Insulin sensitivity and the risk of incident hypertension: insights from the Insulin Resistance Atherosclerosis Study.

Objective: The insulin resistance syndrome has been described as including hypertension. Previous studies have documented cross-sectional associations between insulin sensitivity (S(I)) and blood pressure or prevalent hypertension. Prospective data have been sparse.

Prediction of type 2 diabetes using simple measures of insulin resistance: combined results from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study.

To determine and formally compare the ability of simple indexes of insulin resistance (IR) to predict type 2 diabetes, we used combined prospective data from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study, which include well-characterized cohorts of non-Hispanic white, African-American, Hispanic American, and Mexican subjects with 5-8 years of follow-up. Poisson regression was used to assess the ability of each candidate index to predict incident diabetes at the follow-up examination (343 of 3,574 subjects developed diabetes). The areas under the receiver operator characteristic (AROC) curves for each index were calculated and statistically compared.

Atherosclerosis in type 2 diabetes mellitus and insulin resistance: mechanistic links and therapeutic targets.

The ongoing heavy burden of cardiovascular disease associated with diabetes mellitus highlights the failure of current treatment strategies to address effectively the cardiovascular risk profile in such patients. Insulin resistance is not only an underlying feature in most cases of type 2 diabetes, but is also associated, through the Insulin Resistance Syndrome, with cardiovascular risk factors that promote atherothrombosis through diverse mechanisms. Growing evidence suggests that treatment with anti-diabetic agents that improve insulin sensitivity, such as the thiazolidinediones, improve multiple components of the Insulin Resistance Syndrome, have beneficial effects on various atherothrombotic mechanisms, and reduce atherosclerosis in animal models and perhaps humans as well.

Lipoprotein disorders associated with type 2 diabetes mellitus and insulin resistance.

Type 2 diabetes is associated with a marked increase in coronary artery disease (CAD). In subjects with type 2 diabetes, the characteristic lipoprotein abnormality is increased triglycerides, increased small, dense low-density lipoprotein (LDL) particles, and decreased concentrations of high-density lipoprotein (HDL) cholesterol but relatively normal absolute concentrations of LDL cholesterol. In observational studies, both increased LDL and decreased HDL cholesterol predict the development of CAD.

Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study.

Objective: Recent evidence suggests that C-reactive protein (CRP) may predict development of diabetes in Caucasian populations. We evaluated CRP as a possible risk factor of the development of diabetes and metabolic syndrome in a 6-year study of 515 men and 729 women from the Mexico City Diabetes Study.

Research Design And Methods: Baseline CRP, indexes of adiposity, and insulin resistance (homeostasis model assessment [HOMA-IR]) were used to predict development of the metabolic syndrome, defined as including two or more of the following: 1) dyslipidemia (triglyceride >/=2.

Sex steroid hormones, upper body obesity, and insulin resistance.

Low plasma levels of SHBG and free testosterone have been associated with increased insulin resistance and risk for type 2 diabetes in males. As truncal obesity, a condition accompanied by increased insulin resistance, is also associated with low SHBG and testosterone levels, the independent association of low free testosterone and SHBG with excessive insulin resistance remains to be determined. In this study we evaluated whether in normogonadic men, plasma levels of SHBG and free testosterone are primarily related to insulin resistance or to generalized and regional adiposity.

Predicting future cardiovascular disease: do we need the oral glucose tolerance test?

Objective: Our objective was to compare the performance of oral glucose tolerance tests (OGTTs) and multivariate models incorporating commonly available clinical variables in their ability to predict future cardiovascular disease (CVD).

Research Design And Methods: We randomly selected 2,662 Mexican-Americans and 1,595 non-Hispanic whites, 25-64 years of age, who were free of both CVD and known diabetes at baseline from several San Antonio census tracts. Medical history, cigarette smoking history, BMI, blood pressure, fasting and 2-h plasma glucose and serum insulin levels, triglyceride level, and fasting serum total, LDL, and HDL cholesterol levels were obtained at baseline.

A diabetes outcome progression trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes.

Objective: Therapies with metformin, sulfonylureas, or insulin improve glycemic control in the short term but do not prevent progressive islet beta-cell failure or long-term deterioration in glycemia. Our goal was to evaluate, in patients recently diagnosed with type 2 diabetes (<3 years), the long-term efficacy of monotherapy with rosiglitazone on glycemic control and on the progression of pathophysiological abnormalities associated with type 2 diabetes as compared with metformin or glyburide monotherapy.

Research Design And Methods: A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind, parallel-group study consisting of a screening visit, a 4-week placebo run-in, a 4-year treatment period, and an observational follow-up of approximately 3,600 drug-naïve patients with type 2 diabetes diagnosed within the previous 3 years.

Analysis of obesity and hyperinsulinemia in the development of metabolic syndrome: San Antonio Heart Study.

Objective: To use standardized cut-offs of body mass index (BMI), waist circumference, waist-to-hip ratio, and fasting insulin levels to predict the development of metabolic disorders and metabolic syndrome.

Research Methods And Procedures: We performed an 8-year follow-up study of 628 non-Hispanic whites and 1340 Mexican Americans, ages 25 to 64 years, from the second cohort of the San Antonio Heart Study. We defined metabolic disorders as dyslipidemia (triglycerides > or =2.

Can reducing peaks prevent type 2 diabetes: implication from recent diabetes prevention trials.

In recent years, a great deal of discussion has been focused on the role of postprandial hyperglycaemia in terms of development of type 2 diabetes (T2D), coronary heart disease (CHD) and their outcomes in patients with impaired glucose tolerance (IGT). With the incidence of T2D and its projected rise over the next 20 years, both the understanding of the pathophysiology of postprandial hyperglycaemia before development of frank T2D and the efficacy of interventions directed at lowering the postprandial glycaemic load to prevent the development of T2D have gained public health importance worldwide. Clinical trials have demonstrated that postprandial hyperglycaemia carries not only pathophysiological but also prognostic importance with regard to the quality of glycaemic control and forecasts the development of T2D, its complications, and patient mortality.

Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus.

Background: Markers of systemic inflammation (eg, C-reactive protein [CRP] and interleukin-6 [IL-6]) have been proposed to be "nontraditional" risk factors for cardiovascular disease in patients with type 2 diabetes mellitus. Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of atherosclerotic plaque rupture, which raises the possibility of the use of MMP-9 levels as a marker for future myocardial infarction or unstable angina. In vitro and animal studies suggest that thiazolidinediones can reduce the expression of these markers.

Factor analysis of metabolic syndrome using directly measured insulin sensitivity: The Insulin Resistance Atherosclerosis Study.

Factor analysis, a multivariate correlation technique, has been used to provide insight into the underlying structure of metabolic syndrome, which is characterized by physiological complexity and strong statistical intercorrelation among its key variables. The majority of previous factor analyses, however, have used only surrogate measures of insulin sensitivity. In addition, few have included members of multiple ethnic groups, and only one has presented results separately for subjects with impaired glucose tolerance.

Homeostasis model assessment of insulin resistance in relation to the incidence of cardiovascular disease: the San Antonio Heart Study.

Objective: The prospective association between insulin levels and risk of cardiovascular disease (CVD) is controversial. The objective of the present study was to investigate the relationship of the homeostasis model assessment of insulin resistance (HOMA-IR), as well as insulin levels, with risk of nonfatal and fatal CVD over the 8-year follow-up of the San Antonio Heart Study.

Research Design And Methods: Between 1984 and 1988, randomly selected Mexican-American and non-Hispanic white residents of San Antonio participated in baseline examinations that included fasting blood samples for glucose, insulin, and lipids, a glucose tolerance test, anthropometric measurements, and a lifestyle questionnaire.

Elevated risk of cardiovascular disease prior to clinical diagnosis of type 2 diabetes.

Objective: To examine whether the risk of cardiovascular disease (CVD) is elevated before clinical diagnosis of type 2 diabetes in women.

Research Design And Methods: A total of 117,629 female nurses aged 30-55 years who were free of diagnosed CVD at baseline were recruited in 1976 and followed for 20 years.

Results: A total of 1,508 women had diagnosed type 2 diabetes at baseline in 1976.

Identification of persons at high risk for type 2 diabetes mellitus: do we need the oral glucose tolerance test?

Background: The standard method of identifying persons at high risk for type 2 diabetes mellitus involves detection of impaired glucose tolerance, which requires a costly and inconvenient 2-hour oral glucose tolerance test. Because clinical trials have indicated that diabetes is preventable by using behavioral or pharmacologic interventions, less expensive methods of identifying high-risk persons are needed.

Objective: To determine whether multivariable models are superior to glucose tolerance tests for identifying persons at high risk for diabetes mellitus.

Increased proinsulin levels and decreased acute insulin response independently predict the incidence of type 2 diabetes in the insulin resistance atherosclerosis study.

Previous studies have indicated that beta-cell dysfunction predicts the development of diabetes, although it is unknown whether the use of combinations of insulin secretory measures further improves prediction. The Insulin Resistance Atherosclerosis Study is a prospective, multicenter, epidemiological study of the relationship between insulin sensitivity and the risk of diabetes and cardiovascular disease. At baseline, fasting concentrations of insulin, intact proinsulin (PI), and split PI were measured, and acute insulin response (AIR) was determined during a frequently sampled intravenous glucose tolerance test (FSIGTT).

Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study.

Elevated serum levels of acute-phase proteins, indicating chronic subclinical inflammation, have been associated with cardiovascular disease as well as the insulin resistance syndrome. Chronic inflammation may also be a risk factor for developing type 2 diabetes. We studied the concentrations of C-reactive protein (CRP), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) in 1,047 nondiabetic subjects in relation to incident diabetes within 5 years in the Insulin Resistance Atherosclerosis Study.

Prevalence of hypertension in Hispanic and non-Hispanic white populations.

Mexican nationals in Mexico City and Mexican Americans in San Antonio, Tex, have a lower adjusted prevalence of hypertension than San Antonio non-Hispanic whites, especially after adjusting for the greater obesity of San Antonio Mexican Americans. The concomitant examination of a new study from Spain may better explain the association of genetic and environmental factors with hypertension. Three population-based epidemiological studies conducted in Mexico City, Spain, and San Antonio, Tex, were available for comparisons.