Increased blood glucose and insulin, body size, and incident colorectal cancer.

BACKGROUND: Abdominal obesity--an elevated level of visceral adipose tissue--has been linked to colorectal cancer. Furthermore, elevated levels of visceral adipose tissue have been associated with hyperinsulinemia, and insulin is a growth factor in the colon. We assessed whether waist circumference, a surrogate measure of visceral adipose tissue, and metabolic parameters associated with visceral adipose tissue were related to colorectal cancer. METHODS: In the Cardiovascular Health Study cohort, we examined the relationship of baseline measurements of body size, glucose, insulin, and lipoproteins to incident colorectal cancer. All P values are two-sided. RESULTS: Among 5849 participants, 102 incident cases of colorectal cancer were identified. Individuals in the highest quartile of fasting glucose had a nearly twofold increased risk of colorectal cancer (relative risk [RR] = 1.8; 95% confidence interval [CI] = 1.0-3.1), and the linear trend RR (LT RR = 1.2; 95% CI = 1.0-1.5) for fasting glucose level was statistically significant (P =. 02). Glucose and insulin levels 2 hours after oral glucose challenge also exhibited statistically significant associations with colorectal cancer (2-hour glucose levels: RR = 2.4 [95% CI = 1.2-4. 7]/LT RR = 1.3 [95% CI = 1.0-1.6; P =.02]; 2-hour insulin levels: RR = 2.0 [95% CI = 1.0-3.8]/LT RR = 1.2 [95% CI = 1.0-1.5; P =.04]). Analysis of fasting insulin levels suggested a threshold effect, with values above the median associated with colorectal cancer (RR = 1.6; 95% CI = 1.1-2.4; P =.02). Higher levels of waist circumference were also statistically significantly associated with colorectal cancer (RR = 1.9; 95% CI = 1.1-3.3; P =.02). CONCLUSIONS: These data provide, to our knowledge, the first direct evidence of an association between elevated visceral adipose tissue level, its associated metabolic effects, and colorectal cancer.

A simplified method using somatostatin to assess in vivo insulin resistance over a range of obesity.

Twenty-one nondiabetic subjects, their weights ranging from 56 to 165 kg, received an infusion of glucose (420 mg/min), insulin (0.77 mU/kg/min), and somatostatin (500 microgram/h) for 150 min. A steady state level of plasma insulin and glucose was attained after 90 min. Endogenous insulin secretion determined by C-peptide measurement, and glucagon secretion remained suppressed throughout the period. With similar steady state levels of plasma insulin (SSPI) maintained in all subjects, the height of the steady state plasma glucose concentration (SSPG) was considered an index of total body sensitivity to insulin-mediated glucose uptake. A positive correlation between SSPG and the degree of obesity, as determined by the body mass index (BMI), was demonstrated (r = 0.70, P less than 0.001). No correlation was found between SSPI and BMI. The fasting plasma insulin concentration correlated with BMI (r = 0.82, P less than 0.0001) and SSPG (r = 0.80, P less than 0.0001). This method provides a simple safe measure of total body insulin resistance over a wide range of obesity and is independent of endogenous insulin secretion.

High prevalence of diabetes in young Pima Indians: evidence of phenotypic variation in a genetically isolated population.

Medical records of the Pima Indian population aged 0--24 yr were reviewed for a diagnosis of diabetes before initiation of glucose tolerance testing. None of 1556 subjects below age 15, but 6 of 657 aged 15--24, had a previous diagnosis. Of the six known diabetics, five had been treated with insulin and four had had ketoacidosis. Subsequently, plasma glucose levels were determined after a 75-g oral carbohydrate load in 1712 subjects aged 5--24 yr, which is about 78% of the eligible population. Previously diagnosed diabetes and asymptomatic hyperglycemia were more frequent in subjects 15--24 yr old than were reported in other populations. Glucose intolerance in young Pimas was associated with obesity. In Pima offspring, the presence of diabetes in both parents was related to glucose tolerance in those above but not below the age of 15 yr. Both asymptomatic hyperglycemia and insulin-requiring diabetes occurred frequently in young Pimas, suggesting that these syndromes represent the clinical spectrum of a single disease in the Pima Indian.

Cardiac arrhythmias during epinephrine-propranolol infusions for measurement of in vivo insulin resistance.

Sixty-eight determination of in vivo insulin resistance were conducted in 35 males (aged 29-63 yr) by measurement of steady-state plasma glucose levels during a combined intravenous infusion of propranolol, epinephrine, glucose, and insulin. Subjects were mildly diabetic and/or hyperlipidemic. All were asymptomatic, denied taking medication, and had no history of cardiac disease. All had normal resting electrocardiograms. During the infusion, mean increases in systolic and diastolic blood pressure were 27 +/- 12.2 (x +/- SD) and 14 +/- 5.7 mm Hg, respectively; mean reduction in heart rate was 19 +/- 6.1 beats/min. Six out of the 35 subjects developed cardiac arrhythmias during the infusion test. Maximal exercise treadmill tests failed to predict all subjects who subsequently developed arrhythmias during the infusion test. These results suggest that this infusion test should be performed under continuous cardiac monitoring and promptly terminated if major arrhythmias develop.

Bimodality of glycosylated hemoglobin distribution in Pima Indians: relationship to fasting hyperglycemia.

Glycosylated hemoglobin (HbA1) concentrations were determined in 300 Pima Indians aged 15 yr and older. Frequency distributions of HbA1 were unimodal in the 15--24-yr-old age group, but were bimodal in those aged 25 yr and over. The bimodality indicated that the subpopulation with diabetes could be identified by the presence of elevated HbA1 levels. This group was comprised primarily of subjects who also had fasting plasma glucose levels of less than or equal to 140 mg/dl, but subjects with impaired glucose tolerance without fasting hyperglycemia had HbA1 levels that were not significantly higher than those with normal glucose tolerance. The prevalence of diabetic retinopathy was much higher in the subgroup with elevated HbA1 levels and increased with increasing HbA1 level. HbA1 levels and triglyceride concentrations showed only a modest association. HbA1 determinations provided no advantage over fasting or post challenge glucose levels in the diagnosis of diabetes.

Risk factors for coronary heart disease in diabetic and nondiabetic Native Americans. The Strong Heart Study.

The Strong Heart Study is a study of cardiovascular disease and its risk factors among diabetic and nondiabetic Native Americans. The study includes 12 tribes in Arizona, Oklahoma, and North and South Dakota. Phase I, initiated in October 1988, included a mortality survey to determine CVD death rates in individuals 35-74 yr old between 1984 and 1988, and a medical record review to determine rates of myocardial infarction and stroke for individuals ages 45-74 during the same time. In addition, a physical examination was performed on persons 45-74 yr old to measure the prevalence of cardiovascular and peripheral vascular diseases and known and suspected risk factors. In Phase II, CVD mortality and morbidity rates will be determined in the examined cohort by surveillance. CVD risk factors, changes in risk factors over time, and the relationship between risk factors and CVD incidence will be assessed longitudinally. This study provides data on the relative importance of cardiovascular risk factors in nondiabetic and diabetic Native Americans and will provide insight into possible variations in the quantitative or qualitative importance of CVD risk factors among diverse population groups.

Insulin sensitivity and acute insulin response in African-Americans, non-Hispanic whites, and Hispanics with NIDDM: the Insulin Resistance Atherosclerosis Study.

NIDDM is usually characterized by beta-cell failure and decreased insulin sensitivity. It has been reported that a high proportion of African-American NIDDM subjects are insulin sensitive. To examine this issue, we determined insulin sensitivity (S(I)) in 479 NIDDM subjects by minimal model analyses of frequently sampled intravenous glucose tolerance (FSIGT) from the Insulin Resistance Atherosclerosis Study (IRAS), a large multicenter study of insulin sensitivity and cardiovascular risk in African-Americans, Hispanics, and non-Hispanic whites. The African-Americans and non-Hispanic whites were sampled in Los Angeles and Oakland, California. The non-Hispanic whites and Hispanics were sampled in San Antonio, Texas, and San Luis Valley, Colorado. We defined the proportion of insulin-sensitive (S(I)) subjects as > or =1.61 min-1 x microU-1 x ml-1, which is above the median for nondiabetic subjects of all ethnic groups in the IRAS. Using this definition, the proportion of insulin-sensitive diabetic subjects was very low in all ethnic groups (non-Hispanic whites [14.3%] vs. African-Americans [6.5%], P = 0.039 in Los Angeles and Oakland; non-Hispanic whites [6.8%] vs. Hispanics [4.9%], P = 0.737 in San Luis Valley and San Antonio). These results were also similar in newly diagnosed mildly hyperglycemic diabetic subjects. In addition, these results were not affected by the adjustment for differences in obesity, body fat distribution, and severity of hyperglycemia. Even in nonobese subjects (with BMI <30 kg/m2), the proportion of insulin-sensitive subjects (S(I) > or =1.61 min-1 x microU-1 x ml-1) was low (3.6-9.7%). The acute insulin response (AIR) was significantly higher in African-Americans than in non-Hispanic whites; there were no ethnic differences in AIR between Hispanics and non-Hispanic whites. There were no significant ethnic differences for non-insulin-mediated glucose disposal (S(G)). We conclude that the number of insulin-sensitive NIDDM subjects is low and similar among non-Hispanic whites, Hispanics, and African-Americans in the U.S.

Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study.

The etiology of NIDDM is still controversial, with both insulin resistance and decreased insulin secretion postulated as potential important factors. African-Americans and Hispanics have a two- to threefold excess risk of developing NIDDM compared with non-Hispanic whites. Yet little is known concerning the prevalence of insulin resistance and secretion defects in minorities, especially in African-Americans in population-based studies. Fasting and 2-h post-glucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index) (S(I)), glucose effectiveness (S(G)), and first-phase insulin response (acute insulin response [AIR]) were determined in nondiabetic African-Americans (n= 288), Hispanics (n= 363), and non-Hispanic whites (n= 435) as part of the Insulin Resistance Atherosclerosis Study. Subjects received a standard 2-h oral glucose tolerance test on the first day and an insulin-modified frequently sampled intravenous glucose tolerance test on the second day. African-Americans and Hispanics were more obese than non-Hispanic whites. Both African-Americans and Hispanics had higher fasting and 2-h insulin concentrations and AIR but lower S(I) than non-Hispanic whites. No ethnic difference was observed in S(G). After further adjustments for obesity, body fat distribution, and behavioral factors, African-Americans continued to have higher fasting and 2-h insulin levels and AIR, but lower S(I) than non-Hispanic whites. In contrast, after adjustment for these covariates, no significant ethnic differences in S(I) or fasting insulin levels were observed between Hispanics and non-Hispanic whites. Hispanics continued to have higher 2-h insulin levels and AIRs than those in non-Hispanic whites. In this report, the association between S(I) and upper body adiposity (waist-to-hip, ratio) was similar in each ethnic group. Both nondiabetic African-Americans and Hispanics have increased insulin resistance and higher AIR than nondiabetic non-Hispanic whites, suggesting that greater insulin resistance may be in large part responsible for the higher prevalence of NIDDM in these minority groups. However, in Hispanics. the greater insulin resistance may be due to greater adiposity and other behavioral factors.

Hyperinsulinemia and hypoinsulinemai. Insulin responses to oral carbohydrate over a wide spectrum of glucose tolerance.

Oral glucose tolerance tests using a 75 gm. carbohydrate load were performed on 396 Pima Indians. Subjects were divided into groups on the basis of two-hour plasma glucose levels and the patterns of insulin response examined. Two-hour insulin levels were highest in the group with two-hour plasma glucose levels between 140-169 mg,/100 ml. and then fell progressively until levels about 400 mg./100 ml. were reached. Half and one-hour insulin levels showed little change in the groups with two-hour glucose levels up to 170 mg,/100 ml., but at higher glucose levels these insulin levels also progressively diminished. Fasting insulin levels were relatively unchanged over the entire range of glucose inintolerance. Obesity was the most important factor influencing the fasting insulin levels. Glucose level was the major determinant of post-load insulin responses, but these were also significantly influenced by obesity. No effect of age or sex on insulin levels was demonstrated. Comparison with other published data indicated that different interpretations of insulin response in subjects with "mild diabetes" have resulted from comparisons of groups with different degrees of glucose tolerance.

A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study.

An insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis was compared with the glucose clamp in 11 subjects with normal glucose tolerance (NGT), 20 with impaired glucose tolerance (IGT), and 24 with non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity index (SI) was calculated from FSIGTT using 22- and 12-sample protocols (SI(22) and SI(12), respectively). Insulin sensitivity from the clamp was expressed as SI(clamp) and SIP(clamp). Minimal model parameters were similar when calculated with SI(22) and SI(12). SI could not be distinguished from 0 in approximately 50% of diabetic patients with either protocol. SI(22) correlated significantly with SI(clamp) in the whole group (r = 0.62), and in the NGT (r = 0.53), IGT (r = 0.48), and NIDDM (r = 0.41) groups (P < 0.05 for each). SI(12) correlated significantly with SI(clamp) in the whole group (r = 0.55, P < 0.001) and in the NGT (r = 0.53, P = 0.046) and IGT (r = 0.58, P = 0.008) but not NIDDM (r = 0.30, P = 0.085) groups. When SI(22), SI(clamp), and SIP(clamp) were expressed in the same units, SI(22) was 66 +/- 5% (mean +/- SE) and 50 +/- 8% lower than SI(clamp) and SIP(clamp), respectively. Thus, minimal model analysis of the insulin-modified FSIGTT provides estimates of insulin sensitivity that correlate significantly with those from the glucose clamp. The correlation was weaker, however, in NIDDM. The insulin-modified FSIGTT can be used as a simple test for assessment of insulin sensitivity in population studies involving nondiabetic subjects. Additional studies are needed before using this test routinely in patients with NIDDM.

Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study.

BACKGROUND: Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events. Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure. METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination, and all subsequent cardiovascular events were ascertained and classified. RESULTS: At baseline, 1961 men and 2941 women were at risk for an incident myocardial infarction or stroke. During follow-up that averaged 6.7 years, 572 subjects had a coronary event, 385 had a stroke, and 896 died. After adjustment for potential confounders, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were directly associated with the risk of incident myocardial infarction and stroke. Only SBP was associated with total mortality. Importantly, SBP was a better predictor of cardiovascular events than DBP or pulse pressure. In the adjusted model for myocardial infarction, a 1-SD change in SBP, DBP, and pulse pressure was associated with hazard ratios (95% confidence intervals) of 1.24 (1.15-1.35), 1.13 (1.04-1.22), and 1.21 (1.12-1.31), respectively; and adding pulse pressure or DBP to the model did not improve the fit. For stroke, the hazard ratios (95% confidence intervals) were 1.34 (1.21-1.47) with SBP, 1.29 (1.17-1.42) with DBP, and 1.21 (1.10-1.34) with pulse pressure. The association between blood pressure level and cardiovascular disease risk was generally linear; specifically, there was no evidence of a J-shaped relationship. In those with treated hypertension, the hazard ratios for the association of SBP with the risks for myocardial infarction and stroke were less pronounced than in those without treated hypertension. CONCLUSION: In this population-based study of older adults, although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events, SBP was the best single predictor of cardiovascular events.

Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group.

BACKGROUND: Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-blockers adversely alters levels of other cardiovascular disease risk factors. METHODS: The Systolic Hypertension in the Elderly Program was a community-based, multicenter, randomized, double-blind, placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older. This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program, including changes in serum chemistry test results in a subgroup for 3 years. Patients were randomized to receive placebo or treatment with active drugs, with the dose increased in stepwise fashion if blood pressure control goals were not attained: step 1, 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo. RESULTS: After 3 years, the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group (both groups, P<.001). New cases of diabetes were reported by 8.6% of the participants in the active treatment group and 7.5% of the participants in the placebo group (P=.25). Small effects of active treatment compared with placebo were observed with fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P<.01), total cholesterol (+0.09 mmol/L [+3.5 mg/dL]; P<.01), high-density lipoprotein cholesterol (-0.02 mmol/L [-0.77 mg/dL]; P<.01) and creatinine (+2.8 micromol/L [+0.03 mg/dL]; P<.001). Larger effects were seen with fasting levels of triglycerides (+0.9 mmol/L [+17 mg/dL]; P<.001), uric acid (+35 micromol/L [+.06 mg/dL]; P<.001), and potassium (-0.3 mmol/L; P<.001). No evidence was found for a subgroup at higher risk of risk factor changes with active treatment. CONCLUSIONS: Antihypertensive therapy with low-dose chlorthalidone (supplemented if necessary) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels.

Factor VIII and other hemostasis variables are related to incident diabetes in adults. The Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: Our objective was to evaluate whether selected hemostasis variables, some of which may reflect inflammation or endothelial dysfunction, are independently associated with the development of diabetes. RESEARCH DESIGN AND METHODS: We studied a biethnic cohort of 12,330 men and women, 45-64 years of age, of the Atherosclerosis Risk in Communities Study. New cases of diabetes were diagnosed by a reported physician diagnosis, hypoglycemic medication use, or a casual or fasting serum glucose level of > or = 11.1 or > or = 7 mmol/l, respectively. RESULTS: Over an average follow-up of 7 years, 1,335 new cases of diabetes were detected. The odds ratios (4th versus 1st quartile) of developing diabetes, adjusted by logistic regression for age, sex, race, study center, family history of diabetes, fasting glucose, physical activity, and smoking, were 1.2 (95% CI 1.0-1.5) for fibrinogen and 1.4 (1.1-1.6) for factor VII. Associations for factor VIII, von Willebrand factor, and activated partial thromboplastin time were found to be 1.8 (1.3-2.3), 1.4 (1.1-1.8), and 0.63 (0.49-0.82), respectively, in women. Although further adjustment for BMI and waist-to-hip ratio diminished the relationships, a highly statistically significant association (P = 0.001) remained for factor VIII (1.6 [1.2-2.1]) in women. CONCLUSIONS: Factor VIII and other hemostasis variables are associated with the development of diabetes in middle-aged adults. These findings support a role for inflammation and, particularly in women, endothelial dysfunction in the pathogenesis of type 2 diabetes.

Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: the Insulin Resistance Atherosclerosis Study.

OBJECTIVE: To assess whether people with impaired glucose tolerance (IGT) exhibit an increased risk of atherosclerosis as measured by the thickness of the carotid artery. RESEARCH DESIGN AND METHODS: We examined the relationship between glucose tolerance status and subclinical atherosclerosis in the Insulin Resistance Atherosclerosis Study (IRAS). The IRAS is an epidemiological study of 1,625 Hispanic, African-American, and white men and women, with approximately equal numbers of subjects with normal glucose tolerance (NGT), IGT, and type 2 diabetes as assessed by an oral glucose tolerance test. Half of those with diabetes were previously unaware of their condition and were defined as having new diabetes. Persons using insulin were excluded. The intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA) was measured as an index of subclinical atherosclerosis using B-mode ultrasonography. RESULTS: Adjusted for demographics and smoking, CCA-IMT increased most notably at the level of established diabetes (802, 822, 831, and 896 microm for NGT, IGT, new diabetes, and established diabetes, respectively). Adjustment for coronary heart disease (CHD) risk factors, which tended to worsen across glucose tolerance category, further minimized the slightly graded relationship. The relationship with the ICA-IMT was steeper and again suggested that the increased wall thickness is associated with diabetes, not with IGT. The relationship between glucose tolerance category and IMT was similar in men and women. CONCLUSIONS: We observed considerably greater IMT among persons with established diabetes but no significant increase in persons with IGT. These data suggest that the increased risk of CHD observed in persons with diabetes may largely develop after the onset of overt diabetes.

Prevalence of undiagnosed diabetes in three American Indian populations. A comparison of the 1997 American Diabetes Association diagnostic criteria and the 1985 World Health Organization diagnostic criteria: the Strong Heart Study.

OBJECTIVE: In 1997, the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association (ADA) recommended three new sets of criteria for the diagnosis of diabetes that were different from those established by the World Health Organization (WHO) in 1985. One of these three methods was based on a fasting plasma glucose value only. This article compares ADA criteria with WHO criteria by applying them to three subgroups of American Indians in the Strong Heart Study who had no known diabetes. RESEARCH DESIGN AND METHODS: The Strong Heart Study is a prospective epidemiological study of vascular disease in three American Indian populations aged 45-74 years. During the baseline examination from 1988 to 1991, participants without diagnosed diabetes underwent a fasting glucose test and a 2-h oral glucose tolerance test. These values were used to compare the ADA and WHO diagnostic criteria. RESULTS: By using fasting and 2-h glucose values, prevalence rates of undiagnosed diabetes were 15.9% according to WHO criteria and 14.4% according to ADA criteria. The overall agreement rate was 65%, and the weighted kappa statistic was 0.474, which indicates moderate agreement. The age-specific analysis showed that, among participants between 45 and 54 years of age, the prevalence rates of undiagnosed diabetes were 13.4% according to WHO criteria and 12.7% according to ADA criteria. Among those aged 55-74 years, the rates were 18.7% according to WHO criteria and 16.3% according to ADA criteria. Thus, the difference in the prevalence rates when using WHO and ADA criteria, although generally small in this population, was three times higher in the older group (2.4%) than the difference in the younger group (0.7%). CONCLUSIONS: The Strong Heart Study found that prevalence rates of undiagnosed diabetes determined by ADA criteria and WHO criteria were similar in its American Indian population. The data suggest that the difference between the two criteria may increase as age increases. Longitudinal data will be needed to evaluate further the utility of the two criteria.

Insulin sensitivity in subjects with type 2 diabetes. Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study.

OBJECTIVE: Among nondiabetic subjects, insulin resistance has been associated with increased cardiovascular risk factors, including dyslipidemia, hypertension, impaired fibrinolysis, and coagulation. Less is known about the relationship between insulin resistance and cardiovascular risk factors in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: To examine this issue, we determined insulin sensitivity (SI) in 479 type 2 diabetic subjects by minimal model analyses of frequently sampled intravenous glucose tolerance tests in the Insulin Resistance Atherosclerosis Study (IRAS), a large multicenter study of insulin sensitivity and cardiovascular disease in African-Americans, Hispanics, and non-Hispanic whites. We defined insulin-sensitive subjects as having SI > or = 1.61 x 10(-4) min-1.microU-1.ml-1 (above median in nondiabetic subjects of all ethnic groups in the IRAS). Using this definition, only 37 type 2 diabetic subjects were insulin sensitive, and the remaining 442 were insulin resistant. RESULTS: After adjustment for age, sex, ethnicity, and clinic, insulin resistance was significantly correlated with total triglycerides, VLDL cholesterol, VLDL triglyceride, fibrinogen, PAI-1, and fasting glucose, and was inversely correlated with HDL cholesterol level and LDL size. Carotid intimal-medial thickness was greater in insulin-resistant than in insulin-sensitive subjects, but this difference was not statistically significant. After further adjustment for waist circumference (marker of visceral adiposity), insulin-resistant subjects continued to have higher plasminogen activator inhibitor 1 and VLDL triglyceride levels, lower HDL cholesterol levels, and smaller LDL particle size than did insulin-sensitive subjects. After further adjustment for fasting glucose levels, these results were very similar. CONCLUSIONS: We conclude that insulin-resistant type 2 diabetic subjects have more atherogenic cardiovascular risk factor profiles than insulin-sensitive type 2 diabetic subjects and that this is only partially related to increased obesity and an adverse body fat distribution.

Antidiabetic treatment trends in a cohort of elderly people with diabetes. The cardiovascular health study, 1989-1997.

OBJECTIVE: This study characterizes the pharmaceutical treatment of type 2 diabetes from 1989-1990 to 1996-1997 in an elderly cohort. RESEARCH DESIGN AND METHODS: A total of 5,888 adults aged > or = 65 years were recruited and attended a baseline clinic visit in 1989-1990 (n = 5,201, original cohort) or 1992-1993 (n = 687. African-American [new] cohort) as participants of the Cardiovascular Health Study. Fasting serum glucose (FSG) was measured at baseline. Medication use was ascertained by drug inventory at all annual clinic visits. Diabetes was defined at baseline as insulin or oral hypoglycemic agent (OHA) use or as having an FSG > or = 7.0 mmol/l (126 mg/dl), the current consensus definition of diabetes. RESULTS: A total of 387 (7%) original (FSG = 9.8 mmol/l [177 mg/dl]) and 115 (17%) new (FSG = 10.6 mmol/l [191 mg/dl]) cohort members had pharmacologically treated diabetes at baseline. Among those in the original and in the new cohorts who survived follow-up, respectively, OHA use decreased from 80 to 48% (P < 0.001) and from 67 to 50% (P < 0.003) and insulin use increased from 20 to 33% (P = 0.001) and from 33 to 37% (P = 0.603). There were 396 (8%) original (FSG = 8.8 mmol/l [159 mg/dl]) and 45 (7%) new (FSG = 10.0 mmol/l [181 mg/dl]) cohort members with diabetes untreated at baseline. Among them, respectively, OHA use reached 38 and 30% and insulin use reached 6 and 16% in 1996-1997. CONCLUSIONS: Diabetes was common in this elderly cohort, and > 80% of treated patients with diabetes at baseline were not achieving fasting glucose goals of < or = 6.7 mmol/l (120 mg/dl). Many untreated at baseline remained untreated after 7 years of follow-up.

A comparison of accuracy and estimated cost of methods for home blood glucose monitoring.

Venous serum glucose concentrations determined by a laboratory hexokinase technique were compared over a wide range of glucose concentrations with concentrations of capillary blood glucose determined by three reflectance meter techniques currently available in the United States (Eyetone and Dextrometer, Ames Company; StatTek, Bio-Dynamics BMC) and by visual interpretation of reagent strips (Chemstrip bG, Bio-Dynamics BMC). The Chemstrip bG reagent strip was read by patients, nurses, and a physician. In all cases, there was an excellent correlation between laboratory serum glucose concentrations and reflectance meter blood glucose determinations (r = 0.90-0.94, P less than 0.0001) or visual interpretation of Chemstrip bG (r = 0.85-0.92, P less than 0.0001). Chemstrip bG appears to be the least expensive method of glucose measurement. This method offers additional advantages in not requiring a reflectance meter, which needs frequent recalibration and other ancillary equipment for blood glucose determination.

Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study.

OBJECTIVE: Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes. RESEARCH DESIGN AND METHODS: Participants in the Cardiovascular Health Study, aged > or = 65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease. RESULTS: Approximately 30% of the cohort had clinical disease, and approximately 60% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75% of men and 66% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was approximately 88% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes. CONCLUSIONS: Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.

Diabetes and impaired glucose tolerance in three American Indian populations aged 45-74 years. The Strong Heart Study.

OBJECTIVE: To estimate prevalence rates of diabetes and impaired glucose tolerance (IGT) in three American Indian populations, using standardized diagnostic criteria, and to assess the association of diabetes with the following selected possible risk factors: age, obesity, family history of diabetes, and amount of Indian ancestry. RESEARCH DESIGN AND METHODS: This cross-sectional study involved enrolled members, men and women aged 45-74 years, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota. Eligible participants were invited to the clinic for a personal interview and a physical examination. Diabetes and IGT status were defined by the World Health Organization criteria and were based on fasting plasma glucose and oral glucose tolerance test results. Data on age, family history of diabetes, and amount of Indian ancestry were obtained from the personal interview, and measures of obesity included body mass index, percentage body fat, and waist-to-hip ratio. RESULTS: A total of 4,549 eligible participants were examined, and diabetes status was determined for 4,304 (1,446 in Arizona, 1,449 in Oklahoma, and 1,409 in the Dakotas). In all three centers, diabetes was more prevalent in women than in men. Arizona had the highest age-adjusted rates of diabetes: 65% in men and 72% in women. Diabetes rates in Oklahoma (38% in men and 42% in women) and South and North Dakota (33% in men and 40% in women), although considerably lower than in Arizona, were several times higher than those reported for the U.S. population. Rates of IGT among the three populations (14-17%) were similar to those in the U.S. population. Diabetes rates were positively associated with age, level of obesity, amount of Indian ancestry, and parental diabetes status. CONCLUSIONS: Diabetes is found in epidemic proportions in Native American populations. Prevention programs and periodic screening should be implemented among American Indians. Standards of care and intervention have been developed by the Indian Health Service for individuals in whom diabetes is diagnosed. These programs should be expanded to include those with IGT to improve glycemic control or to reduce the risk of development of diabetes as well as to reduce the risk of diabetic complications.