Spontaneous Hypoglycemia as an Early Manifestation of Diabetes Mellitus

Jw, Conn; Ss, Fajans; Hs, Seltzer

doi:10.2337/diab.5.6.437

Cited by 112 publications

(21 citation statements)

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“…Moreover, when comparable glucose curves of obese and nonobese controls Introduction That the normal beta cell responds promptly and proportionally to a rising blood glucose concentration was shown by Metz (1) and confirmed by Seltzer (2). Moreover, the interpretation invoked by Seltzer, Fajans, and Conn (3), that the occurrence of symptomatic postprandial hypoglycemia in patients with mild diabetes mellitus might be due to delayed initial release of insulin followed by subsequent excessive hormonal secretion, was suggestively confirmed when Yalow and Berson (4) found subnormal plasma insulin concentrations at 30 minutes during glucose tolerance testing of mild diabetics but supernormal levels at 2 hours. The present study was designed to determine whether this postulated "biochemical inertia" of beta cell response is in fact demonstrable in the earliest stage of clinical diabetes, and, if so, whether it seems causally related to the delayed clearance of postprandial hyperglycemia.…”

mentioning

confidence: 81%

“…Corresponding over-all indexes after oral glucose were 4.93 + 0.54 (100o), 2.43 ± 0.39 (49%o), and 0.47 +0.13 (10%o). 3 Respective increments above fasting levels, instead of absolute values, were used for two reasons. First, blood glucose and plasma insulin levels remained constant in fasting subjects or patients lying supine for 4 hours (11).…”

Section: Resultsmentioning

confidence: 99%

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Insulin Secretion in Response to Glycemic Stimulus: Relation of Delayed Initial Release to Carbohydrate intolerance in Mild Diabetes Mellitus*

Seltzer¹,

Allen²,

Herron³

et al. 1967

J. Clin. Invest.

784

387

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Summary. Insulin secretory responses to paired intravenous and oral glucose loads were determined in 38 nonobese individuals classified as normal (nondiabetic) subjects, "mild" diabetics (fasting blood glucose below 105 mg per 100 ml), or "moderate" diabetics (fasting glucose below 192 mg per 100 ml). Studies were also performed in 29 obese persons who were similarly grouped. The intravenous load was given to assess the alacrity of hormonal release after glycemic stimulus, and the oral glucose to determine how the speed of initial insulinogenesis modifies the disposition of ingested carbohydrate.In the nonobese group, normal subjects responded to massive hyperglycemia after rapid injection of glucose with immediate and maximal outpouring of insulin, in contrast to a desultory insulinogenic response in patients with mild diabetes, and no initial response at all in moderate diabetics. During oral glucose tolerance tests, the much faster clearance of blood sugar in nondiabetic subjects was actually associated with lower absolute insulin output than was found in mildly diabetic patients, since the latter exhibited delayed hyperinsulinemia in concert with prolonged hyperglycemia. Moderate diabetics never showed excessive insulin release despite even greater hyperglycemia. An empirical "insulinogenic index," the ratio relating enhancement of circulating insulin to magnitude of corresponding glycemic stimulus, was used to compare the secretory capacities of respective groups. Despite the higher absolute hormonal output after oral glucose in mild diabetics, the index revealed that insulin release in normal subjects was proportionally more than twice as great. This relatively greater normal secretory response declared itself shortly after the administration of glucose by either route, and was maintained throughout both tests.In the 29 obese individuals, differences among groups were essentially the same as in persons of normal weight. Obese nondiabetics did show much larger absolute insulinogenic responses during both tests than did nonobese controls. Since corresponding glucose tolerance curves were also higher, the mean insulinogenic indexes for obese subjects were not statistically greater. Moreover, when comparable glucose curves of obese and nonobese controls * Submitted for publication September 13, 1965; ac- were matched, the apparent hyperinsulinemia associated with obesity was again reduced to insignificance. At the same time, a tendency toward perpetuation of higher insulin levels in overweight normal subjects and mild diabetics, in response to both glucose loads, suggested that obesity per se does induce a state of peripheral insulin resistance.The data indicate that normal beta cells respond instantly to a glycemic stimulus, whereas diabetic islets react sluggishly, and that proportionally greater insulinogenesis accounts for faster disposal of postprandial hyperglycemia in nondiabetics than in diabetics, in both nonobese and obese individuals. By tracing a rational sequence of events within the beta cell-fro...

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mentioning

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Insulin Secretion in Response to Glycemic Stimulus: Relation of Delayed Initial Release to Carbohydrate intolerance in Mild Diabetes Mellitus*

Seltzer¹,

Allen²,

Herron³

et al. 1967

J. Clin. Invest.

784

387

View full text Add to dashboard Cite

show abstract

“…At present her glucose tolerance is normal, with a tendency toward hypoglycemia several hours after glucose ingestion. It is impossible to determine whether this hypoglycemia represents a manifestataion of "pre-diabetes" (27) or reflects the residual hyperfunction of her islets which was thought to be present during the period of insulin-unresponsive diabetes. Although temporary remissions have been frequently observed soon after the diagnosis and energetic treatment of diabetes mellitus in some juvenile patients, remission of such severe diabetes as the present patient had is most unusual (9).…”

Section: Discussionmentioning

confidence: 99%

Insulin-Resistant Diabetes Associated With Increased Endogenous Plasma Insulin Followed by Complete Remission

Field¹,

Johnson²,

Herring³

1961

J. Clin. Invest.

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Insulin unresponsiveness may be associated with a multitude of conditions and reflect diverse etiologies (1). In most cases of chronic insulin resistance it has been possible to demonstrate insulin antagonists in the plasma which have many of the characteristics of antibodies (2-4). The resistance to insulin has usually been attributed to these antibodies, but several cases of insulin resistance associated with increased amounts of insulin in the plasma have been reported (5-8). In these cases tissue unresponsiveness was postulated as the cause for the resistance. In all of these cases circulating insulin could be demonstrated only at a time when the patients were receiving large doses of exogenous insulin, and therefore the insulin in the plasma probably represented injected insulin. We recently have had occasion to study a patient with severe insulin resistance whose plasma contained large amounts of insulin 3 months after her last known injection. Over the ensuing 18 months she had a gradual but complete remission of both diabetes and insulin unresponsiveness. The purpose of this paper is to report studies on this case which indicate that the insulin-like activity in her plasma did, in fact, represent endogenous insulin and that the cause for her insulin resistance was probably due to decreased tissue responsiveness to the hormone. The explanation for her remission is unknown, although there are occasional reports in the literature of spontaneous remission in severe diabetics (9). As far as we know this is the first reported case of insulin-resistant diabetes associated with greatly increased levels of endogenous insulin. METHODSThe rat hemidiaphragm. studies were done as follows.Fed rats weighing between 120 and 170 g were killed by a blow on the head; the diaphragms were removed as rapidly and with as little trauma as possible. Each hemidiaphragm was trimmed, blotted, weighed on a torsion balance and then put into a flask holding 2 ml of incubation medium which contained 0.5 ml of 1,000 mg per 100 ml glucose in Krebs-Ringer bicarbonate buffer (pH 7.4), variable amounts up to 1 ml of dialyzed plasma to be tested, and enough Krebs-Ringer bicarbonate buffer to make the final volume 2 ml.

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“…Hypoglycaemia occurring several hours post prandially may be due to pre-diabetes (Seltzer, Fajans, and Conn, 1956). However, a family history of diabetes, which would increase the chance of the patient having pre-diabetes, was found about as frequently in those with as those without hypoglycaemia in the present series.…”

Section: Methodsmentioning

confidence: 99%

Insulin response to carbohydrate ingestion after gastric surgery with special reference to hypoglycaemia

Cameron¹,

Ellis²,

McGill³

et al. 1969

Gut

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SUMMARY Factors responsible for spontaneous hypoglycaemia were investigated in 23 gastrectomy patients and two patients with vagotomy and pyloroplasty. Plasma insulin and capillary blood glucose levels were followed after giving 175 ml of 50% glucose orally. In gastrectomy patients a significant correlation was found between the height of the peak blood glucose and insulin levels for the same individual. Patients with high peak glucose and insulin levels were significantly more likely to develop hypoglycaemia later in the test. These findings are compatible with the suggestion that the major factor predisposing to hypoglycaemia is a faster than average rate of emptying of the gastric remnant, but this does not explain all the results. In two cases, hypoglycaemia followed an abnormally large insulin response to oral glucose. The results of insulin injection tests in 14 patients do not exclude the further possibility that in some cases hypoglycaemia is due to excessive insulin sensitivity.

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Spontaneous Hypoglycemia as an Early Manifestation of Diabetes Mellitus

Cited by 112 publications

References 0 publications

Insulin Secretion in Response to Glycemic Stimulus: Relation of Delayed Initial Release to Carbohydrate intolerance in Mild Diabetes Mellitus*

Insulin Secretion in Response to Glycemic Stimulus: Relation of Delayed Initial Release to Carbohydrate intolerance in Mild Diabetes Mellitus*

Insulin-Resistant Diabetes Associated With Increased Endogenous Plasma Insulin Followed by Complete Remission

Insulin response to carbohydrate ingestion after gastric surgery with special reference to hypoglycaemia

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