Orthognathic surgery for the Asian patient and the influence of the surgeon's background on treatment.

The aim of this study was to determine whether there are differences in esthetic preferences and orthognathic treatment for Asian patients between US- and Asian-trained surgeons. Twenty-five Caucasian-American, 23 Asian-American, 24 Asian oral and maxillofacial surgeons (OMFS) completed an Institutional Review Board (IRB)-approved survey. They were asked to rate seven Asian male and female profiles from most attractive to least attractive and to choose maxillary advancement, mandibular setback, or no treatment for an Asian male and female patient with a maxillomandibular discrepancy. There was no statistical difference for the most and least attractive rankings among the OMFS. Variations in ranking for intermediate profiles showed a statistical difference between the Asian- and US-trained OMFS. These intermediate profile rankings appeared to explain the differences in surgical treatment. Treatment recommendations for the Asian male among the OMFS, regardless of ethnicity, preferred maxillary advancement. For the Asian female, all Asian-trained OMFS preferred mandibular setback, while nearly 40% of US-trained OMFS preferred maxillary advancement (p=0.003). Differences in surgical management of the Asian patient were dependent on whether the surgeon trained in the US or in Asia and the gender of the patient. There was concordance between the Asian-American and Caucasian-American surgeons.

Analyses of variable panoramic radiographic characteristics of maxillo-mandibular fibrous dysplasia in McCune-Albright syndrome.

OBJECTIVE: Fibrous dysplasia (FD) is a rare skeletal disease caused by activating GNAS1 gene mutations often found in association with the McCune-Albright syndrome (MAS). Multiple bones may be affected in FD, including maxilla and mandible. Patients with MAS have different endocrinopathies that can further influence bone metabolism. The purposes of this cross-sectional study are to characterize FD panoramic radiographic patterns, and to evaluate the effects of age, endocrinopathies and renal phosphate wasting on radiographic characteristics of maxillo-mandibular FD in MAS. SUBJECTS AND METHODS: Fifty-one consecutive MAS patients were screened and panoramic radiographs of 43 patients with craniofacial FD were evaluated and analyzed for FD involvement. Clinical chemistries were evaluated for associations between radiographic patterns and age, endocrinopathies or renal phosphate wasting using Fisher's Exact Test. RESULTS: Four types of radiographic changes were observed: ground glass (granular/condensed trabeculae), radiolucent (lytic), mixed radiolucent/radio-opaque (mixed density) or radio-opaque (sclerotic). Masking or displacement of the maxillary sinus (range: 77.8-86.4%) and mandibular canal (range: 55.6-75.0%) were prevalent in FD sites. Sixty-three percent of the MAS patients had multiple dysregulated endocrine/metabolic functions, the most common were hyperthyroidism, precocious puberty and renal phosphate wasting. There were no statistically significant associations between radiographic patterns and age, endocrinopathies or renal phosphate wasting. CONCLUSIONS: Maxillo-mandibular FD images in panoramic radiographs fall within a spectrum of four different patterns. Patients with facial asymmetry and any of these radiographic patterns should be promptly referred for further radiographic tests and endocrine evaluation if MAS is suspected.

Androgen-responsive aspects of cognition in girls with Turner syndrome.

Turner syndrome (TS) represents a unique, sex hormone-deficient model in which to study the biological effects of androgen treatment (replacement) on cognition in females because TS girls have gonadal dysgenesis and absent ovarian androgen and estrogen production. We investigated the effects of androgen replacement therapy in TS girls, ages 10-14 yr, on cognitive function. A total of 64 TS girls were randomized to receive oxandrolone or placebo for 2 yr. They had a cognitive evaluation of four domains (verbal abilities, spatial cognition, executive function, and working memory) at baseline, 1, and 2 yr of the study. In addition, all subjects were examined for study safety every 6 months. Three of the four domains studied did not change significantly in response to oxandrolone treatment (verbal abilities, spatial cognition, and executive function). In contrast, the working memory summary score had a significant group by time interaction. The oxandrolone-treated group demonstrated improved performance after 2 yr, compared with the placebo group (P < 0.03). Minimal or no side effects were observed. In conclusion, oxandrolone treatment for 2 yr improves working memory in adolescent girls with TS. What this degree of improvement will mean in real life terms for TS girls remains to be determined.

Persistent cognitive deficits in adult women with Turner syndrome.

BACKGROUND: Turner syndrome (TS) has a characteristic neurocognitive profile. Verbal abilities are, in general, normal; however, women with TS, as a group, have specific deficits in visual-spatial abilities, visual-perceptual abilities, motor function, nonverbal memory, executive function, and attentional abilities. Observed deficits could be caused by genetic or endocrine factors. OBJECTIVE: To evaluate the specific cognitive deficits that appear to persist in adulthood, are not estrogen-responsive, and may be genetically determined. METHODS: The cognitive performance of adult women with TS (n = 71) who were estrogen repleted was compared with verbal IQ- and socioeconomic status-matched female controls (n = 50). Sixty-one women with TS had ovarian failure and received estrogen replacement and 10 had preserved endogenous ovarian function and were not receiving estrogen replacement at the time of evaluation. RESULTS: Similar to children and adolescents with TS, adults with TS have normal verbal IQ but have relative difficulty on measures of spatial/perceptual skills, visual-motor integration, affect recognition, visual memory, attention, and executive function despite estrogen replacement. These deficits are apparent in women with TS despite apparently adequate estrogen effect, either endogenous or by hormone replacement. CONCLUSION: The cognitive phenotypes of adults with TS, with or without ovarian failure, are similar, indicating that estrogen replacement does not have a major impact on the cognitive deficits of adults with TS.

Phenotypes Associated with SHOX Deficiency.

Leri-Weill dyschondrosteosis (LWD) (MIM 127300) is a dominantly inherited skeletal dysplasia characterized phenotypically by Madelung wrist deformity, mesomelia, and short stature. LWD can now be defined genetically by haploinsufficiency of the SHOX (short stature homeobox-containing) gene. We have studied 21 LWD families (43 affected LWD subjects, including 32 females and 11 males, ages 3-56 yr) with confirmed SHOX abnormalities. We investigated the relationship between SHOX mutations, height deficit, and Madelung deformity to determine the contribution of SHOX haploinsufficiency to the LWD and Turner syndrome (TS) phenotypes. Also, we examined the effects of age, gender, and female puberty (estrogen) on the LWD phenotype. SHOX deletions were present in affected individuals from 17 families (81%), and point mutations were detected in 4 families (19%). In the LWD subjects, height deficits ranged from -4.6 to +0.6 SD (mean +/- SD = -2.2 +/- 1.0). There were no statistically significant effects of age, gender, pubertal status, or parental origin of SHOX mutations on height z-score. The height deficit in LWD is approximately two thirds that of TS. Madelung deformity was present in 74% of LWD children and adults and was more frequent and severe in females than males. The prevalence of the Madelung deformity was higher in the LWD vs. a TS population. The prevalence of increased carrying angle, high arched palate, and scoliosis was similar in the two populations. In conclusion, SHOX deletions or mutations accounted for all of our LWD cases. SHOX haploinsufficiency accounts for most, but not all, of the TS height deficit. The LWD phenotype shows some gender- and age-related differences.

Specificity of Doppler echocardiography for the assessment of changes in valvular regurgitation: comparison of side-by-side versus serial interpretation.

OBJECTIVES: We sought to determine the specificity of two different methods for assessing change in aortic (AR), mitral (MR) and tricuspid (TR) valvular regurgitation. BACKGROUND: Echocardiographic imaging with Doppler is the standard noninvasive diagnostic tool for assessing valvular structure and function. Change can be assessed using either independent evaluations (serial) or using a side-by-side comparison. METHODS: Subjects were from the placebo arm of a randomized, double-blind, clinical trial. Three echocardiograms over 10 months were performed. An initial and three-month echocardiogram were read as independent groups, blinded to all parameters except sequence. The initial and 10-month echocardiograms were read side-by-side, blinded to all parameters including sequence. RESULTS: Two hundred nineteen predominantly healthy, obese, white, middle-aged women had initial and three-month echocardiograms (acquisition interval 105 +/- 28 days) evaluated by the serial method (mean 167 +/- 61 days between interpretations). The same subjects had the initial and 10-month studies (acquisition interval 303 +/- 27 days) compared side-by-side. The specificity of the serial versus side-by-side method for determining change in MR grade was 55.8% versus 93.2% (p < 0.001); TR: 63.8% versus 97.6% (p < 0.001) and AR: 93.7% versus 97.6 (p = 0.08). Notably, most of the change occurred in a range (none versus physiologic/mild) that has limited clinical significance. Furthermore, the percentage of echocardiograms interpreted as nonevaluable was lower with the side-by-side method for MR (5.0% vs. 16.0%, p = 0.06), TR (4.6% vs. 15.5%, p < 0.001) and AR (4.1% vs. 12.3%, p = 0.002). CONCLUSIONS: The side-by-side method of assessing change in valvular regurgitation appears to be the more reliable method with a higher specificity and minimal data loss.

Renal phosphate wasting in fibrous dysplasia of bone is part of a generalized renal tubular dysfunction similar to that seen in tumor-induced osteomalacia.

Fibrous dysplasia (FD) of bone is characterized by focal replacement of normal bone and marrow with abnormal bone and fibrous tissue. It arises from postzygotic activating mutations of the GNAS1 gene. Hypophosphatemia due to renal phosphate wasting has been reported in association with FD as a part of the McCune-Albright Syndrome (MAS), which is characterized by FD, skin hyperpigmentation, and precocious puberty. To date, the prevalence and mechanism of phosphate wasting has not been well studied. We evaluated 42 patients with FD/MAS. Serum and urine samples were tested for indices of mineral metabolism, amino acid handling, and markers of bone metabolism. Twenty (48%) patients had some degree of renal phosphate wasting. Nephrogenous cyclic adenosine monophosphate (cAMP) was normal in FD patients, suggesting that the underlying cause of phosphate wasting is not the presence of activating GNAS1 mutations in the kidney. In addition, there was evidence of a more generalized renal tubulopathy as represented by the presence of abnormal vitamin D metabolism, proteinuria in 36 (86%) patients, and aminoaciduria in 39 (94%) patients. Renal phosphate wasting significantly correlated with the degree of bone involvement, as assessed by serum and urine markers of bone metabolism, suggesting that a circulating factor produced by FD bone and impacting on the kidney may be the mechanism. These data show that phosphaturia as part of a generalized renal tubulopathy represents the most common extraskeletal manifestation of FD and that the observed tubulopathy is similar to that seen in tumor-induced osteomalacia (TIO).

Psychosocial development in adolescents with Turner syndrome.

Turner syndrome is a genetic condition in which part or all of the second X chromosome is missing. Our goal in this study was to examine the psychosocial adjustment of a sample of adolescent girls with Turner syndrome. Subjects included 122 girls with a diagnosis of Turner syndrome (TS) and a control group of 108 girls with no genetic disorder or chronic illness. Subjects were 13 to 18 years of age. A battery of questionnaires assessing social, academic, school, and behavioral functioning was administered. TS girls were seen as having significantly more problems in terms of social relationships and school progress and were more likely to meet criteria for attention-deficit hyperactivity disorder than control girls. The TS girls were also rated by a parent as less socially competent (e.g., fewer friends, less time with friends) than the control group. Social difficulties appear to be an area of vulnerability for TS girls. Counseling individuals with Turner syndrome and their families about the need to carefully develop and nurture social skills and relationships may prove useful in advancing the social adaptation of these young women.

Dietary nutrients and blood pressure in urban minority adolescents at risk for hypertension.

OBJECTIVE: To determine if blood pressure (BP) level is associated with dietary micronutrients in adolescents at risk for hypertension. DESIGN: Adolescents aged 14 to 16 years, with BP higher than the 90th percentile on 2 separate measurements in a school setting, had diet assessments. A 24-hour intake recall was obtained on 180 students (108 boys and 72 girls). Folic acid intake was used as an index of fruit, vegetable, and whole grain intake; the high folate group had a folate intake greater than the recommended daily allowance and the low folate group had a folate intake less than the recommended daily allowance. Data were analyzed by 2-way analysis of variance. RESULTS: Mean diastolic BP was significantly higher in the low folate vs the high folate group (boys: 72 vs. 67 mm Hg; girls: 76 vs. 73 mm Hg; P =.008). The difference in systolic blood pressure was not significant. There was no difference in body mass index between the diet groups. Sodium intake per 4184 kJ was not different. The low folate group had significantly lower intakes per 4184 kJ of potassium (P =.002), calcium (P = .001), magnesium (P<.001), and total intake of beta carotene, cholecalciferol, vitamin E, and all B vitamins. CONCLUSIONS: Among adolescents at risk for hypertension, BP was lower in those with higher intakes of a combination of nutrients, including potassium, calcium, magnesium, and vitamins. Dietary benefits on BP observed on diets rich in a combination of nutrients derived from fruits, vegetables, and low-fat dairy products could contribute to primary prevention of hypertension when instituted at an early age.

The Turner syndrome-associated neurocognitive phenotype maps to distal Xp.

Turner syndrome (TS) is associated with a characteristic neurocognitive profile that includes impaired visuospatial/perceptual abilities. We used a molecular approach to identify a critical region of the X chromosome for neurocognitive aspects of TS. Partial deletions of Xp in 34 females were mapped by FISH or by loss of heterozygosity of polymorphic markers. Discriminant function analysis optimally identified the TS-associated neurocognitive phenotype. Only subjects missing approximately 10 Mb of distal Xp manifested the specified neurocognitive profile. The phenotype was seen with either paternally or maternally inherited deletions and with either complete or incomplete skewing of X inactivation. Fine mapping of informative deletions implicated a critical region of <2 Mb within the pseudoautosomal region (PAR1). We conclude that haploinsufficiency of PAR1 gene(s) is the basis for susceptibility to the TS neurocognitive phenotype.

Kawasaki disease: A brief history.

Tomisaku Kawasaki published the first English-language report of 50 patients with Kawasaki disease (KD) in 1974. Since that time, KD has become the leading cause of acquired heart disease among children in North America and Japan. Although an infectious agent is suspected, the cause remains unknown. However, significant progress has been made toward understanding the natural history of the disease and therapeutic interventions have been developed that halt the immune-mediated destruction of the arterial wall. We present a brief history of KD, review progress in research on the disease, and suggest avenues for future study. Kawasaki saw his first case of KD in January 1961 and published his first report in Japanese in 1967. Whether cases existed in Japan before that time is currently under study. The most significant controversy in the 1960s in Japan was whether the rash and fever sign/symptom complex described by Kawasaki was connected to subsequent cardiac complications in a number of cases. Pathologist Noboru Tanaka and pediatrician Takajiro Yamamoto disputed the early assertion of Kawasaki that KD was a self-limited illness with no sequelae. This controversy was resolved in 1970 when the first Japanese nationwide survey of KD documented 10 autopsy cases of sudden cardiac death after KD. By the time of the first English-language publication by Kawasaki in 1974, the link between KD and coronary artery vasculitis was well-established. KD was independently recognized as a new and distinct condition in the early 1970s by pediatricians Marian Melish and Raquel Hicks at the University of Hawaii. In 1973, at the same Hawaiian hospital, pathologist Eunice Larson, in consultation with Benjamin Landing at Los Angeles Children's Hospital, retrospectively diagnosed a 1971 autopsy case as KD. The similarity between KD and infantile periarteritis nodosa (IPN) was apparent to these pathologists, as it had been to Tanaka earlier. What remains unknown is the reason for the simultaneous recognition of this disease around the world in the 1960s and 1970s. There are several possible explanations. KD may have been a new disease that emerged in Japan and emanated to the Western World through Hawaii, where the disease is prevalent among Asian children. Alternatively, KD and IPN may be part of the spectrum of the same disease and clinically mild KD masqueraded as other diseases, such as scarlet fever in the preantibiotic era. Case reports of IPN from Western Europe extend back to at least the 19th century, but, thus far, cases of IPN have not been discovered in Japan before World War II. Perhaps the factors responsible for KD were introduced into Japan after the World War II and then reemerged in a more virulent form that subsequently spread through the industrialized Western world. It is also possible that improvements in health care and, in particular, the use of antibiotics to treat infections caused by organisms including toxin-producing bacteria reduced the burden of rash/fever illness and allowed KD to be recognized as a distinct clinical entity. Itsuzo Shigematsu, Hiroshi Yanagawa, and colleagues have conducted 14 nationwide surveys in Japan. These have indicated that: 1) KD occurred initially in nationwide epidemics but now occurs in regional outbreaks; 2) there are approximately 5,000 to 6,000 new cases each year; 3) current estimates of incidence rates are 120 to 150 cases per 100,000 children <5 years old; 4) KD is 1.5 times more common in males and 85% of cases occur in children <5 years old; and 5) the recurrence rate is low (4%). In 1978, David Morens at the Centers for Disease Control and Prevention published a case definition based on Kawasaki's original criteria. The Centers for Disease Control and Prevention developed a computerized database in 1984, and a passive reporting system currently exists in 22 states. Regional investigations and national surveys suggest an annual incidence of 4 to 15 cases per 100 000 children <5 years o

The association of left ventricular mass with cardiovascular risk factors in African American women.

BACKGROUND: African American women have disproportionately high rates of myocardial infarction and stroke. Left ventricular hypertrophy is an independent risk factor for cardiovascular disease. Increases in left ventricular mass (LVM) may precede the expression of hypertension. The purpose of this study was to determine whether LVM is related to cardiovascular risk variables in healthy, premenopausal African American women. METHODS: Normotensive or borderline hypertensive nondiabetic African American women (N = 52; mean age, 31 years) underwent anthropometric and blood pressure measurements, oral glucose tolerance test, euglycemic clamp, fasting lipid profile, and two-dimensional echocardiography. LVM was calculated by the cube root formula and adjusted for height [LVM index (LVMI)]. RESULTS: LVMI correlated with body mass index (r = .36, P = 0.009), systolic blood pressure (r = .44, P = 0.001), diastolic blood pressure (r = .43, P = 0.002), and central body fat (r = .42, P = 0.002). LVMI also directly correlated with lipoprotein (a) (r = .34, P = 0.02). Significant independent relationships of other metabolic variables with LVMI were not detected. DISCUSSION: These data show that increased LVMI is associated with body mass index and central obesity, but not with lipids, insulin resistance, or insulin sensitivity. LVMI is also associated with blood pressure before the expression of severe hypertension in healthy, premenopausal African American women.

The association of RBC sodium-lithium countertransport (Vmax) with left ventricular mass in African American women.

In Caucasian hypertensives and diabetics, increased RBC sodium-lithium countertransporter activity (SLC) is a marker for end-organ complications of vascular disease. A subgroup of African Americans with high Vmax for SLC show strong correlations with dyslipidaemia, insulin resistance, microalbuminuria and higher blood pressure. The purpose of our study was to determine if Vmax in premenopausal African American women correlates with left ventricular mass (LVM) before the onset of clinically diagnosed hypertension. Non-diabetic African American women (n = 35, mean age 31 years) were evaluated for cardiovascular disease risk factors, including anthropometric and blood pressure measurements, oral glucose tolerance test (OGTT), and euglycaemic hyperinsulinaemic clamp for insulin sensitivity. Fasting blood specimens were assayed for SLC activity (Vmax) and lipids. Cardiac structure was determined by 2-D echocardiography. LVM was calculated by the cube root formula and adjusted for height (LVM index). Vmax correlated significantly with average systolic blood pressure (r = 0.45, P = 0.007), diastolic blood pressure (r = 0.48, P = 0.004), mean blood pressure (r = 0.48, P = 0.003) and LVM index (r = 0.40, P = 0.02). Vmax was also associated with fasting insulin (r = 0.39, P = 0.01), the sum of insulin (r = 0.52, P = 0.002), and insulin sensitivity adjusted for fat-free mass (r = -0.55, P = 0.001). There was no statistically significant relationship between Vmax and body mass or lipids. Vmax for SLC correlates with cardiac structure in premenopausal African American women. Vmax is also associated with insulin sensitivity and insulin resistance in this non-diabetic sample. SLC activity may be useful in identifying a subgroup of young African American women with left ventricular hypertrophy and insulin resistance before the onset of clinically diagnosed hypertension and diabetes. Journal of Human Hypertension (2000) 14, 213-219.

Use of estrogen in young girls with Turner syndrome: effects on memory.

BACKGROUND: The Turner syndrome (TS) phenotype is characterized by a specific neurocognitive profile of normal verbal skills, impaired visual-spatial and visual-perceptual abilities, and impaired nonverbal more than verbal memory. We compared verbal and nonverbal memory in estrogen- and placebo-treated girls with TS (ages 7 to 9 years) and age-matched female controls. METHODS: Children received either estrogen (ethinyl estradiol, 25 ng/kg/d) or placebo for 1 to 3 years (mean, 2.1+/-0.9 years) in a randomized, double-blind study. Memory and language tasks administered included the Wechsler Intelligence Scale for Children-Revised, Digit Span (forward and backward), the Children's Word List, the Denman Paragraph, the Peabody Picture Vocabulary Test, Boston Naming, immediate and delayed Recall of the Rey Complex Figure, Nonword Reading, Wide Range Achievement Test-Revised reading subtest, Verbal fluency, and the Token Test. RESULTS: The estrogen-treated TS group performed better than the placebo-treated TS group for the Children's Word List immediate and delayed recall and the Digit Span backwards test (p<0.01 to 0.04), although the results were not significant after adjusting for multiple comparisons. The placebo-treated TS group performed less well than the controls for recall of Digit Span backward (p<0.0001; placebo-treated, 2.8+/-1.3; estrogen-treated, 3.4+/-1.2; and controls, 4.2+/-1.3) and immediate and delayed recall of the Children's Word List (delayed recall, p<0.0001; placebo-treated, 6.2+/-3.1; estrogen-treated, 8.0+/-2.9; and controls, 9.0+/-2.9). Performance for these measures was similar for the estrogen-treated TS group and the control group. CONCLUSIONS: Estrogen replacement therapy in young girls with Turner Syndrome is associated with improved verbal and nonverbal memory. The optimal patient age, dose, and duration of estrogen replacement require further study.

Gender differences in the relationship between insulin-mediated glucose utilization and sex hormones in young African-Americans.

OBJECTIVE: To determine whether there are gender differences in insulin-mediated glucose utilization and if sex hormones correlate with measures of insulin sensitivity in young adult African-Americans. DESIGN: Cross-sectional case (women)-control (men) study. PARTICIPANTS: African-American men and women aged 27 to 35 years. Excluded were known diabetics, individuals on antihypertensive therapy, and women taking exogenous estrogen preparations. METHODS: Procedures included anthropometric and blood pressure measurement, oral glucose tolerance test, sex hormone assay, and euglycemic hyperinsulinemic clamp. Procedures for data analysis included two-way analysis of variance and Pearson's correlation coefficients. RESULTS: Data were analyzed on 104 men and 142 women with a mean age of 31.5 years. Insulin sensitivity was lower in women than in men. When insulin-mediated glucose utilization was corrected for body fat, there was no gender difference in insulin sensitivity. There was a significant correlation of androgen status with insulin sensitivity, but this relationship was divergent between men and women. For men, the correlation between insulin sensitivity and free testosterone was positive (r = .36, P < .001). For women, this correlation was negative (r = -.28, P = .001). CONCLUSION: These data on young African-Americans demonstrate no gender differences in insulin sensitivity when glucose utilization is corrected for adipose mass. Androgen status is significantly linked with insulin sensitivity, but the relationship is divergent in men and women. Insulin resistance in young women is strongly associated with relative androgen excess, which may augment the risk for cardiovascular disease.

Blood pressure increase with impaired glucose tolerance in young adult american blacks.

Hypertension and non-insulin-dependent diabetes mellitus are more prevalent in blacks than whites. The convergence of these 2 disorders augments the expression and severity of cardiovascular disease. The purpose of this study was to determine whether alterations in glucose metabolism are related to an increase in blood pressure (BP). This study was conducted on 304 nondiabetic blacks (mean age=32 years). Measurements in all subjects included BP, anthropometric measures, oral glucose tolerance test, insulin clamp to measure insulin sensitivity, and plasma lipids. The sample was stratified according to plasma glucose on oral glucose tolerance test to normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM). A 2-way ANOVA was performed to determine differences between the metabolic groups. With the use of American Diabetic Association criteria, 20.4% of the samples were classified as IGT and 5.9% were diabetic. A significant increase in BP existed from NGT to IGT to DM, which was stronger in women than men (systolic blood pressure in women: NGT=122, IGT=127, and DM=140 mm Hg, P<0.001) with a significant linear trend (P<0.001). With the use of body mass index as a covariate, the group difference in BP remained significant (P=0.006). Measures of insulin sensitivity demonstrated significant metabolic group differences (P<0.001) with a linear trend (P<0.001) of decreasing insulin sensitivity from NGT to DM. These results indicate that early alterations in glucose metabolism effects an upward shift in BP. The higher BP in IGT and DM may be due to vascular endothelial cell resistance to insulin action.

Low dietary magnesium is associated with insulin resistance in a sample of young, nondiabetic Black Americans.

In both humans and experimental animals, dietary induced magnesium deficiency is correlated with insulin resistance. The purpose of this study was to determine whether dietary magnesium intake is associated with insulin sensitivity or blood pressure in a sample of nondiabetic, young adult black Americans. We also examined dietary calcium, potassium, and sodium intake. The study was conducted on a sample (n = 179) of young adults aged 30 +/- 3.4 years who had been followed longitudinally. Nutrient intake was assessed by obtaining a 24-h recall interview of dietary intake. Intake data were entered in a nutrient analysis program (Nutritionist III), which quantitated micronutrients, macronutrients, and minerals. We classified the sample into insulin-sensitive (IS) and insulin-resistant (IR) groups, according to insulin-stimulated glucose use (M) measured during insulin clamp. M correlated positively with magnesium intake in mg/kg of fat-free mass (r = 0.15, P < .05 overall; in men, r = 0.25, P < .02). There was a significant negative correlation of total dietary magnesium intake with the sum of insulin levels measured during an oral glucose tolerance test (OGTT) (r = -0.13, P < .05). When corrected for body fat, in men there was also a significant correlation of dietary magnesium intake, measured in mg/kg of fat-free mass, with the sum of insulin concentrations on the OGTT (r = -0.22, P < .05). When cases were categorically classified as IS versus IR, magnesium intake in mg/kg of fat-free mass was lower in IR (2.97 +/- 1.4) than in IS (3.68 +/- 2.2; P = .022). These results suggest a possible role for dietary magnesium in insulin resistance.

Sex differences in African-Americans regarding sensitivity to insulin's glucoregulatory and antilipolytic actions.

OBJECTIVE: The purpose of this study was to determine if there are sex differences in African-Americans regarding the effect of obesity on sensitivity to insulin as a glucoregulatory and antilipolytic hormone. RESEARCH DESIGN AND METHODS: Data from study participants, 127 nondiabetic African-Americans (mean age 32 +/- 4 years), included anthropometric measurements, an oral glucose tolerance test (OGTT), a 2-h euglycemic-hyperinsulinemic clamp, and a fasting triglyceride level. Sensitivity to insulin as a glucoregulatory hormone was determined by M/FFM, where M is the mean glucose infusion rate during the second hour of the clamp and FFM is fat-free mass. Sensitivity to insulin's antilipolytic action was assessed during the OGTT by the percent suppression of free fatty acid (FFA) concentrations between 0 and 120 min. The higher the suppression of FFAs, the greater the sensitivity to insulin's antilipolytic action. RESULTS: The participants were classified by BMI into three groups: nonobese (31 men, 24 women), obese (17 men, 14 women), and severely obese (12 men, 29 women). The women had higher percentages of body fat (P < 0.001), and the men had greater FFM (P < 0.001). The M/FFM values for men versus women in each BMI group were nonobese, 8.8 +/- 2.8 vs. 10.8 +/- 4.4; obese, 7.2 +/- 3.4 vs. 8.5 +/- 3.4; and severely obese, 4.7 +/- 2.1 vs. 6.1 +/- 2.2. The difference between the BMI groups was significant (P < 0.001), as was the difference between men and women (P < 0.01). In addition, there was a significant sex difference in percent suppression of FFAS (P < 0.001). The men and women had similar fasting insulin and FFA concentrations; however, in the men only, the percent suppression of FFA declined with increasing obesity (nonobese, 83 +/- 15%; obese, 73 +/- 18%; and severely obese, 69 +/- 19%; P = 0.02). The women in all three BMI groups had lower FFA levels of 86-88%. CONCLUSIONS: Obese African-American men and women are resistant to insulin as a glucoregulatory hormone, but only obese men are resistant to insulin's antilipolytic action; obese African-American women are sensitive to insulin's antilipolytic action. The combined presence of sensitivity to insulin's antilipolytic action with resistance to insulin's glucoregulatory action in obese African-American women may contribute to their high prevalence of obesity and type 2 diabetes.

Hyperinsulinism and sex hormones in young adult African Americans.

Hyperinsulinemia is a risk factor for cardiovascular disease, and is linked with non-insulin-dependent diabetes mellitus (NIDDM), hyperlipidemia, obesity, and hypertension. Sex hormones also play a role in the metabolic alterations associated with the risk for cardiovascular disease. A reduction in sex hormone-binding globulin (SHBG) may be predictive of future NIDDM particularly in women. The postmenopausal decline in estrogen is also associated with an increase in risk factor expression in women. Since African Americans experience a greater prevalence of NIDDM, obesity, and hypertension, conditions associated with hyperinsulinemia, the purpose of this study was to determine if alterations in sex hormone levels are associated with the plasma insulin concentration in young adult African Americans, and to determine if there are sex differences in the effect of insulin on lipids and sex hormones. In a sample of 221 nondiabetic African American men (n = 105) and women (n = 116) with a mean age of 31 years, we examined the relationship of the plasma insulin concentration with the body mass index (BMI), blood pressure, plasma lipids, and sex hormones, including free testosterone, estradiol, and SHBG. Plasma insulin increased with the BMI and other measures of adiposity (P<.001) in men and women. Significant correlations of insulin with plasma lipids were also present in both sexes. There was a significant inverse correlation of insulin with SHBG in both men (r = .28, P = .007) and women (r = .27, P = .02). There was a significant direct correlation of insulin with free testosterone in women (r = .032, P<.001). Stepwise multiple regression analyses with insulin as the dependent variable detected the BMI, triglyceride, and apolipoprotein A1 as significant contributors to the plasma insulin concentration in men. In women, the multiple regression model detected percent body fat, low-density lipoprotein (LDL) cholesterol, and free testosterone as significant contributors to plasma insulin. These data on young African Americans demonstrate a significant relationship between hyperinsulinemia and obesity, atherogenic lipid status, and lower SHBG. In the premenopausal women, the lower SHBG is linked with higher free testosterone, favoring a condition of relative androgen excess.