Behavioral correlates of metabolic control in people with IDDM in Taipei.
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Diabetes Mellitus, Type 1↗
Biomedical subjects
B J Lin
Publications and source records attributed to B J Lin.
HLA-DQB1 codon 57 and IDDM in Chinese living in Taiwan.
OBJECTIVE: To study the human leukocyte antigen (HLA)-DQB1 genetic background in the Chinese population in Taiwan and its association with the low incidence of insulin-dependent diabetes mellitus (IDDM) in this population. RESEARCH DESIGN AND METHODS: Forty-eight IDDM patients and 59 nondiabetic unrelated control subjects were recruited from the population in Taiwan. HLA-DQB1 exon 2 was enzymatically amplified by polymerase chain reaction. HLA-DQB1 alleles were diagnosed by dot blotting and hybridization with 16 sequence-specific oligonucleotide probes. RESULTS: DQB1*0201 and DQB1*0302 alleles were more frequent and DQB1*0301 and DQB1*0601 were less frequent in Chinese with IDDM than in control subjects. Genotypes for homozygous non-aspartic acid residue (NA/NA) at position 57 were positively associated with IDDM at a relative risk of 4.34 (P < 0.001), and those for homozygous aspartic acid (A/A) were negatively associated with IDDM at a relative risk of 0.14 (P < 0.001). Among the NA/A heterozygotes, only DQB1*0201/DQB1*0303 was significantly increased in IDDM subjects. CONCLUSIONS: The amino acid residue at position 57 of HLA-DQ beta-chain is significantly associated with the development or prevention of IDDM in Chinese subjects living in Taiwan. Other genetic and environmental factors may also play important roles in pathogenesis of IDDM.
Adolescent↗
Mortality in diabetic patients after lower extremity amputations.
This study evaluates the prognostic factors and causes associated with mortality in Chinese diabetic patients after lower extremity amputations. Medical records of all diabetic patients admitted to the National Taiwan University Hospital for leg amputations from 1982 to 1991 were reviewed. Demographic data, medical history, amputation levels and admission routines, including fasting plasma glucose, cholesterol, triglycerides, blood urea nitrogen, creatinine, urine protein and electrocardiograms, and bacterial culture done during the admission period were recorded. The vital status of the patients was followed by personal contact and mortality was ascertained from government computer records. The causes of death were recorded according to the death certificates. Univariate analysis and multivariate Cox's proportional hazards model were used to identify the prognostic factors associated with mortality. A total of 87 diabetic amputees, of whom 34 died, were found within this 10-year period. Cerebral infarction, infection and diabetes mellitus were the most commonly reported causes of death. Their calculated mortality was 5.95 times higher than the mortality rate of the age-comparable population in Taiwan. A history of hypertension and coronary heart disease were found to be the best indicators for predicting a fatal outcome with rate ratios of over two-fold. This study shows that post-amputational mortality is high in diabetic patients and that the major cause of death is cerebral infarction. The major cause of death in this study differs from that reported for Caucasians, for whom cardiovascular disease is the most important cause of death.
Adult↗
Atherosclerotic risk factors for peripheral vascular disease in non-insulin-dependent diabetic patients.
The purpose of this study was to evaluate risk factors associated with peripheral vascular disease (PVD) in patients with non-insulin-dependent diabetes mellitus (NIDDM). A group of 100 patients (50 men and 50 women) aged 50 years or over with PVD and another group of 200 age-sex-matched patients (100 men and 100 women) without PVD were studied. The mean +/- standard error of ages for subjects with and without PVD were 60.8 +/- 0.6 years and 59.7 +/- 0.3 years, respectively. Doppler ultrasound was used to measure the systolic pressures of the brachial, posterior tibial and dorsal pedal arteries bilaterally. The diagnosis of PVD was made by an ankle-brachial index (ABI) < 0.90 and the diagnosis of non-PVD by an ABI > 1.00. The association of PVD with diabetic duration, body mass index (BMI), cerebral infarction (CI), coronary heart disease (CHD), proteinuria, diabetic retinopathy, neuropathy, hypertension, and cigarette smoking was evaluated. In addition, biochemical data including fasting plasma glucose, hemoglobin (HD)Alc, cholesterol, triacylglycerol, high- and low-density lipoprotein cholesterol, uric acid, blood urea nitrogen (BUN) and creatinine (Cr) were studied. In univariate analysis, PVD was associated with an increased level of systolic blood pressure (SBP), BUN and Cr, cigarette smoking, CI, CHD, proteinuria and retinopathy. In stepwise logistic regression analysis, the level of SBP, cigarette smoking and CI remained statistically significant. The log odds of PVD could be expressed as: -2.834 + 0.013 (SBP in mmHg) + 0.577 (cigarette smoking) + 1.320 (CI). PVD is the result of aggregation of atherosclerotic risk factors; among those factors noted in this study, SBP, cigarette smoking and CI are important.
Arteriosclerosis↗
Ten-year clinical analysis of diabetic leg amputees.
The clinical characteristics of 234 amputees admitted to the National Taiwan University Hospital during a 10-year period were analyzed. Diabetes mellitus accounted for 37.2% (87 cases) of the amputations and was the most commonly associated disease. Malignancy was the second cause of amputation (16.2%). Traffic accidents and atherosclerosis (without diabetes mellitus) each accounted for about 13% of the amputations. Below-knee amputation was the most commonly performed procedure among the diabetics, while above-knee, below-knee and ray amputations were roughly equally performed among non-diabetic patients. Reamputations were done in 16 diabetic and 12 non-diabetic patients, mostly within a short period of time after the first amputation. Four of the diabetic reamputations and nine of the non-diabetic reamputations were performed on the same side as the first amputation. The mean +/- standard error of admission days and total expenses for each episode of amputation were 36.2 +/- 2.7 days and 116.5 +/- 1.7 thousand New Taiwan dollars for the non-diabetics and 41.3 +/- 4.0 days and 134.0 +/- 16.0 thousand New Taiwan dollars for the diabetics, respectively. We concluded that: 1) diabetes mellitus was the main cause of amputation; 2) diabetes mellitus was associated with a higher rate of reamputations of the contralateral legs; and 3) a multidisciplinary foot-care team is essential for the management of lower leg amputations.
Adult↗
Association of insulin-dependent diabetes mellitus in Taiwan with HLA class II DQB1 and DRB1 alleles.
The allelic constitution at HLA class II DRB1, DQB1, DQA1, and DPB1 loci of IDDM patients from Taiwan was compared with that of ethnically matched nondiabetic individuals by PCR-based DNA typing. Of the three haplotypes found to be positively associated with IDDM in Taiwan, two (DRB1*0301-DQA1*0501-DQB1*0201 and DR4-DQA1*0301-DQB1*0302) appear to be identical to the susceptible haplotypes in Caucasian and black populations, whereas the third haplotype (DR4-DQA1*0301-DQB1*04) has been reported to be positively associated with IDDM only in the Japanese population. The three haplotypes, DRB1*1502-DQA1*0102-DQB1*0601 and DRB1*1201 (or 1202)-DQA1*0501-DQB1*0301 and DRB1*0803-DQA1*0103-DQB1*0601, were negatively associated with IDDM in Taiwan; a protective effect of the last haplotype has not been reported previously. Neither DQ beta non-Asp-57 nor DQA1*0301 alone appears sufficient to account for the HLA-associated susceptibility to IDDM in Taiwan. Also, the DQ alpha beta heterodimer encoded by the alleles DQA1*0301/DQB1*0201, DQA1*0301/DQB1*0302, or DQA1*0501/DQB1*0201 does not explain the susceptibility of a larger fraction of the IDDM patients than the residue at position 57 of the DQ beta chain or DQA1*0301. Finally, the DRB1 alleles appear to affect IDDM susceptibility, although for most haplotypes the effect of individual loci cannot be assessed due to the linkage disequilibrium between the DQ and the DR region.
Adult↗
[Epidemiological study of gestational diabetes mellitus in Taipei and factors effecting blood glucose].
The prevalence of non-insulin-dependent diabetes mellitus has increased significantly in the last decade. Meanwhile, it has been found that patients with gestational diabetes have a greater chance of developing diabetes than normal subjects. This study was designed to survey the prevalence of GDM in metropolitan Taipei. A screening test with 50 g of glucose was performed on pregnant patients between 24 and 28 weeks of gestation, and a blood sample was collected one hour after ingestion. The subjects with a plasma glucose level over 130 g/dL were scheduled for a standard 75 g oral glucose tolerance test for diagnosis. Altogether, 872 pregnant women participated in the study. According to the WHO criteria which were published in 1985, a total of 224 (25.7%) subjects had a positive screening test. Thirty-seven (4.2%) subjects had impaired glucose tolerance (IGT) and five (0.6%) subjects were found to have GDM after the 75 g OGTT. Comparisons of the glucose levels of women of different ages (< 30 and > or = 30), BMI (< or = 24 and > 24), and parity (0 and > or = 1) demonstrated that women over 30, with a BMI over 24, or a parity over 1 had a significantly higher plasma glucose level than their counterparts in the screening test. Even after BMI-adjustment, the difference was still significant for the age and parity comparisons.
Adult↗
The effect of oral buflomedil on microalbuminuria in non-insulin-dependent diabetic patients.
A total of 26 non-insulin-dependent diabetic patients were enrolled for a clinical study of the effect of buflomedil on microalbuminuria. None of the subjects had hypertension or macroproteinuria. Sixteen cases without previously known urinary albumin excretion rate (AER) were enrolled as experimental group. Buflomedil (Loftyl) was administered orally 600 mg daily in two divided doses in the experimental group while AER was determined 3 times with 3 weeks apart in all of the subjects. Ten cases with known microalbuminuria (greater than 8.55 micrograms/min) were enrolled as control group to check the extent of fluctuation in AER from collection to collection in the absence of urinary tract infection. Six of the experimental group showed AER of microalbuminuric level at the time before buflomedil administration and the remaining 10 patients were normoalbuminuric. The effects of buflomedil were compared between the microalbuminuric and normoalbuminuric subjects in the experimental group. The microalbuminuric group showed a significant decrease of AER from a baseline of 30.4 micrograms/min to 19.8 and 16.8 micrograms/min, respectively, after 3 and 6 weeks of treatment (P less than 0.05, Friedman two-way ANOVA). However, the respective values in the normoalbuminuric group were 5.3, 5.6 and 5.0 micrograms/min (P greater than 0.05, Friedman two-way ANOVA). The AER in the control group remained stationary during the study period (14.0, 12.1 and 11.4, respectively, Friedman two-way ANOVA, P greater than 0.05). These results suggest that buflomedil might be beneficial for the patients with microalbuminuria.
Adult↗
Inhibitory effect of islet amyloid polypeptide of glucose-induced proinsulin biosynthesis in rat insulinoma cells.
Islet amyloid polypeptide (IAPP) has been recently identified as the principal constituent of amyloid deposits in pancreatic islets of patients with type 2 (non-insulin-dependent) diabetes mellitus and causes insulin resistance in some target cells. In addition, glucose-induced insulin secretion is inhibited by IAPP. We studied the effect of IAPP on proinsulin biosynthesis in rat insulinoma (RINr) cells. Glucose at concentrations of 0, 15, 30, 60, 100, and 300 mg/dl stimulated proinsulin biosynthesis in a dose-responsive and and actino-mycin D-inhibitable manner after 6 h of incubation. At a glucose concentration of 300 mg/dl, IAPP decreased the mean responses of proinsulin biosynthesis to 61.2 and 29% at concentrations of 0.1 and 1 microM, respectively, compared with the IAPP-free control. In conclusion, IAPP inhibits glucose-induced proinsulin biosynthesis in RINr cells. IAPP might play an important role in the pathogenesis of type 2 diabetes mellitus.
Amyloid↗
Therapeutic effect of guar gum in patients with non-insulin-dependent diabetes mellitus.
Diets with a high-fiber content have been shown to produce some beneficial effects on metabolic factors in subjects with NIDDM. However, some controversies still exist. In this report, the long-term effect of guar gum (Guarina) on both glycemic and blood lipid profiles was assessed in a randomized, double-blind and cross-over study on 16 (seven male and nine female) subjects with NIDDM. Each subject received placebo (P) and Guarina (G) treatment for two eight-week periods separated by a four-week period to facilitate wash-out. Fasting plasma glucose levels showed significant improvement during G treatment but not during P treatment (151.7 +/- 7.9 vs 168.6 +/- 12.2 mg/dl, p less than 0.01 by paired Student's t test). Hemoglobin Alc levels decreased significantly during G treatment but not during P treatment (6.9 +/- 0.2 vs 7.2 +/- 0.8%, p less than 0.001). Fasting insulin concentrations also showed significant lowering during G treatment but not during P treatment (18.3 +/- 2.1 vs 23.1 +/- 2.9 U/ml, p less than 0.005). Other variables, including serum total cholesterol, triglyceride, HDLc, LDLc, sodium, potassium, chloride, magnesium and calcium levels showed no significant changes during G or P treatment. Ten out of the 16 patients (62.5%) suffered from side effects; these included abdominal cramps (one case), diarrhea (seven cases) and skin itching (one case). In conclusion, guar gum effectively lowers fasting plasma glucose and HbAlc levels in subjects with NIDDM. Hyperinsulinemia could also be ameliorated. The effectiveness and side effects of guar gum treatment should be cautiously evaluated in each NIDDM subject.
Adult↗
Effect of tocopherol on platelet aggregation in non-insulin-dependent diabetes mellitus: ex vivo and in vitro studies.
Tocopherol has been shown to have antiplatelet effects in insulin-dependent diabetes mellitus. However, its antiplatelet effect in non-insulin-dependent diabetes mellitus (NIDDM) remains to be established. In this report, the antiplatelet effect of tocopherol was assessed in a randomized, double-blind and crossover study of 15 NIDDM subjects. Each subject received tocopherol (dl-alpha-tocopherol nicotinate, 200 mg, tid) and a placebo for two six-week treatment periods separated by a three-week period in between for wash-out. The mechanisms of the antiplatelet effect of tocopherol were also studied in vitro. A significant decrease in platelet reactivity was observed after tocopherol treatment as compared with the pretest, and the magnitude of the decrease during tocopherol treatment was significantly evident when compared with that of the placebo treatment, as assessed by collagen (5, 10 micrograms/mL)-induced platelet aggregation of whole blood. A dose-dependent reduction in both ADP-and collagen-induced platelet aggregation was observed with tocopherol from 0.1 to 3.0 mM in vitro. No corresponding changes in ATP secretion and thromboxane synthesis were observed. Tocopherol also significantly inhibited fibrinogen-induced aggregation of elastase-treated platelets at a concentration of 0.1 mM. We demonstrated that platelet aggregation of whole blood ex vivo, among 15 NIDDM subjects was suppressed in tocopherol treatment, so tocopherol may have an antiplatelet effect in NIDDM subjects. The inhibitory effect of the platelet aggregation of tocopherol may be partially accomplished through interference with fibrinogen binding towards its receptor.
Adult↗
Bedtime intermediate-acting insulin in the treatment of secondary failure to oral hypoglycemic agents.
Low-dose bedtime insulin therapy in combination with oral hypoglycemic agents (OHAs) has become an alternative treatment for NIDDM subjects with secondary failure to OHA. To assess its clinical efficacy, patient compliance, and its possible side effects, 33 patients with secondary OHA failure were recruited in this study. All of the subjects had experienced poor glycemic control for at least six months on their maximal OHAs before the institution of the bedtime insulin injection. Monotard HM (human insulin zinc suspension) was given at an initial dose of 0.15-0.2 U/kg body weight and was adjusted thereafter. As a whole, low-dose bedtime insulin with OHAs improved glycemic control. According to the clinical response, 10 patients (30.3%) were graded as responders, 12 (36.4%) were partial responders, 10 (30.3%) were non-responders, and one (3%) discontinued insulin therapy. There was no difference in demographic features among these three groups of patients. During this period, eight (25%) cases experienced mild hypoglycemic symptoms. In conclusion, combination of OHAs with a low-dose bedtime insulin injection is an alternative therapy for NIDDM patients with OHA failure.
Diabetes Mellitus, Type 2↗
Endogenous Klebsiella pneumoniae endophthalmitis in diabetic patients.
We describe 12 patients with endogenous endophthalmitis caused by Klebsiella pneumoniae seen between 1983 and 1988. Three patients had bilateral involvement. Eleven patients had diabetes mellitus, either newly diagnosed or poorly controlled. In six cases the infection was associated with a liver abscess. In all eyes the outcome was light perception or worse; nine eyes had no light perception. Six eyes were enucleated or eviscerated.
Adult↗
Esterase D and retinoblastoma gene loci are tightly linked to Wilson's disease in Chinese pedigrees from Taiwan.
Wilson's disease (WD) is a rare autosomal recessive disorder and has been mapped to the long arm of chromosome 13 (q14.1). We have analyzed the segregation of esterase D (ESD) and retinoblastoma (RB) gene loci in ten families of Chinese WD subjects living in Taiwan. The polymorphic information content (PIC) for ESD and RB was 0.18 and 0.31, respectively. We confirmed a tight linkage between these loci and WD with a lod score of 3.33 by multipoint linkage analysis. The data from this limited number of pedigrees also suggested the following order: centromere-WD-RB-ESD or centromere-ESD-RB-WD. ESD in conjunction with RB polymorphism would be useful in prenatal and presymptomatic diagnosis, as well as in carrier detection in informative pedigrees.
Alleles↗
A case of basophilic leukemia bearing simultaneous translocations t(8;21) and t(9;22).
We report a case of basophilic leukemia with simultaneous translocations of t(8;21) and t(9;22). The patient's clinical and hematologic findings were characteristic only of t(9;22) but not of t(8;21). This unusual cytogenetic phenomenon raises a challenge to the current concepts of primary chromosomal abnormalities in cancer.
Antineoplastic Combined Chemotherapy Protocols↗
Link between hypertension and diabetes mellitus epidemiological study of Chinese adults in Taiwan.
OBJECTIVE: To elucidate the relationship between hypertension and non-insulin-dependent diabetes. RESEARCH DESIGN AND METHODS: The study consisted of a random sample of adults aged greater than or equal to 40 yr from the Ta-An district of Taipei City and 5 of 12 villages of Taiwan province, which had established primary health-care centers since 1984. A total of 11,478 subjects were recruited into the survey with a response rate of 65.3 and 72%, respectively. Blood glucose and blood pressure levels were measured, and a structured questionnaire was given to each participant. Those identified as having diabetes received further blood tests for lipids and creatinine and were evaluated for vascular complications. RESULTS: The age- and sex-adjusted prevalence of hypertension among diabetic subjects was twice that of nondiabetic subjects (30.6 vs. 16.4%, P less than 0.0005). Hypertensive subjects had a higher prevalence of diabetes than normotensive subjects (10.2 vs. 4.9%, P less than 0.0005). Among hypertensive subjects, the prevalence of diabetes was 12.7% for those taking antihypertensive drugs and 9.1% for those not taking any drug (P less than 0.05). The prevalence of diabetes significantly increased as mean arterial pressure rose, whether the subjects were stratified by various factors. Multiple regression analysis, including sex, age, body mass index, and other risk factors as independent variables, also showed a significant association between diabetes and hypertension. CONCLUSIONS: The univariate and multivariate analyses revealed that there seemed to be a tight link between hypertension and non-insulin-dependent diabetes. Family history of diabetes, diabetes duration, diabetes regimen, control of blood glucose, and the presence of nephropathy, as attested by proteinuria, did not contribute to the risk of hypertension. Further studies are necessary to determine whether these two conditions are causally related.
Adult↗
Lysis of herpes simplex virus-infected cells by lymphokine-activated killer cells.
Activation of human peripheral blood mononuclear cells (PBMC) or murine splenocytes with recombinant interleukin-2 (rIL-2) has been found to be able to generate cells which are lytic in vitro for a variety of cells infected by herpes simplex virus (HSV). Lymphokine-activated killer (LAK) cells were generated by the incubation of human PBMC or murine splenocytes with 500 u/ml of rIL-2 for 3 to 4 days in a CO2 incubator at 37 degrees C. These cells were lytic to cultured tumor cell lines, yet sparing normal primary cell cultures as has been reported. Human PBMC infected with HSV, however, were susceptible to the lytic effect of these LAK cells. From 30 to 50 percent lysis of HSV-infected human PBMC was observed when the effector-to-target ratios were 40:1 and 100:1 respectively by four hr 51Cr-release assays. Similar cytolytic effect was observed when mouse embryonic fibroblasts (MEF) were infected with HSV and used as targets when rIL-2-activated mouse splenocytes were used as effectors. The cytolytic effects of LAK cells on the HSV-infected cells can be demonstrated even after lowering of NK activities by the treatment of effector cells with anti-NK antibody Leu-11b plus complement. Cytolytic effects were not restricted to the autologous system, and could be demonstrated in the heterologous system as well. Human LAK cells killed not only HSV-infected autologous PBMC but also infected mouse embryonic fibroblasts. However, mouse LAK cells exhibit species-specific cytotoxicity. In conclusion, it was demonstrated that LAK cells are cytolytic to HSV-infected cells in both human and murine systems.
Animals↗
Lack of binding effect of insulin on RNA synthesis to isolated nuclei.
Insulin stimulates RNA synthesis in the human hepatoma cell line J5. The mechanisms of insulin action on nuclear functions are not fully understood. To assess the possible action of nuclear insulin binding on RNA synthesis, we studied the insulin action by an in vitro transcription system using the nuclei isolated from control cells and insulin-stimulated J5 cells. Insulin binding was done by ligand binding assay. RNA synthesis was also studied in the nuclei treated with insulin in vitro. We found that a large pool of low-affinity binding sites existed in the isolated nuclei preparation without site-to-site interactions. These data suggest that the majority of nuclear insulin binding sites are located inside the nuclear envelope. Nuclear RNA synthesis was stimulated by the insulin (about a 4-fold increase when compared to the control) added to intact cells but not to isolated nuclei. We conclude that insulin stimulates nuclear RNA synthesis via interaction with plasma membrane receptors.
Binding Sites↗