Biomedical subjects

S C Lim

Publications and source records attributed to S C Lim.

At least 37 records · Page 2Linked to original sources

PubMed2001

Severe diabetes in remission: a Singapore's perspective.

INTRODUCTION: Diabetic ketoacidosis is generally thought to be the classical presentation of individuals with Type 1 diabetes. Clinicians are beginning to see individuals with atypical diabetes presenting with severe hyperglycaemia associated with or without ketosis and after the initial period of intensive insulin therapy, becoming non-insulin dependent and remaining in remission for years. So far, these patients have only been identified amongst African Americans and have only recently been reported amongst the Japanese and the Chinese in Hong Kong. We therefore set out to identify the existence of such patients in our population. MATERIALS AND METHODS: We have a database of patients admitted for diabetic ketoacidosis. From this, we recruited patients who fulfilled the criteria for atypical diabetes and proceeded to perform a retrospective analysis together with a prospective analysis of their outcome. RESULTS: We identified 10 individuals with atypical diabetes with characteristics similar to those previously described. Our data showed that these patients deferred from classical individuals with Type 1 diabetes in the following ways--older age of onset, relatively higher BMI, marked elevation in HBA1c suggesting a significant period and degree of hyperglycaemia and prolonged remission after reversal of hyperglycaemia. CONCLUSIONS: Atypical Type 2 diabetes exists in our population. Clinicians looking after individuals with diabetes should be made aware of this as there are important implications in the subsequent management of such patients.

Adult↗

PubMed2001

Latent autoimmune diabetes in adults (LADA): a case series.

An adult presenting with diabetes is usually assumed to have type 2 diabetes. Since the 1980s, type 2 diabetic subjects who had failed sulphonylurea therapy soon after diagnosis have been thought to be actually slowly progressive type I patients. This diabetes sub-type is currently referred to as latent autoimmune diabetes in adults (LADA). Early recognition of such patients has important clinical implications. To assist local doctors in the recognition of such patients, we performed a retrospective study to profile and highlight distinctive features of thirteen LADA patients. We found that these patients were mostly females with a mean body mass index of 17.2 kg/m2, diagnosed with type 2 diabetes in their fourth decade of life and becoming insulin dependent after a mean of 2.5 years.

Adult↗

PubMed2000

Homeostasis model assessment in a population with mixed ethnicity: the 1992 Singapore National Health Survey.

We studied insulin resistance and beta-cell function with reference to ethnic group, glucose tolerance and other coronary artery disease risk factors in a cross section of the Singapore population which comprises Chinese, Malays and Asian Indians. 3568 individuals aged 18-69 were examined. Blood pressure, anthropometric data, blood lipids, glucose and insulin were assayed in the fasting state. Glucose and serum insulin were measured 2 h after an oral glucose challenge. Insulin resistance and beta-cell function were calculated using homeostasis model assessment. Asian Indians had higher insulin resistance than Chinese or Malays. Impaired glucose tolerance (IGT) and diabetes mellitus (DM) were associated with greater insulin resistance and impaired beta-cell function compared to normal glucose tolerance (NGT). Insulin resistance was positively correlated with blood pressure in women and total cholesterol, LDL cholesterol and triglyceride in both men and women. It was negatively correlated with HDL cholesterol and LDL/apolipoprotein B ratio. beta-cell function showed no significant correlations with the cardiovascular risk factors studied. It appears that both impaired beta-cell function and insulin resistance are important for the development of hyperglycemia whereas insulin resistance alone seems more important in the development of coronary artery disease as it correlates with several known coronary artery disease risk factors.

Adolescent↗

PubMed2000

Different cutoff values of Cyfra 21-1 for cavitary and noncavitary lung cancers.

STUDY OBJECTIVES: Cell lysis and tumor necrosis release cytokeratin, a tumor marker of lung cancer, into the serum. The serum cytokeratin level can also be elevated in benign cavitary lung diseases. The purpose of this study was to evaluate whether Cyfra 21-1 can differentiate malignant lung diseases from benign diseases with cavitary lesions. DESIGN: This study is a retrospective review of the case records of patients with lung lesions seen during a 4-year period from January 1993 to May 1996. SETTING AND PATIENTS: Serum Cyfra 21-1 levels were measured in 306 patients with lung cancer (n = 143) or benign lung disease (n = 163). The patients were grouped according to radiologic evidence of cavitary lung lesions. Lung cancer included both non-small cell (n = 123) and small cell (n = 20) lung cancers, and the benign diseases include tuberculosis (n = 87), abscess (n = 26), pneumonia (n = 4), and others (n = 46). MEASUREMENTS AND RESULTS: Although Cyfra 21-1 clearly differentiated cavitary lung cancer (15.0, 9.1-29.8 ng/ml, median and interquartile range, n = 39) from benign cavitary disease (P < 0.001), and noncavitary lung cancer from benign noncavitary disease (1.7, 0.9-2.6 ng/ml, n = 108, P < 0.001), it could not differentiate noncavitary lung cancer (5.0, 2.1-12.4 ng/ml, n = 104) from benign cavitary diseases (3.3, 1.4-8.3 ng/ml, n = 55, P = 0.45). CONCLUSIONS: Serum Cyfra 21-1 is a useful tumor marker for differentiating benign from malignant lung diseases. However, different cutoff values are needed, depending on the presence of cavitary lesions. We recommend cutoff values of 30 ng/ml for cavitary lung diseases and 6 ng/ml for noncavitary lung diseases. If there are no radiologic data, a cutoff value of 15 ng/ml is recommended.

Adult↗

PubMed2000

Effects of various implant materials on regeneration of calvarial defects in rats.

The purpose of the present study was to determine the best implant material, the best conditions to substitute absorbable membrane for non-absorbable membrane, and the factors influencing guided regeneration of critical size defects using experimental rats. An 8-mm circular transosseous calvarial bony defect was made and implant materials, such as demineralized freeze-dried bone (DFDB), absorbable membrane (BioMesh; Samyang Co., Seoul Korea), non-absorbable membrane (Millipore filter; Micro Filtration System, MA, USA) or a combination of these materials, was placed on the defect. As for the results of sequential time-based guided bone regeneration, histological, histochemical, immunohistochemical and histomorphometric aspects were observed, and a statistical comparative analysis was performed, with control group of a soft tissue flap. Bone formation was significantly enhanced when DFDB was retained within the defect with a protective absorbable membrane. Inframembranous DFDB-filling was required to prevent membrane collapse and to preserve spaces for bone regeneration. The absorbable membrane which was recommended to overcome the disadvantages of the non-absorbable membrane should remain intact for more than 5 weeks in order for it to be effective. The macrophages recruited by grafts were involved partly in decreasing bone regeneration via the sequential events of releasing fibronectin, and in chemotactic effect of the fibronectin to fibroblasts and collagen lay-down. Thus, the activity of new bone formation was dependent upon the physical barrier effect of the membrane, such as the preserving ability to secure spaces and the suppression ability of early infiltration of collagen and epithelium, inducible ability of inflammation by the implant material, and potential in guiding bone regeneration of the grafts.

Animals↗

PubMed2000

Screening for diabetes mellitus--a two-step approach in individuals with impaired fasting glucose improves detection of those at risk of complications.

AIMS: To compare the new American Diabetes Association (ADA) fasting plasma glucose (FPG) criteria to the 1985 World Health Organization (WHO) 2-h post glucose (2hPG) criteria when used for screening of those with no prior history of diabetes mellitus. METHODS: The study included 3,407 subjects without a history of diabetes in whom both FPG and 2hPG were available from the 1992 Singapore National Health Survey. The agreement (kappa) between FPG and 2hPG for the diagnosis of DM was assessed. The optimal cut-off of FPG for the detection of individuals with 2hPG > or = 11.1 mmol/l was determined by receiver-operating characteristics analysis. RESULTS: The prevalence of diabetes diagnosed by FPG alone was 7.3% compared to 8.4% diagnosed by 2hPG. The prevalence of impaired fasting glucose was 8.0%. FPG and 2hPG showed moderate agreement (kappa = 0.646, 95% confidence interval 0.584-0.708). Age, ethnic group and obesity did not affect the degree of agreement. Of those with 2hPG > or = 11.1 mmol/l, 40.8% had FPG in the non-diabetic range while 24.8% of those with FG > or = 7.0 mmol/l had 2hPG in the non-diabetic range. The optimal FPG for the detection of 2hPG > or =11.1 mmol/l was 6.1 mmol/l. Oral glucose tolerance tests (OGTT) in those with 6.0 mmol/ < FPG < 7.0 mmol/l resulted in the diagnosis of diabetes in 90.7% of individuals at risk of microvascular complications. CONCLUSIONS: FPG provides a simple screening test for diabetes, which shows moderate agreement with the 2hPG. A two-step strategy of OGTT in those with impaired fasting glucose improves the detection of at-risk individuals. However, diabetes should not be diagnosed on a single test. The test should be repeated on another day if an individual tests positive for diabetes.

Adult↗

PubMed2000

Comparison of Tc-99m sestamibi, serum neuron-specific enolase and lactate dehydrogenase as predictors of response to chemotherapy in small cell lung cancer.

Neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) are tumor markers of small cell lung cancer (SCLC) which were reported to predict outcome of patients with SCLC. We previously reported that dipyridamole-modulated Tc-99m sestamibi (dipyridamole-MIBI) single photon emission computed tomography (SPECT) could predict the response to chemotherapy in SCLC patients. The purpose of this study was to compare dipyridamole-MIBI and pretreatment serum levels of NSE and LDH for the prediction of response to chemotherapy in SCLC. Twenty-eight SCLC patients underwent dipyridamole-MIBI SPECT 3 to 7 days before starting chemotherapy (80 mg/m2 etoposide and 80 mg/m2 cisplatin every 3 or 4 weeks for at lease two cycles). Serum levels of NSE and LDH were also measured at the same day of the imaging. Tomographic images before and after 0.84 mg/kg dipyridamole infusion were acquired 1 hour after injection of 370 (10 mCi) and 1,110 (30 mCi) MBq MIBI, respectively. The response to chemotherapy was grouped as specified as complete (CR), partial response (PR), no change (NC), and progressive disease (PD), according to the change in tumor size on chest roentgenography and CT. Patients showing CR and PR were classified as responders, and those who showed NC and PD were considered nonresponders. Among the 28 patients, 15 were responders (2 CR, 13 PR) and 13 were nonresponders (11 NC, 2 PD). The change of tumor-to-normal lung ratio (T:NL) after infusion of dipyridamole was significantly higher in responders as compared with nonresponders (0.38 +/- 0.64 vs. -0.38 +/- 0.50, respectively, p = 0.002). However, pretreatment serum NSE and LDH levels did not correlate with the response to chemotherapy. Increase of T:NL after dipyridamole infusion was a strong negative predictor of chemotherapeutic response in SCLC patients, while NSE and LDH could not predict it.

Aged↗

PubMed2000

Cardiovascular risk profile in individuals with borderline glycemia: the effect of the 1997 American Diabetes Association diagnostic criteria and the 1998 World Health Organization Provisional Report.

OBJECTIVE: In 1997, the American Diabetes Association (ADA) recommended a new diagnostic category, impaired fasting glucose (IFG), to describe individuals with borderline glucose tolerance. On the other hand, the World Health Organization (WHO) suggested retaining the category of impaired glucose tolerance (IGT). We studied the prevalence of IFG and IGT in a multiethnic society and compared the cardiovascular risk profiles of subjects with IFG, IGT, or both IFG and IGT. RESEARCH DESIGN AND METHODS: A total of 3,568 subjects were examined from the 1992 National Health Survey of Singapore, which involved a combination of disproportionately stratified sampling and systematic sampling. Anthropometric, blood pressure, insulin, lipid profile, and uric acid measurements were taken, and a standard 75-g oral glucose tolerance test was performed after a 10-h overnight fast. RESULTS: The prevalence rates of IFG only, IGT only, and both IFT and IGT were 3.45, 10.2, and 3.4%, respectively. The degree of agreement (kappa) between the two diagnostic criteria (the ADA IFG and the WHO IGT) was only 0.25. A fasting glucose level of 5.5 mmol/l was the optimal cutoff for predicting a 2-h postload glucose level of > or =7.8 mmol/l. The following cardiovascular risk factors were higher in subjects with both IFG and IGT compared with those with either IFG or IGT alone: systolic blood pressure (131 +/- 20 vs. 125 +/- 21 and 125 +/- 19 mmHg, respectively; P < 0.05 and P < 0.001, respectively); diastolic blood pressure (77 +/- 12 vs. 73 +/- 12 and 74 +/- 12 mmHg, respectively; P < 0.05); BMI (26.2 +/- 4.2 vs. 24.4 +/- 4.0 and 24.6 +/- 4.4 kg/m2, respectively; P < 0.01 and P < 0.001, respectively); waist circumference (84.1 +/- 10.3 vs. 79.3 +/- 10.7 and 79.3 +/- 10.6 cm, respectively; P < 0.001); waist-to-hip ratio (0.84 +/- 0.08 vs. 0.82 +/- 0.09 and 0.81 +/- 0.08, respectively; P < 0.05 and P < 0.001, respectively); fasting insulin (12.1 +/- 9.7 vs. 9.2 +/- 5.3 and 9.9 +/- 7.7 mU/l; P < 0.01); insulin resistance (by homeostasis model assessment [HOMA]) (3.41 +/- 2.77 vs. 2.58 +/- 1.50 and 2.43 +/- 1.83, respectively; P < 0.01 and P < 0.001, respectively); total cholesterol (5.81 +/- 1.1 vs. 5.51 +/- 1.1 and 5.53 +/- 1.1 mmol/l, respectively; P < 0.05) and apolipoprotein(B) [apo(B)] (1.5 +/- 0.38 vs. 1.40 +/- 0.34 and 1.39 +/- 0.35 mmol/l, respectively; P < 0.01). The pattern of difference remained significant only for fasting insulin, insulin resistance (HOMA), and apo(B) (borderline) after adjustment for age, sex, and ethnic differences. CONCLUSIONS: Obvious discordance was evident in the classification of glycemic status when applying the criteria proposed by the ADA (IFG) or WHO (IGT) in a multiethnic society like Singapore. However, subjects with either IFG or IGT had similar cardiovascular risk profiles. Therefore, both criteria identified individuals at high risk for cardiovascular disease. Individuals with both IFG and IGT had a greater incidence of the cardiovascular dysmetabolic syndrome.

Adolescent↗

PubMed2000

Vascular endothelial growth factor in malignant and tuberculous pleural effusions.

The purpose of this study is to assess the usefulness of soluble vascular endothelial growth factor (VEGF) in the effusions of patients with malignant and tuberculous diseases. Using a sandwich enzyme-linked immunoadsorbent assay, VEGF concentration was measured in malignant (n=17) and tuberculous (n=11) pleural effusions. Pleural biopsy, cytology or microbiological methods were used to make final diagnoses. Adenosine deaminase (ADA) levels in tuberculous pleural effusions were significantly higher than those in malignant pleural effusions. The median level of VEGF in patients with malignant effusions (median, 2418 pg/mL; range, 97-62103 pg/mL) was significantly higher than tuberculous effusions (median, 994 pg/mL; range, 44-3552 pg/mL). There were no significant differences in pleural VEGF levels in patients with different histological types of lung cancer. The VEGF level was not correlated with ADA, lactate dehydrogenase and total protein levels of pleural fluid. In conclusion, pleural VEGF levels in patients with malignant effusions were significantly higher than tuberculous effusions, and the measurement of pleural VEGF is helpful in discriminating between malignant and tuberculous effusions. Further studies are needed to determine the clinical value of VEGF as a tumor marker and a prognostic factor.

Endothelial Growth Factors↗

PubMed2000

The role of E-cadherin expression in non-small cell lung cancer.

The purpose of this study is to evaluate the clinical significance of E-cadherin expression in lung cancer. E-cadherin expression was detected by immunohistochemistry using a monoclonal antibody (HECD-1). Strongly positive (++) E-cadherin tumors were classified as a type of preserved E-cadherin expression (Pr type), while the others (+, - tumors) were classified as a type of reduced E-cadherin expression (Rd type). The frequency of Pr type in squamous cell carcinomas (59.0%) was higher than Rd type. However, in adenocarcinomas, the frequency of Rd type was higher than Pr type. E-cadherin expression pattern was significantly correlated with differentiated state (Pearson correlation coefficient 0.394, p<0.001). E-cadherin expression of well-differentiated tumors was more frequently preserved than that of poorly differentiated tumors (60.0% vs. 25.9%). With regard to the correlation between E-cadherin expression and stages of lymph node metastasis in non-small cell lung cancers, the percentage of tumors with Pr type E-cadherin expression declined from 66.3% (< or = N1) to 38.6% (> or = N2), indicating that loss of E-cadherin expression is responsible for acquisition of invasive potential of lung cancer as well as the possible role of E-cadherin in the histological differentiation of lung cancer.

Adult↗

PubMed2000

Pleural empyema due to Salmonella: a case report.

Pleuropulmonary involvement of salmonella infection is very rare and only two cases of salmonella empyema have been reported in Korea. We report the case of a 70-year-old female diabetic patient who presented with right flank pain and right lower chest pain. The chest radiographs revealed fibrostreaky and hazy density at right lower lung field and blunting of right costophrenic angle. Thoracentesis revealed turbid yellowish fluid. Salmonella group B was identified from the cultures of blood and pleural fluid. After antimicrobial therapy and repeated therapeutic thoracentesis, the patient was improved.

Aged↗

PubMed2000

A man with osteoblastic metastasis and hypocalcaemia.

We report a case of an 80-year-old man with osteoblastic metastases from advanced carcinoma of the prostate presenting with a grand mal seizure resulting from severe hypocalcaemia. He had low serum phosphate and ionised calcium levels, elevated serum skeletal alkaline phosphatase and intact parathormone levels. 99mTc radioisotope bone scan revealed a "super bone scan" suggestive of osteomalacia. The serum 1, 25-dihydroxycholecalciferol level was unexpectedly elevated. The biochemical abnormalities persisted despite high dose calcium replacement, but improved with supraphysiological doses of 1,25 (OH)2 vitamin D3 (Rocaltrol) therapy. We hypothesise that the hypocalcaemia in this patient was due to vitamin D resistance secondary to a humoral factor secreted by the tumour.

Aged↗

PubMed1999

Cerebellar pleomorphic xanthoastrocytoma in an infant.

Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor and typically occurs in the superficial cerebral hemispheres of young subjects. We report a case of PXA in the cerebellum of a 3-month-old infant in view of its unusual location and age. The patient presented with a 1-month history of upward eyeball gazing difficulty. To the authors' knowledge, this is the first report of occurrence of this neoplasm in the cerebellum of an infant. We report the morphologic and immunophenotypical features, and literature review with regard to the clinicopathologic aspects of a case of unusual PXA.

Astrocytoma↗

PubMed1999

Dipyridamole modulated Tc-99m sestamibi lung SPECT in small cell lung cancer.

PURPOSE: In this study, the authors wanted to determine whether dipyridamole-modulated MIBI (dipyridamole-MIBI) could enhance the prediction of the response to chemotherapy in patients with small cell lung cancer. METHODS: Twenty-seven patients with biopsy-proved small cell lung cancer (25 men, 2 women; mean age, 61 +/- 7 years) underwent dipyridamole-MIBI SPECT 3 to 7 days before starting chemotherapy (80 mg/m2 etoposide and 80 mg/m2 cisplatin every 3 or 4 weeks for at least two cycles). Tomographic images before and after dipyridamole (0.84 mg/kg) were acquired 1 hour after injection of 370 (10 mCi) and 1,110 (30 mCi) MBq MIBI, respectively. The response to chemotherapy was grouped as specified as complete response (CR), partial (PR), no change (NC), or progressive disease (PD), according to the change in tumor size on chest roentgenography and CT. Patients showing CR and PR were classified as responders, and those who showed NC and PD were considered nonresponders. RESULTS: Among the 27 patients, 22 were responders (3 CR, 19 PR) and 5 were nonresponders (3 NC, 2 PD). The tumor-to-normal lung ratio (T:NL) of responders was significantly higher than that of nonresponders. The diagnostic accuracy of the T:NL ratio to differentiate responders and nonresponders was 33.3%, with a cutoff value of 2.5, which was significantly improved to 77.8% when an increased T:NL ratio after dipyridamole was assigned to a nonresponder. Furthermore, all patients with CR showed diminished T:NL ratios after dipyridamole, and all patients with NR showed an increased T:NL ratio after dipyridamole. CONCLUSION: Dipyridamole-MIBI SPECT could enhance the prediction of response to chemotherapy in patients with small cell lung cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

The effect of hormonal replacement therapy on the vascular reactivity and endothelial function of healthy individuals and individuals with type 2 diabetes.

Estrogens protect healthy women from cardiovascular disease. However, epidemiological data suggest that women with diabetes are denied the cardioprotection associated with estrogens. Whether or not hormonal replacement therapy (HRT) confers cardiovascular benefits in postmenopausal women with diabetes is not known. The aim of this study was to examine the effects of HRT on the microvascular reactivity and endothelial function of individuals with and without diabetes. We studied the following groups of individuals: premenopausal healthy women [n = 28, age 41 +/- 8 yr (mean +/- SD)], premenopausal women with type 2 diabetes (n = 16, age 43 +/- 6 yr); postmenopausal healthy women (n = 12, age 57 +/- 4 yr), postmenopausal women with diabetes (n = 17, age 62 +/- 5 yr); postmenopausal healthy women on HRT (n = 13, age 51 +/- 5 yr), postmenopausal women with diabetes on HRT (n = 11, age 57 +/- 7 yr). We used laser Doppler flowmetry to measure forearm cutaneous vasodilatation in response to iontophoresis of 1% acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium independent). The endothelium-dependent vasodilation was significantly higher in premenopausal healthy women (180 +/- 67%; increase over baseline) compared to premenopausal diabetic women (87 +/- 41%; P < 0.001). endothelium-dependent vasodilation was also higher in postmenopausal healthy women on HRT (143 +/- 52) compared with postmenopausal diabetic women on HRT (86 +/- 61), postmenopausal healthy women without HRT (104 +/- 43), and postmenopausal diabetic women without HRT (74 +/- 28; P < 0.001). A similar pattern of responses was observed in the endothelium-independent vasodilation (premenopausal healthy women, 126 +/- 56; premenopausal diabetic women, 88 +/- 26; postmenopausal healthy women on HRT, 121 +/- 37; postmenopausal diabetic women on HRT, 88 +/- 41; postmenopausal healthy women without HRT, 84 +/- 36; and postmenopausal diabetic women without HRT, 73 +/- 36; P < 0.001). Soluble intercellular adhesion molecule (sICAM) was also measured among all the women with diabetes. Premenopausal women with diabetes (248.9 +/- 56 ng/ml) and postmenopausal women with diabetes on HRT (257.7 +/- 49 ng/ml) had lower sICAM levels compared with the postmenopausal diabetic women without HRT (346.4 +/- 149 ng/ml; P < 0.05). We conclude that menopausal status and type 2 diabetes are associated with impaired microvascular reactivity. HRT substantially improves microvascular reactivity in postmenopausal healthy women. In contrast, the effect of HRT on the microvascular reactivity of postmenopausal diabetic women is less apparent. However, the use of HRT among women with diabetes is associated with lower sICAM levels, suggesting an attenuation in endothelial activation.

Acetylcholine↗

PubMed1999

Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes.

Abnormalities in vascular reactivity in the micro- and macrocirculation are well established in type 2 diabetes. However, little is known about changes in vascular reactivity in those at risk for developing type 2 diabetes. To address this situation, the vascular reactivity in both the micro- and macrocirculation was studied in four age and sex comparable groups: 30 healthy normoglycemic subjects with no history of type 2 diabetes in a first-degree relative (controls), 39 healthy normoglycemic subjects with a history of type 2 diabetes in one or both parents (relatives), 32 subjects with impaired glucose tolerance (IGT), and 42 patients with type 2 diabetes without vascular complications (diabetes). Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent) and 1% sodium nitroprusside (SNP) (endothelium-independent), whereas high-resolution ultrasound images were used to measure brachial artery diameter changes during reactive hyperemia. Plasma concentrations of endothelin-1 (ET-1), von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The vasodilatory responses to Ach, expressed as percent increase of blood flow over baseline, were reduced in relatives (98 +/- 48, mean +/- SD), IGT (94 +/- 52), and diabetes (74 +/- 45) compared with controls (126 +/- 67) (P < 0.001 controls versus relatives, IGT, and diabetes). The responses to SNP were similarly reduced: controls (123 +/- 46), relatives (85 +/- 46), IGT (83 +/- 48), and diabetes (65 +/- 31) (P < 0.001 controls versus relatives, IGT, and diabetes) as were the responses in the brachial artery diameter during reactive hyperemia: controls (13.7 +/- 6.1), relatives (10.5 +/- 6.7), IGT (9.8 +/- 4.5), and diabetes (8.4 +/- 5.0) (P < 0.01 controls versus relatives, IGT, and diabetes). Women had greater responses than men in both the micro- and macrovascular circulatory tests, but a similar progressive reduction was observed in both sexes with increasing degrees of glucose intolerance. A significant inverse correlation was found between microvascular reactivity and systolic blood pressure, fasting plasma glucose, HDL cholesterol, fasting plasma insulin, and homeostasis model assessment (HOMA) values, an index of insulin resistance. BMI and diastolic blood pressure had a significant inverse correlation only with endothelium-dependent vasodilation. In the macrocirculation, systolic blood pressure, HbA1c, HDL cholesterol, and HOMA had significant correlation with brachial artery diameter changes. Compared with control subjects, ET-1 was significantly higher in all groups, vWF was higher only in the diabetic group, sICAM levels were higher in the IGT and diabetic groups, while sVCAM concentrations were higher in the relatives and those with diabetes (P < 0.05). On stepwise multivariate analysis, age, sex, fasting plasma glucose, and BMI were the most important contributing factors to the variation of vascular reactivity. Addition of all clinical and biochemical measures explained only 32-37% of the variation in vascular reactivity. These results suggest that abnormalities in vascular reactivity and biochemical markers of endothelial cell activation are present early in individuals at risk of developing type 2 diabetes, even at a stage when normal glucose tolerance exists, and that factors in addition to insulin resistance may be operative.

Acetylcholine↗

PubMed1999

Soluble intercellular adhesion molecule, vascular cell adhesion molecule, and impaired microvascular reactivity are early markers of vasculopathy in type 2 diabetic individuals without microalbuminuria.

OBJECTIVE: Using von Willebrand Factor (vWF) as a marker of endothelial function, previous studies have shown that the development of microalbuminuria is associated with the onset of endothelial dysfunction in individuals with type 2 diabetes. We tested the hypothesis that endothelial dysfunction is already evident in normoalbuminuric individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: We used laser Doppler imaging scanning to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent). Multiple indicators of endothelial function--soluble intercellular adhesion molecule (sICAM), soluble vascular cell adhesion molecule (sVCAM), vWF, and microvascular reactivity--were measured in 20 healthy control subjects, 45 normoalbuminuric (urinary albumin/creatinine ratio < 30 micrograms/mg) individuals with type 2 diabetes, and 14 microalbuminuric (urinary albumin/creatinine ratio between 30 and 300 micrograms/mg) individuals with type 2 diabetes. RESULTS: Serum sICAM and sVCAM levels were elevated in the normoalbuminuric (305 +/- 120, 851 +/- 284 ng/ml) and microalbuminuric (300 +/- 89, 845 +/- 252 ng/ml) individuals with diabetes when compared with the healthy control subjects (213 +/- 58, 661 +/- 176 ng/ml) (P < 0.01). Furthermore, the microvascular endothelium-dependent and -independent vasodilation was reduced in the normoalbuminuric (76 +/- 44, 70 +/- 33) (percent increase in perfusion over baseline) and microalbuminuric (74 +/- 41, 73 +/- 28) individuals with diabetes compared with healthy control subjects (126 +/- 67, 120 +/- 47) (P < 0.05). In contrast, plasma vWF was elevated only in the microalbuminuric individuals with diabetes (129 +/- 35%) compared with the normoalbuminuric individuals with diabetes (110 +/- 34) and healthy control subjects (111.3 +/- 39) (P < 0.05). On stepwise multivariate analysis, fasting blood glucose was the most important contributing factor to the variation in microvascular reactivity and sVCAM, whereas insulin resistance (by homeostasis model assessment) was the most important contributing factor to the variation in sICAM. Addition of all clinical and biochemical measures explained only 15-22% of the variation in sICAM, sVCAM, and microvascular reactivity. CONCLUSIONS: Multiple markers of endothelial dysfunction were evident in normoalbuminuric individuals with type 2 diabetes. The pathogenic process of vasculopathy in type 2 diabetes occurs early and may be operative before the development of microalbuminuria.

Adult↗

PubMed1999

In search of hyperglycaemia--tracing the path that leads to the new diagnostic criteria for diabetes mellitus.

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus announced the new diagnostic criteria for diabetes mellitus on 23 July 1997. The most notable change in the new criteria is a reduction in the cut-off point for fasting plasma glucose to that of 7.0 mmol/L (126 mg/dL). The present criteria have evolved through many years of intensive research and discussions. We intend to trace the path that leads to this latest recommendation so as to understand the evolution of the present criteria and its implications.

Blood Glucose↗