The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes

Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender. Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD. Heteroplasmy levels are at least one of the determinants of the severity of the phenotype of maternally inherited diabetes and deafness

Central blood pressure and pulse wave velocity: relationship to target organ damage and cardiovascular morbidity-mortality in diabetic patients or metabolic syndrome. An observational prospective study. LOD-DIABETES study protocol

<p>Abstract</p> <p>Background</p> <p>Diabetic patients show an increased prevalence of non-dipping arterial pressure pattern, target organ damage and elevated arterial stiffness. These alterations are associated with increased cardiovascular risk.</p> <p>The objectives of this study are the following: to evaluate the prognostic value of central arterial pressure and pulse wave velocity in relation to the incidence and outcome of target organ damage and the appearance of cardiovascular episodes (cardiovascular mortality, myocardial infarction, chest pain and stroke) in patients with type 2 diabetes mellitus or metabolic syndrome.</p> <p>Methods/Design</p> <p><b>Design</b>: This is an observational prospective study with 5 years duration, of which the first year corresponds to patient inclusion and initial evaluation, and the remaining four years to follow-up.</p> <p><b>Setting</b>: The study will be carried out in the urban primary care setting.</p> <p><b>Study population</b>: Consecutive sampling will be used to include patients diagnosed with type 2 diabetes between 20-80 years of age. A total of 110 patients meeting all the inclusion criteria and none of the exclusion criteria will be included.</p> <p><b>Measurements</b>: Patient age and sex, family and personal history of cardiovascular disease, and cardiovascular risk factors. Height, weight, heart rate and abdominal circumference. Laboratory tests: hemoglobin, lipid profile, creatinine, microalbuminuria, glomerular filtration rate, blood glucose, glycosylated hemoglobin, blood insulin, fibrinogen and high sensitivity C-reactive protein. Clinical and 24-hour ambulatory (home) blood pressure monitoring and self-measured blood pressure. Common carotid artery ultrasound for the determination of mean carotid intima-media thickness. Electrocardiogram for assessing left ventricular hypertrophy. Ankle-brachial index. Retinal vascular study based on funduscopy with non-mydriatic retinography and evaluation of pulse wave morphology and pulse wave velocity using the SphygmoCor system. The medication used for diabetes, arterial hypertension and hyperlipidemia will be registered, together with antiplatelet drugs.</p> <p>Discussion</p> <p>The results of this study will help to know and quantify the prognostic value of central arterial pressure and pulse wave velocity in relation to the evolution of the subclinical target organ damage markers and the possible incidence of cardiovascular events in patients with type 2 diabetes mellitus.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier: NCT01065155</p

Diabetes mellitus in the elderly: from the epidemiological challenge to a personalized approach

peer reviewedDiabetes mellitus is a common chronic disease in the elderly, being either a known disease with a long history (type 1 or even more often type 2 diabetes) and then frequently associated with various diabetic complications, or a recently diagnosed diabetes that may, however, have been ignored for a rather long time. In this latter case, diabetes may present as the occurrence or aggravation of one or several geriatric syndromes that overall result in a loss of autonomy. The global geriatric assessment, the estimation of life expectancy and the justification of glucose-lowering treatments should be performed at regular intervals in elderly diabetic people as they determine the right choice of glucose target levels and the best selection of glucose-lowering agents. Medications that can induce hypoglycaemia should ideally be avoided, especially in the frailty older population. The benefit-risk ratio of the proposed therapies should be analyzed first, and then regularly reassessed because of a potentially rapidly progressing condition. The recommended approach is a tailored management of diabetes that should integrate the clinical, functional and psycho-social aspects of elderly individuals.Le patient âgé, atteint de diverses maladies chroniques, est généralement confronté à une polymédication qui l’expose à des manifestations indésirables potentielles. Cellesci peuvent s’expliquer par des particularités pharmacocinétiques ou pharmacodynamiques qui rendent le patient âgé plus vulnérable vis-à-vis des effets de certains médicaments. Le recrutement des patients âgés dans les essais cliniques laisse souvent à désirer de telle sorte qu’il n’est pas toujours aisé de déterminer le réel rapport bénéfices/risques d’un médicament dans cette population. A l’évidence, l’iatrogénie y est fréquente de telle sorte qu’une altération inexpliquée de l’état de santé d’un sujet âgé doit faire évoquer une éventuelle origine médicamenteuse. Ce constat doit inciter le clinicien à une prescription raisonnée et raisonnable des médicaments chez la personne âgée, en s’interrogeant non seulement sur l’intérêt d’initier un traitement pharmacologique, mais aussi sur l’opportunité d’interrompre éventuellement une thérapie en cours, inutile, voire dangereuse. Plutôt que la polymédication en tant que telle, c’est plutôt la prescription inappropriée qui doit être évitée chez la personne âgée

Haemoglobin A1c and 5-year all-cause mortality in French type 2 diabetic patients aged 70 years and older: The GERODIAB observational cohort.

peer reviewedAIM: The role of glycaemic control in the mortality of elderly diabetic patients remains uncertain. GERODIAB is the first multi-centre, prospective, observational study that aims to describe the link between HbA1c and 5-year mortality in French, type 2 diabetic patients aged >/=70 years. METHODS: Consecutive patients (n=987; mean age 77 years) were included from 56 diabetes centres and followed for five years. Individual histories, risk factors, standard diabetes parameters and geriatric evaluations were regularly recorded. Survival was studied using the Kaplan-Meier method. Multivariable analyses used Cox regression. RESULTS: Twenty-one percent of the patients died, 13% were lost during follow-up. Patients with a 5-year mean HbA1c in the range [40-50) mmol/mol ([5.8-6.7) %) had the highest survival (84%); those in the range [50-70) mmol/mol ([6.7-8.6) %) or /=70mmol/mol (>/=8.6%) the worst survival (71%). Patients with mean HbA1c >/=70mmol/mol (>/=8.6%) had a significantly higher mortality than those with lower HbA1c (P=0.011), and HbA1c remained a significant predictor of mortality after adjusting for individual, diabetic and geriatric factors (hazards ratio [95%CI]: 1.76 [1.21 to 2.57], P=0.0033). Survival was also significantly associated with both HbA1c variability and with the frequency of HbA1c determinations. CONCLUSION: In this large sample of elderly French type 2 diabetic patients, an HbA1c level <70mmol/mol (<8.6%) was associated with lower mortality. The range [40-50) mmol/mol ([5.8-6.7) %) could be an acceptable target provided patients are not exposed to hypoglycaemia

GERODIAB: Glycaemic control and 5-year morbidity/mortality of type 2 diabetic patients aged 70 years and older: 1. Description of the population at inclusion.

International audienceAIMS: The GERODIAB study is the first French multicentre, prospective, observational study that aims, through a 5-year cohort follow-up, to evaluate the link between glycaemic control and morbidity/mortality of type 2 diabetic (T2D) patients aged 70 years and older. This first report describes the study population at inclusion. PATIENTS AND METHODS: A total of 987 T2D autonomous patients, aged ≥70 years, were recruited between June 2009 and July 2010 at 56 investigator centres. Their general parameters, diabetes characteristics and standard geriatric parameters were recorded. RESULTS: The patients' mean age was 77±5 years, with 65.2% aged 75 years or more. The mean BMI was close to 30 kg/m(2). Hypertension was found in 89.7% of patients, and 85.0% had at least one cholesterol abnormality. The mean duration of the diabetes was around 18 years, and the mean HbA(1c) level was about 7.5%. During the previous six months, 33.6% of patients had experienced one or several hypoglycaemias. Also, 26% of patients presented with diabetic retinopathy, 37.3% had a GFR<60 mL/min, 31.2% had coronary insufficiency, 10.1% had heart failure, 15.8% had cerebrovascular involvement and 25.6% had peripheral vascular disease of the lower extremities. In addition, 30.5% of patients had orthostatic hypotension, 12.4% had malnutrition and 28.8% had cognitive impairment, all of which were often diagnosed at inclusion. Three-quarters of patients were taking an oral antidiabetic drug and nearly six in every 10 patients were using insulin. CONCLUSION: This population can be considered representative of elderly, autonomous T2D patients, and its follow-up should clarify the link between glycaemic control and mortality/morbidity

Evaluation of Boys with Marked Breast Development at Puberty

During the 10-year period from 1979 to 1988 we evaluated 60 boys who were more than 9 years old and who had significant breast development (greater than 4 cm in diameter) around the time of puberty. An endocrine abnormality was identified in seven subjects. The pathology included Klinefelter's syndrome; 46, XX maleness; primary testicular failure; partial androgen insensitivity; fibrolamellar hepatocarcinoma; and increased aromatase activity. Eight of the remaining 53 subjects had underlying medical problems, five of them having neurologic disorders. The 45 remaining subjects were considered to have significant idiopathic gynecomastia, a condition sometimes referred to as macromastia. These boys tended to be both taller and heavier than average, the mean Z score for height being 1.4 SDs above the mean and the mean weight score being 2.7 SDs above the mean. This study underscores the observation that pathologic causes of marked pubertal gynecomastia are unusual. However, the potential for significant health problems among boys with marked breast development supports the need for an endocrine evaluation of all affected subjects. Our data also indicate that boys with marked idiopathic breast development have greater body mass than other boys of similar age. This may contribute in part to the greater breast development in these subjects