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Biomedical subjects

B Zinman

Publications and source records attributed to B Zinman.

At least 73 records · Page 4Linked to original sources
PubMed1999

Effect of intensive therapy on early macrovascular disease in young individuals with type 1 diabetes. A systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review of randomized controlled trials (RCTs) of intensive insulin therapy (IIT) in type 1 diabetes to determine the effect on macrovascular complications. RESEARCH DESIGN AND METHODS: MEDLINE (1966-1996), Citation Index, reference lists, and personal files were used to identify RCTs of > 2 years' duration comparing IIT to conventional therapy (CT) in type 1 diabetes. Two independent reviewers applied selection criteria and identified 11 studies; 5 were subsequently excluded because no data were available for macrovascular complications. Data were extracted on macrovascular disease and cardiovascular risk factors. Macrovascular disease was defined as angina, myocardial infarction, angioplasty, coronary artery bypass graft, stroke, claudication, or peripheral bypass. The first event of each type was counted. RESULTS: IIT decreased the number of macrovascular events (odds ratio [OR] 0.55, [95% CI 0.35-0.88], P = 0.015) but had no significant effect on the number of patients developing macrovascular disease (OR 0.72, [95% CI 0.44-1.17], P = 0.22) or on macrovascular mortality (OR 0.91, [95% CI 0.31-2.65], P = 0.93). CONCLUSIONS: IIT decreases the extent of early macrovascular disease in young individuals with type 1 diabetes but has no effect on the number of patients affected or on macrovascular mortality. These data suggest that IIT may stabilize macrovascular disease or prevent progression in those at risk.

Adolescent↗
PubMed1998

Bioelectrical impedance analysis (BIA) using bipolar foot electrodes in the assessment of body composition in Type 2 diabetes mellitus.

The use of bioelectrical impedance analysis (BIA) for determining human body composition is widely accepted as a safe, rapid, and reliable technique. Although this technique has been validated in normal and obese individuals, only limited studies have been done in special populations. The use of BIA for the measurement of body composition in Type 2 (non-insulin dependent) diabetic patients would be of particular interest for both clinical and investigative studies. The aim of this study was to evaluate the validity of a new bipedal BIA device for the measurement of body composition in a population of individuals with Type 2 diabetes mellitus. The body composition of 48 male and 48 female Type 2 subjects was measured by BIA and dual energy X-ray absorptiometry (DXA). The percentage body fat determined by BIA was significantly correlated with % body fat determined by DXA (r = 0.89, p < 0.0001). Agreement analysis showed that BIA consistently overestimated % fat in female diabetic subjects by approximately 5% and underestimated % fat in male diabetic subjects by approximately 10% of the predicted value obtained with DXA. These differences were statistically significant but probably of minor clinical relevance. We conclude that BIA measurement by TBF 105 is a useful and reliable technique for measuring body composition in subjects with Type 2 diabetes mellitus.

Adult↗
PubMed1998

-6A promoter variant of angiotensinogen and blood pressure variation in Canadian Oji-Cree.

We previously reported significant associations between variation in the AGT gene at codon 235 and both systolic pressure and hypertension in Canadian Oji-Cree. Recently, Inoue et al suggested that the AGT T235 variant was not causative, but was rather in linkage disequilibrium with a variant in the AGT promoter, namely -6A, that was associated with increased in vitro expression of angiotensinogen and was thus a strong candidate to be the functional basis of the previously observed associations. We genotyped 518 adult Oji-Cree for the AGT promoter polymorphism and tested for its association with blood pressure and hypertension. We found that the frequency of the -6A variant was 0.85 in the Oji-Cree, which is much higher than the frequency observed in other human samples. We also found strong linkage disequilibrium between the AGT -6A and T235 variants. However, genetic variation of the AGT promoter was only marginally associated with variation in systolic pressure, with a trend to significantly higher systolic pressure seen in AGT -6A/A homozygotes than in subjects with other genotypes. In addition, genetic variation of the AGT promoter tended to be associated with a diagnosis of hypertension. Despite the very high prevalence of -6A, our native sample was essentially normotensive. Our findings are consistent with a marginally deleterious effect of the AGT -6A allele on blood pressure, but linkage disequilibrium with another causative variant cannot be ruled out in this sample of aboriginal Canadians.

Adult↗
PubMed1998

Glucose control in type 1 diabetes: from conventional to intensive therapy.

The discovery of insulin at the University of Toronto in 1921 and its first administration on January 11, 1922, dramatically revolutionized the management and outcome of type 1 diabetes. Type 1 diabetes was transformed from a condition that was almost uniformly fatal into a chronic disease characterized by the long-term microvascular and macrovascular complications of diabetes. The Diabetes Control and Complications Trial (DCCT) (1), following the lead of smaller European studies, demonstrated conclusively that improved glycemic control, as assessed by glycated hemoglobin (Hb A1c), markedly reduced the development and progression of retinopathy, neuropathy, and nephropathy. These benefits were achieved by the implementation of intensive diabetes management regimens (2). Unfortunately, the advantages of intensive diabetes management were also accompanied by an increased rate of severe hypoglycemia and weight gain. Nonetheless, on balance, it is clear that the benefits of intensive therapy far outweigh the risks. Indeed, the concluding recommendation of the DCCT is that most patients with type 1 diabetes should be treated with intensive diabetes management with the goal of achieving the best possible glycemic control. This article will be divided into four sections providing clinically relevant information relating to the transferral of patients from conventional to intensive diabetes management. We will review the principles of intensive diabetes therapy: selection of patients; implementation of therapy; and assessment of outcome measures.

Biomarkers↗
PubMed1998

Specific patterns of food consumption and preparation are associated with diabetes and obesity in a Native Canadian community.

We examined the relationship between usual patterns of food intake, fattiness of food preparation and consumption, and diabetes and obesity status in a Native Canadian reserve in northwestern Ontario. Patterns of intake were estimated using a 34-item food frequency instrument. Scales and scores were developed using factor analysis procedures and were tested for reliability using coefficient alpha. Impaired glucose tolerance (IGT) and diabetes status was determined by administering a 75-g glucose tolerance test. A number of the food groups appear to have a protective effect in regard to IGT and diabetes, including vegetables [odds ratio (OR) = 0.41, confidence interval (CI) = 0.18-0.91], breakfast foods (OR = 0.41, CI = 0.18-0. 93) and hot meal foods (OR = 0.29, CI = 0.11-0.78). Most of these foods are relatively high in fiber and low in fat. High consumption of junk foods and the bread and butter group was associated with substantial increases in risk for diabetes (OR = 2.40, CI = 1.13-5. 10; OR = 2.22, CI = 1.22-4.41, respectively). These foods tend to be high in simple sugars, low in fiber and high in fat. More fatty methods of food preparation are also associated with increased risk for diabetes in this population (OR = 2.58, CI = 1.11-6.02). This information has been incorporated into an ongoing community-based diabetes prevention program in the community.

Adolescent↗
PubMed1998

Genetic variation in paraoxonase-2 is associated with variation in plasma lipoproteins in Canadian Oji-Cree.

We report studies of the association between genetic variation in PON2 and variation in plasma quantitative traits in a sample of 334 non-diabetic Oji-Cree. We detected associations between PON2 variation in codon 148 (Ala --> Gly) and variation in fasting plasma concentrations of total and low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B. In particular, homozygotes for a PON2 allele that encoded A148 had significantly higher plasma total, LDL cholesterol and apo B than subjects having the other two genotypes (p < 0.01). Taken together, our results suggest that common genetic variation on chromosome 7q21.3-22.1 in PON2 is associated with significant variation of intermediate traits in plasma lipoprotein metabolism.

Adult↗
PubMed1998

G protein beta3 subunit gene variant and blood pressure variation in Canadian Oji-Cree.

The subunits of the heterotrimeric G proteins are attractive candidate gene products for both susceptibility to essential hypertension and interindividual variation in blood pressure. There is alternative splicing of exon 9 of the gene encoding the beta3 subunit of heterotrimeric G proteins (GNB3) associated with a C-->T change at nucleotide 825, which activates a cryptic splice site. The 825T allele results in a gene product that is 41 amino acids smaller than the wild-type gene product. G protein heterotrimers containing the shorter variant are more reactive than those containing the wild type, and the 825T allele appears to be associated with essential hypertension. To evaluate whether this variant is associated with hypertension or blood pressure in other human samples, we genotyped 447 young adult Oji-Cree for the GNB3 C825T variation. We found that the frequency of the GNB3 825T allele was 0.501 in the Oji-Cree, which is considerably higher than the frequency observed in whites. Furthermore, genetic variation of the GNB3 nucleotide 825 was significantly associated with variation in systolic pressure but not diastolic pressure. Specifically, subjects with the 825T/T genotype had significantly lower systolic pressure than subjects with the 825C/T and 825C/C genotypes; the association was independent of sex. Furthermore, the 825T allele frequency tended to be higher in subjects who took antihypertensive medications than in subjects who did not (0.571 versus 0.496; P=NS), although this young sample had relatively few subjects with hypertension. The findings support an association of variation in this gene with variation in blood pressure.

Adolescent↗
PubMed1998

Variation in the AU(AT)-rich element within the 3'-untranslated region of PPP1R3 is associated with variation in plasma glucose in aboriginal Canadians.

We are investigating associations between variations in candidate genes on chromosome 7q and diabetes-related phenotypes in Canadian Oji-Cree. One of these genes encodes the skeletal muscle regulatory G subunit of the glycogen-associated form of protein phosphatase 1 (PPPIR3), which may play a key role in muscle glycogen metabolism. There is a common 5-bp insertion-deletion polymorphism in a messenger ribonucleic acid-stabilizing AU(AT)-rich element within the 3'-untranslated region (UTR) of PPPIR3. The D allele had a frequency of 0.30 in the Oji-Cree. We found that this 3'-UTR variation of PPPIR3 was significantly associated with variation in 2-h postprandial glucose in adult Oji-Cree with type 2 diabetes or impaired glucose tolerance (IGT). Specifically, Oji-Cree with diabetes or IGT who were D/D homozygotes had significantly lower 2-h postprandial plasma glucose than subjects with the other genotypes. There was no association of the PPPIR3 genotype either with the presence of type 2 diabetes or IGT or with other quantitative traits in this sample. These findings suggest that common PPPIR3 3'-UTR variation that potentially affects messenger ribonucleic acid stability is associated with variation in glycemia in Oji-Cree subjects with type 2 diabetes.

3' Untranslated Regions↗
PubMed1998

Glucose production, utilization, and cycling in response to moderate exercise in obese subjects with type 2 diabetes and mild hyperglycemia.

The glucoregulatory and hormonal responses to moderate-intensity exercise (50% VO2max for 45 min) were examined in subjects with type 2 diabetes and mild hyperglycemia. We studied seven obese subjects with type 2 diabetes and seven lean and seven obese control subjects (fasting plasma glucose levels, 7.5 +/- 0.5, 4.8 +/- 0.1, and 5.2 +/- 0.1 mmol/l, respectively). Glucose production, utilization, and cycling (flux between glucose and glucose-6-phosphate [G-6-P]) were measured with [6-(3)H]glucose and [2-(3)H]glucose using the constant specific-activity method. Insulin levels decreased normally during exercise in diabetic subjects. Plasma glucose levels decreased in diabetic subjects, but remained constant in control subjects. Basal glucose production was not different among groups and increased similarly during exercise. The decrease in plasma glucose in diabetic subjects was due to greater glucose utilization (867 +/- 83 vs. 726 +/- 143 micromol x m(-2) x min(-1); P < 0.05). This was a consequence of the mass effect of hyperglycemia, since glucose metabolic clearance increased similarly in all groups. Glucose cycling, expressed as a percentage of total glucose output (i.e., flux through G-6-P) was elevated at rest (P < 0.01), but decreased during exercise (P < 0.01). The catecholamine response to exercise was blunted in diabetic subjects, presumably indicating autonomic dysfunction. In conclusion, during moderate-intensity exercise in obese diabetic subjects with mild hyperglycemia, 1) insulin secretory responses were normally regulated; 2) glucose homeostasis was different from that in nondiabetic subjects because glucose levels decreased during exercise; 3) the decrease in plasma glucose was due to greater-than-normal rates of glucose utilization, which were sustained by hyperglycemia; and 4) elevated basal rates of glucose cycling decreased during exercise, presumably because exercise simultaneously lowered plasma glucose, was associated with a blunted catecholamine response, and accentuated an underlying defect in hepatic glucokinase activity in type 2 diabetes.

Adult↗
PubMed1998

Counterregulatory hormone responses after long-term continuous subcutaneous insulin infusion with lispro insulin.

OBJECTIVE: To determine whether the long-term use of insulin lispro (LP) affects the counterregulatory hormone response to hypoglycemia. RESEARCH DESIGN AND METHODS: Ten patients (age range 26-51 years; ratio of men to women 9:1; BMI 24.9 +/- 0.48; mean HbA1c 7.84 +/- 0.25%) with IDDM, treated with continuous subcutaneous insulin infusion (CSII; Disetronic H-TRON V100) were studied using a double-blind, crossover design. Patients were randomized to LP or human regular insulin (HR) for 3 months and then crossed over to the other insulin for an additional 3 months. All meal boluses were given 0-5 min before breakfast, lunch, and dinner. Counterregulatory hormone responses to a stepped hypoglycemic clamp (consecutive glucose levels in mmol/l: 4.2; 3.5; 2.8, each for 1 h) were evaluated at the end of each treatment period. RESULTS: HbA1c was significantly lower with LP versus HR (7.47 +/- 0.28% vs. 7.9 +/- 0.26%, P = 0.04). The incidence of hypoglycemia per 30 days (capillary blood glucose < 3.0 mmol/l and/or symptoms) during the last month of the study was significantly lower with LP versus HR (8.7 +/- 2.9 vs. 11.8 +/- 2.9, P = 0.03). The total daily insulin dosage was not different in the two treatment periods. There was no episode of severe hypoglycemia or diabetic ketoacidosis. The peak growth hormone, cortisol, glucagon, and epinephrine responses during the same period of hypoglycemia were not different for each treatment period. CONCLUSIONS: The use of LP in CSII results in improved glycemic control and a decrease in the frequency of hypoglycemia without adversely affecting counterregulatory hormone response to hypoglycemia.

Adult↗
PubMed1998

Effect of continuous subcutaneous insulin infusion with lispro on hepatic responsiveness to glucagon in type 1 diabetes.

OBJECTIVE: People with type 1 diabetes frequently develop a blunted counterregulatory hormone response to hypoglycemia coupled with a decreased hepatic response to glucagon, and consequently, they have an increased risk of severe hypoglycemia. We have evaluated the effect of insulin lispro (Humalog) versus regular human insulin (Humulin R) on the hepatic glucose production (HGP) response to glucagon in type 1 diabetic patients on intensive insulin therapy with continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND METHODS: Ten subjects on CSII were treated for 3 months with lispro and 3 months with regular insulin in a double-blind randomized crossover study After 3 months of treatment with each insulin, hepatic sensitivity to glucagon was measured in each subject. The test consisted of a 4-h simultaneous infusion of somatostatin (450 microg/h) to suppress endogenous glucagon, regular insulin (0.15 mU x kg(-1) x min(-1)), glucose at a variable rate to maintain plasma glucose near 5 mmol/l, and D-[6,6-2H2]glucose to measure HGP During the last 2 h, glucagon was infused at 1.5 ng x kg(-1) x min(-1). Eight nondiabetic people served as control subjects. RESULTS: During the glucagon infusion period, free plasma insulin levels in the diabetic subjects were 71.7+/-1.6 vs. 74.8+/-0.5 pmol/l after lispro and regular insulin treatment, with plasma glucagon levels of 88.3+/-1.8 and 83.7+/-1.5 ng/l for insulin:glucagon ratios of 2.8 and 3.0. respectively (NS). However, plasma glucose increased to 9.2+/-1.1 mmo/l after lispro insulin compared with 7.1+/-0.9 mmol/l after regular insulin (P < 0.01), and the rise in HGP was 5.7 +/-2.8 micromol x kg(-1) x min(-1) after lispro insulin versus 3.1+/-2.9 micromol x kg(-1) x min(-1) after regular insulin treatment (P=0.02). In the control subjects, HGP increased by 10.7+/-4.2 micromol x kg(-1) x min(-1) under glucagon infusion. CONCLUSIONS: Insulin lispro treatment by CSII was associated with a heightened response in HGP to glucagon compared with regular human insulin. This suggests that insulin lispro increases the sensitivity of the liver to glucagon and could potentially decrease the risk of severe hypoglycemia.

Adult↗
PubMed1998

Absence of association between genetic variation of the beta 3-adrenergic receptor and metabolic phenotypes in Oji-Cree.

OBJECTIVE: To assess the association between the common missense variant, Y64R, in the gene encoding the beta 3-adrenergic receptor, ADRB3, and intermediate phenotypes related to obesity and NIDDM in Canadian Oji-Cree. RESEARCH DESIGN AND METHODS: We determined genotypes of the ADRB3 Y64R polymorphism in 508 clinically and biochemically well-characterized adult Oji-Cree, of whom 115 had NIDDM. We tested for associations with multivariate analysis of variance. RESULTS: We found the ADRB3 R64 allele frequency to be 0.40 in this population, which is the highest yet observed in a human population. Furthermore, 15% of subjects were R64/R64 homozygotes, compared with a virtual absence of homozygotes in European study samples. However, we found no statistically significant associations of the ADRB3 Y64R genotype either with the presence of NIDDM, with indexes of obesity, or with intermediate quantitative biochemical traits related to NIDDM. CONCLUSIONS: Despite the very high frequency of the ADRB3 R64 allele in this sample of aboriginal people, it was not associated with any metabolic phenotype. This suggests that the ADRB3 R64 allele is probably not a major determinant of obesity or NIDDM in these aboriginal Canadians.

Adipose Tissue↗