[Acquired partial lipodystrophy. Insulin resistance, hepatic lipase activity and small and dense LDL particles]. / Lipodistrofia parcial adquirida. Resistencia insulínica, actividad lipasa hepática y partículas LDL pequeñas y densas.

Partial lipodystrophy (PLD) is an infrequent condition characterized by symmetric loss of subcutaneous adipose tissue in the upper or lower part of the body, although occasionally it affects only the extremities. In all cases it appears along with acantosis nigricans (AN), insulin resistance and impairment in the metabolism of lipids and carbohydrates. The case depicted pertains to a 49 year old female with no family history involving loss of adipose tissue in face and upper body. No fat in lower part of body was observed. The patient showed facial thinning at age 8, AN at 11 and gestational diabetes during her fourth pregnancy at 33. At present, the patient presents severe hyperglycemia and hyperinsulinemia with a marked insulin resistance. Type IV hyperlipoproteinemia (OMS), declined C-HDL and Apo A1 and low C-LDL but with a high proportion of small and dense LDL particles were present. Non esterified fatty acids were high. Lipoprotein lipase and hepatic lipase activities are in the lower limit and increased respectively. Fraction C3 of the complement was diminished. No mutations were observed either in codons 170, 809 and 972 of the IRS-1 receptor or in codon 276 of the adrenergic beta 2 gene.

Lipodistrofia parcial adquirida. Resistencia insulínica, actividad lipasa hepática y partículas LDL pequeñas y densas. / [Acquired partial lipodystrophy. Insulin resistance, hepatic lipase activity and small and dense LDL particles]

Partial lipodystrophy (PLD) is an infrequent condition characterized by symmetric loss of subcutaneous adipose tissue in the upper or lower part of the body, although occasionally it affects only the extremities. In all cases it appears along with acantosis nigricans (AN), insulin resistance and impairment in the metabolism of lipids and carbohydrates. The case depicted pertains to a 49 year old female with no family history involving loss of adipose tissue in face and upper body. No fat in lower part of body was observed. The patient showed facial thinning at age 8, AN at 11 and gestational diabetes during her fourth pregnancy at 33. At present, the patient presents severe hyperglycemia and hyperinsulinemia with a marked insulin resistance. Type IV hyperlipoproteinemia (OMS), declined C-HDL and Apo A1 and low C-LDL but with a high proportion of small and dense LDL particles were present. Non esterified fatty acids were high. Lipoprotein lipase and hepatic lipase activities are in the lower limit and increased respectively. Fraction C3 of the complement was diminished. No mutations were observed either in codons 170, 809 and 972 of the IRS-1 receptor or in codon 276 of the adrenergic beta 2 gene.

Urinary heparan sulphate is increased in normoalbuminuric diabetic patients.

Forty-nine normoalbuminuric diabetic patients were studied: 22 males and 27 females, in whom urinary heparan sulphate (HS), albuminuria, creatininemia, creatininuria, creatinine clearance, HbA1c and arterial pressure (AP) were determined. Two groups were discerned: group 1, Type 1 DM, diabetic cases (n = 16); and group 2, Type 2 DM diabetic cases (n = 33). Patients were compared with 24 healthy controls: 12 men and 12 women, who showed a mean value +/- SD of 0.36 +/- 0.18 mg/24 h HS with significant differences between males and females (0.43 +/- 0.15 versus 0.28 +/- 0.17, respectively; p = 0.02). The total population of diabetic cases rendered a mean of 0.68 +/- 0.44 and comparison with controls proved highly significant (p < 0.001). Globally, male patients had a mean of 0.82 +/- 0.48 and females 0.54 +/- 0.35, with p < 0.02. Group 1 and 2 values of HS were not significantly different. HS levels failed to correlate either with age, body mass index (BMI), time since onset of diabetes, albuminuria, creatininemia, creatininuria, creatinine clearance, HbA1c or arterial hypertension. To conclude: both normal and diabetic males eliminate a greater quantity of HS than females. Normoalbuminuric diabetic patients of both types eliminate a greater quantity of HS regardless of arterial pressure and time since onset of diabetes.

Urinary heparan sulphate is increased in normoalbuminuric diabetic patients.

Forty-nine normoalbuminuric diabetic patients were studied: 22 males and 27 females, in whom urinary heparan sulphate (HS), albuminuria, creatininemia, creatininuria, creatinine clearance, HbA1c and arterial pressure (AP) were determined. Two groups were discerned: group 1, Type 1 DM, diabetic cases (n = 16); and group 2, Type 2 DM diabetic cases (n = 33). Patients were compared with 24 healthy controls: 12 men and 12 women, who showed a mean value +/- SD of 0.36 +/- 0.18 mg/24 h HS with significant differences between males and females (0.43 +/- 0.15 versus 0.28 +/- 0.17, respectively; p = 0.02). The total population of diabetic cases rendered a mean of 0.68 +/- 0.44 and comparison with controls proved highly significant (p < 0.001). Globally, male patients had a mean of 0.82 +/- 0.48 and females 0.54 +/- 0.35, with p < 0.02. Group 1 and 2 values of HS were not significantly different. HS levels failed to correlate either with age, body mass index (BMI), time since onset of diabetes, albuminuria, creatininemia, creatininuria, creatinine clearance, HbA1c or arterial hypertension. To conclude: both normal and diabetic males eliminate a greater quantity of HS than females. Normoalbuminuric diabetic patients of both types eliminate a greater quantity of HS regardless of arterial pressure and time since onset of diabetes.

Valores de referencia de apoproteínas B100, A-I, A-II y E en mujeres premenopáusicas de la República Argentina / Reference values of apoproteins B100, A-I, A-II and E in premenopausal argentine women

Existe una relación epidemiológica entre el perfil apolipoproteico y el riesgo cardiovascular. Se han realizado pocos estudios en mujeres y menos aún en la mujeres premenopáusicas. Los objetivos del presente trabajo fueron determinar los valores de referencia en mujeres premenopáusicas clínicamente sanas de las apolipoproteínas B100, A-I, A-II y E, y correlacionarlos con los valores lipídicos de: colesterol de HDL Total (C-HDL Total), C-HDL2, C-HDL3, C-LDL y triglicéridos de VLDL (Tg-VLDL). Para ello se estudiaron 129 mujeres con perfil lipoproteico normal, de edades entre 37 y 50 años. Los valores de las apolipoproteínas fueron: apo B100: 1,17 ñ0,21 g/L (Media ñ 0,21 g/L (Media ñ DE), apo A-I: 1,34 ñ 0,24 g/L, apo A-II: 0,343 ñ 0,07 g/L y apo E: 0,065 ñ 0,017 g/L. Se obtuvieron: una media para C-HDL Total de 54,0 ñ 13,1 mg/dl, de C-HDL2 de 13,6 ñ 8,6 mg/dl y de C-HDL3 de 39,3 ñ 7,9 mg/dl. El C-LDL fue de 116,0 ñ 26,00 mg/dl. En este trabajo se informan por primera vez en Argentina los valores de referencia de concentración plasmática de apo B100, apo A-I vs C-HDL Total: 0,61 (p < 0,019), apo A-I vs C-HDL 2: 0,32 (p < 0,01), apo A-I vs C-HDL3: 0,52 (p < 0,01). La correlación de apo A-II vs C-HDL fue de 0,28 (p < 0,01). La correlación de apo E y Tg-VLDL fue de 0,25 (p < 0,025). Se calculó el índice de Breslow que evalúa el tamaño de HDL como cociente C-HDL/apo A-I + apo A-II expresados en moles, el valor obtenido fue de 21,06 ñ 4,08. Este coincide con las referencias sugiriendo que en la premenopáusica no hay cambio de tamaño en las HDL (AU)

Valores de referencia de apoproteínas B100, A-I, A-II y E en mujeres premenopáusicas de la República Argentina / Reference values of apoproteins B100, A-I, A-II and E in premenopausal argentine women

Existe una relación epidemiológica entre el perfil apolipoproteico y el riesgo cardiovascular. Se han realizado pocos estudios en mujeres y menos aún en la mujeres premenopáusicas. Los objetivos del presente trabajo fueron determinar los valores de referencia en mujeres premenopáusicas clínicamente sanas de las apolipoproteínas B100, A-I, A-II y E, y correlacionarlos con los valores lipídicos de: colesterol de HDL Total (C-HDL Total), C-HDL2, C-HDL3, C-LDL y triglicéridos de VLDL (Tg-VLDL). Para ello se estudiaron 129 mujeres con perfil lipoproteico normal, de edades entre 37 y 50 años. Los valores de las apolipoproteínas fueron: apo B100: 1,17 ñ0,21 g/L (Media ñ 0,21 g/L (Media ñ DE), apo A-I: 1,34 ñ 0,24 g/L, apo A-II: 0,343 ñ 0,07 g/L y apo E: 0,065 ñ 0,017 g/L. Se obtuvieron: una media para C-HDL Total de 54,0 ñ 13,1 mg/dl, de C-HDL2 de 13,6 ñ 8,6 mg/dl y de C-HDL3 de 39,3 ñ 7,9 mg/dl. El C-LDL fue de 116,0 ñ 26,00 mg/dl. En este trabajo se informan por primera vez en Argentina los valores de referencia de concentración plasmática de apo B100, apo A-I vs C-HDL Total: 0,61 (p < 0,019), apo A-I vs C-HDL 2: 0,32 (p < 0,01), apo A-I vs C-HDL3: 0,52 (p < 0,01). La correlación de apo A-II vs C-HDL fue de 0,28 (p < 0,01). La correlación de apo E y Tg-VLDL fue de 0,25 (p < 0,025). Se calculó el índice de Breslow que evalúa el tamaño de HDL como cociente C-HDL/apo A-I + apo A-II expresados en moles, el valor obtenido fue de 21,06 ñ 4,08. Este coincide con las referencias sugiriendo que en la premenopáusica no hay cambio de tamaño en las HDL

[Low density lipoprotein rich in triglycerides and hepatic lipase activity in insulin-dependent diabetic patients]. / Lipoproteína de baja densidad rica en triglicéridos y actividad de lipasa hepática en pacientes diabéticos insulino-dependientes.

Genetic hepatic lipase (HL) deficiency is associated with low density lipoprotein (LDL) rich in triglycerides (TG), whose affinity for B:E receptors is decreased. In rats, experimental hypoinsulinemia produces HL deficiency. However, the relation between human insulin-dependent Diabetes Mellitus (IDDM), HL activity and the characteristics of LDL have not been studied. The objective of our study is to evaluate the relation between HL activity and the chemical composition of LDL in treated IDDM patients. Subjects were 15 IDDM patients and 15 controls (C), matched for sex and body mass index (BMI). The IDDM patients were classified by the WHO criteria, were free of nephropathy and hypothyroidism, and received no medication except insulin. Controls were clinically healthy and normolipidemic with no family history of diabetes. The IDDM group was divided into two subgroups: subgroup IDDM-A (n = 9) with HL values > or = 4.3 and IDDM-B (n = 6) with HL < or = than 4.2 mumoles glycerol/ml h. the HL in IDDM was lower than in C (p < 0.001). Table 1 shows clinical data. Blood samples were drawn after 12 h fasting. Percentage of HbA1c and plasma concentrations of glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and TG were assayed. LDL was separated by sequential ultracentrifugation at densities of 1.019-1.063 g/ml and its chemical composition was analyzed. The most relevant results were: plasma TG concentration was higher in IDDM than in C (p < 0.05) (Table 2), although average values DMID not exceed the reference values of 200 mg/dl. The TG-LDL were higher in IDDM than in C: 24.8 +/- 2.7 vs 17.5 +/- 1.1 mg/dl plasma, media +/- SE, (p < 0.02). This difference reflected the values of IDDM-B, whose plasma concentrations of TG-LDL were higher than in C: 32.3 +/- 3.6 vs 17.5 +/- 1.1 mg/dl (p < 0.001), and also higher than in IDDM-A (p < 0.02). (Table 3). The chemical composition of LDL in IDDM-B contained a higher percentage of TG than C: 8.5 +/- 0.7 vs 6.8 +/- 0.3% (p < 0.05), a lower percentage of cholesterol than IDDM-A: 39.0 +/- 1.7 vs 45.2 +/- 2.2% (p < 0.05) and also a larger percentage of proteins than IDDM-A: 28.9 +/- 1.9 vs 20.8 +/- 1.0% (p < 0.01). The correlations between TG/cholesterol and HL activity in IDDM were r = -0.53 (p < 0.05) and in IDDM-B, r = -0.81 (p = 0.05). The noteworthy result of this study is the modification of the LDL particle in IDDM, rich in TG in patients with low HL activity. Anomalies in the chemical composition of LDL like those described decrease the uptake of this particle by its physiological B:E receptors. It has recently been demonstrated that LDL is an indisoluble association of lipids and apoproteins, and that both act simultaneously to hold the apoB in a spatial position that expresses normal epitopes. It has been described that particles of LDL rich in TG and poor in cholesterol, shows low affinity for LDL receptors in human fibroblasts. Also in IDDM the interaction of LDL rich in TG with B:E receptors is decreased. This might be one more mechanism contributing to the accelerated atherosclerosis of these patients. Our results suggest that there may be a threshold of HL activity for the complete hydrolysis of the TG of LDL, for the normalization of the TG/cholesterol relation and for the conformation of typical LDL particles.

Lipoproteína de baja densidad rica en triglicéridos y actividad de lipasa hepática en pacientes diabéticos insulino-dependientes. / [Low density lipoprotein rich in triglycerides and hepatic lipase activity in insulin-dependent diabetic patients]

Genetic hepatic lipase (HL) deficiency is associated with low density lipoprotein (LDL) rich in triglycerides (TG), whose affinity for B:E receptors is decreased. In rats, experimental hypoinsulinemia produces HL deficiency. However, the relation between human insulin-dependent Diabetes Mellitus (IDDM), HL activity and the characteristics of LDL have not been studied. The objective of our study is to evaluate the relation between HL activity and the chemical composition of LDL in treated IDDM patients. Subjects were 15 IDDM patients and 15 controls (C), matched for sex and body mass index (BMI). The IDDM patients were classified by the WHO criteria, were free of nephropathy and hypothyroidism, and received no medication except insulin. Controls were clinically healthy and normolipidemic with no family history of diabetes. The IDDM group was divided into two subgroups: subgroup IDDM-A (n = 9) with HL values > or = 4.3 and IDDM-B (n = 6) with HL < or = than 4.2 mumoles glycerol/ml h. the HL in IDDM was lower than in C (p < 0.001). Table 1 shows clinical data. Blood samples were drawn after 12 h fasting. Percentage of HbA1c and plasma concentrations of glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and TG were assayed. LDL was separated by sequential ultracentrifugation at densities of 1.019-1.063 g/ml and its chemical composition was analyzed. The most relevant results were: plasma TG concentration was higher in IDDM than in C (p < 0.05) (Table 2), although average values DMID not exceed the reference values of 200 mg/dl. The TG-LDL were higher in IDDM than in C: 24.8 +/- 2.7 vs 17.5 +/- 1.1 mg/dl plasma, media +/- SE, (p < 0.02). This difference reflected the values of IDDM-B, whose plasma concentrations of TG-LDL were higher than in C: 32.3 +/- 3.6 vs 17.5 +/- 1.1 mg/dl (p < 0.001), and also higher than in IDDM-A (p < 0.02). (Table 3). The chemical composition of LDL in IDDM-B contained a higher percentage of TG than C: 8.5 +/- 0.7 vs 6.8 +/- 0.3

(p < 0.05), a lower percentage of cholesterol than IDDM-A: 39.0 +/- 1.7 vs 45.2 +/- 2.2

(p < 0.05) and also a larger percentage of proteins than IDDM-A: 28.9 +/- 1.9 vs 20.8 +/- 1.0

(p < 0.01). The correlations between TG/cholesterol and HL activity in IDDM were r = -0.53 (p < 0.05) and in IDDM-B, r = -0.81 (p = 0.05). The noteworthy result of this study is the modification of the LDL particle in IDDM, rich in TG in patients with low HL activity. Anomalies in the chemical composition of LDL like those described decrease the uptake of this particle by its physiological B:E receptors. It has recently been demonstrated that LDL is an indisoluble association of lipids and apoproteins, and that both act simultaneously to hold the apoB in a spatial position that expresses normal epitopes. It has been described that particles of LDL rich in TG and poor in cholesterol, shows low affinity for LDL receptors in human fibroblasts. Also in IDDM the interaction of LDL rich in TG with B:E receptors is decreased. This might be one more mechanism contributing to the accelerated atherosclerosis of these patients. Our results suggest that there may be a threshold of HL activity for the complete hydrolysis of the TG of LDL, for the normalization of the TG/cholesterol relation and for the conformation of typical LDL particles.

[Incorporation of squid oil fatty acids to plasma lipoproteins in rats]. / Incorporación de ácidos grasos de aceite de calamar a lipoproteínas plasmáticas en ratas.

There is clinical and epidemiologic evidence that long chain polyunsaturated fatty acids of the n-3 series, (AGPI n-3): eicosapentaenoic acid (EPA 20:5 n-3) and docosahexaenoic acid (22:6 n-3) decrease the incidence of heart attack, coronary restenosis and also platelet aggregation, leukotriene synthesis and arterial pressure. They also decrease significantly the severity of atherosclerosis in hyperlipidemic models. Some of these results are obtained after daily intake of 3g or more of AGPI n-3. Marine oils are very rich in AGPI n-3 but rarely the amount is larger than 20%. Due to this fact there is great interest in the possibility of obtaining concentrates of AGPI n-3 with a high coefficient of intestinal absorption. EPA and DHA ethyl esters are able to be concentrated over 90% but their absorption is incomplete. For the moment AGPI n-3 can be concentrated as free fatty acids (AGL). Squid oil (Illex argentinus) is one of the natural oils with the highest concentration of AGPI n-3 (31 to 34%). In this paper, we have studied the incorporation of AGPI n-3 to plasmatic lipoproteins of rats fed during 28 days with diets supplemented with squid oil (Ac) or AGL obtained from the same oil. Both groups were compared with a control group (C, n = 5) fed on a standard diet. The composition of oil fatty acids and of AGL is almost identical: EPA 13.6% and DHA 17.7% (Table 1). Daily intake of AGPI n-3 was very similar: in the Ac group (n = 7) 80 mg/day and in the AGL group (n = 7) 90 mg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Incorporacion de acidos grasos de aceite de calamar a lipoproteinas plasmaticas en ratas / Incorporation of squid oil fatty acids to plasma lipoproteins in rats

Se estudió la absorción e incorporación de ácidos grasos poliinsaturados de cadena larga de la serie n-3 (AGPI n-3) a lipoproteínas plasmáticas de ratas. Se suplementó la dieta de 2 grupos de 7 ratas durante 28 días con aceite de calamar (Ac) n=7 o con ácidos grasos libres de aceite de calamar (AGL) n=7. Ambos preparados tenían igual composición de ácidos grasos y 13,6% de elcosapentanoico, EPA 20:5 n-3 y 17.7% de docosahexaenoico, DHA 22:6 n-3. El grupo Ac ingirió 80 mg/día de AGPI n-3 el AGL 90 mg/día. Se verificó un similar incremento del EPA y DHA plasmáticos en ambos grupos (p < 0,01), descenso del ácido araquidónico, AA 20Ñ4 n-6 (Acp < y AGL p < 0,02) e incremento del linoleico, LA 18:2 n-6 (Ac p<0,01 y AGL p<0,02) y en menor grado del dihomogammalinolénico, DHGLA 20:3 N-6 (Ac p<0,05). Las modificaciones del AA, LA y DHGLA se deberían al efecto inhibidor de los AGPI n-3 sobre las d 6 y d 5 desaturasas, que produce disminución de la síntesis endógena de AA y acumulación de sus respectivos sustratos (LA y DHGLA). A pesar de que el aporte de DHA fue mayor que el de EPA el incremento porcentual del EPA fue mayor, lo que se debería a la retroconvensión del DHA. No se verificó modificación en los niveles de ácidos grasos no esteritificados, colesterol y triglicéridos plasmáticos ni en la seudocolinesterasa, alanino-amino-transferasa y aspartato-amino transferasa séricas. Se concluyó que la absorción intestinal de AGPI n-3 como AGL es equivalente a la de los aportados como triglicéridos (AU)

Incorporación de ácidos grasos de aceite de calamar a lipoproteínas plasmáticas en ratas. / [Incorporation of squid oil fatty acids to plasma lipoproteins in rats]

There is clinical and epidemiologic evidence that long chain polyunsaturated fatty acids of the n-3 series, (AGPI n-3): eicosapentaenoic acid (EPA 20:5 n-3) and docosahexaenoic acid (22:6 n-3) decrease the incidence of heart attack, coronary restenosis and also platelet aggregation, leukotriene synthesis and arterial pressure. They also decrease significantly the severity of atherosclerosis in hyperlipidemic models. Some of these results are obtained after daily intake of 3g or more of AGPI n-3. Marine oils are very rich in AGPI n-3 but rarely the amount is larger than 20

. Due to this fact there is great interest in the possibility of obtaining concentrates of AGPI n-3 with a high coefficient of intestinal absorption. EPA and DHA ethyl esters are able to be concentrated over 90

but their absorption is incomplete. For the moment AGPI n-3 can be concentrated as free fatty acids (AGL). Squid oil (Illex argentinus) is one of the natural oils with the highest concentration of AGPI n-3 (31 to 34

). In this paper, we have studied the incorporation of AGPI n-3 to plasmatic lipoproteins of rats fed during 28 days with diets supplemented with squid oil (Ac) or AGL obtained from the same oil. Both groups were compared with a control group (C, n = 5) fed on a standard diet. The composition of oil fatty acids and of AGL is almost identical: EPA 13.6

and DHA 17.7

(Table 1). Daily intake of AGPI n-3 was very similar: in the Ac group (n = 7) 80 mg/day and in the AGL group (n = 7) 90 mg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Incorporacion de acidos grasos de aceite de calamar a lipoproteinas plasmaticas en ratas / Incorporation of squid oil fatty acids to plasma lipoproteins in rats

Se estudió la absorción e incorporación de ácidos grasos poliinsaturados de cadena larga de la serie n-3 (AGPI n-3) a lipoproteínas plasmáticas de ratas. Se suplementó la dieta de 2 grupos de 7 ratas durante 28 días con aceite de calamar (Ac) n=7 o con ácidos grasos libres de aceite de calamar (AGL) n=7. Ambos preparados tenían igual composición de ácidos grasos y 13,6% de elcosapentanoico, EPA 20:5 n-3 y 17.7% de docosahexaenoico, DHA 22:6 n-3. El grupo Ac ingirió 80 mg/día de AGPI n-3 el AGL 90 mg/día. Se verificó un similar incremento del EPA y DHA plasmáticos en ambos grupos (p < 0,01), descenso del ácido araquidónico, AA 20Ñ4 n-6 (Acp < y AGL p < 0,02) e incremento del linoleico, LA 18:2 n-6 (Ac p<0,01 y AGL p<0,02) y en menor grado del dihomogammalinolénico, DHGLA 20:3 N-6 (Ac p<0,05). Las modificaciones del AA, LA y DHGLA se deberían al efecto inhibidor de los AGPI n-3 sobre las d 6 y d 5 desaturasas, que produce disminución de la síntesis endógena de AA y acumulación de sus respectivos sustratos (LA y DHGLA). A pesar de que el aporte de DHA fue mayor que el de EPA el incremento porcentual del EPA fue mayor, lo que se debería a la retroconvensión del DHA. No se verificó modificación en los niveles de ácidos grasos no esteritificados, colesterol y triglicéridos plasmáticos ni en la seudocolinesterasa, alanino-amino-transferasa y aspartato-amino transferasa séricas. Se concluyó que la absorción intestinal de AGPI n-3 como AGL es equivalente a la de los aportados como triglicéridos