Biomedical subjects

Patricia Vuguin

Publications and source records attributed to Patricia Vuguin.

5 recordsLinked to original sources

PubMed2006

Prediction models for insulin resistance in girls with premature adrenarche. The premature adrenarche insulin resistance score: PAIR score.

AIM: The purpose of this study was to develop an accurate regression model to predict insulin resistance in girls with premature adrenarche. METHODS: The insulin sensitivity index was calculated from the frequently sampled intravenous glucose tolerance test with tolbutamide. Thirty-five prepubertal girls (23 Caribbean-Hispanic and 12 African-American; mean age 6.8 years) were studied. The insulin sensitivity index was compared to birth weight, body mass index (BMI), the presence of acanthosis nigricans (AN), insulin-like growth factor 1, insulin-like growth factor binding protein 1, sex hormone binding globulin, lipid profile, and adrenocorticotropic hormone stimulated androgens. RESULTS: The best prediction models included birth weight, BMI, and AN (model 1: R(2) = 0.78) and BMI, AN, and serum 17-OH pregnenolone (model 2: R(2) = 0.76). When viewed as screening tests, a cutoff value <5.5 (premature adrenarche insulin resistance score) in both equations showed a sensitivity of 100% and a specificity of 85%. CONCLUSION: Born small for gestational age, premature adrenarche, obesity, AN, and higher serum 17-OH pregnenolone levels may confer negative, but independent, health risks.

Acanthosis Nigricans↗

PubMed2006

Central and opposing effects of IGF-I and IGF-binding protein-3 on systemic insulin action.

IGF-I is recognized as an insulin sensitizer at the liver and muscle, while recent evidence suggests that IGF-binding protein (IGFBP)-3 acts as an insulin antagonist. As there is a paucity of IGF-I receptors in the liver and as the IGF-IGFBP system in the central nervous system is emerging as physiologically relevant, we examined whether the effects of IGF-I and IGFBP-3 on insulin action are mediated through central mechanisms. Intracerebroventricular (ICV) infusion of IGF-I during the insulin clamp (3 mU x kg(-1) x min(-1)) resulted in significant improvement in hepatic insulin action (50%, P < 0.05). In contrast, ICV infusion of IGFBP-3 significantly impaired insulin action at the liver (45% increase in hepatic glucose production, P < 0.01). While IGF-I marginally increased peripheral glucose uptake, IGFBP-3 significantly decreased peripheral glucose uptake (approximately 30%, P < 0.01). As the nuclear localization signal mutant IGFBP-3, which has a normal affinity to IGFs but binds other IGFBP-3 partners poorly and fails to normally internalize, has reduced central activity on metabolism, we conclude that the effects of IGFBP-3 on the hypothalamus involve activity mediated by interfacing with other molecules in addition to IGFs. Marked, opposing, and independent physiological effects of IGF-I and IGFBP-3 through central mechanisms may have implications on potential strategies in specific modulation of peripheral insulin action.

Animals↗

PubMed2004

Hepatic insulin resistance precedes the development of diabetes in a model of intrauterine growth retardation.

Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in adulthood. We developed an IUGR model in rats whereby at age 3-6 months the animals develop a diabetes that is associated with insulin resistance. Hyperinsulinemic-euglycemic clamp studies were performed at age 8 weeks, before the onset of obesity and diabetes. Basal hepatic glucose production (HGP) was significantly higher in IUGR than in control rats (14.6 +/- 0.4 vs. 12.3 +/- 0.3 mg. kg(-1). min(-1); P < 0.05). Insulin suppression of HGP was blunted in IUGR versus control rats (10.4 +/- 0.6 vs. 6.5 +/- 1.0 mg. kg(-1). min(-1); P < 0.01); however, rates of glucose uptake and glycogenolysis were similar between the two groups. Insulin-stimulated insulin receptor substrate 2 and Akt-2 phosphorylation were significantly blunted in IUGR rats. PEPCK and glucose-6-phosphatase mRNA levels were increased at least threefold in liver of IUGR compared with control rats. These studies suggest that an aberrant intrauterine milieu permanently impairs insulin signaling in the liver so that gluconeogenesis is augmented in the IUGR rat. These processes occur early in life, before the onset of hyperglycemia, and indicate that uteroplacental insufficiency causes a primary defect in gene expression and hepatic metabolism that leads to the eventual development of overt hyperglycemia.

Animals↗

PubMed2004

Decrease in glucose-stimulated insulin secretion with aging is independent of insulin action.

While the incidence of diabetes increases with age, a decrease in beta-cell function independent of age-related insulin resistance has not been conclusively determined. We studied insulin secretion (by hyperglycemic clamp) in 3-, 9-, and 20-month-old chronically catheterized, awake, Sprague Dawley (SD) rats (n = 78). Insulin action was modulated in a group of old rats by caloric restriction (CR) or by surgical removal of visceral fat (VF-). During the first 2 h of the clamp (11 mmol/l glucose), insulin secretion and insulin resistance (S(i hyper clamp)) demonstrated the characteristic hyperbolic relationship. However, after hyperglycemia for an additional 2 h, the ability to maintain insulin secretion, commensurate with the degree of insulin resistance, was decreased in all aging rats (P < 0.05). Increasing plasma glucose levels to 18 mmol/l glucose, after clamp at 11 mmol/l, increased insulin secretion by approximately threefold in young rats, but failed to induce similar magnitude of response in the aging rats ( approximately 50%). However, elevation of plasma free fatty acid (FFA) levels by twofold (by intralipid infusion during 11 mmol/l glucose clamp) resulted in a robust, approximate twofold response in both young and old rats. Thus, prolonged stimulation by hyperglycemia unveiled a functional defect in insulin secretion with aging. This age-related defect is independent of insulin action and is specific to glucose and not FFAs. We suggest that prolonged hyperglycemic stimulation can be a tool to identify functional defects in insulin secretion, particularly in the context of the hyperbolic relationship with insulin action, in elderly subjects or those at risk for type 2 diabetes.

Aged↗

PubMed2003

Presentation and 5-year follow-up of type 2 diabetes mellitus in African-American and Caribbean-Hispanic adolescents.

OBJECTIVE: We report the presentation and 5-year follow-up of 89 African-American (AA) and Caribbean-Hispanic (CH) youths with type 2 diabetes mellitus (T2DM) followed at the Montefiore Medical Center, Bronx, N.Y., USA, from 1990 to 2000. METHODS: The medical records of 89 patients with T2DM diagnosed between 1990 and 2000 were reviewed. RESULTS: Over a 10-year period, the number of pediatric patients less than 18 years of age diagnosed with T2DM at the Montefiore Medical Center increased tenfold. At presentation, the mean age was 14 +/- 2.3 years, the mean body mass index (BMI) was 34.4 +/- 9 kg/m(2), the female/male ratio was 1.6:1, and all these patients were pubertal. Acanthosis nigricans was present in 89% of the patients, polyuria and polydipsia occurred in 48%, weight loss occurred in 22%, and nearly 30% of the patients were asymptomatic at diagnosis. Diabetic ketoacidosis occurred in 5 patients. By 5 years after diagnosis, 45% of the patients were able to maintain an HgbA1C <7% with oral medications (metformin and/or glipizide); 18% required insulin (<0.4 U/kg/day) in addition to oral medications, and 37% did not require any medication. The mean insulin level, BMI and HgbA1C at the time of diagnosis did not predict treatment requirements for 3 years after diagnosis. CONCLUSIONS: Because the incidence of T2DM is increasing in adolescents, the natural history and optimal therapy for adolescents with T2DM need to be established.

Adolescent↗