[Study of the links between type 2 diabetes and geriatric criteria]. / Étude des liens entre diabète de type 2 et critères gériatriques.

Type 2 diabetes in the elderly remains a major concern for all healthcare professionals and is itself considered a "global pandemic". Its prevalence is high and will continue to increase in years to come, becoming more and more prevalent in the elderly and very elderly. We offer a general summary of the work focusing on the links between type 2 diabetes and geriatric criteria.

Cardiovascular protective effects of GLP-1: a focus on the MAPK signaling pathway.

Cardiovascular and related metabolic diseases are significant global health challenges. Glucagon-like peptide 1 (GLP-1) is a brain-gut peptide secreted by the ileal endocrine system and is now an established drug target in type 2 diabetes (T2DM). GLP-1 targeting agents have been shown not only to treat T2DM, but also to exert cardiovascular protective effects by regulating multiple signaling pathways. The mitogen-activated protein kinase (MAPK) pathway, a common signal transduction pathway for transmitting extracellular signals to downstream effector molecules, is involved in regulating diverse cellular physiological processes, including cell proliferation, differentiation, stress, inflammation, functional synchronization, transformation, and apoptosis. The purpose of this review is to highlight the relationship between GLP-1 and cardiovascular disease (CVD) and discuss how GLP-1 exerts cardiovascular protective effects through the MAPK signaling pathway. This review also discusses the future challenges in fully characterizing and evaluating the CVD protective effects of GLP-1 receptor agonists (GLP-1RA) at the cellular and molecular levels. A better understanding of the MAPK signaling pathway that is dysregulated in CVD may aid in the design and development of promising GLP-1RA.

The anti-anginal ranolazine does not confer beneficial actions against hepatic steatosis in male mice subjected to high-fat diet and streptozotocin-induced type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess fat in the liver in the absence of alcohol and increases one's risk for both diabetes and cardiovascular disease (e.g., angina). We have shown that the second-line anti-anginal therapy, ranolazine, mitigates obesity-induced NAFLD, and our aim was to determine whether these actions of ranolazine also extend to NAFLD associated with type 2 diabetes (T2D). Eight-week-old male C57BL/6J mice were fed either a low-fat diet or a high-fat diet for 15 weeks, with a single dose of streptozotocin (STZ; 75 mg/kg) administered in the high-fat diet-fed mice at 4 weeks to induce experimental T2D. Mice were treated with either vehicle control or ranolazine during the final 7 weeks (50 mg/kg once daily). We assessed glycemia via monitoring glucose tolerance, insulin tolerance, and pyruvate tolerance, whereas hepatic steatosis was assessed via quantifying triacylglycerol content. We observed that ranolazine did not improve glycemia in mice with experimental T2D, while also having no impact on hepatic triacylglycerol content. Therefore, the salutary actions of ranolazine against NAFLD may be limited to obese individuals but not those who are obese with T2D.

Prediabetes and deprivation: A couple at high risk of diabetes.

AIM: The higher prevalence of diabetes in deprived populations is well documented but little is known about the risk of diabetes associated with deprivation among pre-diabetic subjects. The aim of the study was to evaluate the risk of diabetes in a population of deprived pre-diabetic patients. METHODS: 2743 pre-diabetic subjects identified using the American Diabetes Association (ADA) criteria, 16 to 85 years old, 1656 non-deprived and 1087 deprived, had at least two health check-ups at an interval of 4.95 (2.04) vs 3.20 (1.71) years, P<0.0001, respectively. At the first visit, socioeconomic status was assessed using the EPICES score to differentiate deprived and non-deprived subjects. RESULTS: At the second visit, the prevalence of overt diabetes was 9.5% among deprived vs 5.1% in the non-deprived group (P<0.001). After adjustment on confounding factors, deprivation was found independently associated with occurrence of diabetes [1.70 (1.15-2.51), P=0.01]. Beyond social deprivation, Fasting Plasma Glucose and waist circumference were the main independent predictors of new-onset diabetes. CONCLUSION: After 4 years of follow-up, among subjects with prediabetes, prevalence of diabetes was twice as high among deprived compared with non-deprived subjects. Deprived populations with pre-diabetes may require specific public health approaches to avoid the occurrence of overt diabetes.

Improving management of type 2 diabetes, hypertension and dyslipidaemia in the Caribbean: a systematic review of intervention studies.

OBJECTIVE: To evaluate published interventions aimed at improving the management of type 2 diabetes, hypertension and dyslipidaemia in the Caribbean. METHODS: We conducted a systematic review of four databases in accordance with PRISMA guidelines. Inclusion criteria were conducted in the Caribbean among adults ≥ 18 years who had type 2 diabetes, hypertension or dyslipidaemia; controlled trials, interventions, or comparative studies with pre-post designs and reported on at least one of the clinical outcomes of interest. RESULTS: Seventeen studies met the criteria for inclusion. The majority were conducted in Cuba and Trinidad and Tobago, and 35% were conducted over 10 years ago. Samples were small and largely consisted of older adult females and patients with type 2 diabetes. Four of eight (50%) studies that reported on HbA1c, 5 of 12 (42%) that reported on blood pressure and 2 of 7 (29%) that reported on body mass index observed significant improvements. Study heterogeneity precluded our ability to conduct a meta-analysis. The overall quality of evidence based on GRADE criteria was low for all outcomes assessed. CONCLUSION: There is insufficient evidence on interventions to address type 2 diabetes, hypertension and dyslipidaemia in the Caribbean.

OBJECTIF: Evaluer les interventions publiées visant à améliorer la prise en charge du diabète de type 2, de l'hypertension et de la dyslipidémie dans les Caraïbes. MÉTHODES: Nous avons effectué une revue systématique de quatre bases de données conformément aux directives PRISMA. Les critères d'inclusion étaient: menée dans les Caraïbes auprès d'adultes de 18 ans et plus qui souffraient de diabète de type 2, d'hypertension ou de dyslipidémie; essais contrôlés, interventions ou études comparatives avec des conceptions pré/post; et rapportant au moins 1 des résultats cliniques d'intérêt. RÉSULTATS: 17 études répondaient aux critères d'inclusion. La majorité a été réalisée à Cuba et à Trinité-et-Tobago et 35% ont été réalisées il y a plus de 10 ans. Les échantillons étaient petits et portaient en grande partie sur des femmes adultes plus âgées et des patients atteints de diabète de type 2. Quatre des 8 études (50%) qui rapportaient sur l'HbA1c, 5 des 12 (42%) qui rapportaient sur la pression artérielle et 2 des 7 (29%) qui rapportaient sur l'indice de masse corporelle ont observé des améliorations significatives. L'hétérogénéité de l'étude a empêché notre capacité de mener une méta-analyse. La qualité globale des données basées sur les critères de GRADE était faible pour résultats évalués. CONCLUSION: Il n'y a pas suffisamment de données sur les interventions pour lutter contre le diabète de type 2, l'hypertension et la dyslipidémie dans les Caraïbes.

Socioeconomic inequalities in the utilisation of hypertension and type 2 diabetes management services in Indonesia.

OBJECTIVES: To describe socioeconomic inequalities in the utilisation of hypertension and type 2 diabetes (T2D) management services in the Indonesian population and to determine whether education level and geographical location contribute to inequalities. METHODS: Cross-sectional study using data from the 2014 Indonesia Family Life Survey (N = 30 762 for hypertension; N = 6758 for T2D). Socioeconomic status was measured by household consumption. The prevalence of hypertension and T2D was determined using internationally standardised clinical measurement, while disease management was defined by participation in screening and current use of medication. The relative index of inequality (RII) was used to estimate inequalities, adjusted to education level and geographical location. RESULTS: For all household consumption quintiles, we observed low rates of screening participation for T2D and low medication use in both hypertension and T2D. We found socioeconomic inequalities in screening participation for hypertension (RII 2.68, 95% CI 2.42-2.96) and T2D (RII 7.30, 95% CI 5.48-9.72) and also for medication use in hypertension (RII 3.09, 95% CI 2.28-4.18) and T2D (RII 2.81, 95% CI 1.09-7.27). Education level contributed to socioeconomic inequalities in screening utilisation for both hypertension and T2D. Geographical location contributed to inequalities in screening utilisation and medication use for T2D. Socioeconomic inequalities in medication use for hypertension and T2D were larger among men than women. CONCLUSIONS: Large socioeconomic inequalities were found in the utilisation of hypertension and T2D management services in Indonesia. Improving affordability, availability and approachability of services is crucial to reduce such inequalities.

INÉGALITÉS SOCIOÉCONOMIQUES DANS L'UTILISATION DES SERVICES DE PRISE EN CHARGE DE L'HYPERTENSION ET DU DIABÈTE DE TYPE 2 EN INDONÉSIE: OBJECTIFS: Décrire les inégalités socioéconomiques dans l'utilisation des services de prise en charge de l'hypertension et du diabète de type 2 (DT2) au sein de la population indonésienne et déterminer si le niveau d'éducation et la localisation géographique contribuent aux inégalités. MÉTHODES: Etude transversale utilisant les données de l'enquête 2014 sur la vie de famille en Indonésie (N = 30.762 pour l'hypertension; N = 6.758 pour le DT2). Le statut socioéconomique a été mesuré par la consommation des ménages. La prévalence de l'hypertension et du DT2 a été déterminée à l'aide de mesures cliniques standardisées à l'échelle internationale, tandis que la prise en charge de la maladie était définie par la participation au dépistage et à l'utilisation courante de médicaments. L'indice relatif d'inégalité (RII) a été utilisé pour estimer les inégalités, ajustées à l'échelle de l'éducation et à la localisation géographique. RÉSULTATS: Pour tous les quintiles de consommation des ménages, nous avons observé de faibles taux de participation au dépistage du DT2 et une faible utilisation de médicaments dans l'hypertension et le DT2. Nous avons constaté des inégalités socioéconomiques dans la participation au dépistage de l'hypertension (RII= 2,68; IC95%: 2,42 à 2,96) et du DT2 (RII= 7,30; IC95%: 5,48 à 9,72), ainsi que de l'utilisation de médicaments pour l'hypertension (IIR= 3,09; IC95%: 2,28 à 4.18) et pour le DT2 (RII= 2,81; IC95%: 1,09-7,27). Le niveau d'éducation a contribué aux inégalités socioéconomiques dans l'utilisation du dépistage pour l'hypertension et le DT2. La localisation géographique a contribué aux inégalités dans l'utilisation du dépistage et de l'utilisation de médicaments pour le DT2. Les inégalités socioéconomiques dans l'utilisation des médicaments contre l'hypertension et le DT2 étaient plus importantes chez les hommes que chez les femmes. CONCLUSIONS: De grandes inégalités socioéconomiques ont été constatées dans l'utilisation des services de prise en charge de l'hypertension et du DT2 en Indonésie. Améliorer l'aspect abordable, la disponibilité et l'accessibilité des services est crucial pour réduire ces inégalités.

Artefactual inflation of type 2 diabetes prevalence in WHO STEP surveys.

OBJECTIVES: In view of erroneous type 2 diabetes prevalence reported in 3 small Pacific Island countries, a study was conducted to investigate whether this error occurred in other countries which have conducted WHO STEPS surveys associated with glucose thresholds for point-of-care (POC) measuring devices calibrated to plasma. METHODS: Published STEPS surveys conducted over 2001-2017 were obtained. For each survey, information was obtained on diabetes prevalence, POC glucose measuring device, blood sample tested and the fasting glucose threshold used for prevalence calculations. POC device user manuals were obtained to determine calibration. The current WHO glucose threshold for type 2 diabetes was used: ≥7.0 mmol/l for plasma glucose; ≥6.1 mmol/l for whole blood glucose. RESULTS: POC devices were used in 75 of the STEPS surveys identified to measure blood glucose. An incorrect glucose threshold was employed in 17 surveys (23%) to define diabetes. The correct threshold was applied in 20 surveys (27%). Estimates from meta-analysis and meta-regression show that diabetes prevalence in surveys using the incorrect glucose thresholds have prevalences 50% higher than surveys which use the correct glucose threshold. A definite conclusion could not be made for 38 surveys (51%) because of the absence or unclear information on the glucose metre and/or the threshold employed. CONCLUSION: WHO STEPS surveys with likely incorrect published diabetes prevalences have been conducted across the globe, resulting in a 50% artefactual inflation. Inaccurate reporting of diabetes prevalence from widely cited STEPS surveys would have significant impacts on disease burden monitoring, policy development and resource allocation.

OBJECTIFS: Compte tenu de la prévalence erronée du diabète de type 2 rapportée dans 3 petits pays insulaires du Pacifique, une étude a été menée pour déterminer si cette erreur s'était produite dans d'autres pays ayant mené des surveillances STEPS de l'OMS, associées à des seuils de glucose pour des appareils de mesure aux points de soins, calibrés sur du plasma. MÉTHODES: Les surveillances STEPS publiées, menées entre 2001 et 2017 ont été obtenues. Pour chaque surveillance, les informations ont été obtenues sur la prévalence du diabète, l'appareil de mesure du glucose aux points des soins, les échantillons de sang testés et le seuil de glycémie à jeun utilisé pour les calculs de prévalence. Les manuels d'utilisation des appareils ont été obtenus pour déterminer l'étalonnage. Le seuil de glucose actuel de l'OMS pour le diabète de type 2 a été utilisé: ≥ 7,0 mmol/L pour le glucose plasmatique; ≥ 6,1 mmol/L pour le glucose du sang total. RÉSULTATS: Les dispositifs de mesure aux points des soins ont été utilisés dans 75 des surveillances STEPS identifiées pour mesurer la glycémie. Un seuil de glucose incorrect a été utilisé dans 17 surveillances (23%) pour définir le diabète. Le seuil correct a été appliqué dans 20 surveillances (27%). Les estimations issues de méta-analyses et de méta-régressions montrent que la prévalence du diabète dans les surveillances utilisant des seuils de glucose incorrects est supérieure de 50% à celle des surveillances utilisant le seuil de glucose correct. Une conclusion définitive n'a pu être tirée pour 38 surveillances (51%) à cause de l'absence ou du manque de clarté des informations sur le glucomètre et/ou le seuil utilisé. CONCLUSION: Les enquêtes STEPS de l'OMS avec des prévalences de diabète publiées probablement incorrectes ont été menées dans le monde entier, entraînant une inflation artéfactuelle de 50%. Des reports inexacts de la prévalence du diabète provenant de surveillances STEPS largement citées auraient des impacts significatifs sur la surveillance de la charge de morbidité, l'élaboration de politiques et l'allocation des ressources.

Short telomere subtelomeric hypomethylation is associated with telomere attrition in elderly diabetic patients 1.

Telomere shortening is well known to be associated with the aging process and aging-associated diseases, including diabetes. The telomere length and subtelomeric methylation status in peripheral leucocytes (LTL) were compared in elderly type 2 diabetes (T2D) patients and diabetes-free controls (C). The methylation status was analyzed between MspI-TRF lengths and HpaII-TRF lengths by using methylation-sensitive and -insensitive restriction enzyme isoschizomers, MspI and HpaII, respectively. The mean telomere lengths, MspI-TRF or HpaII-TRF, were not significantly different between C and T2D patients. The percentage of fractionated densitometry showed that long and middle telomeres (>9.4 kb, 4.4-9.4 kb) were unaltered but short telomeres (<4.4 kb) in T2D patients were increased compared with C group. The methylation status revealed subtelomeric hypomethylation in short telomeres of T2D patients. When some patients with T2D were treated with 3-hydroxy-3-methylglutaril coenzyme A (HMG-CoA) reductase inhibitors (statin), results seen in short telomere of T2D patients were not observed and were not different from C. This suggested that this altered subtelomeric hypomethylation may be associated with the accelerated telomere shortening in elderly diabetic patients. These results also mean that the subtelomeric hypomethylation can also be influenced by statin treatment in T2D.

[Comorbidity schizophrenia and diabetes mellitus in Algeria - A study of risk factors]. / Comorbidité schizophrénie et diabète de type 2 en Algérie ­ étude des facteurs de risque.

BACKGROUND: The combination of schizophrenia and diabetes mellitus presents a public health problem in the world. Several studies have been carried out for the analysis of this comorbidity, including prognostic factors. OBJECTIVE: The objective of our study is to determine the risk factors associated with the comorbidity schizophrenia and diabetes mellitus. METHODS: From a sample of 200 cases of schizophrenic patients hospitalized at the Sidi Chami psychiatric hospital of Oran in Algeria, we carried out a descriptive transversal and analytical study during the period of one year. RESULTS: Our results are consistent with those of the different studies carried out in neighboring countries. Among the risk factors recorded in our study, we mention the age of 40 and over, divorce, dyslipidemia, high blood pressure, overweight and severe and moderate obesity, the age of schizophrenia of 30 to 40 years, the first-generation neuroleptic treatment and family history related to diabetes. While the male sex, celibacy and second-generation neuroleptics were found in the study as protective factors against the onset of diabetes mellitus in schizophrenic patients. CONCLUSION: The factors associated with comorbidity schizophrenia and type 2 diabetes are manifold. These factors must be taken into account when introducing preventive behaviors that must be multidisciplinary in order to ensure better patient care.

Follow-up of glycemic index before and after Ramadan fasting in type 2 diabetes patients under antidiabetic medications.

INTRODUCTION: Fasting has no adverse effects on healthy Muslims during Ramadan. However, it can induce serious complications for patients with type 2 diabetes (T2D). We aimed to follow the variation of some biochemical and clinical parameters in T2D patients before and after Ramadan; and to determine the incidence of fasting on hypoglycaemia and lactic acidosis associated with antidiabetic agents such as metformin. MATERIALS AND METHODS: This work is a prospective study conducted during Ramadan on 150 patients, recruited 2 to 3 weeks prior to the start. These patients were sensitized about the Ramadan lifestyle and diet as well as the medications to take. RESULTS: This study results indicated a significant decrease of glycated haemoglobin (from 8.06% to 7.42%) and a similar trend in the fasting plasma glucose (from 1.81 to 1.36g/L) before and after Ramadan respectively. The serum lipid profile showed significant variations during the study period, and antidiabetic medications was associated with low serum lactate. The plasma creatinine and uric acid were reduced but remained insignificant. DISCUSSION AND CONCLUSION: Based on data from our study, we concluded that a safe fasting with a lower risk hypoglycaemia, can be achieved in a well-controlled patients, under antidiabetic drugs. However, the diabetes medication was associated with a small increase in serum lactate levels that seemed to be dose-independent and not affected by treatment duration.

[Factors associated with medication non-adherence in patients with type 2 diabetes mellitus: The first Algerian survey]. / Facteurs associés à la non-observance thérapeutique chez les diabétiques de type 2 : première enquête algérienne.

BACKGROUND: Non-adherence in patients with type 2 diabetes is a frequent phenomenon with important impact in terms of management of this disease. The aim of this study was to assess the level of medication adherence and to identify the factors associated with non-adherence in type 2 diabetic patients. METHODS: A cross-sectional study was conducted in type 2 diabetic patients at the endocrinology and diabetology department of University Medical Center of Sidi Bel Abbes (Algeria) in 2017. Medication adherence was determined using a morisky 8-Item medication adherence questionnaire. A logistic regression was used to identify factors associated with non-adherence. RESULTS: The study enrolled 403 type 2 diabetic patients. The mean age was 60 years and sex-ratio was 0.8. Medication non-adherence rate was 31.3% (95% CI: 26.8-35.8%). The factors significantly associated with non-adherence in multivariate analysis were: health insurance status, self-monitoring of blood glucose, disease duration, education level and need for information on diabetes. CONCLUSION: Our study had demonstrated a low adherence in patients with type 2 diabetes. The results suggest that implementation of a therapeutic education program could be important in management of diabetes.

Coumarins improved type 2 diabetes induced by high-fat diet and streptozotocin in mice via antioxidation.

Coumarins extensively exist in plants and are utilized against diabetes in some folk medicines. Recent studies have demonstrated that oxidative stress plays a crucial role in the etiology and pathogenesis of diabetes mellitus. We investigated the antioxidant ability of 3 coumarins (osthole, esculin, and fraxetin) in type 2 diabetes. After being fed a high-fat diet, ICR mice were exposed to low doses of streptozotocin and then treated with experimental coumarins for 5 weeks. We found osthole, esculin, and metformin significantly lowered fasting blood glucose, HOMA-IR, and 3 blood lipids (total cholesterol, total triglyceride, free fatty acids), and increased insulin levels, while fraxetin only enhanced insulin levels and lessened free fatty acids. Both osthole and esculin had antioxidative effects in pancreas through elevating the activities of glutathione peroxidase, catalase, and superoxide dismutase; fraxetin, however, merely heightened catalase activity. By contrast, 3 coumarins significantly increased those antioxidase activities in liver. Hematoxylin and eosin staining revealed 3 coumarins, especially osthole, attenuated cellular derangement, blurry fringes of hepatic sinusoid and extensive vacuolization due to hepatocellular lipid accumulation, and lessened inflammatory infiltration in pancreas. The glomerular and islet structure of diabetic mice were improved, with reduced mesangial matrix and glomerular basement membrane thickening. Therefore, our study supports that coumarins could be promising candidates against type 2 diabetes through antioxidative mechanisms.

Potential role of liver enzyme levels as predictive markers of glucose metabolism disorders in a Tunisian population.

The relationship between liver enzymes and T2D risk is inconclusive. We aimed to evaluate the association between liver markers and risk of carbohydrate metabolism disorders, as well as their discriminatory power, for T2D prediction. This cross-sectional study enrolled 216 participants classified as normoglycemic, prediabetic, newly diagnosed diabetics, and diagnosed diabetics. All participants underwent anthropometric and biochemical measurements. The relationship between hepatic enzymes and glucose metabolism markers was evaluated by analyses of covariance. The associations between liver enzymes and incident carbohydrate metabolism disorders were analyzed through logistic regression and their discriminatory capacity to predict T2D by ROC analysis. High AP, ALT, γGT, and AST levels were independently related to decreased insulin sensitivity. Interestingly, a higher AP level was significantly associated with an increased risk of prediabetes (p = 0.017), newly diagnosed diabetes (p = 0.004), and T2D (p = 0.007). An elevated γGT level was an independent risk factor for T2D (p = 0.032) and undiagnosed T2D (p = 0.010) in prediabetic and normoglycemic subjects, respectively. In ROC analysis, AP was a powerful predictor of incident diabetes and significantly improved T2D prediction. Liver enzymes within the normal range, specifically AP levels, are associated with increased risk of carbohydrate metabolism disorders and significantly improved T2D prediction.

MicroRNAs in the pathogenesis of type 2 diabetes: new research progress and future direction.

miRNA is a short non-coding RNA that can influence mRNA processing at the post-transcriptional level. A large number of miRNAs have been found in virtually all species so far, and these small molecules play an important role in many different physiological processes and various pathologic conditions, such as cell metabolism, cancer, autoimmune disease, and diabetes mellitus. T2D arises from a dysregulated response to the elevated glucose level in the circulation. The prevalence of T2D has increased dramatically in all age groups, and T2D in older adults is associated with more T2D complications and higher mortality. Despite the existing findings describing the pathological mechanism, T2D pathology is more complex and the pathophysiology of the disease is still not fully elucidated. In this review, we summarize the current understanding of miRNA-mediated modulation of gene expression in T2D pathogenesis, as well as related signaling pathways, and insight into the important role of miRNA in various T2D complications. Furthermore, the potential therapeutic value of miRNA for T2D patients is also discussed in detail.

Connecting homocysteine and obesity through pyroptosis, gut microbiome, epigenetics, peroxisome proliferator-activated receptor γ, and zinc finger protein 407.

Although homocysteine (Hcy), a part of the epigenome, contributes to cell death by pyroptosis and decreases peroxisome proliferator-activated receptor γ (PPARγ) levels, the mechanisms are unclear. Hcy is found in high concentrations in the sera of obese individuals, which can elicit an immune response as well by hypermethylating CpG islands of specific gene promoters, a marker of epigenetics. Hcy has also been established to chelate divalent metal ions like Cu2+ and Zn2+, but this role of Hcy has not been established in relationship with obesity. It has been known for a while that PPARγ dysregulation results in various metabolic disorders including glucose and lipid metabolism. Recently, zinc finger protein 407 (Zfp407) is reported to regulate PPARγ target gene expression without affecting PPARγ transcript and protein levels by synergistically working with PPARγ. However, the mechanism(s) of this synergy, as well as other factors contributing to or inhibiting this synergism, have not been proven. This review suggests that Hcy contributes to pyroptosis, changes gut microbiome, and alters PPARγ-dependent mechanism(s) via Zfp407-mediated upregulated adipogenesis and misbalanced fatty acid metabolism, which can predispose to obesity and, consequently, obesity-related metabolic disorders.

Relationship between PDK1 and contraction in carotid arteries in Goto-Kakizaki rat, a spontaneous type 2 diabetic animal model.

We studied the relationship between 3-phosphoinositide-dependent protein kinase 1 (PDK1) and contractions induced by serotonin, phenylephrine, and thromboxane A2 mimetic (U46619) in the presence of nitric oxide synthase inhibitor in the carotid arteries of Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic model, in the chronic stage of disease. Serotonin-induced contraction was greater in the GK rats than in the control Wistar rats. A specific PDK1 inhibitor (GSK2334470) decreased the serotonin-induced contraction in the GK rats but not in the Wistar rats, and the difference in such contraction was abolished with this treatment. In GK rats, phenylephrine-induced contraction exhibited a leftward shift and U46619-induced contraction was greater still. Phenylephrine- and U46619-induced contractions were reduced by GSK2334470 in both groups. These results suggest, for the first time, that the contribution of PDK1 is different among 3 vasoconstrictors and that PDK1 contributed to increased serotonin-induced contraction in the carotid arteries of GK rats.

[Analysis of direct medical costs of type 2 diabetes in Mali]. / Analyse des coûts médicaux directs des soins du diabète de type 2 au Mali.

BACKGROUND: Type 2 Diabetes (T2D) is rapidly increasing in Africa, but it is still rather neglected. Demonstrating the medical costs for treating type 2 diabetes would be useful for improving awareness and proposing solutions. The purpose of this study was to compare the estimated medical costs for basic chronic treatment and the actual expenditures of diabetic patients, and to identify determinants of these expenditures. METHODS: The estimated medical costs were based on price data collected from three public hospitals and their pharmacies (one university and two district hospitals), as well as from three private clinics and three private pharmacies, in Bamako. A standard treatment protocol for diabetes care, with and without complications, was first established by a working group prior to pricing of consultations, medication, care devices and specialized tests and treatments. Costs were computed using an Excel® software program. We calculated actual expenditures for medical care and examined some determinants using the data from a cross-sectional survey on 500 adult diabetic subjects in Mali. Participants were randomly selected from registries of known diabetics. RESULTS: The estimated costs for basic medical care of uncomplicated diabetes ranged from 108 to 298 € per year in the public sector, and 325 to 756 € in the private sector. Median annual expenditures of survey subjects without complications for chronic care amounted to 178 € (range: 98-331) and were therefore in the estimated range in the public sector. Total median expenditures of all survey subjects, including 78% with complications, reached 241 € per year (142-386). Additional expenditures for the treatment of complications were lower than the estimated costs, except for retinopathy. Independent predictors of higher expenditures were insulin treatment, residence in Bamako, and the number of complications. The minimum estimated cost of medical treatment for uncomplicated diabetes in the public sector represented 29% of GNP per capita. Total medical expenditures as reported by survey respondents amounted to an average of 24% of their income. CONCLUSION: Treatment of T2D is expensive and beyond reach for many patients in Mali, particularly when there are complications. Prevention of diabetes is an urgent challenge in Africa, along with early screening in order to delay and reduce the occurrence of complications.

[Pharmacist's interview with type 2 diabetes: Development of a follow-up form]. / L'entretien pharmaceutique pour le patient diabétique de type 2 : élaboration d'une fiche de suivi.

OBJECTIVES: Type 2 diabetes is a major public health concern because of its prevalence, the severity of complications and the financial implications. Compliance and patient's autonomy in medications intake play key roles in the success of treatment. Pharmacists' interviews ensure an optimized and individual follow-up. Type 2 diabetes is not one of the targeted diseases to perform pharmacists' interviews on under Health Insurance. We thus judged useful to contribute to their development. METHODS: We applied a cross-disciplinary methodological process in order to define the specifications of the follow-up form useful to conduct the pharmacist's interview 1 by focusing on the identification of a non-compliance and its origins. A feasibility study was carried out in order to check its workability to the pharmacy practice. RESULTS: The follow-up form, associated with a pharmacist practical guide, includes 3 parts: (1) General informations, (2) Survey establishing patient's knowledge, (3) Summary including a level of knowledge assessment grid. Outcomes provide a long but appropriate-felt duration, few difficulties to conduct the interview and a proven usefulness in 90% of all cases that make the follow-up form suitable to the pharmacy practice. CONCLUSIONS: This tool could serve as a model for the pharmacist to conduct his future interviews for the type 2 diabetes patients, thus improving patient care, together with other health professionals.

Beneficial effects of kinin B1 receptor antagonism on plasma fatty acid alterations and obesity in Zucker diabetic fatty rats.

Kinins are the endogenous ligands of the constitutive B2 receptor (B2R) and the inducible B1 receptor (B1R). Whereas B2R prevents insulin resistance, B1R is involved in insulin resistance and metabolic syndrome. However, the contribution of B1R in type 2 diabetes associated with obesity remains uncertain. The aim of the present study was to examine the impact of 1-week treatment with a selective B1R antagonist (SSR240612, 10 mg/kg per day, by gavage) on hyperglycemia, hyperinsulinemia, leptinemia, body mass gain, and abnormal plasma fatty acids in obese Zucker diabetic fatty (ZDF) rats. Treatment with SSR240612 abolished the body mass gain and reduced polyphagia, polydipsia, and plasma fatty acid alterations in ZDF rats without affecting hyperglycemia, hyperinsulinemia, and hyperleptinemia. The present study suggests that the upregulated B1R plays a role in body mass gain and circulating fatty acid alterations in ZDF rats. However, mechanisms other than B1R induction would be implicated in glucose metabolism disorder in ZDF rats, based on the finding that SSR240612 did not reverse hyperglycemia and hyperinsulinemia.

Inhibition of islet amyloid polypeptide aggregation and associated cytotoxicity by nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute an important pharmacotherapeutic class that, over the past decade, have expanded in application to a panoply of medical conditions. They have been tested for neurodegenerative diseases such as Alzheimer's to reduce inflammation and also in the attempt to abrogate amyloid deposition. However, the use of NSAIDs as aggregation inhibitors has not been extensively studied in pancreatic amyloid deposition. Pancreatic amyloidosis involves the misfolding of islet amyloid polypeptide (IAPP) and contributes to the progression of type-2 diabetes in humans and felines. To ascertain their antiamyloidogenic activity, several NSAIDs were tested using fluorometric thioflavin-T assays, circular dichroism, photo-induced cross-linking assays, and cell culture. Celecoxib, diclofenac, indomethacin, meloxicam, niflumic acid, nimesulide, phenylbutazone, piroxicam, sulindac, and tenoxicam reduced fibrillization at a molar ratio of 1:10. The circular dichroism spectra of diclofenac, piroxicam, and sulindac showed characteristic spectral signatures found in predominantly α-helical structures. The oligomerization of human IAPP was abrogated with diclofenac and sulindac at a molar ratio of 1:5. The cytotoxic effects of pre-incubated human IAPP on cultured INS-1 cells were noticeably reduced in the presence of diclofenac, meloxicam, phenylbutazone, sulindac, and tenoxicam at a molar ratio of 1:10. Our results demonstrate that NSAIDs can provide chemical scaffolds to generate new and promising antiamyloidogenic agents that can be used alone or as a coadjuvant therapy.