Biomedical subjects

H Beck-Nielsen

Publications and source records attributed to H Beck-Nielsen.

At least 109 records · Page 6Linked to original sources

PubMed1996

Troglitazone, an insulin action enhancer, improves metabolic control in NIDDM patients. Troglitazone Study Group.

The effects of troglitazone, a novel thiazolidinedione, in non-insulin-dependent diabetic (NIDDM) patients were studied in a double-blind, parallel-group, placebo-controlled, dose-ranging trial. A total of 330 patients (63% male), mean age 57 years (range 39-72), with two fasting capillary blood glucose values > or = 7 and < or = 15 mmol/l (within 2.5 mmol/l of each other) were randomised to treatment with placebo or troglitazone at doses of 200, 400, 600 or 800 mg once daily, or 200 or 400 mg twice daily, for 12 weeks. Prior to the study, treatment had been with diet alone (38% patients) or with oral hypoglycaemic agents which were stopped 3-4 weeks before study treatment started. During treatment, HbA1c tended to rise in patients taking placebo (7.2-8.0%), but remained unchanged with all doses of troglitazone. After 12 weeks of treatment, HbA1c was significantly lower in the troglitazone-treated (mean 7.0-7.4%) compared to the placebo-treated (8.0%) patients (p = 0.055 to < 0.001), as was fasting serum glucose concentration (troglitazone, 9.3-11.0 mmol/l vs placebo, 12.9 mmol/l, p < 0.001). All doses of troglitazone were equally effective. Troglitazone also lowered fasting plasma insulin concentration, by 12-26% compared to placebo (p = 0.074 to < 0.001). Insulin sensitivity assessed by homeostasis model assessment (HOMA) was greater after 12 weeks of treatment in troglitazone-treated patients (troglitazone, 34.3-42.8% vs placebo, 29.9%, p < 0.05). In addition, serum triglyceride and non-esterified fatty acid concentrations were significantly lower and HDL cholesterol higher at troglitazone doses of 600 and 800 mg/day. LDL cholesterol increased at 400 and 600 mg doses only (from 4.3 and 3.9 mmol/l at baseline to 4.8 and 4.5 mmol/l, respectively at 12 weeks, p < 0.05), but not at doses of 800 mg once daily or 400 mg twice daily. LDL/HDL ratio did not change during treatment. All doses were well tolerated; incidence of adverse events in troglitazone-treated patients was no higher than in those treated with placebo. However, a tendency to reduced neutrophil counts was observed in patients taking the highest doses of troglitazone. We conclude that troglitazone is effective and well-tolerated and shows potential as a new therapeutic agent for the treatment of NIDDM.

Adult↗

PubMed1996

Altered basal and insulin-stimulated phosphotyrosine phosphatase (PTPase) activity in skeletal muscle from NIDDM patients compared with control subjects.

To measure possible changes in basal and insulin-stimulated phosphotyrosine phosphatase (PTPase) activity in skeletal muscle from insulin-resistant individuals, soluble and particulate muscle fractions were prepared from biopsies taken before and after a 3-h hyperinsulinaemic euglycaemic clamp in eight non-insulin-dependent diabetic (NIDDM) patients and nine control subjects. We used a sensitive sandwich-immunofluorescence assay and the human insulin receptor as the substrate. PTPase activity was expressed as percentage of dephosphorylation of phosphotyrosyl-residues in immobilized insulin receptors per 2 h incubation time per 83 micrograms and 19 micrograms muscle fraction protein (soluble and particulate fraction, respectively). In the diabetic soluble muscle fractions, the basal PTPase activity was decreased compared with that of control subjects (11.5 +/- 5.5 vs 27.5 +/- 3.3, p < 0.04, mean +/- SEM). In the particulate muscle fractions from the control subjects, PTPase activity was increased after 3 h hyperinsulinaemia (20.0 +/- 3.2 vs 30.2 +/- 3.6, p < 0.03) and in the corresponding soluble fractions PTPase activity seemed decreased (27.5 +/- 3.3 vs 19.9 +/- 5.9, NS). No effect of insulin on PTPase activity was found in NIDDM patients (25.1 +/- 4.1 vs 27.2 +/- 5.2, 11.5 +/- 5.5 vs 15.1 +/- 4.5 [particulate and soluble fractions], NS). In conclusion, we found that the basal PTPase activity in soluble muscle fractions was decreased in NIDDM patients; furthermore, insulin stimulation was unable to increase PTPase activities in the particulate fractions, as opposed to the effect of insulin in control subjects.

Biopsy↗

PubMed1996

Glucose processing during the intravenous glucose tolerance test.

The impact of the dynamic changes in plasma glucose and insulin levels observed during a frequently sampled intravenous (IV) glucose tolerance test (FSIGT) on whole-body glucose processing and muscle glycogen metabolism is not known. Paired randomized FSIGTs were performed in eight healthy subjects (age, 31 years; range, 28 to 35; BMI, 25.4 kg/m2; range, 22.3 to 32.1), one with muscle biopsy samples and one without. The mean time average (0- to 40- and 0- to 120-minute) insulin levels during the test were 26.6 and 11.4 mU/1, respectively. Glucose oxidation increased following the IV glucose bolus (basal 1.34 +/- 0.21 v mean value at 0 to 120 minutes 2.09 +/- 0.22 mg/kg fat-free mass [FFM]/min, P < .02). In contrast, fractional glucose-6-phosphate [G-6-P]) (0.1/10 mmol/L) skeletal muscle glycogen synthase activity in muscle biopsies obtained before and following the IV glucose bolus (-30, 30,60, and 120 minutes, respectively) were unchanged (38.1% +/- 2.3%, 38.3% +/- 2.9%, 38.1% +/- 2.3%, 35.4% +/- 2.3%, NS). Skeletal muscle glycogen concentration decreased slightly (449 +/- 54, 439 +/- 55, and 383 +/- 29, and 438 +/- 48 mmol/kg dry weight, P =.05), indicating no net storage of glucose into glycogen during the FSIGT. G-6-P decreased (0.77 +/- 0.08, 0.64 +/- 0.07, 0.66 +/- 0.07, and 0.54 +/- 0.04 mmol/kg dry weight, P < .05). Levels of the insulin-regulatable glucose transporter, GLUT-4, were unchanged. Insulin sensitivity (Si), glucose effectiveness, and insulin secretion parameters (01 and 02) were not affected by the muscle biopsy procedure. In conclusion, the FSIGT is associated predominantly with increased whole-body glucose oxidation with no apparent activation of muscle glucose storage as glycogen. Thus, the Si measured by the FSIGT, although similar in magnitude to the clamp-derived parameter, represents primarily glucose oxidation, in contrast to the euglycemic clamp, which involves glucose oxidation and storage.

Adult↗

PubMed1996

Effects of insulin on glucose turnover rates in vivo: isotope dilution versus constant specific activity technique.

The conventional isotope dilution technique was compared with the more accurate constant specific activity (SA) method at six different insulin levels. Paired euglycemic clamp studies were performed in 30 normal subjects (4-hour insulin infusion: 5, 10, 20, 40, 80, and 160 mU . m-2 . min-1) using primed-constant 3-3H-glucose infusion and either conventional unlabeled glucose infusates (Cold-GINF) or labeled glucose infusates (Hot-GINF) to maintain constant SA. At all insulin levels, both glucose disappearance (Rd) and hepatic glucose production (HGP) were underestimated by the conventional technique, and errors during the first 2 hours correlated with glucose infusion rates (GIRs) (r = .93, P < .00001). During the second hour, mean underestimation of HGP varied from 20% +/- 9% to 84% +/- 16% of basal rates from low-dose to high-dose insulin infusion studies. During prolonged equilibration (3 to 4 hours), errors decreased but were still significant in the two low-dose insulin infusion protocols during the fourth hour. In conclusion, using the conventional isotope dilution technique, suppression of glucose production was overestimated and stimulation of glucose Rd was underestimated, and these errors were greater the higher the GIR. Thus, artifactually greater hepatic and smaller peripheral effects may have been assumed for factors or therapies that influence insulin sensitivity in previous studies using a conventional isotope dilution technique, and therefore, reevaluation of these issues may be relevant in future studies.

Adult↗

PubMed1996

beta-cell function and glucose and lipid oxidation in Graves' disease.

OBJECTIVE: Abnormal glucose metabolism with impaired glucose tolerance has been documented in patients with thyrotoxicosis but the pathogenesis is not fully understood. Therefore, the aim of the present study was to study the beta-cell function and the meal induced oxidative glucose and lipid metabolism in patients with thyrotoxicosis. DESIGN: After an overnight fast the impact of hyperthyroidism on standard mixed meal induced glucose oxidation, lipid oxidation and beta-cell function was studied. PATIENTS: Nine untreated patients with Graves' disease were compared to 9 age and weight matched healthy controls. MEASUREMENTS: Glucose and lipid oxidation were studied by indirect calorimetry before and after the meal. The insulin secretion rate was calculated by the 'combined model' approach, after which the insulin secretion rates and the ambient glucose levels were cross-correlated. The slope of these regression lines was used as a measure of beta-cell sensitivity to glucose and denotes the insulin secretory capacity. beta-Cell function was further evaluated by measurement of proinsulin and its conversion intermediates. Glucoregulatory hormones were also measured. The findings were correlated to the thyroid hormone levels. RESULTS: Fasting blood glucose and post-prandial glucose response were increased in patients (P < 0.01). The hyperthyroid patients displayed a 'dual' beta-cell defect: (a) inability to increase the insulin response appropriately to hyperglycaemia and (b) increased proinsulin levels both in the fasting state and in response to a meal. Indirect calorimetry showed increased lipid oxidation in the fasting state and at the end of the meal (P < 0.01). No difference in glucose oxidation was demonstrated in the fasting state but the post-prandial glucose oxidation was enhanced in the patients (P < 0.01). The adrenaline response was normal, whereas the noradrenaline response was impaired or absent in the patients. The thyroid hormone levels were significantly correlated to fasting levels of blood glucose, insulin, free fatty acids and lipid oxidation, but not to fasting C-peptide, glucose oxidation or catecholamines. CONCLUSIONS: Untreated Graves' disease was associated with glucose intolerance due to quantitative as well as qualitative beta-cell defects. The lipid oxidation was increased in the fasting state and at the end of the meal; after the meal the increase in glucose oxidation was more pronounced in the patients. Thyroid hormones thus increased the oxidation but not by an increase in catecholamines. Indeed, the post-prandial sympathetic response was blunted.

Adult↗

PubMed1996

Impact of hemodialysis on dual X-ray absorptiometry, bioelectrical impedance measurements, and anthropometry.

Dual X-ray absorptiometry (DXA) performs noninvasive assessment of bone and soft tissue with high precision. However, soft tissue algorithms assume that 73.2% of the lean body mass is water, a potential source of error in fluid retention. We evaluated DXA (model QDR-2000; Hologic Inc, Waltham, MA), bioelectrical impedance analysis (BIA), and simple anthropometry in 19 patients (9 women and 10 men, mean age 46 y) before and after hemodialysis, removing 0.9-4.3 L (x: 2.8L) of ultrafiltrate. The reduction in fat-free mass (FFM) measured by DXA was highly correlated with the ultrafiltrate, as determined by the reduction in gravimetric weight (r = 0.975, P < 0.0001; SEE: 233 g), whereas BIA was considerably less accurate in assessing FFM reductions (r = 0.66, P < 0.01; SEE: 757 g). Lumbar bone mineral density (BMD) was unaffected by dialysis, as were whole-body fat and BMD. Whole-body bone mineral content, however, was estimated to be 0.6% lower after dialysis. None of the simple anthropometric measurements correlated significantly with the reduction in FFM. In an unmodified clinical setting, DXA appears to be superior to other simple noninvasive methods for determining body composition, particularly when the emphasis is on repeated measurements.

Absorptiometry, Photon↗

PubMed1996

Insulin resistance in growth hormone-deficient adults: defects in glucose utilization and glycogen synthase activity.

Fourteen GH-deficient (GHD) adults were compared with 12 age-, sex-, and body mass index-matched control subjects using a baseline tritiated glucose equilibration period and euglycemic-hyperinsulinemic (approximately 55 mU/L) clamp in conjunction with paired muscle biopsies for measurement of glycogen synthase fractional velocity (FV0.1). Despite similar basal rates of total glucose disposal (Rd), there was a 64% reduction in the insulin-stimulated rise (delta) in Rd in the GHD adults compared to that in controls [16.6 +/- 2.8 vs. 44.7 +/- 6.0 mumol/kg fat free mass (FFM)/min; P < 0.001], which was mainly due to a decreased glucose storage (GS) rate (delta GS, 12.6 +/- 2.9 vs. 39.5 +/- 7.5 mumol/kg FFM/min; P < 0.01). Furthermore, the insulin sensitivity indexes of Rd (0.39 +/- 0.07 vs. 0.85 +/- 0.11; P < 0.05) and GS (0.25 +/- 0.07 vs. 0.72 +/- 0.13 mumol/kg FFM/min per mU/L; P < 0.02) were reduced in GHD adults compared to the control values. The insulin sensitivity of the glycolytic pathway was also reduced by approximately 50% in GHD adults (P = 0.07 vs. controls). Insulin-stimulated FV0.1 was decreased in GHD adults (0.31 +/- 0.02 vs. 0.47 +/- 0.03; P < 0.005) despite similar basal FV0.1. Using multiple and stepwise regression analysis, duration of GH deficiency, fasting triglycerides and fasting insulin accounted for 67% of the variance in the insulin sensitivity index of Rd. In conclusion, the severe insulin resistance in GHD adults is mainly due to the inhibition of the GS pathway and glycogen synthase activity in peripheral tissues, which is related to the duration of GH deficiency, fasting triglycerides, and fasting insulin.

Adult↗

PubMed1996

Insulin action and age. European Group for the Study of Insulin Resistance (EGIR).

Evidence that age is associated with insulin resistance is discordant. We analyzed euglycemic insulin clamp (1 mU x min(-1) x kg(-1)) data collected at 20 centers throughout Europe from 1,146 men and women with normal glucose tolerance, ranging in age from 18 to 85 years. In the whole group, insulin action (as the M value) declined slightly with age (at a rate of 0.9 micromol x min(-1)-kg(-1) per decade of life, 95% CI = 0.4-1.3, P = 0.0002). When adjusted for BMI, this relationship was no longer statistically significant. The same result was obtained whether insulin action was expressed per kilogram of body weight or per kilogram of fat-free mass, expressed as the M:I ratio, or estimated from fasting plasma insulin concentrations. Subgroup analysis showed that a significant BMI-adjusted decrease in insulin action with age was present only in lean (BMI <25 kg/m2) women (a rate of 1.6 micromol x min(-1) x kg(-1) per decade, 95% CI = 0.6-2.5, P = 0.001), in whom percentage fat mass also increased with age (by 0.38% body weight per decade, P = 0.0007). Insulin action was positively associated with insulin suppression of circulating free fatty acids (FFAs) (+1.5 micromol x min(-1) x kg(-1) for each 10% increase in FFA suppression, P < 0.0001) in a multivariate model accounting for sex, BMI, age, and fasting FFA levels. Furthermore, insulin suppression of FFAs improved with age in men (2% per decade, P < 0.0001) but not in women. In the subgroup of lean women in whom insulin action declined with age, adding FFA suppression to a multiple regression equation canceled the association between age and insulin action. Thus, the small effect of age on insulin action could be adequately explained on the basis of age-related changes in body composition and substrate competition. We conclude that in healthy Europeans, age per se is not a significant cause of insulin resistance of glucose metabolism or lipolysis.

Adult↗

PubMed1996

In vivo glucose metabolism, insulin secretion and, insulin action in Europids with non-insulin-dependent diabetes mellitus (NIDDM) and their first-degree relatives.

In this review we will mainly concentrate on the most common form of NIDDM in Europe, namely the form linked to overweight, arterial hypertension, dyslipoproteinaemia and coronary heart disease (CHD)-the Insulin Resistance Syndrome (IRS). This form of NIDDM seems to be growing epidemically world wide following the industrial growth or the 'cocacolanization', as it has been mentioned. Around 2-3% of the population in Europe suffers from this disease, but for subjects beyond 60 years of age the prevalence is 5-20%. Thus, we face an enormous economical, social, and humanitarian challenge. Therefore it is important to continue the research on aetiology and pathophysiology of this syndrome. The results of treatment of NIDDM patients (often started at 60 years of age) have been rather disappointing; even properly treated NIDDM patients develop substantial complications, especially macroangiopathy. Coronary heart disease is the main cause of death in these patients and the overall mortality rate in NIDDM patients is 3-4 times higher than in comparable non diabetic-subjects. Furthermore, several complications may already be present at the diagnosis of the disease, which indicate that macroangiopathy may not be secondary to the diabetic state itself, but rather a part of the NIDDM phenotype. Based on these findings it seems obvious that the IRS must be diagnosed in the prediabetic states before macroangiopathy has started or reached a clinically manifest level. In this review, therefore, we will discuss the metabolic background of NIDDM and especially focus on the pathophysiological mechanisms leading to hyperglycaemia, i.e. alterations in glucose effectiveness, insulin action and insulin secretion in prediabetic states.

Adult↗

PubMed1995

Concordance rates of insulin dependent diabetes mellitus: a population based study of young Danish twins.

OBJECTIVE: To study the genetic contribution to the aetiology of insulin dependent diabetes mellitus. DESIGN: Historical cohort study of twins, with information on diabetes being gathered by questionnaire, verification of the diagnosis by the subject's diabetologist or general practitioner, and clinical examination in available twins. SETTING: Danish twin register and diabetic clinics and general practices throughout Denmark. SUBJECTS: 20,888 twin pairs born during 1953-82, included in a population based nationwide register. MAIN OUTCOME MEASURES: Crude and cumulative concordance rates and heritability in monozygotic and dizygotic twins. RESULTS: The crude probandwise concordance rate was 0.53 (95% confidence interval 0.33 to 0.73) for monozygotic twin pairs and 0.11 (0.05 to 0.21) for dizygotic twin pairs. When adjusted for age at onset of diabetes and age at last observation among unaffected twin partners the cumulative proband-wise risk from birth to age 35 was estimated as 0.70 (0.45 to 0.95) for monozygotic twins and 0.13 (0.05 to 0.20) for dizygotic twins. The correlations of liability for monozygotic and dizygotic twin pairs were estimated as 0.96 (SE 0.09) and 0.58 (0.07), with a heritability estimate of 0.72 (0.21). CONCLUSIONS: The risk of insulin dependent diabetes in monozygotic twins is higher than previously thought and for dizygotic twins is higher than in ordinary first degree relatives. Based on the findings of this study the genetic component to the disease seems more important than hitherto believed.

Cohort Studies↗

PubMed1995

Multiple defects of both hepatic and peripheral intracellular glucose processing contribute to the hyperglycaemia of NIDDM.

Non-insulin-dependent diabetic (NIDDM) patients were studied during a modified euglycaemic state when fasting hyperglycaemia was normalized by a prior (-210 to -150 min)--and later withdrawn (-150-0 min)--intravenous insulin infusion. Glucose metabolism was assessed in NIDDM patients (n = 10) and matched control subjects (n = 10) using tritiated glucose turnover rates, indirect calorimetry and skeletal muscle glycogen synthase activity determinations. Total and non-oxidative exogenous glycolytic flux rates were measured using appearance rates of tritiated water. A + 180 min euglycaemic hyperinsulinaemic (40 mU.m-2.min-1) clamp was performed to determine the insulin responsiveness of the various metabolic pathways. Plasma glucose concentration increased spontaneously during baseline measurements in the NIDDM patients (-120 to 0 min: 4.8 +/- 0.3 to 7.0 +/- 0.3 mmol/l; p < 0.01), and was primarily due to an elevated rate of hepatic glucose production (3.16 +/- 0.13 vs 2.51 +/- 0.16 mg.kg FFM-1.min-1; p < 0.01). In the NIDDM subjects baseline glucose oxidation was decreased (0.92 +/- 0.17 vs 1.33 +/- 0.14 mg.kg FFM-1.min-1; p < 0.01) in the presence of a normal rate of total exogenous glycolytic flux and skeletal muscle glycogen synthase activity. The simultaneous finding of an increased lipid oxidation rate (1.95 +/- 0.13 vs 1.61 +/- 0.07 mg.kg FFM-1.min-1; p = 0.05) and increased plasma lactate concentrations (0.86 +/- 0.05 vs 0.66 +/- 0.03 mmol/l; p = 0.01) are consistent with a role for both the glucose-fatty acid cycle and the Cori cycle in the maintenance and development of fasting hyperglycaemia in NIDDM during decompensation. Insulin resistance was demonstrated during the hyperinsulinaemic clamp in the NIDDM patients with a decrease in the major peripheral pathways of intracellular glucose metabolism (oxidation, storage and muscle glycogen synthase activity), but not in the pathway of non-oxidative glycolytic flux which was not completely suppressed during insulin infusion in the NIDDM patients (0.55 +/- 0.15 mg.kg FFM-1.min-1; p < 0.05 vs 0; control subjects: 0.17 +/- 0.29; NS vs 0). Thus, these data also indicate that the defect(s) of peripheral (skeletal muscle) glucose processing in NIDDM goes beyond the site of glucose transport across the cell membrane.

Biopsy↗

PubMed1995

Pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM).

In this review, the pathophysiologycal events leading to hyperglycemia in NIDDM patients are discussed, i.e. glucose effectiveness, insulin action (in muscle and liver) and insulin secretion. The natural history of the insulin resistance syndrome is demonstrated and a new staging system is proposed. We conclude that NIDDM is a life-long disease characterized by intraabdominal obesity and macrovascular events several years in advance of hyperglycemia, and that insulin resistance in skeletal muscle plays an important pathophysiological part and also may be used in prediction of the disease.

Adult↗

PubMed1995

Cross calibration of QDR-2000 and QDR-1000 dual-energy X-ray densitometers for bone mineral and soft-tissue measurements.

Replacement of dual energy X-ray densitometry (DXA) equipment may be necessary in many labs with time, or new equipment may be added. In this context we compared patient scans between a Hologic QDR-1000W and a QDR-2000 (n = 29-43, depending on anatomic region) and between QDR-2000 single beam (SB) and fan beam (FB) modes (n = 40-62) as a quality control measure. A total of 83 subjects (79 females and four males) with a wide range of bone mineral densities (BMD) were studied. There was a linear relationship between results with the QDR-1000W and QDR-2000 in SB mode, and between SB and FB mode on the QDR-2000, but the magnitude of the coefficients and constants differed for the different anatomic regions. In SB mode the QDR-2000 underestimated whole body and forearm BMD by 3% relative to the QDR-1000W, even after cross calibration using a spine phantom. Femoral total BMD was slightly, but not significantly, underestimated. Thus, additional postanalysis correction had to be applied to forearm and whole-body scans. In FB with the QDR-2000, spine and whole-body BMD was underestimated by 3%, but femur total and neck BMD was overestimated by 2.2 and 2.8%, respectively, compared with SB scans on the same device. Soft-tissue composition with FB (enhanced analysis protocol) on the QDR-2000 differed greatly from that obtained using SB (standard protocol). Lean tissue mass was 4 kg lower and fat mass 4 kg higher in FB mode.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

PubMed1995

Biological variation of serum and urinary magnesium in apparently healthy males.

The biological variations of serum (S-) magnesium and urinary (U-) magnesium concentrations and excretions have been investigated. Serum samples, 24-h and fasting urinary samples were collected from each of 60 supposedly healthy male volunteers. In addition, 12 volunteers collected additional samples 7 and 112 days after the initial sample. The reference interval for S-magnesium was 0.765-0.997 mmol l-1. The biological variation for S-magnesium was 3.2% within subjects and 7.4% between subjects. This indicated an index of indivduality of 0.5, which means that significant changes in S-magnesium can occur within the limits of the reference interval, and that serial determinations of S-magnesium might prove useful as an indicator of changes in whole body magnesium status. It is, on the other hand, unlikely that a single determination of S-magnesium can be used in assessing whole-body magnesium status in the individual. The reference interval for the 24-h U-magnesium excretion, corrected for surface area, was 1.306-4.762 mumol min-1 1.73 m-2. The 24-h U-magnesium excretion exhibited a biological within-subject variation of 36% and a between-subject variation of 26%. The 24-h U-magnesium excretion did not correlate with S-magnesium, and only slightly (r = 0.58) with the fasting U-magnesium/creatinine concentration. This, and the very large coefficients of variation, make it unlikely that the renal magnesium excretion can be used as a measure of whole body magnesium status, or that changes in the renal magnesium excretion can be used as a measure of changes in whole body magnesium status.

Adult↗

PubMed1995

The new Danish Twin Register: establishment and analysis of twinning rates.

BACKGROUND: Twin registers provide a valuable source for research into disease causation. The existing population-based registers comprise mostly old twins. In order to be able to study diseases which occur in childhood and youth a new Danish twin register has been established. METHODS: The register is based on the Danish Civil Registration, with information on number of twin births from the Danish Vital Statistics Office as the source of validation. All twins resident in Denmark at 1 March 1991 were sent a one-side questionnaire asking about diabetes, willingness to participate in other research projects and similarity in the twins. RESULTS: The register, comprising 20,888 twin pairs, covers 74.4% of all twin pairs born 1953-1967 (incl.) and 97.4% of those born 1968-1982 (incl.). The response rate to the questionnaire study was 92.3%. The responders represented 19,180 twin pairs distributed as 5304 monozygotic pairs, 6861 same-sex dizygotic pairs, 6244 opposite-sex dizygotic pairs and 771 pairs of unknown zygosity. Of the respondent twins, 96% declared their willingness to participate in additional studies. An analysis of trends in the twinning rates for the years 1968-1982 showed that the rate of monozygotic twinning is increasing and the twinning rate of opposite-sex twin pairs is decreasing. CONCLUSIONS: Earlier estimated trends in twinning rates have been confirmed. Due to the high response rate and opportunities for linkage with other Danish registers, the present material provides a valuable resource for twin studies in diseases and human traits.

Adolescent↗

PubMed1995

Insulin increases renal magnesium excretion: a possible cause of magnesium depletion in hyperinsulinaemic states.

The effects of insulin upon renal magnesium excretion were examined. Urinary magnesium excretion rates were measured in seven healthy volunteers (three men, four women) before and during a euglycaemic, hyperinsulinaemic clamp. Insulin was infused at 120 pmol m-2 min-1 and at 240 pmol m-2 min-1. Compared to baseline, the renal magnesium excretion increased 30% during the infusion of insulin at a rate of 120 pmol m-2 min-1. During infusion of insulin, 240 pmol m-2 min-1, renal magnesium excretion increased 50% compared to baseline. There were no changes in either glomerular filtration rates, plasma magnesium, urinary volume or general changes in the renal handling of divalent ions as judged by an unchanged urinary excretion rate of calcium (0% during infusion of insulin, 120 pmol m-2 min-1, and 8% increase during infusion of 240 pmol m-2 min-1 (NS). During the 120 pmol m-2 min-1 insulin infusion rate, plasma insulin rose from 46.1 pmol I-1 to 158.8 pmol I-1 and during the 240 pmol m-2 min-1 insulin infusion rate, mean plasma insulin concentration was 361.4 pmol I-1. Thus, physiological concentrations of insulin induce a specific increase in the renal excretion of magnesium. This might partly explain the magnesium depletion observed in various hyperinsulinaemic states, diabetes mellitus, atherosclerosis, hypertension, and obesity.

Adult↗

PubMed1995

Insulin secretion, insulin action, and hepatic glucose production in identical twins discordant for non-insulin-dependent diabetes mellitus.

12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) were studied for insulin sensitivity (euglycemic insulin clamp, 40 mU/m2 per min), hepatic glucose production (HGP, [3-3H]glucose infusion), and insulin secretion (oral glucose tolerance test and hyperglycemic [12 mM] clamp, including glucagon administration). Five of the nondiabetic twins had normal and seven had impaired glucose tolerance. 13 matched, healthy subjects without a family history of diabetes were included as control subjects. The NIDDM twins were more obese compared with their non-diabetic co-twins. The nondiabetic twins were insulin resistant and had a delayed insulin and C-peptide response during oral glucose tolerance tests compared with controls. Furthermore, the nondiabetic twins had a decreased first-phase insulin response and a decreased maximal insulin secretion capacity during hyperglycemic clamping and intravenous glucagon administration. Nondiabetic twins and controls had similar rates of HGP. Compared with both nondiabetic twins and controls, the NIDDM twins had an elevated basal rate of HGP, a further decreased insulin sensitivity, and a further impaired insulin secretion pattern as determined by all tests. In conclusion, defects of both in vivo insulin secretion and insulin action are present in non- and possibly prediabetic twins who possess the necessary NIDDM susceptibility genes. However, all defects of both insulin secretion and glucose metabolism are expressed quantitatively more severely in their identical co-twins with overt NIDDM.

Age of Onset↗

PubMed1995

Proinsulin immunoreactivity in identical twins discordant for noninsulin-dependent diabetes mellitus.

Disproportionate elevation [increased proinsulin/insulin (PI/INS) ratio] of PI immunoreactivity is associated with noninsulin-dependent diabetes mellitus (NIDDM). The nature of this abnormality is not known. To address the question of whether genetic factors contribute to hyperproinsulinemia, we measured fasting levels of PI immunoreactivity, intact INS, and C peptide (CP) in 12 pairs of monozygotic twins discordant for NIDDM for a mean (+/- SEM) period of 9 +/- 3 yr. Thirteen age- and body mass index-matched healthy subjects without any family history of NIDDM acted as controls. The nondiabetic twins had levels of fasting INS, CP, PI, PI/CP, and PI/INS similar to those of control subjects. Fasting levels of PI, and PI/CP and PI/INS ratios were significantly 2- to 3-fold elevated in NIDDM twins compared to those in both nondiabetic twins and control subjects. To investigate whether hyperproinsulinemia in these NIDDM patients was due to a differential elevation of intact PI or conversion intermediates, we analyzed PI profiles in NIDDM twins and normal subjects by high pressure liquid chromatography. PI was heterogeneous and consisted mainly of des(31,32)-PI and intact PI in both NIDDM patients and normal subjects, with no major difference in composition between the groups. Small amounts of des(64,65)-PI (0-11%) were measured in some patients and normal subjects. The results suggest that hyperproinsulinemia is not a genetically determined trait per se in NIDDM. Disproportionately elevated PI levels seem to be related to the actual disease process. Further conversion of intact PI and des(31,32)-PI may be equally impaired in NIDDM.

Adult↗