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J S Skyler

Publications and source records attributed to J S Skyler.

At least 19 recordsLinked to original sources
PubMed2001

Modeling preclinical cardiovascular risk for use in epidemiologic studies: Miami community health study.

To develop a method for assessing preclinical cardiovascular disease risk, models of resting cardiovascular regulation and of insulin metabolic syndrome were derived from information collected from 1991 to 1996 in a culturally heterogeneous sample of 319 healthy men and women (aged 25-44 years) from Miami-Dade County, Florida. The model of resting cardiovascular regulation used 8 noninvasive measures of autonomic and cardiovascular function. Three factors were derived: 1) parasympathetic, 2) inotropy, and 3) systemic vascular resistance. The model of insulin metabolic syndrome used 12 measures assessing body mass, insulin, glucose, and lipid metabolism. Four factors were derived: 1) body mass and fat distribution, 2) glucose level and regulation, 3) insulin level and regulation, and 4) plasma lipid levels. Analyses of the association of the two models revealed that subjects with lower cardiac contractility had greater body mass, higher fasting and postload insulin and glucose levels, and lower insulin sensitivity. Subjects with greater vascular resistance had greater body mass, higher total cholesterol and triglyceride levels, and lower high density lipoprotein cholesterol levels. These findings indicate that preclinical cardiovascular disease risk may involve pathophysiologic processes in which cardiac inotropic and vasodilatory functions are linked to specific aspects of insulin metabolic syndrome.

Adult↗
PubMed2001

Inhaled human insulin treatment in patients with type 2 diabetes mellitus.

BACKGROUND: Despite demonstrated benefits, intensive insulin therapy has not gained widespread clinical acceptance for several reasons: Multiple daily injections are inconvenient, adherence is a concern, and the time-activity profile may not mimic normal insulin secretion. As such, alternate means of administering insulin are being evaluated. OBJECTIVE: To assess the efficacy and safety of pulmonary delivery of insulin in type 2 diabetic patients who require insulin. DESIGN: Randomized, open-label, 3-month study consisting of a screening visit, a 4-week baseline lead-in phase, and a 12-week treatment phase. SETTING: General clinical research center and outpatient research clinics. PATIENTS: 26 patients (16 men, 10 women) with type 2 diabetes (average age, 51.1 years; average duration of diabetes, 11.2 years). INTERVENTION: Patients received inhaled insulin before each meal plus a bedtime injection of ultralente insulin, performed home glucose monitoring, and had weekly adjustment of insulin dose; target level for preprandial plasma glucose was 5.55 to 8.88 mmol/L (100 to 160 mg/dL). MEASUREMENTS: Glycemic control (hemoglobin A(1c) level) obtained at baseline and monthly for 3 months. Pulmonary function tests were done at baseline and at the end of the study. RESULTS: Inhaled insulin treatment for 3 months significantly improved glycemic control compared with baseline: Mean hemoglobin A(1c) levels decreased by 0.0071 +/- 0.0072 (0.71% +/- 0.72%). Patients experienced an average of 0.83 mild to moderate hypoglycemic event per month; no severe events were recorded. Patients showed no significant weight gain or change in pulmonary function compared with baseline. CONCLUSIONS: Pulmonary delivery of insulin in type 2 diabetic patients who require insulin improved glycemic control, was well tolerated, and demonstrated no adverse pulmonary effects. Larger-scale studies are ongoing to provide long-term efficacy and safety data.

Administration, Inhalation↗
PubMed2001

Efficacy of inhaled human insulin in type 1 diabetes mellitus: a randomised proof-of-concept study.

BACKGROUND: Effective glycaemic control in type 1 diabetes mellitus usually requires two or more insulin injections daily. Inhaled intrapulmonary delivery of insulin offers a potential new way to deliver meal-related insulin, eliminating the need for preprandial injections. METHODS: 73 patients with type 1 diabetes mellitus were studied in an open-label, proof-of-concept, parallel-group randomised trial. Patients in the experimental group received preprandial inhaled insulin plus a bedtime subcutaneous ultralente insulin injection. Patients in the control group received their usual insulin regimen of two to three injections per day. Participants monitored their blood glucose four times daily, and adjusted insulin doses weekly to achieve preprandial glucose targets of 5.6-8.9 mmol/L. The primary outcome measure was change in glycosylated haemoglobin (HbA1c) after 12 weeks. Secondary outcomes were fasting and postprandial glucose response to a mixed meal; hypoglycaemia frequency and severity; pulmonary function; and patients' satisfaction. FINDINGS: Changes in HbA1c were indistinguishable between groups (difference 0.2% [95% CI -0.2 to 0.5]). Changes in fasting and postprandial glucose concentrations, and occurrence and severity of hypoglycaemia were also similar between groups. Inhaled insulin was well tolerated and had no effect on pulmonary function (ie, spirometry, lung volumes, diffusion capacity, and oxygen saturation). INTERPRETATION: This proof-of-concept study shows that preprandial insulin can be given by inhalation in individuals with insulin-deficient type 1 diabetes as a less invasive alternative to conventional preprandial insulin injections.

Administration, Inhalation↗
PubMed2001

Microvascular complications. Retinopathy and nephropathy.

Diabetic retinopathy and diabetic nephropathy extract an enormous toll on patients with diabetes and an enormous burden on the health care system. With aggressive control of glycemia and blood pressure, coupled with aggressive use of laser photocoagulation and treatment of microalbuminuria, these problems can largely be eliminated. In the future, specific interventions may emerge that will allow interdiction of the pathophysiologic processes that lead to initiation and progression of these microvascular complications. The challenge for the primary care physician and diabetologist is to attain excellent glycemic control and aggressive control of blood pressure, while assuring that every patient has appropriate dilated fundus examinations at least annually, preferably by an ophthalmologist or retinal specialist, and regular screening for microalbuminuria. With such medical management, appropriate intervention can occur to reduce the risk of blindness and renal failure and to lessen the burden from diabetic retinopathy and nephropathy.

Adult↗
PubMed2000

Validation of the insulin sensitivity index (ISI(0,120)): comparison with other measures.

The purpose of this study was to explore possible calculations using oral glucose tolerance test (OGTT) values in order to develop a simple measure of insulin sensitivity. We devised a formula for an insulin sensitivity index, ISI(0,120), that uses the fasting (0 min) and 120 min post-oral glucose (OGTT) insulin and glucose concentrations. It appears to be generalizable across a spectrum of glucose tolerance and obesity. Most importantly, our data show that ISI(0,120) correlates well, when applied prospectively in comparative studies, with the insulin sensitivity index obtained from the euglycemic hyperinsulinemic clamp (r = 0.63, P < 0.001). This correlation was demonstrably superior to other indices of insulin sensitivity such as the HOMA formula presented by Matthews, and performed comparably to the computerized HOMA index. Measurement of insulin sensitivity has traditionally been possible only in research settings because of the invasiveness and expense of the methods used. Clinical investigators have therefore sought more practical methods to obtain an index of insulin sensitivity. Such an index should approximate insulin sensitivity as measured by the euglycemic hyperinsulinemic clamp (M). We present ISI(0,120), a simple yet sensitive measure of insulin sensitivity which is adaptable for use in clinical settings as well as large epidemiologic studies.

Adolescent↗
PubMed1999

Is fasting leptin associated with insulin resistance among nondiabetic individuals? The Miami Community Health Study.

OBJECTIVE: Whether serum leptin levels are associated with insulin resistance independent of the effects of hyperinsulinemia and adiposity is an important unanswered question. We examined the relationship between the rate of insulin-mediated glucose uptake and serum leptin concentrations among nondiabetic men and women. RESEARCH DESIGN AND METHODS: A cross-sectional analysis was performed among 49 young to middle-aged men and women who participated in the Miami Community Health Study. All participants had measures of insulin resistance (euglycemic-hyperinsulinemic clamp), postchallenge insulin levels, fasting serum leptin levels, and several measures of adiposity. RESULTS: The rate of insulin-mediated glucose uptake (M in milligrams per kilogram per minute) was significantly associated with leptin concentrations in both men (r = -0.83; P < 0.001) and women (r = -0.59; P < 0.001). M was also inversely related to percent body fat and to the 2-h insulin area under the curve (AUC). After covariate adjustment for sex, percent body fat, and AUC, leptin remained a significant correlate of M (P = 0.04). CONCLUSIONS: Cross-sectionally, leptin was significantly associated with insulin resistance in this nondiabetic sample of men and women. There may be a different physiological mechanism to explain the leptin/insulin resistance association apart from the insulin/adiposity link. Confirmatory evidence awaits the results of clinical trials.

Adult↗
PubMed1998

Prevention of type 1 diabetes.

This article discusses type 1 diabetes mellitus, which results from insulin deficiency caused by autoimmune destruction of the insulin-producing beta-cells in the pancreatic islets of Langerhans. The autoimmune response against islet beta-cells is believed to result from a disorder of immunoregulation. According to this concept, T lymphocytes (T cells) autoreactive to certain beta-cell constituents exist normally but are restrained by regulatory (suppressor) T cells. Activation of beta-cell autoreactive T cells together with deficient regulatory T cell responses is believed to result in clonal expansion of autoreactive T cells, and these cells may elicit a cascade of beta-antigen specific (T cell) immune and nonspecific inflammatory responses that destroy islet beta-cells. Islet beta-cells autoreactive T cells seem to secrete type 1 cytokines, whereas regulatory T cells may secrete type 2 and type 3 cytokines; therefore, type 1 diabetes may result from a relative dominance of type 1 cytokines over type 2 and type 3 cytokines. These concepts derive mainly from studies in animal models with spontaneous autoimmune diabetes, and the evidence in humans with type 1 diabetes is sparse. Nevertheless, the concept of type 1 diabetes as a disorder of immunoregulation has spurred clinical trials of diabetes prevention based on strategies directed at diverting the immune response from autoimmunity to self-tolerance, for example, by administration of beta-cell autoantigens, and by attempting to tip the immune balance in favor of the production or action of type 2 and type 3 cytokines over type 1 cytokines.

Animals↗
PubMed1998

The relation of fasting insulin to blood pressure in a multiethnic population: the Miami Community Health Study.

PURPOSE: The aim of this study was to examine the associations among fasting insulin, adiposity, waist girth, and blood pressure among a nondiabetic multiethnic population. METHODS: A cross-sectional study was performed among 25-44-year-old African-Americans (n = 159), Cuban-Americans (n = 128), and non-Hispanic whites (n = 207) selected from Dade County, Florida. Fasting insulin levels were correlated with resting blood pressure level within each ethnic group. The separate effects of percentage body fat and waist girth on the association between blood pressure and insulin were analyzed in multiple linear regression and analysis of covariance. RESULTS: Fasting insulin was positively associated with systolic (r = 0.26-0.39; P < 0.01) and diastolic blood pressure (r = 0.19-0.30; P = 0.10 to P < 0.001) among women of all ethnic groups and among non-Hispanic white men (r = 0.27; P < 0.05). Stepwise linear regression analyses revealed statistically significant associations between systolic and diastolic blood pressure and fasting insulin level in non-Hispanic whites independent of other covariates, including sex and percentage body fat (P < 0.001). Fasting insulin was also independently and significantly related to systolic blood pressure among African-Americans (P = 0.02). Among Cuban-Americans, sex and percentage body fat were the main correlates of blood pressure level. Analysis of covariance revealed a relationship between insulin and blood pressure that was independent of waist girth among men and women. CONCLUSIONS: Fasting insulin level and blood pressure were positively associated among African-Americans and non-Hispanic whites. This association was not entirely due to the common association with percentage body fat or waist girth.

Adipose Tissue↗
PubMed1997

Tactics for type I diabetes.

This article discusses the evolution of therapy for type I diabetes and considers how physicians should be thinking about the disease in the late 1990s. The biases herein are that management strategy has evolved such that contemporary practice should routinely entail a system of "flexible intensive therapy" directed at meticulous glycemic control. To accomplish this requires a skilled management team including an educated, motivated patient and family working in a negotiated therapeutic alliance; a further goal should be the development of effective approaches to interdict the pathogenetic process such that disease prevention is possible.

Diabetes Mellitus, Type 1↗
PubMed1997

Insulin therapy in type II diabetes: who needs it, how much of it, and for how long?

Insulin therapy can control glucose levels in patients with type II diabetes. Because of insulin resistance, high doses may be required initially to attain satisfactory control; however, also because of insulin resistance, hypoglycemia with insulin therapy is much less common among patients with type II diabetes than among those with type I diabetes. Insulin therapy need not be permanent. In some cases, temporary worsening of disease is the result of glucose toxicity and insulin can be discontinued or doses reduced when disease severity subsides. On the other hand, beta-cell failure is progressive, and with long duration of diabetes, permanent insulin therapy may be necessary to achieve satisfactory glucose control.

Aged↗
PubMed1996

Insulin sensitivity and blood pressure in a biethnic sample: the Miami Community Health Study.

An association between blood pressure and insulin sensitivity among normotensive African-Americans has not been demonstrated consistently in epidemiologic studies. Part of the discrepancy may be due to studying persons with profound obesity-an insulin-resistant state itself. The association between insulin-mediated glucose uptake (i.e., insulin sensitivity) and blood pressure was examined among 25 nondiabetic African-American and 28 white non-Hispanic persons aged 25-44 years who ranged from normal weight to obese, using the hyperinsulinemic euglycemic clamp technique. In bivariate analyses, insulin sensitivity was inversely related to systolic (p < 0.01) and diastolic blood pressure (p = 0.08) among African-American persons and to diastolic blood pressure among white non-Hispanic subjects (p < 0.05). Covariate adjustment for age and sex had only a marginal effect on these results. When the data were pooled and further adjusted for ethnicity, insulin sensitivity remained significantly associated with both systolic and diastolic blood pressure (p < 0.01 for each). To consider the effect of obesity, body mass index (BMI) was divided at the sample median (26.5 kg/m2) and the analyses were repeated within each stratum. Among those whose BMI was below the median value, each increment in insulin sensitivity was associated with a 2-mmHg decrease in systolic blood pressure (p = 0.02). These results suggest that ethnicity was not a strong effect modifier in this sample and indicated that insulin sensitivity was inversely related to blood pressure level in these normotensive African-American and white, non-Hispanic participants.

Adult↗