Genetic Variants Associated with Insulin Resistance and Metabolic Syndrome in Young Asian Indians with Myocardial Infarction

Cardiovascular disease (CVD), principally myocardial infarction (MI) and stroke, is the leading clinical and public health problem in the United States and is rapidly becoming so worldwide. Their primary prevention is promising, in theory, but difficult to achieve in practice. The principal modalities that have demonstrated efficacy include therapeutic lifestyle changes (TLCs) and adjunctive drug therapies under the guidance of the health-care provider and tailored to the individual patient. The prevention and treatment of the pandemic of overweight and obesity and lack of regular physical activity, both of which are alarmingly common in the United States, prevention and treatment of hypertension, avoidance and cessation of cigarette smoking, adoption and maintenance of a healthy diet, and avoidance of heavy alcohol consumption all have proven benefits in decreasing the risks of a first MI and stroke as well as other clinical manifestations of CVD. Although adoption of TLCs would avoid the need for adjunctive drug therapies in many primary prevention subjects, this strategy is difficult to achieve or maintain for most and may be insufficient for many, especially those at high risk with metabolic syndrome. The criteria for metabolic syndrome, affecting over 40% of the adult population older than 40 in the United States, include overweight or obesity, dyslipidemia, hypertension, and insulin resistance, a precursor of diabetes. The adjunctive therapies of proven benefit in the primary prevention of MI and stroke include statins, blood pressure medications, aspirin, and drugs to treat insulin resistance and hyperglycemia. Fortunately, even for patients who prefer prescription of pills to proscription of harmful lifestyles, these drug therapies still have net benefits. The adoption and maintenance of TLCs and adjunctive drug therapies into clinical practice will reduce both the incidence of and mortality from a first MI and stroke as well as other major clinical manifestations of CVD.

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Metabolic syndrome identifies normal weight insulin-resistant stroke patients at risk for recurrent vascular disease

International Journal of Stroke ◽

10.1177/1747493018816425 ◽

2018 ◽

Vol 14 (6) ◽

pp. 639-645 ◽

Cited By ~ 1

Author(s):

Jennifer L Dearborn ◽

Catherine M Viscoli ◽

Silvio E Inzucchi ◽

Lawrence H Young ◽

Walter N Kernan

Keyword(s):

Myocardial Infarction ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Obesity Paradox ◽

Normal Weight ◽

Diabetic Patients ◽

Insulin Resistant ◽

Increased Risk ◽

All Cause Mortality ◽

Patients At Risk

Background The obesity paradox refers to the finding in observational studies that patients with obesity have a better prognosis after stroke than normal weight patients. Aim To test the hypothesis that there might be important heterogeneity within the obese stroke population, such that those with metabolic syndrome would be at higher risk for stroke or myocardial infarction and all-cause mortality compared to patients without metabolic syndrome. Methods The Insulin Resistance Intervention after Stroke trial enrolled non-diabetic patients with a recent ischemic stroke or transient ischemic attack and insulin resistance. We examined the association between metabolic syndrome and outcome risk in patients with normal weight at entry (body mass index (BMI) = 18.5–24.9 kg/m2), overweight (BMI = 25–29.9 kg/m2), or obesity (BMI ≥ 30 kg/m2). Analyses were adjusted for demographic features, treatment assignment, smoking, and major comorbid conditions. Results Metabolic syndrome was not associated with greater risk for stroke or myocardial infarction among 1536 patients who were overweight (adjusted hazard ratio (HR), 0.95; 95% confidence interval (CI): 0.69–1.31) or 1626 obese patients (adjusted HR, 1.00; 95% CI: 0.70–1.41). However, among 567 patients with a normal BMI, metabolic syndrome was associated with increased risk for stroke or myocardial infarction (adjusted HR, 2.05; 95% CI: 1.25–3.37), and all-cause mortality (adjusted HR, 1.70; 95% CI: 1.03–2.81) compared to patients without metabolic syndrome. Conclusions The presence of metabolic syndrome identified normal weight patients with insulin resistance but no diabetes who have a higher risk of adverse cardiovascular outcomes, compared with patients without metabolic syndrome.

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A clinically confirmed family history for early myocardial infarction is associated with increased risk of obesity, insulin resistance and metabolic syndrome

Journal of Hypertension ◽

10.1097/hjh.0b013e328351c285 ◽

2012 ◽

Vol 30 (5) ◽

pp. 948-953 ◽

Cited By ~ 5

Author(s):

Martin Magnusson ◽

Philippe Burri ◽

Olle Melander

Keyword(s):

Myocardial Infarction ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Family History ◽

Increased Risk

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Diabetes, Insulin Resistance, and the Metabolic Syndrome in Patients With Acute Myocardial Infarction Without Previously Known Diabetes

Diabetes Care ◽

10.2337/diacare.26.10.2770 ◽

2003 ◽

Vol 26 (10) ◽

pp. 2770-2776 ◽

Cited By ~ 72

Author(s):

A. Tenerz ◽

A. Norhammar ◽

A. Silveira ◽

A. Hamsten ◽

G. Nilsson ◽

...

Keyword(s):

Myocardial Infarction ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Acute Myocardial Infarction ◽

The Metabolic Syndrome

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Association of genetic variants with myocardial infarction in Japanese individuals with or without metabolic syndrome

Experimental and Therapeutic Medicine ◽

10.3892/etm.2010.147 ◽

2010 ◽

Vol 1 (6) ◽

pp. 969-975 ◽

Cited By ~ 3

Author(s):

TOSHIKI KAWAMIYA ◽

KIMIHIKO KATO ◽

HIDEKI HORIBE ◽

KIYOSHI YOKOI ◽

MITSUTOSHI OGURI ◽

...

Keyword(s):

Myocardial Infarction ◽

Metabolic Syndrome ◽

Genetic Variants

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Abstract P086: Circulating MicroRNAs are Associated with Abdominal Adiposity and Fatty Liver in Asian Indians

Circulation ◽

10.1161/circ.133.suppl_1.p086 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Kevin Miles ◽

Alka M Kanaya ◽

Elena Flowers

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Waist Circumference ◽

Fatty Liver ◽

Asian Indians ◽

Circulating Microrna ◽

Abdominal Adiposity ◽

Circulating Micrornas ◽

The Metabolic Syndrome ◽

Computed Tomography Images

Background: Fatty liver is associated with abdominal adiposity, insulin resistance, and risk for diabetes and liver disease. Asians Indians have a high prevalence of fatty liver and abdominal visceral adiposity compared to other racial groups, and the causes are not well understood. Circulating microRNAs (miRs) identify latent risk factors for diabetes and biologic mechanisms underlying disease. Previous studies identified associations between circulating microRNAs and obesity in Caucasians. No prior studies evaluated association between circulating microRNAs and fatty liver and abdominal adiposity in Asian Indians. Hypothesis: Circulating microRNAs are associated with the presence of fatty liver and elevated waist circumference in Asian Indians. Methods: We studied 136 participants (49% women, age 56 ± 8 years) from the Metabolic syndrome and Atherosclerosis in South Asians Living in America (MASALA) pilot study. Elevated waist circumference at baseline was defined as >90cm for men and >80cm for women. Fatty liver was measured using computed tomography images of the liver and spleen (in Hounsfield units) and was defined as liver to spleen ratio <1. Circulating microRNAs (n=30) were measured from plasma collected during the baseline visit using the Firefly Circulating microRNA assay. Unadjusted and multivariate-adjusted logistic regression models were created. Results: Elevated waist circumference was present in 115 (85%) and fatty liver was present in 24 (18%). In age and sex adjusted models, miR-423 was inversely associated with elevated waist circumference (p<0.05). This miR was also inversely associated with metabolic syndrome (p<0.1) in the subset of individuals not taking hypertension or diabetes medications (n=88). MiR-146a, miR-146b, miR-197, miR-20b, miR-21, miR-222, and miR-24 were inversely associated with fatty liver (p<0.05 for all). These microRNAs show moderate to high inter-correlations (r=0.4-0.9). None of these miRs were significantly associated with metabolic syndrome or diabetes. MiR-486, which is associated with glycemic impairment and progression in Asian Indians and insulin resistance and response to thiazolidenidones, was positively associated with fatty liver (p<0.1). Conclusions: We found significant relationships between fatty liver and waist circumference and numerous circulating microRNAs. MicroRNAs inversely associated with fatty liver are correlated and may be co-expressed in order to regulate biologic pathways related to fatty liver. There is no overlap between miRs associated with fatty liver and miRs associated with diabetes and metabolic syndrome. Additional studies are needed to determine whether circulating microRNAs might be useful biomarkers for the detection of fatty liver, which biologic pathways are implicated, and whether there are differences between race/ethnic groups.

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