Pioglitazone increases non-esterified fatty acid clearance in upper body obesity.

AIMS/HYPOTHESIS: Plasma NEFA concentrations are largely determined by adipose tissue lipolysis. Insulin suppression of lipolysis is commonly impaired with insulin resistance and improves with thiazolidinedione treatment of type 2 diabetes. The present studies were designed to assess the effects of thiazolidinedione on NEFA (oleate) metabolism that are independent of improved glycaemic control. MATERIALS AND METHODS: We measured plasma oleate concentration and flux ([(3)H]oleate), glucose kinetics ([6-(2)H(2)]glucose) and substrate oxidation (indirect calorimetry) before and after pioglitazone (30 mg/day for approximately 20 weeks) in 20 non-diabetic adults with upper body obesity. To assess the effects of improved insulin sensitivity per se we performed the same measurements in a matched group of volunteers treated with diet/exercise. Half of the two groups underwent these measurements during a hyperinsulinaemic-euglycaemic clamp, and the other half had their measurements taken during a (control) saline infusion before and after the intervention. RESULTS: Both interventions increased insulin-stimulated glucose disposal and reduced plasma oleate concentrations during the insulin clamp. After diet/exercise, oleate flux decreased (p=0.03) during the insulin clamp and oleate clearance remained unchanged (p=0.55), whereas in the pioglitazone group, oleate flux during the clamp was unchanged (p=0.97) and oleate clearance increased (p=0.003). Oleate clearance in the saline control condition was increased in the pioglitazone group compared with the diet/exercise group (p=0.02). CONCLUSIONS/INTERPRETATION: In insulin-resistant, non-diabetic adults, pioglitazone increases NEFA clearance during physiological hyperinsulinaemia, whereas improved insulin sensitivity achieved by diet/exercise does not alter NEFA clearance but enhances insulin suppression of NEFA release. This action of pioglitazone may contribute to improved glucose metabolism in type 2 diabetes.

[Diagnosis of maternal and infant health in Palestine]. / Diagnóstico de salud maternoinfantil en Palestina.

OBJECTIVE: To describe the health situation of the target population (women between 15 and 45 and children from 0 to 3), living in the towns on the West Bank in which the 12 dispensaries of the Palestine NGO Health Services Council were located, in order to plan a programme of support activities for that NGO. DESIGN: Crossover survey. Descriptive analysis of the data. SETTING: 12 towns in the 5 districts of the West Bank (Palestine) between May and July 1994. PARTICIPANTS: Women of a fertile age (15 to 45) and children between 0 and 3 living in the towns where the 12 dispensaries of the NGO Health Services Council were located. MEASUREMENTS AND MAIN RESULTS: Social, demographic and health variables of the population group involved, the availability of primary care services and the pattern of health service use were studied. Worthy of mention were the average fertility of fertile women of 4.55 deliveries (CI 95%, 4.30-4.80), the use of family planning methods by 61% of the women surveyed, the low indices of mother and infant malnutrition, and the frequency of episodes of acute respiratory infections and diarrhoea in the under-3s. The availability of health services in these communities is wide. The non-governmental and private Palestinian services were preferred for antenatal control, whereas the Israeli government services were preferred for deliveries, as these services had more resources. CONCLUSIONS: The findings were typical of an intermediately developed society, similar to neighbouring countries. The multiplicity of health services available and their lack of coordination could make the application of a unitary health policy in the area difficult.

Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition.

There is net outward flow of fatty acids from adipose tissue in the fasted state but net inward flow and storage in the postprandial state. We investigated how this is regulated. Arteriovenous differences were measured across a subcutaneous adipose depot in six normal subjects before and for 5 h after a meal containing 80 g fat and 80 g carbohydrate. In five further experiments, insulin was infused at 40 mU.m-2.min-1 from 30 min after the meal, clamping the plasma glucose. Net transcapillary fatty acid flow changed from negative (outward flow from tissue to capillaries) in the postabsorptive state to consistently positive (net inward flow, implying fat storage) after the meal despite continued net efflux of fatty acids into venous blood. In the "clamped" experiments (with additional insulin), net fatty acid efflux in the venous blood was suppressed and positive transcapillary flux (storage) was more marked. Regulation of fatty acid flow appeared to depend on coordinated changes in hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL) action and fatty acid esterification. Additional insulin caused no further suppression of HSL or activation of LPL but markedly stimulated fatty acid retention (presumed to represent esterification). In the absence of additional insulin, a high proportion of the fatty acids liberated by LPL are released into the venous plasma in both postabsorptive and postprandial states. We hypothesize that this "loss" of fatty acids is necessary to give precise control to the pathway of fat storage.