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E J Boyko

Publications and source records attributed to E J Boyko.

At least 37 records · Page 2Linked to original sources

Etiology of the metabolic syndrome: potential role of insulin resistance, leptin resistance, and other players.

Obesity and Type 2 diabetes are now major public health issues in developed nations and have reached epidemic proportions in many developing nations, as well as disadvantaged groups in developed countries, e.g., Mexican-Americans, African-Americans, and Australian Aborigines. These groups all show hyperinsulinemia and insulin resistance, which have been demonstrated to be future predictors of Type 2 diabetes and have also been suggested as key factors in the etiology of the Metabolic Syndrome. It is now increasingly recognized that Type 2 diabetes is part of a cluster of cardiovascular disease (CVD) risk factors comprising the Metabolic Syndrome. This group is at very high risk of atherosclerosis because each of the risk factors in the Metabolic Syndrome cluster in its own right is an important CVD risk factor. They also contribute cumulatively to atherosclerosis. A key strategy in reducing macrovascular disease lies in the better understanding of the Metabolic Syndrome--glucose intolerance, hypertension, hyperlipidemia, and central obesity. Although it has been suggested that hyperinsulinemia/insulin resistance is the central etiological factor for the Metabolic Syndrome, epidemiological data do not support the idea that this can account for all of the cluster abnormalities. We have animal and human data suggesting that hyperleptinemia rather than, or synergistically with, hyperinsulinemia may play a central role in the genesis of the CVD risk factor cluster that constitutes the syndrome. Studies in Psammomys obesus (the Israeli sand rat) suggest hyperinsulinemia/insulin resistance is an early metabolic lesion in the development of obesity and Type 2 diabetes. This animal also develops other features of the Metabolic Syndrome, making it an excellent model to investigate etiology. Psammomys, when placed on an ad libitum laboratory diet, develops hyperinsulinemia, insulin resistance, impaired glucose tolerance, diabetes, and dyslipidemia. It also develops hyperleptinemia and leptin insensitivity, and hyperleptinemia is correlated with insulin resistance independent of changes in body weight. It is likely that a similar sequence occurs in the transition from the prediabetic state to Type 2 diabetes in humans. More recently, other potential players in the etiology of the Metabolic Syndrome have been suggested including endothelial dysfunction and acetylation-stimulating protein (ASP). It has been suggested that endothelial dysfunction may be an antecedent for both Type 2 diabetes and the Metabolic Syndrome. In addition, ASP is a serious new candidate for an important role in insulin resistance. The ASP pathway plays a critical role in fatty acid metabolism and storage, and it has been suggested that ineffective storage of fatty acids by adipocytes due to a defect in the ASP pathway may lead to insulin resistance and Type 2 diabetes.

Acetylation↗

Diagnosing pneumonia by physical examination: relevant or relic?

BACKGROUND: The reliability of chest physical examination and the degree of agreement among examiners in diagnosing pneumonia based on these findings are largely unknown. OBJECTIVES: To determine the accuracy of various physical examination maneuvers in diagnosing pneumonia and to compare the interobserver reliability of the maneuvers among 3 examiners. METHODS: Fifty-two male patients presenting to the emergency department of a university-affiliated Veterans Affairs medical center with symptoms of lower respiratory tract infection (cough and change in sputum) were prospectively examined. A comprehensive lung physical examination was performed sequentially by 3 physicians who were blind to clinical history, laboratory findings, and x-ray results. Examination findings by lung site and whether the examiner diagnosed pneumonia were recorded on a standard form. Chest x-ray films were read by a radiologist. RESULTS: Twenty-four patients had pneumonia confirmed by chest x-ray films. Twenty-eight patients did not have pneumonia. Abnormal lung sounds were common in both groups; the most frequently detected were rales in the upright seated position and bronchial breath sounds. Relatively high agreement among examiners (kappa approximately 0.5) occurred for rales in the lateral decubitus position and for wheezes. The 3 examiners' clinical diagnosis of pneumonia had a sensitivity of 47% to 69% and specificity of 58% to 75%. CONCLUSIONS: The degree of interobserver agreement was highly variable for different physical examination findings. The most valuable examination maneuvers in detecting pneumonia were unilateral rales and rales in the lateral decubitus position. The traditional chest physical examination is not sufficiently accurate on its own to confirm or exclude the diagnosis of pneumonia.

Adult↗

Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings.

OBJECTIVE: To determine the frequency and constellations of anatomic, pathophysiologic, and environmental factors involved in the development of incident diabetic foot ulcers in patients with diabetes and no history of foot ulcers from Manchester, U.K., and Seattle, Washington, research settings. RESEARCH DESIGN AND METHODS: The Rothman model of causation was applied to the diabetic foot ulcer condition. The presence of structural deformities, peripheral neuropathy, ischemia, infection, edema, and callus formation was determined for diabetic individuals with incident foot ulcers in Manchester and Seattle. Demographic, health, diabetes, and ulcer data were ascertained for each patient. A multidisciplinary group of foot specialists blinded to patient identity independently reviewed detailed abstracts to determine component and sufficient causes present and contributing to the development of each patient's foot ulcer. A modified Delphi process assisted the group in reaching consensus on component causes for each patient. Estimates of the proportion of ulcers that could be ascribed to each component cause were computed. RESULTS: From among 92 study patients from Manchester and 56 from Seattle, 32 unique causal pathways were identified. A critical triad (neuropathy, minor foot trauma, foot deformity) was present in > 63% of patient's causal pathways to foot ulcers. The components edema and ischemia contributed to the development of 37 and 35% of foot ulcers, respectively. Callus formation was associated with ulcer development in 30% of the pathways. Two unitary causes of ulcer were identified, with trauma and edema accounting for 6 and < 1% of ulcers, respectively. The majority of the lesions were on the plantar toes, forefoot, and midfoot. CONCLUSIONS: The most frequent component causes for lower-extremity ulcers were trauma, neuropathy, and deformity, which were present in a majority of patients. Clinicians are encouraged to use proven strategies to prevent and decrease the impact of modifiable conditions leading to foot ulcers in patients with diabetes.

Adult↗

Association between baseline plasma leptin levels and subsequent development of diabetes in Japanese Americans.

OBJECTIVE: Plasma leptin levels correlate strongly with increased total adipose tissue, a known risk factor for type 2 diabetes, yet the role of leptin in the etiology of diabetes remains unclear. We sought to determine whether leptin is a risk factor for development of diabetes in Japanese Americans. RESEARCH DESIGN AND METHODS: We compared baseline leptin levels in 370 nondiabetic Japanese Americans who remained nondiabetic for 5-6 years of follow-up with those of 40 nondiabetic Japanese Americans who developed diabetes during follow-up. All participants had computed tomography measurements of baseline subcutaneous chest, abdomen, thigh, and intra-abdominal fat, with total fat defined as the sum of all these measurements. RESULTS: The mean age was 51.7 +/- 11.7 years for men and 51.9 +/- 12.0 years for women. The 23 men who developed diabetes had significantly higher leptin levels than the 212 men who remained nondiabetic (P < 0.01). Among men, baseline leptin levels predicted diabetes risk independent of baseline total fat, insulin, insulin resistance, glucose, or age in separate multiple logistic regression models (relative risk adjusted for baseline total fat = 1.80 per SD increase [2.7 ng/ml], 95% CI 1.02-3.17). This association was particularly strong among men in the top decile for intra-abdominal fat. In contrast, the 17 women who developed diabetes had leptin levels similar to those of the 158 women who remained nondiabetic (P = 0.31). CONCLUSIONS: Among Japanese Americans, increased baseline leptin levels are associated with increased risk of developing diabetes in men but not in women.

Adipose Tissue↗

Visceral adiposity and incident coronary heart disease in Japanese-American men. The 10-year follow-up results of the Seattle Japanese-American Community Diabetes Study.

OBJECTIVE: To identify risk factors for incident coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: A total of 175 Japanese-American men without CHD were followed for up to 10 years. Baseline variables were blood pressure, weight, BMI, fat areas by computed tomography, skinfold thicknesses, abdominal circumference, plasma insulin, C-peptide, cholesterol, LDL cholesterol, HDL cholesterol, HDL2 cholesterol, and HDL3 cholesterol, triglycerides, apoproteins A1 and B, and diagnosis of diabetes and hypertension. CHD was diagnosed by electrocardiogram and clinical events. Logistic regression was used to estimate odds ratio. RESULTS: There were 50 incident cases of CHD. Using univariate logistic regression analysis, significant risk factors were intra-abdominal fat (P = 0.0090), fasting glucose (P = 0.0002), 2-h glucose (P = 0.0008), fasting HDL cholesterol (P = 0.0086), fasting HDL2 cholesterol (P = 0.030), fasting HDL3 cholesterol (P = 0.018), fasting triglycerides (P = 0.013), systolic (P = 0.0007) and diastolic blood pressure (P = 0.0002), and presence of diabetes (P = 0.0023). Multiple logistic regression models adjusted for BMI and age showed that intra-abdominal fat accounted for the effects of HDL cholesterol or triglycerides. In a multiple logistic regression model that included intra-abdominal fat, all systolic blood pressure and fasting glucose were significant. Substituting diastolic blood pressure for systolic blood pressure and 2-h glucose or diabetes status for fasting glucose produced similar results. CONCLUSIONS: Visceral adiposity, blood pressure, and plasma glucose are important independent risk factors for incident CHD in this population of diabetic and nondiabetic Japanese-American men.

Adipose Tissue↗

Impact of new diagnostic criteria for diabetes on different populations.

OBJECTIVE: For epidemiological purposes, it has now been recommended that a fasting plasma glucose value of 7.0 mmol/l can be used to diagnose diabetes, instead of a 2-h value of 11.1 mmol/l. This study assesses the impact of making this change on the prevalence of diabetes and on the phenotype of individuals identified. RESEARCH DESIGN AND METHODS: Data were collated from nine population based southern hemisphere studies in which a 75-g oral glucose tolerance test was performed. Comparisons were made between the prevalence derived from fasting values only and the prevalence derived from 2-h values only. Cardiovascular risk was assessed in all individuals. RESULTS: There were 20,624 subjects in the nine surveys of whom 1,036 had previously diagnosed diabetes and 1,714 had newly diagnosed diabetes, according to either fasting or 2-h glucose. The differences in prevalence within each population resulting from changing the diagnostic criteria ranged from +30 to -19% (relative difference) and +4.1 percentage points to -2.8 percentage points (absolute difference). BMI was the most important determinant of disagreement in classification. A total of 31% of those individuals who were diabetic on the fasting value were not diabetic on the 2-h value, and 32% of those with diabetes on the 2-h value were not diabetic on the fasting value. Apart from obesity, there were no differences in cardiovascular risk between those identified by the fasting and the 2-h values. CONCLUSIONS: Changing the diagnostic criteria is likely to have variable and sometimes quite large effects on the prevalence of diabetes in different populations. Furthermore, the fasting criterion identifies different people as being diabetic than those identified by the 2-h criterion.

Adult↗

Clinical correlates of plantar pressure among diabetic veterans.

OBJECTIVE: To assess the relationship between diabetes characteristics, medical history, foot deformity, sensory neuropathy, and plantar foot pressure. RESEARCH DESIGN AND METHODS: There were 517 subjects from a cohort of diabetic veterans enrolled in a prospective study of risk factors for foot complications who contributed 1,017 limbs for study. We interviewed subjects to collect data on demographics, diabetes characteristics, and medical history. A research nurse practitioner performed a directed physical exam of the lower extremities, assessing foot deformities and including quantitative sensory testing with a 5.07 monofilament. In-shoe foot-pressure measurements were obtained with F-scan insoles on subjects wearing their own footwear while walking 10 m at their usual pace. RESULTS: In univariate analyses, significant associations were seen between at least one measure of plantar pressure and body mass, sex, race, age, insulin use, certain foot deformities, plantar callus, and sensory neuropathy. Diabetes duration, HbA1c, and history of foot ulcer or amputation were unrelated to plantar pressure. In multiple regression analyses, body mass measured as log (weight), insulin use, white race, male sex, plantar callus, and diabetes duration were significantly related to certain pressures. Foot deformities were related primarily to forefoot pressures. With high pressure at two or more sites defined as the outcome, only body mass remained statistically significant as a predictor of this outcome in a backwards elimination logistic regression model. CONCLUSIONS: High in-shoe plantar pressure in diabetic subjects can be predicted in part from readily available clinical characteristics. The mechanisms by which these characteristics may be related to plantar pressure require further study.

Aged↗

Lower-extremity amputation in diabetes. The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers.

OBJECTIVE: To identify risk factors for lower-extremity amputation (LEA) in individuals with diabetes and to estimate the incidence of LEA. RESEARCH DESIGN AND METHODS: This is a prospective study of 776 U.S. veterans in a general medicine clinic in Seattle, Washington. The outcome was first LEA during follow-up. Potential risk factors evaluated in proportional hazards models included, among others, peripheral vascular disease (PVD), sensory neuropathy, former LEA, foot deformities and ulcers, diabetes duration and treatment, and hyperglycemia. RESULTS: Associated with an increased risk for LEA were PVD defined as transcutaneous oxygen < or = 50 mmHg (relative risk [RR] = 3.0, 95% CI 1.3-7.1), insensitivity to monofilament testing (RR = 2.9, odds ratio = 1.1-7.8), lower-extremity ulcers (RR = 2.5, CI 1.1-5.4), former LEA, and treatment with insulin when controlling for duration of diabetes and other factors in the model. PVD defined as absent or diminished lower-extremity pulses or an ankle arm index < or = 0.8 was also associated with a significantly higher risk of LEA in separate models. Foot ulcers were associated with an increased ipsilateral risk of amputation. The age-adjusted incidence among men only for LEA standardized to the 1991 U.S. male diabetic population was 11.3/1,000 patient-years. CONCLUSIONS: This prospective study shows that peripheral sensory neuropathy, PVD, foot ulcers (particularly if they appear on the same side as the eventual LEA), former amputation, and treatment with insulin are independent risk factors for LEA in patients with diabetes.

Adult↗

A prospective study of risk factors for diabetic foot ulcer. The Seattle Diabetic Foot Study.

OBJECTIVE: Little prospective research exists on risk factors for diabetic foot ulcer that considers the independent effects of multiple potential etiologic agents. We prospectively studied the effects of diabetes characteristics, foot deformity, behavioral factors, and neurovascular function on foot ulcer risk among 749 diabetic veterans with 1,483 lower limbs. RESEARCH DESIGN AND METHODS: Eligible subjects included all diabetic enrollees of a general internal medicine clinic without foot ulcer, of whom 83% agreed to participate. Baseline assessment included history and lower-limb physical examination, tests for sensory and autonomic neuropathy, and measurements of macro- and microvascular perfusion in the foot. Subjects were followed for the occurrence of a full thickness skin defect on the foot that took > 14 days to heal, with a mean follow-up of 3.7 years. RESULTS: Using stepwise Cox regression analysis, the following factors were independently related to foot ulcer risk: foot insensitivity to the 5.07 monofilament (relative risk [95% CI]) 2.2 (1.5-3.1), past history of amputation 2.8 (1.8-4.3) or foot ulcer 1.6 (1.2-2.3), insulin use 1.6 (1.1-2.2), Charcot deformity 3.5 (1.2-9.9), 15 mmHg higher dorsal foot transcutaneous PO2 0.8 (0.7-0.9), 20 kg higher body weight 1.2 (1.1-1.4), 0.3 higher ankle-arm index 0.8 (0.7-1.0), poor vision 1.9 (1.4-2.6), and 13 mmHg orthostatic blood pressure fall 1.2 (1.1-1.5). Higher ulcer risk was associated with hammer/claw toe deformity and history of laser photocoagulation in certain subgroups. Unrelated to foot ulcer risk in multivariate models were diabetes duration and type, race, smoking status, diabetes education, joint mobility, hallux blood pressure, and other foot deformities. CONCLUSIONS: Certain foot deformities, reduced skin oxygenation and foot perfusion, poor vision, greater body mass, and both sensory and autonomic neuropathy independently influence foot ulcer risk, thereby providing support for a multifactorial etiology for diabetic foot ulceration.

Amputation, Surgical↗

Physical examination and chronic lower-extremity ischemia: a critical review.

OBJECTIVE: To determine the clinical utility of physical examination in patients with suspected chronic ischemia of the lower extremities. DATA SOURCES: MEDLINE search (January 1966 to January 1997), personal files, and bibliographies of textbooks on physical diagnosis, surgery, and vascular surgery. STUDY SELECTION: Both authors independently graded the studies as level 1, 2, or 3, according to predetermined criteria. Criteria deemed essential for analysis of sensitivity, specificity, and likelihood ratios were (1) clear definition of study population, (2) clear definition of physical examination maneuver, and (3) use of an acceptable criterion standard test for comparison. RESULTS: The following positive findings help clinicians diagnose the presence of peripheral arterial disease: abnormal pedal pulses, a unilaterally cool extremity, a prolonged venous filling time, and a femoral bruit. Other physical signs help determine the extent and distribution of vascular disease, including an abnormal femoral pulse, lower-extremity bruits, warm knees, and the Buerger test. The capillary refill test and the findings of foot discoloration, atrophic skin, and hairless extremities are unhelpful in diagnostic decisions. Mathematical formulas, derived from 2 studies using multivariate analysis, allow clinicians to estimate the probability of peripheral arterial disease in their patients. CONCLUSION: Certain aspects of the physical examination help clinicians make accurate judgments about the presence of peripheral arterial disease and its distribution.

Aged↗

Use of spermicide-coated condoms and other risk factors for urinary tract infection caused by Staphylococcus saprophyticus.

BACKGROUND: Staphylococcus saprophyticus is the second most common cause of urinary tract infection (UTI) in young women. Relatively little is known about risk factors for this infection including exposure to vaginal spermicides, which increases the risk of UTI caused by Escherichia coli. PATIENTS AND METHODS: We conducted a case-control study in a large health maintenance organization Case patients were sexually active young women with acute UTIs caused by S saprophyticus identified from computerized laboratory files during 1990 to 1993. Population-based control patients were randomly selected from the organization's enrollment files. Exposures such as sexual activity and contraceptive practice were determined by interview. RESULTS: Of 1299 eligible women, 66% (96 case patients and 629 control patients) were interviewed. Case patients were more often unmarried and were more sexually active. Ninety-nine percent of case patients and 57% of control patients reported previous UTIs. Exposure to any type of condom during the previous year was reported by 53% of case patients and 31% of control patients. Exposure to spermicide-coated condoms during the previous month was associated with a higher risk of UTI (odds ratio [OR], 3.8; 95% confidence interval, 1.4-10.3). The OR for exposure during the previous year ranged from 2.2 (95% confidence interval, 1.0-4.8) for less than once weekly to 6.05 (95% confidence interval, 2.2-16.6) for more than twice weekly. In multivariate analyses, younger age (OR, 0.97 per year), intercourse frequency (OR, 1.2 per weekly episode), prior UTI (OR, 3.3), and frequency of exposure to spermicide-coated condoms (OR, 8.4 for more than once weekly and 10.9 for more than twice weekly) were independent predictors of UTI. Among women exposed to spermicide-coated condoms, 74% of UTIs caused by S saprophyticus were attributable to this exposure. CONCLUSIONS: Spermicide-coated condoms were associated with an increase risk of UTI caused by S saprophyticus. Because sexual activity and spermicide exposure are important risk factors for UTI caused by both S saprophyticus and E coli, it is likely that they share a similar pathogenesis.

Case-Control Studies↗

Reliability of F-scan in-shoe measurements of plantar pressure.

Research by our group and others indicates that many amputations of the lower limb occur after foot ulceration in patients with diabetes. It has been proposed that diabetic foot ulcers are mainly caused by repetitive trauma in areas of high plantar pressure during walking. Recent technology permits in-shoe measurement of plantar pressure. We assessed the reliability of the F-Scan in-shoe system for measurement of plantar pressure (Tekscan Inc., Boston, MA) in 51 subjects from a cohort of 977 diabetic veterans enrolled in a prospective study of risk factors for foot ulceration and amputation (the Seattle Diabetic Foot Study). Subjects were tested twice, wearing their own shoes. We used the coefficient of variation (CV) and the intra-class correlation coefficient (ICC) to estimate the reliability of F-Scan measurements of pressure. Peak pressure over the metatarsal heads proved to have the best indices of reliability, with CVs of 0.150 and 0.155, and ICCs of 0.755 and 0.751. Coefficients of variation for the heel, whole foot, and hallux ranged from 0.148 to 0.240, with ICCs ranging from 0.493 to 0.832. By published standards, peak pressures over the metatarsal heads and right hallux met the criteria for excellent reliability. Our ICCs for high pressures under the foot, heel, metatarsal heads, and hallux, and for peak pressures under the heel and left hallux represented fair-to-good reliability. No F-Scan plantar measurements could be judged by these criteria as having poor reliability. This clinical study found that for elderly patients with diabetes who were wearing their own shoes and were tested on two different days with different insoles, the F-Scan insole system was generally reliable for measurements of high pressure and peak pressure.

Adult↗

Increased plasma leptin levels are associated with fat accumulation in Japanese Americans.

Although the hormone leptin seems to play a role in ensuring the maintenance of adequate energy stores and thereby protects against starvation, its role in the regulation of body weight and adiposity under normal circumstances is unclear. Overweight individuals have markedly elevated circulating leptin levels, suggesting that leptin's effect on food intake and thermogenesis is diminished or absent in obesity. Recent evidence, though, indicates that weight gain in Pima Indians is associated with relatively decreased levels of the hormone. Because it is important to understand whether a deficiency in circulating leptin contributes to the development of obesity, we sought to determine whether there is a relationship between leptin levels and subsequent changes in adiposity in a more typical population. We compared baseline plasma leptin concentrations to changes over 5 years in body weight, BMI, and computed tomography-determined total fat in 492 second- and third-generation Japanese Americans. Subjects were of 100% Japanese ancestry; male subjects had a mean BMI at baseline of 25.4 kg/m2 and a mean age of 54 years; female subjects had a mean BMI of 23.1 kg/m2 and a mean age of 53 years. Changes in weight (men: r = 0.17, P < 0.05; women: r = 0.20, P < 0.05), BMI (men: r = 0.17, P < 0.05; women: r = 0.18, P < 0.05), and total fat (men: r = 0.19, P < 0.05; women: r = 0.20, P < 0.01) were positively correlated with baseline leptin levels adjusted for baseline adiposity, fasting insulin, and age. In Japanese Americans, then, relatively increased leptin levels are associated with greater subsequent gains in weight and adiposity. We concluded that in this population, fat accumulation is associated not with leptin deficiency but possibly with leptin resistance and is preceded by increased leptin levels.

Adipose Tissue↗

Reduced amylin release is a characteristic of impaired glucose tolerance and type 2 diabetes in Japanese Americans.

Islet amyloid is a characteristic feature of type 2 diabetes. Its major component is the normal beta-cell secretory product amylin, or islet amyloid polypeptide (IAPP). To determine whether increased or disproportionate release of amylin may explain the propensity for amyloid deposition in type 2 diabetes, we measured plasma amylin-like immunoreactivity (ALI) and immunoreactive insulin (IRI) release in response to an oral glucose load in 94 Japanese-American subjects with normal glucose tolerance (NGT; n=56), impaired glucose tolerance (IGT; n=10), and type 2 diabetes (n=28) as defined by World Health Organization criteria. The incremental increase in ALI, IRI, and glucose (G) at 30 min after oral glucose ingestion was used to calculate deltaALI/deltaG and deltaIRI/deltaG as measures of beta-cell function. Overall glucose metabolism was assessed as the incremental glucose area (glucose AUC) during the 2 h of the oral glucose tolerance test. As expected, plasma glucose concentrations at both fasting (NGT, 5.0+/-0.4; IGT, 5.5+/-0.1; type 2 diabetes, 6.2+/-0.3 mmol/l; P < 0.0001) and 2 h (NGT, 6.7+/-0.1; IGT, 9.4+/-0.3; type 2 diabetes, 13.2 +/-0.5 mmol/l; P < 0.0001) were elevated in individuals with IGT and type 2 diabetes. In response to glucose ingestion, plasma IRI and ALI increased in all subjects, but these increments were lower in individuals with reduced glucose tolerance, as reflected in the deltaIRI/deltaG (NGT, 119+/-10.3; IGT, 60.7+/-7.1; type 2 diabetes, 49.7 +/-5.4 pmol/l; P < 0.0001) and deltaALI/deltaG (NGT, 2.6+/-0.2; IGT, 1.8+/-0.3; type 2 diabetes, 1.2+/-0.1 pmol/l; P < 0.0001). Moreover, these reductions in the 30-min incremental ALI and IRI responses were proportionate such that the molar ratio of ALI to IRI was not different among the three groups (NGT, 2.6+/-0.2; IGT, 2.9 +/-0.3; type 2 diabetes, 2.9+/-0.3%; NS). Further, the relationship between beta-cell function, measured as either deltaIRI/deltaG or deltaALI/deltaG, and glucose metabolism, assessed as glucose AUC, was nonlinear and inverse in nature, with r2 values of 0.38 (P < 0.0001) and 0.33 (P < 0.0001), respectively. We conclude that the reduced beta-cell function of IGT and type 2 diabetes includes proportionate reductions in both IRI and ALI release. Thus, it is unlikely that the development of islet amyloid in type 2 diabetes is the result of increased release of ALI.

Amyloid↗

Glucose tolerance and insulin-resistance syndrome among St. Lawrence Island Eskimos.

OBJECTIVES: Non-insulin-dependent diabetes mellitus (NIDDM) prevalence in Alaska Natives is rising but remains lower than the U.S. average. We conducted a screening study for diabetes mellitus and cardiovascular disease in a remote Yup'ik Eskimo community in Alaska. RESEARCH DESIGN AND METHODS: The study population included Siberian Yup'ik Eskimo residents of Gambell, Alaska, > or = age 40 years who underwent a 2 h 75 gm oral glucose tolerance test interpreted by WHO criteria. Other measurements included fasting serum insulin and lipid levels, bioimpedance body fat %, body-mass-index (BMI), waist-to-hip ratio (WHR), and blood pressure. RESULTS: Of 114 eligible subjects, 65 (57%) participated. These subjects had lower mean systolic or diastolic blood pressure, lower triglyceride, and higher mean HDL cholesterol levels compared to a similarly aged U.S. all races sample. The mean fasting insulin level of 50.9 pmol/L appeared low given the high mean BMI (27.2). Six subjects had NIDDM (9%, 95% CI 2%-16%) and eight had impaired glucose tolerance (IGT) (12%, 95% CI 4%-20%). Compared to normoglycemic subjects, diabetic subjects were more frequently female (83% vs 53%) and had higher mean systolic BP (138 mm Hg vs 117 mm Hg) than normoglycemic subjects. We used multiple regression to analyze associations between fasting insulin and either blood pressure or serum lipids, while adjusting for % body fat, WHR, age, sex, and antihypertensive medication use. Fasting insulin was significantly related to both diastolic blood pressure (p = .0430) and fasting serum triglyceride (p = .0182) but not to systolic BP, total cholesterol, or LDL and HDL subfractions. CONCLUSIONS: Although NIDDM prevalence was not high compared to non-Native U.S. residents, elements of the insulin-resistance syndrome exist in this subarctic population.

Adult↗

Fasting insulin level underestimates risk of non-insulin-dependent diabetes mellitus due to confounding by insulin secretion.

Fasting insulin has been used as a surrogate measure of insulin sensitivity in studies of non-insulin-dependent diabetes mellitus (NIDDM) risk, but the fasting insulin-NIDDM association may be confounded by insulin secretion, which correlates negatively with NIDDM risk and positively with fasting insulin level. In a prospective 5-year study of 137 nondiabetic Japanese-American men in King County, Washington State, higher fasting insulin was not strongly related to NIDDM (odds ratio (OR) = 1.37, 95% confidence interval (CI) 0.80-2.34), but this odds ratio increased substantially after adjustment for insulin secretion (OR = 2.92, 95% CI 1.41-6.06). Research on NIDDM risk in relation to fasting insulin may yield biased effect measures unless adjusted for insulin secretion.

Asian↗

Diagnostic utility of the history and physical examination for peripheral vascular disease among patients with diabetes mellitus.

BACKGROUND: We assessed the value of the medical history and physical examination in the diagnosis of peripheral vascular disease in diabetic subjects. METHODS: We performed a cross-sectional study in 631 diabetic veteran enrollees of a general internal medicine clinic that compared data obtained from a history and clinical evaluation with the presence of severe peripheral vascular disease defined as an ankle-arm index (AAI) < or = 0.5 derived from Doppler blood pressure measurement. RESULTS: We identified 90 limbs with an AAI < or = 0.5. Results presented below apply to the right leg, but do not differ from the left. Diminished or absent foot peripheral pulses (sensitivity 65%, specificity 78%), venous filling time > 20 sec (sensitivity 22%, specificity 93.9%), age > 65 years (sensitivity 83%, specificity 54%), claudication symptoms in < 1 block (sensitivity 50%, specificity 87%), and patient reported history of physician diagnosed peripheral vascular disease (PVD) (sensitivity 80%, specificity 70%) had the largest positive (or smallest negative) likelihood ratios. Capillary refill time > 5 sec or foot characteristics (absent hair, blue/purple color, skin coolness, or atrophy) conveyed little diagnostic information. Individual factors did not change disease probability to a clinically important degree. A stepwise logistic regression model identified four factors significantly (p < 0.05) associated with low AAI: absent or diminished peripheral pulses, patient reported history of PVD, age, and venous filling time. Substitution of < 1 block claudication for PVD history in this model resulted in a small reduction in model accuracy. CONCLUSIONS: Many purportedly useful historical and exam findings need not be elicited in diabetic patients suspected of having severe peripheral vascular disease, since most information related to probability of this disorder may be obtained from patient age, self-reported history of physician diagnosed PVD (or < 1 block claudication), peripheral pulse palpation, and venous filling time.

Aged↗