Associations between omega-6 polyunsaturated fatty acids, hyperinsulinemia and incident diabetes by race/ethnicity: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND & AIMS: Omega-6 polyunsaturated fatty acids (PUFAs) have been shown to relate to insulin resistance and type 2 diabetes (T2D), but influence of race/ethnicity has not been investigated. The aim of this study was to determine whether omega-6 PUFAs, and estimated desaturase enzyme activity, are associated with fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and incident T2D, and whether associations differ by race/ethnicity. METHODS: This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) (N = 6282). Associations between baseline plasma phospholipid fatty acids (LA, Linoleic Acid; GLA, γ-linoleic acid; DGLA, Dihomo-γ-linolenic acid; AA, arachidonic acid; D5D, delta-5 desaturase; D6D, delta-6 desaturase), fasting glucose, insulin, and HOMA-IR [(fasting insulin - fasting glucose)/22.5] were evaluated using linear regression. Associations between omega-6 PUFAs (N = 5508 after excluding diabetics at baseline) and T2D incidence were assessed using Cox proportional hazards regression. Analyses were replicated/stratified by race/ethnicity (White, Black, Chinese, Hispanic) and tests for interaction were assessed by inclusion of a cross-product term in models. RESULTS: In fully adjusted models, insulin and HOMA-IR were positively associated with LA (insulin: 0.213 per SD, p = 0.01; HOMA-IR: 0.252 per SD, p < 0.001), GLA (insulin: 0.010 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), DGLA (insulin: 0.279 per SD, p < 0.001; HOMA-IR: 0.175 per SD, p < 0.001) and D6D activity (insulin: 0.001 per SD, p < 0.001; HOMA-IR: 0.006 per SD, p < 0.001), and inversely associated with AA (insulin -0.272 per SD, p < 0.001; HOMA-IR: -0.125 per SD, p = 0.03) and D5D activity (insulin: -0.530 per SD, p < 0.001; HOMA-IR: -0.322 per SD, p < 0.001), while weak or no associations were observed with fasting glucose, and associations appeared to differ by race/ethnicity. After accounting for HOMA-IR at baseline, LA was inversely (HR: 0.87, p = 0.003) and DGLA (HR: 1.17, p < 0.001) and AA (HR: 1.15, p = 0.001) were positively associated with T2D in the overall population, but associations were attenuated or no longer present when stratified by race/ethnicity (P-interaction >0.05). CONCLUSIONS: Results confirm previous reports that omega-6 PUFAs are associated with hyperinsulinemia. Findings suggest omega-6 PUFAs are more likely markers of hyperinsulinemia rather than a protective/risk factor for T2D and indicate racial/ethnic differences in associations, but further research is needed to confirm findings.

Novel aspects of the role of the liver in carbohydrate metabolism.

Malfunction of the liver is a central factor in metabolic disease. Glucose production by liver is complex and controlled via indirect mechanisms; insulin regulates adipose tissue lipolysis, and free fatty acids in turn regulate liver glucose output. This latter concept is confirmed by studies in L-Akt-Foxo1 knockout mice. The adipocyte is a likely locus of hepatic insulin resistance. Also, kidneys play a role in regulating glucose production; denervated kidneys abrogate the effect of fat feeding to cause insulin resistance. Glucose itself is an important regulator of liver metabolism ("glucose effectiveness"); after entering liver, glucose is phosphorylated and can be exported as lactate. Using the dynamic glucose/lactate relationship, we have been able to estimate glucose effectiveness in intact animals and human subjects. Families have been identified with a glucokinase regulatory protein defect; modeling demonstrates elevated glucokinase activity. Insulin clearance by liver is highly variable among normal individuals, and is under environmental control: high fat diet reduces clearance by 30%. Liver insulin clearance is significantly lower in African American (AA) adults and children compared to European American participants, accounting for fasting hyperinsulinemia in AA. We hypothesize that reduced hepatic insulin clearance causes peripheral insulin resistance and increased Type 2 diabetes in AA.

Triglyceride-rich very low-density lipoproteins (VLDL) are independently associated with insulin secretion in a multiethnic cohort of adolescents.

Excess insulin secretion and hyperinsulinaemia contribute to the progression of type 2 diabetes. However, the mechanisms leading to insulin hypersecretion remain largely unknown. Based on our preliminary data, we examined whether triglycerides and very low-density lipoprotein (VLDL) are independently associated with insulin secretion, and whether ethnicity/race modulates these associations. Fasting triglycerides and VLDL were measured in a multiethnic cohort of 630 non-diabetic adolescents. Insulin secretion, ß-cell function parameters, insulin sensitivity and insulin clearance were estimated through a 3-h oral glucose tolerance test. Metabolic assessments were repeated after 2 years in 239 subjects. Triglycerides and triglyceride-rich VLDL (large and medium size fractions) were associated with both basal and glucose-stimulated insulin secretion, after adjustment for age, sex, ethnicity, BMI z-score, plasma glucose, and insulin sensitivity. Ethnicity per se had an impact on lipid profile and ß-cell function, but did not modulate the effect of triglycerides/VLDL on insulin secretion. At follow-up, changes in triglyceride levels were proportional to changes in insulin secretion. These findings support the hypothesis that hypertriglyceridaemia is an important stimulus for ß-cell insulin release in young people under both fasting and fed conditions.

The association of breastfeeding with insulin resistance at 17 years: Prospective observations from Hong Kong's "Children of 1997" birth cohort.

Breastfeeding has many benefits for mother and infant. Whether breastfeeding also protects against type 2 diabetes is unclear. To clarify the role of breastfeeding in type 2 diabetes, we assessed the association of breastfeeding with insulin resistance in late adolescence in a birth cohort from a non-Western setting where breastfeeding was not associated with higher socio-economic position. We used multivariable linear regression, with multiple imputation and inverse probability weighting, to examine the adjusted associations of contemporaneously reported feeding in the first 3 months of life (exclusively breastfed, mixed feeding, or always formula-fed) with fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) at 17 years in a subset (n = 710, 8.6% of entire cohort) of the Hong Kong Chinese birth cohort "Children of 1997." We found a graded association of breastfeeding exclusivity in the first 3 months of life with lower fasting insulin and HOMA-IR (p-for-trend < .05), but not fasting glucose, at 17 years. Exclusively breastfed adolescents (7%) had nonsignificantly lowest fasting insulin and HOMA-IR, adjusted for sex, birth weight, parity, length of gestation, pregnancy characteristics, parents' education, and mother's place of birth. Exclusively breastfeeding for 3 months may be causally associated with lower insulin resistance in late adolescence. Further follow-up studies into adulthood are required to clarify the long-term protection of breastfeeding from type 2 diabetes.

Long-term Impact of Temporal Sequence from Childhood Obesity to Hyperinsulinemia on Adult Metabolic Syndrome and Diabetes: The Bogalusa Heart Study.

This study aims to delineate the temporal relations between body mass index (BMI) and insulin in childhood and their impact on adult metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM).The longitudinal cohort consisted of 609 whites and 339 blacks who had BMI and fasting insulin measured twice in childhood (mean age = 10.5 years at baseline and 15.9 years at follow-up). Incident MetS and T2DM were identified in adulthood (mean age = 30.5 years). Cross-lagged panel and mediation analysis models were used. After adjusting for age, race, gender, and follow-up years, the cross-lagged path coefficient of BMI → insulin (ß = 0.326, p < 0.001) was significantly greater than that of insulin → BMI (ß = -0.023, p = 0.207) in childhood, with p < 0.001 for the difference in ßs. The path coefficient for BMI → insulin was significantly greater in MetS than in non-MetS groups (0.510 vs 0.190, p < 0.001), and greater in hyperglycemia than in normoglycemia groups (0.503 vs 0.285, p = 0.026). The mediation effect of childhood insulin on the BMI-MetS and BMI-hyperglycemia associations was estimated at 19.2% (p < 0.001) and 18.3% (p < 0.001), respectively. These findings provide evidence that higher BMI levels precede hyperinsulinemia during childhood, and this one-directional relation plays a significant role in the development of MetS and T2DM in adult life.

Determinants of High Fasting Insulin and Insulin Resistance Among Overweight/Obese Adolescents.

Hyperinsulinaemia is the earliest subclinical metabolic abnormality, which precedes insulin resistance in obese children. An investigation was conducted on the potential predictors of fasting insulin and insulin resistance among overweight/obese adolescents in a developing Asian country. A total of 173 overweight/obese (BMI > 85th percentile) multi-ethnic Malaysian adolescents aged 13 were recruited from 23 randomly selected schools in this cross-sectional study. Waist circumference (WC), body fat percentage (BF%), physical fitness score (PFS), fasting glucose and fasting insulin were measured. Insulin resistance was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). Adjusted stepwise multiple regression analysis was performed to predict fasting insulin and HOMA-IR. Covariates included pubertal stage, socioeconomic status, nutritional and physical activity scores. One-third of our adolescents were insulin resistant, with girls having significantly higher fasting insulin and HOMA-IR than boys. Gender, pubertal stage, BMI, WC and BF% had significant, positive moderate correlations with fasting insulin and HOMA-IR while PFS was inversely correlated (p < 0.05). Fasting insulin was primarily predicted by gender-girls (Beta = 0.305, p < 0.0001), higher BMI (Beta = -0.254, p = 0.02) and greater WC (Beta = 0.242, p = 0.03). This study demonstrated that gender, BMI and WC are simple predictors of fasting insulin and insulin resistance in overweight/obese adolescents.

Progression from impaired glucose tolerance to type 2 diabetes in obese children and adolescents: a 3-6-year cohort study in southern Thailand.

BACKGROUND: Childhood obesity is associated with abnormal glucose metabolism and type 2 diabetes mellitus (T2DM). This study evaluated the prevalence of abnormal glucose metabolism in asymptomatic obese children and adolescents, and determined the percentage of T2DM development after 3-6 years of follow-up. METHODS: During 2007-2013, 177 obese children and adolescents who had normal fasting plasma glucose (FPG<100 mg/dL) were given an oral glucose tolerance test (OGTT). The participants were classified into four groups: normal glucose tolerance (NGT), NGT-hyperinsulinemia (NGT-HI), impaired glucose tolerance (IGT), and diabetes mellitus (DM). Blood chemistries, including FPG, glycated hemoglobin, and lipid profiles, and liver function test were performed every 6-12 months or when the patient developed any symptom or sign indicative of diabetes. RESULTS: Glucose metabolism alterations were detected in 81.4% of the participants: 63.8% with NGT-HI, 15.3% with IGT, and 2.3% with T2DM. The median levels of homeostasis model assessment-insulin resistance (HOMA-IR) in patients with IGT (8.63) were significantly greater than those in the patients with NGT (4.04) (p<0.01). During the follow-up, 22 patients (14.4%) developed T2DM significantly more from the IGT group (nine of 33 cases, 27.3%) than the NGT-HI group (12 of 108 cases, 11.1%) (p=0.022). The predicting parameters for T2DM conversion were weight status, body mass index (BMI), FBG, fasting insulin, alanine transaminase (ALT) levels, and HOMA-IR. CONCLUSIONS: Glucose metabolism alteration was commonly found among obese adolescents. Factors associated with T2DM development were greater weight status and the severity of insulin resistance as shown by higher HOMA-IR levels.

Metabolic markers associated with insulin resistance predict type 2 diabetes in Koreans with normal blood pressure or prehypertension.

BACKGROUND: Questions remain as to the association between essential hypertension and increased incidence of type 2 diabetes (T2DM). The premise of this analysis is that insulin resistance/compensatory hyperinsulinemia is a major predictor of T2DM, and the greater the prevalence of insulin resistance within any population, normotensive or hypertensive, the more likely T2DM will develop. The hypothesis to be tested is that surrogate estimates of insulin resistance will predict incident T2DM to a significant degree in persons with normal blood pressure or prehypertension. METHODS: Analysis of data from a population-based survey of 10, 038 inhabitants of rural and urban areas of Korea, ≥40 years-old, initiated in 2001, with measures of demographic and metabolic characteristics at baseline and 8-years later. Participants were classified as having normal blood pressure or prehypertension, and three simple manifestations of insulin resistance related to the pathophysiology of T2DM used to predict incident T2DM: (1) glycemia (plasma glucose concentration 2-hour after 75 g oral glucose challenge = 2-hour PG); (2) hyperinsulinemia (plasma insulin concentration 2-hour after 75 g oral glucose challenge = 2-hour PI); and (3) dyslipidemia (ratio of fasting plasma triglyceride/high/density lipoprotein cholesterol concentration = TG/HDL-C ratio). RESULTS: Fully adjusted hazard ratios (HR, 95 % CI) for incident T2DM were highest (P < 0.001) in the quartile of individuals with the highest 2-hour PG concentrations, ranging from 5.84 (3.37-10.1) in women with prehypertension to 12.2 (7.12-21.00) in men with normal blood pressure. T2DM also developed to a significantly greater degree in subjects within the highest quartile of TG/HDL-C ratios, with HRs varying from 2.91 (1.63-2.58) in women with prehypertension (P < 0.001) to 1.77 (1.12-2.81, P < 0.05) in men with prehypertension. The least predictive index of insulin resistance was the 2-hour PI concentration. Subjects with normal blood pressure in the highest quartile of 2-hour PI concentrations were significantly associated with incident T2DM, with HRs of 1.5 (1.02-2.20, P = 0.25) and 2.02 (1.35-3.02, P < 0.001), in men and women, respectively. Finally, incidence of T2DM in the highest quartile was somewhat greater in patients with prehypertension, irrespective of predictor. CONCLUSIONS: Metabolic variables associated with insulin resistance (glycemia, insulinemia, and dyslipidemia) predict the development of T2DM in patients with either normal blood pressure or prehypertension.

Observation of phenotypic variation among Indian women with polycystic ovary syndrome (PCOS) from Delhi and Srinagar.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder that demonstrates ethnic and regional differences. To assess the phenotypic variability among Indian PCOS women, we evaluated clinical, biochemical and hormonal parameters of these women being followed in two tertiary care institutions located in Delhi and Srinagar. A total of 299 (210 PCOS diagnosed by Rotterdam 2003 criteria and 89 healthy) women underwent estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, and lipid profile, in addition to post OGTT, C-peptide, insulin, and glucose measurements. Among women with PCOS, mean age, age of menarche, height, systolic, diastolic blood pressure, and serum LH were comparable. PCOS women from Delhi had significantly higher BMI (26.99 ± 5.38 versus 24.77 ± 4.32 kg/m(2); P = 0.01), glucose intolerance (36 versus 10%), insulin resistance as measured by HOMA-IR (4.20 ± 3.39 versus 3.01 ± 2.6; P = 0.006) and QUICKI (0.140 ± 0.013 versus 0.147 ± 0.015; P = 0.03) while PCOS from Srinagar had higher FG score (12.12 ± 3.91 versus 10.32 ± 2.22; P = 0.01) and serum total testosterone levels (0.65 ± 0.69 versus 0.86 ± 0.41 ng/ml; P = 0.01. Two clear phenotypes, i.e. obese hyperinsulinaemic dysglycemic women from Delhi and lean hyperandrogenic women from Srinagar are emerging. This is the first report on North Indian women with PCOS showing phenotypic differences in clinical, biochemical and hormonal parameters despite being in the same region.

An 8-Year Prospective Study of Depressive Symptoms and Change in Insulin From Adolescence to Young Adulthood.

OBJECTIVE: To evaluate whether depressive symptoms predict change in fasting insulin among adolescents followed into young adulthood. We hypothesized that higher depressive symptoms would predict increased insulin and that puberty and race/ethnicity would moderate this relationship. METHODS: Data came from the Princeton School District Study, a school-based longitudinal cohort of non-Hispanic black and white adolescents (2001-2011). Depressive symptoms, fasting insulin, and body mass index were measured at baseline (adolescence) and 8 years later (young adulthood) in 685 participants. Puberty was assessed using a validated protocol measuring sex steroids and physical changes. The primary outcome was change in fasting insulin. Analyses accounted for age, sex, race, parental education, baseline insulin, body mass index z score, puberty, and time to follow-up. RESULTS: At baseline, depressive symptoms were correlated with insulin (ρ = 0.13, p = .001). High baseline insulin predicted insulin change (B = -11.50, standard error [SE] = 2.30, p < .001). Depressive symptoms also predicted insulin change, but only for pubertal adolescents (B = -0.23, SE = 0.11, p = .038). This relationship was moderated by race (p = .047); depressive symptoms predicted insulin change only among pubertal black adolescents (p = .030), not white (p = .49), and in the direction opposite that hypothesized (Bblacks = -0.51, SE = 0.23). Post hoc analyses revealed that pubertal black adolescents with high depressive symptoms had the highest baseline insulin, which stayed high across the follow-up period. CONCLUSIONS: Among pubertal black adolescents, elevated depressive symptoms are associated with increased risk for sustained hyperinsulinemia from adolescence into adulthood. These youths may be particularly vulnerable for Type 2 diabetes.

Genotype and phenotype correlations in Iranian patients with hyperinsulinaemic hypoglycaemia.

BACKGROUND: Hyperinsulinaemic hypoglycaemia (HH) is a group of clinically and genetically heterogeneous disorders characterized by unregulated insulin secretion. Abnormalities in nine different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A, UCP2 and HNF1A) have been reported in HH, the most common being ABCC8 and KCNJ11. We describe the genetic aetiology and phenotype of Iranian patients with HH. METHODS: Retrospective clinical, biochemical and genetic information was collected on 23 patients with biochemically confirmed HH. Mutation analysis was carried out for the ATP-sensitive potassium (K(ATP)) channel genes (ABCC8 and KCNJ11), GLUD1, GCK, HADH and HNF4A. RESULTS: 78% of the patients were identified to have a genetic cause for HH. 48% of patients had mutation in HADH, whilst ABCC8/KCNJ11 mutations were identified in 30% of patients. Among the diazoxide-responsive patients (18/23), mutations were identified in 72%. These include two novel homozygous ABCC8 mutations. Of the five patients with diazoxide-unresponsive HH, three had homozygous ABCC8 mutation, one had heterozygous ABCC8 mutation inherited from an unaffected father and one had homozygous KCNJ11 mutation. 52% of children in our cohort were born to consanguineous parents. Patients with ABCC8/KCNJ11 mutations were noted to be significantly heavier than those with HADH mutation (p = 0.002). Our results revealed neurodevelopmental deficits in 30% and epilepsy in 52% of all patients. CONCLUSIONS: To the best of our knowledge, this is the first study of its kind in Iran. We found disease-causing mutations in 78% of HH patients. The predominance of HADH mutation might be due to a high incidence of consanguineous marriage in this population. Further research involving a larger cohort of HH patients is required in Iranian population.

Diagnosis of hyperinsulinaemia in a normoglycaemic healthy Indian Population--developing ethnic reference ranges.

CONTEXT: Reference limits for diagnosing hyperinsulinaemia are currently derived from non-Indian cohorts and have not been validated in Indians even though it is acknowledged that different patterns of insulin secretion are seen across ethnicities. AIMS: To develop ethnicity specific reference limits for insulin levels in a normoglycaemic healthy Indian cohort in order to derive a clinical cut off for hyperinsulinaemia as an effective screening tool for predicting future risk of metabolic and cardiovascular disease. SETTINGS AND DESIGN: Prospective analysis of plasma insulin levels in healthy normoglycaemic volunteers availing diagnostic facilities at a central reference laboratory in Mumbai. METHODS AND MATERIAL: 122 normoglycaemic males between 19-73 years and 126 females between 19-55 years of age were selected based on a screening questionnaire as per the Clinical Laboratory and Standards Institute (CLSI) guidance document for deriving reference ranges. Fasting insulin levels were analysed using a Chemiluminescent Microparticle Immunoassay platform and derived results were analysed to determine reference limits for insulin. STATISTICAL ANALYSIS USED: A non-parametric method of statistical analysis was used to determine the 2.5 and 97.5% limits with 90% confidence intervals. RESULTS: Reference range for insulin in a normoglycemic Indian cohort was derived as 2.7-17 uIU/ml which established 17 uIU/ml as the clinical cut off for diagnosing hyperinsulinemia in healthy Indians. CONCLUSIONS: Reference limits for insulin in normoglycemic Indians needs to be revised to 2.7-17 uIU/ ml. Clinical cut off for hyperinsulinemia needs to be lowered to 17 uIU/ml from currently used cut offs which range from 25-31 ulU/ml. KEY MESSAGES: Reference limits currently used for diagnosing hyperinsulinemia in healthy normoglycemic adults need to be revised and made specific for different ethnicities. In Indians the upper limit of the normal reference range for insulin levels needs to be brought down to 17 uIU/ml from the existing 25-31 u IU/ml. This modified cut off would help clinicians identify apparently healthy individuals who may need to be screened for a future risk of metabolic and cardiovascular disorders.

Effects of consumption of main and side dishes with white rice on postprandial glucose, insulin, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 responses in healthy Japanese men.

The co-ingestion of protein, fat and fibre with carbohydrate reportedly affects postprandial glucose, insulin and incretin (glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)) responses. However, the effects of combination dishes with carbohydrate-rich foods at typically eaten amounts remain unclear. The objective of the present study was to evaluate the effects of consuming recommended amounts of side dishes with boiled white rice in the same meal on postprandial plasma glucose, insulin and incretin hormone responses. A total of nine healthy male volunteers consumed four different meals in a random order on separate days. The test meals were as follows: S, white rice; SM, addition of protein-rich main dishes to the S meal; SMF, addition of a fat-rich food item to the SM meal; SMFV, addition of vegetables to the SMF meal. Plasma glucose, GIP and GLP-1 and serum insulin concentrations were determined during a 3 h period after consumption of these meals. Postprandial glucose responses were lower after SMFV meal consumption than after consumption of the other meals. The incremental AUC for GIP (0-180 min) were largest after consumption of the SMF and SMFV meals, followed by that after SM meal consumption, and was smallest after S meal consumption (P< 0·05). Furthermore, we found GIP concentrations to be dose dependently increased by the fat content of meals of ordinary size, despite the amount of additional fat being small. In conclusion, the combination of recommended amounts of main and vegetable side dishes with boiled white rice is beneficial for lowering postprandial glucose concentrations, with an increased incretin response, when compared with white rice alone.

Assessment of the ability of the triglyceride to high density lipoprotein cholesterol ratio to discriminate insulin resistance among Caribbean-born black persons with and without Hispanic ethnicity / Evaluación de la capacidad de la proporción de los triglicéridos en relación con el colesterol de las lipoproteínas de alta densidad para identificar la resistencia a la insulina entre personas negras nacidad en el Caribe con o sin etnicidad Hispánica

OBJECTIVE: The objective of this research was to determine if the triglyceride (TG) to high density lipoprotein (HDL) cholesterol (TG/HDL) ratio has similar utility for discriminating insulin resistance in Caribbean-born black persons with and without Hispanic ethnicity. METHODS: Serum lipids, glucose and insulin were determined and compared for 144 Hispanic blacks and 655 non-Hispanic blacks living in the US Virgin Islands. Area under the receiver operating characteristics (AUROC) curve statistics were used to evaluate the ability of the TG/HDL ratio to discriminate insulin resistance in the two ethnic groups. RESULTS: Hispanic blacks had significantly higher levels of triglycerides and insulin resistance and a lower level of HDL cholesterol than non-Hispanic blacks. The AUROC curve for the ability of the TG/HDL to discriminate insulin resistance was 0.71 (95% CI = 0.62, 0.79) for Hispanic blacks and 0.64 (95% CI = 0.59, 0.69) for non-Hispanic blacks. CONCLUSIONS: Among Caribbean-born black persons living in the US Virgin Islands, the TG/HDL ratio is a useful screening measure for discriminating insulin resistance in those with Hispanic ethnicity but not in those without Hispanic ethnicity.

OBJETIVO: El objetivo de esta investigación fue determinar si la proporción (TG/HDL) de los triglicéridos (TG) con respecto al colesterol de las lipoproteínas de alta densidad (HDL) tiene una utilidad similar a la hora de identificar la resistencia a la insulina en personas negras nacidas en el Caribe, con o sin etnicidad hispánica. MÉTODOS: Se determinaron y compararon la insulina, la glucosa y los lípidos séricos de 144 negros hispánicos y 655 negros no hispánicos residentes en Islas Vírgenes, USA. Las estadísticas del área bajo la curva de las características operativas del receptor (AUROC) se utilizaron para evaluar la capacidad de la proporción TG/HDL para establecer la resistencia a la insulina en los dos grupos étnicos. RESULTADOS: Los negros hispánicos tenían niveles significativamente más altos de triglicéridos y resistencia a la insulina y un menor nivel de colesterol HDL que los negros no hispánicos. La curva AUROC para la capacidad del TG/HDL para establecer la resistencia a la insulina fue 0.71 (95% CI = 0.62, 0.79) para los negros hispánicos y 0.64 (95% CI = 0.59, 0.69) para los negros no hispánicos. CONCLUSIONES: Entre las personas negras que viven en las Islas Vírgenes, la proporción de TG/HDL es una medida útil de tamizaje pata establecer la resistencia a la insulina en las personas de etnia hispana, pero no en las personas de etnicidad no hispánica.

Assessment of the ability of the triglyceride to high density lipoprotein cholesterol ratio to discriminate insulin resistance among Caribbean-born black persons with and without Hispanic ethnicity.

OBJECTIVE: The objective of this research was to determine if the triglyceride (TG) to high density lipoprotein (HDL) cholesterol (TG/HDL) ratio has similar utility for discriminating insulin resistance in Caribbean-born black persons with and without Hispanic ethnicity. METHODS: Serum lipids, glucose and insulin were determined and compared for 144 Hispanic blacks and 655 non-Hispanic blacks living in the US Virgin Islands. Area under the receiver operating characteristics (AUROC) curve statistics were used to evaluate the ability of the TG/HDL ratio to discriminate insulin resistance in the two ethnic groups. RESULTS: Hispanic blacks had significantly higher levels of triglycerides and insulin resistance and a lower level of HDL cholesterol than non-Hispanic blacks. The AUROC curve for the ability of the TG/HDL to discriminate insulin resistance was 0.71 (95% CI = 0.62, 0.79) for Hispanic blacks and 0.64 (95% CI = 0.59, 0.69) for non-Hispanic blacks. CONCLUSIONS: Among Caribbean-born black persons living in the US Virgin Islands, the TG/HDL ratio is a useful screening measure for discriminating insulin resistance in those with Hispanic ethnicity but not in those without Hispanic ethnicity.

Hyperinsulinemia, insulin resistance, vitamin D, and colorectal cancer among whites and African Americans.

African Americans have the highest incidence and mortality rates of colorectal cancer among all US racial and ethnic groups. Dietary factors, lifestyle factors, obesity, variability in screening rates, socioeconomic differences, barriers to screening, and differences in access to health care may be contributory factors to racial and ethnic disparities. African Americans are more likely to demonstrate microsatellite instability in their colorectal tumors leading to malignancy. However, these differences do not completely explain all the variances. Ample evidence implicates insulin resistance and its associated conditions, including elevated insulin and insulin-like growth factor-1 (IGF-1), in colorectal carcinogenesis. African Americans have a high risk for and a high prevalence of insulin resistance and subsequent overt type 2 diabetes. Recent clinical studies revealed that ethnic differences between whites and African Americans in early diabetes-related conditions including hyperinsulinemia already exist during childhood. African Americans have a much higher prevalence of vitamin D deficiency than whites throughout their life spans. Vitamin D deficiency has been associated with higher rates of diabetes and colorectal cancer, particularly in individuals with high serum insulin and IGF-1 levels. Moreover, African Americans have lower insulin sensitivity in tissues, independent of obesity, fat distribution, and inflammation. Further development of measures of biomarkers of tumor biology and host susceptibility may provide further insight on risk stratification in African Americans.

Hyperinsulinemia correlates with low levels of plasma B-type natriuretic peptide in Japanese men irrespective of fat distribution.

BACKGROUND: B-type natriuretic peptide (BNP), a member of the natriuretic peptide family, is a cardiac-derived secretory hormone with natriuretic, diuretic, and vasorelaxant activities. Intraabdominal fat accumulation is associated with atherosclerotic cardiovascular diseases and cardiac dysfunction. Circulating BNP levels are relatively low (within the normal limits) in obesity and the metabolic syndrome. However, the relationship between plasma BNP levels and visceral fat accumulation in general population has not been reported. The present study analyzed the relationships between plasma BNP levels and various clinical variables, including insulin, visceral and subcutaneous fat area (VFA and SFA, respectively), in normal Japanese men. METHODS: The study (Victor-J study) subjects were consecutive 500 Japanese male workers, who underwent a health checkup and were measured VFA and SFA by computed tomography. RESULTS: Age-adjusted simple linear regression analysis showed that log-BNP correlated positively with HDL-cholesterol, and negatively with VFA, log-immunoreactive insulin (IRI), log-triglyceride, and LDL-cholesterol, but not body mass index or SFA. Stepwise multiple regression analysis identified log-IRI and HDL-cholesterol as significant determinants of log-BNP. Subjects with IRI ≥5.5 µIU/mL had lower plasma BNP levels than those with IRI < 5.5 µIU/mL, irrespective of obesity (body mass index, cutoff value 25 kg/m2), visceral fat accumulation (VFA, cutoff value 100 cm2) and subcutaneous fat accumulation (SFA, cutoff value 128 cm2). CONCLUSIONS: Our study showed that hyperinsulinemia correlated with low levels of plasma BNP in general men, irrespective of fat distribution. TRIAL REGISTRATION: UMIN 000004318.

Race, childhood insulin, childhood caloric intake, and class 3 obesity at age 24: 14-year prospective study of schoolgirls.

The prevalence of Class 3 obesity (BMI ≥40 kg/m(2)) has more than doubled in the past 25 years. In a 14-year prospective study from age 10 to 24 of a biracial schoolgirl cohort (293 black, 256 white), we assessed childhood correlates of Class 3 BMI at age 24. Of 42 girls with Class 3 BMI at age 24, 36 (86%) were black. By logistic regression, significant explanatory variables of Class 3 BMI at age 24 included top decile waist circumference at age 11 (odds ratio (OR) 5.7, 95% confidence interval (CI) 2.3-13.9, P = 0.0002), age 10 BMI ≥ the Center for Disease Control (CDC) 2000 top 15% (OR 7.0, 95% CI 2.5-19.3, P = 0.0002), and a three-way interaction between race, childhood insulin, and average caloric intake from age 10 to age 19 (for each unit increase, OR 1.7 95% CI 1.3-2.2, P = 0.0003). Age 10 BMI, age 11 waist circumference, and interaction of race, childhood insulin, and childhood caloric intake predict Class 3 obesity in young adulthood, facilitating childhood identification of girls at high risk for developing Class 3 obesity.

Hyperinsulinemia and metabolic syndrome at mean age of 10 years in black and white schoolgirls and development of impaired fasting glucose and type 2 diabetes mellitus by mean age of 24 years.

The objective of the study was to evaluate preteen insulin and metabolic syndrome (MS) as independent predictors of impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) in black and white females by mean age of 24 years. This was a prospective cohort study. There were 8 measures of fasting glucose and insulin from mean age of 10 years through mean age of 24 years, and insulin also at mean age of 25 years. Childhood MS was defined by at least 3 abnormal values among waist circumference, triglyceride, high-density lipoprotein cholesterol, blood pressure, and glucose. Hyperinsulinemia was defined by insulin greater than or equal to race-specific 75th percentile. Patients with type 1 diabetes mellitus were excluded. The study was held in schools and in an outpatient clinical center. Participants were schoolgirls (260 white, 296 black). There was no intervention. The outcome measures were IFG (fasting glucose of at least 100 to 125 mg/dL) and T2DM (fasting glucose of at least 126 mg/dL). By the age of 24 years, there were 11 cases of T2DM (2%) and 108 cases of IFG (19%). By the age of 24 years, IFG + T2DM was present in 18% of women (73/412) who had normal insulin-no MS at the age of 10 years vs 28% (34/122) of those with high insulin-no MS at the age of 10 years (P = .014) and 67% (10/15) of those with high insulin + MS at the age of 10 years (P < .0001). By stepwise logistic regression, significant, independent, positive predictors of IFG + T2DM were first insulin measure in childhood, age at last sampling, childhood MS, change in body mass index over 15 years, and, separately, initial glucose of at least 100 mg/dL and average of all insulin quartile ranks over 15 years. The correlation between childhood insulin z score and insulin z score 15 years later was r = .30, P < .0001. Insulin and MS at a mean age of 10 years plus change in body mass index over 15 years, and 15-year average insulin rank independently predict IFG + T2DM by mean age of 24 years, suggesting avenues for primary prevention.