Fasting plasma glucose and clustering of cardiometabolic risk factors in normoglycemic outpatient children and adolescents

OBJECTIVE

To evaluate whether fasting plasma glucose (FPG) within a normoglycemic range is associated with cardiometabolic risk factors (CMRF) among children and adolescents in an outpatient setting.

RESEARCH DESIGN AND METHODS

Subjects (780; age 6–16 years) with FPG <100 mg/dL were divided into tertiles of FPG.

RESULTS

BMI, waist circumference, homeostasis model assessment-insulin resistance, systolic blood pressure, and white blood cell (WBC) count (P < 0.0001) increased across tertiles of FPG. Subjects with high-normal FPG (89–99 mg/dL) showed a higher risk of insulin resistance, hypertension, and high WBC count compared with subjects with low-normal FPG, independent of BMI z score.

CONCLUSIONS

In outpatient children and adolescents, higher FPG within the normal range is associated with several CMRF, independent of obesity. Thus the simple measurement of FPG may help identify subjects who warrant some monitoring in relation to cardiovascular risk.The prevalence of prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), is increasing in the pediatric population (1). Similar to adults, prediabetes in children is associated with both an elevated risk of developing type 2 diabetes and a worsened cardiovascular risk profile compared with normoglycemic subjects (2,3). Recent studies have shown that in obese children some impairment of glucose homeostasis might already be present at fasting glucose concentrations below the threshold for IFG (4–6). However, the question whether fasting plasma glucose (FPG) in the normal range is associated with some cardiometabolic risk factors (CMRF) is little explored. Therefore, we assessed whether FPG clustered with CMRF in an outpatient setting of normoglycemic Caucasian children and adolescents. In addition we evaluated whether subjects with high-normal FPG showed a worse cardiometabolic risk profile.     

Comprehensive management of cardiometabolic risk factors

Comprehensive management of cardiometabolic risk requires management of a patient's underlying risk factors. The initial approach to treatment demands a careful assessment of patient risk, using formal risk assessment tools (eg, the Framingham Risk Score and the National Cholesterol Education Program Adult Treatment Panel III definition of metabolic syndrome), combined with comprehensive knowledge of the patient. There is increasing evidence that lifestyle modification and pharmacotherapy can delay or prevent the progression of insulin resistance to diabetes and cardiovascular disease. Periodic reassessment of a patient's risk can assist in guiding long-term therapy to achieve optimal cardiometabolic health.     

Cardiovascular disease and modifiable cardiometabolic risk factors

Cardiovascular disease (CVD) is the leading cause of death in the United States and many parts of the world. Potentially modifiable risk factors for CVD include tobacco use, physical inactivity, hypertension, elevated low-density lipoprotein cholesterol, and a cluster of interrelated metabolic risk factors. Over the last several decades, efforts to prevent or treat CVD risk factors have resulted in significantly lower rates of CVD-related mortality. However, many patients never achieve adequate control of CVD risk factors even when these factors have been identified. In addition, the growing prevalence of obesity and type 2 diabetes mellitus (DM) threatens to undermine the improvements in CVD that have been achieved. In the United States, approximately two thirds of adults are overweight or obese, and even modest excess body weight is associated with a significantly increased risk of CVD-related mortality. Lifestyle interventions to promote weight loss reduce the risk of CVD-related illness but are difficult for patients to sustain over long periods of time. The increased incidence of obesity has also contributed to significant increases in the prevalence of other important CVD risk factors, including hypertension, dyslipidemia, insulin resistance, and type 2 DM. Pharmacologic therapies are currently available to address individual CVD risk factors, and others are being evaluated, including endocannabinoid receptor antagonists, inhibitors of peroxisome proliferator-activated receptor subtypes alpha and gamma, and several agents that modulate the activity of glucagon-like peptide-1. The new agents have the potential to significantly improve several CVD risk factors with a single medication and may provide clinicians with several new strategies to reduce the long-term risk of CVD.     

Plasma adiponectin does not correlate with insulin resistance and cardiometabolic variables in nondiabetic Asian Indian teenagers

OBJECTIVE—The objectives of this study were to determine age- and sex-specific concentrations of adiponectin in Asian Indian teenagers and adults and to assess whether its blood levels correlated with insulin resistance and other cardiometabolic parameters.RESEARCH DESIGN AND METHODS—We studied 196 teenagers (94 boys, 102 girls) 12–18 years of age, selected from a cohort of 2,640 individuals from a cross-sectional school-based survey in Chennai, India. For comparison, adiponectin and plasma insulin were measured in 84 healthy adults. Correlation of adiponectin with plasma levels of insulin, proinsulin, insulin resistance, anthropometry, and family history of diabetes were studied.RESULTS—Adiponectin showed a sex dimorphism, with girls having higher values (in μg/ml) (10.3 ± 5.0) than boys (8.4 ± 3.5) (P < 0.0001), and it showed a positive correlation with HDL cholesterol in boys only and not with other lipid parameters, insulin resistance, proinsulin, anthropometry, and family history of diabetes. In the adults, adiponectin correlated with fasting glucose and inversely with triglycerides.CONCLUSIONS—In Asian Indian adults and teenagers, adiponectin did not correlate directly with measures of insulin sensitivity, overweight, and other cardiometabolic variables. This was at variance with several reports in other populations showing an inverse association of adiponectin with insulin resistance, proinsulin, and BMI, suggesting ethnic differences in the relationship of adiponectin with insulin sensitivity. The role of adiponectin in relation to action of insulin needs more detailed studies in Asian Indians.A variety of adipokines have been implicated in causation of insulin resistance, systemic inflammation, and atherosclerotic processes (1–5). Among these, Adiponectin is the most abundant and is shown to have insulin-sensitizing, antiatherogenic, and anti-inflammatory properties (3–5). Sex dimorphism is generally observed, with females having higher concentrations (5–7). Hypoadiponectinemia is common in obese adults (4), obese children and adolescents (5,6,8–10), and subjects having insulin resistance at all ages (3,9,10). Low adiponectin is shown to be predictive of future diabetes, in many populations, including the Asian Indians (7,11). Adiponectin is inversely related to proinsulin (9). Higher concentrations of proinsulin are associated with cardiovascular risk in adults (12,13) and also in adolescents (14). A raised proinsulin-to-insulin ratio, often found in diabetes, is considered an index of β-cell dysfunction.Our recent study in adolescents showed a high prevalence of insulin resistance and cardiovascular risk factors; 65% of normal weight and 85% of overweight children and adolescents showed presence of at least one cardiovascular risk factor (15). Whereas many studies in white teenagers had demonstrated such abnormalities in obese subjects (10), we observed these abnormalities even in nonobese subjects. In light of evidence showing an important role for adiponectin in regulation of insulin action and having antiatherogenic properties, we studied its association with cardiometabolic variables including insulin resistance and proinsulin in Asian Indian teenagers. A subsample from the cohort of our previous study (15) was used for this analysis.The objectives of the study were 1) to determine age- and sex-specific values of adiponectin and proinsulin in Asian Indian teenagers, 2) to assess the association of adiponectin with cardiometabolic risk variables, 3) to see if abnormal proinsulin-to-insulin ratio suggestive of early β-cell dysfunction was present in association with other abnormalities, and 4) to see if positive family history of diabetes influenced the levels of adiponectin, insulin, proinsulin, and proinsulin/insulin.     

体脂分布类型和胰岛素抵抗对心血管病危险因素聚集性的影响

目的探讨体脂分布类型和胰岛素抵抗对心血管病危险因素聚集性的影响。方法在2 668名自然人群中调查体质量指数、腰围/臀围比值、血压、血胆固醇、三酰甘油、高密度脂蛋白-胆固醇、低密度脂蛋白-胆固醇、血糖、胰岛素及胰岛素敏感性指数。结果外周型超重组血压、三酰甘油、胰岛素高于非超重组,高密度脂蛋白-胆固醇、胰岛素敏感性指数低于非超重组;而中心型超重组血压、胰岛素及危险因素聚集程度高于外周型超重组,胰岛素敏感性指数低于外周型超重组;分析显示胰岛素敏感性指数与血脂、血糖及危险因素聚集程度密切相关。结论体脂分布类型是影响心血管危险因素聚集的重要因素。     

Epidemiology and risk factors of the cardiometabolic syndrome in the Middle East

The metabolic syndrome (MetS), a constellation of cardiovascular risk factors, is a growing health challenge worldwide. Most studies on MetS epidemiology are from developed countries. The Middle East is lagging behind in understanding the epidemiology of MetS and its risk factors in the region. This is partly owing to a scarcity of high-quality, nationally representative studies. In a series of recent national surveys, we have studied the epidemiology of MetS and its risk factors in Iran. We review the current situation in the region and highlight current gaps of knowledge and epidemiological concepts that need to be taken into account when doing population-level health programming. We explore the results of our national surveys as successful examples along this path.     

青少年心理障碍的危险因素分析

目的　分析导致青少年心理障碍的主要危险因素,为制定干预措施提供依据。方法　将300例青少年心理障碍求诊 者的临床资料进行整理,并采用自编青少年心理障碍调查表及Logistic多元回归分析法进行评定分析。结果　300例青少年 心理障碍者中女性193例(64.33%),男性107例(35.67%);主要临床表现为情绪低落,不听话,焦虑,注意力不集中,缺乏兴 趣等;心理障碍发生率随年龄增高而增高,>16a增高比率更显著。多元回归分析显示:家庭管教方式粗暴、家庭关系不融洽、 缺乏沟通、居住地社会风气恶劣及青少年业余时间沉迷于电脑游戏是导致青少年心理障碍的主要危险因素。结论　早期的心 理干预,对提高青少年心理健康水平尤为重要。     

Insulin resistance and cardiovascular disease risk factors in children of parents with the insulin resistance (metabolic) syndrome

OBJECTIVE: To evaluate whether children of parents with the insulin resistance syndrome (IRS) themselves have greater insulin resistance and unfavorable patterns of cardiovascular disease (CVD) risk factors. RESEARCH DESIGN AND METHODS: This cross-sectional study included 220 white and 36 black children aged 11-15 years identified through a school-based blood pressure screening program, along with 378 of their parents. Measures of insulin resistance (glucose disposal per minute per kilogram of lean body mass in a euglycemic-hyperinsulinemic clamp [Mlbm] and fasting insulin), adiposity, and other CVD risk factors were compared in children with and without a parental history of IRS, defined according to the National Cholesterol Education Program Adult Treatment Panel III consensus definition. RESULTS: Compared with children in whom neither parent had IRS, children who had at least one parent with the syndrome had statistically significantly lower mean Mlbm (12.1 vs. 13.6 mg.kg(-1).min(-1); P=0.04) and higher fasting insulin (geometric means 99 vs. 76 pmol/l; P=0.01) after adjustment for sex, race, age, and Tanner stage. Mean BMI, waist circumference, waist-to-hip ratio, triceps and subscapular skinfolds, and percentage of body fat were also significantly higher in children of an affected parent, but there were no significant differences in lipid or blood pressure levels between the two groups. CONCLUSIONS: Insulin resistance and obesity may be the earliest manifestations of IRS in children with a parental history of the syndrome.     

Adipocytes and cardiometabolic risk

To describe the link between adipocytes and cardiometabolic risk and present mechanisms by which obesity contributes to dysglycemia, dyslipidemia, hypertension, and a prothrombotic, inflammatory state favoring atherogenesis. Review of relevant literature compiled via a literature search (PUBMED) of English-language literature publications between 1994 and 2010. Cardiometabolic risk is a term that includes a series of conditions and factors, which contribute to increased risk of developing atherosclerosis. Cardiometabolic risk encompasses traditional coronary risks factors such as smoking, arterial hypertension, diabetes, obesity, elevated cholesterol, old age, male gender, and a positive family history of early coronary events plus additional contributing factors such as insulin resistance, atherogenic dyslipidemia, physical inactivity, unhealthy eating, inflammation, and hypercoagulable state. Adipocyte accumulation and dysfunction contribute to most, if not all, of the cardiometabolic risk factors. A number of different pathologic mechanisms through which adipocytes contribute to cardiometabolic risk and promote atherosclerosis are reviewed. Dysfunctional adipocytes are associated with the development of insulin resistance, hyperglycemia, atherogenic dyslipidemia and arterial hypertension, and favor a prothrombotic and proinflammatory state. Adipocytes dysfunction increases cardiometabolic risk through a variety of mechanisms.     

Prevalence of cardiovascular risk factors in an urban adult population from southern Spain. IMAP Study

Aims: To study the prevalence of cardiovascular risk factors in an urban population of Malaga, Spain and its relationship with educational level. Methods: A cross‐sectional study was performed with a random representative sample of 2270 individuals from the adult population (18–80 years) from a specific Health‐Care Centre in Malaga City. All participants underwent a clinical interview, including social‐demographical information and a physical examination. A blood sample was also drawn. Results: The mean age of the participants was 43.6 ± 15.6 years and 57.6% had a low educational level. The prevalence of cardiovascular risk factors was: smoking 27.7%, hypertension 33.1%, diabetes 7.1% and dyslipidaemia 65.4%. Over 60% were either overweight or obese, and 76.7% had a sedentary lifestyle. Except for smoking and a low‐HDL cholesterol, the prevalence of the other cardiovascular risk factors increased with age. A low educational level was associated with a high prevalence of cardiovascular risk factors, and this association was significant with regard to smoking, obesity, abdominal obesity and hypertriglyceridaemia. Conclusions: The population studied presents a high prevalence of cardiovascular risk factors, especially dyslipidaemia and obesity. The low academic level was associated with an increased prevalence of smoking, obesity and dyslipidaemia. People with a low socio‐cultural level are a priority target for introducing policies to prevent and control cardiovascular disease.     

Pubertal timing and growth influences cardiometabolic risk factors in adult males and females

OBJECTIVE

Early pubertal onset in females is associated with increased risk for adult obesity and cardiovascular disease, but whether this relationship is independent of preceding childhood growth events is unclear. Furthermore, the association between male puberty and adult disease remains unknown. To clarify the link between puberty and adult health, we evaluated the relationship between pubertal timing and risk factors for type 2 diabetes and cardiovascular disease in both males and females from a large, prospective, and randomly ascertained birth cohort from Northern Finland.

RESEARCH DESIGN AND METHODS

Pubertal timing was estimated based on pubertal height growth in 5,058 subjects (2,417 males and 2,641 females), and the relationship between puberty and body weight, glucose and lipid homeostasis, and blood pressure at age 31 years was evaluated with linear regression modeling.

RESULTS

Earlier pubertal timing associated with higher adult BMI, fasting insulin, diastolic blood pressure, and decreased HDL cholesterol in both sexes (P < 0.002) and with higher total serum cholesterol, LDL cholesterol, and triglycerides in males. The association with BMI and diastolic blood pressure remained statistically significant in both sexes, as did the association with insulin levels and HDL cholesterol concentrations in males after adjusting for covariates reflecting both fetal and childhood growth including childhood BMI.

CONCLUSIONS

We demonstrate independent association between earlier pubertal timing and adult metabolic syndrome-related derangements both in males and females. The connection emphasizes that the mechanisms advancing puberty may also contribute to adult metabolic disorders.Accumulating evidence suggests an association between early timing of puberty and adverse health outcomes later in life. Typically evaluating females only, these studies show that early menarche is correlated with increased risk for several metabolic syndrome-associated disorders in adulthood [e.g., obesity, type 2 diabetes (1,2), and cardiovascular disease (3)]. The relationship between pubertal timing and BMI is particularly well-documented. Declining ages of pubertal onset associate with increased BMI in childhood (4–7). Likewise, studies addressing the link between pubertal timing and later risk for obesity show that pubertal onset is a negative predictor of adult BMI. Some studies claim that the link between puberty and adult BMI is a secondary consequence of a correlation between prepubertal BMI and puberty (6–8), but there are studies suggesting that the association between pubertal timing and adult BMI is independent of the degree of childhood obesity (9–12).Data on the relationship between male pubertal timing and adult metabolic traits are scarce. Although abnormal levels of metabolic syndrome related-traits are more common in males than females, most studies exploring the relationship between pubertal timing and risk of adult disease have used age of menarche as the marker of puberty. One study showed that early pubertal timing may predict central adiposity in adult males (9). In addition, early puberty has been associated with elevated blood pressure in two reports, although the sample size was limited to only 135 males and 148 females in one of the studies (13,14). In contrast, early puberty was not associated with increased serum triglyceride levels in adult males, even if early puberty correlated with elevated triglycerides in adult females (12). Studies on the relationship between pubertal timing and adult glucose homeostasis in males appear to be lacking.Because the risk for adult metabolic disease is shaped over the life course, detailed knowledge of the link with critical developmental events may highlight important pathogenic mechanisms. Therefore, to disentangle the relationship between puberty and cardiometabolic risk in both sexes, we studied 2,417 males and 2,641 females of a large, unique, and genetically homogenous birth cohort with data on longitudinal childhood growth and a wide spectrum of adult of cardiometabolic risk factors. Our study had the following specific aims: 1) to assess the relationship between pubertal timing and adult body size, glucose, lipids, and blood pressure, both by evaluating the effect of pubertal timing alone and adjusting for patterns of prepubertal growth, and 2) to quantify the size of the pubertal timing effect on adult metabolic risk. Pubertal timing was assessed based on height growth during adolescence using a previously validated measurement, which allowed us to estimate the timing of puberty similarly in both sexes.     

Low-Grade Chronic Inflammation in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) Population: Associations with insulin resistance and cardiometabolic risk profile

OBJECTIVE

Low-grade chronic inflammation has been hypothesized to underlie the constellation of cardiometabolic risk factors, possibly by inducing insulin resistance. In the present study, we investigated associations between inflammation markers, insulin sensitivity (expressed as the ratio of the M value to the mean plasma insulin concentrations measured during the final 40 min of the clamp [M/I]), and a range of cardiometabolic risk factors in a large, healthy population.

RESEARCH DESIGN AND METHODS

The Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort includes 1,326 nondiabetic European men and women, aged between 30 and 60 years. We measured cardiometabolic risk factors and performed a hyperinsulinemic-euglycemic clamp. We determined total white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) as markers of chronic inflammation.

RESULTS

WBC and ESR were both strongly associated with M/I. WBC and ESR were further associated with a range of cardiometabolic risk factors. Associations between WBC and HDL cholesterol, triglycerides, heart rate, fasting C-peptide, and insulin and 2-h insulin in men and women and between WBC and 2-h glucose in women remained significant after adjustment for both M/I and waist circumference. Associations between ESR and HDL cholesterol, heart rate, fasting, and 2-h insulin in men and women and between ESR and fat mass in women remained significant after adjustment for M/I and waist circumference.

CONCLUSIONS

This study showed that low-grade chronic inflammation is associated with the cardiometabolic risk profile of a healthy population. Insulin resistance, although strongly associated with inflammation, does not seem to play a large intermediary role.Several inflammation markers have been shown to be associated with cardiometabolic risk profile. A study in a diabetic population showed that abnormalities of the immune system including elevated levels of acute-phase reactants, interleukin-6 (IL-6), C-reactive protein (CRP), and cortisol were all associated with the metabolic syndrome (1). The Insulin Resistance Atherosclerosis Study (IRAS) showed in a nondiabetic population that white blood cell count (WBC), CRP, and fibrinogen were all related to elements of the metabolic syndrome (2). In a range of prospective studies, inflammation markers have also been shown to relate to the development of type 2 diabetes and coronary heart disease. The Atherosclerosis Risk in Communities (ARIC) study reported associations between raised WBC, fibrinogen, and low serum albumin and diagnosis of diabetes 7 years later in a large middle-aged population (3). In a large cohort study in patients undergoing angiography, the erythrocyte sedimentation rate (ESR) was related to coronary atherosclerosis and was a predictor of cardiac death in patients with probable ischemic heart disease (4). A meta-analysis of prospective studies investigating the relationship between inflammatory factors and subsequent coronary heart disease showed associations between fibrinogen, CRP, albumin, and WBC and the development of coronary heart disease (5).Low-grade inflammation may lead to cardiometabolic disease by inducing insulin resistance, a major contributor to the development of cardiovascular and metabolic disease. Insulin resistance has been shown to be associated with several inflammatory factors (2,6,7). A prospective study in Pima Indians showed that a high WBC predicted development of diabetes, independent of body fat (8). The effect seemed to be mediated by a worsening of insulin sensitivity during the 5 years of follow-up.Limitations of the existing literature on the association between low-grade inflammation, insulin resistance, and cardiometabolic disease include the lack of direct measurement of insulin sensitivity by the standard technique, the hyperinsulinemic-euglycemic clamp, in a large healthy population. Often, fasting hyperinsulinemia has been used as a surrogate measure of insulin sensitivity (6,7). However, along with others, our group has shown that hyperinsulinemia contributes to cardiovascular risk independently of insulin resistance as measured by the hyperinsulinemic-euglycemic clamp (9). The question is whether low-grade inflammation is associated with insulin sensitivity as measured by the hyperinsulinemic-euglycemic clamp and whether clamp-derived insulin resistance mediates the association between inflammation and cardiometabolic disease. In the present study we tried to answer these questions by using data from the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) study cohort.     

Endocannabinoid system and cardiometabolic risk

The increasing prevalence of overweight and obesity counteracts the favorable advances of risk factor management achieved for cardiovascular disease (CVD) prevention. Obese and overweight individuals are at increased risk for CVDs and diabetes mellitus, a risk pattern called "cardiometabolic risk." There is a growing interest concerning the role of the endocannabinoid system in energy metabolism and how blockade of cannabinoid receptors (CB(1)) may optimize fat distribution, insulin sensitivity, and blood lipids to improve cardiovascular risk profile.     

Trunk versus extremity adiposity and cardiometabolic risk factors in white and African American adults

OBJECTIVE

To determine contributions of trunk and extremity adiposity to cardiometabolic risk factors (blood pressure, fasting blood glucose, HDL cholesterol, and triglycerides) among white and African American adults.

RESEARCH DESIGN AND METHODS

The sample consisted of 1,129 white women, 779 African American women, 1,012 white men, and 300 African American men.

RESULTS

Higher trunk adiposity was significantly associated with an increased risk of having two or more cardiometabolic risk factors among African American and white men and women. After adjustment for trunk and arm adiposity, higher leg adiposity was significantly associated with a decreased risk of having two or more cardiometabolic risk factors among white men and women and African American women.

CONCLUSIONS

In contrast with adverse risk with high trunk adiposity, high leg adiposity is associated with a decreased risk of having two or more cardiometabolic risk factors in both African American and white adults.Obesity, a significant public health problem throughout the world (1), is strongly associated with cardiometabolic risk (2–5). There is growing recognition that adipose tissue stored in different body depots may have differential impacts on health. Several studies have assessed the associations of leg and trunk adiposity with cardiometabolic risk factors (6–12). Some, but not all, of these studies have found an inverse association of leg adiposity with blood pressure (11,12), glucose (7–12), dyslipidemia (6–8,11), and the metabolic syndrome (12). Moreover, these studies were carried out in white (6–10), Japanese (11), and Chinese (12) populations, and no studies included African Americans. Because African Americans have higher mortality rates from cardiovascular disease, diabetes, and cancer than white Americans (13), it is necessary to understand these differences and their clinical implications. The aim of this study is to determine the contribution of trunk and extremity adiposity to cardiometabolic risk factors among white and African American men and women.     

Insulin resistance and classic risk factors in type 2 diabetic patients with different subtypes of ischemic stroke.

OBJECTIVE: In addition to classic risk factors (e.g., hypertension), insulin resistance is an important risk factor for the development of atherosclerosis. To investigate the risk factors for ischemic stroke in type 2 diabetes, we measured insulin sensitivity and several risk factors in 94 Japanese type 2 diabetic patients with different types of stroke. RESEARCH DESIGN AND METHODS: Stroke was classified by magnetic resonance imaging (MRI) and magnetic resonance (MR) angiography into the following subtypes: 1) patients with normal MRI and MR angiography (NOR; n = 30), 2) patients with lacunar infarction (LAC; n = 28), 3) patients with atherothrombotic infarction (ATI; n = 22), and 4) patients with large-artery atherosclerosis (LAA; n = 14). Insulin sensitivity was assessed by the K index of the insulin tolerance test (KITT). RESULTS: Patients with LAC, ATI, and LAA were significantly older and were more likely to be hypertensive than patients with NOR. Significantly higher insulin resistance was observed in patients with LAC, ATI, and LAA than in patients with NOR (KITT 2.21 +/- 0.17, 2.10 +/- 0.17, 2.19 +/- 0.25, and 3.25 +/- 0.21% per min, respectively, P < 0.001). Adjustment for age, sex, BMI, and duration of diabetes did not influence this result. Multiple logistical regression analysis showed that insulin resistance was an independent risk factor for all subtypes of ischemic stroke in type 2 diabetic patients. The same analysis showed that a high pulse pressure was a risk factor for LAC, postprandial C-peptide (hyperinsulinemia) was a risk factor for ATI, and longstanding hyperglycemia was a risk factor for LAA.     

Type 2 diabetes mellitus is associated with multiple cardiometabolic risk factors

The risk for cardiovascular disease (CVD) is multifactorial and includes such risk factors as diabetes, hypertension, smoking, and dyslipidemia. Thus, targeting the hyperglycemia in type 2 diabetes mellitus (DM) alone will not eliminate all of the excess cardiovascular risk; rather aggressive treatment is needed for all of the modifiable cardiometabolic risk factors. Therapeutic lifestyle change is considered primary therapy for hyperglycemia in type 2 DM. Currently, however, the focus in treatment is on preventing CVD rather than controlling glucose, lipid, or blood pressure (BP) levels. The American Diabetes Association guidelines identify low-density lipoprotein cholesterol as the first priority of lipid lowering, with optimal level set at <100 mg/dL (2.6 mmol/L). To reach the target BP level of <130/85 mm Hg, >65% of patients with DM and hypertension will require 2 or more different antihypertensive drugs. Strategies that combine thiazolidinediones and statins may have complementary effects on cardiovascular risk-factor profiles in type 2 DM, in addition to controlling glycemia. Despite the range of treatment options available, therapeutic agents that target new steps in the progression of CVD are needed, as patients with type 2 DM remain at increased risk and many do not achieve therapeutic targets with the drugs available.