Fucoidan-based particles for diabetes mellitus treatment

Marine organisms are rich in a variety of materials with potential use in Tissue Engineering and Regenerative Medicine. One important example is fucoidan, a sulfated polysaccharide extracted from the cell wall of brown seaweeds.  Fucoidan is composed by L-fucose, sulfate groups and glucuronic acid. It has important bioactive properties such as anti-oxidative, anticoagulant, anticancer and reducing the blood glucose (1). In this work, the biomedical potential of fucoidan-based materials as drug delivery system was assessed by processing modified fucoidan (MFu) into particles by photocrosslinking using superamphiphobic surfaces and visible light. Fucoidan was modified by methacrylation reaction using different concentrations of methacrylate anhydride, namely 8% v/v (MFu1) and 12% v/v (MFu2). Further, MFu particles with and without insulin (5% w/v) were produced by pipetting a solution of 5% MFu with triethanolamine and eosin-y onto a superamphiphobic surface and then photocrosslinking using visible light (2). The developed particles were characterized to assess their chemistry, morphology, swelling behavior, drug release, insulin content and encapsulation efficiency. Moreover, the viability assays of fibroblast L929 cells in contact with MFu particles showed good adhesion and proliferation up to 14 days. Furthermore, the therapeutic potential of these particles using human beta cells is currently under investigation. Results obtained so far suggest that modified fucoidan particles could be a good candidate for diabetes mellitus therapeutic approaches.  

Use of Sensors in the Treatment and Follow-up of Patients with Diabetes Mellitus

Glucose control is the cornerstone of Diabetes Mellitus (DM) treatment. Although self-regulation using capillary glycemia (SRCG) still remains the best procedure in clinical practice, continuous glucose monitoring systems (CGM) offer the possibility of continuous and dynamic assessment of interstitial glucose concentration. CGM systems have the potential to improve glycemic control while decreasing the incidence of hypoglycemia but the efficiency, compared with SRCG, is still debated. CGM systems have the greatest potential value in patients with hypoglycemic unawareness and in controlling daily fluctuations in blood glucose. The implementation of continuous monitoring in the standard clinical setting has not yet been established but a new generation of open and close loop subcutaneous insulin infusion devices are emerging making insulin treatment and glycemic control more reliable.

Serum sCD163 levels are associated with type 2 diabetes mellitus and are influenced by coffee and wine consumption: results of the Di@bet.es study.

OBJECTIVE Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. RESEARCH DESIGN AND METHODS This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. RESULTS sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46-2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). CONCLUSIONS High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes.

Lack of correlation between the optimal glycaemic control and coronary micro vascular dysfunction in patients with diabetes mellitus: a cross sectional study.

Background Coronary microvascular dysfunction (CMD) is associated with cardiovascular events in type 2 diabetes mellitus (T2DM). Optimal glycaemic control does not always preclude future events. We sought to assess the effect of the current target of HBA1c level on the coronary microcirculatory function and identify predictive factors for CMD in T2DM patients. Methods We studied 100 patients with T2DM and 214 patients without T2DM. All of them with a history of chest pain, non-obstructive angiograms and a direct assessment of coronary blood flow increase in response to adenosine and acetylcholine coronary infusion, for evaluation of endothelial independent and dependent CMD. Patients with T2DM were categorized as having optimal (HbA1c < 7 %) vs. suboptimal (HbA1c ≥ 7 %) glycaemic control at the time of catheterization. Results Baseline characteristics and coronary endothelial function parameters differed significantly between T2DM patients and control group. The prevalence of endothelial independent CMD (29.8 vs. 39.6 %, p = 0.40) and dependent CMD (61.7 vs. 62.2 %, p = 1.00) were similar in patients with optimal vs. suboptimal glycaemic control. Age (OR 1.10; CI 95 % 1.04–1.18; p < 0.001) and female gender (OR 3.87; CI 95 % 1.45–11.4; p < 0.01) were significantly associated with endothelial independent CMD whereas glomerular filtrate (OR 0.97; CI 95 % 0.95–0.99; p < 0.05) was significantly associated with endothelial dependent CMD. The optimal glycaemic control was not associated with endothelial independent (OR 0.60, CI 95 % 0.23–1.46; p 0.26) or dependent CMD (OR 0.99, CI 95 % 0.43–2.24; p = 0.98). Conclusions The current target of HBA1c level does not predict a better coronary microcirculatory function in T2DM patients. The appropriate strategy for prevention of CMD in T2DM patients remains to be addressed. Keywords: Endothelial dysfunction; Diabetes mellitus; Coronary microcirculation

Essstörungen bei Adipositas und Diabetes mellitus [Eating disorders associated with obesity and diabetes].

Binge eating disorder is one of the most frequent comorbid mental disorders associated with overweight and obesity. Binge eating disorder patients often suffer from other mental disorders and longitudinal studies indicate a continuous weight gain during the long-term course. As in other eating disorders gender is a risk factor, but the proportion of male binge eating disorder patients is surprisingly high.In young women with type 1 diabetes the prevalence of subclinical types of bulimia nervosa is increased. In addition, insulin purging as a characteristic compensatory behavior in young diabetic women poses a considerable problem. In patients with type 1 diabetes, disturbed eating and eating disorders are characterized by insufficient metabolic control and early development of late diabetic sequelae. Patients with type 2 diabetes are often overweight or obese. Binge eating disorder does not occur more frequently in patients with type 2 diabetes compared to healthy persons. However, the comorbidity of binge eating disorder and diabetes type 2 is associated with weight gain and insulin resistance. Especially in young diabetic patients a screening procedure for disturbed eating or eating disorders seems to be necessary. Comorbid patients should be offered psychotherapy.

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.

Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus--a prospective single-blinded randomised crossover trial.

Aims/hypothesis We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type I diabetes at euglycaemia and hyperglycaemia with identical insulin levels.Methods This was a single-blinded randomised crossover study at a university diabetes unit in Switzerland. We studied seven physically active men with type I diabetes (mean +/- SEM age 33.5 +/- 2.4 years, diabetes duration 20.1 +/- 3.6 years, HbA(1c) 6.7 +/- 0.2% and peak oxygen uptake [VO2peak] 50.3 +/- 4.5 ml min(-1) kg(-1)). Men were studied twice while cycling for 120 min at 55 to 60% of VO2peak, with a blood glucose level randomly set either at 5 or 11 mmol/l and identical insulinaemia. The participants were blinded to the glycaemic level; allocation concealment was by opaque, sealed envelopes. Magnetic resonance spectroscopy was used to quantify intramyocellular glycogen and lipids before and after exercise. Indirect calorimetry and measurement of stable isotopes and counter-regulatory hormones complemented the assessment of local and systemic fuel metabolism.Results The contribution of lipid oxidation to overall energy metabolism was higher in euglycaemia than in hyperglycaemia (49.4 +/- 4.8 vs 30.6 +/- 4.2%; p<0.05). Carbohydrate oxidation accounted for 48.2 +/- 4.7 and 66.6 +/- 4.2% of total energy expenditure in euglycaemia and hyperglycaemia, respectively (p<0.05). The level of intramyocellular glycogen before exercise was higher in hyperglycaemia than in euglycaemia (3.4 +/- 0.3 vs 2.7 +/- 0.2 arbitrary units [AU]; p<0.05). Absolute glycogen consumption tended to be higher in hyperglycaemia than in euglycaemia (1.3 +/- 0.3 vs 0.9 +/- 0.1 AU). Cortisol and growth hormone increased more strongly in euglycaemia than in hyperglycaemia (levels at the end of exercise 634 52 vs 501 +/- 32 nmol/l and 15.5 +/- 4.5 vs 7.4 +/- 2.0 ng/ml, respectively; p<0.05).Conclusions/interpretation Substrate oxidation in type I diabetic patients performing aerobic exercise in euglycaemia is similar to that in healthy individuals revealing a shift towards lipid oxidation during exercise. In hyperglycaemia fuel metabolism in these patients is dominated by carbohydrate oxidation. Intramyocellular glycogen was not spared in hyperglycaemia.

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.

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.

Extreme self-monitoring, fear of hypoglycemia and obsessive-compulsive disorder in type 1 diabetes mellitus: when less is better

Background: Pre-existing psychological factors can strongly influence coping with type 1 diabetes mellitus and interfere with self-monitoring. Psychiatric disorders seem to be positively associated with poor metabolic control. We present a case of extreme compulsive blood testing due to obsessive fear of hypoglycemia in an adolescent with type 1 diabetes mellitus. Case report: Type 1 diabetes mellitus (anti GAD-antibodies 2624 U/l, norm < 9.5) was diagnosed in a boy aged 14.3 years [170 cm (+ 0.93 SDS), weight 50.5 kg (+ 0.05 SDS)]. Laboratory work-up showed no evidence for other autoimmune disease. Family and past medical history were unremarkable. Growth and developmental milestones were normal. Insulin-analog based basal-bolus regime was initiated, associated to standard diabetic education. Routine psychological evaluation performed at the onset of diabetes revealed intermittent anxiety and obsessivecompulsive traits. Accordingly, a close psychiatric follow-up was initiated for the patient and his family. An adequate metabolic control (HbA1c drop from >14 to 8%) was achieved within 3 months, attributed to residual -cell function. In the following 6 months, HbA1c rose unexpectedly despite seemingly adequate adaptations of insulin doses. Obsessive fear of hypoglycemia leading to a severe compulsive behavior developed progressively with as many as 68 glycemia measurements per day (mean over 1 week). The patient reported that he could not bear leaving home with glycemia < 15 mmol/l, ending up with school eviction and severe intra-familial conflict. Despite intensive psychiatric outpatient support, HbA1c rose rapidly to >14% with glycemia-testing reaching peaks of 120 tests/day. The situation could only be discontinued through psychiatric hospitalization with intensive behavioral training. As a result, adequate metabolic balance was restored (HbA1c value: 7.1 %) with acceptable 10-15 daily glycemia measurements. Discussion: The association of overt psychiatric disorders to type 1 diabetes mellitus is very rare in the pediatric age group. It can lead to a pathological behavior with uncontrolled diabetes. Such exceptional situations require long-term admissions with specialized psychiatric care. Slow acceptation of a "less is better" principle in glycemia testing and amelioration of metabolic control are difficult to achieve.

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.

Metformin in gestational diabetes mellitus

METFORMIININ KÄYTTÖ RASKAUSDIABETEKSESSA Raskausdiabeteksella tarkoitetaan sokeriaineenvaihdunnan häiriötä, joka todetaan ensimmäisen kerran raskauden aikana. Hoidolla voidaan vähentää raskausdiabetekseen liittyviä äidin ja vastasyntyneen haittoja. Lääkitystä tarvitaan, jos ruokavaliohoidolla ei saavuteta hyvää sokeritasapainoa. Perinteisesti lääkityksenä on käytetty insuliinia, mutta metformii¬nin käyttöä insuliinin vaihtoehtona on ehdotettu. Metformiini läpäisee istukan, mutta sen läpäisymekanismi ei ole selvillä. Tämän tutkimuskokonaisuuden pääasiallisin tarkoitus oli verrata metformiinin tehokkuutta ja turvallisuutta insuliiniin raskausdiabeteksen hoidossa selvittämällä lääkkeen vaiku¬tusta äitiin ja vastasyntyneeseen. Lisäksi haluttiin tutkia, mitkä tekijät ennustavat insulii¬nin tarvetta metformiinin lisänä, jotta saavutettaisiin hyvä sokeritasapaino. Metformiinin annoksen vaikutus äitiin ja vastasyntyneeseen arvioitiin mittaamalla metformiinin pitoisuus äidistä, ja sikiön puolelta napanuoran veressä. Tässä tutkimuksessa selvitettiin myös aktiivisen kuljetusproteiinin (OCT) merkitystä metformiinin kulkeutumiseen istukan läpi perfusiomalla istukkaa ex vivo . Ex vivo istukkaperfuusiotutkimuksen tulokset viittasivat siihen, että OCT-kuljetusproteiinilla ei ollut todennäköisesti merkittävää osuutta metformiinin kulkeutumisessa istukan läpi. Metformiinin pitoisuusmittaukset synnytyksen yhteydessä osoittivat metformiinin siirtyvän sikiöön istukan läpi suuressa määrin (96 %) kertymättä kuitenkaan sikiön verenkiertoon. Metformiinin pitoisuudella ei ollut vaikutusta vastasyntyneen hyvinvointiin. Maksi¬maalisella metformiinin annostuksella ja korkealla metformiinipitoisuudella todettiin olevan suotuisa vaikutus äidin painon nousuun raskauden aikana. Insuliiniin verrattuna metformiini ei lisännyt äidin, sikiön tai vastasyntyneen haittatapahtumia, eikä sillä ollut vaikutusta synnytystapaan. Sokeritasapaino insuliini- ja metformiinilääkityksen aikana oli yhtäläinen arvioitaessa sitä HbA1c- ja fruktosamiinimittauksilla, mutta 21 % metformiinin käyttäjistä tarvitsi lisäksi insuliinia hyvän sokeritasapainon saavuttamiseksi. Tutkimuksesssa todettiin, että mitä iäkkäämpi äiti oli, mitä varhaisemmassa raskauden vaiheessa sokerirasitus oli tehty ja lääkitys aloitettu, ja mitä korkeammat HbA1c ja fruktosamiinipitoisuudet olivat, sitä suuremmalla todennäköisyydellä metformiinin lisänä tarvittiin insuliinia.

Autoradiographic thyroid evaluation in short-term experimental diabetes mellitus

Previous studies have shown that in vitro thyroid peroxidase (TPO) iodide oxidation activity is decreased and thyroid T4-5'-deiodinase activity is increased 15 days after induction of experimental diabetes mellitus (DM). In the present study we used thyroid histoautoradiography, an indirect assay of in vivo TPO activity, to determine the possible parallelism between the in vitro and in vivo changes induced by experimental DM. DM was induced in male Wistar rats (about 250 g body weight) by a single ip streptozotocin injection (45 mg/kg), while control (C) animals received a single injection of the vehicle. Seven and 30 days after diabetes induction, each diabetic and control animal was given ip a tracer dose of 125I (2 µCi), 2.5 h before thyroid excision. The glands were counted, weighed, fixed in Bouin's solution, embedded in paraffin and cut. The sections were stained with HE and exposed to NTB-2 emulsion (Kodak). The autohistograms were developed and the quantitative distribution of silver grains was evaluated with a computerized image analyzer system. Thyroid radioiodine uptake was significantly decreased only after 30 days of DM (C: 0.38 ± 0.05 vs DM: 0.20 ± 0.04%/mg thyroid, P<0.05) while in vivo TPO activity was significantly decreased 7 and 30 days after DM induction (C: 5.3 and 4.5 grains/100 µm2 vs DM: 2.9 and 1.6 grains/100 µm2, respectively, P<0.05 ). These data suggest that insulin deficiency first reduces in vivo TPO activity during short-term experimental diabetes mellitus