumption were negatively associated. Among participants presenting with Type 2 diabetes, increasing age was positively associated with awareness of Type 2 diabetes. Among subjects diagnosed with Type 2 diabetes, male gender and increasing age were positively associated with treatment. Conclusion Prevalence of Type 2 diabetes in Switzerland is estimated to be between 5.7% and 7.0%. Two-thirds of patients with Type 2 diabetes are aware of their status, and over three quarters of those aware are treated.

Potential Role of TRAIL in the Management of Autoimmune Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, due to the immune-mediated destruction of pancreatic β-cells, whose incidence has been steadily increasing during the last decades. Insulin replacement therapy can treat T1DM, which, however, is still associated with substantial morbidity and mortality. For this reason, great effort is being put into developing strategies that could eventually prevent and/or cure this disease. These strategies are mainly focused on blocking the immune system from attacking β-cells together with functional islet restoration either by regeneration or transplantation. Recent experimental evidences suggest that TNFrelated apoptosis-inducing ligand (TRAIL), which is an immune system modulator protein, could represent an interesting candidate for the cure for T1DM and/or its complications. Here we review the evidences on the potential role of TRAIL in the management of T1DM.

Circulating microRNAs as novel biomarkers for diabetes mellitus.

Diabetes mellitus is characterized by insulin secretion from pancreatic β cells that is insufficient to maintain blood glucose homeostasis. Autoimmune destruction of β cells results in type 1 diabetes mellitus, whereas conditions that reduce insulin sensitivity and negatively affect β-cell activities result in type 2 diabetes mellitus. Without proper management, patients with diabetes mellitus develop serious complications that reduce their quality of life and life expectancy. Biomarkers for early detection of the disease and identification of individuals at risk of developing complications would greatly improve the care of these patients. Small non-coding RNAs called microRNAs (miRNAs) control gene expression and participate in many physiopathological processes. Hundreds of miRNAs are actively or passively released in the circulation and can be used to evaluate health status and disease progression. Both type 1 diabetes mellitus and type 2 diabetes mellitus are associated with distinct modifications in the profile of miRNAs in the blood, which are sometimes detectable several years before the disease manifests. Moreover, circulating levels of certain miRNAs seem to be predictive of long-term complications. Technical and scientific obstacles still exist that need to be overcome, but circulating miRNAs might soon become part of the diagnostic arsenal to identify individuals at risk of developing diabetes mellitus and its devastating complications.

Subclinical coronary and aortic atherosclerosis detected by magnetic resonance imaging in type 1 diabetes with and without diabetic nephropathy.

BACKGROUND: Patients with type 1 diabetes and nephropathy maintain an excess cardiovascular mortality compared with diabetic patients with normoalbuminuria. We sought to evaluate coronary and aortic atherosclerosis in a cohort of asymptomatic type 1 diabetic patients with and without diabetic nephropathy using cardiovascular magnetic resonance imaging. METHODS AND RESULTS: In a cross-sectional study, 136 subjects with long-standing type 1 diabetes without symptoms or history of cardiovascular disease, including 63 patients (46%) with nephropathy and 73 patients with normoalbuminuria, underwent cardiovascular magnetic resonance imaging. All subjects underwent cardiac exercise testing and noninvasive tests for peripheral artery disease and autonomic neuropathy. Coronary artery stenoses were identified in 10% of subjects with nephropathy (versus 0% with normoalbuminuria; P=0.007). Coronary plaque burden, expressed as right coronary artery mean wall thickness (1.7+/-0.3 versus 1.3+/-0.2 mm; P<0.001) and maximum right coronary artery wall thickness (2.2+/-0.5 versus 1.6+/-0.3 mm; P<0.001), was greater in subjects with nephropathy. The prevalence of thoracic (3% versus 0%; P=0.28) and abdominal aortic plaque (22% versus 16%; P=0.7) was similar in both groups. Subjects with and without abdominal aortic plaques had similar coronary plaque burden. CONCLUSIONS: In asymptomatic type 1 diabetes, cardiovascular magnetic resonance imaging reveals greater coronary plaque burden in subjects with nephropathy compared with those with normoalbuminuria.