Therapeutic management of orally treated type 2 diabetic patients, by French general practitioners in 2010: the DIAttitude Study.

AIM: To describe the behaviour of French general practitioners (GP) regarding intensification of hypoglycaemic agents in orally treated type 2 diabetic (T2D) patients, according to their HbA(1c) level. METHODS: General practitioners were recruited from a panel of office-based general practitioners. T2D patients who had been orally treated for at least 6 months were included in the study; their characteristics were recorded, and their HbA(1c) values and hypoglycaemic treatments over the previous 24 months extracted from electronic records The major reasons for intensification (or no intensification) of hypoglycaemic agents were recorded at the inclusion visit. RESULTS: A total of 236 general practitioners recruited 2109 T2D patients: 1732 had at least one HbA(1c) value recorded in the previous 6 months, and 52%, 33% and 14% had been treated, with oral hypoglycaemic agents in monotherapy, bitherapy or tri-or quadritherapy, respectively. Of these patients, 702 (41%) remained uncontrolled (47%, 39% and 20% respectively) and according to the current French guidelines needed treatment intensification. Only 46 (7%) had their treatment intensified at inclusion. Of those without intensified treatment, 60% were treated with monotherapy; the main reason given by the general practitioners for not intensifying treatment was a satisfactory HbA(1c) level (53%), although 32% had an HbA(1c)>7%. Other reasons were: lifestyle advice had greater priority (20%); decision was postponed until the next visit (11%); HbA(1c) had decreased since last visit (7%; not confirmed by available data in 58% of cases); a medical priority other than diabetes (6%) and other reasons related to the patient (3%). CONCLUSION: For T2D patients managed by French general practitioners, guidelines are not consistently followed: HbA(1c) should be monitored more frequently and treatment adjusted according to HbA(1c) levels.

Key priorities in managing glucose control in older people with diabetes.

Older people with diabetes represent a major and increasing proportion of our elderly population and their care requires better organisation. Targets for risk factor control and pathways of care must be adjusted to the subject's general health status. It is thus advisable to screen for frailty. We have carried out a detailed literature review of the studies published on diabetes in older people since 1990. Studies were considered if they included groups or subgroups of diabetic patients > 65 years old. This review discusses the elaboration of general targets for care, the approach to risk factor control, the screening and the specific prevention or management of complications, the integration of geriatric concepts in diabetes care and the specificity of education with respect to frailty status.

A call to incorporate the prevention and treatment of geriatric disorders in the management of diabetes in the elderly.

The prevalence of type 2 diabetes increases with age. However, the management of diabetes in the elderly has received surprisingly little attention. Diabetes in the elderly is associated with a high risk of geriatric syndromes including malnutrition and sarcopenia, functional impairments, falls and fractures, incontinence, depression and dementia. Tight glycaemic control for the prevention of vascular complications is often of limited value in the elderly. However, glycaemic control and non-pharmacological therapy may prevent diabetes symptoms and delay geriatric syndromes. The prevention, screening and treatment of both conventional diabetic complications and geriatric syndromes should be integrated in a management plan to optimize the patients' overall health status and quality of life.

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 HbA(1c) 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.

Insulin glargine provides greater improvements in glycaemic control vs. intensifying lifestyle management for people with type 2 diabetes treated with OADs and 7-8% A1c levels. The TULIP study.

AIM: To determine whether earlier administration of insulin glargine (glargine) vs. the intensification of lifestyle management (LM) improves glycaemic control in type 2 diabetes patients with A1c 7-8% treated with oral therapy. METHODS: TULIP [Testing the Usefulness of gLargine when Initiated Promptly in type 2 diabetes mellitus (T2DM)] was a 9-month, 12-visit, open-label, multinational, multicentre, randomized study to evaluate starting glargine or intensifying LM in T2DM patients aged 40-75 years, body mass index (BMI) 24-35 kg/m2 and A1c 7-8%, treated with maximum doses of metformin and sulphonylurea for > or = 2 years. Glargine was injected once daily (evening) and titrated to fasting blood glucose 0.7-1.0 g/l. In the LM arm, dietary and physical activity counselling recommended stable weight for people with BMI < 27 kg/m2 or weight loss of 3 kg for patients with BMI > or = 27 kg/m2. A total of 215 patients were randomized to glargine (n = 106) or LM (n = 109). The primary objective was patients achieving A1c < 7% at endpoint. Secondary endpoints included changes in A1c, in fasting plasma glucose (FPG), body weight and hypoglycaemia incidence. RESULTS: Two hundred and eleven (52.6% male) patients were randomized and treated; mean (+/- s.d.) age 60.7 +/- 7.9 years, weight 84.5 +/- 13.1 kg, BMI 29.9 +/- 3.5 kg/m2 and A1c 7.6 +/- 0.4%. More patients reached A1c < 7% (66 vs. 38%; p < 0.0001) or < 6.5% (34 vs. 11%; p = 0.0001) with glargine vs. LM. The change in FPG from baseline to study endpoint was significantly greater in the glargine vs. the LM arm (-0.50 +/- 0.47 vs. -0.05 +/- 0.39 g/l respectively; p < 0.0001). Compared with the glargine group, the LM group showed a decrease in weight (+0.9 +/- 2.9 vs. -2.5 +/- 3.2 kg; p < 0.0001), as well as the expected lower symptomatic hypoglycaemia (55.3 vs. 25.0%; p < 0.0001) and nocturnal hypoglycaemia (20.4 vs. 5.6%; p = 0.0016). No significant changes were observed from baseline to study endpoint in any of the lipid parameters tested. CONCLUSIONS: In patients with T2DM with A1c 7-8%, who were previously treated by conventional LM and OAD therapy, adding glargine resulted in greater improvements in glycaemic control vs. intensifying LM.

Retinal and renal complications in patients with a mutation of mitochondrial DNA at position 3,243 (maternally inherited diabetes and deafness). A case-control study.

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.

Type 2 diabetes mellitus: epidemiology, pathophysiology, unmet needs and therapeutical perspectives.

In France, prevalence of drug-treated diabetes reached 3.60% in 2005, with 92% of type 2 diabetic patients. In 2007, there are probably nearly 3000 000 diagnosed or undiagnosed diabetic patients. Ageing of the population and increase in obesity are the main causes of this "diabetes epidemic". Type 2 diabetes is a multifactorial disease, defined as resulting from defects in insulin secretion (including abnormalities in pulsatility and kinetics, quantitative and qualitative abnormalities of insulin, beta-cell loss progressing with time) associated with insulin resistance (affecting liver, and skeletal muscle) and increased glucagon secretion. The lack of compensation of insulin resistance by augmented insulin secretion results in rise in blood glucose. To achieve satisfactory glycaemic control in order to prevent diabetes related complications, drug therapy is generally required in addition to life style changes. Currently available oral therapies offer a large panel of complementary drugs, but they have several contraindications and side effects. In spite of major advances in the management of type 2 diabetes, and the strictness of new guidelines, some goals remain unachieved and the new family of insulin-secretors (DPP-IV inhibitors, GLP-1 analogues) should enrich therapeutic approaches.

Diabetic nephropathy in the elderly.

Renal impairment is frequent in aged diabetic patients, notably with type 2 diabetes. It results from a multifactorial pathogeny, particularly the combined actions of hyperglycaemia, arterial hypertension and ageing. Diabetic nephropathy (DN) is associated with an increased cardiovascular mortality. DN often leads to end stage renal failure (ESRF) which causes specific problems of decision and practical organization of extra-renal epuration in diabetic and aged patients. In the absence of renal biopsy, clinical signs are often insufficient to assess the diabetic origin of a nephropathy in an elderly diabetic patient. Prevention of DN is principally based on tight glycaemic and blood pressure control. The progression of renal lesions can be retarded by strict blood pressure control, notably by blocking of the renin-angiotensin system, if well tolerated in aged patients. It is absolutely necessary to avoid the worsening of renal lesions by potentially nephrotoxic products, notably non steroidal anti-inflammatory drugs (NSAIDs) and iodinated contrast media. At the stage of renal failure, it is important to adapt the antidiabetic treatment, and in the majority of the cases, to switch to insulin when glomerular filtration rate (GFR) is below 30 ml/mn/1.73 m2.

Thiazolidinediones for the treatment of type 2 diabetes.

Thiazolidinediones (TZD), or glitazones, represent a new generation of antidiabetic drugs that have recently been introduced in Europe. They improve insulin resistance, one of the key anomalies involved in the pathogenesis of type 2 diabetes mellitus, by activating the nuclear peroxoxisome proliferator activated receptor-gamma (PPAR-gamma), leading to crucial metabolic alterations in adipose tissue. Rosiglitazone and pioglitazone have been shown to be active as monotherapy, in combination therapy with metformin or sulfonylureas, and even in triple therapy. They are generally well tolerated but can induce fluid retention. Cardiac failure is a contraindication for the use of TZDs, as is the concomitant administration of insulin. Aside from their effect on glycemic control, TZDs act on several cardiovascular risk factors and may protect pancreatic beta cells from apoptosis. The cardiovascular protective effect of TZDs has recently been demonstrated with the results of the PROactive study, and long-term preservation of beta-cell function is currently under further investigation.

Meglitinide analogues: a review of clinical data focused on recent trials.

Glinides represent a chemically heterogeneous new class of insulin-secreting agents characterized by a rapid onset and short duration of action. They act by closure of the ATP-dependant K channel. Repaglinide, the only glinide available in France, has an equivalent HbA1c lowering effect to conventional sulfonylureas but reduces predominantly postprandial glucose levels. Several studies indicate a decreased risk of hypoglycaemias, particularly nocturnal or in case of a shift or omission of a meal. This drug appears particularly useful in early stage type 2 diabetes or in combination with metformin. The only significant drug-drug interaction concerns gemfibrozil. Due to its hepatic metabolism and biliary elimination, repaglinide can be used in patients with renal insufficiency. Nateglinide has a even shorter duration of action and has almost no effect on fasting plasma glucose levels. For this reason, this drug is only indicated in combination with metformin in the countries where it is licensed. Several experimental data suggest that glinides could preserve B cell function over time better than hypoglycaemic sulfonylureas, and that the improvement of post-prandial glucose levels could exert a long term protective cardiovascular effect.

Hematological response to short-term oral cyanocobalamin therapy for the treatment of cobalamin deficiencies in elderly patients.

OBJECTIVES: The aim of this trial was to demonstrate the efficacy of one month of oral cobalamin (vitamin B12) therapy in elderly patients with cobalamin deficiency related to food-cobalamin malabsorption (FCM). PATIENTS AND METHOD: Twenty elderly patients (mean age: 78+/-17 years) with established cobalamin deficiency related to FCM were included in an open-label, non-randomized, non-placebo trial. They were treated with a maximum of 1,000 microgram per day of oral crystalline cyanocobalamin for at least 1 month. Serum cobalamin levels (primary endpoint), blood count abnormalities and reticulocytes count (secondary endpoints) were determined at baseline and during the first month of treatment. RESULTS: 85% of the patients normalized their serum cobalamin levels with a mean increase of+167 pg/ml (p<0.001 compared with baseline). 100% of the patients corrected their initial macrocytosis and 25% their anemia; 100% of the patients had medullar regeneration with a mean increase of reticulocytes count of 32+/-11.3 x 106/l (p=0.03 compared with baseline). CONCLUSIONS: Our findings support the view that one month of oral crystalline cyanocobalamin is effective to correct serum vitamin B12 levels and to obtain hematological responses in elderly patients with cobalamin deficiency related to FCM.

Current hematological findings in cobalamin deficiency. A study of 201 consecutive patients with documented cobalamin deficiency.

With the introduction of automated assays for measuring serum cobalamin levels over the last decades, the hematological manifestations related to cobalamin deficiency have been changed from the description reported in 'old' studies or textbooks. We studied the hematological manifestations or abnormalities in 201 patients (median age: 67 +/- 6 years) with well-documented cobalamin deficiency (mean serum vitamin B12 levels 125 +/- 47 pg/ml) extracted from an observational cohort study (1995-2003). Assessment included clinical features, blood count and morphological review. Hematological abnormalities were reported in at least two-third of the patients: anemia (37%), leukopenia (13.9%), thrombopenia (9.9%), macrocytosis (54%) and hypegmented neutrophils (32%). The mean hemoglobin level was 10.3 +/- 0.4 g/dl and the mean erythrocyte cell volume 98.9 +/- 25.6 fl. Approximately 10% of the patients have life-threatening hematological manifestations with documented symptomatic pancytopenia (5%), 'pseudo' thrombotic microangiopathy (Moschkowitz; 2.5%), severe anemia (defined as Hb levels <6 g/dl; 2.5%) and hemolytic anemia (1.5%). Correction of the hematological abnormalities was achieved in at least two-thirds of the patients, equally well in patients treated with either intramuscular or oral crystalline cyanocobalamin. This study, based on real data from a single institution with a large number of consecutive patients with well-documented cobalamin deficiency, confirms several 'older' findings that were previously reported before the 1990s in several studies and in textbooks.

[A urachus cyst revealing a torpid Crohn's disease in a young adult with chronic fever]. / Kyste de l'ouraque révélateur d'une maladie de Crohn torpide chez un adulte jeune atteint d'une fievre nue chronique.

INTRODUCTION: This case report describes a rare situation in which a superinfected cyst of the urachus complicated initially unknown and inactive Crohn's disease. CASE: A 21-year-old man presented a chronic fever finally attributed to a superinfected urachal cyst. Six months after ablation of the cyst, progressive Crohn's disease was diagnosed. DISCUSSION: The association of Crohn's disease and a superinfected urachal cyst is extremely rare. The case reported here is original in two aspects: the slowly progressive Crohn's disease was diagnosed after its complication; the superinfection developed through local bacterial translocation (ileal loop adjacent to the urachal cyst).

Management of hypertension in elderly diabetic patients.

Hypertension is a major vascular risk factor in the elderly diabetic. The benefit of proper management is well recognized, even if treatment has no influence on overall mortality or might even tend to increase it in very elderly subjects. Globally, the efficacy of the major classes of antihypertensive drugs, diuretics, beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin II receptor antagonists appears to be equivalent so that the therapeutic choice depends on the type of hypertension, systolic or systolic-diastolic, and the rapidity of the desired effect, co-morbid conditions, particularly coronary or renal disease, or drug tolerance. Blood pressure goals are similar to those in middle-aged persons, except in very old, frail or sick subjects.

Heterogeneity of diabetes phenotype in patients with 3243 bp mutation of mitochondrial DNA (Maternally Inherited Diabetes and Deafness or MIDD).

OBJECTIVE: In patients with maternally inherited diabetes and deafness (MIDD), due to 3 243 A > G mutation of mitochondrial DNA (mtDNA), diabetes may present with variable phenotypes. OBJECTIVE: To ascertain the existence of two distinct phenotypes, MIDD1 and MIDD2, in a series of patients with MIDD. DESIGN: Multicenter prospective study. PATIENTS: 77 patients with diabetes and the mtDNA 3243 mutation and 139 control patients with type 1 (T1D) or type 2 (T2D) diabetes, matched according to initial presentation of diabetes, age at onset, sex, and duration of diabetes (24 T1D and 115 T2D, including 55 treated with insulin). MEASUREMENTS: Anthropometric characteristics (height, body weight, body mass index [BMI], sex), family history of diabetes, and characteristics of diabetes (age at onset, treatment, hemoglobin A1c [HbA1c]), extrapancreatic manifestations. RESULTS: In 13 cases (17%, MIDD1), diabetes presented as insulin-dependent from the onset, with ketoacidosis in 6 cases. In 64 cases (83%, MIDD2), diabetes resembled T2D, and was treated with diet in 12 cases, oral hypoglycemic agents in 21 cases, or insulin in 31 cases. Compared with patients with MIDD2, patients with MIDD1 were characterized by lower age at onset of first manifestation of MIDD (25.4 +/- 9.6 vs 33.7 +/- 13.2 Years, P<0.0005), lower body weight (49.1 +/- 7.4 vs 56.3 +/- 10.9 kg, P<0.0025), lower BMI (18.2 +/- 2.3 vs 20.9 +/- 3.6 kg/m2, P<0.0005), and higher HbA1c levels (9.5 +/- 2.0 vs 7.5 +/- 1.6%, P<0.0005). Frequency of family history of diabetes and of extrapancreatic manifestations was the same in both MIDD subtypes. No difference was found within the MIDD2 subtype when comparing patients treated with or without insulin. Compared with matched controls, patients with MIDD had a lower BMI (MIDD1/T1D 18.2 +/- 2.3 vs 24.0 +/- 3.6 kg/m2 and MIDD2/T2D 20.9 +/- 3.6 vs 30.2 +/- 5.9 kg/m2, P<0.0025). Lastly, male patients with MIDD had a shorter height than controls (MIDD1/T1D: 166.1 +/- 3.2 vs 177.3 +/- 6.6 cm and MIDD2/T2D: 168.4 +/- 7.2 vs 173.6 +/- 6.6 cm P<0.025). CONCLUSIONS: These results confirm the existence of two different phenotypes in MIDD, MIDD1 and MIDD2, which may be related to the severity of the mitochondrial disease. The role of other genetic and/or environmental factors in the variable phenotype of MIDD remains to be elucidated.

Current management of adult idiopathic thrombocytopenic purpura in practice: a cohort study of 201 patients from a single center.

To define usefulness and response to therapy and outcome in adults with idiopathic thrombocytopenic purpura (ITP) in clinical practice. We retrospectively reviewed a cohort of 201 consecutive patients with ITP, diagnosed between 1985 and 1994. In particular, we analyzed the therapies used, their response rates, prognostic indicators of response and outcome. In 62 patients, with minor bleeding episodes and a mean (+/- SD) platelet count of 88 +/- 23 x 10(9)/l, no treatment was used and chronic ITP was diagnosed in 59%. A total of 139 patients, with bleeding episodes in 71.2% cases and a mean platelet count of 20 +/- 13 x 10(9)/l, received at least one treatment. Three patients died (1.5% of the series). Corticosteroids were used in 118 patients, with an initial response rate of 82.2% and a long-term complete response (CR) of only 22.9%. Intravenous immunoglobulin was used in 26 patients, with an initial transient response in more than 60%. A splenectomy was performed in 55 patients, with an initial response rate of 92.5% and a long-term CR in 60%. Young age and prior response to corticosteroids were significant predictors of a durable response to splenectomy. Danazol was given in 37 patients, with a favorable response in 73% of cases. Our results illustrate the guidelines of the American Society of Hematology. Patients with moderate thrombocytopenia do not require treatment. In severe cases, splenectomy is the only treatment giving durable cures in a significant proportion of patients. Despite frequent chronicity, ITP is life-threatening only in a minor subset of patients.