Use Of Glucose-lowering Medications Research Articles

Egg consumption is associated with a lower risk of type 2 diabetes in middle-aged and older men.

BACKGROUND/OBJECTIVESThis prospective study examined gender-specific associations between egg intake and the risk of developing type 2 diabetes using data from a large-scale cohort study.SUBJECTS/METHODSA total of 7,002 Korean adults (40–69 years) without type 2 diabetes at baseline were analyzed. Dietary intake was evaluated by a food frequency questionnaire administered at baseline (2001–2002) and the second follow-up examination (2005–2006). Type 2 diabetes was diagnosed as a fasting glucose concentration ≥ 126 mg/dL or current use of glucose-lowering medications or insulin injection. Multivariate Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident type 2 diabetes according to egg consumption or cholesterol intake.RESULTSDuring a 14-year follow up period, 857 subjects developed type 2 diabetes. In men, frequent egg intake (2- < 4 servings/week) was associated with a 40% lower risk of developing type 2 diabetes than infrequent egg intake (0- < 1 serving/week) (HR = 0.60, 95% CI: 0.37–0.97), whereas no association between egg intake and incidence of type 2 diabetes was observed in women (HR = 0.61, 95% CI: 0.27–1.37). There was no association between cholesterol intake and risk of incident type 2 diabetes in either men or women.CONCLUSIONSEgg consumption was inversely related to the risk of incident type 2 diabetes in men, but not in women, suggesting gender differences in the relationship between diet and disease risk.

Ethnic Differences in the Prevalence and Risk Factors of Diabetic Retinopathy: The Singapore Epidemiology of Eye Diseases Study

To evaluate the prevalence and risk factors for diabetic retinopathy (DR) in the Singapore Epidemiology of Eye Diseases (SEED) Study. Population-based, cross-sectional study. Persons of Malay, Indian, and Chinese ethnicity aged 40+ years, living in Singapore. Diabetes was defined as nonfasting plasma glucose ≥200 mg/dl (11.1 mmol/l), glycated hemoglobin A1c (HbA1c) >6.5%, self-reported physician-diagnosed diabetes, or the use of glucose-lowering medication. Retinal photographs, were graded for the presence and severity of DR using the modified Airlie House classification system. Diabetic retinopathy, diabetic macular edema (DME), vision-threatening diabetic retinopathy (VTDR), defined as the presence of severe nonproliferative or proliferative DR, or clinically significant macular edema (CSME). Of the 10 033 subjects, 2877 (28.7%) had diabetes and gradable photographs for analysis. The overall age-standardized prevalence (95% confidence interval [CI]) was 28.2% (25.9-30.6) for any DR, 7.6% (6.5-9.0) for DME, and 7.7% (6.6-9.0) for VTDR. Indians had a higher prevalence of any DR (30.7% vs. 26.2% in Chinese and 25.5% in Malays, P= 0.012); a similar trend was noted for any DME (P= 0.001) and CSME (P= 0.032). Independent risk factors for any DR were Indian ethnicity (odds ratio [OR], 1.41; 95% CI, 1.09-1.83, vs. Chinese), diabetes duration (OR, 1.10; 95% CI, 1.08-1.11, per year), HbA1c (OR, 1.25; 95% CI, 1.18-1.32, per %), serum glucose (OR, 1.03; 95% CI, 1.00-1.06, per mmol/l), and systolic blood pressure (OR, 1.14; 95% CI, 1.09-1.19, per 10 mmHg). Diastolic blood pressure (OR, 0.74; 95% CI, 0.65-0.84, per 10 mmHg increase), total cholesterol (OR, 0.87; 95% CI, 0.80-0.95, per mmol/l increase), and low-density lipoprotein (LDL) cholesterol (OR, 0.83; 95% CI, 0.74-0.92, per mmol/l increase) were associated with lower odds of any DR. Risk factors were largely similar across the 3 ethnic groups. Indian Singaporeans have a higher prevalence of DR and DME compared with Chinese and Malays. Major risk factors for DR in this study were similar across the 3 ethnic groups. Addressing these risk factors may reduce the impact of DR in Asia, regardless of ethnicity.

Diabetes and CKD in the United States Population, 2009-2014.

Diabetes is an important cause of CKD. However, among people with diabetes, it is unclear to what extent CKD is attributable to diabetes itself versus comorbid conditions, such as advanced age and hypertension. We examined associations of diabetes with clinical manifestations of CKD independent of age and BP and the extent to which diabetes contributes to the overall prevalence of CKD in the United States. We performed a cross-sectional study of 15,675 participants in the National Health and Nutrition Examination Surveys from 2009 to 2014. Diabetes was defined by use of glucose-lowering medications or hemoglobin A1c ≥6.5%. eGFR was calculated using the CKD Epidemiology Collaboration formula, and albumin-to-creatinine ratio was measured in single-void urine samples. We calculated the prevalence of CKD manifestations by diabetes status as well as prevalence ratios, differences in prevalence, and prevalence attributable to diabetes using binomial and linear regression, incorporating data from repeat eGFR and urine albumin-to-creatinine ratio measurements to estimate persistent disease. For participants with diabetes (n=2279) versus those without diabetes (n=13,396), the estimated prevalence of any CKD (eGFR<60 ml/min per 1.73 m2; albumin-to-creatinine ratio ≥30 mg/g, or both) was 25% versus 5.3%, respectively; albumin-to-creatinine ratio ≥30 mg/g was 16% versus 3.0%, respectively; albumin-to-creatinine ratio ≥300 mg/g was 4.6% versus 0.3%, respectively; eGFR<60 ml/min per 1.73 m2 was 12% versus 2.5%, respectively; and eGFR<30 ml/min per 1.73 m2 was 2.4% versus 0.4%, respectively (each P<0.001). Adjusting for demographics and several aspects of BP, prevalence differences were 14.6% (P<0.001), 10.8% (P<0.001), 4.5% (P<0.001), 6.5% (P<0.001), and 1.8% (P=0.004), respectively. Approximately 24% (95% confidence interval, 19% to 29%) of CKD among all United States adults was attributable to diabetes after adjusting for demographics. Diabetes is strongly associated with both albuminuria and reduced GFR independent of demographics and hypertension, contributing substantially to the burden of CKD in the United States.

Adiposity, Prediabetes and Diabetes in Foreign versus Native Blacks in the United States

IntroductionBlacks in the United States (U.S.) face a disproportionately high burden of diabetes. The foreign‐born are a growing subgroup of blacks who have had unique environmental exposures. Possible heterogeneity in adiposity and dysglycemia (diabetes and prediabetes) between native and foreign blacks is understudied. This is in large part due to the paucity of datasets with biochemical assessment of disease, anthropometric measures and an adequate sample size of foreign‐born blacks. Pooling two national studies, we created a large dataset of U.S. blacks to examine differences in diabetes and prediabetes by nativity, and the contribution of adiposity in explaining these differences.MethodsWe concatenated data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort with five cycles of the National Health and Nutrition Examination Survey (NHANES) 2005–2014, restricting our analysis to those self‐identifying as black. Diabetes was defined as previous physician diagnosis, use of glucose lowering medication, fasting glucose ≥ 126 mg/dL or non‐fasting glucose ≥ 200 mg/dL. Prediabetes was defined as fasting glucose 100–125 mg/dL and non‐fasting glucose 140–199 mg/dL. We compared Body Mass Index (BMI), Waist Circumference (WC), crude prevalence of diabetes and prediabetes by nativity using t‐tests and chi‐squared tests. Using polytomous regressions, we estimated the prevalence ratio of nativity on dysglycemia while adjusting for age and adiposity (BMI and WC). All models additionally control for data source to account for unmeasured differences in study methods.ResultsCharacteristics of native versus foreign blacks are presented in Table 1. Mean age and BMI were significantly lower in foreign black men and women than their native counterparts. Mean WC was significantly lower in foreign black men than native black men. Crude prevalence of diabetes and prediabetes was not significantly different by nativity. Associations of nativity with dysglycemia using native blacks as referent is presented in Figure 1. Adjusting for age and WC, the prevalence ratio of diabetes comparing foreign black women to native black women was statistically significant (PR= 1.22, 95% CI: 1.02, 1.45).ConclusionsThe crude prevalence of dysglycemia was similarly high in foreign‐born and native‐born blacks, even though foreign‐born blacks had significantly lower adiposity. This susceptibility in foreign blacks may be due to a heightened metabolic response to obesity or presence of other obesity‐unrelated risk factors. Further understanding of these factors can inform targeted prevention strategies. Characteristics of Native versus Foreign Blacks in a Pooled Sample from REGARDS and NHANES Men Native Black (n=5411) Foreign Black (n=228) p‐value Age (year) 61.90 (61.57, 62.22) 56.10 (54.13, 58.07) &lt;0.01 BMI (kg/m2) 29.14 (28.99, 29.29) 27.26 (26.69, 27.84) &lt;0.01 Waist circumference (cm) 100.3 (99.87, 100.70) 95.27 (93.77, 96.77) &lt;0.01 % Diabetes 32.45 (31.20, 33.70) 31.58 (25.55, 37.61) 0.78 % Prediabetes 18.28 (17.25, 19.31) 22.37 (16.96, 27.78) 0.12 Women Native Black (n=8191) Foreign Black (n=200) p‐value Age (year) 62.02 (61.77, 62.28) 56.35 (54.38, 58.31) &lt;0.01 BMI (kg/m2) 32.01 (31.85, 32.17) 30.26 (29.43, 31.09) &lt;0.01 Waist circumference (cm) 97.84 (97.50, 98.19) 96.31 (94.36, 98.26) 0.18 % Diabetes 29.80 (28.81, 30.79) 36.00 (29.35, 42.65) 0.06 % Prediabetes 16.65 (15.85, 17.46) 21.50 (15.81, 27.19) 0.07

Abstract P020: Predictors of Depressive Symptoms Across the Spectrum of Hyperglycemia: the Atherosclerosis Risk in Communities (ARIC) Study

Background: Determinants of depressive symptoms in older adults according to diabetes status have not been widely investigated. Here we examine correlates of depressive symptoms in persons without diabetes, with prediabetes, and with diagnosed diabetes. Methods: We used data from visit 5 (2011-2013) of the ARIC Study. Depressive symptoms were ascertained using the 11-item CES-D, with scores ≥9 indicating probable major depression, and via self-reported diagnosis of depression in the past 2 years. Diabetes was defined based on self-reported diagnosis or use of glucose lowering medication. We defined prediabetes as HbA1c of 5.7-6.4% in persons without diabetes. We examined demographic factors, markers of health status, and metrics of health care access as correlates of depressive symptoms. Prevalence ratios (PRs) were calculated using Poisson regression with robust variance estimation. Results: Among 6319 participants (mean age 76 years, 59% female, and 77% white), the prevalence of depressive symptoms in persons with prediabetes (8.6%) and diabetes (14.7%) was significantly higher than in persons with no diabetes (6.9%). Correlates of depressive symptoms were similar across diabetes categories. In fully adjusted models, the strongest predictors of depressive symptoms were self-reported fair or poor health (compared to excellent health) and variables related to access to, and satisfaction with, health care. In persons with diabetes, insulin use, but not HbA1c control, was significantly associated with depressive symptoms. Measures of socioeconomic status (education, income) were significantly associated with depressive symptoms in all three groups (Table). Conclusions: The strongest predictors of depressive symptoms were metrics of health care access and satisfaction, suggesting that system-level factors may be important in addressing depression in diabetes and prediabetes.

Abstract P049: Mitochondrial DNA Copy Number and Diabetes in the ARIC Study

Introduction: In the United States, the rising number of adults with type 2 diabetes (T2D) is thought to be associated with the rise in obesity. Obesity may be associated with T2D through biologic pathways where excess weight strains the body’s metabolic machinery, such as mitochondria. Mitochondria are dynamic organelles whose regulation and function respond to cell stress, such as insulin resistance. Previous research reveals that insulin resistance is associated with obesity prior to hyperglycemia. Mitochondrial DNA copy number is a measure of mitochondrial DNA content, and correlates with both the number and size of mitochondria. We assessed the hypothesis that mitochondrial DNA copy number is associated with T2D in a community-based, prospective cohort study. A lower mitochondrial DNA copy number in these analyses represents worse mitochondrial function. Methods: We included 6,633 white ARIC participants without coronary heart disease who had mitochondrial DNA copy number measured from visit 2 (1990-1992). Our sample had a mean age of 57 ± 5.6 years, was 43% male, average BMI of 27 ± 4.9 kg/m2, and 27% with hypertension. Those with diabetes had an average hemoglobin A 1c of 7.2 ± 1.8 (n=681). The mitochondrial DNA copy number value used in analyses represents a sample’s standard deviation (SD) from a mean of zero for age- and sex-adjusted distributions. The mitochondrial DNA copy number data was then divided into quintiles, with the most negative mitochondrial DNA copy number in quintile 1 (Q1), the mean of zero in Q3, and the most positive in Q5. We defined T2D as self-report of doctor diagnosis, current use of glucose-lowering medication, or fasting blood glucose ≥ 126 mg/dL or non-fasting blood glucose ≥ 200 mg/dL measured at study visits. We used logistic regression to estimate the odds of prevalent T2D for each quintile group compared to Q3. Confounders considered in the base model included age at sample collection, sex, education level, and medication use (thyroid and estrogen). All analyses were done in Stata 14.1. Results: The prevalence of T2D was higher in the lower mitochondrial DNA copy number quintiles: 15% in Q1 (mean copy number: -1.40 SD) 11% in Q2 (-0.46 SD), and 9% in Q3-Q5 (0.04 SD, 0.52 SD, 1.33 SD). There was increased odds of T2D in lower mitochondrial DNA copy number quintiles, but with no additional benefit of copy number above the mean. The odds of T2D in each quintile compared to Q3 was 1.9 in Q1 (95% CI 1.49, 2.46), 1.36 in Q2 (95% CI 1.05, 1.77), 0.99 in Q4 (95% CI 0.76, 1.30) and 0.96 in Q5 (95% CI 0.74, 1.26). Conclusion: Examining the association of mitochondrial dysfunction and diabetes in a large community-based cohort connects results from experimental studies to epidemiologic studies and provides the opportunity to characterize the complex pathogenesis of diabetes using cohort data.

Comparison of use of diabetic medication and clinical guidelines in four Nordic countries

Background Clinical guidelines form one of the cornerstones for providing high-quality care for patients with diabetes. We compare the national guidelines and the use of glucose lowering medication for type 2 diabetes (T2D) in Denmark, Finland, Norway and Sweden.Methods We compared how guidelines take comprehensive care into consideration, what treatment targets and what antihyperglycemic medication was recommended. The use of glucose-lowering medication was based on the sales of diabetes drugs in these countries.Results All guidelines stress the importance of comprehensive diabetes care. Individualized glycemic targets are emphasized especially in the Danish and Finnish guidelines. In 2013, sulfonylureas were the most common second-line treatment after metformin in Denmark, Norway and Sweden; in Finland, this position was taken by DPP-4 inhibitors. Recommended initial insulin type for patients with T2D differs between the four countries. Danish, Norwegian and Swedish guidelines also take economic aspects into account.Conclusions All guidelines stress regular and comprehensive diabetes care. Danish and Finnish guidelines strongly underline the importance of individualized glycemic targets. All guidelines recommend metformin as the initial oral antihyperglycemic drug. In relation to recommended second line drug therapy and initial insulin type for patients with T2D, the guidelines vary largely between the four countries. Key messagesAll Nordic guidelines for treating type 2 diabetes stress the importance of comprehensive care.The Danish and Finnish guidelines underline the importance of individualized glycemic targets.The first line and most commonly used oral antihyperglycemic drug is metformin in all four countries.Recommended second line antihyperglycemic treatment differs largely between the four Nordic guidelines.Recommended initial insulin type for patients with T2D differs between the guidelines.

Strategies for glucose control in a study population with diabetes, renal disease and anemia (Treat study)

Glucose lowering medication use among patients with type 2 diabetes and advanced renal disease (eGFR<60) in a large multinational outcome trial (TREAT) is assessed. We demonstrate statistically significant differences regionally in use of metformin at lower eGFR and increasing reliance upon insulin with/without other medications at low eGFR. IntroductionAs renal disease advances, most of the oral anti-diabetic agents requiring renal clearance must be reduced or discontinued. The potential for prolonged hypoglycemia, fluid/volume overload and congestive heart failure may complicate medication choices. In order to evaluate patterns of glycemia management we describe glucose lowering medication use among patients with advanced renal disease and type 2 diabetes in a large multinational outcome trial designed to focus on patients with eGFR<60 in order to commence a dialog on best practices. We felt that analysis of this data would be able to describe regional variations in treatment within a multinational trial in order to understand potential outcome differences attributed to complications. ResultsThe patients entering this study had moderate glycemic control. Insulin therapy either alone (32%) or in combination with other agents (17%) reflected a shift towards insulin use in those subjects with decreased renal function when compared with standard populations with normal kidney function. The use of multiple oral agents, or oral agents plus insulin was quite common. While gender did not appear to play a role in medication choices, there were significant regional variations. For example, oral agents were used more in North America compared with other regions (Latin America, Australia/Western Europe, Russia/Eastern Europe). Patients enrolled at more advanced ages were less likely to be on a regimen of rapid-acting insulin alone consistent with recommendations that suggest a preference for longer-acting preparations in the geriatric population (1). Higher degrees of obesity were associated more complex treatment regimens. Despite this population being at high risk for cardiovascular events, the use of beta blockers (50%), statins (64%) and aspirin (48%) were relatively low, especially in the group that did not require medications to achieve adequate glycemic control. ConclusionsCurrent attempts to compare strategies for diabetes therapy must control for baseline demographic group differences influencing treatment choice. Future recommendations for glycemic control in patients with Grade 3 or higher chronic kidney disease require additional studies, with matched populations. We suggest that evaluation of studies similar to TREAT will assist in determining the optimal therapeutic regimens for populations with moderate to severe renal dysfunction, a condition in which repeated hospitalizations for fluid overload/heart failure add to the high cost of diabetes care.

PDB14 - Patterns of Pharmacological Treatment in Type 2 Diabetes in France in 2013

With the introduction and delisting of some glucose-lowering medications, pharmacological treatments in T2D have changed in the recent years and details of the current drug use patterns are not known. This descriptive study aims to describe characteristics of patients with type 2 diabetes and patterns of use of antihyperglycemic agents in France in 2013. A random sample of ≈ 600,000 patients registered in the French national health insurances reimbursement database was used. Patients with diabetes were identified through their use of glucose-lowering medication and coding of hospital stays and long-standing condition insurance coverage in the database. Drug utilization pattern of antihyperglycemic agents were estimated considering prescriptions in Q4 2013 and compared to data from Q4 2007. Overall 28,708 patients with T2D (estimated database prevalence 4.5%, 8.8% in people aged 40 and over) were identified in 2013. Mean age was 67.5 (SD 12.9), 54.1% were male. In Q4, 41.2% of T2D pharmacologically treated patients received a monotherapy, 25.6% a dual therapy, 13.7% a multi-therapy and 19.5% an insulin therapy with or without other hypoglycemic agents. Compared to 2007 data, a slight but significant increasing trend toward combination therapies and insulin was observed. The use of metformin increased over time especially in monotherapy (66% among monotherapy in 2013 versus 50% in 2007). All thiazolidinediones and some sulfonylureas treatments were replaced by DPP-4 inhibitors and to a much lesser extent with GLP-1 analogues. Antihyperglycemic prescription patterns in France have changed in recent years in parallel with the introduction of different classes of medications to the marketplace but probably also in an attempt to improve glycemic control of patients. Knowledge of real life pattern of drug utilization remains an important dimension to better understand therapeutic needs in T2D management.

Changing Patterns of Glucose-Lowering Medication Use in VA Nursing Home Residents With Diabetes, 2005 to 2011

ObjectiveAlthough nursing home (NH) residents make up a large and growing proportion of Americans with diabetes mellitus, little is known about how glucose-lowering medications are used in this population. We sought to examine glucose-lowering medication use in Veterans Affairs (VA) NH residents with diabetes between 2005 and 2011. Research Design and MethodsRetrospective cohort study, using linked laboratory, pharmacy, administrative, and NH Minimum Dataset (MDS) 2.0 databases in 123 VA NHs. A total of 9431 long-stay (>90 days) VA NH residents older than 65 followed for 52,313 person-quarters. We identified receipt of glucose-lowering medications, including insulin, metformin, sulfonylureas, thiazolidinediones, and others (alpha-glucosidase inhibitors, meglitinides, glucagonlike peptide-1 analogs, dipeptidyl peptidase-4 inhibitors and amylin analogs) per quarter. ResultsThe rates of sulfonylurea use in long-stay NH residents dropped dramatically from 24% in 2005 to 12% in 2011 (P < .001), driven in large part by the dramatic decrease in glyburide use (10% to 2%, P < .001). There was sharp drop in thiazolidinedione use in 2007 (4% to <1%, P < .001). Metformin use was stable, ranging between 7% and 9% (P = .24). Insulin use increased slightly from 30% to 32% (P < .001). Use of other classes of glucose-lowering medications was stable (P = .22) and low, remaining below 1.3%. Conclusions and RelevanceBetween 2005 and 2011, there were dramatic declines in use of sulfonylureas and thiazolidinediones in VA NH residents, suggesting that prescribing practices can be quickly changed in this setting.

The characteristic of cognitive function in Type 2 diabetes mellitus

AimTo identify characteristics of neuropsychological function among elderly individuals with Type 2 diabetes mellitus with mild cognitive impairment (T2DM-MCI) and evaluate domain-specific effects of T2DM on cognition. MethodsThis was a cross-sectional study conducted in Tianjin, China. MCI subjects (n=246) and controls were identified in elderly individuals with diabetes, and groups were matched in a 1:1 ratio for sex, age and educational level. Cognitive function was assessed using WAIS-III (block design, digit span), Trail Making Test A, Trail Making Test B, WMS-III (word list learning, logical memory), verbal fluency and MMSE. We used multivariable logistic regression to find diabetic factors associated with MCI. ResultsThe mean MMSE score was 22.73±2.32 in subjects with T2DM-MCI, versus 26.71±2.43 in subjects cognitive normal (P<0.001). Executive and visuospatial functions were more impaired in individuals with T2DM-MCI than in those without, as assessed using block design (P<0.001), digit span test (P<0.001), and Trails B (P<0.001). For memory, subjects with T2DM-MCI did worse than those cognitive normal on the word learning list delayed recall (P=0.015). Diabetic-related factors such as longer duration of T2DM, higher HbA1c, insulin treatment was associated with a lower level of cognitive functioning using MMSE, block design, delayed recall and Trails B test. ConclusionsT2DM should be considered a risk factor for MCI. This risk may be associated with duration of diabetes, use of glucose-lowering medications, degree of glucose control. To decrease risk of MCI, it is important to monitor glucose control and adjust medications appropriately in elderly patients.

Abstract P296: Racial Differences in Hyperglycemia: Comparative Prognostic Value of Traditional and Nontraditional Glycemic Markers

Background: Associations of nontraditional measures of hyperglycemia with clinical outcomes in blacks and whites are unknown and could help address the debate over race-specific cut-points for hemoglobin A1c (HbA1c). Methods: We included 9,434 white and 2,898 black participants from the ARIC Study with measures of HbA1c, fructosamine, glycated albumin and 1,5-anhydroglucitol (1,5-AG) at visit 2 (1990-92). Diagnosed diabetes was defined by self-reported physician diagnosis of diabetes or glucose-lowering medication use. We created cut-points for the nontraditional markers corresponding to accepted HbA1c clinical cut-points. For each glycemic marker, we used Cox models to assess adjusted associations with incident coronary heart disease (CHD), ischemic stroke, heart failure and end-stage renal disease (ESRD) through 2011; and logistic regression for concurrent retinopathy. We included an interaction term for category of glycemia and race. Results: Median levels in blacks versus whites without diagnosed diabetes were 5.7 and 5.4% for HbA1c; 234 and 225 μmol/L for fructosamine; 13.3 and 12.5% for glycated albumin; and 17.3 and 19.0 μg/mL for 1,5-AG, respectively. Median levels in blacks versus whites with diagnosed diabetes were 8.8 and 7.4% for HbA1c; 344 and 292 μmol/L for fructosamine; 22.5 and 17.7% for glycated albumin; and 3.5 and 6.6 μg/mL for 1,5-AG, respectively. Associations of hyperglycemia, as assessed by different glycemic markers, with CHD and ESRD were similar by race (p-values for interaction &gt;0.20, Figure ). Results were similar for stroke, heart failure and retinopathy (p-values for interaction &gt;0.10). Conclusions: Blacks had consistently higher levels of glycemia than whites as assessed by higher HbA1c, fructosamine, and glycated albumin, and lower 1,5-AG. However, associations of all glycemic markers with outcomes were similar by race. Our results support the use of similar clinical cut-points for diagnosis and management of diabetes using HbA1c in blacks and whites.

Characterization of metabolic syndrome among diverse Hispanics/Latinos living in the United States: Latent class analysis from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Background/objectivesEmpirical investigation of the adequacy of metabolic syndrome (MetS) diagnostic criteria, and whether meaningful subtypes of MetS exist, is needed among Hispanics/Latinos. MethodsIn 15,825 US Hispanics/Latinos from HCHS/SOL, latent class analysis of MetS components (waist circumference, systolic and diastolic blood pressure, HDL cholesterol, triglycerides, glucose, and antihypertensive, lipid- and glucose-lowering medication use) was used to investigate (1) whether distinct subtypes of MetS could be identified, and how component levels differed between them, and (2) how identified subtypes related to covariates and cardiovascular disease (CVD) prevalence. ResultsTwo latent clusters emerged in both men (n=6317) and women (n=9508): one characterized by relatively healthy mean levels (Non-MetS cluster, 77.1% of men and 67.1% of women) and the other by clinically elevated mean levels (MetS cluster, 22.9% of men and 32.9% of women) across most MetS components. These clusters showed expected associations with covariates and CVD prevalence. Notable results suggest that (1) HDL cholesterol may poorly differentiate between US Hispanics/Latinos with and without MetS (mean=45.4 vs. 44.6mg/dL for men and 51.3 vs. 52.0mg/dL for women in the MetS vs. Non-MetS clusters, respectively) and (2) the NCEP-ATP III 88cm waist circumference cutoff for US females may not optimize diagnosis among Hispanic/Latino women (MetS cluster mean waist circumference=102.5cm). ConclusionsBeyond classification into having MetS or not, additional subtypes of MetS do not clearly emerge in US Hispanics/Latinos. Current diagnostic cutoffs for some components may not optimize MetS identification among this population.

Statins and glycaemic control in individuals with diabetes: a systematic review and meta-analysis.

Current evidence indicates that statins increase the risk of incident diabetes; however, the relationship between statins and glycaemic control in people with established diabetes has not been well characterised. To address this question, we conducted a meta-analysis of randomised controlled trials (RCTs) of statins in patients with diabetes for whom there was available data on glycaemic control. We identified studies published between January 1970 and November 2013 by searching electronic databases and reference lists. We included RCTs in which the intervention group received statins and the control group received placebo or standard treatment, with >200 participants enrolled, with the intervention lasting >12 weeks and with pre- and post-intervention HbA1c reported. We combined study-specific estimates using random-effects model meta-analysis. In a pooled analysis of nine trials involving 9,696 participants (4,980 statin, 4,716 control) and an average follow-up of 3.6 years, the mean HbA1c of participants randomised to statins was higher than those randomised to the control group: mean difference (95% CI) was 0.12% (0.04, 0.20) or 1.3 mmol/mol (0.4, 2.2); p = 0.003. There was moderate heterogeneity across the studies (I (2) = 54%, p = 0.014) not explained by available study-level characteristics. This review was limited by the small number of studies, available data on only three statins and sparse reporting on changes in use of glucose-lowering medications. Statin treatment is associated with a modest increase in HbA1c in patients with diabetes.

Detection bias may be the main cause of increased cancer incidence among diabetics: Results from the Rotterdam Study

AimType 2 diabetes is associated with an increased cancer risk. Most studies on this topic analyse diabetes as a risk factor without adjusting for diabetes duration before cancer occurrence. This study aimed to investigate the association between diabetes duration and cancer risk in more detail. MethodsIn this prospective cohort study, diabetes diagnosis was based on clinical information and use of glucose lowering medication. Details on incident cancers were obtained via general practitioners and linkage to pathology registers. Cox proportional hazards models were used with onset and duration of diabetes as time-varying determinants. ResultsThe study comprised 10,181 individuals. Diabetes was associated with an increased overall risk of incident cancers (hazard ratio (HR) 1.2, 95% confidence interval (CI) 1.07–1.39) and pancreatic cancer (HR 2.9, 95% CI 1.75–4.89). A diagnosis of diabetes less than three months before the diagnosis of cancer was associated with strongly increased risks of all- (HR 3.3, 95% CI 2.50–4.32) and pancreatic cancers (HR 28.7, 95% CI 6.32–130.58). ConclusionThe magnitude of the association between diabetes and an increased risk of cancer seems to be inflated by detection- or protopathic bias. Future studies investigating this association should adjust for diabetes duration and include a plausible aetiological risk window.

Bariatric Surgery versus Intensive Medical Therapy for Diabetes — 3-Year Outcomes

BackgroundIn short-term randomized trials (duration, 1 to 2 years), bariatric surgery has been associated with improvement in type 2 diabetes mellitus.MethodsWe assessed outcomes 3 years after the randomization of 150 obese patients with uncontrolled type 2 diabetes to receive either intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy. The primary end point was a glycated hemoglobin level of 6.0% or less.ResultsThe mean (±SD) age of the patients at baseline was 48±8 years, 68% were women, the mean baseline glycated hemoglobin level was 9.3±1.5%, and the mean baseline body-mass index (the weight in kilograms divided by the square of the height in meters) was 36.0±3.5. A total of 91% of the patients completed 36 months of follow-up. At 3 years, the criterion for the primary end point was met by 5% of the patients in the medical-therapy group, as compared with 38% of those in the gastric-bypass group (P<0.001) and 24% of those in the sleeve-gastrectomy group (P=0.01). The use of glucose-lowering medications, including insulin, was lower in the surgical groups than in the medical-therapy group. Patients in the surgical groups had greater mean percentage reductions in weight from baseline, with reductions of 24.5±9.1% in the gastric-bypass group and 21.1±8.9% in the sleeve-gastrectomy group, as compared with a reduction of 4.2±8.3% in the medical-therapy group (P<0.001 for both comparisons). Quality-of-life measures were significantly better in the two surgical groups than in the medical-therapy group. There were no major late surgical complications.ConclusionsAmong obese patients with uncontrolled type 2 diabetes, 3 years of intensive medical therapy plus bariatric surgery resulted in glycemic control in significantly more patients than did medical therapy alone. Analyses of secondary end points, including body weight, use of glucose-lowering medications, and quality of life, also showed favorable results at 3 years in the surgical groups, as compared with the group receiving medical therapy alone. (Funded by Ethicon and others; STAMPEDE ClinicalTrials.gov number, NCT00432809.)

Risk of cancer and use of glucose-lowering medications: The DIABMON project.

e12508 Background: Efficacy of glucose-lowering medications is demonstrated in clinical trials but effectiveness in practice depends on a number of factors including the safety profile. Methods: A ...

Type 2 diabetes mellitus, glycemic control, and cancer risk

Type 2 diabetes mellitus is characterized by prolonged hyperinsulinemia, insulin resistance, and progressive hyperglycemia. Disease management relies on glycemic control through diet, exercise, and pharmacological intervention. The goal of the present study was to examine the effects of glycemic control and the use of glucose-lowering medication on the risk of breast, prostate, and colon cancer. Patients diagnosed with type 2 diabetes mellitus (N=9486) between 1 January 1995 and 31 December 2009 were identified and data on glycemic control (hemoglobin A1c, glucose), glucose-lowering medication use (insulin, metformin, sulfonylurea), age, BMI, date of diabetes diagnosis, insurance status, comorbidities, smoking history, location of residence, and cancer diagnoses were electronically abstracted. Cox proportional hazards regression modeling was used to examine the relationship between glycemic control, including medication use, and cancer risk. The results varied by cancer type and medication exposure. There was no association between glycemic control and breast or colon cancer; however, prostate cancer risk was significantly higher with better glycemic control (hemoglobin A1c ≤ 7.0%). Insulin use was associated with increased colon cancer incidence in women, but not with colon cancer in men or breast or prostate cancer risk. Metformin exposure was associated with reduced breast and prostate cancer incidence, but had no association with colon cancer risk. Sulfonylurea exposure was not associated with risk of any type of cancer. The data reported here support hyperinsulinemia, rather than hyperglycemia, as a major diabetes-related factor associated with increased risk of breast and colon cancer. In contrast, hyperglycemia appears to be protective in the case of prostate cancer.

Abstract P433: Associations of CD4+ T Lymphocyte Subpopulations with Insulin Levels and Type 2 Diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Chronic inflammation is a characteristic feature of insulin resistance (IR) and type 2 diabetes (T2D). Elevated circulating levels of pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β) and interleukin-6 (IL-6), are predictive of disease onset suggesting contributions of adaptive immune responses in the etiology of T2D. Therefore, we hypothesized that increased populations of CD4 + effector/memory (EM) and T helper 1 (Th1) cells, and decreased populations of CD4 + naive cells, would be associated with high insulin levels and an increased risk of T2D. Methods: T cell subpopulations were measured in peripheral blood by flow cytometry, using CD4 + CD45RO + , CD4 + CD45RA + , CD4 + IFN-γ + , and CD4 + IL4 + as markers for EM, naive, Th1, and Th2 cells, respectively. Data for each subpopulation were reported as a percent of total CD4 + cells. Associations were explored with components of the metabolic syndrome, insulin measures, and type 2 diabetes in a random subset ( n =917) of the Multi-Ethnic Study of Atherosclerosis (MESA). T2D was defined by fasting glucose ≥126 mg/dL or use of glucose-lowering medications ( n =151). All variables were measured at Exam 4 (2005-2007), except for insulin which was measured at Exam 5 (2010-2012), and inflammatory biomarkers measured at Exam 1 (2000-2002). Results: Naive cells were inversely, and EM, and Th1 cells positively associated with insulin levels in minimally adjusted (age, gender, race/ethnicity) linear regression analyses that modeled insulin as the dependent variable. No significant associations were observed with Th2 cells. After further adjustment for the metabolic- and cardiovascular disease (CVD)-related variables, waist circumference, systolic blood pressure (BP), use of anti-hypertensive medication, smoking status, total- and HDL-cholesterol, use of lipid lowering medication, and IL-6, the association of insulin with Th1 cells, but not naive or EM cells, remained significant [β= 6.4 mU/L (± 1.69 mU/L) per standard deviation (SD) increase in Th1 cells (8.3%); p=0.0002]. Adjusting for body mass index (BMI) in place of waist circumference did not alter interpretation of the results. In standardized logistic regression models including cell subpopulations and metabolic- and CVD-related variables (as above) as the independent variables, naive cells were inversely associated with prevalent T2D [odds ratio (95% confidence interval)=0.78 (0.61-0.99)]. Conclusion: Increased populations of Th1 cells and decreased populations of CD4 + naive cells are associated with insulin levels and T2D, respectively, independent of measures of adiposity. These cross-sectional findings suggest that excess immune activation and Th1 bias, as reflected by these differences, may contribute to the etiology of IR and T2D.

Metabolic markers or conditions preceding Parkinson's disease: A case‐control study

Several metabolic markers or conditions have been explored as possible risk or protective factors for Parkinson's disease (PD); however, results remain conflicting. We further investigated these associations using a case-control study design. We used the medical records-linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, Minnesota, from 1976 through 1995. Each incident case was matched by age (±1 year) and sex to a general population control. We reviewed the complete medical records of cases and controls in the medical records-linkage system to abstract information about body mass index (BMI), cholesterol level, hypertension, and diabetes mellitus preceding the onset of PD (or the index year). There were no significant differences between cases and controls for the metabolic markers or conditions investigated. No significant associations were found using 2 cutoffs for BMI level (BMI ≥ 25 or BMI ≥ 30 kg/m(2) ) and 3 cutoffs for cholesterol levels (>200, >250, or >300 mg/dL). Neither a diagnosis of hypertension or the documented use of antihypertensive medications was significantly associated with the subsequent risk of PD (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.65-1.54; P = .99) nor was a diagnosis of diabetes mellitus or the use of glucose-lowering medications (OR, 0.77; 95% CI, 0.37-1.57; P = .47). Our study, based on historical information from a records-linkage system, does not support an association between BMI, cholesterol level, hypertension, or diabetes mellitus with later development of PD.