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R A Jackson

Publications and source records attributed to R A Jackson.

At least 55 records · Page 3Linked to original sources
PubMed1991

Predictive value of intravenous glucose tolerance test insulin secretion less than or greater than the first percentile in islet cell antibody positive relatives of type 1 (insulin-dependent) diabetic patients.

We have followed-up 35 islet cell antibody-positive first degree relatives of patients with Type 1 (insulin-dependent) diabetes mellitus for an average of 1,300 days with sequential intravenous glucose tolerance tests. At the time of analysis and manuscript submission approximately half (18 of 35) had developed diabetes during follow-up. At initial intravenous glucose tolerance test, 11 had a 1 + 3 min insulin secretion below the first percentile of insulin secretion compared to 225 similarly studied normal control subjects. Six islet cell antibody positive relatives on follow-up developed an intravenous glucose tolerance test less than the first percentile. Fifteen out of 17 (88%) of these islet cell antibody positive relatives with secretion ever found to be below the first percentile are now overtly diabetic (positive predictive value = 88%) and insulin-treated, while only 3 of 18 (17%) without an intravenous glucose tolerance test demonstrating loss of first phase insulin secretion have progressed to diabetes (with approximately 1,300 days of follow-up for both groups relative risk or odds ratio with intravenous glucose tolerance test ever below vs never below the first percentile = 38, p less than 0.001). Intravenous glucose tolerance test response below the first percentile preceded diabetes by an average of 656 days. Even when first phase insulin secretion is below the first percentile, the absolute value of 1 + 3 min insulin above basal insulin correlates with the time to development of diabetes (r = 0.586, p less than 0.001). With our current duration of follow-up, the negative predictive value (intravenous glucose tolerance test never below the first percentile) is 83%, and overall accuracy 86%. Incidence rates of diabetes development amongst our islet cell antibody positive relatives with follow-up while intravenous glucose tolerance test is below the first percentile is 0.48 per year (15 conversions to diabetes amongst 17 relatives in 30.8 patient years of follow-up) vs 0.05 per year (three diabetic patients in 55.5 patient years) with intravenous glucose tolerance test greater than the first percentile.

Administration, Oral↗
PubMed1991

Specific association of HLA-DR4 with increased prevalence and level of insulin autoantibodies in first-degree relatives of patients with type I diabetes.

First-degree relatives of patients with insulin-dependent (type I) diabetes (n = 264 from 106 families) were evaluated with HLA typing and determination of competitive insulin autoantibodies (CIAAs) and islet cell autoantibodies (ICAs). The levels of CIAAs in 30 relatives exceeded our upper limit of normal (greater than or equal to 39 nU/ml), and 30 had high-titer ICAs (greater than or equal to 40 Juvenile Diabetes Foundation units [JDF U]). Eleven of the HLA-typed relatives developed diabetes during follow-up. Twenty-three percent (28 of 123) of the relatives with at least one HLA-DR4 allele were CIAA+ (CIAA greater than or equal to 39 nU/ml) versus 4% (6 of 141) among DR4- relatives (P less than 0.0001). Twenty-one of 22 of the highest CIAA values were all in the DR4+ group (DR4+ vs. DR4-, P = 0.003, Wilcoxon's rank-sum test). HLA-DR3 did not correlate with the level of CIAAs, and neither DR3 nor DR4 correlated with titer of ICAs measured in JDF U. We conclude that, in first-degree relatives of patients with type I diabetes, there is a striking association with HLA-DR4 in both the prevalence of relatives exceeding the normal CIAA range and in the level of CIAAs. These data suggest that a gene on HLA-DR4 haplotypes contributes to the level of anti-insulin autoimmunity, and we hypothesize that DR4-associated diabetes susceptibility, distinct from DR3-associated susceptibility, may be secondary to this influence.

Autoantibodies↗
PubMed1990

Analysis of metabolic progression to type I diabetes in ICA+ relatives of patients with type I diabetes.

We intensively studied 5 islet cell-antibody-positive (ICA+) first-degree relatives of type I (insulin-dependent) diabetic patients before overt diabetes. In total, 55 intravenous glucose tolerance tests (IVGTTs) and 83 fasting plasma glucose determinations were made over a maximum 4-yr period before diabetes. The 5 prediabetic relatives (not diabetic when initially studied but subsequently progressed to overt diabetes) as a group showed a progressive rise in fasting glucose (r = 0.58, P less than 0.001, slope = 23.1 mg.dl-1.yr-1) and glucose at 60 min in IVGTT (r = 0.46, P = 0.01, slope = 47.5 mg.dl-1.yr-1) beginning 1.5 yr before diabetes. During the 4.0- to 1.5-yr period before overt diabetes, no change was observed in fasting glucose or glucose at 60 min on IVGTT (fasting glucose: r = 0.21, P = 0.18, slope = 2.1 mg.dl-1.yr-1; 60-min glucose: r = 0.08, P = 0.72, slope = 2.9 mg.dl-1.yr-1). The positive predictive value for a fasting glucose greater than 108 mg/dl to be within 1.5 yr of diabetes was 100% (11 of 11 values). The negative predictive value of a stimulated insulin (1-min + 3-min insulin - 2 X basal insulin) level greater than 24 microU/ml to be greater than 1.5 yr from diabetes was 90% (9 of 10 values) and 100% (10 of 10 values) at greater than 1 yr from overt diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Predicting type I diabetes.

Currently, there are three markers that are being studied with the potential to give a high positive predictive value for the development of type I diabetes (insulin-dependent diabetes caused by autoimmune beta-cell destruction) and that can be utilized to predict the disease in susceptible relatives: 1) high-titer cytoplasmic islet cell antibodies, 2) insulin autoantibodies detected with fluid-phase radiobinding assays, and 3) first-phase insulin release after intravenous glucose less than 1st percentile. With the combination of these assays, it seems to be possible to identify first-degree relatives with a high probability of developing type I diabetes within a limited time span (i.e., less than 10 yr). The ability to predict type I diabetes with selected assays will allow trials for prevention of diabetes and trials to assess whether prediction will decrease morbidity and mortality at onset of diabetes.

Autoantibodies↗
PubMed1989

Life-table analysis of progression to diabetes of anti-insulin autoantibody-positive relatives of individuals with type I diabetes.

Cytoplasmic islet cell antibody-negative (ICA-; less than 20 Juvenile Diabetes Foundation units, n = 1670) and ICA+ (n = 42) first-degree relatives of type I (insulin-dependent) diabetic individuals were studied for competitive insulin autoantibodies (CIAAs) with a radioassay. Overall, 3.7% of first-degree relatives (64 of 1712) were CIAA+. Of ICA- relatives, 2.7% (45 of 1670) exceeded the upper limit of our normal CIAA range (greater than 39 nU/ml), and 45% (19 of 42) of ICA+ relatives exceeded this normal range. Follow-up serums for repeat CIAA determination have been obtained from 16 of the nondiabetic CIAA+/ICA- individuals (time between samples, 0.4-5.8 yr). Fourteen of these 16 (87%) CIAA+/ICA- relatives were found to still be positive on follow-up, and 2 of the relatives who were positive on the first determination were negative on their follow-up test. With a mean follow-up of approximately 2 yr, 4 of 45 (9%) of the CIAA+/ICA- relatives, 5 of 23 (22%) of the ICA+/CIAA- relatives, and 12 of 19 (63%) of the CIAA+/ICA+ relatives developed diabetes. Life-table analysis indicated that, overall, 53% of CIAA+ relatives become diabetic after 5 yr of follow-up versus 65% of ICA+ relatives. Also by life-table analysis, the predicted risk after 5 yr of follow-up for progression to diabetes is 17% for CIAA+/ICA- relatives, 42% for ICA+/CIAA- relatives, and 77% for CIAA+/ICA+ relatives. The highest rate of progression to diabetes was found in ICA+ relatives with CIAA levels greater than 150 nU/ml (100% projected to be diabetic within 5 yr, P less than .008 vs. ICA+/CIAA- relatives).

Autoantibodies↗
PubMed1988

T-cell antigen receptor alpha chain polymorphisms in insulin-dependent diabetes.

Insulin-dependent diabetes is a chronic autoimmune disease probably mediated by T cells. We examined the alpha chain of the T-cell antigen receptor in two models of this illness (man and BB rat) to determine any association with autoimmune diabetes. We conducted a population study in man, using a human alpha chain probe, pGA-5, and restriction enzyme Bgl 11. Two allelic forms and three RFLP patterns, 2.8 and 3.0 kb homozygous and 2.8/3.0 heterozygous, were detected. There was no difference in the frequency of these RFLPs among the 50 Type I diabetic patients and 48 controls tested. BB rats develop a spontaneous T-cell mediated autoimmune diabetes. The diabetes has been linked in several breeding studies to an undetermined autosomal recessive gene causing T-cell lymphopenia. We were able to differentiate the T-cell antigen receptor alpha chain of the diabetic BB and control BBN rats using the restriction enzyme EcoR1 and a murine alpha chain probe, TT11. The BB rat had a haplotype characterized by the presence of 4.7 and 5.8 kb bands, and the absence of 1.4, 2.2, 2.6, 3.6, 3.9, 4.1, and 6.1 kb bands. In a breeding study with BB and BBN rats, diabetic animals of the F2 generation demonstrated no linkage with the BBs' alpha chain, nor was lymphopenia linked to the alpha chain of the BB rat. These results suggest that autoimmune diabetes is not linked to the T-cell antigen receptor alpha chain in the BB rat, nor is it associated with alpha chain constant region polymorphisms in Type I diabetes in man.

Alleles↗
PubMed1988

Influence of aging on hepatic and peripheral glucose metabolism in humans.

Mechanisms of glucose intolerance with aging were studied by comparing the metabolic response to glucose ingestion in 10 young (20-23 yr) and 10 elderly (73-80 yr) normal men with the simultaneous application of the forearm and double-isotope techniques. The latter technique consisted of a primed-constant infusion of [3-3H]glucose followed by the administration of an oral glucose load (mean +/- SE, 90.7 +/- 0.7 g) containing [1-14C]glucose. Fasting plasma glucose and insulin concentrations were similar in young and elderly subjects, but in the elderly, glucose tolerance was markedly impaired. Although in the elderly the initial rise in insulin levels (delta, i.e., the incremental area under the curve) from 0 to 30 min was delayed (P less than .02), the response from 0 to 45 min, 0 to 60 min, and thereafter equaled that in the young group, and from 90 to 240 min insulin concentrations in the elderly exceeded those in young subjects. Basal hepatic glucose output (HGO) was similar in young and elderly men (2.13 +/- 0.10 and 1.97 +/- 0.14 mg.kg-1.min-1, respectively). Similar proportional reductions in HGO from 0 to 270 min after glucose loading occurred in young (59.7 +/- 10.3%) and elderly (50.3 +/- 4.9%) subjects but was delayed in the elderly. Suppression of HGO was observed in the young 30 min after glucose ingestion (P less than .02), but not before 60 min in the elderly subjects (P less than .05). The systemic appearance of ingested glucose (0-270 min) was slowed with age (80.7 +/- 3.1 and 66.9 +/- 4.3% of the oral load in the young and elderly groups, respectively; P less than .02). Initial increments in both total glucose disappearance (Rd) and forearm glucose uptake (FGU) from 0 to 60 min after glucose loading were decreased in the elderly (Rd, 4.1 +/- 0.7 vs. 11.5 +/- 1.3 g, P less than .001; FGU, 17.2 +/- 1.4 vs. 24.6 +/- 2.5 md/dl forearm, P less than .02). The overall increment (delta, 0-270 min) in Rd was reduced with age (47.2 +/- 2.9 and 34.5 +/- 3.6 g, P less than .02 in the young and elderly, respectively), but the corresponding data for FGU were similar in the two groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1987

Basal glucose homeostasis with and without fixed concentrations of glucagon and insulin.

The aim of this study was to investigate the extent to which the basal steady state could be maintained with fixed concentrations of glucagon and insulin. To this end, arterial plasma glucose concentrations and peripheral glucose uptake (using the forearm technique) were compared in healthy men (age 19 to 23 years) in the normal postabsorptive state and after suppression of endogenous pancreatic secretion. Two groups (A and B), each consisting of four men, were studied. In group A, the study comprised a control period (I) of 40 minutes followed by a test period (II) of 180 minutes during which normal pancreatic secretion was maintained throughout. In group B, the study comprised a control period (I) of 40 minutes, a stabilization period (II) of 120 minutes, and a test period (III) of 120 minutes. After the control period with normal pancreatic secretion, a new steady state with fixed hormone concentrations was established during the first 90 minutes of period II using simultaneous infusions of somatostatin (250 micrograms/h), insulin (0.15 mU/kg/min) and glucagon, the latter being adjusted to maintain a stable arterial glucose level similar to the preceding control concentration. Thereafter, without further adjustment of the glucagon infusion rate, observations were continued during period III to assess the maintenance of the steady state. In group A, the range of variation in arterial glucose concentrations during periods I and II was 4.0 +/- 0.9 and 6.5 +/- 1.3 mg/dL, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Peripheral lactate and oxygen metabolism in man: the influence of oral glucose loading.

We investigated the influence of oral glucose loading (100 g) on glucose, lactate, and oxygen metabolism by deep (mainly muscle) and superficial (mainly skin and adipose tissue) forearm tissues. In normal men aged 19 to 32 years (mean +/- SE, 24 +/- 1), basal arterialized venous-deep venous (A-DV) and arterialized venous-superficial venous (A-SV) plasma glucose concentration differences were 4.1 +/- 1.0 (P less than 0.001) and 4.7 +/- 1.0 (P less than 0.005) mg/dL, respectively, but increased markedly following glucose loading. During the first, second, and third hours after glucose ingestion, A-DV differences were 54 +/- 6,43 +/- 3, and 20 +/- 4 mg/dL, respectively, while the corresponding A-SV differences were 39 +/- 4, 17 +/- 2, and 8 +/- 2 mg/dL, respectively. Forearm glucose uptake by deep (FGU-D) and superficial (FGU-S) tissues basally was 0.057 +/- 0.010 and 0.012 +/- 0.002 mg/100 mL forearm/min respectively. From 15 to 180 minutes after glucose loading, mean FGU-D and FGU-S rose to 0.524 +/- 0.083 and 0.056 +/- 0.006 mg/100 mL forearm/min, respectively. Basal A, SV, and DV lactate concentrations were 0.55 +/- 0.04, 0.78 +/- 0.03, and 0.57 +/- 0.04 mmol/L, respectively (A-SV, P less than 0.001; SV-DV, P less than 0.001; A-DV, NS). Lactate production by superficial tissues (0.079 +/- 0.015 mumol/100 mL forearm/min) accounted for 62% of concurrent FGU-S.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Isolation of oxfendazole resistant Cooperia oncophora in cattle.

A field strain of Cooperia oncophora resistant to oxfendazole was isolated from a commercial cattle rearing property in Waikato, New Zealand. Resistance to oxfendazole was assessed by means of a faecal egg count depression test and an in vitro egg hatch test. This is the first documented case of anthelmintic resistance in Cooperia spp. and the first report of anthelmintic resistance in cattle in New Zealand.

Journal Article↗
PubMed1987

Mechanism of metformin action in non-insulin-dependent diabetes.

The mechanism of action of metformin was studied by comparing glucose turnover before and after a 75-g oral glucose load in 10 nonobese men with non-insulin-dependent diabetes mellitus (NIDDM) during metformin and placebo therapy by the combined application of the forearm and double-isotope techniques. During the study, 9 of the 10 patients were regularly receiving glibenclamide therapy. In 5 of the men, the first study was performed during metformin therapy, and the second study was done during placebo administration; in the other 5 subjects, the order was reversed. The interval between the studies was at least 3 mo. The metformin dosage was 1 g twice daily in 9 of the patients and 850 mg thrice daily in the 10th subject. In the basal state, metformin administration reduced plasma glucose levels from 172 +/- 14 to 103 +/- 9 mg/dl (P less than .005), hepatic glucose output (HGO) from 2.67 +/- 0.15 to 2.20 +/- 0.20 mg X kg-1 X min-1 (P less than .02), and forearm glucose uptake (FGU) from 0.106 +/- 0.18 to 0.039 +/- 0.016 mg X 100 ml-1 forearm X min-1 (P less than .005), whereas insulin (23 +/- 6 microU/ml) and lactate (1.56 +/- 0.18 mM) levels were unchanged. Although the oral glucose tolerance curve (OGTC) was significantly lowered by metformin, the incremental area under the curve and the insulin response were unchanged. The systemic appearance of ingested glucose was unaffected by metformin; 64 +/- 2% of the load was recovered peripherally in 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗