Biomedical subjects

D C Simonson

Publications and source records attributed to D C Simonson.

At least 55 records · Page 3Linked to original sources

PubMed1990

Glycemic control and neuropsychologic function during hypoglycemia in patients with insulin-dependent diabetes mellitus.

STUDY OBJECTIVE: To evaluate counterregulatory hormone secretion and neuropsychologic function during hypoglycemia in two groups of patients with insulin-dependent diabetes mellitus: those with good and those with poor glycemic control. DESIGN: Cross-sectional physiologic and neuropsychologic evaluation. SETTING: Clinical research unit of a referral-based diabetes clinic. PATIENTS: Eight patients with well controlled diabetes (glycosylated hemoglobin [HgbA1], 8.0% +/- 0.2%), nine patients with poorly controlled diabetes (HgbA1, 11.8% +/- 0.4%), and ten healthy persons. INTERVENTIONS: The insulin clamp technique was used to produce a stepwise decline in plasma glucose from 5.0 to 2.2 mmol/L over 3 hours. Tests of attention, memory, visual-spatial skills, visual-motor skills, and global cognition; a symptom survey; and counterregulatory hormone measurements were done at glucose decrements of 0.6 mmol/L. MEASUREMENTS AND MAIN RESULTS: Patients with well controlled diabetes did not differ statistically from those with poorly controlled diabetes regarding the median glucose threshold for dysfunction in visual-spatial skills, visual-motor skills, or global cognition. In contrast, glycemic thresholds for an increase in adrenergic symptoms and release of epinephrine, norepinephrine, cortisol, and growth hormone were lower in patients with well controlled diabetes than in those with poorly controlled diabetes (P less than 0.05 to 0.005). CONCLUSIONS: Despite alterations in the glucose levels at which adrenergic symptoms of hypoglycemia occur and counterregulation begins, there is no statistically detectable change in the glucose threshold at which cognitive deterioration occurs in diabetic persons with strict glycemic control. This dissociation of neuropsychologic function and counterregulatory hormone secretion suggests that diabetic patients with good glycemic control are at increased risk for developing cognitive impairment before the onset of adrenergic symptoms during hypoglycemia.

Adult↗

PubMed1990

Indirect calorimetry: methodological and interpretative problems.

The technique of indirect calorimetry is now widely used to examine rates of energy production and substrate oxidation in humans. Although the basic principles of indirect calorimetry are well established, it is important to recognize that there are several potential pitfalls in the methodology and data interpretation that must be appreciated to properly understand and apply the results derived from this technique. In particular, one must recognize that the fundamental measurement provided by indirect calorimetry is the net disappearance rate of a substrate regardless of the metabolic interconversions that the substrate may undergo before its disappearance from its metabolic pool. Under most circumstances, direct oxidation represents the major route by which a substrate disappears from its metabolic pool, and the two terms are often used interchangeably. However, under conditions when rates of gluconeogenesis, ketogenesis, or lipogenesis are elevated, the presumed equivalence between oxidation and disappearance may no longer apply, even though the actual measurements derived from indirect calorimetry remain valid. When indirect calorimetry is combined with other in vivo metabolic techniques (e.g., the insulin clamp or radioisotope turnover methods) it can provide a powerful tool for noninvasively examining complex metabolic processes.

Body Temperature Regulation↗

PubMed1990

Leucine metabolism in IDDM. Role of insulin and substrate availability.

The effect of insulin on plasma amino acid concentrations and leucine metabolism was examined in 18 healthy nondiabetic young volunteers and in 7 subjects with insulin-dependent diabetes mellitus (IDDM) with the euglycemic insulin-clamp technique (40 mU.m-2.min-1) in combination with [1-14C]leucine. All diabetic subjects were studied while in poor metabolic control (fasting glucose 13.3 +/- 1.1 mM; HbA1c 10.8 +/- 0.2%) and again after 2 mo of intensified insulin therapy (fasting glucose 7.2 +/- 0.5 mM; HbA1c 8.0 +/- 0.2%). Insulin-mediated total-body glucose uptake in poorly controlled diabetic subjects (3.6 +/- 0.5 mg.kg-1.min-1) was significantly reduced compared with control subjects (7.5 +/- 0.2 mg.kg-1.min-1; P less than .001) and improved slightly after insulin therapy (4.8 +/- 0.3 mg.kg-1.min-1; P less than .05), although it still remained significantly lower than in control subjects (P less than .01). During the insulin-clamp study performed in subjects with poorly controlled IDDM, endogenous leucine flux (ELF), leucine oxidation (LO), and nonoxidative leucine disposal (NOLD) all decreased (50.1 +/- 2.0 to 26.4 +/- 0.4; 9.2 +/- 0.4 to 6.0 +/- 0.3; 40.9 +/- 2.0 to 20.4 +/- 2.0 mumol.m-2.min-1, respectively) to the same extent as in control subjects. After 2 mo of intensified insulin therapy, the effect of acute hyperinsulinemia on ELF, LO, and NOLD was comparable to that of control subjects, whereas insulin-stimulated glucose metabolism was still impaired. To examine the effect of substrate availability on leucine turnover, well-regulated IDDM and control subjects underwent a repeat insulin-clamp study combined with a balanced amino acid infusion designed to increase circulating plasma amino acid levels approximately twofold. Under these conditions, NOLD was equally enhanced above baseline in both control and IDDM subjects (P less than .01), whereas ELF was inhibited to a greater extent (P less than .01) than during the insulin clamp performed without amino acid infusion (control vs. diabetic subjects, NS). In conclusion, insulin-mediated glucose metabolism is severely impaired in subjects with both poorly controlled and well-controlled IDDM, whereas the effect of acute insulin infusion on leucine turnover is normal, and combined hyperaminoacidemia/hyperinsulinemia stimulated NOLD to a similar extent in both IDDM and control subjects.

Adult↗

PubMed1990

Hyperinsulinemia and its sequelae.

It is now well recognized that insulin resistance and/or hyperinsulinemia are characteristic of a number of common human disease states including obesity, non-insulin dependent diabetes mellitus (NIDDM), essential hypertension, and atherosclerotic cardiovascular disease. More recent evidence suggests that impaired insulin action and elevated levels of circulating insulin may also be present in a substantial proportion of apparently healthy nonobese individuals. Considerable attention is now being focused on the potential long term adverse consequences of elevated circulating insulin levels. In particular, the frequent concurrence of these clinical disorders of carbohydrate metabolism, lipid metabolism, and vascular disease has led to the hypothesis that insulin resistance and the ensuing hyperinsulinemia may be a common pathophysiologic factor in the etiology of these disease states. In this review, we will examine the evidence for this hypothesis with particular attention to the adverse effects of chronic hyperinsulinemia.

Arteriosclerosis↗

PubMed1989

Fasting hyperglycemia in non-insulin-dependent diabetes mellitus: contributions of excessive hepatic glucose production and impaired tissue glucose uptake.

The factors responsible for fasting hyperglycemia were investigated in 77 normal weight non-insulin-dependent diabetic (NIDD) and 72 age-, sex-, and weight-matched control individuals. In diabetic subjects with mild fasting hyperglycemia (less than 140 mg/dL) hepatic glucose production (1.85 +/- 0.03 mg/kg.min) was similar to controls (1.84 +/- 0.02); the major factor responsible for the elevated basal glucose level in the diabetic group was a decreased efficiency in the tissue uptake of glucose, as reflected by a 30% decline in the rate of glucose clearance (1.56 +/- 0.03 v 2.00 +/- 0.03 mL/kg.min, P less than .001). In contrast, in diabetic subjects with fasting plasma glucose concentrations above 140 mg/dL, basal hepatic glucose production was significantly elevated (2.42 +/- 0.08 mg/kg.min, P less than .001) and correlated closely with the increase in fasting plasma glucose concentration (r = .796, P less than .001). The basal rate of whole body glucose clearance reached a plateau value at fasting glucose levels of 160 to 180 mg/dL and did not contribute to the further rise in fasting plasma glucose concentrations above 160 to 180 mg/dL. Decreased efficiency of tissue glucose uptake is responsible the development of fasting hyperglycemia in patients with mild NIDDM (fasting plasma glucose less than 140 mg/dL). As the diabetic state worsens, an increase in basal hepatic glucose production is the major factor responsible for the progressive rise in fasting glucose levels.

Blood Glucose↗

PubMed1989

Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity.

Recent studies have suggested that insulin action is reduced during puberty in normal children. To determine whether such resistance leads to excessive insulin secretion, we used the hyperglycemic clamp technique to produce a standard hyperglycemic stimulus (125 mg/dl above fasting levels for 120 minutes) in 9 preadolescent and 14 adolescent healthy children and in 14 normal adults. Fasting plasma insulin and C-peptide concentrations were higher in adolescents than in preadolescents and adults (p less than or equal to 0.02). Despite identical glucose increments during the glucose clamp procedure, both first- and second-phase plasma insulin and C-peptide responses were also markedly greater in adolescents than in preadolescents or adults (p less than 0.01 vs. other groups). Despite sharply increased insulin responses in adolescents, the amount of exogenous glucose required to maintain hyperglycemia was similar in all three groups. Insulin responses in the children were directly correlated with fasting plasma levels of insulin-like growth factor I (r = 0.60 to 0.70, p less than 0.01). We conclude that glucose-stimulated insulin secretion is normally increased during puberty, a response that may compensate for puberty-induced defects in insulin sensitivity.

Adolescent↗

PubMed1989

Menstrual cyclicity has a profound effect on glucose homeostasis.

Results from oral glucose tolerance tests have frequently demonstrated a deterioration in glucose metabolism during the luteal phase of the menstrual cycle. To examine this issue further, eight women underwent both midfollicular (days 3 to 10) and midluteal (days 20 to 25) phase hyperglycemic clamp studies (+125 mg glucose/dl) after an overnight fast. Glucose levels rose from 83 +/- 1 to 207 +/- 2 and 87 +/- 1 to 207 +/- 2 mg/dl, respectively, during the follicular and luteal phases. The basal (6 +/- 1 versus 7 +/- 1 microU/ml) and glucose-stimulated (42 +/- 5 versus 43 +/- 6 microU/ml) insulin responses were similar in the follicular and luteal studies. However, glucose uptake was significantly higher during the follicular versus the luteal phase (10.99 +/- 0.97 versus 6.93 +/- 0.37 mg/kg-min; P less than 0.01), as was the ratio of glucose uptake to insulin concentration (30.0 +/- 5.5 versus 19.7 +/- 3.7, P less than 0.01). The authors conclude that: (1) Glucose metabolism is impaired in the luteal phase of the menstrual cycle; (2) This defect cannot be explained by differences in the plasma insulin response; and (3) This impairment in the ability to promote glucose uptake under hyperglycemic conditions suggests a defect in the mass action effect of glucose per se.

Adult↗

PubMed1988

Insulin resistance and hyperinsulinemia in patients with thalassemia major treated by hypertransfusion.

Diabetes mellitus in patients receiving hypertransfusion for thalassemia major is usually attributed to damage to beta cells. To determine whether iron overload leads to insulin resistance before the development of insulin deficiency, insulin was infused (by euglycemic insulin-clamp technique) into 12 children with thalassemia (4 of whom were prepubertal, and 8 pubertal) who had normal or only moderately impaired glucose tolerance and who were receiving chelation therapy. Although insulin-stimulated glucose metabolism in the prepubertal children with thalassemia was similar to that in controls (normal prepubertal children) (319 +/- 23 vs. 314 +/- 41 mg per square meter of body-surface area per minute, P not significant), the response to insulin was markedly impaired in the pubertal children with thalassemia (155 +/- 18 vs. 224 +/- 15 mg per square meter per minute in normal pubertal controls, P less than 0.01). Plasma insulin levels rose excessively after oral glucose administration in the pubertal subjects with thalassemia, but not in the prepubertal patients (P less than 0.001). Furthermore, in response to a standard hyperglycemic stimulus, insulin levels in the pubertal patients rose to two to three times greater than normal and C-peptide levels became significantly elevated. Our data suggest that insulin resistance and increased insulin secretion develop in older children with thalassemia treated with long-term hypertransfusion therapy before the development of diabetes.

Adolescent↗

PubMed1988

Oxidative and non-oxidative glucose metabolism in non-obese type 2 (non-insulin-dependent) diabetic patients.

Insulin resistance is a common feature of Type 2 (non-insulin-dependent) diabetes mellitus. This defect in insulin-mediated glucose metabolism could result from a defect in either glucose oxidation or non-oxidative glucose disposal. To examine this question, euglycaemic insulin clamp studies were performed in 16 normal weight Type 2 and 11 age-matched control subjects. In Type 2 diabetic patients the fasting plasma glucose concentration, 8.39 +/- 0.50 mmol/l, was allowed to decline (over 54 +/- 6 min) to 5.33 +/- 0.11 mmol/l before starting the insulin clamp. Total body glucose uptake was significantly decreased in Type 2 diabetic patients vs control subjects (148 +/- 15 vs 264 +/- 25 mg/min.m2, p less than 0.001). Both total glucose oxidation (59 +/- 6 vs 89 +/- 6 mg/min.m2, p less than 0.005) and non-oxidative glucose disposal (89 +/- 15 vs 179 +/- 24 mg/min.m2, p less than 0.005) were significantly reduced in the Type 2 diabetic patients. Basal glucose oxidation was also reduced in the Type 2 diabetic patients (22 +/- 3 vs 38 +/- 5 mg/min.m2, p less than 0.01). In conclusion, during the postabsorptive state and under conditions of euglycaemic hyperinsulinaemia, impairment of glucose oxidation and non-oxidative glucose disposal both contribute to the insulin resistance observed in normal weight Type 2 diabetic patients. Since lipid oxidation was normal in this group of diabetic patients, excessive non-esterified fatty acid oxidation cannot explain the defects in glucose disposal.

Blood Glucose↗

PubMed1988

The disposal of an oral glucose load in patients with non-insulin-dependent diabetes.

Following glucose ingestion, tissue glucose uptake is enhanced and endogenous glucose production is inhibited, thus contributing to the maintenance of normal glucose tolerance. To examine whether these responses are disturbed in diabetes, glucose kinetics after oral glucose administration were studied in 12 non-insulin-dependent diabetic and 10 age- and weight-matched control subjects. A double tracer approach was used, whereby the endogenous glucose pool was labeled with 3-3H-glucose and the oral load with 1-14C-glucose. The two glucose tracers were separated in plasma by a two-step chromatographic procedure, and the two sets of isotopic data were analyzed according to a two-compartment model for the glucose system. Basally, glucose production was slightly higher in diabetics than in controls (2.51 +/- 0.24 v 2.28 +/- 0.11 mg/kg.min, NS) even though the former had higher plasma glucose (189 +/- 19 v 93 +/- 2 mg/dL, P less than .001) and insulin (23 +/- 4 v 12 +/- 1 microU/mL, P less than .05) concentrations. Following the ingestion of 1 g/kg of glucose, oral glucose appeared in the peripheral circulation in similar time-course and amount in the two groups (75 +/- 2% of the load over 3.5 hours in the diabetics v 76 +/- 3% in controls). Endogenous glucose production was promptly inhibited in diabetic and normal subjects alike, but the mean residual hepatic glucose production after glucose ingestion was significantly greater in the diabetic group (17 +/- 2 v 10 +/- 3 g/3.5 h, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1988

Normalization of carbohydrate-induced thermogenesis by fructose in insulin-resistant states.

To examine whether defects in carbohydrate oxidation and thermogenesis in aging, obesity, and diabetes are secondary to impaired insulin action or to a primary defect in intracellular metabolism, we compared substrate oxidation and energy expenditure in 9 younger, 9 older, 9 obese, and 10 non-insulin-dependent diabetic subjects after the ingestion of 75 g of glucose or fructose (a monosaccharide whose transport into the cell and subsequent metabolism are independent of insulin). In young control subjects fructose produced a significantly greater increase in carbohydrate oxidation and energy expenditure than glucose despite significantly lower plasma glucose and insulin levels. In aged, obese, and diabetic individuals the increments in carbohydrate oxidation and energy expenditure after glucose ingestion were significantly imparied versus the younger controls. After fructose ingestion the increase in carbohydrate oxidation in the three insulin-resistant groups remained below that observed in the younger volunteers, whereas carbohydrate-induced thermogenesis was enhanced to levels that were comparable with those seen in the younger group. These data suggest that 1) the stimulation of thermogenesis after fructose ingestion is related to an augmentation of intracellular metabolism rather than an increase in the plasma insulin concentration per se, 2) the insulin resistance of aging, obesity, and diabetes is associated with a defect in intracellular carbohydrate oxidation, and 3) the cellular mechanisms involved in carbohydrate-induced thermogenesis are not primarily impaired in insulin-resistant states.

Blood Glucose↗

PubMed1988

Effect of intensive insulin therapy on glycemic thresholds for counterregulatory hormone release.

To evaluate the effect of strict glycemic control of insulin-dependent diabetes mellitus (IDDM) on the plasma glucose threshold initiating counterregulatory hormone responses to hypoglycemia, we used the glucose clamp technique to produce a standardized gradual glucose decline from 90 to 40 mg/dl in seven young IDDM patients before and after 2-6 mo of intensified insulin therapy. Before intensive therapy [hemoglobin A1 (HbA1) 9.6 +/- 1.1%], epinephrine responses were triggered at a higher plasma glucose level (67 +/- 4 mg/dl) than in normal control subjects (56 +/- 1 mg/dl, P less than .05), and clinical symptoms of hypoglycemia appeared at glucose levels of 50-60 mg/dl. After intensive therapy (HbA1 7.1 +/- 0.7%), the glucose threshold for epinephrine release consistently declined to values (46 +/- 2 mg/dl) below normal (P less than .01). Furthermore, epinephrine concentrations were markedly reduced at each hypoglycemic level, and a greater hypoglycemic stimulus was required to elicit symptoms. The glucose threshold stimulating release of growth hormone also significantly declined after intensive therapy. We conclude that strict glycemic control of IDDM lowers the plasma glucose level required to generate epinephrine release during hypoglycemia. This may diminish patient recognition of moderate hypoglycemia and increase the risk of severe hypoglycemia in intensively treated IDDM.

Adolescent↗

PubMed1988

Insulin sensitivity and the effects of antihypertensive agents: implications for the treatment of hypertension in the patient with diabetes mellitus.

It is now well established that non-insulin dependent diabetes mellitus is characterized by insulin resistance. Independent data have suggested that essential hypertension also is associated with abnormal glucose tolerance and an impairment of insulin action. These observations have led to the hypothesis that insulin resistance and/or hyperinsulinaemia may provide a common pathophysiological basis for the high concordance of these two diseases in many individuals. The relationship between insulin resistance, diabetes and hypertension assumes additional importance when one considers that many antihypertensive medications may impair insulin sensitivity or insulin secretion, thus leading to a further impairment of glucose tolerance or deterioration of glycaemic control. In the present review, the epidemiological and pathophysiological evidence supporting this hypothesis will be examined and the implications for treating hypertension in the patient with diabetes will be discussed.

Antihypertensive Agents↗

PubMed1988

Measuring quality of life in hypertensive patients with diabetes.

A general health status measurement instrument which assessed quality of life components was developed for diabetic patients with hypertension. The instrument was conceptualized using a broad definition of health status including measures of physical, emotional and social well-being. Because certain antihypertensive agents can alter the metabolic state of the diabetic patient, the instrument was designed to evaluate diabetes-specific symptomatology as well as interactions between antihypertensive agents and metabolic control. The background and structure of the instrument is discussed and the basic item content outlined. A preliminary pilot study consisting of 58 volunteers including healthy normals, patients with diabetes and patients with hypertension indicated that the instrument was practical for the clinic setting and that the scales and composite scores obtained from individual item responses were internally consistent and reliable over repeated trials. Discrimination among the groups also indicated the instrument's ability to be sensitive to a broad range of responses.

Adult↗

PubMed1987

Defective glucose counterregulation after strict glycemic control of insulin-dependent diabetes mellitus.

We infused small doses of insulin (0.3 mU per kilogram of body weight per minute; range, 0.9 to 1.7 U per hour) for three hours into 8 subjects who did not have diabetes, 11 patients with well-controlled diabetes (hemoglobin A1, 7.6 +/- 0.7 percent), and 10 patients with poorly controlled diabetes (hemoglobin A1, 11.5 +/- 1.7 percent) to simulate the mild peripheral hyperinsulinemia observed during insulin treatment. Normoglycemia was established in the patients during the night before study. During the insulin infusion, the plasma glucose level stabilized at 60 to 70 mg per deciliter (3.3 to 3.9 mmol per liter) in the subjects without diabetes and the patients with poorly controlled diabetes, because of a rebound increase in hepatic glucose production. In contrast, hypoglycemia developed in the patients with well-controlled diabetes (42 +/- 2 mg of glucose per deciliter, or 2.3 +/- 0.1 mmol per liter, P less than 0.01) as glucose production remained suppressed. The hypoglycemia in the patients with well-controlled diabetes was associated with a lowering of the plasma threshold of glucose that triggered a release of epinephrine (less than 45 mg of glucose per deciliter, or 2.5 mmol per liter, vs. greater than 55 mg per deciliter, or 3.1 mmol per liter, in the other groups, P less than 0.01) as well as an enhanced sensitivity to the suppressive effects of insulin on hepatic glucose production. Nearly identical disturbances in glucose counterregulation and decreased perception of hypoglycemia developed when four of the subjects with poorly controlled diabetes were restudied after intensive treatment. We conclude that strict control of diabetes induces physiologic alterations (delayed release of epinephrine and persistent suppression of glucose production) that impair glucose counterregulation to doses of insulin in the therapeutic range. These defects may contribute to the increased incidence of severe hypoglycemia reported during intensive insulin therapy.

Adult↗

PubMed1987

Exaggerated epinephrine responses to hypoglycemia in normal and insulin-dependent diabetic children.

To determine whether children with insulin-dependent diabetes mellitus (IDDM) might have exaggerated hormonal responses to hypoglycemia, the euglycemic-hypoglycemic glucose clamp procedure was used to provide a uniform hypoglycemic stimulus (plasma glucose kept at 90 mg/dL for 2 hours, then reduced to 50 to 55 mg/dL for 1 hour) in children and adults with and without IDDM. The chidren with IDDM showed an exaggerated rise in plasma epinephrine levels (625 +/- 112 pg/mL) compared with adults with IDDM (259 +/- 57 pg/mL, P less than 0.02); the same was true for children and adults without IDDM (811 +/- 100 vs 458 +/- 85 pg/mL, P less than 0.05). Among the children, the increase in epinephrine during hypoglycemia was similar in prepubertal and pubertal patients. Children with IDDM showed a greater rise in plasma norepinephrine than did adults with IDDM (P less than 0.001), and both diabetic groups failed to mount a glucagon response. Growth hormone and cortisol responses were unaffected by either childhood or diabetes. Enhanced secretion of epinephrine, induced by mild reductions in plasma glucose, may contribute to the management difficulties characteristically observed in the young patient with diabetes.

Adult↗

PubMed1987

Adrenergic modulation of potassium metabolism during exercise in normal and diabetic humans.

The effect of acute and chronic beta- and alpha-adrenergic blockade on potassium homeostasis during moderate intensity exercise (40% VO2max) was investigated in control and insulin-dependent diabetic subjects. In protocol I, subjects were studied during exercise alone, exercise plus intravenous propranolol, and exercise plus intravenous phentolamine. In both the control and diabetic groups, exercise alone produced a modest increase in the plasma potassium concentration (0.31 +/- 0.06 meq/l), while propranolol exacerbated this hyperkalemic response. In contrast, the increment in plasma potassium during phentolamine was similar to exercise alone in normals but was 26% (P less than 0.05) lower in the diabetic group. In protocol II, the effect of chronic (5 days) beta-adrenergic blockade on potassium homeostasis was examined. Subjects participated in three studies: exercise alone, exercise plus propranolol (beta 1/beta 2-antagonist), and exercise plus metoprolol (beta 1 antagonist). In the nondiabetic group, both propranolol and metoprolol were associated with a 40% greater increase in potassium compared with exercise alone. In the diabetic group, propranolol, but not metoprolol, was associated with a deterioration in potassium tolerance. In no study could the alterations in potassium homeostasis be explained by a change in urinary potassium excretion. In summary, alpha-adrenergic blockade ameliorates exercise-induced hyperkalemia in diabetic but not in control subjects, nonspecific beta-adrenergic blockade causes a greater increment in potassium when compared with exercise alone, and specific beta 1-adrenergic blockade exacerbates exercise-induced hyperkalemia in control, but not in diabetic subjects. These results indicate that both alpha- and beta-adrenergic regulation of extrarenal potassium metabolism is altered in insulin-dependent diabetes mellitus.

Adult↗

PubMed1987

Hyperglucagonemia and insulin-mediated glucose metabolism.

The effect of chronic physiologic hyperglucagonemia on basal and insulin-mediated glucose metabolism was evaluated in normal subjects, using the euglycemic insulin clamp technique (+50, +100, and +500 microU/ml). After glucagon infusion fasting glucose increased from 76 +/- 4 to 93 +/- 2 mg/dl and hepatic glucose production (HGP) rose from 1.96 +/- 0.08 to 2.25 +/- 0.08 mg/kg X min (P less than 0.001). Basal glucose oxidation after glucagon increased (P less than 0.05) and correlated inversely with decreased free fatty acid concentrations (r = -0.94; P less than 0.01) and decreased lipid oxidation (r = -0.75; P less than 0.01). Suppression of HGP and stimulation of total glucose disposal were impaired at each insulin step after glucagon (P less than 0.05-0.01). The reduction in insulin-mediated glucose uptake was entirely due to diminished non-oxidative glucose utilization. Glucagon infusion also caused a decrease in basal lipid oxidation and an enhanced ability of insulin to inhibit lipid oxidation and augment lipid synthesis. These results suggest that hyperglucagonemia may contribute to the disturbances in glucose and lipid metabolism in some diabetic patients.

Adolescent↗