Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Japanese IDDM patients have been demonstrated to have unique and different HLA associations from white patients. To elucidate the effect of HLA-associated genetic factors on the clinical heterogeneity of IDDM in Japanese people, HLA-DRB1, DQA1, and DQB1 genotypes in 88 childhood-onset Japanese IDDM patients were examined by polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) or sequence-specific primers (SSP). Of the 88 IDDM patients, 26 (29.5%) had DRB1*0405-DQA1*0302-DQB1*0401/X (DR4-DQ4/X), 38 (43.2%) had DRB1*0901-DQA1*0302-DQB1*0303/X (DR9-DQ9/X), and 9 (10.2%) were DR4/9-DQ4/9 heterozygous in the present study (X does not contain protective alleles). Clinical heterogeneity such as age distribution at onset, prevalence and serum level of anti-GAD antibodies (GADAb), and residual pancreatic beta-cell function after diagnosis were compared between patients with HLA-DR4-DQ4 and DR9-DQ9. The frequency of DR9-DQ9 genotype was significantly higher in the younger (0-10 years) than in the older (11-16 years) age-group of onset, but the frequency of DR4-DQ4 was higher in the older (11-16 years) age-group. Although no association of DR-DQ genotypes with the prevalence and serum level of GADAb was found among newly diagnosed patients, long-standing DR9-DQ9 patients had significantly higher levels of GADAb than those with DR4-DQ4. While no difference in time course of serum C-peptide (CPR) levels was detected between GADAb+ and GADAb- patients, a remarkable difference was demonstrated between DR9-DQ9 and DR4-DQ4 patients. The residual pancreatic beta-cell function was retained more in patients with DR4-DQ4 than in those with DR9-DQ9 at diagnosis through 12-18 months after diagnosis. These results suggest that the DR9-DQ9 genotype may induce stronger autoimmune destructive response (T-helper 1 function) against target beta-cells than the DR4-DQ4 genotype does. Our findings may warrant further studies on the association of diabetogenic autoimmune response with HLA class II molecules and contribute to a clarification of interracial differences in HLA-encoded susceptibility to IDDM.
Diabetes 1997 Nov
PMID:Association of HLA-DR, DQ genotype with different beta-cell functions at IDDM diagnosis in Japanese children. 935 42

We report a 79-year-old woman case of slowly progressive IDDM (SPIDDM) with rheumatoid arthritis (RA) and Hashimoto disease. High titer of anti-glutamic acid decarboxylase antibody (GAD) with a value of 16,400 U/ml (normal value: less than 5 U/ml) and deteriorated secretion of insulin, and clinical course led to the diagnosis of SPIDDM. Both anti-islet cell and anti-insulin antibodies were negative. One year prior to the diagnosis, at 78 years of age, she was newly diagnosed with NIDDM and had been medicated with sulfonylurea and voglibose, resulting her glucose levels well-controlled. Four months before admission, a gradual increase of plasma glucose was noticed, while oral hypoglycemic agents were fully administrated. On admission, her glycemic control was revealed as follows; a fasting blood glucose level of 458 mg/dl and an HbA1 C level of 14.3%. Urinary CPR was 22.5 micrograms day. Her insulin secretion was proved not to be induced with intravenous glucagon injection. Hyperinsulinemic euglycemic glucose clamp test showed the normal glucose uptake ratio; 9.5 mg/kg/min. Moderate doses of subcutaneous insulin (20 units daily) were effective on her diabetes control. She was newly diagnosed with Hashimoto disease that required thyroid hormone replacement 50 micrograms per day after having developed NIDDM. High titer of anti-thyroglobulin antibody (46.9 U/ml) and anti-thyroid peroxidase antibody (81.5 U/ml) were observed. The patient had been medicated for RA with anti-inflammatory drugs since her early seventieth. Rheumatoid factor was elevated to 127.7 IU/L and, anti-nuclear antibody (x 80) and anti-DNA antibody (x 80) were present. It may be of interest that a specific phenotype of HLA; A24 (9) and DR9 recognized to be susceptible to IDDM was detected in the high-elderly onset SPIDDM. Taken together HLA typing with her history of both RA and Hashimoto disease, our case may provide the information to the mechanism of pathogenesis of SPIDDM. Furthermore, to out knowledge, this is the first case of SPIDDM in the aged; 75-year-old or more.
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PMID:[Slowly progressive IDDM with rheumatoid arthritis and Hashimoto disease in high elderly]. 977 59

To evaluate the effects of cilnidipine (CNP), L- and N-type calcium channel blocker and nilvadipine (NVP) on 24-h urinary epinephrine (U-EP), norepinephrine (U-NE), dopamine (U-DA) and C-peptide (U-CPR) in patients associated with hypertension and non-insulin-dependent diabetes mellitus (HT-NIDDM), a randomized crossover study was performed with 35 HT-NIDDM patients. The patients were given CNP (10 mg/day) and NVP (8 mg/day), separately, for 4 weeks each. After CNP treatment, U-NE, U-DA and U-CPR levels were significantly reduced compared with pre-treatment levels: 160.4 +/- 12.7 to 111.7 +/- 8.9 microg/day (mean +/- S.E., P < 0.005); 934.8 +/- 163.4 to 590.3 +/- 33.4 microg/day (P < 0.05); 86.7 +/- 9.9 to 57.6 +/- 7.4 microg/day (P < 0.05), respectively. Although no significant differences were observed in U-EP, U-NE, U-DA and U-CPR levels by NVP treatment, U-NE, U-DA and U-CPR levels after CNP treatment were significantly lower than those after NVP treatment: 111.7 +/- 8.9 versus 155.0 +/- 13.7 microg/day (P < 0.02); 590.3 + 33.4 versus 822.2 +/- 104.3 microg/day (P < 0.05); 57.6 +/- 7.4 versus 80.6 +/- 8.1 microg/day (P < 0.05), respectively. In conclusion, it was demonstrated that CNP treatment significantly reduced U-NE, U-DA and U-CPR excretion compared with NVP treatment in HT-NIDDM patients.
Diabetes Res Clin Pract 1999 Jun
PMID:Cilnidipine, the N- and L-type calcium channel antagonist, reduced on 24-h urinary catecholamines and C-peptide in hypertensive non-insulin-dependent diabetes mellitus. 1046 43

Quantitation of C-peptide is important for the assessment of insulin secretion, in particular in patients receiving insulin therapy. Since the CPR levels become much higher than the concentration of C-peptide for several reasons, such as the high concentration of proinsulin, CPR values sometimes need to be assessed carefully. We have had two diabetic patients whose CPR values were abnormally high when determined with a Daiichi C-peptide kit III (method 1). CPR values determined by other methods were from two to ten times lower, indicating considerable interference when method 1 was used. Since method 1 uses mouse monoclonal antibodies (mmab) for detection antibodies, we suspected that human anti-murine antibodies (HAMA) were responsible for the interference. HAMA were detected in serum from both patients (45 and 460 ng/ml in case 1 and case 2 (at peak), respectively). Removal of HAMA from serum eliminated the interference. Modification of method 1 to exclude mmab from the assay system removed all interference. HAMA were, therefore, considered to be the cause of the interference. In case 2, the peak concentration of HAMA was recorded 16 months earlier than the maximum of interference. Further analysis revealed that HAMA with high affinities were responsible for the interference.
Diabetes Res Clin Pract 2000 May
PMID:Human anti-murine antibodies interfere with CPR assays performed with commercial kits. 1080 47

By screening 204 diabetes patients, a male with age 38 was found to have increased C-peptide levels in plasma (over 6 ng/ml) and urine (430 microg/day), both of which were the highest among the screened subjects. He developed type 2 diabetes at age 31, without history of obesity (weight was 52 kg and height 170 cm). He had bilateral testicular atrophy. Fasting plasma glucose level was 160 mg/dl and HbA1c was 8% at age 38. There was hypertriglycemia (290-662 mg/dl). There were no abnormal peaks of IRI or CPR in the serum fractionated by gel filtration (Biogel P 30). Molar ratio of p-CPR/s-IRI was 10.8. Islet cell antibody, anti-insulin binding antibody and anti-insulin receptor antibody were negative. LSH and FSH were both elevated, and free testosterone was decreased. TSH and Leptin levels were elevated. Other laboratory data were within normal range. CT scan revealed fatty liver and horse-shoe kidney. These clinical pictures do not match the criteria to known syndromes associated with diabetes. Although the single case report is insufficient to discuss the C-peptide mechanism of action, this case may give us a hint to understand an aspect of the pathophysiology of C-peptide's bioactivity dysfunction.
Diabetes Res Clin Pract 2004 Dec
PMID:A case of type 2 diabetes with high levels of plasma and urinary C-peptide. 1556 62

Attempts to increase the number of African-Americans participating in clinical trials, regardless of age, have been hampered by a lack of published data regarding successful recruitment and retention strategies. Successful strategies can be used as a guide for future researchers in the design of studies to recruit African-Americans, regardless of age, into clinical as well as qualitative studies to promote health among this vulnerable population. The goal of the primary study was to recruit 400 families with 2 or more family members affected with diabetes, totaling 800 participants. Project Sugar utilized the coordinated research principals known as CPR (Community, Plan, Reward) to recruit 615 African-American families totalling 1,230 people known as the Sea Island people (Gullahs) in the first five years of the study. The intention of the study was to identify markers for diabetes among these Sea Island natives who tended to be genetically homogenous. In so doing, specific strategies were identified as serendipitous findings for this study. Nonetheless, these serendipitous findings were thought to be so integral to success in the recruitment of African-Americans, mainly because of their success among this fairly close-knit, historically isolated, and significantly genetically homogenous Sea Islanders (Gullah). In recognizing the success of this model, an alternate aim was examined to devise rigorous scientific strategies to promote methods for recruitment of African-Americans into clinical trials aimed at reducing health disparities among this vulnerable population. This projects success can be attributed to the involvement of a local citizen advisory committee and rewards in the form of services, benefits, and incentives to the community. Findings from this alternative aim, which was scientifically built on the CPR model, suggest that when services are provided to the community, coupled with the use of local community advisory committees, the possibilities of recruiting participants into a clinical trial are significantly enhanced and augmented.
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PMID:Project Sugar: a recruitment model for successful African-American participation in health research. 1585 86

We report a 38-year-old female with severe insulin resistance who developed type 1 diabetes after being diagnosed with type 2 diabetes. At the initial examination, BMI was 31.8 kg/m(2) and HbA1c 10.8%. Her insulin secretion was sufficient (urinary CPR 80 microg/day) and the GAD antibody was negative. Following treatment with insulin and glimepiride, HbA1c decreased to 6.3%, though diabetic control deteriorated after 1 year (HbA1c, 11.0%) and her body weight was reduced in a short period, from 78 to 67 kg. Re-examination revealed that the GAD antibody was high (1870 U/mL, normal <1.5) and the anti-islet cell antibody positive, and insulin secretion decreased (urinary CPR 18 microg/day). Further, a hyperinsulinemic-euglycemic cramp study using an artificial pancreas showed that the patient had severe insulin resistance [glucose infusion rate 1.8 mg/(min kg); normal, 7.4+/-2.4 (mean+/-S.D.)]. An HLA-analysis showed that she was a homozygote of haplotype DRB1*0901-DQB1*0303. In spite of strict insulin therapy, glucose control was not improved. Pioglitazone could not be used because of side effects, however, metformin was effective for glucose control. The accumulation of case reports of patients with type 1 diabetes and insulin resistance is important for studying the relationship between the onset of the disease and insulin resistance, and for developing an effective treatment strategy.
Diabetes Res Clin Pract 2005 Dec
PMID:Type 1 diabetes developed in a type 2 diabetic patient with severe insulin resistance. 1595 87

To clarify the actual usage of insulin preparations and their effectiveness on glycaemic control in patients with Type 1 diabetes mellitus in Japan, we analyzed clinical data collected via CoDiC, an electronic system for diabetes data collection and management, at 28 institutes. Of 18,470 diabetic patients registered with CoDiC in June, 2003, 12,279 patients were being treated with insulin preparations and/or oral hypoglycemic agents, with 861 of these patients having Type 1 diabetes mellitus and 11,418 patients having Type 2 diabetes. Three analytical surveys were carried out with the Type 1 diabetes patients. Study I: Cross-sectional survey on the treatment in 2002. Six hundred and thirteen patients received intensive conventional insulin treatment (ICT). The number of patients receiving rapid-acting insulin analogue (RA) was greater than that of patients receiving regular insulin (R). Serum CPR was lower in the patients with ICT than in the patients with conventional insulin treatment (CT). Study II: Survey on the changes in the actual usage and clinical effectiveness of insulin preparations, based on the data input in 2001 and 2002. The number of patients with ICT using RA insulin markedly increased. Study III: Analysis of the participants' clinical course over the 18-month period of the study from the time of first consultation. The dose of insulin increased during the term. The average HbA1c level fell drastically and reached to 7.5% over the first 9 months of the study and then remained between a range of 7.5% and 8% for the rest of the study period. In conclusion, ICT is actively performed and the RA insulin analogues are widely used in Type 1 diabetic patients in Japan. Basal-bolus therapy should be used to treat Type 1 diabetic patients with postprandial serum CPR of less than 0.5 ng/ml. It is difficult to obtain the ideal glycaemic control in Type 1 diabetic patients with the currently available insulin preparations.
Diabetes Res Clin Pract 2006 Jun
PMID:Actual usage and clinical effectiveness of insulin preparations in patients with Type 1 diabetes mellitus in Japan: CoDiC-based analysis of clinical data obtained at multiple institutions (JDDM 3). 1661 94

Evaluation of a patient's pancreatic beta-cell function is important in both diagnosis and treatment of diabetes. We sought to determine beta-cell function with a single sampling of blood. Examination of fasting blood glucose (F-BG, mM) and C-peptide (F-CPR, nM) levels in seven post-islet-transplanted states of four patients revealed a linear relationship between F-BG and F-CPR. Assuming that normal subjects aged <40 years have 100% pancreatic beta-cell function, we developed the secretory units of islets in transplantation (SUIT) as an index of beta-cell function by the formula: 250 x F-CPR/(F-BG-3.43). The SUIT index was correlated with the stimulated C-peptide levels not only in islet-transplanted patients (R2 = 0.68, P < 0.05) but also in type 2 patients (R2 = 0.34, P < 0.001). Since the SUIT index can be calculated from data obtained at a single fasting blood sampling and predict the pancreatic beta-cell function, the formula may be a useful tool in clinical management of diabetes.
Diabetes Res Clin Pract 2006 Dec
PMID:SUIT, secretory units of islets in transplantation: An index for therapeutic management of islet transplanted patients and its application to type 2 diabetes. 1670 90

Waist circumference (WC) was measured in 200 Japanese patients with type 2 diabetes mellitus (T2DM: male 106, female 94, mean age 61 years old) who had been admitted in our hospital, and relationship with various risk factors to predict future cardiovascular disease (CVD) was analyzed. There was a positive and statistically significant trend in WC levels with an increasing number of CVD risk factors in male patients, whereas no significant trend of WC was observed in female patients. The receiver operator characteristic (ROC) curve for WC to predict the presence of two or more risk factors of CVD depicted greater area under the curve in male patients (0.732) than that in female patients (0.571). Apart from positive correlation with fasting serum C-peptide (S-CPR) and log-transformed high-sensitivity C-reactive protein (log HS-CRP) in both genders, WC was positively correlated with log-transformed triglyceride (log TG), systolic and diastolic blood pressure (SBP and DBP) and negatively with HDL-cholesterol (HDL-C) in male patients, whereas it was negatively correlated with HbA1c and fasting plasma glucose (FPG) in female patients. The change of WC after administration (DeltaWC) was correlated with DeltaS-CPR, DeltaLDL-C, DeltaSBP and DeltaDBP in male patients, while no relationship was observed in female patients. In conclusion, WC is a reliable marker to predict future CVD events at least in Japanese male, but not female patients with T2DM.
Diabetes Res Clin Pract 2008 Oct
PMID:Attenuated metabolic effect of waist measurement in Japanese female patients with type 2 diabetes mellitus. 1878 39


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