Iron status markers in 224 indigenous Greenlanders: influence of age, residence and traditional foods

OBJECTIVE: To evaluate iron status in indigenous Greenlanders and its relationship to gender, age and intake of traditional Greenlandic foods. Methods: Serum ferritin, serum transferrin saturation and haemoglobin were evaluated in a population survey in 1993-1994 comprising 224 Greenlandic individuals (109 men) aged 19-82 yr. The participants were residents in the capital Nuuk (n=73) with a predominantly Western style of living, the town Ilulissat (n=60) with a mixture of Western and Greenlandic style of living, and the small town Uummannaq (n=91) with a predominantly Greenlandic style of living. Consumption of traditional foods was assessed by questionnaire. RESULTS: Intake of traditional foods was more prevalent among elderly than among young individuals and more frequent in Uummannaq than in Ilulissat and Nuuk. Ferritin levels were higher in men than in women (p<0.0001). Median ferritin levels were lowest in Nuuk (men, 92 microg/L; women, 40 microg/L), higher in Ilulissat (men, 104 microg/L; women, 69 microg/L) and in Uummannaq (men, 118 microg/L; women, 46 microg/L) (p<0.001). The prevalence of iron load (ferritin >200 microg/L) was lowest in Nuuk (men: 13.8%, women: 2.3%) intermediate in Ilulissat (men, 11.1%; women, 9.1%) and highest in Uummannaq (men, 32.1%; women, 21.1%). The prevalence of iron depletion (ferritin <16 microg/L) was high in Nuuk (men, 0%; women, 20.5%), and lower in Ilulissat (men, 3.7%; women, 6.1%) and in Uummannaq (men, 0%; women, 10.5%). The prevalence of iron deficiency anaemia (ferritin <13 microg/L and Hb <5th percentile for iron-replete men and women) was 0.92% in men and 0.87% in women. Correlations between age and ferritin were lowest in Nuuk (men, r(s)=0.26, p=0.2; women, r(s)=0.50, p=0.001) intermediary in Ilulissat (men, r(s)=0.37, p=0.06; women, r(s)=0.73, p<0.0001) and highest in Uummannaq (men, r(s)=0.59, p<0.0001; women, rs=0.74, p<0.0001). Intake of traditional foods was correlated with ferritin in men (r(s)=0.29, p=0.01) and women (r(s)=0.40, p<0.0001). CONCLUSION: The observed differences in estimated body iron stores in Greenlanders from the three residential areas can be explained by differences in the dietary intake of haem iron.     

Iron status in young Danes. Evaluation by serum ferritin and haemoglobin in a population survey of 634 individuals aged 14–23 yr

Abstract: Iron status was assessed by serum ferritin and haemoglobin in a population survey comprising 634 randomly selected urban Danes (312 males, 322 females) 14–23 yr old. At all ages, males had significantly higher serum ferritin and haemoglobin values than females. Males: median serum ferritin displayed a steady increase with age from 33 to 109 μg/l (r_s=0.53, p<0.0001). The prevalence of absent mobilizable body iron stores (serum ferritin <13 μg/l) was 3.5% at 16–17 yr of age, gradually declining to 0% at 22–23 yr. None of the males had iron deficiency anaemia (serum ferritin <13 μg/l and haemoglobin <129 g/l). Females: median ferritin values displayed a slight increase with age from 28 to 39 μg/l (r_s=0.19, p<0.001). The prevalence of absent iron stores was 12.5% at 16–17 yr of age, declining to 6.6% at 22–23 yr. The prevalence of iron deficiency anaemia (serum ferritin <13 μg/l and haemoglobin <121 g/l) was 4.7% at 16–17 yr of age, declining to 1.3% at 22–23 yr of age. Compared with surveys in other parts of Scandinavia, young Danes had slightly higher serum ferritin levels, and a lower prevalence of iron deficiency.     

Hemoglobin concentrations in 358 apparently healthy 80-year-old Danish men and women. Should the reference interval be adjusted for age?

BACKGROUND AND AIMS: In elderly Danes, reference intervals for hemoglobin (Hb) concentrations are derived from younger population groups. The aim was to examine reference intervals for Hb and cut-off limits for anemia by application of criteria for normality to a representative population of 80-year-olds. METHODS: Participants in this epidemiological health survey cohort were 358 subjects (171 men) 80 years of age. A dietary survey was performed in 232 subjects. Blood samples included Hb, red cell indices, serum ferritin, serum C-reactive protein, renal and hepatic function tests. Normality criteria for Hb were: 1) values in all participants; 2) values in apparently healthy subjects; 3) values in 10-year survivors. Hb was compared with muscle strength, physical performance and diet. RESULTS: In the entire series, median Hb was 140 g/L, 5-95 percentile 116-160 g/L in men, and 131 g/L, 5-95 percentile 114-147 g/L in women (p<0.001). The prevalence of anemia, as defined by World Health Organization (WHO) criteria, was 18% in men and 17% in women. Apparently healthy iron-replete men (n=129) and women (n=141) had median Hb of 141 g/L and 131 g/L. Median Hb levels were higher in 10-year surviving men (143 g/L) than in deceased men (139 g/L), whereas surviving and deceased women had similar median Hb (131 g/L). Hb and muscle strength were significantly correlated. Subjects with physical performance score >or=20 had a lower frequency of anemia. There was no correlation between Hb and dietary or supplemental iron intake. In men, Hb was correlated to meat consumption. CONCLUSIONS: WHO decision limits for anemia should not be lowered in 80-year-old subjects. "Optimal" Hb concentrations with respect to survival appear to be at least 140 g/L in men and 131 g/L in women. Further research should evaluate whether not only treating anemia, but also increasing Hb by using erythropoietin and hematinics, may improve functional status and survival in the elderly.     

Iron status in Danish men 1984-94: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload

BACKGROUND AND OBJECTIVES: From 1954 to 1987, flour in Denmark was fortified with 30 mg carbonyl iron per kg. This mandatory fortification was abolished in 1987. The aim of this study was to compare iron status in Danish men before and after abolition of iron fortification. METHODS: Iron status (serum ferritin, haemoglobin), was assessed in population surveys in Copenhagen County during 1983-84 comprising 1324 Caucasian men (1024 non-blood-donors, 300 blood donors) and in 1993-94 comprising 1288 Caucasian men (1103 non-blood-donors, 185 donors), equally distributed in age cohorts of 40, 50, 60 and 70 yr. RESULTS: In the 1984 survey median serum ferritin values in the four age cohorts in non-blood-donors were 136, 141, 133 and 111 microg/L, and in the 1994 survey 177, 173, 186 and 148 microg L(-1), respectively. The difference was significant in all age groups (P<0.001). There was no significant difference between the two surveys concerning the prevalence of small iron stores (ferritin 16-32 micro g L(-1)), depleted iron stores (ferritin <16 microg L(-1)) or iron-deficiency anaemia (ferritin <13 microg L(-1) and Hb <5th percentile for iron-replete men). However, from 1984 to 1994, the prevalence of iron overload (ferritin >300 microg L(-1)) increased from 11.3% to 18.9% (P<0.0001). During the study period there was an increase in body mass index (P<0.0001), alcohol consumption (P<0.03) and use of non-steroid anti-inflammatory drugs (NSAID) (P<0.0001), and a decrease in the use of vitamin-mineral supplements (P<0.04) and in the prevalence of tobacco smoking (P<0.0001). In contrast, median ferritin in blood donors showed a significant fall from 1984 to 1994 (103 vs. 74 micro g L(-1), P<0.02). CONCLUSION: Abolition of iron fortification reduced the iron content of the Danish diet by an average of 0.24 mg MJ(-1), and the median dietary iron intake in men from 17 to 12 mg d(-1). From 1984 to 1994, body iron stores and the prevalence of iron overload in Danish men increased significantly, despite the abolition of food iron fortification. The reason appears to be changes in dietary habits, with a lower consumption of dairy products and eggs, which inhibit iron absorption, and a higher consumption of alcohol, meat, and poultry, containing haem iron and enhancing iron absorption. The high prevalence of iron overload in men may constitute a health risk.     

Influence of age and gender on gastric acid secretion as estimated by integrated acidity in patients referred for 24-hour ambulatory pH monitoring

OBJECTIVES: Earlier studies have suggested that gastric acid secretion declines with age. Integrated acidity (IA) calculated from ambulatory 24-h pH studies provides an estimation of gastric acid secretion that is less cumbersome than nasogastric aspiration. The aim of this study was to calculate IA as a function of age and gender. METHODS: In a retrospective study, 753 ambulatory 24-h pH studies from 1994 to 2001 were analyzed. Subjects were classified according to nine age groups: <35 yr (n = 124), 35-39 yr (n = 90), 40-44 yr (n = 92), 45-49 yr (n = 111), 50-54 yr (n = 96), 55-59 yr (n = 61), 60-64 yr (n = 59), 65-69 yr (n = 42), and > or =70 yr (n = 64). Basal integrated acidity (BIA) was defined as IA between 12 midnight and 8 AM when no meals were consumed. Daytime and nocturnal IA/h was measured from 8 AM to 8 PM and from 8 PM to 8 AM. Postprandial IA (PIA) was measured for 2 h after the largest meal peak in each patient. RESULTS: Gender distribution was similar between groups (chi(2) = 6.42, 3 df, p = 0.093). Mean gastric pH was similar between genders (2.96 +/- 1.36 women; 3.01 +/- 1.42 men; p = 0.71). Women and men had similar BIA (361.1 +/- 384.1 vs 434.6 +/- 436.6 mmol/L/h, p = 0.10), daytime IA (33.5 +/- 33.0 vs 34.1 +/- 33.7 mmol/L, p = 0.90) and nocturnal IA (43.3 +/- 42.1 vs 48.0 +/- 46.6 mmol/L, p = 0.42), and PIA (38.2 +/- 58.7 vs 36.0 +/- 58.5 mmol/L/h, p = 0.47). Mean gastric pH, daytime and nocturnal IA, BIA, and PIA did not differ between age groups (p > 0.1). None of the parameters studied had a linear association with age (mean gastric pH, r = 0.106; BIA, r = -0.124; daytime IA, r = -0.046; nocturnal IA, r = -0.104; PIA, r = -0.117). CONCLUSIONS: Based on this study, we conclude that IA is unaffected by gender or age.     

Iron status in Danish women, 1984-1994: a cohort comparison of changes in iron stores and the prevalence of iron deficiency and iron overload

BACKGROUND AND OBJECTIVES: From 1954 to 1986, flour in Denmark was fortified with 30 mg carbonyl iron per kilogram. This mandatory enrichment of cereal products was abolished in 1987. The aim was to evaluate iron status in the Danish female population before and after abolishment of iron fortification. METHODS: Iron status, serum ferritin and haemoglobin, was assessed in population surveys in 1983-1984 comprising 1221 Caucasian women (1089 non-blood-donors, 130 donors) and in 1993-1994 comprising 1261 women (1155 non-blood-donors, 104 donors) equally distributed in age cohorts of 40, 50, 60 and 70 yr. RESULTS: In the 1984 survey, median ferritin values in the four age cohorts in non-blood-donors were 44, 57, 84 and 80 microg/L, and in the 1994 survey 40, 67, 97 and 95 microg/L, respectively. In 1984, premenopausal women had median ferritin of 43 microg/L and in 1994 of 39 microg/L (NS). In 1984, postmenopausal women had median ferritin of 75 microg/L and in 1994 of 93 microg/L (P < 0.0001). The prevalence of depleted iron stores (ferritin < 16 microg/L) was not significantly different in 1984 and 1994 either in premenopausal or in postmenopausal women. The prevalence of small + depleted iron stores (ferritin 300 microg/L) was unchanged in premenopausal women and had increased from 2.4% to 5.5% in postmenopausal women (P = 0.003). During the study period there was an increase in body mass index both in premenopausal and postmenopausal women (P = 0.06 and P = 0.008). Postmenopausal women displayed an increase in alcohol consumption (P < 0.0001) and a decrease in tobacco smoking (P < 0.001). In premenopausal women, there was a marked increase in the use of non-steroid anti-inflammatory drugs (P < 0.0001) in the study period, while this was unchanged in postmenopausal women. In premenopausal blood donors, median ferritin decreased from 1984 to 1994 (36 microg/L vs. 24 microg/L, P < 0.06). In postmenopausal blood donors, ferritin was not significantly different from 1984 to 1994 (50 microg/L vs. 41 microg/L, P = 0.15). CONCLUSION: Abolition of iron fortification reduced the median dietary iron intake in Danish women from 12 to 9 mg/d. Despite the absence of food iron fortification, from 1984 to 1994, body iron stores were unchanged in premenopausal women, whereas iron stores and the prevalence of iron overload in postmenopausal women had increased significantly. The reason appears to be the changes in dietary habits with a lower consumption of dairy products and eggs, which inhibit iron absorption, and a higher consumption of alcohol, meat and poultry, containing heme iron and enhancing iron absorption.     

Serum ferritin and other haematological measurements in apparently healthy adults with malaria parasitaemia in Lagos, Nigeria

We studied 300 apparently healthy residents of Lagos aged 16-57 years. Their mean ferritin levels were 99.6 +/- 50.5 microg/l (men aged 20-57) and 66.5 +/- 44 microg/l (women aged 20-53) in aparasitaemic individuals. In parasitaemic subjects, mean ferritin levels were 133.1 +/- 48.3 microg/l (men aged 20-56) and 114.8 +/- 51.1 microg/l (women aged 16-50). Mean haematocrit values for aparasitaemic males were 45.7 +/- 5.6% and 37.9 +/- 5% for females, while mean haemoglobin levels were 153.2 +/- 1.5 microg/l and 124 +/- 3 microg/l, respectively. The mean values for MCV (mean corpuscular volume), MCH (mean corpuscular haemoglobin), MCHC (mean corpuscular haemoglobin concentration) were 101.7 +/- 8fl, 30.6 +/- 2.2 pg, 335 +/- 0.4 g/l and 99.8 +/- 10.1fl, 29.1 +/- 6.5 pg, 335 +/- 6 g/l. Serum iron levels were 34.2 +/- 5 micromol/l and 29.5 +/- 77 micromol/l. All haematological parameters measured were similar in both malaria parasitaemia positive and negative subjects, except ferritin level which was significantly higher in parasitaemic individuals (P < 0.05). Ferritin concentration and malaria density (r = 0.76 in males, r = 0.74 in females, P < 0.05) were positively correlated. Ferritin levels of subjects infected with Plasmodium falciparum were significantly higher than of those infected with P. malariae (P < 0.05). Hence ferritin estimation without examination for malaria parasitaemia in a malaria-endemic region such as Nigeria is not reliable. Asymptomatic malaria parasitaemia increases the ferritin level. Considering the mean ferritin level we found in normal subjects on a balanced diet, routine iron supplementation may not be necessary in the treatment of malaria-induced anaemia in Nigeria.     

Iron status in Danes 1994

 Iron status, i.e. serum ferritin and haemoglobin (Hb) levels, was assessed in a population survey in 1994 (Dan-Monica 10) comprising 1319 Caucasian Danish women in age cohorts of 40, 50, 60 and 70 years. In the entire series, ferritin levels increased significantly from 40 years to 60 years of age. The prevalence of small iron stores (ferritin 16–32 μg/l), depleted iron stores (ferritin <16 μg/l) and of iron deficiency anaemia (ferritin <13 μg/l and Hb <121 g/l) decreased steadily with age. Blood donors (n=109) had lower ferritin levels than non-donors (P<0.0001). Ferritin levels in donors were inversely correlated with the cumulated number of lifetime phlebotomies (r _s =–0.25, P<0.01). Ferritin levels in non-donors (n=1208) were low in 40-year-old women (median 40 μg/l) and increased to a median of 95 μg/l in 60- and 70-year-old women (P<0.0001). In non-donors 40 years of age, the prevalence of small iron stores was 40.4%, the prevalence of depleted iron stores 10.8% and the prevalence of iron deficiency anaemia 2.16%. The prevalence of iron overload (ferritin >300 μg/l) was 1.54%. Ferritin levels in 60- and 70-year-old non-donors were correlated with the body mass index (r _s =0.11, P=0.01). Ferritin levels in 50- to 60-year-old non-donors were correlated with alcohol intake (r _s =0.23, P<0.0001). In the entire series, 37.5% of non-donors took supplemental ferrous iron (median 14 mg iron per day). Iron supplements had a significant positive influence on iron status in 40-year-old premenopausal non-donors but no effect in postmenopausal women or in donors. Non-donors (n=170) treated with acetylsalicylic acid had lower ferritin levels (median 55 μg/l) than non-treated (n=1038; median 75 μg/l) (P<0.0001). Compared with the Dan-Monica 1 iron status survey in 1984, the prevalence of iron deficiency and iron deficiency anaemia was unchanged, whereas the prevalence of iron overload displayed a slight increase. The 1987 abolition of the mandatory iron fortification of flour apparently had no negative effect on iron status. Received: 8 November 1999 / Accepted: 17 April 2000     

Iron status in 358 apparently healthy 80-year-old Danish men and women: relation to food composition and dietary and supplemental iron intake

In Denmark, the intake of dietary iron has decreased since 1987, when the mandatory iron fortification of flour (30 mg carbonyl iron/kg) was stopped. Since there have been no studies of iron status in elderly Danes after the abolishment of iron fortification, there is a need to assess actual iron status in the elderly population. The objective was to evaluate iron status and the relationship with food composition and dietary and supplemental iron intake in an elderly population in Copenhagen County. Participants in this health examination survey were 358 subjects (171 men, 187 women) 80 years of age from a 1914 cohort study. Blood samples included serum ferritin and hemoglobin (Hb). A dietary survey was performed in 232 subjects (120 men, 112 women) using a dietary history method. Median serum ferritin was 100 g/l in men and 78 g/l in women (p<0.001). Ferritin concentrations <16 g/l (i.e., depleted iron stores) were found in three men (2%) and in ten women (5%). Median Hb was 140 g/l in men and 131 g/l in women (p<0.001). Three subjects (0.84%) had iron deficiency anemia (i.e., ferritin <13 g/l and Hb <5th percentile for iron-replete subjects (121 g/l in men, 114 g/l in women). Ferritin concentrations >300 g/l (i.e., iron overload) were found in 15 (9%) men and in 5 (3%) women. Median dietary iron intake was higher in men (8.7 mg/day) than in women (7.3 mg/day) (p<0.001). Serum ferritin was positively correlated to dietary intake of iron, meat, and alcohol and to body mass index in men. Serum ferritin displayed a negative correlation to the consumption of tea. The use of vitamin-mineral supplements containing iron had no influence on iron status. Dietary intake of iron and/or the bioavailability of dietary iron were adequate to maintain a favorable iron status in 80-year-old subjects displaying a low prevalence of iron deficiency and a moderate prevalence of iron overload.     

Haemoglobin and albumin as markers of HIV disease progression in the highly active antiretroviral therapy era: relationships with gender

OBJECTIVES: The aims of the study were to describe gender differences in haemoglobin and albumin and to investigate the prognostic value of these measurements in relation to highly active antiretroviral therapy (HAART). METHODS: Anaemia was defined as haemoglobin <13.5 g/dL for men and <11.5 g/dL for women. Albumin <35 g/L was defined as hypoalbuminaemia. Proportional hazards models were used to describe relationships between these markers and HIV progression and death. RESULTS: A total of 291 patients had pre-HAART and 1-year measurements. Mean haemoglobin and albumin levels pre-HAART were lower in women than in men (haemoglobin: 11.2 vs 13.2 g/dL, respectively, P<0.0001; albumin: 37.4 vs 40.2 g/L, respectively, P<0.0001), and a higher proportion of women were anaemic and hypoalbuminaemic compared with men. Despite a rise in both markers in the first year on HAART, mean haemoglobin levels remained lower by 2.08 g/dL (P<0.0001) and albumin by 2.88 g/L (P<0.0001) in women. In the 495 patients included in this analysis, haemoglobin and albumin levels were both significantly related to short-term risk of AIDS and death independently of CD4 count [hazards ratio (HR)=0.73/g/dL higher haemoglobin, 95% confidence interval (CI) 0.55-0.82, P<0.0001 and HR=0.87/g/L higher albumin, 95% CI 0.83-0.91, P<0.0001]. The prognostic value did not differ by gender. CONCLUSIONS: Women were more likely to be anaemic and/or hypoalbuminaemic pre-HAART, but post-HAART increases were similar to those in men. Both haemoglobin and albumin were strong independent prognostic factors for risk of AIDS and death, regardless of gender.     

Reference intervals for haematological variables during normal pregnancy and postpartum in 434 healthy Danish women

AIM: To report reference intervals for haematological variables during normal pregnancy and postpartum. MATERIAL AND METHODS: The series comprised 434 healthy ethnic Danish women with a normal pregnancy > or =37 wk duration and a normal delivery with newborns weight >2500 g. Blood samples were obtained at 18, 32 and 39 wk gestation and at 8 wk postpartum. The following variables were analysed: Haemoglobin (Hb), haematocrit (Hct), blood erythrocyte count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, white cell count, platelet count, erythrocyte folate, plasma folate, plasma cobalamin, plasma methylmalonic acid, plasma total homocysteine, serum ferritin, serum soluble transferrin receptor and plasma creatinine. Reference intervals were calculated using log(10)-transformed values (which showed normal distributions) as mean +/- 1.96 x SD. RESULTS: The lower reference value for Hb during pregnancy was 6.45 mmol/L (105 g/L) and 7.3 mmol/L (118 g/L) postpartum. The lower reference value for Hct was 0.31 in pregnancy and 0.35 postpartum. There was a gradual decline in the lower reference value for erythrocyte folate during pregnancy and postpartum from 0.46 to 0.29 micromol/L and in plasma folate from 6 to 4 nmol/L. Lower reference value for plasma cobalamin declined during pregnancy from 96 to 71 pmol/L, but increased postpartum to 148 pmol/L. Upper reference value for plasma homocysteine increased gradually during pregnancy and postpartum from 11.0 to 20.6 micromol/L. Geometric mean serum ferritin at 18 wk gestation was 32 microg/L. Plasma creatinine values were low during pregnancy and displayed a significant increase postpartum. CONCLUSION: The characteristic changes occurring in haematological indices during pregnancy and postpartum are described in this study. The results may be used as reference values in the assessment of health status of pregnant women with a similar socio-economic and racial background.     

Effects of NK-104, a new hydroxymethylglutaryl-coenzyme reductase inhibitor, on low-density lipoprotein cholesterol in heterozygous familial hypercholesterolemia. Hokuriku NK-104 Study Group

The clinical efficacy of NK-104, a novel and totally synthetic hydroxymethylglutaryl-coenzyme A reductase inhibitor, was assessed in 30 patients (men/women = 15/15, mean age 51 years) with heterozygous familial hypercholesterolemia. After a placebo phase of >4 weeks, NK-104 was given at an initial dose of 2 mg/day for 8 weeks, which was increased to 4 mg/day for a further 8 weeks. As a result of 2 mg/day of NK-104 treatment, mean +/- SD of total and low-density lipoprotein cholesterol levels decreased significantly (p<0.0001) from baseline, namely from 8.80+/-1.38 to 6.11+/-1.09 mmol/L (-31%) and from 6.81+/-1.52 to 4.09+/-1.03 mmol/L (-40%), respectively. They decreased further (p<0.0001) as a result of 4-mg/day administration, to 5.52+/-0.81 mmol/L (-37%) and 3.55+/-0.85 mmol/L (-48%), respectively. Changes in high-density lipoprotein cholesterol levels failed to reach statistical significance. Serum triglyceride levels decreased significantly (p<0.0001) from baseline as a result of 4 mg/day of NK-104, from 1.99+/-1.72 to 1.35+/-0.90 mmol/L (-23%). Serum apolipoprotein B, CII, CIII, and E levels significantly decreased: mean changes from baseline at the end of the study were -41% (p<0.0001), -27% (p<0.0001), -19% (p = 0.002), and -37% (p<0.0001), respectively. On the other hand, apolipoprotein AI and All levels significantly increased as a result of the treatment: + 10% (p = 0.002) and +6% (p = 0.008), respectively. There were no adverse events observed in either clinical or laboratory findings that could be attributed to the treatment. These results suggest that the potency of NK-104 appears to be dose-dependent, and that NK-104 is safe and well tolerated in the treatment of patients with heterozygous familial hypercholesterolemia, and thus also provides a new therapeutic choice for subjects requiring lipid-modifying therapy.     

Low dose hexarelin and growth hormone (GH)-releasing hormone as a diagnostic tool for the diagnosis of GH deficiency in adults: comparison with insulin-induced hypoglycemia test.

GH deficiency (GHD) in adults must be shown by provocative testing of GH secretion. Insulin-induced hypoglycemia (ITT) is the test of choice, and severe GHD, treated with recombinant human GH replacement, is defined by a GH peak response to ITT of less than 3 microg/L. GHRH plus arginine (ARG) is a more provocative test and is as sensitive as ITT provided that appropriate cut-off limits are assumed. GH secretagogues are a family of peptidyl and nonpeptidyl GH-releasing molecules that strongly stimulate GH secretion and, even at low doses, truly synergize with GHRH. Our aim was to verify the diagnostic reliability of the hexarelin (HEX; 0.25 microg/kg, iv) and GHRH (1 microg/kg, iv) test for the diagnosis of adult GHD. To this goal, in the present study we 1) defined the normal ranges of the GH response to GHRH+HEX in a group of normal young adult volunteers (NS; n = 25; 18 men and 7 women; age, 28.5+/-0.6 yr) and in 11 of them verified its reproducibility in a second session, and 2) compared the GH response to GHRH+HEXwith that to ITT in a group of normal subjects (n = 33; 12 men and 21 women; age, 34.1+/-1.5 yr) and hypopituitaric adults with GHD (n = 19; 10 men and 9 women; age, 39.9+/-2.2 yr; GH peak <5 microg/L after ITT). The GH response to GHRH+ARG was also evaluated in all GHD and in 77 normal subjects (40 men and 37 women; age, 28.1+/-0.6 yr). The mean GH peak after GHRH+HEX in NS was 83.6+/-4.5 microg/L; the third and first percentile limits of the normal GH response were 55.5 and 51.2 microg/L, respectively). The GH response to GHRH+HEX in NS showed good intraindividual reproducibility. In GHD the mean GH peak after GHRH+HEX (2.6+/-0.7 microg/L) was similar to that after GHRH+ARG (3.6+/-1.0 microg/L), and both were higher (P < 0.001) than that after ITT (0.6+/-0.1 microg/L); the GH responses to GHRH+HEX were positively associated with those to ITT and GHRH+ARG. Analyzing individual GH responses, 100% had severe GHD after ITT (GH peak, <3 microg/L). After GHRH+HEX all GHD had GH peaks below the third percentile limit of normality appropriate for this test (i.e. 55.5 microg/L). Thirteen of 19 (68.4%) GHD subjects had GH peaks below 3 microg/L after GHRH+HEX but all 19 (100%) had GH peaks below the first percentile limit of normality (i.e. 51.2 microg/L). The GH responses to GHRH+HEX were highly concordant with those after GHRH+ARG. In conclusion, the present results define normal limits of the GH response to stimulation with low dose HEX+GHRH in normal adults and show that this test is as sensitive as ITT for the diagnosis of adult GHD provided that appropriate cut-off limits are considered.     

Fasting decreases rates of noninsulin-mediated glucose uptake in man

Although fasting decreases insulin-mediated glucose uptake (IMGU), its effect on noninsulin-mediated glucose uptake (NIMGU) is not known. To examine this issue we studied seven obese men [mean (+/- SD) age, 36 +/- 5 yr; weight, 91 +/- 13 kg] after an overnight fast (day 0) and 3 days (day 4) and 9 days (day 10) of total fasting and six normal weight men (age, 32 +/- 4 yr; weight, 73 +/- 6 kg) after an overnight and 3 days of fasting. To study NIMGU, somatostatin (0.16 micrograms/kg.min) was infused to create severe insulin deficiency and [3H]3-glucose to measure glucose disappearance (Rd), while serum glucose was sequentially clamped at a level of about 4.7 mmol/L for 180 min and about 11 mmol/L for an additional 100 min. The results from the last 60 min of each glycemic plateau were used for analysis. Under these conditions insulin action is absent and Rd = NIMGU. Since under conditions of euglycemic insulinopenia, NIMGU into noncentral nervous system tissues is negligible, and central nervous system (CNS) glucose uptake saturates at physiological glucose concentrations, it follows that at a glucose level of about 4.7 mmol/L, NIMGU reflects CNS glucose uptake and at about 11 mmol/L, NIMGU reflect CNS plus non-CNS tissues. Thus, non-CNS NIMGU = NIMGU at 11 mmol/L - NIMGU at about 4.7 mmol/L. The obese subjects' mean weight fell to 88 +/- 5 kg on day 4 and 85 +/- 5 kg on day 10 (P less than 0.001 between all values). The mean basal serum glucose level fell from 5.3 +/- 0.1 on day 0 to 4.2 +/- 0.2 and 3.8 +/- 0.2 mmol/L on days 4 and 10, respectively (P less than 0.01 between all values). During insulinopenia plasma FFA and serum beta-hydroxybutyrate levels on day 10 were 3- and 30-fold higher than the basal prefast levels, respectively. Noninsulin-mediated glucose clearance at about 4.7 mmol/L did not change during fasting [0.0016 +/- 0.0001 (day 0) vs. 0.0016 +/- 0.0001 (day 4) and 0.0014 +/- 0.0001 L/kg.min (day 10); P = NS between all values]; at about 11 mmol/L noninsulin-mediated glucose clearance fell from 0.0016 +/- 0.0001 on day 0 to 0.0001 +/- 0.0001 dL/kg.min on day 10 (P less than 0.001). Results in the lean group were similar to those in the obese group after a 3-day fast.(ABSTRACT TRUNCATED AT 400 WORDS)     

Haemoglobin and anaemia in a gender perspective: the Tromsø Study

Abstract: Objectives: To examine the gender‐specific distribution of haemoglobin (Hb) and the World Health Organization (WHO) criteria for anaemia compared with the 2.5 percentile for Hb. Methods: A population‐based study from Tromsø, Northern Norway. All inhabitants above 24 yr were invited. In total, 26 530 (75%) had their Hb analysed. Results: The 2.5–97.5 percentile of Hb was 129–166 and 114–152 g/L for all men and women, respectively. In men, mean Hb decreased from 148 to 137 g/L between 55–64 and 85+ yr. In women, mean Hb increased from 132 to 137 g/L between 35–44 and 65–74 yr and then decreased to 131 g/L among the oldest. Using the WHO criteria for anaemia (Hb: <130 and <120 g/L, men and women respectively), the prevalence of anaemia in men increased with age from 0.6% aged 25–34 to 29.6% aged 85+. For women, the prevalence of anaemia varied from 9.1%, 2.2% and 16.5% in the age groups of 35–44, 55–64 and 85+ yr, respectively. The WHO criteria gave a two to three times higher prevalence of anaemia compared with the 2.5 percentile of Hb in women, but the difference was small in men. Poor self‐rated health was not associated with low values of Hb in women. In men, there was an association in some age groups. Conclusion: The WHO criteria for anaemia and the 2.5 percentile for Hb corresponded well for men, but not for women. The WHO criteria of anaemia may result in medicalization of healthy women.     

Iron deficiency anaemia in young women

OBJECTIVES: The expression density of GPIaIIa, the primary platelet collagen receptor (integrin alpha2beta1), is linked to two polymorphisms (GPIa-807C/T and HPA-5a/b). During evolution a gene shift from the genotypes GPIa-807CC-HPA-5bb to the genotypes GPIa-807CT-HPA-5aa has taken place. The aim of the study was to assess whether iron deficiency anaemia (e.g. increased blood loss) in young women could be associated with a specific genotype, indicating a role as potential evolutionary selection factor. STUDY DESIGN: Women between 18 and 40 yr of age presenting for their first blood donation were asked about alimentary habits and use of oral contraception. Haemoglobin and serum ferritin were measured and the GPIa-C807T and HPA-5 genotypes were determined. RESULTS: Two hundred women were included and grouped according to the WHO definition for iron deficiency anaemia (haemoglobin <121 g L(-1) and ferritin <15 microg L(-1)). Eight women fulfilled both WHO-criteria for iron deficiency anaemia, 145 women fulfilled none. No differences regarding age, use of oral contraceptives, alimentary habits, and HPA-5 were found between the groups. The GPIa-807CC genotype was strongly over-represented in the WHO-anaemic women as compared to the non-WHO-anaemic women (87.5% vs. 33.1%, P=0.003). CONCLUSION: Iron deficiency anaemia in young women might have been the evolutionary disadvantage causing the gene shift from GPIa-807CC to 807CT.     

Subclinical hypothyroidism may be associated with elevated high-sensitive c-reactive protein (low grade inflammation) and fasting hyperinsulinemia

The association between coronary heart disease and subclinical hypothyroidism (SCH) is unclear. We aimed to determine hs-CRP concentrations in patients with SCH. Seventy-seven patients (age 34.6 +/- 13.7 yr) with SCH (TSH > 4.2 microIU/ml and serum free thyroxine level between 0.932-1.71 ng/dL), and 80 control subjects (age 33.9 +/- 13.3 yr) were studied. Thyroid hormones, C-reactive protein, insulin, glucose, total, HDL, LDL and VLDL-cholesterol levels and HOMA-IR index were also determined. TSH levels of SCH group were higher than control (7.4 +/- 2.9 and 1.55 +/- 0.78 microIU/ml, respectively, p = 0.0001). However, FT4 levels were lower than control subjects (1.18 +/- 0.22 ng/dL and 1.38 +/- 0.26, respectively, p = 0.001). Serum hs-CRP levels of subjects with SCH were higher than control subjects (4.2 +/- 0.8 mg/l and 1.05 +/- 0.3 mg/l respectively, p = 0.0001). Insulin levels of SCH group were higher than control (8.5 +/- 4.3 microU/ml and 7.1 +/- 3.1 microU/ml respectively, p<0.02) but, Homa-IR levels of the two groups were not different. Mean total and LDL-cholesterol levels of SCH group were higher than control (p = 0.01 and p<0.02). We also found a positive correlation between hs-CRP levels and insulin (r = 0.362, p = 0.002 in men, r = 0.358, p = 0.0001 in women), TSH (r = 0.611, p = 0.0001 in men, r = 0.411 p = 0.0001 in women), and prolactin (r = 0.340, p = 0.01 in men r = 0.553, p = 0.0001 in women). Conclusions: Patients with SCH, irrespective of gender, have higher serum hs-CRP, insulin, total and LDL-cholesterol levels than healthy subjects. 2- High hs-CRP level, and thereby low grade inflammation may be associated with fasting hyperinsulinemia before insulin resistance becomes evident in patients with SCH.     

Haemoglobin levels are associated with bone mineral density in the elderly: a population-based study

Hypoxemia has been associated with low bone mineral density (BMD) in animal and human models. We assessed the association of haemoglobin levels with ultrasound-derived (UD) T score, Z score and the stiffness index in all 358 subjects aged 75+ living in Tuscania (Italy). Also, we searched for the haemoglobin cutoff levels that might best identify participants with osteoporosis. In the multivariable linear regression analysis, haemoglobin levels were associated among participants with the UD T score [β = 0.13; 95% confidence interval (CI) = 0.01–0.25; p = 0.030], Z score (β = 0.11; 95% CI = 0.01–0.22; p = 0.045) and stiffness index (β = 1.87; 95% CI = 0.51–3.21; p = 0.007) after adjusting for potential confounders. Haemoglobin levels <140 g/L in men and <130 g/L in women best predicted osteoporosis in linear discriminant analysis. Haemoglobin is independently associated with all UD-BMD parameters. Haemoglobin levels <140 g/L in men and 130 g/L in women might be adopted in clinical practice to identify older subjects in whom screening for osteoporosis might yield higher effectiveness.     

Haemoglobin predicts survival in patients with chronic heart failure: a substudy of the ELITE II trial.

AIMS: The correction of anaemia in chronic heart failure (CHF) has been suggested to be associated with an improvement in symptoms and cardiac function. We aimed to investigate the relationship between the concentration of haemoglobin and survival in CHF. METHODS AND RESULTS: We analysed haemoglobin concentrations in 3044 patients recruited in the Evaluation of Losartan In The Elderly (ELITE II) trial. Patients of mean age 71.5 +/- 6.8 years (+/-SD) and New York Heart Association (NYHA) class 2.5 +/- 0.6 were enrolled from June 1997 to May 1998 and followed-up for survival (range 1-780 days, median 551). In univariate analysis, age, NYHA class, serum creatinine, left ventricular ejection fraction (all P<0.0001) and sex (P=0.046) all predicted survival. Haemoglobin as a continuous variable for all patients was not a significant prognostic marker (P=0.26). However, sub-dividing patients according to 1.0 g/dL increments of haemoglobin revealed that the survival relationship was non-linear. The results from the polynomial regression suggest that the optimal interval is a symmetric one centred around 14.5 g/dL. This was independent of age, sex, NYHA class, left ventricular ejection fraction, creatinine, co-existing chronic obstructive pulmonary disease and treatment allocation (P<0.001). There was a minor fall in plasma haemoglobin at the 12-month follow-up (mean change for all patients 0.3 +/- 2.2 g/dL, P<0.0001), with no difference between captopril and losartan groups (P>0.3). CONCLUSION: Haemoglobin is an independent predictor of mortality in CHF patients, with anaemic and polycythaemic patients having the worst survival.     

Relationship between angiotensin-converting enzyme gene polymorphism and insulin resistance in never-treated hypertensive patients

The association between angiotensin-converting enzyme (ACE) gene polymorphism and insulin resistance (IR) in hypertensive subjects remains controversial. Thus, we evaluated the possible association between IR and ACE gene polymorphism in a group of hypertensive, never-treated patients compared with that in a normotensive control group. We enrolled 200 (114 men and 86 women; age, 45.5 +/- 4.7 yr) hypertensive patients and 96 (54 men and 42 women; age, 44.0 +/- 4.7 yr) normotensive subjects. A double PCR assay was used to identify ACE genotypes. We determined fasting glucose and insulin by the glucose oxidase method and using a standard RIA technique. IR was estimated using the homeostasis model assessment (HOMA(IR)). Both fasting glucose (5.0 +/- 0.3 vs. 4.7 +/- 0.3 mmol/L; P < 0.0001), insulin levels (12.3 +/- 4.7 vs. 4.9 +/- 1.5 muU/mL; P < 0.0001), and HOMA(IR) (2.7 +/- 1.1 vs. 1.1 +/- 0.3; P < 0.0001) were significantly higher in hypertensive patients than in the normotensive control group. When we subdivided hypertensive patients according to ACE genotype, we observed that fasting insulin and HOMA(IR) were 16.3 +/- 3.3 and 3.6 +/- 0.8 in the DD genotype, 9.4 +/- 3.1 and 2.1 +/- 0.7 in the ID genotype, and 8.3 +/- 2.8 and 1.9 +/- 0.7 muU/mL in the II group (P < 0.0001, by ANOVA). No significant differences were observed in the normotensive control group. In conclusion, we extended previous data regarding the relationship of hypertension and IR by demonstrating a dependence of this relationship upon the ACE gene polymorphism.