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H Beck-Nielsen

Publications and source records attributed to H Beck-Nielsen.

At least 73 records · Page 4Linked to original sources
PubMed2000

Cytokines and bone loss in a 5-year longitudinal study--hormone replacement therapy suppresses serum soluble interleukin-6 receptor and increases interleukin-1-receptor antagonist: the Danish Osteoporosis Prevention Study.

The proinflammatory cytokines interleukin-1 beta (IL-1 beta) and IL-6 may play a central role in the acceleration of postmenopausal bone loss, but observational studies have led to contradictory results. Estrogen-dependent changes in the production of IL-1 receptor antagonist (IL-1ra) and the soluble IL-6 receptor (sIL-6R) potentially modify cytokine bioactivity. We therefore assessed the impact of menopause and hormone replacement therapy (HRT) on cytokines and activity modifiers in serum within a 5-year longitudinal study. One hundred sixty perimenopausal women (age 50.1 +/- 2.8 years) were randomized to HRT or no treatment. Serum IL-6 increased with age (r = 0.16; p < 0.05), but cytokines did not correlate with baseline bone mineral density (BMD). HRT led to small increases in IL-1ra (p < 0.001) and IL-6 (p < 0.05), with a decrease in sIL-6R (p < 0.01) and no change in IL-1 beta. No changes were observed in the control group. IL-1ra was inversely correlated with bone loss at the ultradistal forearm (r = 0.29; p < 0.05) and to a lesser degree at the spine (r = 0.20; p = 0.09). In addition, there was a weak positive correlation between sIL-6R and bone loss at the ultradistal forearm (r = 0.26; p < 0.05). High IL-6 levels were associated with slower bone loss (spine r = 0.31, p < 0.01) and controlling for age did not diminish this association. The percent change in sIL-6R during HRT was correlated with the bone loss at the femoral neck (r = -0.29; p < 0.01) and weakly with bone loss in the spine (r = -0.16; p = 0.17). In conclusion, serum IL-1ra and sIL-6R are influenced by HRT and are associated with the rate of bone loss in perimenopausal women.

Adult↗
PubMed2000

The nicotinic acid analogue acipimox increases plasma leptin and decreases free fatty acids in type 2 diabetic patients.

The effect of 3 days of intensive treatment with acipimox, an antilipolytic nicotinic acid derivative, on plasma leptin levels was studied in eight patients with Type 2 diabetes mellitus in a double-blind, placebo-controlled, cross-over study. Acipimox reduced plasma free fatty acids (FFA) markedly and lowered plasma triglycerides, glucose and insulin. Plasma leptin levels were elevated in all eight patients during 3 days of acipimox treatment (mean increase+/-s.e.: 2.38+/-0.57ng/ml, P<0.005) and the 24h mean effect of acipimox on leptin levels increased during the experimental period (P<0.03). The effect on plasma insulin and glucose resembled a mirror image of the effect on plasma leptin during 3 days of treatment. The suggestion that leptin mediates insulin resistance and may be involved in the development of the diabetic syndrome cannot be supported by the present results. It has been reported that FFA stimulates leptin secretion. Surprisingly, despite a markedly reduced FFA level, leptin concentration increased in the present study. We suggest that a primary acipimox effect is to increase leptin secretion, and that this prevails over the reduced FFA stimulus.

Area Under Curve↗
PubMed2000

Glucose-mediated glucose disposal in insulin-resistant normoglycemic relatives of type 2 diabetic patients.

With the aim of investigating glucose-mediated glucose disposal (glucose effectiveness [GE]) in 15 (3 female and 12 male subjects) insulin-resistant normoglycemic relatives of patients with type 2 diabetes (DM2), and 15 age-, sex-, and BMI-matched control subjects without a family history of DM2, we performed 2 studies: 1) a 5-h euglycemic near-normoinsulinemic pancreatic clamp with somatostatin (360 microg/h), insulin (0.25 mU x kg(-1) x min(-1)), glucagon (0.5 ng x kg(-1) x min(-1)), growth hormone (6 ng x kg(-1) x min(-1)), and tritiated glucose infusion and indirect calorimetry; and 2) on a separate day, an identical 5-h clamp but at hyperglycemia (approximately 12 mmol/l) over the last 2 h. Fasting plasma insulin (PI) concentrations were elevated in the relatives compared with control subjects (49 +/- 6 vs. 32 +/- 5 pmol/l, P < 0.04), whereas plasma glucose (PG) was not (5.6 +/- 0.1 vs. 5.5 +/-0.1 mmol/l). At the end (i.e., 4.5-5.0 h) of the euglycemic clamp (PG, 6.1 +/- 0.4 vs. 5.6 +/- 0.1 mmol/l; PI, 78 +/- 5 vs. 73 +/-6 pmol/l), peripheral glucose uptake (Rd(euglycemia)) was decreased in the relatives (2.93 +/- 0.08 vs. 3.70 +/-0.23 mg x min(-1) x kg(-1) fat free mass [FFM], P < 0.005), due to a decreased nonoxidative glucose disposal (0.83 +/-0.21 vs. 1.62 +/- 0.19 mg x min(-1) x kg(-1) FFM, P < 0.01), but hepatic glucose production (HGP) was increased (1.97 +/-0.19 vs. 1.50 +/- 0.13 mg x min(-1) x kg(-1) FFM, P < 0.05). At the matched end of the hyperglycemic clamp (PG, 12.7 +/-0.2 vs. 12.6 +/- 0.2 mmol/l; PI, 87 +/- 5 vs. 78 +/- 7 pmol/l), peripheral glucose disposal (Rd(hyperglycemia)) (5.52 +/- 0.22 vs. 5.92 +/- 0.29 mg x min(-1) x kg(-1) FFM, NS), nonoxidative glucose disposal (2.93 +/- 0.18 vs. 2.78 +/- 0.25 mg x min(-1) x kg(-1) FFM, NS), and HGP(hyperglycemia) (1.20 +/- 0.09 vs. 1.37 +/-0.23 mg x min(-1) x kg(-1) FFM, NS) were all identical. When the effectiveness of glucose itself on glucose uptake and production [(Rd(hyperglycemia) - Rd(euglycemia))/deltaPG and (HGP(euglycemia)- HGP(hyperglycemia))/deltaPG] was calculated, the relatives had a 22% increase in peripheral uptake (0.022 +/- 0.002 vs. 0.018 +/- 0.002 mg x min(-1) x kg(-1) FFM per mg/dl), due to a significantly increased nonoxidative glucose metabolism and enhanced suppression of HGP (0.0076 +/- 0.0021 vs. 0.0011 +/- 0.0022 mg x min(-1) x kg(-1) FFM per mg/dl, P < 0.05). In conclusion, in insulin-resistant relatives of DM2 patients, whole-body glucose-mediated glucose disposal is increased by GE enhancement of the muscle nonoxidative glucose pathway and by GE enhancement of the suppression of HGP. These mechanisms may represent a compensatory mechanism to the ongoing insulin resistance of these relatives.

Adult↗
PubMed1999

[The clinical impact of gestational diabetes mellitus].

In Denmark, gestational diabetes mellitus (GDM) develops in about 2% of all pregnant women. The discussion of GDM is complicated by lack of consensus regarding screening methods, diagnosis and treatment. Observational studies indicate that untreated GDM is associated with an increased risk of maternal and perinatal morbidity, and that the offspring of GDM mothers tend to be at increased risk of developing diabetes and adiposity as a result of an abnormal intrauterine environment. Several follow-up studies have shown that women with previous GDM run a considerable risk of developing diabetes (especially type 2 diabetes) later in life. Intervention strategies for this high risk group are suggested.

Diabetes, Gestational↗
PubMed1999

Does zygosity influence the metabolic profile of twins? A population based cross sectional study.

OBJECTIVE: To study the influence of zygosity on the metabolic variables involved in the pathophysiology of type 2 diabetes. DESIGN: Population based cross sectional study. SETTING: Odense University Hospital, Denmark. PARTICIPANTS: 125 monozygotic twin pairs and 178 dizygotic twin pairs of the same sex born between 1921 and 1940. MAIN OUTCOME MEASURES: Clinical characteristics of monozygotic and dizygotic twins with or without a family history of type 2 diabetes. RESULTS: Absolute prevalences of type 2 diabetes and impaired glucose tolerance according to the World Health Organisation criteria were similar in both the monozygotic and the dizygotic twins as were measurements of height, weight, body mass index, waist to hip ratio, and fasting plasma glucose and insulin concentrations. During the oral glucose tolerance test, monozygotic twins had a higher incremental plasma insulin area under the curve than dizygotic twins (10.05 (SD 0.68) v 9.89 (0.72) pmol/lxminutes, P<0.01) indicating insulin resistance. In twins with normal glucose tolerance and without first degree relatives or co-twins with type 2 diabetes or impaired glucose tolerance, both the glucose and insulin areas under the curve were higher among monozygotic twins (glucose 214.4 (88.3) v 189.8 (78.4) mmol/lxminutes, P<0.05; insulin 20 040 (14 865-32 554) v 17 625 (12 330-23 640) pmol/lxminutes, P=0.08). CONCLUSION: Zygosity influences both plasma glucose and plasma insulin concentrations during an oral glucose tolerance test. This supports an intrauterine influence on glucose homeostasis and perhaps on insulin resistance in humans.

Aged↗
PubMed1999

The Danish Osteoporosis Prevention Study (DOPS): project design and inclusion of 2000 normal perimenopausal women.

OBJECTIVE: In 1990 we initiated a 20 year, partly randomised study (Danish Osteoporosis Prevention Study, DOPS) in order to (a) evaluate clinical, biochemical and osteodensitometric variables as predictors of low bone mass and future osteoporotic fractures, and (b) test the hypothesis, that hormone replacement therapy (HRT) initiated shortly after menopause reduces the risk of later osteoporotic fractures. This report describes study design and baseline characteristics of the DOPS-cohort. METHODS: The study design is pragmatic, attempting to mimic the normal clinical situation. Several HRT alternatives are available according to clinical need. It was considered futile, impractical and unethical to use placebo for 20 years. Instead the study focus on hard endpoints (fractures) confirmed by independent persons (peripheral fractures) or by methods which allow investigator blinding (spinal X-rays). Statistical evaluation will focus on intention to treat analyses evaluating the decision of HRT and it's feasibility. With a compliance of 60% we will have sufficient statistical power (88%) to detect a fracture reduction of 40% in the treatments group. Clinical risk factors, current daily intakes of macronutrients, vitamins and minerals, anthropometric variables, biochemical variables (including bone markers and 25-hydroxyvitamin D), regional bone mineral density (BMD) and total body composition were assessed in all participants at entry and at various follow up intervals. RESULTS: 2016 study participants were recruited by direct mailing to a random sample of 45-58 years old women. In the randomised arm 501 were allocated to HRT and 505 to no treatment. In the non-randomised arm 219 preferred HRT and 791 preferred no treatment. Post-randomisation analysis revealed a slight but significant difference in age (50.01 versus 50.44 years) but no difference in menopausal age, prevalence of hysterectomy, educational level, BMI, serum bone alkaline phosphatase, serum osteocalcin, urine hydroxyproline or serum 25-hydroxyvitamin D. In the non-randomised arm women preferring HRT were closer to menopause, had a higher prevalence of hysterectomy, were better educated, were leaner, and had lower bone turnover than the women, who refused HRT. CONCLUSION: It is possible to include a sufficient number of perimenopausal women in a randomised 20 year study on the antifracture effect of HRT.

Body Composition↗
PubMed1999

Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance--a population-based twin study.

To elucidate the relative importance of genetic and environmental factors on the development of Type II (non-insulin dependent) diabetes mellitus, we examined a sample of twins (n = 606) ascertained from the population-based Danish Twin Register. Based on a standard 75 g oral glucose tolerance test and current WHO criteria we identified 62 pairs in which one or both had Type II diabetes. The probandwise concordance (monozygotic: 0.50; dizygotic: 0.37) for Type II diabetes per se was not very different. When including the twins with impaired glucose tolerance (IGT), however, the probandwise concordance for abnormal glucose tolerance was significantly different between monozygotic (0.63) and dizygotic (0.43) twin pairs, (p < 0.01). These findings were supported by the heritability estimates for Type II diabetes per se (26%) and for abnormal glucose tolerance (61%). The metabolic variables, insulin resistance and insulin secretion, and anthropometric variables, body mass index and waist to hip ratio, known to be associated with the development of glucose intolerance had a heritability of 26, 50, 80 and 6% respectively. This study confirms the notion of a multifactorial aetiology of Type II diabetes. It supports the contribution of non-genetic aetiological components in the development of Type II diabetes per se. The study also indicates a role for genes in the aetiology of abnormal glucose tolerance. We therefore propose that genetic predisposition is important for the development of abnormal glucose tolerance. Non-genetic factors, however, might play a predominant role in controlling whether a genetically predisposed individual progresses to overt Type II diabetes.

Body Constitution↗
PubMed1999

Intracellular skeletal muscle glucose metabolism is differentially altered by dexamethasone treatment of normoglycemic relatives of type 2 diabetic patients.

Young first-degree relatives of type 2 diabetic patients are insulin-resistant, with the insulin resistance mainly located in skeletal muscle due to decreased insulin-induced nonoxidative glucose metabolism and muscle glycogen synthase activation. We investigated whether the mechanism differs for dexamethasone (dex)-induced insulin resistance in first-degree relatives of type 2 diabetics versus healthy control subjects by quantifying intracellular glucose processing in muscle biopsies taken before and after 5 days of dex treatment (4 mg/d) in 20 normal glucose-tolerant relatives of type 2 diabetic patients and 20 matched controls (age, 29.4 +/- 1.7 v 29.4 +/- 1.6 years; body mass index, 25.1 +/- 1.0 v 25.1 +/- 0.9 kg/m2). In addition, an intravenous glucose tolerance test (IVGTT) combined with continuous indirect calorimetry was performed. Following 5 days of dex treatment, glucose tolerance deteriorated in both the relatives and the control subjects. Fasting dry-weight muscle glucose and fasting intracellular muscle glucose concentrations increased in response to dex only in the relatives (2.43 +/- 0.21 v 2.97 +/- 0.26 mmol/kg dry weight, P < .05; 0.28 +/- 0.07 v 0.45 +/- 0.08 mmol/L intracellular water, P < .05); no increases were observed in the control subjects. Fasting dry-weight muscle lactate also increased post-dex only in the relatives (7.37 +/- 0.40 v 10.77 +/- 1.22 mmol/kg dry weight, P < .001). Both basal muscle glucose and lactate concentrations from the IVGTT study correlated with the 2-hour post-dex glucose value obtained during the OGTT study in the relatives (R = .76 and R = .74, respectively, both P < .0001) but not in the control subjects. Basal intramuscular glycogen synthase activity decreased approximately 25% in both the relatives and control subjects post-dex; the decrement was significant (P < .01) only in control subjects. Indirect calorimetry during the post-dex IVGTT demonstrated increased glucose oxidation (P < .03) and reduced lipid oxidation (P < .03) in the relatives only. We postulate that the insulin resistance induced by dex in first-degree relatives of type 2 diabetic patients is associated with a preferential channeling of glucose into the glycolytic pathway (increased glucose oxidation and lactate production), probably associated with a preexisting downregulation of the glycosen synthase pathway.

Adult↗
PubMed1999

Lumbar vertebral body compressive strength evaluated by dual-energy X-ray absorptiometry, quantitative computed tomography, and ashing.

Bone densitometry with DXA (dual energy X-ray absorptiometry) and QCT (quantitative computed tomography) techniques are used for in vivo assessment of bone strength and thereby prediction of fracture risk. However, only few in vitro studies have investigated and compared these techniques' ability to determine vertebral compressive strength. The aim of the present study was to (1) assess the predictive value of DXA, QCT, and pQCT (peripheral QCT) for vertebral bone compressive strength assessed by mechanical testing; (2) describe both linear and power relationship between density and strength; and (3) evaluate whether gender-related differences in the above relations were present. The material comprised human lumbar vertebrae L3 from 51 women and 50 men (age range: 18 to 96 years). The study showed that both DXA and CT techniques (QCT and pQCT) have a high predictive value for vertebral strength. The DXA BMD had a high correlation with maximum compressive load (r2 = 0.86). The QCT and pQCT had high correlations with maximum compressive stress (r2 = 0.75 and r2 = 0.86, respectively). The correlation between ash density of the biomechanically tested specimen and maximum compressive stress was r2 = 0.88. There were no differences between linear and power fit in the degree of determination between density and strength. There was no gender-related difference in the relationship between volumetric density and maximum compressive stress. In conclusion, it was demonstrated that DXA, QCT, and pQCT are ex situ equally capable of predicting vertebral compressive strength with a degree of determination (r2) between 75% and 86%. No differences were found between linear and power analysis of the relationship between density and strength, and no difference was found in the density strength relationship between women and men.

Absorptiometry, Photon↗
PubMed1999

Impact of ubiquinone (coenzyme Q10) treatment on glycaemic control, insulin requirement and well-being in patients with Type 1 diabetes mellitus.

AIM: To investigate the effect of ubiquinone (coenzyme Q10) on glycaemic control and insulin requirement in patients with Type 1 diabetes mellitus (DM). METHODS: We investigated 34 patients with Type 1 DM in a randomized, double-blind, placebo-controlled study. Patients received either 100 mg Q10 or placebo daily for 3 months. The insulin doses were adjusted according to patients' home measurements of blood glucose concentrations and reported experience of hypoglycaemia. RESULTS: At randomization no differences existed between the Q10 and the placebo groups in age, body mass index (BMI), HbA1c, daily insulin dose or mean daily blood glucose concentration. Serum Q10 concentration increased in the Q10 group (mean +/- SD: 0.9+/-0.2 vs. 2.0+/-1.0 microg/ml, P<0.005), with no change in the placebo group (0.9+/-0.3 vs. 0.9+/-0.3 microg/ml, not significant (NS)). Following intervention no differences existed between the Q10 and the placebo groups regarding HbA1c (7.86+/-0.88 vs. 7.84+/-0.84%), mean daily blood glucose concentrations (8.06+/-1.86 vs. 8.53+/-1.88 mM), mean insulin dose (52.1+/-13.2 vs. 52.6+/-21.4 U), hypoglycaemic episodes (2.0+/-1.8 vs. 2.5+/-2.1 episodes/week), or cholesterol concentrations (4.81+/-0.91 vs. 4.78+/-1.07 mM). Furthermore, no differences existed in the well-being of the patients reported from a visual analogue scale (physical: 0.67+/-0.21 vs. 0.71+/-0.18, psychological: 0.70+/-0.25 vs. 0.73+/-0.24). CONCLUSION: Q10 treatment does not improve glycaemic control, nor does it reduce insulin requirement, and it can therefore be taken by patients with Type 1 DM without any obvious risk of hypoglycaemia. No major beneficial or unfavourable effects on the investigated parameters could be demonstrated and no major changes in the sense of well-being occurred in the patients.

Adult↗
PubMed1999

The Trp64Arg mutation of the adrenergic beta-3 receptor gene impairs insulin secretion: a twin study.

AIMS: The physiological role of the adrenergic beta-3 receptor is poorly understood in man but the Trp64Arg mutation of the receptor gene has been related to the insulin resistance syndrome, an earlier onset of diabetes and rapid weight gain. This study set out to examine the effects of the mutation on glycaemic responses after an oral glucose tolerance test. METHODS: A standard oral glucose tolerance test (75 g glucose) was performed in 196 dizygotic twins. Serum insulin and glucose responses were measured at 0, 30 and 120 min. RESULTS: In the twins discordant for the mutation (21 pairs), no effects of the mutation were found on the plasma glucose responses. The insulin response given as incremental area under curve (iAUC) (median 13.8 (25-75th percentile 9.3-21.0) vs. 23.3 (14.2-29.2) mmol x l(-1) x min, P<0.021) and the insulinogenic index ((insulin30min - insulin0min)/ (glucose30min - glucose0min)), a measure of the insulin secretory capacity (44 (34-58) vs. 75 (42-124), P<0.006), were considerably lower in the variant type. The results were confirmed when using non-paired statistics on all subjects. CONCLUSION: It was concluded that the adrenergic beta-3 receptor, in addition to its already known effects, may be involved in the regulation of insulin secretion and that patients with the Trp64Arg mutation present an impaired insulin secretion.

Aged↗
PubMed1999

Independent influence of age on basal insulin secretion in nondiabetic humans. European Group for the Study of Insulin Resistance.

Glucose tolerance deteriorates with aging. To test whether age per se impairs basal beta-cell function, we analyzed retrospective clamp data from a large group (n = 957) of nondiabetic Europeans over the 18-85 yr age range (the European Group for the Study of Insulin Resistance database). In this cohort, the fasting posthepatic insulin delivery rate [IDR, obtained as the product of clamp-derived posthepatic insulin MCR and fasting plasma insulin concentration] was 8.9 (6.6) mU/min (median and interquartile range), and it gradually increased with age. In univariate association, IDR was positively related to body mass index (P < 0.0001), fasting plasma glucose (P < 0.01), and waist-to-hip ratio (P < 0.001), and negatively related to insulin sensitivity (P < 0.0001). After controlling for these factors in a multivariate model, IDR declined significantly with age (P < 0.0001). This intrinsic effect of age on IDR was similar in men and women, and it averaged 25% between 18-85 yr. In the same statistical model, insulin MCR (but not fasting plasma insulin concentration) showed a significant (P < 0.0001) inverse relation to age. We conclude that, in nondiabetic Caucasian subjects of either sex, senescence per se is associated with a progressive decline in both insulin clearance and basal insulin release.

Adolescent↗
PubMed1999

Age- and gender-related differences in vertebral bone mass, density, and strength.

This study was designed to evaluate age- and gender-related differences in vertebral bone mass, density, and strength by dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), peripheral QCT (pQCT), ash measurements, and biomechanical testing. The material comprised human lumbar vertebral bodies (L3) from 51 females and 50 males (age-range: 18-96 years). The results showed that females had significantly lower vertebral body bone mass (ash weight) than males at any given age. The decline in bone mass with age was parallel for females and males. The different bone density measurements-cancellous ash density, total vertebral body ash density, DXA bone mineral density, QCT, and pQCT-showed no gender-related difference concerning numeric value or changes with age. Morphometrical measurements showed that females had smaller vertebral bodies (volumes) than males. Hence the females had significantly smaller cross-sectional area (CSA) of L3 than males (11.6 cm2 and 14.4 cm2, respectively). This led to females having lower maximum compressive load (N) than males at all ages, whereas maximum compressive stress (load/CSA) showed no gender-related difference. In conclusion, females have lower vertebral body bone mass than males at any given age, due to smaller vertebral bodies. Hence, maximum compressive load (strength not corrected for size) was lower in females. Vertebral body cancellous bone density and total-vertebral body density were equal when comparing genders, and no gender differences were found in the size-corrected strength: maximum compressive stress. The decrease with age in vertebral body compressive strength decrease was twice as large as the age decrease in density.

Absorptiometry, Photon↗
PubMed1999

General characteristics of the insulin resistance syndrome: prevalence and heritability. European Group for the study of Insulin Resistance (EGIR).

It has recently been recommended by a WHO expert committee that the insulin resistance syndrome, a cluster of cardiovascular risk factors linked to insulin resistance, should be termed 'the metabolic syndrome'. Characterisation with data from 2 large databases [the European Group for the study of Insulin Resistance (EGIR) and the Danish Twin Register] has shown that insulin resistance correlates closely with the various components of the metabolic syndrome, and that the prevalence of the syndrome is approximately 16% among Caucasians. Both genetically determined and environmentally induced insulin resistance may precipitate onset of the metabolic syndrome, and increased levels of abdominal fat may be of primary importance in its development.

Adolescent↗
PubMed1999

Triglyceride-induced diabetes associated with familial lipoprotein lipase deficiency.

Raised plasma triglycerides (TGs) and nonesterified fatty acid (NEFA) concentrations are thought to play a role in the pathogenesis of insulin-resistant diabetes. We report on two sisters with extreme hypertriglyceridemia and overt diabetes, in whom surgical normalization of TGs cured the diabetes. In all of the family members (parents, two affected sisters, ages 18 and 15 years, and an 11-year-old unaffected sister), we measured oral glucose tolerance, insulin sensitivity (by the euglycemic-hyperinsulinemic clamp technique), substrate oxidation (indirect calorimetry), endogenous glucose production (by the [6,6-2H2]glucose technique), and postheparin plasma lipoprotein lipase (LPL) activity. In addition, GC-clamped polymerase chain reaction-amplified DNA from the promoter region and the 10 coding LPL gene exons were screened for nucleotide substitution. Two silent mutations were found in the father's exon 4 (Glu118 Glu) and in the mother's exon 8 (Thr361 Thr), while a nonsense mutation (Ser447 Ter) was detected in the mother's exon 9. Mutations in exons 4 and 8 were inherited by the two affected girls. At 1-2 years after the appearance of hyperchylomicronemia, both sisters developed hyperglycemia with severe insulin resistance. Because medical therapy (including high-dose insulin) failed to reduce plasma TGs or control glycemia, lipid malabsorption was surgically induced by a modified biliopancreatic diversion. Within 3 weeks of surgery, plasma TGs and NEFA and cholesterol levels were drastically lowered. Concurrently, fasting plasma glucose levels fell from 17 to 5 mmol/l (with no therapy), while insulin-stimulated glucose uptake, oxidation, and storage were all markedly improved. Throughout the observation period, plasma TG levels were closely correlated with both plasma glucose and insulin concentrations, as measured during the oral glucose tolerance test. These cases provide evidence that insulin-resistant diabetes can be caused by extremely high levels of TGs.

Adolescent↗