ABSTRACT
AIMS: This study aimed to assess the relationship between blood pressure and cognitive function in elderly patients with diabetes mellitus (DM). METHODS: A total of 32 patients with DM aged ≥ 65 years (seven women and 25 men; mean ± SD age: 74.3 ± 6.4 years) were included in this cross-sectional study. Relationships between blood pressure and neuropsychological tests were determined using Spearman's rank correlations (ρ) and multivariable linear regression models. RESULTS: Lower diastolic blood pressure was associated with lower scores on the Frontal Assessment Battery (ρ=0.32, P=0.02), longer times to complete the Trail Making Test Part B (ρ=0.51, P=0.003), lower scores for the Finger Tapping Test (ρ=0.36, P=0.046) and less verbal fluency (ρ=0.36, P=0.047). In multivariable models, these relationships were attenuated after adjusting for levels of education. CONCLUSION: There was an association between lower diastolic blood pressure and poorer executive function in this cohort of elderly DM patients. These results underline the importance of systematic cognitive evaluation in elderly patients with DM, and suggest that a too-low diastolic blood pressure may have deleterious effects on mental function. Larger studies in the future are required to confirm these preliminary results.
Subject(s)
Blood Pressure , Cognition Disorders/physiopathology , Cognition , Diabetes Mellitus/physiopathology , Diabetes Mellitus/psychology , Educational Status , Executive Function , Age Factors , Aged , Aged, 80 and over , Aging , Biomarkers/blood , Blood Glucose/metabolism , Cognition Disorders/blood , Cognition Disorders/epidemiology , Cognition Disorders/psychology , Cross-Sectional Studies , Diabetes Mellitus/blood , Diabetes Mellitus/epidemiology , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 1/psychology , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/psychology , Female , France/epidemiology , Humans , Linear Models , Male , Neuropsychological TestsABSTRACT
AIMS: Atypical forms of diabetes may be caused by monogenic mutations in key genes controlling beta-cell development, survival and function. This report describes an insulin-dependent diabetes patient with a syndromic presentation in whom a homozygous SLC29A3 mutation was identified. METHODS: SLC29A3 was selected as the candidate gene based on the patient's clinical manifestations, and all exons and flanking regions in the patient's genomic DNA were sequenced. RESULTS: A homozygous splice mutation (c.300+1G>C) resulting in a frameshift and truncated protein (p.N101LfsX34) was identified. The patient had insulin-dependent diabetes, congenital deafness, short stature, hyperpigmented patches on the skin, dysmorphic features, cardiomegaly, arthrogryposis, hepatosplenomegaly, anaemia with erythroblastopenia, and an inflammatory syndrome with fever and arthritis; she also presented with a fibrotic mediastinal mass. These clinical features overlapped with pigmented hypertrichosis with insulin-dependent diabetes (PHID), H syndrome, Faisalabad histiocytosis and sinus histiocytosis with massive lymphadenopathy (SHML), all of which are also caused by SLC29A3 mutations. CONCLUSION: This is the most severe case reported of SLC29A3 mutations with cumulative features of all these syndromes. This extreme severity coincides with the most N-terminal location of the truncation mutation, thereby affecting all alternative transcripts of the gene. This case report extends the clinical variability of homozygous SLC29A3 mutations that result in a spectrum of multisystemic manifestations.
Subject(s)
Contracture/genetics , Diabetes Mellitus, Type 1/genetics , Hearing Loss, Sensorineural/genetics , Histiocytosis/genetics , Nucleoside Transport Proteins/genetics , Adolescent , Child , DNA Mutational Analysis , Female , Humans , Mutation , SyndromeABSTRACT
AIM: Spontaneous diurnal variations measured by optical coherence tomography (OCT) have been reported in diabetic macular oedema (DME) together with a daytime decrease in central macular thickness (CMT). For this reason, this study aimed to investigate the influence of acute glucose and blood pressure changes on daytime variations in CMT in patients with DME. METHODS: In this prospective observational study of type 1 (n=4) and type 2 (n=18) diabetic patients with DME, OCT scans, capillary blood glucose, and systolic and diastolic blood pressure measurements were performed at 9 a.m., 12 a.m., 3 p.m., 6 p.m. and again at 9 a.m. the day after. At the same time, the study protocol included simultaneous ambulatory blood pressure and glucose monitoring over a 24-h period. Hypoglycaemic episodes, defined as glucose values<60mg/dL, were also recorded. RESULTS: CMT decreased consistently between 9 a.m. and 6 p.m. in 10 patients (from 374±82µm to 337±72µm; P=0.01) and increased or remained steady in 12 others (from 383±136µm to 390±149µm; P=0.58), with a significant difference in CMT absolute change between the two groups (P<0.001). In the study population as a whole, the lower the mean diurnal blood glucose, the smaller the decrease in CMT during the day (P=0.027). Also, eight (67%) of the 12 patients with a flat CMT profile experienced a diurnal hypoglycaemic event whereas none of those with a CMT decrease had hypoglycaemia (P=0.002). CONCLUSION: Hypoglycaemic events may explain the lack of diurnal CMT decrease in diabetic patients with DME. However, further studies need to be conducted to evaluate whether having no diurnal CMT decrease is associated with a poorer visual prognosis and whether it can be modified by better glucose control.
Subject(s)
Blood Glucose/metabolism , Diabetic Retinopathy/diagnosis , Hypoglycemia/complications , Macular Edema/diagnosis , Adolescent , Adult , Aged , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Diabetic Retinopathy/blood , Diabetic Retinopathy/epidemiology , Female , Follow-Up Studies , France/epidemiology , Glycated Hemoglobin/metabolism , Humans , Hypoglycemia/blood , Hypoglycemia/epidemiology , Macular Edema/blood , Macular Edema/complications , Male , Middle Aged , Prospective Studies , Retina/physiopathology , Tomography, Optical Coherence , Vascular Endothelial Growth Factor A/bloodABSTRACT
AIM: The study aimed to determine the effectiveness and tolerability of rosiglitazone, and its profile in terms of treatment adherence, treated patients and prescribing recommendations under everyday conditions of care. METHODS: This was a "real-life" observational longitudinal study including patients with type 2 diabetes mellitus (T2DM) starting treatment with rosiglitazone and followed for up to 2 years. A questionnaire was completed at the time of inclusion and during routine consultations at around 6, 12, 18 and 24 months following inclusion. Information was collected on sociodemographics, clinical history, treatments, co-morbidities, laboratory data and compliance with treatment. There were three primary outcome measures: treatment response (defined as an HbA1c ≤ 8.0% or a decrease in HbA1c ≥ 0.7%); switch to insulin (as considered necessary by the physician); and occurrence of adverse events requiring a change or discontinuation of treatment. RESULTS: The evaluation included 670 patients (61.1%) treated with rosiglitazone/metformin as fixed-dose combination tablets and 427 (38.9%) with standard rosiglitazone tablets. Rates of HbA1c response, defined as an HbA1c less than or equal to 8.0% or a decrease in HbA1c greater than or equal to 0.7%, ranged from 80.6% to 92.1% depending on the follow-up time. The percentage of patients with an HbA1c less than 7% was 18.4% before rosiglitazone was prescribed, and ranged from 48.2% to 57.8% depending on the follow-up period. Sixty-two patients (6.1%, 95% CI: 4.6-7.6%) switched to insulin therapy during the follow-up period. Spontaneously reported adverse events leading to a change or discontinuation of treatment were seen in 45 patients (4.4%, 95% CI: 3.2-5.6%). CONCLUSION: Rosiglitazone showed sustained efficacy, with around 90% of patients defined as responders to the treatment in terms of reduction in HbA1c, and was relatively well tolerated. The adverse-event profile was consistent with the known effects of rosiglitazone, and no signs of increased cardiovascular ischaemic risk were observed. These results are in agreement with previous studies on rosiglitazone.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Thiazolidinediones/therapeutic use , Adult , Aged , Blood Glucose/metabolism , Comorbidity , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetic Angiopathies/epidemiology , Diabetic Angiopathies/prevention & control , Female , Follow-Up Studies , France/epidemiology , Glycated Hemoglobin/metabolism , Humans , Hypercholesterolemia/epidemiology , Hypertension/epidemiology , Hypoglycemic Agents/administration & dosage , Longitudinal Studies , Male , Medication Adherence/statistics & numerical data , Middle Aged , Practice Patterns, Physicians'/statistics & numerical data , Rosiglitazone , Smoking/epidemiology , Surveys and Questionnaires , Thiazolidinediones/administration & dosage , Time Factors , Treatment OutcomeABSTRACT
AIM: This study evaluated the incidence of diabetic retinopathy (DR) over a 3-year period in a French population that was followed by OPHDIAT®, and assessed the clinical and biological risk factors associated with incident retinopathy. METHODS: The studied patients were screened for DR during hospitalization for their annual diabetes check-up in the endocrinology department by two examinations three years apart. DR screening used the OPHDIAT® telemedical network, and the examination included clinical and biological data. RESULTS: A total of 254 patients were studied. At the 3-year follow-up, the incidence was 14.0%, (CI: 9.5-18.4%). Longer duration of diabetes and the presence of micro- or macroalbuminuria were significantly associated with incident retinopathy (P<0.05). Other potential risk factors were not statistically significantly related to DR progression, and only treatment with insulin showed a trend towards significance (P<0.20). CONCLUSION: This study provides the first French data on the incidence of DR, which was estimated after a 3-year follow-up at 14.0%. Longer duration of time from the onset of diabetes and higher baseline albuminuria were the only statistically significant risk factors found for the incidence of DR after our 3-year study. Nevertheless, microalbuminuria should be more widely used in ophthalmological practice in the assessment of DR, as is already the case for both blood pressure and HbA(1c).
Subject(s)
Albuminuria/epidemiology , Diabetic Retinopathy/epidemiology , Albuminuria/metabolism , Albuminuria/physiopathology , Cohort Studies , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/physiopathology , Disease Progression , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Paris/epidemiology , Retrospective Studies , Risk Factors , Telemedicine , Time Factors , White People/statistics & numerical dataABSTRACT
AIM: Type 2 diabetes mellitus (T2DM) is often associated with chronic kidney disease. For this reason, this article reviews the relationship between treatment of T2DM and renal disease. METHOD: The review presents the recent French data on the management of diabetes in patients with renal impairment, and discusses the implications of renal disease for the treatment of such patients. Prescribing data are presented for various antidiabetic treatments, and the use of the more commonly prescribed medications is discussed with reference to T2DM patients with renal disease. RESULTS: In France, it is estimated that 4-5% of the general population has T2DM and that almost 40% of patients with end-stage renal failure have diabetes. Diabetes and renal disease are both risk factors for cardiovascular morbidity and mortality. Glycaemic control is pivotal in T2DM patients for minimizing the risk of vascular complications and hypoglycaemic episodes, particularly in patients with renal disease who also have a higher risk of hypoglycaemia. Whereas poorly controlled glycaemia increases the risk of renal disease and its progression, the risk is diminished in patients treated intensively for diabetes and in those who achieve stable glycaemic control. Intensive multitargeted treatment can also help to decrease cardiovascular morbidity and mortality, especially if started early in patients who have not yet developed macrovascular complications. CONCLUSION: In recent years, considerable improvement has been observed in France regarding the follow-up of diabetic patients. Less extensive, but nonetheless significant, improvement has also been observed in glycaemic control. However, even though treatment decisions generally take renal function into account, some at-risk treatments are often still being used in patients with renal insufficiency.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Diabetic Nephropathies/drug therapy , Hypoglycemic Agents/therapeutic use , Proteinuria/drug therapy , Renal Insufficiency, Chronic/drug therapy , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Diabetic Nephropathies/blood , Diabetic Nephropathies/epidemiology , Disease Progression , Female , France/epidemiology , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/administration & dosage , Male , Prevalence , Proteinuria/blood , Proteinuria/epidemiology , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/epidemiology , Risk FactorsABSTRACT
AIM: This study evaluated the profiles of patients with type 2 diabetes (T2DM) to identify sets of opinions and attitudes towards the disease that might influence self-care behaviours. METHODS: Altogether, 1,092 patients with T2DM, aged 45 or older from a large representative French cohort, completed a self-questionnaire exploring their knowledge and perceptions of diabetes, its impact on various aspects of daily life and self-management practices. Canonical and cluster analyses were used to identify sets of homogeneous 'profiles' of patients linking attitudes and opinions to specific disease-related behaviours (such as changes in lifestyle, drug compliance, treatment satisfaction, impact on everyday life and weight gain). RESULTS: Demographics of the T2DM study population were previously reported along with the main results (60% male; mean age: 66 years; mean age at diagnosis: 55 years; mean BMI: 29kg/m(2)). Five distinct patient types emerged from the typological approach: 'committed' (25%); 'carefree' (23%); 'bitter' (19%); 'disheartened' (19%); and 'overwhelmed' (15%). Each patient type defined a set of attitudes and beliefs towards T2DM that influenced disease-related behaviours, leading to different degrees of diabetes self-management. CONCLUSION: The DIABASIS survey provides important information for diabetes care by identifying distinct patients' profiles that express different degrees of difficulty in implementing self-management. For this reason, patients in each category require different kinds of customized support from their physician to induce behavioural changes that may be key in improving their metabolic control.
Subject(s)
Attitude to Health , Diabetes Mellitus, Type 2/psychology , Diabetes Mellitus, Type 2/therapy , Health Behavior , Self Care/psychology , Activities of Daily Living , Aged , Body Mass Index , Cohort Studies , Cost of Illness , Female , France , Health Knowledge, Attitudes, Practice , Health Surveys , Humans , Male , Middle Aged , Patient Compliance/psychology , Patient-Centered Care , Statistics as TopicABSTRACT
Mitochondrial diabetes affects up to 1% of patients with diabetes and is often unrecognised by the physicians. Maternally inherited diabetes and deafness (MIDD) resulting from the mutation 3243A>G of the mitochondrial DNA is the most frequent mutation associated with mitochondrial diabetes. This review summarizes the range of clinical phenotypes associated with MIDD and outlines the advances in genetic diagnosis, pathogenesis and management of these patients.
Subject(s)
DNA, Mitochondrial/genetics , Diabetes Mellitus/diagnosis , Diabetes Mellitus/therapy , Mitochondria/genetics , Point Mutation , Age of Onset , Deafness/genetics , Diabetes Mellitus/genetics , Genetic Predisposition to Disease , Genetic Testing , Genetic Variation , Genomic Imprinting , Humans , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/therapy , Pedigree , Phenotype , Retinal Diseases/geneticsABSTRACT
AIM: One objective of Ophdiat, a telemedical network using digital non-mydriatic cameras in Ile-de-France, is to develop a comprehensive screening programme that provides access to annual fundus examinations to all diabetic patients. The aim of this study was to evaluate the benefits of this programme in a hospital setting. METHODS: A retrospective analysis of 500 case reports of diabetic patients hospitalized before and after Ophdiat setup was performed in five reference hospital centres. At each centre, 100 case reports (50 before, 50 after) of patients aged greater than 18 years, hospitalized for their annual check-up, with no known diabetic retinopathy (DR) before hospitalization and with the last fundus examination performed greater than 11 months previously, were randomly selected. The primary endpoint was the proportion of patients whose fundus examinations were performed during hospitalization; secondary endpoints were the number of cases of DR found and the time taken by ophthalmologists to make the diagnosis. RESULTS: The mean proportion of patients with fundus examinations was 50.4% and 72.4% before and after, respectively, Ophdiat (P<0.01). The prevalence of DR was 11.1% before and 12.7% after (not significant). The mean time taken by an ophthalmologist per diagnosis of DR was 0.90 half-day before and 0.32 half-day after Ophdiat. CONCLUSION: This evaluation shows that Ophdiat, combined with the availability of modern and effective devices, has improved DR screening in diabetology departments in hospitals. Additional human resources would certainly ensure more effective use of the system.
Subject(s)
Telemedicine/methods , Adult , Aged , Aged, 80 and over , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Diabetic Retinopathy/epidemiology , Diabetic Retinopathy/prevention & control , Female , France/epidemiology , Humans , Male , Mass Screening/methods , Middle Aged , Retrospective Studies , Young AdultABSTRACT
UNLABELLED: Interest of statins in terms of morbid-mortality reduction in primary and secondary prevention in type 2 diabetic patients has broadly been proven in recent studies, while evidence for fibrates preventive effect is considerably weaker. HMGCoA reductase inhibitors are known to decrease low density lipoprotein cholesterol (LDL C) in a greater extension than triglycerides (TG). In type 2 diabetic patients, the dyslipidemic profile is commonly associated with reduced high-density lipoproteins (HDL C), increased TG and normal or mildly elevated LDL C. PATIENTS AND METHODS: Type 2 diabetic outpatients (n=45) treated with fibrate with or without history of cardiovascular disease were included. Mean age was 57.7+/-13.2 yr, sex ratio was 16/39 (F/M), and BMI was 29.3+/-4.4 kg/m(2). Non-inclusion criteria were TG>or=3.5 g/L and intolerance to statins or a combined lowering lipid therapy. Serum lipid profile, HbA(1c) and creatin kinase (CK) were assessed under treatment with fibrate, then after a 3-month wash-out period, and after a 6-month treatment with a low dose of atorvastatin (10 mg/day). RESULTS: After a 3-month wash-out period, total cholesterol (TC) was 1.98+/-0.31 g/L (m+/-SD), TG 1.63+/-1.09 g/L, HDL C 0.46+/-0.12 g/L, and LDL C 1.22+/-0.31 g/L. Comparing lipid profile with atorvastatin vs fibrate, we observed a significant decrease in TC and LDL C (1.56 vs 1.79 g/L P=0.001, and 0.84 vs 1.09 g/L, P=0.001, respectively). No significant difference between treatments was observed for TG (1.35 vs 1.17 g/L, P=0.06), and HDL C (0.44 vs 0.48 g/L, P=0.15). When treated with atorvastatin, 90% of patients achieved a LDL C<1 g/L, compared to 51% when treated with fibrate (P=0.001). HbA(1c) remained about 7.6+/-1.5%, and CK in the normal range. CONCLUSION: In well-controlled type 2 diabetic patients previously treated with fibrate, short-term (6 months) treatment with low-dose atorvastatin (10 mg/day) improves TC and LDL C levels, without any alteration in TG and HDL C levels.
Subject(s)
Clofibric Acid/administration & dosage , Diabetes Mellitus, Type 2/drug therapy , Dyslipidemias/drug therapy , Heptanoic Acids/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Pyrroles/administration & dosage , Adult , Aged , Atorvastatin , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Diabetes Mellitus, Type 2/blood , Dyslipidemias/blood , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Triglycerides/bloodABSTRACT
AIM: The main purpose of this survey was to describe type 2 diabetes (T2DM) from the patient's standpoint in a representative French panel in 2008. METHODS: Fourteen thousand two hundred and one individuals from the general population aged 45 or older completed a self-questionnaire exploring knowledge about diabetes; 1092 replies were from patients with T2DM. RESULTS: The prevalence of T2DM in this population was 7.7%, with demographics as follows: 60% men; mean age: 66 years; mean age at diagnosis: 55 years; mean BMI: 29 kg/m(2). Eighty-five percent of T2DM patients reported that they wanted more information about at least one aspect of the disease at diagnosis; they reported feeling anxious (30%), frightened (13%), angry (4%) or that the disease was unfair (12%). Half of the patients had modified their dietary habits but 71% found it difficult to engage in regular physical activity. Most patients (90%) were treated with drugs: 81% with oral antidiabetic drugs (OAD) (44% in monotherapy) while 19% received insulin (alone or in combination with OAD). Twenty-three percent complained of weight gain since start of current therapy (average gain of 7.3 kg). Insulin initiation represented a turning point for patients who became more aware of the disease severity, more willing to follow advice and to take greater control over their disease management. The mean time from diagnosis to insulin initiation was 13.8 years. Half of the patients perceived their disease as severe especially women, patients who initially reacted with anxiety, insulin-treated patients and those actively involved in their disease management. Some gender differences emerged: women took the disease more seriously, were more engaged in self-management, and reported a higher impact on daily life. CONCLUSIONS: DIABASIS provides important information for diabetes care by highlighting patients' views of the disease, such as distress at diagnosis, lack of adequate information to cope with this distress and the important supportive role played by the family. A deeper understanding of patients' perception of the disease would help optimize customized care.
Subject(s)
Diabetes Mellitus, Type 2/psychology , Perception , Aged , Anxiety , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Fear , Female , France/epidemiology , Health Knowledge, Attitudes, Practice , Health Surveys , Humans , Male , Middle Aged , Prevalence , Surveys and QuestionnairesABSTRACT
CONTEXT: Early prophylactic thyroidectomy in patients with multiple endocrine neoplasia (MEN) type 2 offers the best chance for a normal life expectancy. OBJECTIVE: To analyze the results of thyroidectomy performed during the first year of life in six patients with MEN 2A (codon 634) or MEN 2B (codon 918) syndrome. DESIGN AND SETTING: A university hospital-based prospective study from 2001 to 2008. SUBJECTS AND METHODS: Six family members affected either by MEN 2A (n=3) or MEN 2B (n=3) syndrome were identified through neonatal genetic screening. RESULTS: Total thyroidectomy was performed at a median age of 0.8 year in the six patients, with central lymph node dissection in five. Bilateral millimetric medullary thyroid carcinoma (MTC) was found in all patients, with a unilateral lymph node micrometastasis in two of the three MEN 2B patients. Before thyroidectomy, MEN 2B patients had much higher basal serum calcitonin levels than those with MEN 2A and controls. After thyroidectomy, with a median follow-up of 3.3 years, the six patients had no evidence of persistent MTC. CONCLUSION: Bilateral millimetric MTC may be present during the first year of life in these patients, with lymph node metastases also occurring in MEN 2B patients. These results support a total thyroidectomy at the age of about one year in MEN 2A (codon 634) children with an abnormal serum calcitonin level, and a total thyroidectomy with central neck dissection within the first weeks of life in MEN 2B patients.
Subject(s)
Carcinoma, Medullary/diagnosis , Multiple Endocrine Neoplasia Type 2a/complications , Multiple Endocrine Neoplasia Type 2b/complications , Thyroid Neoplasms/diagnosis , Carcinoma, Medullary/complications , Carcinoma, Medullary/surgery , Child , Child, Preschool , Codon/genetics , Family , Female , Follow-Up Studies , Genetic Testing , Humans , Infant , Infant, Newborn , Male , Multiple Endocrine Neoplasia Type 2a/diagnosis , Multiple Endocrine Neoplasia Type 2a/genetics , Multiple Endocrine Neoplasia Type 2b/diagnosis , Multiple Endocrine Neoplasia Type 2b/genetics , Neonatal Screening , Thyroid Neoplasms/complications , Thyroid Neoplasms/surgery , ThyroidectomyABSTRACT
AIMS: The receptor for advanced glycation end-products (RAGE) has been implicated in diabetic microvascular complications, but several lines of evidence suggest that the soluble isoform of RAGE (sRAGE) may protect against AGE-mediated vessel damage. The characterized AGE Nepsilon-carboxymethyllysine (CML) is associated with diabetic microvascular complications. In the present study, we measured blood levels of sRAGE and CML-protein in diabetic patients with and without microvascular complications. METHODS: Thirty patients with type-2 diabetes were recruited into the study, comprising 20 who had no microvascular complications, and 10 who had both retinal and renal complications. sRAGE was measured in serum by ELISA, and CML by competitive ELISA. RESULTS: sRAGE blood levels were similar in both the controls and diabetic patients without microvascular complications. In patients with complications, the mean sRAGE blood level was significantly decreased (1068+/-231pg/mL) compared with diabetic patients without complications (P=0.028). CML-protein was increased in all diabetic patients, but to a higher extent in those who had microvascular complications. CONCLUSION: The association of low sRAGE with high CML-protein levels in diabetic patients who developed severe diabetic complications supports the hypothesis that sRAGE protects vessels against AGE-mediated diabetic microvascular damage.
Subject(s)
Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/physiopathology , Diabetic Retinopathy/physiopathology , Receptors, Immunologic/blood , Diabetes Mellitus, Type 2/blood , Diabetic Nephropathies/blood , Diabetic Retinopathy/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lysine/analogs & derivatives , Lysine/blood , Male , Middle Aged , Receptor for Advanced Glycation End ProductsABSTRACT
A case of maternally inherited diabetes and deafness (MIDD)-associated macular pattern dystrophy with a 15-year follow-up is reported. On initial examination at age 37, visual acuity was normal, but chorioretinal atrophy at the posterior pole was already present in both eyes. At age 52, visual acuity remained normal in the right eye and was only slightly decreased in the left eye despite notable extension of the areas of chorioretinal atrophy in that eye. No evidence of diabetic retinopathy was present at any time. This case shows that visual acuity can remain stable in the long term despite extensive lesions of macular pattern dystrophy.
Subject(s)
Deafness/genetics , Diabetes Mellitus/genetics , Macular Degeneration/pathology , Adult , Diabetes Mellitus/pathology , Diabetes Mellitus/physiopathology , Diabetic Retinopathy/genetics , Diabetic Retinopathy/pathology , Diabetic Retinopathy/physiopathology , Fluorescein Angiography , Humans , Macular Degeneration/physiopathology , Male , Mutation , Visual AcuityABSTRACT
Type 2 diabetes mellitus is a multifactorial disease, due to decreased glucose peripheral uptake, and increased hepatic glucose production, due to reduced both insulin secretion and insulin sensitivity. Multiple insulin secretory defects are present, including absence of pulsatility, loss of early phase of insulin secretion after glucose, decreased basal and stimulated plasma insulin concentrations, excess in prohormone secretion, and progressive decrease in insulin secretory capacity with time. beta-cell dysfunction is genetically determined and appears early in the course of the disease. The interplay between insulin secretory defect and insulin resistance is now better understood. In subjects with normal beta-cell function, increase in insulin is compensated by an increase in insulin secretion and plasma glucose levels remain normal. In subjects genetically predisposed to type 2 diabetes, failure of beta-cell to compensate leads to a progressive elevation in plasma glucose levels, then to overt diabetes. When permanent hyperglycaemia is present, progressive severe insulin secretory failure with time ensues, due to glucotoxicity and lipotoxicity, and oxidative stress. A marked reduction in beta-cell mass at post-mortem examination of pancreas of patients with type 2 diabetes has been reported, with an increase in beta-cell apoptosis non-compensated by neogenesis.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Insulin/metabolism , Diabetes Mellitus, Type 2/blood , Disease Progression , Humans , Insulin Secretion , Insulin-Secreting Cells/metabolism , Islets of Langerhans/metabolism , Islets of Langerhans/physiopathologyABSTRACT
AIMS/HYPOTHESIS: We assessed the prevalence and determinants of retinal and renal complications in patients with maternally inherited diabetes and deafness (MIDD). METHODS: This was a multicentre prospective study comparing the prevalence of retinopathy and renal disease in 74 patients with MIDD and 134 control patients matched for sex, age and clinical presentation at onset of diabetes, duration of diabetes and current treatment. Comparisons were adjusted for HbA(1c) and hypertension. RESULTS: In MIDD patients, HbA(1c) (7.6 +/- 1.6 vs 8.5 +/- 2.0%, p < 0.002), systolic blood pressure (126.6 +/- 16.2 vs 133.1 +/- 17.3 mmHg, p < 0.007) and prevalence of hypertension (33.8 vs 64.2%, p < 0.0001) were lower than in control patients. Prevalence of diabetic retinopathy was 3.7-fold lower in MIDD patients (6/74, 8 vs 40/134, 29.6%, p < 0.0001). Differences between groups remained significant after adjustment for hypertension, systolic blood pressure and HbA(1c). In MIDD, urinary albumin excretion (314.8 vs 80.1 mg/24 h, p = 0.035) and creatinine plasma levels (103.5 vs 82.2 micromol/l, p = 0.0178) were higher and GFR was lower. Impaired renal function (GFR <60 ml/min) was four- to sixfold more frequent in MIDD. Differences between MIDD and control diabetic patients further increased when adjusted for HbA(1c) and systolic blood pressure (p < 0.0001). Adjustment for treatment with an ACE inhibitor or angiotensin II receptor antagonist did not modify the results. CONCLUSIONS/INTERPRETATION: This study indicates that diabetic retinopathy is less prevalent in MIDD than in control diabetes. This suggests that retinal alterations due to mitochondrial disease may have a protective role. By contrast, nephropathy is far more frequent in MIDD, suggesting the presence of a specific renal disease independent of diabetic nephropathy.
Subject(s)
DNA, Mitochondrial/genetics , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 2/genetics , Diabetic Nephropathies/genetics , Diabetic Retinopathy/genetics , Kidney Diseases/genetics , Mitochondrial Diseases/genetics , Mutation , Retinal Diseases/genetics , Blood Pressure , DNA, Mitochondrial/chemistry , Diabetic Angiopathies/genetics , Female , Glomerular Filtration Rate , Glycated Hemoglobin/analysis , Humans , Kidney Diseases/epidemiology , Phenotype , Retinal Diseases/epidemiologyABSTRACT
OBJECTIVE: International and national guidelines recommend an annual funduscopic examination for all diabetic patients, but such annual fundus examinations are not sufficiently performed in France. Non-mydriatic fundus photography is a valid method of evaluation for diabetic retinopathy (DR) and a viable alternative to ophthalmoscopy. After two pilot studies demonstrated the feasibility of telemedical screening for diabetic retinopathy in both hospital and primary-care settings, we developed a regional telemedical network, OPHDIAT, designed to facilitate access to regular annual evaluations of patients with diabetes while saving medical time. MATERIALS AND METHODS: OPHDIAT comprises peripheral screening centres equipped with non-mydriatic cameras, where fundus photographs are taken by technicians linked by telemedicine to a reference centre, where ophthalmologists grade the images. Currently in the Ile-de-France region, 16 screening centres are linked through a central server to an ophthalmologic reading centre and includes 11 centres located in the diabetes departments of 11 hospitals, one diabetic retinopathy screening centre located in northern Paris, three in healthcare centres and one in a prison. RESULTS: During the 28-month evaluation period, 15,307 DR screening examinations were performed. Retinal photographs of at least one eye could not be graded in 1332 patients (9.7%) and diabetic retinopathy was detected in 3350 patients (23.4%). After the screening examination, 3478 patients (25.2%) were referred to an ophthalmologist for either DR, cataract and/or non-gradable photographs. CONCLUSION: Fundus photography combined with telemedicine has the potential to improve the regular annual evaluation for diabetic retinopathy. The organization of the network around a central reading centre serves to guarantee quality control.
Subject(s)
Diabetic Retinopathy/epidemiology , Mass Screening/methods , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Female , Health Services , Hospitals , Humans , Male , Paris/epidemiology , Physicians, Family , Prisons , TelemedicineABSTRACT
Ketosis-prone diabetes (KPD) is a phenotypically defined form of diabetes characterized by male predominance and severe insulin deficiency. Neurogenin3 (NGN3) is a proendocrine gene, which is essential for the fate of pancreatic beta cells. Mice lacking ngn3 develop early insulin-deficient diabetes. Thus, we hypothesized that gender and variants in NGN3 could predispose to KPD. We have studied clinical and metabolic parameters according to gender in patients with KPD (n = 152) and common type 2 diabetes (T2DM) (n = 167). We have sequenced NGN3 in KPD patients and screened gene variants in T2DM and controls (n = 232). In KPD, male gender was associated with a more pronounced decrease in beta-cell insulin secretory reserve, assessed by fasting C-peptide [mean (ng/ml) +/- s.d., M: 1.1 +/- 0.6, F: 1.5 +/- 0.9; p = 0.02] and glucagon-stimulated C-peptide [mean (ng/ml) +/- s.d., M: 2.2 +/- 1.1, F: 3.1 +/- 1.7; p = 0.03]. The rare affected females were in an anovulatory state. We found two new variants in the promoter [-3812T/C (af: 2%) and -3642T/C (af: 1%)], two new coding variants [S171T (af: 1%) and A185S (af: 1%)] and the variant already described [S199F (af: 69%)]. These variants were not associated with diabetes. Clinical investigation revealed an association between 199F and hyperglycaemia assessed by glycated haemoglobin [HbA1c (%, +/-s.d.) S199: 12.6 +/- 1.6, S199F: 12.4 +/- 1.4 and 199F: 14.1 +/- 2.2; p = 0.01]. In vitro, the P171T, A185S and S199F variants did not reveal major functional alteration in the activation of NGN3 target genes. In conclusion, male gender, anovulatory state in females and NGN3 variations may influence the pathogenesis of KPD in West Africans. This has therapeutic implications for potential tailored pharmacological intervention in this population.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/genetics , Diabetes Mellitus, Type 2/etiology , Diabetic Ketoacidosis/etiology , Nerve Tissue Proteins/genetics , Promoter Regions, Genetic , Sex Factors , Adult , Anovulation , Biomarkers/blood , Black People/genetics , C-Peptide/analysis , Case-Control Studies , Chi-Square Distribution , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/ethnology , Diabetic Ketoacidosis/blood , Diabetic Ketoacidosis/ethnology , Female , Gene Expression , Genotype , Glucagon , Humans , Insulin/metabolism , Insulin Secretion , Male , Middle AgedABSTRACT
We present the first case of muscle infarction in a 30-year-old woman who had a 5-year history of type 1 diabetes mellitus that was not complicated by nephropathy, retinopathy or neuropathy. All common causes of muscle infarction were excluded, particularly microangiopathy and a hypercoagulable state. The differential diagnosis included infection (pyomyositis, necrotic fasciitis), focal inflammatory myositis, vascular events, trauma, tumor and diabetic amyotrophy, all of which were excluded. In spite of good glycaemic control, her diabetes remained brittle; alternating states of transient acute hypoglycaemia and hyperglycaemia may have been responsible for the infarction. Brittleness resumed after treatment with subcutaneous insulin infusion using a portable pump. No recurrence of muscle infarction was observed during a 18-month follow-up.