Insulin Secretion in Type 1 Diabetes

Department of Medicine, Division of Endocrinology, and the Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Diabetes (Impact Factor: 8.1). 02/2004; 53(2):426-33. DOI: 10.2337/diabetes.53.2.426
Source: PubMed


Type 1 diabetes, a chronic autoimmune disease, causes destruction of insulin-producing beta-cells over a period of years. Although many markers of the autoimmune process have been described, none can convincingly predict the rate of disease progression. Moreover, there is relatively little information about changes in insulin secretion in individuals with type 1 diabetes over time. Previous studies document C-peptide at a limited number of time points, often after a nonphysiologic stimulus, and under non-steady-state conditions. Such methods do not provide qualitative information and may not reflect physiologic responses. We have studied qualitative and quantitative insulin secretion to a 4-h mixed meal in 41 patients with newly diagnosed type 1 diabetes and followed the course of this response for 24 months in 20 patients. Newly diagnosed diabetic patients had an average total insulin secretion in response to a mixed meal that was 52% of that in nondiabetic control subjects, considerably higher than has been described previously. In diabetic patients there was a decline of beta-cell function at an average rate of 756 +/- 132 pmol/month to a final value of 28 +/- 8.4% of initial levels after 2 years. There was a significant correlation between the total insulin secretory response and control of glucose, measured by HbA(1c) (P = 0.003). Two persistent patterns of insulin response were seen depending on the peak insulin response following the oral meal. Patients with an early insulin response (i.e., within the first 45 min after ingestion) to a mixed meal, which was also seen in 37 of 38 nondiabetic control subjects, had a significantly accelerated loss of insulin secretion, as compared with those in whom the insulin response occurred after this time (P < 0.05), and significantly greater insulin secretory responses at 18 and 24 months (P < 0.02). These results, which are the first qualitative studies of insulin secretion in type 1 diabetes, indicate that the physiologic metabolic response is greater at diagnosis than has previously been appreciated, and that the qualitative insulin secretory response is an important determinant of the rate of metabolic decompensation from autoimmune destruction.

8 Reads
  • Source
    • "However, individuals with a stimulated C-peptide value of .0.5 pmol/mL were specifically excluded from the DCCT, so these findings may underestimate the prevalence of significant insulin production with longer duration. Steele et al. (2004) reported an average decline of 756 +132 pmol/mo in the C-peptide response to a mixed meal, to a final value of 28 + 8.4% of initial levels 2 years after diagnosis. These studies, which are now more than a decade old, should be replicated with contemporary data because it is clear that glucose control may affect the decline in b-cell function. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Type 1 diabetes (T1D), also known as insulin-dependent diabetes mellitus, is a chronic disorder that results from autoimmune destruction of insulin-producing β cells in the islets of Langerhans within the pancreas ( Atkinson and Maclaren 1994). This disease becomes clinically apparent only after significant destruction of the β-cell mass, which reduces the ability to maintain glycemic control and metabolic function. In addition, it continues for years after clinical onset until, generally, there is complete destruction of insulin secretory capacity. Because prevention and therapy strategies are targeted to this pathologic process, it becomes imperative to have methods with which it can be monitored. This work discusses current research-based approaches to monitor the autoimmunity and metabolic function in T1D patients and their potential for widespread clinical application.
    Cold Spring Harbor Perspectives in Medicine 06/2012; 2(6):a007708. DOI:10.1101/cshperspect.a007708 · 9.47 Impact Factor
  • Source
    • "With standard assays, many patients are assessed as having lost considerable insulin secretion by the time type 1 diabetes is diagnosed (2,3). Yet even low levels of insulin or C-peptide are consistently linked to lower frequency of late-stage complications (10). "
    [Show abstract] [Hide abstract]
    ABSTRACT: To examine persistence of C-peptide production by ultrasensitive assay years after onset of type 1 diabetes and factors associated with preserving β-cell function. Serum C-peptide levels, a marker of insulin production and surviving β-cells, were measured in human subjects (n = 182) by ultrasensitive assay, as was β-cell functioning. Twenty-two times more sensitive than standard assays, this assay's lower detection limit is 1.5 pmol/L. Disease duration, age at onset, age, sex, and autoantibody titers were analyzed by regression analysis to determine their relationship to C-peptide production. Another group of four patients was serially studied for up to 20 weeks to examine C-peptide levels and functioning. The ultrasensitive assay detected C-peptide in 10% of individuals 31-40 years after disease onset and with percentages higher at shorter duration. Levels as low as 2.8 ± 1.1 pmol/L responded to hyperglycemia with increased C-peptide production, indicating residual β-cell functioning. Several other analyses showed that β-cells, whose C-peptide production was formerly undetectable, were capable of functioning. Multivariate analysis found disease duration (β = -2.721; P = 0.005) and level of zinc transporter 8 autoantibodies (β = 0.127; P = 0.015) significantly associated with C-peptide production. Unexpectedly, onset at >40 years of age was associated with low C-peptide production, despite short disease duration. The ultrasensitive assay revealed that C-peptide production persists for decades after disease onset and remains functionally responsive. These findings suggest that patients with advanced disease, whose β-cell function was thought to have long ceased, may benefit from interventions to preserve β-cell function or to prevent complications.
    Diabetes care 03/2012; 35(3):465-70. DOI:10.2337/dc11-1236 · 8.42 Impact Factor
  • Source
    • "In addition to that, it would be prefer to study effects on the insulin secretion from the pancreas in type 1 diabetes mellitus. Process in the insulin synthesis and secretion is disregulated and is related with the destruction of the β cells in Langerhan's islets (Gorsuch et al., 1981; Steele et al., 2004; Weir & Bonner-weir, 2004). Clinically, insulin activities have been assessed by peripheral blood insulin and C-peptide measurements. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cassia tora L. seeds have previously been reported to reduce blood glucose level in human and animals with diabetes. In the present study, the effects of Cassia tora L. seed butanol fraction (CATO) were studied on postprandial glucose control and insulin secretion from the pancreas of the normal and diabetic rats. Diabetes was induced by an i.p. injection of Streptozotocin (55 mg/kg BW) into the male Sprague-Dawley rats. The postprandial glucose control was monitored during a 240 min-period using a maltose loading test. In normal rats, rats fed CATO (20 mg/100 g BW/d) showed lower postprandial glucose levels in all the levels from 30 min up to 180 min than those in the control rats without CATO (p<0.05). In diabetic rats, those levels in the CATO group seemed to be lower during the 30~180 min, but only glucose level at 30 min showed significant difference compared to that in the control group. Moreover, CATO delayed the peak time of the glucose rise in both normal and diabetic rats in the glucose curves. On the other hand, when CATO was administered orally to the diabetic rats for 5 days, 12 hr fasting serum glucose level was decreased in the diabetic rats (p<0.05). Degree of a decrease in 12 hr fasting serum insulin levels was significantly less in the diabetic CATO rats as compared to diabetic control rats. On the last day of feeding, beta cells of the pancreas were stimulated by 200 mg/dL glucose through a 40 min-pancreas perfusion. Amounts of the insulin secreted from the pancreas during the first phase (11~20 min) and the second phase (21~40 min) in the CATO fed diabetic rats were significantly greater than those in the diabetic control group (p<0.05). These findings indicated that constituents of Cassia tora L. seeds have beneficial effect on postprandial blood glucose control which may be partially mediated by stimulated insulin secretion from the pancreas of the diabetic rats.
    Nutrition research and practice 12/2008; 2(4):240-6. DOI:10.4162/nrp.2008.2.4.240 · 1.44 Impact Factor
Show more