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Biomedical subjects

M A Charles

Publications and source records attributed to M A Charles.

At least 19 recordsLinked to original sources
PubMed1996

Relationship between prorenin, IGF-I, IGF-binding proteins and retinopathy in diabetic patients.

Plasma prorenin and renin, serum insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP-2 and IGFBP-3) concentrations were measured in 22 randomly selected male and female patients with insulin-dependent diabetes mellitus (IDDM) or non-IDDM (NIDDM). Plasma prorenin concentration was significantly elevated in patients with proliferative retinopathy (1869.5 +/- 785.0 mUL-1, mean +/- SEM) compared to patients with nonproliferative retinopathy (325.5 +/- 73.2 mUL-1, P < 0.003) and those without retinopathy (318.6 +/- 47.3 mUL-1, P < 0.007). Similarly, serum insulin-like growth factor-I (IGF-I) concentration in patients with proliferative retinopathy (126.3 +/- 21.5 micrograms L-1) was significantly higher than in patients with nonproliferative retinopathy (126.3 +/- 14.85 micrograms L-1, P < 0.004) and without retinopathy (135.2 +/- 37.26, P < 0.05). There was moderately strong positive correlation between plasma prorenin and serum IGF-I concentrations (r = 0.56, P < 0.01). Plasma prorenin concentration was uninfluenced by change in renal function (creatinine clearance, serum creatinine or BUN), but IGF-I levels were inversely related to creatinine clearance (r = 0.67, P < 0.002). There was no demonstrable relationship between IGF-binding proteins and prorenin or renin concentrations. In view of some overlap between plasma prorenin and serum IGF-I concentrations in diabetic patients with proliferative and nonproliferative retinopathy, measurement of both markers may be more useful in predicting the development of proliferative retinopathy in patients with diabetes mellitus than either measurement alone.

Adult↗
PubMed1996

Use of an integrated sideport for diagnosis and management of decreased flow rates in a programmable implanted insulin delivery system. Implantable Insulin Pump Trial Study Group.

The aim of this study was to develop procedures for the diagnosis and nonsurgical management of decreased insulin flow in an implantable programmable pump for long-term intraperitoneal or intravenous insulin delivery featuring a sideport. Patency of the catheter lumen was tested by measuring the time needed for sideport pressure to decrease by 50% after the injection of 0.1 ml of buffer solution. Pumping unit performances were assessed by measuring the volume of pump pulses after diverting the pump flow at the sideport. A catheter flush with buffer solution through the sideport was effective in clearing 79% of intraperitoneal and 84% of intravenous catheter occlusions. Washing the pumping unit with an alkaline solution after diverting pump flow at the sideport was effective in dissolving insulin aggregates inside the pumping unit and in restoring normal pump flow. These procedures were associated with a 1.3% rate of hypoglycemic episodes.

Buffers↗
PubMed1996

The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group.

OBJECTIVE: The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS: Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS: Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS: The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.

Adipose Tissue↗
PubMed1995

Early and late insulin response as predictors of NIDDM in Pima Indians with impaired glucose tolerance.

Risk factors predicting deterioration to diabetes mellitus were examined in 181 subjects with impaired glucose tolerance. Fifty-seven subjects had impaired glucose tolerance on one occasion followed by normal glucose tolerance at a repeat oral glucose tolerance test, and 124 subjects had impaired glucose tolerance on two successive oral glucose tolerance tests. Subjects were followed for a median period of 5.0 years (range 1.0-17.2). The age- and sex-adjusted cumulative incidence of diabetes at 10 years of follow-up was higher in subjects who had impaired glucose tolerance on both tests (70%) than in those whose glucose tolerance was normal at the repeat test (53%), [rate ratio (RR) = 1.6, 95% confidence intervals (CI) = 1.0-2.5]. Proportional hazards analyses were used to identify baseline risk factors (measured at the repeat oral glucose tolerance test) for subsequent diabetes, and incidence rate ratios were calculated for the 90th percentile compared with the 10th percentile of each continuous variable for the whole group. In all subjects, in separate models, higher body mass index [RR = 2.0, 95% CI = 2.2-9.9], high fasting serum insulin concentrations [RR = 2.4, 95% CI = 1.4-4.2], and low early insulin response [RR = 0.5, 95% CI = 0.3-0.8] 30 min after a glucose load were significant predictors for deterioration to diabetes. In a multivariate analysis which controlled for age and sex, 120-min post-load glucose, fasting insulin and late insulin response predicted diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

The effects of nicotinamide and glimepiride on diabetes prevention in BB rats.

Glimepiride is an oral sulfonylurea drug; nicotinamide is an inhibitor of poly (ADP-ribose) synthetase and a precursor of NAD. Three studies were carried out to determine whether glimepiride and/or nicotinamide could prevent diabetes in BB rats. In Study I, we administered glimepiride treatment 200 mg/kg/day orally from the 35th to 143rd day of age. The incidence of diabetes in the glimepiride group was lower than in the control group (32% vs 55%, p < 0.02). In Study II, the treatment period was from the 35th to 147th day of age, and rats received glimepiride combined with nicotinamide (500 mg/kg/day IP). The treatment group showed a 22% incidence of diabetes compared to 53 in controls (p < 0.03). In Study III, nicotinamide treatment alone (1000 mg/kg/day orally) and combined with glimepiride were compared to untreated controls. The treatment period was from the 35th to 167th day of age. Nicotinamide-treated rats showed a 42% incidence of diabetes compared to 60% in controls (p = NS). In the nicotinamide combined with glimepiride treatment group, a lower incidence (28%) was observed when compared to the controls (60%, p < 0.05). These findings suggest that glimepiride can prevent diabetes in BB rats; however, nicotinamide when used in young animals shows only a trend to lower the incidence of diabetes, and when combined with glimepiride, no significant effect is observed.

Administration, Oral↗
PubMed1995

Glimepiride-induced prevention of diabetes and autoimmune events in the BB rat: revised.

The purpose of this study was to determine whether Glimepiride, an oral sulfonylurea drug, prevents the onset of diabetes in diabetic prone BB rats. S750181, a sulfonylurea drug that has minimal in vivo glucose metabolic effects, was also tested. In addition, the shortest period of sulfonylurea treatment required for prevention was determined. Eighty rats were studied for all treatment periods with 40 receiving a daily oral gavage dosage of glimepiride and 40 receiving a daily oral gavage dosage of vehicle solution. Diabetes onset was monitored by glycosuria and blood glucose levels. In study I, with a treatment period of 35-142 days of age, Glimepiride-treated rats showed a 32% incidence of diabetes, whereas control rats had a diabetes incidence of 55% (p < 0.04). In study II, with a treatment period of 60-140 days of age, Glimepiride-treated rats showed a 29% incidence of diabetes compared to 54% in controls (p < 0.03). Further, comparing the time of diabetes onset between the Glimepiride and control groups showed that Glimepiride delays diabetes onset (p < 0.02). In study III, with a treatment period of 60-100 days of age, Glimepiride-treated rats showed a 17% overall diabetes incidence at 170 days, whereas the controls were 43% (p < 0.01). In study IV, with a treatment period of 60-140 days of age, S750181-treated rats showed a 38% diabetes incidence and the control group showed a 43% diabetes incidence. There was no significant delaying or prevention effect observed in the S750181 group. To determine if Glimepiride affected autoimmune events, the severity of islet inflammation was examined. In study I, islet histology from total and nondiabetic animals indicated that Glimepiride-treated rats had a lower severity of islet inflammation than that of the control rats (p = 0.023). These studies show that a) Glimepiride has diabetes preventive effects, b) shorter treatment periods of only 40 days can be effective and c) Glimepiride decreases the severity of islet inflammation.

Animals↗
PubMed1995

Diagnostic procedures for catheter malfunction in programmable implantable intraperitoneal insulin infusion devices.

OBJECTIVE: To evaluate the roles of 1) abdominal radiography, 2) a pressure diagnostic procedure (PDP) using a standardized diluent infusion into the catheter sideport, and 3) radiocontrast imaging of the catheter lumen as procedures for diagnosing catheter malfunction in diabetic patients implanted with a programmable intraperitoneal infusion device. RESEARCH DESIGN AND METHODS: Sixteen type I diabetic patients implanted with Infusaid programmable intraperitoneal insulin pumps were studied. The ability of the above three procedures to assist diagnosis of catheter malfunction and distinguish between occlusion and catheter breakage was retrospectively analyzed. Glycated hemoglobin was measured to determine the clinical importance of catheter malfunctions and decreases in pump flow due to insulin aggregation in the pump chamber. RESULTS: Mean glycated hemoglobin levels increased significantly from 8.0 +/- 0.3 to 9.0 +/- 0.4% (P < 0.05) before and after catheter malfunction, but not during pump flow slowdowns. Mean peak pressure during PDP was 1.96 +/- 0.14 psi (P < 0.01 vs. normal) in reversibly occluded catheters and 1.86 +/- 0.35 psi (P < 0.05 vs. normal) in broken catheters, compared with 1.32 +/- 0.23 psi in normal catheters. Decay times during PDP were > 50 s for both reversibly occluded and broken catheters (P < 0.001 vs. normal of 3.6 +/- 0.82 s). Abdominal radiographs and sideport injections of contrast material were used to distinguish the types of broken catheters. CONCLUSIONS: Catheter breakage and occlusion are complications in implantable insulin infusion systems and result in metabolic deterioration. The presence of a sideport allows pressure data and radiographic procedures to assist in determining the cause of catheter malfunction. A diagnostic algorithm was generated to improve efficiency in investigating catheter problems.

Adult↗
PubMed1995

Comparison of body size measurements as predictors of NIDDM in Pima Indians.

OBJECTIVE--To determine and compare the abilities of various anthropometric measurements to predict the development of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indian men and women. RESEARCH DESIGN AND METHODS--A total of 290 male and 443 female Pima Indians were followed for up to 6 years for the development of NIDDM. A proportional hazards analysis was used to assess the ability of anthropometric measurements evaluated at baseline to predict NIDDM. Receiver operating characteristic (ROC) curves were used to compare individual variables in predicting NIDDM. RESULTS--In separate models controlled for age and sex, body mass index (BMI), waist circumference, thigh circumference, waist-to-thigh ratio (WTR), weight, and percentage body fat (PBF) estimated by bioelectric resistance each predicted NIDDM, which developed in 30 men and 52 women. The highest incidence rate ratios (IRRs; for 1 SD of a variable) were for WTR in men and for PBF in women, although the confidence interval (CI) for PBF was wide. In stepwise analyses, WTR was the most significant predictor in men (IRR for 1 SD = 1.58, 95% CI = 1.20-2.07), and BMI was the most significant predictor in women (IRR for 1 SD = 1.65, 95% CI = 1.29-2.11). However, by ROC analyses, thigh circumference was the only variable significantly worse than WTR in men or BMI in women at predicting NIDDM. CONCLUSIONS-- Measurements such as waist circumference, WTR, weight, and BMI may be useful as more complicated measurements, such as PBF by bioelectrical resistance, for identifying groups of individuals whose body habitus places them at high risk of developing NIDDM.

Adolescent↗
PubMed1995

Evaluation of a low-air-loss mattress system in the treatment of patients with pressure ulcers.

Many individuals who are on prolonged bed rest suffer from pressure-induced ulcers. Pressure ulcers result from soft tissue being compressed between the skeleton or other supporting body structures and the relatively immovable surfaces commonly found with conventional mattresses in homes, hospitals, and prolonged care nursing facilities. In this study, we have evaluated the utility of a low-air-loss mattress system* in the treatment of patients with pressure ulcers by measuring stabilized ulcers before and after use of this system to determine if such ulcers worsened, improved or healed. Our observations indicate that use of this low-air-loss mattress system reduces the size and facilitates the healing of previously stable, chronic pressure ulcers.

Aged↗
PubMed1994

Familial and metabolic factors related to blood pressure in Pima Indian children.

High blood pressure, abnormal glucose tolerance, and obesity are frequently associated with each other, but the mechanism of these associations is poorly understood. Studying them in children may help in understanding the pathogenesis of hypertension. Blood pressure, height, weight, and plasma glucose and serum insulin concentrations during a 75-g oral glucose tolerance test were measured in 1,698 Pima Indian children aged 6-17 years who participated in an ongoing epidemiologic study. Weight relative to height was used as an index of obesity. The parents of many of the children were also examined. Fasting and 2-hour glucose and insulin concentrations, adjusted for age, sex, and relative weight, were positively related to systolic blood pressure but not to diastolic blood pressure. Relative weight, 2-hour glucose, and fasting insulin concentrations were independently and significantly associated with systolic blood pressure in a stepwise regression analysis that included age and sex. After parental hypertension was taken into account, maternal but not paternal non-insulin-dependent diabetes mellitus, controlled for the child's relative weight and glucose and insulin concentrations, was significantly associated with higher blood pressure in children. The stronger association with maternal diabetes suggests a greater sharing of environmental factors between mother and child than between father and child, but familial similarities in obesity and glucose and insulin concentrations, the diabetic intrauterine milieu, and shared environmental factors probably all contribute to this association.

Adolescent↗
PubMed1994

Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes.

OBJECTIVE: To compare the ability of tests measuring two hour plasma glucose, fasting plasma glucose, and glycated haemoglobin concentrations in predicting the specific microvascular complications of non-insulin dependent diabetes mellitus. DESIGN: Cross sectional and longitudinal analysis of the relation between complications and concomitant results of the three tests. SETTING: Gila River Indian Community, Arizona. SUBJECTS: Pima Indians (cross sectional, n = 960), aged 25 years or above who were not receiving insulin or oral hypoglycaemic treatment at the baseline examination. MAIN OUTCOME MEASURES: Development of retinopathy and nephropathy. RESULTS: Cross sectionally, frequency distributions of logarithms of the three sets of results were bimodal, with the prevalence of retinopathy and nephropathy being, respectively, 12.0-26.7 and 3.9-4.2 times as high above as below cut off points which minimised overlap (two hour plasma glucose concentration 12.6 mmol/l; fasting plasma glucose concentration 9.3 mmol/l; glycated haemoglobin (HbA1c) concentration 7.8%). Longitudinally, each of the three measures of glycaemia significantly predicted the development of retinopathy (P < 0.0001) and nephropathy (P < 0.05). Receiver operating characteristic curves showed that two hour plasma glucose concentration was superior to fasting plasma glucose concentration (P < 0.05) for prevalent cases of retinopathy, but otherwise no variable had a significant advantage for detecting incident or prevalent cases of either complication. CONCLUSIONS: These findings suggest that determination of glycated haemoglobin or fasting plasma glucose concentrations alone may be acceptable alternatives to measuring glucose concentration two hours after challenge with 75 g glucose for the diagnosis of diabetes.

Adult↗
PubMed1994

Blood glucose distribution and prevalence of diabetes in Hanoi (Vietnam).

Few epidemiologic surveys have been performed to assess the prevalence of diabetes in representative samples, and few data are available on the epidemiologic features of diabetes in Southeast Asia. We report the results of a 1990 study performed in the Hanoi area (Vietnam) on 4,912 subjects (95.0% of the eligible population), aged 15 years or over, selected by a stratified random cluster procedure using the 1989 census list. A two-step design was used: 1) screening for diabetes by measuring capillary blood glucose (CBG) before dinner with a Glucometer II device; and 2) for subjects with a CBG measurement of > or = 105 mg/dl, a diagnostic test on the following morning, using a 75-g oral glucose tolerance test and World Health Organization criteria (93.9% of the positive screenees took this test). CBG values before dinner were unimodally distributed and skewed to the right, increasing with age in both sexes. Women had a significantly higher level of age-adjusted CBG than did men before dinner (p < 0.0001) as well as when fasting (p < 0.0001) and 2 hours after the oral glucose tolerance test (p = 0.013). The prevalence of diabetes was 1.2% (95% confidence interval (CI) 0.9-1.5) and of impaired glucose tolerance, 1.6% (95% CI 1.3-2.0). Women had a significantly higher age-adjusted prevalence of diabetes than did men (relative risk = 2.3; 95% CI 1.3-4.1). Of the 63 diabetic subjects, nine (14.3%) had been diagnosed before the study, only one was obviously insulin dependent, and only one was obese with a body mass index of > or = 27 kg/m2. The subjects living in the urban areas had higher levels of fasting and 2-hour CBG and a higher diabetes prevalence than did the rural inhabitants (relative risk = 1.3; 95% CI 1.04-3.23). Diabetes appears to be a rare disease in the Hanoi area (1.4% for subjects aged 30-64 years, after age standardization using the Segi distribution), affecting women two times as often as men. Typical insulin-dependent (type I) or obese non-insulin-dependent (type II) diabetes mellitus patients are uncommon.

Adolescent↗
PubMed1994

Glipizide-induced prevention of diabetes and autoimmune events in the BB rat.

To determine whether glipizide, a sulfonylurea, can prevent diabetes in the diabetic-prone BB rat model, rats were studied from 35 to 240 days of age. Treated animals received oral glipizide (10 or 100 mg/kg/day) from 35 to 200 days of age, and control rats received oral placebo. From 80 to 135 days of age at both drug doses, glipizide decreased the incidence of diabetes, thus delaying disease onset (P < 0.02). At the higher dose of glipizide, a diabetes preventive effect was observed (P < 0.025). There were no significant differences in body weights between the treated and control groups. At 240 days, i.e. 40 days after stopping glipizide and placebo treatments, diabetes incidence remained stable in the two groups; thus the effect of glipizide persisted after discontinuation of the drug. Serum glucose and insulin levels measured at 90 and 200 days did not reveal differences between the glipizide treated and control groups. To determine whether the sulfonylurea affected autoimmune events, the prevalence and severity of islet inflammation were examined. In glipizide-treated BB rats at 240 days, only 44% of rats had islet inflammation compared to 86% in the control group (P < 0.01). At both 90 and 240 days the severity of islet inflammation was decreased in the glipizide treatment groups compared with the control groups (P < 0.01). These data indicate that glipizide (a) prevents diabetes in the diabetic-prone BB rat strain, (b) decreases the prevalence and severity of islet inflammation even after drug withdrawal and (c) may dampen autoimmune events leading to diabetes onset.

Age Factors↗
PubMed1994

Gravidity, obesity, and non-insulin-dependent diabetes among Pima Indian women.

PURPOSE: To evaluate the relationships among gravidity, obesity, and non-insulin-dependent diabetes mellitus in Pima Indian women. SUBJECTS AND METHODS: Pima Indian women (n = 2,779) participating in a longitudinal epidemiologic study of diabetes were evaluated in both cross-sectional and longitudinal analyses. RESULTS: The prevalence of non-insulin-dependent diabetes was higher among women who had never been pregnant than among those who had been pregnant (age- and obesity-adjusted odds ratio = 2.0; 95% confidence interval = 1.5 to 2.7). Controlled for age and obesity, nondiabetic women who had never been pregnant had significantly higher fasting plasma glucose concentrations by 2% (P = 0.004), higher fasting serum insulin concentrations by 8% (P = 0.09), and higher 2-hour serum insulin concentrations by 10% (P = 0.07) than nondiabetic women who had been pregnant. Among 1,025 women observed for an average of 8 years, those who had not been pregnant by the baseline examination were at significantly higher risk for developing non-insulin-dependent diabetes before the age of 40 years (incidence rate ratio = 1.5; 95% confidence interval = 1.2 to 2.1), but that difference could be accounted for by a higher degree of obesity. CONCLUSIONS: We hypothesize that Pima Indian women who have a high risk for non-insulin-dependent diabetes develop obesity and hyperinsulinemia at an early age, and that may be responsible for decreased fertility because of associated changes in sex hormones.

Adult↗
PubMed1994

Alterations in reverse cholesterol transport associated with programmable implantable intraperitoneal insulin delivery.

Our previous studies have suggested that intraperitoneal (IP) insulin delivery may be associated with alterations of reverse cholesterol transport (RCT). We thus studied two parameters of RCT. We performed RCT studies in 10 C-peptide-negative type I diabetic patients who were randomized into two groups. The experimental (A) and control (B) groups were studied at -3 and 0 months before and +3 and +6 months after IP pump subcutaneous (SC) insulin use. The first step in RCT was estimated by measuring patient serum-mediated 3H-cholesterol efflux from cultured fibroblasts. Cholesteryl ester transport protein (CETP) activity was assessed by a solid-phase assay. No changes in glucose control occurred during the study. Total low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, apoprotein B, and apoprotein A-I remained unchanged during the study. Cholesterol efflux from group A increased from baseline after 3 months of IP insulin by 9.5% +/- 3.4% (mean +/- SE, P < .05), whereas in group B patients it decreased negligibly by 1.5% +/- 2.9% (P = .045 for changes between groups). CETP activity increased from baseline by 25.3% +/- 7.7% (P < .05) in group A after 3 months of IP insulin, whereas in group B it changed little, -1.5% +/- 7.9%, with modest differences between groups (P = .16). These data indicate that (1) serum from patients treated long-term with IP insulin delivery may enhance cholesterol efflux from fibroblasts and CETP activity, and (2) these effects appear independent from glucose control, implying a direct effect by IP insulin.

Adult↗
PubMed1994

Hyperinsulinemia is associated with menstrual irregularity and altered serum androgens in Pima Indian women.

To determine whether hyperinsulinemia is associated with menstrual irregularity or hyperandrogenemia among Pima Indians, a population with a high prevalence of hyperinsulinemia, we retrospectively studied 20 hyperinsulinemic (higher insulin [HI ) and 20 relatively nonhyperinsulinemic (lower insulin [LI]) nondiabetic Pima women 18 to 45 years of age. Reproductive histories were obtained by review of medical records. Stored serum samples were used for measurement of total testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEAS) levels. Fifty percent (nine of 18) of HI women had irregular menses, as compared with none of the LI women (0 of 19, P = .0004). HI women were significantly more obese than LI women. Serum testosterone and androstenedione levels were similar in HI and LI women (median testosterone, 1.13 v 1.13 nmol/L, P = .55; median androstenedione, 3.79 v 3.26 nmol/L, P = .90). Serum DHEAS was lower in HI than in LI women (median, 2.85 v 4.55 mumol/L, P < .01). HI women with irregular menses had significantly higher testosterone levels than HI women with regular menses (median, 1.62 v 0.76, nmol/L, P = .04). Androstenedione and DHEAS levels were not different between these women. In conclusion, the association of obesity, hyperinsulinemia, irregular menstruation, and high testosterone concentration described in the polycystic ovarian syndrome (PCO) also occurs in Pima Indian women. Moreover, low concentrations of DHEAS are associated with hyperinsulinemia in these women.

Adolescent↗