Biomedical subjects

J W Eriksson

Publications and source records attributed to J W Eriksson.

At least 37 records · Page 2Linked to original sources

PubMed2003

Evaluation of the new ADA and WHO criteria for classification of diabetes mellitus in young adult people (15-34 yrs) in the Diabetes Incidence Study in Sweden (DISS).

AIMS/HYPOTHESIS: We aimed to evaluate how an aetiology-based classification, as recommended in the ADA and WHO guidelines for classification of diabetes mellitus, matches clinical judgement in the Diabetes Incidence Study in Sweden (DISS), a study covering incident cases of diabetic patients aged 15 to 34 years. METHODS: During a 1-year period (1998), blood samples were taken at diagnosis and 4 months (median) thereafter. Patients were classified according to clinical judgement by the reporting physicians and assessments of islet antibodies (ICA, GADA, and IA-2A) and plasma C-peptide. RESULTS: In 1998, 422 patients were registered in DISS. Among the 313 patients participating in the follow-up, most with clinical Type 1 diabetes (185/218, 85%, 95% CI 79-89%) were islet antibody positive (ab+) at diagnosis. In addition, 14 out of 58 (24%, 14-37%) with clinical Type 2 diabetes and 21 out of 37 (57%, 40-73%) with unclassifiable diabetes were antibody positive at diagnosis. Further to this, 4 out of 33 (12%, 3-28%) were antibody negative with clinical Type 1 diabetes and 4 out of 44 (9%, 3-22%) with Type 2 had converted to antibody positive at follow-up. Among those who were constantly antibody negative, 10 out of 29 (34%, 18-54%) with clinical Type 1 and 1 out of 16 (6%, 0-30%) with unclassifiable diabetes had fasting plasma C-peptide concentrations below the normal range (<0.25 nmol/l) at follow-up. CONCLUSION/INTERPRETATION: Most young adults with clinical Type 1 diabetes (199/218, 91%) had objective Type 1 (ab+ at diagnosis/follow-up and/or low fasting plasma C-peptide concentrations at follow-up), as did one third (18/58, 31%) with clinical Type 2 diabetes and more than half (22/37, 59%) with unclassifiable diabetes. About 10% of those who were antibody negative converted to antibody positive. Our study underlines that a classification considering aetiology is superior to clinical judgement.

Adolescent↗

PubMed2003

Combined near-infrared spectroscopy and multifrequency bio-impedance investigation of skin alterations in diabetes patients based on multivariate analyses.

A group of 34 diabetic men, with different degrees of diabetes complications, including skin changes, were studied by near-infrared (NIR) spectroscopy and total body multi-frequency bio-impedance analyses (MFBIA-body). Skin reflectance spectra were measured with a fibre-optic probe in four locations (sites): hand, arm, leg and foot. As control subjects, a group of 23 healthy males were also measured. A combined multivariate analysis of the two types of spectrum was performed. It was concluded that the NIR method has the potential to detect diabetes-related skin conditions and also that the combination of the two techniques provides a higher potential for classification and discrimination of the skin conditions, with correct classification increasing from 63% to 85%.

Adult↗

PubMed2003

Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the Diabetes Incidence Study in Sweden (DISS).

OBJECTIVE: To study trends in body mass index (BMI) at diagnosis of diabetes in all young Swedish adults in the age range of 15-34 years registered in a nation-based registry. DESIGN: The BMI was assessed at diagnosis in diabetic patients 15-34 years of age at diagnosis, for a period of 17 years (1983-1999). Islet cell antibodies (ICA) were measured during three periods (1987-1988, 1992-1993 and 1998-1999). SETTING: A nationwide study (Diabetes Incidence Study in Sweden). SUBJECTS: A total of 4727 type 1 and 1083 type 2 diabetic patients. MAIN OUTCOME MEASURES: Incidence-year specific BMI adjusted for age, gender and time of diagnosis (month). RESULTS: Body mass index at diagnosis increased significantly both in type 1 (21.4 +/- 3.6 to 22.5 +/- 4.0; P < 0.0001) and in type 2 (27.4 +/- 6.8 to 32.0 +/- 6.0; P < 0.0001) diabetic patients, also when adjusted for age, gender and month of diagnosis. A similar significant increase in BMI was found in type 1 diabetic patients and in type 2 diabetic patients in the periods 1987-1988, 1992-1993 and 1998-1999; years when ICA were assessed and considered in the classification of diabetes. Despite this increase in BMI, there was no increase in the incidence of diabetes in young-adult people in Sweden. CONCLUSION: Body mass index at diagnosis of diabetes in subjects 15-34 years of age has substantially increased during 1983-1999 in Sweden when adjusted for age, gender and month of diagnosis.

Adolescent↗

PubMed2003

Does the autonomic nervous system play a role in the development of insulin resistance? A study on heart rate variability in first-degree relatives of Type 2 diabetes patients and control subjects.

AIMS: To investigate dysregulation of the autonomic nervous system as a potential mechanism for early insulin resistance in the development of Type 2 diabetes. METHODS: Thirteen healthy individuals with first-degree relatives with Type 2 diabetes (R) were compared with 14 control subjects without family history of diabetes (C), matched for age, body mass index and sex. An oral glucose tolerance test and a hyperinsulinaemic euglycaemic clamp were performed. Analysis of heart rate variability during rest, controlled breathing, an orthostatic manoeuvre and a standardized physical stress (cold pressor test (CPT)), were used to evaluate the activity of the autonomic nervous system. RESULTS: Fasting blood glucose, HbA1c and serum insulin were similar in the R and C groups. The M-value, reflecting insulin sensitivity, did not differ significantly between the groups. Total spectral power and high-frequency power were lower in R during controlled breathing (P = 0.05 and P = 0.07, respectively), otherwise there were no significant differences between R and C in heart rate variability. However, low-frequency (LF)/high-frequency (HF) spectral power ratio during CPT, reflecting sympathetic/parasympathetic balance, was negatively associated with insulin sensitivity (r = -0.53, P = 0.006). When all subjects were divided into two groups by the mean M-value, the low M-value group displayed an overall higher LF/HF ratio (P = 0.04). HF power was lower in the low M-value group during controlled breathing and CPT (P = 0.01 and P = 0.03, respectively). CONCLUSION: An altered balance of the parasympathetic and sympathetic nervous activity, mainly explained by an attenuated parasympathetic activity, might contribute to the development of insulin resistance and Type 2 diabetes.

Adult↗

PubMed2003

Metabolic effects of mealtime insulin lispro in comparison to glibenclamide in early type 2 diabetes.

The efficacy and safety of the preprandial injection of insulin lispro was compared with the oral administration of glibenclamide in patients with early type 2 diabetes. In this open-label, multicenter study, 143 patients with a glucagon-stimulated increase in C-peptide of at least 0.4 nmol/L were randomized to receive preprandial insulin lispro (LP) or glibenclamide (GB) for 26 weeks. Seventy-five patients received LP (51 male/24 female; age 40 to 70 years, duration of diabetes 4.4 +/- 2.9 years) and 68 patients received GB (39 male/29 female; age 39 to 70 years; duration of diabetes 4.3 +/- 3.4 years). After 12 weeks, mean 90 minute blood glucose excursions were 0.9 +/- 1.0 mmol/L for LP and 1.8 +/- 1.2 mmol/L for GB (p < 0.0001). After 24 weeks, mean blood glucose excursions were 1.0 +/- 1.1 mmol/L for LP and 1.7 +/- 1.2 mmol/L for GB (p = 0.002). Body weight decreased slightly from 87.2 +/- 2.3 to 86.5 +/- 12.2 kg in the LP group and increased from 84.1 +/- 13.7 to 84.4 +/- 13.3 kg in the GB group. LP versus GB induced changes from baseline to endpoint in fasting C-peptide (nmol/L), proinsulin and insulin levels (pmol/L) were - 0.2 +/- 0.4 versus - 0.1 +/- 0.6 (p = 0.04), - 11.2 +/- 26.0 versus - 1.1 +/- 17.3 (p = 0.03), and - 27.8 +/- 147.4 versus + 32.6 +/- 286.2 (not significant), respectively. HbA 1c at baseline was 7.5 +/- 1.0 % for LP and 7.7 +/- 1.2 % for GB and did not change significantly in either group during the investigation. No significant difference was observed between the groups with respect to hypoglycemic episodes. Treatment with LP improved postprandial blood glucose control more than GB without increasing body weight or hypoglycemic episodes. In addition, use of LP was associated with a decrease in fasting C-peptide and proinsulin levels, suggesting a potential down regulation of endogenous insulin production and improved proinsulin processing efficiency.

Age of Onset↗

PubMed2002

The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0-34 years group in Sweden 1983-1998.

AIMS/HYPOTHESIS: To analyse the incidence of Type I (insulin-dependent) diabetes mellitus in the 0-34 years age group in Sweden 1983-1998. METHODS: Incidence and cumulative incidence per 100 000 and Poisson regression analysis of age-period effects was carried out using 11 751 cases from two nation-wide prospective registers. RESULTS: Incidence (95%-CI) was 21.4 (20.8-21.9) in men and 17.1 (16.6-17.5) in women between 0 and 34 years of age. In boys aged 0-14 and girls aged 0-12 years the incidence increased over time, but it tended to decrease at older age groups, especially in men. Average cumulative incidence at 35 years was 748 in men and 598 in women. Cumulative incidence in men was rather stable during four 4-year periods (736, 732, 762, 756), while in women it varied more (592, 542, 617, 631). In males aged 0-34 years, the incidence did not vary between the 4-year periods ( p=0.63), but time changes among the 3-year age groups differed ( p<0.001). In females the incidence between the periods varied ( p<0.001), being lower in 1987-1990 compared to 1983-1986, but time changes in the age groups did not differ ( p=0.08). For both sexes median age at diagnosis was higher in 1983-1986 than in 1995-1998 ( p<0.001) (15.0 and 12.5 years in males; 11.9 and 10.4 in females, respectively). CONCLUSION/INTERPRETATION: During a 16-year period the incidence of Type I diabetes did not increase in the 0-34 years age group in Sweden, while median age at diagnosis decreased. A shift to younger age at diagnosis seems to explain the increasing incidence of childhood Type I diabetes.

Adolescent↗

PubMed2002

A small reduction in glomerular filtration is accompanied by insulin resistance in type I diabetes patients with diabetic nephrophathy.

BACKGROUND: Insulin sensitivity and insulin clearance are compromised in end-stage renal disease but it has not been fully established whether they are altered in earlier stages of diabetic nephropathy. DESIGN: We studied three groups of patients with type 1 diabetes; 10 with no sign of nephropathy, 11 with albuminuria (> 20 microg min-1) but normal glomerular filtration rate (GFR) and eight with a small reduction in GFR, (43-73 mL min-1 1.73 m-2). The groups were matched for age (range 36-61 years), body mass index (BMI), diabetes duration and glycaemic control. The euglycaemic hyperinsulinaemic clamp technique was utilized to study insulin sensitivity (M-value) and metabolic clearance rate for insulin. Needle biopsies from abdominal subcutaneous fat tissue were obtained to study insulin binding, insulin degradation, insulin-stimulated glucose uptake and anti-lipolysis in adipocytes in vitro. RESULTS: Patients with reduced GFR were more insulin-resistant (M-value 5.7 +/- 0.7 mg kg LBM-1 min-1) than those without nephropathy (9.6 +/- 0.7, P = 0.001) and those with only albuminuria (8.9 +/- 1.2, P = 0.044). In all subjects taken together there was a strong association between insulin sensitivity and GFR (r = 0.46, P = 0.012). Patients with reduced GFR displayed no significant difference in insulin clearance (12.2 +/- 1.6 mL kg-1 min-1) compared to controls (13.8 +/- 1.3) but a slightly lower insulin clearance than patients with only albuminuria (16.6 +/- 1.0, P = 0.027). There were no significant differences between patient groups in the adipocyte studies in vitro, i.e. with respect to insulin binding, insulin degradation and the effects of insulin on glucose uptake and lipolysis. This is compatible with humoral factors causing whole-body insulin resistance and in the group with reduced GFR, we found that serum parathyroid hormone, interleukin-6 and tumour necrosis factor-alpha levels were elevated whereas the morning cortisol was decreased. CONCLUSIONS: In type 1 diabetes, the appearance of albuminuria does not seem to alter insulin sensitivity and clearance. A marked insulin resistance but no consistent impairment in insulin clearance seems to accompany progression to a stage with a slight reduction in GFR. These alterations are not accompanied by general defects in insulin target cells. Instead, alterations in the regulation of insulin-antagonistic hormones and cytokines could potentially contribute to the development of insulin resistance in diabetic nephropathy.

Adipose Tissue↗

PubMed2002

Endocrine abnormalities in healthy first-degree relatives of type 2 diabetes patients--potential role of steroid hormones and leptin in the development of insulin resistance.

BACKGROUND: First-degree relatives of type 2 diabetes patients are at risk of developing diabetes and they display several metabolic and hormonal perturbations. The interplay between insulin resistance, steroid hormones and circulating leptin is, however, still not fully explored in this group. DESIGN: Thirty-three healthy first-degree relatives of type 2 diabetic patients (relatives; M/F 19/14) were compared to 33 healthy subjects without a family history of diabetes (controls) and the groups were matched for gender, age and body mass index (BMI). We performed euglycaemic hyperinsulinaemic clamps and blood was sampled for hormone analyses. RESULTS: Relatives exhibited decreased insulin sensitivity (index of metabolic clearance rate of glucose; MCRI) but when genders were analysed separately, this difference was significant only in males (11.3 +/- 1.3 vs. 15.0 +/- 1.5 units, means +/- SEM, P = 0.030). In male relatives morning cortisol and testosterone levels were lower, whereas leptin was higher than in male controls (P = 0.018, 0.008 and 0.063, respectively). In male relatives plasma testosterone levels were significantly associated with insulin sensitivity (r = 0.48, P = 0.040). Circulating leptin levels were inversely correlated with insulin sensitivity in all subject groups (r-values -0.49 to -0.66; P < 0.05, except in female control subjects P = 0.063). These associations were present also when age and BMI or waist:hip ratio were included in stepwise multiple regression analyses. CONCLUSION: Male subjects genetically predisposed for type 2 diabetes display several endocrine abnormalities including leptin, cortisol and testosterone levels. Dysregulation of these hormones may be important in the development of insulin resistance and type 2 diabetes.

Adipose Tissue↗

PubMed2002

No direct link between albumin excretion rate and insulin resistance--a study in type 1 diabetes patients with mild nephropathy.

AIMS: Albuminuria is thought to be associated with insulin resistance in patients with type 1 and type 2 diabetes as well as in non-diabetic subjects. The aim of this study was to find out about any direct correlation between the albumin excretion rate (AER) and insulin resistance; this was investigated in patients with type 1 diabetes. METHODS: Euglycemic hyperinsulinemic clamps were performed in 18 patients with type 1 diabetes and incipient nephropathy-elevated albumin excretion rate (AER > 20 microg/min) but normal glomerular filtration rate (GFR) (81 - 135 ml/min/1.73 m (2)). RESULTS: AER, determined as mean of two overnight urine collections, was 137 +/- 157 (mean +/- S.D.) microg/min (range 24 - 447). Insulin sensitivity, expressed as the M-value, was 6.8 +/- 2.9 mg/kg/min, insulin sensitivity index (ISI = 100 x M/plasma insulin) 7.9 +/- 3.4 and insulin clearance (MCR ins ) 17.0 +/- 4.0 ml/kg/min. Simple regression analyses showed no direct association between AER and M, ISI or MCR ins. GFR was not associated with M, ISI or MCR ins in this group, either. AER was, however, positively associated with poor glucose control (high HbAlc) and tobacco use. CONCLUSIONS: These results suggest that the degree of albuminuria is not directly linked to insulin resistance. This was shown in type 1 diabetics, but could possibly be applicable in other subjects as well.

Adult↗

PubMed2001

Insulin can enhance GLUT4 gene expression in 3T3-F442A cells and this effect is mimicked by vanadate but counteracted by cAMP and high glucose--potential implications for insulin resistance.

UNLABELLED: It is well-established that high levels of cAMP or glucose can produce insulin resistance. The aim of this study was to characterize the interaction between these agents and insulin with respect to adipose tissue/muscle glucose transporter isoform (glucose transporter 4, GLUT4) gene regulation in cultured 3T3-F442A adipocytes and to further elucidate the GLUT4-related mechanisms in insulin resistance. Insulin (10(4) microU/ml) treatment for 16 h clearly increased GLUT4 mRNA level in cells cultured in medium containing 5.6 mM glucose but not in cells cultured in medium with high glucose (25 mM). 8-Bromo-cAMP (1 or 4 mM) or N(6)-monobutyryl cAMP, a hydrolyzable and a non-hydrolyzable cAMP analog, respectively, markedly decreased the GLUT4 mRNA level irrespective of glucose concentrations. In addition, these cAMP analogs also inhibited the upregulating effect of insulin on GLUT4 mRNA level. Interestingly, the tyrosine phosphatase inhibitor vanadate (1-50 microM) clearly increased GLUT4 mRNA level in a time- and concentration-dependent manner. Furthermore, cAMP-induced inhibition of the insulin effect was also prevented by vanadate. In parallel to the effects on GLUT4 gene expression, both insulin, vanadate and cAMP produced similar changes in cellular GLUT4 protein content and cAMP impaired the effect of insulin to stimulate (14)C-deoxyglucose uptake. In contrast, insulin, vanadate or cAMP did not alter insulin receptor (IR) mRNA or the cellular content of IR protein. IN CONCLUSION: (1) Both insulin and vanadate elicit a stimulating effect on GLUT4 gene expression in 3T3-F442A cells, but a prerequisite is that the surrounding glucose concentration is low. (2) Cyclic AMP impairs the insulin effect on GLUT4 gene expression, but this is prevented by vanadate, probably by enhancing the tyrosine phosphorylation of signalling peptides and/or transcription factors. (3) IR gene and protein expression is not altered by insulin, vanadate or cAMP in this cell type. (4) The changes in GLUT4 gene expression produced by cAMP or vanadate are accompanied by similar alterations in GLUT4 protein expression and glucose uptake, suggesting a role of GLUT4 gene expression for the long-term regulation of cellular insulin action on glucose transport.

3T3 Cells↗

PubMed2001

Food deprivation increases post-heparin lipoprotein lipase activity in humans.

OBJECTIVE: To study the effect of fasting on lipoprotein lipase (LPL) activity in human post-heparin plasma, representing the functional pool of LPL. DESIGN: Fourteen healthy volunteers were recruited for the study. The subjects were fasted for 30 h. Activities of LPL and hepatic lipase (HL), and LPL mass, were measured in pre- and post-heparin plasma in the fed and in the fasted states, respectively. For comparison, LPL and HL activities were measured in pre- and post-heparin plasma from fed and 24-h-fasted guinea pigs. RESULTS: Fasting caused a significant drop in the levels of serum insulin, triglycerides and glucose in the human subjects. Post-heparin LPL activity increased from 79 +/- 6.4 mU mL-1 in the fed state to 112 +/- 10 mU mL-1 in the fasted state (P < 0.01), while LPL mass was 361 +/- 29 in the fed state and 383 +/- 28 in the fasted state, respectively (P = 0.6). In contrast, fasting of guinea pigs caused an 80% drop in post-heparin LPL activity. The effect of fasting on human and guinea pig post-heparin HL activity were moderate and statistically not significant. CONCLUSIONS: In animal models such as rats and guinea pigs, post-heparin LPL activity decreases on fasting, presumably due to down-regulation of adipose tissue LPL. In humans, fasting caused increased post-heparin LPL activity.

Adipose Tissue↗

PubMed2001

Increased lactate release per fat cell in normoglycemic first-degree relatives of individuals with type 2 diabetes.

The aim of this study was to examine subcutaneous lactate production in the relatives of individuals with type 2 diabetes. Therefore, we recruited seven healthy first-degree relatives of type 2 diabetic patients and seven pairwise, matched, healthy control subjects without any heredity for diabetes. All subjects were studied with a euglycemic insulin clamp at approximately 600 pmol/l, abdominal subcutaneous microdialysis, and (133)Xe clearance. Furthermore, a subcutaneous needle biopsy was performed to determine fat cell size. In the fasting state, interstitial lactate was 40% higher in relatives than in control subjects (P = 0.043), but net lactate production was similar in both groups. However, during the insulin clamp, interstitial lactate (2.50 +/- 0.29 vs. 1.98 +/- 0.26 mmol/l, P = 0.018), interstitial-arterial lactate concentration difference (1.08 +/- 0.30 vs. 0.53 +/- 0.24 mmol/l, P = 0.028), and net lactate release per fat cell (10.9 +/- 3.7 vs. 2.8 +/- 1.3 fmol. cell(-1). min(-1), P = 0.018) were increased in the relatives. We conclude that first-degree relatives of type 2 diabetic patients may have an enhanced net lactate release per fat cell in abdominal subcutaneous tissue. This could suggest a pathological regulation in adipose tissue that is of importance for the metabolic defects known in type 2 diabetic relatives.

Abdomen↗

PubMed2001

Family characteristics and life events before the onset of autoimmune type 1 diabetes in young adults: a nationwide study.

OBJECTIVE: To elucidate whether family characteristics and stressful life events were associated with onset of autoimmune type 1 diabetes in young adults. RESEARCH DESIGN AND METHODS: This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of newly diagnosed patients aged 15-34 years. Patients clinically classified as type 1 diabetic with antibodies to islet cells and/or to GAD65 were compared with age- and sex-matched control subjects via questionnaire. The questionnaire covered diabetes heredity, social environment, educational level, and life events experienced during the 12 months before diagnosis. RESULTS: The rate of response was 82% for the diabetic patients and 65% for the control subjects. Questionnaires from 349 diabetic patients and 979 control subjects were considered. Diabetes in relatives was more frequent in the patients (odds ratio [OR]2.6) who were born in Sweden and whose mothers were of Swedish origin. No major stress factors were detected in the diabetic patients; however, in comparison with the control subjects, the diabetic patients had experienced fewer conflicts with their parents and had less often broken contacts with friends. CONCLUSIONS: Young adults with recent-onset type 1 diabetes were more exposed to heredity for diabetes, but no major prediabetic stress factors were detected. Our study does not directly support the concept that psychosocial stressful life events are involved in the development of autoimmune type 1 diabetes in young adults.

Adult↗

PubMed2000

The upregulating effect of insulin and vanadate on cell surface insulin receptors in rat adipocytes is modulated by glucose and energy availability.

The aim of this study was to further characterize the rapid effects of insulin and the tyrosine phosphatase inhibitor vanadate to amplify cell surface insulin binding capacity in isolated rat adipocytes. The effect of 20 min insulin treatment (1000 microU/ml) was 2- to 3-fold (p < 0.01) when cells were treated in medium containing 5.6 mM D-glucose, but it was totally absent in glucose-free medium. Other carbon energy sources, such as fructose and pyruvate, could only partly substitute for D-glucose, with an approximately 1.5-fold insulin effect. Moreover, inhibiting transmembrane glucose transport with cytochalasin B completely blocked the effect of insulin to enhance cell surface binding. The effect of vanadate was only partly glucose-dependent, since a submaximal effect (1.5- to 2-fold, p<0.05) was seen also in the absence of glucose. The tyrosine kinase inhibitor genistein markedly blunted the effect of vanadate (from 3- to 4-fold to approximately 2-fold, p < 0.05) also indicating the importance of tyrosine phosphorylation-related mechanisms in the upregulation of cell surface insulin binding. Glycosylation of insulin receptors as a mechanism for this effect appears unlikely since neither the effect of insulin nor that of vanadate was altered by the glycosylation inhibitor tunicamycin. The time course for the insulin effect displayed a long duration (at least 6 h), suggesting a maintenance role of insulin keeping its receptors accessible for ligand binding at the cell surface. In conclusion, the effect of insulin and vanadate to upregulate cell-surface insulin receptors is energy-dependent and to some extent specifically glucose-dependent.

Adipocytes↗

PubMed1999

[Ketoacidosis also occurs in type 2 diabetes. Important risk factors are other concomitant diseases]].

Although ketoacidosis has traditionally been regarded as a complication occurring only in conjunction with type I diabetes, there have recently been reports of its occurrence in cases of type II diabetes, e.g. in Afro-American and Japanese patients. The article reports a few cases suggesting that ketoacidosis may not be a rare phenomenon even in Swedish type II diabetes patients. This severe complication is usually precipitated by the occurrence of other concomitant disease.

Aged↗

PubMed1999

Postprandial hypertriglyceridemia and insulin resistance in normoglycemic first-degree relatives of patients with type 2 diabetes.

BACKGROUND: Impaired ability to eliminate lipids in the postprandial state is an atherogenic trait associated with insulin resistance. OBJECTIVE: To assess insulin sensitivity and postprandial triglyceride metabolism in prediabetic persons. DESIGN: Cross-sectional study. SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. PARTICIPANTS: 13 healthy, normotriglyceridemic men with two first-degree relatives with type 2 diabetes and 13 carefully matched controls without known diabetes heredity. MEASUREMENTS: Oral glucose tolerance test, insulin sensitivity (euglycemic clamp technique), and fasting and postprandial triglyceride levels after a mixed meal. RESULTS: Relatives of persons with type 2 diabetes were insulin resistant but had normal glucose tolerance. They exhibited postprandial hypertriglyceridemia; the 6-hour triglyceride incremental area under the curve was 50% higher than that of the control group (P = 0.037). CONCLUSIONS: These healthy male first-degree relatives of patients with type 2 diabetes are insulin resistant and exhibit postprandial lipid intolerance despite having normal fasting triglyceride levels. These characteristics, which occur in the absence of glucose intolerance, are associated with an increased risk for macroangiopathy.

Adult↗

PubMed1999

Life-threatening ventricular tachycardia due to liquorice-induced hypokalaemia.

We report on a patient with hypokalaemia and severe ventricular tachycardia of torsades de pointes type which turned out to be caused by an apparent mineralocorticoid excess syndrome associated with liquorice consumption. The patient, a 44-year-old woman, attended the hospital because of irregular heart rhythm and she displayed repeated episodes of life-threatening torsades de pointes ventricular tachycardia. The initial serum potassium was low: 2.3 mmol L-1. The patient was treated with potassium and magnesium infusions, and the dysrhythmias eventually ceased. Endocrinological investigations showed no indication of Cushing's syndrome or hyperaldosteronism. After some time it became clear that the patient had ingested moderately large amounts of liquorice every day for 4 months. After the patient stopped this habit the hypokalaemia and dysrhythmias did not recur and after more than 1 year there are no signs of cardiac illness.

Adult↗

PubMed1999

Low cellular IRS 1 gene and protein expression predict insulin resistance and NIDDM.

We examined the gene and protein expression of IRS 1 (insulin receptor substrate 1) in adipocytes from two groups of healthy individuals with an increased propensity for non-insulin-dependent diabetes mellitus (NIDDM): those with two first-degree relatives with diabetes and another group with massive obesity. A low expression of IRS 1 (</=50% of the matched control group) was seen in approximately 30% of both groups and these individuals were characterized by insulin resistance and its hallmarks: higher levels of insulin, glucose, and triglycerides. Two individuals with previously unknown NIDDM were diagnosed and both had low IRS 1 expression. Low IRS 1 protein expression was associated with low mRNA levels but not with the common Gly972Arg polymorphism of the IRS 1 gene. Taken together, our present and previous findings show that a low expression of IRS 1 in fat cells predicts insulin resistance and NIDDM. Furthermore, they support the likelihood that an impaired transcriptional activation may play a key role in the pathogenesis of NIDDM.-Carvalho, E., Jansson, P.-A., Axelsen, M., Eriksson, J. W., Huang, X., Groop, L., Rondinone, C., Sjöström, L., Smith, U. Low cellular IRS 1 gene and protein expression predict insulin resistance and NIDDM.

Adult↗