Peter Hornnes

A Longitudinal Study of Plasma Insulin and Glucagon in Women With Previous Gestational Diabetes

OBJECTIVE To investigate whether plasma insulin or glucagon predicts later development of diabetes in women with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS The subjects studied were 91 women with diet-treated GDM and 33 healthy women. Plasma insulin and glucagon during a 50-g oral glucose tolerance test (OGTT) were measured during pregnancy, postpartum, and at follow-up 5-11 years later. At follow-up, the women were also examined with a 75-g OGTT or an intravenous glucagon test. RESULTS Twenty-seven (30%) of the women with previous GDM had abnormal glucose tolerance at follow-up (2 had insulin-dependent diabetes mellitus, 13 had non-insulin-dependent diabetes mellitus, and 12 had impaired glucose tolerance). Compared with the control subjects, women with previous GDM had relatively impaired insulin secretion (decreased insulinogenic index and delayed peak insulin response) at all time points investigated; this was also found when only nonobese glucose-tolerant women were examined. Low insulin secretion during pregnancy together with a high fasting plasma glucose level at the diagnostic OGTT in pregnancy and hyperglycemia during the postpartum OGTT were predictive for subsequent development of overt diabetes (logistic regression analysis). CONCLUSIONS Women who develop GDM have a relative insulin secretion deficiency, the severity of which is predictive for later development of diabetes. Furthermore, our data indicate that their relatively reduced β-cell function may be a significant pathogenic factor in relation to the high incidence of subsequent diabetes in women with GDM. This could be important in the design of follow-up programs for women with previous GDM.

Insulin dose during glucocorticoid treatment for fetal lung maturation in diabetic pregnancy: test of analgoritm

Objective.  Poor glycemic control is often a serious clinical problem during glucocorticoid treatment for fetal lung maturation in pregnant women with diabetes. An algorithm for improved subcutaneous insulin treatment during glucocorticoid treatment in insulin‐dependent diabetic women was developed and tested.

Review: Etiology and Pathophysiology of Gestational Diabetes Mellitus

In pregnancy, several physiologic changes take place, the sum of which tends to reset the glucose homeostasis in the direction of diabetes. About 1–2% of all pregnant women develop an abnormal glucose tolerance in pregnancy, but most often glucose tolerance returns to normal postpartum. This condition is called gestational diabetes mellitus (GDM). The possibility that glucose tolerance deteriorates in pregnancy because of diabetes-like changes in the secretory function of the endocrine pancreas has been investigated in healthy controls and in normal-weight gestational diabetic subjects. The insulin responses to oral glucose and mixed meals are equally large in these two groups, but the insulin response per unit of glycemic stimulus is significantly lower in the gestational diabetic subjects than in the controls. Diabetes-like changes in glucagon secretion are not observed in either group. Insulin degradation is unaffected by human pregnancy and the proinsulin share of the total plasma insulin immunoreactivity does not increase in pregnancy. Insulin receptor binding to monocytes from normal pregnant women is increased in midpregnancy but is significantly decreased in late pregnancy. No difference in insulin binding (at tracer insulin concentration) to monocytes from healthy pregnant controls and gestational diabetic subjects is found. The insulin concentration necessary to reduce tracer insulin binding by 50% (ID50) is lower in the gestational diabetic subjects diagnosed in late pregnancy than in the pregnant controls. Together, these findings indicate that the number of insulin receptors on monocytes is decreased in GDM at this stage of pregnancy. Thus, the cause of GDM could be a decreased insulin receptor binding to target cells combined with a relative lack of circulating insulin, but the possibility of postreceptor defects does also exist.

Simultaneous recording of the gastro-entero-pancreatic hormonal peptide response to food in man

The serum or plasma concentrations of gastrin, gastric inhibitory polypeptide (GIP), gut glucagon-like-immunoreactivity (gut GLI), secretin, vasoactive intestinal polypeptide (VIP), insulin, glucagon, and pancreatic polypeptide (PP) were recorded simultaneously following the ingestion of a normal, mixed meal in seven healthy, normal weight men. The concentrations of PP and gastrin increased within 10 min. Subsequently GIP, insulin, glucagon, and gut GLI increased in the order mentioned. The mean concentrations of secretin and VIP were not affected by the meal, athough transient decreases in secretion concentrations could be detected in all subjects. The concentrations of the other hormones remained elevated for 4 hr or more. Perhaps the period of observation following food stimulation of gastro-entero-pancreatic hormones should be extended.

Gastrointestinal Insulinotropic Hormones in Normal and Gestational-Diabetic Pregnancy: Response to Oral Glucose

The responses of gastric inhibitory polypeptide (GIP), gut glucagon-like-immunoreactivity (gut GLI), insulin, and pancreatic glucagon to a 50-g oral glucose load were studied in late pregnancy and postpartum in 11 normal women, 10 normal weight gestational diabetics, and 10 overweight gestational diabetics. The GIP response to glucose was impaired in pregnancy in all three groups. In pregnancy, the GIP response was smaller in both groups of gestational diabetics than in normal women, whereas postpartum, the GIP response was lower than normal in the normal weight gestational diabetics only. In pregnancy, the gut GLI response to glucose was reduced in the overweight gestational diabetics and abolished in the normal women. The insulin response to glucose was increased in pregnancy in all three groups. Moreover, it was higher in the overweight gestational diabetics than in the other two groups in pregnancy and postpartum. In the normals, the suppression of glucagon levels after glucose ingestion was more marked in pregnancy than postpartum, whereas no such effect was seen in gestational-diabetic pregnancy. It is concluded that pregnancy—normal as well as gestational-diabetic—is accompanied by profound changes in the secretion of gastrointestinal insulinotropic hormones after glucose ingestion. These findings may be important for the understanding of changes in metabolism and gastrointestinal physiology in gestation.

Studies of the Ala/Val98 polymorphism of the hepatocyte nuclear factor-1alpha gene and the relationship to beta-cell function during an OGTT in glucose-tolerant women with and without previous gestational diabetes mellitus

Aims  In pregnancies complicated by gestational diabetes mellitus (GDM) an increased demand for insulin is not met due to β‐cell dysfunction. An Ala/Val polymorphism at codon 98 of the hepatocyte nuclear factor‐1α (HNF‐1α) gene has been associated with decreased serum insulin and C‐peptide responses during an oral glucose tolerance test (OGTT) in glucose‐tolerant subjects. The aims of the present study were to evaluate the influence of the polymorphism on the serum insulin and C‐peptide responses to an OGTT in glucose‐tolerant women with and without previous GDM and to investigate if this polymorphism is associated with GDM.

Guar Gum and Glycemic Control of Pregnant Insulin-dependent Diabetic Patients

The effect of a guar gum preparation on the glycemic control of 12 pregnant insulin-dependent diabetic patients was investigated. The study was performed on inpatients and lasted 3 wk (from week 32 of pregnancy and onward). Weeks 32 and 34 were control periods during which time the patients had their normal diet only. During week 33, the diet was supplemented with guar. The mean blood glucose level of week 33 was 14% lower than that of week 32 (P < 0.01) but equal to that of week 34. Mean fluctuations of blood glucose during individual days of the 3 wk were similar. The M-value declined significantly from week 32 to week 33, but the M-value of week 33 was not different from that of week 34. The average 24-h glycosuria declined by 63% from week 32 to week 33 (P < 0.05), whereas the values of weeks 33 and 34 were not significantly different. The mean daily insulin doses of weeks 32, 33, and 34 were similar. The results show that whereas admission of pregnant insulin-dependent diabetic women to a diabetes ward exerts a favorable influence on diabetes control, no further improvement is obtainable if the diet is supplemented with guar.

Endocrine pancreatic sensitivity to glucose in women with gestational diabetes.

To study whether gestational diabetes is the result of abnormal endocrine pancreatic adaptation to pregnancy, alpha- and beta-cell sensitivity to glucose was determined during pregnancy and post partum in seven women of normal weight who had gestational diabetes. Glucose was infused intravenously in quantities producing similar increases in plasma glucose in pregnancy and post partum, and the plasma glucose curves obtained closely resembled those found during an oral glucose tolerance test. The insulin response to the infusion was 3.5 times greater in pregnancy (P less than .02), whereas glucagon was suppressed similarly in pregnancy and post partum. These findings resemble previous ones in normal women. It is concluded that pancreatic alpha and beta cells adapt similarly to pregnancy in women with gestational diabetes and in normal women.

Screening for Gestational Diabetes

Gestational diabetes is an asymptomatic condition associated with adverse outcome for mother and child. Overweight and obesity confer a higher risk of gestational diabetes – up to 11-fold. Health care providers of pregnant women should ensure that a strategy for screening gestational diabetes is in place. Either general screening programmes or selective screening programmes may be employed. Women with gestational diabetes should be monitored and treated vigorously. After delivery, glucose metabolism is most often normalised, but women with previous gestational diabetes have an increased risk of developing type-2 diabetes in later years. Therefore, they should be counselled about healthy lifestyles and offered exanimations for diabetes or pre-diabetes with 1–3 year intervals.

EBCOG and the Nordic countries

The European Board and College of Obstetrics and Gynecology (EBCOG) was founded in 1996 as a result of the fusion of several societies, each in various ways representing European obstetrics and gynecology (O&G). EBCOG is the O&G Board and Section within Union Européenne des Médicines Specialistes or European Union of Medical Specialists (UEMS), the European Union (EU) body for medical specialties, and EBCOG contributes actively to the work of UEMS. EBCOG itself has 37 member societies and the names of the participating countries and of the officers, executives, and national representatives are readily found at www.ebcog.org. EBCOG works closely with the four major European subspecialty organizations: European Association of Perinatal Medicine, European Society for Gynecological Oncology, European Society for Human Reproduction and Embryology, and the European Urogynecological Association. We also work very closely with the European Network of Trainees in Obstetrics and Gynecology (ENTOG). Furthermore, we cooperate with a number of other specialist organizations in Europe through our Standing Committee for Training and Assessment (SCTA). The aims and objectives of EBCOG are to improve the health of women and their babies by seeking to achieve the highest possible standards of training and care in the field of O&G in all European countries. EBCOG works to attain these aims and objectives by advocating for O&G issues to be advanced in EU political institutions and in EU-related nongovernmental organizations and platforms, and by providing information about current and upcoming EU legislation and directives relevant to O&G to EBCOG member societies and also by seeking to provide input from member societies to various EU institutions. We also seek personal contacts within the EU system, also through UEMS, but our ultimate goal is to establish a presence in Brussels in order to ensure that issues of womens’ health are prioritized and the needs of O&G as a speciality are respected within the EU and other European countries. For more than 10 years, EBCOG has been accrediting training centres in O&G and in the subspecialties, and we have been active in encouraging national visitation and accreditation systems, that, as a result, are now in place in a number of European countries. Thus EBCOG is now more active than ever, both in general O&G and with regard to the subspecialties. Through the SCTA EBCOG has produced logbooks and training curricula both in general O&G and in the subspecialties. These training programs have been inspirational towards improving and establishing national training programs in a number of European countries. Moreover, the SCTA has produced training courses, especially for training of the trainers. This is an activity which EBCOGwill develop further in the future. In cooperation with ENTOG, EBCOG also wishes to support a program enabling trainees to visit centers abroad; an activity that will also be mediated through the SCTA. At present the development of common European practiceguidelines isnotfeasible.Theconditionsunder which care is being delivered throughout Europe still vary greatly, and commonEuropean guidelines are still simply unattainable. On the other hand, common European standards of care are within reach, and EBCOG wishes to develop such standards for both obstetrics and gynecology. Standards of Care do not regulate the actual medical treatment of our patients, but they will set up a framework that can help all European obstetricians and gynecologists to understand what issues we need to address and how. One example of a standard is that all pregnant women in Europemusthaveaccess toawell-describedprogramof antenatal carewhich ensures that a specifiednumber of particular issues will be addressed during pregnancy. Another standard stipulates how our patients may expect to be treated with respect and to be thoroughly informed. These standards should be available to the patients so that they will know what they may expect fromus. The development of standards would be facilitated ifwecouldsucceed inengaging theEUtogive full backing and momentum for such developments.