OBJECTIVE

The association between high glycemic variability and all-cause mortality has been widely investigated in epidemiological studies but rarely validated in glucose-lowering clinical trials. We aimed to identify the prognostic significance of visit-to-visit HbA_1c variability in treated patients in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial population.

RESEARCH DESIGN AND METHODS

We studied the risk of all-cause mortality in relation to long-term visit-to-visit HbA_1c variability, expressed as coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV), from the 8th month to the transition. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (HR) and 95% CI.

RESULTS

Compared with the standard therapy group (n = 4,728), the intensive therapy group (n = 4,755) had significantly lower mean HbA_1c (6.6% [49 mmol/mol] vs. 7.7% [61 mmol/mol], P < 0.0001) and lower CV, VIM, and ARV (P < 0.0001). In multivariate adjusted analysis, all three HbA_1c variability indices were significantly associated with total mortality in all patients as well as in the standard- and intensive-therapy groups analyzed separately. The hazard ratios for a 1-SD increase in HbA_1c variability indices for the all-cause mortality were 1.19 and 1.23 in intensive and standard therapy, respectively. Cross-tabulation analysis showed the third tertile of HbA_1c mean and VIM had significantly higher all-cause mortality (HR 2.05; 95% CI, 1.17–3.61; P < 0.01) only in the intensive-therapy group.

CONCLUSIONS

Long-term visit-to-visit HbA_1c variability was a strong predictor of all-cause mortality. HbA_1c VIM combined with HbA_1c mean conferred an increased risk for all-cause mortality in the intensive-therapy group.

OBJECTIVE

In 2017, the American Academy of Pediatrics introduced a new guideline (2017 Clinical Practice Guideline of the American Academy of Pediatrics [AAP 2017]) to diagnose arterial hypertension (HTN) in children that included revised, lower normative blood pressure (BP) values and cut points for diagnosing high BP in adolescents. We studied the impact of the new AAP 2017 guideline on prevalence of HTN in children with type 1 diabetes mellitus (T1DM).

RESEARCH DESIGN AND METHODS

Up to September 2018, 1.4 million office BP measurements in 79,849 children and adolescents (aged 5–20 years) with T1DM have been documented in the DPV (Diabetes Prospective Follow-up) registry. BP values of the most recent year were aggregated, and BP values of 74,677 patients without antihypertensive medication were analyzed (median age 16 years and diabetes duration 5.3 years and 52.8% boys). BP values were classified according to AAP 2017 and the references of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) (2011) and the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (fourth report) (2004).

RESULTS

Of the patients, 44.1%, 29.5%, and 26.5% were hypertensive according to AAP 2017, KiGGS, and fourth report, respectively. Differences in prevalence of HTN were strongly age dependent: <10 years, AAP 2017 31.4%, KiGGS 30.7%, fourth report 19.6%; 10 to <15 years, AAP 2017 30.9%, KiGGS 31.2%, fourth report 22.4%; and ≥15 years, AAP 2017 53.2%, KiGGS 28.4%, fourth report 30.0%. Among teenagers ≥15 years, 59.1% of boys but only 46.3% of girls were classified as hypertensive by AAP 2017 but only 21.1%/26% of boys and 36.7%/34.4% of girls by KiGGS/fourth report, respectively.

CONCLUSIONS

Classification of BP as hypertension depends strongly on the normative data used. Use of AAP 2017 results in a significant increase in HTN in teenagers ≥15 years with T1DM, particularly in boys. AAP 2017 enhances the awareness of elevated BP in children, particularly in patients with increased risk for cardiovascular disease.

OBJECTIVE

1) To examine trends in the use of diabetes medications and 2) to determine whether physicians individualize diabetes treatment as recommended by the American Diabetes Association (ADA).

RESEARCH DESIGN AND METHODS

We conducted a retrospective, cross-sectional analysis of 2003–2016 National Health and Nutrition Examination Survey (NHANES) data. We included people ≥18 years who had ever been told they had diabetes, had an HbA_1C >6.4%, or had a fasting plasma glucose >125 mg/dL. Pregnant women, and those aged <20 years receiving only insulin were excluded. We assessed trends in use of ADA’s seven preferred classes from 2003–2004 to 2015–2016. We also examined use by hypoglycemia risk (sulfonylureas, insulin, and meglitinides), weight effect (sulfonylureas, thiazolidinediones [TZDs], insulin, and meglitinides), cardiovascular benefit (canagliflozin, empagliflozin, and liraglutide), and cost (brand-name medications and insulin analogs).

RESULTS

The final sample included 6,323 patients. The proportion taking any medication increased from 58% in 2003–2004 to 67% in 2015–2016 (P < 0.001). Use of metformin and insulin analogs increased, while use of sulfonylureas, TZDs, and human insulin decreased. Following the 2012 ADA recommendation, the choice of drug did not vary significantly by older age, weight, or presence of cardiovascular disease. Patients with low HbA_1C, or HbA_1C <6%, and age ≥65 years were less likely to receive hypoglycemia-inducing medications, while older patients with comorbidities were more likely. Insurance, but not income, was associated with the use of higher-cost medications.

CONCLUSIONS

Following ADA recommendations, the use of metformin increased, but physicians generally did not individualize treatment according to patients’ characteristics. Substantial opportunities exist to improve pharmacologic management of diabetes.

OBJECTIVE

Transient neonatal diabetes mellitus (TNDM) occurs during the 1st year of life and remits during childhood. We investigated glucose metabolism and socioeducational outcomes in adults.

RESEARCH DESIGN AND METHODS

We included 27 participants with a history of TNDM currently with (n = 24) or without (n = 3) relapse of diabetes, and 16 non-TNDM relatives known to be carriers of causal genetic defects and currently with (n = 9) or without (n = 7) diabetes. Insulin sensitivity and secretion were assessed by hyperinsulinemic-euglycemic clamp and arginine-stimulation testing in a subset of 8 TNDM participants and 7 relatives carrying genetic abnormalities, with and without diabetes, compared with 17 unrelated control subjects without diabetes.

RESULTS

In TNDM participants, age at relapse correlated positively with age at puberty (P = 0.019). The mean insulin secretion rate and acute insulin response to arginine were significantly lower in TNDM and relatives of participants with diabetes than in control subjects (4.7 [3.6–5.9] vs. 13.4 [11.8–16.1] pmol/kg/min, P < 0.0001; and 84.4 [33.0–178.8] vs. 399.6 [222.9–514.9] µIU/mL, P = 0.0011), but were not different between participants without diabetes (12.7 [10.4–14.3] pmol/kg/min and 396.3 [303.3–559.3] µIU/mL, respectively) and control subjects. Socioeducational attainment was lower in TNDM participants than in the general population, regardless of diabetes duration.

CONCLUSIONS

Relapse of diabetes occurred earlier in TNDM participants compared with relatives and was associated with puberty. Both groups had decreased educational attainment, and those with diabetes had lower insulin secretion capacity; however, there was no difference in insulin resistance in adulthood. These forms of diabetes should be included in maturity-onset diabetes of the young testing panels, and relatives of TNDM patients should be screened for underlying defects, as they may be treated with drugs other than insulin.

OBJECTIVE

Screening for diabetes is typically done using hemoglobin A_1c (HbA_1c) or fasting plasma glucose (FPG). The 2019 Endocrine Society guidelines recommend further testing using an oral glucose tolerance test (OGTT) in older adults with prediabetic HbA_1c or FPG. We evaluated the impact of this recommendation on diabetes prevalence, eligibility for glucose-lowering treatment, and estimated cost of implementation in a nationally representative sample.

RESEARCH DESIGN AND METHODS

We included 2,236 adults aged ≥65 years without known diabetes from the 2005–2016 National Health and Nutrition Examination Survey. Diabetes was defined using: 1) the Endocrine Society approach (HbA_1c ≥6.5%, FPG ≥126 mg/dL, or 2-h plasma glucose ≥200 mg/dL among those with HbA_1c 5.7–6.4% or FPG 100–125 mg/dL); and 2) a standard approach (HbA_1c ≥6.5% or FPG ≥126 mg/dL). Treatment eligibility was defined using HbA_1c cut points (≥7 to ≥9%). OGTT screening costs were estimated using Medicare fee schedules.

RESULTS

Diabetes prevalence was 15.7% (~5.0 million) using the Endocrine Society’s approach and 7.3% (~2.3 million) using the standard approach. Treatment eligibility ranged from 5.4 to 0.06% and 11.8–1.3% for diabetes cases identified through the Endocrine Society or standard approach, respectively. By definition, diabetes identified exclusively through the Endocrine Society approach had HbA1_1c <6.5% and would not be recommended for glucose-lowering treatment. Screening all older adults with prediabetic HbA_1c/FPG (~18.3 million) with OGTT could cost between $737 million and $1.7 billion.

CONCLUSIONS

Adopting the 2019 Endocrine Society guidelines would substantially increase the number of older adults classified as having diabetes, require significant financial resources, but likely offer limited benefits.

OBJECTIVE

To compare the risk of lactic acidosis hospitalization between patients treated with metformin versus sulfonylureas following development of reduced kidney function.

RESEARCH DESIGN AND METHODS

This retrospective cohort combined data from the National Veterans Health Administration, Medicare, Medicaid, and the National Death Index. New users of metformin or sulfonylureas were followed from development of reduced kidney function (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m² or serum creatinine ≥1.4 mg/dL [female] or 1.5 mg/dL [male]) through hospitalization for lactic acidosis, death, loss to follow-up, or study end. Lactic acidosis hospitalization was defined as a composite of primary discharge diagnosis or laboratory-confirmed lactic acidosis (lactic acid ≥2.5 mmol/L and either arterial blood pH <7.35 or serum bicarbonate ≤19 mmol/L within 24 h of admission). We report the cause-specific hazard of lactic acidosis hospitalization between metformin and sulfonylureas from a propensity score–matched weighted cohort and conduct an additional competing risks analysis to account for treatment change and death.

RESULTS

The weighted cohort included 24,542 metformin and 24,662 sulfonylurea users who developed reduced kidney function (median age 70 years, median eGFR 55.8 mL/min/1.73 m²). There were 4.18 (95% CI 3.63, 4.81) vs. 3.69 (3.19, 4.27) lactic acidosis hospitalizations per 1,000 person-years among metformin and sulfonylurea users, respectively (adjusted hazard ratio [aHR] 1.21 [95% CI 0.99, 1.50]). Results were consistent for both primary discharge diagnosis (aHR 1.11 [0.87, 1.44]) and laboratory-confirmed lactic acidosis (1.25 [0.92, 1.70]).

CONCLUSIONS

Among veterans with diabetes who developed reduced kidney function, occurrence of lactic acidosis hospitalization was uncommon and not statistically different between patients who continued metformin and those patients who continued sulfonylureas.

OBJECTIVE

To investigate the association of metabolic and lifestyle factors with possible diabetic polyneuropathy (DPN) and neuropathic pain in patients with early type 2 diabetes.

RESEARCH DESIGN AND METHODS

We thoroughly characterized 6,726 patients with recently diagnosed diabetes. After a median of 2.8 years, we sent a detailed questionnaire on neuropathy, including the Michigan Neuropathy Screening Instrument questionnaire (MNSIq), to identify possible DPN (score ≥4) and the Douleur Neuropathique en 4 Questions (DN4) questionnaire for possible associated neuropathic pain (MNSIq ≥4 + pain in both feet + DN4 score ≥3).

RESULTS

Among 5,249 patients with data on both DPN and pain, 17.9% (n = 938) had possible DPN, including 7.4% (n = 386) with possible neuropathic pain. In regression analyses, central obesity (waist circumference, waist-to-hip ratio, and waist-to-height ratio) was markedly associated with DPN. Other important metabolic factors associated with DPN included hypertriglyceridemia ≥1.7 mmol/L, adjusted prevalence ratio (aPR) 1.36 (95% CI 1.17; 1.59); decreased HDL cholesterol <1.0/1.2 mmol/L (male/female), aPR 1.35 (95% CI 1.12; 1.62); hs-CRP ≥3.0 mg/L, aPR 1.66 (95% CI 1.42; 1.94); C-peptide ≥1,550 pmol/L, aPR 1.72 (95% CI 1.43; 2.07); HbA_1c ≥78 mmol/mol, aPR 1.42 (95% CI 1.06; 1.88); and antihypertensive drug use, aPR 1.34 (95% CI 1.16; 1.55). Smoking, aPR 1.50 (95% CI 1.24; 1.81), and lack of physical activity (0 vs. ≥3 days/week), aPR 1.61 (95% CI 1.39; 1.85), were also associated with DPN. Smoking, high alcohol intake, and failure to increase activity after diabetes diagnosis associated with neuropathic pain.

CONCLUSIONS

Possible DPN was associated with metabolic syndrome factors, insulin resistance, inflammation, and modifiable lifestyle habits in early type 2 diabetes.

OBJECTIVE

Type 2 diabetes (T2D) is increasingly diagnosed at younger ages. We investigated the association of adolescent obesity with incident T2D at early adulthood.

RESEARCH DESIGN AND METHODS

A nationwide, population-based study evaluated 1,462,362 adolescents (59% men, mean age 17.4 years) during 1996–2016. Data were linked to the Israeli National Diabetes Registry. Weight and height were measured at study entry. Cox proportional models were applied.

RESULTS

During 15,810,751 person-years, 2,177 people (69% men) developed T2D (mean age at diagnosis 27 years). There was an interaction among BMI, sex, and incident T2D (P_interaction = 0.023). In a model adjusted for sociodemographic variables, the hazard ratios for diabetes diagnosis were 1.7 (95% CI 1.4–2.0), 2.8 (2.3–3.5), 5.8 (4.9–6.9), 13.4 (11.5–15.7), and 25.8 (21.0–31.6) among men in the 50th–74th percentile, 75th–84th percentile, overweight, mild obesity, and severe obesity groups, respectively, and 2.2 (1.6–2.9), 3.4 (2.5–4.6), 10.6 (8.3–13.6), 21.1 (16.0–27.8), and 44.7 (32.4–61.5), respectively, in women. An inverse graded relationship was observed between baseline BMI and mean age of T2D diagnosis: 27.8 and 25.9 years among men and women with severe obesity, respectively, and 29.5 and 28.5 years among low-normal BMI (5th–49th percentile; reference), respectively. The projected fractions of adult-onset T2D that were attributed to high BMI (≥85th percentile) at adolescence were 56.9% (53.8–59.9%) and 61.1% (56.8–65.2%) in men and women, respectively.

CONCLUSIONS

Severe obesity significantly increases the risk for incidence of T2D in early adulthood in both sexes. The rise in adolescent severe obesity is likely to increase diabetes incidence in young adults in coming decades.

OBJECTIVE

This study evaluated the ability of the Building, Relating, Assessing, and Validating Outcomes (BRAVO) risk engine to accurately project cardiovascular outcomes in three major clinical trials—BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME), Canagliflozin Cardiovascular Assessment Study (CANVAS), and Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction (DECLARE-TIMI 58) trial—on sodium–glucose cotransporter 2 inhibitors (SGLT2is) to treat patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

Baseline data from the publications of the three trials were obtained and entered into the BRAVO model to predict cardiovascular outcomes. Projected benefits of reducing risk factors of interest (A1C, systolic blood pressure [SBP], LDL, or BMI) on cardiovascular events were evaluated, and simulated outcomes were compared with those observed in each trial.

RESULTS

BRAVO achieved the best prediction accuracy when simulating outcomes of the CANVAS and DECLARE-TIMI 58 trials. For the EMPA-REG OUTCOME trial, a mild bias was observed (~20%) in the prediction of mortality and angina. The effect of risk reduction on outcomes in treatment versus placebo groups predicted by the BRAVO model strongly correlated with the observed effect of risk reduction on the trial outcomes as published. Finally, the BRAVO engine revealed that most of the clinical benefits associated with SGLT2i treatment are through A1C control, although reductions in SBP and BMI explain a proportion of the observed decline in cardiovascular events.

CONCLUSIONS

The BRAVO risk engine was effective in predicting the benefits of SGLT2is on cardiovascular health through improvements in commonly measured risk factors, including A1C, SBP, and BMI. Since these benefits are individually small, the use of the complex, dynamic BRAVO model is ideal to explain the cardiovascular outcome trial results.

OBJECTIVE

We analyzed data from inpatients with diabetes admitted to a large university hospital to predict the risk of hypoglycemia through the use of machine learning algorithms.

RESEARCH DESIGN AND METHODS

Four years of data were extracted from a hospital electronic health record system. This included laboratory and point-of-care blood glucose (BG) values to identify biochemical and clinically significant hypoglycemic episodes (BG ≤3.9 and ≤2.9 mmol/L, respectively). We used patient demographics, administered medications, vital signs, laboratory results, and procedures performed during the hospital stays to inform the model. Two iterations of the data set included the doses of insulin administered and the past history of inpatient hypoglycemia. Eighteen different prediction models were compared using the area under the receiver operating characteristic curve (AUROC) through a 10-fold cross validation.

RESULTS

We analyzed data obtained from 17,658 inpatients with diabetes who underwent 32,758 admissions between July 2014 and August 2018. The predictive factors from the logistic regression model included people undergoing procedures, weight, type of diabetes, oxygen saturation level, use of medications (insulin, sulfonylurea, and metformin), and albumin levels. The machine learning model with the best performance was the XGBoost model (AUROC 0.96). This outperformed the logistic regression model, which had an AUROC of 0.75 for the estimation of the risk of clinically significant hypoglycemia.

CONCLUSIONS

Advanced machine learning models are superior to logistic regression models in predicting the risk of hypoglycemia in inpatients with diabetes. Trials of such models should be conducted in real time to evaluate their utility to reduce inpatient hypoglycemia.

OBJECTIVE

Preanalytical processing of blood samples can affect plasma glucose measurement because on-going glycolysis by cells prior to centrifugation can lower its concentration. In June 2017, ACT Pathology changed the processing of oral glucose tolerance test (OGTT) blood samples for pregnant women from a delayed to an early centrifugation protocol. The effect of this change on the rate of gestational diabetes mellitus (GDM) diagnosis was determined.

RESEARCH DESIGN AND METHODS

All pregnant women in the Australian Capital Territory (ACT) are recommended for GDM testing with a 75-g OGTT using the World Health Organization diagnostic criteria. From January 2015 to May 2017, OGTT samples were collected into sodium fluoride (NaF) tubes and kept at room temperature until completion of the test (delayed centrifugation). From June 2017 to October 2018, OGTT samples in NaF tubes were centrifuged within 10 min (early centrifugation).

RESULTS

A total of 7,509 women were tested with the delayed centrifugation protocol and 4,808 with the early centrifugation protocol. The mean glucose concentrations for the fasting, 1-h and 2-h OGTT samples were, respectively, 0.24 mmol/L (5.4%), 0.34 mmol/L (4.9%), and 0.16 mmol/L (2.3%) higher using the early centrifugation protocol (P < 0.0001 for all), increasing the GDM diagnosis rate from 11.6% (n = 869/7,509) to 20.6% (n = 1,007/4,887).

CONCLUSIONS

The findings of this study highlight the critical importance of the preanalytical processing protocol of OGTT blood samples used for diagnosing GDM. Delay in centrifuging of blood collected into NaF tubes will result in substantially lower rates of diagnosis than if blood is centrifuged early.

OBJECTIVE

In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34⁺ cells predicted cardiovascular mortality at 18 months after revascularization. This study aimed to provide long-term validation and mechanistic understanding of the biomarker.

RESEARCH DESIGN AND METHODS

The association between CD34⁺ cell migration and cardiovascular mortality was reassessed at 6 years after revascularization. In a new series of T2D-CLI and control subjects, immuno-sorted bone marrow CD34⁺ cells were profiled for miRNA expression and assessed for apoptosis and angiogenesis activity. The differentially regulated miRNA-21 and its proapoptotic target, PDCD4, were titrated to verify their contribution in transferring damaging signals from CD34⁺ cells to endothelial cells.

RESULTS

Multivariable regression analysis confirmed that CD34⁺ cell migration forecasts long-term cardiovascular mortality. CD34⁺ cells from T2D-CLI patients were more apoptotic and less proangiogenic than control subjects and featured miRNA-21 downregulation, modulation of several long noncoding RNAs acting as miRNA-21 sponges, and upregulation of the miRNA-21 proapoptotic target PDCD4. Silencing miR-21 in control subject CD34⁺ cells phenocopied the T2D-CLI cell behavior. In coculture, T2D-CLI CD34⁺ cells imprinted naïve endothelial cells, increasing apoptosis, reducing network formation, and modulating the TUG1 sponge/miRNA-21/PDCD4 axis. Silencing PDCD4 or scavenging reactive oxygen species protected endothelial cells from the negative influence of T2D-CLI CD34⁺ cells.

CONCLUSIONS

Migration of CD34⁺ cells predicts long-term cardiovascular mortality in T2D-CLI patients. An altered paracrine signaling conveys antiangiogenic and proapoptotic features from CD34⁺ cells to the endothelium. This damaging interaction may increase the risk for life-threatening complications.

OBJECTIVE

To examine whether low baseline diastolic blood pressure (DBP) modifies the effects of intensive systolic blood pressure (SBP) lowering on cardiovascular outcomes in type 2 diabetes mellitus (T2DM).

RESEARCH DESIGN AND METHODS

The Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP), a two-by-two factorial randomized controlled trial, examined effects of SBP (<120 vs. <140 mmHg) and glycemic (HbA_1c <6% vs. 7.0–7.9% [<42 vs. 53–63 mmol/mol]) control on cardiovascular events in T2DM (N = 4,731). We examined whether effects of SBP control on cardiovascular composite were modified by baseline DBP and glycemic control.

RESULTS

Intensive SBP lowering decreased the risk of the cardiovascular composite (hazard ratio [HR] 0.76 [95% CI 0.59–0.98]) in the standard glycemic arm but not in the intensive glycemic arm (HR 1.06 [95% CI 0.81–1.40]). Spline regression models relating the effects of the intervention on the cardiovascular composite across the range of baseline DBP did not show evidence of effect modification by low baseline DBP for the cardiovascular composite in the standard or intensive glycemic arms. The relation between the effect of the intensive SBP intervention and baseline DBP was similar between glycemic arms for the cardiovascular composite three-way interaction (P = 0.83).

CONCLUSIONS

In persons with T2DM, intensive SBP lowering decreased the risk of cardiovascular composite end point irrespective of baseline DBP in the setting of standard glycemic control. Hence, low baseline DBP should not be an impediment to intensive SBP lowering in patients with T2DM treated with guidelines recommending standard glycemic control.

OBJECTIVE

The LEADER trial (ClinicalTrials.gov reg. no. NCT01179048) demonstrated a reduced risk of cardiovascular (CV) events for patients with type 2 diabetes who received the glucagon-like peptide 1 receptor agonist liraglutide versus placebo. The mechanisms behind this CV benefit remain unclear. We aimed to identify potential mediators for the CV benefit observed with liraglutide in the LEADER trial.

RESEARCH DESIGN AND METHODS

We performed exploratory analyses to identify potential mediators of the effect of liraglutide on major adverse CV events (MACE; composite of CV death, nonfatal myocardial infarction, or nonfatal stroke) from the following candidates: glycated hemoglobin (HbA_1c), body weight, urinary albumin-to-creatinine ratio (UACR), confirmed hypoglycemia, sulfonylurea use, insulin use, systolic blood pressure, and LDL cholesterol. These candidates were selected as CV risk factors on which liraglutide had an effect in LEADER such that a reduction in CV risk might result. We used two methods based on a Cox proportional hazards model and the new Vansteelandt method designed to use all available information from the mediator and to control for confounding factors.

RESULTS

Analyses using the Cox methods and Vansteelandt method indicated potential mediation by HbA_1c (up to 41% and 83% mediation, respectively) and UACR (up to 29% and 33% mediation, respectively) on the effect of liraglutide on MACE. Mediation effects were small for other candidates.

CONCLUSIONS

These analyses identify HbA_1c and, to a lesser extent, UACR as potential mediators of the CV effects of liraglutide. Whether either is a marker of an unmeasured factor or a true mediator remains a key question that invites further investigation.

OBJECTIVE

Despite evidence of a relationship among obstructive sleep apnea (OSA), metabolic dysregulation, and diabetes, it is uncertain whether OSA treatment can improve metabolic parameters. We sought to determine effects of long-term continuous positive airway pressure (CPAP) treatment on glycemic control and diabetes risk in patients with cardiovascular disease (CVD) and OSA.

RESEARCH DESIGN AND METHODS

Blood, medical history, and personal data were collected in a substudy of 888 participants in the Sleep Apnea Cardiovascular End Points (SAVE) trial in which patients with OSA and stable CVD were randomized to receive CPAP plus usual care, or usual care alone. Serum glucose and glycated hemoglobin A_1c (HbA_1c) were measured at baseline, 6 months, and 2 and 4 years and incident diabetes diagnoses recorded.

RESULTS

Median follow-up was 4.3 years. In those with preexisting diabetes (n = 274), there was no significant difference between the CPAP and usual care groups in serum glucose, HbA_1c, or antidiabetic medications during follow-up. There were also no significant between-group differences in participants with prediabetes (n = 452) or in new diagnoses of diabetes. Interaction testing suggested that women with diabetes did poorly in the usual care group, while their counterparts on CPAP therapy remained stable.

CONCLUSIONS

Among patients with established CVD and OSA, we found no evidence that CPAP therapy over several years affects glycemic control in those with diabetes or prediabetes or diabetes risk over standard-of-care treatment. The potential differential effect according to sex deserves further investigation.

CNN reports that a study confirms that early autism intervention in toddlers is effective. A study was completed with a program called the Early Start Denver Model (ESDM). This program involves about twenty hours a week in the child's own home. It involves play and parents can easily learn some of the skills that can be applied in other settings. The study compared a group of toddlers that were given ESDM intervention to a group of toddlers receiving typical community interventions. Both groups showed improvement, but the ESDM group improved IQ by 18 points compared to 8 points with traditional interventions. The study is reporting that some of the children "virtually caught up to the typical kids their age." However, they are not claiming it is a cure for autism. According to the article they are working on a replication study to determine if there are similar results. Personally, I'm looking forward to the results of the replication study and want to find out more about this method. From what I understand it is less of a time constraint than ABA therapy.

This study also demonstrated the need for early intervention, which also includes early identification. When children are diagnosed early, they can begin receiving interventions that are proven effective. The study showed that current methods are working, but there may be a new program that can be even more effective on the horizon.

I'd love to hear more from my readers if you have any experience with ESDM or more information about it.

Two years into my position in a culturally diverse school system has taught me many things that I never would have learned in my previous position in a school system with much less diversity. I had hoped to be bilingual by now, but I’m not even close to that goal. However, I do have the training to conduct assessments with bilingual students. Thanks to Samuel Ortiz, Ph.D. for his workshops, research, and books that we use so much in our system. Thanks to the other Psychologists in my system for mentoring me and helping me learn this process. It has helped us to better identify which students have a disability and which students only look like they have a disability because of their performance on tests that are not standardized on children with different cultural and linguistic backgrounds. Learning a second language is not a disability. Just because a student is struggling academically, does not mean he should qualify for special education.

What everyone involved in school needs to know:
It takes many years for a person learning a language to develop academic use of language to the same level as monolingual individuals. It does not always seem that way when a person has excellent conversational skills in English. However, social use of language is not as sophisticated as academic use of language. Students can appear to be fluent, when in actuality the language and vocabulary is not on grade level. If a student’s comprehension and expression of language is below grade level, academics will naturally be below grade level as well. This is not the same as having a disabling condition.

A child with good social use of language, but developing academic use of language often looks to teachers like a student with a disability, when in reality the student may be a typically developing second language learner. Special education is not the answer for this student; the answer comes through hard work, patience, and instruction through a high quality English as a Second Language Program. In the past (and currently in many systems) this child would be misidentified as a student with a disability and inappropriately put into special education programs.

What Parents need to know:
Traditional assessments are not standardized for use with culturally and linguistically diverse students, so typical interpretation of scores on these assessments are inappropriate. When school systems try to use these assessments in the traditional way and then apply the unreliable scores into eligibility criteria, it’s frankly scary.

If you are a parent of an English Language learner, insist that a bilingual assessment be administered. I recognize that the irony of this statement is that many parents of bilingual students are not reading this blog as it is in English only. I don’t really have a good answer for that at this time.

What Teachers need to know:
If you are a teacher, recognize that academic language competency takes time and it requires additional assessment tools to tease out if the difficulties are primarily the result of language and cultural differences or if it is the result of a disability.

What School Psychologists need to know:
If you are a School Psychologist and not using the Cattell-Horn-Carroll Cross-Battery Assessment, I strongly encourage you to take a look. Here is an article from the National Association of School Psychologists Website by Samuel Ortiz, Ph.D. on resources for cultural competency. http://www.nasponline.org/resources/culturalcompetence/ortiz.pdf Advocate that all School Psychologists in your system be trained to administer bilingual assessments or at least have someone competent on hand for these assessments. You can’t hire a School Psychologist in every possible language you might need, so it only makes sense for all School Psychologists to be trained to assess all students. It takes more time to do the assessment, interpret data, and write a report and it requires the use of hiring an interpreter for portions of the assessment, but it is well worth the time and money to properly identify these students. If your school system does not see it this way, bring it up as a solution to disproportionality.

Parents are asked to sign paperwork when services begin, when changes are made, and if services end. Let's not stop there. Parents must sign before any assessments begin. Parents must sign that they attended meetings. Parents sign that they received a copy of special education rights. The reasoning is to protect everyone involved. It gives documentation to show who attended the meetings, shows parental consent for what is outlined in the plan, and documents what has occurred at the meeting.

Dedicated to the lady at Walmart with the screaming kid and all of us "good parents" who have been that lady at Walmart.

One of the most difficult behaviors for parents or teachers to address is explosive behavior, a child who has little control over emotions and "melts down" in the classroom or at home.  It is frustrating, it is embarrassing, it is anxiety producing, it causes intense emotions in ourselves.  Parents agonize over why it happens or what they did wrong?  Often the parents are blamed or judged by bystanders in stores, family members, friends, or school staff.  However, I have seen parents with a variety of parenting styles have kids with poor emotional control, including those who are strict, those who are quick to give in, those who spank, those who use time out, those who take away privileges, and a whole lot of parents who feel like they have tried everything.  I know children with very little emotional control from homes that are falling apart, from homes that are loving and supportive, from poor families, from affluent families, from parents who have no clue how to parent, from parents with excellent skills, even from School Psychologists.  This is not to say that parenting styles do not have a role in this, but there IS more to it.  We have to stop judging each other and get to the root of the problem.  

What is the Root of the Problem?

The problem, the reason some children "explode" or act out with little emotional control, is because he or she is lacking a skill.  Emotional control is a skill.  Most kids will learn this skill through consistent discipline strategies, but some do not. 

Another way to look at it.

We don't tell our kids how to read and then expect them to do it.  We show them step by step.  Some kids will pick it up easy, others will need to be taught and retaught and retaught and will need extensive help in doing so.  Do we blame ourselves?  Do we look at our friends judgementally and think to ourselves "look at the book she is using, it's all wrong?"  No, we assume the child has a problem learning to read and we find a way to teach him.  WE HAVE TO START LOOKING AT BEHAVIOR IN THE SAME WAY.  When a child is exploding, the first step should not be to label the child or blame the parent.  Lets start looking for the skill that is lacking.  When we find that skill, lets teach it.

It's NOT always a control issue.  Sometimes kids act out because they have not been taught to obey and respect authority, but sometimes they act out in spite of good training at home.  The explosions lead to self esteem problems in the child and the child feeling like a "bad kid," which in turn makes explosions bigger and more frequent.  Have you ever looked at a screaming child and demanded he control himself right now or "act your age."  It's a common thing to do.  Have you ever looked at a child with a Learning Disability and said "read on your grade level, now!" or "I have told you and told you how to read, why aren't you reading?"  Of course you haven't.  We work with the reader at his level and patiently try different strategies to improve reading.  We can't demand them to be good readers and we can't demand that a child who does not have the skills to control his emotions "act his age."  These explosive kids need skills and truth be told, we who work with these kids need skills. 

If you are a parent with a child who acts "out of control" stop blaming yourself.  It isn't necessarily because you spanked or didn't spank or were too strict or too lenient.  Your child is lacking the skills she needs to control her emotions.  Also, realize you are going to need to learn new skills to help your child learn the lacking skills.  You are no longer in the Parenting 101 class, you need to move on to the Advanced skill- teaching parenting class. 

The BEST book I have read on this topic is The Explosive Child by Ross Greene.  He addresses the skills these children might be lacking and he has great strategies to address the issue. (see Amazon link below)

If you are a teacher and have an "explosive child" in your class, rethink your perspective of the student.  The child needs to learn skills, so lets focus on teaching the skills and being patient with the children who are slower to learn emotional control.  We as school staff can not make excuses or blame the parents.  We have to reach the child at her level.  We teach a child to read at her level.  We must teach a child to control emotions at her level as well. 

Challenge for Everyone
Let us stop labeling these kids with emotional skill deficits as "bad kids" and stop judging the parents.  Let's be honest with ourselves and recognize we all have shortcomings and could use skills in certain areas.  Maybe our kids need skills in emotional control, maybe we do, maybe we need skills in teaching emotional control, or maybe we need skills in some other area all together.  Let's be patient with our children and our peers and ourselves. Let's stop criticizing ourselves and others and start learning and teaching new skills.   We don't live in a world with bad kids, we live in a world will kids who need skills, so let's teach.

Our senses help us understand and navigate our world. They help us feel, see, taste, etc. When one or more of those processes is more or less sensitive to world, life feels different to that person. It is hard to understand what it feels like to have sensory differences unless you have sensory differences. It’s easy to tell someone to ignore a noise that doesn’t seem excessively annoying to you. It’s hard to understand when someone has an intense need for pressure unless you have a similar need. Having these sensory differences can be anxiety producing and stressful. In a classroom, it can make that person less attentive or have a more difficult time sitting still. Kids don’t always have the words or understanding to express what they are feeling. As a result, children who have sensory processing issues are often misunderstood. Sensory issues are often associated with children who have an Autism Spectrum Disorder. There is also an association between Attention Deficit Hyperactivity Disorder and sensory issues. Many times a child will have sensory issues and not have any other disability. Those children may have Sensory Processing disorder, which is a neurological disorder that makes processing and responding to sensory information more difficult. A person with Sensory Processing Disorder may be more or less sensitive than most people to any or all of the senses. Sensory Processing Disorder is not yet widely understood by the majority of people. Most people have an idea about what Autism is or ADHD, but people often do not know about Sensory Processing Disorder. Many school professionals have not learned about it and do not understand it. Many parents have never heard of it. If you have any concerns that your child may have difficulty with sensory processing, I strongly recommend The Out-of-Sync Child: Recognizing and Coping with Sensory Processing Disorder, Revised Edition This book was explains the various types of sensory processing and helps parents to understand what their child may be feeling. It is transformative for a parent to finally understand what is going on with their child. Strategies for the Classroom:

 Often making small changes to the environment can help a child regulate his own body and focus in the classroom. A seating disk fits on a chair and is filled with air. It allows a child to wiggle in his seat, without moving around and causing a distraction. The bumps and the movement can provide the sensory input needed to help a child focus better. The ball chair also allows movement and is good for low tone as well. Weighted lap pads help provide proprioceptive input that helps establish increased body awareness, improves attention span and concentration, and has calming benefits.   Strategies for home: Trampolines provide deep pressure. Also, it is great exercise. For some children, when they start having difficulty regulating his or her body, jumping on the trampoline helps provide the needed pressure and will calm the body after a few minutes. The Body Sock is made of tight material that pushes back against the child's movement. This can help children with coordination and spatial positioning.

 Disclaimer: I am not an Occupational Therapist and am not an expert in this area. I am writing this article to raise awareness in sensory issues that can have a huge impact in the classroom and within a family. Sometimes, minor accommodations can make significant improvements in the life of a child, which I have witnessed firsthand. I encourage any parents who think his or her child may have a sensory issue to seek help through an Occupational Therapist. In most cases, this will fall outside of Special Education and schools, unless the sensory issues are associated with a disability, such as Autism. Some schools are more proactive than others and have more Occupational Therapy support than others. Because OT services are not mandated outside of an IEP or 504 Plan, many schools will not be equipped to help you with this. It is recommended that you seek support through an OT, who can provide individual strategies to use in the classroom and at home.

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The mission of Medip Academy Resources site is to provide teaching and learning materials to medical students (UG and PG) and medical professionals. Medip Academy Resources is a platform for sharing University Examination Papers, Medical Educational Materials, Practical Guides, MCQs, Problem solving etc. The resources available on this site are easily searchable and free to download. URL: http://www.medipacademy.com/resources Email: resources@medipacademy.com How to add a resource? Please share your useful resource by email to resources@medipacademy.com Happy Sharing! Dr. Bhaven Kataria Department of Pharmacology, GMERS Medical College, Sola Ahmedabad, Gujarat, India

The virus responsible for chronic bee paralysis is spreading rapidly among honey bee colonies in Britain, according to a new study.

The duration of SpaceX's first mission with astronauts on board -- planned for launch at 4:32 p.m. EDT on May 27 from Florida -- has been extended from a few days to potentially weeks aboard the space station.

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The global COVID-19 pandemic has brought into sharp focus the intersection of U.S. immigration and public health policy, and the unique challenges that immigrants face. This article analyzes the Trump administration’s introduction of some of the most stringent immigration restrictions in modern times, the often disparate fallout of the outbreak on immigrant communities, the status of federal immigration agency operations, and more.

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