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Background: Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/2019-nCoV). Though many classes of drugs have been advocated/used for the treatment of this disease, vaccines are being targeted for its ultimate prevention. Indian Government has approved Covishield (ChAdOx1 nCoV19 Corona Virus Vaccine-Recombinant) for restricted use in emergency circumstances. Objective: This study is aimed at evaluating the safety profile of the Covishield vaccine among healthcare workers in a tertiary care hospital. Methods: All Adverse Drug Reactions (ADRs) reported to the ADR monitoring centre by healthcare workers who received the Covishield vaccine during the study period of 3 months were analysed on various parameters, and the assessment was done using the WHO-UMC scale. Results: During the study period, a total of 1216 beneficiaries were vaccinated with 1st dose of Covishield, and out of these, 727 beneficiaries also received 2nd dose of the vaccine. Out of the 1216 beneficiaries vaccinated, 69 ADRs were reported in 24 healthcare workers. The most common ADR reported was fever (24.64%), followed by myalgia (18.84%). No death or any serious anaphylactic reaction was observed. None of the healthcare workers experienced any adverse event during the observation period of 30 minutes. Serious reactions were reported in 4 healthcare workers as per the Pharmacovigilance Programme of India (PvPI) criteria of serious AEFI. 92% of healthcare workers recovered from ADRs during the study period. 84% of ADRs were classified as probable as per the WHO-UMC scale. Conclusion: As per the Government of India directives, all the healthcare workers in the institute were encouraged to take both doses of the Covishield vaccine. The beneficiaries were kept under observation for 30 minutes and monitored for any adverse drug reaction following vaccination. The vaccine was found to be safe with a very low incidence of ADRs.

PURPOSE This study used functional slit lamp biomicroscopy (FSLB) to quantify conjunctival microvessel parameters in individuals with and without diabetes and examined whether these metrics could be used as surrogate markers of diabetes-related complications. METHODS A cross-sectional study of 98 controls (C), 13 individuals with diabetes without complications (D-C), and 21 with diabetes and related complications (D+C), which included retinopathy, nephropathy, neuropathy, and cardiovascular-, peripheral vascular-, and cerebrovascular diseases, was performed. Bulbar conjunctival metrics (venule diameter, length, axial velocity [Va], cross-sectional velocity [Vs], flow [Q], and branching complexity) were measured using FSLB (digital camera mounted on traditional slit lamp). RESULTS The mean age was 60 ± 11 years, and demographics were similar across the groups. Va and Vs significantly differed between groups. Va was 0.51 ± 0.17 mm/s, 0.62 ± 0.17 mm/s, and 0.45 ± 0.17 mm/s in the C, D-C, and D+C groups, respectively (P = 0.025). Similarly, Vs was 0.35 ± 01.12, 0.43 ± 0.13, and 0.32 ± 0.13 mm/s in the C, D-C, and D+C groups, respectively (P = 0.031). Black individuals had increased Va, Vs, and Q compared with White individuals (P < 0.05), but differences in velocities persisted after accounting for race. Among patients with diabetes, Va and Vs correlated with number of organ systems affected (Va: ρ = -0.42, P = 0.016; Vs: ρ = -0.41, P = 0.021). Va, Vs, and Q significantly (P ≤ 0.005) discriminated between diabetic patients with and without complications (area under the receiver operating curve for Va = 0.81, Vs = 0.79, Q = 0.81). CONCLUSIONS Bulbar conjunctival blood flow metrics measured by FSLB differed between controls, diabetic patients without complications, and diabetic patients with complications. FSLB is a quick, easily accessible, and noninvasive alternative that might estimate the burden of vascular complications in diabetes.

The aim of this study was to evaluate whether preoperative diabetes management can improve glycemic control and clinical outcomes after elective surgery.There is lack of data on the importance of diabetes treatment before elective surgery. Diabetes is often ignored before surgery and aggressively treated afterwards.Patients with diabetes were identified and treated proactively before their scheduled surgeries. Data for all elective surgeries over 2 years before and 2 years after implementation of the program were collected.Out of 31,392 patients undergoing first surgery, 3909 had diabetes; 2072 before and 1835 after the program. Mean blood glucose on the day of surgery was 146.4 ± 51.9 mg/dL before and 139.9 ± 45.6 mg/dL after the program (P = 0.0028). Proportion of patients seen by the inpatient diabetes team increased. Mean blood glucose during hospital stay was 166.7 ± 42.9 mg/dL before and 158.3 ± 46.6 mg/dL after program (P0.0001). The proportion of patients with hypoglycemic episodes (50 mg/dL) was 4.93% before and 2.48% after the program (P0.0001). Length of hospital stay (LOS) decreased among patients with diabetes (4.8 ± 5.3 to 4.6 ± 4.3 days; P = 0.01) and remained unchanged among patients without diabetes (4.0 ± 4.5 and 4.1 ± 4.8, respectively; P = 0.42). Changes in intravenous antibiotic use, patients discharged to home, renal insufficiency, myocardial infarction, stroke, and in-hospital mortality were similar among diabetic and nondiabetic groups.Preoperative and inpatient diabetes management improves glycemic control on the day of surgery and postoperatively and decreases the incidence of hypoglycemia. These changes may eventually improve clinical outcomes. Although statistically significant, the decrease in LOS was of equivocal clinical significance in this study.

IntroductionDiabetes-related distress is present in a high proportion of people with type 2 diabetes mellitus. We hypothesized that complexity of the antidiabetic medication regimen is a factor that is associated with diabetes-related distress.Research design and methodsThis was a retrospective study including a group of 74 patients managed at a tertiary care center. Patients with type 1 diabetes mellitus, steroid-induced diabetes, post-transplant diabetes, and other types of diabetes were excluded. Patients were screened using the Diabetes Distress Scale-2 (DDS-2). A Diabetes Medication Complexity Scoring (DMCS) system was developed to objectively assess the diabetes medication complexity. Based on DMCS, participants were categorized into three groups: low (n=26), moderate (n=22), and high (n=26) medication complexity.ResultsComplexity groups were similar in sociodemographic characteristics, diabetes duration, body mass index, and blood pressure as well as the prevalence of hypertension, hyperlipidemia and hypoglycemic episodes. However, there were significant differences for HbA1c with higher HbA1c in the high and moderate complexity groups than in the low group (p=0.006). The microvascular complications were also more common in higher complexity groups (p=0.003). The prevalence of diabetes-related distress (DDS-2 ≥6) was 34.6% in the low, 36.4% in the moderate and 69.2% in the high complexity groups (p=0.021). There were significant differences in DDS-2 score among complexity groups (p=0.009), with higher DDS-2 score in the high complexity group compared with the moderate (p=0.008) and low complexity groups (p=0.009). The difference in DDS-2 score remained significant after adjusting for HbA1c (p=0.024) but did not reach statistical significance after controlling for both HbA1c and microvascular complications (p=0.163).ConclusionsA complex antidiabetic medication regimen may be associated with high levels of diabetes-related distress.

Aim This study was conducted to evaluate the effect of continued follow-up by a hospital diabetes team on HbA1c at 1-year after discharge. Methods Adults with HbA1c ≥8% (64 mmol/mol), undergoing an elective surgery, were treated in the perioperative period and randomized to continued care (CC) or the usual care (UC) after discharge. Patients in the CC group received weekly to monthly phone calls from a diabetes specialist nurse practitioner (NP) to review their home blood glucose values, diet, exercise, and medications. Patients in the UC group followed with their diabetes care providers. Results Out of 151 patients, 77 were randomized to the CC group and 74 to the UC group. HbA1c (%) at 1-year was 8.2 ± 1.4 in the CC group and 8.5 ± 1.5 in the UC group (p = NS). Change in HbA1c from baseline was similar between the groups; −0.7 ± 1.4 in the CC versus −0.7 ± 1.5 in the UC group (p = NS). A higher number of calls was not associated with lower HbA1c or reduction in HbA1c. There were 41 insulin-treated patients in the CC group and 53 in the UC group and among them, HbA1c reduction was 0.5 ± 1.5 and 0.6 ± 1.3 respectively (p = NS). Conclusions Optimal perioperative treatment of diabetes is associated with an improvement in HbA1c but continued follow-up by a hospital diabetes team after discharge does not have an additional impact on long-term glycemic control. ClinicalTrials.gov identifier NCT02065050.

The short-chain fatty acid propionate is a potent inhibitor of molds that is widely used as a food preservative and endogenously produced by gut microbiota. Although generally recognized as safe by the U.S. Food and Drug Administration, the metabolic effects of propionate consumption in humans are unclear. Here, we report that propionate stimulates glycogenolysis and hyperglycemia in mice by increasing plasma concentrations of glucagon and fatty acid-binding protein 4 (FABP4). Fabp4-deficient mice and mice lacking liver glucagon receptor were protected from the effects of propionate. Although propionate did not directly promote glucagon or FABP4 secretion in ex vivo rodent pancreatic islets and adipose tissue models, respectively, it activated the sympathetic nervous system in mice, leading to secretion of these hormones in vivo. This effect could be blocked by the pharmacological inhibition of norepinephrine, which prevented propionate-induced hyperglycemia in mice. In a randomized, double-blind, placebo-controlled study in humans, consumption of a propionate-containing mixed meal resulted in a postprandial increase in plasma glucagon, FABP4, and norepinephrine, leading to insulin resistance and compensatory hyperinsulinemia. Chronic exposure of mice to a propionate dose equivalent to that used for food preservation resulted in gradual weight gain. In humans, plasma propionate decreased with weight loss in the Dietary Intervention Randomized Controlled Trial (DIRECT) and served as an independent predictor of improved insulin sensitivity. Thus, propionate may activate a catecholamine-mediated increase in insulin counter-regulatory signals, leading to insulin resistance and hyperinsulinemia, which, over time, may promote adiposity and metabolic abnormalities. Further evaluation of the metabolic consequences of propionate consumption is warranted.

This study evaluated the effect of nurse practitioner (NP) mediated interventions on diabetes control before elective surgery.A program was initiated to improve preoperative diabetes control in patients with HbA1c8%. The intervention was initially mediated by a physician alone and subsequently changed to involve NPs. The goal of intervention was fasting blood glucose (BG)200 mg/dL on the day of surgery (DOS). Data were collected before the program (control group), during physician-mediated intervention (phase 1), and during NP-mediated intervention (phase 2).There were 222 patients in the control group, 226 in phase 1, and 160 in phase 2. Mean BG (mg/dL) on DOS was 171.4 ± 66.5 in control group, 162.6 ± 58.1 in phase 1, and 153.4 ± 46.6 in phase 2 (p = NS for control vs. phase 1 and0.01 for control vs. phase 2). More patients received an intervention in phase 2 (93%) than in phase 1 (75%). Among those receiving intervention, 87% achieved target BG in phase 2 and 82% in phase 1 (p = NS). Duration of diabetes, baseline HbA1c, time available before surgery, and diabetes intervention were independent predictors of achieving target BG.NP-mediated interventions increased access to care and resulted in lower BG levels and may be a good strategy for preoperative diabetes control.

Plasminogen activator inhibitor-1 (PAI-1) is implicated in the pathophysiology of cardiovascular disease (CVD) and increased in individuals with type 2 diabetes mellitus (T2DM). Adipose tissue produces PAI-1, and pericardial fat is a CVD risk factor. We sought to determine the relationship between PAI-1 and pericardial fat in males and females with well-controlled T2DM.The study population consisted of 32 males and 19 females, aged 35-70 years with T2DM, without clinical evidence of CVD or other active medical problems except for hypertension. Subjects were studied under good cardiometabolic control. Study procedures included fasting blood work and cardiovascular imaging. Cardiac magnetic resonance imaging of the heart was used to identify and quantify pericardial fat from the bifurcation of the pulmonary trunk to the last slice containing cardiac tissue.PAI-1 was positively correlated with pericardial fat (β = 0.72, r = 0.72, P 0.001) as well as with homeostatic model assessment of insulin resistance (r = 0.31, P = 0.03) and serum triglycerides (r = 0.27, P = 0.05). In a multivariable regression model, controlling for insulin sensitivity, triglycerides, and body mass index, pericardial fat was independently associated with PAI-1 (β = 0.80, P 0.001).PAI-1 is positively associated with pericardial fat in individuals with T2DM.

Accumulating evidence shows an increase in insulin resistance on salt restriction. We compared the effect of low salt diet on insulin resistance in salt-sensitive versus salt-resistant hypertensive subjects. We also evaluated the relationship between salt sensitivity of blood pressure and salt sensitivity of insulin resistance in a multivariate regression model. Studies were conducted after 1 week of high salt (200 mmol per day sodium) and 1 week of low salt (10 mmol per day sodium) diet. Salt sensitivity was defined as the fall in systolic blood pressure >15 mm Hg on low salt diet. The study includes 389 subjects (44% women; 16% blacks; body mass index, 28.5±4.2 kg/m 2 ). As expected, blood pressure was lower on low salt (129±16/78±9 mm Hg) as compared with high salt diet (145±18/86±10 mm Hg). Fasting plasma glucose, insulin, and homeostasis model assessment were higher on low salt diet (95.4±19.4 mg/dL; 10.8±7.3 mIU/L; 2.6±1.9) as compared with high salt diet (90.6±10.8 mg/dL; 9.4±5.8 mIU/L; 2.1±1.4; P P =NS). On multivariate regression analysis, change in systolic blood pressure was not associated with change in homeostasis model assessment after including age, body mass index, sex, change in serum and urine aldosterone, and cortisol into the model. We conclude that the increase in insulin resistance on low salt diet is not affected by salt sensitivity of blood pressure.

Reduced coronary flow reserve (CFR), an indicator of coronary microvascular dysfunction, is seen in type 2 diabetes mellitus (T2DM) and predicts cardiac mortality. Since aldosterone plays a key role in vascular injury, the aim of this study was to determine whether mineralocorticoid receptor (MR) blockade improves CFR in individuals with T2DM. Sixty-four men and women with well-controlled diabetes on chronic ACE inhibition (enalapril 20 mg/day) were randomized to add-on therapy of spironolactone 25 mg, hydrochlorothiazide (HCTZ) 12.5 mg, or placebo for 6 months. CFR was assessed by cardiac positron emission tomography at baseline and at the end of treatment. There were significant and similar decreases in systolic blood pressure with spironolactone and HCTZ but not with placebo. CFR improved with treatment in the spironolactone group as compared with the HCTZ group and with the combined HCTZ and placebo groups. The increase in CFR with spironolactone remained significant after controlling for baseline CFR, change in BMI, race, and statin use. Treatment with spironolactone improved coronary microvascular function, raising the possibility that MR blockade could have beneficial effects in preventing cardiovascular disease in patients with T2DM.

OBJECTIVE To evaluate the relationship between preoperative A1C and clinical outcomes in individuals with diabetes mellitus undergoing noncardiac surgery. RESEARCH DESIGN AND METHODS Data were obtained from the National Surgical Quality Improvement Program database and the Research Patient Data Registry of the Brigham and Women’s Hospital. Patients admitted to the hospital for ≥1 day after undergoing noncardiac surgery from 2005 to 2010 were included in the study. RESULTS Of 1,775 patients with diabetes, 622 patients (35%) had an A1C value available within 3 months before surgery. After excluding same-day surgeries, patients with diabetes were divided into four groups (A1C ≤6.5% [N = 109]; >6.5–8% [N = 202]; >8–10% [N = 91]; >10% [N = 47]) and compared with age-, sex-, and BMI-matched nondiabetic control subjects (N = 888). Individuals with A1C values between 6.5 and 8% had a hospital length of stay (LOS) similar to the matched control group (P = 0.5). However, in individuals with A1C values ≤6.5 or >8%, the hospital LOS was significantly longer compared with the control group (P < 0.05). Multivariate regression analysis demonstrated that a higher A1C value was associated with increased hospital LOS after adjustments for age, sex, BMI, race, type of surgery, Charlson Comordity Index, smoking status, and glucose level on the day of surgery (P = 0.02). There were too few events to meaningfully evaluate for death, infections, or readmission rate. CONCLUSIONS Our study suggests that chronic hyperglycemia (A1C >8%) is associated with poor surgical outcomes (longer hospital LOS). Providing a preoperative intervention to improve glycemic control in individuals with A1C values >8% may improve surgical outcomes, but prospective studies are needed.

The management of hyperglycemia in patients with kidney failure is complex, and the goals and methods regarding glycemic control in chronic kidney disease (CKD) are not clearly defined. Although aggressive glycemic control seems to be advantageous in early diabetic nephropathy, outcome data supporting tight glycemic control in patients with advanced CKD (including end-stage renal disease [ESRD]) are lacking. Challenges in the management of such patients include therapeutic inertia, monitoring difficulties, and the complexity of available treatments. In this article, we review the alterations in glucose homeostasis that occur in kidney failure, current views on the value of glycemic control and issues with its determination, and more recent approaches to monitor or measure glycemic control. Hypoglycemia and treatment options for patients with diabetes and ESRD or earlier stages of CKD also are addressed, discussing the insulin and noninsulin agents that currently are available, along with their indications and contraindications. The article provides information to help clinicians in decision making in order to provide individualized glycemic goals and appropriate therapy for patients with ESRD or earlier stages of CKD.

ObjectivePostoperative hyperglycemia is associated with poor clinical outcomes in patients undergoing cardiac surgery. However, some experts consider hyperglycemia to be an epiphenomenon related to acute stress. We investigated whether preoperative patient characteristics can predict hyperglycemia after cardiac surgery in nondiabetic patients.MethodsThis is a retrospective study of nondiabetic patients undergoing cardiac surgery at a single center during the years 2004 to 2009. Hyperglycemia was defined as 2 consecutive blood glucose readings of 150 mg/dL or greater during the 72 hours after cardiac surgery.ResultsThis study included 1453 patients with hyperglycemia and 2205 patients without hyperglycemia. Hyperglycemic patients were older, were more likely to be men, had higher body mass index, were more likely to be hypertensive and hypercholesterolemic, and had lower left ventricular ejection fractions; in addition, a greater proportion had a history of cardiovascular disease and renal failure. Multivariate logistic regression analysis showed age, gender, body mass index, preoperative serum creatinine, left ventricular ejection fraction, previous cardiac surgery, and preoperative cardiogenic shock to be independently associated with hyperglycemia (P

OBJECTIVE Hypoglycemia is associated with increased mortality in hospitalized patients. We investigated the relationship between spontaneous hypoglycemia versus insulin-associated hypoglycemia and mortality in hospitalized patients. RESEARCH DESIGN AND METHODS Data for this retrospective cohort study were obtained from electronic databases of patients admitted between 1 April 2008 and 30 November 2010. Patients with one or more blood glucose values ≤50 mg/dL on point-of-care glucose testing were considered hypoglycemic. Patients treated with insulin were assumed to have insulin-associated hypoglycemia. Age-, sex-, and race-matched patients with all blood glucose values >70 mg/dL were selected as controls. The Charlson comorbidity index (CCI) was used to control for severity of illness. RESULTS There were four groups: 1) noninsulin-treated hypoglycemia (NTH) (n = 135), 2) insulin-treated hypoglycemia (ITH) (n = 961), 3) noninsulin-treated control (NTC) (n = 1,058), and 4) insulin-treated control (ITC) (n = 736). Mortality was higher in the ITH group compared with the ITC group (20.3 vs. 4.5%, P < 0.0001), with a relatively higher CCI (1.8 vs. 1.5%, P < 0.0001), but much higher in the NTH group compared with the NTC group (34.5 vs. 1.1%, P < 0.0001), with much higher CCI (2.4 vs. 1.1%, P < 0.0001). Mortality was higher in the NTH group compared with the ITH group (P < 0.0001) but lower in the NTC group compared with the ITC group (P < 0.0001). After controlling for age, sex, CCI, and admission to the intensive care unit, insulin treatment was associated with a lower mortality among the hypoglycemic patients; hazard ratio of death in the ITH group relative to the NTH group was 0.34 (95% CI 0.25–0.47, P < 0.0001). CONCLUSIONS Insulin-associated and spontaneous hypoglycemia are associated with increased mortality among hospitalized patients.

Hyperglycemia management in chronic kidney disease (CKD) patients presents difficult challenges, partly due to the complexity involved in treating these patients, and partly due to lack of data supporting benefits of tight glycemic control. While hyperglycemia is central to the pathogenesis and management of diabetes, hypoglycemia and glucose variability also contribute to outcomes. Multiple agents with different mechanisms of action are now available; some can lower glucose levels without the risk of hypoglycemia. This article reviews metabolic changes present in kidney impairment/failure, current views about glycemic goals, and treatment options for the diabetic patient with CKD.

ObjectiveWomen with type 2 diabetes mellitus (T2DM) have a higher risk of fractures despite increased bone mineral density (BMD) as compared to women without diabetes. We hypothesized that bone strength is diminished in women with T2DM after accounting for lean body mass, which may contribute to their increased fracture risk.MethodsParticipants from Women's Health Initiative Observational Study were included in this cross-sectional study. These analyses include 3 groups of women: 1) T2DM women on diet or oral hypoglycemic agents (n=299); 2) T2DM women on insulin therapy (with or without oral agents) (n=128); and 3) Non-diabetic control women (n=5497). Hip structural analyses were done using the validated Beck's method on hip scans from dual energy x-ray absorptiometry (DXA). We compared BMD and section modulus (bending strength) at the narrow neck with and without correcting for total body DXA lean body mass.ResultsWomen in all three groups were of similar ages (63.7, 64.6 and 64.2 years, respectively) and heights, but those with T2DM were heavier, with greater lean body weight vs controls (P

Poorly controlled diabetes in hospitalized patients is associated with poor clinical outcomes. We hypothesized that computer-based diabetes training could improve house staff knowledge and comfort for the management of diabetes in a large tertiary-care hospital.We implemented a computer-based training program on inpatient diabetes for internal medicine house staff at the Brigham and Women's Hospital (Boston, MA) in September 2009. House staff were required to complete the program and answer a set of questions, before and after the program, to evaluate their level of comfort and knowledge of inpatient diabetes. Chart reviews of all non-critically ill patients with diabetes managed by house staff in August 2009 (before the program) and December 2009 (after the program) were performed. Chart reviews were also performed for August 2008 and December 2008 to compare house staff management practices when the computer-based educational program was not available.A significant increase in comfort levels and knowledge in the management of inpatient diabetes was seen among house staff at all levels of training (P0.02), but the increase was smaller for senior house staff compared with junior house staff. Nonsignificant trends suggesting increased use of basal-bolus insulin (P=0.06) and decreased use of sliding-scale insulin (P=0.10) were seen following the educational intervention in 2009, whereas no such change was seen in 2008 (P0.90). Overall, house staff evaluated the training program as "very relevant" and the technology interface as "good."A computer-based diabetes training program can improve the comfort and knowledge of house staff and potentially improve their insulin administration practices at large academic centers.

Recent data suggest that mineralocorticoid receptor activation can affect insulin resistance independent of its effects on blood pressure. This review discusses new evidence linking mineralocorticoid receptor to insulin resistance and the underlying mechanisms of these effects.Observational studies have shown mineralocorticoid activity to be associated with insulin resistance irrespective of race, blood pressure or body weight. Increased mineralocorticoid activity may be the common link between obesity, hypertension, dyslipidemia and insulin resistance, features that make up the metabolic syndrome. Treatment of primary aldosteronism is associated with a decrease in insulin resistance and provides one of the most convincing evidences in favor of the contribution of mineralocorticoid receptor to insulin resistance. Dietary salt restriction, which increases aldosterone levels, is also associated with an increase in insulin resistance. Potential mechanisms by which mineralocorticoid receptor may contribute to insulin resistance include a decreased transcription of the insulin receptor gene, increased degradation of insulin receptor substrates, interference with insulin signaling mechanisms, decreased adiponectin production and increased oxidative stress and inflammation. Advantages of mineralocorticoid receptor antagonists on insulin resistance have been demonstrated in animal models.There may be a benefit of mineralocorticoid receptor antagonists in human insulin resistance states, but more clinical research is needed to explore these possibilities.

Low-salt (LS) diet activates the renin-angiotensin-aldosterone and sympathetic nervous systems, both of which can increase insulin resistance (IR). We investigated the hypothesis that LS diet is associated with an increase in IR in healthy subjects. Healthy individuals were studied after 7 days of LS diet (urine sodium20 mmol/d) and 7 days of high-salt (HS) diet (urine sodium150 mmol/d) in a random order. Insulin resistance was measured after each diet and compared statistically, unadjusted and adjusted for important covariates. One hundred fifty-two healthy men and women, aged 39.1 ± 12.5 years (range, 18-65) and with body mass index of 25.3 ± 4.0 kg/m(2), were included in this study. Mean (SD) homeostasis model assessment index was significantly higher on LS compared with HS diet (2.8 ± 1.6 vs 2.4 ± 1.7, P.01). Serum aldosterone (21.0 ± 14.3 vs 3.4 ± 1.5 ng/dL, P.001), 24-hour urine aldosterone (63.0 ± 34.0 vs 9.5 ± 6.5 μg/d, P.001), and 24-hour urine norepinephrine excretion (78.0 ± 36.7 vs 67.9 ± 39.8 μg/d, P.05) were higher on LS diet compared with HS diet. Low-salt diet was significantly associated with higher homeostasis model assessment index independent of age, sex, blood pressure, body mass index, serum sodium and potassium, serum angiotensin II, plasma renin activity, serum and urine aldosterone, and urine epinephrine and norepinephrine. Low-salt diet is associated with an increase in IR. The impact of our findings on the pathogenesis of diabetes and cardiovascular disease needs further investigation.

The onset of menstruation is one of the most important physiological changes occurring among girls during the adolescent years. Menstruation heralds the onset of physiological maturity in girls. It becomes the part and parcel of their lives until menopause. Apart from personal importance, this phenomenon also has social significance. In India, menstruation is surrounded by myths and misconceptions with a long list of "do's" and "don'ts" for women. Hygiene-related practices of women during menstruation are of considerable importance, as it may increase vulnerability to Reproductive Tract Infections (RTI's). Poor menstrual hygiene is one of the major reasons for the high prevalence of RTIs in the country and contributes significantly to female morbidity. Most of the adolescent girls in villages use rags and old clothes during menstruation, increasing susceptibility to RTI's. Adolescents constitute one-fifths of India's population and yet their sexual health needs remain largely unaddressed in the national welfare programs. Poor menstrual hygiene in developing countries has been an insufficiently acknowledged problem. In June 2010, the Government of India proposed a new scheme towards menstrual hygiene by a provision of subsidized sanitary napkins to rural adolescent girls. But there are various other issues like awareness, availability and quality of napkins, regular supply, privacy, water supply, disposal of napkins, reproductive health education and family support which needs simultaneous attention for promotion of menstrual hygiene. The current article looks at the issue of menstrual hygiene not only from the health point of view, but also considers social and human rights values attached to it.

OBJECTIVE Cases of acute pancreatitis have been reported in association with exenatide, sitagliptin, and type 2 diabetes without use of these medications. It remains unknown whether exenatide or sitagliptin increase the risk of acute pancreatitis. RESEARCH DESIGN AND METHODS A retrospective cohort study of a large medical and pharmacy claims database was performed. Data for 786,656 patients were analyzed. Cox proportional hazard models were built to compare the risk of acute pancreatitis between diabetic and nondiabetic subjects and between exenatide, sitagliptin, and control diabetes medication use. RESULTS Incidence of acute pancreatitis in the nondiabetic control group, diabetic control group, exenatide group, and sitagliptin group was 1.9, 5.6, 5.7, and 5.6 cases per 1,000 patient years, respectively. The risk of acute pancreatitis was significantly higher in the combined diabetic groups than in the nondiabetic control group (adjusted hazard ratio 2.1 [95% CI 1.7–2.5]). Risk of acute pancreatitis was similar in the exenatide versus diabetic control group (0.9 [0.6–1.5]) and sitagliptin versus diabetic control group (1.0 [0.7–1.3]). CONCLUSIONS Our study demonstrated increased incidence of acute pancreatitis in diabetic versus nondiabetic patients but did not find an association between the use of exenatide or sitagliptin and acute pancreatitis. The limitations of this observational claims-based analysis cannot exclude the possibility of an increased risk.

Context: Aldosterone production is associated with insulin resistance in obese and hypertensive subjects. However, its effect on insulin sensitivity in healthy subjects is not clear. Objective: The objective of this study was to test the hypothesis that increased aldosterone production is associated with lower insulin sensitivity in healthy subjects. Design: This is an analysis of data previously collected during studies conducted as part of the International Hypertensive Pathotype Consortium. Participants and Interventions: Eighty-four subjects free of any medical or psychiatric illness were included in this study. They were studied after 7 d of a standardized high-sodium diet confirmed by 24-h urine sodium above 200 mEq. Insulin sensitivity index (ISI) was calculated after a 75-g oral glucose load with glucose and insulin measurements at 0, 30, 60, and 120 min. Serum aldosterone levels were measured after 45 min of angiotensin II (3 ng/kg/min) infusion. Results: There were significant negative correlations between ISI and age, body mass index (BMI), diastolic blood pressure, and angiotensin II-stimulated aldosterone level (P < 0.01). On multivariate regression analysis, stimulated aldosterone level was an independent predictor of ISI after adjusting for age, BMI, and diastolic blood pressure. Stimulated aldosterone level predicted 8% of the variance in ISI (P = 0.003) with age, BMI, and diastolic blood pressure together predicting 23% of the variance in ISI. Thus, the final regression model predicted 31% of the variance in ISI (P < 0.0001). Conclusions: Aldosterone production is associated with insulin resistance in normotensive healthy subjects independent of traditional risk factors.

Diabetes is a complex metabolic syndrome that is characterized by prolonged high blood glucose levels and frequently associated with life-threatening complications(1,2). Epidemiological studies have suggested that diabetes is also linked to an increased risk of cancer(3–5). High glucose levels may be a prevailing factor that contributes to the link between diabetes and cancer, but little is known about the molecular basis of this link and how the high glucose state may drive genetic and/or epigenetic alterations that result in a cancer phenotype. Here we show that hyperglycaemic conditions have an adverse effect on the DNA 5-hydroxymethylome. We identify the tumour suppressor TET2 as a substrate of the AMP-activated kinase (AMPK), which phosphorylates TET2 at serine 99, thereby stabilizing the tumour suppressor. Increased glucose levels impede AMPK-mediated phosphorylation at serine 99, which results in the destabilization of TET2 followed by dysregulation of both 5-hydroxymethylcytosine (5hmC) and the tumour suppressive function of TET2 in vitro and in vivo. Treatment with the antidiabetic drug metformin protects AMPK-mediated phosphorylation of serine 99, thereby increasing TET2 stability and 5hmC levels. These findings define a novel ‘phospho-switch’ that regulates TET2 stability and a regulatory pathway that links glucose and AMPK to TET2 and 5hmC, which connects diabetes to cancer. Our data also unravel an epigenetic pathway by which metformin mediates tumour suppression. Thus, this study presents a new model for how a pernicious environment can directly reprogram the epigenome towards an oncogenic state, offering a potential strategy for cancer prevention and treatment.

Context: The mechanisms underlying obesity-mediated cardiovascular disease are not fully understood. Aldosterone and insulin resistance both are associated with obesity and cardiovascular disease. Objectives: The objectives of this study were to test the hypotheses that aldosterone production is elevated and associated with insulin resistance in overweight adults on a high-sodium diet. Participants/Interventions: Healthy normotensive adults were categorized as lean body mass index (BMI) less than 25 kg/m2 (n = 63) or overweight BMI 25 kg/m2 or greater (n = 57). After 7 d of a high-sodium diet, participants fasted overnight and remained supine throughout hemodynamic and laboratory assessments and angiotensin II (AngII) stimulation. Results: The overweight group, compared with the lean group, had higher 24-h urinary aldosterone (9.0 ± 0.8 vs. 6.6 ± 0.5 μg per 24 h; P = 0.003) and higher AngII-stimulated serum aldosterone (11.4 ± 1.0 vs. 9.0 ± 0.6 ng/dl; P = 0.04). There were no differences in 24-h urinary cortisol or sodium or supine measurements of plasma renin activity, serum aldosterone, or serum potassium. The homeostasis model assessment of insulin resistance was predicted by urinary aldosterone excretion (r = 0.32, P = 0.03) and serum aldosterone response to AngII stimulation (r = 0.28, P = 0.02) independent of age and BMI. Conclusion: Urinary aldosterone excretion and AngII-stimulated aldosterone are increased in overweight, compared with lean, normotensive adults. The correlation of these measures of aldosterone production with insulin resistance suggests a potential role for aldosterone in the pathophysiology of obesity-mediated insulin resistance.

Preclinical studies have convincingly demonstrated a role for the mineralocorticoid receptor (MR) in adipose tissue physiology. These studies show that increased MR activation causes adipocyte dysfunction leading to decreased production of insulin-sensitizing products and increased production of inflammatory factors, creating an environment conducive to metabolic and cardiovascular disease. Accumulating data also suggest that MR activation may be an important link between obesity and metabolic syndrome. Moreover, MR activation may mediate the pathogenic consequences of metabolic syndrome. Recent attempts at reversing cardiometabolic damage in patients with type 2 diabetes using MR antagonists have shown promising results. MR antagonists are already used to treat heart failure where their use decreases mortality and morbidity over and above the use of traditional therapies alone. However, more data are needed to establish the benefits of MR antagonists in diabetes, obesity, and metabolic syndrome.

Received June 28, 2004; revision received August 26, 2004; accepted October 15, 2004. The original description of the metabolic syndrome by Reaven1 consisted of obesity, insulin resistance, hypertension, impaired glucose tolerance or diabetes, hyperinsulinemia and dyslipidemia characterized by elevated triglyceride, and low HDL concentrations. All of the features described above are risk factors for atherosclerosis, and thus, metabolic syndrome constituted a significant risk for coronary heart disease2–5 (Table). The features of obesity/overweight and insulin resistance also provided a significant risk for developing type 2 diabetes.5,6 The risks for coronary heart disease and diabetes with metabolic syndrome are greater than those for simple obesity alone, and therefore, an understanding of the pathogenesis and through it, a rational approach to its therapy are of prime importance. View this table: Classic Biological Effects of Insulin and Classic Metabolic Syndrome Based on Resistance to the Metabolic Effects of Insulin As our understanding of the action of insulin evolves to comprehensively include the recent discoveries,7 we can better see that insulin resistance is the basis of most if not all of the features of this syndrome. The original conceptualization of this syndrome was on the basis of resistance to the metabolic actions of insulin. Thus, hyperinsulinemia, glucose intolerance, type 2 diabetes, hypertriglyceridemia, and low HDL concentrations could be accounted for by resistance to the actions of insulin on carbohydrate and lipid metabolism. Although the features described above would to some extent explain the atherogenesis, Reaven has maintained that hyperinsulinemia itself contributes to atherogenicity, and thus, insulin is atherogenic, leading to the coronary heart disease and cerebrovascular disease associated with this syndrome. Obesity probably leads to hypertension through (1) increased vascular tone created by a reduced bioavailability of NO because of increased oxidative stress,8 (2) increased asymmetric dimethylarginine (ADMA) concentrations,9 (3) increased sympathetic …

To establish a relationship between the control of blood glucose levels and the severity of congestive heart failure (CHF) in a retrospective review of medical records of patients with diabetes admitted with acute exacerbation of CHF and to assess the potential correlation between the number of days of hospitalization and the baseline and in-hospital glycemic status.Medical records were reviewed to identify patients with diabetes admitted to a tertiary care center with exacerbation of CHF. Patients in whom any new complications developed that could have prolonged the hospitalization were excluded from the study. The number of days of hospitalization attributable to CHF were noted and statistically correlated with the glycemic control.Data on 100 patients included in the study are presented. The duration of hospitalization ranged from 1 day to 2 weeks (mean, 4.79 +/- 3.03 days). The in-hospital glycemic control strongly correlated positively with the number of days of hospitalization (r = 0.499; 95% confidence interval [CI], 0.325 to 0.643). The admission blood glucose level also showed a strong positive correlation with the days of hospitalization (r = 0.587; 95% CI, 0.426 to 0.720). The mean hemoglobin A1c (HbA1c) correlated positively with the number of days in the hospital (r = 0.653; 95% CI, 0.508 to 0.764). The 51 patients with uncontrolled diabetes (HbA1c7%) were hospitalized for a mean period of 6.3 +/- 3.2 days, in comparison with a mean duration of 3.2 +/- 1.9 days for the 49 patients with good outpatient glycemic control (HbA1cor =7%).Patients with diabetes admitted with exacerbation of CHF who have poor baseline or in-hospital glycemic control have a prolonged hospitalization.

HbA1c = glycated hemoglobin.

In view of the pro-oxidant and proinflammatory effects of angiotensin II, we have tested the hypothesis that valsartan, an angiotensin receptor blocker, may exert a suppressive action on reactive oxygen species (ROS) generation, nuclear factor kappa B (NF-kappa B) in mononuclear cells. Four groups of eight normal subjects were given 1) 160 mg daily of valsartan, 2) 80 mg daily of simvastatin, 3) 40 mg quinapril, or 4) no treatment. Fasting blood samples were obtained before treatment and at d 1, 8, and 14 (7 d after the cessation of the drug). After valsartan, ROS generation by polymorphonuclear cells and mononuclear cells fell significantly by more than 40% (P0.01). NF-kappa B binding activity and the expression of total cellular p65, a protein component of NF-kappa B, fell significantly (P0.01). The expression of inhibitor kappa B (I kappa B) increased significantly (P0.05). Plasma C-reactive protein (CRP) concentration fell significantly (P0.01). All indices, except I kappa B, reverted toward baseline, 7 d after the cessation of the drug. I kappa B persisted in an elevated state. Neither quinapril nor simvastatin given for 7 d produced a suppression of ROS generation, intranuclear NF-kappa B, p65, or CRP, and these two agents did not alter cellular I kappa B either. The untreated controls also did not demonstrate a change in their ROS generation or NF-kappa B binding activity or plasma CRP concentration. We conclude that valsartan at a modest dose exerts a profound and rapid ROS and inflammation-suppressive effect that may be relevant to its potential beneficial effects in atherosclerosis, diabetes, and congestive cardiac failure. In contrast, quinapril and simvastatin produced no similar effect over the period of 1 wk. Our observations may also have implications to clinical situations in which a rapid antiinflammatory effect is required.

BACKGROUND It was recently shown that glucose challenge leads to increased generation of reactive oxygen species (ROS) by polymorphonuclear leukocytes (PMNs) and mononuclear cells (MNCs). OBJECTIVE To further elucidate the relation between nutrition and ROS generation, we investigated the effect of lipid and protein challenges on ROS generation by leukocytes. DESIGN After having fasted overnight, one group of healthy subjects consumed a carbohydrate- and protein-free cream preparation (1257 kJ) and another group of healthy subjects consumed an equienergetic pure preparation of casein. Sequential blood samples were obtained after the intake of cream and casein. ROS were measured by chemiluminescence after stimulation by N-formyl-methionyl-leucinyl-phenylalanine. Lipid peroxidation was measured as thiobarbituric acid-reactive substances (TBARS) and alpha-tocopherol was measured by HPLC. RESULTS ROS generation by MNCs and PMNs increased significantly 1, 2, and 3 h after cream intake and 1 h after protein intake. Cholesterol concentrations did not change significantly, whereas triacylglycerol concentrations increased significantly 2 h after cream intake. Total TBARS concentrations increased 1 h after cream intake and remained elevated 3 h after intake, but the increase was not significant when corrected for changes in triacylglycerol. After casein intake, total cholesterol, triacylglycerol, and TBARS concentrations did not change significantly. alpha-Tocopherol concentrations did not change significantly after either cream or casein intake. CONCLUSIONS Both fat and protein intakes stimulate ROS generation. The increase in ROS generation lasted 3 h after cream intake and 1 h after protein intake. Cream intake also caused a significant and prolonged increase in lipid peroxidation. These data are important because increased ROS generation and lipid peroxidation are key events in atherogenesis.

To describe a process improvement strategy that increased the identification of individuals with poorly controlled diabetes (glycated hemoglobin [A1C] ≥8%) undergoing elective surgery at a major academic medical center and increased their access to specialist care.An algorithm was developed to ensure A1C measurements were obtained as per the American Association of Clinical Endocrinologists/American Diabetes Association (AACE/ADA) guidelines. The diabetes management team worked collaboratively with anesthesiologists, surgeons, and preoperative nurse practitioners to improve the glycemic control of patients with an A1C ≥8%.Before implementing the program, A1C testing was recorded in 854 out of 2,335 (37%) patients with diabetes seen in the preoperative clinic from January 1, 2011 to December 31, 2012. The program was instituted in February 2013. From February 2013 to February 2014, A1C testing occurred in 1,236 out of 1,334 (93%) patients with diabetes. After excluding those scheduled for same day surgery, 228 patients were considered high risk with A1C ≥8%, and 175 were available for endocrine preoperative consultation. The program led to significant blood glucose level improvements on the day of surgery.A process improvement strategy to evaluate and treat diabetes in the preoperative period of elective surgery patients was implemented by a multidisciplinary team (endocrinologists, nurse practitioners, anesthesiologists, and surgeons) and resulted in a substantial improvements in obtaining A1C tests, access to specialist diabetes care, and glycemic control on the day of surgery. The impact of improved glycemic control on hospital and surgical outcomes needs further evaluation.

We appreciate Dr. Dhatariya’s comments (1) and are glad to know that the Joint British Diabetes Societies have developed guidelines for optimal A1C levels before surgery. We were not aware of these guidelines and believe that most surgeons and anesthesiologists in the U.S. are not aware of them either. In our opinion, the literature to date has focused on perioperative glycemic control—on the day of …

Development sectors like health cannot function in isolation. Intersectoral coordination between various departments helps in bringing a positive change in the health-seeking behavior of society in the long run. The decision by the Government of India to provide free solar lanterns (lamps) to the school-going girls of below poverty line families is a welcome step in this context. This initiative would help in reducing the number of school dropout girls and thus help in improving the health indicators that are directly related to women's education. Thus it is an initiative that will help in attainment of Millennium Development Goals through women's education and empowerment. Along with that, the environment-friendly approach will definitely have an impact on health of the girls by switching from kerosene/wood stoves to solar lantern light. Also this initiative would pave the path of real "intersectoral coordination" in the health sector in India that is marred with watertight functioning of various departments. There is an urgent need to popularize the scheme and involve different stakeholders like corporate houses, media, nongovernment organizations, multinational welfare agencies, and local governing bodies for ensuring the availability and utilization of solar lanterns in India.

Diabetes mellitus is associated with increased ROS generation, oxidative injury and obesity. To elucidate the relationship between nutrition and ROS generation, we have investigated the effect of glucose challenge on ROS generation by leucocytes, p47phox protein, a key protein in the enzyme NADPH oxidase and alpha-tocopherol levels. Blood samples were drawn from 14 normal subjects prior to, at 1, 2 and 3 h following ingestion of 75 g glucose. ROS generation by polymorphonuclear leucocytes (PMNL) and mononuclear cells (MNC) increased to a peak of 244 +/- 42% and 233 +/- 34% of the basal respectively at 2h. The levels of p47phox in MNC homogenates increased significantly at 2 h and 3 h after glucose intake. alpha-Tocopherol levels decreased significantly at 1 h, 2 h and 3 h. We conclude that glucose intake stimulates ROS generation and p417phox of NADPH oxidase; increases oxidative load and causes a fall in alpha-tocopherol concentration.

After the demonstration that hydrocortisone inhibits reactive oxygen species (ROS) generation by leukocytes in vivo in a highly predictable manner, we investigated the effect of dexamethasone at a dose of 4 mg, which is thought to be roughly equivalent to 100 mg hydrocortisone. We also tested the hypothesis that dexamethasone may increase the plasma concentration of interleukin-10 (IL-10), an immunomodulatory cytokine that inhibits T(H)1 cells. Dexamethasone (4 mg given intravenously) markedly inhibited ROS generation by mononuclear cells and polymorphonuclear leukocytes. The onset of the effect on polymorphonuclear leukocytes occurred at 1 hour (76.3% +/- 9.3% of basal value), and the peak effect occurred at 4 hours (22.9% +/- 6.4% of basal value), with a significant inhibition still persistent at 8 hours (51.3% +/- 14.3% of basal value; F = 66.7; P < .001). ROS generation was restored to baseline at 24 hours (97.6% +/- 9.5%). The inhibitory effect of dexamethasone on mononuclear cells was 78.3% +/- 9.5% of baseline at 1 hour, 11.4% +/- 6.6% at 4 hours, 30.3% +/- 14.1% at 8 hours, and 102.3% +/- 18% at 24 hours (F = 66.5; P < .001). The peak inhibitory effect of dexamethasone on mononuclear cells (11.4% +/- 6.6%) was significantly greater (P < .05) than that on polymorphonuclear leukocytes (22.9% +/- 6.4%). Plasma IL-10 concentrations increased consistently from 4.8 +/- 1.8 pg/mL within 1 hour of dexamethasone injection and peaked at 4 hours (8.8 +/- 2.3 pg/mL), declining to baseline at 8 hours (F = 4.26; P < .004). Dexamethasone (and possibly other glucocorticoids) therefore exerts its immunosuppressive and anti-inflammatory effects by inhibiting ROS generation by leukocytes and by increasing the plasma concentrations of IL-10.

In view of the fact that glucocorticoids have an immunosuppressive effect and the fact that interleukin-10 (IL-10) is inhibitory to T helper cell function, we have now investigated the effect of hydrocortisone on plasma IL-10 concentrations. Seven normal subjects were injected with 100 mg hydrocortisone intravenously between 8 and 9:00 a.m. Sequential blood samples were obtained prior to and 1, 2, 4, 8 and 24 h after the injection. Plasma IL-10 concentrations increased significantly and consistently following the injection in all subjects. The peak increase of IL-10 occurred at 4 h and the restoration to baseline by 8 h. The sequential values were (mean+/-SD): 3.0+/-1.3 pg/ml at 2 h, 9+/-4.2 pg/ml at 4 h, 3.7+/-1.8 pg/ml at 8 h and 3.7+/-1.4 pg/ml at 24 h. The magnitude of increase was 436% of the basal at peak effect. This effect of hydrocortisone (and possibly other glucocorticoids) may contribute to the immunosuppressive effect of this drug. IL-10 may also be potentially useful in the assessment of Cushing's Syndrome as a marker of end organ effect of glucocorticoids.

BACKGROUND Risk of hypoglycemia is a major barrier to the implementation of tight blood glucose (BG) control in hospitalized patients. The objective of this study was to evaluate the changes in diabetes treatment after an episode of hypoglycemia. METHODS The study was a retrospective data analysis of patients who received 50% dextrose for an episode of hypoglycemia. Data on immediate and subsequent changes in the antidiabetic medications the patients received were collected and evaluated by 2 diabetes specialists. RESULTS Data from 52 patients were included in the study. Mean BG at the time of dextrose administration was 52.1 ± 9.3 mg/dL (range 31-68). Mean BG during the 24 hours before the hypoglycemic episode was 137.5 ± 57.0 mg/dL (range 63-287). Insulin dose was held at the time of the hypoglycemic episode in all 52 patients. Diabetes specialists agreed with this decision 100% of the time. Changes were subsequently made in the treatment of only 21 patients (40%), and diabetes specialists agreed with the changes made for 11 of these patients (52%). Thirty-one patients (60%) received no changes in treatment, and diabetes specialists agreed with that decision for 10 patients (32%). CONCLUSIONS Provider response in making treatment changes after an episode of hypoglycemia is suboptimal. Standardized protocols to make changes in diabetes treatment after an episode of hypoglycemia need to be tested. Journal of Hospital Medicine 2007;2:258–260. © 2007 Society of Hospital Medicine.

While hyperglycemia is central to the pathogenesis and management of diabetes mellitus, hypoglycemia and glucose variability also contribute to outcomes. We previously reported on the relationship of glycemic control to outcomes in a large population of diabetic end-stage renal disease (ESRD) patients. Recognizing that ESRD is a risk factor for severe hypoglycemia, we have now analyzed the association between glycosylated hemoglobin A1c (HgbA1c) levels and glycemic variability in those with hypoglycemia. This is a retrospective study of patients with diabetes enrolled in a large hemodialysis program. Hypoglycemia was identified from hospital discharge diagnostic codes. Glycemic variability was assessed by the standard deviation of HgbA1c and glucose levels over time. Hypoglycemia as a discharge diagnosis was documented in 4.1% of patients. Higher baseline HgbA1c was associated with greater risk for hypoglycemia hospitalization, a finding confirmed by time-lagged HgbA1c levels drawn a quarter earlier. Higher baseline HgbA1c categories were also associated with greater variability in HgbA1c levels during the analysis period. Similarly, greater glucose variability was associated with higher mean glucose levels by trend analysis. High, not low, HgbA1c levels are associated with greater risk of severe hypoglycemia, which may derive from glucose variability in the setting of treatment for hyperglycemia. High HgbA1c and glycemic variability are associated with increased risk of hypoglycemia in individuals with diabetes and ESRD.

Observational studies in primary hyperaldosteronism suggest a positive relationship between aldosterone and parathyroid hormone (PTH); however, interventions to better characterize the physiological relationship between the renin–angiotensin–aldosterone system (RAAS) and PTH are needed. We evaluated the effect of individual RAAS components on PTH using 4 interventions in humans without primary hyperaldosteronism. PTH was measured before and after study (1) low-dose angiotensin II (Ang II) infusion (1 ng/kg per minute) and captopril administration (25 mg×1); study (2) high-dose Ang II infusion (3 ng/kg per minute); study (3) blinded crossover randomization to aldosterone infusion (0.7 µg/kg per hour) and vehicle; and study (4) blinded randomization to spironolactone (50 mg/daily) or placebo for 6 weeks. Infusion of Ang II at 1 ng/kg per minute acutely increased aldosterone (+148%) and PTH (+10.3%), whereas Ang II at 3 ng/kg per minute induced larger incremental changes in aldosterone (+241%) and PTH (+36%; P P P

Observational studies suggest that hydroxychloroquine (HCQ) may reduce the risk of developing diabetes mellitus in patients with rheumatoid arthritis (RA). We examined the effect of HCQ on insulin resistance in subjects without diabetes mellitus with stable RA.Twenty-three RA subjects not currently using HCQ completed a 16-week, double-blind crossover study. Subjects were randomly allocated to receive HCQ (6.5 mg/kg/day) or placebo for the first 8 weeks, followed by crossover to the other arm for the final 8 weeks. Subjects underwent oral glucose tolerance testing and fasting lipid measurements at baseline, 8 weeks, and 16 weeks. The change ± SD from baseline in insulin sensitivity index (ISI), homeostatic model assessment for insulin resistance (HOMA-IR), and lipid parameters were compared between placebo and HCQ using linear regression.The mean patient age was 56 years, with 96% women, and the median body mass index was 26.0 kg/m2. After 8 weeks of HCQ, the mean ± SD ISI increase was 0.4 ± 2.9 compared with a small increase during placebo of 0.14 ± 3.1 (adjusted P = 0.785), and the mean ± SD HOMA-IR decrease was 0.3 ± 1.5 during HCQ versus a decrease of 0.42 ± 1.4 during placebo (adjusted P = 0.308). Small decreases in total cholesterol (12.7 mg/dl) and low-density lipoprotein (LDL) cholesterol (12.4 mg/dl) were observed during the HCQ treatment periods (both adjusted P0.05 compared to placebo).HCQ use for 8 weeks in patients without diabetes mellitus with stable RA produced no significant change in insulin resistance. We observed small and statistically significant improvements in total and LDL cholesterol during HCQ treatment.

The Government of India initiated a cash incentive scheme--Janani Suraksha Yojana (JSY)--to promote institutional deliveries with an aim to reduce maternal mortality ratio (MMR). An observational study was conducted in a tertiary-care hospital of Madhya Pradesh, India, before and after implementation of JSY, with a sample of women presenting for institutional delivery. The objectives of this study were to: (i) determine the total number of institutional deliveries before and after implementation of JSY, (ii) determine the MMR, and (iii) compare factors associated with maternal mortality and morbidity. The data were analyzed for two years before implementation of JSY (2003-2005) and compared with two years following implementation of JSY (2005-2007). Overall, institutional deliveries increased by 42.6% after implementation, including those among rural, illiterate and primary-literate persons of lower socioeconomic strata. The main causes of maternal mortality were eclampsia, pre-eclampsia and severe anaemia both before and after implementation of JSY. Anaemia was the most common morbidity factor observed in this study. Among those who had institutional deliveries, there were significant increases in cases of eclampsia, pre-eclampsia, polyhydramnios, oligohydramnios, antepartum haemorrhage (APH), postpartum haemorrhage (PPH), and malaria after implementation of JSY. The scheme appeared to increase institutional delivery by at-risk mothers, which has the potential to reduce maternal morbidity and mortality, improve child survival, and ensure equity in maternal healthcare in India. The lessons from this study and other available sources should be utilized to improve the performance and implementation of JSY scheme in India.

Myocardial extracellular matrix expansion and reduced coronary flow reserve (CFR) occur in patients with type 2 diabetes mellitus without heart failure or coronary artery disease. Because aldosterone is implicated in the pathophysiology of cardiac fibrosis and vascular injury, the aim of this study was to test the hypothesis that aldosterone is associated with extracellular matrix expansion and reduced CFR in type 2 diabetes mellitus. Patients with type 2 diabetes mellitus without evidence of coronary artery disease were recruited. Blood pressure, lipid management, and glycemic control were optimized over 3 months. Cardiac magnetic resonance imaging with T1 mapping was used to measure myocardial extracellular volume (ECV). Cardiac positron emission tomography was used to assess CFR. On a liberal, 250 mEq/day sodium diet, 24-hour urinary aldosterone and change in serum aldosterone with angiotensin II stimulation were measured. Fifty-three participants with type 2 diabetes (68% men, mean age 53 ± 7 years, mean body mass index 32.2 ± 4.3 kg/m², mean glycosylated hemoglobin 6.8 ± 0.7%, mean systolic blood pressure 126 ± 14 mm Hg) without infarction or ischemia by cardiac magnetic resonance and positron emission tomography were studied. Subjects had impaired CFR (2.51 ± 0.83) and elevated ECV (0.36 ± 0.05), despite normal echocardiographic diastolic function and normal left ventricular function. Myocardial ECV, but not CFR, was positively associated with 24-hour urinary aldosterone excretion (r = 0.37, p = 0.01) and angiotensin II-stimulated aldosterone increase (r = 0.35, p = 0.02). In a best-overall multivariate model (including age, gender, body mass index, glycosylated hemoglobin, and blood pressure), 24-hour urinary aldosterone was the strongest predictor of myocardial ECV (p = 0.004). In conclusion, in patients with type 2 diabetes mellitus without coronary artery disease, aldosterone is associated with myocardial extracellular matrix expansion. These results implicate aldosterone in early myocardial remodeling in type 2 diabetes mellitus.

It is assumed that in individuals with type 2 diabetes mellitus (T2DM), blood pressure sensitivity to salt intake and the frequency of a low renin state are both increased compared with the nondiabetic population. However, studies supporting these assumptions may have been confounded by participant inclusion criteria, and study results may reflect target organ damage.The objective of this study was to examine in a cohort of T2DM 1) the frequency of salt sensitivity of blood pressure and 2) whether alterations of the renin-angiotensin-aldosterone system (RAAS) contribute to salt sensitivity in this population.Within participants of the HyperPATH cohort, four groups were analyzed: 1) T2DM with hypertension (HTN), n=51; 2) T2DM without HTN, n=30; 3) HTN only, n=451; and 4) normotensive, n=209. Phenotype studies were conducted after participants completed two dietary phases: liberal sodium (200 mmol/d) and low sodium (10 mmol/d) for 7 d each. Participants were admitted overnight to a clinical research center after each diet, and supine measurements of the RAAS before and after a 60-min angiotensin II infusion (3 ng/kg·min) were obtained.Multivariate regression analysis demonstrated that T2DM status (all individuals with T2DM vs. individuals without T2DM) was not associated with the change in mean arterial pressure between the low and liberal sodium diets after accounting for age, gender, body mass index, race, and baseline blood pressure (T2DM status, P=0.5). Furthermore, two intermediate phenotypes of altered RAAS, low renin, and nonmodulation (NMOD), were associated with salt-sensitive blood pressure but occurred at different frequencies in the T2DM-HTN and HTN groups (low renin, 12% T2DM-HTN vs. 29% HTN; NMOD, 41% T2DM-HTN vs. 27% HTN; P=0.01).The frequency of NMOD in participants with T2DM was significantly higher compared with HTN, suggesting that the salt sensitivity often seen in T2DM is driven by NMOD.

To study the epidemiology of occupational hand injuries and associated social and industrial factors. DESIGN. For this retrospective case series of patients with occupational hand injuries, case records were retrieved to gather data. In addition, all the subjects were interviewed by a single interviewer using a predesigned questionnaire.Division of Hand Surgery, Department of Orthopaedics and Traumatology, Queen Mary Hospital, Hong Kong.A total of 250 patients with occupational hand injuries were treated during the period from 1999 to 2001. This period was chosen to obtain 10 years of follow-up data to assess return to work and any secondary injuries.Personal particulars (gender, age, marital status, education level, length of stay in Hong Kong, type of employment, wage system, personal habits, family size, number of breadwinners, income), type of industry and mode of injury, causes of injury according to the worker, work conditions, type of injury, and treatment given.Two groups of workers in our study had more occupational hand injuries, namely those with less than 1 year of experience on a new job and immigrants from China. Factors associated with a large proportion of occupational hand injuries were male gender with personal risk factors (smoking and regular consumption of alcohol, long working hours), and in the case of machine operators, inadequate training and use of safety devices.Occupational hand injuries lead to loss of working hours and compensation. For prevention, the workplace should be made into a safer and work-friendly environment. Workers should also have sufficient training.

Introduction Hydroxychloroquine (HCQ) is a common disease modifying therapy for the treatment of rheumatoid arthritis (RA). Prior research suggests that HCQ may reduce the risk of diabetes mellitus in patients with RA. To investigate the mechanism of this effect, we examined the effect of HCQ on insulin resistance, insulin sensitivity, and pancreatic β-cell secretion of insulin in non-diabetic, obese subjects. Methods We recruited 13 obese, non-diabetic subjects without systemic inflammatory conditions for an open-label longitudinal study of HCQ 6.5 mg per kilogram per day for six weeks. Subjects underwent an oral glucose tolerance test at three time points: 0 weeks (pre-treatment with HCQ), 6 weeks (at the end of the HCQ treatment), and 12 weeks (6 weeks post HCQ-treatment). The Matsuda Insulin Sensitivity Index (ISI), HOMA-IR, and HOMA-B were compared across time-points. Results The mean age of the cohort was 49 years, 77% females and median body mass index was 36.1 kg/m2. After 6 weeks of HCQ therapy, ISI increased from a median (interquartile range) of 4.5 (2.3-7.8) to 8.9 (3.7-11.4) with a p-value of 0.040, and HOMA-IR decreased from a median of 2.1 (1.6-5.4) to 1.8 (1.02-2.1) with a p-value of 0.09. All these variables returned toward baseline at week 12. Conclusion HCQ use for 6 weeks in non diabetic obese subjects was associated with a significant increase in ISI and trends toward reduced insulin resistance and insulin secretion. These data suggest that HCQ, a common medication used to treat RA, possesses beneficial effects upon insulin sensitization. Further study of the insulin sensitizing effects of HCQ in patients with RA is warranted.

To test the hypothesis that subcutaneous administration of basal insulin begun immediately after cardiac surgery can decrease the need for insulin infusion in patients without diabetes and save nursing time.After cardiac surgery, 36 adult patients without diabetes were randomly assigned to receive either standard treatment (control group) or insulin glargine once daily in addition to standard treatment (basal insulin group). Standard treatment included blood glucose measurements every 1 to 4 hours and intermittent insulin infusion to maintain blood glucose levels between 100 and 150 mg/dL. The study period lasted up to 72 hours.There were no differences in demographics or baseline laboratory characteristics of the 2 study groups. Mean daily blood glucose levels were lower in the basal insulin group in comparison with the control group, but the difference was not statistically significant (129.3 ± 9.4 mg/dL versus 132.6 ± 7.3 mg/dL; P = .25). The mean duration of insulin infusion was significantly shorter in the basal insulin group than in the control group (16.3 ± 10.7 hours versus 26.6 ± 17.3 hours; P = .04). Nurses tested blood glucose a mean of 8.3 ± 3.5 times per patient per day in the basal insulin group and 12.0 ± 4.7 times per patient per day in the control group (P = .01). There was no occurrence of hypoglycemia (blood glucose level60 mg/dL) in either group.Once-daily insulin glargine is safe and may decrease the duration of insulin infusion and reduce nursing time in patients without diabetes who have hyperglycemia after cardiac surgery.