Search

Ocular allergy in the form of Seasonal Allergic Conjunctivitis is one of the most common conditions that ophthalmologists deal with. The signs and symptoms can be distressing and debilitating. The search is still on for the perfect topical drug with maximum efficacy and minimum side effects. We decided to undertake a study to compare and evaluate the efficacy of 3 commonly used drugs, topical Ketorolac tromethamine 0.5%, Ketotifen fumarate 0.05% and Azelastine hydrochloride in patients of Seasonal Allergic Conjunctivitis. 150 patients of Seasonal Allergic Conjunctivitis of both sexes in the age group of 15- 55 years were included. Patients included in the study had bilateral signs and symptoms of Seasonal Allergic Conjunctivitis. Group A patients were given Ketorolac tromethamine 0.5% to be instilled four times a day; Group B patients were given Ketotifen fumarate 0.05% to be instilled two times a day, and Group C patients were given Azelastine hydrochloride 0.05% to be instilled two times a day. The drops were dispensed in identical containers labeled A to C so that the patient did not know the type of drug administered. Informed consent was taken from all the patients. Patients were given the drugs on day 0 and the responses were assessed at 30 minutes (day 0), day 2, day 7, day 14, day 28 and 3 months. The drugs were instilled in both the eyes but the efficacy variables were studied in the eye with greater sign and symptoms. If both eyes had same grades of signs and symptoms, left eye of the patient was assessed. All 3 groups were age and sex matched. On each visit, the patient’s signs and symptoms were graded by the investigator and the total score was noted. During the course of the study, patients were asked regarding any side effects pertaining to the drugs being instilled. Drug A (Ketorolac) had a statistically significant difference as compared to Drug B (Ketotifen) at all follow-up intervals (p< 0.05), except at three month follow up, when there was no significant difference between them (p = 0.07). Also, Drug A had a statistically significant difference as compared to Drug C (Azelastine) throughout the study period (p< 0.05). On comparing Drug B and Drug C, we observed a significant difference from the seventh day onwards. All three drugs had a statistically significant improvement in the total score over baseline from the 30 minute period (p< 0.001).

Racial differences in the incidence of type 2 diabetes (T2D) are well established.1 Southeast Asians living in Western countries as well as those living in their native countries are at a higher risk of developing T2D as compared with the Whites.2 3 Similarly, Blacks and Native Americans in the USA are at a higher risk of developing T2D.4 Many studies have been conducted to understand the racial differences in the pathogenesis of T2D. Insulin resistance and insulin secretion defects have been the focus of most of these studies. South Asians, known to have more body fat for the same body mass index (BMI), have been shown to be more insulin resistant than Whites.5 6 Previous studies did not find South Asians to have higher degrees of insulin deficiency than Whites.7 However, two epidemiological studies in the current issue of BMJ-DRC suggest otherwise.8 9 The first study compared the incidence of T2D in South Asians living in urban India and Pakistan with Blacks and Whites living in urban and suburban areas in the USA.8 South Asian data were obtained from the Cardiometabolic Risk Reduction in South Asia Study that recruited healthy …

People with diabetes (DM) hospitalized with COVID-19 infection have a 2-3 fold higher risk of death compared with those without DM, and mechanical ventilation (MV) has been identified as a major risk factor for death. While stress hyperglycemia (StH) has been established as a risk factor for death in some critically ill cohorts, it is not a well-established risk factor for MV in COVID-19. The COVIDEastDM consortium pooled data from 5 academic hospitals on the East Coast of the US to study the relationship between hyperglycemia and COVID-19 outcomes. Data were obtained retrospectively from electronic records of adults with COVID-19 and either DM or StH (defined in this cohort as day-1 admission blood glucose >180 mg/dl and A1c Disclosure M. E. Mcdonnell: Stock/Shareholder; Spouse/Partner; Abbott Diabetes. N. E. Palermo: None. R. Radhakrishnan: None. G. P. Westcott: None. R. S. Weinstock: Research Support; Self; Boehringer Ingelheim International GmbH, Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Kowa Research Institute, Inc., Medtronic, Tolerion, Inc. R. Garg: None. D. C. Simonson: Stock/Shareholder; Spouse/Partner; Phase V Technologies, Inc. G. Cromwell: None. G. Gopalakrishnan: None. M. Greenfield: None. M. Johnson: None. S. R. Katta: None. J. Lebastchi: None. J. Mitri: Consultant; Self; L-Nutra. Funding TechFoundation; Brigham Education Institute

Type 2 diabetes mellitus (T2DM) is a progressive disease with many patients requiring insulin treatment. Basal insulin (BI) is often added first followed by escalation to a multiple subcutaneous insulin injection (MSI) regimen. However, many patients with T2DM struggle managing the MSI regimen. As a result, their glycemic control remains poor after starting MSI. Our study investigates whether switching back to BI alone would improve glycemic control. Patients with T2DM and A1C ≥9.0% on MSI regimen seen in our clinic over two years were included in this analysis. Main study outcome was the A1C after ≥3 months of switching back to BI as compared to continuing MSI. We found 24 patients who were switched from MSI to BI and compared them with 58 patients who were continued on MSI (see Table). There were no significant differences at baseline between the two groups. On follow-up, the BI group had a mean change in A1C (%) of -1.6 ± 2.0 compared to -0.7 ± 1.5 in the MSI group. In addition, the daily dose of prescribed insulin on follow-up was lower in the BI group at 46 ± 14 units/day compared to 90 ± 70 units/day in the MSI group. Hypoglycemia rates were also lower in the BI group at 12% compared to 20% in the MSI group. We conclude that simplification of insulin regimen may improve A1C and decrease the risk of hypoglycemia in patients poorly controlled on MSI regimen. The improved glycemic control is likely related to improved adherence and lower risk of errors. Disclosure A. Arunachalam: None. R. Garg: None.

Objective: Diabetes-related distress is present in a high proportion of people with type 2 diabetes mellitus (T2DM). We hypothesized that complexity of the antidiabetic medication regimen is a factor that increases diabetes-related distress. Research Design and Methods: We studied 74 consecutive patients with T2DM managed at a tertiary care center. Patients were screened for diabetes-related distress 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 one of three groups: low (n = 26), moderate (n = 22) and high (n = 26) medication complexity. Results: 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 (χ2(2) = 7.75, p= 0.021). Complexity groups were similar on sociodemographic characteristics, diabetes duration, BMI and blood pressure as well as the prevalence of hypertension, hyperlipidemia and hypoglycemic episodes over the last year (ps>0.05). The prevalence of microvascular complications varied as a function of low (28%), moderate (45%), and high (76%) regimen complexity (χ2(2) = 11.8, p = 0.003). One-way ANOVA showed significant complexity group differences for HbA1c (F(2,70) = 5.47, p = 0.006) with higher HbA1c in the high and moderate complexity groups than in the low group. Analysis of covariance adjusting for HbA1c showed that DDS-2 significantly differed as a function of complexity group (F (2,69) = 3.93, p = .024). The model explained 16.2% of the variance in DDS-2 (R2 = 0.162). Post hoc analyses revealed that diabetes-related distress was significantly greater for the high (DDS-2 = 6.6) complexity group compared to the moderate complexity group (DDS-2 = 4.5) (p = .031). Conclusions: A complex antidiabetic medication regimen is associated with high levels of diabetes distress. Disclosure M. Luzuriaga: None. R. Leite: None. H. Ahmed: None. P. G. Saab: None. R. Garg: None.

Glycemic control in patients with diabetes mellitus receiving total parenteral nutrition (TPN) can be challenging due to multiple factors. These patients often have a high burden of illness and receive medications that raise blood glucose (BG) levels. Moreover, TPN delivers a large amount of glucose directly into the systemic circulation without the benefit of incretin effect. Therefore, relatively large amounts of insulin are expected to be required for glycemic control. However, there are no studies to guide insulin dosing in patients with diabetes being started on TPN. We conducted a retrospective study including all patients with diabetes admitted to our hospital over a 1-year period who received TPN for ≥ 3 days. The goal of this study was to estimate a safe starting dose of insulin for TPN. Patients receiving enteral nutrition along with TPN were excluded. Insulin doses and blood glucose levels on the last day of TPN were used for data analysis. We found 25 patients who fulfilled our inclusion/exclusion criteria. All patients had type 2 diabetes and were receiving antidiabetic drugs before hospitalization. Mean age was 68 ± 7 years, 56% were men, 80% were White, 44% had microvascular and 44% had macrovascular complications. Mean BMI was 26.7 ± 6.7 kg/m2, systolic BP 131 ± 27 mmHg, diastolic BP 65 ± 15 mmHg, HbA1c 7.7 ± 2.3% and serum creatinine 2.7 ± 3.3 mg/dl. The mean daily BG on TPN was 212 ± 47 mg/dl. Out of 171 BG values available on the last day of TPN, 116 (68%) were >180 mg/dl, 4 (2%) were Disclosure R. Garg: None. A. Arunachalam: None. L.E. Bermudez: None. M. Ramirez: None.

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.

Cardiovascular (CV) disease fatality rates are higher for women compared with men with diabetes despite lower rates of obstructive coronary artery disease (CAD). Impaired coronary flow reserve (CFR), the ratio of adenosine-stimulated to rest myocardial blood flow (MBF), is an indicator of coronary microvascular dysfunction and predicts major adverse CV events. We performed a post hoc analysis to determine whether there was a sex disparity in coronary microvascular dysfunction among 46 men and 27 women with well-controlled type 2 diabetes and without clinical evidence of obstructive CAD. We found that women had a higher rest MBF, lower CFR, and worse diastolic function compared with men. In addition, rest MBF was positively correlated with worse diastolic function in women. We previously showed that mineralocorticoid blockade improved CFR in men and women with type 2 diabetes, implicating aldosterone in the pathophysiology of coronary microvascular dysfunction. We therefore examined aldosterone levels and found that women had larger increases in aldosterone in response to an angiotensin-II infusion than did men. In conclusion, among individuals with type 2 diabetes and good cardiometabolic control, women had worse myocardial perfusion and diastolic function compared with men. The greater aldosterone responsivity in women may be a mechanism for this sex effect.

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.

Acute hyperglycemic emergencies are a common cause of diabetes-related hospitalization. Diabetes ketoacidosis (DKA) is typically seen in patients with type 1 diabetes, and hyperosmolar hyperglycemic state (HHS) is typically seen in patients with type 2 diabetes. Presentation of DKA is acute with polyuria, polydipsia, and abdominal symptoms and characterized by hyperglycemia, ketonemia, and anion gap metabolic acidosis. Presentation of HHS is subacute with symptoms similar to DKA followed by altered mental status and extremely high blood glucose levels with high plasma osmolarity. The common precipitating causes of acute hyperglycemic emergencies include medication nonadherence, infections, and ischemic events. The key to treatment, for both DKA and HHS, is rehydration, insulin therapy, and electrolyte management. With proper treatment, mortality from acute hyperglycemic emergencies has been going down, but the morbidity is still very high.

Hypoglycemia with or without diabetes is associated with increased mortality risk in hospitalized patients. Before proceeding with investigations for hypoglycemia in those without major acute or chronic illness, there must be documentation of a low blood glucose associated with symptoms of hypoglycemia that resolve by restoring normoglycemia (Whipple’s triad). When major illness is present, glucose levels

Treatment of hyperglycemia in hospitalized patients reduces adverse clinical outcomes. When a patient with diabetes is admitted, HbA1c should be obtained. Antidiabetic medications usually have to be modified. In general, this means using some form of insulin treatment in order to achieve moderate glycemic control while avoiding hypoglycemia. Frequent blood glucose testing and adjusting insulin treatment during the course of hospitalization are required. Diabetes treatment at the time of discharge must be transitioned to a regimen that can be followed as an outpatient and reevaluated shortly afterward.

The prevalence of type 2 diabetes mellitus (T2DM) is increasing, especially in the elderly population. Many of these patients have co-morbidities like renal insufficiency, cognitive impairment and lack of social support, increasing the risk of hypoglycemia. Moreover, the benefits of tight glycemic control have not been established in the elderly. Therefore, the American Diabetes Association recommends relaxed glycemic goals (HbA1c ∼8%) in the elderly population. De-intensification of diabetes treatment is recommended to prevent potential harm. We conducted a retrospective study to evaluate the rate of de-intensification of antidiabetic treatment in patients aged ≥75 years with HbA1c ≤7% at the time of their clinic visits. All patients with ≥2 clinic visits over 1-year period at a major academic diabetes center were included. Out of 1,417 unique patients treated during 2017, 174 were ≥75 years old on the day of their last clinic visit. Out of these, 80 patients had an HbA1c ≤7%. Medical records of these 80 patients were manually reviewed for comorbidities, hypoglycemic episodes and drug therapy. A mention of de-intensification of antidiabetic treatment was found in physicians’ notes in only 12 cases. After excluding those with type 1 diabetes, inadequate documentation or controlled on medications without hypoglycemia potential, we found 36 patients treated with a sulfonylurea drug or insulin. Only 10 (27%) patients were advised to reduce the dose of sulfonylurea drug or insulin after an HbA1c Disclosure D.V. Pirela: None. R. Garg: None.

Factors affecting utilization of diabetes care are not well-studied. This information may help develop strategies to improve the efficiency of healthcare systems. We conducted a study to determine factors associated with repeatedly missing an appointment at a major diabetes care center. Data were obtained from electronic medical records. All patients with two or more appointments during the year 2017 were included in analysis. Patients who missed ≥50% of their clinic visits without cancelling an appointment were defined as the repeatedly missed appointment (RMA) group and those who missed Disclosure R. Garg: None. W.H. Cade: None. E. Bernal-Mizrachi: None.

Several studies have demonstrated the benefits of glycemic control in the perioperative period and there is ongoing interest in development of systematic approaches to achieving glycemic control. This review discusses currently available data and proposes a new approach to the management of hyperglycemia in the perioperative period. In a recent study, we demonstrated that early preoperative identification of patients with poorly controlled diabetes and proactive treatment through various phases of surgery improves glycemic control, lowers the risk of surgical complications, and decreases the length of hospital stay. Implementation of a perioperative diabetes program that systematically identifies and treats patients with poor glycemic control early in the preoperative period is feasible and improves clinical care of patients undergoing elective surgery.

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.

Background Patients with metabolic syndrome (MetS) are at increased risk of asymptomatic hyperuricemia (i.e., elevated serum uric acid (SUA) level without gout) and cardiovascular disease. We conducted a cross-sectional study to examine associations between SUA levels and coronary flow reserve and urate deposits in carotid arteries in patients with asymptomatic hyperuricemia and MetS. Methods Adults aged ≥40 years with MetS and SUA levels ≥6.5 mg/dl, but no gout, were eligible. Using a stress myocardial perfusion positron emission tomography (PET), we assessed myocardial blood flow (MBF) at rest and stress and calculated coronary flow reserve (CFR). CFR

Objectives Dual-energy CT (DECT) scan is a sensitive and specific tool used to visualise and quantify monosodium urate (MSU) crystal deposits in the joints. Few studies have examined MSU crystal deposits in patients with asymptomatic hyperuricemia (ie, hyperuricemia in the absence of gout) using DECT. Methods We conducted a prospective, non-interventional cross-sectional study to detect MSU crystal deposits on DECT scans among patients with asymptomatic hyperuricemia. We also examined patient factors associated with subclinical MSU crystal deposits. Out of 130 subjects aged ≥40 years with metabolic syndrome screened for serum uric acid (sUA) levels ≥6.5 mg/dL, 46 underwent a foot/ankle DECT scan. Results The mean age of the study participants was 62 (±8) years, 41% were men and the mean sUA level was 7.8 (±1.0) mg/dL. Seven (15%) of 46 patients had MSU crystal deposits on DECT with a mean total volume of 0.13 (±0.14) cm 3 . In the univariable logistic regression analysis, older age had a significant association with presence of MSU crystal deposits (OR 1.20, 95% CI 1.03 to 1.39), but sUA did not (OR 1.36, 95% CI 0.63 to 2.95). In the univariable analysis, sUA levels showed a trend towards a modest linear association (β=0.11, P=0.09) with total volume of MSU crystal deposits. Conclusions Fifteen per cent of patients with asymptomatic hyperuricemia had subclinical MSU crystal deposits on foot/ankle DECT scans. Older age, but not sUA, was significantly associated with presence of subclinical MSU crystal deposits among patients with asymptomatic hyperuricemia. Clinical significance of these subclinical MSU crystal deposits needs to be determined.

Objective The hippocampus is crucial for paired-associate learning. Obesity is associated with increased mineralocorticoid receptor (MR) activity in peripheral and possibly central tissues, decreased hippocampal size in humans, and impaired hippocampal learning in rodents. The MR is expressed in hippocampal neurons, and MR blockade improves hippocampal learning in obese animals. The goal of the study was to determine whether MR blockade would modulate paired-associate learning in men and women with obesity. Methods Men and women ages 20-61 years with BMI between 30-45 kg/m2 were randomly assigned to placebo (n = 11; 7 women) or 50 mg spironolactone daily (n = 12; 7 women) for six weeks. At baseline and post-treatment, subjects underwent a clinical and hormonal evaluation. They also underwent a computerized task that assesses paired-associate learning and has been shown by functional magnetic resonance imaging to activate the hippocampus. Results In an ANCOVA model that adjusted for baseline paired-associate learning, age, and race, spironolactone treatment was associated with a significant (P = 0.043) improvement in hippocampal memory as compared to placebo treatment. Conclusions Our findings demonstrate, for the first time, that blocking MR with chronic, low-dose spironolactone treatment improves paired-associate learning in individuals with obesity, suggesting that MR activation contributes to hippocampal memory modulation in humans.

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.

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 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. Methods 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. Results 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 P < 0.05 compared to placebo). Conclusion 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.

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.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortatlity worldwide. Malnourishment in COPD patients is very common and is a prognostic factor in its treatment. The present study has been conducted to assess nutritional status in COPD patients and its correlation with severity of disease.Methods: This institutional based analytical cross sectional study was conducted in the Department of Pulmonary Medicine at tertiary care hospital in Himachal Pradesh (India) from 1 Dec 2017 to 31st May 2018. A total of 52 COPD participants attending the pulmonary Medicine OPD and fulfilling the inclusion criteria were enrolled.Results: All participants reported being smoker since long with the mean years of smoking since 31 years and about 13.6 cigarettes being smoked per day. 22 (42%) of the participants were undernourished as per BMI criteria But when compared with MUAC criteria, a large number 38 (73%) came out to be undernourished. haemoglobin and cholesterol levels were less in patients with severe diseases than mild and moderate category (76.9%).Conclusions: The malnourishment and severity of the disease has direct correlation. More the severity of COPD, more is the malnourishment. Biochemical parameters, although not deranged significantly in any group, but more on the lower side in patients with severe COPD. There is a need for regular nutritional assessment of every COPD patient and recommendation of supplementary food for them.

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.

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.

Objective To evaluate whether saxagliptin is non-inferior to basal-bolus insulin therapy for glycemic control in patients with controlled type 2 diabetes mellitus (T2DM) admitted to hospital with non-critical illnesses. Research design and methods This was an open-label, randomized controlled clinical trial. Patients received either saxagliptin or basal-bolus insulin, both with correctional insulin doses. The main study outcome was the mean daily blood glucose (BG) after the first day of randomization. Results Of 66 patients completing the study, 33 (age 69±10 years, 40% men) were randomized to saxagliptin and 33 (age 67±10 years, 52% men) to basal-bolus insulin therapy. The mean daily BG was 149.8±22.0 mg/dL in the saxagliptin group and 146.9±30.5 mg/dL in the insulin group (p=0.59). With an observed group difference of 2.9 mg/dL and an a priori margin of 20 mg/dL, inferiority of saxagliptin was rejected in favor of non-inferiority (p=0.007). There was no significant difference in the percentage of high or low BG values. The insulin group received a higher number of insulin injections (2.3±1.7/day vs 1.2±1.9/day; p

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.

In this paper we report a novel approach to reduce the Energy-Delay Product (EDP) and energy for graphical data transmission over serial buses. For any symbol that is to be transmitted on the bus, we select the best code (from an EDP or energy minimization standpoint) from among a set of codebooks. In particular, our implementation utilizes 3 codebooks. Our approach is compared with other reported techniques in the literature, and the results are quite promising. We demonstrate that our technique achieves a 10% improvement in EDP over the best approach known for serial data transmission, with a significant improvement in encoding/decoding complexity and energy. We also show that the average number of transitions of our scheme is 10.9% above the theoretical lower bound (in contrast to the best approach known for serial transmission of LCD data, which is 37.6% above the theoretical lower bound).