Postprandial interstitial insulin concentrations in type 2 diabetes relatives.

BACKGROUND: An endothelial barrier for the insulin transport from the circulation to the target tissues of insulin has previously been suggested to contribute to insulin resistance. The interstitial insulin concentration (I-insulin) and insulin kinetics following a mixed meal have, however, previously not been characterized in human adipose tissue. SUBJECTS AND METHODS: Eight nondiabetic first-degree relatives (FDR) of type 2 diabetes patients were recruited. Their I-insulin was measured by microdialysis after a test meal with or without oral administration of the insulin secretagogue nateglinide (120 mg). In parallel, adipose tissue blood flow and lipolysis were measured by xenon-clearance and microdialysis, respectively. RESULTS: The I-insulin increased after the test meal, and this response was more prominent on the day the subjects received the nateglinide tablet when compared with the day the subjects received the placebo tablet [I-insulin incremental area under the curve (IAUC) nateglinide 7612 +/- 3032 vs. Plac 4682 +/- 2613 pmol L(-1) min; P < 0.05, mean +/- SE]. However, the postprandial I-insulin(max)/P-insulin(max) ratio was similar on the two test days (nateglinide: 213 +/- 62 vs. 501 +/- 92 pmol L(-1), I/P-ratio: 0.38 +/- 0.06 and placebo: 159 +/- 39 vs. 410 +/- 74 pmol L(-1), I/P-ratio: 0.36 +/- 0.05). There was no difference in time of onset of insulin action in situ, or responsiveness, when comparing placebo and nateglinide. CONCLUSIONS: Microdialysis can now be used to measure the I-insulin in human adipose tissue following a mixed meal. The data also showed that the transendothelial delivery of insulin occurs rapidly, supporting the concept that transcapillary insulin transfer is a nonsaturable process in nondiabetic first-degree relatives of type 2 diabetes patients.

No acute effect of nateglinide on postprandial lipid and lipoprotein responses in subjects at risk for type 2 diabetes.

BACKGROUND: To study the acute effect of nateglinide, an insulinotropic agent, on the postprandial triglyceride and lipoprotein responses in subjects at risk for type 2 diabetes. METHODS: Six women and 10 men, with at least one first-degree relative with type 2 diabetes were included (Age: 48 +/- 7 years, BMI: 27.5 +/- 2.8 kg m(-2), P-triglycerides: 1.3 +/- 0.4 mmol L(-1), P-cholesterol: 5.4 +/- 0.6 mmol L(-1), B-glucose: 4.6 +/- 0.3 mmol L(-1)). They each had two 8-h meal tolerance tests with either nateglinide or placebo given 10 min prior to the meals in randomized order. Lipoprotein fractions were separated by density gradient ultracentrifugation. First-phase insulin secretion was assessed by an intravenous glucose tolerance test (300 mg kg(-1) body weight) and insulin sensitivity by a hyperinsulinaemic euglycaemic clamp (40 mU m(-2) min(-1)). RESULTS: The 1-h insulin levels during the meal tolerance test were significantly higher with nateglinide (577 +/- 81 vs 376 +/- 58 pmol L(-1), p < 0.001), as well as the response during the first two hours (IAUC: 41 243 +/- 5844 vs 29 956 +/- 4662 pmol L(-1) min, p < 0.01). Accordingly, nateglinide lowered the 8-h postprandial glucose response by around 60% compared to placebo (p < 0.001). In contrast, no significant lowering was seen in the excursion of postprandial triglycerides in total plasma or lipoprotein fractions. Consistently, the concentration of exogenous (apoB-48) and endogenous (apoB-100) lipoproteins was not reduced by nateglinide. CONCLUSIONS: Acute administration of nateglinide reduces, as expected, the postprandial glucose concentration, but no reduction in triglyceride or lipoprotein responses are seen in subjects at risk for type 2 diabetes.

Early alterations in the postprandial VLDL1 apoB-100 and apoB-48 metabolism in men with strong heredity for type 2 diabetes.

OBJECTIVES: To study the postprandial triglyceride-rich lipoprotein (TRL) metabolism, specifically the concentrations of very low-density lipoproteins (VLDL); from intestine (apoB-48) and liver (apoB-100), in men with normal fasting triglycerides but at increased risk of developing type 2 diabetes. DESIGN: Cross-sectional study. SUBJECTS AND SETTINGS: Sixteen healthy men with at least two first-degree relatives with type 2 diabetes were individually matched with 16 control subjects without known diabetes heredity for: age, body mass index, and fasting triglyceride level. They underwent an 8-h meal tolerance test (919 kcal, 51 g fat) during which lipoproteins were separated by density gradient ultracentrifugation. They were characterized by euglycaemic hyperinsulinaemic clamp, peak VO2, 7-day diet registration and computed tomography. RESULTS: The relatives were, as expected, more insulin resistant than the controls and had increased concentration of postprandial VLDL1 particles (49% higher for VLDL1 apoB-48, P = 0.04 and 21% higher for VLDL1 apoB-100, P = 0.048). The elevation was related to insulin sensitivity, but not to lifestyle and body composition. Moreover, the concentration of postprandial triglycerides in VLDL1 fraction was inversely related to low-density lipoprotein (LDL) size in both relatives (rs = -0.60, P = 0.03) and controls (rs = -0.72, P = 0.004). There were no differences in the concentration of triglycerides or apoB-48 and apoB-100 particles in the other fractions (plasma, chylomicron or VLDL2). CONCLUSION: Increased postprandial concentration of TRLs in the VLDL1 fraction seems to be present at an early stage in the development of diabetes and probably contributes to the excess risk of future coronary events in insulin-resistant men.

Back extensor muscle fatigability in chronic low back pain patients and controls: Relationship between electromyogram power spectrum changes and body mass index.

Back extensor muscle fatigability and its relationship to body mass index (BMI) was measured in 12 chronic nonspecific low back pain (CNLBP) patients (7 women and 5 men) and 12 healthy age-and gender-matched controls. Subjects performed Sørensen back isometric endurance test until exhaustion while EMG spectral mean power frequency (MPF) over the lumbar erector spinae muscle and endurance time were recorded. The CNLBP patients had significantly shorter endurance time than healthy controls. Spectral MPF significantly declined as time of isometric contraction progressed. Relative decrease of the MPF per minute (MPF slope) for left and right side, and pooled MPF slope was significantly higher in CNLBP patients compared with controls. In CNLBP patients the isometric endurance time correlated significantly negatively with BMI (r=-0.71). In controls BMI correlated significantly positively with MPF slopes of left (r=0.68) and right (r=0.57) side, and pooled MPF slope (r=0.62).

Aryl phosphate complexation by cationic cyclodextrins. An enthalpic advantage for guanidinium over ammonium and unusual enthalpy-entropy compensation.

The enthalpies and entropies for phosphate complexation by ammonium and guanidinium groups have been compared using cationic cyclodextrins. Aryl phosphate binding by guanidinium hosts is associated with more favorable enthalpies and less favorable entropies, consistent with the idea that guanidinium-phosphate interactions are stronger but more directional than ammonium-phosphate interactions. The slope of an enthalpy-entropy plot suggests that complexation occurs with surprisingly small changes in the order of these systems.

[Children are losers in the African AIDS epidemic. Protective network of the extended family is diminishing]. / Barnen förlorarna i Afrikas AIDSepidemi. Storfamiljens skyddsnät börjar glesna.

PIP: Africa continues to be the continent that has the most HIV-infected people, with about 7.5 million HIV-positive cases at the end of 1992. In many regions 20-40% of pregnant women were found infected at maternal health centers. It is estimated that 5% of the population of Africa is comprised of children who have lost their mother or both parents. The World Health Organization has estimated that by the year 2000 up to 9 million children will be orphans. The African extended family has always been active in the care of children, particularly the grandparents, who have experience and take in grandchildren during the weaning period. The African extended family assures that the survivors are helped in a crisis situation. The social transformation, urbanization, and migration for employment in the last decades have diminished the social significance of the extended family, especially in cities, where traditions rapidly disappear. The AIDS epidemic has decimated the productive population, spreading fear coupled with ignorance about its routes of infection, and led to a situation where almost all such children are left without care in the worst affected areas. These children, abandoned at a young age, are very vulnerable psychologically, physically, and socially. Many such children have been abused sexually, and other turn to crime in groups. Organizations like Save the Children, the Red Cross, and various churches have organized help programs for orphans. In the Kagera region of Tanzania, which is one of the most afflicted areas, the Lutheran Church has initiated an aid program for children to make sure that every children has a place to live and is provided with clothes and meals, medical care, and schooling. If not all of these orphans find the opportunity to grow up in such a safe milieu, there is a high risk that their fate will be the same as that of their parents.^ieng

The development of new psychiatric legislation in Sweden.

The development of Swedish psychiatric legislation is summarized, from the law that came into force on 1 January 1967 to the new law promulgated on 1 January 1992. There are now separate laws for (a) patients who are seriously mentally disturbed and urgently in need of psychiatric hospital care; who oppose care or evidently lack capacity to express a well-grounded opinion as to their needs; and (b) patients sentenced by court to forensic psychiatric care, who have to be seriously mentally disturbed but need not oppose care. As earlier, it seems to be possible to take care of them in general psychiatric wards but special wards for forensic psychiatric care are anticipated. Sweden so far has few such facilities.