Visit-to-visit variability in systolic blood pressure is correlated with diabetic nephropathy and atherosclerosis in patients with type 2 diabetes

ObjectiveRecent studies make remarks on the effect of variability in systolic blood pressure (SBP) on the development of cardiovascular disease. The aim of this study was to investigate the relationship between the variability in SBP and the degree of diabetic nephropathy and atherosclerosis in patients with type 2 diabetes.MethodsWe measured SBP in 422 consecutive patients with type 2 diabetes at every visit during a year, and we calculated the coefficient of variation (CV) of SBP. Then, we evaluated relationships of variability of SBP to degree of urinary albumin excretion (UAE), which is a useful marker for cardiovascular disease as well as diabetic nephropathy, ankle-brachial index (ABI) and pulse wave velocity (PWV).ResultsCV of SBP positively correlated with log UAE (r = 0.210, P < 0.0001) or PWV (r = 0.409, P < 0.0001), whereas CV of SBP inversely correlated with ABI (r = ?0.098, P = 0.0463). Multiple regression analysis demonstrated that CV of SBP independently correlated with log UAE (β = 0.149, P = 0.0072), PWV (β = 0.337, P < 0.0001) or ABI (β = ?0.162, P = 0.0101).ConclusionsNot only average SBP but also variability in SBP is correlated with diabetic nephropathy and atherosclerosis in patients with type 2 diabetes.     

Systemic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk

ObjectiveIn recent years high sensitive C-reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) were recognized as risk factors for cardiovascular disease (CVD). The aim of the present study was to investigate the relationship between these vascular and systemic markers of low-grade inflammation and traditional risk factors, the metabolic syndrome (MetS) or insulin resistance (IR).Methods and resultsIn 137 adults (41–78 years) with at least 2 risk factors for atherosclerosis the following parameters were determined: hsCRP, sVCAM-1, sICAM-1, PAI-1, fibrinogen, waist circumference (WC), blood pressure, Body Mass Index (BMI), fasting serum glucose (FSG), insulin, triglycerides (TG), total cholesterol (TC), LDL, and HDL. The presence or absence of MetS according to the AHA/NHLBI Scientific Statement criteria was assessed. IR was defined using the homeostasis model (HOMA-IR). Subjects with MetS had significantly higher values of hsCRP, sICAM-1, sVCAM-1, PAI-1, fibrinogen (each P < 0.05) and lower HDL-levels (P < 0.05) compared with subjects without MetS. Similar results were found using HOMA-IR-quartiles. Subjects in the bottom quartile (HOMA-IR ≤ 1.32) had significantly lower levels of hsCRP, sVCAM-1, sICAM-1, and PAI-1 (each P < 0.05) than subjects in the top quartile (HOMA-IR ≥ 5.03). HDL was significantly higher (P < 0.05) in subjects in the lowest quartile versus those in the highest quartile. Incidentally we found no significant differences in total and LDL cholesterol among MetS, HOMA, and traditional CVD risk factor groups, respectively.ConclusionSystemic and vascular markers of inflammation showed significant associations with IR and the MetS and may be incorporated into traditional CVD risk prediction models. Such models should be established and validated in forthcoming large scale prospective studies on CVD risk.     

Prevalence and risk factors for diabetic microvascular complications in newly diagnosed type II diabetes mellitus. Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS, report 27)

PurposeThe aims of this study were to report the prevalence of various microvascular complications and to identify the various clinical and biochemical characteristics related to these complications in subjects with newly diagnosed type II diabetes.MethodsOf the 5999 subjects enumerated, 1414 subjects with diabetes (both known and newly diagnosed) were analyzed for the study. Among the diabetic subjects, 248 (17.5%) were newly diagnosed with diabetes and the remaining had history of diabetes. All subjects underwent a detailed standard evaluation to detect diabetic retinopathy (fundus photography), neuropathy (vibration pressure threshold), and nephropathy (microalbuminuria).ResultsThe prevalence of any form of microvascular complication was 30.2% (95% confidence interval [CI] = 24.5–35.9). The prevalence of diabetic retinopathy was 4.8%, and that of diabetic nephropathy and neuropathy was 10.5%. The risk factors for developing any form of microvascular complication were increasing age (odds ratio [OR] = 1.07, 95% CI = 1.04–1.11, P < .0001), increasing systolic blood pressure (OR = 1.03, 95% CI = 1.01–1.06, P = .001), and increasing hemoglobin (OR = 1.39, 95% CI = 1.09–1.79, P = .011). The risk factors for diabetic retinopathy and diabetic nephropathy were increasing systolic blood pressure (OR = 1.06 [P = .001] for retinopathy and OR = 1.04 [P = .012] for nephropathy) and increasing hemoglobin (OR = 2.20 [P = .007] for retinopathy and OR = 1.57 [P = .023] for nephropathy). The risk factor for diabetic neuropathy was increasing age (OR = 1.12, P < .0001).ConclusionsNearly one third of the newly diagnosed type II diabetes subjects had some form of microvascular complication; nephropathy, and neuropathy being commoner than retinopathy.     

Non-linear association between ankle-brachial pressure index and prevalence of silent cerebral infarction in Japanese patients with type 2 diabetes

ObjectivePatients with peripheral artery disease (PAD), defined as having low ankle-brachial pressure index (ABI), have increased risk for incident stroke compared with those without PAD. We aimed to reveal whether ABI abnormality, especially high ABI is associated with prevalent silent cerebral infarction (SCI) in type 2 diabetic patients.MethodsWe studied 538 Japanese type 2 diabetic patients, 227 women and 311 men, with a mean [±SD] age of 64 ± 11 years. All patients underwent cranial magnetic resonance imaging (MRI). Values of ABI were classified as low (<0.9), normal (0.9≤ and <1.3), and high (1.3≤). Logistic regression model was used to calculate odds ratio and 95% confidence interval (95% CI) for prevalent SCI.ResultsThe mean ABI among the overall 538 patients was 1.09 ± 0.16. Low and high ABI values were found in 52 (9.7%) and 33 (6.1%) patients, respectively. SCI was detected in 297 (55.2%) patients. The prevalence in patients with low, normal, and high ABI values were 88.5%, 49.7%, and 78.8 (p < 0.001), respectively. In the multivariate logistic regression analysis, both patients with high and low ABI were significantly increased risk of prevalent SCI (odds ratio 4.53, 95% CI 1.67–12.34, p = 0.003 and odds ratio 3.50, 95% CI 1.50–10.29, p = 0.005), independently of other traditional cardiovascular risk factors, than those with normal ABI.ConclusionsBoth high and low ABI may be strongly associated with prevalent SCI in Japanese patients with type 2 diabetes.     

White blood cell count is associated with carotid and femoral atherosclerosis

ObjectiveRelationship of high sensitivity C-reactive protein (hsCRP) with Metabolic Syndrome (MetS) is well documented in many populations, but comprehensive data is lacking in Indian population. Thus, we set out to investigate the association of hsCRP levels with MetS and its features and the effect of obesity and insulin resistance on this association in urban Indians.MethodsThis is a cross-sectional study that included 9517 subjects comprising 4066 subjects with MetS. MetS was defined according to the modified National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP III) criteria for Asians.ResultsMedian levels of hsCRP were considerably higher in individuals with MetS with higher levels in women compared to men. Among the features of MetS, waist circumference was most strongly correlated with hsCRP levels (r = 0.28) and contributed maximally (β = 0.025 mg/l ln hsCRP, P = 7.4 × 10^?147). Subjects with high risk hsCRP levels (>3 mg/l) were at high risk of MetS (OR (95% CI) = 1.65(1.41–1.92), P = 1.7 × 10^?10). Risk of MetS increased in a dose dependent manner from low risk to high risk hsCRP category with increase in BMI and HOMA-IR.ConclusionsOur findings suggest that hsCRP predicts the risk of MetS, independent of obesity and insulin resistance, and therefore, can be a valuable tool to aid the identification of individuals at risk of MetS. The study provides a lead for future investigation for effects of hsCRP, obesity, and insulin resistance on MetS in this population.     

Effects of fenofibrate therapy on circulating adipocytokines in patients with primary hypertriglyceridemia

BackgroundWe investigated effects of fenofibrate therapy on endothelial dysfunction and adipocytokine profiles.MethodsA randomized, single-blind, placebo-controlled, cross-over study was conducted in 53 patients with primary hypertriglyceridemia. We administered placebo or fenofibrate 160 mg daily for 8 weeks.ResultsWhen compared with placebo, fenofibrate therapy substantially lowered plasma levels of TNF-α by 6 ± 3% (P = 0.014) and hsCRP from 1.10 to 0.90 mg/l (P = 0.004). When compared with placebo, fenofibrate therapy increased plasma levels of adiponectin by 17 ± 4% (P = 0.001), insulin sensitivity by 4 ± 1% (as assessed by QUICKI, P = 0.009), and decreased plasma levels of leptin and resistin by 4 ± 7% (P = 0.022) and 10 ± 3% (P = 0.001), respectively. There were correlations between percent changes in QUICKI and percent changes in adiponectin levels (r = 0.279, P = 0.043) or leptin (r = ?0.280, P = 0.042).ConclusionsFenofibrate therapy significantly reduced pro-inflammatory biomarkers and improved adipocytokines levels and insulin sensitivity in hypertriglyceridemic patients.     

Elevated level of C-reactive protein is associated with risk of prediabetes in Indians

BackgroundRelationship of high sensitivity C-reactive protein (hsCRP) with prediabetes has not been explored extensively in Indians. Here we sought to investigate the association of hsCRP levels with prediabetes, as represented by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and the influence of risk factors like obesity, decreased HDL cholesterol, hypertension, family history of diabetes and current smoking habit on the relationship.MethodsA cross-sectional study on 1726 Indians, comprising of 1276 individuals with normal glucose tolerance (NGT), 250 IFG and 200 IGT individuals. Subjects were defined according to WHO criteria based on fasting plasma and 2 h glucose levels.ResultsMedian levels of hsCRP were significantly higher in IFG (2.20 mg/l) and IGT (2.32 mg/l) compared to NGT (1.64 mg/l) subjects. Individuals with high risk hsCRP levels (>3 mg/l) had an odds ratio (OR) (95% confidence interval (CI)) of 2.60 (1.56–5.34) [P = 1.3 × 10^?4] for IGT after adjusting the effect of age, sex, medication, body mass index (BMI), waist circumference (WC) and risk factors like decreased high-density lipoprotein cholesterol (HDL-cholesterol), hypertension, family history of diabetes and current smoking. Significant increase in risk of IGT was found with a unit increase in natural log transformed hsCRP levels after adjustment for covariates [OR (95%CI) = 1.57 (1.27–1.94), P = 3.0 × 10^?5]. When subjects were stratified on the basis of risk factors, we found stronger association of elevated hsCRP levels with risk of IFG and IGT in subjects having HDL-cholesterol ≤50 mg/dl and with hypertension.ConclusionsOur study demonstrates that elevated hsCRP levels are independently associated with risk of IFG and IGT in Indians.     

Homocysteine is a determinant of ApoA-I and both are associated with ankle brachial index, in an ambulatory elderly population

ObjectiveThe ankle brachial index (ABI) is an indicator of lower extremity peripheral arterial disease (PAD) and a predictor of atherothrombosis. ApoA-I and HDL are associated with PAD, in humans. Homocysteine influences the liver expression of ApoA-I and decreases its blood level and HDL in genetic mice models. We aimed therefore to evaluate whether homocysteine and its nutritional determinants, folate and vitamin B12 are associated with ABI by influencing HDL metabolism, in an ambulatory elderly population.Methods667 elderly volunteers from rural Sicily were assessed for ABI, homocysteine and its determinants, lipid markers and other predictors of PAD. HDL size was assessed in 15 sera in upper and lower quartiles of Hcy distribution.ResultsIn multivariate analysis, ApoA-I and homocysteine were two predictors of ABI (β-coefficient = 2.86, P < 0.004 and β-coefficient = ?3.41, P < 0.001, respectively). Homocysteine correlated negatively with ApoA-I (R = ?0.147, P < 0.001) and with HDL-Cholesterol (R = ?0.113, P = 0.003). The associations of homocysteine, vitamin B12 and methylmalonic acid with ApoA-I and HDL2a particles and that of homocysteine with increased small size HDL3c suggested mechanisms related with impaired synthesis of ApoA-I and HDL and abnormal maturation of HDL particles.ConclusionThe influence of homocysteine on ApoA-I and HDL metabolism provides new insights on its role on vascular diseases, at a cross-point between atherosclerosis and atherothrombosis.     

Low ankle-brachial index predicts early risk of recurrent stroke in patients with acute cerebral ischemia

ObjectiveLow Ankle-Brachial Blood Pressure Index (ABI) identifies patients with symptomatic and asymptomatic peripheral arterial disease (PAD). We sought to investigate the association of low ABI with early risk of stroke recurrence in patients with acute cerebral ischemia (ACI) and without history of symptomatic PAD.MethodsConsecutive patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) and no previous history of PAD were prospectively evaluated with ABI measurements. Demographic characteristics, vascular risk factors and secondary prevention therapies were documented. An ABI ≤0.90 in either leg was considered as evidence of asymptomatic PAD, and an ABI >0.90 was considered as normal. Patients with elevated ABI (>1.30) were excluded. The outcome of interest was recurrent stroke during 30-day follow-up.ResultsA total of 176 patients with acute cerebral ischemia (mean age 64 ± 14 years, 59.1% men, 76.7% AIS) were evaluated. Asymptomatic PAD was detected in 14.8% (95%CI: 10.2–20.8%) of the studied population. The following factors were independently associated with low ABI on multivariate logistic regression models, after adjustment for potential confounders: coronary artery disease (p = 0.008), diabetes mellitus (p = 0.017) and increasing age (p = 0.042). The cumulative 30-day recurrence rate was higher in patients with low ABI (19.2%; 95%CI: 4.1–34.3) compared to the rest (3.3%; 95%CI: 0.4–6.2%; p = 0.001). Atherothrombotic stroke (ASCO grade I; p < 0.001), increasing age (p = 0.002) and low ABI (p = 0.004) were independent predictors of stroke recurrence on multivariate Cox regression models adjusting for confounders.ConclusionsLow ABI appears to be associated with a higher risk of early recurrent stroke in patients with ACI and no history of symptomatic PAD.     

Circulating high-mobility group box 1 and cardiovascular mortality in unstable angina and non-ST-segment elevation myocardial infarction

ObjectiveHigh-mobility group box 1 (HMGB1) is a damage-associated molecular pattern molecule, which suggests a potential role of this protein in the pathophysiology of acute coronary syndrome (ACS). Circulating HMGB1 has been shown to be independently associated with cardiac mortality in ST-segment elevation myocardial infarction. However, its prognostic value remains unclear in unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI).MethodsHMGB1, high-sensitivity C-reactive protein (hsCRP), cardiac troponin I and B-type natriuretic peptide concentrations were measured on admission in 258 consecutive patients (mean age of 67 years) hospitalized for UA/NSTEMI within 24 h (mean, 7.4 h) of the onset of chest symptoms.ResultsA total of 38 (14.7%) cardiovascular deaths, including 10 in-hospital deaths, occurred during a median follow-up period of 49 months after admission. In a stepwise Cox regression analysis including 19 well-known clinical predictors of ACS, HMGB1 [relative risk (RR) 3.24 per 10-fold increment; P = 0.0003], cardiac troponin I (RR 1.83 per 10-fold increment, P = 0.0007), Killip class > 1 (RR 4.67, P = 0.0001) and age (RR 1.05 per 1-year increment, P = 0.03), but not hsCRP, were independently associated with cardiovascular mortality. In-hospital and cardiovascular mortality rates were higher in patients with increased HMGB1 (≥2.4 ng/mL of median value) than those without increased HMGB1 (6.3% vs. 1.5%, P = 0.04; and 23% vs. 6.9%, P = 0.0003).ConclusionCirculating concentration of HMGB1 on admission may be a potential and independent predictor of cardiovascular mortality in patients hospitalized for UA/NSTEMI within 24 h of onset.     

Oxidized to non-oxidized lipoprotein ratios are associated with arteriosclerosis and the metabolic syndrome in diabetic patients

Background and aimType 2 diabetic patients have a greater prevalence of the metabolic syndrome, oxidative stress and accelerated atherosclerosis, compared to non-diabetics. We examined the association between biomarkers of lipid peroxidation and the presence of atherosclerosis and the metabolic syndrome in diabetic patients.Methods and resultsWe studied oxidized LDL (OxLDL), OxLDL/LDL, OxLDL/HDL, lipoperoxides, autoantibodies against OxLDL (OxLDL-Ab), diene formation of LDL (lag phase), vitamin E, vitamin E/cholesterol and PON1 polymorphisms (−108C > T, 55T > A, and 192A > G) in 166 non-smoking type 2 diabetic patients, 119 fulfilling the criteria for the metabolic syndrome, 73 with atherosclerosis and 93 without atherosclerosis. Patients with macrovascular disease had higher values of OxLDL/LDL (11%; P = 0.016), OxLDL/HDL (18%; P = 0.024) and OxLDL-Ab (12%; P = 0.046). OxLDL/LDL and OxLDL/HDL were correlated with the number of components of the metabolic syndrome (P < 0.001). PON1 polymorphisms were not associated to LDL oxidation markers, only PON1 (−108TT) was weakly associated with higher OxLDL-Ab concentrations (22%; P = 0.040) in patients with atherosclerosis.ConclusionOxLDL/LDL, OxLDL/HDL and OxLDL-Ab are the most useful clinical parameters of lipoprotein oxidation for discriminating the presence of macrovascular disease in diabetic patients. The presence of the metabolic syndrome in these patients is also associated with an increase in the oxidized lipoprotein ratios.     

Relationship between total oxidant status and severity of diabetic nephropathy in type 2 diabetic patients

Background and aimData on oxidative stress in type 2 diabetic patients with diabetic nephropathy is scant. The objective of this study was to investigate possible associations between total oxidant status (TOS) and the severity of diabetic nephropathy in type 2 diabetic patients by using a novel automated measurement method.Methods and resultsThirty-six patients with diabetic nephropathy (group 1), 25 diabetic patients without nephropathy (group 2) and 30 controls (group 3) were enrolled. Serum total antioxidant capacity (TAC), TOS levels and oxidative stress index (OSI) were determined. The severity of the disease was determined with microalbuminuria levels. TAC was lower, while TOS and OSI were higher in group 1 than in group 3 (P < 0.01, P < 0.001, P < 0.001; respectively). There were no statistically significant differences between group 2 and group 3 with respect to TAC, TOS and OSI (all P > 0.05). Group 1 had higher TOS and OSI than group 2 (both P < 0.05), but there was no statistically significant difference with respect to TAC. Significant correlations were observed between microalbuminuria levels, and TAC, TOS and OSI levels (r = −0.616, P < 0.001; r = 0.488, P < 0.01; r = 0.567, P < 0.001; respectively).ConclusionOur results suggest that oxidative stress is increased in patients with diabetic nephropathy compared to diabetic patients without nephropathy and this increase seems to be related to the severity of microalbuminuria levels.     

Carotid extra-medial thickness in childhood: early life effects on the arterial adventitia

ObjectiveStructural modification of the arterial adventitia may be an early event in atherosclerosis. Carotid extra-medial thickness is a new measure of arterial adventitial thickness. We examined the association of cardiovascular risk factors with extra-medial thickness, in childhood.MethodsCarotid extra-medial thickness was assessed by high-resolution ultrasound in 389 non-diabetic children aged 8-years. A non-fasting blood sample was collected from 314 participants. Associations of gender, age, lipoproteins, blood pressure, BMI z-score, waist:height ratio and parental history of early vascular disease, with extra-medial thickness were examined.ResultsCarotid extra-medial thickness was lower in girls (r = ?.163, P = .001) and directly associated with systolic (r = .128, P = .009), diastolic blood pressure (r = .130, P = .009), and height (r = .170, P = .0006). These associations remained after adjustment for carotid intima-media thickness. In multivariable analysis including carotid intima-media thickness, only gender and height were significantly associated with carotid extra-medial thickness. In gender-stratified analysis, the strongest associations with extra-medial thickness were BMI z-score (r = .181, P = .01), height (r = .210, P = .003) and diastolic blood pressure (r = .167, P = .02) for boys; and systolic blood pressure (r = .153, P = .03) and parental history of premature cardiovascular disease (r = .139, P = .05) for girls. The association of BMI z-score with extra-medial thickness differed by gender (P-interaction = .04).ConclusionsCarotid extra-medial thickness is independently associated with gender and height in childhood. Extra-medial thickness may provide important information concerning early arterial health, particularly related to the arterial adventitia.     

The effect of exercise on neuropathic symptoms, nerve function, and cutaneous innervation in people with diabetic peripheral neuropathy

Although exercise can significantly reduce the prevalence and severity of diabetic complications, no studies have evaluated the impact of exercise on nerve function in people with diagnosed diabetic peripheral neuropathy (DPN). The purpose of this pilot study was to examine feasibility and effectiveness of a supervised, moderately intense aerobic and resistance exercise program in people with DPN. We hypothesized that the exercise intervention can improve neuropathic symptoms, nerve function, and cutaneous innervation.MethodsA pre-test post-test design was used to assess change in outcome measures following participation in a 10-week aerobic and strengthening exercise program. Seventeen subjects with diagnosed DPN (8 males/9 females; age 58.4 ± 5.98; duration of diabetes 12.4 ± 12.2 years) completed the study. Outcome measures included pain measures (visual analog scale), Michigan Neuropathy Screening Instrument (MNSI) questionnaire of neuropathic symptoms, nerve function measures, and intraepidermal nerve fiber (IENF) density and branching in distal and proximal lower extremity skin biopsies.ResultsSignificant reductions in pain (? 18.1 ± 35.5 mm on a 100 mm scale, P = .05), neuropathic symptoms (? 1.24 ± 1.8 on MNSI, P = .01), and increased intraepidermal nerve fiber branching (+ 0.11 ± 0.15 branch nodes/fiber, P = .008) from a proximal skin biopsy were noted following the intervention.ConclusionsThis is the first study to describe improvements in neuropathic and cutaneous nerve fiber branching following supervised exercise in people with diabetic peripheral neuropathy. These findings are particularly promising given the short duration of the intervention, but need to be validated by comparison with a control group in future studies.     

Dietary fatty acids and peripheral artery disease in adults

BackgroundPeripheral artery disease (PAD) is a debilitating condition involving atherosclerosis. Although saturated, monounsaturated and polyunsaturated fatty acids have strong associations with atherosclerosis, it is unclear if diets high in these fatty acids affect PAD.MethodsWe studied 6352 adults aged 40 years and older who participated in the U.S. National Health and Nutrition Examination Survey between 1999 and 2004. Ankle brachial index (ABI) was assessed by standardized blood pressure measurements, and we defined PAD as an ABI < 0.9. Fatty acid intake was assessed by validated 24-h dietary recall. We used multivariable linear and logistic regression to estimate associations between intakes of dietary saturated fatty acids (SFAs), monounsaturated fatty acids (MFAs), marine omega-3 fatty acids (N-3), linolenic acid (LNA), and omega-6 fatty acids (N-6) and ABI/PAD.ResultsThe prevalence and 95% confidence interval (CI) of PAD was 5.2% (95% CI 4.6–5.8).There were no associations between ABI and intakes of marine N-3 (p = 0.83) or N-6 (p = 0.19) in adjusted models. In contrast, LNA was associated with higher ABI (p = 0.04) and SFA tended to be associated with lower ABI (p = 0.06) in adjusted models. In addition, higher SFA was associated with a higher prevalence of PAD: adjusted odds ratio 1.30 (95% CI 1.01–1.67; p = 0.04) and a trend toward slower gait speed (p = 0.08).ConclusionIn this nationally representative sample, higher dietary intakes of LNA and SFAs were associated with higher and lower ABI, respectively. Prospective studies are needed to confirm the potential protective effects of dietary LNA and detrimental effects of dietary SFAs on PAD.     

The association of macro- and micronutrient intake with growth hormone secretion

ContextGrowth hormone (GH) is known to be nutritionally regulated, but the effect of dietary composition on detailed GH secretion parameters has not previously been comprehensively evaluated.ObjectiveThe objective of the study was to determine whether specific macro- and micronutrients are associated with discrete parameters of GH secretion among subjects with wide ranges of body mass index.DesignDetailed macro- and micronutrient intake was assessed by 4-day food records while GH secretion was assessed by standard stimulation testing in 108 men and women in one study (Study 1), and by overnight frequent blood sampling in 12 men in another study (Study 2).ResultsPeak stimulated GH was positively associated with vitamin C (r = + 0.29; P = 0.003), dietary fiber (r = + 0.27; P = 0.004), arachidic acid (r = + 0.25; P = 0.008), and behenic acid (r = + 0.30; P = 0.002) intake in univariate analysis. Controlling for age, gender, race/ethnicity, visceral fat, HOMA-IR, total caloric intake and these four dietary factors in step-wise multivariate modeling, peak GH remained significantly associated with vitamin C and visceral fat (both P < 0.05). In addition, vitamin C intake was associated with various parameters of endogenous GH secretion including basal GH secretion (r = + 0.95; P < 0.0001), GH half-life (r = + .75; P = 0.005), total GH production (r = + 0.76; P = 0.004), GH area-under-the-curve (r = + 0.89; P = 0.0001), mean log₁₀ GH pulse area (r = + 0.67; P = 0.02), and overnight maximum (r = + 0.62; P = 0.03), nadir (r = + 0.97; P < 0.0001), and mean GH secretion (r = + 0.89; P = 0.0001).ConclusionsThese results suggest that certain micronutrients such as vitamin C intake are strongly and uniquely associated with stimulated and endogenous spontaneous GH secretion.     

Risk factors of mild cognitive impairment in middle aged patients with type 2 diabetes: a cross-section study

The aim of this study was to evaluate the risk factors of mild cognitive impairment (MCI) in middle-aged patients with type 2 diabetes (T2DM).MethodsMontreal Cognitive Assessment (MoCA) was applied as cognition assessment implement. One hundred and fifty-seven middle-aged type 2 diabetic patients were enrolled in this cross-section study (age 40～69, mean age 55 ± 7). There were 93 patients with MCI (MoCA score < 26) in MCI group and 64 with normal cognitive function (MoCA score ≥ 26) in control group. Information of history of disease, family history, data of BMI, WHR, HbA1c, FINS, C-Peptide (C-P), SBP, DBP, blood lipid (TG, TC, LDL-C, HDL-C and carotid ultrasound (carotid IMT, carotid resistance index [RI]) was collected.ResultsThere were significant differences in the rate of patients with hypertension ([40.63 vs. 58.06%], P = 0.026), duration of diabetes mellitus ([3.09 ± 4.04 y vs. 4.80 ± 4.94 y], P = 0.024), C-P ([2.79 ± 1.09 ng/ml vs. 2.26 ± 1.00 ng/ml], P = 0.008), Max C-IMT ([0.81 ± 0.15 mm vs. 0.91 ± 0.15 mm], P < 0.001), Min C-RI (0.71 ± 0.06 vs. 0.68 ± 0.06, P < 0.05), and no significant differences in the duration of hypertension and hyperlipidemia, BMI, WHR, HbA1c, SBP, DBP and blood lipid between control group and MCI group. MoCA scores were positively correlated with C-P (r = 0.252, P = 0.005), and negatively correlated with the history of hypertension (r = ?0.244, P = 0.002), duration of DM (r = ?0.161, P = 0.044), Max C-IMT (r = ?0.253, P = 0.005) and Min C-RI (r = ?0.183, P = 0.023). Multiple regression analysis showed that history of hypertension (Beta = ?0.267, P = 0.002), C-P (Beta = 0.281, P = 0.001) and Min C-RI (Beta = ?0.221, P = 0.011) were significantly independent determinants for the MoCA scores.ConclusionsThe longer duration of diabetes, history of hypertension, lower serum C-P levels, thickened C-IMT and higher C-RI could be risk factors of MCI in type 2 diabetic patients. This finding could have an important impact on the management of cognitive decline in diabetic patients.     

Effect of foot-ankle flexibility and resistance exercise in the secondary prevention of plantar foot diabetic ulcer

AimsThe study aimed to evaluate the effects of foot-ankle flexibility and resistance exercises on the recurrence rate of plantar foot diabetic ulcers, HbA1c levels, diabetic neuropathy examination (DNE) scores, ankle brachial index (ABI), and walking speed within 12 and 24 weeks.MethodsWe conducted a double-blind randomized clinical trial. Fifty patients with recently healed plantar foot diabetic ulcers were randomized to an intervention group that performed foot-ankle flexibility and resistance exercise three times a week in their home (n = 25) or a control group (n = 25). Both groups were given foot care education. Outcomes were assessed at plantar foot diabetic ulcer recurrence or at 12 and 24 weeks whichever came first. Outcome measures included plantar foot diabetic ulcer recurrence, changes of HbA1c levels, DNE scores, ankle brachial index ABI, and walking speed.ResultsThere were significant difference between groups in ulcer recurrence at either 12 weeks (intervention 8%, control 68%, RR 0.288; 95% CI 0.156–0.534, P = 0.000) within 12 weeks.or 24 weeks (intervention 16%, control 72%, RR 0.222; 95% CI 0.088–0.564, P = 0.000).). There were significant differences in the DNE score delta (P = 0.000) and walking speed delta (P = 0.000), but there were no significant differences in the HbA1c delta and ABI delta between groups at either 12 or 24 weeks.ConclusionsFoot-ankle flexibility and resistance exercises can reduce the recurrence of plantar foot diabetic ulcer incidence and improve diabetic neuropathy and walking speed.Clinical trial number: NCT04624516     

Markers of atherosclerosis and inflammation and mortality in patients with HIV infection

ObjectiveHIV-infected patients are at increased risk for cardiovascular disease, which may be mediated in part by inflammation. Surrogate marker studies suggest an increased prevalence of vascular abnormalities in HIV infection. We examined the association of all-cause mortality in HIV-infected patients with carotid artery intima-media thickness (cIMT) and high-sensitivity C-reactive protein (hsCRP).Design and methodsBaseline risk factors, cIMT and hsCRP were prospectively measured in 327 HIV-infected participants. Follow-up time with median of 3.1 years was calculated from baseline to death or censored dated 7/31/07. Cox Proportional Hazards models were used to study risk factors associated with mortality.ResultsThirty-eight (11.6%) of participants have died since study enrollment. cIMT was significantly higher in those who died and decedents were significantly more likely to have cIMT above the 75th percentile. Those who died had higher hsCRP than those alive and more had hsCRP values above 3 mg/L. CD4 count was lower and log₁₀ viral load was higher in decedents, but antiretroviral regimens were similar in both groups. cIMT and hsCRP levels were significantly associated with mortality (HR = 2.74, 95% CI 1.26–5.97, p = 0.01; HR = 2.38, 95% CI 1.15–4.9, p = 0.02).ConclusionsOur study demonstrated a strong association of carotid IMT and hsCRP with all-cause death in this HIV-infected population despite being similar with respect to exposure to antiretroviral medications. Together these surrogate markers may be indices of chronic inflammation and unfavorable outcomes in HIV-positive patients.     

Exercise ameliorates serum MMP-9 and TIMP-2 levels in patients with type 2 diabetes

AimThis study assessed the impact of regular exercise on inflammatory markers (high-sensitivity C-reactive protein [hsCRP], fibrinogen), and matrix metalloproteinases (MMPs) and their inhibitors (TIMPs), in patients with type 2 diabetes mellitus (T2DM).PatientsFifty overweight patients with T2DM were randomly assigned to two groups: (A) an exercise group (EXG, n = 25), with self-controlled exercise for at least 150 min/week and one additional supervised exercise session/week; and (B) a control group (COG, n = 25), with no exercise instructions. All participants were taking oral antidiabetic drugs, and none had diabetic complications. Clinical parameters, exercise capacity (VO_2peak), ventilatory threshold (VT), insulinresistance indices (fasting insulin, HOMA-IR, HOMA%S), hsCRP, fibrinogen, MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed at baseline and after 16 weeks.ResultsNo significant changes were found in body mass index, waist/hip ratio, insulin-resistance indices, MMP-2 and TIMP-1 throughout the study in either group (P > 0.05). Compared with controls, the EXG showed a significant decrease in systolic and mean blood pressure, total and LDL cholesterol, and HbA_1c (P < 0.05). Also, exercise significantly suppressed levels of fibrinogen (P = 0.047), hsCRP (P = 0.041) and MMP-9 (P = 0.028), and the MMP-9-to-TIMP-1 ratio (P = 0.038), whereas VO_2peak (P = 0.011), VT (P = 0.008) and plasma TIMP-2 levels (P = 0.022) were considerably upregulated in the EXG vs. COG. Standard multiple-regression analyses revealed that MMP-9 changes were independently associated with fibrinogen and HbA_1c changes, while fibrinogen changes independently predicted TIMP-2 alterations with exercise.ConclusionMostly self-controlled exercise of moderate intensity ameliorated serum levels of pro- and anti-atherogenic markers in patients with T2DM, with no effects on body weight. These data offer further insight into the cardioprotective mechanisms of exercise in patients with T2DM.