Lipoprotein metabolism in patients with type 1 diabetes under intensive insulin treatment.

BACKGROUND: Type 1 diabetes (T1DM) is frequently accompanied by dyslipidemia related with insulin-dependent steps of the intravascular lipoprotein metabolism. T1DM dyslipidemia may predispose to precocious cardiovascular disease and the lipid status in T1DM under intensive insulin treatment has not been sufficiently explored. The aim was to investigate the plasma lipids and the metabolism of LDL and HDL in insulin-treated T1DM patients with high glycemic levels. METHODS: Sixteen male patients with T1DM (26 ± 7 yrs) with glycated hemoglobin >7%, and 15 control subjects (28 ± 6 yrs) were injected with a lipid nanoemulsion (LDE) resembling LDL and labeled with (14)C-cholesteryl ester and (3)H-free-cholesterol for determination of fractional clearance rates (FCR, in h-1) and cholesterol esterification kinetics. Transfer of labeled lipids from LDE to HDL was assayed in vitro. RESULTS: LDL-cholesterol (83 ± 15 vs 100 ± 29 mg/dl, p=0.08) tended to be lower in T1DM than in controls; HDL-cholesterol and triglycerides were equal. LDE marker 14C-cholesteryl ester was removed faster from plasma in T1DM patients than in controls (FCR=0.059 ± 0.022 vs 0.039 ± 0.022h-1, p=0.019), which may account for their lower LDL-cholesterol levels. Cholesterol esterification kinetics and transfer of non-esterified and esterified cholesterol, phospholipids and triglycerides from LDE to HDL were also equal. CONCLUSION: T1DM patients under intensive insulin treatment but with poor glycemic control had lower LDL-cholesterol with higher LDE plasma clearance, indicating that LDL plasma removal was even more efficient than in controls. Furthermore, HDL-cholesterol and triglycerides, cholesterol esterification and transfer of lipids to HDL, an important step in reverse cholesterol transport, were all normal. Coexistence of high glycemia levels with normal intravascular lipid metabolism may be related to differences in exogenous insulin bioavailabity and different insulin mechanisms of action on glucose and lipids. Those findings may have important implications for prevention of macrovascular disease by intensive insulin treatment.

[Metabolic profile according to leptin levels in obese patients]. / Relação entre o perfil metabólico e níveis de leptina em indivíduos obesos.

Increased body mass index and waist circumference are related to cardiovascular risk factors. Leptin is an adipocyte-produced hormone and regulates body weight. Leptin is directly related to body fat. To evaluate the relationship between leptin and metabolic profile in obese subjects, we studied 119 patients. Anthropometric, laboratory, body composition (by bioelectrical impedance) and co-morbidity data were collected. The analysis was performed in the female population (86.6%): average age: 42 +/- 13 years; hypertension, type 2 diabetes and grade III obesity were present in 61.9%, 20.2% and 58.3%, respectively. Leptin levels were positively related to insulin resistance (IR). HOMA-IR was related to metabolic abnormalities of IR. No differences were demonstrated between lipid profile, glycemia, body composition and tertiles of leptin corrected by fat weight. A significant difference in HOMA-IR was present when the 2nd and 3rd tertiles of leptin corrected by fat weight [3.4 (2.8-4.1) vs. 5.3 (4.1-6.5), p=0.011] were compared. In conclusion, leptin corrected by fat weight did not influence lipid profile and glycemia in moderate to severe obese women with similar percent body fat. Leptin should not be considered an independent factor affecting lipid metabolism.

Heterozygous Nonsense Mutation in the Androgen Receptor Gene Associated with Partial Androgen Insensitivity Syndrome in an Individual with 47,XXY Karyotype.

There are only 2 patients with 47,XXY karyotype and androgen receptor (AR) gene mutation reported in the literature, and both are diagnosed as complete androgen insensitivity syndrome (CAIS). We report a 22-year-old female with 47,XXY karyotype and atypical external genitalia. Sequencing of AR revealed the heterozygous p.Asn849Lys*32 mutation, and extensive X chromosome microsatellite analysis showed homozygosity for Xp and heterozygosity for Xq, suggesting partial X maternal isodisomy. Partial androgen insensitivity syndrome (PAIS) developed in this case, probably because of the presence of the heterozygous AR mutation and random X- inactivation of the healthy allele. This is the first report of a female patient with 47,XXY karyotype and PAIS phenotype.

Relação entre o perfil metabólico e níveis de leptina em indivíduos obesos / Metabolic profile according to leptin levels in obese patients

O aumento do índice de massa corpórea e circunferência abdominal relacionam-se com fatores de risco cardiovascular. A leptina é um hormônio secretado pelos adipócitos, que exerce funções na regulação do peso corporal e tem relação direta com a gordura. Para avaliar a relação entre leptina e perfil metabólico em indivíduos obesos, estudamos 119 pacientes. Dados antropométricos, laboratoriais, distribuição da composição corpórea pela bioimpedância e co-morbidades foram coletados. Devido ao predomínio feminino (86,6 por cento), optamos pela análise apenas das mulheres: idade média de 42 ± 13 anos, hipertensão, diabetes tipo 2 e obesidade grau III em 61,9; 20,2 e 58,3 por cento da população. Leptinemia correlacionou-se positivamente com resistência à insulina (RI) e HOMA-IR, com anormalidades metabólicas características de RI. Não observamos diferenças no perfil lipídico, glicemia e composição corpórea entre os tercis de leptinemia corrigida por quilo de gordura. O segundo tercil de leptinemia apresentou HOMA-IR menor que o terceiro tercil. [3,4 (2,8­4,1) vs. 5,3 (4,1­6,5), p= 0,011]. Concluímos que leptina corrigida por quilo de gordura não influenciou o perfil lipídico e a glicemia em mulheres com obesidade moderada a grave com semelhante percentual de gordura. A leptina não deve ser considerada como fator que atue de forma independente no metabolismo lipídico.

Increased body mass index and waist circumference are related to cardiovascular risk factors. Leptin is an adipocyte-produced hormone and regulates body weight. Leptin is directly related to body fat. To evaluate the relationship between leptin and metabolic profile in obese subjects, we studied 119 patients. Anthropometric, laboratory, body composition (by bioelectrical impedance) and co-morbidity data were collected. The analysis was performed in the female population (86.6 percent): average age: 42 ± 13 years; hypertension, type 2 diabetes and grade III obesity were present in 61.9 percent, 20.2 percent and 58.3 percent, respectively. Leptin levels were positively related to insulin resistance (IR). HOMA-IR was related to metabolic abnormalities of IR. No differences were demonstrated between lipid profile, glycemia, body composition and tertiles of leptin corrected by fat weight. A significant difference in HOMA-IR was present when the 2nd and 3rd tertiles of leptin corrected by fat weight [3.4 (2.8­4.1) vs. 5.3 (4.1­6.5), p= 0.011] were compared. In conclusion, leptin corrected by fat weight did not influence lipid profile and glycemia in moderate to severe obese women with similar percent body fat. Leptin should not be considered an independent factor affecting lipid metabolism.