Metformin prescription patterns among US adolescents aged 10-19 years: 2009-2013.

WHAT IS KNOWN AND OBJECTIVE: Metformin is the only oral antihyperglycemic agent approved for use in adolescents with type 2 diabetes mellitus (T2DM). There are reports of metformin used to treat conditions such as obesity, hyperinsulinemia, prediabetes, metabolic syndrome and polycystic ovarian syndrome (PCOS). It is important to understand metformin prescription patterns and underlying diagnoses in adolescents as it can provide estimates of the extent of on-label (i.e. treatment of T2DM) and off-label use of metformin in this population. Our study sought to assess metformin prescription patterns among US adolescents from 2009 to 2013. METHODS: Data from the National Disease and Therapeutic Index (NDTI) database, the MarketScan(®) Commercial Claims and Encounters database and the Multi-State Medicaid database were analysed. The proportion of diagnoses associated with metformin that was recommended during a clinical visit was identified in the NDTI database. In the MarketScan(®) Commercial and Medicaid databases, adolescents with at least one metformin prescription with ±6 months continuous enrolment from the date of the index metformin prescription were included in the analyses. All diagnosis and procedure codes were extracted within ±6 months of the index metformin prescription. The proportion of T2DM was calculated irrespective of any other medical conditions, whereas all other prespecified conditions were classified as positive only if no concurrent T2DM diagnosis codes were present. RESULTS AND DISCUSSION: In the NDTI database, the most common diagnoses associated with metformin use were diabetes (34·9%), followed by metabolic syndrome (20·9%), PCOS (17·2%) and obesity (6·5%). In the MarketScan(®) Commercial database, T2DM was the most common diagnosis among girls aged 10-14 years (22·8-23·6%), boys aged 10-14 years (20·5-24·5%) and boys aged 15-19 years (37·1-43·1%), whereas PCOS (24·1-28·3%) was the most common diagnosis among girls aged 15-19 years. In the Medicaid database, T2DM was the most common diagnosis among all four groups and the proportions were higher than their counterparts in the Commercial database. WHAT IS NEW AND CONCLUSION: Analyses from three separate US data sources suggest that off-label prescribing of metformin is common among US adolescents aged 10-19 years. To avoid potential overestimation, caution should be exercised when utilizing metformin prescription as a proxy measure to estimate the burden of T2DM in adolescents.

Metabolic syndrome risk for cardiovascular disease and diabetes in the ARIC study.

OBJECTIVE: The metabolic syndrome is associated with increased risk for cardiovascular disease and diabetes. Several analyses from the Atherosclerosis Risk in Communities (ARIC) study have been performed to examine the role of the metabolic syndrome and its components in predicting risk for cardiovascular disease and diabetes. DESIGN AND SUBJECTS: The large, biracial, population-based ARIC study enrolled 15792 middle-aged Americans in four communities in the United States and has followed them for the development of cardiovascular disease and diabetes. MEASUREMENTS: Outcome parameters included prevalence of the metabolic syndrome and its individual components, carotid intima-media thickness, incident coronary heart disease, incident ischemic stroke and incident diabetes. RESULTS AND CONCLUSION: Several analyses from the ARIC study have shown that the metabolic syndrome, as well as individual metabolic syndrome components, is predictive of the prevalence and incidence of coronary heart disease, ischemic stroke, carotid artery disease and diabetes.

Selected contribution: cerebrovascular nos and cyclooxygenase are unaffected by estrogen in mice lacking estrogen receptor-alpha.

Estrogen alters reactivity of cerebral arteries by modifying production of endothelium-dependent vasodilators. Estrogen receptors (ER) are thought to be involved, but the responsible ER subtype is unknown. ER-alpha knockout (alphaERKO) mice were used to test whether estrogen acts via ER-alpha. Mice were ovariectomized, with or without estrogen replacement, and cerebral blood vessels were isolated 1 mo later. Estrogen increased levels of endothelial nitric oxide synthase and cyclooxygenase-1 in vessels from wild-type mice but was ineffective in alphaERKO mice. Endothelium-denuded middle cerebral artery segments from all animals constricted when pressurized. In denuded arteries from alphaERKO but not wild-type mice, estrogen treatment enhanced constriction. In endothelium-intact, pressurized arteries from wild-type estrogen-treated mice, diameters were larger compared with arteries from untreated wild-type mice. In addition, contractile responses to indomethacin were greater in arteries from wild-type estrogen-treated mice compared with arteries from untreated wild-type mice. In contrast, estrogen treatment of alphaERKO mice had no effect on diameter or indomethacin responses of endothelium-intact arteries. Thus ER-alpha regulation of endothelial nitric oxide synthase and cyclooxygenase-1 pathways appears to contribute to effects of estrogen on cerebral artery reactivity.

Relaxant effects of 17 beta-estradiol in the rat tail artery are greater in females than males.

To investigate whether sex differences contribute to the variability reported for acute effects of 17 beta-estradiol on vascular reactivity, the response to 17 beta-estradiol was compared in male and female isolated perfused rat tail arteries. 17 beta-Estradiol (10(-7)-10(-5) M) attenuated the contractile response to norepinephrine in female, but not male, arteries, but had no effect when the endothelium was removed. Relaxation to 17 beta-estradiol reached a steady state within approximately 15 min. This hormone appears to acutely relax pre-contracted arteries from females but not males by a non-genomic effect requiring an intact endothelium.

Gender difference in levels of alpha2-adrenoceptor mRNA in the rat tail artery.

To investigate the hypothesis that differing mRNA levels underlie gender differences in the contractile response of the rat tail artery, alpha2-adrenoceptor mRNA was measured using in situ hybridization. Messenger RNA for the alpha2A- and alpha2C-adrenoceptor subtypes was found localized to the smooth muscle layer. There was no detectable mRNA present for the alpha2B-adrenoceptor subtype. Levels of alpha2C-adrenoceptor mRNA were greater in female compared to male tail arteries (417 +/- 35 vs. 263 +/- 38 dpm/mg, P = 0.01), while levels of alpha2A-adrenoceptor mRNA were the same in both sexes. Levels of alpha2-adrenoceptor mRNA may parallel levels of functioning protein present in the rat tail artery.

The ongoing hazard of BB and pellet gun-related injuries in the United States.

STUDY OBJECTIVE: To characterize BB and pellet gun-related injuries treated in US hospital emergency departments. DESIGN: We obtained data through the National Electronic Injury Surveillance System of the US Consumer Product Safety Commission and weighted them to obtain national estimates. RESULTS: We estimate that from June 1, 1992, through May 31, 1993, 32,997 (95% confidence interval [CI], 27,823 to 38,171) people or 12.9 per 100,000 population (95% CI, 10.9 to 14.9) were treated for BB and pellet gun-related injuries. Of this total, 96% (31,547 [95% CI, 26,600 to 36,494]; 12.3 per 100,000 population [95% CI, 10.4 to 14.2]) sustained gunshot wounds. The incidence of BB and pellet gunshot wounds was highest among males (21.0 per 100,000 population [95% CI, 17.7 to 24.3]), children aged 10 through 14 years (71.4 per 100,000 population [95% CI, 57.4 to 85.4]), and blacks (14.6 per 100,000 population [95% CI, 10.3 to 18.9]). Boys aged 10 through 14 years had the highest risk of injury (121.1 per 100,000 population [95% CI, 95.0 to 147.2]). Although most patients (62%) were victims of unintentional shootings, 13.7% were victims of assault. Males aged 10 through 24 years (49.1% of assault cases) had the greatest risk of assault-related BB and pellet gunshot wounds. CONCLUSION: BB and pellet gunshot injuries continue to represent a substantial public health problem, especially to children and adolescents. Although BB and pellet guns are designed and intended for recreational use and competitive sport, they are sometimes used to inflict harm, most often among teenagers aged 15 through 19 years. Intervention strategies must be developed and implemented to reduce unintentional shootings and assaults associated with BB and pellet guns.

Chronic estrogen treatment increases levels of endothelial nitric oxide synthase protein in rat cerebral microvessels.

BACKGROUND AND PURPOSE: A number of studies indicate that the female gonadal hormone, estrogen, confers protection against cerebrovascular disorders such as stroke. One postulated mechanism for these effects of estrogen is an action on the enzyme endothelial nitric oxide synthase (eNOS), which produces the vasodilatory molecule NO. We have investigated the hypothesis that estrogen increases expression of eNOS in cerebral microvessels of male and female rats. METHODS: We measured levels of eNOS protein by Western blot in cerebral microvessels isolated from 7 groups of animals: females, ovariectomized females, ovariectomized females treated with estrogen, males, castrated males, castrated males treated with estrogen, and castrated males treated with testosterone. RESULTS: Ovariectomized female rats treated with estrogen had 17. 4-fold greater levels of eNOS protein in cerebral microvessels than ovariectomized females, and intact females had 16.6-fold greater levels than ovariectomized females (P<0.01). In intact females, cerebral microvessel eNOS protein levels were 9.2-fold higher than those of intact males (P<0.05). Levels of eNOS protein in castrated males, castrated males treated with testosterone, and males were not different from each other. Estrogen treatment of castrated animals resulted in an 18.8-fold increase in cerebral microvessel eNOS protein (P<0.05). CONCLUSIONS: Chronic estrogen treatment increases levels of eNOS protein in cerebral microvessels of male and female rats. This increase in eNOS protein correlates with our previous functional findings indicating that estrogen exposure increases NO modulation of cerebrovascular reactivity in both male and female animals. Upregulation of eNOS expression may contribute to the neuroprotective effect of estrogen.