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Biomedical subjects

John N Clore

Publications and source records attributed to John N Clore.

8 recordsLinked to original sources

Differential effect of saturated and polyunsaturated fatty acids on hepatic glucose metabolism in humans.

Prolonged infusions of lipid and heparin that achieve high physiological free fatty acid (FFA) concentrations inhibit hepatic (and peripheral) insulin sensitivity in humans. These infusions are composed largely of polyunsaturated fatty acids (PUFA; linoleic and linolenic). It is not known whether fatty acid composition per se affects hepatic glucose metabolism in humans. To address this issue, we examined the impact of enteral infusions of either palm oil (48% palmitic, 35% oleic, and 8% linoleic acids) or safflower oil (6% palmitic, 12% oleic, 74% linoleic acids) in 14 obese nondiabetic subjects. (2)H(2)O was administered to determine the contribution of gluconeogenesis to endogenous glucose production (EGP), and a primed continuous infusion of [6,6-(2)H]glucose was administered to assess glucose appearance. As a result of the lipid infusions, plasma FFA concentrations increased significantly in both the palm oil (507.5 +/- 47.4 to 939.3 +/- 61.3 micromol/l, P < 0.01) and safflower oil (588.2.0 +/- 43.0 to 857.8 +/- 68.7 micromol/l, P < 0.01) groups after 4 h. EGP was similar at baseline (12.4 +/- 1.8 vs. 11.2 +/- 1.0 micromol x kg FFM(-1) x min(-1)). During a somatostatin-insulin clamp, the glucose infusion rate was significantly lower (AUC glucose infusion rate 195.8 +/- 50.7 vs. 377.8 +/- 38.0 micromol/kg FFM, P < 0.01), and rates of EGP were significantly higher (10.7 +/- 1.4 vs. 6.5 +/- 1.5 micromol x kg FFM(-1) x min(-1), P < 0.01) after palm oil compared with safflower oil, respectively. Baseline rates of gluconeogenesis and glycogenolysis were also similar. However, after lipid infusion, rates of glycogenolysis were suppressed by safflower oil but not by palm oil. Thus these studies demonstrate, for the first time in humans, a differential effect of saturated fatty acids and PUFA on hepatic glucose metabolism.

Adult↗

Assessing the health of future physicians: an opportunity for preventive education.

INTRODUCTION: Research shows that physicians who model prevention are more likely to encourage preventive behaviors in their patients. Therefore, understanding the health of medical students ought to provide insight into the development of health promotion programs that influence the way these future physicians practice medicine. A university-based General Clinical Research Center (GCRC) provides a venue well suited to the health assessment and education of medical students. This research explores the utility of a GCRC in a program measuring the prevalence of clinical risk factors and related health behaviors in first-year medical students. METHODS: A 6-year cross-sectional study of first-year medical students measured clinical and behavioral variables associated with metabolic syndrome. Statistical testing was used to determine the prevalence of risk factors and the influence of gender in these variables. RESULTS: This group of medical students displayed better health indicators than did the general young adult population; however a small proportion of medical students exhibited early risk factors for chronic disease. There were significant gender differences in mean values for clinical risk factors, with males displaying higher cardiovascular risk overall. Males and females demonstrated significant differences in dietary intake and exercise programs. DISCUSSION: A GCRC can be used to provide a health assessment of medical students. Moreover, some students may benefit from health promotion programs incorporated into medical school curricula. This study provides a foundation for further research on the health of future physicians and the development of health promotion programs for this population. It also begins to explore the use of a GCRC as a teaching resource for medical students.

Adult↗

Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats.

Dietary fatty acid composition modifies hepatic lipid metabolism. To determine the effects of fatty acids on hepatic triglyceride storage, rats were fed diets enriched in carbohydrates (control), fish oil, or lard. After 4 weeks, the animals were fasted overnight. In the morning, the animals were either sacrificed or fed 8 g of their respective diets before sacrifice. Animals ingested more food calories with diets containing fish oil than with other diets. However, fish oil-fed animals weighed less and had less body fat. In fish oil-fed animals, liver triglyceride was lower by 27% (P <.05) and 73% (P <.01) than in control- and lard-fed animals, respectively. Fish oil altered the postprandial gene expression of hepatic regulators of fatty acid degradation and synthesis. Fish oil feeding blunted the normal postprandial decline in fatty acid degradation genes (PPARalpha, CPT1, and ACO) and blunted the normal postprandial rise in triglyceride synthesis genes (SREBP1-c, FAS, SCD-1). Therefore, the direct postprandial effect of fish oil ingestion decreases the propensity for hepatic triglyceride storage. In conclusion, n-3 polyunsaturated fatty acids decrease total body weight, total body fat, and hepatic steatosis.

Animals↗

Basal insulin therapy.

The initiation of insulin therapy is a significant event for patients with diabetes and the physicians who care for them. Reluctance to begin insulin is multifactorial, with a major stumbling block being the perceived complexity of insulin. However, this complexity can be easily overcome by separation of insulin administration into its two components: basal and bolus therapy. An understanding of the role of basal insulin in the regulation of glucose and the development of strategies to implement basal insulin therapy can provide a transition that is rational and highly effective in most patients. The strategy also offers a unique approach to diabetes education, which permits a focused and patient-specific correction to glucose abnormalities.

Circadian Rhythm↗

Diabetes and hypertension in severe obesity and effects of gastric bypass-induced weight loss.

OBJECTIVE: To evaluate the preoperative relationships of hypertension and diabetes mellitus in severe obesity and the effects of gastric bypass (GBP)-induced weight loss. SUMMARY BACKGROUND DATA: Severe obesity is associated with multiple comorbidities, particularly hypertension and type 2 diabetes mellitus, that may affect life expectancy. METHODS: The database of patients who had undergone GBP by one general surgeon at a university hospital between September 1981 and January 2000 was queried as to weight, body mass index (BMI), pre- and postoperative diabetes, hypertension, and other comorbidities, including sleep apnea, hypoventilation, gastroesophageal reflux, degenerative joint disease, urinary incontinence, venous stasis, and pseudotumor cerebri. RESULTS: Of 1,025 patients treated, 15% had type 2 diabetes mellitus and 51% had hypertension. Of those with diabetes, 75% also had hypertension. There was a progressive increase in age between patients who had neither diabetes nor hypertension, either diabetes or hypertension, or both diabetes and hypertension. At 1 year after GBP (91% follow-up), patients lost 66 +/- 18% excess weight (%EWL) or 35 +/- 9% of their initial weight (%WL). Hypertension resolved in 69% and diabetes in 83%. Patients who resolved their hypertension or diabetes had greater %EWL and %WL than those who did not. African-American patients had a higher risk of hypertension than whites before GBP and were less likely to correct their hypertension after GBP. There was significant resolution of other obesity comorbidity problems. At 5 to 7 years after GBP (50% follow-up), %EWL was 59 +/- 24 and %WL was 31 +/- 13; resolution of hypertension was 66% and diabetes 86%. CONCLUSIONS: These data suggest that type 2 diabetes mellitus and hypertension may be indirectly related to each other through the effects of obesity, but not directly as to cause and effect. The longer a person remains severely obese, the more likely he or she is to develop diabetes, hypertension, or both. GBP-induced weight loss is effective in correcting diabetes, hypertension, and other comorbidities but is related to the %EWL achieved. Severely obese African-Americans were more likely to have hypertension and respond less well to GBP surgery than whites. These data suggest that GBP surgery for severe obesity should be provided earlier to patients to prevent the development of diabetes and hypertension and their complications.

Adolescent↗

Relation of diabetic patients' health-related control appraisals and physician-patient interpersonal impacts to patients' metabolic control and satisfaction with treatment.

Desire for healthcare control, health locus of control, perceived control over diabetes, satisfaction with diabetes treatment, and general personality traits were assessed in 54 Type 1 and Type 2 diabetic patients of the same male endocrinologist during a regularly scheduled office visit. At the end of the consultation, both patients and the physician completed a measure describing the interpersonal impacts produced in each by the other's control and affiliation behaviors. Patient success at diabetes control was assessed via glycosylated hemoglobin A1C (HA1C) level on the day of the visit and variability in HA1C levels across several visits. Patients' satisfaction with treatment was unrelated to diabetes control measures. Patients' desire for behavioral involvement in their own healthcare and NEO Agreeableness scores were positively associated with diabetes control. Better diabetes control also resulted when the physician perceived patients to be more controlling and less submissive, and when there was more reciprocity in patient and physician's perceptions of the other's controlling interpersonal behavior. Findings support the conclusion that both a patient's self-reported desire for involvement in his or her healthcare and the transactional fit of patient-physician interpersonal behaviors are potentially important contributors to better diabetes outcomes.

Adult↗

The role of plasma fatty acid composition in endogenous glucose production in patients with type 2 diabetes mellitus.

Hepatic insulin resistance and increased endogenous glucose production (EGP) are associated with increased plasma free fatty acids (FFA). However, the contribution of FFA composition to the regulation of EGP is not known. Six obese nondiabetic subjects and 6 patients with type 2 diabetes mellitus (DM2) were studied after an overnight and a 3-day fast. Plasma insulin concentrations after an overnight fast were similar in the DM2 and nondiabetic patients (88.8 +/- 26.4 v 57.6 +/- 12.6 pmol/L, not significant [NS]) despite increased plasma glucose (9.9 +/- 1.8 v 5.1 +/- 0.1 mmol/L, P <.01) and EGP (510.3 +/- 77.7 v 298.3 +/- 18.3 micromol x m(-2) x min(-1), P <.05) in the patients with DM2. Absolute rates of gluconeogenesis using the heavy water method were also increased in the patients with DM2 (346.8 +/- 74.9 v 198.8 +/- 16.4 micromol x m(-2). min(-1), P <.05). No differences were observed in plasma polyunsaturated fatty acids (PUFA) between the diabetic and nondiabetic subjects. However, total saturated fatty acid (SFA) concentrations (350 +/- 37.4 v 230.9 +/- 33.3 micromol/L, P <.02) were significantly increased in the diabetic subjects. Rates of EGP were correlated with total plasma FFA concentration (r =.71, P <.01) and the concentration of SFA (r =.71, P <.01), but not monounsaturated fatty acids or PUFA. Rates of gluconeogenesis were also correlated with plasma FFA (r =.64, P <.05) and SFA (r =.67, P <.05). We observed no relationship between EGP and either total FFA or fatty acid composition after a 3-day fast. We conclude that increases in EGP are associated with concentrations of plasma SFA after an overnight fast.

Adult↗

Lipid metabolism and resistin gene expression in insulin-resistant Fischer 344 rats.

The interrelationship between insulin and leptin resistance in young Fischer 344 (F344) rats was studied. Young F344 and Sprague-Dawley (SD) rats were fed regular chow. F344 animals had two- to threefold higher insulin and triglyceride concentrations and increased stores of triglycerides within liver and muscle. F344 animals gained more body fat. Both acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase I gene expression were 20-50% less in F344 animals than in age-matched SD animals. Peroxisome proliferator-activated receptor-alpha gene expression was reduced in 70-day-old F344 animals. Finally, resistin gene expression was similar in 70-day-old SD and F344 animals. Resistin gene expression increased fivefold in F344 animals and twofold in SD animals from 70 to 130 days, without a change in insulin sensitivity. We conclude that young F344 animals have both insulin and leptin resistance, which may lead to diminished fatty oxidation and accumulation of triglycerides in insulin-sensitive target tissues. We did not detect a role for resistin in the etiology of insulin resistance in F344 animals.

Acyl-CoA Oxidase↗