Use of focus groups to explore nutrition practices and health beliefs of urban Caribbean Latinos with diabetes.

OBJECTIVE: Although Caribbean Latinos are two to three times more likely than non-Hispanic whites to develop diabetes, cultural influences on nutrition and health are poorly understood. To provide insight into important features of diabetes prevention and management, we conducted focus groups to explore nutrition practices and health beliefs. RESEARCH DESIGN AND METHODS: Thirty low-income urban Caribbean Latinos with non-insulin-dependent diabetes mellitus (NIDDM) and four family members participated in four focus group interviews that were conducted in Boston and Cambridge, Massachusetts. Interviews were conducted in Spanish, were tape recorded, and were led and analyzed by Latino professionals from a community-based health organization. RESULTS: Consistent themes described by participants were feelings of social isolation, little understanding of long-term consequences of diabetes, fatalism regarding the course of the disease, multiple barriers to diet and exercise interventions, skepticism regarding the value of preventive health behaviors, prevalent use of traditional nonmedical remedies, and a clear need for culturally sensitive health-care providers and services. CONCLUSIONS: The information from focus groups provides useful information for planning innovative intervention programs for chronic disease risk reduction that emphasize practical skills development, family/peer networks, empowerment techniques, and bilingual providers. We conclude that the focus group technique can be used effectively with low-income, urban minority populations to provide information on lifestyle behaviors and beliefs regarding chronic diseases that impact on health and nutritional status.

The isoquinoline sulfonamide inhibitors of protein phosphorylation, H-7, H-8, and HA-1004, also inhibit RNA synthesis: studies on responses of adipose tissue to growth hormone.

To evaluate the possibility that some of the metabolic effects of GH in rat adipose tissue depend upon phosphorylation-dephosphorylation reactions, we examined the effects of the isoquinoline sulfonamide family (H-7, H-8, and HA-1004) of protein kinase inhibitors on the actions of GH. In the course of these studies it became clear that these compounds may also block RNA synthesis. In the concentration range of 50-200 microM, H-7, H-8, and HA-1004 completely blocked lipolysis in response to the combination of 100 ng/ml dexamethasone and 30 ng/ml human GH in segments of epididymal fat from normal rats, but were less effective in blocking lipolysis in response to either 1 mM (Bu)2cAMP or 1 ng/ml isoproterenol, which are known to depend upon activation of protein kinase-A. Activation of protein kinase-C with phorbol myristate nearly doubled the rate of glucose oxidation in segments of normal adipose tissue, and this insulin-like response was completely inhibited with 200 microM H-7. At concentrations as high as 500 microM, H-7, H-8, and HA-1004 failed to inhibit the insulin-like response to GH in tissue segments of either normal or hypophysectomized rats. However, when 200 microM H-7 or H-8, but not HA-1004, was present during the first 3 h of treatment with GH, it prolonged the duration of the insulin-like response (acceleration of glucose oxidation) from its normal termination within 2-3 h to more than 4 h. Identical results were obtained with 5 micrograms/ml actinomycin-D. The effect of H-7 or H-8 was reversible and required the continuous presence of these agents, whereas actinomycin-D was required only during the first 60 min after GH. Termination of the insulin-like response normally is followed by a period of several hours in which the tissues are refractory to further insulin-like stimulation by GH. When actinomycin-D, H-7, H-8, or HA-1004 was added to tissues of hypophysectomized rats 60 min after GH, the insulin-like response terminated at its normal time, but the tissues were not refractory to insulin-like stimulation upon reexposure to GH. These agents also prevented GH from sustaining refractoriness in normal adipose tissue.(ABSTRACT TRUNCATED AT 400 WORDS)

Different growth hormone-receptor interactions mediate insulin-like and lipolytic responses of rat adipose tissue.

The GH receptor in adipocytes is a glycoprotein that has a half-life of less than 1 h. After 2 h of treatment with the alkaloid swainsonine, which interferes with carbohydrate processing, virtually all of the GH receptors on the surface of adipocytes are replaced with receptors whose carbohydrate side-chains are incomplete. We examined the effects of swainsonine on the responsiveness of adipose tissue to GH to determine whether these receptors, which bind GH normally, retain biological competence. In the concentration range of 100-300 ng/ml human (h) GH rapidly evokes insulin-like responses in adipose tissue or adipocytes that have been deprived of GH for at least 3 h. hGH, at concentrations ranging from 1-10 ng/ml, also increases lipolysis after a delay of at least 2 h. Pretreatment with 50 micrograms/ml swainsonine failed to influence insulin-like responsiveness to hGH, as judged by increased glucose oxidation, but nearly completely abolished the lipolytic response. Pretreatment with swainsonine, however, did not reduce lipolysis in response to isoproterenol, suggesting that signal transmission rather than the lipolytic apparatus per se had been affected. To determine whether the same receptors mediate lipolytic and insulin-like responses, the binding properties of hGH were compared to those of Da1, a chemically modified form of hGH, whose insulin-like potency is reduced relative to its lipolytic potency. Da1 and hGH were equipotent in promoting lipolysis and had an ED50 of about 3 ng/ml, but hGH was at least 6 times as potent as Da1 in promoting glucose oxidation (ED50 of 65 vs. 400 ng/ml). Scatchard plots of both Da1 and hGH binding data were linear, consistent with a single class of binding sites whose affinity for hGH was about 3.5 times higher for hGH than Da1. hGH and Da1 both produced half-maximal stimulation of glucose oxidation when about 90% of the GH receptors were occupied. In contrast, half-maximal lipolysis was produced by Da1 when 8% of GH receptors were occupied, but 21% occupancy was required for a similar effect of hGH. If a subclass of GH receptors mediates lipolysis, it is likely to comprise 10% or less of the total receptor population.

Frequency of painless myocardial ischemia during exercise tolerance testing in patients with and without diabetes mellitus.

To evaluate the frequency of painless myocardial ischemia, all patients with positive exercise tolerance test responses (at least 2 mm of ST depression) from 1983 to 1985 were examined. Of the 211 patients with exercise-induced ischemia, 101 (48%) did not have pain during the ischemic period; 26 (12%) had diabetes mellitus, 24 of whom (92%) had type II diabetes mellitus. Lack of pain was not correlated with age, gender, history of cigarette smoking, systemic hypertension, past acute myocardial infarction, coronary artery bypass grafting, use of beta-blocking or calcium-channel blocking drugs, number of narrowed coronary arteries or average calculated ejection fraction at cardiac catheterization. Patients with painless myocardial ischemia were less often taking nitrates (39% vs 55%, p less than 0.05) and reported prior episodes of chest pain less often (50% vs 82%, p less than 0.01) than control subjects. There was no difference in the frequency of painless myocardial ischemia between patients with and without diabetes mellitus (54% vs 47%). Duration of exercise was shorter in patients with diabetes mellitus and in patients who had pain with myocardial ischemia. No significant difference in age, gender, use of nitrates, beta-blocking or calcium-channel blocking drugs, history of myocardial infarction, angina pectoris or cigarette smoking was found between diabetic and nondiabetic patients. Systemic hypertension was more common in diabetic patients. Thus, painless myocardial ischemia is common in our patients with positive exercise tolerance test responses, but its frequency is similar in diabetic and nondiabetic patients.

Immunohistochemical evidence for neural mediation of VIP activity in the dogfish rectal gland.

Vasoactive intestinal peptide (VIP) has been shown to increase chloride secretion from the rectal gland of the spiny dogfish, Squalus acanthias. Immunohistochemistry was used to localize the distribution of immunoreactive VIP (iVIP). Rectal glands were perfused with either buffered acrolein or paraformaldehyde/glutaraldehyde, sectioned (20 micron) and processed by either avidin-biotin complex (ABC) or peroxidase anti-peroxidase (PAP) methods. At the light microscopic level, iVIP was observed in thick fibers which traversed the fibromembranous capsule of the rectal gland. In the parenchyma, smaller iVIP-containing fibers were noted within connective tissue and in close approximation to tubule cells. At the ultrastructural level, iVIP axons in the fibromembranous capsule were unmyelinated. Immunoreactive fibers within the parenchyma frequently terminated on the basal side of tubule cells. Within the glands, iVIP bouton terminals were observed and contained vesicles of different sizes, with reaction product in dense core vesicles (60-120 nm). We conclude that iVIP is distributed in nerve fibers throughout the dogfish rectal gland. The anatomic distribution suggests that VIP may act as a neurotransmitter in this model of chloride ion transport.

Exercise and diabetes.

As rates of diabetes mellitus and obesity continue to increase, physical activity continues to be a fundamental form of therapy. Exercise influences several aspects of diabetes, including blood glucose concentrations, insulin action and cardiovascular risk factors. Blood glucose concentrations reflect the balance between skeletal muscle uptake and ambient concentrations of both insulin and counterinsulin hormones. Difficulties in predicting the relative impact of these factors can result in either hypoglycemia or hyperglycemia. Despite the variable impact of exercise on blood glucose, exercise consistently improves insulin action and several cardiovascular risk factors. Beyond the acute impact of physical activity, long-term exercise behaviors have been repeatedly associated with decreased rates of type 2 diabetes. While exercise produces many benefits, it is not without risks for patients with diabetes mellitus. In addition to hyperglycemia, from increased hepatic glucose production, insufficient insulin levels can foster ketogenesis from excess concentrations of fatty acids. At the opposite end of the glucose spectrum, hypoglycemia can result from excess glucose uptake due to either increased insulin concentrations, enhanced insulin action or impaired carbohydrate absorption. To decrease the risk for hypoglycemia, insulin doses should be reduced prior to exercise, although some insulin is typically still needed. Although precise risks of exercise on existing diabetic complications have not been well studied, it seems prudent to consider the potential to worsen nephropathy or retinopathy, or to precipitate musculoskeletal injuries. There is more substantive evidence that autonomic neuropathy may predispose patients to arrhythmias. Of clear concern, increased physical activity can precipitate a cardiac event in those with underlying CAD. Recognizing these risks can prompt actions to minimize their impact. Positive actions that are part of exercise programs for diabetic patients emphasize SMBG, foot care and cardiovascular functional assessment. SMBG provides critical information on the impact of exercise and is recommended for all patients before, during and after exercise. More frequent monitoring (and for longer periods following exercise) is recommended for those with hypoglycemia unawareness or those performing high-intensity exercise. Preventing the sequelae of an exercise-induced severe hypoglycemic reaction can be as simple as carrying glucose tablets or gel, a diabetic identification bracelet or card, or exercising with an individual who is aware of the circumstances. In addition to blood glucose concentrations, proper foot care is critical to people with diabetes who exercise and includes considering type of shoe, type of exercise, inspection of skin surfaces and appropriate evaluation and treatment of lesions (calluses and others). Those with severe neuropathy can consider alternatives to weight-bearing exercises. Precipitation of clinical CAD is of great concern for all diabetic patients participating in exercise activities. Although a sufficiently sensitive and specific screening test for coronary disease has not been identified, those planning an exercise program of moderate intensity or greater should be evaluated. Initial cardiac assessment should include exercise testing as well as identifying risk for autonomic neuropathy. In addition to noting maximal heart rate and blood pressure as well as ischemic changes, exercise tolerance testing can identify anginal thresholds and patients with asymptomatic ischemia. Those without symptoms should be counseled regarding target pulse rates to avoid inducing ischemia. Ischemic changes need to be evaluated for either further diagnostic testing or pharmacological intervention. For patients with diabetes mellitus, the overall benefits of exercise are clearly significant. Clinicians and patients must work together to maximize these benefits while minimizing risks for negative consequences. Identifying and preventing potential problems beforehand can reduce adverse outcomes and promote this important approach to healthy living.

Compliance with guidelines for thyroid nodule evaluation.

OBJECTIVE: To determine whether guidelines recommended by the American Association of Clinical Endocrinologists (AACE) for assessment of a solitary thyroid nodule have been applied in clinical practice. METHODS: We retrospectively examined the pattern of testing in patients with solitary thyroid nodules at our institution during a 2-year period. We also attempted to determine whether consultation with an endocrinologist affected the workup. Patients who underwent a thyroid scan, ultrasonography, fine-needle aspiration (FNA) biopsy, or a thyroid surgical procedure for investigation of a solitary thyroid nodule between Jan. 1, 1996, and Dec. 31, 1997, were included in the study. Test results were reviewed for these patients. Patients were categorized into two groups, those with and those without a consultation with an endocrinologist. RESULTS: Inclusion criteria were met by 89 patients, 65% of whom had an FNA biopsy in their evaluation (the sole test in only 9%). A thyroid scan was done in 90% of patients, and an ultrasound study was done in 25%. Patients seen by an endocrinologist were more likely to undergo FNA biopsy than those who were not (82% versus 29%; P<0.001). Many patients who underwent assessment because of solitary nodules had normal findings on thyroid scans (21% of scans). CONCLUSION: The AACE guidelines for evaluation of thyroid nodules have not yet been fully implemented. Although a third of all study patients with a solitary thyroid nodule did not have an FNA biopsy, endocrine referral increased the rate of performance of this procedure. Thyroid scans seem to be overutilized; the high number with normal findings suggests that nuclear imaging studies are done to confirm physical findings. Early referral to an endocrinologist may be a more cost-effective workup of a possible thyroid nodule.

Buena Alimentacion, Buena Salud: a preventive nutrition intervention in Caribbean Latinos with type 2 diabetes.

A culturally sensitive 3-month intervention was provided to 18 Caribbean Latino men and women with non-insulin-dependent (type 2) diabetes mellitus. Compared to the randomly assigned control group, the intervention group showed statistically significant decreases in total calories, fat calories, percent of calories from fat, saturated fat calories, and percent of calories from saturated fat The intervention group showed increases in calories from carbohydrates and in the percent of calories from fiber.

Self-reported factors that affect glycemic control in college students with type 1 diabetes.

PURPOSE: This study examined the self-reported impact of different factors on the overall diabetes care of college students with type 1 diabetes. METHODS: An 18-item questionnaire was mailed to 164 students with type 1 diabetes attending college away from home; results from 42 students fulfilled study criteria and were analyzed. Metabolic control was assessed by relative changes in glycosylated hemoglobin (HbA1c) levels from medical records. RESULTS: HbA1c levels did not change significantly between high school and college, yet most college students reported that diabetes was more difficult to manage in college. Commonly reported barriers to diabetes control included diet, irregular schedules, lack of parental involvement, peer pressure, drugs and alcohol, fear of hypoglycemia, and finances. Factors identified as improving diabetes control were an increased sense of responsibility, increased frequency of blood glucose testing, exercise, contact with healthcare providers, fear of hyperglycemia, and knowledge of the results of the Diabetes Control and Complications Trial. Many students reported testing their blood more frequently and taking more injections than in high school; most were on intensive insulin regimens. CONCLUSIONS: Despite the perception that diabetes management was more difficult in college, metabolic control was maintained during college, possibly due to a more intensive treatment approach.

Nutritional risk in an urban homebound older population. The nutrition and healthy aging project.

PURPOSE: To establish the prevalence of nutritional problems and their related socio-demographic and health-related risk factors in the homebound elderly population. METHODS: Subjects included 239 men and women, ages 65 to 105 years. Trained, two-person field teams conducted comprehensive in-home assessments. Medical record reviews assessed co-morbidity and medication use. RESULTS: The majority of these urban study subjects are of very advanced age (mean age 81 years), female (72%), non-white (73%), living alone (51%), of low income (76%), and somewhat socially isolated (26% had no weekly social contact). More older women than men were widowed (60 vs. 33%, respectively) and poor (80 vs. 67%). The disease burden and functional dependency were both high in men and women; 77% had three or more chronic medical conditions; 76% were functionally dependent in one or more ADL's and 95% in one or more IADL's. Poor dietary quality was universal in these older men and women; half or more consumed diets that deviated from recommended standards for at least 13 of the 24 nutritional guidelines studied. Five percent of subjects were underweight (Body Mass Index (BMI) <18.5); 22% were overweight (BMI 25.0-29.9); and 33% were obese (BMI >30.0). Fasting albumin, hemoglobin, and absolute lymphocyte concentrations were borderline to very low in 18-32%. Dyslipidemia was more common in women; however, men and women had similar Total:HDL cholesterol ratios. CONCLUSIONS: Nutritional status is poor in homebound persons of very advanced age with substantial co-morbidity and functional dependency. The complexities of nutritional risk necessitate multi-disciplinary and individualized nutritional intervention strategies.

Health status and practices of urban Caribbean Latinos with diabetes mellitus.

Although Caribbean Latinos are more likely than non-Hispanic whites to develop diabetes, their health status has been poorly characterized. Information on diabetes management, metabolic control, dietary habits, and diabetes knowledge was gathered from a group of urban Caribbean Latinos with diabetes in order to characterize the nutritional behaviors, diabetes attitudes, health perceptions, and metabolic control of this high risk group. Interviews and medical record reviews were conducted among seventy low-income urban Caribbean Latinos with type 2 diabetes mellitus. Patients attending outpatient clinics were interviewed by bilingual interviewers. Medical records were reviewed to ascertain prevalence of diabetes-related complications, medications, and metabolic parameters. Participants were primarily Spanish-speaking and of Puerto Rican origin. Eighty-one percent were unemployed, and only 27% had completed high school or higher educational levels. Average hemoglobin A1c was 10.6%. Among those with hypertension and hyperlipidemia, many were not receiving treatment. Participants' estimation of their own degree of metabolic control was poor, as was their understanding of desirable blood glucose and weight goals. A second evening meal was common. Diets were higher in fat and sugar content than currently recommended. More effective treatment strategies for both patients and providers are needed to improve glycemic control and cardiovascular risk factors among indigent urban Caribbean Latinos. Essential features of such strategies for patient programs include culturally appropriate dietary counseling and low literacy materials to better communicate glycemic and weight goals and dietary guidelines. Provider education is needed regarding established guidelines and cultural influences on diabetes-related practices.

Cellular effects of growth hormone on adipocytes.

Adipocytes are physiological targets for GH in both growing and nongrowing individuals. In adipocytes that have been deprived of GH for at least 3 h, GH initially produces a response that is characterized by increased metabolism of glucose and inhibition of the lipolytic effects of catecholamines. This insulin-like effect disappears within 2-3 h despite continued stimulation and cannot be elicited again unless cells are deprived of GH for at least 3 h. Despite refractoriness to the insulin-like action of GH, the lipolytic effect of GH is evident at this time. Although termination of the insulin-like response and induction of both refractoriness and lipolysis all depend upon synthesis of RNA and proteins, these 3 effects of GH appear to be neither temporally nor causally related. Scatchard analysis of ligand binding data suggests that these various effects are produced by interaction of GH with a single class of receptors. However, since modification of either the hormone or the carbohydrate moiety of the receptor can selectively attenuate either the insulin-like or the lipolytic response, more than one hormone receptor interaction is likely. Northern analysis indicates the presence of at least 2 alternately spliced mRNA transcripts for the GH receptor, and at least 3 different complexes are seen after GH is covalently crosslinked to intact adipocytes. Refractoriness does not result from changes in either the number or affinity of GH receptors, but may result from increased cytosolic calcium. Although the protein kinase C activator phorbol myristate acetate mimics both the insulin-like and lipolytic actions of GH, increased activity of protein kinase C probably does not mediate either action of GH. The intracellular mediators of the diverse actions of GH are unknown at this time.

Accuracy and optimal timing of activity measurements in estimating the absorbed dose of radioiodine in the treatment of Graves' disease.

Calculation of the therapeutic activity of radioiodine (131)I for individualized dosimetry in the treatment of Graves' disease requires an accurate estimate of the thyroid absorbed radiation dose based on a tracer activity administration of (131)I. Common approaches (Marinelli-Quimby formula, MIRD algorithm) use, respectively, the effective half-life of radioiodine in the thyroid and the time-integrated activity. Many physicians perform one, two, or at most three tracer dose activity measurements at various times and calculate the required therapeutic activity by ad hoc methods. In this paper, we study the accuracy of estimates of four 'target variables': time-integrated activity coefficient, time of maximum activity, maximum activity, and effective half-life in the gland. Clinical data from 41 patients who underwent (131)I therapy for Graves' disease at the University Hospital in Pisa, Italy, are used for analysis. The radioiodine kinetics are described using a nonlinear mixed-effects model. The distributions of the target variables in the patient population are characterized. Using minimum root mean squared error as the criterion, optimal 1-, 2-, and 3-point sampling schedules are determined for estimation of the target variables, and probabilistic bounds are given for the errors under the optimal times. An algorithm is developed for computing the optimal 1-, 2-, and 3-point sampling schedules for the target variables. This algorithm is implemented in a freely available software tool. Taking into consideration (131)I effective half-life in the thyroid and measurement noise, the optimal 1-point time for time-integrated activity coefficient is a measurement 1 week following the tracer dose. Additional measurements give only a slight improvement in accuracy.

Transient myocardial perfusion abnormalities in diabetic patients: a prospective study using thallium exercise tolerance testing.

To determine whether diabetic patients without known cardiovascular disease have exercise-induced perfusion abnormalities without symptoms, we performed thallium-201 exercise tolerance testing (ETT) on 16 subjects with diabetes mellitus (8 men and 8 women; mean age = 51 +/- 2 years). To compare these patients to another group at risk for coronary disease and painless myocardial infarction, 13 hypertensive (7 men and 6 women; mean age = 50 +/- 2 years) patients without symptoms of atherosclerotic disease served as controls. Diabetic and hypertensive patients were similar with regard to age, sex, years since diagnosis and other cardiac risk factors. Abnormal exercise thallium testing was more common among diabetic patients (11/16 = 69%; p less than 0.05) as compared to hypertensive patients (4/13 = 31%). None of the patients reported chest pain or its equivalent. There was no difference between diabetic and hypertensive subjects in the number of minutes exercised, percentage of maximal heart rate attained or final heart rate achieved. Diabetic subjects as a group had greater evidence of peripheral neuropathy but no abnormality of autonomic nerve function. Using ETT with thallium scintigraphy, diabetic patients without known cardiovascular disease were more likely to have transient myocardial perfusion defects than were hypertensive patients.

In vivo effects of dexamethasone and sucrose on glucose transport (GLUT-4) protein tissue distribution.

Tissue-specific changes in GLUT-4 were compared in the following three different rat models by inducing varying degrees of hyperinsulinemia with or without hyperglycemia and hypertriglyceridemia: 1) sucrose feeding (Suc), 2) subcutaneous dexamethasone administration (Dex), and 3) a combination of both treatments (Dex/Suc). Suc raised circulatory insulin and triglyceride levels without affecting plasma glucose, whereas both Dex and Dex/Suc induced significant hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. In adipocytes and skeletal muscle, Suc feeding was not associated with any change in total cellular GLUT-4 levels. However, Suc induced a sevenfold increase in fat cell plasma membrane GLUT-4 levels in the basal state and inhibited GLUT-4 translocation in response to insulin. Administration of Dex or Dex/Suc diminished GLUT-4 expression in fat cells, increased it in skeletal muscle, but did not induce any change in heart. Similar to Suc feeding, Dex and Dex/Suc also increased the amount of GLUT-4 detected at the plasma membrane of adipocytes in the basal state and inhibited GLUT-4 translocation in response to insulin. These results emphasize the specific regulation of GLUT-4 in insulin-sensitive tissues.

Effects of dexamethasone in vivo and in vitro on hexose transport in brain microvasculature.

Glucocorticoids induce hyperinsulinemia, hyperglycemia, and depress glucose transport by aortic endothelium. High glucocorticoid doses are used for many diseases, but with unknown effects on brain glucose transport or metabolism. This study tested the hypothesis that glucocorticoids affect glucose transport or metabolism by brain microvascular endothelium. Male rats received dexamethasone (DEX) s.c. with sucrose feeding for up to seven days. Cerebral microvessels from rats treated with DEX/sucrose demonstrated increased GLUT1 and brain glucose extraction compared to controls. Glucose transport in vivo correlated with hyperinsulinemia. Pre-treatment with low doses of streptozotocin blunted hyperinsulinemia and prevented increased glucose extraction induced by DEX. In contrast, isolated brain microvessels exposed to DEX in vitro demonstrated suppression of 2-deoxyglucose uptake and glucose oxidation. We conclude that DEX/sucrose treatment in vivo increases blood-brain glucose transport in a manner that requires the effects of chronic hyperinsulinemia. These effects override any direct inhibitory effects of either hyperglycemia or DEX.

Vasodilator responses in the forearm skin of patients with insulin-dependent diabetes mellitus.

The integrity of endothelium-dependent vasodilation in the skin of patients with insulin-dependent diabetes mellitus (IDDM) is unclear, especially with respect to the role of nitric oxide. To examine this, forearm skin blood flow by laser Doppler flowmetry and total blood flow by venous occlusion plethysmography was measured in response to brachial artery infusions of an endothelium-dependent (methacholine) and -independent (sodium nitroprusside) vasodilator. Peak hyperemic forearm blood flow, following 5 min of arterial occlusion, was also determined. Responses were compared in 11 control subjects and 16 patients with insulin-dependent diabetes mellitus. In ten normal subjects, co-infusion of NG-monomethyl-L-arginine with methacholine produced a significant reduction in total forearm blood flow response to methacholine (p < 0.002), measured by venous occlusion plethysmography, as well as vascular conductance (p < 0.001), confirming that nitric oxide contributes to this response. In contrast, NG-monomethyl-L-arginine had no significant effect on the methacholine-induced increase in forearm skin blood flow measured by laser Doppler flowmetry indicating that factors other than nitric oxide may be involved. Increases in forearm skin blood flow in response to methacholine, sodium nitroprusside and to an ischemic stimulus were not significantly different between the normal subjects and patients with IDDM. Dose-related increases in total forearm blood flow and vascular conductance were not significantly different between control subjects and diabetic patients during infusions of methacholine. The increases in these parameters during infusions of sodium nitroprusside, however, were significantly less in the diabetic group than in the control group (p < 0.05) as was the peak reactive hyperemic blood flow (p < 0.05). Since skin blood flow was not affected, the reduced vasodilator responses to sodium nitroprusside and an ischemic stimulus in the diabetic group are in forearm skeletal muscle. The reduced muscle blood flow does not reflect a decreased vasodilatory capacity, but rather a functional impairment in response to nitric oxide and ischemia since the methacholine dilation was normal. The normal vasodilator responses in the forearm skin, which is predominantly capillary as opposed to arteriovenous anastomatic blood flow, indicate that the response to nitric oxide and an ischemic stimulus in this vascular bed is intact in patients with IDDM. This is, therefore, an unlikely cause of diabetic skin, complications in these areas.