C. Popp-Snijders

Intra-individual variation of glucose, specific insulin and proinsulin concentrations measured by two oral glucose tolerance tests in a general Caucasian population: the Hoorn Study.

SummaryWe studied the intra-individual variation in plasma glucose, specific serum insulin and serum pro-insulin concentrations, measured by two 75-g oral glucose tolerance tests in an age, sex, and glucose tolerance stratified random sample from a 50–74-year-old Caucasian population without a history of diabetes mellitus. The intra-individual variation was assessed by the standard deviation of the test-retest differences (SDdif). For subjects with normal (n=246), impaired glucose tolerance (n=198), and newly detected diabetes (n=80) classified at the first test, the following (SDdif/median level of individual average scores) were found: fasting glucose: 0.4/5.4, 0.5/5.9 and 0.7/7.2 mmol/l; 2-h glucose: 1.3/5.6, 1.8/8.5 and 2.3/12.8 mmol/l; fasting insulin: 23/76, 32/89 and 30/ 116 pmol/l; 2-h insulin: 190/303, 278/553 and 304/626 pmol/l; fasting proinsulin: 4/8, 6/13 and 9/18 pmol/l; 2-h proinsulin: 19/49, 23/84 and 33/90 pmol/l, respectively. In both glucose, proinsulin and insulin concentrations the total intra-individual variation was predominantly determined by biological variation, whereas analytical variation made only a minor contribution. The SDdif can easily be interpreted, as 95% of the random test-retest differences will be less than 2 · SDdif, or in terms of percentage, less than (2 · SDdif/median level of individual average scores) · 100. Therefore, for subjects with normal glucose tolerance, 95% of the random test-retest differences will be less than 15% (fasting glucose), 46% (2-h glucose), 61% (fasting insulin), 125% (2-h insulin), 100% (fasting proinsulin) and 78% (2-h proinsulin) of the median value of the individual average scores. No substantial independent association of either age, gender or obesity with the intra-individual variation in glucose, proinsulin, or insulin concentrations was found.

Ultraviolet Irradiation Corrects Vitamin D Deficiency and Suppresses Secondary Hyperparathyroidism in the Elderly

The objective of this study was to compare the effect of ultraviolet radiation (UV) and oral vitamin D3 on the vitamin D status and parathyroid hormone (PTH) concentration in elderly nursing home patients. The design of the study was a randomized clinical trial. The setting was a psychogeriatric nursing home. Subjects included 45 female psychogeriatric patients with a mean age of 85 years. Exclusion criteria were going outdoors more than once a week and the presence of actinic or cancer skin lesions. Intervention was random allocation of UV‐B irradiation at half the minimal erythemal dose of the lower back, three times per week during 12 weeks (UV‐B), or oral vitamin D3 400 IU/day during 12 weeks (VIT‐D), or no treatment (CONTR). Main outcome measures were change in fasting serum levels of vitamin D metabolites at 0, 2, 4, 8, and 12 weeks in the treatment groups, compared with the control group. PTH(1–84) was measured at 0 and 12 weeks. Baseline serum 25‐hydroxyvitamin D (25(OH)D) was lower than 30 nmol/l in 95% of the participants. It increased to a median value of around 60 nmol/l after 12 weeks both in the UV‐B and VIT‐D groups, whereas there was no change in the CONTR group. Serum 1,25‐dihydroxyvitamin D increased significantly in the UV‐B group. Serum calcium increased significantly in both treatment groups. Serum PTH decreased more than 30% in both treatment groups (p < 0.001), whereas there was no significant change in the control group. Irradiation with UV‐B in the very elderly for a few minutes per day leads to adequate improvement of the vitamin D status. It is as effective as oral vitamin D3 in increasing serum 25(OH)D and suppressing secondary hyperparathyroidism.

Determinants of bone mineral density in older men and women : Body composition as mediator

This study aimed to assess the relative importance of several determinants of bone mineral density (BMD) and to examine to what extent these potential determinants influence total hip BMD through body composition. The study population consisted of 522 participants (264 women and 258 men) of the Longitudinal Aging Study Amsterdam (LASA), aged 65 years and over, and living in Amsterdam and its vicinity. BMD of the total hip was measured using dual‐energy X‐ray absorptiometry (DXA). Potential determinants of BMD were age, weight change since age 25 years, lifestyle factors, chronic diseases, medication use, and hormonal factors. Potential mediators between the possible determinants and BMD were two measures of body composition: fat mass (FM) and appendicular muscle mass (AMM). Multiple regression analyses including all potential determinants in one model without body composition identified age, weight change, walking activity, and sex hormone‐binding globulin (SHBG) as independent determinants for total hip BMD in women. In men, current smoking, participation in sports, and parathyroid hormone (PTH) concentration were independently associated with total hip BMD. When total hip BMD was regressed on the potential determinants and each measure of body composition, it appeared that FM, and to a lesser extent, muscle mass (MM), were independently related to BMD. In women, adjustment for FM reduced the strength of the associations of weight change, walking activity, and SHBG with total hip BMD. Adjustments for MM did not influence the associations between the determinants and BMD. In men, neither FM nor MM appeared to play a mediating role between the determinants and BMD. It can be concluded that (1) FM and MM are strong independent determinants of total hip BMD and that (2) FM possibly plays a mediating role in the association of weight change, walking activity, and SHBG with total hip BMD in women.

Predictors of fractures in elderly women

Abstract: In a prospective study of 348 apparently healthy women, aged 70 years and over (mean 80.3 years), we examined bone mineral density (BMD), biochemical markers of bone metabolism, and some easily measurable predictors in relation to hip and osteoporotic fractures. In addition, we constructed risk profiles for hip and osteoporotic fractures. At baseline, BMD at both hips, using dual-energy X-ray absorptiometry, body height and body weight were measured. At the same time, serum and urine samples were obtained for biochemical analysis. Serum samples were analyzed for vitamin D metabolites, sex hormone binding globulin, serum intact parathyroid hormone, osteocalcin, alkaline phosphatase, phosphate, albumin, calcium and creatinine. In 2 h fasting urine, hydroxyproline, type I collagen crosslinked N-telopeptide (NTx) and calcium excretion were measured. Furthermore, easily measurable predictors, such as previous fracture, body mass index (BMI) and mobility were assessed. During the follow-up period (mean duration 5.0 years), hip and any osteoporotic fracture (wrist, humerus or hip fracture) occurred in 16 and 33 participants, respectively. Data were analyzed using Cox regression analysis. BMD of the trochanter (per 1 SD decrease) and previous fracture were most strongly associated with hip fractures (adjusted relative risk (RR) = 3.0, 95% confidence interval (CI): 1.4–6.6; RR = 4.2, 95% CI: 1.5–11.6, respectively) and osteoporotic fractures (RR = 1.8, 95% CI: 1.1–2.8; RR = 2.9, 95% CI: 1.5–5.7, respectively). Previous fracture, BMI and mobility were identified as easily measurable predictors for hip fractures, whereas previous fracture, use of loop diuretics and age were predictors for osteoporotic fractures in the risk profile model. The risk of fractures can be predicted with three easily measurable predictors. This study confirms the importance of previous fracture as a predictor for hip fractures and other fractures. It also shows that the use of loop diuretics is a predictor for osteoporotic fractures.

The Effects of Intra-Uterine Growth Retardation and Postnatal Undernutrition on Onset of Puberty in Male and Female Rats

The nutritional status, prenatally and early postnatally, plays a critical role in postnatal growth and development. Early malnutrition may change the original programming of organs, especially those in developmental phases, which can result in long-term changes in metabolism. The association between a low birth weight and the increased risk on type 2 diabetes, hypertension and cardiovascular disease is well known.In the present study we investigated whether intrauterine malnutrition or direct postnatal food restriction affects the onset of puberty in male and female rats. Intrauterine growth retardation (IUGR) was induced by uterine artery ligation on day 17 of gestation and postnatal food restriction (FR) by litter-enlargement to 20 pups per mother from day 2 after birth until weaning (24 d). Both models of malnutrition resulted in a persistent growth failure postnatally. The parameter of the onset of puberty was balano-preputial-separation (BPS) in the male rat and vaginal opening (VO) in the female rat.In both male IUGR (n = 26) and FR (n = 20) rats, the age at BPS was significantly delayed, with 48.1 ± 1.9 d (p < 0.0001) and 50.4 ± 2.9 d (p < 0.0001), respectively, compared with controls (n = 30) with 45.8 ± 1.4 d. In female IUGR rats (n = 37) the age at VO was significantly delayed, with 37.4 ± 2.7 d (p < 0.04) compared with 36.1 ± 1.5 d in controls (n = 23), but not in female FR rats (n = 18) with 36.5 ± 2.2 d. Weight at onset of puberty did not differ between male IUGR and control rats, 194.5 ± 20.0 g and 201.7 ± 16.8 g, respectively, but was significantly lower in male FR rats with a weight of 175.6 ± 17.5 g (p < 0.0001). In female IUGR as well as in female FR rats, weight at onset of puberty was significantly lower compared with controls: weight in IUGR 106.1 ± 13.1 g (p < 0.001), weight in FR 85.3 ± 7.6 g (p < 0.0001) and weight in controls 116.9 ± 9.3 g.We conclude that early malnutrition, during late gestation or direct postnatally, results in a delayed onset of puberty in IUGR and FR male rats and in IUGR female rats, but not in FR female rats. The onset of puberty in these growth retarded rats as well as in controls does not depend on the achievement of a certain, crucial weight. The perinatal period appears to be a “critical time period” for the maturational process of pubertal development.

Changes in membrane lipid composition of human erythrocytes after dietary supplementation of (n − 3) polyunsaturated fatty acids. Maintenance of membrane fluidity

The effect of dietary (n-3) polyunsaturated fatty acids on erythrocyte membrane lipid composition, fluidity, and flexibility was studied in seven healthy subjects. An eight weeks daily supplementation of 3 g of the (n-3) fatty acids eicosapentaenoic and docosahexaenoic acid resulted in an increased unsaturation of erythrocyte phosphatidylcholine (PC) and phosphatidylethanolamine (PE). This change was accompanied by a slight decrease in PC and PE content (P less than 0.05) and an increase in sphingomyelin content (P less than 0.01). The erythrocyte membrane fluidity, measured with electron spin resonance of intact erythrocytes and with fluorescence polarization of erythrocyte ghosts did not change. No change was seen in the viscosity of erythrocyte suspensions of haematocrit = 0.80, measured at various shear rates. The supplementation caused a 42% decrease in plasma triacylglycerol levels. We suggest that the change in the erythrocyte membrane fatty acid composition induced by the dietary supplementation of (n-3) fatty acids might be counteracted by a change in the phospholipid class distribution, resulting in overall maintenance of membrane fluidity.

Body Mass Index, Body Composition, and Leptin at Onset of Puberty in Male and Female Rats after Intrauterine Growth Retardation and after Early Postnatal Food Restriction

In this study we examined the body composition at onset of puberty in intrauterine growth retarded (IUGR), postnatal food restricted (FR), and control male and female rats. IUGR was induced by ligation of the uterine artery on d 17 of gestation and FR by litter enlargement to 20 pups per mother from d 2 after birth until weaning (d 24). We defined onset of puberty as balanopreputial separation in male rats and vaginal opening in female rats. We calculated body mass index, measured body composition with dual-energy x-ray absorptiometry, and measured leptin concentrations in serum. It was reported previously that early malnutrition, either during late gestation or immediately postnatally, results in a delayed onset of puberty in IUGR and FR male rats and in IUGR female rats, but not in FR female rats. In IUGR male rats at balanopreputial separation and in IUGR female rats at vaginal opening no differences were found in body mass index, body composition, and leptin levels compared with controls. FR male rats had a significantly lower percentage of fat and serum leptin concentrations at balanopreputial separation. FR female rats had a significantly lower body mass index, percentage of fat, and serum leptin concentrations at vaginal opening. We conclude that the onset of puberty in the rat is not dependent on a certain percentage of body fat or a certain threshold of circulating levels of leptin and that food deprivation during different “critical” time periods around birth results in different effects in later life.

Effect of dietary cod-liver oil on the lipid composition of human erythrocyte membranes

The effect of dietary cod-liver oil on factors which characterize membrane lipid fluidity was studied. To six volunteers a daily supplement of 15 ml of cod-liver oil, providing 3 g of omega 3 fatty acids, was given for 2 weeks. Changes induced by the supplement in the fatty acid patterns of the individual erythrocyte phospholipid classes did not occur at the same rate or in the same degree. A rapid incorporation of omega 3 fatty acids in plasma lipids and in erythrocyte phosphatidyl choline, at the expense of linoleic acid, was seen, resulting in increased total unsaturation. A slower and quantitatively smaller incorporation of omega 3 fatty acids in erythrocyte phosphatidyl ethanolamine and phosphatidyl serine was seen. No change in the fatty acid pattern of sphingomyelin was seen. Withdrawal of the supplement for 2 weeks did partly reverse the cod-liver oil induced changes in erythrocyte phosphatidyl choline, while the changes in erythrocyte phosphatidyl ethanolamine and phosphatidyl serine lasted. Neither a change in distribution of erythrocyte phospholipid classes, nor in the erythrocyte cholesterol/phospholipid ratio was found. The observed changes in lipid composition are indicative of an increased lipid fluidity.

Fasting proinsulin and 2-h post-load glucose levels predict the conversion to NIDDM in subjects with impaired glucose tolerance: The Hoorn Study

SummaryThe aims of the present study were to observe the natural history of impaired glucose tolerance and to identify predictors for development of non-insulin-dependent diabetes mellitus (NIDDM). A survey of glucose tolerance was conducted in subjects aged 50–74 years, randomly selected from the registry of the middle-sized town of Hoorn in the Netherlands. Based on the mean values of two oral glucose tolerance tests subjects were classified in categories of glucose tolerance according to the World Health Organization criteria. All subjects with impaired glucose tolerance (n=224) were invited to participate in the present study, in which 70% (n=158) were subsequently enrolled. During follow-up subjects underwent a repeated paired oral glucose tolerance test. The mean follow-up time was 24 months (range 12–36 months). The cumulative incidence of NIDDM was 28.5% (95% confidence interval 15–42%). Age, sex, and anthropometric and metabolic characteristics at baseline were analysed simultaneously as potential predictors of conversion to NIDDM using multiple logistic regression. The initial 2-h post-load plasma glucose levels and the fasting proinsulin levels were significantly (p<0.05) related to the incidence of NIDDM. Anthropometric characteristics, the 2-h post-load specific insulin levels and the fasting proinsulin/fasting insulin ratio were not related to the incidence of NIDDM. These results suggest that beta-cell dysfunction rather than insulin resistance plays the most important role in the future development of diabetes in a high-risk Caucasian population.

Bone mineral density and markers of bone turnover in young adult survivors of childhood lymphoblastic leukaemia

In order to determine if a serious disease like childhood acute lymphoblastic leukaemia (ALL) and the treatment necessary to cure the patients has long term effects on bone mass, we assessed bone mineral density (BMD) and several parameters involved in bone formation in a group of young adult survivors of ALL.