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Look AHEAD (Action for Health in Diabetes) was a randomized clinical trial designed to examine the long-term health effects of weight loss in overweight and obese individuals with type 2 diabetes. The primary result was that the incidence of cardiovascular events over a median follow-up of 9.6 years was not reduced in the Intensive Lifestyle Group relative to the control group. This finding is discussed, with emphasis on its implications for design of trials and clinical treatment of obese persons with type 2 diabetes.

This article was migrated. The article was not marked as recommended. Introduction: Although evidence based medicine (EBM) is part of undergraduate training in several countries, Indian medical schools are yet to make a meaningful start. We report our experience with EBM training for undergraduate. Methods: Third year students undergoing clinical clerkship at a teaching hospital underwent an 8 week course on EBM with modules on concepts, formulating questions, searching for evidence and critical appraisal. Feedback was taken and assessment done on knowledge and searching skills. Results: 90% of students had poor awareness of EBM. 92% considered evidence the most important component of EBM; 5% considered clinical expertise and patient values as part of EBM. At baseline majority cited Google the most reliable search tool. Only 27% felt EBM relevant to their curriculum. 66% rated the course good, very good or excellent. Hands-on training enhanced learning lack of background knowledge of diseases hindered it. Conclusion: Awareness of EBM is low among undergraduates and most find it irrelevant to their curriculum. Our experience suggests that it is feasible to integrate EBM training into undergraduate curriculum. More studies reporting knowledge and skills before and after EBM courses would strengthen the cause for making it part of undergraduate medical curriculum in India.

We report a 49-year-old diabetic with dengue hemorrhagic fever who developed fulminant hepatitis, severe coagulopathy, shock, and refractory metabolic acidosis and died on the eighth day of illness. This is the only second report of an adult with fatal fulminant hepatic failure due to dengue, and the first case arising from a primary dengue infection.

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.

We have quantitatively determined gluconeogenesis (GNG) from all precursors, using a novel method employing 2H20 to address the question of whether changes in plasma free fatty acids (FFA) affect GNG in healthy, nonobese subjects. In the first study (n = 6), plasma FFA were lowered at 16 to 20 hours with nicotinic acid (NA) and were then allowed to rise at 20 to 24 hours (FFA rebound after administration of NA). FFA decreased from 387 μM at 16 hours to 43 μM at 20 hours, and then rebounded to 1,823 μM at 24 hours. GNG decreased from 58.1% at 16 hours to 38.6% of endogenous glucose production at 20 hours (P < 0.005) and then rebounded to 78.9% at 24 hours (P < 0.05). Conversely, glycogenolysis (GL) increased from 41.9% at 16 hours to 61.4% at 20 hours (P < 0.05), and then decreased to 21.1% at 24 hours (P < 0.05). In the second study (controls; n = 6), volunteers were analyzed between 16 and 24 hours after the last meal. FFA rose from 423 to 681 μM (P < 0.05), and GNG from 50.3% to 61.7% (P < 0.02), whereas GL decreased from 49.7% to 38.3% (P < 0.05). Endogenous glucose production decreased at the same rate in both studies, from 10.7 to 8.6 μmol/kg/min (P < 0.05). In study 3 (n = 6), in which the NA-mediated decrease of plasma FFA was prevented by infusion of lipid and heparin, neither FFA nor GNG changed significantly. In summary, our data suggest that (a) acute changes in plasma FFA produce acute changes in GNG and reciprocal changes in GL; (b) the decrease in EGP between 16 and 24 hours of fasting is due to a fall in GL; and (c) NA has no direct effect on GNG.

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.

ObjectiveDapagliflozin is a highly selective, orally active inhibitor of renal sodium-glucose cotransporter 2 that reduces hyperglycemia by increasing urinary glucose excretion. The goal of this study was to evaluate dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes whose disease was inadequately controlled with diet and exercise.MethodsIn this Phase III, multicenter, parallel-group, double-blind study, drug-naive patients with glycosylated hemoglobin (HbA1c) levels ≥7.0% to ≤10.5% (≥53–≤91 mmol/mol) were randomized (by using an interactive voice response system) to receive placebo (n = 132), dapagliflozin 5 mg (n = 128), or dapagliflozin 10 mg (n = 133). The primary end point was mean change from baseline in HbA1c level at week 24 (last-observation-carried-forward). Secondary end points included changes in fasting plasma glucose, 2-hour postprandial glucose, body weight, and other glycemic parameters.ResultsBaseline characteristics were balanced across groups. Most patients (89%) were Chinese, median disease duration was 0.2 year, and mean HbA1c level was 8.26%. Most patients (87%) completed the study. At week 24, mean reductions in HbA1c were −0.29% for placebo versus −1.04% and −1.11% for dapagliflozin 5 and 10 mg, respectively (P < 0.0001 for both doses). Changes in fasting plasma glucose were 2.5, −25.1, and –31.6 mg/dL (0.14, −1.39, and −1.75 mmol/L) for placebo, dapagliflozin 5 mg, and dapagliflozin 10 mg. Changes in 2-hour postprandial glucose were 1.1, −46.8, and −54.9 mg/dL (0.06, −2.60, and −3.05 mmol/L). Reductions in body weight were −0.27, −1.64, and −2.25 kg. Proportions of patients achieving HbA1c levels

A post hoc pooled analysis was undertaken to evaluate the safety of saxagliptin in patients with type 2 diabetes mellitus, with attention to events of special interest for dipeptidyl peptidase-4 inhibitors.Pooled analyses were performed for 20 randomized controlled studies (N = 9156) of saxagliptin as monotherapy or add-on therapy, and a subset of 11 saxagliptin + metformin studies. Adverse events and events of special interest (gastrointestinal adverse events, infections, hypersensitivity, pancreatitis, skin lesions, lymphopenia, thrombocytopenia, hypoglycaemia, bone fracture, severe cutaneous adverse reactions, opportunistic infection, angioedema, malignancy, worsening renal function, and specific laboratory events) were assessed; incidence rates (events/100 person-years) and incidence rates ratios (saxagliptin/control) were calculated (Mantel-Haenszel method).In both pooled datasets, the incidence rates for deaths, serious adverse events, discontinuations due to adverse events, pancreatitis, malignancy, and most other events of special interest, excepting bone fractures and hypersensitivity, were similar between treatments, with 95% confidence intervals (CIs) for incidence rates ratios including 1. In the 20-study pool, the incidence rates per 100 person-years was higher with saxagliptin versus control for bone fractures [1.1 vs 0.6; incidence rates ratio (95% CI), 1.81 (1.04-3.28)] and hypersensitivity adverse events [1.3 vs 0.8; 1.67 (1.01-2.87)].Pooled data from 20 studies confirm that saxagliptin has a favourable safety and benefit-risk profile.

Background Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population. Methods This was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (≥1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight. Results A total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P

Background Concurrent infection with multiple pathogens is common in tropics, posing diagnostic and treatment challenges. Although co-infections of dengue, malaria, leptospirosis and typhoid in various combinations have been described, data on dengue and scrub typhus co-infection is distinctly limited. Methodology This was a retrospective analysis of dengue and scrub typhus co-infection diagnosed between January 2010 and July 2014 at a tertiary care center. Clinical and laboratory features of these cases were compared with age and gender matched patients with isolated dengue fever and isolated scrub typhus. Positive test for dengue non-structural 1 (NS1) antigen was considered diagnostic of dengue whereas scrub typhus was diagnosed by IgM scrub antibodies demonstrated by ELISA. Results There were 6 cases of dengue-scrub co-infection during the review period which fitted clinical and laboratory profile with a mean age of 42.5 years. Fever, headache and arthralgia were common. Normal haemoglobin, significant thrombocytopenia, transaminitis and hypoalbuminemia were identified in these patients. Compared to patients with isolated dengue, those with co-infection had higher pulse rate, lower systolic blood pressure, normal leucocyte counts, higher levels of liver enzymes, greater prolongation of partial thromboplastin time (aPTT) and lower serum albumin. Co-infection was characterized by a lower nadir platelet count compared to scrub typhus, and lesser time to nadir platelet count and longer duration of hospital stay compared to either isolated dengue or scrub typhus. Conclusion Dengue-scrub typhus co-infection may be under-diagnosed in tropics, particularly confounded during dengue epidemics. Normal leucocyte counts, early drop in platelets and hypoalbuminemia in dengue patients could be clues to concurrent scrub typhus infection. Prompt recognition and treatment of scrub typhus in such cases may reduce unnecessary hospital stay and cost.

Scrub typhus is one of the most common causes of acute febrile illness in South India. The clinical features vary from mild illness to severe complications such as gastrointestinal bleed, acute respiratory distress syndrome, meningoencephalitis, and acute kidney injury. The pathological findings are characterized by vasculitis of small vessels of the involved organs. We report probably the first case of scrub typhus-related hemothorax in a 72-year-old diabetic male who presented with acute febrile illness with shortness of breath and acute kidney injury. The patient improved with azithromycin and hemodialysis.

We describe a 32-year-old lady who was admitted with a urinary tract infection following vacuum-assisted delivery. She was diagnosed with Enterococcus faecium related emphysematous cystitis, bladder gangrene and rupture necessitating emergency laparotomy and partial cystectomy. She had a repeat laparotomy nine days later due to continuing bladder necrosis on cystoscopy. The patient stayed in hospital for over two months due to complications including hospital acquired Klebsiella pneumonia, adult respiratory distress syndrome and malnutrition. Discharge occurred one week after an ileal conduit and ileostomy were performed.

We describe a 32-year-old lady who was admitted with a urinary tract infection following vacuum-assisted delivery. She was diagnosed with Enterococcus faecium related emphysematous cystitis, bladder gangrene and rupture necessitating emergency laparotomy and partial cystectomy. She had a repeat laparotomy nine days later due to continuing bladder necrosis on cystoscopy. The patient stayed in hospital for over two months due to complications including hospital acquired Klebsiella pneumonia, adult respiratory distress syndrome and malnutrition. Discharge occurred one week after an ileal conduit and ileostomy were performed.

The association of plasma adipokines beyond waist circumference (WC) with coronary artery calcification (CAC), a measure of subclinical atherosclerosis, is unknown.Asymptomatic Caucasian individuals from two community-based cross-sectional studies (n = 1,285) were examined and multivariate analysis of traditional risk factors was performed, then WC and adipokines (adiponectin and leptin) were added. Incremental value of each was tested with likelihood ratio testing.Beyond traditional risk factors, WC (Tobit regression ratio 1.69, P0.001) and plasma leptin (1.57, P0.001) but not plasma adiponectin (P = 0.75) were independently associated with CAC. In nested models, neither adiponectin (χ(2) = 0.76, P = 0.38) nor leptin (χ(2) = 1.32, P = 0.25) added value to WC beyond traditional risk factors, whereas WC added incremental value to adiponectin (χ(2) = 28.02, P0.0001) and leptin (χ(2) = 13.58, P = 0.0002).In the face of important biomarkers such as plasma adiponectin and leptin, WC remained a significant predictor of CAC beyond traditional risk factors underscoring the importance of WC measurement during cardiovascular risk assessment.

Plasma C-reactive protein (CRP) is associated with cardiovascular disease (CVD), but effects may vary by gender and degree of CVD risk. Whether CRP has value as a CVD risk marker in type-2 diabetes (T2DM) is unclear. We examined whether CRP has gender differences in association with coronary artery calcium (CAC) in diabetic and nondiabetic samples without clinical CVD.We performed cross-sectional analyses of gender influence on CRP association with CAC in the Penn Diabetes Heart Study (N = 1299 with T2DM), the Study of Inherited Risk of Coronary Atherosclerosis (N = 860 nondiabetic subjects) and a combined sample.Female gender was associated with higher plasma CRP in diabetic and nondiabetic samples after adjustment for covariates. There was a strong interaction by gender in the association of CRP with CAC (interaction P0·001). In diabetic women, CRP was associated with higher CAC even after further adjustment for age, race, medications, metabolic syndrome, Framingham risk score and body mass index [Tobit ratio 1·60, 95% CI (1·03-2·47)]. Although this relationship was attenuated in nondiabetic women, the combined sample maintained this association in fully adjusted models [1·44, 95% CI (1·13-1·83)]. There was no association of CRP with CAC in either diabetic or nondiabetic men.CRP may be a useful marker of cardiovascular risk in women, particularly in diabetic women who otherwise have no known CVD. Prospective studies are needed to better assess the gender differences in CRP utility and the use of CRP in T2DM.

Metabolic syndrome (MS) definitions predict cardiovascular events beyond traditional risk factors in patients with type 2 diabetes mellitus (DM) as well as subjects without DM. It has been shown that apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol are associated with coronary artery calcification in DM. However, the relative value of MS, apoB lipoproteins, and estimates of insulin resistance is unknown in predicting atherosclerosis in DM. Cross-sectional analyses of white subjects in 2 community-based studies were performed (n = 611 patients with DM, n = 803 subjects without DM) using multivariate analysis of traditional risk factors and then adding MS, apoB, and homeostasis model assessment of insulin resistance (HOMA-IR). Incremental value was tested using likelihood ratio testing. Beyond traditional risk, HOMA-IR (tobit regression ratio 1.86, p = 0.002), apoB (tobit regression ratio 1.55, p = 0.001), and MS (tobit regression ratio 2.37, p = 0.007) were independently associated with coronary artery calcification in DM. In nested models, HOMA-IR added value to apoB (tobit regression ratio 1.72, p = 0.008), MS (tobit regression ratio 1.72, p = 0.011), and apoB and MS (tobit regression ratio 1.64, p = 0.021). ApoB showed a similar pattern when added to HOMA-IR (tobit regression ratio 1.51, p = 0.004), MS (tobit regression ratio 1.46, p = 0.005), and HOMA-IR and MS (tobit regression ratio 1.48, p = 0.006). MS added to apoB (tobit regression ratio 1.99, p = 0.032) but not HOMA-IR (tobit regression ratio 1.54, p = 0.221) or apoB and HOMA-IR (tobit regression ratio 1.32, p = 0.434). In conclusion, insulin resistance estimates add value to MS and apoB in predicting coronary artery calcification scores in DM and warrant further evaluation in clinic for identification of patients with DM at higher risk for atherosclerotic cardiovascular disease.

High-density lipoprotein (HDL) cholesterol and its apolipoproteins each capture unique lipid and cardiometabolic information important to risk quantification. It was hypothesized that metabolic factors, including insulin resistance and type 2 diabetes, would confound the association of HDL cholesterol with coronary artery calcification (CAC) and that apolipoprotein A-I (apoA-I) and/or apolipoprotein A-II (apoA-II) would add to HDL cholesterol in predicting CAC. Two community-based cross-sectional studies of white subjects were analyzed: the Penn Diabetes Heart Study (PDHS; n = 611 subjects with type 2 diabetes, 71.4% men) and the Study of Inherited Risk of Coronary Atherosclerosis (SIRCA; n = 803 subjects without diabetes, 52.8% men) using multivariable analysis of apoA-I, apoA-II, and HDL cholesterol stratified by diabetes status. HDL cholesterol was inversely associated with CAC after adjusting for age and gender in whites with type 2 diabetes (tobit ratio for a 1-SD increase in HDL cholesterol 0.58, 95% confidence interval [CI] 0.44 to 0.77, p

Coronary artery calcification (CAC) is a strong predictor of atherosclerotic cardiovascular disease (CVD). Whites appear to have a higher prevalence of CAC than African-Americans (AAs), but it is unknown if type 2 diabetes, a major cardiovascular risk factor, attenuates this difference. We investigated the relationship of race and CAC in a sample of patients with type 2 diabetes without clinical CVD.multivariable analyses of self-reported ethnicity and CAC scores, stratified by gender, in 861 subjects [32% AA, 66.9% male] with type 2 diabetes.AA race was associated with lower CAC scores in age-adjusted models in males [Tobit ratio for AAs vs. Whites 0.14 (95% CI 0.08-0.24, p0.001)] and females [Tobit ratio 0.26 (95% CI 0.09-0.77, p=0.015)]. This persisted in men after adjustment for traditional, metabolic and inflammatory risk factors, but adjustment for plasma triglycerides [0.48 (95% CI 0.15-1.49, p=0.201)] and HOMA-IR [0.28 (95% CI 0.08-1.03, p=0.055)] partially attenuated the association in women.relative to African-Americans, White race is a strong predictor of CAC, even in the presence of type 2 diabetes. The relationship in women appears less robust possibly due to gender differences in metabolic risk factors.

Low-carbohydrate diets have been associated with significant reductions in weight and HbA(1c) in obese, diabetic participants who received high-intensity lifestyle modification for 6 or 12 months. This investigation sought to determine whether comparable results to those of short-term, intensive interventions could be achieved over a 24-month study period using a low-intensity intervention that approximates what is feasible in outpatient practice. A total of 144 obese, diabetic participants were randomly assigned to a low-carbohydrate diet (

Bariatric surgery leads to substantial and durable weight reduction. Nearly 30% of patients who undergo bariatric surgery have type 2 diabetes, and for many of them, diabetes resolves after surgery (84% to 98% for bypass procedures and 48% to 68% for restrictive procedures). Glycemic control improves in part because of caloric restriction but also because gut peptide secretion changes. Gut peptides, which mediate the enteroinsular axis, include the incretins glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, as well as ghrelin and peptide YY. Bariatric surgery (particularly bypass procedures) alters secretion of these gut hormones, which results in enhanced insulin secretion and sensitivity. This review discusses the various bariatric procedures and how they alter the enteroinsular axis. Familiarity with these effects can help physicians decide among the different surgical procedures and avoid postoperative hypoglycemia.

Objective To determine the prevalence and correlates of low bone mineral density (BMD) in ambulatory outpatients with end-stage heart failure who were awaiting cardiac transplantation. Methods Fifty-five cardiac transplant candidates with end-stage heart failure were enrolled in this study. Bone mineral density at the lumbar spine and proximal femur was determined by dual-energy x-ray absorptiometry. Laboratory studies included serum alkaline phosphatase, calcium, intact parathyroid hormone, and 25-hydroxyvitamin D. Results The mean proximal femur and lumbar spine Z scores were 0.3 ± 1.1 and 0.3 ± 1.5, respectively. The mean BMD was not lower than that of the age- and sex- matched reference population. Z scores were less than -1 in 23% at the lumbar spine and 15% at the proximal femoral neck. On the basis of T scores, osteopenia (T scores between -1 and -2.5) was present in 24% (confidence interval, 13% to 35%) of patients at the lumbar spine and in 20% (confidence interval, 10% to 30%) at the proximal femur; osteoporosis (T scores of less than -2.5) was present in 4% of the study population. Half of the patients in this study sample had elevated intact parathyroid hormone levels, and a third of the patients had low 25-hydroxyvitamin D levels. Conclusion Lumbar spine and hip BMD measurements were not significantly low relative to age and sex in ambulatory patients with heart failure awaiting cardiac transplantation. (Endocr Pract. 2008;14:704-712)

Background & Aims: The impact of capsule endoscopy (CE) findings on patient management is unknown. We assessed the impact of CE findings on patient management, and whether physicians use these to alter management plans. Methods: Physicians requesting CE were contacted before the examination and asked what their management recommendations would be if CE were not available. These responses were compared with management recommendations by the same requesting physician after the CE. The responses were recorded on a data form. The physicians reading the CE were blinded to the pre-CE responses. The end points assessed were change in overall management and specific change in diagnostic and treatment strategy. Results: Responses were obtained from physicians before and after CE in 98 patients. Requesting physicians (n = 40) were composed of gastroenterologists (92%), internists (3%), and other specialties (5%). Physicians changed post-CE overall management plans in 67% of patients. Of these physicians, 74% did so as a result of CE findings (P = .001). Specifically, physicians changed post-CE diagnostic strategy in 61% of patients; the diagnostic strategy was changed to less complex or decreased risk associated in 43% of patients. Of those requesting physicians who changed their diagnostic strategy, 75% did so as a result of CE (P = .004). When treatment strategy was evaluated before and after CE, there was a change in 31% of patients. Conclusions: Physicians requesting CE alter management in the majority of patients on the basis of CE findings. Diagnostic strategy is changed in the majority of patients, and often a less complex approach is pursued.

Objectives: Adipocyte-fatty acid binding protein (aP2) or FABP4 is expressed predominantly in adipose and macrophages. Its less abundant family member, FABP5 (Mal1), is more diffusely expressed but also found in adipocytes and macrophages. Gene deletion studies in rodents suggest that FABP4, to a greater extent than FABP5, modulates obesity and atherosclerosis. Preliminary clinical studies support a relationship of circulating FABP4 with obesity and the metabolic syndrome (MetSyn). However, there are no studies of circulating FABPs and atherosclerosis in humans. Methods: We evaluated the association of FABP4 and 5 (ELISA, Biovender) with cardiovascular risk factors, NCEP-defined MetSyn and Coronary Artery Calcification (CAC) in 846 asymptomatic, type 2 DM subjects (62.5% Caucasian, 32.5% African-American; 60% male; aged 58.6±9.2) recruited to the Penn Diabetes Heart Study. Findings : Levels [(median (IQ range)] of FABP4 [37.1 (23.0–55.2) vs 20.9 (14.0–31.0) ng/mL; p2 =29.8, p2 =36.2, p Conclusion: Both FABP 4 and 5 are biomarkers of adiposity and MetSyn. In the first study of its kind, plasma FABP4, but not FABP5, was associated with CAC in type 2 DM, but neither were independent predictors of this subclinical atherosclerosis measure.

Leptospirosis and tuberculosis (TB) are widely prevalent in the tropics, with the former presenting acutely ranging from a flu-like illness to severe hepatorenal dysfunction (Weil's disease) and hemorrhage. TB is a smoldering illness, which rarely presents acutely as community-acquired pneumonia or acute lung injury. We present a 35-year-old farmer who had acute onset breathlessness and oliguria following a short febrile illness, which required mechanical ventilation and renal replacement therapy. His diagnostic workup revealed concomitant pulmonary TB and anicteric leptospirosis which improved with appropriate antibiotics and supportive care.

Obesity in the past was only seen in great numbers in Western countries but is now gaining prevalence in India with a growing Indian economy. Historically a favourable phenotype, obesity has been associated with multiple diseases affecting almost all organ systems. In addition, the cost of obesity to a health care system is enormous. Weight loss improves many of the outcomes and yet is a difficult process for most patients with even the medical community baffled about methods for weight loss. Our group and others have looked at weight loss in obese individuals using a low carbohydrate diet and have shown some success at six months and one year. Many studies have also shown a decrease in insulin resistance and improvement in lipid profiles when obese individuals are placed on a low carbohydrate diet. The reason for weight loss on this diet was initially thought to be diuresis from increased ketone production but it may be due to decreased insulin concentrations causing a decrease in appetite. In addition, lowering carbohydrates limits food choice and in the process decreases overall calorie consumption. In the United States, an increase in calories, predominantly from carbohydrates, appears to parallel the obesity epidemic. However, it is not known if guidelines or policies lowering carbohydrates in normal or slightly overweight individuals may help prevent obesity and its complications. Equally less known, is the applicability of a low carbohydrate diet to populations like India where many main dishes are carbohydrate-based.

Objective To describe a case of diabetic muscle infarction affecting an upper extremity in a patient with long-term poorly controlled diabetes. Methods A case report of a patient with diabetes who presented with pain and swelling of his left arm is described, including clinical, laboratory, and radiologic findings. The results of pathologic examination are also illustrated. Moreover, we review the literature in a discussion of the evaluation, pathogenesis, and treatment of diabetic muscle infarction. Results A 41-year-old man with type 1 diabetes presented with a 1-week history of painful swelling of the left forearm. The leukocyte count and creatine kinase levels were normal. Magnetic resonance imaging of the left forearm revealed extensive deep tissue edema and an increase in T2 signal in the involved muscles. The patient was initially treated for cellulitis with intravenously administered antibiotics for 3 weeks without improvement. Muscle biopsy revealed skeletal muscle with prominent muscle fiber degeneration, myophagocytosis, and fibrosis, consistent with the diagnosis of diabetic muscle infarction. Once this diagnosis was made, antibiotic therapy was discontinued, and the condition was managed with narcotics and aggressive insulin therapy. Eight weeks after initial presentation, the patient reported complete resolution of symptoms. Conclusion Diabetic muscle infarction is a rare but underrecognized complication of diabetes. To our knowledge, we present only the second such reported case of upper extremity involvement in the literature. The results of pathologic examination interpreted in the context of the patient’s clinical history were consistent with the diagnosis. (Endocr Pract. 2006;12:188-192)

Background— PPAR-γ agonists improve insulin sensitivity and glycemic control in type 2 diabetes and may reduce atherosclerosis progression. Thus, PPAR-γ agonists may be an effective therapy for metabolic syndrome. However, the full spectrum of potentially antiatherogenic mechanisms of PPAR-γ agonists have not been fully tested in nondiabetic patients with metabolic syndrome. Methods and Results— We performed a prospective, double-blinded, placebo-controlled study of 60 nondiabetic subjects with low high-density lipoprotein cholesterol (HDL-C) level and metabolic syndrome to rosiglitazone 8 mg daily or placebo for 12 weeks. We found no significant effect of rosiglitazone on HDL-C (+5.5% versus +5.8%, P =0.89), and an increase in total cholesterol (+8% versus −1%; P =0.03). Nevertheless, rosiglitazone significantly increased adiponectin (+168% versus +25%; P P =0.009), C-reactive protein (−32% versus +36%, P =0.002), interleukin (IL)-6 (−22% versus +4%, P P Conclusions— These findings suggest that rosiglitazone, presumably through its PPAR-γ agonist properties, has direct effects on inflammatory markers and adipokines in the absence of favorable lipid effects. These findings may help explain the mechanism underlying the possible antiatherosclerotic effects of rosiglitazone.

To describe a case of severe gestational hyperlipidemic pancreatitis successfully managed with minimal-lipid-containing parenteral nutrition (PN) followed by a minimal-fat diet, which resulted in delivery of a healthy full-term neonate.We present the case of a young woman with gestational hyperlipidemic pancreatitis whose management included the use of PN during pregnancy. In addition, we review the literature pertaining to the management of hyperlipidemic pancreatitis during pregnancy and discuss the role for PN.A 32-year-old gravida 2, para 1 woman at 27 weeks 3 days of gestation presented with 1 day of nausea, bilious emesis, and severe abdominal pain caused by pancreatitis attributable to hypertriglyceridemia. Her initial serum triglyceride concentration was 9,450 mg/dL. She received fluids intravenously and minimal-lipid PN until resolution of her symptoms. The serum triglyceride level remained less than 850 mg/dL during administration of PN. She subsequently tolerated a minimal-fat diet, while the serum triglyceride level was maintained at less than 1,400 mg/dL, until delivery of a full-term, healthy neonate.In severe gestational hyperlipidemic pancreatitis, PN offers a safe and flexible treatment option by providing pancreatic rest and controlling serum triglyceride concentrations while maintaining fetal and maternal nutritional support.

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.

The risk of cardiovascular disease (CVD) is two- to fourfold greater in type 2 diabetics than in non-diabetics and cannot be accounted for by traditional risk factors alone. Coronary artery calcification (CAC) at electron beam computed tomography (EBCT) is a non-invasive index of coronary atherosclerosis. We hypothesized that the presence and extent of CAC would be greater in asymptomatic type 2 diabetics than in non-diabetics independent of traditional risk factors.We reviewed CAC data of all asymptomatic subjects referred for EBCT between 1996-1999 and compared CAC scores in type 2 diabetics ( n= 71) to all non-diabetics ( n= 1481) and to a randomly selected group of non-diabetics matched for all traditional CVD risk factors ( n= 71).CAC scores were greater in type 2 diabetics (272 +/- 472, median 41) than in all non-diabetics (104 +/- 288, median 4;0.01) and matched non-diabetics (188 +/- 354;0.05, median 12;0.05). The odds ratio (OR) for the presence of CAC (scores0) in type 2 diabetics was 2.9 [95% confidence intervals (CI) 1.1-7.8] after adjustment for traditional CVD risk factors. Type 2 diabetes was also associated (adjusted OR 2.15, 95%CI 1.3-3.6) with the extent of CAC when categorized as an ordinal outcome (CAC scores 0, 1-79, 80-399 and400). In type 2 diabetics, age, sex and body mass index were associated with extent of CAC.CAC scores at EBCT are greater in type 2 diabetics than non-diabetic subjects, cannot be accounted for by traditional risk factors alone and may be useful for identifying novel factors for coronary atherosclerosis in type 2 diabetes.

Nayyar Iqbal,1 Elsie Allen,1 Peter Öhman2 1Bristol-Myers Squibb, Princeton, NJ, USA; 2AstraZeneca, Wilmington, DE, USA Background: Treatment decisions for older patients with type 2 diabetes mellitus must balance glycemic control and adverse event risk. The objective of this study was to evaluate the long-term safety and tolerability of saxagliptin 5 mg as add-on therapy to common antihyperglycemic drugs in patients aged ≥65 years and

471 Background: Currently limited biomarkers are available to monitor disease status in cancer patients. Although host factors are critical in regulating cancer, the role of immune responses in aCRC is less clear. A predominant T helper 1 (Th1) response may be more effective to contain cancer than one with a substantial Th2 component. The Th1/Th2 phenotype can be inferred from relative prevalence of IgG isotypes among anti-cancer antibodies and may provide an innovative way to assess disease activity. The study aims to develop an ELISA assay to monitor IgG1:IgG2 and its utility in predicting disease status in aCRC. Methods: A validated ELISA assay (Bertech Pharma) utilizing CRC cell lines was developed to measure IgG1 (Th2) and IgG2 (Th1) levels. A sample size of 44 (24 CRC and 20 healthy control [HC]) was estimated to achieve 80% power and α error of 0.05 assuming that the assay correctly detect CRC specific antibody in > 80% cases. The IgG1:IgG2 was compared between/within groups with HC and aCRC. Results: Samples were collected from 62/66 individuals recruited at 2:1 over 1 yr. 43 CRC patients had median age of 65 yrs (39-86) and M:F 2.3:1. 25 had >1 metastatic site, 31 underwent primary tumor resection and 37 received chemotherapy. Using standard criteria, 14/43 (33%) CRC patients had elevated 1gG1 titer compared with 2/19 (10%) HCs (p = 0.06). Mean IgG1 of CRC group was 0.18±0.05 compared with 0.15±0.01 in HC (p = 0.01). Conversely, mean IgG2 level of CRC group was 0.26±0.11 compared with 0.38±0.15 in HC (p = 0.003). Mean IgG2:IgG1 of CRC group was 1.5±0.35 compared with 2.5±0.97 in HC (p < 0.001). Among 43 CRC patients, 7/12 (58%) with disease progression (DP) had elevated IgG1 compared 7/31 (23%) with stable disease (p = 0.03). Strikingly, 9/12 (75%) patients who died had elevated IgG1 compared with 5/31 (16%) who were alive during the follow up, p = 0.001. Logistic regression revealed positive association among elevated IgG1 and DP, HR:4.8 (95% CI:1.2-19.9) and mortality, HR:15 (95% CI:3.1-78.8). Conclusions: Our results revealed that patients with aCRC have abnormal IgG1:IgG2 compared with HC and elevated IgG1 (a predominant Th2 response) levels in aCRC correlate with DP and mortality.

OBJECTIVE: To investigate the effect of thalidomide on glucose turnover (glucose production and uptake), on intracellular pathways of glucose utilization (glycogen synthesis [GS], glycolysis [GLS], carbohydrate oxidation, and nonoxidative GLS), and on free fatty acid (FFA) turnover (lipolysis, FFA oxidation, and FFA reesterification). RESEARCH DESIGN AND METHODS: A total of 6 patients with type 2 diabetes were studied with 4-h isoglycemic-hyperinsulinemic clamps (approximately 8 mmol/l and 500-600 pmol/l, respectively) before treatment (Prestudy), after 3 weeks of thalidomide (150 mg orally at bedtime), and after 3 weeks of placebo. RESULTS: Thalidomide reduced insulin-stimulated glucose uptake by 31% (from 27.7 to 19.2 pmol x kg(-1) x min(-1), P < 0.05) compared with the prestudy and by 21% (from 24.2 to 19.2 pmol x kg(-1) x min(-1), P < 0.05) compared with placebo. Thalidomide also reduced insulin-stimulated GS by 48% (from 14.1 to 8.2 micromol x kg(-1) x min(-1), P < 0.05) compared with the prestudy and by 40% (from 13.6 to 8.2 micromol x kg(-1) x min(-1), P < 0.5) compared with placebo. Thalidomide had no effect on rates of GLS, carbohydrate oxidation, nonoxidative GLS, lipolysis, FFA oxidation, and reesterification. CONCLUSIONS: We conclude that thalidomide increased insulin resistance in obese patients with type 2 diabetes by inhibiting insulin-stimulated GS and that patients taking thalidomide should be monitored for possible deterioration in their glucose tolerance.

The objective of this study was to determine whether basal plasma free fatty acid (FFA) concentrations affect basal insulin secretion rates (ISRs). Effects of FFA levels on basal ISRs were evaluated by lowering basal plasma FFA levels with nicotinic acid (NA) (100-150 mg p.o., q 30 min x 4 h) in type 2 diabetic patients and in normal volunteers. Lowering of FFAs (from approximately 600 to approximately 100 micromol/l) lowered ISRs in type 2 diabetic patients during isoglycemic clamping (from 139 to 101 pmol/min; -23%; P < 0.02) and euglycemic clamping (from 99 to 63 pmol/min; -36%; P < 0.03) and in normal subjects during euglycemic clamping (from 127 to 96 pmol/min; -25%; P < 0.03). In addition, peripheral insulin concentrations decreased by approximately 30% in diabetic and nondiabetic subjects. NA had no direct effect on ISRs; that is, NA did not change ISRs when plasma FFAs were prevented from decreasing with a lipid/heparin infusion. We concluded that 1) basal plasma FFAs exerted physiologically important, long-lasting effects supporting 25-33% of basal insulin secretion in nondiabetic and diabetic subjects; 2) basal plasma FFAs were responsible for some of the hyperinsulinemia in normoglycemic obese subjects; and 3) NA had no direct effect on insulin secretion.

Marion L Vetter1,2,3, Alisha Wade1, Leslie G Womble3, Cornelia Dalton-Bakes1, Thomas A Wadden3, Nayyar Iqbal1,21Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; 2Division of Endocrinology, Department of Medicine, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA; 3Department of Psychiatry, Center for Weight and Eating Disorders, University of Pennsylvania School of Medicine, Philadelphia, PA, USAAbstract: The effect of dietary macronutrient composition on adipokine concentrations remains unclear. Greater reductions in leptin have been reported in participants who followed low-carbohydrate versus low-fat diets, although these studies did not adjust for the important effects of weight loss on adipokines. We investigated the effect of macronutrient composition on adipokine levels in 144 obese, diabetic participants who were randomly assigned to a low-carbohydrate ( 0.05 for all variables). However, significant changes in leptin and adiponectin occurred over time (P < 0.001 and P < 0.012, respectively). Modest weight loss, rather than macronutrient composition, likely accounted for the favorable changes observed in leptin and adiponectin over time.Keywords: diet, adipokine, obesity, diabetes, carbohydrate, hormone

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

Participants on a low-carbohydrate diet had better results overall at 1 year than those on a low-fat, restricted-calorie diet. Weight loss was the same in the 2 groups, but patients on the low-carb...

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.