[Show abstract][Hide abstract] ABSTRACT: H�ydosebehandling med autolog stamcellest�tte (HMAS) er rutinebehandling hos selekterte grupper av pasienter med malignt lymfom og myelomatose. Hva er kostnadene ved denne type behandling? I perioden mai 2001-desember 2001 utf�rte vi en prospektiv kostnadsanalyse av behandlingsforl�p som grovt kan deles i 3 faser: 1) den tumorreduserende kjemoterapifasen, 2) fasen med mobilisering, h�sting og nedfrysing av autologe stamceller og 3) selve h�ydosefasen (HMAS-fasen). 30 pasienter med myelomatose ble fulgt ved tre forskjellige universitetssykehus og 10 pasienter med lymfom ble fulgt ved det fjerde sykehuset. Direkte pasientrelaterte kostnader ble registrert daglig. Indirekte kostnader ble fordelt p� pasientene basert p� estimater og ut fra forh�ndsdefinerte fordelingsn�kler fra relevante avdelinger. Alle kostnadsdata ble beregnet i 2001 priser. Den gjennomsnittlige totale kostnaden for alle tre faser var kr. 306 904 kr (variasjonsbredde 244 035-379 127). Vi fant en statistisk signifikant korrelasjon mellom varighet av sykehusopphold og sykehusenes kostnader i alle tre behandlingsfaser. En stor del av kostnadene i h�stefasen var knyttet til medikamenter brukt til stamcellemobilisering. I h�ydosefasen, som var den mest kostnadskrevende fasen, var de st�rste kostnadene knyttet til sykepleiepersonalet. Det var betydelige variasjoner i kostnader mellom sykehusene. Den gjennomsnittlige totalkostnaden var vesentlig h�yere enn full DRG-pris for myelomatose og myelomatose i 2001. Sykehusene m�tte selv b�re differansen mellom de reelle kostnadene og DRG-prisen. Per i dag (2008) er differansen redusert da det er etablert en sideutbetaling for HMAS- behandling.
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to determine the temporal changes in the prevalence of type 2 diabetes mellitus and its associated risk factors in a rural population of Bangladesh. A total of 4757 subjects age >/=20 years both male and female were enrolled randomly in a cross-sectional study in 1999. The same area and population was reinvestigated in 2004 following the same selection procedure, on a sample of 3981 individuals. Structural and economical changes were noted for the last 5 years in the locality. An increased prevalence of diabetes was found with 6.8% in the present survey compared with 2.3% in the earlier survey (p<0.05). Age, BMI and systolic blood pressure were found to be significant risk factors following both for FBG and for OGTT. WHR was found to be a significant risk factor for men only. A substantial agreement was observed between FBG and OGTT (kappa 0.63) compared to the previous investigation in 1999 (kappa 0.40). Differences in the indices of obesity, that is BMI, WHR and waist girth, may in part explain the increased prevalence, which in turn may explain due to fast-expanded urbanization. The state of affairs warrants immediate measures necessary to prevent the epidemic particularly in the localities that are in the transition phase from rural to semi-urban facilities.
Diabetes Research and Clinical Practice 08/2007; 77(2):300-5. DOI:10.1016/j.diabres.2006.11.010 · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diabetes is a fast expanding global health problem but more so in the developing countries. Therefore, it is of particular interest to study the epidemiological transition of the state and to identify the risk factors in order to recognize the extent of the problem.
A random sample of 5000 rural individuals (age >/=20 years) were included in a cross-sectional study. Fasting capillary blood glucose levels were measured from 4757 individuals. Height, weight, waist, hips including blood pressure and demographic information was collected.
The study population was lean [mean body mass index (BMI) 19.4] with a low prevalence of type 2 diabetes but relatively high impaired fasting glucose. No relationship between type 2 diabetes and BMI in men, but an overall relationship was observed for women (P = 0.04) (data not shown). Age, sex, and waist/hip ratio appeared to be important risk factors for the occurrence of type 2 diabetes in this population.
Low prevalence of type 2 diabetes and relative high impaired fasting blood glucose was observed. The factors associated with the occurrence of diabetes in this population appeared to differ than its known relations with BMI. This may indicate that the risk factors for type 2 diabetes are likely to differ in different population. Our results are likely to be in line with the Indian data suggesting that a revised guideline for anthropometric measures in the South Asian population is called for, in order to classify people at risk.
The European Journal of Public Health 06/2007; 17(3):291-6. DOI:10.1093/eurpub/ckl235 · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine whether the present system of reimbursement, based on diagnosis-related groups and regular financial budgeting, covers the costs incurred during hospitalisation of 7 children undergoing the three stages of the Norwood sequence for surgical treatment of hypoplastic left heart syndrome.
Between January and September 2003, 7 patients underwent initial surgical palliation with the Norwood procedure at the Rikshospitalet University Hospital. A prospective methodology was developed by our group to measure the costs associated with each individual patient. The patients were closely observed, and the relevant data was collected during their stay in hospital. The stay was divided into four different periods of requirements of resources, defined as heavy intensive care, light intensive care, intermediate care, and ordinary care. At each stage, we recorded the number of staff involved and the duration of surgery and other major procedures, as well as the cost of pharmaceuticals and other consumables. Based on these data, we calculated the cost for each patient. These costs were compared with the corresponding revenue received by the hospital for each of the patients.
We found the total mean cost for the three stages of the Norwood sequence was 138,934 American dollars, while the corresponding revenue received by the hospital was 43,735 American dollars. During this period, one patient died during the first stage of the Norwood sequence.
Our study shows that steps involved in the Norwood sequence are low-volume but high-cost procedures. The reimbursement received by our hospital for the procedures was less than one-third of the recorded costs.
Cardiology in the Young 11/2005; 15(5):493-7. DOI:10.1017/S1047951105001368 · 0.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High-dose therapy with autologous blood progenitor cell support is now routinely used for patients with certain malignant lymphomas and multiple myeloma. We performed a prospective cost analysis of the mobilization, harvesting and cryopreservation phases and the high-dose therapy with stem cell reinfusion and hospitalization phases. In total, 40 consecutive patients were studied at four different university hospitals between 1999 and 2001. Data on direct costs were obtained on a daily basis. Data on indirect costs were allocated to the specific patient based on estimates of relevant department costs (ie the service department's costs), and by means of predefined allocation keys. All cost data were calculated at 2001 prices. The mean total costs for the two phases were US$ 32,160 (range US$ 19,092-50,550). The mean total length of hospital stay for two phases was 31 days (range 27-37). A large part of the actual cost in the harvest phase was attributed to stem cell mobilization, including growth factors, harvesting and cryopreservation. In the high-dose chemotherapy phase, the most significant part of the costs was nursing staff. Average total costs were considerably higher than actual DRG-based reimbursement from the government, indicating that the treatment of these patients was heavily subsidized by the basic hospital grants.
Bone Marrow Transplantation 07/2005; 35(12):1149-53. DOI:10.1038/sj.bmt.1704988 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To describe differences in prevalence of Type 2 diabetes mellitus with its associated risk factors between rural and urban populations in Bangladesh. Diagnostic criteria [fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT)] were compared and reviewed for both populations.
A total of 1555 subjects from urban and 4757 from rural communities (age > or = 20 years) with similar cultural and ethnic backgrounds were randomly selected in a cross-sectional survey. FBG values were determined from all and 2-h post-glucose capillary blood samples were determined after a 75-g oral glucose load for a selected number (urban 476, rural 1046).
A higher prevalence of diabetes was found in urban (8.1%) compared with rural populations (2.3%). Age, sex and waist-to-hip ratio for men were significant risk factors for both urban and rural subjects following fasting and 2-h post-glucose values adjusted for a number of confounding variables. Poor agreement was observed between FBG and OGTT for both urban (kappa 0.41) and rural (kappa 0.40) areas.
A higher prevalence of diabetes mellitus (DM) in the urban population was observed compared with rural subjects despite similar body mass indexes (BMI). Differences in obesity, waist/hip ratio or hypertension failed to explain the increasing occurrence of T2DM in the urban population.
Diabetic Medicine 07/2005; 22(7):931-6. DOI:10.1111/j.1464-5491.2005.01558.x · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The study was undertaken to compare the effect of ADA and WHO criteria for screening of diabetes mellitus (DM) and intermediate glucose abnormality (Impaired fasting glucose/Impaired glucose tolerance-IFG/IGT) and to explore an acceptable fasting cut-off in a population-based study. Ten suburb villages with a population of 11,895 were selected purposively. Of the total 6235 eligible (> or = 20y) subjects, 4144 volunteered. We took height, weight, hip- and waist-girth, blood pressure and fasting blood glucose (FBG). All participants were classified into Group-1 (Gr-1: n=453) and Group-2 (Gr-2: n=3691), based on FBG above and below 5.4 mmol/l, respectively. All from Gr-1 and 610 randomized subjects from Gr-2 were investigated for oral glucose tolerance test (OGTT), HbA1c and lipids. The mean (SD) of age, body mass index (BMI) and FBG of all participants was 37.6 (15.2) y, 19.4 (2.9), and 4.7 (0.9) mmol/l, respectively. The prevalence of diabetes and IFG/IGT using American Diabetes Association (ADA) criteria were compared with WHO criteria separately in Gr-1 and Gr-2. For group-1, ADA criteria could diagnose 5.9% as diabetes and 2.1% as IFG, whereas, WHO criteria diagnosed 11.5% diabetes and 19% IGT. Likewise, in Gr-2, ADA detected much less than WHO criteria (DM: 0.3 vs. 2.3%; IFG/IGT 1.0 vs. 14.6%). We compared fasting and 2 hours post-load glucose (2-hBG) values according to percentiles. We found that 11.1 of 2-hBG corresponded with a fasting value that lies between 90 to 95th percentile, equivalent to 5.1-5.7 mmol/l. Using receiver operating characteristics (ROC) curve, we determined the cut-offs 4.6 - 5.4 mmol/l for IFG and > or = 5.5 for diabetes. Taking age and BMI into account the kappa agreements were better between the estimated cut-offs and the given 2-hBG values. The ADA cut-offs were found ineffective for screening. We proposed the modified fasting cut-offs for screening IFG and diabetes among the non-obese population.
Bangladesh Medical Research Council Bulletin 12/2004; 30(3):105-14.
[Show abstract][Hide abstract] ABSTRACT: This cross-sectional study was conducted to estimate the prevalence of type 2 diabetes along with its risk factors in urban slum population of Dhaka, Bangladesh. A random sample of 1555 slum dwellers of Dhaka city (age > or = 20 years) were included in the study. Capillary blood glucose levels, fasting and 2-h after 75g oral glucose load (for a selected subjects, n = 476), were measured. Height, weight, waist and hip circumferences, blood pressure and some other important socio-demographic information on age, sex, education, income, and occupation status were collected. The overall prevalence of type 2 diabetes was found to be 8.1 percent, and the prevalence for men and women were 7.7 percent and 8.5 percent respectively. Prevalence of diabetes was found to be lower following 2-h glucose values in the selected population compared to the FBG procedure. Age, sex, literacy and waist to hip ratio for men were found as significant risk factors following both fasting blood glucose and 2-h post glucose values adjusted for a number of confounding variables. Poor to moderate agreement was observed between fasting blood glucose and 2-h glucose (kappa 0.41, p < 0.001). The agreement was even poorer between impaired fasting glucose and impaired glucose tolerance. Poor agreement between FBG and 2-h BG may raise concern for the dependability of diagnostic procedures. Higher prevalence of type 2 diabetes in the urban slum may indicate an epidemiological transition due to fast urban migration and possibly urbanization. However, this issue needs further exploration.
Bangladesh Medical Research Council Bulletin 08/2004; 30(2):60-70.
[Show abstract][Hide abstract] ABSTRACT: High-dose chemotherapy (HDC) with autologous peripheral blood stem cell (PBSC) support is a common but expensive treatment for various hematological malignancies. A prospective cost analysis of evaluation/mobilization and the HDC + PBSC phase for patients with multiple myeloma was performed. Eleven consecutive patients at the National University Hospital Oslo, taking part in a Nordic treatment protocol, were included in the analysis during the period from May 1999 to December 2000. Clinical and resource use data were obtained prospectively on a daily basis registration and from patient records. The total cost for the evaluation/mobilization and the HDC + PBSC phase varied from 22,999 US dollars to 61,722 US dollars (mean 38,186 US dollars; median 30,569 US dollars). The mean length of hospital stay for the evaluation/mobilization phase was 8 days (range 4-17 days) and for the HDC + PBSC phase 19 days (range 14-29 days). A statistically significant correlation was found between the length of hospital stay and hospital costs for both phases (P < 0.003 and P < 0.010, respectively). A large part of the actual cost in the harvest phase was attributed to stem cell mobilization, including growth factors, harvesting and cryopreservation. In the HDC + PBSC phase, the most important part of the cost was paying nursing care personnel.
[Show abstract][Hide abstract] ABSTRACT: The present study investigated the variability in insulin sensitivity and beta-cell function and their relationship to anti-glutamic acid decarboxylase (GAD) positivity and the metabolic syndrome in a group of patients with non-insulin-dependent diabetes mellitus (NIDDM).
Fifty-four subjects aged 59.5 +/- 6.1 (mean +/- SD) years with NIDDM for 7.9 +/- 3.9 years referred to hospital due to poor glycaemic control, were investigated. Insulin sensitivity was determined by the euglycaemic hyperinsulinaemic glucose clamp technique as the glucose disposal rate relative to the insulin level obtained (GDRI), and also estimated with the homeostasis model assessment (HOMA-S). beta-cell function was measured by assaying the fasting and glucagon-stimulated C-peptide levels and with the HOMA-B.
The insulin sensitivity varied 18-fold between subjects when estimated with the clamp and six-fold when estimated with HOMA-S, and was lower the more criteria for the metabolic syndrome present (P = 0.0001 by anova). The beta-cell function varied four-fold when measured as stimulated C-peptide, and eight-fold when estimated with the HOMA-B. The levels of fasting C-peptide and HOMA-B values tended to be lower in anti-GAD+ (n = 11) than in anti-GAD-subjects (P = 0.06 and P = 0.08, respectively). From previously published coronary risk charts, we estimated the 10-year risk of a coronary heart disease (CHD) event to be > 20% in 17 of 39 patients free from cardiovascular disease at the time of study, 16 of whom qualified for a diagnosis of the metabolic syndrome.
The wide variations in insulin sensitivity and beta-cell function found among subjects with NIDDM support the notion that the disorder is highly heterogeneous. Reduced insulin sensitivity was clearly related to the metabolic syndrome and an increased risk for CHD.
Diabetic Medicine 01/2003; 20(1):37-45. DOI:10.1046/j.1464-5491.2003.00838.x · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As more and more nations are scrutinizing their health care costs, attention has been focused on high-cost low-density disease. Assessment of actual total cost of care for haemophilia and its positive outcome becomes essential to justify support for these patients. In this study, we assessed hospital cost and diagnosis-related group (DRG) reimbursement for patients undergoing elective orthopaedic surgical procedures from May 1999 to December 1999. Hospital cost was assessed by a prospective microcost-analysis method. To identify real hospital costs, we performed registration of preoperative phase, operative phase and 1-year follow-up costs. Hospital cost included personnel costs and costs for clinical and laboratory procedures, blood products, prosthetic implants, coagulation factor concentrates and drugs. These data were compared with hospital DRG reimbursement. We included nine consecutive patients, with a mean age 38 years (19-54 years) who had had 10 major orthopaedic surgical procedures performed during the study period. Six patients had haemophilia A, two had haemophilia B and one had factor VII deficiency. Data analysis showed a mean cost of US$ 54,201 (range US$ 25,795-105,479; 1US$ = 8.5 NOK). The average actual hospital revenue (50% DRG reimbursement + income related to length of stay) was $4,730 (range $ 1,308-13,601). Our study confirms that orthopaedic surgery in patients with severe bleeding disorders puts the hospital to a considerable expense. Activity-based financing, as used in Norway, does not provide a proper reimbursement for this part of the haemophilia care.
[Show abstract][Hide abstract] ABSTRACT: The financing of health care services in Norway has been changed from a system of global budgeting to a system partly based on Diagnosis-Related Groups (DRG). The government has decided to derive a part of the hospital revenue from DRG-based, per-patient financing. The aim of this study is to determine whether the present remuneration system covers the actual hospital expenses of liver transplant patients, and whether the present method of calculating DRG-costs is adequate for our institution. Our group developed a prospective method of determining the actual cost per patient. We closely observed and collected the data of eight liver transplant patients during their hospital stay. We divided each of the patients' resource requirements into four categories; heavy intensive care, light intensive care, intermediate care, and ordinary care. In addition, we recorded the number of staff involved, the duration of surgery, the major procedures, and the medical- and material costs. The actual cost of each patient was calculated, based on these data. The actual cost was compared with the corresponding hospital remuneration for each patient. Median cost for liver transplantation was NOK 536.785 (range: NOK 295.113-NOK 844.345) (1$=7,5 NOK), while the corresponding hospital refund was NOK 457.785 (range: NOK 436.465-NOK 483.040). The difference is not statistically significant ( P=0.2). The average 100% DRG-based cost of a liver transplantation was NOK 730.321, which is significantly higher than the actual cost ( P=0.02). The hospital's reimbursement for liver transplantation did not differ significantly from the actual registered cost. The computed cost was significantly lower than the DRG-based cost.
Transplant International 11/2002; 15(9-10):439-45. DOI:10.1007/s00147-002-0430-0 · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Norwegian health care system, like other health care systems in the world, is in the midst of a changing financial environment for hospital reimbursement for patient care. Since 1997 the Norwegian government has introduced a new financing model of block grant and activity-based financing. In this model, diagnosis-related groups (DRGs) play an important role in hospital financing. The initial motive for developing the DRGs was to improve hospital productivity and efficiency and to develop a tool to control increasing hospital costs better. We raised the question as to whether the DRG system in fact covers actual costs in patient groups undergoing heart transplantation (n = 12), lung transplantation (n = 4), and thoracotomy for other diseases (n = 10). A new prospective cost model was developed to measure actual costs related to individual patients. The patients were closely observed and the related data collected during the hospital stay. Each patient's hospital stay was divided into four different categories of resource requirements, defined as heavy intensive care, light intensive care, intermediate care, and ordinary care. In addition, the number of staff involved and the duration of surgery and procedures were recorded, as were medicine costs and material costs. Based on these data, the actual costs for each patient were calculated. These were then compared with the respective DRG reimbursement (100 % coverage) for the corresponding group. We found that the median cost for heart transplantation was US$ 50,590 (1 US$ = 7.5 NOK based on the exchange rate at the time of the study), while the respective DRG reimbursement was US$ 65,662. For lung transplantation, the respective figures were US$ 46,668 vs US$ 65,662, and for thoracotomy, US$ 24,307 vs. US$ 11,004. We found that our method was applicable to a hospital setting. DRG coverage for heart and lung transplantation seems to overestimate the actual costs. For the thoracotomy procedure, the DRG coverage did not cover the actual costs.
Transplant International 01/2002; 14(6):361-9. DOI:10.1007/s001470100001 · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Norwegian Ministry of Health and Social Affairs recently introduced activity-based financing for hospitals partly based on diagnosis-related groups (DRG). We soon observed that there seemed to be a considerable discrepancy between the reimbursement amount and the real cost of allogeneic haemopoietic stem cell transplantation. It was therefore decided to undertake a prospective micro-cost analysis to define a more realistic reimbursement. To identify real costs, we undertook a registration of pre-transplant procedures, transplantation and 1 year follow-up costs, including harvesting, personnel costs, clinical and laboratory procedures, together with blood products and drugs related to patients and donors. These data were compared to hospital DRG reimbursement. This information was registered for 17 consecutive patients, with a mean age 40 years (range 17-58 years). Ten patients had chronic myeloid leukaemia, three had acute lymphatic leukaemia, two had acute myeloid leukaemia and two had myelodysplastic syndrome. The data analysis showed a mean cost of US$ 106825 (NOK 901982), (range US$ 42376-362430). The average actual hospital revenue (50% DRG reimbursement + income related to length of stay + special procedure funding) was US$ 36404 (range US$ 26228-55998). Activity-based financing as applied in Norway, under-compensates hospital costs for allogeneic bone marrow transplantation. The government should make realistic estimates of real costs before introducing financial reforms in the health care system.
Bone Marrow Transplantation 01/2002; 28(12):1111-6. DOI:10.1038/sj.bmt.1703310 · 3.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Erectile dysfunction (ED) is prevalent and often associated with chronic diseases and previous operations on the prostate. Our aims were to investigate the prevalence of ED among males seeking general practitioners and to register known risk factors.
During a short period in late 1998, 49 Norwegian general practitioners in the county of Østfold asked all their male patients over 40 years of age to anonymously fill in a questionnaire.
1,182 men completed the study. 20% stated that they had moderate ED, while 13% had complete ED. The prevalence of ED increased with age. Complete ED was found in 2% of those between 40 and 50, 5% between 50 and 60, 16% between 60 and 70, and in 37% of those above 70 years of age. The corresponding values for moderate ED was 6, 16, 32 and 28%. Moderate/complete ED was increased in the subgroups with hypertension, depression, diabetes, > one concomitant disease, and post prostate surgery. Physically "very active" individuals had less ED than the "non-active". No significant association was found with alcohol or tobacco. Most patients with ED wanted to discuss the problem with their general practitioners, but only 6% received treatment.
Tidsskrift for Den norske legeforening 01/2001; 121(1):28-32.
[Show abstract][Hide abstract] ABSTRACT: The effects and kinetics of oral glibenclamide (Gb) and glipizide (Gz) were studied in Caucasian and Chinese patients (ten in each group) with type-2 diabetes. In randomised order, 2.5 mg Gb, 2.5 mg Gz or placebo was given orally before the administration of 75 g oral glucose. Concentrations of insulin and proinsulin were determined using radioimmunoassay (RIA) without cross-reactivities, and sulphonylurea concentrations were determined using high-performance liquid chromatography (HPLC). There were no significant interethnic differences in Gb or Gz effects whether on glucose, insulin or proinsulin/insulin ratio at any time point. Following Gz, however, Chinese patients had greater increments of serum proinsulin at 10-30 min compared with Caucasians. Apart from the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of Gz being higher among the Chinese, no significant interethnic differences in pharmacokinetics were found. It appears that the same dosage principles could be used for Caucasian and Chinese patients with type-2 diabetes when Gb or Gz are prescribed.
European Journal of Clinical Pharmacology 11/2000; 56(9):711-714. DOI:10.1007/s002280000214 · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diagnose Related Groups (DRG) are defined on the basis of the principal diagnosis, secondary diagnoses, procedures, age, sex and discharge status, and were developed to improve hospital productivity and efficacy. Existing code systems do not cover all medical specialties equally well; examples are neonatal medicine, cancer treatment and rehabilitation. We have developed a prospective method to measure actual costs related to patients individually. The major element in this method is based upon the hospital stay being divided into types of treatment with different resource requirements: heavy intensive care, light intensive care, intermediate care and ordinary care. In addition, costs related to surgery and other procedures are measured. Our method was used to calculate costs related to neonatal surgery due to various inborn diseases in the gastrointestinal tract and the urinary system. All patients needed immediate care and competent medical intervention. Mean costs for the group was NOK 291,181 while total reimbursement to the hospital was NOK 100,390, resulting in a net negative balance of NOK 190,970. Neonatal surgery does not seem to be adequately covered by the DRG system. This complex patient group provides a comprehensive test of the prospective method, and after evaluation we feel that it can be used in most other patient groups to verify actual cost.
Tidsskrift for Den norske legeforening 10/2000; 120(22):2666-71.
[Show abstract][Hide abstract] ABSTRACT: We analysed the kinetics and effects of glibenclamide (Gb) on glucose, insulin and proinsulin secretion in two ethnic groups (10 in each) of type-2 diabetic patients, one of Caucasian, the other of Chinese origin.
Diabetes mellitus type 2 is a global disease affecting all ethnic groups. There are ethnic differences in both the prevalence and metabolic characteristics of the disease. Important interethnic pharmacodynamic and pharmacokinetic differences have been reported for several drugs. With few exceptions, detailed studies on sulphonylurea are lacking.
The patients were studied on two occasions when either no Gb (control) or 1.25 mg Gb was administered i.v., immediately before the administration of a 75-g oral glucose tolerance test. Concentrations of insulin and proinsulin were determined by means of radioimmunoassay without cross-reactivities. Gb concentration was determined using high-performance liquid chromatography. Pharmacodynamic results were calculated using net areas under the curves, with basal values set as zero. A P value less than 0.05 was considered significant.
When glucose was administered orally without Gb, Chinese patients had higher plasma glucose increases at 10 min (7.6 mmol/l x min vs 2.6 mmol/l x min) and higher increases of plasma insulin levels than Caucasians at both 10 min (198 pmol/l x min vs 54 pmol/l x min) and 30 min (2286 pmol/l x min vs 1198 pmol/l x min). When Gb was administered, the plasma glucose increases were reduced, and the increases of serum insulin and proinsulin levels were greater in both ethnic groups. Compared with the basal values (-1 min), proinsulin/insulin ratios (RPI) were lowest at 10-30 min, followed by an increase. Chinese patients had higher increases of serum insulin levels at 10 min (1109 pmol/l x min vs 550 pmol/l x min) and a lower RPI at 30 min (6. 0% vs 7.6%) and 240 min (15.0% vs 21.0%) relative to Caucasians. Serum Gb data were best fitted to a biexponential i.v. model. There were no interethnic differences in any of the pharmacokinetic parameters.
In summary, following oral glucose administration without Gb, Chinese type-2 diabetic patients had higher plasma insulin levels but also higher plasma glucose levels during the first 10 min, which might reflect reduced insulin sensitivity or more rapid glucose absorption. Gb augmented glucose-induced release of both insulin and proinsulin in both ethnic groups; the effect on insulin secretion was more pronounced. In conclusion, minor pharmacodynamic but no pharmacokinetic differences were found between the two groups. It seems appropriate to employ the same dosage principles when using Gb in Caucasians and Chinese.
European Journal of Clinical Pharmacology 02/2000; 55(10):721-7. DOI:10.1007/s002280050004 · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the effect of oral antihyperglycaemic therapy on fasting proinsulin and the relation between proinsulin levels and cardiovascular risk factors in type 2 diabetes.
One hundred and sixty-five patients with type 2 diabetes, fasting blood glucose concentration (FBG) > or = 6.7 mmol/l, were recruited from five diabetes outpatient clinics in primary health care. Diet and antihyperglycaemic medication, aiming at FBG < 6.7 mmol/l, was maintained for 6 months after completed dose titration in a randomized, double-blind, double-dummy trial with metformin (M), glibenclamide (G) and primary combination of both drugs (MG). The study compared M, G and MG in low dose (MGL) and also different high-dose regimens, i.e. G added to M (M/G), M added to G (G/M) and primary combination (MGH). Outcome measures were fasting proinsulin, glycaemia, body mass index, blood pressure, lipids, insulin and C-peptide.
Lower proinsulin levels were found when therapy was initiated with metformin (M vs. G, p = 0.013 and M/G vs. G/M, p = 0.033). M and G were equally effective on glucose levels. In the group as a whole FBG decreased from (mean +/- s.d.) 10.2 +/- 2.7 to 7.0 +/- 1.2 mmol/l with no change in proinsulin. Proinsulin was associated with cardiovascular risk factors, linking high proinsulin to an atherogenic risk marker profile. Mean proinsulin change from baseline was inconsistently associated with markers of insulin resistance. Meal-stimulated glucose (net AUC) decreased after treatment only in those with low baseline proinsulin levels.
It may be advantageous to initiate oral antihyperglycaemic therapy with metformin rather than with sulphonylurea. High proinsulin levels are associated with an atherogenic-risk marker profile and an impaired therapeutic postprandial glucose response after treatment in patients with type 2 diabetes. Proinsulin change after therapy is inconsistently associated with markers of insulin resistance and unrelated to fasting blood glucose reduction.