Search

Summary Background The DEPICT-1 and DEPICT-2 studies showed that dapagliflozin as an adjunct to insulin in individuals with inadequately controlled type 1 diabetes improved glycaemic control and bodyweight, without increase in risk of hypoglycaemia. We aimed to determine the effect of dapagliflozin on urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) using pooled data from the DEPICT studies. Methods In this post-hoc analysis, we used data pooled from both DEPICT studies (DEPICT-1 ran from Nov 11, 2014, to Aug 25, 2017; DEPICT-2 ran from July 8, 2015, to April 18, 2018), in which participants were aged 18–75 years, with inadequately controlled type 1 diabetes and with a baseline UACR of at least 30 mg/g. In the DEPICT studies, participants were randomly assigned (1:1:1) to receive dapagliflozin (5 mg or 10 mg) or placebo all plus insulin, for 24 weeks, with a 28-week long-term extension (ie, 52 weeks in total). In this post-hoc analysis, we assessed the percentage change from baseline in UACR and in eGFR, up to 52 weeks. UACR, eGFR, and safety were assessed in all eligible participants who had received at least one dose of study drug. HbA1c, bodyweight, and systolic blood pressure were assessed in all participants who received at least one dose of study drug during the first 24-week period, and who had a baseline and any post-baseline assessment for that parameter. The DEPICT trials were registered with ClinicalTrials.gov , NCT02268214 (DEPICT-1), NCT02460978 (DEPICT-2), and are now complete. Results 251 participants with albuminuria at baseline were included in this post-hoc analysis; of whom 80 (32%) had been randomly assigned to dapagliflozin 5 mg, 84 (33%) to dapagliflozin 10 mg, and 87 (35%) to placebo. Compared with placebo, treatment with both dapagliflozin doses improved UACR over 52 weeks. At week 52, mean difference in change from baseline versus placebo in UACR was −13·3% (95% CI −37·2 to 19·8) for dapagliflozin 5 mg and −31·1% (−49·9 to −5·2) for dapagliflozin 10 mg. No notable change from baseline was seen in eGFR, with a mean difference in change from baseline versus placebo of 3·27 mL/min per 1·73 m2 (95% CI −0·92 to 7·45) for dapagliflozin 5 mg and 2·12 mL/min per 1·73 m2 (–2·03 to 6·27) for dapagliflozin 10 mg. Similar proportions of participants in each treatment group had adverse events and serious adverse events, including hypoglycaemia and diabetic ketoacidosis; no new safety signals were identified in this population. Interpretation Treatment with dapagliflozin resulted in UACR reduction, which might provide renoprotective benefits in individuals with type 1 diabetes and albuminuria. Dedicated prospective studies are needed to confirm these findings as prespecified endpoints. Funding AstraZeneca.

Aims To investigate the glycemic efficacy, effects on cardiovascular risk factors, and safety of exenatide once weekly (QW) in patients with type 2 diabetes over 7 years in the DURATION-1 study. Methods Patients were initially randomized to exenatide QW 2 mg or exenatide twice daily for 30 weeks, after which they received open-label, open-ended treatment with exenatide QW 2 mg for up to 7 years. Efficacy analyses included changes from baseline in glycated hemoglobin (HbA1C) and cardiovascular risk factors. Results Of 295 patients in the intention-to-treat population, 122 (41%) completed 7 years of treatment. Patients in the 7-year completer population showed sustained glycemic improvements from baseline (7-year least-squares mean [LSM] change in HbA1C, −1.53%) and significant improvements in several cardiovascular risk factors, including body weight, diastolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Seven-year completers who received no additional glucose-lowering therapies (n = 65 [53%]) had similar improvements in HbA1C, and numerically greater reductions in body weight (7-year LSM change, −6.46 kg vs −3.87 kg), compared with the overall cohort. There were no unexpected safety findings. Conclusions Treatment with exenatide QW for 7 years was associated with sustained improvements in glycemic control and several cardiovascular risk factors.

Background EXSCEL is a randomized, double-blind, placebo-controlled trial examining the effect of exenatide once-weekly (EQW) versus placebo on time to the primary composite outcome (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) in patients with type 2 diabetes mellitus (DM) and a wide range of cardiovascular (CV) risk. Methods Patients were enrolled at 688 sites in 35 countries. We describe their baseline characteristics according to prior CV event status and compare patients with those enrolled in prior glucagon-like peptide-1 receptor agonist (GLP-1RA) outcomes trials. Results Of a total of 14,752 participants randomized between June 2010 and September 2015, 6,788 (46.0%) patients were enrolled in Europe; 3,708 (25.1%), North America; 2,727 (18.5%), Latin America; and 1,529 (10.4%), Asia Pacific. Overall, 73% had at least one prior CV event (70% coronary artery disease, 24% peripheral arterial disease, 22% cerebrovascular disease). The median (IQR) age was 63 years (56, 69), 38% were female, median baseline HbA1c was 8.0% (7.3, 8.9) and 16% had a prior history of heart failure. Those without a prior CV event were younger with a shorter duration of diabetes and better renal function than those with at least one prior CV event. Compared with prior GLP-1RA trials, EXSCEL has a larger percentage of patients without a prior CV event and a notable percentage who were taking a dipeptidyl peptidase-4 inhibitor at baseline (15%). Conclusions EXSCEL is one of the largest global GLP-1RA trials, evaluating the safety and efficacy of EQW with a broad patient population that may extend generalizability compared to prior GLP-1RA trials (ClinicalTrials.gov number, NCT01144338).

To analyze changes in plasma glucose, insulin, and glucagon in relation to glycemic response during treatment with dual add-on of saxagliptin (SAXA) plus dapagliflozin (DAPA) to metformin XR (MET) compared with SAXA add-on or DAPA add-on alone to MET in patients with type 2 diabetes mellitus (T2DM) poorly controlled with MET.Double-blind trial in adults with glycated hemoglobin (HbA1c) ≥8.0 to ≤12.0% randomized to SAXA 5 mg/day plus DAPA 10 mg/day (n = 179), or SAXA 5 mg/day and placebo (n = 176), or DAPA 10 mg/day and placebo (n = 179) added to background MET ≥1,500 mg/day. The mean change from baseline in the area under the curve from 0 to 180 minutes (AUC0-180 min) was calculated for glucose, insulin, and glucagon obtained during a liquid meal tolerance test (MTT).Glucose AUC0-180 min was reduced more from baseline with SAXA + DAPA + MET (-12,940 mg/dL) compared with SAXA + MET (-6,309 mg/dL) and DAPA + MET (-11,247 mg/dL). Insulin AUC0-180 min significantly decreased with SAXA + DAPA + MET (-1,120 μU/mL) and DAPA + MET (-1,019 μU/mL) and increased with SAXA + MET (661 μU/mL). Glucagon AUC0-180 min only increased with DAPA + MET (2,346 pg/mL). The changes in glucose (P.0001) and insulin (P = .0003) AUC0-180 min correlated with change in HbA1c, whereas the change in glucagon AUC0-180 min did not (P = .27).When added to background MET, the combination of SAXA + DAPA provided additional reductions in glucose AUC0-180 min and HbA1c without the increase in insulin seen with SAXA and without the increase in glucagon seen with DAPA. Changes in insulin and glucose but not glucagon AUC0-180 min correlated with change in HbA1c.

Large studies in patients with diabetes mellitus (DM) have identified agents that lower major adverse cardiovascular (CV) event (MACE) rates, but certain agents increase rates of lower extremity amputation (LEA). Patients with peripheral artery disease (PAD) have greater incidence of DM and risk for

Lp(a), implicated in both atherogenesis and thrombosis pathways, varies significantly by demographic and metabolic factors, providing challenges for its use in Coronary Heart Disease (CHD) risk. The purpose of this study was to investigate whether type-2 diabetic subjects, relative to non-diabetics, might benefit more from Lp(a) measurement in the prediction of CHD risk, as measured by coronary artery calcium (CAC).We performed cross sectional analyses in two community-based studies: the Penn Diabetes Heart Study [N = 1299 with type-2 diabetes] and the Study of Inherited Risk of Coronary Atherosclerosis [N = 860 without diabetes].Blacks had 2-3 fold higher Lp(a) levels than whites in diabetic and non-diabetic samples. There was significant difference by gender (interaction p0.001), but not race, in the association of Lp(a) with CAC in type-2 diabetic subjects. In age and race adjusted analysis of diabetic women, Lp(a) was associated with CAC [Tobit regression ratio 2.76 (95% CI 1.73-4.40), p0.001]. Adjustment for exercise, medications, Framingham risk score, metabolic syndrome, BMI, CRP and hemoglobin A1c attenuated this effect, but the association of Lp(a) with CAC remained significant [2.25, (1.34-3.79), p = 0.002]. This relationship was further maintained in women stratified by race, or by the use of HRT or lipid lowering drugs. In contrast, Lp(a) was not associated with CAC in diabetic men, nor in non-diabetic men and women.Lp(a) is a strong independent predictor of CAC in type-2 diabetic women, regardless of race, but not in men. Lp(a) does not relate to CAC in men or women without type-2 diabetes.

Objective To determine whether insulin sensitizers lower androgen levels and whether androgen suppression improves insulin resistance in nondiabetic postmenopausal women. Design Randomized, double-blind, placebo-controlled study. Setting Clinical and Translational Research Center of a university hospital. Patient(s) Thirty-five postmenopausal women aged 50–79 years with insulin resistance and higher T levels. Intervention(s) Subjects were randomized to metformin plus leuprolide acetate (LA) placebo, LA plus metformin placebo, or LA placebo plus metformin placebo in a 1:1:1 fashion during a 12-week period. Main Outcome Measure(s) Insulin sensitivity (M) assessed by euglycemic–hyperinsulinemic clamp and free T by equilibrium dialysis. Result(s) In those randomized to metformin, free T decreased by 19% compared with placebo, along with an expected improvement in M. Total T also decreased significantly, whereas sex hormone-binding globulin (SHBG) did not change. In those randomized to LA, the percent change in M was not different from placebo, despite a 48% relative decrease in free T levels. Conclusion(s) These data are the first to establish a causal link between insulin resistance and T in postmenopausal women. They confirm that treatment of insulin resistance decreases T production in this population and demonstrate that pharmacologic lowering of T does not affect insulin resistance.

Fatty acid-binding proteins (FABPs) 4 and 5 play coordinated roles in rodent models of inflammation, insulin resistance, and atherosclerosis, but little is known of their role in human disease. The aim of this study was to examine the hypothesis that plasma adipocyte and macrophage FABP4 and FABP5 levels would provide additive value in the association with metabolic and inflammatory risk factors for cardiovascular disease as well as subclinical atherosclerosis. Using the Penn Diabetes Heart Study (PDHS; n = 806), cross-sectional analysis of FABP4 and FABP5 levels with metabolic and inflammatory parameters and with coronary artery calcium, a measure of subclinical coronary atherosclerosis, was performed. FABP4 and FABP5 levels had strong independent associations with the metabolic syndrome (for a 1-SD change in FABP levels, odds ratio [OR] 1.85, 95% confidence interval [CI] 1.43 to 2.23, and OR 1.66, 95% CI 1.41 to 1.95, respectively) but had differential associations with metabolic syndrome components. FABP4 and FABP5 were also independently associated with C-reactive protein and interleukin-6 levels. FABP4 (OR 1.26, 95% CI 1.05 to 1.52) but not FABP5 (OR 1.13, 95% CI 0.97 to 1.32) was associated with the presence of coronary artery calcium. An integrated score combining FABP4 and FABP5 quartile data had even stronger associations with the metabolic syndrome, C-reactive protein, interleukin-6, and coronary artery calcium compared to either FABP alone. In conclusion, this study provides evidence for an additive relation of FABP4 and FABP5 with the metabolic syndrome, inflammatory cardiovascular disease risk factors, and coronary atherosclerosis in type 2 diabetes mellitus. These findings suggest that FABP4 and FABP5 may represent mediators of and biomarkers for metabolic and cardiovascular disease in type 2 diabetes mellitus.

To review the association of the tyrosine kinase inhibitor sunitinib with hypothyroidism as well as the mean time to onset, possible mechanisms, reversibility, and mean duration.We performed a MEDLINE search of the English-language literature using a combination of words ("sunitinib," "tyrosine kinase inhibitors," "thyroid," and "hypothyroidism") to identify original studies and reviews on sunitinib and thyroid function.Hypothyroidism was reported in 36% to 46% of patients who took sunitinib in prospective studies. A higher incidence (53% to 85%) was reported in studies containing both retrospective and prospective data. The mean time to onset of hypothyroidism after initiation of sunitinib therapy ranged from 12 to 50 weeks. The risk of development of hypothyroidism appears to increase with the increasing duration of sunitinib therapy, and the condition is likely reversible once therapy has been discontinued.Baseline thyroid function tests should be performed before the initiation of sunitinib treatment. Because hypothyroidism can develop early in the course of therapy, thyroid function tests should be monitored frequently throughout the duration of treatment. Possible mechanisms for thyroid dysfunction include impaired thyroid hormone synthesis, a destructive thyroiditis preceding the development of hypothyroidism, and increased thyroid hormone clearance. If hypothyroidism is identified, levothyroxine therapy should be promptly initiated.

To compare the lipid-lowering effects of an alternative regimen (lifestyle changes, red yeast rice, and fish oil) with a standard dose of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin).This randomized trial enrolled 74 patients with hypercholesterolemia who met Adult Treatment Panel III criteria for primary prevention using statin therapy. All participants were randomized to an alternative treatment group (AG) or to receive simvastatin (40 mg/d) in this open-label trial conducted between April 1, 2006, and June 30, 2006. The alternative treatment included therapeutic lifestyle changes, ingestion of red yeast rice, and fish oil supplements for 12 weeks. The simvastatin group received medication and traditional counseling. The primary outcome measure was the percentage change in low-density lipoprotein cholesterol (LDL-C). Secondary measures were changes in other lipoproteins and weight loss.There was a statistically significant reduction in LDL-C levels in both the AG (-42.4%+/-15%) (P.001) and the simvastatin group (-39.6%+/-20%) (P.001). No significant differences were noted between groups. The AG also demonstrated significant reductions in triglycerides (-29% vs -9.3%; 95% confidence interval, -61 to -11.7; P=.003) and weight (-5.5% vs -0.4%; 95% confidence interval, -5.5 to -3.4; P.001) compared with the simvastatin group.Lifestyle changes combined with ingestion of red yeast rice and fish oil reduced LDL-C in proportions similar to standard therapy with simvastatin. Pending confirmation in larger trials, this multifactorial, alternative approach to lipid lowering has promise for a subset of patients unwilling or unable to take statins.

Type 2 diabetes mellitus (DM) is associated with increased cardiovascular risk, in part due to accelerated subclinical atherosclerosis. Electrocardiographic (ECG) and ankle–brachial index (ABI) abnormalities are used to screen for cardiovascular risk in the clinic. However, their capacity to identify patients with type 2 DM with nonobstructive subclinical atherosclerosis is unknown. Associations of ECG and ABI abnormalities with coronary artery calcium (CAC), a measure of coronary atherosclerosis, were examined using multivariable ordinal regression modeling in 589 asymptomatic patients with type 2 DM. Sensitivity, specificity, and positive and negative predictive values were determined. CAC was prevalent (44% CAC >100; 32% CAC >75th percentile score) despite normal electrocardiograms (64%) and ABIs (97%) in most subjects. Neither ECG nor ABI changes predicted CAC after adjusting for age, gender, and race. ECG abnormalities were neither sensitive nor specific for detection of CAC >100, >400, or >75th percentile (sensitivities 0.43, 0.45, and 0.34; specificities 0.69, 0.66, and 0.63, respectively). ABI abnormalities were not sensitive (0.03, 0.04, and 0.03) but had high specificity (0.98, 0.98, and 0.98). In subjects with normal electrocardiograms and ABIs, extensive CAC was remarkably prevalent (CAC >100 in 24%). In conclusion, ECG and ABI abnormalities failed to detect patients with subclinical coronary atherosclerosis and therefore may be of limited value in identifying many asymptomatic patients with type 2 DM at increased risk of cardiovascular disease.

Background Effective clinical weight management approaches are needed to reach African-Americans. Methods African-Americans recruited through outpatient practices for a culturally-adapted Healthy Eating and Lifestyle Program were offered 10 weekly weight loss classes (Phase 1) with the option of continuing for another 8–18 months (Phase 2) in a randomized comparison of further group counseling or staff-facilitated self-help vs. follow-up clinic visits only. Results. Of 237 enrollees (91% women; mean age 43.5 years; mean body mass index 38.0 kg/m 2 ), 167 attended no classes or only the first Phase 1 class, 134 provided Phase 1 follow-up data, 128 were randomized in Phase 2, and 87 provided final follow-up data (“completers”). Mean weight changes for completers were: −1.5 ( P P = 0.47), and −1.2 ( P = 0.04) kg, respectively, for Phase 1, Phase 2, and overall (baseline to final visit; average 18 months total duration), with no Phase 2 treatment effect ( P = 0.55). Final study weight was ≥5% below baseline for 25% of completers and was strongly predicted by Phase 1 weight loss. Conclusions Weight loss achieved in Phase 1 was maintained even with relatively minimal follow-up contact. Increasing the percent who achieve clinically significant weight loss initially would improve long-term results.

To assess whether shortening of the corrected QT (QTc) interval is most closely associated with changes in weight, insulin resistance, or free fatty acids (FFAs) (or some combination of these factors).We randomized 75 severely obese subjects without diabetes to either a low-carbohydrate or a conventional low-fat weight-loss diet for 6 months. We measured QTc, insulin sensitivity, body mass index, and FFAs at baseline and at 6 months. Analysis was performed to determine whether improvement in weight, in insulin resistance, or in FFAs has the greatest effect on reducing the QTc interval."Completers" of both the low-carbohydrate diet (N = 25) and the low-fat diet (N = 22) had a decrease in weight, but the weight loss was greater in the low-carbohydrate group. A statistically significant decrease in QTc from baseline was observed only in the low-carbohydrate group. QTc in the low-carbohydrate group correlated with improvement in insulin resistance, but this finding was not significant after correction for the greater weight loss. FFAs or weight loss was not correlated with QTc in either dietary group.Low-carbohydrate dieting is associated with a greater decrease in the QTc interval in comparison with low-fat dieting. Improvements in insulin resistance seem to have a relatively weak mechanistic role, and a decrease in FFAs has no apparent role in the reduction of the QTc interval.

Purpose To compare the effects of a low-carbohydrate diet and a conventional (fat- and calorie-restricted) diet on lipoprotein subfractions and inflammation in severely obese subjects. Methods We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects, including 86% with either diabetes or metabolic syndrome, who were randomly assigned to either a low-carbohydrate or conventional diet for 6 months. Results Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein (VLDL) levels (difference = −0.26 mg/dL, P = 0.03) but more frequently developed detectable chylomicrons (44% vs. 22%, P = 0.04). Both diet groups experienced similar decreases in the number of low-density lipoprotein (LDL) particles (difference = −30 nmol/L, P = 0.74) and increases in large high-density lipoprotein (HDL) concentrations (difference = 0.70 mg/dL, P = 0.63). Overall, C-reactive protein levels decreased modestly in both diet groups. However, patients with a high-risk baseline level (>3 mg/dL, n=48) experienced a greater decrease in C-reactive protein levels on a low-carbohydrate diet (adjusted difference=−2.0 mg/dL, P = 0.005), independent of weight loss. Conclusion In this 6-month study involving severely obese subjects, we found an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions, and on inflammation in high-risk subjects. Both diets had similar effects on LDL and HDL subfractions.

To report a case of life-threatening hypercalcemia attributable to primary hyperparathyroidism in a pregnant patient and discuss the management of severe hypercalcemia during pregnancy.We describe a 28-year-old pregnant woman who had life-threatening hypercalcemia (serum calcium level of 25.8 mg/dL). Primary hyperparathyroidism was diagnosed. The patient's management and the published medical literature on primary hyperparathyroidism during pregnancy are reviewed.Our patient had the highest reported serum calcium level that we could find attributable to primary hyperparathyroidism during pregnancy. After initial stabilization, parathyroidectomy was successfully performed during pregnancy. To our knowledge, this is the first report in which this profound degree of hypercalcemia did not result in an adverse maternal or fetal outcome.Although uncommon, primary hyperparathyroidism during pregnancy may be associated with severe maternal and perinatal complications. Life-threatening hypercalcemia due to primary hyperparathyroidism during pregnancy can be successfully managed surgically during pregnancy, with good maternal and fetal outcome.

To report two cases of resistance to thyroid hormone and to promote increased awareness of this syndrome, which is frequently misdiagnosed and incorrectly treated.We describe a young woman and her father, both of whom were diagnosed at a younger age as having thyrotoxicosis and were treated with thyroidectomy and radioactive iodine. Both patients later proved to have resistance to thyroid hormone and required supraphysiologic doses of levothyroxine to normalize the thyroid-stimulating hormone (TSH) while remaining euthyroid.Laboratory evaluation revealed increased serum total thyroxine and triiodothyronine levels as well as normal to increased TSH levels. The free alpha sub-unit/TSH ratio was normal, and magnetic resonance imaging of the pituitary gland showed no tumor. Metabolic studies in the daughter, with use of graded doses of triiodothyronine, supported the diagnosis.Both patients shown to have resistance to thyroid hormone were misdiagnosed and inappropriately treated in the past. The resultant hypothyroidism has been difficult to treat, particularly in the father who has coronary artery disease.

Dengue is the commonest arboviral illness in the tropics and subtropics with most infections remaining mild. Bleeding complications are uncommon. Rare bleeding problems that have been reported include hematoma in the spleen, tongue and central nervous system. We report a lady with a gluteal hematoma and a gluteal abscess each, following dengue fever, thrombocytopenia, coagulopathy and intramuscular injections.

Low-carbohydrate diets are frequently used as part of weight-loss programs. These are typically associated with increased fat intake. Therefore, cholesterol absorption inhibition is a logical therapeutic strategy to lower low-density lipoprotein cholesterol (LDL-C) in subjects following a low-carbohydrate diet. However, the efficacy of cholesterol absorption inhibition added to statin therapy has not been studied in this common clinical setting.We performed a randomized controlled trial to compare the effects of ezetimibe on LDL-C when added to simvastatin among subjects following a low-carbohydrate diet. We enrolled 65 subjects who were overweight or obese (body mass index 25-45 kg/m(2)) and had a moderately elevated LDL-C (130-190 mg/dL). During a 4-week diet run-in, subjects were instructed to restrict carbohydrate intake to30 g/day. Subjects demonstrating adequate adherence to a low-carbohydrate diet (n = 58) were randomized to simvastatin (20 mg) or simvastatin (20 mg) plus ezetimibe (10 mg) for 8 weeks.Body weight decreased by 3.1% (95% CI 2.1%-4.0%, P.0001), but the magnitude of weight change did not differ between the groups (P = .92). The LDL-C decreased by 32 mg/dL (95% CI 21-42 mg/dL) in the simvastatin arm and 60 mg/dL (95% CI 45-75 mg/dL) in the combined simvastatin-ezetimibe arm (P = .002). This corresponded to a 20.9% reduction (95% CI 14.5%-27.4%) in LDL-C on simvastatin alone, compared with a 37.4% reduction (95% CI 29.3%-45.6%) on simvastatin-ezetimibe (P = .002). A significant 15.8% reduction in triglycerides was observed among enrolled subjects, which did not differ between the groups.Among subjects following a low-carbohydrate diet, combined statin and cholesterol absorption inhibitor therapy is more effective than statin monotherapy for LDL-C lowering.

a Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA b Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA c Department of Family Practice and Community Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA

Objetivo Comparar la eficacia al ano de una dieta baja en hidratos de carbonos y una dieta hipocalorica convencional de adelgazamiento. Diseno Ensayo clinico aleatorizado con evaluacion a los 6 meses (publicado previamente) y al ano. Emplazamiento Consultas externas de un centro medico en Filadelfia (Estados Unidos). Poblacion de estudio Ciento treinta y dos obesos ambos sexos (un 80% varones) mayores de 18 anos (edad media, 55 ± 9 anos), con un indice de masa corporal (IMC) ≥ 35 kg/m 2 (media, 44 ± 7 k/m 2 ), un 55% de ellos afroamericanos. Criterios de exclusion: enfermedad hepatica, medicacion o programa para adelgazar, creatinina > 1,5 mg/dl, enfermedad invalidante o incapacidad para automedicion de glucosa capilar. El 83% presentaba sindrome metabolico o diabetes mellitus; el 49%, hiperlipemia; el 16%, enfermedad coronaria, y el 60-75%, HTA. Intervencion Sesenta y cuatro pacientes recibieron consejo para restringir su ingesta de hidratos de carbono a menos de 30 g/dia (dieta baja en hidratos de carbono) y 68 para reducir en 500 kcal su ingesta diaria con Medicion del resultado Cambios de peso, valor de lipidos, glucemia, sensibilidad a la insulina y presion arterial. Se realizaron calculos con los casos que completaron el estudio (variables metabolicas) y con todos. Resultados principales Al ano de tratamiento, la disminucion de peso fue de 5,1 ± 8,7 kg en el grupo bajo en hidratos de carbono y de 3,1 ± 8,4 kg en el de dieta convencional, pero sin diferencias entre los grupos (p = 0,2). La ingesta calorica en la dieta convencional disminuyo en 97 ± 1.067 kcal/dia (de 1.919 a 1.822 kcal/dia) y la baja en hidratos de carbono disminuyo en 510 ± 1.187 kcal/dia (de 1.972 a 1.462 kcal/dia); las calorias ingeridas fueron similares en ambos casos. La ingesta de proteinas no difirio entre grupos. Con la dieta baja en hidratos de carbono los trigliceridos disminuyeron mas (55 mg/dl) y el colesterol ligado a lipoproteinas de alta densidad (cHDL) menos (3 mg/dl) que con la dieta convencional. Entre los diabeticos (n = 54), la hemoglobina glucosilada (HbA1c) bajo mas con la dieta baja en hidratos de carbono (el –0,7 frente al 0,1%). El colesterol total y el colesterol ligado a lipoproteinas de baja densidad (cLDL), la creatinina, la presion arterial y la sensibilidad a la insulina no variaron significativamente en ningun grupo. Conclusion Al ano de seguimiento, la disminucion de peso de la dieta baja en hidratos de carbono no difiere de la dieta convencional, pero los efectos sobre los trigliceridos, el cHDL y el control metabolico de la diabetes es mas favorable.

Nephrolithiasis secondary to primary hyperparathyroidism infrequently complicates pregnancy. It can cause severe maternal and fetal complications. We present a case of a pregnant woman with nephrolithiasis and primary hyperparathyroidism. We reviewed the management of nephrolithiasis due to primary hyperparathyroidism during pregnancy. We believe that early recognition and timely intervention can significantly reduce the incidence of complications.