Biomedical subjects

R G Josse

Publications and source records attributed to R G Josse.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effect of acarbose on insulin sensitivity in elderly patients with diabetes.

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on insulin release and insulin sensitivity in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Elderly patients with type 2 diabetes were randomly treated in a double-blind fashion with placebo (n = 23) or acarbose (n = 22) for 12 months. Before and after randomization, subjects underwent a meal tolerance test and a hyperglycemic glucose clamp study designed to measure insulin release and sensitivity. RESULTS: After 12 months of therapy there was a significant difference in the change in fasting plasma glucose levels (0.2 +/- 0.3 vs. -0.5 +/- 0.2 mmol/l, placebo vs. acarbose group, respectively; P < 0.05) and in incremental postprandial glucose values (-0.4 +/- 0.6 vs. -3.5 +/- 0.6 mmol/l, placebo vs. acarbose group, P < 0.001) between groups. There was a significant difference in the change in HbA(1c) values in response to treatment (0.4 +/- 0.2 vs. -0.4 +/- 0.1%, placebo vs. acarbose group, P < 0.01). The change in fasting insulin in response to treatment (-2 +/- 2 vs. -13 +/- 4 pmol/l, placebo vs. acarbose group, P < 0.05) and incremental postprandial insulin responses (-89 +/- 26 vs. -271 +/- 59 pmol/l, placebo vs. acarbose group, P < 0.01) was also significantly different between groups. During the hyperglycemic clamps, glucose and insulin values were similar in both groups before and after therapy However, there was a significant difference in the change in insulin sensitivity in response to treatment between the placebo and the acarbose groups (0.001 +/- 0.001 vs. 0.004 +/- 0.001 mg/kg x min(-1) [pmol/l](-1), respectively, P < 0.05) CONCLUSIONS: Acarbose increases insulin sensitivity but not insulin release in elderly patients with diabetes.

Acarbose↗

PubMed2000

Day-to-day consistency in amount and source of carbohydrate intake associated with improved blood glucose control in type 1 diabetes.

OBJECTIVE: To determine if a relationship exists between blood glucose control and variability in nutrient intake from day-to-day in subjects with type 1 diabetes. METHODS: Two three-day diet records and one measurement of glycated hemoglobin (HbA1c) were obtained from 272 subjects with type 1 diabetes treated with a mixture of regular and NPH insulins before breakfast and supper and using a standardized algorithm to adjust insulin dose according to the results of self-monitoring of blood glucose two to four times daily. Day-to-day variation in nutrient intake was expressed as the coefficient of variation (CV = SDx100/mean). RESULTS: Nutrient intakes in the study population (mean +/- SD) were energy 8.35+/-2.43 MJ, fat 81+/-30 g, protein 94+/-28 g, carbohydrate 227+/-68 g, starch 126+/-38 g and dietary fiber 20+/-6 g with diet glycemic index being 84.2+/-7.4. Neither energy, nutrient intakes nor insulin dose was significantly related to HbA1c. Day-to-day variation of carbohydrate (p = 0.0097) and starch (p = 0.0016) intakes and diet glycemic index (p = 0.033) was positively related to HbA1c, and the associations remained significant when adjusted for age, sex, duration of diabetes and BMI. Day-to-day variation in energy, protein or fat intakes was not related to HbA1c. CONCLUSIONS: Consistency in the amount and source of carbohydrate intake from day-to-day is associated with improved blood glucose control in people with type 1 diabetes, a result which supports continued educational efforts to achieve adherence to a diabetes diet plan. This conclusion may not apply to people on intensified insulin therapy who adjust their insulin dose based on their actual carbohydrate intake at each meal.

Adolescent↗

PubMed1998

No relationship between carbohydrate intake and effect of acarbose on HbA1c or gastrointestinal symptoms in type 2 diabetic subjects consuming 30-60% of energy from carbohydrate.

OBJECTIVE: To determine the relationship between carbohydrate intake and the effect of acarbose on HbA1c in subjects with type 2 diabetes treated with acarbose alone, acarbose plus sulfonylurea, acarbose plus metformin, or acarbose plus insulin. RESEARCH DESIGN AND METHODS: We conducted a double-blind randomized placebo-controlled study in which subjects with diabetes in four treatment strata (77 on diet alone, 83 treated with metformin, 103 treated with sulfonylurea, and 91 treated with insulin) were randomized to treatment with placebo or acarbose for 12 months. Before randomization, and 3, 6, 9, and 12 months after randomization, fasting blood was obtained for HbA1c, and 3-day diet records were collected. Subjects who completed at least 6 months of acarbose therapy and provided at least three 3-day diet records were included. RESULTS: In the 114 subjects included in this analysis, carbohydrate intake varied from approximately 30-60% of energy There was no significant relationship between carbohydrate intake and change in HbA1c in any of the four treatment strata (diet: n=26, r=0.35, P=0.076; metformin: n=27, r=0.26, P=0.19; sulfonylurea: n=35, r=0.24, P=0.16; insulin: n=25, r=-0.27, P=0.19). In the 80 subjects consuming <50% of energy from carbohydrate, the fall in HbA1c (7.83 +/-0.17% at baseline to 6.72+/-0.13% on acarbose, P < 0.001) was no different from that of the 34 subjects consuming >50% of energy from carbohydrate (7.55+/-0.25% at baseline to 6.66+/-0.23% on acarbose, P < 0.001). There was no difference in carbohydrate intake between those who dropped out of the study because of gastrointestinal side effects and those who did not, and there was no relationship between severity of symptoms and the composition of the diet. CONCLUSIONS: In subjects with type 2 diabetes consuming 30-60% of energy from carbohydrate, the effect of acarbose on HbA1c and gastrointestinal symptoms was not related to carbohydrate intake. Because most people consume at least 30% of energy from carbohydrate, we conclude that no special diet is needed for acarbose to be effective in improving blood glucose control in the treatment of type 2 diabetes.

Acarbose↗

PubMed1998

The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus.

OBJECTIVE: To describe the rationale and design, and to discuss the preliminary screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an international study on the efficacy of the alpha-glucosidase inhibitor acarbose in preventing or delaying the development of type 2 diabetes in a population with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 1,418 subjects diagnosed with IGT according to the World Health Organization's criteria and having a fasting plasma glucose concentration > or =5.6 mmol/L were randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.) or placebo for a predictive median follow-up period of 3.9 years. The primary outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose tolerance test according to the new criteria. The secondary outcomes are changes in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and morphometric profile. RESULTS: Screening was performed in a high-risk population. As of 1 March 1997, 4,424 subjects had been screened, and data were available for 3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance. Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%) subjects were eligible for the study This population had the following characteristics: the mean age was 54.8 years, 52% of the subjects were female, 53% had more than one risk factor for type 2 diabetes, >90% had a family history of diabetes, 78.2% had a BMI > or =27 kg/m2, 47.5% had high blood pressure, 51.2% had dyslipidemia, and 22.8% of the women had a history of gestational diabetes. CONCLUSIONS: Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.

Acarbose↗

PubMed1997

Current and projected rates of hip fracture in Canada.

OBJECTIVE: To determine the current values and estimate the projected values (to the year 2041) for annual number of proximal femoral fractures (PFFs), age-adjusted rates of fracture, rates of death in the acute care setting, associated length of stay (LOS) in hospital, and seasonal variation by sex and age in elderly Canadians. DESIGN: Hospital discharge data for fiscal year 1993-94 from the Canadian Institute for Health Information were used to determine PFF incidence, and Statistics Canada population projections were used to estimate the rate and number of PFFs to 2041. SETTING: Canada. PARTICIPANTS: Canadian patients 65 years of age or older who underwent hip arthroplasty. OUTCOME MEASURES: PFF rates, death rates and LOS by age, sex and province. RESULTS: In 1993-94 the incidence of PFF increased exponentially with increasing age. The age-adjusted rates were 479 per 100,000 for women and 187 per 100,000 for men. The number of PFFs was estimated at 23,375 (17,823 in women and 5552 in men), with a projected increase to 88,124 in 2041. The rate of death during the acute care stay increased exponentially with increasing age. The death rates for men were twice those for women. In 1993-94 an estimated 1570 deaths occurred in the acute care setting, and 7000 deaths were projected for 2041. LOS in the acute care setting increased with advancing age, as did variability in LOS, which suggests a more heterogeneous case mix with advancing age. The LOS for 1993-94 and 2041 was estimated at 465,000 and 1.8 million patient-days respectively. Seasonal variability in the incidence of PFFs by sex was not significant. Significant season-province interactions were seen (p < 0.05); however, the differences in incidence were small (on the order of 2% to 3%) and were not considered to have a large effect on resource use in the acute care setting. CONCLUSIONS: On the assumption that current conditions contributing to hip fractures will remain constant, the number of PFFs will rise exponentially over the next 40 years. The results of this study highlight the serious implications for Canadians if incidence rates are not reduced by some form of intervention.

Age Distribution↗

PubMed1997

Time of day and glucose tolerance status affect serum short-chain fatty acid concentrations in humans.

Short-chain fatty acids (SCFA) are derived from endogenous (metabolism of fat, carbohydrate, and amino acids) and exogenous (colonic fermentation) sources. To see how time of day and glucose tolerance status influenced serum SCFA concentrations, we determined serum SCFA throughout the day in 22 subjects with impaired glucose tolerance (IGT) and 10 young and eight middle-aged normal controls. On 1 day, insulin sensitivity was assessed as the steady-state plasma glucose (SSPG) level achieved during intravenous infusion of glucose insulin, and somatostatin. On another day, plasma glucose and insulin and serum SCFA levels were measured 12 times over 12 hours with subjects eating a standard diet. SSPG in young controls (5.5 +/- 1.1 mmol/L) was less than in middle-aged controls (9.3 +/- 1.6 mmol/L), which in turn was less than in IGT subjects (13.7 +/- 0.6 mmol/L; P < .01). Mean plasma glucose in IGT subjects was greater than in normal controls, and mean plasma insulin in IGT subjects was higher than in young controls but similar to the levels in middle-aged controls. Mean 12-hour serum acetate in young controls (143 +/- 13 mumol/L) was greater than in middle-aged controls (104 +/- 11 mumol/L) and IGT subjects (113 +/- 5 mumol/L; P < .05). Mean 12-hour serum propionate in young controls (3.8 +/- 0.5 mumol/L) was less than in IGT subjects (5.4 +/- 0.3 mumol/L; P < .01), with middle-aged controls being intermediate (4.6 +/- 0.3 mumol/L). Both young (1.6 +/- 0.3 mumol/L) and middle-aged (1.0 +/- 0.2) controls had lower mean butyrate than IGT subjects (3.1 +/- 0.4 mumol/L; P < .05). Levels of all three SCFA varied significantly during the day, tending to decrease after breakfast and increase transiently after lunch and dinner. It is concluded that both time of day and glucose tolerance status affect serum SCFA levels in nondiabetic humans. The results suggest that serum acetate is derived primarily from colonic fermentation, serum butyrate primarily from endogenous fatty acid metabolism, and serum propionate from both exogenous and endogenous sources.

Adult↗

PubMed1997

Small weight loss on long-term acarbose therapy with no change in dietary pattern or nutrient intake of individuals with non-insulin-dependent diabetes.

OBJECTIVES: To see if the long-term treatment of non-insulin dependent diabetes (NIDDM) with the alpha-glucosidase inhibitor acarbose affects food intake and body weight. DESIGN: Randomized, double-blind, placebo-controlled, parallel design clinical trial of 12 months duration. SUBJECTS: Subjects with NIDDM in four treatment strata: 77 on diet alone, 83 also treated with metformin, 103 also treated with sulfonylurea and 91 also treated with insulin. MEASUREMENTS: Two 3 day diet records were obtained before randomization to acarbose or placebo therapy, and additional 3 day diet records were obtained at 3, 6, 9 and 12 months after randomization. Body weight was also measured at these times. RESULTS: Of the 354 subjects randomized, 279 (79%) completed at least 9 months of therapy and, of these, 263 (94%) provided at least one diet record during the baseline period and two diet records during the treatment period. After one year, subjects on acarbose had lost 0.46 +/- 0.28 kg, which differed significantly from the 0.33 +/- 0.25 kg weight gain on placebo (P = 0.027). The difference in weight change between acarbose and placebo did not differ significantly in the different treatment strata. Being in the study had significant effects on diet, including a reduction in energy intake from 1760-1700 Kcal/d (P < 0.05), a reduction in simple sugars intake from 18.5-17.4% of energy (P < 0.001), and reductions in the number of different foods consumed (33-30, P < 0.001) and the number of meals eaten per day (4.7-4.3, P < 0.001). However, compared to placebo treatment, acarbose had no effect on energy intake, nutrient intakes, or dietary patterns. CONCLUSIONS: In subjects with NIDDM on weight-maintaining diets, long-term acarbose therapy results in a small weight loss, but has no effect on energy or nutrient intakes. The weight loss induced by acarbose may be due partly to reduced doses of concomitant oral agents and insulin and partly to energy loss due to increased colonic fermentation.

Acarbose↗

PubMed1996

Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 1. Introduction.

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Aged↗

PubMed1996

Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 3. Effects of ovarian hormone therapy on skeletal and extraskeletal tissues in women.

OBJECTIVE: To present recent evidence on the use of ovarian hormone therapy (OHT) for osteoporosis and outline safe and effective regimens. OPTIONS: Estrogen alone, estrogen and progestins, progestins alone; various treatment regimens. OUTCOMES: Fracture and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures and improved quality of life associated with OHT. EVIDENCE: Relevant clinical studies and reports, including the Nurses' Health Study and the Post-menopausal Estrogen/Progestin Interventions (PEPI) Trial, were studied with emphasis on recent prospective, randomized, controlled trials. Current clinical practice was determined by survey. VALUES: Reducing fractures, increasing bone mineral density and minimizing side effects of treatment were given a high value. BENEFITS, HARMS AND COSTS: Proper management of osteoporosis minimizes injury and disability, improves quality of life and reduces the personal and social costs associated with the condition. OHT is the front-line pharmaceutical therapy for prevention and treatment of osteoporosis in post-menopausal women. In those who are able and willing to comply with therapy, OHT prevents bone loss and fractures. Hormone therapy may also decrease risk of coronary artery disease. Cyclic progestin protects against endometrial cancer in patients receiving estrogen. Potential harms include breast cancer and endometrial cancer related to dosage and duration of therapy. Mastalgia and especially resumption of menstrual bleeding affect compliance. RECOMMENDATIONS: Use of OHT should be considered as early as possible in the perimenopausal period for women at increased risk of osteoporosis. Guidelines are provided for assessment of osteoporosis risk. Physicians and their patients should take into account the absolute and relative contraindications to OHT. Women with a uterus should be given estrogen in combination with a progestin. Ideally, therapy would be continued for a minimum of 10 years beyond menopause for maximum bone protection. Women using OHT should be carefully monitored and evaluated for possible adverse events. This should include regular screening mammography, breast examination and, for some, endometrial surveillance. Specific dosages and treatment regimens are outlined.

Adult↗

PubMed1996

Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 9. Calcitonin in the treatment of osteoporosis.

OBJECTIVE: To describe potential therapeutic uses of calcitonin in the prevention and treatment of osteoporosis. OPTIONS: Parenterally and intranasally administered calcitonin (eel, salmon or human). OUTCOMES: Fracture, fracture pain and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures, reduction of pain and improved quality of life associated with calcitonin treatment. EVIDENCE: Relevant clinical studies and reports were examined, with an emphasis on recent randomized, placebo-controlled trials. In vitro and in vivo studies of osteoclast activity were also considered. VALUES: Reducing fractures and fracture pain, increasing bone mineral density and minimizing side effects of treatment were given a high value. BENEFITS, HARMS AND COSTS: Calcitonin reduces acute pain associated with osteoporotic fractures and has been found useful in treating chronic back pain following vertebral fractures in spinal osteoporosis. It can prevent bone loss and may be effective in preventing fractures. Side effects are dose related and generally mild; they include gastrointestinal, vascular and dermatologic conditions that can be treated symptomatically or by varying the dosage. Side effects are much rarer with nasal administration than with injection. True allergic reactions are rare. RECOMMENDATIONS: Calcitonin in both intramuscular and intranasal forms can reduce the pain of acute osteoporotic vertebral fractures and may be effective in treating that associated with chronic vertebral osteoporotic fractures. Calcitonin may also prevent postmenopausal bone loss and increase bone density in those with established osteoporosis. Current evidence for long-term prevention of fractures is limited and does not support the use of calcitonin as a first-line treatment for established osteoporosis. Most side effects can be avoided with nasal administration. Further trials are needed to assess fracture prevention and effective dose ranges for treating pain and increasing bone mineral density and to determine the long-term efficacy of calcitonin in secondary osteoporosis, in premenopausal women, in men and in elderly people.

Aged↗

PubMed1996

Normal parathyroid hormone responsiveness of bone-derived cells from a patient with pseudohypoparathyroidism.

Pseudohypoparathyroidism (PHP) is characterized by a lack of response to parathyroid hormone (PTH); however, normal skeletal responsiveness to PTH in some patients with PHP type Ia was previously suggested on the basis of clinical observations. To test this hypothesis, we measured cyclic adenosine monophosphate (cAMP) production in response to various agonists in bone-derived osteoblast-like (OBL) cells from trabecular explants obtained from an iliac crest biopsy of a 25-year-old woman with PHP. The patient was proved to have PHP type Ia on the basis of Albright's hereditary osteodystrophy and decreased activity of stimulatory guanine nucleotide-binding protein (Gs) in erythrocytes. Responsiveness of the patient's OBL cells was compared with OBL cells from eight subjects aged 18-39 years who had no evidence of metabolic bone disease. OBL cells from the patient responded to the following agonists (expressed in multiples of elevation of cAMP, stimulated/basal, mean +/- SE, n = 3): PTH, 3.8 +/- 0.3; forskolin, 8.2 +/- 0.2; and cholera toxin, 56.8 +/- 10.0. These responses were not significantly different from those of control OBL cells: PTH, 4.5 +/- 1.1 (range 2.4-7.5); forskolin, 7.7 +/- 1.4; and cholera toxin, 57.9 +/- 16.2. The normal cholera toxin response indicated the presence of functional Gs. Bone cells from patients with PHP type Ia may exhibit a normal PTH receptor-coupled adenylyl cyclase system in vitro despite clinical evidence of impaired hormone-responsive adenylyl cyclase in other tissues, including the kidney. Skeletal responsiveness to PTH may explain the long periods of spontaneous normocalcemia observed in this patient.

Adenylyl Cyclases↗

PubMed1996

The effect of acarbose on insulin sensitivity in subjects with impaired glucose tolerance.

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on postprandial plasma glucose and insulin and insulin sensitivity in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Subjects with IGT were randomly treated in a double-blind fashion with placebo (n = 10) or acarbose (n = 8) at 100 mg t.i.d. for 4 months. All subjects were submitted before randomization and at the end of the study to a standardized breakfast and a 12-h daytime plasma glucose and plasma insulin profile, and insulin sensitivity was measured as steady-state plasma glucose (SSPG) using the insulin suppression test. RESULTS: While placebo had no effect on postprandial plasma glucose and plasma insulin incremental area under the curve (AUC) (3.03 +/- 0.5 vs. 3.76 +/- 0.6 mmol.h-1.l-1, P = NS; 1,488 +/- 229 vs. 1,609 +/- 253 pmol.h-1.l-1, P = NS), acarbose resulted in a significant reduction for both glucose (1.44 +/- 0.3 vs. 4.45 +/- 0.9 mmol.h-1.l-1, P = 0.002) and insulin (626.7 +/- 104.3 vs. 1,338.3 +/- 220.5 pmol.h-1.l-1, P = 0.003). The reduction in 12-h plasma glucose and insulin AUC on acarbose (11.2 +/- 2.1 mmol.h-1.l-1 and 7.5 +/- 0.7 nmol.h-1.l-1) was significantly greater than that on placebo (4.0 +/- 1.6 mmol.h-1.l-1 and 0.8 +/- 0.4 nmol.h-1.l-1) (P = 0.014 and 0.041). While SSPG was not affected by placebo (13.9 +/- 0.4 vs. 13.8 +/- 0.3 mmol/l; P = NS), it was significantly improved by acarbose (10.9 +/- 1.4 vs. 13.1 +/- 1.5 mmol/l, P < 0.004) and was also significantly different from placebo at 4 months (P < 0.02). CONCLUSIONS: It is concluded that in subjects with IGT, acarbose treatment decreases postprandial plasma glucose and insulin and improves insulin sensitivity. Acarbose may therefore be potentially useful to prevent the progression of IGT to NIDDM.

Acarbose↗

PubMed1995

Metaiodobenzylguanidine imaging in diabetes mellitus: assessment of cardiac sympathetic denervation and its relation to autonomic dysfunction and silent myocardial ischemia.

OBJECTIVES: This study in patients with diabetes mellitus was undertaken 1) to evaluate cardiac sympathetic innervation in diabetic patients using metaiodobenzylguanidine (MIBG) imaging; 2) to study the relation between autonomic function assessed by clinical maneuvers and abnormalities in MIBG uptake; and 3) to examine the basis for our previous observation of an association between abnormalities in autonomic nervous system dysfunction and silent myocardial ischemia. BACKGROUND: The clinical detection of autonomic dysfunction in diabetes mellitus has been linked to both abnormal perception of pain, including angina, and poor prognosis. METHODS: Uptake of MIBG was measured by dual-isotope imaging in 23 normal subjects and 65 asymptomatic diabetic patients. Silent myocardial ischemia was defined as the presence of a reversible perfusion defect in patients with ST segment depression. RESULTS: The MIBG uptake in the diabetic patients was significantly lower than that in normal subjects in the apex (67 +/- 17% vs. 82 +/- 7%, p = 0.0001), distal third (77 +/- 11% vs. 85 +/- 3%, p = 0.0001), proximal third (77 +/- 9% vs. 84 +/- 3%, p = 0.0001) and base (71 +/- 9% vs. 80 +/- 4%, p = 0.0001) of the left ventricle. Similarly, MIBG uptake was variable across different vascular territories. When MIBG uptake was corrected for perfusion abnormalities, diabetic patients had a greater MIBG uptake defect than normal subjects on visual score assessment (16 +/- 13 vs. 8 +/- 7%, p = 0.0002) and on quantitative MIBG mismatch assessment (13 +/- 15% vs. 2 +/- 2%, p = 0.0001). Diabetic patients with versus without autonomic dysfunction had more extensive MIBG uptake mismatch (17 +/- 17% vs. 4 +/- 6%, p = 0.0001). There was a greater diffuse abnormality in diabetic patients with versus without silent myocardial ischemia detected by sestamibi/MIBG uptake ratio (68 +/- 35% vs. 19 +/- 33%, p = 0.001). CONCLUSIONS: Sympathetic cardiac innervation in normal subjects is inhomogeneous. In contrast to normal subjects, diabetic patients have evidence of a significant reduction in MIBG uptake, most likely on the basis of autonomic dysfunction. Furthermore, diabetic patients with silent myocardial ischemia have evidence of a diffuse abnormality in MIBG uptake, suggesting that abnormalities in pain perception may be linked to sympathetic denervation.

3-Iodobenzylguanidine↗

PubMed1995

Acarbose for the treatment of type II diabetes: the results of a Canadian multi-centre trial.

The treatment of Type II diabetes (NIDDM) includes an appropriate diet and prudent exercise program. If these measures are insufficient to control the blood sugar, oral agents (sulphonylureas or biguanides) or insulin are added to the therapeutic regimen. Although the diet prescription has undergone some changes and refinements, this approach has been the traditional treatment for NIDDM for nearly 40 years. Recently a new class of oral agents, the alpha-glucosidase inhibitors, has become available. These drugs are competitive inhibitors of the alpha-glucosidase enzymes in the brush border of the bowel wall. They act to slow and delay the rate of carbohydrate absorption, thereby decreasing postprandial hyperglycemia. A recent study was designed to evaluate the long-term efficacy of acarbose, an alpha-glucosidase inhibitor, in improving the glycemic control of patients with NIDDM who were sub-optimally controlled on either diet alone, or diet plus sulphonylurea, metformin or insulin. A total of 354 patients with NIDDM were studied, 77 on diet alone, 83 on metformin, 103 and sulphonylurea and 91 on insulin. Subjects in each treatment stratum were randomized, double-blind to either acarbose or placebo, for 1 year. At baseline and every 3 months thereafter, fasting and postprandial glucose and C-peptide, HbA1c and fasting lipids were measured. Compared to placebo, acarbose treatment resulted in a decrease in mean postprandial glucose in all four strata (19 +/- 0.8 to 15.3 +/- 0.7 mmol/l: P < 0.001). This effect was even more pronounced and highly statistically significantly different when comparing the postprandial plasma glucose incremental area under the curve between placebo and acarbose treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acarbose↗

PubMed1995

One-year acarbose treatment raises fasting serum acetate in diabetic patients.

alpha-Glucosidase inhibitors such as acarbose improve blood glucose control in diabetes by delaying or reducing carbohydrate absorption. The fermentation of malabsorbed carbohydrate in the colon is associated with the production of gas, leading to flatulence, and short chain fatty acids such as acetate, which may have systemic effects. To see if acarbose raised fasting serum acetate in diabetic patients, we studied 85 subjects selected from the 267 who had completed a 1-year, double-blind, placebo-controlled, parallel design study of the effects of acarbose in the treatment of diabetes. At baseline, there was no significant difference between the 44 subjects subsequently randomized to placebo and the 41 randomized to acarbose, respectively, in fasting serum acetate (80 +/- 5 vs 71 +/- 4 mumoll-1) or glycosylated haemoglobin (HbA1C; 7.2 +/- 0.3 vs 7.4 +/- 0.3%). Compared to placebo, acarbose treatment significantly increased fasting serum acetate by 11 +/- 4 vs 2 +/- 3 mumoll-1 (p < 0.02) and reduced HbA1C by -0.59 +/- 0.16 vs -0.13 +/- 0.20% (p < 0.02). Acarbose treatment had no significant effect on serum cholesterol or non-esterified fatty acids, but was associated with a significant increase in flatulence. There was no relationship between changes in serum acetate and changes in HbA1C, serum cholesterol or symptoms. We conclude, in subjects with diabetes who tolerate therapy for a 1-year period, that acarbose treatment increases serum acetate. The magnitude of change in acetate was unrelated to side-effects or changes in blood glucose control or serum lipids.

Acarbose↗

PubMed1995

Positive methane-producing status associated with increased serum cholesterol in subjects with impaired glucose tolerance.

OBJECTIVE: To determine if those who produce methane (i.e., have presence of methane in breath) have higher serum cholesterol than those who do not produce methane in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: We measured breath gases and fasting serum total and high-density lipoprotein (HDL) cholesterol and triglyceride (TG) levels in 21 subjects with IGT. RESULTS: The 11 methane-producers were well matched to the 10 non-methane-producers for age, sex, and body mass index. Methane-producers had higher fasting serum total (6.5 +/- 0.3 vs. 5.5 +/- 0.2 mmol/l; P < 0.02) and low-density lipoprotein (4.3 +/- 0.3 vs. 3.4 +/- 0.2 mmol/l; P < 0.05) cholesterol concentrations with no difference in TG or HDL levels. CONCLUSIONS: The results suggest that in subjects with IGT, positive methane-producing status may be associated with increased serum cholesterol levels.

Blood Glucose↗

PubMed1995

Implications of altering the rate of carbohydrate absorption from the gastrointestinal tract.

The rate of absorption of carbohydrate from the small intestine plays a major role in determining the metabolic effects of dietary carbohydrate. Factors which reduce the rate of absorption include the nature of the starch and sugars, and the presence of vegetable proteins, fats, viscous fibre, and antinutrients, including lectins and phytates. The rate of absorption can also be manipulated by the use of specific enzyme inhibitors and by increasing the number and frequency of meals while holding caloric intake constant. All these factors contribute to the creation of what may be termed slow release or "lente carbohydrate". The slowing of small intestinal absorption, as exemplified by increased meal frequency ("nibbling"), results in reduced postprandial insulin secretion and lower low-density lipoprotein (LDL) cholesterol and apolipoprotein B concentrations. A further effect of some manipulations which reduce the rate of absorption is increased delivery of carbohydrate to the colon and its absorption after bacterial fermentation to short-chain fatty acids (SCFA). These SCFA may have beneficial effects on colonic health(butyrate) or further inhibit cholesterol synthesis in the liver (propionate). Thus the absorption of "lente carbohydrate" takes place along the full length of the gastrointestinal tract with a wide variety of physiological consequences.

Carbohydrates↗