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Biomedical subjects

R G Josse

Publications and source records attributed to R G Josse.

At least 55 records · Page 3Linked to original sources
PubMed1995

Clinical experience with acarbose: results of a Canadian multicentre study.

Current therapeutic options for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) focus on regimens that primarily lower fasting blood glucose concentrations. In several short-term studies, the alpha-glucosidase inhibitor, acarbose, has been reported to significantly lower post-prandial plasma glucose levels as well as HbA1c. The primary objective of this present study was to assess the long-term efficacy of adjunctive acarbose therapy to improve metabolic control. Over a 1-y period, acarbose or placebo was administered to 4 groups of patients: those managed by diet only, diet and sulfonylurea, diet and biguanide, and diet and insulin. In all treatment groups, the addition of acarbose resulted in significant reductions in postprandial blood glucose levels. Additionally, HbA1C was significantly lower after 12 months of acarbose therapy, compared with placebo, in all groups except the diet and insulin group. The addition of acarbose consequently expands the armamentarium available to clinicians for the optimization of glycemic control in patients with NIDDM.

Acarbose↗
PubMed1994

The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial.

OBJECTIVE: To evaluate the long-term efficacy of acarbose, an alpha-glucosidase inhibitor, in improving glycemic control in patients with non-insulin-dependent diabetes mellitus. DESIGN: A 1-year, multicenter, randomized, double-blind, placebo-controlled study. SETTING: Seven university-affiliated, community-based, tertiary care diabetes clinics. PATIENTS: 354 patients with non-insulin-dependent diabetes mellitus were recruited; 77 were being treated with diet alone, 83 with diet and metformin, 103 with diet and sulfonylurea, and 91 with diet and insulin. Patients in each treatment group were randomly assigned to either acarbose or placebo for 1 year. Eighty-seven percent of patients receiving acarbose and 92% of those receiving placebo were included in the efficacy analysis (n = 316). MEASUREMENTS: At baseline and at 3-month intervals, levels of hemoglobin A1c (HbA1c), fasting and postprandial plasma glucose, fasting and postprandial serum C-peptide, and fasting serum lipids were measured. RESULTS: Compared with placebo, acarbose treatment caused a significant decrease in the mean postprandial plasma glucose peak (90 minutes) in all four groups (19.0 +/- 0.4 mmol/L to 15.5 +/- 0.4 mmol/L; P < 0.001). Analysis of the postprandial plasma glucose incremental area under the curve showed that the change from baseline to the end of the treatment period differed for placebo and acarbose recipients by 4.73 mmol.h/L in the diet alone group (P < 0.001), 2.06 mmol.h/L in the metformin group (P = 0.01), 2.65 mmol.h/L in the sulfonylurea group (P < 0.001), and 3.13 mmol.h/L in the insulin group (P = 0.001). Corresponding decreases in HbA1c levels occurred; these were 0.9% in the diet alone group (P = 0.005), 0.8% in the metformin group (P = 0.011), 0.9% in the sulfonylurea group (P = 0.002), and 0.4% in the insulin group (P = 0.077). Acarbose did not significantly affect mean serum C-peptide or mean serum lipid levels. CONCLUSIONS: Acarbose improved long-term glycemic control in patients with non-insulin-dependent diabetes mellitus regardless of concomitant antidiabetic medication.

Acarbose↗
PubMed1994

In vitro study of osteoblastic cells from patients with idiopathic osteoporosis and comparison with cells from non-osteoporotic controls.

We have examined bone cells derived from iliac crest trabecular explants of 30 patients with idiopathic osteoporosis and 45 control subjects in order to determine whether intrinsic abnormalities in osteoblast function may contribute to the decreased bone formation observed in this disease. Bone cells isolated from all subjects expressed several in vitro characteristics of the osteoblast phenotype including adenylate cyclase responsiveness to parathyroid hormone (PTH) and prostaglandin E1 (PGE1), basal and 1,25(OH)2D3-stimulated alkaline phosphatase activity and osteocalcin production. Results were compared amongst three subject groups; young controls less than 40 years old, older controls over 40 years old, and osteoporotics. Osteoporotic cells were found in general to be fully active in vitro. There were no differences between osteoporotic and control cells in their basal levels of adenylate cyclase, or alkaline phosphatase, in their growth rates, or cell morphology. The cyclic AMP (cAMP) response to PTH was significantly lower in osteoporotic cells (71%, p < 0.01) and older control cells (64%, p < 0.005) relative to the response in cells from younger controls, suggesting that the decreased responsiveness in osteoporotic cells was due to subject age rather than the osteoporotic state. At the same time, the cAMP responses to PGE1 and cholera toxin were similar in cells from all three subject groups. The response to forskolin was reduced to about 40% in osteoporotic cells compared with controls, but this was not mirrored by similar differences in the responses to PTH, PGE1 or cholera toxin, suggesting that the availability of catalytic subunits is not rate-limiting in these cells. 1,25(OH)2D3-stimulated osteocalcin production was 220% higher in osteoporotics than in older controls, but the numbers tested were small and the difference did not reach significance. The one significant abnormality we observed in osteoporotic cells was in alkaline phosphatase activity: 1,25(OH)2D3-stimulated alkaline phosphatase activity was twofold higher in osteoporotics than in younger (p < 0.05), older (p < 0.05) and pooled controls (p < 0.025). The significance of this finding is unknown, but we postulate that it may reflect an intrinsic abnormality in osteoblast function in patients with idiopathic osteoporosis.

Adolescent↗
PubMed1994

Low glycemic index: lente carbohydrates and physiological effects of altered food frequency.

Many factors influence carbohydrate absorption. Slower rates of absorption may have advantages in reducing postprandial glycemia and insulinemia and, in time, reduce serum low-density-lipoprotein (LDL) cholesterol and apolipoprotein B concentrations. Foods high in viscous fiber or antinutrients, or foods that are resistant to gelatinization, show slower rates of digestion and absorption and may be called low glycemic index or lente carbohydrate foods. Specific enzyme inhibitors may also cause lente effects. Certain small-intestinal effects of lente carbohydrate may be mimicked by altering feeding frequency (eg, nibbling vs gorging). Increased meal frequency reduces post-prandial insulin and glucose responses in people with non-insulin-dependent diabetes and in nondiabetic volunteers and lowers serum concentrations of LDL cholesterol and apolipoprotein B. Reduced hepatic cholesterol synthesis has been reported. Increased meal frequency may also slow small-intestinal absorption in the treatment of conditions such as diabetes, hyperlipidemia, and possibly obesity.

Blood Glucose↗
PubMed1994

Determinants of diet glycemic index calculated retrospectively from diet records of 342 individuals with non-insulin-dependent diabetes mellitus.

Controlled trials have shown that a diet with a low glycemic index improves blood glucose and lipid control in patients with diabetes. To study the distribution and determinants of diet glycemic index, we obtained two 3-d diet records from 342 free-living subjects with non-insulin-dependent diabetes. Mean +/- SD 24-h intakes were as follows: energy, 7170 +/- 1890 kJ; fat, 33.6 +/- 6.5% of energy; protein, 20.1 +/- 3.2% of energy; available carbohydrate, 45.3 +/- 7.2% of energy; and dietary fiber, 17.2 +/- 6.4 g. Diet glycemic index values (85.4 +/- 4.55, range, 70-97.8) were normally distributed. Diet glycemic index was inversely associated with intake of simple sugars, whether expressed in grams (r = -0.426), percent of energy (r = -0.446), or percent of carbohydrate (r = -0.453, P < 0.001). By step-wise-multiple-linear regression, grams carbohydrate and percent protein were also independently related to diet glycemic index. Differences in diet glycemic index between men and women, and between subjects on different types of diabetes therapy were explained by differences in intake of simple sugars.

Blood Glucose↗
PubMed1992

Beneficial effect of a low glycaemic index diet in type 2 diabetes.

Low glycaemic index foods produce low blood glucose and insulin responses in normal subjects, and improve blood glucose control in Type 1 and well-controlled Type 2 diabetic patients. We studied the effects of a low glycaemic index diet in 15 Type 2 diabetic patients with a mean fasting blood glucose of 9.5 mmol l-1 using a randomized, crossover design. Patients were given pre-weighed diets (59% energy as carbohydrate, 21% fat, and 24 g 1000-kcal-1 dietary fibre) for two 2-week periods, with a diet glycaemic index of 60 during one period and 87 during the other. On the low glycaemic index diet, the blood glucose response after a representative breakfast was 29% less than on the high glycaemic index diet (874 +/- 108 (+/- SE) vs 204 +/- 112 mmol min l-1; p less than 0.001), the percentage reduction being almost identical to the 28% difference predicted from the meal glycaemic index values. After the 2-week low glycaemic index diet, fasting serum fructosamine and cholesterol levels were significantly less than after the high glycaemic index diet (3.17 +/- 0.12 vs 3.28 +/- 0.16 mmol l-1, p less than 0.05, and 5.5 +/- 0.4 vs 5.9 +/- 0.5 mmol l-1, p less than 0.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Beneficial effect of low-glycemic index diet in overweight NIDDM subjects.

OBJECTIVE: To determine whether low-glycemic index (GI) diets have clinical utility in overweight patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Six patients with NIDDM were studied on both high- and low-GI diets of 6-wk duration with metabolic diets with a randomized crossover design. Both diets were of similar composition (57% carbohydrate, 23% fat, and 34 g/day dietary fiber), but the low-GI diet had a GI of 58 compared with 86 for the high-GI diet. RESULTS: Small and similar amounts of weight were lost on both diets: 2.5 kg on high-GI diet and 1.8 kg on low-GI diet. On the low-GI diet, the mean level of serum fructosamine, as an index of overall blood glucose control, was lower than on the high-GI diet by 8% (P less than 0.05), and total serum cholesterol was lower by 7% (P less than 0.01). CONCLUSIONS: In overweight patients with NIDDM, reducing diet GI improves overall blood glucose and lipid control.

Blood Glucose↗
PubMed1991

Detection of silent myocardial ischemia in diabetes mellitus.

The prevalence of silent myocardial ischemia and its relation to autonomic dysfunction and pain threshold was studied in 58 men with diabetes mellitus and without cardiac symptoms. All patients underwent 48-hour ambulatory electrocardiographic monitoring and exercise testing after assessment of their autonomic function and pain threshold. Silent myocardial ischemia, defined as greater than or equal to 1 mm of ST-segment depression on either exercise testing or ambulatory electrocardiographic monitoring, was corroborated by exercise-induced reversible defect(s) on tomographic thallium scintigraphy. Autonomic function was assessed by heart rate response to: (1) Valsalva maneuver, (2) deep breathing, and (3) upright posture, as well as by diastolic blood pressure response to sustained handgrip and systolic blood pressure response to upright posture. Autonomic dysfunction was defined as greater than or equal to 2 abnormal responses. Pain threshold measurements were performed using electrical cutaneous stimulation of both forearms. Of the 58 diabetic patients, 21 were found to have autonomic dysfunction (36%). Silent myocardial ischemia was detected in 10 patients (17%), and was significantly more frequent in patients with than without autonomic dysfunction (38 vs 5%, p = 0.003). There was no difference in the electrical pain threshold or tolerance in subjects with and without silent myocardial ischemia. It is concluded that silent myocardial ischemia in asymptomatic diabetic men occurs frequently and in association with autonomic dysfunction, suggesting that diabetic neuropathy may be implicated in the mechanism of silent myocardial ischemia.

Adult↗
PubMed1991

The glycemic index: methodology and clinical implications.

There is controversy regarding the clinical utility of classifying foods according to their glycemic responses by using the glycemic index (GI). Part of the controversy is due to methodologic variables that can markedly affect the interpretation of glycemic responses and the GI values obtained. Recent studies support the clinical utility of the GI. Within limits determined by the expected GI difference and by the day-to-day variation of glycemic responses, the GI predicts the ranking of the glycemic potential of different meals in individual subjects. In long-term trials, low-GI diets result in modest improvements in overall blood glucose control in patients with insulin-dependent and non-insulin-dependent diabetes. Of perhaps greater therapeutic importance is the ability of low-GI diets to reduce insulin secretion and lower blood lipid concentrations in patients with hypertriglyceridemia.

Blood Glucose↗
PubMed1990

Fluoride-induced fractures: relation to osteogenic effect.

The possible effects of fluoride in inducing fractures were studied in 61 patients treated with sodium fluoride (NaF), 40-60 mg daily in combination with calcium and vitamin D. Nine patients developed the fluoride-(F) related lower extremity pain syndrome. Four other patients had stress fractures associated with trauma. Seven of the 61 patients had 10 upper femur fractures of which 5 were stress fractures. The bone mineral mass of the central skeleton including the hips was measured by neutron activation and the results expressed as a calcium bone index (CaBI) which normalizes the results to that of young adults of the same body size (normal range 0.75-1.2). At the time of hip fracture, 4 patients with a minimal increase in bone mass (mean delta CaBI 0.01) had 4 femur fractures and 3 patients with a marked increase (mean delta CaBI 0.24) had 6. The 7 patients with upper femur fractures at 4 years had a significantly higher bone fluoride retention, 30 mg/g Ca compared with 23.9 mg/g Ca for the other 54 (p less than 0.02) and were older, 73.1 versus 64.2 years (p less than 0.01). Using all 61 fluoride-treated patients, femur fractures/patient were significantly correlated to bone fluoride (p less than 0.05) and to age (p less than 0.05). By partial correlation, only the correlation between hip fractures/patient and bone fluoride remained significant after controlling for the effect of age (p less than 0.05). These results suggest that fluoride therapy may be implicated in the pathogenesis of hip fractures which may occur in treated patients despite a rapid, marked increase in bone mass. The lower extremity pain syndrome is not frequently associated with stress fractures in this study.

Aged↗
PubMed1990

Fluoride treatment of postmenopausal osteoporosis: age, renal function, and other clinical factors in the osteogenic response.

We report on 61 women with postmenopausal osteoporosis who were treated with either plain sodium fluoride (NaF) capsules or enteric-coated NaF tablets for 4 years, in whom possible therapeutic and toxic effects were monitored. In these patients there was a mean increase in axial bone mineral mass, assessed by neutron activation analysis, of 26.2% +/- 2.4% (SEM) during the 4 years. This corresponds to a decrease in the bone deficit (compared with reference values) of 48.6%. The response was linear over 4 years. The main predictors of the osteogenic response were bone fluoride (r = 0.52, p less than 0.01), serum fluoride (r = 0.50, p less than 0.01), and age (0.39, p less than 0.01). Patients over 65 years of age achieved higher bone fluoride (F) levels and a significantly greater increase in bone mineral than younger patients (32.8 vs. 17.9%, p less than 0.01), associated with an age-related decline in renal function; serum fluoride was significantly and negatively correlated to creatinine clearance (r = -0.52, p less than 0.01). Although the effect of NaF on fracture rate could not be assessed in this uncontrolled study, the major factors associated with the occurrence of new vertebral fractures were the number of vertebral fractures and the bone mineral mass at the beginning of therapy. There was no correlation between vertebral fracture rate and serum or bone fluoride or other parameters of the osteogenic response, but patients who did not experience new vertebral fractures achieved a normal bone mineral content sooner than those who had new fractures during therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Bone mineral mass associated with postmenopausal vertebral deformities.

Vertebral morphometry on thoracic and lumbar spine radiographs and bone mass measurements were carried out on 215 patients investigated for postmenopausal osteoporosis. Bone mineral mass was measured on the central third of the skeleton by neutron activation analysis and the result, normalized for body size, expressed as a calcium bone index (CaBI). The normal CaBI value for females (20-40 years) is 0.97 (0.11) with a lower limit for these young, normal women, of 0.75. Vertebral compression deformity was defined as a mean height more than 15% lower than adjacent normal vertebrae. Thoracic and lumbar anterior wedge deformities and central compression were defined as anterior/posterior (A/P) or mid/posterior (M/P) height ratios of less than 0.75. For the 129 patients without vertebral deformities, the mean CaBI was 0.80 (0.12) (1 SD) and 32% of these patients had CaBI values below the normal young adult range (CaBI less than 0.75). In 20 patients, vertebral deformities were limited to 1 or 2 mid-thoracic vertebrae, and the mean CaBI values for these 20 patients was 0.81 (0.15), equal to that for patients without any vertebral deformity. For the remaining 67 patients, (i.e., patients with one or more vertebral deformities involving at least one distal thoracic or one lumbar vertebra) the mean CaBI value was 0.66 (0.10), 17% below the value for patients without vertebral deformities. Low CaBI values (CaBI less than 0.75) were observed in 87% of these patients, consistent with the diagnosis of osteoporotic fractures. Based on our CaBI results, however, mid-thoracic deformity was not associated with significant osteopenia and is not, therefore, diagnostic of osteoporotic fracture.

Adult↗
PubMed1990

Glycemic index of foods in individual subjects.

We studied 12 subjects with diabetes to determine how well the glycemic index (GI) predicted the ranking of glycemic responses of different foods in individuals. All subjects ate three mixed meals (bread, rice, or spaghetti with GIs of 100, 79, and 61, respectively) four times in a randomized complete block design. The mean glycemic response areas of the different meals ranked according to the predicted GI in every individual. The observed mean +/- SD GI values of the meals were significantly different from each other (bread 100 +/- 7, rice 75 +/- 9, spaghetti 54 +/- 9), with no significant difference in response between subjects. It is concluded that individuals share common mean GI values for different foods. Within confidence limits determined by the variability of glycemic responses, the number of repeated tests conducted, and the expected GI difference, the GI can be used to predict the ranking of the mean glycemic responses of mixed meals taken by individuals.

Adult↗
PubMed1989

Hypocholesterolemic effect of vegetable protein in a hypocaloric diet.

Eleven obese volunteers took part in a 12-week study during 8 weeks of which 2 meals of their control 1000 kcal diets were replaced by a soya based liquid formula (1 month) or a milk based liquid formula (1 month). The mean weight loss per month was 2.5 kg (P less than 0.05). On the soya formula total and LDL cholesterol levels were reduced significantly over the month by 10.0 +/- 2.7% (P less than 0.01) and 17.5 +/- 5.6% (P less than 0.02), respectively. Neither the milk based formula or the control low calorie diet lowered serum cholesterol significantly over the diet period. No change was seen in serum triglycerides on any of the 3 diets. No difference was seen between treatments in 24-h urinary C-peptide excretion. The results indicated that use of a vegetable protein supplement in a weight loss program which induced moderate weight loss was associated with a reduction in blood lipids, whereas moderate weight loss on a control low calorie diet or milk based formula was not.

Adult↗
PubMed1989

The glycemic index: variation between subjects and predictive difference.

It is not known whether the variability of the glycemic index (GI) in different subjects is due to within- or between-individual variation. In addition, it is not known how large a difference in GI between different meals is clinically important for individuals with diabetes. Therefore, insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic subjects tested four foods, with each food taken by each subject on two separate occasions. For each food, most of the variation of absolute glycemic responses was due to differences between the subjects. However, when the results were expressed as the GI, there were no significant differences between the subjects, and most of the variation was due to within-individual variation. Using the within-individual variance, we estimated the so-called "predictive difference" of GI values. Its reliability was assessed by consideration of published data from eight studies where different mixed meals were taken by the same group of subjects. There were 37 cases where the difference between the GI of any two meals was greater than the predictive difference. Of these 37 pairs of meals, the GI correctly ranked the glycemic responses in 36 (97%). We conclude that GI values for the same food do not vary significantly between different individuals. For a subject with NIDDM a difference in GI of 34 will predict the ranking of glycemic responses of two meals with 95% probability. The corresponding value for a subject with IDDM is 50.

Blood Glucose↗
PubMed1988

Wholemeal versus wholegrain breads: proportion of whole or cracked grain and the glycaemic response.

STUDY OBJECTIVE: To determine the effect on the glycaemic response to bread of the ratio of whole cereal grains to milled flour. DESIGN: Randomised assignment of groups of diabetic volunteers to test and control meals, taken after an overnight fast. Test foods were also analysed for in vitro digestion with human saliva. SETTING: Tertiary care centre. PATIENTS: Groups of six drawn from pool of 16 volunteers with diabetes mellitus (11 men, five women; mean age 64 (SE 3); 10 taking insulin, five taking oral agents, one controlled by diet; other characteristics comparable). INTERVENTIONS: All patients took standard white bread control meals on three occasions spanning the study and on different mornings took test meals containing varying ratios of whole cereal grains (barley or cracked wheat) to milled flour (75:25, 50:50, 0:100). All meals contained 50 g available carbohydrate and were eaten in 15 minutes. Capillary blood samples were taken for determination of glucose concentrations every 30 minutes for three hours. END POINT: Glycaemic index of foods (= increase in area under blood glucose concentration curve for test food divided by increase in area under curve for white bread control X 100). MEASUREMENTS AND MAIN RESULTS: Significant trend to lower glycaemic index with increasing proportion of whole cereal grains in test bread (p less than 0.05) and lower in vitro digestibility (p less than 0.001). Breads containing up to 75% whole grain were considered palatable. CONCLUSIONS: Breads containing a high proportion of whole cereal grains may be useful in reducing the postprandial blood glucose profile in diabetics because they are more slowly digested. These breads should be called "wholegrain" in distinction to "wholemeal" breads made from milled flour.

Blood Glucose↗
PubMed1988

The effect of fluoride on bone histology in postmenopausal osteoporosis depends on adequate fluoride absorption and retention.

Forty-one women with idiopathic postmenopausal osteoporosis have been followed for 2 years after initiation of sodium fluoride at 40-50 mg/day, given together with a daily calcium supplement of 1 gram and vitamin D2, at 50,000 IU weekly. Histological and histomorphometric analyses were done on bone biopsies taken prior to and after 1 year of treatment (mean 1.25 +/- 0.35 years). Thirty patients (74%) developed the histological fluoride effect of hyperosteoidosis, while the remaining 11 patients (26%) had no change from pretreatment biopsies. Hyperosteoidosis was based on increased values for osteoid volume and/or thickened osteoid with greater than 3 lamellar bands. Based on previously reported findings, this histological evidence of hypersoteoidosis within 12-18 months of initiation of therapy provides a useful predictor of ultimate satisfactory fluoride response in terms of bone mineral accretion. No increases in bone mass (measured by neutron activation analysis) were observed at the time of the posttreatment biopsy but, according to this previous work, increases are anticipated over a further 2-3 years of treatment. Factors affecting the development of hyperosteoidosis were analyzed. Hyperosteoidosis was associated with a significantly higher dose of sodium fluoride and a significantly higher level of bone fluoride retention but without significant increase in fasting serum fluoride. Results suggest that fluoride retention depends not only on fluoride dose but also on body size, renal function, and intestinal absorptions of calcium and fluoride. There were no differences in the initial investigations between patients with and without hyperosteoidosis, with respect to age, years of postmenopause, estrogen use, initial biochemistry, or initial bone histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗