Lack of control by glucose of ultradian insulin secretory oscillations in impaired glucose tolerance and in non-insulin-dependent diabetes mellitus.

O'Meara, N M; Sturis, Jeppe; Cauter, Eve Van; Polonsky, Kenneth S.

doi:10.1172/jci116560

Cited by 122 publications

(88 citation statements)

References 54 publications

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“…9 In vivo, an oral glucose tolerance test 15 or euglycaemic-hyperinsulinaemia 20 do not affect circulating plasma leptin concentrations, whereas long-term hyperinsulinemia 32 or 72 h hyperglycemia may increase plasma leptin. 33 Thus, the long-term loss of the physiological pulsatility of insulin secretion 34 could be responsible for the decreased plasma leptin levels in diabetes mellitus observed in the present study. Even more there is evidence that hyperinsulinemia with concomitant hypoglycaemia, that usually occurs in well controlled diabetic patients, leads to a reduction of plasma leptin levels.…”

Section: Discussionmentioning

confidence: 56%

Relative hypoleptinemia in patients with type 1 and type 2 diabetes mellitus

et al. 2000

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OBJECTIVE: To determine the relation between plasma leptin concentrations and metabolic control in human diabetes mellitus. DESIGN AND SUBJECTS: Cross sectional study consisting of 156 patients with diabetes mellitus type 1 (n 42), type 2 (n 114), and non-diabetic subjects (n 74). RESULTS: Plasma leptin concentrations were lower (P`0.05) in type 1 (8.3 AE 1.7 ngaml) and type 2 diabetic (14.9 AE 1.8 ngaml) than in non-diabetic humans (18.3 AE 1.9 ngaml). Only female type 1 and type 2 diabetic subjects also had decreased leptinaBMI ratios (P`0.05 vs non-diabetic females). The log rank test identi®ed age-adjusted correlation of plasma leptin concentration with sex (P`0.0004) and body mass index (P`0.0218), but not with glycosylated haemoglobin A 1c (P b 0.5) in all groups. Plasma leptin was correlated with age (P`0.0058) and serum triglycerides (P`0.0199) in type 1 diabetic patients, and with serum cholesterol (P`0.0059) and LDL (P`0.0013) in type 2 diabetic patients. CONCLUSIONS: Defective leptin production andaor secretion might be present independently of metabolic control in female patients with type 1 or type 2 diabetes mellitus.

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Section: Discussionmentioning

confidence: 56%

Relative hypoleptinemia in patients with type 1 and type 2 diabetes mellitus

et al. 2000

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“…Support for this interpretation exists in previous findings in IGT subjects. In particular, there is a progressive decline in the normally tight temporal coupling between glucose and insulin secretion as glucose tolerance deteriorates from normal to IGT to frank diabetes [6]. We previously reported that this defect, present in those with IGT, improves after treatment with the insulinsensitizing agent troglitazone [25,26].…”

Section: Discussionmentioning

confidence: 99%

Insulin secretory responses to rising and falling glucose concentrations are delayed in subjects with impaired glucose tolerance

et al. 2002

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Impaired glucose tolerance (IGT) is defined by an increase in plasma glucose in response to an oral glucose challenge to levels intermediate between normal and diabetic [1] and is a risk factor for the subsequent development of diabetes [2]. The transition from normal glucose tolerance to IGT is characterized by a reduction in the ability of the pancreatic beta cell to sustain its compensatory response to insulin resistance [3]. When compared to subjects with normal glucose tolerance, those with IGT have a blunted insulin secretory response to the rise in glucose during a rapidly sampled intravenous glucose tolerance test (IVGTT) and a shift to the right in the dose-response curve relating the plasma glucose concentration to the insulin secretion rate [4,5]. IGT is additionally Diabetologia (2002) Abstract Aims/hypothesis. We hypothesized that beta-cell responses to changes in glucose would not be normal in subjects with impaired glucose tolerance (IGT). Methods. Three groups of 6 subjects were studied: normal weight with normal glucose tolerance (control subjects); obese with normal glucose tolerance (Obese-NGT); and obese with IGT (Obese-IGT). All subjects had a graded glucose infusion protocol to increase (step-up) and then decrease (step-down) plasma glucose. We obtained average insulin-secretion rates (ISR) over the glucose range common to all three groups during step-up and step-down phases, minimal model indices of beta-cell function (φ b , φ d , φ s , T up , T down ), and insulin sensitivity (Si). Results. ISR differed significantly between step-up and -down phases only in Obese-IGT individuals. Basal (φ b ) and stimulated (φ d , φ s ) beta-cell sensitivity to glucose were similar in the three groups. Delays between glucose stimulus and beta-cell response during both step-up (T up ) and -down (T down ) phases were higher in Obese-IGT compared to Controls and Obese-NGT individuals. The product ISR Si (10 ±5´m in ±2 l) was lower in Obese-IGT compared to Controls, both during step-up (919 851 vs 3192 1185, p < 0.05) and step-down (1455 1203 vs 3625 691, p < 0.05) phases. Consistently, the product φ s Si (10 ±14´m in ±2´p mol ±1 l) was lower in Obese-IGT than in control subjects (27.6 25.4 vs 103.1 20.2, p < 0.05). Conclusion/interpretation. Subjects with IGT are not able to secrete insulin to compensate adequately for insulin resistance. They also show delays in the timing of the beta-cell response to glucose when glucose levels are either rising or falling. [Diabetologia (2002) 45:509±517]

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“…We determined whether the control by glucose of the ultradian oscillations in insulin secretion is altered in impaired glucose tolerance IGT and in noninsulin-dependent diabetes mellitus (NIDDM). 6 Patients with NIDDM (n 7), IBT (n 4), and matched non-diabetic controls (n 5) were studied under three separate protocols that involved administration of glucose at either a constant rate of 6 mgakg per min for 28 h or in one of two oscillatory patterns at the same overall mean rate. The amplitude of the oscillations was 33% above and below the mean infusion rate, and their respective periods were 144 min (slow oscillatory infusion) or 96 min (rapid oscillatory infusion).…”

Section: Introductionmentioning

confidence: 99%

“…Further studies are needed to determine how early in the course of beta-cell dysfunction this lack of control by glucose of the ultradian oscillations in insulin secretion occurs and to de®ne more precisely if this phenomenon plays a pathogenetic role in the onset of hyperglycemia in genetically susceptible individuals. 6 To determine whether non-insulin-dependent diabetes is associated with speci®c alterations in the pattern of insulin secretion, we studied 16 patients with untreated diabetes and 14 matched controls. 7 The rates of insulin secretion were calculated from measurements of peripheral C-peptide in blood samples taken at 15 ± 20 minute intervals during a 24 h period in which the subjects ate three mixed meals.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of insulin secretion in obesity and diabetes

Polonsky

2000

Int J Obes

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Insulin resistance and compensatory hyperinsulinemia are commonly present in obesity. The biochemical mechanisms responsible for the maintenance of basal hypersecretion of insulin are reviewed in this article. Under basal, fasting and fed conditions the hyperinsulinemia of obesity largely depends on increased insulin secretion, without any alteration of the temporal secretion. This suggests that the functioning beta cell mass is enhanced, but normal regulatory mechanisms are maintained. A number of alterations in b-cell function are present in conditions of impaired glucose tolerance which precede the onset of overt diabetes.

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Lack of control by glucose of ultradian insulin secretory oscillations in impaired glucose tolerance and in non-insulin-dependent diabetes mellitus.

Cited by 122 publications

References 54 publications

Relative hypoleptinemia in patients with type 1 and type 2 diabetes mellitus

Relative hypoleptinemia in patients with type 1 and type 2 diabetes mellitus

Insulin secretory responses to rising and falling glucose concentrations are delayed in subjects with impaired glucose tolerance

Dynamics of insulin secretion in obesity and diabetes

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