Gastric electrical stimulation treatment of type 2 diabetes: effects of implantation versus meal-mediated stimulation. A randomized blinded cross-over trial.

Gastric electrical stimulation with the implanted DIAMOND device has been shown to improve glycemic control and decrease weight and systolic blood pressure in patients with type 2 diabetes inadequately controlled with oral antidiabetic agents. The objective of this study was to determine if device implantation alone (placebo effect) contributes to the long-term metabolic benefits of DIAMOND(®) meal-mediated gastric electrical stimulation in patients with type 2 diabetes. The study was a 48 week randomized, blinded, cross-over trial in university centers comparing glycemic improvement of DIAMOND(®) implanted patients with type 2 diabetic with no activation of the electrical stimulation (placebo) versus meal-mediated activation of the electrical signal. The endpoint was improvement in glycemic control (HbA1c) from baseline to 24 and 48 weeks. In period 1 (0-24 weeks), equal improvement in HbA1c occurred independent of whether the meal-mediated electrical stimulation was turned on or left off (HbA1c -0.80% and -0.85% [-8.8 and -9.0 mmol/mol]). The device placebo improvement proved to be transient as it was lost in period 2 (25-48 weeks). With electrical stimulation turned off, HbA1c returned toward baseline values (8.06 compared to 8.32%; 64.2 to 67.4 mmol/mol, P = 0.465). In contrast, turning the electrical stimulation on in period 2 sustained the decrease in HbA1c from baseline (-0.93%, -10.1mmol/mol, P = 0.001) observed in period 1. The results indicate that implantation of the DIAMOND device causes a transient improvement in HbA1c which is not sustained beyond 24 weeks. Meal-mediated electrical stimulation accounts for the significant improvement in HbA1c beyond 24 weeks.

Treatment of type 2 diabetes using meal-triggered gastric electrical stimulation.

BACKGROUND: The TANTALUS System (MetaCure Limited) is a minimally invasive implantable device for the treatment of type 2 diabetes. The system detects food intake by sensing gastric electrical variations and applies electrical stimulation to the gut synchronized to natural gastric activity. The system is commercially available in Europe and Israel and is in clinical trials in the United States. It has been tested in 132 patients worldwide to date. OBJECTIVES: To re-analyze previously reported datafrom different studies. This retrospective analysis of the type 2 diabetes subpopulation analyzed the expected benefit and characterized the significance of baseline A1c in the determination of the expected clinical outcome. METHODS: From the total cohort of 132 patients implanted with the TANTALUS device in 10 different centers in Europe and the U.S., we identified 50 subjects (27 females, 23 males) who were obese with uncontrolled T2DM on a stable regime of oral medication for 3 months prior to implant. This population had similar inclusion/exclusion criteria as well as treatment protocols and were all treated for at least 24 weeks. The analysis was based on the A1c change compared to baseline. RESULTS: Data after 24 weeks demonstrated a reduction in A1c in 80% of the patients with average drop in A1c of 1.1 +/- 0.1%. The average weight loss was 5.5 +/- 0.7 kg. CONCLUSIONS: The results suggest that the TANTALUS stimulation regime can improve glucose levels and induce moderate weight loss in obese T2DM patients.

Normal DXA bone mineral density but frail cortical bone in Turner's syndrome.

CONTEXT: Patients with Turner's syndrome have normal bone mineral density by dual energy X-ray absorptiometry (DXA), but a predisposition for fractures. Quantitative ultrasonography (QUS) measures cortical bone strength. OBJECTIVE: To compare QUS with DXA in patients with Turner's syndrome. PATIENTS AND METHODS: Twenty-seven Turner's syndrome patients, aged 21.1 +/- 6.3 years (mean +/- SD), were evaluated by DXA, measuring two-dimensional bone mineral density (BMD), and QUS, measuring speed of sound (SOS) of the radius and tibia. The results were compared to sex- and age-matched (Ctr A, n = 53) and height-matched (Ctr B, n = 34) control groups. RESULTS: Fracture incidence per 1000 women years was 4.76 in Ctr A, 5 in Ctr B and 7.69 in Turner's patients. In Turner's syndrome patients, QUS results were significantly lower than in controls, whereas DXA Z-scores were not different from reference values. Correlation between tibia and radius SOS and height and age in controls (P < 0.0001) was not evident in Turner's syndrome. Oestrogen or growth hormone therapy had no effect on either QUS or DXA parameters. CONCLUSIONS: Bone fragility in Turner's syndrome is reflected by low SOS but not by DXA BMD. Low QUS, which assesses the cortical bone only, supports a defect in cortical bone in Turner's syndrome. Lack of SOS correlation with age, height and hormonal therapy in Turner's syndrome suggests a primary bone defect, rather than enhanced resorption of endocrine origin.

Quantitative ultrasound in the evaluation of bone status in premature and full-term infants.

Metabolic bone disease of prematurity (MBDP) is a common and significant problem that often gives rise to osteopenia, fractures, osteomalacia, and osteoporosis. The purpose of our study is to establish normative data on bone status in premature and full-term infants to help future studies on MBDP. Bone status was prospectively determined as part of a multicenter study among newborns within 96 hours of life. The patients were divided into 2 groups: group 1 included those neonates 25-36 wk gestational age (premature), and group 2 neonates were born at 37-42 wk gestational age (full term). Demographic data were collected. The Omnisense 7000 Bone Sonometer (Sunlight Medical Ltd., Tel-Aviv, Israel) was used to determine the speed of sound (SOS) through the mid tibia, which reflects bone strength. A total of 235 patients were enrolled in this study. Group 1 (i.e., the premature infants) had a statistically lower age-adjusted SOS as compared with group 2 (i.e., the full-term infants) (analysis of variance; p=0.001). There was also a correlation between SOS and birth weight (r=0.3; p<001). This study represents the largest database of normative data for bone status measuring in preterm and term infants.

Assessment of skeletal age at the wrist in children with a new ultrasound device.

BACKGROUND: Determination of skeletal development in children is important. The most common method of evaluation uses the standards of Greulich and Pyle (G and P) to assess the left hand radiograph. Numerous assessments may be made during follow-up. OBJECTIVE: The aim of our study was to compare the accuracy of a new sonographic method with the standard radiographic method. MATERIALS AND METHODS: Seventy consecutive patients (age 6-17 years; 34 girls, 36 boys) underwent radiography of the left hand, followed by sonographic examination of the same hand using the BonAge system (Sunlight Medical Ltd., Israel). This system evaluates the relationship between the velocity of sound passing thorough the distal radial and ulna epiphysis and growth, using gender- and ethnicity-based algorithms. One experienced paediatric radiologist analysed the radiograph and assigned bone age scores based on the G and P atlas for the whole left hand and for the distal radius alone. The radiologist was blinded to the chronological age (CA), height of the patient and the BonAge result. Correlation between BonAge and G and P was undertaken. RESULTS: In 65 patients, BonAge measurement could be performed successfully. In five patients, the scanning process was impossible using the ultrasound device. The r(2) (r is the Pearson correlation coefficient) of the BonAge ultrasound measurement and the G and P method was 0.82. The averaged accuracy (i.e. absolute difference in years between G and P reading and BonAge ultrasonic results) was calculated. Results were similar for boys and girls: 1.0+/-0.8 years for the whole left hand and 0.8+/-0.7 year for the distal radius. On average, the difference between BonAge and CA is the same as the difference between G and P and CA, i.e. 1.4 years. CONCLUSIONS: The BonAge device demonstrates the ability of ultrasound to produce an accurate assessment of bone age. The results are highly correlated with skeletal age evaluated conventionally using the G and P method. Obvious advantages of the ultrasound device are objectivity, lack of ionizing radiation, and easy accessibility.

Longitudinal monitoring of bone accretion measured by quantitative multi-site ultrasound (QUS) of bones in patients with delayed puberty (a pilot study).

OBJECTIVE: to compare the effect of anabolic agents on bone accretion in boys with constitutional delay of puberty (CGDP). RATIONALE: it has been suggested that an appropriate timing of puberty is necessary for normal bone mineral density (BMD) acquisition. Proper bone development during childhood is the key factor in achieving higher peak bone mass during middle age, which may not be achievable in CGDP children, and thereby osteoporosis may appear at an earlier age then expected. PATIENTS AND METHODS: 45 boys with CGDP aged 14-16 years were monitored longitudinally, every 3 months over 12 months with Sunlight Omnisense, a quantitative ultrasound device (Tel Aviv, Israel). The apparatus is a multi-site bone sonometer that obtains axial Speed of Sound (SOS). Based on a reference database obtained on n=1,085 (490 boys) 0-18 years, a normative curve was determined. Fifteen (14-16 years old) of the CGDP patients were treated with I.M. testovirone depot 100 mg monthly for 6 months, 15 (14-16 years old) were treated with oxandrolone 5 mg/m(2) daily for 6 months, and 15 (14-16 years old) were in an observation group. RESULTS: whereas the quantitative ultrasound (QUS) Z-score had shown some increase over time in CGDP-treated patients, an increase was found in tibia Z-score from -0.5(-0.64, -0.36) to -0.4(-0.54, -0.26) and from -0.52(-0.67, -0.38) to -0.31(-0.44, -0.11) in the testosterone and oxandrolone-treated groups, respectively, [median (25%, 75%)]. An increase in radius Z-score from -0.52(-0.65, -0.25) to -0.4(-0.54, -0.15) and from -0.51(-0.61, -0.21) to -0.37(-0.47, -0.07) in the testosterone- and oxandrolone-treated groups respectively [median (25%,75%)]. Z-score SOS decreased in the observation group -0.5(-0.66, -0.3) to -0.69(-0.85, -0.54) and -0.5(-0.59, -0.41) to -0.81(-0.95, -0.55) in tibia (P = 0.032) and radius (P = 0.029), respectively. Despite the fact that QUS remained in the normative range in all patients, a clear deterioration was demonstrated in untreated CGDP patients. CONCLUSION: longitudinal follow-up of patients with CGDP may detect an early pattern of deterioration of bone mass.

Bone density in axial and appendicular skeleton in patients with lactose intolerance: influence of calcium intake and vitamin D status.

BACKGROUND: Lactose intolerance (LI) is a common enzymatic insufficiency, manifesting by poor tolerance of dairy products, leading to low calcium intake and poor calcium absorption from dairy products. These changes might lead to an impairment of bone metabolism [1]. OBJECTIVES: To evaluate the impact of LI on quantitative bone parameters in axial and appendicular skeletal sites. To assess the impact of calcium intake from dairy and non-dairy nutritional sources, calcium regulating hormones and bone turnover on quantitative bone parameters in LI patients. METHODS: We evaluated calcium intake and bone status in sixty-six patients with LI, 49 women and 17 men, aged 20 to 78. Bone mass was assessed at the lumbar spine (LS), total hip (TH) and femoral neck (FN) by dual-energy x-ray absorptiometry (DEXA) and at the radius, tibia, phalanx by quantitative ultrasound. Serum calcium, albumin, inorganic phosphate, calcium regulating hormones and markers of bone turnover were evaluated. RESULTS: Total daily calcium intake was below the recommended by the American Dietetic Association [2] in all study participants (mean 692 mg/day +/- 162). Elevated level of urinary deoxypyridinoline crosslinks (DPD) was observed in 63 (96%) patients and was negatively correlated with total daily calcium intake (r = -0.998, p = 0.025) and with nondairy calcium intake (r = -0.34, p = 0.015). Parathyroid hormone (PTH) level in the upper third of normal range (45-65 ng/L) was observed in 11 (17%) patients. Parathyroid hormone (PTH) was inversely correlated with total calcium intake (r = -0.4, p = 0.001), dairy calcium intake (r = -0.83, p = 0.05), non-dairy calcium intake (r = -0.29, p = 0.043), 25OHD(3) serum level (r = -0.3, p = 0.007) and positively correlated with bone turnover markers (deoxypyridinoline crosslinks [DPD], r = 0.36, p = 0.01 and bone specific alkaline phosphatase [BSAP] r = 0.36, p = 0.01). Decrease in quantitative bone parameters compared to age-matched controls was observed in the axial and in the appendicular skeleton in men and in postmenopausal women: mean z-score for LS -0.87 +/- 0.22 and -1.32 +/- 0.65, p = 0.004 and 0.015, tibia -1.15 +/- 0.53 and -0.44 +/- 0.044, p < 0.001 and 0.27, phalanx -0.98 +/- 0.22 and -0.52 +/- 0.98, p < 0.001. We observed decrease in bone mass in patients with serum PTH in the upper tertile of normal range in the FN (z-score -0.57 +/- 0.6 versus -0.03 +/- 0.9, p = 0.025), TH (-0.51 +/- 0.96 versus 0.04 +/- 0.9, p = 0.05) and radius (-1.84 +/- 0.27 versus -0.07 +/- 1.61, p = 0.025, respectively). z-scores in FN and TH positively correlated with serum 25OHD(3) level (r = 0.31, 0.29; p = 0.014, 0.019). In postmenopausal women serum 25OHD(3) level correlated also with LS z-scores (r = 0.52, p = 0.004); FN and TH z-scores negatively correlated with DPD level (r = -0.51, p = 0.02 and r = -0.55, p = 0.04). CONCLUSION: LI state may lead to increased bone turnover and decreased bone mass especially in men and postmenopausal women. Impaired vitamin D status and low calcium intake may be deleterious to bone in this condition.