Addressing Therapeutic Inertia in 2020 and Beyond: A 3-Year Initiative of the American Diabetes Association.

Research has shown that getting to glycemic targets early on leads to better outcomes in people with type 2 diabetes; yet, there has been no improvement in the attainment of A1C targets in the past decade. One reason is therapeutic inertia: the lack of timely adjustment to the treatment regimen when a person's therapeutic targets are not met. This article describes the scope and priorities of the American Diabetes Association's 3-year Overcoming Therapeutic Inertia Initiative. Its planned activities include publishing a systematic review and meta-analysis of approaches to reducing therapeutic inertia, developing a registry of effective strategies, launching clinician awareness and education campaigns, leveraging electronic health record and clinical decision-support tools, influencing payer policies, and potentially executing pragmatic research to test promising interventions.

Impact of differing glucose-lowering regimens on the pattern of association between glucose control and survival.

AIMS: To characterize survival in relation to achieved glycated haemoglobin (HbA1c) level within alternative glucose-lowering regimens with differing risks of hypoglycaemia. METHODS: Data were extracted from the UK Clinical Practice Research Datalink and the corresponding Hospital Episode Statistics. Patients with type 2 diabetes prescribed glucose-lowering therapy in monotherapy or dual therapy with metformin between 2004 and 2013 were identified. Risk of all-cause mortality within treatment cohorts was evaluated using the Cox proportional hazards model, introducing mean HbA1c as a quarterly updated, time-dependent covariable. RESULTS: There were 6646 deaths in a total follow-up period of 374 591 years. Survival for lower (<7%) vs moderate HbA1c levels (≥7%, <8.5%) differed by cohort: metformin, adjusted hazard ratio (aHR) 1.03 (95% confidence interval [CI] 0.95-1.12); sulphonylurea, aHR 1.11 (95% CI 0.99-1.25); insulin, aHR 1.47 (95% CI 1.25-1.72); combined regimens with low hypoglycaemia risk, aHR 1.02 (95% CI 0.94-1.10); and combined regimens with higher hypoglycaemia risk excluding insulin, aHR 1.24 (95% CI 1.13-1.35) and including insulin, aHR 1.28 (95% CI 1.18-1.37). Higher HbA1c levels were associated with increased mortality in regimens with low hypoglycaemia risk. Post hoc analysis by HbA1c deciles revealed an elevated risk of all-cause mortality for the lowest deciles across all cohorts, but particularly in those regimens associated with hypoglycaemia. High HbA1c was associated with no difference, or a small increase in mortality risk in regimens with increased risk of hypoglycaemia. CONCLUSIONS: The pattern of mortality risk across the range of HbA1c differed by glucose-lowering regimen. Lower HbA1c was associated with increased mortality risk compared with moderate control, especially in those regimens associated with hypoglycaemia. High levels of HbA1c were associated with the expected elevated mortality risk in regimens with low hypoglycaemia risk.

Sulfonylurea use and the risk of hospital readmission in patients with type 2 diabetes.

BACKGROUND: Hospital inpatient care for patients with diabetes was estimated to cost $76 billion in 2012. Substantial expense resulted from those patients having multiple hospitalizations. The objective was to compare the risk for diabetes-related hospital readmission in patients with type 2 diabetes treated with sulfonylureas (SUs) compared to those treated with other oral antihyperglycemic agents (AHAs). METHODS: A retrospective cohort analysis was conducted using two-year panels, from 1999 to 2010, from the Medical Expenditure Panel Survey. The study included patients with type 2 diabetes taking an oral AHA who experienced a diabetes-related hospitalization. A Cox proportional hazard regression predicting time to readmission was used to estimate and compare the risks of readmission for SU-monotherapy versus other-AHA-monotherapy patients. Covariates included age, gender, marital status, cardiovascular disease, kidney disease, and eye disease, along with a propensity score to control for selection bias. The lack of clinical data on disease severity and progression limited our ability to estimate causal relationships between drug use and risk of hospital readmission. RESULTS: From 1999 to 2010, an estimated 13.5 million patients experienced a diabetes-related hospital admission and subsequent AHA treatment. While 23.2 % (n = 746,579) of patients in the SU monotherapy cohort had a readmission, only 16.1 % (n = 881,984) in the other-AHA monotherapy group were readmitted. Average readmission expenditure for readmitted SU users (in 2010 dollars) was $11,148 (±$1,558) compared to $7,673 (±$763) for users of other oral AHAs. The estimated readmission hazard ratio was 1.29 (95 % CI: 1.01-1.65; p-value = 0.04) for SU monotherapy users. If a patient's first hospital admission was during the time period 2008-2010, a readmission was significantly less likely (HR 0.49, 95 % CI: 0.31-0.78; p = 0.003) relative to 2004-2007. CONCLUSIONS: Among patients with type 2 diabetes, SU use was associated with an approximately 30 % increased risk for readmission compared to other-AHA use, while each readmission for an SU user cost on average 45 % more than one for an other-AHA patient. Because of the rapidly rising prevalence of diabetes in the U.S. and the large number of patients with prediabetes, preventing hospital readmissions will continue to be an important cost-saving strategy in the future.

Suboptimal adherence to food restrictions requirements related to drug regimens for chronic diseases.

BACKGROUND: Oral medications for chronic conditions often involve a variety of instructions, including time of day/dosing, drug interactions, and food intake restrictions. However, the extent to which patients follow these instructions is unclear. METHODS: We surveyed patients from the US and Europe (UK, France, Germany, Italy, Spain) who were prescribed sulfonylureas (SU: glimepiride, glipizide, or gliclazide) for diabetes or levothyroxine for hypothyroidism. Patients kept a daily diary for 3-5 days documenting their adherence to three criteria: dosing regimen including time of day, warning labels including drug interactions, and food restrictions. RESULTS: A total of 421 US and 493 European patients took the study medications; 546 patients took SU and 368 took levothyroxine. Overall, 48% of patients were males; 46% were age 65 years or older. Despite most patients having received instructions on medication requirements (US 71%, EU 75%), most patients reported being only somewhat knowledgeable (US 69%; EU 71%). Adherence, measured by the proportion of the days a participant was adherent to each category out of the observational period (ranging from 3-5 days), varied by type of instruction, with the poorest adherence observed for food restriction requirements (US 34% of the observation days, EU 26%) compared to warning labels (US 77%, EU 67%) and dosing regimen (US 85%, EU 87%). CONCLUSIONS: Patients adhered to dosing and cautionary instructions across the majority of the study period but were largely non-adherent to food intake restrictions. Improved communication and increased emphasis on food intake restrictions is needed when advising patients on their medications.

Resistin, but not adiponectin and leptin, is associated with the risk of ischemic stroke among postmenopausal women: results from the Women's Health Initiative.

BACKGROUND AND PURPOSE: Adipose tissue is considered an endocrine organ that secretes adipokines, which possibly mediate the effects of obesity on the risk of cardiovascular disease. However, there are yet limited prospective data on the association between circulating adipokine levels and the risk of ischemic stroke. We aimed to examine the associations of 3 adipokines (adiponectin, leptin, and resistin) with the risk of ischemic stroke. METHODS: We conducted a prospective nested case-control study (972 stroke cases and 972 matched control subjects) within the Women's Health Initiative Observational Study cohort. The control subjects were matched to cases on age, race/ethnicity, date of study enrollment, and follow-up time. RESULTS: Adipokine levels were associated with established stroke risk factors such as obesity and systolic blood pressure. Adjusted for body mass index, the ORs for incident ischemic stroke comparing the highest (Quartile 4) with the lowest quartile (Quartile 1) were 0.81 (95% CI, 0.61 to 1.08; P trend=0.068) for adiponectin, 1.15 (95% CI, 0.83 to 1.59; P trend=0.523) for leptin, and 1.57 (95% CI, 1.18 to 2.08; P trend=0.002) for resistin. The association for resistin remained significant even after accounting for established stroke risk factors (OR, 1.39; 95% CI, 1.01 to 1.90; P trend=0.036). Further adjustment for markers for inflammation, angiogenesis, and endothelial function also did not affect our results. CONCLUSIONS: Circulating levels of resistin, but not those of adiponectin or leptin, are associated with an increased risk of incident ischemic stroke in postmenopausal women, independent of obesity and other cardiovascular disease risk factors.

The role of iron in type 2 diabetes in humans.

The role of micronutrients in the etiology of type 2 diabetes is not well established. Several lines of evidence suggest that iron play may a role in the pathogenesis of type 2 diabetes. Iron is a strong pro-oxidant and high body iron levels are associated with increased level of oxidative stress that may elevate the risk of type 2 diabetes. Several epidemiological studies have reported a positive association between high body iron stores, as measured by circulating ferritin level, and the risk of type 2 diabetes and of other insulin resistant states such as the metabolic syndrome, gestational diabetes and polycystic ovarian syndrome. In addition, increased dietary intake of iron, especially that of heme iron, is associated with risk of type 2 diabetes in apparently healthy populations. Results from studies that have evaluated the association between genetic mutations related to iron metabolism have been inconsistent. Further, several clinical trials have suggested that phlebotomy induced reduction in body iron levels may improve insulin sensitivity in humans. However, no interventional studies have yet directly evaluated the effect of reducing iron intake or body iron levels on the risk of developing type 2 diabetes. Such studies are required to prove the causal relationship between moderate iron overload and diabetes risk.

High-molecular-weight adiponectin and incident ischemic stroke in postmenopausal women: a Women's Health Initiative Study.

BACKGROUND AND PURPOSE: Although low levels of adiponectin are associated with coronary heart disease and cardiovascular disease risk factors, it is unclear whether adiponectin levels are related to the risk of developing ischemic stroke. METHODS: We examined the relationship between baseline high-molecular-weight (HMW) adiponectin levels and incident ischemic stroke in postmenopausal women using data and specimens from the Hormones and Biomarkers Predicting Stroke Study, a case-control study nested within the Women's Health Initiative Observational Study. Included were 855 incident ischemic stroke cases and 855 control subjects matched for age, race-ethnicity, date of entry into the cohort, and follow-up time. ORs of incident ischemic stroke associated with baseline HMW adiponectin levels were calculated using conditional logistic regression modeling adjusting for body mass index, type 2 diabetes, hypertension, smoking, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, physical activity, C-reactive protein, and aspirin use. RESULTS: Lower levels of HMW adiponectin were significantly associated with type 2 diabetes, hypertension, higher body mass index, waist circumference, glucose, and insulin levels and lower high-density lipoprotein cholesterol levels. The distribution of incident stroke cases by HMW adiponectin quartiles was 49.9%, 50.5%, 50.7%, and 48.9%, respectively (P=0.96). Multivariable-adjusted ORs of stroke associated with the top 3 quartiles of HMW adiponectin versus the first quartile were 0.99 (95% CI, 0.71 to 1.37), 1.37 (0.99 to 1.91), and 1.25 (0.88 to 1.79), respectively (P trend=0.14). CONCLUSIONS: Despite moderate associations between HMW adiponectin and cardiovascular disease risk factors, we found no evidence of an association between HMW adiponectin levels and incident ischemic stroke in these postmenopausal women.

Hepatocyte growth factor and the risk of ischemic stroke developing among postmenopausal women: results from the Women's Health Initiative.

BACKGROUND AND PURPOSE: Hepatocyte growth factor (HGF) is a potent angiogenic factor and may play a role in the development and progression of atherosclerotic lesions, the underlying mechanism of cardiovascular disease. However, there have been no prospective studies examining the relationship between HGF levels and risk of stroke. METHODS: We conducted a nested case-control study (972 incident stroke cases and 1:1 age-matched and race-matched controls) to prospectively evaluate the association between plasma HGF and risk of ischemic stroke within the Women's Health Initiative Observational Study, a cohort of postmenopausal women aged 50 to 79 years. RESULTS: Baseline HGF levels were correlated positively with body mass index, systolic blood pressure, low-density lipoprotein cholesterol, insulin resistance, and inflammatory markers, such as C-reactive protein, and inversely with high-density lipoprotein cholesterol (all P<0.05). Baseline HGF levels were higher among cases than controls (geometric means, 601.8 vs 523.2 pg/mL; P=0.003). Furthermore, the risk of incident ischemic stroke was significantly greater among women in the highest vs lowest quartile of plasma HGF levels (OR, 1.46; 95% CI, 1.12-1.91; P(trend)=0.003) in a conditional logistic regression model that adjusted for body mass index. These results were only slightly attenuated after further adjustment for additional stroke risk factors (OR, 1.39; 95% CI, 1.04-1.85; P(trend)=0.023). CONCLUSIONS: Circulating levels of HGF are associated with an increased risk of incident ischemic stroke, independent of obesity and other risk factors for cardiovascular disease, among postmenopausal women aged 50 to 79 years.

Multifactorial intervention to reduce cardiovascular events in type 2 diabetes.

Type 2 diabetes is associated with a significantly increased risk of cardiovascular disease (CVD) morbidity and mortality. Although several clinical trials have evaluated the effects of interventions to reduce CVD risk in people with diabetes, such studies are primarily conducted to target individual risk factors such as hypertension, hyperglycemia, and dyslipidemia rather than using a multifactorial interventional approach. Existing clinical trial data suggest that intensive multifactorial interventions that target several important risk factors simultaneously result in a significantly greater risk reduction in CVD risk compared with single risk factor interventions. However, few studies have evaluated the efficacy and effectiveness of such interventions on CVD hard end points. A multidisciplinary team management of diabetes should focus on weight control, diet, physical activity, diabetes education, and adherence to pharmacotherapy. An individually tailored aggressive management program to reduce multiple CVD risk factors simultaneously has great potential to prevent CVD morbidity and mortality among patients with type 2 diabetes.

Alcohol consumption and the risk of coronary heart disease in postmenopausal women with diabetes: Women's Health Initiative Observational Study.

BACKGROUND: Although several observational studies have consistently reported an inverse association between moderate alcohol consumption and risk of coronary heart disease (CHD), it is yet not well established if this association also exists among people with type 2 diabetes. The aim of this study is to evaluate the association between the frequency and quantity of alcohol intake and the risk of developing CHD among postmenopausal women with diabetes. METHODS: We conducted a prospective cohort study, which included 3,198 women with self-reported diabetes and without any history of cardiovascular disease at baseline, in the Women's Health Initiative Observational Study. Alcohol intake was assessed by a semiquantitative food frequency questionnaire. The primary outcome of this study was CHD, which was validated by medical record review. Cox proportional hazards regression was used to estimate the hazard ratio (HR) for the association of alcohol intake and risk of incident CHD while adjusting for several potential confounders. RESULTS: During the 22,546 person-years of follow-up, there were 336 incident cases of CHD. Both frequency and quantity of alcohol intake were inversely associated with the risk of developing CHD. Compared to nondrinkers, the multivariable HRs across categories of frequency of alcohol consumption (or=2 drinks/week) were 0.89 (95% confidence intervals [CI]: 0.63, 1.26), 0.84 (95% CI: 0.56, 1.25) and 0.65 (95% CI: 0.43, 0.99), respectively (p for trend: 0.04). This association did not appear to differ based on the type of the alcoholic beverage consumed. CONCLUSIONS: Moderate alcohol consumption of postmenopausal women with type 2 diabetes may have a benefit on CHD similar to that seen in postmenopausal nondiabetic women. The potential risks of alcohol on noncardiac outcomes may need consideration when recommending alcohol to women with diabetes.

Elevated risk of type 2 diabetes and metabolic syndrome among Asians and south Asians: results from the 2004 New York City HANES.

OBJECTIVE: Although numerous studies have identified an elevated risk of diabetes or impaired fasting glucose among Asians, there are limited data examining variability in risk among Asian subpopulations. We estimated prevalence of diabetes (DM), metabolic syndrome (MS) and impaired fasting glucose (IFG), by race/ethnicity and by Asian subgroup. DESIGN, SETTINGS AND PARTICIPANTS: This study was conducted using the fasting subsample of the 2004 New York City Health and Nutrition Examination Survey (NYC HANES; n = 1,324), a local version of the NHANES. Using country of origin information, we constructed South Asian and other Asian categories. MAIN OUTCOME MEASURES: DM, MS and IFG. RESULTS: Age-standardized prevalence estimates of DM, MS and IFG were 10.8%, 13.3% and 21.4% among Whites, 16.1%, 12.0% and 32.4% among all Asians, and 35.4%, 17.7% and 15.9% among foreign-born South Asians, respectively. After adjusting for potential confounders, Asians had significantly higher odds of prevalent IFG (Adjusted odds ratio [AOR]:2.64; 95% confidence interval [CI]: 1.60-4.38) and MS (AOR:2.09; 95%CI: 1.19-3.68), compared to Whites. South Asians were more likely to have DM (AOR:4.88; 95%CI: 1.52-15.66) and MS (AOR:5.59; 95%CI: 1.69-18.50) compared to Whites, while other Asians were at increased prevalence of IFG (AOR:2.89; 95%CI: 1.65-5.07). CONCLUSION: Our findings suggest that the observed White/Asian disparity in DM risk may be primarily attributable to elevated risk among South Asians.

The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes.

This review addresses the possible role of the insulin-like growth factor (IGF)-axis in normal glucose homoeostasis and in the etiopathogenesis of type 2 diabetes. IGF-I, a peptide hormone, shares amino acid sequence homology with insulin and has insulin-like activity; most notably, the promotion of glucose uptake by peripheral tissues. Type 2 diabetes as well as pre-diabetic states, including impaired fasting glucose and impaired glucose tolerance, are associated cross-sectionally with altered circulating levels of IGF-I and its binding proteins (IGFBPs). Administration of recombinant human IGF-I has been reported to improve insulin sensitivity in healthy individuals as well as in patients with insulin resistance and type 2 diabetes. Further, IGF-I may have beneficial effects on systemic inflammation, a risk factor for type 2 diabetes, and on pancreatic beta-cell mass and function. There is considerable inter-individual heterogeneity in endogenous levels of IGF-I and its binding proteins; however, the relationship between these variations and the risk of developing type 2 diabetes has not been extensively investigated. Large prospective studies are required to evaluate this association.

Prevalence of Established Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus in the UK.

INTRODUCTION: The results of recently completed cardiovascular outcomes trials in patients with type 2 diabetes mellitus (T2DM) suggest that sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide (GLP) 1 receptor agonists have enhanced cardioprotective properties in patients with established cardiovascular disease (eCVD), but to a lesser degree in those without eCVD. SGLT2 inhibitors appear to be particularly beneficial in patients with heart failure. As recent data for the UK are lacking, we undertook to identify the percentage of T2DM patients with eCVD and heart failure in the UK. METHODS: This was a retrospective cohort study that utilized the Clinical Practice Research Datalink (CPRD) database in the UK. We included de-identified adult patients with T2DM with at least one encounter in the CPRD database between 1 January 2018 and 31 December 2018 in the analysis and extracted the full health records of these patients. eCVD was defined as myocardial infarction, stroke, unstable angina pectoris, coronary artery disease and peripheral artery disease. We further assessed the number of patients with heart failure. RESULTS: From the total of 148,803 patients with T2DM analyzed (53% were male; mean age was 65 years), 52,601 (35.4%) suffered from eCVD and 8650 (5.8%) suffered from heart failure (73.7% of patients with heart failure overlap with those with atherothrombotic eCVD). Glycated hemoglobin levels of < 7% were attained by 49.5% of patients (with eCVD, 49.7%; without eCVD, 49.3%) (p < 0.001). CONCLUSION: Approximately one-third of patients with T2DM in the UK have concomitant CVD. FUNDING: Merck Sharp & Dohme Corp., a subsidiary Merck & Co., Inc., Kenilworth, NJ, USA.

Insulin-like growth factor-(IGF)-axis, inflammation, and glucose intolerance among older adults.

Increasing evidence suggests that the insulin-like growth factor (IGF)-axis may play a role in glucose metabolism and may also be associated with systemic inflammation. The aim of this study was to evaluate the association of insulin-like growth factor-1 (IGF-I) and its binding proteins, IGFBP-1 and IGFBP-3, with glucose intolerance and inflammation among older adults. We conducted a cross-sectional analysis in a in a random subsample (n=922) of the Cardiovascular Health Study (CHS), a prospective cohort of men and women > or = 65 years. Mean IGFBP-1 levels were significantly lower in older adults with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and diabetes compared to those with normal fasting and post-load glucose. High IGFBP-1 was associated with a reduced prevalence of IGT and IFG; the multivariable OR between extreme quartiles of IGFBP-1 was 0.60 (95% CI: 0.37, 0.95; p-trend: 0.03) for IGT and 0.41 (95% CI: 0.26, 0.64; p-trend: <0.01) for IFG. We did not find any significant association between IGF-I and glucose intolerance in this study and the association for IGFBP-3 was less clear. However, low levels of IGF-I and IGFBP-3 were associated with increased levels of markers of inflammation including C-reactive protein and interleukin-6 levels. We conclude that among adults > or = 65 years, low IGFBP-1 levels are associated with increased prevalence of glucose intolerance. We did not confirm prior associations of low IGF-I with glucose intolerance in this cohort of older individuals.

Severity of hypoglycaemia and health-related quality of life, work productivity and healthcare costs in patients with type 2 diabetes in Europe.

AIMS: Hypoglycaemia in patients with type 2 diabetes mellitus (T2DM) is associated with poor health outcomes, such as reduced health-related quality of life (HRQoL). This study aimed to assess the impact of hypoglycaemic events by severity on HRQoL, work productivity and healthcare costs in patients with T2DM. MATERIALS AND METHODS: European patients with T2DM selected from the National Health and Wellness Survey who were currently receiving pharmacologic therapy were stratified into 3 groups based on the reported history and severity of hypoglycaemic events (no event, nonsevere, severe) experienced in the previous 3 months. Patients' work productivity, HRQoL, healthcare resource use (HCRU) and associated costs were assessed as self-reported outcomes. RESULTS: Of 1269 patients included in the study, 652 (51.4%) patients had not experienced an event, while 533 (42.0%) and 84 (6.6%) patients had experienced nonsevere and severe hypoglycaemic events, respectively, in the previous 3 months. An increase in hypoglycaemia severity was associated with a decrease in HRQoL, and an increase in HCRU and healthcare costs. CONCLUSIONS: The impact of hypoglycaemia varies by severity and has a negative impact on HRQoL and overall HCRU and costs.

Effect of Medication Copayment on Adherence and Discontinuation in Medicare Beneficiaries with Type 2 Diabetes: A Retrospective Administrative Claims Database Analysis.

INTRODUCTION: Nonadherence to antihyperglycemic agents (AHAs) increases the incidence of morbidity and mortality, as well as healthcare-related costs, in patients with type 2 diabetes (T2D). This study examined the association between medication copayment and adherence and discontinuation among elderly patients with T2D who use generic versus branded AHAs. METHODS: A retrospective, observational cohort study used Medicare administrative claims data (index period: 1 June 2012 to 31 December 2013). Drug copayments were measured as the copayment of the index medication for a 30-day supply after patients met their plan deductible. Patients were stratified into a branded or generic cohort based on the index medication. Adherence was measured by the proportion of days covered (≥ 80%) and discontinuation by a treatment gap of > 60 days in 10 months during the follow-up period. Poisson regressions were conducted for medication adherence and discontinuation, while controlling for demographic, clinical, and comorbid conditions. RESULTS: Overall, 160,250 patients on AHA monotherapy were included in the analysis; 131,594 (82%) were prescribed a generic and 28,656 (18%) a branded AHA with a mean copay of $6 and $41, respectively. Increases in copayment increased nonadherence and discontinuation for branded medications but not for generic AHA medications. In both cohorts, elderly patients (≥ 75 years of age) had a lower risk of nonadherence and discontinuation. Black patients had a higher risk of nonadherence or discontinuing medication. Patients having more frequent inpatient, emergency room, and/or physician visits were at higher risk of nonadherence or discontinuing therapy in the branded and generic cohorts (P < 0.001). CONCLUSION: The impact of drug copayment on adherence and discontinuation varied considerably between branded and generic AHAs. Medicare patients taking branded AHAs had a higher risk of nonadherence with increasing copayment and were more likely to discontinue medication, whereas this association was not observed in patients taking generic medications. FUNDING: Merck & Co, Inc., Kenilworth, NJ, USA. Plain language summary available for this article.

Statin use and risk of developing diabetes: results from the Diabetes Prevention Program.

OBJECTIVE: Several clinical trials of cardiovascular disease prevention with statins have reported increased risk of type 2 diabetes (T2DM) with statin therapy. However, participants in these studies were at relatively low risk for diabetes. Further, diabetes was often based on self-report and was not the primary outcome. It is unknown whether statins similarly modify diabetes risk in higher risk populations. RESEARCH DESIGN AND METHODS: During the Diabetes Prevention Program Outcomes Study (n=3234), the long-term follow-up to a randomized clinical trial of interventions to prevent T2DM, incident diabetes was assessed by annual 75 g oral glucose tolerance testing and semiannual fasting glucose. Lipid profile was measured annually, with statin treatment determined by a participant's own physician outside of the protocol. Statin use was assessed at baseline and semiannual visits. RESULTS: At 10 years, the cumulative incidence of statin initiation prior to diabetes diagnosis was 33%-37% among the randomized treatment groups (p=0.36). Statin use was associated with greater diabetes risk irrespective of treatment group, with pooled HR (95% CI) for incident diabetes of 1.36 (1.17 to 1.58). This risk was not materially altered by adjustment for baseline diabetes risk factors and potential confounders related to indications for statin therapy. CONCLUSIONS: In this population at high risk for diabetes, we observed significantly higher rates of diabetes with statin therapy in all three treatment groups. Confounding by indication for statin use does not appear to explain this relationship. The effect of statins to increase diabetes risk appears to extend to populations at high risk for diabetes. TRIAL REGISTRATION NUMBER: NCT00038727; Results.

Calcium and dairy intakes in relation to long-term weight gain in US men.

BACKGROUND: The role of calcium in the maintenance of body weight remains controversial. OBJECTIVE: We investigated the association between calcium and dairy intakes and 12-y weight change in US men. DESIGN: This study was conducted with the use of data from the Health Professionals Follow-up Study, a prospective cohort of men aged 40-75 y in 1986. Data on lifestyle factors and diet were updated biennially with self-administered questionnaires. The participants reported their body weight in 1986 and in 1998. The outcome in our study was 12-y weight change. We used multivariate linear regression to examine how baseline calcium intake (n = 23,504) and change in calcium intake (n = 19,615) were associated with weight change. Because dairy foods are the predominant source of calcium in the diet, we also evaluated a similar association with dairy intake. RESULTS: In a multivariate analysis with adjustment for potential confounders, baseline or change in intake of total calcium was not significantly associated with weight change. In addition, we did not find any association with dietary, dairy, or supplemental calcium intake when evaluated separately. The men with the largest increase in total dairy intake gained slightly more weight than did the men who decreased intake the most (3.14 compared with 2.57 kg; P for trend = 0.001). This association was primarily due to an increase in high-fat dairy intake. Low-fat dairy intake was not significantly associated with weight change. CONCLUSION: Our data do not support the hypothesis that an increase in calcium intake or dairy consumption is associated with lower long-term weight gain in men.