Evidence for a Long Prediabetic Period in Type I (Insulin-Dependent) Diabetes Mellitus

Gorsuch, A.N.; Lister, John; Dean, B M; Spencer, K M; McNally, J. M.; Bottazzo, Gian Franco; Cudworth, A G

doi:10.1016/s0140-6736(81)92795-1

Cited by 477 publications

(178 citation statements)

References 17 publications

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“…So far there is no evidence that individuals who are positive for CF-ICA in the prediabetic period become ICA-negative before diagnosis of the disease [5][6][7][8]. This fact supports the hypothesis that patients who are CF-ICA negative at the clinical onset have a different pathogenesis of their fl-cell destruction than those who are positive for CF-ICA.…”

Section: Discussionmentioning

confidence: 87%

“…CF-ICA have been reported to appear in the circulation for as long as 3 years before the clinical manifestation of Type 1 diabetes [5,6]. The appearance of CF-ICA may be the first indicator of minimal t-cell damage.…”

Section: Discussionmentioning

confidence: 99%

“…Also, CF-ICA disappear at an earlier stage in the disease than ICA-IgG [3,4]. It has been suggested in recent reports that the presence of CF-ICA may be of some value in predicting Type 1 diabetes [5][6][7], and these antibodies have even been shown to appear years before the clinical onset of the disease [5,8].…”

mentioning

confidence: 99%

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Evidence of delayed ?-cell destruction in Type 1 (insulin-dependent) diabetic patients with persisting complement-fixing cytoplasmic islet cell antibodies

et al. 1984

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Summary. Forty-four children with Type 1 (insulin-dependent) diabetes (aged 0.7-16.7 years) were observed from diagnosis for cytoplasmic islet cell antibodies and serum C-peptide concentrations. Islet cell antibodies were analysed by indirect immunofluorescence for both conventional IgG and complement-fixing antibodies. Thirty-seven children (84%) were found to be positive for conventional islet cell antibodies at diagnosis, and 21 (48%) remained positive over the observation period. Twenty-six patients (59%) were positive for complement-fixing antibodies at diagnosis and eight remained so during the follow-up period. The serum C-peptide concentrations increased significantly during the first 3 months after diagnosis, after which there was a gradual decrease in the levels. Those children who remained positive for complement-fixing antibodies over the observation period had significantly higher serum C-peptide concentrations on several occasions during the second year and had also a higher integrated serum C-peptide concentration over the initial 2 years than those who became negative for complement-fixing antibodies. These observations suggest that the continuous production of complement-fixing islet cell antibodies in those patients who are positive for these antibodies at diagnosis presupposes the preservation of a sufficient amount of functioning/~ cells for antigenic stimulation. These results support the view that the complement-fixing islet cell antibodies reflect ongoing destructive processes in the/3 cells.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Evidence of delayed ?-cell destruction in Type 1 (insulin-dependent) diabetic patients with persisting complement-fixing cytoplasmic islet cell antibodies

et al. 1984

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“…Subjects at risk of developing type 1 diabetes mellitus may be identified by the detection of anti-pancreatic humoral markers (1,2). An increased risk of type 1 diabetes mellitus was reported in patients with other endocrine autoimmune diseases, including thyroid diseases (3).…”

Section: Introductionmentioning

confidence: 99%

Anti-pancreatic autoimmunity and Graves' disease: study of a cohort of 600 Caucasian patients

Maugendre¹,

Verite²,

Guilhem³

et al. 1997

European Journal of Endocrinology

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The aim of this study was to investigate the frequencies of clinical diabetes and humoral markers of anti-pancreatic autoimmunity in a homogeneous population of 600 Caucasian patients with recently diagnosed Graves' disease (GD), in order to characterize the specific features of this group of endocrine patients among subjects at risk of diabetes.Ten were already diabetic at GD diagnosis. Among the 590 non-diabetic patients, 29 had islet cell antibodies (ICA), including 15 with low titre ICA and only 1 ICA-positive subject with a familial history of diabetes. Twenty-four patients had insulin autoantibodies, including three in association with ICA. Glutamic acid decarboxylase (GAD)/64 kDa antibodies were found in 16 of the 150 tested sera, including 13 of the 29 ICA-positive sera. Four ICA-positive patients displayed 37/40 kDa antibodies, including three in association with GAD/64 kDa antibodies. During follow-up, one of the ICA-positive patients developed insulin-dependent diabetes, 14 years after the GD diagnosis.To summarize, this anti-pancreatic autoimmunity study was focused on a large but specific and homogeneous group of subjects at risk for diabetes: recently diagnosed GD patients. This population was characterized by a high prevalence of GAD/64 kDa antibodies but also by a low frequency of evolution towards diabetes and the slowness of the process which could be due to the fact that only a minority of subjects possessed a sufficient combination of anti-pancreatic markers at the same time.

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“…Loss of the first phase insulin response to intravenous glucose is the earliest detectable metabolic abnormality in subjects who later develop Type 1 (insulin-dependent) diabetes [1], and the intravenous glucose tolerance test (IVGTT) is used to complement immunological markers [2] in identifying individuals at risk.…”

mentioning

confidence: 99%

Between and within subject variation of the first phase insulin response to intravenous glucose

et al. 1988

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Summary. Eight normal subjects underwent two intravenousglucose tolerance tests to determine the between and within subject variation of the first phase insulin response. Variability was represented by the coefficient of variation. The between subject variation for the incremental 0-10 rain insulin area was 58%, and the within subject variation was 22% (median value), range 3-55%. The variation of the first phase response expressed in four different ways was compared. The total and incremental (above fasting levels) 0-10 rain areas provided less variable results (variation 52 and 58%) than the l + 3 rain insulin levels (variation 72%) or mean of the incremental 3-5 rain insulin levels (variation 66%). The ratio of the incremental 0-10 min insulin to glucose areas was as variable (variation 53%) as the insulin responses alone. The variability of insulin responses to intravenous glucose severely limits their value as early predictors of B-cell failure. Key words: Variability, insulin, glucose.Loss of the first phase insulin response to intravenous glucose is the earliest detectable metabolic abnormality in subjects who later develop Type 1 (insulin-dependent) diabetes [1], and the intravenous glucose tolerance test (IVGTT) is used to complement immunological markers [2] in identifying individuals at risk.The insulin response to the IVGTT is already known to be highly variable [3], but we have concentrated on variability of the first phase insulin response, since this appears to have the greatest prognostic value [I]. We have investigated the between and within subject variation of the first phase insulin response because these seem crucial for interpretation of cross-sectional or longitudinal data.

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Evidence for a Long Prediabetic Period in Type I (Insulin-Dependent) Diabetes Mellitus

Cited by 477 publications

References 17 publications

Evidence of delayed ?-cell destruction in Type 1 (insulin-dependent) diabetic patients with persisting complement-fixing cytoplasmic islet cell antibodies

Evidence of delayed ?-cell destruction in Type 1 (insulin-dependent) diabetic patients with persisting complement-fixing cytoplasmic islet cell antibodies

Anti-pancreatic autoimmunity and Graves' disease: study of a cohort of 600 Caucasian patients

Between and within subject variation of the first phase insulin response to intravenous glucose

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