Effect of Insulin Resistance, Dyslipidemia, and Intra-abdominal Adiposity on the Development of Cardiovascular Disease and Diabetes Mellitus

Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
The American journal of medicine (Impact Factor: 5). 04/2007; 120(3 Suppl 1):S12-8. DOI: 10.1016/j.amjmed.2007.01.003
Source: PubMed


Abdominal obesity contributes to insulin resistance, a metabolic abnormality linked to the development of type 2 diabetes mellitus and cardiovascular disease (CVD). Insulin resistance generally precedes the development of type 2 diabetes. Currently, an estimated 10 million US adults have diabetes and another 25 million have impaired glucose tolerance (IGT), an intermediate step between insulin resistance and diabetes. The pathophysiologic mechanisms known to increase CVD risk in individuals with insulin resistance include formation of advanced glycation end products, hypertension, proinflammatory and prothrombotic states, and dyslipidemia (i.e., low levels of high-density lipoprotein cholesterol, increased levels of triglycerides, small, dense low-density lipoprotein cholesterol particles, apoplipoprotein B, and inflammation). The increased flux of free fatty acids from adipose tissue to the liver promotes dyslipidemia. Insulin resistance and impaired glucose tolerance are associated with increased CVD risk. Individuals with coexisting metabolic syndrome and diabetes have the highest prevalence rates of CVD. The Nurses' Health Study showed that CVD risk was elevated even before the development of diabetes compared with women who never developed diabetes. Lifestyle modification is recommended as the first-line treatment for obesity and its metabolic sequelae. Pharmacotherapy may be useful in patients for whom nonpharmacologic approaches alone are ineffective or insufficient. Primary care physicians play a critical role in the early identification and treatment of patients at increased risk for the development of type 2 diabetes and CVD because of their obesity and associated complications.

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    • "A major subtype of T2DM is insulin-resistant T2DM (IR-T2DM), which mainly develops when insulin secretion in peripheral tissues is unable to compensate for insulin resistance (Turkoski, 2006). IR-T2DM is of importance because it is associated with multiple complications such as cardiovascular anomalies (Rader, 2007). Although the first-line treatment for IR-T2DM usually includes a healthy diet and exercise, patients with DM, which cannot be controlled with healthy diet and exercise alone, are treated with drugs such as sulfonylureas, dipeptidyl peptidase (DPP)-4 inhibitors, biguanides and thiazolidine derivatives (Inzucchi, 2002; Duez et al., 2012). "
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    ABSTRACT: Rhizoma Coptidis (the rhizome of Coptis chinensis Franch) has commonly been used for treatment of diabetes mellitus in traditional Chinese medicine due to its blood sugar-lowering properties and therapeutic benefits which highly related to the alkaloids therein. However, a limited number of studies focused on the Coptis alkaloids other than berberine. In the present study, we investigated the anti-diabetic potential of Coptis alkaloids, including berberine (1), epiberberine (2), magnoflorine (3), and coptisine (4), by evaluating the ability of these compounds to inhibit protein tyrosine phosphatase 1B (PTP1B), and ONOO(‒)-mediated protein tyrosine nitration. We scrutinized the potentials of Coptis alkaloids as PTP1B inhibitors via enzyme kinetics and molecular docking simulation. The Coptis alkaloids 1‒4 exhibited remarkable inhibitory activities against PTP1B with the IC50 values of 16.43, 24.19, 28.14, and 51.04μM, respectively, when compared to the positive control ursolic acid. These alkaloids also suppressed ONOO(-)-mediated tyrosine nitration effectively in a dose dependent manner. In addition, our kinetic study using Lineweaver-Burk and Dixon plots revealed that 1 and 2 showed a mixed-type inhibition against PTP1B, while 3 and 4 noncompetitively inhibited PTP1B. Moreover, molecular docking simulation of these compounds demonstrated negative binding energies (Autodock 4.0=-6.7 to -7.8kcal/mol; Fred 2.0=-59.4 to -68.2kcal/mol) and a high proximity to PTP1B residues, including Phe182 and Asp181 in the WPD loop, Cys215 in the active sites and Tyr46, Arg47, Asp48, Val49, Ser216, Ala217, Gly218, Ile219, Gly220, Arg221 and Gln262 in the pocket site, indicating a higher affinity and tighter binding capacity of these alkaloids for the active site of the enzyme. Our results clearly indicate the promising anti-diabetic potential of Coptis alkaloids as inhibitors on PTP1B as well as suppressors of ONOO(-)-mediated protein tyrosine nitration, and thus hold promise as therapeutic agents for the treatment of diabetes and related disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Journal of ethnopharmacology 08/2015; 171(1):28-36. DOI:10.1016/j.jep.2015.05.020 · 3.00 Impact Factor
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    • "The last two are called prediabetes and are included among the metabolic syndrome (MetS) criteria, together with dyslipidemia and abdominal obesity (given by the pathological waist circumference), hypertension (> 130/85 mmHg) with or without treatment, and insulin resistance. An important cluster of risk factors for total cardiovascular morbi-mortality are the abdominal or visceral obesity defined by waist circumference values larger than 102 cm in men and 88 cm in women, dyslipidemia which may include high values for total Cholesterol (more than 180 mg/dL), or LDL-Cholesterol (more than 130 mg/dL), or triglycerides (> 150 mg/dL), or lower HDL-Cholesterol (< 40 mg/dL for men and < 50 mg/dL for women), Rader (2007). Waist circumference, although is not related to height, is correlated to visceral adiposity. "
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    ABSTRACT: Disregarding age, type 2 diabetes mellitus represents a major health problem for patients as well as for their families. Complications induced by the evolution of diabetes and the related conditions have a negative impact on the autonomy and quality of life, and imply a heavy burden on health and social care system. The increase of life-expectancy has induced higher disease prevalence in elderly population together with a strong financial contribution, which sometimes exceeds their resources. Firstly, we aimed to study whether the socioeconomic status explains the tendency for the hypertension status, both for the elderly and adult groups studied. Secondly, we focused on hypertension and other risk factors that may increase these patients risk of developing diabetes. The analysis was carried out on a number of 259 people included into the study. They were selected from two primary care offices in the urban area of Iasi, Romania. Using logistic regression for the hypertensive status, we found that the variables describing the socioeconomic status are all significant predictors, except for the current level of income. For a cut-off level of 0.5 for the predicted probability, in the groups with high and medium education, the threshold age of becoming hypertensive is around 50 years old, about 10 years earlier than for people with low education level. The hypertensive status and the duration of hypertension had a significant influence over the occurrence of diabetes mellitus. This influence was surpassed by that of the heredo-collateral antecedents of diabetes mellitus and by the presence of the abdominal obesity assessed by waist circumference.
    Procedia Economics and Finance 12/2014; 10:61-67. DOI:10.1016/S2212-5671(14)00278-0
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    • "These products may directly promote atherosclerosis through changes in endothelial, macrophage, and smooth muscle cells functions. Therefore, improving dyslipidemia would be effective to prevent complications of diabetic patients.[8] Several treatments including consumption of herbal medicines,[9] soy protein,[10] w-3 fatty acids,[11] and fiber[12] have been suggested to improve dyslipidemia in diabetic patients. "
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    ABSTRACT: Background: Alteration in plasma lipid and lipoprotein profile has been documented in diabetic patients. The purpose of this study was to compare the effect of probiotic and conventional yogurt on lipid profile in type 2 diabetes mellitus patients. Materials and Methods: A total of 44 patients with type 2 diabetes aged 30-60 years old who had low density lipoprotein cholesterol (LDL-c) ≥100 mg/dl enrolled in this randomized, double – blind controlled trial and were assigned to two intervention and control groups. The subjects in the intervention group consumed 300 g/d probiotic yogurt containing Lactobacillus acidophilus La-5 and Bifidobacterium lactis Bb-12 and subjects in the control group consumed 300 g/d conventional yogurt for 8 weeks. Anthropometric indices, dietary intake, and serum lipid profile were evaluated at the beginning and end of the intervention. Independent-sample t-test, paired sample t-test, ANCOVA, and repeated measures were used for statistical analysis. Results: The consumption of probiotic yogurt caused significant decrease in LDL-c/high density lipoprotein cholesterol (HDL-c) ratio (3.13 ± 1.00-2.07 ± 0.71, P = 0.016). The levels of HDL-c were increased significantly (43.66 ± 6.80-50.42 ± 6.64, P = 0.023) in the intervention group postintervention. However, there were no significant differences in triglyceride and total cholesterol levels between two groups postintervention (P < 0.05). Conclusion: It is suggested that probiotic yogurt consumption may be used as an alternative prevention approach and treatment method to improve dyslipidemia in patients with type 2 diabetes.
    Journal of research in medical sciences 06/2014; 19(6):531-6. · 0.65 Impact Factor
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