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Biomedical subjects

J B Halter

Publications and source records attributed to J B Halter.

At least 37 records · Page 2Linked to original sources
PubMed1998

Differential effects of BMI on diabetes risk among black and white Americans.

OBJECTIVE: To determine whether the associations of BMI and fat distribution with diabetes risk are modified by race. RESEARCH DESIGN AND METHODS: Data from the National Health and Nutrition Examination Survey, Epidemiologic Follow-up Study (1971-1992), were used to investigate potential interactions of BMI and fat distribution with race. Incident diabetes was defined by self-report of physician-diagnosed diabetes, hospital and nursing home discharge records, and death certificates. RESULTS: Among the 1,531 black and 9,852 white subjects who were nondiabetic at baseline, 1,139 (10.0%) developed diabetes during 20 years of follow-up. Although the cumulative risk of diabetes increased with baseline BMI in all four race-sex groups, the sex-specific odds ratios (ORs) for black:white subjects decreased with increasing BMI. In particular, for BMI of 22 kg/m2, the OR of diabetes for black:white individuals was 1.87 and 1.76 (P < 0.01) for men and women, respectively; for BMI of 32 kg/m2, the OR decreased to 0.99 and 1.20 (NS) for men and women, respectively. Skinfold ratio was also associated with increased diabetes risk in all race-sex groups, but did not modify the association between race and diabetes. CONCLUSIONS: These findings suggest that the effect of BMI on diabetes risk is different for black and white Americans, with a larger risk for blacks than whites at low BMI and an equivalent risk for both groups at high BMI. A lower degree of visceral adiposity among blacks at higher BMI or a greater impact of visceral adiposity among blacks at low BMI may help explain the interaction of race and BMI on diabetes risk.

Adult↗
PubMed1997

Glucose metabolism in older adults: a study including subjects more than 80 years of age.

OBJECTIVE: This study was undertaken to understand the dynamics of glucose metabolism in healthy non-diabetic subjects older than age 80 (old-old) compared with subjects aged 61 to 79 (young-old), as well as to compare healthy older subjects with impaired glucose tolerance (IGT) with older subjects with normal glucose tolerance (NGT). DESIGN: A cross sectional, observational study. SETTING: A university hospital clinical research center. PARTICIPANTS: There were 28 community-dwelling adults, 10 older than age 80 and 18 aged 61 to 79. Thirteen of these people had NGT and 15 had IGT. Subjects were not taking any medication that interfered with glucose tolerance. MEASUREMENTS: Status of glucose tolerance was determined by an oral glucose tolerance test categorized as NGT or IGT according to WHO criteria. Insulin sensitivity (SI) and glucose effectiveness (SG) were assessed using a tolbutamide-assisted intravenous glucose tolerance test (IVGTT). The data were analyzed using the Minmod modeling program. Glucose tolerance (K(g)) and the acute insulin response to glucose (AIRg) were calculated from the IVGTT. RESULTS: There were no significant differences between the young-old and old-old in body mass index or in plasma glucose, insulin, or C-peptide levels in the fasting state or during the OGTT. Values for K(g), SI, SG, and AIRg from the IVGTT were similar in the two age groups. When the subjects were classified by glucose tolerance status, the subjects with NGT had age, gender, and body mass index similar to the subjects with IGT. Older people with IGT had a lower K(g) and tended to have higher fasting glucose and similar fasting insulin compared with people with NGT. IGT subjects had lower SI and tended to have lower SG. The AIRg in IGT subjects tended to be low rather than high when compared with older people with NGT. CONCLUSION: Otherwise healthy adults more than 80 years of age have measures of glucose metabolism similar to people aged 61 to 79. The presence of IGT in older adults is associated with insulin resistance, regardless of patient age. We hypothesize that the lack of pancreatic islet compensation for insulin resistance may contribute to impaired glucose tolerance in older adults.

Aged↗
PubMed1997

Functional deficits in medial gastrocnemius grafts in rats: relation to muscle metabolism and beta-AR regulation.

This study tested the hypothesis that alterations in the metabolic integrity of grafted muscle contribute to its diminished ability to sustain power. Compared with control muscles, muscles studied 120 days after the grafting procedure had lower specific force and sustained power. The sustained power protocol resulted in a depletion of muscle glycogen in control (83%) and grafted (85%) animals. Grafts had lower pre- and poststimulation glycogen, diminished citrate synthase activity, and greater hexokinase activity. No differences were observed in phosphofructokinase activity, glucose transporter GLUT-4 content, fiber type, beta-adrenergic-receptor (beta-AR) density, or binding affinity. Isoproterenol-stimulated adenylyl cyclase activity was lower in grafted vs. control muscle, suggesting an uncoupling of the beta-AR-effector complex. Thus the diminished ability of the grafted muscle to sustain power may be explained, in part, by a decrease in energy available from glycogen stores and/or a decrease in oxidative capacity.

Adenylyl Cyclases↗
PubMed1997

Diminished insulin and glucagon secretory responses to arginine in nondiabetic subjects with a mutation in the hepatocyte nuclear factor-4alpha/MODY1 gene.

Nondiabetic subjects with the Q268X mutation in the hepatocyte nuclear factor (HNF)-4alpha/MODY1 gene have impaired glucose-induced insulin secretion. To ascertain the effects of the nonglucose secretagogue arginine on insulin and glucagon secretion in these subjects, we studied 18 members of the RW pedigree: 7 nondiabetic mutation negative (ND[-]), 7 nondiabetic mutation positive (ND[+]), and 4 diabetic mutation positive (D[+]). We gave arginine as a 5-g bolus, followed by a 25-min infusion at basal glucose concentrations, and after glucose infusion to clamp plasma glucose at approximately 200 mg/dl. The acute insulin response (AIR), the 10-60 min insulin area under the curve (AUC), and the insulin secretion rate (ISR) were compared, as were the acute glucagon response (AGR) and glucagon AUC. The ND[+] and D[+] groups had decreased insulin AUC and ISR and decreased glucose potentiation of AIR, insulin AUC, and ISR to arginine administration when compared with the ND[-] group. At basal glucose concentrations, glucagon AUC was greatest for the ND[-] group, intermediate for the ND[+] group, and lowest for the D[+] group. During the hyperglycemic clamp, there was decreased suppression of glucagon AUC for both ND[+] and D[+] groups compared with the ND[-] group. The decreased ISR to arginine in the ND[+] group compared with the ND[-] group, magnified by glucose potentiation, indicated that HNF-4alpha affects the signaling pathway for arginine-induced insulin secretion. The decrease in glucagon AUC and decreased suppression of glucagon AUC with hyperglycemia suggest that mutations in HNF-4alpha may lead to alpha-cell as well as beta-cell secretory defects or a reduction in pancreatic islet mass.

Adult↗
PubMed1997

Characteristics related to poor glycemic control in NIDDM patients in community practice.

OBJECTIVE: To identify clinical characteristics related to poor glycemic control in patients with NIDDM cared for by Michigan primary care physicians. RESEARCH DESIGN AND METHODS: This study was a cross-sectional secondary analysis of data from 393 NIDDM patients (mean age, 63 +/- 11 years; 54% female; 92% white) in the 1990-1991 Michigan Diabetes in Communities II Study. We evaluated patient demographic, clinical, and physiological characteristics, attitudes toward diabetes, and self-care ability. Logistic regression was used for multivariate evaluation of the characteristics of those patients whose glycosylated hemoglobin (normal GHb 4-8%) was in the upper 25% of the study sample (GHb > 11.6%). RESULTS: A high meal-stimulated plasma C-peptide was associated with a lower likelihood of poor control (odds ratio [OR] for highest quartile vs. all others = 0.37; 95% CI 0.23-0.58). Longer time since diagnosis (OR for each 5 years duration = 1.28; 95% CI 1.07-1.53), poor self-care ability (OR = 1.85; 95% CI 1.27-2.71), and perceived absence of dietary recommendations (OR = 2.37; 95% CI 1.11-5.08) were also independently associated with presence in the highest GHb quartile. Characteristics that were not significantly related to poor glycemic control included sex, age, obesity, educational level, exercise, self-rated health status, and pharmacological treatment. CONCLUSIONS: 1) Poor glycemic control may reflect progressive failure of islet function, although the independent relationships of C-peptide level and time since diagnosis are consistent with concepts of heterogeneous mechanisms underlying NIDDM. 2) Despite the important relationships of biological characteristics of NIDDM to glycemic control, patient attitudes and self-care ability may be useful targets for designing management strategies for certain poorly controlled patients.

Aged↗
PubMed1996

Effect of aging on rat skeletal muscle beta-AR function in male Fischer 344 x brown Norway rats.

In this study, we tested the hypothesis that, in the male Fischer 344 x Brown Norway (F344xBN) rat, aging would be associated with an increase in sympathetic nervous system activity and a decrease in skeletal muscle beta-adrenergic-receptor (beta-AR) density and function. Radioligand-binding studies using [125I] iodocyanopindolol were done to evaluate beta-AR density (Bmax) and antagonist-binding affinity in gastrocnemius and cardiac muscle from 6-, 18-, and 28-mo-old male F344xBN rats. beta-AR function was measured as adenylyl cyclase (AC) activity stimulated by the beta-AR agonist isoproterenol (Iso, 10(-4) M). Basal arterial plasma norepinephrine (pNE) concentrations were higher in the 28-than in the 6- and 18-mo-old rats. Bmax was greatest and Iso-stimulated AC activity was unchanged in gastrocnemius muscle of the 28-mo-old age group. In contrast, there was an age-associated decrease in Bmax and Iso-stimulated AC activity in cardiac muscle. In conclusion, there was an age-associated increase in pNE concentrations in male F344xBN rats, suggesting an increase in sympathetic nervous system activity. In addition, there was an age-associated increase in skeletal muscle beta-AR density, whereas in skeletal muscle beta-AR-stimulated AC activity remained unchanged with age.

Adenylyl Cyclases↗
PubMed1996

The roles of catecholamines in glucoregulation in intense exercise as defined by the islet cell clamp technique.

Exercise at > 85% VO2max causes the greatest known physiological increases in glucose production rates (Ra). To define the relative roles of catecholamine versus glucagon/insulin responses in stimulating Ra, normal subjects in the postabsorptive state exercised at 87 +/- 2% VO2max during an islet cell clamp (IC): intravenous octreotide (somatostatin analog), 30 ng.kg-1.min-1; glucagon, 0.8 ng.kg-1.min-1; growth hormone, 10 ng.kg-1.min-1; and insulin adjusted to achieve euglycemia, then constant 56 +/- 7 min before exercise. Seven control subjects exercised without an IC. In four subjects (IC-1) with hormone infusions held constant during exercise, plasma insulin rose 76% and glucagon 35%, perhaps because of altered hemodynamics. In seven subjects (IC-2), hormone infusions were decreased stepwise during exercise and returned stepwise to initial rates during early recovery. Ra increased sixfold in control and both IC groups. Plasma norepinephrine and epinephrine likewise increased > 12-fold with no differences among groups; both catecholamines correlated closely with Ra. Because mixed venous blood plasma insulin declined and glucagon did not change in control subjects, the glucagon-to-insulin ratio increased from 0.20 to 0.26 (P = 0.02). In IC subjects, plasma insulin increased and glucagon was either constant (IC-2) or increased less than insulin, resulting in nonsignificant declines in the immunoreactive glucose-to-immunoreactive insulin ratio. Although a rise in insulin would have been expected to attenuate the Ra increment, this effect was overridden. The strong correlations of Ra with catecholamines and the similar Ra responses despite divergent glucagon-to-insulin responses are consistent with the primacy of catecholamines in regulation of Ra in intense exercise.

Adult↗
PubMed1996

Maturity onset diabetes of the young (MODY).

MODY is a sub-type of NIDDM. It is characterized by an early age of onset and autosomal dominant mode of inheritance. These features, and the availability of large multigenerational pedigrees, make MODY useful for genetic studies of diabetes. In the large 5-generational RW pedigree, MODY is tightly linked to genetic markers on chromosome 20q. Affected subjects in this family show abnormalities of carbohydrate metabolism, varying from impaired glucose tolerance (IGT) to severe diabetes. Approximately 30% of diabetic subjects become insulin-requiring, and vascular complications occur. MODY is also linked to the glucokinase gene on chromosome 7p and many different mutations associated with MODY have been identified in this gene. MODY, due to mutations in the glucokinase gene, is a relatively mild form of diabetes with mild fasting hyperglycaemia and IGT in the majority. Clinical investigative studies indicate that the genetic or primary defect in MODY is characterized by deranged and deficient insulin secretion and not by insulin resistance. There are quantitative and qualitative differences in insulin secretory defects which differentiate subjects with MODY due to mutation in the gene on chromosome 20q from those with glucokinase mutations. These differences correlate with the severity of diabetes between these two genetic forms of MODY.

Blood Glucose↗
PubMed1995

Altered insulin secretory responses to glucose in subjects with a mutation in the MODY1 gene on chromosome 20.

This study was undertaken to test the hypothesis that the diabetes susceptibility gene on chromosome 20q12 responsible for maturity-onset diabetes of the young (MODY) in a large kindred, the RW family, results in characteristic alterations in the dose-response relationships between plasma glucose concentration and insulin secretion rate (ISR) that differentiate this form of MODY from MODY in subjects with glucokinase mutations. Ten marker-positive subjects and six matched nondiabetic marker-negative subjects from the RW family received graded intravenous glucose infusions on two occasions separated by a 42-h continuous intravenous glucose infusion designed to prime the beta-cell to secrete more insulin in response to glucose. ISR was derived by deconvolution of peripheral C-peptide levels. Basal glucose and insulin levels were similar in marker-negative and marker-positive groups (5.3 +/- 0.2 vs. 5.0 +/- 0.2 mmol/l, P > 0.2, and 86.1 +/- 3.9 vs. 63.7 +/- 12.1 pmol/l, P > 0.1, respectively). However, the marker-positive subjects had defective insulin secretory responses to an increase in plasma glucose concentrations. Thus, as the glucose concentration was raised above 7 mmol/l, the slope of the curve relating glucose and ISR was significantly blunted in the marker-positive subjects (13 +/- 4 vs. 68 +/- 8 pmol.min-1.mmol-1 x 1, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Primacy of liver glucosensors in the sympathetic response to progressive hypoglycemia.

The impact of hepatic glucose concentration on the sympathetic response to progressive hypoglycemia was examined in chronically cannulated conscious male dogs (n = 6). Graded hypoglycemia was induced via peripheral insulin infusion (30 pmol.kg-1.min-1) with either peripheral (PER) or portal (POR) glucose infusion. Over the 260-min experimental period, arterial glycemia was adjusted from 5.2 +/- 0.1 to 2.5 +/- 0.1 mM in decrements of approximately 0.5 mM every 40 min. Arterial glycemias were not significantly different between PER and POR at any measured level. However, hepatic glycemia was significantly elevated at all times during POR (8.4 +/- 0.8 to 3.4 +/- 0.2 mM) when compared to PER (5.2 +/- 0.2 to 2.5 +/- 0.1 mM). Plasma epinephrine values were significantly greater during PER vs. POR at all arterial glycemias below 4.0 mM. At the lowest level of arterial glycemia studied (2.5 +/- 0.2 mM) the epinephrine response above basal was 3-fold greater for PER (8.7 +/- 1.7 nM) when compared to POR (2.6 +/- 0.6 nM) (P < 0.01). Plasma norepinephrine results were similar for the two protocols, with PER demonstrating a 3-fold greater response above basal when compared to POR at 2.5 mM arterial glycemia (P < 0.05). While the sympathetic response was markedly different between protocols when expressed as a function of arterial glycemia, when expressed as a function of hepatic glycemia this discrepancy was largely eliminated. This latter observation supports the liver as the primary locus for glycemic detection relevant to the sympathoadrenal response when hypoglycemia develops slowly--i.e., over a period of 2-3 h. A comparison of the current findings with our previous observations suggests that the hepatic glucosensors may play a greater role in hypoglycemic counterregulation as the rate of fall in glycemia is less.

Animals↗
PubMed1994

Maturity-onset diabetes of the young.

Maturity-onset diabetes of the young (MODY) is a subtype of noninsulin dependent diabetes mellitus (NIDDM). It is characterized by an early age of onset and autosomal dominant mode of inheritance. These features and the availability of large multigenerational pedigrees make MODY useful for genetic studies of diabetes. In the large, 5-generational RW pedigree, MODY is tightly linked to genetic markers on chromosome 20q. Affected subjects in this family show abnormalities of carbohydrate metabolism varying from impaired glucose tolerance (IGT) to severe diabetes. Approximately 30% of diabetic subjects become insulin requiring and vascular complications occur. MODY is also linked to the glucokinase gene on chromosome 7p and many different mutations associated with MODY have been identified in this gene. MODY due to mutations in the glucokinase gene is a relatively mild form of diabetes with mild fasting hyperglycemia and IGT in the majority. IT is rarely insulin requiring and rarely has vascular complications. Clinical studies indicate that the genetic or primary defect in MODY is characterized by deranged and deficient insulin secretion and not by insulin resistance and that there are quantitative and qualitative differences in insulin secretory defects which differentiate subjects with MODY due to glucokinase mutations from those with mutations in the gene on chromosome 20q. These differences correlate with the severity of diabetes between these two genetic forms of MODY.

Diabetes Mellitus, Type 2↗
PubMed1994

Interdisciplinary team training in geriatrics: reaching out to small and medium-size communities.

Since 1989, six teams in the state of Michigan have been involved in a team training program designed to promote the development of geriatric services in small to medium-size communities. The program was enthusiastically received by participants, but after 18 months, only half of the teams had implemented clinical services for older adults. Monitoring the progress of the teams over 18 months and analyzing the activities of two teams revealed that financially stable and supportive sponsoring agencies and the community were critical factors in the implementation of interdisciplinary clinical services in geriatrics. Future team training programs trying to promote the development of geriatric services in small to medium-size communities should try to address these issues through community organization interventions.

Community Participation↗
PubMed1994

Hypoglycemia counterregulation in elderly humans: relationship to glucose levels.

This study was designed to define the effect of human aging on hypoglycemia counterregulatory mechanisms. A hyperinsulinemic (2 mU.kg-1.min-1) glucose clamp procedure was used to control glucose and insulin levels during stepwise lowering of plasma glucose. Counterregulatory hormones, hepatic glucose production (HGP), glucose utilization, and symptoms of hypoglycemia were studied in 13 healthy young [age 24 +/- 1 (SE) yr] and 11 healthy old (age 65 +/- 1 yr) nondiabetic volunteers on two occasions: 1) at matched euglycemia and 70 and 60 mg/dl (study 1) and 2) at matched euglycemia and 60 and 50 mg/dl (study 2). The old had consistently lower epinephrine (P < 0.005), glucagon (P < 0.02), cortisol (P < 0.05), and pancreatic polypeptide (P < 0.02) responses at the 60-mg/dl glucose step in study 1. However, these differences were no longer detectable at the more severe hypoglycemic stimulus of 50 mg/dl in study 2. A consistent increase in HGP occurred in both groups only at the 50-mg/dl glucose step (study 2) and was not different between young and old. There were also no differences in symptom responses between young and old. In summary, we found that elderly individuals have a subtle impairment of the glucose counterregulatory response during moderate hypoglycemia, but this impairment is no longer detectable during more severe hypoglycemia.

Adult↗
PubMed1994

Glucoregulation during and after intense exercise: effects of beta-blockade.

To define the roles of beta- and alpha-adrenergic receptors in intense exercise, 17 lean healthy fit young males underwent 13.6 +/- 0.2 (+/-SE) min of cycle ergometer exercise: 6 at 100% maximum oxygen uptake (VO2max; MAX), 7 at their maximum possible (87 +/- 2.3%) during iv propranolol (P; 150 micrograms/kg bolus 30 min preexercise, then 80 micrograms/kg.min), and 7 (including 3 of the P subjects) at 87% VO2max (C) as controls for P. Plasma glucose increased from similar resting values to a peak in the early recovery period at 7.2 +/- 0.44 in MAX and 6.8 +/- 0.37 in P, but only 5.2 +/- 0.3 mmol/L in C. The rate of glucose appearance (Ra) rose about 8-fold in both MAX and P, but only 4-fold in C (P = 0.001). The rate of glucose disappearance (Rd) increased 4-fold in MAX, 5.5-fold in P, and 3-fold in C (P = 0.001). Plasma insulin declined during exercise (P < 0.05) in MAX and P, but not in C, whereas plasma glucagon increased modestly in all groups. The mean peak plasma norepinephrine level was 36.3 +/- 4.5 in MAX, 20.2 +/- 3.4 in P, and 15.2 +/- 2.9 nmol/L in C (P = 0.002); epinephrine reached 7141 +/- 1790 in MAX and 5605 +/- 1532 in P (P = NS), but only 1715 +/- 344 pmol/L in C (P = 0.03). Therefore, 1) an "unmasked" alpha-adrenergic effect, directly and/or via an altered glucagon/insulin ratio, probably contributed to increased Ra with P treatment; and 2) the marked facilitation of the increase in Rd with P supports a major role for beta-adrenergic restraint of Rd at this exercise intensity.

Adolescent↗