Soup Kettle Topics: Diet and Carbohydrates

Title: Rate of Glucose Fall Does Not Affect Counterregulatory Hormone Responses to Hypoglycemia in Normal and Diabetic Humans
Author: Amiel, S. A.; Simonson, D. C.; Tamborlane, W. V.; DeFronzo, R. A.; Sherwin, R. S.; (Date: Apr, 1987)
Journal: Diabetes; V. 36; Issue: 4; Pages: 518-22

Abstract: To test the hypothesis that variations in rate of glucose fall influence counterregulatory hormone responses to hypoglycemia, we have modified the glucose-clamp technique to provide a reproducible hypoglycemic stimulus in normal and type I diabetic subjects that varied only in the rate of glucose fall. Responsive elevations in plasma epinephrine and norepinephrine and in growth hormone, glucagon, and cortisol were not significantly affected by a ninefold change in the rate at which plasma glucose was lowered from 83 +/- 1 to 50 +/- 1 mg/dl in normal subjects. Similarly, wide variation in the rate of fall produced no substantive differences in counterregulatory hormone responses to hypoglycemia in diabetic subjects. The plasma glucose threshold at which epinephrine release began, determined from the slow-fall studies, was 63 +/- 3 mg/dl in normal subjects but exhibited a wide range (48-74 mg/dl). Similar values were found in the diabetics. Thresholds for growth hormone, cortisol, and glucagon were slightly lower, ranging from 45 to 68 mg/dl in the normals. Our data suggest that counterregulatory hormone responses to hypoglycemia are triggered by the glucose level per se and not by its rate of fall. Furthermore, individual differences in glucose thresholds for epinephrine release may contribute to variations in the glucose level associated with hypoglycemic symptoms.
Notes: Journal Article

Title: Paradoxical Effects of an Intense Sweetener (Aspartame) on Appetite
Author: Blundell, J. E.; Hill, A. J.; (Date: May 10, 1986)
Journal: Lancet; V. 1; Issue: 8489; Pages: 1092-3

Notes: Clinical Trial
Controlled Clinical Trial

Title: Glucocorticoids as Modulators in the Control of Feeding
Author: Castonguay, T. W.; (Date: Sep-Oct, 1991)
Journal: Brain Res Bull; V. 27; Issue: 3-4; Pages: 423-8

Abstract: Three sets of experiments have been conducted that suggest that adrenal glucocorticoids play a role in the long-term control of intake and in dietary preferences. First, obesity is dependent upon glucocorticoid-modulated metabolic pathways. Surgical or pharmacological manipulations in obese animals that eliminate or diminish corticosterone activity result in levels of intake, meal patterns, macronutrient self-selection and weight gain that revert to levels seen in lean controls. Glucocorticoid replacement of adrenalectomized genetically obese Zucker rats restores the phenotypic expression of the obese rat’s genetic heritage: increased weight gain, increased fat and total daily caloric intake and adiposity are restored in a dose-dependent fashion. Second, the increased fat intake observed subsequent to fasting in Sprague-Dawley rats is correlated with an increase in circulating corticosterone. Adrenalectomy blocks the fat specific refeeding response, and corticosterone treatment of adrenalectomized rats restores the increase in fat, carbohydrate and protein observed during refeeding. Third, humans suffering from Cushing’s Disease have an increased preference for dietary fat. Weight-matched but disease-free obese controls show only slight increases in fat preference when compared to normal weight controls.
Notes: Journal Article
Author Address: Department of Human Nutrition and Food Systems, University of Maryland, College Park 20742.

Title: Influence of Sympathetic Nervous System on Hypoglycaemic Warning Symptoms
Author: Heller, S. R.; Macdonald, I. A.; Herbert, M.; Tattersall, R. B.; (Date: Aug 15, 1987)
Journal: Lancet; V. 2; Issue: 8555; Pages: 359-63

Abstract: The effect of mild insulin-induced hypoglycaemia on symptoms, physiological changes, and adrenaline responses was assessed in 10 normal subjects and 15 insulin-dependent diabetic patients (5 with reduced awareness of hypoglycaemic symptoms). When blood glucose was maintained at 3.2 mmol/l, reaction time was prolonged in both normal and diabetic subjects and plasma adrenaline levels increased in the normals and some diabetics; there were no other physiological responses. 2 normals and 1 diabetic were aware that their blood glucose was low. When blood glucose was maintained at 2.5 mmol/l for 30 min, 9/10 normals but only 4/15 diabetics recognised hypoglycaemia. Increases in hypoglycaemic symptom score, tremor, and sweating, and falls in diastolic blood pressure were significant only in the normal subjects and the 4 “aware” patients. Adrenaline levels increased in all cases, but were more pronounced in the normals and aware diabetics. Reaction time remained prolonged in all groups. All measurements returned to baseline when blood glucose was raised to 4.5 mmol/l. Impairments in adrenaline response may be common, even in diabetic patients without autonomic neuropathy and in those who do not complain of hypoglycaemic unawareness; consequent failure to recognise a falling blood glucose may predispose to a risk of severe hypoglycaemia.
Notes: Clinical Trial
Controlled Clinical Trial
Journal Article

Title: Independent Effects of Youth and Poor Diabetes Control on Responses to Hypoglycemia in Children
Author: Jones, T. W.; Boulware, S. D.; Kraemer, D. T.; Caprio, S.; Sherwin, R. S.; Tamborlane, W. V.; (Date: Mar, 1991)
Journal: Diabetes; V. 40; Issue: 3; Pages: 358-63

Abstract: To evaluate the effects of childhood and poorly controlled insulin-dependent diabetes mellitus (IDDM) on counterregulatory hormone and symptomatic responses to hypoglycemia, we studied 16 nondiabetic children (13 +/- 2 yr), 19 nondiabetic adults (26 +/- 3 yr), and 13 children with IDDM (14 +/- 2 yr, HbA, 15.1 +/- 3.3%) during a gradual reduction in plasma glucose with the glucose-clamp technique. Plasma glucose was reduced from approximately 5 to approximately 2.8 mM over 240 min with serial assessment of counterregulatory hormone levels and symptom awareness. The plasma glucose level that triggered a sustained rise in plasma epinephrine was consistently higher in nondiabetic children than in adults (3.9 +/- 0.06 vs. 3.2 +/- 0.06 mM, P less than 0.001). Poorly controlled IDDM further elevated the glucose threshold for epinephrine release to normoglycemic levels (4.9 +/- 0.2 mM, P less than 0.001 vs. both control groups). Age and IDDM also produced an upward shift in the glucose level at which growth hormone release and symptom awareness were initiated. In contrast to the effect on glucose thresholds, maximal epinephrine responses and symptom scores were increased only by age and not IDDM (2-fold higher in children). We conclude that childhood and poor diabetes control independently contribute to an upward shift in glucose thresholds for counterregulatory hormone release and symptom awareness during mild hypoglycemia. Normoglycemic counterregulation may interfere with efforts to control diabetes in young patients.
Notes: Journal Article
Author Address: Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510.

Title: Enhanced Adrenomedullary Response and Increased Susceptibility to Neuroglycopenia: Mechanisms Underlying the Adverse Effects of Sugar Ingestion in Healthy Children
Author: Jones, T. W.; Borg, W. P.; Boulware, S. D.; McCarthy, G.; Sherwin, R. S.; Tamborlane, W. V.; (Date: Feb, 1995)
Journal: J Pediatr; V. 126; Issue: 2; Pages: 171-7

Abstract: OBJECTIVE: Eating simple sugars has been suggested as having adverse behavioral and cognitive effects in children, but a physiologic mechanism has not been established. This study was performed to address this issue. DESIGN: Metabolic, hormonal, and symptomatic responses to a standard oral glucose load (1.75 gm/kg; maximum, 120 gm) were compared in 25 healthy children and 23 young adults, and the hypoglycemic clamp, together with measurements of P300 auditory evoked potentials, was used to assess whether children are more vulnerable than adults to neuroglycopenia. SETTING: Children’s Clinical Research Center, Yale University School of Medicine. RESULTS: Baseline and oral glucose-stimulated plasma glucose and insulin levels were similar in both groups, including the nadir glucose level 3 to 5 hours after oral administration of glucose (3.4 +/- 0.1 mmol/L (61 +/- 1.8 mg/dl) in children and 3.5 +/- 0.1 mmol/L (63 +/- 1.8 mg/dl) in adults). The late glucose decrease stimulated a rise in plasma epinephrine levels that was twofold higher in children than in adults (2260 +/- 289 vs 1031 +/- 147 pmol/L (407 +/- 52 vs 186 +/- 26 pg/ml), p < 0.01) and a significant increase in hypoglycemic symptom scores in children (p < 0.01), but not in adults. During control experiments, in which six of the healthy children ingested a sugar-free drink, there were no significant changes in plasma glucose levels, hormone concentrations, or hypoglycemic symptom scores. During the hypoglycemic clamp, P300 potentials did not change in any of eight adult subjects until the plasma glucose concentration was lowered to 3.0 mmol/L (54 mg/dl), whereas similar changes in P300 potentials were observed in six of seven children at glucose levels 3.6 to 4.2 mmol/L (65 to 75 mg/dl). CONCLUSION: Enhanced adrenomedullary responses to modest reductions in plasma glucose concentration and increased susceptibility to neuroglycopenia may be important contributing factors to adverse behavioral and cognitive effects after sugar ingestion in healthy children.
Notes: Journal Article
Author Address: Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06510-8064.

Title: Baseline Ventilatory Function Predicts the Development of Higher Levels of Fasting Insulin and Fasting Insulin Resistance Index: The Normative Aging Study
Author: Lazarus, R.; Sparrow, D.; Weiss, S. T.; (Date: Sep, 1998)
Journal: Eur Respir J; V. 12; Issue: 3; Pages: 641-5

Abstract: A consistent but as yet unexplained association between baseline ventilatory function and risk of coronary heart disease (CHD) has been reported from many prospective studies. Insulin-resistant states are associated with increased risk of CHD. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow rate (MMEF) at study entry were examined as predictors for indirect measures of insulin resistance after a mean follow-up interval of 20.9 yrs in 1050 nondiabetic male subjects in the Normative Aging Study. Males in the top quintile of insulin or fasting insulin resistance index (FIRI) levels at follow-up were defined as being relatively insulin resistant. FVC was negatively associated with risk of being relatively insulin resistant using the insulin (p=0.002) or FIRI (p=0.0001) criteria at follow-up in logistic regression models adjusting for baseline age, body mass index, fat distribution pattern and cigarette smoking. Similar associations were found for FEV1 and MMEF. Additional adjustment for baseline postcarbohydrate challenge glucose levels made little difference to the results, suggesting that baseline glucose intolerance was not a significant source of bias. These findings are consistent with the possibility that insulin resistance may be one of the factors mediating the previously unexplained prospective association between impairment of ventilatory function and risk of mortality from coronary heart disease.
Notes: Journal Article
Author Address: Dept of Public Health and Community Medicine, Faculty of Medicine, University of Sydney, NSW, Australia.

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