Early and late post-ischaemic recovery of contractile function is affected to different degrees by isoflurane and halothane in the anaesthetized rabbit model

We took advantage of the partial protection exerted by suitable dosages of nicotinamide against the beta-cytotoxic effect of streptozotocin (STZ) to create a new experimental diabetic syndrome in adult rats that appears closer to NIDDM than other available animal models with regard to insulin responsiveness to glucose and sulfonylureas. Among the various dosages of nicotinamide tested in 3-month-old Wistar rats (100-350 mg/kg body wt), the dosage of 230 mg/kg, given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded a maximum of animals with moderate and stable nonfasting hyperglycemia (155 +/- 3 vs. 121 +/- 3 mg/dl in controls; P < 0.05) and 40% preservation of pancreatic insulin stores. We also evaluated beta-cell function both in vitro and in vivo 4-9 weeks after inducing diabetes. In the isolated perfused pancreas, insulin response to glucose elevation (5-11 mmol/l) was clearly present, although significantly reduced with respect to controls (P < 0.01). Moreover, the insulin response to tolbutamide (0.19 mmol/l) was similar to that observed in normal pancreases. Perfused pancreases from diabetic animals also exhibited a striking hypersensitivity to arginine infusion (7 mmol/l). In rats administered STZ plus nicotinamide, intravenous glucose tolerance tests revealed clear abnormalities in glucose tolerance and insulin responsiveness, which were interestingly reversed by tolbutamide administration (40 mg/kg i.v.). In conclusion, this novel NIDDM syndrome with reduced pancreatic insulin stores, which is similar to human NIDDM in that it has a significant response to glucose (although abnormal in kinetics) and preserved sensitivity to tolbutamide, may provide a particularly advantageous tool for pharmacological investigations of new insulinotropic agents.     

The 75-g glucose tolerance test in pregnancy: a reference range determined on a low-risk population and related to selected pregnancy outcomes

OBJECTIVE: To determine a reference range for the 75-g glucose tolerance test (GTT) in pregnancy using a group of women at low risk for gestational diabetes mellitus (GDM) and to determine the validity of this reference range by examining selected pregnancy outcomes for glucose-tolerant women with a 2-h result on the GTT up to 1.0 mmol/l below the diagnostic level for GDM compared with treated women with GDM. RESEARCH DESIGN AND METHODS: The reference range for the GTT was determined in 573 Caucasian women with an age <25 years and a BMI of <25 kg/m2. Selected pregnancy outcomes were compared between 272 treated women with GDM (diagnosed on the basis of a 2-h glucose level > or =8.0 mmol/l) and 308 women with a 2-h glucose level of 7.0-7.9 mmol/l. RESULTS: There was 95% confidence that at least 95% of all the fasting glucose levels are < or =5.1 mmol/l(92 mg/dl) and 95% confidence that at least 95% of all the 2-h glucose levels were < or =7.8 mmol/l (140 mg/dl). Treated women with GDM had a significantly reduced rate of large-for-gestational-age infants compared with glucose-tolerant women, without any increase in the rate of small-for-gestational-age infants or obstetric interventions. CONCLUSIONS: The reference range for the GTT in pregnancy should be determined on a low-risk population rather than on a total population. Consideration should be given to lowering the fasting glucose level to 5.0 mmol/l (90 mg/dl) and the 2-h level to 7.8 mmol/ (140 mg/dl). Glucose-tolerant women below this relatively low reference range have an increased rate of large-for-gestational-age infants and may benefit from treatment.     

Changes of calcitonin reserve function in patients with primary osteoporosis]

Postpartal determination of lactate and glucose in the umbilical cord whole blood of 139 successive deliveries utilizing biosensors (blood gas analysator 865, Ciba Corning) are presented. The median lactate value in the umbilical arterial blood is 4.45 mmol/l and in the venous blood 4.23 mmol/l. Following categorization into control and high-risk groups, the arterial mean values are 4.23 mmol/l and 6.39 mmol/l and the respective venous values are 3.95 mmol/l and 5.04 mmol/l. Using the U-test these differences between the control and high-risk groups are significant. The mean of the measured lactate correlates significantly with the mean of the calculated base excess (< 0.001). The mean glucose value in the umbilical arterial blood is 78 mg/dl and in the venous 93 mg/dl. Between high-risk and control group no significant difference is found.     

Multicenter evaluation of the Micral-Test II test strip, an immunologic rapid test for the detection of microalbuminuria

OBJECTIVE: To assess the performance of the Micral-Test II immunologic test strip for the detection of microalbuminuria, a multicenter evaluation in eight European study sites was performed. RESEARCH DESIGN AND METHODS: Using both the Micral-Test II test strip and the routine method for the determination of albumin concentration, we investigated 2,228 urine samples from diabetic patients. Additionally, interperson variability, color stability, and possible interfering factors (temperature, pH, leucocyturia, erythrocyturia, and drugs) were tested. RESULTS: For a cutoff concentration of 20 mg/l with respect to the routine methods, a sensitivity of 96.7% and a specificity of 71% were calculated for the Micral-Test II test strip. The negative predictive value was 0.95, and the positive predictive value was 0.78, with a prevalence of positive samples (laboratory method) of 52%. The interperson variability of color interpretation showed 93% concordant readings. The interference study showed an influence of oxytetracycline, leading to higher readings. There was no interference from pH. A sample temperature of < 10 degrees C led to lower readings. In the case of samples with massive leucocyturia and erythrocyturia that may delete the chromatographic process, waiting an additional 1-2 min is needed before reading. CONCLUSIONS: The results of the multicenter evaluation show that the Micral-Test II test strip permits an immediate and reliable semiquantitative determination of low albumin concentrations in urine samples with an almost user-independent color interpretation.     

Measurement of vitamin D3 metabolites in smelter workers exposed to lead and cadmium

OBJECTIVES: To investigate the effects of lead and cadmium on the metabolic pathway of vitamin D3. METHODS: Blood and urinary cadmium and urinary total proteins were measured in 59 smelter workers occupationally exposed to lead and cadmium. In 19 of these workers, the plasma vitamin D3 metabolites, (25-hydroxycholecalciferol (25 OHD3), 24R, 25-dihydroxycholecalciferol (24R,25(OH)2D3) and 1 alpha,25-dihydroxycholecalciferol (1 alpha, 25(OH)2D3)) were measured together with blood lead. Vitamin D3 metabolites were measured by radioimmunoassay, (RIA), lead and cadmium by atomic absorption spectrophotometry, and total proteins with a test kit. RESULTS: Ranges for plasma 25(OH)D3, 24R,25(OH)2D3 and 1 alpha,25(OH)2D3 were 1.0-51.9 ng/ml, 0.6-5.8 ng/ml, and 0.1-75.7 pg/ml, respectively. Ranges for blood lead were 1-3.7 mumol/l, (21-76 micrograms/dl), blood cadmium 6-145 nmol/l, and urinary cadmium 3-161 nmol/l. Total proteins in random urine samples were 2.1-32.6 mg/dl. Concentrations of lead and cadmium in blood showed no correlation (correlation coefficient -0.265) but there was a highly significant correlation between blood and urinary cadmium. Concentrations for 24R,25(OH)2D3 were depressed below the normal range as blood and urinary cadmium increased, irrespective of lead concentrations. High cadmium concentrations were associated with decreased plasma 1 alpha,25(OH)2D3 when lead concentrations were < 1.9 mumol/l and with above normal plasma 1 alpha,25(OH)2D3 when lead concentrations were > 1.9 mumol/l, Kruskal-Wallis analysis of variance (K-W ANOVA) chi 2 = 10.3, p = 0.006. Plasma 25(OH)D3 was negatively correlated with both urinary total proteins and urinary cadmium, but showed no correlation with plasma 24R,25(OH)2D3, 1 alpha,25(OH)2D3, blood lead, or blood cadmium. CONCLUSION: Continuous long term exposure to cadmium may result in a state of equilibrium between blood and urinary cadmium. Cadmium concentrations in blood could be predicted from the cadmium concentration of the urine, (regression coefficient +0.35 SE 0.077). Exposure to cadmium alone decreased the concentrations of 1 alpha,25(OH)2D3 and 24R,25(OH)2D3, whereas exposure to both cadmium and lead increased the concentrations of 1 alpha,25(OH)2D3. It has been suggested that cadmium and lead interact with renal mitochondrial hydroxylases of the vitamin D3 endocrine complex. Perturbation of the vitamin D metabolic pathway by cadmium may result in health effect, such as osteoporosis or osteomalacia, risks which are possibly increased in the presence of lead.     

The effects of glucose-induced oxidative stress on growth and extracellular matrix gene expression of vascular smooth muscle cells

Vascular smooth muscle cell (VSMC) dysfunction plays a role in diabetic macrovasculopathy and this may include abnormalities in growth characteristics and the extracellular matrix. As the actual mechanisms by which glucose induces VSMC dysfunction remain unclear, the aim of this study was to assess the potential role of glucose-induced oxidative stress. Porcine aortic VSMCs were cultured for 10 days in either 5 mmol/l normal glucose or 25 mmol/l D-glucose (high glucose). There was evidence of oxidative stress as indicated by a 50% increase in intracellular malondialdehyde (p < 0.05), increased mRNA expression of CuZn superoxide dismutase and Mn superoxide dismutase (by 51% and 37% respectively, p < 0.01) and a 50% decrease in glutathione in 25 mmol/l D-glucose (p < 0.001). Growth was increased by 25.0% (p < 0.01). mRNA expression of extracellular matrix proteins (collagens I, III, IV and fibronectin) was not altered by high glucose in these experimental conditions. Repletion of glutathione with N-acetyl L-cysteine (1 mmol/l) in VSMC grown in high glucose was associated with reduction in malondialdehyde and restored growth to that of normal glucose. The water soluble analogue of vitamin E, Trolox (200 mumol/l), reduced malondialdehyde concentrations, but had no effect on glutathione depletion or the increased growth rate seen with high glucose. The addition of buthionine sulphoximine (10 mumol/l) to VSMC cultured in normal glucose reduced glutathione, increased malondialdehyde and increased growth to a similar extent as that found in high glucose alone. These results suggest that thiol status, rather than lipid peroxides, is a key factor in modulating VSMC growth and that mRNA expression of extracellular matrix proteins is not increased in VSMC under conditions of glucose-induced oxidative stress.     

Insulin and glucose response following oral glucose administration in well-conditioned ponies

Twenty-three well-conditioned ponies were evaluated for insulin and glucose response following oral glucose administration (1 g/kg bodyweight [bwt] as a 20 per cent solution). Ponies were defined as normal if total insulin secretion (TIS) was less than 149 mu iu/ml h and the glucose concentration was below 11.1 +/- 0.11 mmol/litre (200 +/- 2 mg/dl) at all times following oral glucose administration. When glucose concentrations were maintained below 11.1 +/- 0.11 mmol/litre, the area under the glucose curve (TG) was less than 17.4 mmol/litre/h (314 mg/dl/h). The ponies were assigned to four groups based on insulin and glucose response: Group 1 (n = 7), normal; Group 2 (n = 5), high insulin, normal glucose; Group 3 (n = 8), high insulin, high glucose and Group 4 (n = 3), high glucose, normal insulin. This classification is an initial attempt to define normal insulin and glucose response in ponies. Additional data need to be accumulated to define further insulin resistance and diabetes in ponies.     

Glucose-stimulated elevation of cytoplasmic calcium is defective in the diabetic Chinese hamster islet B cell

To characterize insulin release and cytoplasmic free Ca2+ ([Ca2+]i) levels in the diabetic Chinese hamster islet B cell, islets from genetically normal (subline M) and diabetic (subline L) hamsters were collagenase isolated. Insulin release and glucose utilization (conversion of D-[5-(3H)]glucose to 3H2O) were measured in whole islets; [Ca2+]i levels were measured in single islet cells using fura-2. The Ca2+ channel agonist, 12 mmol/l perchlorate, ClO4-, increased the subnormal insulin response during 20 mmol/l glucose perifusion, but did not normalize it. Glucose utilization measured over a 2-h period was normal. Glucose induced an initial decrease and then a rise in [Ca2+]i in 85% of the normal (presumably B) cells. In diabetic cells, the [Ca2+]i response was delayed, subnormal and only observed in 23% of the cells. When perchlorate or another Ca2+ channel agonist, 10 mumol/l CGP 28392, was added with glucose, a larger proportion of the diabetic cells (61-67%) showed increased [Ca2+]i and the mean [Ca2+]i response was not different from normal. However, neither perchlorate nor CGP 28392 could normalize glucose-stimulated insulin release, and K(+)-induced insulin release was decreased in diabetic islets. The K(+)-induced [Ca2+]i rise was essentially normal in all the diabetic islet cells. Therefore, the diabetic hamster islet appears to metabolize glucose normally, but has a diminished insulin response to glucose and K+. The Ca2+ channel agonists markedly improve the subnormal [Ca2+]i response but not the insulin response. Glucose-induced elevation of [Ca2+]i and exocytosis appear defective in the diabetic Chinese hamster B cell.     

Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12

One form of maturity-onset diabetes of the young (MODY) results from mutations in a gene, designated MODY3, located on chromosome 12 in band q24. The present study was undertaken to define the interactions between glucose and insulin secretion rate (ISR) in subjects with mutations in MODY3. Of the 13 MODY3 subjects, six subjects with normal fasting glucose and glycosylated hemoglobin and seven overtly diabetic subjects were studied as were six nondiabetic control subjects. Each subject received graded intravenous glucose infusions on two occasions separated by a 42-h continuous intravenous glucose infusion designed to prime the beta-cell to secrete more insulin in response to glucose. ISRs were derived by deconvolution of peripheral C-peptide levels. Basal glucose levels were higher and insulin levels were lower in MODY3 subjects with diabetes compared with nondiabetic subjects or with normal healthy control subjects. In response to the graded glucose infusion, ISRs were significantly lower in the diabetic subjects over a broad range of glucose concentrations. ISRs in the nondiabetic MODY3 subjects were not significantly different from those of the control subjects at plasma glucose levels <8 mmol/l. As glucose rose above this level, however, the increase in insulin secretion in these subjects was significantly reduced. Administration of glucose by intravenous infusion for 42 h resulted in a significant increase in the amount of insulin secreted over the 5-9 mmol/l glucose concentration range in the control subjects and nondiabetic MODY3 subjects (by 38 and 35%, respectively), but no significant change was observed in the diabetic MODY3 subjects. In conclusion, in nondiabetic MODY3 subjects insulin secretion demonstrates a diminished ability to respond when blood glucose exceeds 8 mmol/l. The priming effect of glucose on insulin secretion is preserved. Thus, beta-cell dysfunction is present before the onset of overt hyperglycemia in this form of MODY. The defect in insulin secretion in the nondiabetic MODY3 subjects differs from that reported previously in nondiabetic MODY1 or mildly diabetic MODY2 subjects.     

Blood pressure levels in diabetes mellitus

Levels of fasting plasma glucose, body mass index, serum total lipids, serum total cholesterol, serum triglycerides and blood pressure of 177 Libyan diabetic patients were determined. The respective mean values were 212.4 +/- 5.6 mg/dl, 26.6 +/- 0.45 kg/m2, 825.7 +/- 20.5 mg/dl, 176.4 mg/dl, 144 +/- 5.8 mg/dl and 135.3 +/- 1.7/83 +/- 0.89 mm Hg. The mean levels of all variables except plasma glucose are significantly higher in the female patients than their male counterparts. Correlations were present between blood pressure levels and age/body mass index/serum total lipids. There was a significant correlation between systolic pressure levels and the duration of diabetes. Serum cholesterol and serum triglyceride levels correlated with diastolic blood pressure levels only.     

Effect of hydrochlorothiazide in pseudohypoaldosteronism with hypercalciuria and severe hyperkalemia

Severe hyperkalemia resistant to treatment with sodium chloride (NaCl) supplements plus cation exchange resins can be found in pseudohypoaldosteronism type I. In a patient with the multiple target organ variant of this condition, hyperkalemia persisted at dangerous levels (8.5 mmol/l) despite large doses of NaCl (50 mmol/kg per day) and cation exchange resins (6 g/kg per day). Hypercalciuria was also present. The total volume of fluids and supplements required was not tolerated orally. Indomethacin (2 mg/kg per day) and later hydrochlorothiazide (2 mg/kg per day) were tried to further correct imbalance. Plasma potassium (K) and Na levels, the urinary Na/K ratio, transtubular potassium gradient (TTKG), and urinary calcium/creatinine (Ca/Cr) ratio were used to evaluate the effect of hydrochlorothiazide. Under treatment, plasma Na was stable (137-144 mmol/l), K levels decreased from 8.5 to 5 mmol/l, urinary Na/K from 90 to 24, and TTKG increased from 0.3 to 1.8. Ca/Cr decreased from 3.5 to 1.5 mmol/mmol. The dosage of cation exchange resins was decreased, oral fluids were tolerated, and the patient's general condition improved. Hence: hydroclorothiazide can be useful in the treatment of severe hyperkalemia and hypercalciuria of pseudohypoaldosteronism type I.     

Human plasma CETP deficiency: identification of a novel mutation in exon 9 of the CETP gene in a Caucasian subject from North America

Human plasma cholesteryl ester transfer protein (CETP) is a 476-residue hydrophobic glycoprotein that catalyzes the heterotransfer of cholesteryl esters and triacylglycerols among lipoproteins: Mutations in the CETP gene have been identified, mostly in the Japanese population. These mutations result in hypercholesterolemia due to the presence of large cholesteryl ester-rich HDL particles, elevated plasma apoA-I and apoE, and reduced apoB levels. Here we report the plasma lipoprotein phenotype and molecular defect in a 57-year-old female Nova Scotian subject lacking Japanese ancestry who is homozygous for a novel mutation in the CETP gene. Her total plasma cholesterol was 7.3 mmol/l with an LDL cholesterol of 2.9 mmol/l and HDL cholesterol of 4.4 mmol/l. She was mildly hypertriglyceridemic (1.6 mmol/l) and had markedly elevated apoA-I (256 mg/dl) and apoE (14.4 mg/dl) with only slightly reduced apo/B levels (94 mg/dl). Her VLDL and LDL were cholesteryl ester-poor (1.8 and 37.2% of lipids, respectively) and triacylglycerol-rich (67.3 and 18.9% of lipids, respectively) while her HDL was cholesteryl ester-rich (40.2-45.7% of lipids) and triacylglycerol-poor (3.3-2.5% of lipids). No plasma CETP activity or mass was detected. Bi-directional DNA sequence analysis of PCR products from all 16 exons showed a single base substitution (C-->T at nucleotide 836 in exon 9 resulting in 268 Arg-->STOP) in both alleles. No other mutation was detected. A single base mismatched, 26 bp reverse PCR primer that produced a single Mae III RFLP site upon amplification of the mutated DNA sequence was designed for rapid population screening. This subject is, we believe, the first Caucasian North American patient reported to have CETP deficiency.     

Combined use of a fasting plasma glucose concentration and HbA1c or fructosamine predicts the likelihood of having diabetes in high-risk subjects

OBJECTIVE: To assess the validity of using fasting plasma glucose (FPG) concentrations in conjunction with HbA1c or fructosamine for the screening of diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS: In this study 2,877 Hong Kong Chinese (565 [19.6%] men; 2,312 [80.4%] women) with various risk factors for glucose intolerance underwent a 75-g oral glucose tolerance test (OGTT) for screening of diabetes. The risk factors included a family history positive for diabetes, a history of gestational diabetes or impaired glucose tolerance, and obesity. RESULTS: Using World Health Organization (WHO) criteria, 1,593 (55.4%) had normal glucose tolerance, 657 (22.8%) had impaired glucose tolerance, and 627 (21.8%) had diabetes. When the 1997 American Diabetes Association (ADA) criteria were applied, 394 (13.7%) had diabetes with an FPG > or = 7.0 mmol/l. Using multiple receiver operating characteristic curve analysis, the paired values of an FPG of 5.6 mmol/l and a HbA1c of 5.5% gave an optimal sensitivity of 83.8% and specificity of 83.6% to predict a 2-h plasma glucose (PG) > or = 11.1 mmol/l. Likewise, the paired values of an FPG of 5.4 mmol/l and a fructosamine level of 235 mumol/l (n = 2,408) gave an optimal sensitivity of 81.5% and specificity of 83.2%. An FPG > or = 5.6 mmol/l and an HbA1c > or = 5.5% was 5.4-fold more likely to occur in diabetic subjects (based on the WHO criteria) compared with nondiabetic subjects. For paired parameters less than these values, the likelihood ratio of this occurring in diabetic subjects was only 0.11. Similarly, an FPG > or = 5.4 mmol/l and a fructosamine > or = 235 mumol/l was fivefold more likely to occur in diabetic subjects than in nondiabetic subjects, with both parameters less than these values having a likelihood ratio of 0.04. Using these paired values as initial screening tests, only subjects who had an FPG > or = 5.6 mmol/l and < 7.8 mmol/l and an HbA1c > or = 5.5% (n = 642) required an OGTT to confirm diabetes, thereby saving 77.7% [(2,877-642)/2,877] of the OGTTs performed. Similarly, only subjects who had an FPG > or = 5.4 mmol/l and < 7.8 mmol/l and a fructosamine > or = 235 mumol/l (n = 526) required OGTT to confirm diabetes, meaning that 78.2% [(2,408-526)/2,408] of the OGTTs could have been saved. Based on the 1997 ADA criterion of an FPG cutoff value of 7.0 mmol/l, the corresponding numbers of OGTTs to be saved were 82.6% and 85.5%, respectively. CONCLUSIONS: The paired values of FPG and HbA1c or FPG and fructosamine helped to identify potentially diabetic subjects, the diagnosis of which could be further confirmed by the 75-g OGTT. Using this approach approximately 80% of OGTTs could have been saved, depending on the diagnostic cutoff value of FPG.     

Intermittent chyluria in a young man

Chyluria is the passage of chylus into urine resulting in fistulization through the lymphatic system and the urinary system. This rare condition is usually caused by filaria infestation or malformations, neoplasia or trauma. We report a case of a 18-year-old man. The patient presented milky urine which had appeared after angiography following minor leg trauma. Physical examination revealed asymmetry of the face and cutaneous dyschromia. Blood tests revealed hypogammaglobulinemia and altered CD4/CD8 ratio (0.6). Urine tests showed proteinuria (30 mg/dl), lipiduria (triglycerides 750 mg/dl) and density of 1025. Renal function was normal. Abdomen computed tomography and urography were normal. Cystoscopy revealed the presence of milky urine in the bladder and selective catheterization revealed that the origin was the right ureter alone. Ascendent pyelography did not reveal any malformation of the urinary tract; but after this the chyluria spontaneously disappeared. The patient was rehospitalized 3 months later for recurrence. Lymphography was then performed and revealed a dilated lymphatic network with minute lacunar images projecting into the right kidney. Chyluria again disappeared spontaneously and recurred sporadically over the next two years in a patient who remained in good physical condition. The etiology of chyluria in a patient without filaria infestation is problematic, particularly when the most common causes (tuberculosis, neoplasia, trauma) are excluded as in our case. The asymmetry of the face, together with cutaneous dyschromia and the presence of a subarachnoidea cyst in the right temporal region suggested our patient had multiple congenital malformations.     

Glucose tolerance in patients with cystic fibrosis

In order to define prevalence and incidence of diabetes mellitus in cystic fibrosis, we followed 191 unselected patients above two years of age (median 13.6) in a five-year prospective study with annual oral glucose tolerance tests. The prevalence of diabetes increased from 11 to 24% during the study period with an annual age-dependent incidence rate of 4-9%. Diabetes was diagnosed at a median age of 21 years (range 3-40). At diagnosis of diabetes, hyperglycaemia, fasting hyperglycaemia (> or = 7.8 mmol/l), and increased haemoglobin Alc levels (> 6.4) were present in 33%, 16% and 16% of the diabetic patients, respectively. Impaired glucose tolerance implied a higher risk than normal glucose tolerance for the development of diabetes (odds ratio 5.6). In 58% of cases with impaired glucose tolerance, however, glucose tolerance was normalised at the next annual test. Normal glucose tolerance was found in only 37% of the patients at all five tests. Within this group of patients, median fasting and two-hour post-load plasma glucose concentrations and haemoglobin Alc levels increased by 6-8% during five years. Thus, the prevalence and incidence of diabetes in patients with cystic fibrosis is very high and increases with age. Since symptoms of hyperglycaemia and increased fasting plasma glucose and haemoglobin Alc levels are inconstant findings in newly diagnosed diabetic cystic fibrosis patients, we recommend annual oral glucose tolerance tests in all cystic fibrosis patients above the age of 10 years.     

A simple procedure for easy and safe deflasking

OBJECTIVE: African-Americans have an increased prevalence of both diabetes and diabetes complications, creating an imperative for improved metabolic control. Because American Diabetes Association guidelines recommend that action be taken when HbA1c is > 8.0%, but access to rapid-turnaround HbA1c assays remains limited, we tested the utility of fasting and random plasma glucose cutoffs as indicators of HbA1c > 8.0%. RESEARCH DESIGN AND METHODS: Using receiver operating characteristics (ROC) analysis, we evaluated the sensitivity, specificity, and predictive value of fasting and random plasma glucose measurements in identifying an HbA1c > 8.0% (fasting n = 974, random n = 552). The population studied was predominantly African-American, middle-aged, and non-insulin-dependent. RESULTS: Fasting plasma glucose was a significant indicator of HbA1c > 8.0%, both in the whole group and in subgroups for diet, sulfonylureas, and insulin; the corresponding areas under the ROC curve were 0.87, 0.90, 0.87, and 0.84, respectively (all P < 0.0001). A fasting plasma glucose cutoff of > 9.2 mmol/l (165 mg/dl) provided a sensitivity of 80% and a specificity of 83% for the whole group and a 77% positive predictive value. Random plasma glucose was also a good indicator of HbA1c > 8.0%, both in the whole group and in subgroups for diet, sulfonylureas, and insulin; the corresponding areas under the ROC curve were 0.85, 0.91, 0.85, and 0.77, respectively (all P < 0.0001). A cutoff > 9.8 mmol/l (177 mg/dl) provided a sensitivity of 78% and a specificity of 77% for the whole group and a 78% positive predictive value. Overall, a plasma glucose > 11.1 mmol/l (200 mg/dl) identified an HbA1c > 8.0% with a predictive value of approximately 90% if done while fasting and a predictive value of approximately 80-85% if random. The utility of both fasting and random plasma glucose cutoffs was subsequently confirmed in a prospective study of another 2,309 and 1,396 patients, respectively. CONCLUSIONS: Although glucose levels cannot replace HbA1c determinations, measurement of fasting or random plasma glucose may be used during a clinic visit to identify poorly controlled type 2 patients with reasonable certainty and allow timely patient education and therapeutic intervention.     

A case of adrenal mixed tumor of pheochromocytoma and adrenocortical adenoma presenting diabetes mellitus and hypertension

A 61-year-old woman with hyper-catecholaminemia and hyper-glucocorticoidemia due to a mixed tumor of the right adrenal gland is described. The patient, who had been medicated for hypertension since 1977, complained of thirst and general malaise in 1986. Body weight loss was remarkable. There was neither absolute truncal obesity nor moon face. In September 1986, her blood pressure was 180/110 mmHg and blood glucose level was 400mg/dl. Noradrenaline levels in plasma and in urine were remarkably elevated (1659 pg/ml and 120 micrograms/day, respectively), and adrenaline levels were also high (397 pg/ml in plasma, 34 micrograms/day in urine). Plasma cortisol and urinary 17-OHCS were elevated (39.2 micrograms/dl and 11.9 mg/day, respectively). Plasma ACTH was in the normal range (42.6 pg/ml). Oral administration of neither 1mg nor 8 mg of dexamethasone suppressed plasma cortisol or ACTH levels. Both 131I-metaiodobenzylguanidine and 131I-adosterol accumulated in the right adrenal gland. In 1987 the adrenal tumor (3.0 x 3.5 cm, 30 g) was resected. After the operation, her blood pressure and blood glucose level returned to normal, so that the medication became unnecessary. Histologically it was revealed that the tumor was a mixed adenoma consisting of adreno-medullary and cortical cells (corticomedullary adenoma). The literature on 21 cases of pheochromocytoma associated with Cushing's syndrome was briefly reviewed. Mathison (1969) reported the first case of a mixed tumor of adreno-medullary and cortical cells. So far as we know the present case is the second.     

Effect of oral calcium loading on intact PTH and calcitriol in idiopathic renal calcium stone formers and healthy controls

The calciuric response after an oral calcium load (1000 mg elemental calcium together with a standard breakfast) was studied in 13 healthy male controls and 21 recurrent idiopathic renal calcium stone formers, 12 with hypercalciuria (UCa x V > 7.50 mmol/24 h) and nine with normocalciuria. In controls, serum 1,25(OH)2 vitamin D3 (calcitriol) remained unchanged 6 h after oral calcium load (50.6 +/- 5.1 versus 50.9 +/- 5.0 pg/ml), whereas it tended to increase in hypercalciuric (from 53.6 +/- 3.2 to 60.6 +/- 5.4 pg/ml, P = 0.182) and fell in normocalciuric stone formers (from 45.9 +/- 2.6 to 38.1 +/- 3.3 pg/ml, P = 0.011). The total amount of urinary calcium excreted after OCL was 2.50 +/- 0.20 mmol in controls, 2.27 +/- 0.27 mmol in normocalciuric and 3.62 +/- 0.32 mmol in hypercalciuric stone formers (P = 0.005 versus controls and normocalciuric stone formers respectively); it positively correlated with serum calcitriol 6 h after calcium load (r = 0.392, P = 0.024). Maximum increase in urinary calcium excretion rate, delta Ca-Emax, was inversely related to intact PTH levels in the first 4 h after calcium load, i.e. more pronounced PTH suppression predicted a steeper increase in urinary calcium excretion rate. Twenty-four-hour urine calcium excretion rate was inversely related to the ratio of delta calcitriol/deltaPTHmax after calcium load (r = -0.653, P = 0.0001), indicating that an abnormally up-regulated synthesis of calcitriol and consecutive relative PTH suppression induce hypercalciuria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal and metabolic effects of 1-year treatment with ramipril or atenolol in NIDDM patients with microalbuminuria

The clinical importance of selection of different antihypertensive drugs for the treatment of diabetic patients is still unclear. Thus we performed a randomised, controlled study in 105 hypertensive non-insulin-dependent diabetic (NIDDM) patients with microalbuminuria over 1 year. Patients received either the angiotensin converting enzyme (ACE) inhibitor ramipril (2.5-5.0 mg/day; in addition 24% of patients also received felodipine) or the beta blocking agent atenolol (50-100 mg/day; in addition 24% of patients also received hydrochlorothiazide). Blood pressure, metabolic control, lipid levels and albumin excretion rate were studied during the follow-up. After 1 year an almost identical fall (p < 0.001) in blood pressure was observed with ramipril (170/100 vs 150/ 85 mmHg, median) and atenolol (180/100 vs 150/ 80 mmHg, median). With ramipril a reduction of total cholesterol (6.3 vs 5.9 mmol/l), of LDL cholesterol (3.8 vs 3.6 mmol/l) and HDL cholesterol (1.3 vs 1.2 mmol/l) was found, whereas triglycerides slightly increased (1.8 vs 2.0 mmol/l). With atenolol a similar reduction of total cholesterol (6.3 vs 5.9 mmol/l), LDL cholesterol (3.8 vs 3.7 mmol/l) and HDL cholesterol (1.4 vs 1.2 mmol/l) and an increase of triglycerides (1.4 vs 1.7 mmol/l) was noted. Metabolic control of the patients was maintained with both ramipril and atenolol treatment. With ramipril treatment urinary albumin creatinine ratio (14.4 vs 13.8 mg/mmol) and creatinine clearance (82 vs 84 ml/min) were constant, but with atenolol an increase of albumin creatinine ratio (13.9 vs 19 mg/mmol, p < 0.001) and a slight decrease of creatinine clearance (80 vs 66 ml/min, p < 0.05, not significant after Bonferroni correction) was observed. In conclusion: 1-year treatment of NIDDM patients with ramipril or atenolol does not influence metabolic control, the changes in serum lipids were similar. Despite almost identical blood pressure reduction in both groups the albumin creatinine ratio was constant under ramipril, but increased under atenolol treatment.     

Use of the 1997 American Diabetes Association diagnostic criteria for diabetes in a Hong Kong Chinese population

OBJECTIVE: Recently, the American Diabetes Association (ADA) has proposed revised diagnostic criteria for diabetes. Lowering of the fasting plasma glucose (FPG) cutoff value is intended to reduce the discrepancy with the 2-h plasma glucose (PG) cutoff value and to encourage the use of FPG. We have applied these new criteria to data collected from a population-based prevalence survey in Hong Kong Chinese subjects of working age. RESEARCH DESIGN AND METHODS: The results of 1,513 oral glucose tolerance tests (OGTTs) from a previously published prevalence survey of glucose intolerance and cardiovascular risk factors in a Hong Kong Chinese working population were reexamined using the new criteria. Of the 1,513 subjects, 27 had a known history of diabetes. Of the remaining 1,486 subjects, 228 were also selected randomly for a second OGTT without prior knowledge of the result of the first test. RESULTS: After exclusion of the 27 subjects with a known history of diabetes, the crude prevalence of diabetes was 2.83% (n = 42) when the World Health Organization's (WHO) criteria were applied. When the criterion of FPG > or = 7.0 mmol/l was used, as recommended by the ADA, the prevalence of diabetes was 1.41% (n = 21). Twenty-nine subjects (1.95%) with FPG < 7.0 mmol/l had a 2-h PG > or = 11.1 mmol/l. Eight subjects (0.53%), previously without a diagnosis of diabetes according to the WHO criteria (FPG < 7.8 mmol/l and 2-h PG < 11.1 mmol/l), had FPG between 7.0 and 7.8 mmol/l and were classified as having diabetes by the ADA criteria. This classification gave a net change of -1.42% in the prevalence of diabetes between the use of FPG > or = 7.0 mmol/l alone and the use of WHO criteria. Among the 1,486 subjects with no known history of diabetes, those classified as having diabetes according to the ADA FPG criterion alone had higher HbA1c and fructosamine levels than diabetic subjects defined by the WHO criteria. Of the 228 subjects for whom two FPG measurements were available, those who had consistent definitions (diabetes, impaired fasting glucose, normal fasting glucose) on both occasions were considered to have reproducible tests, giving an overall reproducibility of 90.8% (207 of 228). CONCLUSIONS: Compared with the WHO criteria, the use of FPG to diagnose diabetes, as recommended by the ADA, was a more reproducible test and identified those subjects who had a greater degree of hyperglycemia. Although lowering of the cutoff value from 7.8 to 7.0 mmol/l increased the number of diagnoses among subjects with low FPG, the omission of the 2-h PG would lead to fewer subjects having their diabetes diagnosed.