Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: toward recommendation for molecular testing and management.

SHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had four or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included intrauterine growth restriction (IUGR) <10th percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended.

Per-operative hemodynamic instability in normotensive patients with incidentally discovered pheochromocytomas.

CONTEXT: The per-operative hemodynamic behavior of normotensive incidentally discovered pheochromocytomas is poorly documented. OBJECTIVE: To compare the per-operative hemodynamic instability and early postoperative outcome of normotensive pheochromocytomas, hypertensive pheochromocytomas, and benign non-pheochromocytoma adrenal incidentalomas (AIs). DESIGN: Retrospective cohort treated in a single center. PATIENTS AND METHODS: Fifty patients (10 normotensive pheochromocytomas, 24 hypertensive pheochromocytomas, and 16 AIs) were anesthetized and operated on by the same team, using laparoscopy in 78% of cases. Before surgery, 60% of normotensive and 95.8% of hypertensive pheochromocytomas received pretreatment with α-receptor or calcium channel blockers. All of the patients received the same intraoperative hemodynamic monitoring, including continuous direct intra-arterial pressure recording. RESULTS: All the features of hemodynamic instability, with the exception of the diastolic pressure nadir and fluid volume requirements, differed between hypertensive pheochromocytomas and AIs. Conversely, all features of hemodynamic instability were similar in hypertensive and normotensive pheochromocytomas. More specifically, by comparison with AIs, normotensive pheochromocytomas displayed higher maximal systolic pressure; more hypertensive, severe hypertensive, and hypotensive episodes; and a higher minimal heart rate, and also required more interventions to treat undesirable blood pressure elevations. Postoperative complications, all of which were mild, were more frequent in hypertensive pheochromocytomas than in normotensive pheochromocytomas (P < .03). CONCLUSIONS: Normotensive pheochromocytomas have roughly comparable per-operative hemodynamic instability to hypertensive pheochromocytomas and differ markedly from non-pheochromocytoma AIs. It is therefore crucial to identify normotensive pheochromocytomas among AIs when surgery is scheduled and to apply the standard of care for pheochromocytoma anesthesia.

Early changes in respiratory quotient and resting energy expenditure predict later weight changes in patients treated for poorly controlled type 2 diabetes.

AIM: This study looked at whether early changes in resting energy expenditure (REE) and respiratory quotient (RQ) are correlated with later weight changes in patients with type 2 diabetes (T2D) being treated with insulin or GLP-1 analogues, or diet. METHODS: A total of 67 patients (age: 57 ± 9 years; BMI: 33.7 ± 5.0 kg/m(2); HbA1c: 9.9 ± 1.5%) began taking an insulin analogue at bedtime (INS, n=28; initial dose: 0.2 IU/kg) or a GLP-1 analogue (GLP-1, n=23), or only a dietary intervention (diet, n=16; restricted carbohydrates and calories). Their respiratory exchanges were monitored on days 0, 1 and 2 before breakfast. RESULTS: Two days after starting the bedtime insulin analogue, fasting glycaemia improved (INS: -65 ± 41 mg/dL; GLP-1: -29 ± 48 mg/dL; diet: -31 ± 46 mg/dL; P<0.05), REE decreased (INS: -162 ± 241 kcal/24h; GLP-1: 0 ± 141 kcal/24h; diet: -41 ± 154 kcal/24h; P<0.05) and RQ increased (from 0.76 ± 0.04 to 0.80 ± 0.04; P<0.01), whereas only RQ decreased with diet (from 0.79 ± 0.05 to 0.76 ± 0.04; P<0.05) and remained unchanged with GLP-1 (P<0.005 for ΔRQ across treatments). Only 33 patients attended the scheduled examination three months later. HbA1c improved (INS, n=16: -1.7 ± 1.4%; GLP-1, n=12: -2.1 ± 1.4%; diet, n=5: -1.7 ± 2.8%; NS), while weight changes differed (INS: +1.5 ± 4.3 kg; GLP-1: -2.8 ± 2.8 kg; diet: -2.2 ± 2.7 kg; P<0.005). After three months, weight changes correlated with early changes in REE (r=-0.37, P<0.05) and RQ (r=+0.43, P<0.01), and remained correlated when both changes were included in a multivariate regression analysis (r=0.58, P<0.005). CONCLUSION: In poorly controlled patients with T2D and two days after the introduction of a bedtime insulin analogue, REE decreased by -9% while RQ increased by +5%, pointing to a reduction of lipid oxidation. These changes were predictive of later weight gain.

Telemedicine and type 1 diabetes: is technology per se sufficient to improve glycaemic control?

AIM: In the TELEDIAB-1 study, the Diabeo system (a smartphone coupled to a website) improved HbA1c by 0.9% vs controls in patients with chronic, poorly controlled type 1 diabetes. The system provided two main functions: automated advice on the insulin doses required; and remote monitoring by teleconsultation. The question is: how much did each function contribute to the improvement in HbA1c? METHODS: Each patient received a smartphone with an insulin dose advisor (IDA) and with (G3 group) or without (G2 group) the telemonitoring/teleconsultation function. Patients were classified as "high users" if the proportion of "informed" meals using the IDA exceeded 67% (median) and as "low users" if not. Also analyzed was the respective impact of the IDA function and teleconsultations on the final HbA1c levels. RESULTS: Among the high users, the proportion of informed meals remained stable from baseline to the end of the study 6months later (from 78.1±21.5% to 73.8±25.1%; P=0.107), but decreased in the low users (from 36.6±29.4% to 26.7±28.4%; P=0.005). As expected, HbA1c improved in high users from 8.7% [range: 8.3-9.2%] to 8.2% [range: 7.8-8.7%] in patients with (n=26) vs without (n=30) the benefit of telemonitoring/teleconsultation (-0.49±0.60% vs -0.52±0.73%, respectively; P=0.879). However, although HbA1c also improved in low users from 9.0% [8.5-10.1] to 8.5% [7.9-9.6], those receiving support via teleconsultation tended to show greater improvement than the others (-0.93±0.97 vs -0.46±1.05, respectively; P=0.084). CONCLUSION: The Diabeo system improved glycaemic control in both high and low users who avidly used the IDA function, while the greatest improvement was seen in the low users who had the motivational support of teleconsultations.

Low physical activity in patients with type 2 diabetes: the role of obesity.

AIMS: Few studies have described ambulatory activity in free-living individuals with type 2 diabetes mellitus (T2DM) using motion sensors, and none included a control group. For this reason, our study compared the physical-activity levels of outpatients with T2DM with subjects without diabetes, and examined the relationship between body mass index (BMI) and physical-activity parameters. METHODS: Physical-activity levels in 70 outpatients with T2DM and 30 age-, gender- and employment-matched individuals without diabetes were measured using the SenseWear Armband™, a monitoring device validated against doubly labelled water, to assess total energy expenditure. Patients wore the SenseWear Armband™ on their right arm continuously every day for 1 week. RESULTS: Total energy expenditure (<300 kcal/day), number of steps (<1500/day), physical-activity duration (<130 min/day) and active energy expenditure/day (<300 kcal) were all significantly lower (P<0.05) in patients with T2DM. These measures were inversely correlated with BMI, and remained significant after adjusting for age, gender, employment status and the presence of diabetes. CONCLUSION: Outpatients with T2DM have lower physical-activity levels than their matched controls, a characteristic that is related to their higher BMI.

Early decrease in resting energy expenditure with bedtime insulin therapy.

AIMS: In type 2 diabetes (T2D), insulin-induced weight gain may stem from a reduction in resting energy expenditure (REE). We sought to determine the early effects of insulin introduction on REE in 20 poorly controlled T2D patients. METHODS: After improving the glycaemia, REE was measured on Day 0 and Day 4 during two treatment regimens: bedtime insulin (n=10, group 1); and one off (3-day) intravenous insulin infusion (n=10, group 2). RESULTS: Both groups were similar in age, gender, BMI, C-peptide, HbA(1c) and initial REE. By Day 4, fasting glycaemia had similarly improved in both groups: group 1: -5.3+/-2.7mmol/L vs group 2: -5.8+/-4.2 mmol/L. In group 2, the second REE was measured 12h after stopping the intravenous insulin infusion, whereas subcutaneous insulin was maintained in group 1. REE did not change in group 2 (-1.3+/-6.5%), whereas it decreased significantly in group 1 (-8.0+/-7.0%; P<0.05). CONCLUSION: Bedtime insulin led to an early and specific reduction in REE.

[Surgical excision of subclinical cortisol secreting incidentalomas: Impact on blood pressure, BMI and glucose metabolism]. / Bénéfices tensionnels, anthropométriques et métaboliques de l'exérèse chirurgicale des adénomes cortisoliques infracliniques.

OBJECTIVES: To compare clinical, vascular and metabolic parameters before and after surgery in patients with subclinical cortisol secreting incidentalomas. PATIENTS AND METHODS: Eight patients were investigated before and 12 months after removal of the mass on hemodynamic (blood pressure by MAPA procedure), anthropometric (body weight, body mass index), and metabolic parameters (glucose level, HbA(1c)). RESULTS: In the whole group, 75% of patients displayed decrease in blood pressure (cessation of at least one hypotensive medication) and 33% of them were definitely cured of hypertension. Seventy-one percent of patients lost body weight and 37.5% lost more than 5%. In the whole group of patients, glucose level decreased by 1.1% and medical treatment was discontinuated in two of three diabetic patients. CONCLUSION: Subclinical cortisol secreting adrenal incidentalomas are associated with cardiovascular risk factors that may be corrected after removal of the mass. Therefore, surgery may be an appropriate choice in patients with subclinical Cushing's syndrome to improve hypertension, body weight and impaired glucose level. Controlled studies comparing surgical treatment to a medical follow-up including optimal cardiovascular risk factors treatment are needed to define the usefulness of surgery in hypertensive patients with subclinical cortisol secreting incidentalomas.

[The prevalence of abnormal glucose regulation after myocardial infarction: Comparative study in two French ethnic groups]. / Anomalies du métabolisme glucidique au décours d'un syndrome coronarien aigu : une étude comparative de deux groupes ethniques français.

OBJECTIVES: The aim of this study was to compare the prevalence of abnormal glucose tolerance in patients stemming from two French ethnic groups and admitted for acute coronary syndrome (ACS) to intensive coronary care unit. MATERIALS AND METHODS: During a period of six months, 53 and 60 consecutive patients were enrolled at Fort-de-France (Martinique, French West Indies, Afrocaribbeans, group F) and at Bordeaux (France, Europeans, group B), respectively. Glucometabolic state was classified according to medical history and fasting glycemia measured from the fourth day after ACS. RESULTS: At baseline, 36% of the patients of group F and 20% of the patients of group B had previously known diabetes (p=0.06). Prevalence of hypertension was higher in Afrocaribbeans than in Europeans (60 versus 40%, p<0.05). According to fasting glycemia, newly detected diabetes were found in six Afrocaribbeans and only one was found in Europeans; two patients in group F and three patients in group B displayed impaired fasting glycemia. As a whole, 51% of Afrocaribbeans and 27% of Europeans showed abnormal glucose tolerance (p<0.05). Furthermore, Afrocaribbeans displayed lower levels of triglycerides and higher levels of HDL cholesterol than Europeans (p<0.05). CONCLUSION: Our study suggested a higher prevalence of impaired glucose metabolism in French Afrocaribbeans than in European counterparts after ACS. Furthermore, French Afrocaribbeans displayed a more favorable lipoprotein profile. These characteristics look like that of the American and British Afrocaribbeans, maybe because of a common genetic origin.

Air displacement plethysmography can detect moderate changes in body composition.

OBJECTIVES: To determine the sensitivity of air displacement plethysmography (APD) for evaluation of changes in body composition in normal subjects. DESIGN: Comparison of measurements with and without oil or water loads. SUBJECTS AND METHODS: Ten healthy volunteers were analyzed, without and with 1 l and 2 l of oil or water. The measured and true changes in fat mass and fat-free mass were compared by paired t-tests. A correlation study and a Bland & Altman procedure was performed on the 60 measurements of adiposity changes in 30 subjects carrying 0.5 l (n=8 x 2), 1 l (n=10 x 2) and 2 l (n=12 x 2) oil and water loads. RESULTS: Fat-free mass increased when the 10 subjects were carrying water. When they carried oil, fat mass increased, however, a approximately 0.5 kg increase of fat-free mass was also detected. Two liters loads led to distinct changes: +1.49+/-0.59 kg fat and +0.50+/-0.60 kg fat-free with oil and +0.37+/-0.57 kg fat and +1.70+/-0.56 kg fat-free with water (both P<0.001). Mixed loads (+1 l oil and 1 l water) led to detect +0.85+/-0.48 kg fat and +1.09+/-0.45 kg fat-free (both P<0.005 vs without load). For the 30 subjects analyzed thrice, measured changes in fat and fat-free mass were slightly underestimated (-15%, NS) but correlated with the true changes. Measured changes in adiposity were correlated with the true changes, with no bias as indicated by the Bland & Altman procedure. CONCLUSION: APD detects approximately 2 kg changes in fat or fat-free mass in small populations.