Biomedical subjects

G M Ward

Publications and source records attributed to G M Ward.

At least 19 recordsLinked to original sources

PubMed1998

The Melbourne Pre-Diabetes Study: prediction of type 1 diabetes mellitus using antibody and metabolic testing.

OBJECTIVES: To determine the utility of various autoantibodies in predicting progression to clinical diabetes in first-degree relatives of patients with type 1 diabetes mellitus. PARTICIPANTS: 3315 first-degree relatives of patients with type 1 diabetes (1161 parents, 1206 siblings and 948 offspring) recruited through diabetes clinics, private endocrinologists, Diabetes Australia and the Juvenile Diabetes Foundation. MAIN OUTCOME MEASURES: Prevalence of islet cell antibodies (ICA) levels > or = 20 JDFu, insulin autoantibodies (IAA) levels > 100 nU/mL, and antibodies to glutamic acid decarboxylase (GADAb) and tyrosine phosphatase IA2 (IA2Ab); change in beta cell function over time; and development of clinical diabetes. RESULTS: 2.6% of relatives had elevated ICA levels, 1.3% had elevated IAA levels and 0.3% had both. High ICA levels were significantly more frequent in siblings than in offspring or parents, and were more frequent in relatives younger than 20 years. GADAb were detected in 68% and IA2Ab in 57% of relatives with elevated ICA and/or IAA levels. Diabetes developed in 33 relatives (25 siblings, 2 offspring and 6 parents). Before diagnosis of clinical diabetes, high ICA levels were detected in 18 (58%), high IAA levels in 7 (23%), both in 5 (15%), and either in 19 (61%); GADAb were detected in 26 (84%), IA2Ab in 13 (42%), both in 11 (35%), and either in 28 (90%). First phase insulin release (FPIR) less than 50 mU/L was very strongly associated with progression to diabetes. In relatives with FPIR initially greater than 50 mU/L who eventually developed diabetes, there was a gradual and continuous reduction in FPIR over time before diagnosis. CONCLUSIONS: Type 1 diabetes can be diagnosed in the preclinical stage. The recently described antibodies to glutamic acid decarboxylase and tyrosine phosphatase IA2 appear superior to ICA as screening tools for the preclinical diagnosis of type 1 diabetes.

Adult↗

PubMed1998

Impact of family history of diabetes on the assessment of beta-cell function.

Numerous factors impinge on beta-cell function, and include the genetic background and insulin sensitivity of the individual. The aim of the present study was to evaluate the impact of a family history of non-insulin-dependent diabetes mellitus (NIDDM) on beta-cell function and to determine whether the relationships between beta-cell function and insulin sensitivity and age are influenced by a family history of diabetes. Thirty-three healthy control subjects (CON), 20 normal glucose-tolerant first-degree relatives of known NIDDM patients (REL), and 12 nondiabetic identical twins with an identical twin with known NIDDM were studied. Insulin and C-peptide responses to an acute intravenous glucose (AIRg) and glucagon bolus (at euglycemia [AIR[G.GON]]) were measured, as well as each individual's insulin sensitivity. Fasting insulin and C-peptide levels were similar in all groups. AIRg was significantly reduced by 65% in the nondiabetic twins compared with the CON and REL groups, with the latter group being similar to CON, whereas for the AIR[G.GON], the insulin responses in the twin subjects were reduced only by 35% compared with CON. Following stepwise (default) multiple regression analysis, three independent variables (insulin sensitivity, 23%; family history of NIDDM, 20%; and fasting glucose, 7%) were identified, and these combined to fit a model for prediction of acute beta-cell responses to glucose that yielded an R2 (adjusted) value of 50%. Following analysis of covariance (ANCOVA), a positive family history of NIDDM and insulin sensitivity but not the age of the subject were confirmed as separate factors affecting AIRg. In conclusion, in subjects with normal or mild glucose intolerance, the individual's genetic background and insulin sensitivity are important determinants of insulin secretion.

Adolescent↗

PubMed1997

Risk and mechanism of dexamethasone-induced deterioration of glucose tolerance in non-diabetic first-degree relatives of NIDDM patients.

We tested the hypothesis that glucose intolerance develops in genetically prone subjects when exogenous insulin resistance is induced by dexamethasone (dex) and investigated whether the steroid-induced glucose intolerance is due to impairment of beta-cell function alone and/or insulin resistance. Oral glucose tolerance (OGTT) and intravenous glucose tolerance tests with minimal model analysis were performed before and following 5 days of dex treatment (4 mg/day) in 20 relatives of non-insulin-dependent diabetic (NIDDM) patients and in 20 matched control subjects (age: 29.6 +/- 1.7 vs 29.6 +/- 1.6 years, BMI: 25.1 +/- 1.0 vs 25.1 +/- 0.9 kg/m2). Before dex, glucose tolerance was similar in both groups (2-h plasma glucose concentration (PG): 5.5 +/- 0.2 [range: 3.2-7.0] vs 5.5 +/- 0.2 [3.7-7.4] mmol/l). Although insulin sensitivity (Si) was significantly lower in the relatives before dex, insulin sensitivity was reduced to a similar level during dex in both the relatives and control subjects (0.30 +/- 0.04 vs 0.34 +/- 0.04 10(-4) min(-1) per pmol/l, NS). During dex, the variation in the OGTT 2-h PG was greater in the relatives (8.5 +/- 0.7 [3.9-17.0] vs 7.5 +/- 0.3 [5.7-9.8] mmol/l, F-test p < 0.05) which, by inspection of the data, was caused by seven relatives with a higher PG than the maximal value seen in the control subjects (9.8 mmol/l). These "hyperglycaemic" relatives had diminished first phase insulin secretion (O1) both before and during dex compared with the "normal" relatives and the control subjects (pre-dex O1: 12.6 +/- 3.6 vs 26.4 +/- 4.2 and 24.6 +/- 3.6 (p < 0.05), post-dex O1: 22.2 +/- 6.6 vs 48.0 +/- 7.2 and 46.2 +/- 6.6 respectively (p < 0.05) pmol x l(-1) x min(-1) per mg/dl). However, Si was similar in "hyperglycaemic" and "normal" relatives before dex (0.65 +/- 0.10 vs 0.54 +/- 0.10 10(-4) x min(-1) per pmol/l) and suppressed similarly during dex (0.30 +/- 0.07 vs 0.30 +/- 0.06 10(-4) x min(-1) per pmol/l). Multiple regression analysis confirmed the unique importance of low pre-dex beta-cell function to subsequent development of high 2-h post-dex OGTT plasma glucose levels (R2 = 0.56). In conclusion, exogenous induced insulin resistance by dex will induce impaired or diabetic glucose tolerance in those genetic relatives of NIDDM patients who have impaired beta-cell function (retrospectively) prior to dex exposure. These subjects are therefore unable to enhance their beta-cell response in order to match the dex-induced insulin resistant state.

Adult↗

PubMed1997

The effect of norepinephrine on insulin secretion and glucose effectiveness in non-insulin-dependent diabetes.

It has previously been shown that in normal subjects, physiological elevation of norepinephrine (NE) impairs insulin sensitivity (Si) but does not influence insulin secretion. The aim of this study was to determine the effect of short-term physiological elevation of NE on insulin secretion, Si, and glucose-mediated glucose disposal, or the glucose effectiveness index (Sg), in non-insulin-dependent diabetes mellitus (NIDDM). Two intravenous glucose tolerance tests (IVGTTs) were performed in eight well-controlled NIDDM patients, using a supplemental exogenous insulin infusion to achieve an approximation of normal endogenous insulin secretion. The IVGTTs were performed in random order after 30 minutes of either the saline (SAL) or NE (25 ng/kg/min) infusions, which were continued throughout the 3-hour IVGTT. Sg and Si were estimated by minimal model analysis of the IVGTT data as previously described. Plasma C-peptide was used to estimate insulin secretion rate using the ISEC program. NE infusion produced approximately a threefold increase in plasma NE, associated with (1) a significant reduction in glucose disposal ([KG] SAL v NE, 0.73 +/- 0.06 v 0.61 +/- 0.06 x 10(-2).min-1, P < .05), (2) no reduction in Si (2.33 +/- 0.8 v 2.62 +/- 0.9 x 10(-4).min-1/mU/L, NS), (3) a reduced mean second-phase insulin secretion rate (1.21 +/- 0.19 v 1.01 +/- 0.16 x 10(-3) pmol/kg/min per mmol/L glucose, P < .05), (4) a significant increase in Sg (0.89 +/- 0.08 v 1.63 +/- 0.2 x 10(-2).min-1, P < .05), and (5) a corresponding increase in glucose effectiveness at zero insulin ([GEZI] 0.55 +/- 0.13 v 1.30 +/- 0.33 x 10(-2).min-1, P < .05). These results show that in contrast to normal subjects, physiological elevation of NE in NIDDM does not result in a reduction in Si, but causes a reduction in glucose disposal related to inhibition of insulin secretion that is only partially compensated for by increased Sg.

Adult↗

PubMed1996

A review of countermeasures to reduce radioiodine in milk of dairy animals.

The most effective countermeasure for radioiodine contamination of milk is to provide dairy animals with uncontaminated feed, with the added advantage that it will be effective for other radionuclides in the fallout. Another effective response is to process the milk into storable dairy products for an appropriate length of time to allow for physical decay. The use of additives given to ruminants to reduce radioiodine in milk is an alternative countermeasure which could be effective. Stable iodine administration is a practically feasible option which has the potential to reduce radioiodine levels in milk by at most a factor of three. Stable iodine supplementation should be at sufficiently high rates to be effective (and at least 1 g d-1 for dairy cows), particularly for ruminants already receiving high amounts of iodine in the diet. Currently available data are inadequate to recommend a suitable stable iodine administration rate for different species of ruminants. Other compounds, such as perchlorate and thiocyanate, also reduce the transfer to radioiodine to milk (and thyroid). Some of these compounds seem to be potentially equally as effective as stable iodine. However, currently there is inadequate information on their effectiveness and possible toxicity to both ruminants and humans for these compounds to be considered as suitable countermeasure additives.

Animals↗

PubMed1995

Insulinopenia and hyperglycemia influence the in vivo partitioning of GE and SI.

We determined the impact of variable insulinemia and glycemia on the in vivo partitioning of glucose effectiveness (GE) and insulin sensitivity (SI) and the in vitro intracellular processing of glucose metabolism. Six somatostatin- and [3-3H]glucose-infused dogs underwent euglycemic and hyperglycemic clamps at four physiological insulin (Ins) levels before a muscle biopsy. From the rates of glucose infusion (GINF), total glucose disposal (Rd), total glycolysis (GF), and glucose storage (GS), plots of delta GINF, delta Rd, delta GS vs. delta log Ins concentration were found to be linear for each dog, allowing calculation of the partitioning of GE and SI into their major in vivo sites (periphery vs. liver) and intracellular metabolic pathways (GS vs. GF). Insulinopenia induced a significant reduction in total GE. From insulinopenia to high insulinemia, the 2.3-fold increase in total GE was due to the increased peripheral glucose responsiveness of the GS pathway. Hyperglycemia induced a significant reduction in total SI, with approximately one-half of this reduction due to the decreased peripheral insulin responsiveness of the GF pathway. In skeletal muscle, both glycogen content and glycogen synthase fractional activity were positively correlated with log Ins concentration, Rd, and GS but negatively correlated with glucose 6-phosphate concentration. Moreover, both Rd and GS were negatively correlated with lactate concentration. We conclude that 1) the inhibition of GE and SI induced by insulinopenia and hyperglycemia, respectively, is due mainly to the reduced peripheral responsiveness of contrasting intracellular metabolic pathways; and 2) hyperinsulinemia and/or hyperglycemia stimulates glycogen synthesis and GF but not nonoxidative glycolysis.

Animals↗

PubMed1994

Impact of variable insulinemia and glycemia on in vivo glycolysis and glucose storage in dogs.

To determine the impact of variable plasma insulin concentrations and glycemia on the partitioning of whole body glucose metabolism between glycolysis and glucose storage, we estimated endogenous hepatic glucose production and rates of in vivo glycolytic flux (GF) and glucose storage (GS) in six normal dogs from the generation of plasma tritiated water (3H2O) and [3-3H]glucose specific activity during 150 min of somatostatin euglycemic (E) and hyperglycemic (H) clamps at hypoinsulinemic, basal, intermediate, and high insulin levels. During both E and H clamps, overall rates of GF and GS increased with the rising insulin levels, but the relative contributions to in vivo glucose disposal of GF decreased, whereas GS rose progressively with increasing insulin levels. The relative contribution of GS during H to overall glucose disposal was greater at the lower insulin level. In addition, in absolute terms, GF and GS were significantly higher (P < 0.05) during H than during E at all insulin levels. Moreover, the incremental rise in GF induced by H was equal for the low to intermediate insulin levels tested, independent of the prevailing free fatty acid (FFA) levels. However, when whole body glucose disposal rates were matched, GF and GS rates were independent of the coexisting glycemia, insulin, and/or FFA levels. We conclude that 1) insulin has a major impact on the intracellular fate of infused glucose, with a lesser but significant effect of hyperglycemia per se on these processes; 2) the magnitude of the hyperglycemia-induced increase in GF is independent of the prevailing insulin level from low to intermediate levels; and 3) in vivo GF and GS are dependent on the net rate of glucose uptake into cells but independent of absolute FFA levels or whether glucose uptake is stimulated by raised insulin or glucose levels.

Animals↗

PubMed1994

Increased glucose effectiveness in normoglycemic but insulin-resistant relatives of patients with non-insulin-dependent diabetes mellitus. A novel compensatory mechanism.

20 normoglycemic first degree relatives of non-insulin-dependent diabetes mellitus (NIDDM) patients were compared with 20 matched subjects without any family history of diabetes using the intravenous glucose tolerance test with minimal model analysis of glucose disappearance and insulin kinetics. Intravenous glucose tolerance index (Kg) was similar in both groups (1.60 +/- 0.14 vs 1.59 +/- 0.18, x 10(-2) min-1, NS). However, insulin sensitivity (Si) was reduced (3.49 +/- 0.43 vs 4.80 +/- 0.61, x 10(-4) min-1 per mU/liter, P = 0.05), whereas glucose effectiveness (Sg) was increased (1.93 +/- 0.14 vs 1.52 +/- 0.16, x 10(-2) min-1, P < 0.05) in the relatives. Despite insulin resistance neither fasting plasma insulin concentration (7.63 +/- 0.48 vs 6.88 +/- 0.45, mU/liter, NS) nor first phase insulin responsiveness (Phi1) (3.56 +/- 0.53 vs 4.13 +/- 0.62, mU/liter min-1 per mg/dl, NS) were increased in the relatives. Phi1 was reduced for the degree of insulin resistance in the relatives so that the Phi1 x Si index was lower in the relatives (11.5 +/- 2.2 vs 16.7 +/- 2.0, x 10(-4) min-2 per mg/dl, P < 0.05). Importantly, glucose effectiveness correlated with Kg and with basal glucose oxidation but not with total glucose transporter 4 (GLUT4) content in a basal muscle biopsy. In conclusion we confirm the presence of insulin resistance in first degree relatives of NIDDM patients. However, insulin secretion was altered and reduced for the degree of insulin resistance in the relatives, whereas glucose effectiveness was increased. We hypothesize that increased glucose effectiveness maintains glucose tolerance within normal limits in these "normoinsulinemic" relatives of NIDDM patients.

Adult↗

PubMed1994

The effect of 3 months of recombinant human growth hormone (GH) therapy on insulin and glucose-mediated glucose disposal and insulin secretion in GH-deficient adults: a minimal model analysis.

The effect of 3 months of low dose (120 micrograms/kg.week or 0.24 IU/kg.week) recombinant human GH (rhGH) treatment on glucose tolerance, insulin secretion, and insulin- and glucose-mediated glucose disposal was examined in 10 GH-deficient adults. The frequently sampled iv glucose tolerance test was performed at baseline and after 1 week and 3 months of rhGH therapy and analyzed by the minimal model method of Bergman to provide estimates of the glucose decay rate, first and second phase insulin secretion (phi 1 and phi 2), fractional clearance of insulin, and glucose-mediated and insulin-mediated glucose disposal. Fasting glucose, insulin, C-peptide, nonesterified fatty acids (NEFA), and serum cholesterol and triglycerides were also measured. When the 1 week data were compared to baseline, there was a small but significant rise in mean (+/- SE) fasting glucose (4.62 +/- 0.17 vs. 5.1 +/- 0.15 mmol/L; P < 0.01), NEFA (0.70 +/- 0.09 vs. 1.1 +/- 0.12 mmol/L; P < 0.005), insulin (93.6 +/- 8.9 vs. 238.9 +/- 9.2 pmol/L; P < 0.0001), C-peptide (0.32 +/- 0.13 vs. 0.66 +/- 0.13 nmol/L; P < 0.005), and phi 1 (11.9 +/- 1.3 vs. 16.2 +/- 1.8 pmol/L.min/mmol.L x 10(2)) and phi 2 (1.43 +/- 0.17 vs. 3.15 +/- 0.25 pmol/L.min/mmol.L x 10(3); P < 0.05). Conversely, there were associated decreases in glucose decay rate (1.83 +/- 0.26 vs. 1.28 +/- 0.12 min-1; P < 0.05) and insulin-mediated glucose disposal (0.36 +/- 0.08 vs. 0.18 +/- 0.06 min/pmol.L x 10(-4); P < 0.005). There was no change in glucose-mediated glucose disposal or the fractional clearance of insulin. By 3 months, fasting insulin and C-peptide levels remained significantly elevated, whereas other parameters had returned to baseline. There was a minor reduction in serum cholesterol at 1 week (5.1 +/- 0.15 vs. 4.62 +/- 0.17 mmol/L; P < 0.01), which was not maintained at 3 months. Serum triglycerides remained unchanged throughout the study. We conclude that short term low dose rhGH treatment of GH-deficient adults induces a temporary state of mild glucose intolerance, hyperinsulinemia, insulin resistance, and raised NEFA levels at 1 week. By 3 months, these metabolic disturbances had returned to baseline for a persisting modest hyperinsulinemia. Whether this hyperinsulinemia will last over the longer term and/or has distant detrimental metabolic consequences in the individual must await further studies.

Adult↗

PubMed1993

Impaired glucose tolerance after endurance exercise is associated with reduced insulin secretion rather than altered insulin sensitivity.

Paired frequently sampled intravenous glucose tolerance tests (FSIGT) were performed on five highly trained athletes within 2 hours of completing a 6-day ultramarathon run (E) and after 2 weeks of complete rest (R). Severe exercise increased free fatty acid (FFA) levels (E 1.2 +/- 0.16 v 0.42 +/- 0.07 mmol/L, P < .01) and norepinephrine levels (E 573 +/- 141 v 224 +/- 33 pg/mL, P < .01), with only moderate reductions in glucose tolerance (glucose disappearance [Kg] E 1.06 +/- 0.2 v R 1.7 +/- 0.3 min-1 x 10(2), P < .05). The minimal model analysis of FSIGT data using the method of Bergman et al (Endocr Rev 6:45-86, 1985) showed a reduced second-phase insulin secretion ([phi 2] E 5.2 +/- 1.3 v 13 +/- 2.2 microU/mL.min-2 per mg/dL, P < .05) and glucose disposition index ([SI x phi 2] E 33.8 +/- 10 v 73.9 +/- 11 mg-1.dL.min-3 x 10(4), P < .02). Insulin sensitivity (SI) and glucose-mediated glucose disposal (SG) were unchanged (SI E 6.9 +/- 1.0 v 6.0 +/- 0.6 min-1 per microU/mL x 10(4); SG E 1.8 +/- 0.6 v 1.4 +/- 0.3 min-1 x 10(2)). Reduced glucose tolerance after prolonged extreme physical exercise was accompanied by reduced phi 2 and not by alterations of SI or SG, despite the marked increase of FFA levels. Elevated norepinephrine levels, reflecting activation of the sympathetic noradrenergic system, was also associated with the reduction in Kg. The reduction in phi 2 would promote mobilization of FFA, the predominant metabolic substrate in these endurance events.

Adult↗

PubMed1992

The effect of epinephrine on glucose-mediated and insulin-mediated glucose disposal in insulin-dependent diabetes.

The aim of this study was to determine the relative roles of changes in glucose-mediated glucose disposal (SG) and insulin sensitivity (SI) on the impairment of glucose disposal caused by epinephrine (EPI) infusion in type I (insulin-dependent) diabetes mellitus (IDDM). Seven non-obese young adult diabetics with minimal endogenous insulin secretion had EPI infusions at 25 ng/kg/min for 5.5 hours, after a basal overnight insulin infusion (12 mU/kg/h), and glucose infusion as required to maintain euglycemia. The EPI infusion produced approximately an eightfold increase in plasma EPI. At 2.5 hours, an intravenous glucose tolerance test (IVGTT) was performed with supplemental exogenous insulin infusion to achieve an approximation of normal endogenous insulin secretion. In random order, each subject also had a control (CTR) infusion of basal insulin before the IVGTT. The results were analyzed according to a modification of the minimal model of Bergman et al. EPI infusion was associated with (1) elevated basal plasma glucose (EPI v CTR, 9.8 +/- 0.3 SE v 7.7 +/- 0.7 mmol/L, P less than .05); (2) elevated plasma nonesterified fatty acids (NEFA, 0.9 +/- 0.1 v 0.3 +/- 0.1 mmol/L, P less than .05); and (3) profoundly reduced glucose disposal (KG 0.59 +/- 0.1 v 1.91 +/- 0.33 min-1 x 10(2), P less than .02). Further analysis showed that the reduced glucose disposal was attributable to a marked decrease in SI (EPI 0.9 +/- 0.5 v CTR 7.03 +/- 3.2 min-1.mU-1.L x 10(4), P less than .05) with no significant change in SG (EPI 2.5 +/- 0.2 v CTR 3.1 +/- 0.5 min-1 x 10(2), NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Effects of acute and chronic counterregulatory hormone infusions on glucose tolerance and insulin sensitivity in diabetic dogs.

The effects of elevated EPI and CORT levels on KG, SI, and SG were studied in dogs with alloxan-induced diabetes. Conscious dogs received SAL, EPI 20 ng.kg-1.min-1 for 30 min (short EPI) or 72 h (long EPI), or CORT 200 micrograms.kg-1.min-1 for 60 min (short CORT) or 72 h (long CORT) before assessment of glucose metabolism by rapid sampling for glucose and insulin levels after 300 mg/kg i.v. glucose and exogenous insulin infusion designed to simulate the normal secretory pattern. With EPI infusion, KG fell acutely from 2.9 +/- 0.4 to 2.0 +/- 0.2%/min (SAL vs. short EPI, P < 0.05), but rose to 3.4 +/- 0.4%/min during long EPI. Minimal-model analysis of the glucose response with the insulin data as input showed that SI decreased acutely from 4.7 +/- 1.8 to 2.5 +/- 0.6 x 10(-5) min-1/pM (SAL vs. short EPI, P < 0.05), but rose to 4.5 +/- 2.5 x 10(-5) min-1/pM during long EPI. The effects of EPI on SG paralleled the results for KG and SI, with acute decline from 3.9 +/- 0.4 to 2.1 +/- 0.4 x 10(-2) min-1 (SAL vs. short EPI, P < 0.05) and recovery to 3.3 +/- 0.3 x 10(-2) min-1 during long EPI. During CORT infusion, KG tended to fall (SAL 2.9 +/- 0.4 vs. short CORT 2.5 +/- 0.5 vs. long CORT 2.2 +/- 0.5%/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Masking of diabetic phenotype on a low-energy diet despite persistence of impaired insulin response.

Type 2 diabetes has been postulated to be a "thrifty genotype" that aids fuel conservation; to investigate this hypothesis, type 2 diabetic and nondiabetic subjects, normal weight and obese, were studied after both 6 days on a 700-calorie diet and 6 days on a 2,800-calorie diet. On 2,800 calories per day, the median basal plasma glucose was raised in diabetics compared with nondiabetic subjects (median, 5.5 and 4.5 mmol/L, respectively; P = .003), but on the low-energy diet there was no difference (4.1 and 3.7 mmol/L, respectively; P greater than .05). Basal plasma insulin levels were similar in the diabetic and nondiabetic subjects and were twofold to threefold higher on the high- than low-energy diet in both diabetic (median, 7.8 and 3.1 mU/L on high- and low-energy diets, respectively; P = .007) and nondiabetic subjects (6.8 and 2.6 mU/L, respectively; P = .005). Similarly, the postprandial insulin concentrations increased to the same degree on the high- compared with the low-energy diet in diabetic (median postprandial increment, 14.9 and 3.4 mU/L; P = .005) and nondiabetic patients (9.5 and 3.0 mU/L; P = .005) and the beta cells in type 2 diabetes appeared to modulate normally to different calorie intakes. On both diets, the diabetic subjects had an impaired first-phase insulin response to an intravenous glucose load compared with nondiabetic subjects (high-energy diet median first-phase increment, 4.3 and 21.2 mU/L in diabetic and nondiabetic subjects, P = .0007; low-energy diet, 4.0 and 20.4 mU/L, respectively, P = .003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

A modified minimal model analysis of insulin sensitivity and glucose-mediated glucose disposal in insulin-dependent diabetes.

Although glucose utilization is impaired in insulin-dependent diabetes mellitus (IDDM), it is unclear whether this is due to reductions in insulin sensitivity (Si) and/or glucose-mediated glucose disposal (SG). The minimal model of Bergman et al can be applied to a frequently sampled intravenous glucose tolerance test (FSIGT) to simultaneously estimate Sl and SG, but cannot accommodate data from diabetics. Exogenous insulin approximating the normal pattern of insulin secretion was infused during FSIGTs in eight young non-obese C-peptide-negative IDDM subjects, but with the total dose modified to achieve sufficient glucose disappearance rates (KG) to allow analysis of data. The minimal model was modified to model the effects of the exogenous insulin on glucose kinetics to estimate SI and SG. Despite deliberately achieving supranormal plasma-free insulin levels during the FSIGT ("first-phase insulin" = 62 +/- 9 SE mU/L; "second phase insulin" = 34 +/- 9 mU/L), the diabetics showed low-normal KG values (1.3 +/- 0.29 min-1 X 10(2). Using the model, good parameter resolution (fractional SD [FSD] less than .5) was achieved (IDDM v controls: SI = 2.5 +/- 0.6 v 8.3 +/- 1.5 min-1.mU-1.L-1 X 10(4); SG = 1.6 +/- 0.5 v 2.6 +/- 0.2 min-1 X 10(2); P less than .05). This reduction in SG was confirmed in the same IDDM subjects by FSIGT during basal insulin infusion only (SG = 1.0 +/- 0.3 min-1 X 10(2)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Accuracy, patient acceptance and clinical application of capillary HbA1c monitoring.

HbA1c values in capillary blood (50 microliters) were compared with venous samples, assayed by HPLC (normal less than 6.6%) in 64 Type 1 and Type 2 diabetic patients. One group (n = 43) collected capillary blood in the Outpatient Department simultaneously with a venous sample. The capillary sample collection was not supervised. A second group (n = 21) obtained two capillary samples during routine home blood glucose monitoring in Unistep containers within 2 days of the venous sample and posted them to the laboratory with a questionnaire about the ease of use and acceptance of the method. In the home collection group, 97% returned samples, there were no postal losses, and 75% returned questionnaires. Although 18% of patients had difficulty collecting the samples, all preferred the Unistep method to venepuncture. Correlation of capillary and venous samples was good for patients (r = 0.97, n = 53). The mean absolute difference between the two methods was 0.36 +/- 0.04 (+/- SE) %Hb. Eleven samples had to be excluded (insufficient blood; samples undated). The standard deviation for capillary duplicates was 0.14%, at a mean of 8.7%. During laboratory storage capillary HbA1c was initially slightly higher than corresponding venous values with some decrease (7.7% to 7.2%) over 7 days. HbA1c values in home-collected samples are accurate and reproducible when compared with venous samples assayed by HPLC, and the method was acceptable to patients.

Adolescent↗

PubMed1990

Application of the SAAM modeling program to minimal model analysis of intravenous glucose tolerance test data.

The minimal model approach to analysis of intravenous glucose tolerance tests (IVGTT) yields estimates of parameters representing insulin sensitivity, glucose-mediated glucose disposal and pancreatic responsiveness. The precision of these estimates can deteriorate if the glucose and insulin data lack well-defined structure or freedom from data noise (random error). The precision of parameter estimates can be enhanced if data sets from two or more IVGTTs, obtained under different experimental conditions in the same subject, are analysed together in one data file. Following initial fitting using CONSAM, the conversational version of the modeling program SAAM, those parameters whose estimates remain at the same value under the different experimental conditions are constrained. This effectively reduces the number of adjustable parameters, and their estimates can then be fine-tuned with enhanced precision using the batch version of SAAM.

Animals↗

PubMed1990

Milk distribution and feeding practice data for the PATHWAY model.

Milk is a major source for ingestion of several radionuclides, particularly when it is produced from fresh forage. Estimation of radionuclide ingestion via milk from Nevada Test Site fallout events in the 1950s required information on the sources of milk, feeding practices for cows, and elapsed time between milking and consumption for various geographic areas. These data were essential input to the food-chain model, PATHWAY. A data base was compiled from personal interviews. Milk sources included private cows, local dairies, and regional plants that collected from and distributed to wide geographic areas. Estimates of the contribution of each source were made for communities in a nine-state area. Pasture seasons varied from 3 to 6 mo. Pasture use varied from zero to 80% of the cows' diet. Pasture use declined during the 1950s, as did the number of family cows and local dairy plants. Regional distributors captured a larger portion of the market, and improved technologies increased the shelf life of milk. These factors tended to reduce the human intake of fallout radionuclides from milk in the latter part of the 1950s.

Animals↗