Jacques Bringer

Obesity and pregnancy: complications and cost

The prevalence of obesity is currently rising in developed countries, making pregravid overweight one of the most common high-risk obstetric situations. Although the designs and populations of published studies vary widely, most authors agree that pregravid overweight increases maternal and fetal morbidity. Even moderate overweight is a risk factor for gestational diabetes and hypertensive disorders of pregnancy, and the risk is higher in subjects with overt obesity. Compared with normal weight, maternal overweight is related to a higher risk of cesarean deliveries and a higher incidence of anesthetic and postoperative complications in these deliveries. Low Apgar scores, macrosomia, and neural tube defects are more frequent in infants of obese mothers than in infants of normal-weight mothers. The regional distribution of fat modulates the effects of weight on carbohydrate tolerance, hemodynamic adaptation, and fetal size. Maternal obesity increases perinatal mortality. Long-term complications include worsening of maternal obesity and development of obesity in the infant. The average cost of hospital prenatal and postnatal care is higher for overweight mothers than for normal-weight mothers, and infants of overweight mothers require admission to neonatal intensive care units more often than do infants of normal-weight mothers. Preconception counseling, careful prenatal management, tight monitoring of weight gain, and long-term follow-up could minimize the social and economic consequences of pregnancies in overweight women.

Effect of Topical Basic Fibroblast Growth Factor on the Healing of Chronic Diabetic Neuropathic Ulcer of the foot: A pilot, randomized, double-blind, placebo-controlled study

OBJECTIVE To assess the efficacy and safety of topical human recombinant basic fibroblast growth factor (bFGF) on the healing of diabetic neurotrophic foot ulcers. RESEARCH DESIGN AND METHODS Seventeen diabetic patients suffering from chronic neuropathic ulcer of the plantar surface of the foot entered a pilot, randomized, double-blind study comparing local application of bFGF with placebo. Main inclusion criteria were a typical neuropathic ulcer of Wagner grade I-III, more than 0.5 cm in the largest diameter, with an abnormally high vibration perception threshold in the absence of significant peripheral vascular disease or wound infection. bFGF or placebo was applied daily during the 6 weeks as inpatients then twice a week for 12 weeks. Evolution of ulcer size was assessed through weekly clinical examination and computerized photographs. RESULTS In the bFGF group, three of nine ulcers healed compared with five of eight in the placebo group (NS). The weekly reduction in ulcer perimeter and area was identical in both groups, as was the rate of linear advance from entry to the 6th week of treatment (bFGF: 0.053 ± 0.048 mm vs. placebo: 0.116 ± 1.129 mm): the same result was obtained at the 11th week. Moreover, percent healed area at the end of the study did not differ significantly. No side effects were observed during bFGF application. CONCLUSIONS Topical application of bFGF has no advantage over placebo for healing chronic neuropathic diabetic ulcer of the foot. Because diabetes causes significant wound-healing defects, we hypothesized that using a single growth factor might be insufficient to accelerate wound closure of diabetic ulcers.

Improvement of HbA1c and Blood Glucose Stability in IDDM Patients Treated With Lispro Insulin Analog in External Pumps

OBJECTIVE To compare the efficacy of the short-acting insulin analog lispro (LP) with that of regular insulin in IDDM patients treated with an external pump. RESEARCH DESIGN AND METHODS Thirty-nine IDDM patients (age, 39.4 ± 1.5 years; sex ratio, 22M/17W; BMI, 24.4 ± 0.4 kg/m2; diabetes duration, 22.5 ± 1.6 years) who were treated by external pump for 5.1 ± 0.5 years were involved in an open-label, randomized, crossover multicenter study comparing two periods of 3 months of continuous subcutaneous insulin infusion with LP or with Actrapid HM, U-100 (ACT). Boluses were given 0–5 min (LP) or 20–30 min (ACT) before meals. Blood glucose (BG) was monitored before and after the three meals every day. RESULTS The decrease in HbA1c was more pronounced with LP than with ACT (−0.62 ± 0.13 vs. −0.09 ± 0.15%, P = 0.01). BG levels were lower with LP (7.93 ± 0.15 vs. 8.61 ± 0.18 mmol/l, P < 0.0001), particularly postprandial BG levels (8.26 ± 0.19 vs. 9.90 ± 0.20 mmol/l, P < 0.0001). Standard deviations of all the BG values (3.44 ± 0.10 vs. 3.80 ± 0.10 mmol/l, P = 0.0001) and of postprandial BG values (3.58 ± 0.10 vs. 3.84 ± 0.10 mmol/l. P < 0.02) were lower with LP. The rate of hypoglycemic events defined by BG < 3.0 mmol/l did not significantly differ between LP and ACT (7.03 ± 0.94 vs. 7.94 ± 0.88 per month, respectively), but the rate of occurrences of very low BG, defined as BG < 2.0 mmol/l, were significantly reduced with LP (0.05 ± 0.05 vs. 0.47 ± 0.19 per month, P < 0.05). At the end of the study, all but two (95%) of the patients chose LP for the extension phase. CONCLUSIONS When used in external pumps, LP provides better glycemic control and stability than regular insulin and does not increase the frequency of hypoglycemic episodes.

Artificial β-cell: clinical experience toward an implantable closed-loop insulin delivery system

AIM Restoration of long-term normal blood glucose control in diabetic patients supports the elaboration of an artificial beta cell. The possibility of implantation of the three crucial components of such a system (insulin delivery device, glucose sensor and controller) is analyzed. METHODS The Long-Term Sensor System project, aiming at a fully implantable artificial beta cell, assessed the feasibility of glucose control by the combined implantation of a pump for peritoneal insulin delivery and a central intravenous glucose sensor close to the right atrium, connected via a subcutaneous lead. It was initiated in 10 Type 1 diabetic patients in our clinic from 2000. Data obtained during this experience are reviewed and confronted to reported closed-loop trials using other approaches. RESULTS No significant complication related to prolonged implantation of intravenous sensors occurred and the combined implants were well tolerated. Glucose measurement by the intravenous sensors correlated well with meter values (r=0.83-0.93, with a mean absolute deviation of 16.5%) and accuracy has been sustained for an average duration of 9 months. Uploading of pump electronics by algorithms designed for closed-loop insulin delivery allowed in-patient 48 hour-trials aiming at automated glucose control. Glucose control was similar to that reported by investigations combining subcutaneous sensors to wearable pumps for subcutaneous insulin infusion. The benefits of more physiological insulin kinetics due to intra-peritoneal delivery have been hampered by the slow response time of intravenous sensors. CONCLUSION Although the concept of a fully implantable artificial beta cell has been validated as feasible, the limited performance in achieving glucose control requests improvements in the sensor structure to increase its longevity and decrease sensor delay.

Is Decision Making Really Impaired in Eating Disorders

OBJECTIVE Decision making has been reported to be reduced in eating disorders. However, studies are sparse and have been carried out in various selected populations. In the current study we arranged to confirm previous observations and to assess the relationship between decision making and dimensions relevant to eating disorders. METHOD Patients suffering from anorexia nervosa (n = 49), bulimia nervosa (n = 38), and healthy controls (n = 83) were assessed using the Iowa Gambling Task (IGT). All patients were euthymic and free of psychotropic medication. Self-questionnaires (Eating Disorder Inventory-2; Gardner, 1991; and Eating Attitude Test; Garner & Garfinkel, 1979) were used to assess clinical dimensions relevant to eating disorders. RESULTS No significant differences in IGT performance were observed between patients and healthy controls or between restrictive and purging types of anorexia nervosa. No correlations were found between IGT performance and eating disorder questionnaires. CONCLUSION These results do not support reduced decision making in patients with eating disorders, and suggest that previously reported alterations could be related to other clinical characteristics. This should stimulate new topic-related studies designed to reach a firm conclusion.

Syndrome of body fat redistribution in HIV‐1‐infected patients: relationships to cortisol and catecholamines

Alterations of body fat distribution have been recently reported in HIV‐infected patients. We aimed to investigate whether the hormones modulating adipose tissue metabolism could be implicated.

Insulin Underdelivery From Implanted Pumps Using Peritoneal Route: Determinant role of insulin pump compatibility

OBJECTIVE To evaluate the incidence and investigate determinants of insulin underdelivery events occurring with implanted pumps using peritoneal route from a 103 patient-year experiment. RESEARCH DESIGN AND METHODS Of the MiniMed (MIP 2001) pumps implanted in 47 type I diabetic patients, 70 were refilled quarterly with four successive batches (A, B, C, D) of U400 Hoechst 21 PH neutral insulin during a 3-year study period. Any reduction of insulin flow rate >15% was considered as abnormal insulin delivery. Diagnosis of the cause of underdelivery was established according to the response to the following steps: 1) 0.01 mol/l NaOH rinse of pump circuits to solubilize insulin aggregates, 2) surgical examination and replacement of blocked catheters, and 3) postsurgical 0.01 mol/l NaOH rinse of pump. Step 2 was selected first if the increase of insulin requirements or reduction of flow rate were > 50%. Relative contributions of insulin and the implanted system to underdelivery events were analyzed. RESULTS There were 76 episodes of insulin underdelivery that occurred during the study, resulting in an incidence of 74 events per 100 patient-years. Of 52 NaOH pump rinses, 30 restored normal flow rate. Surgery, performed after rinse failure (n = 22) or as the first step (n = 24), disclosed catheter blockages due to tip obstructions in 28 cases and omental encapsulations in 18 other cases. Five combined severe reductions of pump flow rate requiring pump replacements were diagnosed during surgery, and additional NaOH rinses had to be performed after catheter change in 12 other cases. Analysis of the incidence of underdelivery events indicated that both pump- and catheter-related problems were significantly increased while implanted systems infused batches B, C, and D versus batch A (P < 0.01), whereas the duration of pump implantation had no significant influence. CONCLUSIONS Underdelivery events constitute serious limiting obstacles to prolonged peritoneal insulin infusion from implanted pumps. Progress in insulin pump compatibility is expected to reduce their occurrence and, thus, to improve the feasibility of this treatment.

Closed loop insulin delivery using implanted insulin pumps and sensors in type 1 diabetic patients

Abstract We investigated the feasibility of closed loop insulin delivery by using a model based upon the coupling of an implanted insulin pump that infuses insulin by intra-peritoneal route and an intravenous enzymatic glucose sensor. Closed Loop Control (CLC) by a proportional, integral and derivative algorithm was initiated in 4 type 1 diabetic subjects, already implanted with both devices (MiniMed-Medtronic, Northridge, CA, USA), and continued for 48 hours. Three meals of 40 g and twice 80 g carbohydrates were served daily. Blood glucose was assessed every 10 minutes for the first two hours of meals and every 30 minutes otherwise. Algorithm parameters were empirically adjusted during the experiment based on antecedent blood glucose levels. CLC in one subject was stopped after 24 hours due to inadequate sensor performance. During CLC, the algorithm kept glucose within 80–240 mg/dl for 84.1% of the time. Algorithm retuning did not change the percentage of glucose >240 mg/dl but increased the percentage within the 80–120 mg/dl range during the final 24 hours. Excluding meals, glucose was

Optimizing the outcome of pregnancy in obese women: From pregestational to long-term management

The obesity epidemic is of some concern in women of reproductive age. Maternal obesity is associated with many pregnancy complications, especially gestational diabetes and hypertensive disorders of pregnancy. Delivery in obese women is characterized by a high caesarean-section rate and an increased risk of anaesthetic and postoperative complications. Weight retention after birth may increase the risk of type 2 diabetes in the long term. Foetal risks include macrosomia, malformations and increased perinatal mortality, with the long-term infant health marked by a higher risk of obesity and metabolic disorders. Optimal management includes preconception counselling, pregravid weight-loss programmes, monitoring of gestational weight gain, repeated screening for pregnancy complications and long-term follow-up to minimize the social and economic consequences of pregnancy in overweight women.

A Prospective Prognostic Study of the Hormonal Milieu at the Time of Surgery in Premenopausal Breast Carcinoma

Despite numerous studies, the influence of timing at surgery in relation to the menstrual cycle on the prognosis of breast carcinoma is still controversial. Most studies are retrospective, and the reliability of the menstrual history data is limited by the lack of hormonal assessment at the time of surgery. The authors prospectively studied the influence of the menstrual cycle phase as determined by circulating hormones at the time of surgery on the outcome of breast carcinoma.