Insulin resistance and β‐cell dysfunction in normoglycaemic European women with a history of gestational diabetes

Kousta, Eleni; Lawrence, Natasha J.; Godsland, Ian F.; Penny, Anna; Anyaoku, V.; Millauer, Barbara A.; Cela, Ester; Johnston, Desmond G.; Robinson, Stephen T.; McCarthy, Mark I.

doi:10.1046/j.1365-2265.2003.01820.x

Cited by 63 publications

(53 citation statements)

References 57 publications

(101 reference statements)

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“…Abnormalities in beta cell function as well as in insulin action have been described in other cohorts of women with a history of gestational diabetes [15,[37][38][39][40][41][42]. The heterogeneity between these studies is probably a result of the different ethnic and geographic origins of the populations studied.…”

Section: Discussionmentioning

confidence: 98%

Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes

et al. 2005

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Aims/hypothesis: The insulinotropic effect of gastric inhibitory polypeptide (GIP) is reduced in patients with type 2 diabetes and around 50% of their first-degree relatives under hyperglycaemic conditions. It is unknown whether this is a result of a specific defect in GIP action or of a general reduction in beta cell function. Moreover, impaired secretion of glucagon-like peptide 1 (GLP-1) has been described in patients with type 2 diabetes. Therefore, we studied the insulinotropic effect of GIP in women with previous gestational diabetes (pGDM) under euglycaemic fasting conditions and during a hyperglycaemic clamp experiment. The secretion of GIP and GLP-1 was assessed following oral glucose ingestion. Materials and methods:On separate occasions we performed an OGTT and administered an i.v. bolus of 20 pmol GIP/kg body weight in 20 women with pGDM and 20 control women. An additional hyperglycaemic clamp experiment (140 mg/dl [7.8 mmol/l] over 120 min) with i.v. infusion of GIP (2 pmol kg −1 min −1 ; 30-90 min) was performed in 14 women in each group. Capillary and venous blood samples were drawn for the measurement of glucose (glucose oxidase), insulin, C-peptide, GIP and GLP-1 (specific immunoassays). Indices of insulin sensitivity and beta cell function were calculated. Statistical analyses were carried out using repeated measures ANOVA. Results: Following oral glucose ingestion, plasma glucose, insulin and C-peptide concentrations increased to higher levels in the women with pGDM than in the control women (p<0.05). The women with pGDM were characterised by a higher degree of insulin resistance than the control women (p=0.007 for the Matsuda index), but showed no overt defects in glucosestimulated insulin secretion (p=0.40 for the insulinogenic index following i.v. glucose). The secretion of GLP-1 and GIP was not different between the groups (p=0.87 and p=0.57, respectively). The insulin secretory response to GIP administration was similar in the two groups both after GIP bolus administration and during the hyperglycaemic clamp experiment (p=0.99 and p=0.88, respectively). A hyperbola-like relationship was found between the degree of insulin sensitivity (Matsuda index) and the insulin secretory response to GIP and i.v. glucose administration. Conclusions/interpretation: These results do not support the hypothesis of an early defect in GIP action as a risk factor for subsequent development of diabetes in women with previous gestational diabetes. The inverse relationship between insulin resistance and the insulin secretory response to glucose or GIP suggests that beta cell secretory function in response to different stimuli increases adaptively when insulin sensitivity is diminished.

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Section: Discussionmentioning

confidence: 98%

Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes

et al. 2005

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“…The notion that some metabolic memory persists in women with prior GDM even when they present NGT has emerged from a number of previous studies [12][13][14][15][16][17][18][19]. The majority of these studies have clearly indicated that previous GDM is associated with a significant reduction in insulin sensitivity, insulin secretion or both in women who maintain NGT at follow-up [12][13][14][15][16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

“…The majority of these studies have clearly indicated that previous GDM is associated with a significant reduction in insulin sensitivity, insulin secretion or both in women who maintain NGT at follow-up [12][13][14][15][16][17][18][19]. However, uncertainty remains as a result of some bias in the design of most of these studies.…”

Section: Discussionmentioning

confidence: 99%

“…It has been repeatedly reported (reviewed in [11]) that women with normal glucose tolerance (NGT) and prior GDM carry some trace of altered glucose homeostasis, essentially, insulin resistance [8] and/or beta cell dysfunction [12][13][14][15][16][17][18][19]. Several of these studies, however, have been carried out in obese women or shortly after GDM; moreover, not all have related the abnormalities detected after GDM to those found during GDM.…”

Section: Introductionmentioning

confidence: 99%

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Influence of gestational diabetes on the long-term control of glucose tolerance

et al. 2007

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Aims/hypothesis Gestational diabetes (GDM) carries a high risk of subsequent diabetes. We asked what impact prior GDM has on beta cell function and insulin action in women who maintain normal glucose tolerance (NGT) for a long time. Methods Ninety-one women with NGT (aged 41±8 years, mean±SD) were studied (by mathematical modelling of the C-peptide response to an OGTT) 7 [6] years (median [interquartile range]) after the index pregnancy, during which 52 had GDM (pGDM) and 39 had NGT (pNGT). In all women an OGTT had also been performed at 29± 3 weeks of the index pregnancy. Results Women with pGDM were matched with women with pNGT for age, familial diabetes, time and weight gain since index pregnancy, parity, BMI (25.4±3.9 vs 26.8± 6.4 kg/m 2 ), and fasting (4.64±0.56 vs 4.97±0.46 mmol/l) and 2 h plasma glucose levels (5.91±1.14 vs 5.91± 1.21 mmol/l). Nonetheless, fasting (49 [29] Conclusions Even in women who maintain normal insulin sensitivity, impaired beta cell function is carried over into the NGT status several years after a GDM pregnancy.

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“…Biochemical assays were performed as described previously [5]. Of the women with pGDM, 227 out of 368 (62%) underwent a 75-g OGTT and the remainder (including 37 with known type 2 diabetes) had measurement of fasting glucose and HbA 1 c. The pGDM group was subdivided into two: pGDM with normal glucose regulation post-partum (NG) and pGDM with abnormal glucose regulation post-partum (AG) [4].…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

The impact of ethnicity on glucose regulation and the metabolic syndrome following gestational diabetes

et al. 2005

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Aims/hypothesis: We assessed the impact of ethnic origin on metabolism in women following gestational diabetes mellitus (GDM). Materials and methods: Glucose regulation and other features of the metabolic syndrome were studied at 20.0 (18.2-22.1) months (geometric mean [95% CI]) post-partum in women with previous GDM (185 European, 103 Asian-Indian, 80 African-Caribbean). They were compared with the same features in 482 normal control subjects who had normal glucose regulation during and following pregnancy. Results: Impaired glucose regulation or diabetes by WHO criteria were present in 37% of women with previous GDM (diabetes in 17%), especially in those of African-Caribbean and Asian-Indian origin (50 and 44%, respectively vs 28% in European, p=0.009). BMI, waist circumference, diastolic blood pressure, fasting triglyceride and insulin levels, and insulin resistance by homeostatic model assessment (HOMA), were increased following GDM (p<0.001 for all, vs control subjects).Where glucose regulation was normal following GDM, basal insulin secretion (by HOMA) was high (p<0.001 vs control subjects). Irrespective of glucose regulation in pregnancy, Asian-Indian origin was associated with high triglyceride and low HDL cholesterol levels, and AfricanCaribbean with increased waist circumference, blood pressure, and insulin levels, together with insulin resistance and low triglyceride concentrations. Nonetheless, the GDMassociated features were consistent within each ethnic group. The metabolic syndrome by International Diabetes Federation criteria was present in 37% of women with previous GDM, especially in non-Europeans (Asian-Indian 49%, African-Caribbean 43%, European 28%, p=0.001), and in 10% of controls. Conclusions/interpretation: Following GDM, abnormal glucose regulation and the metabolic syndrome are common, especially in non-European women, indicating a need for diabetes and cardiovascular disease prevention strategies.

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Insulin resistance and β‐cell dysfunction in normoglycaemic European women with a history of gestational diabetes

Abstract: European normoglycaemic women with previous GDM display both glucoregulatory and antilipolytic insulin resistance, reduced beta-cell function and dyslipidaemia. These metabolic abnormalities are likely to contribute to their increased risk of future type 2 diabetes.

Cited by 63 publications

References 57 publications

Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes

Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes

Influence of gestational diabetes on the long-term control of glucose tolerance

The impact of ethnicity on glucose regulation and the metabolic syndrome following gestational diabetes

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