Placental antiangiogenic prolactin fragments are increased in human and rat maternal diabetes.

INTRODUCTION/OBJECTIVES: The role of the placenta in diabetic mothers on fetal development and programming is unknown. Prolactin (PRL) produced by decidual endometrial cells may have an impact. Although full-length PRL is angiogenic, the processed form by bone morphogenetic protein-1 (BMP-1) and/or cathepsin D (CTSD) is antiangiogenic. The objectives were to investigate the involvement of decidual PRL and its antiangiogenic fragments in placentas from type-1 diabetic women (T1D) and from pregnant diabetic rats with lower offspring weights than controls. METHODS: PRL, BMP-1, and CTSD gene expressions and PRL protein level were assessed in T1D placentas (n=8) at delivery and compared to controls (n=5). Wistar rats received, at day 7 of pregnancy, streptozotocin (STZ) (n=5) or nicotinamide (NCT) plus STZ (n=9) or vehicle (n=9). Placental whole-genome gene expression and PRL western blots were performed at birth. RESULTS: In human placentas, PRL (p<0.05) and BMP-1 (p<0.01) gene expressions were increased with a higher amount of cleaved PRL (p<0.05) in T1D than controls. In rats, diabetes was more pronounced in STZ than in NCT-STZ group with intra-uterine growth restriction. Decidual prolactin-related protein (Dprp) (p<0.01) and Bmp-1 (p<0.001) genes were up-regulated in both diabetic groups, with an increased cleaved PRL amount in the STZ (p<0.05) and NCT-STZ (p<0.05) groups compared to controls. No difference in CTSD gene expression was observed in rats or women. CONCLUSIONS: Alterations in the levels of the PRL family are associated with maternal diabetes in both rats and T1D women suggesting that placental changes in these hormones impact on fetal development.

Is the Development of Gestational Diabetes Associated With the ABO Blood Group/Rhesus Phenotype?

Aims: There are few published data on the putative association between the ABO blood group/rhesus (Rh) factor and the risk of developing gestational diabetes mellitus (GDM). Our aim was to explore the link between each one factor and GDM development. Methods: All women having given birth at Lille University Medical Center (Lille, France) between August 1st, 2017, and February 28th, 2018, were tested for GDM, using the method recommended in the French national guidelines. The risk of GDM was assessed for each ABO blood group, each Rh phenotype and combinations thereof, using logistic regression models. Results: 1194 women had at least one GDM risk factor. The percentage of GDM varied with the ABO group (p=0.013). Relative to group O women, group AB women were more likely to develop GDM (OR = 2.50, 95% CI [1.43 to 4.36], p=0.001). Compared with the Rh-positive O group, only the Rh-positive AB group had an elevated risk of developing GDM (OR = 3.02, 95% CI [1.69 to 5.39], p < 0.001). Conclusions: Our results showed that Rh-positive group AB women have a greater risk of GDM. With a view to preventing GDM, at-risk individuals could be identified by considering the ABO blood group phenotype either as a single risk factor or in combination with other risk factors.

Effects of COVID-19 pandemic lockdown on gestational diabetes mellitus: A retrospective study.

OBJECTIVE: The objective of our study was to evaluate the impact of the lockdown period on the glycemic balance in patients with GDM. METHODS: A retrospective study in one center (Lille, France) compared two periods: the COVID-19 lockdown of 18 March 2020 to 7 May 2020 versus the same period during 2019. Glucose targets were defined by a capillary fasting glucose target < 5.1mmol/L and/or a 2-hour postprandial capillary glucose < 6.6 mmol/L. GDM control was defined as: good (< 20% of the glycemic values were not within the target range), acceptable (20 to 40% of the glycemic values were not within the target range) or poor (> 40% of the glycemic values were not within the target range). RESULTS: Two hundred twenty-nine patients were included in 2019 and 222 in 2020. The same mean number of capillary blood sugar tests was performed by the two groups. Postprandial blood sugar was significantly less well controlled in 2020, with a lower rate of good control (61.6% vs 69.4%) and higher rates of acceptable (24.7% vs 21.8%) and poor control (13.7% and 8.7%) (p < 0.05). Use of insulin therapy was significantly higher in 2020 compared with 2019 (47.7% and 36.2%, respectively; p < 0.05). CONCLUSION: Diabetes control was lower during the COVID-19 pandemic lockdown, even if follow-up was not impacted. This may be explained by reduced physical activity, modified dietary habits and anxiety during this period.

Increasing incidence of abnormal glucose tolerance in women with prior abnormal glucose tolerance during pregnancy: DIAGEST 2 study.

AIMS: Mild blood glucose abnormalities during pregnancy may be linked to later glucose tolerance abnormalities or diabetes mellitus. Our aim was to determine the prevalence of diabetes mellitus (DM), impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) 6.75 years after delivery in women with differential blood glucose status during pregnancy. METHODS: We compared long-term outcomes among control women (n = 221), women with abnormal glucose tolerance during pregnancy (AGT; n = 322) and women with gestational diabetes (GDM; n = 466) who participated in DIAGEST 1. Women were recruited from 15 public maternity units in France. Clinical parameters could be determined in 155 control, 220 AGT and 338 GDM subjects. Rates of DM, IGT, IFG and 'Any Abnormality' were compared between the groups (American Diabetes Association criteria). RESULTS: Adherence to follow-up was 70.7%. Rates of DM, IGT and IFG were respectively 0.9% DM, 2.1% IGT and 3.6% IFG in the control group; rates in the AGT group were 6.3%, 11.3% and 6.3%. In GDM women, the rates of DM, IGT and IFG were, respectively, 18.0%, 13.4% and 8.5%. Predictors for DM were previous GDM, medical history of hypertension, age at delivery > or = 33 years, family history of diabetes, fasting glucose during pregnancy > or = 5.5 mmol/l and the severity of hyperglycaemia during pregnancy defined by the number of abnormal blood glucose values fasting, 1, 2 and 3 h during the glucose tolerance test at diagnosis of GDM. CONCLUSION: This study has identified a high prevalence of glucose tolerance abnormalities after AGT during pregnancy. Compared with GDM women, women with AGT have an intermediate risk of later diabetes.

Treatment of diabetes mellitus using an external insulin pump in clinical practice.

Before the initiation of insulin pump therapy, patients must be aware of the different aspects of this form of intensive insulin therapy. Most healthcare professionals recommend a sequential approach to inform patients about CSII. Factors that need to be considered in choosing an insulin pump include its safety features, durability of the device, tolerability and comfort of the catheter, user-friendliness, technical features and appearance. The initial insulin requirements need to be individualized for the given patient, using different methods to determine the appropriate dosages for the basal rate and prandial boluses. Glycaemic targets and algorithms for insulin dose adaptation need to be learned by the patients to enable them to avoid and/or correct hypo- and hyperglycaemia/ketosis episodes. Patients are also advised on how to carry out frequent self-monitoring of blood glucose-and of ketone bodies, if necessary. Insulin pumps are now able to deliver a range of basal rates and boluses that increase the flexibility of CSII. One specific issue is the approach to meal-planning, based on carbohydrate-counting or the equivalent: this method of so-called 'flexible insulin therapy' can improve metabolic control (for instance, by diminishing postprandial excursions) as well as the quality of life of patients. Evaluation of the knowledge and practices of the patient can be made through a continuous educational programme carried out by experienced nurses and physicians at the start of therapy and during follow-up. In addition, it may be necessary to identify the reasons for lack of improvement in metabolic control after several months of therapy, which include pump malfunction, cannula problems, miscalculated insulin dosages and insufficient metabolic control in specific clinical situations with a high risk of metabolic deterioration (illness, exercise, concomitant drugs). Annual assessment of the patient using an itemized checklist is required to verify the continued efficacy and safety of insulin pump therapy, two main factors of success with CSII treatment.

Treatment of diabetes mellitus using an external insulin pump: the state of the art.

The aim of diabetes treatment is to achieve tight glucose control to avoid the development of chronic diabetic complications while reducing the frequency of hypoglycaemic episodes. Continuous subcutaneous insulin infusion (CSII) using an external pump is an intensive diabetes therapy recognized to improve metabolic control and glycaemic instability, and to reduce the frequency of severe hypoglycaemia. For years, the theoretical advantages of the insulin pump (constancy of basal delivery, adjustable basal rates, and low insulin depots allowing the reduction of glycaemic variability) have contributed to its reported superiority compared with multiple daily injections (MDI). However, insulin pump therapy is now challenged by new MDI regimens based on long-acting insulin analogues that could replace the use of CSII. As a consequence, health professionals now have to determine which patients are likely to benefit the most from CSII. Recently, several studies reported that children and adolescents, and patients whose blood glucose imbalance was initially the most pronounced with basal-bolus regimens, would particularly benefit from CSII. Other indications were also proposed in marginal clinical situations with highly selected patients in whom a significant improvement of blood glucose was demonstrated. Finally, the use of CSII in type 2 diabetic patients now appears to be a good alternative to the ineffective MDI regimens observed in some of these patients. However, past experience with CSII indicates that candidates for insulin pump therapy must be carefully selected and strongly motivated to improve their glucose control. Use of CSII also requires strict medical supervision by physicians and a regular programme of patient education by paramedical teams, to ensure optimal responsible use of this technique by healthcare professionals.

No loss of genomic imprinting of IGF-II and H19 in placentas of diabetic pregnancies with fetal macrosomia.

OBJECTIVES: Fetal macrosomia is a common complication of maternal diabetes mellitus and is associated with substantial morbidity, but the precise cellular and molecular mechanisms that induce fetal macrosomia are not well understood. The imprinted genes IGF-II and H19 are crucial for placental development and fetal growth. The term placentas from diabetic pregnancies express more insulin-like growth factor II (IGF-II) than those from normal pregnancies. Deregulation of their imprinting status is observed in the macrosomia-associated syndrome, the Beckwith-Wiedemann syndrome. The aim of this study was to determine whether loss of imprinting hence biallelic expression was also a hallmark of macrosomia in diabetic pregnancies. DESIGN AND METHODS: IGF-II and H19 maternal and paternal expressions were studied in placentas from two groups of type 1 diabetic mothers: one with macrosomic babies and the other with babies of normal weight. Maternal or paternal allele specific expressions were defined by using DNA polymorphic markers of the IGF-II and H19 genes. RFLP analysis was performed on PCR products from genomic DNA of the father, the mother and the child, and on RT-PCR products from placental mRNA. RESULTS: RFLP analysis showed that the IGF-II gene remains paternally expressed and the H19 gene remains maternally expressed in all placentas examined, independently of the birth weight status. CONCLUSIONS: These results suggest that, in contrast with Beckwith-Wiedemann syndrome-associated macrosomia, loss of imprinting for IGF-II or H19 is not a common feature of diabetic pregnancies associated with macrosomia.

[Fifteen practical questions concerning gestational diabetes]. / Quinze questions pratiques concernant le diabète gestationnel.

With a review of the current literature, a clarification on screening and management of gestational diabetes is hereby set out, within the frame of a Clinical Expert Series. According to the ethnic group, the prevalence varies from 1 to 14%. The treatment is based on dietary advice, insulin. The ACHOIS study demonstrates that the treatment of gestational diabetes significantly decreases perinatal complications (4 to 1%). The place of the oral treatment (glyburide) remains to be defined. In most countries, diagnosis rests on oral glucose test tolerance: Sullivan 50 g glucose test (1 hour) and 100 g test of glucose if positive (3 hours); WHO 75 g test (2 hours). The screening can be systematic or only on risk factors (wide variations between studies). Screening of gestational diabetes is required because its management improves pregnancy outcomes. Despite this, there is no consensus on the strategy of screening and diagnosis.

Blood ketone monitoring: a comparison between gestational diabetes and non-diabetic pregnant women.

AIM: To measure ketonemia in a control population of pregnant women and in a population of women with gestational diabetes (GDM). To define a normal ketonemia threshold for the controls and to determine whether or not this value could play a role in the clinical management of women with GDM. METHOD: Fifty-six women with a normal OGTT and 49 women with GDM were included and monitored from the 25th to the 37th week of pregnancy. Control subjects agreed to perform glycaemia and ketonemia self-monitoring 3 times a day. In addition, women with GDM were asked to measure their postprandial glycaemia. Glycaemia and ketonemia measurements were performed using Optium meters. Subjects kept a 24-hour food record twice a week. RESULTS: The mean ketonemia was lower in the control group than in the GDM group (0.01+/-0.10 vs. 0.04+/-0.009 mmol/l; P<0.001). Ketonemia values measured before the midday meal and prior to the evening meal were lower for control subjects than for GDM patients (P=0.002 and P=0.005). Fasting ketonemia was unrelated to ketonuria in the GDM group, whereas there was a correlation in the control group (P=0.006). At least one chronic increase in ketonemia levels was observed in 47% of the women with GDM, compared with only 12% of controls. The lowest levels of evening glycaemia correlated with the highest levels of ketonemia; women with GDM reported lower food and carbohydrate intakes than controls (P<0.001). CONCLUSION: This work has enabled the establishment of ketonemia reference standards in non-diabetic pregnant women. If ketonemia does indeed indicate overly restrictive dietary behavior, this parameter could be employed for monitoring adherence to the nutritional recommendations for GDM.

[Screening for gestational diabetes: Still many unsolved issues]. / Le dépistage du diabète gestationnel : encore de nombreuses questions non résolues.

For many years, there is a debate on gestational diabetes screening, including what screening test and thresholds to use. The purpose of this literature review is to determine whether gestational diabetes screening in France meets the 10 definition criteria of the WHO. The DG is a public health problem, with a natural history partially known and detectable at an early stage. Currently, there is no data showing that there is a benefit to treat patient screens by the new criteria. The one-step approach-screening test can only detect fetal complications and not maternal complications. It seems to be acceptable for the population of pregnant women. The diagnostic test and treatment also seem to be acceptable to us. To this day, its reproducibility is uncertain. Screening leads to an increase in obstetric interventions. Several studies found that screening for gestational diabetes is cost-effective but in a different context of care than in France.

Outcome of twin pregnancies associated with glucose intolerance.

OBJECTIVES: There is little information about the impact of hyperglycaemia in twin pregnancies. The objective of our study was to evaluate the maternal, foetal and neonatal complications in patients with twin pregnancy and glucose intolerance defined by gestational diabetes mellitus and gestational mild hyperglycaemia. STUDY DESIGN: We performed a single-centre retrospective study. Screening for gestational diabetes was achieved by a two-step method. Patients were managed according to the French guidelines. After matching for age and body mass index, outcomes were compared in 177 patients with glucose intolerance and 509 controls. Macrosomia was defined as birth weight above the 90th percentile of gestational age adjusted for parity, foetal sex and maternal biometrics. RESULTS: Prevalence of glucose intolerance was 17.5% in our population. Complications of pregnancy and mode of delivery were similar between the two groups. Caesarean section was associated with age >35 years, vascular complications of pregnancy and non-cephalic presentation of the first twin. Rate of macrosomia was not different between the two groups. The only risk factor for macrosomia was a history of macrosomia in a previous pregnancy (odds ratio = 5.9, 95% confidence interval = 1.8-19.2). CONCLUSION: Twin pregnancies complicated by glucose intolerance were not associated with an increased risk of macrosomia or Caesarean section. Further studies should assess the value of screening gestational diabetes mellitus in twin pregnancies.

Factor VII, tissue factor pathway inhibitor, and monocyte tissue factor in diabetes mellitus: influence of type of diabetes, obesity index, and age.

Changes of the tissue factor (TF) pathway of blood coagulation have been described in diabetes and could be involved in its vascular complications. In order to evaluate the influence of the type of diabetes and of the obesity index and age on these changes, factor VII coagulant activity, factor VII antigen, activated factor VII, monocyte TF expression, and plasma Tissue Factor Pathway Inhibitor (TFPI) were examined in 18 Type 1 and 16 Type 2 diabetic patients compared to non-diabetic control subjects matched for age, sex, and obesity index (Types 1 and 2 controls, respectively). Multicomplicated patients were excluded. FVIIc, FVIIAg, and FVIIa were higher in Type 2 diabetic patients and controls than in Type 1 diabetic patients and controls (P< .03). However, FVIIc and FVIIAg were lower in diabetic patients than in their matched controls (P< .03). Monocyte expression of TF was not different between Types 1 and 2 diabetic patients and their matched controls except for LPS-stimulated monocyte TF activity which was lower in Type 2 diabetic patients than in Type 2 controls (P< .05). Plasma TFPI was slightly but significantly higher in Type 1 diabetic patients than in Type 1 controls (P= .01) and was correlated to glycemia. However, both in Type 2 diabetic patients and controls, TFPI was higher than in Type 1 controls and was correlated with BMI (P< .0003). These results indicate that in not multicomplicated patients, the increase of FVII and TFPI was highly dependent on obesity index and age rather than on diabetes by itself.

[What is the approach to gestational diabetes in 2001?]. / Quelle approche du diabète gestationnel en 2001?

In 2001, gestational diabetes (GD) remains the subject of much debate, particularly as regards screening and diagnosis, therapeutic management and effects on perinatal outcome. It continues to be defined as a disorder of glucose tolerance occurring for the first time during pregnancy, whatever the outcome during the post-partum period. There is as yet still no consensus concerning screening and diagnosis criteria, partly due to the existence of a continuum between maternal blood glucose levels and perinatal outcome, which means that any threshold is necessarily arbitrary. There is no general agreement concerning therapeutic management. As regards diet, there are insufficient randomised prospective studies that could serve to establish minimum required calorie intakes and various regimen. Intervention studies should provide more accurate information concerning the role of diet in therapeutic strategies. It is also necessary to define the role of other therapeutic alternatives such as insulin analogues, or more recently, the sulphonylureas. Nevertheless, although there is still a large debate, the physiopathological mechanisms are becoming increasingly clear. GD and type 2 diabetes appear to be the same entity, with the former constituting an early sign of the latter. Long-term management of women with GD and treatment modalities also require better definition, since these patients are at risk for diabetes, mainly type 2.

[Gestational diabetes: long-term maternal consequences]. / Le diabete gestationnel: devenir maternel a long terme.

Gestational diabetes, a glucose tolerance disorder of variable severity which occurs or is diagnosed for the first time during pregnancy, constitutes a public health problem because of its frequency (1 to 6% of all pregnancies) and its short- or long-term consequences for the fetus and/or the mother. The classical maternal complications are gravidic hypertension, preeclampsia and cesarean section. The dominant short-term effects on the fetus are macrosomia and metabolic complications. Progression to diabetes mellitus (essentially non-insulin-dependent) represents a serious long-term risk for the mother. Systematic screening of gestational diabetes can prevent complications through an optimal care programme and target a very high risk population in order to delay or avoid the occurrence of diabetes and its complications.

Autoimmune markers in slow type 1 diabetes: confrontation to type 1 diabetes.

UNLABELLED: Slow onset type 1 diabetes is an heterogeneous entity. Its clinical features may mimick type 2 diabetes but its pathophysiological mechanisms are close to type 1 diabetes. AIM OF THE STUDY: To find out the frequencies, levels and associations of ICA, GADab and IA-2ab in type 2 diabetic patients with atypical phenotype. To compare it to type 1 diabetes. PATIENTS AND METHODS: ICA, GADab and IA-2ab were determined in: - 61 patients (age at diagnosis 48.2 +/- 10, range 36-73 years) with an initial diagnosis of type 2 diabetes but having at least one symptom suggesting a slow type 1 diabetes (loss of weight, absence of obesity at diagnosis or secondary failure of oral hypoglycaemic agents). - 70 patients with type 1 diabetes (age 18 +/- 8.9, range 2-35 years). Clinical data evaluated in slow type 1 were maximal BMI, BMI and loss of weight at diagnosis and autoimmune disease. Fasting C-peptide and insulinemia were also assessed. RESULTS: (Slow type 1 diabetes versus type 1 diabetes). ICA (43% vs 70%; p <0.01) and IA-2ab (16% vs 75%; p <0.01) were more frequent in type 1. GADab were as frequent (62% vs 74%). Association of the three antibodies (15.7% vs 58.5%; p <0.05) were more frequent in type 1. Prevalence of GADab alone (27.5% vs 7.5%; p <0.05) was higher in slow type 1 diabetes and with higher levels (median 55.5 UI/ml vs 17 UI/ml; p <0.01). There was no difference for levels of ICA (25.5 UJDF/ml vs 28 UJDF/ml) or IA-2ab (11.5 UI/ml vs 38.5 UI/ml). BMI of GADab positive patients was lower. Delay of insulinotherapy was shorter in GADab or ICA positive patients. We did not find any relationship between antibodies presence and fasting C-peptide or insulinemia. CONCLUSION: Slow type 1 diabetes should be evoked in atypical type 2 diabetes. Slow onset type 1 diabetic patients have different autoimmune patterns suggesting a different pathophysiological process. GADab and ICA are useful markers to predict future insulinopenia.

Higher carbohydrate intake is associated with decreased incidence of newborn macrosomia in women with gestational diabetes.

OBJECTIVE: To study the influence of energy and macronutrient intake on infant birthweight in women with gestational diabetes mellitus undergoing intensive management. DESIGN: This prospective study evaluated the impact of intensive management of gestational diabetes on maternal and fetal morbidity, and addressed the relationship between food intake and infant birthweight. SETTING: Fifteen maternity hospitals in northern France. SUBJECTS: Ninety-nine women with gestational diabetes or gestational mild hyperglycemia diagnosed between 24 and 34 weeks of gestation were surveyed. After 1 was excluded because of a premature birth and 18 were excluded as underreporters, 80 women were included in the final analysis. Diet intake was assessed by a dietary history at the first interview, and by two 3-day diet records at the 3rd and 7th week after diagnosis. RESULTS: In a forward-stepwise regression analysis (controlling for maternal age; smoking; parity; prepregnancy BMI; pregnancy weight gain; gestational duration; infant sex; fasting and 2-hour postprandial serum glucose; insulin therapy; and energy, fat, protein and carbohydrate intake during treatment) infant birthweight was positively associated with gestational duration (beta = +0.34, P<.002), and negatively with smoking (beta = -0.27, P<.02) and carbohydrate intake (beta = -0.24, P<.03). There were no large-for-gestational-age infants among women whose carbohydrate intake exceeded 210 g/day. CONCLUSION: For women with gestational diabetes undergoing intensive management, higher carbohydrate intake is associated with decreased incidence of macrosomia. APPLICATION: These findings suggest that nutrition counseling in gestational diabetes must be directed to maintain a sufficient carbohydrate intake (at least 250 g per day), which implies a low-fat diet to limit energy intake. A careful distribution of carbohydrate throughout the day and the use of low-glycemic index foods may help limit postprandial hyperglycemia.

Pregnancy induced hypertension in women with gestational carbohydrate intolerance: the diagest study.

OBJECTIVE: To determine the relationship between pregnancy induced hypertension (PIH) and gestational glucose intolerance. METHODS: A 50g, 1h glucose loading test was offered to all pregnant women between 24 and 28 weeks of gestation in 15 centres in northern France during 8 months in 1992. If the test was positive (> or =7.2 mmol/l), the woman underwent a 3h oral glucose tolerance test (OGTT) as soon as possible. Using the criteria of Carpenter and Coustan, gestational diabetes mellitus (GDM) was defined by two abnormal values (n=218) and gestational mild hyperglycemia (GMH) by one abnormal value (n=130). Each control group was defined by a 50g, 1h loading test result of <7.2 mmol/l (n=108).PIH included gestational hypertension (GH) and preeclampsia (PE). GH was defined as a diastolic pressure of more than 85 mmHg on at least two occasions arising during pregnancy. PE was defined as GH with proteinuria > or =500 mg/24h. RESULTS: The rate of PIH in the three groups (GDM; GMH and control group, C) was, respectively 17.0, 10.8, and 4.6%. All the six PE occurred in the GDM group. Univariate analysis showed significantly higher rate of hypertension in women with a history of PE, increasing body mass index before pregnancy (BMI) and glucose intolerance. In multivariate analysis with adjustment for primiparity, independent risk factors for PIH were a history of PE, BMI>27 and GDM, contrary to GMH and maternal age. CONCLUSIONS: PIH appears to be linked to the level of glucose intolerance during pregnancy, independently of other known factors of hypertension.

[Lipids, hemostasis and diabetes]. / Lipides, hémostase et diabète.

Modifications of hemostasis and plasma lipids are an integral part of diabetes mellitus, and probably play a key role in the evolution of vascular complications. This review points to the important relationships between hemostasis and lipids and their modifications in diabetes, with a special attempt to link the abnormalities described with the pathogenic mechanisms of diabetes.

[Pathophysiology of gestational diabetes]. / Physiopathologie du diabète gestationnel.

During pregnancy, a number of maternal metabolic changes occur early and continue throughout pregnancy which help optimize the transfer of nutrients to the fetus. During normal pregnancy, there are a decrease in insulin sensibility which is physiological, progressive and reverse. For glucose tolerance to be maintained in pregnancy it is necessary for maternal insulin secretion to increase sufficiently to counteract the fall in insulin sensitivity. The metabolic characteristic of women with gestational diabetes is insufficient insulin secretion to counteract the pregnancy related fall in insulin sensitivity. There are a lot of factors that could explain the mechanism of insulin secretion and insulin sensitivity during normal pregnancy and gestational diabetes mellitus. Although glucose tolerance normalizes shortly after pregnancy with gestational diabetes in the majority of women, the risk of developing overt diabetes, especially type 2 diabetes is markedly increased. The mechanisms which could explain gestational diabetes are the same as type 2 diabetes mellitus. We could speculate that these two diseases are identical for alterations in carbohydrate metabolism, but at different stages.