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Biomedical subjects

K Brismar

Publications and source records attributed to K Brismar.

At least 55 records · Page 3Linked to original sources
PubMed1999

Anti-cardiolipin antibodies and circulating immune complexes in type 1 diabetes mellitus: increased prevalence and relation to vascular complications.

Anti-cardiolipin antibodies, oxidatively modified low-density lipoproteins (oxLDL) and circulating immune complexes are humoral factors that have been linked to vascular damage. To analyse their possible role in the vascular complications in type 1 diabetes mellitus, we investigated patients with and without vascular complications (retinopathy, nephropathy, polyneuropathy, foot ulcers). The patients were matched for age, sex and duration of diabetes. The patients were also compared with 102 healthy individuals. Anti-cardiolipin antibodies of IgG and IgA type were more common in patients compared with healthy individuals. There was no difference between patients with and without vascular complications. There was no increased prevalence of IgM anti-cardiolipin antibodies, but the levels of these antibodies were higher in patients with vascular complications compared with patients without complications and controls. Eighty-three percent of patients had circulating immune complexes in comparison with 5% of healthy individuals. Such complexes were more common in patients with complications. Both the prevalence and the levels of immune complexes were higher in patients with null alleles of complement factor C4. Patients with vascular complications had higher prevalence of C4A than of C4B null alleles. Anti-cardiolipin antibodies were present in higher relative concentrations in immune complex form than in serum in all six patients analysed. There was no increased prevalence of antibodies against oxidatively modified LDL in the patients. The higher prevalence and levels of anti-cardiolipin antibodies and circulating immune complexes in patients with vascular complications suggests that these humoral factors might be involved in the vascular complications of type 1 diabetes mellitus.

Adult↗
PubMed1999

Splanchnic exchange of insulin-like growth factor binding protein-1 (IGFBP-1), IGF-I and acid-labile subunit (ALS) during normo- and hyper-insulinaemia in healthy subjects.

OBJECTIVE: The main source of circulating IGF-I, insulin like growth factor binding protein-1 (IGFBP-1) and acid-labile subunit (ALS) is considered to be the liver, but their production rates have not been determined in healthy individuals. Thus, the splanchnic exchange of IGFBP-1, IGF-I, ALS and glucose were studied. STUDY DESIGN: In five overnight fasting healthy, normal weight men (mean age 29 +/- 1 years) blood samples were taken from a hepatic vein, a brachial artery and a peripheral vein in the basal state and during 3 h i.v. infusion of insulin (1.0 mU/kg/min). Normoglycaemia was maintained with a variable glucose infusion and splanchnic blood flow was determined using a constant rate indicator infusion technique. RESULTS: The basal net splanchnic glucose output amounted 0.96 +/- 0. 09 mmol/min and the splanchnic production of IGFBP-1 was 7 +/- 2 microg/min. There was a net splanchnic uptake of IGF-I (7 +/- 2 microg/min) in the basal state, while no significant splanchnic exchange of ALS was found. During the insulin infusion, insulin concentration increased from 78 +/- 12 to 660 +/- 30 pmol/l, resulting in a complete inhibition of splanchnic glucose production after 40 min of infusion. Splanchnic IGFBP-1 production rose initially to 13 +/- 4 microg/min (P < 0.05) and then gradually decreased and was completely inhibited at 180 min (P < 0.05). Insulin infusion influenced neither ALS nor IGF-I splanchnic exchange. CONCLUSION: Splanchnic production of IGFBP-1 in the basal state was demonstrated and it is completely inhibited after 180 min of hyperinsulinaemia. In contrast to what is generally held, there was no net splanchnic production of IGF-I in the basal state or during insulin stimulation.

Adult↗
PubMed1999

Malignant human renin producing paraganglionoma-localization with 123I-MIBG and treatment with 131I-MIBG.

A 22-year-old woman presenting severe hypertension and hypokalaemia is described. Initial evaluation showed a large tumour localized at the position of the left adrenal gland. Subsequent surgery temporarily relieved all signs and symptoms caused by the tumour. The symptoms relapsed after a 2-year disease-free interval. At re-evaluation, the tumour was shown to produce an uncontrolled secretion of renin, thus triggering aldosterone-dependent hypertension. This report describes the diagnosis, treatment and clinical course of this unique patient with a malignant paraganglionoma of adrenal origin.

3-Iodobenzylguanidine↗
PubMed1999

Effects of oxytocin treatment early in pregnancy on fetal growth in ad libitum-fed and food-restricted rats.

The effects of oxytocin on fetal and placental growth and on maternal weight gain and accumulation of body fat were studied in ad libitum-fed and food-restricted (receiving 70% of the food intake of the ad libitum-fed group) pregnant rats. Further, a possible role of the IGF axis in mediating oxytocin-induced changes was assessed. Pregnant rats were injected subcutaneously once a day during gestational d 1-5 with saline or oxytocin (1 mg/kg). Ad libitum-fed oxytocin-treated pregnant rats had higher circulating levels of IGF-I, larger placentas, fetuses, and newborn pups and contained less body fat at the end of pregnancy. In food-restricted dams, oxytocin-treatment had no effect on fetal and placental growth. Additionally, food restriction attenuated the normal increase in IGF binding protein-3 protease proteolysis during pregnancy. The results show that oxytocin may affect maternal adaptations to pregnancy and stimulate fetal growth. We suggest that this effect may be mediated by increased IGF-I in ad libitum-fed animals, whereas food restriction may block this effect by resulting in low levels of circulating IGF-I and by attenuating the pregnancy-associated increase in IGF binding protein-3 protease activity and, thereby, further compromise IGF bioavailability.

Adipose Tissue↗
PubMed1999

Transcutaneous oxygen tension and toe blood pressure as predictors for outcome of diabetic foot ulcers.

OBJECTIVE: The present study was undertaken to compare the predictive values of transcutaneous oxygen tension (TcPO2) and toe blood pressure (TBP) measurements for ulcer healing in patients with diabetes and chronic foot ulcers. RESEARCH DESIGN AND METHODS: Investigated prospectively were 50 diabetic patients (37 men) with chronic foot ulcers. The age was 61 +/- 12 (mean +/- SD), and the diabetes duration was 26 +/- 14 years. TBP (mmHg) was measured in dig I and TcPO2 (mmHg) at the dorsum of the foot. Ulcer healing was continuously evaluated by measuring the ulcer area every 4-6 weeks. After a follow-up time of 12 months, the patients were divided into three groups according to clinical outcome: healed with intact skin, improved ulcer healing, or impaired ulcer healing. RESULTS: Of the 13 patients who deteriorated, 11 had TcPO2 < 25 mmHg, while 34 of the 37 patients who improved had TcPO2 > or = 25 mmHg. The sensitivity and specificity for TcPO2 were 85 and 92%, respectively, when a cutoff level of 25 mmHg was used for determination of outcome of ulcer healing (healing or nonhealing). The corresponding values for TBP at 30 mmHg were 15 and 97%. Measurement of TcPO2 provided a higher positive predictive value (79%) than TBP (67%). CONCLUSIONS: The results indicate that TcPO2 is a better predictor for ulcer healing than TBP in diabetic patients with chronic foot ulcers, and that the probability of ulcer healing is low when TcPO2 is < 25 mmHg.

Blood Pressure↗
PubMed1998

Pronounced skin capillary ischemia in the feet of diabetic patients with bad metabolic control.

Skin capillary circulation is impaired during postocclusive reactive hyperaemia (PRH) in toes of diabetic patients independent of diabetes duration and macrocirculation. The aim of this study was to examine its relation to metabolic control. The skin microcirculation was investigated in 20 patients with insulin-dependent diabetes mellitus: 10 patients with bad [HbA1c > 7.5 (8.7 +/- 0.8) %], and 10 patients with good metabolic control [HbA1c < 7.5 (6.3 +/- 1.0) %]. The diabetes duration was similar in both groups (16 +/- 9 and 16 +/- 6 years, respectively). None had macroangiopathy. Thirteen healthy subjects served as controls. The capillary blood cell velocity (CBV) in the nailfold of the great toe was investigated by videophotometric capillaroscopy, and the total skin microcirculation by laser Doppler fluxmetry (LDF). CBV and LDF were studied during rest and after 1-min arterial occlusion. The vibration perception thresholds (VPT) of the feet were higher (p < 0.05) in the patients with bad (34 +/- 12 V), as compared to patients with good metabolic control (18 +/- 10 V) and to healthy subjects (13 +/- 3 V). Peak CBV during PRH was reduced in both patient groups (p < 0.01), and lowest in the patients with bad metabolic control (p < 0.05). Time to peak CBV was prolonged (p < 0.01) in the patients with bad, while normal in the patients with good metabolic control. LDF was similar in all groups. An inverse correlation was found between HbA1c and peak CBV during PRH (r = 0.60; p = 0.008), while positive correlations were found to time to peak CBV (r = 0.62; p = 0.004) and VPT (r = 0.60; p = 0.01). No associations were seen between VPT and the microcirculatory variables. The results indicate that the metabolic control is of importance for the nutritive capillary circulation and the peripheral nerve function in the diabetic foot.

Adult↗
PubMed1998

Fibroblasts derived from human chronic diabetic wounds have a decreased proliferation rate, which is recovered by the addition of heparin.

We have studied the growth kinetics of fibroblasts derived from uninjured skin and chronic wounds in non-diabetic and diabetic (IDDM) patients. DNA measurements during the first 24 h after cell starvation showed that fibroblasts derived from chronic wounds, both non-diabetic and diabetic, display a decreased adhesion and proliferation. When determining the rate of proliferation after another 48, 72 and 96 h, a significant decrease in the proliferation rate was found in the chronic wound fibroblasts compared to those from uninjured skin. Furthermore, we have investigated the effects of heparin, hyaluronic acid and other heparin-like substances on the proliferation of non-diabetic and diabetic fibroblasts. We found that these substances stimulated the proliferation of human fibroblasts derived from both normal skin and chronic wounds measured as DNA content. Stimulation with heparin normalized the proliferation of the diabetic chronic wound fibroblasts. This effect was independent of the presence of serum. The effect of heparin was dose-dependent and most pronounced during the first 24 h of stimulation. These results suggest that heparin may be of importance in the treatment of chronic diabetic wounds.

Anticoagulants↗
PubMed1998

Insulin-like growth factor-I and insulin-like growth factor binding protein-1 in a representative population of type 2 diabetic patients in Sweden.

OBJECTIVE: To study the influence of type 2 diabetes on the insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) serum levels in an area-based population of type 2 patients previously described. RESULTS: The patients (n = 151) were elderly (70.6 +/- 0.7 years of age) and moderately overweight (BMI 27.0 +/- 0.4 kg/m2). Most patients (83%) were treated with either diet alone or diet in combination with sulphonylurea. Metabolic control measured as HbAlc deteriorated with duration (p < 0.001) and between groups treated with diet (HbA1c 5.8 +/- 0.6), sulphonylurea (7.5 +/- 0.2) and insulin (7.7 +/- 0.4). Mean levels of IGF-I were within reported normal range, but were lower in the insulin-treated as compared to the non-insulin-treated patients. Levels of IGF-I decreased with diabetes duration and with increased blood glucose. There was a positive correlation between IGF-I and insulin levels and also an inverse correlation between IGF-I and IGFBP-1 levels. The IGFBP-1 levels were twofold higher than reported in non-diabetic individuals. In multiple stepwise correlation analysis, 37% of the variability in IGFBP-1 could be explained by BMI, IGF-I SD score, age, IGF-I, and fasting blood glucose. CONCLUSION: Our study indicates that influence of type 2 diabetes on IGF-I bioavailability in individual patients is modulated by insulin, body weight (presumably reflecting insulin sensitivity) and metabolic control. Furthermore, increased levels of IGFBP-1 are strongly associated with decreased b-cell function in type 2 diabetes mellitus.

Aged↗
PubMed1998

Perioperative insulin and glucose infusion maintains normal insulin sensitivity after surgery.

Elective surgery was performed after overnight fasting, a routine that may affect the metabolic response to surgery. We investigated the effects of insulin and glucose infusions before and during surgery on postoperative substrate utilization and insulin sensitivity. Seven patients were given insulin and glucose infusions 3 h before and during surgery (insulin group), and a control group of six patients underwent surgery after fasting overnight. Insulin sensitivity and glucose kinetics (D-[6,6-2H2]glucose) were measured before and immediately after surgery using a hyperinsulinemic, normoglycemic clamp. Glucose infusion rates and whole body glucose disposal decreased after surgery in the control group (-40 and -29%, respectively), whereas no significant change was found in the insulin group (+16 and +25%). Endogenous glucose production remained unchanged in both groups. Postoperative changes in cortisol, glucagon, fat oxidation, and free fatty acids were attenuated in the insulin group (vs. control). We conclude that perioperative insulin and glucose infusions minimize the endocrine stress response and normalize postoperative insulin sensitivity and substrate utilization.

Arthroplasty, Replacement, Hip↗
PubMed1998

Insulin-like growth factor binding protein-1 as a marker of the metabolic syndrome--a study in borderline hypertension.

AIM: To evaluate insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) in borderline hypertension (BHT) in relation to plasma lipoprotein and insulin levels, anthropometric variables and 24-h ambulatory blood pressure (BP). Seventy-five BHT men diastolic BP (DBP) 85-94 mmHg) and 75 age-matched normotensive controls (NT, DBP < or = 80 mmHg) were recruited from a population-based screening program. RESULTS: There was no difference in IGF-I or IGFBP-1 between BHT and NT men. However, subjects with insulin resistance (IR) had decreased levels of IGF-1 (145 +/- 36 vs 153 +/- 28 microg/L, p < 0.05) and IGFBP-1 (41 +/- 15 vs 52 +/- 20 microg/L, p < 0.01) compared to those without IR. IGF-I correlated inversely to BP levels in the BHT group (r = -0.24 to -0.28, p < 0.05). IGFBP-1 correlated inversely with BMI, lipoprotein and insulin levels (r = -0.29 to -0.48, p < 0.01), independent of IR. CONCLUSION: While there are no differences between BHT and NT men in IGF-I and IGFBP-1, both are significantly decreased in IR subjects. IGFBP-1 exhibits a close correlation to metabolic factors. Decreased IGFBP-1 could thus be suggested as a variable marking the "metabolic syndrome" of hypertension.

Adult↗
PubMed1997

Enhanced generation of interleukins 1 beta and 6 may contribute to the cachexia of chronic disease.

The cachexia of disease may be promoted by proinflammatory cytokines, eg, interleukin (IL) 1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6. These, as well as some antiinflammatory cytokines, eg, IL-1 receptor antagonist (IL-1ra), IL-10, and transforming growth factor beta 1 (TGF-beta 1), were analyzed in serum (IL-6, IL-1ra, IL-10, TGF-beta 1) and stimulated blood monocytes (IL-1 beta, TNF alpha, IL-6) obtained from elderly patients with protein-energy malnutrition (PEM). Twenty-one uninfected malnourished patients aged 75 +/- 1 y (mean +/- SD), with a body mass index (BMI; in kg/m2) of 17.2 +/- 0.5 and various noncancer disorders, and 22 healthy matched control subjects aged 72 +/- 1 y, with a BMI of 25.4 +/- 0.7 (significantly different from patients, P < 0.001), were included. Fifteen patients and their corresponding control subjects were reexamined 3 mo later. Isolated monocytes were stimulated with lipopolysaccharide (LPS) and concentrations of IL-1 beta, TNF-alpha, and IL-6 were determined. Serum concentrations of IL-6, IL-1ra, IL-10, TGF-beta 1, and acute-phase reactants were analyzed. Serum concentrations of orosomucoid and IL-6 were higher in the malnourished subjects than in the control subjects (1.14 +/- 0.1 compared with 0.8 +/- 0.3 g/L, P < 0.001; and 5 ng/L compared with undetectable concentrations, P < 0.01, respectively). Higher generation of IL-1 beta (2.7-fold; P < 0.05) and IL-6 (3.7-fold; P < 0.05) was found in monocytes from patients with PEM relative to the control subjects when monocytes were stimulated with 0.1 microgram LPS/L. Monocyte TNF generation and serum concentrations of IL-10, IL-1ra, and TGF-beta 1 did not differ. Similar results were obtained at follow-up. IL-1ra was negatively correlated with delayed cutaneous hypersensitivity (r = -0.34, P < 0.05). We conclude that enhanced generation of proinflammatory cytokines such as IL-6 and IL-1 beta in malnourished patients may contribute to the PEM often encountered in chronic nonmalignant disorders.

Aged↗
PubMed1997

Influence of circulating epinephrine and norepinephrine on insulin-like growth factor binding protein-1 in humans.

The aim of the present study was to investigate the influence of circulating epinephrine (Epi) and norepinephrine (Norepi) on serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations. Healthy men received 0.3 nmol.kg.min Epi iv (n = 6), 0.5 nmol.kg.min Norepi iv (n = 7), or saline (n = 5) during 30 min. Arterial blood samples were obtained before, during, and 120 min after infusion. During the catecholamine infusion arterial Epi and Norepi plasma concentrations reached 6.35 +/- 0.53 and 15.65 +/- 2.71 nmol/L, respectively, which resulted in significant increases in glucose concentrations. When Epi was infused, IGFBP-1 increased from 45 +/- 6 micrograms/L to 76 +/- 10 micrograms/L (P < 0.05) 60 min after the infusion. Epi was also followed by increases in insulin, C-peptide, and glucagon. Norepi resulted in a slight increase in circulating IGFBP-1 (43 +/- 6 to 54 +/- 8 nmol/L, NS). The findings suggest that Epi, at plasma concentrations similar to those reached during physical stress, stimulates the production of IGFBP-1 in humans.

Adult↗
PubMed1997

Associations between insulin-like growth factor-I (IGF-I), IGF-binding protein-1, insulin and other metabolic measures after controlling for genetic influences: results from middle-aged and elderly monozygotic twins.

It has previously been shown that the serum levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin are influenced by genetic effects to various degrees. From a clinical and preventive point of view, however, it is important to identify potentially modifiable non-genetic factors influencing the levels of these measures. Because monozygotic twin pairs share the same genetic background, differences in phenotypic levels within monozygotic twin paris are believed to be due to non-genetic influences. Accordingly, the associations between intrapair differences in one phenotype and intrapair differences in another phenotype are also due to non-genetic influences. The present sample of 97 pairs of monozygotic twins from the population-based Swedish Adoption/Twin Study of Aging (SATSA) provided the opportunity to assess non-genetic influences on the levels of IGF-I, IGFBP-1, and insulin. Several metabolic measures were found to account for the variation of IGF-I, IGFBP-1, and insulin after controlling for the genetic influences. IGFBP-1 and glucose were significant predictors for the levels of IGF-I. IGFBP-1 and glucose together explained about one quarter of the non-genetic variation of IGF-I. However, when IGFBP-1 was dropped from the regression model, insulin was the only independent predictor of IGF-I, and explained about 19% of the non-genetic variation for IGF-I. For IGFBP-1, insulin and IGF-I, were the significant non-genetic predictors. Insulin and IGF-I explained about 28 and 8% respectively of the non-genetic variation for IGFBP-1, while for insulin, IGF-I, triglycerides, body height, glucose, and body mass index (BMI) explained approximately 20, 12, 6, 5 and 5% respectively of the non-genetic variation.

Aged↗
PubMed1997

Determinants of growth in diabetic pubertal subjects.

OBJECTIVE: To analyze the relationship among metabolic control, IGF-I, and growth in pubertal diabetic subjects. RESEARCH DESIGN AND METHODS: In 72 diabetic children, we have studied the pattern of change of IGF-I, IGF-I SD score, IGF binding protein (BP)-1, and growth rate in different pubertal stages and have analyzed their relation to age sex, weight/length index, HbA1c, insulin concentration, insulin dose, and dehydroepiandrosteronesulfate (DHEAS). RESULTS: The serum IGF-I values increased up to Tanner stage 4 and thereafter decreased, whereas IGFBP-1 showed the inverse pattern. When transforming the IGF-I values into SD scores, correcting for age, sex, and pubertal stage, it was shown that the deviation from normal values increased with increasing pubertal stage in boys, but was equal in stages 3-5 in girls. Using multiple regression analysis, HbA1c, insulin dose, and DHEAS were significantly correlated to IGF-I SD score (R2 = 0.253, P = 0.001). IGFBP-I levels in the afternoon were within normal range. LogIGFBP-1 showed an inverse correlation, to insulin concentration in single correlation (r = -0.26, P = 0.02). In single correlation, growth rate correlated significantly to insulin dose (r = 0.25, P = 0.03). In a multiple regression analysis, only DHEAS and IGF-I SD score were found to be significantly correlated to growth rate (R2 = 0.370, P < 0.001). The 18 adolescents who had reached their final height did not deviate from their target final height, according to their recorded growth since birth. CONCLUSIONS: In a group of fairly well-controlled diabetic children, the normal increase in IGF-I during puberty is blunted. Despite decreased IGF-I levels, target final height was attained, probably because of adequate insulin compensation leading to normal IGFBP-l, thus adequate bioavailability of IGF-I. Our results point out the importance of sufficient exogenous insulin in the period of rapid linear growth.

Adolescent↗
PubMed1997

Genetic and environmental architecture of the features of the insulin-resistance syndrome.

The contribution of genetic and environmental effects to the clustering of metabolic factors contained in insulin-resistance syndrome (IRS) is still unclear. To explore the genetic architecture of IRS, we examined a population of elderly twins from the Swedish Adoption/Twin Study of Aging. A sample of 289 pairs of twins (mean age 65.5 years; range 52-86 years), of whom 140 pairs had been reared apart, was studied. The features contained in the IRS consisted of body-mass index (BMI), insulin resistance, triglycerides, HDL cholesterol, and systolic blood pressure. Intraclass correlations, cross-twin correlations, and model-fitting analyses were used to evaluate the relative importance of genetic and environmental influences for variation in and covariation among the components of the syndrome. All of the five principal metabolic components contained in IRS are more or less influenced by a single latent genetic factor, whereas only three of the components (triglycerides, insulin resistance, and HDL cholesterol) are influenced by a latent individual-specific environmental factor. The genetic factor reflected influences of importance to BMI and insulin resistance and to a lesser degree to triglycerides, HDL cholesterol, and systolic blood pressure, whereas the individual-specific environmental factor reflected influences in common to triglycerides and HDL cholesterol and to a lesser degree to insulin resistance. Systolic blood pressure was related to IRS, albeit weakly, only through genetic effects. In conclusion, IRS appears to be influenced by different sets of genetic and environmental mechanisms. The set of genetic influences in common to all the components may initiate the abnormalities underlying IRS.

Aged↗
PubMed1996

Altered properties of the fibrin gel structure in patients with IDDM.

High plasma fibrinogen levels are associated with vascular complications in the general population. Fibrin, the structural element in a clot, is derived from fibrinogen by activation of thrombin. An abnormal fibrin gel structure has been demonstrated in patients with myocardial infarction and in diabetic patients during poor metabolic control. In the present study the properties of fibrin gel structure were investigated in 20 patients with insulin-dependent diabetes mellitus (IDDM): 10 patients without (age: 30 +/- 8; diabetes duration: 7 +/- 6 years), and 10 patients (age: 44 +/- 7; diabetes duration: 27 +/- 9 years) with microangiopathy. Fifteen healthy subjects served as controls (age: 40 +/- 8 years). The glycosylated haemoglobin level (HbA1c) was elevated (p < 0.001) in the patients: 6.5 +/- 1.5% in diabetic patients without, and 7.1 +/- 1.0% in diabetic patients with microangiopathy. C-reactive protein and plasma fibrinogen were similar as compared to healthy control subjects. The properties of the fibrin gel structure; i.e. the permeability coefficient (Ks) and the fibre mass length ratio (mu) formed in recalcified plasma on addition of thrombin were investigated. Ks was decreased in the diabetic patients, with (6.5 +/- 2.0 cm2; p < 0.01) and without microangiopathy (6.5 +/- 2.7 cm2; p < 0.05), as compared to healthy subjects (10.0 +/- 3.4 cm2), while mu was not significantly (p = 0.14) altered. The results indicate a lower fibrin gel porosity in patients with IDDM, despite normal plasma fibrinogen and irrespective of microangiopathy. The abnormal fibrin gel structure may be due to an increased glycosylation of the fibrin (-ogen) molecule caused by long-term hyperglycaemia and may be of importance for the development of angiopathy in diabetic patients.

Adult↗
PubMed1996

Quantitative genetic analyses of insulin-like growth factor I (IGF-I), IGF-binding protein-1, and insulin levels in middle-aged and elderly twins.

With the use of quantitative genetic models, the relative importance of genetic and environmental influences on serum levels of insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin was evaluated in 248 pairs of middle-aged and elderly Swedish twins reared apart and reared together. Heritability estimates (the relative influence of genetic effects) were 48% for insulin, 63% for IGF-I, and 36% for IGFBP-1. There was no indication of differences in heritability estimates for IGF-I, IGFBP-1, and insulin across age and gender groups. Nonshared environmental influences, unique to individuals, explained the remaining variance in the measures. The genetic influences on IGF-I levels were independent of the genetic influences on insulin and IGFBP-1 levels. However, a small, but significant, proportion of the genetic variation in IGFBP-1 was in common with genetic influences for insulin. Furthermore, genetic effects explained 36% of the phenotypic correlation between IGFBP-1 and insulin, whereas the phenotypic associations between IGF-I and both IGFBP-1 and insulin were entirely attributable to environmental effects. Finally, the phenotypic association between IGF-I and IGFBP-1 was mediated wholly by environmental influences in common with insulin.

Aged↗