Ethnic variation in the activity of lipid desaturases and their relationships with cardiovascular risk factors in control women and an at-risk group with previous gestational diabetes mellitus: a cross-sectional study.

BACKGROUND: Lipid desaturase enzymes mediate the metabolism of fatty acids to long chain polyunsaturated fatty acids and their activities are related to metabolic risk factors for Type 2 diabetes (T2DM) and coronary heart disease (CHD). There are marked ethnic differences in risks of CHD and T2DM but little is known about ethnic differences in desaturase activities. METHODS: Samples from a study of CVD risk in women with previous gestational diabetes were analysed for percentage fatty acids in plasma free fatty acid, triglyceride, cholesterol ester and phospholipid pools for 89 white European, 53 African Caribbean and 56 Asian Indian women. The fatty acid desaturase activities, stearoyl-CoA desaturase (SCD, calculated separately for C16 and C18 fatty acids), delta 6 desaturase (D6D) and delta 5 desaturase (D5D) were estimated from precursor-to-product ratios and their relationships with adiposity, blood pressure, cholesterol, triglycerides, HDL cholesterol and insulin sensitivity explored. Ethnic differences in desaturase activities independent of ethnic variation in risk factor correlates of desaturase activities were then identified. RESULTS: There was significant ethnic variation in age, BMI, waist circumference, blood pressure, serum triglycerides and HDL cholesterol concentrations and insulin resistance. Desaturase activities showed significant correlations, independent of ethnicity, with BMI, waist circumference, triglycerides and HDL cholesterol. Independent of ethnic variation in BMI, waist circumference, triglycerides and HDL cholesterol, SCD-16 activity, calculated from each of the four lipid pools measured, was 18-35 percent higher in white Europeans than in African Caribbeans or Asian Indians (all p < 0.001). Similar, though less consistent differences were apparent for SCD-18 activity. Also independently of risk factor variation, but specifically when calculated from the cholesterol ester and phospholipid, pools, D6D activity was significantly lower in Asian Indians, and D5D activity higher in African Caribbeans. CONCLUSIONS: Significant ethnic differences exist in desaturase activities, independently of ethnic variation in other risk factors. These characteristics did not accord with higher risk of T2DM among African Caribbeans and Asian Indians nor with lower risk of CHD among African Caribbeans but did accord with the higher risk of CHD in Asian Indians.

Early metabolic defects following gestational diabetes in three ethnic groups of anti-GAD antibodies negative women with normal fasting glucose.

OBJECTIVE: To characterise early metabolic abnormalities and the impact of ethnicity following gestational diabetes mellitus (GDM). DESIGN: Women with a history of GDM belonging to three different ethnic groups were evaluated. Using the insulin-modified, frequently-sampled intravenous glucose tolerance test (FSIVGTT) and HOMA we studied 34 European, 16 South Asian and 10 Afro-Caribbean women with normal fasting glucose following GDM and 44 European, 16 South Asian and 19 Afro-Caribbean controls to assess insulin action and secretion. RESULTS: European post-GDM women had lower insulin sensitivity by FSIVGTT [0.6 (0.1-5.1) vs 1.5 (0.8-2.8) x10(-4).min(-1).pmol(-1).l(-1), p=0.010, adjusted for BMI p=0.054] and by HOMA [72(22-235) vs 153(55-421)%, p=0.004, adjusted for BMI p=0.006], and reduced -cell function [lower disposition index 0.05(0.01-0.40) vs 0.11(0.05-0.25)min(-1), p=0.017] compared with controls. South Asian post-GDM women had decreased -cell function [lower HOMA (%B) (73 (37-147) vs 124 (59-262) %, p=0.048 and acute insulin response to glucose (463 (131-1639) vs 1039 (393-2748) pmol/l h, p=0.052] than controls. Afro-Caribbean post-GDM women had lower glucose disappearance rate [1.3(0.6-2.8) vs 2.6 (1.8-3.8) 10(-2)/min, p=0.003] than controls, suggesting subtle glucose intolerance. CONCLUSIONS: Women with a history of GDM of three different ethnic groups, even in the presence of normal fasting glucose, display a range of metabolic abnormalities, including -cell dysfunction with variable insulin resistance. These derangements may be influenced by ethnicity.

Sustained endogenous glucose production, diminished lipolysis and non-esterified fatty acid appearance and oxidation in non-obese women at high risk of type 2 diabetes.

OBJECTIVE: To evaluate early defects in glucose production, lipolysis and fatty acid oxidation in non-obese, normally glucose tolerant women, who are nevertheless at risk of type 2 diabetes. METHODS: Ten women with previous gestational diabetes (pGDM) and ten controls were studied in two 4 h infusions of stable isotopes 6,6-(2)H(2)-glucose, 1-(13)C-palmitate, and 1,1,2,3,3-(2)H(5)-glycerol with and without infusion of adrenaline. Fatty acid oxidation was quantified using indirect calorimetry and (13)CO(2) measurements. Insulin sensitivity was evaluated using the short insulin tolerance test. RESULTS: The pGDM and control women were non-obese and carefully matched for body mass index and fat mass. Whole body insulin sensitivity and basal insulin concentrations did not differ significantly but basal glucose concentrations were increased in women with pGDM. During a 0.9% saline infusion, glucose appearance was not significantly different at the first (90-120 min) and second (210-240 min) steady states. However, glucose appearance decreased in controls but was maintained in the pGDM women (-0.33 +/- 0.02 vs -0.03 +/- 0.08 mg/kg per min; P = 0.004). Basal glycerol appearance (0.27 +/- 0.02 vs 0.38 +/- 0.03 mg/kg per min; P = 0.02), palmitate appearance (0.74 +/- 0.09 vs 1.05 +/- 0.09 mg/kg per min; P = 0.03) and palmitate oxidation (0.07 +/- 0.01 vs 0.10 +/- 0.01 mg/kg per min; P = 0.03) were lower in the pGDM women. During the adrenaline infusion, changes in glucose, glycerol and palmitate concentrations and kinetics were similar in both groups. CONCLUSIONS: Sustained glucose production during fasting is an early abnormality in non-obese subjects at risk of type 2 diabetes. Lipolysis and non-esterified fatty acid appearance and oxidation are diminished, suggesting an increased tendency to store fat. The observations are not readily attributable to differences in insulin or catecholamine sensitivity.

Impaired circulating glucagon-like peptide-1 response to oral glucose in women with previous gestational diabetes.

BACKGROUND AND OBJECTIVE: Women with previous gestational diabetes (pGDM) are at risk of developing Type 2 diabetes. Glucagon-like peptide-1 (GLP-1) potentiates the insulin response to oral glucose, and its secretion is diminished in Type 2 diabetes. The aim of the study was to see if decreased GLP-1 secretion might be an early abnormality in the progression to Type 2 diabetes and would therefore be diminished in women with pGDM. PATIENTS AND METHODS: Eleven women with pGDM and previously documented normal glucose tolerance and 11 control women underwent a 75 g oral glucose tolerance test (OGTT). Circulating plasma glucose, insulin, nonesterified fatty acids (NEFA) and GLP-1 concentrations were sampled. RESULTS: One of the women with pGDM had impaired glucose tolerance and was excluded from the study. All other women had normal glucose tolerance. The women with pGDM had higher fasting glucose concentrations than controls (5.1; 4.9-5.3 vs. 4.8; 4.4-5.1 mmol/l, median; interquartile range, P = 0.04) and greater circulating glucose area under the curve (AUC) following the oral glucose load (930; 818-1015 vs. 668; 584-737 min x mmol/l, P = 0.0007). Fasting insulin concentrations and total insulin AUC were similar. The initial (0-30 min) insulin response was decreased in the pGDM women (AUC 3981; 2783-4795 vs. 6167; 5009-8145 min x pmol/l, P = 0.05). The initial (0-30 min) GLP-1 response was reduced in the pGDM women (AUC 816; 663-984 vs. 1163; 872-2024 min x pmol/l, P = 0.02). CONCLUSION: A reduced initial GLP-1 response to oral glucose may therefore be an early abnormality in the progression to Type 2 diabetes.

Insulin resistance and beta-cell dysfunction in normoglycaemic European women with a history of gestational diabetes.

OBJECTIVE: Women with previous gestational diabetes (GDM) are at increased risk of subsequent type 2 diabetes. To characterize early metabolic abnormalities associated with this increased risk, we studied normoglycaemic women with a history of GDM. PATIENTS AND MEASUREMENTS: We performed an insulin-modified, frequently sampled intravenous glucose tolerance test (FSIVGTT) in 34 normoglycaemic European women with previous GDM and 44 European control women, deriving measures of insulin sensitivity, glucose effectiveness, glucose disappearance rate and acute insulin response to glucose. RESULTS: Post-GDM women were more obese than controls [body mass index (BMI), geometric mean (95% confidence interval); 25.3 kg/m2 (23.8-27.1 kg/m2) vs. 23.1 kg/m2 (21.9-24.3 kg/m2), P = 0.03]. Evidence of insulin resistance was provided by their lower insulin sensitivity as measured by FSIVGTT [0.6 x 10-4/min/pmol/l (0.3-1.2 x 10-4/min/pmol/l) vs. 1.5 x 10-4/min/pmol/l (1.2-1.8 x 10-4/min/pmol/l), P = 0.01] and by homeostatic model assessment [72% (49-107%) vs. 153% (113-206%), P = 0.004]; and by their higher fasting triglycerides [1.0 mmol/l (0.7-1.5 mmol/l) vs. 0.7 mmol/l (0.6-0.8 mmol/l), P = 0.001]. Though there was no difference between groups in fasting NEFA levels, acute NEFA suppression was diminished in the post-GDM group (P = 0.01). Concomitant beta-cell dysfunction in the post-GDM women was revealed by their lower disposition index [0.05/min (0.02-0.10/min) vs. 0.11/min (0.09-0.14/min), P = 0.02] compared to controls. The differences in insulin sensitivity, but not those of beta-cell function, were partly, though not completely, attributable to differences in regional and total adiposity. CONCLUSIONS: European normoglycaemic women with previous GDM display both glucoregulatory and antilipolytic insulin resistance, reduced beta-cell function and dyslipidaemia. These metabolic abnormalities are likely to contribute to their increased risk of future type 2 diabetes.

Delayed metabolic and thermogenic response to a mixed meal in normoglycemic European women with previous gestational diabetes.

We assessed postprandial thermogenesis (PPT) for 3 h following a mixed meal in 29 normoglycemic European women with previous gestational diabetes (GDM), compared with 37 control women. Given the potential role of catecholamines and insulin in the regulation of PPT, we assessed insulin and catecholamine responses to the meal. There was no significant difference between the two groups in resting energy expenditure, PPT (although lower in the GDM group), or catecholamine levels. However, we observed a difference in the shape of the PPT curve between groups, and by applying a mathematical model, there was a consistent delay in PPT, insulin, and noradrenaline responses to the meal in the GDM group (T: fitted time constant, geometric mean (95% confidence interval), T(PPT) 58 (47-72) vs. 42 (37-48) min, P = 0.006; T(ins) 32 (28-37) vs. 22 (19-27) min, P = 0.002; T(NA) 30 (23-38) vs. 18 (14-23) min, P = 0.01, respectively). Fidgeting activity during the study was assessed by a novel technique and was lower in the GDM group, resting [427 (381-477) vs. 511 (466-560) kJ/min, P = 0.02] but not postprandially. These delayed PPT, insulin, and noradrenaline responses to the meal in post-GDM women represent early metabolic changes. The decrease in fidgeting activity while resting, observed in the post-GDM group, may have physiological significance for energy balance.

Los efectos de las diferentes fórmulas de los agentes anticonceptivos orales en el metabolismo de los carbohidratos y los lípidos / The effects of different formulations of oral contraceptive agents on carbohydrate metabolism and lipid

Antecedentes. Los anticonceptivos orales pueden producir cambios en el metabolismo de los carbohidratos y los lípidos, similares a aquellos asociadas can un riesgo incrementado de enfermedad coronaria, incluyendo un aumento de los triglicéridos séricos, colesterol con lipoproteína de baja densidad (WL), niveles de insulina y disminución de los niveles del colesterol de la lipoproteína de alta densidad (HDL). En este estudio examinaremos si la modificación del tipo o dosis de la progestina en las preparaciones anticonceptivas orales disminuyen estos cambios. Métodos. Se midieron los niveles de lipoproteína plasmática y se realizaron test orales de tolerancia a la glucosa en un estudio transversal con 1,060 mujeres, quienes llevaban tomando uno de los nueve anticonceptivos orales por 10 menos tres meses, y con 418 mujeres, quienes no tomaban ninguno de ellos. Siete de las fórmulas anticonceptivas contenían varias dosis y tipos de progestina: levonorgestrel en dosis bajas (15 mcg), en dosis altas (250 mcg), y en dosis trifásicas (de 50 a 125 mcg). norethindrone en dosis bajas (500 mcg), en dosis altas (1000 Mcg),y en dosis trifásicas (500 a 1000 mcg); y una nueva progestina, desogestrel en una sola dosis (150 mcg). Las siete fórmulas contenían de 30 a 40 mcg de etinil estradiol. Dos fórmulas adicionales contenían solo progestina.Resultados. Comparado con otros métodos de control, las mujeres que tomaban pastillas combinadas no presentaban un incremento en los niveles totales de colesterol sérico, pero si, presentaban un rápido incremento de 13% a 75% en los niveles de triglicéridos en ayunas. Los niveles de colesterol LDL se redujeron aproximadamente un 14% en mujeres que tomaban combinaciones que contenían desogestrel, y aproximadamente un 12% en aquellas que tomaban bajas dosis de norethidrone. Los niveles de colesterol HDL disminuyeron aproximadamente un 5% y 16% en aquellas mujeres que tomaban combinaciones que contenían bajas dosis y altas dosis...