Dunnigan lipodystrophy syndrome: French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins).

Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal management and care of patients with FPLD2, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Dunnigan syndrome is characterized by a partial atrophy of the subcutaneous adipose tissue and by an insulin resistance syndrome, associated with a risk of metabolic, cardiovascular and muscular complications. Its prevalence, assessed at 1/100.000 in Europe, is probably considerably underestimated. Thorough clinical examination is key to diagnosis. Biochemical testing frequently shows hyperinsulinemia, abnormal glucose tolerance and hypertriglyceridemia. Elevated hepatic transaminases (hepatic steatosis) and creatine phosphokinase, and hyperandrogenism in women, are common. Molecular analysis of the LMNA gene confirms diagnosis and allows for family investigations. Regular screening and multidisciplinary monitoring of the associated complications are necessary. Diabetes frequently develops from puberty onwards. Hypertriglyceridemia may lead to acute pancreatitis. Early atherosclerosis and cardiomyopathy should be monitored. In women, polycystic ovary syndrome is common. Overall, the management of patients with Dunnigan syndrome requires the collaboration of several health care providers. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are described to provide such a support.

The effects of a calf pump device on second half performance of a simulated soccer match in competitive youth players.

During soccer matches, performance decrements have been reported that relate to both physical abilities and technical skills. To investigate the effects of low-frequency electrical stimulation LFES (VeinoplusSport®, Ad Rem Technology, France) administered during half-time recovery on performance alterations during the second half. Twenty-two highly trained young players undertook a soccer-match simulation (SAFT90). During half-time, they were randomly assigned to LFES group or Placebo group. Each half was split into 3 bouts of 12 minutes. Following each bout, maximal strike speed (MSS), sprint test (ST), maximal sprint accelerations (MA) and metabolic power (MP) were determined in both groups. Arterial (AF) and venous flows (VF) were measured at rest and at the end of half-time. LEFS group exhibited beneficial effects on performance compared to the Placebo group with a likely effect for MSS, ST, MA, and a possible effect for MP. AF and VF increased statistically more in LEFS group compared to Placebo group. The use of specific calf-pump LFES during half-time of a youth simulated soccer match attenuated the decrease in performance during the second half compared to Placebo group. This effect is most marked at the beginning of the second half with regards to explosive parameters.

[Familial hypercholesterolemia: A largely underestimated cardiovascular risk]. / Hypercholestérolémie familiale : un risque cardiovasculaire largement sous-estimé.

BACKGROUND: Familial hypercholesterolemia is a monogenic autosomal dominant dyslipidemia characterized by a permanent and isolated increase of cholesterol carried by low-density lipoproteins. The prevalence of its heterozygous form is estimated between 1/500 and 1/250, and in the absence of specific treatment, this form is responsible for an increase by a factor of 13 of the risk of premature coronary artery disease compared to patients non-affected by the disease. OBJECTIVES: To perform an inventory of the knowledge of heterozygous familial hypercholesterolemia in France for physicians involved in the management of the disease. METHODS: A survey was conducted (by phone and internet) among a representative sample of 495 physicians (cardiologists, endocrinologists/diabetologists, gynecologists, general practitioners) who, in parallel, completed 579 patient records. RESULTS: Thirty-two percent (95% CI [27.8; 36.2]) of physicians reported the difference between polygenic hypercholesterolemia and familial hypercholesterolemia. The presence of tendinous xanthomas, a key element of diagnosis, was spontaneously mentioned by 44% (95% CI [34; 54.2]) of cardiologists. Six percent (95% CI [2.2; 12.6]) of them gave a correct estimate of the prevalence of familial hypercholesterolemia. The likelihood of transmission of heterozygous familial hypercholesterolemia, when one parent is affected, was known for 59% (95% CI [48.7; 68.7]) of surveyed cardiologists. A cascade screening was performed systematically by 4% (95% CI [1.1; 9.9]) of them. Eighteen percent (95% CI [11; 26.9]) of cardiologists gave an accurate estimation of cardiovascular risk of heterozygous familial hypercholesterolemia. Fifty-seven percent (95% CI [46.7; 66.8]) of cardiologists admitted being misinformed about the heterozygous familial hypercholesterolemia and 83% (95% CI [74.1; 89.7]) expressed a need for information about this disease. CONCLUSION: The lack of knowledge of heterozygous familial hypercholesterolemia and its associated cardiovascular risk is probably the cause of a diagnostic default leading to inappropriate management of this disease.

Modulation of Gr1low monocyte subset impacts insulin sensitivity and weight gain upon high-fat diet in female mice.

BACKGROUND/OBJECTIVES: Blood monocytes are expanded during obesity. However, the differential contribution of monocyte subsets in obesity-related metabolic disorders remains unknown. The aim of the study was to define the role of the Gr1low monocyte subset upon high-fat diet (HFD). METHODS: We used transgenic female mouse models allowing the modulation of circulating Gr1low monocyte number (decreased number in CX3CR1-/- mice and increased number in CD11c-hBcl2 mice) and studied obesity upon HFD. RESULTS: We reported here that HFD induced monocytosis in mice, preferentially due to Gr1low monocyte expansion, and was associated with a specific upregulation of CD11c on that subset. Using mice models with altered Gr1low monocyte number, we found a striking correlation between Gr1low monocytes, bodyweight (BW) and insulin resistance (RT) status. Indeed, CX3CR1-/- female mice, with reduced Gr1low monocytes upon HFD, showed increased RT and a pro-inflammatory profile of the adipose tissue (AT) despite a lower BW. Conversely, mice expressing the anti-apoptotic gene hBcl2 in CD11c-expressing cells have increased Gr1low monocytes, higher insulin sensitivity upon HFD and an anti-inflammatory profile of the AT. Finally, increasing Gr1low monocytes in Gr1low-defective CX3CR1-/- mice rescued BW loss in these mice. CONCLUSIONS: By using transgenic female mice and adoptive transfer experiments, we established the evidence for a correlation between Gr1low monocyte subset and weight gain and RT. Hence, this specific Gr1low monocyte subset could be used as a target for acting on AT inflammation and RT.

[Statin and cardiovascular diseases after 75 years]. / Statine et pathologies cardiovasculaires après 75 ans.

Statin prescription in persons older than 75 years or with frailty signs raises questions on the role of cholesterol in the genesis of atherosclerosis in this population, on the benefit of this treatment in primary or secondary prevention, and on their side effects in a context of multiple pathology and multiple medications. These questions are approached with the available literature data for this population. In secondary prevention, statin prescription is recommended whatever the age although intensive treatment should be avoided. In primary prevention, in the absence of consensus, their prescription depends on both geriatric and cardiovascular risk assessment.

Metabolic syndrome in adults who received hematopoietic stem cell transplantation for acute childhood leukemia: an LEA study.

We evaluated prospectively the incidence and risk factors of the metabolic syndrome (MS) and its components in 170 adult patients (mean age at evaluation: 24.8±5.4 years) who received an hematopoietic stem cell transplantation for childhood ALL, n=119, or AML, n=51. TBI was carried out in 124 cases; a busulfan-based conditioning was done in 30 patients. Twenty-nine patients developed a MS (17.1%, 95% confidence intervals: 11.7-23.6). The cumulative incidence was 13.4% at 25 years of age and 35.5% at 35 years of age. A higher body mass index (BMI) before transplantation and a growth hormone deficiency were associated with increased MS risk (P=0.002 and 0.01, respectively). MS risk was similar for patients who received TBI or busulfan-based conditioning. The TBI use increased the hyperglycemia risk (odds ratio (OR): 4.7, P=0.02). Women were at the risk of developing increased waist circumference (OR: 7.18, P=0.003) and low levels of high-density lipoprotein cholesterol (OR: 2.72, P=0.007). The steroid dose was not a risk factor. The MS occurs frequently among transplanted survivors of childhood leukemia. Its incidence increases with age. Both intrinsic (BMI, gender) and extrinsic factors (TBI, alkylating agents) contribute to its etiopathogenesis.

Changes in femoral artery blood flow during thermoneutral, cold, and contrast-water therapy.

AIM: The purpose of this study was to examine the changes in femoral artery blood flow during cold water immersion (CWI), contrast water therapy (CWT) and thermoneutral water immersion (TWI). METHODS: Ten athletes came to the laboratory three times, to complete a 20-min procedure in upright position: 4 min in air (baseline), then 16-min full leg TWI (~35 °C), CWI (~12 °C) or CWT (2:2 ~12 °C to ~35 °C) min ratio, in a random order. Blood flow was measured every 2 min: baseline (i.e. min 3 and 1) and throughout water immersion (i.e. min 1, 3, 5, 7, 9, 11, 13 and 15), using Doppler ultrasound in the superficial femoral artery, distal to the common bifurcation (~3 cm), above the water and stocking. RESULTS: Compared with baseline, blood flow was significantly higher throughout TWI (min 1 to 15: P<0.001; +74.6%), significantly lower during CWI (from min 7 to 15: P<0.05; -16.2%) and did not change during CWT (min 1 to 15). No changes in blood flow occurred between the hot and cold transitions of CWT. CONCLUSION: This study shows that external hydrostatic pressure (TWI ~35 °C) significantly increases femoral artery blood flow. We also show that associating hydrostatic pressure with cooling (CWI ~12 °C) decreases femoral artery blood flow after a sufficient duration, whereas associating hydrostatic pressure with alternating brief exposures to contrasted temperatures does not change femoral artery blood flow under resting conditions.

Improvement in LDL-cholesterol levels of patients with familial hypercholesterolemia: can we do better? Analysis of results obtained during the past two decades in 1669 French subjects.

BACKGROUND: Heterozygous Familial Hypercholesterolemia (heFH) is an autosomal disease that affects about 1/500 people. It is characterized by markedly elevated plasma LDL-cholesterol (C) levels and an increased risk of cardiovascular disease (CVD). The aim of this study was to measure changes in LDL-C levels in heFH patients over two decades, and to evaluate if patients achieved LDL-C targets. METHODS: Data from 1669 heFH patients in five academic French centers were recorded between 1988 and 2011. RESULTS: The mean LDL-C concentrations under medical care improved between 1988 and 2011 (245 mg/dL before 1995, 164 mg/dL after 2009; p < 0.0001). However, mean LDL-C level and the number of patients treated with statins (79.3%) have not improved since 2005. In patients registered and treated after 2005 (n = 616), only 10.4% reached target LDL-C levels of <100 mg/dL. Indeed, 29.4% (n = 181) were treated with a maximal therapy (statins with a potency of >45% LDL-C reduction plus at least another lipid-lowering agent). Despite maximal treatment, only 18.8% of these heFH patients (n = 34/181) reached target LDL-C levels of <100 mg/dL. In addition, 75.3% of patients with CVD did not reach the LDL-C of <100 mg/dL. CONCLUSION: This study demonstrates that after significant improvement over the past two decades, the mean LDL-C levels in heFH French patients has remained stable since 2005. We also show that most heFH patients are not achieving their recommended LDL-C goals: this highlights the need for improved treatment and for new therapeutics in this population.

Parallel increase of plasma apoproteins C-II and C-III in Type 2 diabetic patients.

AIMS: To determine plasma levels of apoprotein (apo) C-II and apoprotein C-III in Type 2 diabetic patients and to examine the clinical and biological factors that are associated with elevated apoC concentrations. METHODS: We measured apoC-II and apoC-III in total plasma and in non-high-density lipoprotein fractions by an immunoturbidimetric assay in 88 Caucasian Type 2 diabetic patients and in 138 healthy control subjects. RESULTS: Plasma levels of both apoC-II and apoC-III were increased in Type 2 diabetic patients. The clinical conditions associated with an increase of plasma apoC-II and apoC-III were abdominal obesity, body mass index, poor glycaemic control and lack of insulin treatment. However, when multivariate analysis was used, plasma apoCs levels correlated with triglyceride levels only. The apoC-III/apoC-II ratio was similar in the Type 2 diabetic and control subjects. CONCLUSIONS: Our study shows the parallel increase of apoC-II and C-III in Type 2 diabetic patients. This parallel increase is related to hypertriglyceridaemia only.

Scleredema adultorum of Buschke: an under recognized skin complication of diabetes.

Scleredema of Buschke or scleredema diabetorum is a skin complication of diabetes with deposits of collagen and aminoglycans in the dermis. This disease characterized by thickening and hardening of the skin, is usually localized in nape, back and shoulder areas. Consequences could be a decrease in motility of the shoulders and an impairment of respiratory function. Other possible complications are sleep apnoea syndrome and monoclonal gammapathy. Type 1 or type 2 diabetes may be associated with scleredema of Buschke in more than 50% of cases. Diabetes-related risk factors are long duration of the disease, presence of microangiopathy, overweight and need of insulin. Various specific treatments proposed in the literature are poorly validated. In most severe cases, radiation therapy may be useful.

The refusal of treatment in anorexia nervosa, an ethical conflict with three characters: "the girl, the family and the medical profession". Discussion in a French legislative context.

Anorexic patients are prone to refuse treatment despite life-threatening complications. The therapist's ethical code can be torn between duty to protect life, and law that demands respect of the patient's autonomy. The age of these girls introduces a third participant in this ethical conflict with three characters: "the girl, her family and the physician". Even if her decision to refuse treatment can appear unreasonable, the patient suffering from anorexia nervosa remains "competent" to receive information concerning her state of health and to make up her own mind about what to do next. French law only recognises for the therapist a real duty to make efforts to convince the patient of the absolute necessity of treatment. However it appears important to confront these legal obligations with different situations created by the disease in order to help pave the way to finding medical solutions capable of conciliating the objective of the best treatment, the own ethical code of the physician and the respect of current legislation.

[Monogenic diabetes: a useful dimension for diabetology practice]. / Les diabètes monogéniques: une dimension à intégrer dans la pratique clinique des diabétologues.

The number of identified monogenic diabetes progressively increases with time even if these forms of diabetes represent less than 5% of the cases. Every monogenic diabetes is characterized by an impairment of Beta cell at various levels. They are good models of diabetes-prone mechanisms. Diabetologists should recognize these forms because the management of the patients could be modified as a function of the genetic anomaly, in terms of either choice of hypoglycaemic agents, prognostic, management of associated manifestations or genetic counselling.

Atypical neuroleptics and diabetes.

Since a few years, an increasing number of cases of atypical neuroleptic-associated diabetes are reported in the literature. But few are dedicated to diabetologists. We report here two cases of patients with a severe deterioration of preexisting diabetes, with clozapine for the first case report and olanzapine for the second one. We also make a literature review and discuss the possible mechanisms involved in this atypical neuroleptic-associated diabetes. We recommend a thigh follow-up of weight, glycemic and lipidic parameters during psychotic patients treatment with atypical neuroleptics, in order to prevent or rapidly treat the metabolic complications described in the literature.