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Biomedical subjects

J E Gerich

Publications and source records attributed to J E Gerich.

At least 109 records · Page 6Linked to original sources
PubMed1986

Rationale for inhibition of growth hormone secretion in the management of the diabetic patient.

Patients with diabetes mellitus, especially the insulin-dependent variety, have increased circulating levels of growth hormone. On the basis of currently available information, the potential advantages of inhibition of growth hormone secretion as an adjunct in the treatment of diabetes mellitus include improved metabolic control (less hyperglycaemia, greater stability), resulting from diminution of the insulin-antagonistic actions of this hormone, and reduced micro- and possibly macro-angiopathy, resulting not only from improved metabolic control but also from decreased direct effects of growth hormone on blood vessels.

Diabetes Mellitus↗
PubMed1986

Comparison of glucose counterregulation during short-term and prolonged hypoglycemia in normal humans.

To compare glucose counterregulatory mechanisms during short-term hypoglycemia and prolonged hypoglycemia, insulin was infused either intravenously (160 mU X M-2 X min) for 10 min or subcutaneously (15 mU X M-2 X min) for 12 h in normal volunteers. With each type of insulin infusion, hypoglycemia (approximately 50 mg/dl) was either allowed to develop or was prevented (control experiments) by the glucose-clamp technique. During prolonged hypoglycemia, both increased glucose production (1.55 +/- 0.05 versus 0.33 +/- 0.14 mg X kg-1 X min in control experiments at 12 h, P less than 0.01) and suppressed glucose utilization (1.55 +/- 0.06 versus 3.17 +/- 0.15 mg X kg-1 X min in control studies at 12 h, P less than 0.01) were involved in counterregulation. During short-term hypoglycemia, only increased glucose production (3.23 +/- 0.33 versus 0.06 +/- 0.03 mg X kg-1 X min in control experiments at 60 min) was involved, since glucose clearance actually increased (3.99 +/- 0.20 versus 2.88 +/- 0.02 ml X kg-1 X min in control experiments at 60 min, P less than 0.01). Estimated portal venous insulin concentrations decreased 40% (basal 24 +/- 3 versus 14 +/- 1 mU/ml at 60 min, P less than 0.01) in the short-term hypoglycemia experiments but remained at basal levels (basal 25 +/- 1 versus approximately 26 microU/min between 1 and 12 h) during prolonged hypoglycemia. Despite the fact that hypoglycemia was more gradually induced in the prolonged hypoglycemia model, peak counterregulatory hormone responses were at least as great as those during short-term hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus.

The prevention or correction of hypoglycemia is the result of both dissipation of insulin and activation of counterregulatory systems. In the models studied to date, glucagon and epinephrine have been shown to be the key counterregulatory factors; the potential roles of other hormones, neural factors, or substrate mechanisms in other models and during more gradual recovery from hypoglycemia remain to be defined. Deficient glucagon responses to decrements in plasma glucose, which are common in patients with IDDM and occur in some patients with NIDDM, result in altered counterregulation. But counterregulation is generally adequate, because epinephrine compensates for it. Defective glucose counterregulation due to combined deficiencies of glucagon and epinephrine secretory responses occurs in many patients, typically those with longstanding diabetes, and must be added to the list of factors known to increase the risk of hypoglycemia, at least during intensive therapy. From the material reviewed, it should be apparent that much has been learned about glucose counterregulation. It should be equally clear that much remains to be learned. Among the many possibilities, we consider four worthy of emphasis. First of all, we need to examine the physiology and pathophysiology of glucose counterregulation in additional models (e.g., during exercise) and over longer periods. Secondly, we need to determine whether central nervous system adaptation to antecedent glycemia occurs and, if so, identify its mechanisms. Thirdly, we need to develop better methods of insulin delivery or learn to correct or compensate for defective counterregulatory systems, if we are to achieve euglycemia safely in diabetic patients with defective glucose counterregulation. Finally, we need to know whether effective control of diabetes mellitus prevents development of defective glucose counterregulation.

Blood Glucose↗
PubMed1985

Pathogenesis of the dawn phenomenon in patients with insulin-dependent diabetes mellitus. Accelerated glucose production and impaired glucose utilization due to nocturnal surges in growth hormone secretion.

The early-morning increase in insulin requirements of patients with insulin-dependent diabetes mellitus (IDDM) has been referred to as the "dawn phenomenon." To determine the roles of growth hormone levels and sympathoadrenal activity in this phenomenon, we studied six subjects with IDDM on four occasions during a constant overnight infusion of insulin. In control experiments (infusion of insulin alone), plasma glucose increased from 98 +/- 5 mg per deciliter at midnight to 225 +/- 36 at 8:00 a.m. (P less than 0.001), glucose production increased by 65 per cent (P less than 0.001), and glucose clearance decreased by 50 per cent (P less than 0.001). When nocturnal surges in growth hormone secretion were prevented by infusion of somatostatin plus replacement glucagon, neither plasma glucose levels nor glucose production increased significantly, and glucose clearance did not decrease. When nocturnal surges in growth hormone secretion were simulated by hourly intravenous injections of growth hormone (15 to 100 micrograms) during infusion of somatostatin and glucagon, plasma glucose levels and glucose production increased and glucose clearance decreased to values observed in control experiments. During combined alpha- and beta-adrenergic blockade (phentolamine and propranolol), values for plasma glucose, glucose production, and glucose utilization were not significantly different from those in control experiments. Increases in plasma glucose were significantly correlated with peak plasma growth hormone concentrations (r = 0.58, P less than 0.01). We conclude that nocturnal surges in growth hormone secretion are primarily responsible for the dawn phenomenon in patients with IDDM.

Adult↗
PubMed1985

Production of insulin resistance by hyperinsulinaemia in man.

It has been proposed that hyperinsulinaemia may cause or exacerbate insulin resistance. The present studies were undertaken to test this hypothesis in man. Glucose utilization, glucose production, and overall glucose metabolism at submaximally and maximally effective plasma insulin concentrations (approximately 80 and approximately 1700 mU/l), and monocyte and adipocyte insulin binding were measured in normal volunteers on two occasions: once after 40 h of hyperinsulinaemia (25-35 mU/l) produced by infusion of insulin and once after infusion of saline (75 mmol/l; plasma insulin approximately 10 mU/l). After 40 h of hyperinsulinaemia, glucose utilization and overall glucose metabolism at submaximally and maximally effective plasma insulin concentrations were both slightly, but significantly, reduced compared with values observed after the infusion of saline (p less than 0.05), whereas glucose production rates were unaffected. Monocyte and adipocyte binding were also unaffected. These results indicate that hyperinsulinaemia of the magnitude observed in insulin resistant states, such as obesity, can produce insulin resistance in man. Assuming that human insulin sensitive tissues possess spare insulin receptors and that monocyte and adipocyte insulin binding accurately reflect insulin binding in insulin-sensitive tissues, the decreased maximal responses to insulin and the lack of change in insulin binding suggest that this insulin resistance occurred at a post-binding site.

Adipose Tissue↗
PubMed1985

alpha-Glucosidase inhibition improves postprandial hyperglycemia and decreases insulin requirements in insulin-dependent diabetes mellitus.

In patients with diabetes mellitus, delayed increases in circulating insulin levels followed by prolonged hyperinsulinemia due to slow absorption of subcutaneously administered insulin hinders maintenance of euglycemia. To determine whether a delay in carbohydrate absorption would increase the effectiveness of subcutaneous insulin in controlling postprandial hyperglycemia in patients with insulin-dependent diabetes mellitus and whether it could allow insulin to be taken immediately prior to meals, the effects of an alpha-glucosidase inhibitor (Acarbose Boyer AG, Wuppertal, Germany) on postprandial plasma glucose profiles were determined in six subjects with insulin-dependent diabetes when a subcutaneous insulin infusion was started immediately or 30 minutes prior to meal ingestion. When 25% less insulin (9 v 12 units) was given along with Acarbose 30 minutes prior to meal ingestion, postprandial hyperglycemia decreased by 45% (areas under the curve, AUC, 8193 +/- 1960 v 14783 +/- 2260 mg/dL X min, P less than 0.02). When similar amounts of insulin (12 units) were given immediately prior to meal ingestion, postprandial hyperglycemia decreased 55% (AUC 6187 +/- 2240 v 13642 +/- 1579 mg/dL X min, P less than 0.001). These results indicate that delay in carbohydrate absorption improves the effectiveness of subcutaneous insulin in controlling postprandial hyperglycemia in patients with insulin-dependent diabetes mellitus and may permit satisfactory postprandial glycemic control when insulin is administered immediately prior to meal ingestion. Thus, an agent like Acarbose, which delays carbohydrate absorption, may be useful as an adjunct to insulin in the treatment of diabetes mellitus.

Absorption↗
PubMed1985

Sequence of events during development of the dawn phenomenon in insulin-dependent diabetes mellitus.

During constant insulin infusion (0.15 mU X kg-1 X min-1) from 12 PM to 8 AM in 10 IDDM patients previously rendered euglycemic (Biostator), plasma glucose (5.4 +/- 0.2 mmol/L at 12 PM) increased by 3:30 AM and reached 12.1 +/- 1.6 mmol/L at 8 AM (P less than 0.001). Glucose production also increased at 3:30 AM; hyperglycemia, glucose utilization did not increase until after 5 AM. Plasma growth hormone (12 PM to 4 AM), cortisol (after 3:30 AM), noradrenaline (after 1:30 AM), and adrenaline (after 3:30 AM) but not glucagon increased significantly overnight, although plasma adrenaline and noradrenaline remained at subthreshold levels. Insulin clearance increased (approximately 25%, P less than 0.05) but only after 7 AM, resulting in a 4 mU/L decrease in plasma insulin. A significant correlation was found between increases in plasma glucose and increases in glucose production (r = 0.74, P less than 0.05) which in turn were significantly correlated with nocturnal peaks in plasma growth hormone (r = 0.66, P less than 0.05). From the sequence of events observed, we conclude that the Dawn Phenomenon in IDDM begins earlier than is currently thought (approximately 3:30 AM), that it is due to both accelerated glucose production and impaired glucose utilization, and that nocturnal increases in sympathetic nervous system activity and/or growth hormone secretion, but not changes in secretion of cortisol, adrenaline and glucagon or changes in insulin clearance, may be of pathogenetic importance.

Adult↗
PubMed1985

Sulfonylureas in the treatment of diabetes mellitus--1985.

Despite the fact that sulfonylurea orally administered hypoglycemic agents have been used in the treatment of non-insulin-dependent diabetes mellitus for almost 30 years, only recently have their mechanisms of action been delineated. In addition to the four agents previously available, two so-called second-generation agents were approved last year for use in the United States. The indications, contraindications, and guidelines for the use of these agents, as well as their mechanisms of action and the differences among them, are reviewed in this article. When appropriately used, these agents can provide a safe and effective adjunct to diet therapy in the management of patients with non-insulin-dependent diabetes mellitus and thus should be considered as an alternative to insulin therapy for such patients.

Blood Glucose↗
PubMed1985

Role of hepatic autoregulation in defense against hypoglycemia in humans.

To assess the role of hepatic autoregulation in defense against hypoglycemia, we compared the effects of complete blockade of glucose counterregulation with those of blockade of only neurohumoral counterregulation during moderate (approximately 50 mg/dl) and severe (approximately 30 mg/dl) hypoglycemia induced by physiologic hyperinsulinemia during subcutaneous infusion of insulin in normal volunteers. Compared with observations in control experiments, neurohumoral counterregulatory blockade (somatostatin, propranolol, phentolamine, and metyrapone), during which identical moderate hypoglycemia was achieved using the glucose clamp technique, resulted in suppressed glucose production (0.62 +/- 0.08 vs. 1.56 +/- 0.07 mg/kg per min at 12 h, P less than 0.01) and augmented glucose utilization (2.17 +/- 0.18 vs. 1.57 +/- 0.07 mg/kg per min at 12 h, P less than 0.01). Complete blockade of counterregulation (neurohumoral blockade plus prevention of hypoglycemia) did not further enhance the suppressive effects of insulin on glucose production. However, when severe hypoglycemia was induced during neurohumoral counterregulatory blockade, glucose production was nearly two times greater (1.05 +/- 0.05 mg/kg per min at 9 h) than that observed during complete counterregulatory blockade (0.58 +/- 0.08 mg/kg per min at 9 h, P less than 0.01) and that observed during mere neurohumoral blockade with moderate hypoglycemia (0.59 +/- 0.06 mg/kg per min at 9 h, P less than 0.01). These results demonstrate that glucose counterregulation involves both neurohumoral and hepatic autoregulatory components: neurohumoral factors, which require only moderate hypoglycemia for their activation, augment glucose production and reduce glucose utilization; hepatic autoregulation requires severe hypoglycemia for its activation and may thus serve as an emergency system to protect the brain when other counterregulatory factors fail to prevent threatening hypoglycemia.

Adrenergic alpha-Antagonists↗
PubMed1985

Abnormal glucose modulation of islet A- and B-cell responses to arginine in non-insulin-dependent diabetes mellitus.

To assess the normality of islet A- and B-cell responses to a nonglucose secretogogue as well as the modulating effect of glucose in NIDDM, we examined plasma C-peptide and glucagon responses to arginine in eight patients with NIDDM and in six age- and weight-matched nondiabetic volunteers under conditions of identical hypoglycemia (approximately 70 mg/dl), euglycemia (94 mg/dl), and hyperglycemia (approximately 190 mg/dl). Plasma C-peptide responses to glucose and to arginine in the diabetic subjects were both significantly reduced at all glucose concentrations studied (P less than 0.01-0.005). The modulating effect of glucose on both islet A- and B-cell responses (slope of relation between plasma C-peptide or glucagon response versus plasma glucose concentration) was reduced greater than 80% in the diabetic subjects (P less than 0.01). We conclude that islet A- and B-cell responses to nonglucose secretogogues are abnormal in patients with NIDDM and that this may result from a functional defect in the modulating effect of glucose on insulin and glucagon secretion, which in some patients may be compensated for by hyperglycemia.

Arginine↗
PubMed1985

Comparison of extraction procedures for radioimmunoassay of human plasma somatostatin.

Recovery and chromatography profiles of human plasma somatostatin extracted by three different procedures were compared. Extraction of plasma using acid-acetone-ether and octadecylsilyl silica gave comparable recovery (84 +/- 1 and 93 +/- 2%, respectively), which were nearly twofold greater than recovery achieved with the acid-ethanol method (50 +/- 1%, p less than 0.01). Acid-acetone-ether and octadecylsilyl silica extraction eliminated nearly completely immunoreactive material other than somatostatin-14 and -28, whereas the acid-ethanol-ether method did not. Because of its simplicity, octadecylsilyl silica is probably the method of choice for extraction of somatostatin from human plasma.

Acetone↗
PubMed1984

Glucose counterregulation and waning of insulin in the Somogyi phenomenon (posthypoglycemic hyperglycemia).

To determine the roles of glucose counterregulation and the waning of insulin action in the development of posthypoglycemic hyperglycemia (the Somogyi phenomenon), we studied changes in plasma glucose and glucose turnover in five patients with insulin-dependent diabetes mellitus (IDDM) after subcutaneous injection of insulin under conditions in which hypoglycemic glucose counterregulation and the waning of insulin action were allowed to occur or were prevented. In control experiments, in which both glucose counterregulation and insulin waning were allowed to occur, plasma glucose levels decreased from 94 +/- 3 to 47 +/- 7 mg per deciliter and then increased to 289 +/- 20 mg per deciliter at 12 hours because of a marked increase in glucose production. When the waning of insulin action was prevented by insulin infusion, glucose production increased less (P less than 0.01), but marked rebound hyperglycemia still occurred (188 +/- 26 mg per deciliter at 12 hours). When both insulin waning and glucose counterregulation were prevented by infusion of both glucose and insulin, glucose production did not increase, and rebound hyperglycemia did not occur. We conclude that hypoglycemia can cause rebound hyperglycemia in the absence of insulin waning in patients with IDDM, and that this results primarily from an excessive increase in glucose production due to activation of glucose counterregulatory systems.

Adult↗
PubMed1984

Abnormal glucose counterregulation after subcutaneous insulin in insulin-dependent diabetes mellitus.

We assessed glucose counterregulation during intensive insulin therapy in 20 patients with insulin-dependent diabetes mellitus (IDDM) by injecting therapeutic doses of regular insulin subcutaneously after overnight maintenance of euglycemia. As compared with nondiabetic controls matched for age and weight, 17 of the patients had more severe and more prolonged hypoglycemia (nadir, 42 +/- 2 in patients vs. 60 +/- 2 mg per deciliter in controls P less than 0.01; duration, 6.2 +/- 0.4 vs 2.1 +/- 0.6 hours, P less than 0.01). Most patients had decreased responses of several counterregulatory hormones. Marked rebound hyperglycemia (approximately equal to 300 mg per deciliter) ultimately developed in 11 patients. The only features distinguishing patients with rebound hyperglycemia from those without it were plasma free insulin concentrations during recovery from hypoglycemia (those with vs. those without, 7 +/- 1 vs. 22 +/- 2 microU per milliliter, P less than 0.01) and insulin-antibody binding (5 +/- 1 vs. 30 +/- 5 per cent, P less than 0.01). Rates of plasma glucose recovery from hypoglycemia were inversely correlated with plasma free insulin concentrations (r = -0.84, P less than 0.01); the latter in turn were directly correlated with insulin-antibody binding (r = 0.94, P less than 0.01). We conclude that many patients with IDDM have impaired glucose counterregulation due to multiple defects in counterregulatory-hormone secretion. This is associated with increased insulin-antibody binding, which prolongs the half-life of insulin. In such patients, intensive insulin therapy may be hazardous.

Adult↗
PubMed1984

The "dawn phenomenon"--a common occurrence in both non-insulin-dependent and insulin-dependent diabetes mellitus.

The dawn phenomenon is a condition recently described in patients with insulin-dependent diabetes mellitus (IDDM) that is characterized by abrupt increases in fasting levels of plasma glucose or insulin requirements or both between 5 and 9 a.m., in the absence of antecedent hypoglycemia. To determine its potential clinical relevance, we assessed its frequency and reproducibility in 20 patients with IDDM and in 13 patients with non-insulin-dependent diabetes mellitus (NIDDM) during overnight closed-loop (feedback-controlled) intravenous insulin infusion. After 6 a.m., plasma glucose levels increased similarly in NIDDM (89 +/- 2 mg per deciliter, midnight to 6 a.m., vs. 98 +/- 2 mg per deciliter, 6 to 9 a.m.; P less than 0.01). Insulin requirements increased at least 50 per cent for 1 1/2 hours in 77 per cent of patients with NIDDM and in 75 per cent of patients with IDDM. In five patients with IDDM who were studied on four occasions, the phenomenon occurred during 17 of the 20 observation periods, with insulin requirements after 6 a.m. increasing 225 +/- 34 per cent; coefficients of variation in individual patients ranged from 4 to 25 per cent. Thus, the dawn phenomenon occurs commonly in both NIDDM and IDDM, but its potential variability must be taken into consideration when one is attempting to adjust insulin doses.

Adult↗
PubMed1984

Acute effects of a glucose load on plasma apolipoproteins A-I, A-II, C-II, and C-III in normal and non-insulin-dependent diabetic men.

Changes in plasma levels of apolipoproteins A-I, A-II, C-II, and C-III, cholesterol, triglycerides, glucose, and insulin were studied after administration of a glucose load in six normal subjects and five patients with non-insulin-dependent diabetes mellitus. The main finding of our study was the significantly increased responses of total triglycerides and apolipoproteins C-II and C-III from the baseline values in the normal subjects but not in the diabetic group. High-density lipoprotein cholesterol levels at baseline and after glucose loading were significantly lower in diabetic than in normal subjects. As expected, abnormal glucose tolerance and hyperinsulinemia were observed in the diabetic subjects after the glucose loading. The peak glucose and insulin levels and their decline after the glucose loading were delayed in the diabetic patients. The glucose load did not significantly alter total plasma cholesterol, high-density lipoprotein cholesterol, and apolipoprotein A-I and A-II concentrations in normal and diabetic subjects. The apparent blunted response of total triglycerides and apolipoproteins C-II and C-III in the diabetic subjects may be related to maximal stimulation of synthesis of triglycerides and apolipoproteins C-II and C-III by the hyperglycemia and hyperinsulinemia (or both) present in these patients.

Administration, Oral↗
PubMed1984

Comparison of plasma insulin profiles after subcutaneous administration of insulin by jet spray and conventional needle injection in patients with insulin-dependent diabetes mellitus.

The characteristics of plasma free insulin profiles after conventional subcutaneous injection of regular insulin (10 units) and after jet injection of this amount of insulin were compared in eight subjects with insulin-dependent diabetes mellitus. Although administration of insulin with the jet injector resulted in peak plasma free insulin concentrations (45 +/- 4 microU/ml) similar to those achieved after conventional injection (47 +/- 5 microU/ml), it produced more rapid increases in plasma free insulin concentrations (time to peak concentration, 76 +/- 11 minutes versus 152 +/- 16 minutes; P less than 0.01) and less prolonged hyperinsulinemia. Variability in the peak insulin concentrations and the time to peak concentration was comparable for both methods of administration of insulin. Thus, insulin administered by jet injector may improve control of postprandial hyperglycemia and diminish the risk for late hypoglycemia in some patients with insulin-requiring diabetes mellitus treated with conventional injections of insulin.

Diabetes Mellitus, Type 1↗