Prevalence of and Factors Associated with Lens Opacities in a Korean Adult Population with and without Diabetes: The 2008–2009 Korea National Health and Nutrition Examination Survey

Objective

We examined the prevalence of and factors associated with lens opacities in a Korean adult population with and without diabetes.

Research Design and Methods

Among the 11,163 adults (≥19 years old) from the fourth Korea National Health and Nutrition Examination Survey in 2008–2009, the data from laboratory tests, nutritional surveys, and slit-lamp examinations of 10,248 persons (4,397 men, 5,851 women) were examined. Cataract was defined as the presence of any nuclear, cortical, subcapsular, or mixed cataract in at least one eye, using the Lens Opacities Classification System III.

Results

The weighted prevalence of cataracts were 23.5% [95% confidence interval (CI), 21.7–25.4] in a Korean adult population (19–39 years old, 1.8% [1.3–2.5], 40–64 years old, 25.2% [22.5–28.1],≥65 years old, 87.8% [85.4–89.9])and 54.7% [50.1–59.2] in a diabetic population(19–39 years old, 11.6% [4.5–26.5], 40–64 years old, 41.1% [35.4–47.0], ≥65 years old, 88.3% [83.5–91.8]). In a logistic regression analysis, age, myopia, and the presence of diabetes were independent risk factors. For young (age 19–39 years) and middle aged (age 40–65 years) adults with diabetes, the OR of having a lens opacity is 5.04 [1.41–17.98] and 1.47 [1.11–1.94], respectively, as those without diabetes, whereas for adults aged 65 and older, there was no difference in the prevalence of cataract.

Conclusions

According to these national survey data, ∼ 24% of Korean adults and ∼ 55% of people with diabetes have cataracts. The presence of diabetes was independently associated with cataracts in young and middle aged adults.     

Soluble α-Klotho as a Novel Biomarker in the Early Stage of Nephropathy in Patients with Type 2 Diabetes

Objective

Although α-klotho is known as an anti-aging, antioxidant, and cardio-renal protective protein, the clinical implications of soluble α-klotho levels in patients with diabetes have not been evaluated. Therefore, this study evaluated whether plasma and urinary α-klotho levels are associated with albuminuria in kidney disease in diabetes.

Research Design and Methods

A total of 147 patients with type 2 diabetes and 25 healthy control subjects were enrolled. The plasma and urine concentrations of α-klotho were analyzed by enzyme-linked immunosorbent assay.

Results

Plasma α-klotho (572.4 pg/mL [95% CI, 541.9–604.6 pg/mL] vs. 476.9 pg/mL [95% CI, 416.9–545.5 pg/mL]) and urinary α-klotho levels (59.8 pg/mg creatinine [95% CI, 43.6–82.0 pg/mg creatinine] vs. 21.0 pg/mg creatinine [95% CI, 9.7–45.6 pg/mg creatinine]) were significantly higher in diabetic patients than non-diabetic controls. Among diabetic patients, plasma α-klotho concentration was inversely associated with albuminuria stages (normoalbuminuria, 612.6 pg/mL [95% CI, 568.9–659.6 pg/mL], microalbuminuria, 551.8 pg/mL [95% CI, 500.5–608.3 pg/mL], and macroalbuminuria, 505.7 pg/mL [95% CI, 439.7–581.7 pg/mL] (p for trend  = 0.0081), while urinary α-klotho levels were remained constantly high with increasing urinary albumin excretion.

Conclusions

Soluble α-klotho levels in plasma and urine may be novel and useful early markers of diabetic renal injury.     

Rosiglitazone and Myocardial Infarction in Patients Previously Prescribed Metformin

Objective

Rosiglitazone was found associated with approximately a 43% increase in risk of acute myocardial infarction (AMI) in a two meta-analyses of clinical trials. Our objective is to estimate the magnitude of the association in real-world patients previously treated with metformin.

Research Design and Methods

We conducted a nested case control study in British Columbia using health care databases on 4.3 million people. Our cohort consisted of 158,578 patients with Type 2 diabetes who used metformin as first-line drug treatment. We matched 2,244 cases of myocardial infarction (AMI) with up to 4 controls. Conditional logistic regression models were used to estimate matched odds ratios for AMI associated with treatment with rosiglitazone, pioglitazone and sulfonylureas.

Results

In our cohort of prior metformin users, adding rosiglitazone for up to 6 months was not associated with an increased risk of AMI compared to adding a sulfonylurea (odds ratio [OR] 1.38; 95% confidence interval [CI], 0.91–2.10), or compared to adding pioglitazone (OR for rosi versus pio 1.41; 95% CI, 0.74–2.66). There were also no significant differences between rosiglitazone, pioglitazone and sulfonylureas for longer durations of treatment. Though not significantly different from sulfonylureas, there was a transient increase in AMI risk associated with the first 6 months of treatment with a glitazone compared to not using the treatment (OR 1.53; 95% CI, 1.13–2.07)

Conclusions

In our British Columbia cohort of patients who received metformin as first-line pharmacotherapy for Type 2 diabetes mellitus, further treatment with rosiglitazone did not increase the risk of AMI compared to patients who were treated with pioglitazone or a sulfonylurea. Though not statistically significantly different compared from each other, an increased risk of AMI observed after starting rosiglitazone or sulfonylureas is a matter of concern that requires more research.     

Impact of Glucose-Lowering Agents on the Risk of Cancer in Type 2 Diabetic Patients. The Barcelona Case-Control Study

Background

The aim of the present study is to evaluate the impact of glucose-lowering agents in the risk of cancer in a large type 2 diabetic population.

Methods

A nested case-control study was conducted within a defined cohort (275,164 type 2 diabetic patients attending 16 Primary Health Care Centers of Barcelona). Cases (n = 1,040) comprised those subjects with any cancer diagnosed between 2008 and 2010, registered at the Cancer Registry of Hospital Vall d''Hebron (Barcelona). Three control subjects for each case (n = 3,120) were matched by age, sex, diabetes duration, and geographical area. The treatments analyzed (within 3 years prior to cancer diagnosis) were: insulin glargine, insulin detemir, human insulin, fast-acting insulin and analogues, metformin, sulfonylureas, repaglinide, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and alpha glucosidase inhibitors. Conditional logistic regressions were used to calculate the risk of cancer associated with the use of each drug adjusted by age, BMI, dose and duration of treatment, alcohol use, smoking habit, and diabetes duration.

Results

No differences were observed between case and control subjects for the proportion, dose or duration of exposure to each treatment. None of the types of insulin and oral agents analyzed showed a significant increase in the risk of cancer. Moreover, no cancer risk was observed when glargine was used alone or in combination with metformin.

Conclusions

Our results suggest that diabetes treatment does not influence the risk of cancer associated with type 2 diabetes. Therefore, an eventual increase of cancer should not be a reason for biasing the selection of any glucose-lowering treatment in type 2 diabetic population.     

Cancer Incidence and Mortality in Patients with Type 2 Diabetes Treated with Human Insulin: A Cohort Study in Shanghai

Aim

The aim was to investigate the association between human insulin and cancer incidence and mortality in Chinese patients with type 2 diabetes.

Methods

We recruited 8,774 insulin-naïve diabetes patients from the Shanghai Diabetes Registry (SDR). The follow-up rate was 85.4%. All subjects were divided into the insulin use cohort (n = 3,639) and the non-insulin use cohort (n = 5,135). The primary outcome was the first diagnosis of any cancer. The secondary outcome was all-cause mortality. Cox proportional hazards model was used to estimate the relative risk (RR) of cancer and mortality.

Results

We observed 98 cancer events in the insulin use cohort and 170 in the non-insulin use cohort. Cancer incidence rates were 78.6 and 74.3 per 10,000 patients per year in the insulin users and the non-insulin users, respectively. No significant difference in cancer risk was observed between the two cohorts (adjusted RR = 1.20, 95% CI 0.89–1.62, P = 0.228). Regarding site-specific cancers, only the risk of liver cancer was significantly higher in the insulin users compared to that in the non-insulin users (adjusted RR = 2.84, 95% CI 1.12–7.17, P = 0.028). The risks of overall mortality (adjusted RR = 1.89, 95% CI 1.47–2.43, P<0.0001) and death from cancer (adjusted RR = 2.16, 95% CI 1.39–3.35, P = 0.001) were all significantly higher in the insulin users than in the non-insulin users.

Conclusion

There was no excess risk of overall cancer in patients with type 2 diabetes who were treated with human insulin. However, a significantly higher risk of liver cancer was found in these patients. Moreover, insulin users showed higher risks of overall and cancer mortality. Considering that individuals treated with insulin were more likely to be advanced diabetic patients, caution should be used in interpreting these results.     

Metformin Inhibits Glutaminase Activity and Protects against Hepatic Encephalopathy

Aim

To investigate the influence of metformin use on liver dysfunction and hepatic encephalopathy in a retrospective cohort of diabetic cirrhotic patients. To analyze the impact of metformin on glutaminase activity and ammonia production in vitro.

Methods

Eighty-two cirrhotic patients with type 2 diabetes were included. Forty-one patients were classified as insulin sensitizers experienced (metformin) and 41 as controls (cirrhotic patients with type 2 diabetes mellitus without metformin treatment). Baseline analysis included: insulin, glucose, glucagon, leptin, adiponectin, TNFr2, AST, ALT. HOMA-IR was calculated. Baseline HE risk was calculated according to minimal hepatic encephalopathy, oral glutamine challenge and mutations in glutaminase gene. We performed an experimental study in vitro including an enzymatic activity assay where glutaminase inhibition was measured according to different metformin concentrations. In Caco2 cells, glutaminase activity inhibition was evaluated by ammonia production at 24, 48 and 72 hours after metformina treatment.

Results

Hepatic encephalopathy was diagnosed during follow-up in 23.2% (19/82): 4.9% (2/41) in patients receiving metformin and 41.5% (17/41) in patients without metformin treatment (logRank 9.81; p = 0.002). In multivariate analysis, metformin use [H.R.11.4 (95% CI: 1.2–108.8); p = 0.034], age at diagnosis [H.R.1.12 (95% CI: 1.04–1.2); p = 0.002], female sex [H.R.10.4 (95% CI: 1.5–71.6); p = 0.017] and HE risk [H.R.21.3 (95% CI: 2.8–163.4); p = 0.003] were found independently associated with hepatic encephalopathy. In the enzymatic assay, glutaminase activity inhibition reached 68% with metformin 100 mM. In Caco2 cells, metformin (20 mM) decreased glutaminase activity up to 24% at 72 hours post-treatment (p<0.05).

Conclusions

Metformin was found independently related to overt hepatic encephalopathy in patients with type 2 diabetes mellitus and high risk of hepatic encephalopathy. Metformin inhibits glutaminase activity in vitro. Therefore, metformin use seems to be protective against hepatic encephalopathy in diabetic cirrhotic patients.     

Factors Associated with Beta-Cell Dysfunction in Type 2 Diabetes: The BETADECLINE Study

Aims

Beta-cell dysfunction is an early event in the natural history of type 2 diabetes. However, its progression is variable and potentially influenced by several clinical factors. We report the baseline data of the BetaDecline study, an Italian prospective multicenter study on clinical predictors of beta-cell dysfunction in type 2 diabetes.

Materials and Methods

Clinical, lifestyle, and laboratory data, including circulating levels of inflammatory markers and non-esterified fatty acids, were collected in 507 type 2 diabetic outpatients on stable treatment with oral hypoglycemic drugs or diet for more than 1 year. Beta-cell dysfunction was evaluated by calculating the proinsulin/insulin ratio (P/I).

Results

At baseline, the subjects in the upper PI/I ratio quartile were more likely to be men and receiving secretagogue drugs; they also showed a borderline longer diabetes duration (P = 0.06) and higher serum levels of glycated hemoglobin (HbA_1c), fasting blood glucose, and triglycerides. An inverse trend across all PI/I quartiles was noted for BMI and serum levels of total cholesterol (T-C), LDL-C, HDL-C and C reactive protein (CRP), and with homeostatic model assessment (HOMA-B) and HOMA of insulin resistance (HOMA-IR) values (P<0.05 for all). At multivariate analysis, the risk of having a P/I ratio in the upper quartile was higher in the subjects on secretagogue drugs (odds ratio [OR] 4.2; 95% confidence interval [CI], 2.6–6.9) and in the males (OR 1.8; 95% CI, 1.1–2.9).

Conclusions

In the BetaDecline study population, baseline higher PI/I values, a marker of beta-cell dysfunction, were more frequent in men and in patients on secretagogues drugs. Follow-up of this cohort will allow the identification of clinical predictors of beta-cell failure in type 2 diabetic outpatients.     

Diabetes in Cystic Fibrosis: Multicenter Screening Results Based on Current Guidelines

Background

Published estimates on age-dependent frequency of diabetes in cystic fibrosis (CF) vary widely, and are based mostly on older data. However, CF treatment and prevention of comorbidities changed over recent years. In many studies, definition of cystic fibrosis-related diabetes (CFRD) is not in line with current guideline recommendations. Therefore, we evaluated age-dependent occurrence of glucose abnormalities and associated risk factors in CF patients who participated in a multicenter screening program using oral glucose tolerance tests (OGTT).

Methods

Between 2001 and 2010, 43 specialized CF centers from Germany and Austria serially performed 5,179 standardized OGTTs in 1,658 clinically stable, non-pregnant CF patients with no prior steroid medication or lung transplantation. Age-dependent occurrence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG+IGT, one (DGT) or two consecutive (CFRD) diabetic OGTTs was analyzed, using Kaplan Meier curves. Cox proportional-hazards models were created to elucidate the influence of sex or underweight.

Results

At baseline/last OGTT, median age was 15.9 years/18.2 years and 30.6%/31.8% of patients were underweight. 25% of patients showed IFG at age 14.3 years; IGT at age 16.3 years; IFG+IGT combined at age 17.7 years. DGT was observed in 25% of patients at age 22.6 years; CFRD at age 34.5 years. Females had a 3.54 [95% CI 1.23–10.18] times higher risk for CFRD; risk for DGT was 2.21 [1.22–3.98] times higher. Underweight was a risk factor for IGT (HR [95% CI]: 1.38 [1.11–1.71]) and IFG+IGT (1.43 [1.11–1.83]), and in males also for DGT (1.49 [1.09–2.04]).

Conclusions/Significance

If confirmation of diabetes by a second test is required, as recommended in current guidelines, age at CFRD diagnosis was higher compared to most previous studies. However, known risk factors for glucose abnormalities in CF were confirmed. Confirmation of diabetic OGT by a repeat test is important for a consistent diagnosis of CFRD.     

Low Vitamin D Status Is Associated with Nonalcoholic Fatty Liver Disease Independent of Visceral Obesity in Korean Adults

Objective

To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and nonalcoholic fatty liver disease (NAFLD) independent of visceral obesity in Koreans and to examine whether the associations differ according to the presence of diabetes or insulin resistance.

Research Design and Methods

A total of 1081 adults were enrolled from a population-based cohort in Ansan city. Serum 25(OH)D concentrations were measured in all subjects. Insulin resistance was measured by homeostasis model assessment of insulin resistance (HOMA-IR). Using computed tomography, NAFLD was diagnosed if the liver attenuation index (LAI, the difference between the mean hepatic and splenic attenuation) was <5 Hounsfield Units.

Results

In subjects with diabetes (n = 282), 25(OH)D levels were negatively associated with waist circumference, fasting insulin, HOMA-IR, triglyceride levels, and visceral abdominal fat, and were positively associated with LAI after adjusting for age, sex, season, exercise, and vitamin supplementation. In subjects without diabetes, only triglyceride level was negatively associated with 25(OH)D. The adjusted odds ratio (OR) for NAFLD increased sequentially across decreasing quartiles of 25(OH)D in subjects with diabetes even after adjusting for visceral fat [Q1 vs. Q4; OR for NAFLD 2.5 (95% CI:1.0–6.2)]. In contrast, no significant difference in OR was observed in subjects without diabetes. When we classified non-diabetic subjects by HOMA-IR, an increase in the OR for NAFLD across decreasing quartiles of 25(OH)D was observed in the high HOMA-IR (≥2.5) group [n = 207, Q1 vs. Q4; OR 3.8(1.4–10.3)], but not in the low HOMA-IR (<2.5) group [n = 592, OR 0.8 (0.3–1.9)].

Conclusions

Low vitamin D status is closely associated with NAFLD, independent of visceral obesity in subjects with diabetes or insulin resistance.     

Mortality Associated with Diabetes and Cardiovascular Disease in Older Women

Background

Current guidelines for the prevention of cardiovascular disease (CVD) recommend diabetes as a CVD risk equivalent. However, reports that have examined the risk of diabetes in comparison to pre-existing CVD are lacking among older women. We aimed to assess whether diabetes was associated with a similar risk of total and cause-specific mortality as a history of CVD in older women.

Methodology/Principal Findings

We studied 9218 women aged 68 years or older enrolled in a prospective cohort study (Study of Osteoporotic Fracture) during a mean follow-up period of 11.7 years and compared all-cause, cardiovascular and coronary heart disease mortality among 4 groups: non-diabetic women with and without existing CVD, diabetic women with and without existing CVD. Mean (SD) age of the participants was 75.2 (5.3) years, 3.5% reported diabetes and 6.8% reported existing CVD. During follow-up, 5117 women died with 36% from CVD. The multivariate adjusted risk of cardiovascular mortality was increased among both non-diabetic women with CVD (hazard ratio (HR) 2.32, 95% CI: 1.97–2.74, P<0.001) and diabetic women without CVD (HR 2.06, CI: 1.62–2.64, P<0.001) compared to non-diabetic women without existing CVD. All-cause, cardiovascular and coronary mortality of non-diabetic women with CVD were not significantly different from diabetic women without CVD.

Conclusions/Significance

Older diabetic women without CVD have a similar risk of cardiovascular mortality compared to non-diabetic women with pre-existing CVD. The equivalence of diabetes and CVD seems to extend to older women, supporting current guidelines for cardiovascular prevention.     

Diabetic Patients with Severe Sepsis Admitted to Intensive Care Unit Do Not Fare Worse than Non-Diabetic Patients: A Nationwide Population-Based Cohort Study

Background

We sought to examine whether type 2 diabetes increases the risk of acute organ dysfunction and of hospital mortality following severe sepsis that requires admission to an intensive care unit (ICU).

Methods

Nationwide population-based retrospective cohort study of 16,497 subjects with severe sepsis who had been admitted for the first time to an ICU during the period of 1998–2008. A diabetic cohort (n = 4573) and a non-diabetic cohort (n = 11924) were then created. Relative risk (RR) of organ dysfunctions, length of hospital stay (LOS), 90-days hospital mortality, ICU resource utilization and hazard ratio (HR) of mortality adjusted for age, gender, Charlson-Deyo comorbidity index score, surgical condition and number of acute organ dysfunction, were compared across patients with severe sepsis with or without diabetes.

Results

Diabetic patients with sepsis had a higher risk of developing acute kidney injury (RR, 1.54; 95% confidence interval (CI), 1.44–1.63) and were more likely to be undergoing hemodialysis (15.55% vs. 7.24%) in the ICU. However, the diabetic cohort had a lower risk of developing acute respiratory dysfunction (RR = 0.96, 0.94–0.97), hematological dysfunction (RR = 0.70, 0.56–0.89), and hepatic dysfunction (RR = 0.77, 0.63–0.93). In terms of adjusted HR for 90-days hospital mortality, the diabetic patients with severe sepsis did not fare significantly worse when afflicted with cardiovascular, respiratory, hepatic, renal and/or neurologic organ dysfunction and by numbers of organ dysfunction. There was no statistically significant difference in LOS between the two cohorts (median 17 vs. 16 days, interquartile range (IQR) 8–30 days, p = 0.11). Multiple logistic regression analysis to predict the occurrence of mortality shows that being diabetic was not a predictive factor with an odds ratio of 0.972, 95% CI 0.890–1.061, p = 0.5203.

Interpretation

This large nationwide population-based cohort study suggests that diabetic patients do not fare worse than non-diabetic patients when suffering from severe sepsis that requires ICU admission.     

Human Insulin Does Not Increase Bladder Cancer Risk

Background

Whether human insulin can induce bladder cancer is rarely studied.

Methods

The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan) was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose) were calculated and the hazard ratios were estimated by Cox regression.

Results

There were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52%) and 3,330 (0.48%), and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122–1.366)], but not in the model adjusted for all covariates [1.063 (0.951–1.187)]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted.

Conclusions

This study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication.     

Diabetes Medication Use and Blood Lactate Level among Participants with Type 2 Diabetes: The Atherosclerosis Risk in Communities Carotid MRI Study

Background

The objective of this study is to compare lactate levels between users and non-users of diabetes medications under the hypothesis that the level of lactate is a marker of oxidative capacity.

Methods

The cross-sectional data of 493 participants aged 61–84 with type 2 diabetes who participated in the Atherosclerosis Risk in Communities Carotid MRI study were analyzed using survey weighted linear regression.

Results

Median plasma lactate level was 8.58 (95% CI: 8.23, 8.87) mg/dl. Comparing users of diabetic medications with non-users, thiazolidinedione use was significantly associated with lower lactate level (7.57 (6.95–8.25) mg/dL vs. 8.78 (8.43–9.14) mg/dL), metformin use with a slightly higher lactate level (9.02 (8.51–9.58) mg/dL vs. 8.36 (7.96–8.77) mg/dL), and sulfonylurea and insulin use were not associated with lactate level. After adjustment for demographic and lifestyle factors, the plasma lactate level for thiazolidinedione users was 15.78% lower than that for non-users (p<0.001). Considering use of each medication separately and in combination did not change the results.

Conclusion

In conclusion, thiazolidinedione use was associated with lower plasma lactate level compared to non-use and metformin use was only marginally associated with a slightly higher lactate level. These results are consistent with the previously demonstrated effects of diabetes medications on oxidative metabolism. Further investigation of the role that diabetes medications play in improvement of oxidative metabolism is warranted.     

Cardiometabolic Risk Profiles Associated with Chronic Complications in Overweight and Obese Type 2 Diabetes Patients in South China

Background

Type 2 diabetes is often accompanied by altered cardiometabolic risk profiles, including abdominal obesity, hypertension, and dyslipidaemia. The association of altered cardiometabolic risk profiles with chronic complications of diabetes is not well investigated.

Methods

We recruited 2954 type 2 diabetes patients with a body mass index ≥25 kg/m² who visited the diabetes clinics of 62 hospitals in 21 cities in Guangdong province of China from August 2011 to March 2012. Demographic characteristics, personal and family medical histories, and data on chronic complications of diabetes were collected. Clinical examinations and laboratory assessment were conducted.

Results

Abdominal obesity was found in 91.6% of the study population, elevated blood pressure in 78.3%; elevated serum triacylglycerols in 57.8%, and reduced serum HDL-C in 55.9%. Among the cardiometabolic risk factors, elevated blood pressure was significantly associated with almost all the chronic complications of diabetes. After adjusting for age, gender, duration of diabetes, and HbA1c, elevated blood pressure was significantly associated with diabetic retinopathy (OR 1.63, 95% CI: 1.22–2.19), diabetic nephropathy (OR 3.16, 95% CI: 2.25–4.46), cardiovascular disease (OR 2.71, 95% CI: 1.70–4.32), and stroke (OR 1.90, 95% CI: 1.15–3.12). Abdominal adiposity was significantly associated with diabetic nephropathy (OR 1.39, 95% CI: 1.11–1.74). Elevated triacylglycerols was significantly associated with diabetic retinopathy (OR 1.29, 95% CI: 1.05–1.58) and diabetic nephropathy (OR 1.30, 95% CI: 1.05–1.58). Reduced HDL-C was significantly associated with stroke (OR 1.41, 95% CI: 1.05–1.88).

Conclusions

Altered cardiometabolic risk profiles, and elevated blood pressure in particular, were significantly associated with chronic complications in overweight and obese patients with type 2 diabetes. Future studies on the prevention of chronic complications of diabetes might make lowering blood pressure a primary target.     

Ratio of Trunk to Leg Volume as a New Body Shape Metric for Diabetes and Mortality

Background

Body shape is a known risk factor for diabetes and mortality, but the methods estimating body shape, BMI and waist circumference are crude. We determined whether a novel body shape measure, trunk to leg volume ratio, was independently associated with diabetes and mortality.

Methods

Data from the National Health and Nutritional Examination Survey 1999–2004, a study representative of the US population, were used to generate dual-energy X-ray absorptiometry-derived trunk to leg volume ratio and determine its associations to diabetes, metabolic covariates, and mortality by BMI category, gender, and race/ethnicity group.

Results

The prevalence of pre-diabetes and diabetes increased with age, BMI, triglycerides, blood pressure, and decreased HDL level. After adjusting for covariates, the corresponding fourth to first quartile trunk to leg volume ratio odds ratios (OR) were 6.8 (95% confidence interval [CI], 4.9–9.6) for diabetes, 3.9 (95% CI, 3.0–5.2) for high triglycerides, 1.8 (95% CI, 1.6–2.1) for high blood pressure, 3.0 (95% CI, 2.4–3.8) for low HDL, 3.6 (95% CI, 2.8–4.7) for metabolic syndrome, and 1.76 (95% CI, 1.20–2.60) for mortality. Additionally, trunk to leg volume ratio was the strongest independent measure associated with diabetes (P<0.001), even after adjusting for BMI and waist circumference. Even among those with normal BMI, those in the highest quartile of trunk to leg volume ratio had a higher likelihood of death (5.5%) than those in the lowest quartile (0.2%). Overall, trunk to leg volume ratio is driven by competing mechanisms of changing adiposity and lean mass.

Conclusions

A high ratio of trunk to leg volume showed a strong association to diabetes and mortality that was independent of total and regional fat distributions. This novel body shape measure provides additional information regarding central adiposity and appendicular wasting to better stratify individuals at risk for diabetes and mortality, even among those with normal BMI.     

Twelve-Year Cardiovascular and Mortality Risk in Relation to Smoking Habits in Type 2 Diabetic and Non-Diabetic Men: Tehran Lipid and Glucose Study

Introduction

To examine the associations between smoking and cardiovascular disease (CVD) / coronary heart disease (CHD) and all-cause mortality events in men with and without type 2 diabetes (T2D) in a Middle Eastern cohort during a median follow-up of 12 years.

Methods

The study population included 2230 subjects aged ≥ 40 years, free from CVD, comprised of 367 participants with diabetes (21.2% current smokers) and 1863 without (27.3% current smokers). Multivariate Hazard ratios (HR) and 95% confidence intervals (CI) were calculated for smoking (considering different definitions) for those with and without diabetes. Potential confounding factors including age, body mass index, estimated Glomerular Filtration Rate, hypertension, hypercholesterolemia and educational level were entered in the multivariate analysis.

Results

In men with diabetes, the HR (95% CI) of comparing current and non-smokers was 1.25 (0.74–2.12) for incident CHD, 1.52 (0.96–2.40) for CVD and 2.10 (1.27–3.47) for mortality events; the corresponding values for men without diabetes were 1.65 (1.24–2.20), 1.70 (1.30–2.22) and 1.72 (1.14–2.58), respectively (all P values for interactions > 0.46). After pooling past smokers with current smokers, among diabetic individuals there was no significant risk for CVD [1.29 (0.89–1.86)] or mortality events [1.25 (0.81–1.92)]; however, among non-diabetic individuals the HRs of current/past smokers reached significant levels for CVD [1.53 (1.23–1.91)] but not for mortality outcomes (all P values for interactions > 0.51).

Conclusions

The strength of the associations between smoking habits and incident CVD/CHD and mortality events from all causes did not differ significantly among diabetic and non-diabetic participants. Therefore, a comprehensive community-based smoking prevention program is important, given the increasing trend of smoking among the Iranian population regardless of diabetes status.     

Thyroid Cancer Risk Is Not Increased in Diabetic Patients

Objective

This study evaluated thyroid cancer risk with regards to diabetes status and diabetes duration, and with the use of anti-diabetic drugs including sulfonylurea, metformin, insulin, acarbose, pioglitazone and rosiglitazone, by using a population-based reimbursement database in Taiwan.

Methods

A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. After excluding patients with type 1 diabetes, 999730 subjects (495673 men and 504057 women) were recruited into the analyses. Logistic regression estimated the odds ratios (OR) and their 95% confidence intervals (CI) for independent variables including age, sex, diabetes status/duration, anti-diabetic drugs, other medications, comorbidities, living regions, occupation and examinations that might potentially lead to the diagnosis of thyroid cancer in various models.

Results

The diabetic patients had a significantly higher probability of receiving potential detection examinations (6.38% vs. 5.83%, P<0.0001). After multivariable-adjustment, the OR (95% CI) for diabetes status was 0.816 (0.652–1.021); and for diabetes duration <1 year, 1–3 years, 3–5 years and ≥5 years vs. non-diabetes was 0.071 (0.010–0.507), 0.450 (0.250–0.813), 0.374 (0.203–0.689) and 1.159 (0.914–1.470), respectively. Among the anti-diabetic agents, only sulfonylurea was significantly associated with thyroid cancer, OR (95% CI): 1.882 (1.202–2.947). The OR (95% CI) for insulin, metformin, acarbose, pioglitazone and rosiglitazone was 1.701 (0.860–3.364), 0.696 (0.419–1.155), 0.581 (0.202–1.674), 0.522 (0.069–3.926) and 0.669 (0.230–1.948), respectively. Furthermore, patients with benign thyroid disease or other cancer, living in Kao-Ping/Eastern regions, or receiving potential detection examinations might have a significantly higher risk; and male sex, hypertension, dyslipidemia, chronic obstructive pulmonary disease, vascular complications or use of statin, aspirin or non-steroidal anti-inflammatory drugs might be associated with a significantly lower risk.

Conclusions

There is a lack of an overall association between diabetes and thyroid cancer, but patients with diabetes duration <5 years have a significantly lower risk. Sulfonylurea may increase the risk of thyroid cancer.     

Income Disparity and Risk of Death: The Importance of Health Behaviors and Other Mediating Factors

Background

Income disparities in mortality are profound in the United States, but reasons for this remain largely unexplained. The objective of this study was to assess the effects of health behaviors, and other mediating pathways, separately and simultaneously, including health insurance, health status, and inflammation, in the association between income and mortality.

Methods

This study used data from 9925 individuals aged 20 years or older who participated in the 1999–2004 National Health and Nutrition Examination Survey (NHANES) and were followed up through December 31, 2006 for mortality. The outcome measures were all-cause and CVD/diabetes mortality. During follow-up 505 persons died, including 196 deaths due to CVD or diabetes.

Results

After adjusting for age, sex, education, and race/ethnicity, risk of death was higher in low-income than high-income group for both all-cause mortality (Hazard ratio [HR], 1.98; 95% confidence interval [CI]: 1.37, 2.85) and cardiovascular disease (CVD)/diabetes mortality (HR, 3.68; 95% CI: 1.64, 8.27). The combination of the four pathways attenuated 58% of the association between income and all-cause mortality and 35% of that of CVD/diabetes mortality. Health behaviors attenuated the risk of all-cause and CVD/diabetes mortality by 30% and 21%, respectively, in the low-income group. Health status attenuated 39% of all-cause mortality and 18% of CVD/diabetes mortality, whereas, health insurance and inflammation accounted for only a small portion of the income-associated mortality (≤6%).

Conclusion

Excess mortality associated with lower income can be largely accounted for by poor health status and unhealthy behaviors. Future studies should address behavioral modification, as well as possible strategies to improve health status in low-income people.     

The Impact of SYNTAX Score of Non-Infarct-Related Artery on Long- Term Outcome among Patients with Acute ST Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Objective

We investigated the impact of the severity of stenosis in a non-infarct-related artery (IRA) on the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Methods

Three hundred one consecutive patients (age: 59.7 ± 13.2 years, 85.5% men) underwent primary PCI during 2009–2012. Receiver operating characteristic curve analysis found the optimal cutoff for non-IRA SYNTAX score (SS) to be 2.5. We divided the patients into two groups according to this cutoff value.

Results

By multivariable analysis, non-IRA SS (≥2.5) was an independent predictor of major adverse cardiac events (hazard ratio [HR]: 2.15, 95% confidence interval [CI]: 1.21–3.79, P  =  0.008) and all-cause mortality (HR: 3.49, 95% CI: 1.13–10.8, P  =  0.03). However, the prediction of cardiovascular mortality had only borderline significance (HR: 3.29, 95% CI: 0.90–12.08, P  =  0.07).

Conclusion

STEMI patients treated with primary PCI and moderate to severe non-IRA stenosis (SS ≥2.5) have more subsequent cardiac events. Those populations should be treated with more aggressive preventive and medical management.