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Biomedical subjects

C R Gilkison

Publications and source records attributed to C R Gilkison.

9 recordsLinked to original sources

Altered GLUT1 and GLUT3 gene expression and subcellular redistribution of GLUT4: protein in muscle from patients with acanthosis nigricans and severe insulin resistance.

Multiple isoforms of glucose transporters are found in muscle, the tissue that normally accounts for 85% of insulin-stimulated glucose uptake. Glucose uptake into muscle cells in the fasting state is mediated primarily by GLUT1 and GLUT3 glucose transporters, whereas postprandial (insulin-stimulated) and exercise-related increments in muscle glucose uptake are mediated primarily by GLUT4. To determine if glucose transporters are abnormally expressed in muscle from insulin-resistant subjects, muscle samples were obtained from 10 normal subjects and 6 obese, nondiabetic subjects with severe insulin resistance and acanthosis nigricans. Both GLUT4 total protein and mRNA were normal in the insulin-resistant subjects. Muscle GLUT3 protein and mRNA were lower than controls by 62% and 71%, respectively. GLUT1 mRNA was twice normal, whereas GLUT1 protein content was not significantly increased. GLUT4 protein was markedly redistributed to the muscle plasma membrane in subjects with severe insulin resistance compared with normals (92% v 40% GLUT4 in plasma membrane-enriched fractions, P <.001), whereas the percentage of GLUT1 and GLUT3 protein found in the plasma membrane-enriched fractions was not different from controls. These data document differences in the expression of genes for GLUT1 and GLUT3 in muscle from normal and insulin-resistant subjects. Further, insulin resistance with fasting hyperinsulinemia was associated with a redistribution of GLUT4 to the muscle cell surface with no change in total GLUT4 protein. These data suggest that glucose transporter gene expression and their basal distribution in human muscle are related to insulin resistance and could be determinants of whole body insulin responsiveness.

Acanthosis Nigricans↗

Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury.

Although hypopituitarism is a known complication of head injury, it may be underrecognized due to its subtle clinical manifestations. The nonspecific symptoms may be masked by and may contribute to the physical and psychological sequelae of brain trauma. This study examines the prevalence of neuroendocrine abnormalities in patients rehabilitating from traumatic brain injury. Seventy adults (mean age, 31.5 +/- 1.1 yr; range, 18--58; 46 men and 24 women) with traumatic brain injury an average of 49 +/- 8 months before the study (median, 13 months) underwent a series of standard endocrine tests, including serum levels of TSH, free T(4), insulin-like growth factor I, PRL, testosterone (males), and cosyntropin stimulation. Abnormal results of these tests were followed by dynamic tests of gonadotropin, TSH, and GH secretion. Glucagon stimulation testing in 48 subjects revealed GH deficiency (peak, <3 microg/L) in 14.6%. Free T(4) (n = 6; 8.6%), TSH (n = 7; 10%), or both (n = 2; 2.9%) were low in 21.7%, whereas 87% had both TSH and free T(4) below the midnormal level. Basal morning cortisol was below normal in 45.7% of subjects, whereas cosyntropin-stimulated levels were insufficient (peak, <500 nmol/L) in 7.1%. Hypogonadism and hyperprolactinemia were uncommon. In summary, pituitary hormone deficiencies were identified in a substantial proportion of patients with previous brain injury. GH deficiency, found in 15% by glucagon stimulation testing, may compound the physical and psychological complications of traumatic brain injury and interfere with rehabilitation.

Adult↗

Acanthosis nigricans as a risk factor for non-insulin dependent diabetes mellitus.

The prevalences of obesity and of non-insulin dependent diabetes mellitus (NIDDM) have increased in the United States population over the past two decades, and thus diabetes prevention has become a major concern of public health agencies such as the National Institutes of Health. Identification of individuals at risk for diabetes is an essential first step in designing and implementing intervention programs. Insulin resistance is the hallmark of the pathophysiology of NIDDM. Subjects with hyperinsulinemia, impaired glucose tolerance, or gestational diabetes are well accepted as being at high risk for diabetes. We propose that the easily identifiable skin lesion, acanthosis nigricans, is common in the major minority groups in the United States and that its presence is a surrogate for laboratory-determined hyperinsulinemia.

Acanthosis Nigricans↗

Acanthosis nigricans.

Acanthosis nigricans is a lesion affecting localized areas of the skin in persons with obesity and/or hyperinsulinemia. Roughening of the skin correlates with histological papilomatosis and the apparent darkening is due to hyperkeratosis. Biochemical mechanisms for developing this hyperplastic lesion are unclear, but likely involve local cutaneous growth factors. Cross sectional surveys of unselected populations have demonstrated that young children have low prevalences of obesity and acanthosis nigricans, but the prevalences of both increase with increasing age until plateaus are reached after the age of ten. Nearly 40% of Native American teenagers have acanthosis nigricans, whereas about 13% of African American, 6% of Hispanic, and less than 1% of white, non-Hispanic children aged 10-19 have clinically apparent acanthosis nigricans. We conclude that the presence of this skin lesion is a clinical surrogate of laboratory-documented hyperinsulinemia. Acanthosis nigricans identifies a subgroup within an ethnic group who have the highest insulin concentration, the most severe insulin resistance, and thus the highest risk for the development of type 2 diabetes.

Acanthosis Nigricans↗

Hyperinsulinemia and acanthosis nigricans in African Americans.

Compared with the US white, non-Hispanic population, the African-American population has a nearly two-fold higher prevalence of noninsulin-dependent diabetes mellitus (NIDDM). Obesity, which usually precedes NIDDM, is associated with the skin lesion acanthosis nigricans in African Americans. This study was undertaken to determine what the relationship of acanthosis nigricans was to hyperinsulinemia, a major risk factor for NIDDM. Eighty-nine African-American subjects with acanthosis nigricans and 25 others without the skin lesion were evaluated using oral glucose tolerance testing and responsiveness to insulin. Noninsulin-dependent diabetes mellitus was present in 19 of the subjects with acanthosis nigricans. The prevalence of NIDDM in this group increased with increasing age, reaching 50% among those in their 40s. Fasting plasma insulin concentration was in direct proportion to the severity of the acanthosis nigricans involvement of the neck. These data suggest that among African Americans, this skin lesion is a marker for hyperinsulinemia and insulin resistance. Furthermore, the presence of acanthosis nigricans identifies a subset with a much higher prevalence of NIDDM than is present in African Americans in the general population.

Acanthosis Nigricans↗

Acanthosis Nigricans among Native Americans: an indicator of high diabetes risk.

Prevalence of the skin lesion acanthosis nigricans was determined in two tribal communities in Texas and Nebraska. Thirty-eight percent of the Alabama-Coushatta tribe of Texas had acanthosis nigricans. Nineteen percent of Omaha and Winnebago tribal children had the skin lesion; the youngest children had the least acanthosis nigricans. Among weight-matched Alabama-Coushatta, fasting insulin concentrations were twofold higher in subjects with the lesion. It was concluded that acanthosis nigricans is highly prevalent among Native Americans and that its presence suggests insulin resistance. Thus, it may identify those with the highest risk for non-insulin-dependent diabetes mellitus in this population.

Acanthosis Nigricans↗

Getting the story straight: evaluating the test-retest reliability of a university health history questionnaire.

This study was designed to establish the reliability of a health history questionnaire used as a screening tool for incoming university students. The authors used a test-retest design, with a test interval of 6 months, on a sample of medical and nursing students. The analysis focused on overall reliability of the questionnaire and reproducibility of specific items, based on question format. Questionnaire items of specific interest were those with dichotomous yes/no response options versus open-ended format questions, those using the words frequently or recently, or those that asked multiple questions. Demographic characteristics of the subjects were considered in the evaluation of reliability. Overall reliability of the questionnaire (93.6%) was above the anticipated level of 90%, and subject sex or program of study did not show any significant differences in reproducibility of responses. Although wording of questions did not affect item reliability, dichotomous format questions demonstrated a higher degree of reliability (96.4%) than the overall reliability of the questionnaire. Recommendations for enhancing the reliability of the questionnaire are based on item analysis and information gathered from interviews with subjects.

Adult↗

Effect of adding a sulfonylurea in patients with non-insulin-dependent diabetes mellitus previously well controlled with insulin.

OBJECTIVE: To determine whether insulin-requiring patients with non-insulin-dependent diabetes mellitus (NIDDM) and good glycemic control would benefit in weight control, serum lipid concentrations, or blood pressure from a reduction in exogenous insulin treatment. METHODS: Eighteen patients with well-controlled NIDDM who required insulin therapy were entered into a randomized, placebo-controlled, double-blind, crossover study of the addition for 12 weeks of treatment with a second-generation sulfonylurea agent (micronized glyburide). RESULTS: The mean fasting plasma glucose at entry was 7.00 +/- 0.22 mmol/L and at the end of the 12-week treatment phase was 7.67 +/- 0.39 mmol/L with placebo and 7.28 +/- 0.44 mmol/L with active drug. Hemoglobin A(1c) was unchanged during the study (7.5 +/- 0.2% at entry, 7.5 +/- 0.3% with placebo, and 7.4 +/- 0.3% with active drug). Addition of the orally administered agent resulted in a 29% decrease in exogenous insulin requirements and a 37% increase in 24-hour urinary C-peptide excretion. Patients had no change in weight after 12 weeks of either placebo or active drug. Plasma cholesterol levels declined slightly during the study, but they did not differ significantly during drug and placebo treatment. Blood pressure was unchanged in both the subjects with and without hypertension. CONCLUSION: In patients with NIDDM and good glycemic control with insulin treatment, a glyburide-related increase in endogenous insulin secretion caused a proportionate decrease in exogenous insulin requirements. With continued good glycemic control, however, the orally administered agent showed no additional benefit on weight, blood pressure, plasma triglycerides, or low-density lipoprotein or high-density lipoprotein cholesterol.

Clinical Trial↗

Thyrotoxicosis. Recognition and management.

Thyrotoxicosis is a common endocrine problem encountered in the primary care setting. It can exist in the presence or absence of thyroid disease and is associated with a wide range of causes, including primary hyperthyroidism, thyroid inflammation, and ingestion of exogenous thyroid hormone preparations. presenting complaints and clinical manifestations of this disorder can vary greatly, creating a challenge for the primary care provider. Recognition of clinical signs and symptoms and selection of appropriate laboratory studies can establish the diagnosis promptly. Once the diagnosis is identified, various effective and appropriate treatment options are available. It is important to distinguish between those problems that require subspecialty referral and those that can be treated by primary care providers. Many of the syndromes associated with thyrotoxicosis can be managed in the primary care setting. Interventions include patient counselling, patient education, judicious use of appropriate medications, and careful follow-up.

Aftercare↗