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Biomedical subjects

C F Kwok

Publications and source records attributed to C F Kwok.

16 recordsLinked to original sources

Insulin-pen: preliminary report on its use for multiple injection regiment in insulin-dependent diabetic patients.

Insulin pens are pen-like devices for multiple injection of insulin. They can cut down the equipment necessary for a multidose regimen and thus make the therapy more convenient and flexible to help improve daily-life quality. It is of interest for us to known whether the average diabetic patients are motivated to achieve better metabolic control by means of insulin-pens. Seven insulin-dependent diabetic patients (male: 3, female: 4, age: 21-34 years) from the Veterans General Hospital participated in the study. None of them had diabetic proliferative retinopathy or proteinuria. They are initially treated with twice daily injection of mixtures of short- and intermediate-acting insulin (run-in period, 8 weeks). A multi-dose regimen with three premeal injections of short-acting insulin with insulin-pen plus one injection of long-acting insulin at bedtime was then used during the study period (12 weeks). Improved in metabolic control as assessed by HbAlc (7.6 +/- 0.9 vs 6.9 +/- 0.8%) and mean blood glucose (175.2 +/- 34 vs 152.3 +/- 28.1 mg/dl) in all patients was found. The frequency and severity of hypoglycemic episodes were not changed. In addition, all patients chose to continue multiple injection using insulin-pen, indicating a high acceptability of such device.

Adult

Metabolic control and B cell function in patients with diabetes mellitus secondary to chronic pancreatitis.

To investigate the relationship between metabolic control and beta cell functions in chronic pancreatitis, 30 patients were selected for study, including 10 with diabetes mellitus in insulin-dependent state (group 1, Mean age 37.6), 10 with diabetes mellitus in non-insulin-dependent state (group 2, Mean age 47.8), and 10 with normal fasting glucose levels (group 3, Mean age 42.1). Each patient received urine routine, stool fat, renal function, biochemical study such as: serum lipid and glycosylated hemoglobin, eye fundi and X-ray examinations. Beta cell function was measured by C-peptide concentration six minutes after intravenous infusion of 1 mg glucagon. The results showed that the glycosylated hemoglobin concentrations were higher in group 1 than in group 2 or 3 patients (P less than 0.05), and were higher in group 2 than in group 3 patients (P less than 0.001) as well. The cholesterol and triglyceride levels were not significantly different among three groups. Furthermore, eight and two of group 1 and 2 patients manifested pancreatic calcification on abdomen X-ray examination (P less than 0.05). All and eight of group 1 and 2 patients received insulin injection respectively. In addition, group 1 patients were more likely to develop steatorrhea, other associated diseases and uncontrolled plasma glucose levels as compared with group 2 patients. In conclusion, insulin-dependent pancreatic diabetics had more advanced disease process and were therefore more likely to get other associated diseases than noninsulin-dependent pancreatic diabetics.

Adult

Arginine induced insulin release in patients with newly onset non-insulin-dependent diabetes mellitus.

To examine the release of insulin in response to oral glucose, intravenous glucagon and intravenous arginine, we measured the levels of plasma glucose, immuno-reactive insulin (IRI) and C-peptide levels on fasting and following an oral glucose loading (OGTT), intravenous glucagon (GON) and arginine (ARG) infusion test in nine newly diagnosed non-insulin dependent diabetics. Their ages ranged from 38 to 65. The fasting plasma glucose and hemoglobin A1c levels were 240 +/- 14 mg/dl (Mean +/- SEM) and 10.7 +/- 0.54%, respectively. Mean values of the peak C-peptide/fasting C-peptide ratio and peak IRI/fasting IRI ratio were significantly increased, as compared with the basal level (P < 0.05), but not significantly different from those of the OGTT, GON and ARG test. In conclusion, the effect of arginine-induced insulin secretion in non-insulin dependent diabetes mellitus is as good as those of glucose or glucagon.

Adult

A twelve month double-blind randomized study of the efficacy and immunogenicity of human and porcine insulins in non-insulin-dependent diabetics.

This study aims to compare the effectiveness and immunogenicity of semisynthetic human insulin (NOVO) and highly purified (monocomponent) porcine insulin over a 12 month period in 16 non-insulin-dependent diabetic subjects not previously exposed to insulin. Sixteen patients were randomly allocated for treatment with either human (n = 9) or monocomponent porcine (n = 7) insulin in a double-blind trial. Both groups were identical with respect to age, sex and measures of metabolic control. Significant insulin antibody was detected in seven of the nine patients (78%) 3 months after the commencement of human insulin therapy whereas it was detected in all patients (100%) in the group treated with monocomponent porcine insulin as early as 2 months after insulin therapy. Besides the delayed rise of insulin antibodies during the first 3 months of human insulin therapy, it tended to have a lower mean insulin antibody titer, though statistically insignificant, at the end of the study. No adverse reaction to either type of insulins was noted. It is concluded that both semisynthetic human and monocomponent porcine insulin were safe and effective. Although human insulin showed a slightly lower immunogenicity than monocomponent porcine insulin of the same formulation and purities, it was not non-immunogenic. Hence, there is no reason to treat all insulin-requiring diabetic subjects with human insulin except those who have developed insulin allergy or those at risk or with a history of allergy.

Adult

Insulin treatment improved glucose-induced insulin release in elderly non-insulin-dependent diabetes mellitus, secondary failure to oral hypoglycemic agents.

In order to observe whether the improvement of diabetic control would promote insulin release of elder non-insulin-dependent diabetics, we performed oral glucose tolerance test and glucagon infusion in eight patients before and after fasting plasma glucose normalized with insulin therapy for three weeks. The levels of plasma glucose and C-peptide both on fasting and following intravenous glucagon infusion and oral glucose loading were measured. Their ages ranged from 60 to 72 years old. The initial fasting plasma glucose levels were 261 +/- 18 mg/dl (Mean +/- SEM). After insulin therapy for three weeks, the fasting plasma glucose levels dropped to 130 +/- 8 mg/dl (Mean +/- SEM, P less than 0.001). The fasting C-peptide/glucose ratio showed no difference before and after therapy. On the other hand, the C-peptidogenic index was markedly improved following insulin therapy, as compared with the value before therapy (P less than 0.05). These results suggested that greater C-peptide response was found in non-insulin dependent elderly diabetics following oral glucose after plasma glucose normalized with insulin therapy.

Administration, Oral

Changes of insulin receptor in aortic endothelial cells from diabetic rats.

Endothelial cells are likely to play an important role in the development of diabetic vascular diseases since they are exposed directly to the abnormal circulating metabolites of diabetes and may be easily damaged early in the natural course of vascular complications. Recently, we have demonstrated a decrease of insulin binding and autophosphorylation of the insulin receptor in cultured capillary endothelial cells of diabetic rats. In this study, similar defects in insulin receptor of aortic endothelial cells cultured from diabetic BB rats were found. The specific insulin binding was 45% lower in cells from diabetic than from non-diabetic rats (3.9 +/- 1.3 vs 7.3 +/- 1.2% per mg protein, p less than 0.05), which was due to a decrease of cell surface binding sites. In contrast to the decrease in insulin binding, insulin-like growth factor-I binding was higher in cells of diabetic than control rats (20.6 +/- 5.6 vs 13.7 +/- 4.6% per mg protein). The decrease in insulin binding could not be induced by the two-week treatment of endothelial cells from non-diabetic rats with medium containing high concentration of glucose (400 mg/dl). Insulin-induced tyrosine kinase activity of partially purified insulin receptor measured using poly-glutyr as substrate was also lower in cells from diabetic rats (normal:1.4 +/- 0.6-fold; diabetic 0.5 +/- 0.3-fold above baseline; (p less than 0.05). These data suggest that the diabetic milieu in vivo can induce persistent defects in insulin receptor of aortic endothelial cells. Further studies are warranted to understand the potential pathophysiological role of these defects.

Animals

Intractable diabetic ketoacidosis due to insulin antibody--response to steroid therapy.

To examine the effect of steroid therapy on insulin antibody titer in insulin-dependent diabetes mellitus, we studied a 58 year-old gentleman with recurrent diabetic ketoacidosis. No any overt precipitating factors could be accounted for, except limited pancreatic beta cell reserve and high titers of anti insulin antibodies. Despite the persistence of high titers of plasma antiinsulin antibodies, the clinical manifestations of diabetic ketoacidosis improved greatly by the administration of steroid. Nevertheless, the patient still showed the great excursion of plasma glucose concentration.

Diabetes Mellitus, Type 1

Thyrotropin-and prolactin--secreting pituitary tumor dissociated hormonal response to bromocriptine.

A 41-year-old male with recurrent hyperthyroidism resulting from pituitary tumor was studied. Because of recurrent hyperthyroidism, he had been treated with propylthiouracil for four years and had been operated. At the time of high serum thyroid hormone (T4: 20 micrograms/dl; T3:502 ng/dl), there was also elevated basal serum TSH level (55 microU/ml) which could not be suppressed by exogenous thyroid hormone administration. In addition, the serum TSH showed blunt response to intravenous TRH infusion. An elevated serum prolactin level was also observed (111 ng/ml). After bromocriptine administration (2.5 mg daily), the suppressibility of serum TSH level was found better than that of prolactin level. The existence of a TSH- and PRL-secreting pituitary tumor in this patient exhibited a dissociated hormonal response to low doses of dopaminergic agents.

Adult

Coexisting hyperthyroidism and hyperparathyroidism: two cases report.

To examine the biochemical changes in coexisting hyperthyroidism and hyperparathyroidism, we have studied two female cases in our medical center. Both patients received biochemistry study, thyroid function test, thyroid autoantibody determination, parathyroid function tests and thyroid scan. They all had increased thyroid function. The concentration of parathyroid hormone was found to elevate in both cases. After thyroid function turned normal, hypercalcemia was still present. Both patients underwent neck operation. Parathyroid adenoma was found in both cases. The pictures of thyroid pathology showed diffuse hyperplasia in one case and lymphocytic thyroiditis in the other case.

Adenoma

Severe rhabdomyolysis induced acute renal failure, caused by diabetic ketoacidosis.

A 23 year-old obese Chinese gentleman was admitted to our hospital with the main problem of conscious disturbance for one day. The physical examination and laboratory data confirmed that this is a case of diabetic ketoacidosis complicated with rhabdomyolysis resulting in acute renal failure three days after admission, and regained his renal function after intensive hemodialysis and other conservative treatment.

Acute Kidney Injury

Identification of persistent defects in insulin receptor structure and function capillary endothelial cells from diabetic rats.

Insulin actions and receptors were studied in capillary endothelial cells cultured from diabetic BB rats and their nondiabetic colony mates. The endothelial cells from diabetic rats of 2 mo duration had persistent biological and biochemical defects in culture. Compared with normal rats, endothelial cells from diabetic rats grew 44% more slowly. Binding studies of insulin and insulin-like growth factor I (IGF-I) showed that cells from diabetic rats had 50% decrease of insulin receptor binding (nondiabetic: 4.6 +/- 0.7; diabetic: 2.6 +/- 0.4% per milligram protein, P less than 0.01), which was caused by a 50% decrease in the number of binding sites per milligram protein, whereas IGF-I binding was not changed. Insulin stimulation of 2-deoxy-glucose uptake and alpha-aminoisobutyric acid uptake were also severely impaired with a 80-90% decrease in maximal stimulation, in parallel with a 62% decrease in insulin-stimulated autophosphorylation (P less than 0.05). 125I-insulin cross-linking revealed an 140-kD alpha subunit of the insulin receptor similar to that in cells from nondiabetic rats, although bands at greater than 200 kD were also detected. The molecular weight of the insulin receptor beta subunit (by SDS-PAGE) was smaller in cells from diabetic than from normal rats (88-90 vs. 95 kD). Neuraminadase treatment of the partially purified insulin receptors decreased the molecular weight of the insulin receptors from nondiabetic rats to a greater degree than its diabetic counterpart. In contrast, Northern blot analysis of insulin receptor mRNAs using human cDNA probes revealed two species of 9.4 and 7.2 kb with no difference in mRNA abundance between cells from diabetic and nondiabetic rats. We conclude that the exposure of capillary endothelial cells to a diabetic milieu in vivo can cause specific and persistent changes in the insulin receptor and insulin action.

Animals

Immunogenicity of highly purified porcine and human insulins in diabetic patients with high titers of insulin antibody.

Twenty-nine non-insulin-dependent diabetic Chinese subjects previously treated with conventional porcine isophane insulin (NPH) for a period of time, whose titer of serum insulin antibody was greater than 40% were changed to either highly purified pork insulin (Nordisk, Denmark) or human insulin of recombinant DNA origin (Eli Lilly, USA) for 1 year in a double-blind and randomized trial. The human (n = 16) and pork insulin (n = 13) groups were carefully matched for age, sex and measures of metabolic control. In highly purified pork-insulin-treated patients, the glycated hemoglobin and fasting blood sugar values began to fall significantly from a mean of 13.2% to 12.3% (p less than 0.05) and 228 mg/dl to 183 mg/dl (p less than 0.005), respectively, 2 months after the commencement of this study, whereas insulin antibody levels began to fall significantly from a mean of 61.8% to 49.5% (p less than 0.01) 6 months after the start of the study. Also, daily insulin doses increased significantly from a mean of 58 units to 70 units (p less than 0.005) 6 months after the start of the study. In human-insulin-treated patients, there were no significant changes in the glycated hemoglobin values. The fasting blood sugar levels fell significantly (p = 0.0515) at the end of the study period but the insulin antibody levels did not show any significant change during the same study period. Daily insulin dose increased significantly from a mean of 51 units to 57 units (p less than 0.01) 4 months after beginning the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The establishment of a radioimmunoassay of calcitonin in human serum.

A sensitive sequential radioimmunoassay of calcitonin (CT) is described. Synthetic human CT was used for 125I-labelling and for preparation of anti-sera. The labelled hormone was purified by QUSO and P10 column. The specific activity of the purified 125I-CT was 39.8 Ci/g. The anti-sera was produced by immunization of guinea pigs with human synthetic CT which was conjugated with carbodiimide onto BSA (bovine serum albumin). Separation of free from antibody bound 125I-labelled CT was performed using DCC precipitation. Standard curves of extracted plasma, extracted plasma plus human CT were parallel to the standard curve. Recovery of 62.5 to 500 pg/ml CT were in the range of 80.72 to 113.4%. The Scatchart plot of the binding data showed a straight line with a kd of 56 pM and Bmax of 35 pM. The specificity of the antiserum was good. The lower limit of detection was 31.25 pg/ml. Our results indicate that this assay system may be useful in both clinical use and research.

Calcitonin

Diurnal variation of insulin clearance and sensitivity in normal man.

Sixteen normal healthy volunteers were randomized into two groups, receiving either low doses insulin infusion clamp study (8mU/M2/min) or high dose (40mU/M2/min) to determine the diurnal insulin clearance and sensitivity. Each subject received the assigned dose of insulin clamp twice; one in the morning (0800-1000) and the other in the evening (1800-2000), each with a precedent 9 hours of fasting, respectively. The results showed that there were diurnal variation of serum insulin clearance in the high dose study (AM:791 +/- 54ml/min/M2, PM:947 +/- 53ml/min/M2, p less than 0.01), and the small dose study (AM:411 +/- 32ml/min/M2, PM:716 +/- 87ml/min/M2, p less than 0.001). Diurnal variation of insulin sensitivity as judged by dividing glucose infusion rate by the ambient serum free insulin level (M/FI ration), was only noted in the low dose insulin infusion clamp study (AM:14.6 +/- 2.4, PM:10.5 +/- 1.1, p less than 0.05). In summary, at low physiological levels of insulin the insulin sensitivity is better in the morning, whereas at both high and low insulin levels the insulin clearance of normal subject is greater in the evening. The mechanism of this diurnal variation of insulin clearance and sensitivity awaits further studies.

Adult

The antilipemic effectiveness of pentaerythritol tetranicotinate on hyperlipidemic patients with or without diabetes mellitus--a double-blind, randomized and two-period change-over experiment.

Pentaerythritol tetranicotinate (Perycit), at an oral dosage of 750 mg daily, was given to 12 patients with idiopathic hyperlipidemia and to 12 patients with hyperlipidemia superimposed with diabetes mellitus (DM). With 2 months off-drug period as the baseline, each patient then received 3 months of placebo and 3 months of Perycit. The sequence of treatment was randomized and balanced in frequency. Blood glycosylated hemoglobin (Hb A1) and fasting plasma glucose (FPG) were used as indices of diabetic control. Serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and TC/HDL-C ratio were measured and calculated in order to compare the antilipemic effectiveness of Perycit with that of placebo. The non-parametric Wilcoxon test was used for the statistical analysis. The results showed that in the idiopathic group, Perycit significantly lowered the serum level of TG and the ratio of TC/HDL-C, and elevated the serum level of HDL-C. In the diabetic group, although there was a similar improvement in diabetic control in both periods of placebo and Perycit treatments, there was no change in the serum levels of TG and HDL-C. There was a slight increase of the serum levels of TC in the periods of Perycit treatment, whereas a small increase of HDL-C resulted in a mild decrease of the TC/HDL-C ratio. There was mild and transient facial flushing during the Perycit treatment in 6 out of 12 diabetic patients. Otherwise, there was no side effects in either group. Pooling the two groups' data together, Perycit increased the serum levels of HDL-C and decreased the TC/HDL-C ratio. It is concluded that Perycit has antilipemic effects in patients with idiopathic hyperlipidemia, and may be helpful in reducing the atherogenic risks in these patients. In patients with hyperlipidemia superimposed with DM, although the serum lipids composition was not significantly changed after Perycit, the atherogenic risks might also be reduced as demonstrated by the decrease of the TC/HDL-C ratio.

Clinical Trials as Topic