Hannah Gardener, Tatjana Rundek, Matthew Markert, Clinton B. Wright, Mitchell S. V. Elkind and Ralph L. Sacco FROM ABSTRACT: BACKGROUND: Diet and regular soft drinks have been associated with diabetes and the metabolic syndrome, and regular soft drinks with coronary heart disease. OBJECTIVE: To determine the association between soft drinks and combined vascular events, including stroke. KEY RESULTS: Controlling for age, sex, race/ethnicity, education, smoking, physical activity, alcohol consumption, BMI, daily calories, consumption of protein, carbohydrates, total fat, saturated fat, and sodium, those who drank diet soft drinks daily (vs. none) had an increased risk of vascular events [by 43%], and this persisted after controlling further for the metabolic syndrome, peripheral vascular disease, diabetes, cardiac disease, hypertension, and hypercholesterolemia. There was no increased risk of vascular events associated with regular soft drinks or light diet soft drink consumption. CONCLUSIONS: Daily diet soft drink consumption was associated with several vascular risk factors and with an increased risk for vascular events. KEY POINTS FROM THIS STUDY: 1) This is the first study to examine the association between diet soft drink consumption and incident combined vascular events, including stroke. 2 2) The association between sugar-sweetened soft drinks and obesity, insulin sensitivity, and hypertension may be attributed to their high calorie and sugar load, and lack of nutrients. 3) Artificially-sweetened “diet” soft drinks have been marketed as healthier alternatives due to their lack of calories. However, recent studies suggested that diet soft drink consumption may also be associated with health consequences, particularly type 2 diabetes and the metabolic syndrome, risk factors for cardiovascular disease, ischemic stroke, and all-cause mortality. 4) Frequent diet soft drink consumption was uniquely associated with white race, former smoking, hypertension, elevated blood sugar, lower HDL, elevated triglycerides, increased waist circumference, BMI, peripheral vascular disease, previous cardiac disease, and the metabolic syndrome. 5) Frequent regular soft drink consumption was uniquely associated with male sex, black race, current smoking, carbohydrate consumption, greater diastolic BP, and lower prevalences of diabetes and hypercholesterolemia. 6) We found no association between regular soft drink consumption and risk of combined vascular events, adjusting for demographic and vascular risk factors. 7) Those who drank diet soft drinks daily had a 43% increased risk of vascular events as compared to those who did not drink diet soft drinks. The data of this study also tended to show that the more diet sodas consumed per day the greater the incidence of vascular events. 8) Light diet soft drink users did not have a significantly increased risk of vascular events. 9) Daily diet soft drink consumption was associated with a 66% increased risk of myocardial infarction as compared to no diet soft drink consumption. [The greatest risk from daily consumption of diet sodas was heart attack]. 10) When the authors excluded all participants who were obese, with a history of diabetes or metabolic syndrome, there was a 57% increased risk of vascular events among those who consumed regular soft drinks daily, and a 59% increased risk among those who consumed diet soft drinks daily. [This means that even if you are healthier, either daily consumption of regular sodas or diet sodas are bad for you]. 11) After controlling for these potential confounders, daily diet soft drink consumption at baseline was associated with an increased risk for vascular events during follow-up. 12) There is substantial literature on the negative health consequences of the consumption of sugar-sweetened beverages. 3 13) This study agrees with previous studies that have shown an association between diet soft drink consumption and metabolic syndrome. 14) Diet sodas are significantly associated with elevated blood glucose levels, increased waist circumference and metabolic syndrome. [Ironically, people consume diet sodas precisely to avoid these problems]. 15) The health consequences associated with regular soft drink consumption may be attributed to its high caloric content, glycemic load and consequential inflammatory responses, and added sweeteners such as high fructose corn syrup, which may increase the risk of vascular disease due to its association with blood uric acid levels and triacylglycerol concentrations. 16) Studies show that consumption of artificially sweetened drinks is associated with gaining weight. 17) Consumption of artificial sweeteners may weaken the ability to anticipate the caloric content of foods, leading to increased food intake and gain in body weight. 18) The caramel coloring of both diet and regular soft drinks may contribute to increased levels of proinflammatory advanced glycation end products. [Caramel colored sodas in and of themselves are bad for you].

Ten years prospective data from the Norwegian HUNT 2 study Journal of Evaluation in Clinical Practice February 2011; Vol. 18; No. 1; pp. 159-168 Halfdan Petursson MD, Johann A. Sigurdsson MD, Calle Bengtsson MD, Tom I. L. Nilsenand Linn Getz MD PhD FROM ABSTRACT: Total cholesterol is a frequently used variable in the risk estimates for cardiovascular disease (CVD) prevention. Some studies indicate that the predictive properties of cholesterol might not be as straightforward as widely assumed. Our aim was to document the strength and validity of total cholesterol as a risk factor for mortality in a well-defined, general Norwegian population without known CVD at baseline. These authors assessed the association of total serum cholesterol with total mortality, as well as mortality from CVD and ischaemic heart disease (IHD), in 52,087 Norwegians, aged 20 – 74. The subjects were followed-up at 10 years, giving 510,297 person-years in total. Results Among women: Elevated cholesterol reduced all-cause mortality by 6%. Elevated cholesterol reduced CVD mortality by 3%. The association with IHD mortality was not linear but seemed to follow a U-shaped curve, with the highest mortality below 5.0 [195 mg/dl] and greater than or equal to 7.0 mmol L-1 [271 mg/dl]. Among men, the association of cholesterol with mortality also followed a U-shaped pattern. Conclusion Our study provides an updated epidemiological indication of possible errors in the CVD risk algorithms of many clinical guidelines. If our findings are generalizable, clinical and public health recommendations regarding the dangers of cholesterol should be revised. This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneficial. KEY POINTS FROM THIS STUDY: 1) As cholesterol has become an essential part of lay-peoples basic understanding of their health, and the prevalence of slightly elevated cholesterol levels is so high, we believe that it is important to re-examine old assumptions regarding cholesterol as a risk factor. 2) The common knowledge that total serum cholesterol is an important and strong, independent risk factor for cardiovascular disease (CVD) may be flawed. 3) The common knowledge that the lower the total cholesterol level, the better may also be flawed. 4) Campaigns aimed at the general public to not let their total cholesterol get above 5.0 mmol L-1 [195 mg/dl] may be flawed. 5) According to current authoritative CVD cholesterol guidelines, 75% of the adult Norwegian population would be deemed at risk for CVD and in need of clinical attention. Consequently, we have questioned the theoretical basis of the guidelines. 6) The aim of the present study was to document the strength and validity of total serum cholesterol as a risk factor for mortality, as defined by current CVD prevention guidelines. 7) The phrase U-shaped association indicates that higher mortality (or incidences) can be observed both in individuals with low and high levels of cholesterol compared with individuals with levels in between. 8) Among women, serum cholesterol had an inverse association with all-cause mortality as well as CVD mortality. [Which means elevated total cholesterol levels reduced CVD mortality rates]. 9) In women, the association with IHD mortality appeared to follow a U-shaped curve. [both low levels and high levels increased IHD mortality] 10) Among men, cholesterol did not seem to be linearly associated with mortality but rather the association followed a U-shaped pattern, with the lowest mortality appearing in the second cholesterol category (5.0 – 5.9 mmol L-1 [195 – 228 mg/dl]). This was apparent in all mortality categories. Consequently, cholesterol analysed as a continuous variable did not show a statistically significant linear association with mortality. 11) Having cholesterol levels above 5.5 mmol L-1 [213 mg/dl] was not associated with increased mortality, either among smokers or among non-smokers. 3 12) Smoking was strongly associated with increased mortality in all mortality categories among both sexes. 13) We found total cholesterol to be an overestimated risk factor for CVD prevention. 14) Our results contradict the guidelines well-established demarcation line (5 mmol L-1 [195 mg/dl]) between good and too high levels of cholesterol. They also contradict the popularized idea of a positive, linear relationship between cholesterol and fatal disease. 15) Guideline-based advice regarding CVD prevention may thus be outdated and misleading, particularly regarding many women who have cholesterol levels in the range of 5 – 7 mmol L-1 [195-271 mg/dl]. 16) Our finding of significant discrepancies between epidemiological data and clinical guidelines, suggesting a linear relation between total cholesterol and mortality from CVD is in accord with other studies. 17) In contrast to cholesterol, the detrimental effect of smoking was clearly evident even after stratifying for cholesterol levels. This emphasizes the importance of smoking as a CVD risk factor compared with cholesterol. 18) Based on epidemiological analysis of updated and comprehensive population data, we found that the underlying assumptions regarding cholesterol in clinical guidelines for CVD prevention might be flawed: cholesterol emerged as an overestimated risk factor in our study, indicating that guideline information might be misleading, particularly for women with moderately elevated cholesterol levels in the range of 5 – 7 mmol L-1 [195-271 mg/dl]. 19) Many individuals who could otherwise call themselves healthy struggle conscientiously to push their cholesterol under the presumed danger limit (i.e. the recommended cut-off point of 5 mmol L-1) [195 mg/dl], coached by health personnel, personal trainers and caring family members. Massive commercial interests are linked to drugs and other remedies marketed for this purpose. It is therefore of immediate and wide interest to find out whether our results are generalizable to other populations.

Archives of General Psychiatry November, 2011; Vol. 68; No. 11; pp. 1095-1102 Joachim Hallmayer, MD; Sue Cleveland, BS; Andrea Torres, MA; Jennifer Phillips, PhD; Brianne Cohen, BA; and 11 more authors FROM ABSTRACT Autism is considered the most heritable of neurodevelopmental disorders. Therefore these authors wanted to provide rigorous quantitative estimates of genetic heritability of autism v. the effects of the environment. These authors assessed 192 twin pairs pertaining to Autism Spectrum Disorder (ASD). The authors concluded that the susceptibility to ASD has moderate genetic heritability (37%) and a substantial shared twin environmental component (55%). KEY POINTS FROM THESE AUTHORS: 1) This study is the largest population-based twin study of autism that used contemporary standards for the diagnosis of autism. 2) Autism is a complex neurodevelopmental disorder that interferes with the normal course of social, communicative, and cognitive development. 3) Over the last 30 years there has been a substantial (10-fold) increase in the prevalence of autism. 4) The prevalence for autism spectrum disorders (ASDs) is about 1% [1 in 100 children]. 5) This study found a genetic heritability of 37% and an environmental component of 55% for ASD. 6) The results suggest that environmental factors common to twins explain about 55% of the liability to autism. 7) Although genetic factors also play an important role, they are of substantially lower magnitude than estimates from prior twin studies of autism. 8) This study provides evidence that environmental factors in autism have been seriously underestimated in previous studies and the influence of genetic factors on the susceptibility to develop autism, overestimated. 2 9) Because of the reported high heritability of autism, a major focus of research in autism has been on finding the underlying genetic causes, with less emphasis on potential environmental triggers or causes. 10) These authors hypothesize that at least the environmental factors impacting susceptibility to autism exert their effect during the critical period between prenatal and early postnatal (first year) of life.

2 5) Moreover, a significantly increased risk of DM associated with statin use was observed among women with BMI lower than 25.0 when compared with women with BMI of 30.0 or higher after adjusting for all potential confounders. 6) Statin users had higher fasting glucose levels compared with non – statin users. [This is not surprising. Biochemistry texts show that cholesterol is made from glucose, and statin drugs block the conversion of glucose to cholesterol, thus raising glucose levels]. 7) The results of this study imply that statin use conveys an increased risk of new-onset DM in postmenopausal women. 8) Statin-induced DM is a medication class effect and not related to potency or to individual statin. 9) The consequences of statin-induced DM have not been specifically defined and deserve more attention. Given the wide use of statins in the aging population, further studies among women, men, and diverse ethnicities will clarify DM risk and risk management to optimize therapy. EDITORS NOTE Kirsten L. Johansen, MD Increased Diabetes Mellitus Risk With Statin Use Tipping the Balance In this issue of the Archives, Culver et al report an association between use of statins and increased risk of developing diabetes mellitus in a large cohort of women. These data confirm and extend associations previously demonstrated among participants in randomized trials. The increased risk of diabetes mellitus with statin use was similar among women with and without a history of cardiovascular disease, a finding that may have important implications for the balance of risk and benefit of statins in the setting of primary prevention in which previous meta-analyses show no benefit on all-cause mortality. [This means that meta-analyses show that in those who do not have cardiovascular disease {already have heart signs/symptoms or a prior heart attack} but do have high cholesterol, statin drugs do not help prevent heart attacks, but statin drugs do increase their risk of becoming diabetic].

Archives of Intern Medicine January 23, 2012; Vol. 172; No. 2; pp. 144-152 Annie L. Culver, Ira S. Ockene, Raji Balasubramanian, Barbara C. Olendzki, Deidre M. Sepavich, Jean Wactawski-Wende, JoAnn E. Manson, and 9 more FROM ABSTRACT Background: This study investigates whether the incidence of new-onset diabetes mellitus (DM) is associated with statin use among postmenopausal women. Statin use was captured at enrollment and year 3. Incident DM status was determined annually from enrollment. This investigation included 153,840 women without DM at baseline, and more than 1,004,466 person-years of follow-up. Statin use at baseline was associated with an increased risk of DM (hazard ratio) by 71% [in 3 years]. This association remained after adjusting for other potential confounders and was observed for all types of statin medications. Conclusions: Statin medication use in postmenopausal women is associated with an increased risk for DM. KEY POINTS FROM THESE AUTHORS: 1) The use of statin drugs is progressively increasing, especially among older Americans. 2) Statin use at baseline was significantly associated with an increased DM risk (hazard ratios) by 71% when compared with nonuse. This association was observed for all types of statin. Similar risk associations were found in use of either high- or low potency statins compared with nonusers. 3) Statin use was consistently associated with increased risk of DM across subgroups by age. We observed significantly increased risk of DM by statin use within subgroups of white, Hispanic, and Asian women in both unadjusted and adjusted models. 4) Assessed covariates included demographic and health history information, including race/ethnicity, age, educational attainment, family history of DM, family history of depression, self-report of CVD, hormone therapy use, smoking status, BMI, physical activity, blood pressure, alcohol intake, and energy intake.

Archives of Intern Medicine January 23, 2012; Vol. 172; No. 2; pp. 144-152 Annie L. Culver, Ira S. Ockene, Raji Balasubramanian, Barbara C. Olendzki, Deidre M. Sepavich, Jean Wactawski-Wende, JoAnn E. Manson, and 9 more FROM ABSTRACT Background: This study investigates whether the incidence of new-onset diabetes mellitus (DM) is associated with statin use among postmenopausal women. Statin use was captured at enrollment and year 3. Incident DM status was determined annually from enrollment. This investigation included 153,840 women without DM at baseline, and more than 1,004,466 person-years of follow-up. Statin use at baseline was associated with an increased risk of DM (hazard ratio) by 71% [in 3 years]. This association remained after adjusting for other potential confounders and was observed for all types of statin medications. Conclusions: Statin medication use in postmenopausal women is associated with an increased risk for DM. KEY POINTS FROM THESE AUTHORS: 1) The use of statin drugs is progressively increasing, especially among older Americans. 2) Statin use at baseline was significantly associated with an increased DM risk (hazard ratios) by 71% when compared with nonuse. This association was observed for all types of statin. Similar risk associations were found in use of either high- or low potency statins compared with nonusers. 3) Statin use was consistently associated with increased risk of DM across subgroups by age. We observed significantly increased risk of DM by statin use within subgroups of white, Hispanic, and Asian women in both unadjusted and adjusted models. 4) Assessed covariates included demographic and health history information, including race/ethnicity, age, educational attainment, family history of DM, family history of depression, self-report of CVD, hormone therapy use, smoking status, BMI, physical activity, blood pressure, alcohol intake, and energy intake.