The coexistence of carotid and lower extremity atherosclerosis further increases cardio-cerebrovascular risk in type 2 diabetes.

BACKGROUND: Both carotid and lower limb atherosclerosis are associated with increased cardiovascular and cerebrovascular risks. However, it is still unclear whether the concomitant presence of carotid and lower extremity atherosclerosis further increases the cardiovascular and cerebrovascular risks. Therefore, our aim is to investigate whether the coexistence of carotid and lower extremity atherosclerosis was associated with higher cardiovascular and cerebrovascular risks in patients with type 2 diabetes. METHODS: This cross-sectional study was performed in 2830 hospitalized patients with type 2 diabetes. Based on carotid and lower limb Doppler ultrasound results, the patients were divided into three groups including 711 subjects without atherosclerosis, 999 subjects with either carotid or lower limb atherosclerosis, and 1120 subjects with both carotid and lower limb atherosclerosis. And we compared the clinical characteristics and prevalence of both cardio-cerebrovascular events (CCBVEs) and self-reported cardio- cerebrovascular diseases (CCBVDs) among the three groups. RESULTS: After adjusting for age, sex, and duration of diabetes, there were significant increases in the prevalence of both CCBVEs (3.8 vs. 11.8 vs. 26.4 %, p < 0.001 for trend) and self-reported CCBVDs (6.9 vs. 19.9 vs. 36.5 %, p < 0.001 for trend) across the three groups (diabetics without atherosclerosis, diabetics with either carotid or lower limb atherosclerosis, and diabetics with both carotid and lower extremity atherosclerosis). A fully adjusted logistic regression analysis also revealed that compared with those without atherosclerosis, those with either carotid or lower limb atherosclerosis had higher risk of CCBVEs (OR 1.724, 95 % CI 1.001-2.966) and self-reported CCBVDs (OR 1.705, 95 % CI 1.115-2.605), and those with concomitant presence of carotid and lower extremity atherosclerosis had the highest risk of CCBVEs (OR 2.869, 95 % CI 1.660-4.960) and self-reported CCBVDs (2.147, 95 % CI 1.388-3.320)(p < 0.001 for trend in CCBVEs and p = 0.002 for trend in CCBVDs, respectively). CONCLUSIONS: Either carotid or lower limb atherosclerosis was obviously related to increased cardio-cerebrovascular risk in type 2 diabetes. The concomitant presence of carotid and lower extremity atherosclerosis further increased cardio-cerebrovascular risk in patients with type 2 diabetes. The combined application of carotid and lower extremity ultrasonography may help identify type 2 diabetics with higher cardio-cerebrovascular risk.

Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease.

OBJECTIVES: A randomized, parallel controlled, open-label clinical trial was conducted to evaluate the effect of a botanic compound berberine (BBR) on NAFLD. METHODS: A randomized, parallel controlled, open-label clinical trial was conducted in three medical centers (NIH Registration number: NCT00633282). A total of 184 eligible patients with NAFLD were enrolled and randomly received (i) lifestyle intervention (LSI), (ii) LSI plus pioglitazone (PGZ) 15mg qd, and (iii) LSI plus BBR 0.5g tid, respectively, for 16 weeks. Hepatic fat content (HFC), serum glucose and lipid profiles, liver enzymes and serum and urine BBR concentrations were assessed before and after treatment. We also analyzed hepatic BBR content and expression of genes related to glucose and lipid metabolism in an animal model of NAFLD treated with BBR. RESULTS: As compared with LSI, BBR treatment plus LSI resulted in a significant reduction of HFC (52.7% vs 36.4%, p = 0.008), paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles (all p<0.05). BBR was more effective than PGZ 15mg qd in reducing body weight and improving lipid profile. BBR-related adverse events were mild and mainly occurred in digestive system. Serum and urine BBR concentrations were 6.99ng/ml and 79.2ng/ml, respectively, in the BBR-treated subjects. Animal experiments showed that BBR located favorably in the liver and altered hepatic metabolism-related gene expression. CONCLUSION: BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism. TRIAL REGISTRATION: ClinicalTrials.gov NCT00633282.

High-normal urinary albumin-to-creatinine ratio is independently associated with metabolic syndrome in Chinese patients with type 2 diabetes mellitus: A cross-sectional community-based study.

AIMS/INTRODUCTION: Microalbuminuria is positively related to metabolic syndrome (MetS). Our aim was to investigate whether urinary albumin-to-creatinine ratio (UACR) within the normal range is independently associated with MetS in Chinese community-based patients with type 2 diabetes. MATERIALS AND METHODS: A total of 514 participants (206 males and 308 females; mean age 66 years) with UACR less than 3.5 mg/mmol were enrolled from two downtown areas of Shanghai. The participants were stratified into quartiles according to UACR levels. The prevalence of MetS was assessed and compared among the four groups by binary logistic regression. RESULTS: Compared with participants with UACRs in the first quartile, the other quartiles had a higher prevalence of MetS (65.9%, 74.4% and 81.3%, respectively, P = 0.001) after adjustment for sex and age. After adjusting for potential confounders, participants in the second to the fourth quartile group had a 1.36-, 1.84- and 2.73-fold risk of MetS, respectively, relative to those in the lowest quartile. Furthermore, UACR, whether as quartile groups or as a continuous variable, is an independent predictor of MetS after fully adjusting for other variables. CONCLUSIONS: These results suggest that UACR even within the normal range is independently associated with MetS in Chinese community-based patients with type 2 diabetes mellitus.

Comparison of carotid and lower limb atherosclerotic lesions in both previously known and newly diagnosed type 2 diabetes mellitus.

AIMS/INTRODUCTION: To compare carotid and lower limb atherosclerotic lesions, and examine if carotid atherosclerotic lesions are in line with lower limb atherosclerotic lesions, and can reflect generalized atherosclerosis in inpatients with type 2 diabetes. MATERIALS AND METHODS: This was an observational study carried out in 867 Chinese inpatients with type 2 diabetes, including 573 previously known and 294 newly diagnosed patients. Ultrasonographic assessments of intima-media thickness (IMT), plaques, and stenosis in the carotid and lower limb arteries were evaluated. Atherosclerotic lesions between the carotid and lower limb arteries were compared in both previously known and newly diagnosed diabetes, respectively. RESULTS: In both the known (77.3% vs 49.4%, P < 0.001) and the newly diagnosed diabetes (55.4% vs 29.9%, P < 0.001), the prevalence of atherosclerotic plaques was significantly higher in the lower limb arteries than in the carotid arteries. Likewise, the prevalence of stenosis was also significantly higher (P < 0.001) in the lower limb arteries (16.9%) than in the carotid arteries (4.2%) in the established diabetes patients. However, there was no significant difference in the mean IMT between common carotid and common femoral arteries in both the previously known (0.90 ± 0.24 mm vs 0.89 ± 0.20 mm, P = 0.675) and the newly diagnosed diabetes patients (0.86 ± 0.22 mm vs 0.85 ± 0.16 mm, P = 0.436). CONCLUSIONS: Carotid plaques might underestimate generalized plaques in inpatients with type 2 diabetes, as shown by its significantly lower prevalence compared with that of the lower extremity arteries. A combined carotid and lower limb ultrasound examination can improve the detection of atherosclerotic lesions in inpatients with type 2 diabetes.

Prevalence and clinical characteristics of lower limb atherosclerotic lesions in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study.

BACKGROUND: The clinical features of atherosclerotic lesions in ketosis-onset diabetes are largely absent. We aimed to compare the characteristics of lower limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2 diabetes. METHODS: A cross-sectional study was performed in newly diagnosed Chinese patients with diabetes, including 53 type 1 diabetics with positive islet-associated autoantibodies, 208 ketosis-onset diabetics without islet-associated autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb atherosclerotic plaque and stenosis were evaluated and compared among the four groups based on ultrasonography. The risk factors associated with lower limb atherosclerotic plaque were evaluated via binary logistic regression in patients with diabetes. RESULTS: After adjusting for age and sex, the prevalence of lower limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no difference was observed in comparison to the patients with non-ketotic type 2 diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73 ± 0.17 mm) was markedly greater than that in the control subjects (0.69 ± 0.13 mm, p = 0.045) after controlling for age and sex, but no significant differences were found between the ketosis-onset diabetics and the type 1 diabetics (0.71 ± 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics (0.80 ± 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk factors for the presence of lower limb plaque in both the ketosis-onset and non-ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic patients. CONCLUSIONS: The prevalence and risk of lower limb atherosclerotic plaque in the ketosis-onset diabetes were remarkably higher than in the control subjects without diabetes. The features and risk factors of lower limb atherosclerotic lesions in the ketosis-onset diabetes resembled those in the non-ketotic type 2 diabetes, but different from those in the type 1 diabetes. Our findings provide further evidences to support the classification of ketosis-onset diabetes as a subtype of type 2 diabetes rather than idiopathic type 1 diabetes.

Retinal microvascular abnormalities are associated with early carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes mellitus.

OBJECTIVE: Controversies concerning the association of retinal microvascular abnormalities (RMAs) with atherosclerosis in patients with diabetes exist. The objective of this study was to investigate the association between RMAs and carotid atherosclerotic lesions in Chinese inpatients with type 2 diabetes. METHODS: This cross-sectional study involved 2870 type 2 diabetic patients including 1602 men aged 15-90 years and 1268 women aged 17-88 years. Both retinal arteriosclerosis (RA) and diabetic retinopathy (DR) were determined by digital fundus photography using a standardized protocol. RMAs are defined as the presence of either RA or DR. Carotid atherosclerotic lesions including carotid intima-media thickness (CIMT), carotid atherosclerotic plaque and stenosis were assessed and compared between patients with and without RMAs based on Doppler ultrasound. The association of RMAs with carotid atherosclerotic lesions was analyzed by linear and binary logistic regression analyses. RESULTS: The CIMT values in both male and female diabetics with RMAs were significantly greater than in those without RMAs after controlling for age (0.88±0.21 vs. 0.77±0.20 mm for men, p=0.002; and 0.84±0.19 vs. 0.76±0.21 mm for women, p=0.002). The prevalence of carotid plaque was also markedly higher in patients with RMAs than in those without RMAs after adjusting for age (54.3% vs. 23.9% for men, p<0.001; 48.4% vs. 32.0% for women, p=0.046). However, no significant difference was observed in the prevalence of carotid stenosis in either men or women with or without RMAs. After controlling for multiple confounding factors, RMAs were independently associated with increased CIMT in both men (ß: 0.067, 95% CI: 0.026-0.269, p=0.018) and women (ß: 0.087, 95% CI: 0.058-0.334, p=0.005) with type 2 diabetes, and they were also closely associated with the presence of carotid plaque (OR: 2.17, 95% CI: 1.54-3.05, p<0.001 for men; OR: 1.38, 95% CI: 0.91-2.08, p=0.129 for women) in men with type 2 diabetes. CONCLUSIONS: RMAs were closely associated with early carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes. Our results suggested that changes in retinal microvasculature may play a role in the pathogenesis of atherosclerosis and may be used as an indicator of early atherosclerosis in patients with type 2 diabetes.

[Detection rates of atherosclerosis by carotid versus lower limb ultrasonography in newly diagnosed type 2 diabetics].

OBJECTIVE: To compare the detection rates of atherosclerosis by carotid versus lower limb ultrasound in newly diagnosed type 2 diabetics and analyze the relationship between atherosclerosis and cardio-cerebrovascular events. METHODS: A total of 148 newly diagnosed type 2 diabetics were recruited. Both carotid and lower extremity atherosclerosis were assessed by Doppler ultrasound. Diabetic atherosclerosis was defined as the presence of either carotid or lower extremity plaques in any of the above-mentioned arterial segments. A kappa value was computed to document the agreement between isolated carotid (or lower limb) atherosclerosis and diabetic atherosclerosis. The prevalence of cardio-cerebrovascular events was compared among different distribution types of atherosclerosis. RESULTS: According to the diagnostic criteria, the prevalence of diabetic atherosclerosis was 66.2% in the newly diagnosed type 2 diabetes. Based on carotid or lower extremity ultrasound, the prevalence of diabetic atherosclerosis was 27.0% and 62.2% respectively in newly diagnosed type 2 diabetes. The kappa values for the agreement between carotid/lower limb atherosclerosis and diabetic atherosclerosis were 0.32/0.91 (95% confidence interval 0.22-0.42 for carotid vs 0.84-0.98 for lower extremity). The combination of carotid and lower extremity arterial atherosclerosis was associated with a significantly increased detection rate of cardio-cerebrovascular events (26.5%) versus those with either carotid or lower extremity arterial atherosclerosis (0% and 10.3% respectively). CONCLUSION: The combination of carotid and lower extremity ultrasonography can more accurately reflect the atherosclerotic lesions in type 2 diabetes. Due to a higher prevalence of cardio-cerebrovascular events, type 2 diabetics with both carotid and lower extremity atherosclerosis should be managed more aggressively to reduce the risk of cardio-cerebrovascular events.

Low-grade albuminuria is associated with early but not late carotid atherosclerotic lesions in community-based patients with type 2 diabetes.

BACKGROUND: Low-grade albuminuria is associated with cardiovascular risk factors and mortality. Our aim was to investigate the association between low-grade albuminuria and carotid atherosclerotic lesions in community-based patients with type 2 diabetes. METHODS: A cross-sectional study was performed in 475 community-based patients with type 2 diabetes (190 males and 285 females) with normal urinary albumin-to-creatinine ratios (UACR) (< 3.5 mg/mmol) from Shanghai, China. The subjects were stratified into tertiles based on UACR levels (the lowest tertile was UACR ≤ 1.19 mg/mmol, and the highest tertile was UACR ≥ 2 mg/mmol). Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on ultrasonography. The urinary albumin excretion rate was determined as the mean of the values obtained from three separate early morning urine samples. RESULTS: Compared with the subjects with UACR in the lowest tertile, the subjects with UACR in the middle and highest tertiles had greater CIMT values (0.88 ± 0.35 mm, 0.99 ± 0.43 mm and 1.04 ± 0.35 mm, respectively; all p < 0.05) and a higher prevalence of carotid atherosclerotic plaques (25.3%, 39.0% and 46.2%, respectively; all p < 0.05) after adjusting for sex and age. Fully adjusted multiple linear regression and logistic regression analyses revealed that UACR tertiles were significantly associated with elevated CIMT (p = 0.007) and that, compared with the subjects in the first tertile of UACR, those in the second and third tertiles had 1.878- and 2.028-fold risk of carotid plaques, respectively. However, there was no statistical association between UACR tertile and the prevalence of carotid stenosis. CONCLUSIONS: Higher UACR within the normal range was independently associated with early but not late carotid atherosclerotic lesions in community-based patients with type 2 diabetes. Low-grade albuminuria contributes to the risk of carotid atherosclerosis and may be used as an early marker for the detection of atherosclerosis in patients with type 2 diabetes.

Prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study.

BACKGROUND: The features of carotid atherosclerosis in ketosis-onset diabetes have not been investigated. Our aim was to evaluate the prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed Chinese diabetic patients with ketosis but without islet-associated autoantibodies. METHODS: In total, 423 newly diagnosed Chinese patients with diabetes including 208 ketosis-onset diabetics without islet-associated autoantibodies, 215 non-ketotic type 2 diabetics and 79 control subjects without diabetes were studied. Carotid atherosclerosis was defined as the presence of atherosclerotic plaques in any of the carotid vessel segments. Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on Doppler ultrasound examination. The clinical features of carotid atherosclerotic lesions were analysed, and the risk factors associated with carotid atherosclerosis were evaluated using binary logistic regression in patients with diabetes. RESULTS: The prevalence of carotid atherosclerosis was significantly higher in the ketosis-onset diabetic group (30.80%) than in the control group (15.2%, p=0.020) after adjusting for age- and sex-related differences, but no significant difference was observed in comparison to the non-ketotic diabetic group (35.8%, p=0.487). The mean CIMT of the ketosis-onset diabetics (0.70±0.20 mm) was markedly higher than that of the control subjects (0.57±0.08 mm, p<0.001), but no significant difference was found compared with the non-ketotic type 2 diabetics (0.73±0.19 mm, p=0.582) after controlling for differences in age and sex. In both the ketosis-onset and the non-ketotic diabetes, the prevalence of carotid atherosclerosis was markedly increased with age (both p<0.001) after controlling for sex, but no sex difference was observed (p=0.479 and p=0.707, respectively) after controlling for age. In the ketosis-onset diabetics, the presence of carotid atherosclerosis was significantly associated with age, hypertension, low-density lipoprotein cholesterol and mean CIMT. CONCLUSIONS: The prevalence and risk of carotid atherosclerosis were significantly higher in the ketosis-onset diabetics than in the control subjects but similar to that in the non-ketotic type 2 diabetics. The characteristics of carotid atherosclerotic lesions in the ketosis-onset diabetics resembled those in the non-ketotic type 2 diabetics. Our findings support the classification of ketosis-onset diabetes as a subtype of type 2 diabetes.