The Banting Memorial Lecture 1965: Some Current Controversies in Diabetes Research

Berson, Solomon A.; Yalow, Rosalyn S.

doi:10.2337/diab.14.9.549

Cited by 148 publications

(41 citation statements)

References 24 publications

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“…Similar findings have been found with oral glucose [27]. During oral glucose tolerance testing in some abnormal states, the insulin response to glucose may be delayed in timing, even though values reached may be normal or higher than normal [27][28][29]. This delayed insulin release is reflected by a low 15rain and often 30min insulin level.…”

Section: Discussionsupporting

confidence: 68%

Glucose tolerance in siblings of Type 1 diabetic patients relationship to HLA status

Orchard¹,

Wagener²,

Rabin

et al. 1986

Diabetologia

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Summary. In this report, we present an analysis of glucose and insulin responses during oral glucose tolerance tests in 369 siblings of Type 1 diabetic patients. All have been HLA typed at the A, B and C loci. Though most had normal glucose tolerance by National Diabetes Data Group criteria (92% of the males and 95% of the females), siblings who shared both HLA haplotypes with the diabetic patient in the family had higher mean 3-hour glucose areas than those who shared one or neither HLA haplotype (p <0.01). This difference was more marked in males and older siblings. Insulin concentrations did not differ significantly between the two groups except that, for those aged <16years, the group sharing both haplotypes had lower fasting insulin concentrations (p =0.05); for 16-29 year olds, the corresponding group had marginally higher 3-hour insulin areas than the remainder of siblings (p = 0.17). Little association with specific haplotypes (A1B8 or A2B~s) was seen. Multivariate analyses, adjusting for age and obesity, eliminated the 3-h glucose difference in females by HLA sharing status (p = 0.37) although in males it remained significant (p < 0.001). Failure to account for age, sex and obesity may explain some of the conflicts in the reported literature. The glucose tolerance differences seen by HLA haplotype sharing status did not correlate with the presence of anti-islet cell antibodies. These results are consistent with the hypothesis that the HLA identical siblings, particularly males, have different (i. e. worse) glucose tolerance than their haploidentical and non-HLA identical siblings.Key words: Type 1 diabetes -Genetics -Aetiology -Glucose tolerance -HLA type -Islet cell.Consistent with their known increased risk of developing Type 1 diabetes mellitus, siblings of Type I diabetic patients have been thought to have a higher frequency of glucose tolerance abnormalities than the general population [1][2][3]. The risk for developing Type 1 diabetes, which we estimate from our registry to be approximately 3.5% [4], is further increased for siblings who share both HLA haplotypes with the diabetic patient [5].Recently, therefore, interest has focused on whether a sibling's HLA sharing status with the diabetic patient in the family, or his or her possession of specific HLA antigens, is itself associated with glucose tolerance and/ or insulin secretory abnormalities. Thus far, published data have been conflicting. One recent study reported an exaggerated insulin response [6] while another suggested a lower insulin response in HLA identical siblings [7]. Indeed, different patterns of abnormalities were also seen when we initially looked at our own data three years ago compared to our findings one year later on a larger sample [8]. In this report, we present data on 369 siblings in order to test the hypothesis that those siblings with the greater risk of developing Type 1 diabetes (i. e. the HLA identical) will more frequently demonstrate abnormalities of glucose tolerance and insulin concentrations and/or, as a group...

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Section: Discussionsupporting

confidence: 68%

Glucose tolerance in siblings of Type 1 diabetic patients relationship to HLA status

Orchard¹,

Wagener²,

Rabin

et al. 1986

Diabetologia

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“…Although Yalow and Berson (19,20) and Seltzer et al (13) also noted a deficient early insulin response and late insulin peak in diabetes, some groups of mild diabetics in their series had greater than normal mean insulin responses to glucose independent of obesity. It is difficult to reconcile these results with the present observations.…”

Section: Discussionmentioning

confidence: 99%

The Significance of Basal Insulin Levels in the Evaluation of the Insulin Response to Glucose in Diabetic and Nondiabetic Subjects*

Bagdade¹,

Bierman²,

Porte³

1967

J. Clin. Invest.

632

272

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Abstract. The level of insulin after an overnight fast (basal) in 37 obese and nonobese male subjects with normal and abnormal carbohydrate tolerance was directly related to the increase in insulin concentration during a 3 hr 100 g oral glucose tolerance test. Obesity, but not diabetes, was associated with an elevation of this basal insulin level. Thus obesity predicted with the magnitude of the insulin response to glucose ingestion. When the individual insulin values were expressed as per cent change from the basal level, this effect of obesity was excluded. The insulin levels of all subjects with normal carbohydrate tolerance promptly rose 5-7-fold, and reached peak values 1 hr after oral glucose. In contrast, the diabetic response (as per cent increase) was markedly reduced during the 1st hr, and maximal (but still subnormal) insulin levels were not attained until 2 hr. In all subjects the insulin response (quantitated by calculation of the area circumscribed by a plot of the per cent change in insulin with time) showed a significant inverse correlation with the glucose response. Thus increasing degrees of carbohydrate intolerance were associated with decreasing insulin responses. Elevated levels of insulin, in both the basal state and in response to glucose, were related to obesity.

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“…At times it appeared that almost anything in serum at a high enough concentration could exert some insulin-like effect in these assays. In addition, there was a problem referred to as the dilution effect, i.e., detection of insulin added to serum varied depending on the dilution of serum used in the assays (12). The immunoassay method conquered all of these problems.…”

Section: Assays Of Insulin In Blood Prior To Riamentioning

confidence: 99%

Berson, Yalow, and the JCI: the agony and the ecstasy

Kahn¹,

Roth²

2004

J. Clin. Invest.

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The Banting Memorial Lecture 1965: Some Current Controversies in Diabetes Research

Cited by 148 publications

References 24 publications

Glucose tolerance in siblings of Type 1 diabetic patients relationship to HLA status

Glucose tolerance in siblings of Type 1 diabetic patients relationship to HLA status

The Significance of Basal Insulin Levels in the Evaluation of the Insulin Response to Glucose in Diabetic and Nondiabetic Subjects*

Berson, Yalow, and the JCI: the agony and the ecstasy

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