Alteraciones glucémicas en los pacientes con enfermedad renal crónica / Glycaemic changes in patients with chronic kidney disease

En Argentina no se han realizado estudios destinados a establecer la prevalencia de disglucemias (glucemia alterada en ayunas [GAA], tolerancia alterada a la glucosa [TAG] y diabetes mellitus [DM]) en pacientes con enfermedad renal. Se decidió realizar un estudio observacional, evaluando la frecuencia con prueba de tolerancia oral a glucosa (PTOG) en pacientes con enfermedad renal crónica (ERC), sin registro de disglucemia en sus historias clínicas. Se realizó PTOG a 254 pacientes (60,62% masculinos), con ERC estadios 3, 4 y 5, en tratamiento conservador, hemodiálisis o trasplante. Los resultados mostraron pacientes con valores de DM: 10 pacientes según ayunas exclusivamente (3,94%; IC 95%: 1,35-6,53%); exclusivamente segunda hora, 11 pacientes (4,33%; IC 95%: 1,63-7,03%); por ambos criterios, 15 pacientes (5,91%; IC 95%: 2,81-9,00%); por al menos un criterio, 36 pacientes (14,17%; IC 95%: 9,69-18,66%). En análisis multivariado, la DM se asoció con valor de cintura (OR=1,033 por cm; IC 95%: 1,005-1,062; p=0,019) y con tratamiento sustitutivo vs. conservador (OR=0,41; IC 95%: 0,19-0,92; p=0,028). La GAA (criterio ADA) fue del 19,75% en tratamiento conservador vs. 9,24% en tratamiento sustitutivo, con diferencia estadísticamente significativa. No fue significativa la diferencia de TAG que evidenció 24,6 y 20,3% en tratamiento conservador y sustitutivo, respectivamente. Se propone la realización de PTOG en todo paciente con ERC, ya que permite la detección de todo el rango de disglucemias desconocidas, evitando el subdiagnóstico y favoreciendo la realización de tratamientos para evitar su progresión, en caso de estar ante la presencia de un grupo de riesgo para DM (GAA o TAG), así como la elección de la medicación más adecuada para el trasplante o el inicio del tratamiento de nuevos casos de DM no diagnosticada, para disminuir la morbimortalidad (AU)

In Argentina, there have been no studies aimed at establishing the prevalence of dysglycaemia (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] and diabetes mellitus [DM]) in patients with chronic kidney disease (CKD). Our group decided to conduct an observational study to evaluate the frequency with oral glucose tolerance test (OGTT) in CKD patients with no previous data for dysglycaemia in their medical records. OGTT was performed in 254 patients (60.62% male) with stage 3, 4 and 5 CKD under conservative treatment, haemodialysis or transplantation. Results for DM were found in 10 patients according to fasting glucose alone (3.94%; 95% CI: 1.35-6.53%), 11 patients with exclusively the second hour criterion (4.33%; 95% CI: 1.63-7.03%), 15 with both criteria (5.91%; 95% CI: 2.81-9.00%) and 36 patients with at least one criteria (14.17%; 95% CI: 9.69-18.66%). In a multivariate analysis, DM was associated with waist circumference (OR=1.033 per cm; 95% CI, 1.005 to 1.062; P=.019) and with conservative treatment vs. replacement therapy (OR=0.41; 95% CI: 0.19-0.92;P=.028). IGT was evident in 24.6% and 20.3 on conservative vs. replacement therapy, with no statistically significant difference. IFG (ADA criteria) was 19.75 vs. 9.24% in conservative vs. replacement therapy, with a statistically significant difference. OGTT is suggested for all CKD patients since it is able to detect the full range of unknown dysglycaemias, which avoids underdiagnoses and favours performing treatments to prevent progression in DM risk groups (IFG and/or IGT). It also aids in the selection of the most appropriate medication for transplantation or treatment initiation in new cases of undiagnosed DM to decrease morbidity and mortality (AU)

Hepatic lipase activity is increased in non-alcoholic fatty liver disease beyond insulin resistance.

BACKGROUND AND OBJECTIVE: Hepatic lipase is a lipolytic enzyme mostly synthesized and localized at the surface of liver sinusoidal capillaries, which hydrolyses triglycerides and phospholipids of intermediate density, large low density (LDL) and high density lipoproteins. Hepatic lipase activity is increased in insulin resistant states. Non-alcoholic fatty liver disease (NAFLD) is characterized by insulin resistance. However, at present, no data are available regarding the behaviour of hepatic lipase with regard to the degree of hepatic steatosis. Our aim was to evaluate hepatic lipase activity in NAFLD patients and its relationship to the severity of hepatic steatosis. DESIGN AND PATIENTS: We studied 48 patients with NAFLD (diagnosed by ultrasonography and confirmed by liver biopsy) and 30 controls. Steatosis was semi-quantitatively assessed and considered as mild or grade 1, moderate or grade 2 and severe or grade 3. MEASUREMENTS: hepatic lipase activity, lipid and lipoprotein profile (including intermediate density lipoproteins and dense LDL), adiponectin, insulin, glucose and high sensitivity C-reactive protein were measured. Homeostasis model assessment for insulin resistance (HOMA) index was calculated. RESULTS: Patients with hepatic steatosis presented with higher hepatic lipase activity, HOMA and dense LDL and lower levels of adiponectin, high density lipoproteins, cholesterol and apoA-I. Hepatic lipase activity positively correlated significantly with the severity of hepatic steatosis. Hepatic lipase correlated with a more atherogenic profile and persisted higher in patients even after corrected for age, gender, body mass index, HOMA and adiponectin. CONCLUSION: The higher hepatic lipase activity in NAFLD patients contributes to a more atherogenic profile linked to increased cardiovascular risk, beyond the insulin resistance and the reduction in adiponectin.

Circulating very-low-density lipoprotein characteristics resulting from fatty liver in an insulin resistance rat model.

The close association between nonalcoholic fatty liver and insulin resistance is now widely recognized. While the former is characterized by excessive intrahepatic triglyceride accumulation, the latter induces overproduction of very-low-density lipoprotein (VLDL) particles. It has not been well elucidated whether these apparently opposite mechanisms impact on VLDL characteristics or not. The aim of the present study was to evaluate the VLDL secretion and features resulting from insulin resistance and fatty liver in rats fed a sucrose-rich diet (SRD, i.e. addition of sucrose to drinking water during 12 weeks). No differences in calorie intake were observed in comparison to controls. Both groups showed similar weight gains throughout the treatment period. However, SRD rats showed an increased proportion of body fat as assessed by X-ray absorptiometry, increased visceral obesity, liver weight and fat accumulation in the liver (p < 0.04). Histological study revealed moderate micro- and macrovesicular steatosis. Fasting insulin, triglyceride and free fatty acid (FFA) levels increased while VLDLs decreased in SRD rats (p < 0.05). The chemical composition of VLDLs of SRD rats showed a higher percentage of triglycerides, and the VLDL triglyceride/protein ratio, an estimator of lipoprotein size, suggests that VLDL particles of SRD rats are larger than those of controls (p < 0.0005). FFA levels correlated with VLDL triglycerides (r = 0.49, p = 0.03) and liver fat content correlated with plasma triglycerides (r = 0.65), VLDL triglycerides (r = 0.55) and triglyceride/protein ratio (r = 0.52, p < 0.02). The VLDL secretion rate assay showed an increase in SRD rats (p < 0.02), confirming an overproduction despite liver fat accumulation. Our findings are consistent with an insulin resistance development model in which hepatic lipid content would constitute an important determinant of a triglyceride-rich, large-particle VLDL secretion; both features would increase its atherogenic potential.