Diabetes Mellitus Participants Research Articles

Effect of Type 2 Diabetes Mellitus on Epicardial Adipose Tissue Volume and Coronary Vasomotor Function

Patients with coronary artery disease and/or type 2 diabetes mellitus (DM) generally exhibit more epicardial adipose tissue (EAT) than healthy controls. Recently, it has been proposed that EAT affects vascular function and structure by secreting proinflammatory and vasoactive substances, thereby potentially contributing to the development of cardiovascular disease. In the present study, the interrelation of EAT, coronary vasomotor function, and coronary artery calcium was investigated in patients with and without DM, who were evaluated for coronary artery disease. Myocardial blood flow (MBF) was assessed at rest and during adenosine-induced hyperemia using [(15)O]-water positron emission tomography combined with computed tomography to quantify coronary artery calcium and EAT in 199 patients (46 with DM). In this cohort (mean age 58 ± 10 years), the patients with DM had a greater body mass index, heart rate, and systolic blood pressure at rest (all p <0.05). Coronary artery calcium and the EAT volumes were comparable between those with and without DM. Both patient groups showed comparable MBF at rest and coronary vascular resistance. A lower hyperemic MBF and coronary flow reserve (CFR) and greater hyperemic coronary vascular resistance (all p <0.05) was observed in the patients with DM. A pooled analysis showed a positive association of EAT volume with hyperemic coronary vascular resistance but not with the MBF at rest, hyperemic MBF, or coronary vascular resistance at rest. In the group analysis, the EAT volume was inversely associated with hyperemic MBF (r = -0.16, p = 0.05) and CFR (r = -0.17, p = 0.04) and positively with hyperemic coronary vascular resistance (r = 0.26, p = 0.002) only in patients without DM. Multivariate regression analysis, adjusted for age, gender, and body mass index, showed an independent association between the EAT volume and hyperemic MBF (β = -0.16, p = 0.02), CFR (β = -0.16, p = 0.04), and hyperemic coronary vascular resistance (β = 0.25, p <0.001) in the non-DM group. In conclusion, these results suggest a role for EAT in myocardial microvascular dysfunction; however, once DM has developed, other factors might be more dominant in contributing to impaired myocardial microvascular dysfunction.

Exercise Stress Tests for Detecting Myocardial Ischemia in Asymptomatic Patients With Diabetes Mellitus

The predominant cause of death in diabetes mellitus (DM) is coronary artery disease (CAD). Little is known about prevalence of silent ischemia in developing nations. We compared prevalence of silent ischemia in DM to a control group by exercise myocardial perfusion imaging (MPI) and electrocardiogram (ECG) in developing nations. The prospective multinational Ischemia Assessment with Exercise imaging in Asymptomatic Diabetes study recruited participants at 12 sites in Asia, Africa, and Latin America. DM participants were age- and gender-matched 2:1 to non-DM individuals with ≥1 CAD risk factor. Subjects underwent exercise tests that were interpreted in core labs in blinded fashion. The study included 392 DM and 205 control participants. Among participants with diagnostic ECGs, a similar proportion of DM and controls had ischemic ECG (15% vs 12%, p = 0.5). A significantly higher proportion of DM group had MPI abnormalities compared with controls (26% vs 14%, p <0.001). In participants with ischemia on MPI, only 17% had ischemic ECG, whereas in those without ischemia on MPI, 10% had ischemic ECG. In a multivariable model, DM was independently associated with abnormal MPI (odds ratio 2.1, 95% confidence interval 1.3-3.5, p = 0.004). Women were less likely to have ischemia by MPI than men (10% vs 30%, p <0.001) and concordance between ECG and MPI was much worse in women. In conclusion, in this large prospective study, asymptomatic DM participants had (1) more ischemia by exercise MPI than ECG, (2) more ischemia by MPI but not ECG than control group, and (3) ischemia by MPI was less in women than men.

Hyperfiltration and effect of nitric oxide inhibition on renal and endothelial function in humans with uncomplicated type 1 diabetes mellitus

Studies of experimental diabetes mellitus (DM) suggest that increased nitric oxide (NO) bioactivity contributes to renal hyperfiltration. However, the role of NO in mediating hyperfiltration has not been fully elucidated in humans. Our aim was to examine the effect of NO synthase inhibition on renal and peripheral vascular function in normotensive subjects with uncomplicated type 1 DM. Renal function and brachial artery flow-mediated vasodilatation (FMD) were measured before and after an intravenous infusion of the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NMMA) in 21 healthy control and 37 type 1 DM patients. Measurements in DM participants were made under clamped euglycemic conditions. The effect of l-NMMA on circulating and urinary NO metabolites (NO(x)) and cGMP and on urinary prostanoids was also determined. Baseline characteristics were similar in the two groups. For analysis, the DM patients were divided into those with hyperfiltration (DM-H, n = 18) and normal glomerular filtration rate (GFR) levels (DM-N, n = 19). Baseline urine NO(x) and cGMP were highest in DM-H. l-NMMA led to a decline in GFR in DM-H (152 ± 16 to 140 ± 11 ml·min(-1)·1.73 m(-2)) but not DM-N or healthy control participants. The decline in effective renal plasma flow in response to l-NMMA (806 ± 112 to 539 ± 80 ml·min(-1)·1.73 m(-2)) in DM-H was also exaggerated compared with the other groups (repeated measures ANOVA, P < 0.05), along with declines in urinary NO(x) metabolites and cGMP. Baseline FMD was lowest in DM-H compared with the other groups and did not change in response to l-NMMA. l-NMMA reduced FMD and plasma markers of NO bioactivity in the healthy control and DM-N groups. In patients with uncomplicated type 1 DM, renal hyperfiltration is associated with increased NO bioactivity in the kidney and reduced NO bioactivity in the systemic circulation, suggesting a paradoxical state of high renal and low systemic vascular NO bioactivity.

Association between Serum Uric Acid Levels and Diabetes Mellitus

Serum uric acid has been shown to be associated with cardiovascular disease, hypertension, and chronic kidney disease in previous studies. However, few studies have examined the association between serum uric acid and diabetes mellitus and their findings are not consistent. Therefore, we examined the association between serum uric acid levels and diabetes mellitus in participants from the third National Health and Nutrition Examination Survey (n = 18, 825, 52.5% women). Serum uric acid levels were categorized into quartiles. Diabetes mellitus was defined as fasting glucose ≥126 mg/dL, nonfasting glucose ≥200 mg/dL, or use of oral hypoglycemic medication or insulin (n = 395). In multivariable logistic regression models, we found that higher serum uric acid levels were inversely associated with diabetes mellitus after adjusting for age, sex, race/ethnicity, education, smoking, alcohol intake, body mass index, hypertension, and serum cholesterol. Compared to quartile 1 of serum uric acid, the odds ratio (95% confidence interval) of diabetes mellitus was 0.48 (0.35–0.66; P trend <0.0001). The results were consistent in subgroup analysis by gender and hypertension status. Higher serum uric acid levels were inversely associated with diabetes mellitus in a representative sample of US adults.

Vitamin E reduces cardiovascular disease in individuals with diabetes mellitus and the haptoglobin 2-2 genotype.

Individuals with both diabetes mellitus (DM) and the Haptoglobin (Hp) 2-2 genotype are at increased risk of cardiovascular disease. As the antioxidant function of the Hp 2-2 protein is impaired, we sought to test the pharmacogenomic hypothesis that antioxidant vitamin E supplementation would provide cardiovascular protection to Hp 2-2 DM individuals. We determined the Hp genotype on DM participants from two trials (HOPE and ICARE) and assessed the effect of vitamin E by Hp genotype on their common prespecified outcome, the composite of stroke, myocardial infarction and cardiovascular death. Data was analyzed with a fixed-effect model. These results were input into a simulation model, the Evidence Based Medicine Integrator, in order to estimate their long-term implications in a real-world population from Kaiser Permanente (CA, USA). Meta-analysis of the two trials demonstrated a significant overall reduction in the composite end point in Hp 2-2 DM individuals with vitamin E (odds ratio: 0.58; 95% CI: 0.40-0.86; p = 0.006). There was a statistically significant interaction between the Hp genotype and vitamin E on the composite end point. In these trials, Hp typing of 69 DM individuals and treating those with the Hp 2-2 with vitamin E prevented one myocardial infarct, stroke or cardiovascular death. Lifelong administration of vitamin E to Hp 2-2 DM individuals in the Kaiser population would increase their life expectancy by 3 years. A pharmacogenomic strategy of screening DM individuals for the Hp genotype and treating those with Hp 2-2 with vitamin E appears to be highly clinically effective.

Prevalence of diabetes mellitus in the rural southern Free State

SA Fam Pract 2009;51(6):502-505 Background: A worldwide increase in the prevalence of diabetes mellitus (DM) has been reported and an even further increase is expected as a result of lifestyle changes. The objectives of this study were to determine the prevalence of DM in the rural southern Free State and to investigate the contribution of risk factors such as age, physical activity, body mass index (BMI), waist-to-hip ratio and waist circumference to the development of impaired fasting glucose (IFG) or DM. Methods: Fasting venous plasma glucose (FVPG) levels were obtained from a total of 552 participants from Springfontein (n = 195), Trompsburg (n = 162) and Philippolis (n = 180). Participants were between 25 and 64 years of age, with 28.1% male (mean age 47.3 years) and 71.9% female (mean age 46 years). Anthropometric status was determined using standardised techniques. Levels of physical activity were determined using a 24-hour recall of physical activity as well as frequency of performing certain activities. Relative risks (RR) as well as 95% confidence intervals (95% CI) were used to distinguish significant risk factors for having IFG or DM. Results: In the study population the prevalence of DM was 7.6% (5.2% in men and 8.6% in women) and that of IFG was 6.3% (4.5% in men and 7.1% in women). The majority of nondiabetic (34%), IFG (55%) and DM (61%) participants were between the ages of 51 and 60 years. Age was found to be a statistically significant risk factor for having IFG or DM in participants older than 40 years of age (RR 2.3; 95% CI (1.22; 4.34)). Crude measurements (not age- and gender-adjusted) of waist circumference (RR 3.23; 95% CI (1.82; 5.74)), BMI (RR 2.32; 95% CI (1.43; 3.78)) and waist-to-hip ratio (RR 2.51; 95% CI (1.55; 4.07)) were statistically significant risk factors for having IFG or DM. Physical inactivity in men ≥ 40 years was also a statistically significant risk factor (RR 3.23; 95% CI (1.15; 9.05)) for having IFG or DM. Conclusions: In this study, 37.5% of diabetics were newly discovered. A high waist circumference, BMI and waist-to-hip-ratio were associated with an increased risk for developing IFG or DM, with a high waist circumference being the most significant general risk factor. Physically inactive men (≥ 40 years) were also at a higher risk of having IFG or DM. Follow-up FVPG and glucose tolerance tests should be performed on participants in the IFG group. A need for intervention regarding the identification and treatment of DM in these rural areas has been identified. a van Wyk HJ, MBChB, MMed (Clin Pathol) b

Oxidative Stress and Platelet Activation: Markers of Myocardial Infarction in Type 2 Diabetes Mellitus

We compared lipids, lipid peroxidation product malondialdehyde (MDA), the acute phase reactant high-sensitivity C-reactive protein (hsCRP), interleukin 1beta (IL-1beta), and platelet selectin (P-selectin) between healthy controls, type 2 diabetes mellitus (DM) participants without myocardial infarction (MI), as well as type 2 DM participants with MI. Malondialdehyde, IL-1beta, and P-selectin levels were significantly higher in the diabetic participants with MI than in either healthy controls or diabetic participants without MI. In the diabetic groups, fasting blood glucose (FBG) level, glycated hemoglobin (HbA(1c)), MDA, hsCRP, and P-selectin were all significantly positively correlated with each other. This study suggests that increased levels of oxidative stress markers, proinflammatory markers, and adhesion molecules contribute to the atherosclerotic process that eventually leads to coronary artery disease in diabetic patients.

Urinary albumin excretion is a risk factor for diabetes mellitus in men, independently of initial metabolic profile and development of insulin resistance. The DESIR Study

Elevated urinary albumin excretion (UAE) is more frequent in patients with the metabolic syndrome or insulin resistance. Whether UAE predicts the development of diabetes mellitus, independently of the presence or the development of the metabolic syndrome, is unclear, in particular, in women. We prospectively assessed the association between baseline UAE and subsequent diabetes mellitus in participants selected from the general population. Four thousand and seventy-four nondiabetic patients (aged 30-64 years) included in the Data from an Epidemiological Study on the Insulin Resistance syndrome Study had a baseline UAE. Among them, 3851 patients had complete data regarding diabetes mellitus. Diabetes mellitus occurred in 171 out of 3851 patients during the 9-year follow-up (132/2056 men and 39/1795 women). UAE was associated with diabetes mellitus in a dose-dependent manner in men [as compared to men with UAE<9 mg/l, hazard ratios were 1.81 (P=0.0160), 1.83 (P=0.0134), 2.31 (P=0.0008) and 4.43 (P=0.0005) for men with UAE: 9-12 mg/l, 12-19 mg/l, 20-200 mg/l and >200 mg/l, respectively] but not in women; the association was more marked after exclusion of men with baseline impaired fasting glucose [hazard ratios were 3.28 (P=0.0007), 3.08 (P=0.0012), 3.27 (P=0.0022), 9.23 (P<0.0001), respectively]. The association remained significant after adjustments on BMI, sporting activity, diet, smoking, waist circumference, insulin and homeostasis model assessment of insulin resistance, lipids, C-reactive protein and family of history of diabetes mellitus. Adjustment on the first 3-year change in weight, glucose, insulin and homeostasis model assessment of insulin resistance did not modify the results. Elevated UAE predicts the 9-year risk of diabetes mellitus in men, independent of baseline or early development of metabolic abnormalities or insulin resistance.

The relationship of heart rate and heart rate variability to non‐diabetic fasting glucose levels and the metabolic syndrome: The Cardiovascular Health Study

Increased heart rate (HR) and diminished heart rate variability (HRV) are signs of early cardiovascular autonomic neuropathy. We tested the hypotheses that increased HR and diminished HRV are present in people: (i) with increased fasting glucose (FG) levels not in the range of diabetes mellitus (DM), and (ii) in people with the metabolic syndrome (MetS) independent of elevated FG levels. HR and HRV were determined in 1267 adults (mean age 72 years) who had Holter monitoring and FG measures: 536 had normal FG levels (NORM, FG 4.5-5.5 mmol/l), 363 had mildly impaired FG (IFG-1, FG 5.6-6.0 mmol/l), 182 had significantly impaired FG (IFG-2, FG 6.1-6.9 mmol/l) and 178 had DM (FG > 6.9 mmol/l or use of glucose-lowering agents/insulin). HR and HRV in NORM/IFG-1 was further compared by the number of components of the MetS and compared by the presence or absence of MetS in IFG-2/DM. HRV indices were more impaired in IFG-2 and DM than in NORM or IFG-1. There were few differences in HRV indices between NORM and IFG-1 or between IFG-2 and DM. In NORM/IFG-1 participants, having > or = 2 components of the MetS was associated with a greater decrease in HRV compared with having no or one components. In IFG-2/DM participants, MetS was associated with decreased HRV compared with no MetS. Increased HR and diminished HRV occur in the non-diabetic FG range. Diminished HRV is associated with the MetS, independent of FG levels. Both these results suggest that factors associated with increasing non-diabetic FG levels and the MetS play a role in the onset of cardiac autonomic impairment.

Diabetes mellitus and the risk of nephrolithiasis

Insulin resistance is a central feature of type 2 diabetes mellitus (DM) and may increase the risk of kidney stone formation. Existing cross-sectional data on the association between DM and nephrolithiasis are limited, and no prospective study to date has evaluated the relation between DM and the risk of kidney stones. To evaluate the relation between DM and prevalent kidney stones, we conducted a cross-sectional study of 3 large cohorts including over 200,000 participants: the Nurses' Health Study I (older women), the Nurses' Health Study II (younger women), and the Health Professionals Follow-up Study (men). We then prospectively studied the association between DM and incident nephrolithiasis over a combined 44 years of follow-up. Because insulin resistance can precede the diagnosis of DM by decades, we also prospectively examined the relation between kidney stones and the diagnosis of incident DM. Multivariate regression models adjusted for age, body mass index, thiazide diuretic use, fluid intake, and dietary factors. At baseline, the multivariate relative risk of prevalent stone disease in individuals with DM compared to individuals without was 1.38 (95% CI 1.06-1.79) in older women, 1.67 (95% CI 1.28-2.20) in younger women, and 1.31 (95% CI 1.11-1.54) in men. Prospectively, the multivariate relative risk of incident kidney stone formation in participants with DM compared to participants without was 1.29 (95% CI 1.05-1.58) in older women, 1.60 (95% CI 1.16-2.21) in younger women, and 0.81 (95% CI 0.59-1.09) in men. The multivariate relative risk of incident DM in participants with a history of kidney stones compared to participants without was 1.33 (95% CI 1.18-1.50) in older women, 1.48 (95% CI 1.14-1.91) in younger women, and 1.49 (95% CI 1.29-1.72) in men. DM is a risk factor for the development of kidney stones. Additional studies are needed to determine if the increased risk of DM in stone formers is due to subclinical insulin resistance.

Clinical Outcomes in Antihypertensive Treatment of Type 2 Diabetes, Impaired Fasting Glucose Concentration, and Normoglycemia

Optimal first-step antihypertensive drug therapy in type 2 diabetes mellitus (DM) or impaired fasting glucose levels (IFG) is uncertain. We wished to determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor decreases clinical complications compared with treatment with a thiazide-type diuretic in DM, IFG, and normoglycemia (NG). Active-controlled trial in 31 512 adults, 55 years or older, with hypertension and at least 1 other risk factor for coronary heart disease, stratified into DM (n = 13 101), IFG (n = 1399), and NG (n = 17 012) groups on the basis of national guidelines. Participants were randomly assigned to double-blind first-step treatment with chlorthalidone, 12.5 to 25 mg/d, amlodipine besylate, 2.5 to 10 mg/d, or lisinopril, 10 to 40 mg/d. We conducted an intention-to-treat analysis of fatal coronary heart disease or nonfatal myocardial infarction (primary outcome), total mortality, and other clinical complications. There was no significant difference in relative risk (RR) for the primary outcome in DM or NG participants assigned to amlodipine or lisinopril vs chlorthalidone or in IFG participants assigned to lisinopril vs chlorthalidone. A significantly higher RR (95% confidence interval) was noted for the primary outcome in IFG participants assigned to amlodipine vs chlorthalidone (1.73 [1.10-2.72]). Stroke was more common in NG participants assigned to lisinopril vs chlorthalidone (1.31 [1.10-1.57]). Heart failure was more common in DM and NG participants assigned to amlodipine (1.39 [1.22-1.59] and 1.30 [1.12-1.51], respectively) or lisinopril (1.15 [1.00-1.32] and 1.19 [1.02-1.39], respectively) vs chlorthalidone. Our results provide no evidence of superiority for treatment with calcium channel blockers or angiotensin-converting enzyme inhibitors compared with a thiazide-type diuretic during first-step antihypertensive therapy in DM, IFG, or NG.

Incidence of Diabetes Mellitus in Participants in Intensive Health Check-ups

Incidence of Diabetes Mellitus in Participants in Intensive Health Check-ups