Socioeconomic, lifestyle and biological determinants of cervical screening coverage: Lolland-Falster Health Study, Denmark.

BACKGROUND: Cervical cancer is preventable. Screening is important for early detection. However, even in high-income countries, coverage is sub-optimal. We identified socioeconomic, lifestyle and biological determinants of cervical screening coverage. METHODS: In Denmark, women aged 23-64 are free of charge personally invited to screening. All cervical cell samples are registered centrally in the Patobank. We linked data from the Lolland-Falster Health Study (LOFUS) with Patobank data. LOFUS was a population-based health survey undertaken in 2016-2020. With logistic regression, coverage defined as ≥1 cervical sample registered within a 6-year period from 2015 to 2020 was compared across levels of risk factors expressed as adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: Among 13 406 women of screening aged 23-64 and invited to LOFUS, 72% had ≥1 cervical sample registered. Non-participation in LOFUS was a strong predictor of low coverage; aOR 0.32; 95% CI 0.31-0.36. Among LOFUS participants, education was a strong predictor of coverage in univariate analysis, OR 0.58; 95% CI 0.48-0.71, but this association disappeared in multi-variate analysis, aOR 0.86; 95% CI 0.66-1.10. In multi-variate analysis, predictors of low coverage were high age, living without a partner, retired, current smoker, poor self-rated health, elevated blood pressure and elevated glycated haemoglobin. CONCLUSIONS: Women with low cervical screening coverage had limited contact to healthcare, exemplified by non-participation in LOFUS, and pertinent health and social problems, exemplified by elevated blood pressure and glycated haemoglobin, poor self-rated health, and retirement already in screening age. Structural changes in screening are needed to reach non-screened women.

A flexible silicone patch for treatment of hemorrhoids after birth: a pilot study of HEMOCIN® Patch.

PURPOSE: To test a non-pharmacological silicone patch for treatment of symptomatic hemorrhoids with focus on usability, safety, and self-reported short-term effect. METHODS: Puerperal women in a Danish maternity ward were cluster randomized to treatment with the HEMOCIN® patch (intervention) or no systematic treatment (control group). On inclusion and after 2 weeks, they completed a questionnaire regarding history and hemorrhoid symptoms scored from 0 to 10. Women in the intervention group also reported on the usability of the patch and any side effects. RESULTS: We included 31 women in the intervention group and 33 in the control group. Twenty-eight (90.3%) women in the intervention group and 27 (81.8%) women in the control group responded to follow-up. Except from a difference in the severity of swelling at inclusion, there were no differences between the two groups for any symptoms, neither at inclusion, nor at follow-up, or in the change of symptoms during the two weeks (p > 0.05). Twenty-three women (85.2%) in the control group used medical treatment vs. one woman in the intervention group. The patch was used on an average of 9.3 days, 15.5 h/day and for 7.1 h before changing the patch. No severe side effects were reported. CONCLUSION: This pilot study finds that the HEMOCIN® patch is a safe and feasible treatment option for hemorrhoids. However, we did not detect any significant effect on hemorrhoid symptoms. The patch could be an option for people who seek non-pharmacological treatment for symptomatic hemorrhoids or need long-term treatment without steroid side effects.

Validity of bladder volume measurement by ultrasound in women postpartum.

INTRODUCTION: Vaginal birth increases the risk of urinary retention and overdistention of the bladder. To avoid unnecessary discomfort by catheterization, it is preferable to use ultrasound for diagnosis of these conditions. The aim of this study was to determine the validity of transabdominal ultrasound and a portable ultrasound system, Biocon-700, to measure bladder volume in women postpartum. METHODS: Fifty women were included in this method comparison study. Within 48 h of giving birth, their bladder volume was measured in randomized order with both transabdominal ultrasound and Biocon-700. After urination, participants were scanned with Biocon-700 to measure residual bladder volume, and finally the bladder was emptied by catheterization. The total bladder volume was calculated as the voided volume plus the catheterized volume. RESULTS: Biocon-700 measured 43.4 ml ± 117.4 ml (mean ± SD) lower than the total bladder volume, while volumes measured by transabdominal ultrasound were 117.8 ml ± 110.0 ml (mean ± SD) lower. Linear regression showed significant proportional bias in both methods. The Biocon-700 could detect a residual bladder volume > 150 ml with a positive predictive value of 66.7% and a negative predictive value of 100%. CONCLUSIONS: Neither transabdominal ultrasound nor the portable ultrasound system, Biocon-700, can be used to measure bladder volume precisely after vaginal delivery. However, both ultrasound methods can be used as screening tools to prevent overdistention of the bladder, and Biocon-700 can furthermore be used to screen women for a residual bladder volume > 150 ml.

Gestational diabetes and the human salivary microbiota: a longitudinal study during pregnancy and postpartum.

BACKGROUND: An aberrant composition of the salivary microbiota has been found in individuals with type 2 diabetes, and in pregnant women salivary microbiota composition has been associated with preeclampsia and pre-term birth. Pregnant women, who develop gestational diabetes (GDM), have a high risk of developing type 2 diabetes after pregnancy. In the present study we assessed whether GDM is linked to variation in the oral microbial community by examining the diversity and composition of the salivary microbiota. METHOD: In this observational study the salivary microbiota of pregnant women with GDM (n = 50) and normal glucose regulation (n = 160) in third trimester and 9 months postpartum was assessed by 16S rRNA gene amplicon sequencing of the V1-V3 region. GDM was diagnosed in accordance with the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Cross-sectional difference in alpha diversity was assessed using Student's t-test and longitudinal changes were assessed by mixed linear regression. Cross-sectional and longitudinal difference in beta diversity was assessed by permutational multivariate analyses of variance. Differentially abundant genera and OTUs were identified by negative binomial regression. RESULTS: In the third trimester, two species-level operational taxonomic units (OTUs), while eight OTUs postpartum were differentially abundant in women with GDM compared with normoglycaemic women. OTU richness, Shannon diversity and Pielou evenness decreased from late pregnancy to 9 months after delivery regardless of glycaemic status. CONCLUSION: GDM is associated with a minor aberration of the salivary microbiota during late pregnancy and postpartum. For unknown reasons richness of the salivary microbiota decreased from late pregnancy to postpartum, which might be explained by the physiological changes of the immune system during human pregnancy.

Changing incidence of obstetric anal sphincter injuries-A result of formal prevention programs?

INTRODUCTION: Obstetric anal sphincter injuries (OASIS) are serious complications to vaginal delivery causing anal incontinence in 50% of the women in the long term. In Norway, the incidence of OASIS has been significantly reduced from 4%-5% to 1%-2% after implementation of prevention programs focusing on perineal protection. The aim of our study was to evaluate whether implementation of formal prevention programs was associated with a reduced incidence of OASIS over time. MATERIAL AND METHODS: We performed a historical cohort study, evaluating incidence, change of incidence and risk factors of OASIS during the years 2011-2015 at the four delivery departments in the Capital Region of Denmark. Two of the four departments implemented formal prevention programs in 2012-2013. We performed trend tests and uni- and multivariable analyses, adjusting for important risk factors and calculating interactions between risk factors. RESULTS: There were 75 173 vaginal deliveries during the study period; of those, 2670 (3.6%) were complicated by OASIS. The incidence of OASIS decreased during the study period from 4.3% (n = 636) in 2011 to 2.6% (n = 399) in 2015. There was a significant decrease in the incidence of OASIS at both the departments with formal prevention programs and those without. After adjustment for other important risk factors of OASIS, we found no significant difference in the risk reduction between departments with and without formal prevention programs. CONCLUSIONS: We found that the general focus on prevention of OASIS in Denmark was associated with a significant decrease in the incidence of OASIS, but implementation of formal prevention programs did not lead to a further reduction. It is possible that more rigorous interventions at the hospitals with formal prevention programs could have resulted in a significant difference in incidence of OASIS.

The increasing role of a retained placenta in postpartum blood loss: a cohort study.

PURPOSE: To describe the association between quantity of blood loss, duration of the third stage of labour, retained placenta and other risk factors, and to describe the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage. METHODS: Cohort study of all vaginal deliveries at two Danish maternity units between 1 January 2009 and 31 December 2013 (n = 43,357), univariate and multivariate linear regression statistical analyses. RESULTS: A retained placenta was shown to be a strong predictor of quantity of blood loss and duration of the third stage of labour a weak predictor of quantity of blood loss. The predictive power of the third stage of labour was further reduced in the multivariate analysis when including retained placenta in the model. There was an increase in the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage, increasing from 12% in cases of blood loss ≥ 500 ml to 53% in cases of blood loss ≥ 2000 ml CONCLUSION: The predictive power of duration of the third stage of labour in regard to postpartum blood loss was diminished by the influence of a retained placenta. A retained placenta was, furthermore, present in the majority of most severe cases.

Ponderal index at birth associates with later risk of gestational diabetes mellitus.

PURPOSE: Low birth weight (BW) and low ponderal index (PI) are associated with increased risk of type 2 diabetes mellitus. This study has two purposes: first to investigate the influence of PI on the risk of gestational diabetes mellitus (GDM); second, to study the association between glucose metabolism and BW in women with previous GDM. METHODS: GDM cohort: 185 women with GDM in 1978-1996, attending a follow-up study in 2000-2002. Control cohort: 1137 women from a population-based diabetes screening study (Inter99) in a neighbouring county in 1999-2001. BW and birth length were collected from the original midwifery records. BW and PI were stratified into tertiles for analysis. RESULTS: PI in the lower tertiles was associated with an increased risk of GDM [odds ratio 1.59 (95% confidence interval 1.07-2.36, p = 0.021)]. Among women with previous GDM, the area under the curve (AUC) for plasma levels of glucose and insulin during an OGTT was highest for the lower tertiles of BW (for AUCglucose p = 0.048, for AUCinsulin p = 0.047 adjusted for age and BMI). CONCLUSIONS: Lower PI is associated with increased risk of GDM. In women with previous GDM, lower BW is associated with a more severe impairment of glucose metabolism one to two decades after the pregnancy complicated by GDM.

Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark.

Gestational diabetes mellitus (GDM) is defined as glucose intolerance of varying severity and is present in about 2-6% of all pregnancies in Europe, making it one of the most common pregnancy disorders. Aside from the short-term maternal, fetal and neonatal consequences associated with GDM, there are long-term consequences for both mother and child. Although maternal glucose tolerance often normalises shortly after pregnancy, women with GDM have a substantially increased risk of developing type 2 diabetes later in life. Studies have reported that women are more than seven times as likely to develop diabetes after GDM, and that approximately 50% of mothers with GDM will develop diabetes within 10 years, making GDM one of the strongest predictors of type 2 diabetes. In women with previous GDM, development of type 2 diabetes can be prevented or delayed by lifestyle intervention and/or medical treatment. Systematic follow-up programmes would be ideal to prevent progression of GDM to diabetes, but such programmes are unfortunately lacking in the routine clinical set-up in most countries. Studies have found that the risks of obesity, the metabolic syndrome, type 2 diabetes and impaired insulin sensitivity and secretion in offspring of mothers with GDM are two- to eightfold those in offspring of mothers without GDM. The underlying pathogenic mechanisms behind the abnormal metabolic risk profile in offspring are unknown, but epigenetic changes induced by exposure to maternal hyperglycaemia during fetal life are implicated. Animal studies indicate that treatment can prevent long-term metabolic complications in offspring, but this remains to be confirmed in humans. Thus, diabetes begets diabetes and it is likely that GDM plays a significant role in the global diabetes epidemic. This review summarises a presentation given at the 'Gestational diabetes: what's up?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Marja Vääräsmäki, DOI: 10.1007/s00125-016-3976-6 , and by Cuilin Zhang and colleagues, DOI: 10.1007/s00125-016-3979-3 ) and an overview by the Session Chair, Kerstin Berntorp (DOI: 10.1007/s00125-016-3975-7 ).

Prophylactic progesterone and preterm birth.

This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality and morbidity worldwide. The incidence varies globally but remains low in the Nordic countries (5-6%). Prediction and prevention are complicated due to diverse aetiology, but obstetric history and cervical length can improve prediction. Prophylactic vaginal progesterone initiated between 12 and 24 weeks of gestation is recommended to reduce preterm birth less-than 33-35 weeks in singleton pregnancies with a history of preterm birth or with a short cervix (less-than 25 mm) and can be considered for twin pregnancies with the same risk factors.

The prevention of adverse pregnancy outcomes by periodontal treatment during pregnancy (PROBE) intervention study-A controlled intervention study: Protocol paper.

INTRODUCTION: Pregnancy increases the risk of periodontitis due to the increase in progesterone and estrogen. Moreover, periodontitis during pregnancy is associated with development of pregnancy and birth related complications. The aim of this study is to determine, whether periodontal treatment during pregnancy can reduce systemic inflammation and lower the risk of adverse pregnancy and birth related outcomes. METHODS AND ANALYSIS: The PROBE study is a non-randomized controlled intervention study conducted among 600 pregnant women with periodontitis. The women will be recruited among all pregnant women at two Danish hospitals in Region Zealand during their nuchal translucency scan and will subsequently be screened for periodontitis. The intervention group includes 300 pregnant women, who will be offered state-of-the-art periodontal treatment during pregnancy. The control group includes additional 300 pregnant women, who will be offered periodontal treatment after giving birth. Outcome measures include periodontal measures, inflammatory, hormonal and glycaemic markers as well as the prevalence of preterm birth risk, low birth weight and risk markers of gestational diabetes mellitus (GDM) and preeclampsia that will be collected from all screened women and further during pregnancy week 20 and pregnancy week 35 for women enrolled in the intervention. ETHICS AND DISSEMINATION: The study's findings will be published in peer reviewed journals and disseminated at national and international conferences and through social media. The PROBE study is designed to provide important new knowledge as to whether periodontal treatment during pregnancy can reduce the prevalence of complications related to pregnancy and birth. CLINICAL TRIALS REGISTRATION: The study was registered on clinicaltrials.gov (NCT06110143).

Danish Diabetes Birth Registry 2: a study protocol of a national prospective cohort study to monitor outcomes of pregnancies of women with pre-existing diabetes.

INTRODUCTION: Despite technological developments and intensified care, pregnancies in women with pre-existing diabetes are still considered high-risk pregnancies. The rate of adverse outcomes in pregnancies affected by diabetes in Denmark is currently unknown, and there is a limited understanding of mechanisms contributing to this elevated risk. To address these gaps, the Danish Diabetes Birth Registry 2 (DDBR2) was established. The aims of this registry are to evaluate maternal and fetal-neonatal outcomes based on 5 years cohort data, and to identify pathophysiology and risk factors associated with short-term and long-term outcomes of pregnancies in women with pre-existing diabetes. METHODS AND ANALYSIS: The DDBR2 registry is a nationwide 5-year prospective cohort with an inclusion period from February 2023 to February 2028 of pregnancies in women with all types of pre-existing diabetes and includes registry, clinical and questionnaire data and biological samples of mother-partner-child trios. Eligible families (parents age ≥18 years and sufficient proficiency in Danish or English) can participate by either (1) basic level data obtained from medical records (mother and child) and questionnaires (partner) or (2) basic level data and additional data which includes questionnaires (mother and partner) and blood samples (all). The primary maternal outcome is Hemoglobin A1c (HbA1c) levels at the end of pregnancy and the primary offspring endpoint is the birth weight SD score. The DDBR2 registry will be complemented by genetic, epigenetic and metabolomic data as well as a biobank for future research, and the cohort will be followed through data from national databases to illuminate possible mechanisms that link maternal diabetes and other parental factors to a possible increased risk of adverse long-term child outcomes. ETHICS AND DISSEMINATION: Approval from the Ethical Committee is obtained (S-20220039). Findings will be sought published in international scientific journals and shared among the participating hospitals and policymakers. TRIAL REGISTRATION NUMBER: NCT05678543.

Characterization of genetic variants of GIPR reveals a contribution of ß-arrestin to metabolic phenotypes.

Incretin-based therapies are highly successful in combatting obesity and type 2 diabetes1. Yet both activation and inhibition of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in combination with glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) activation have resulted in similar clinical outcomes, as demonstrated by the GIPR-GLP-1R co-agonist tirzepatide2 and AMG-133 (ref. 3) combining GIPR antagonism with GLP-1R agonism. This underlines the importance of a better understanding of the GIP system. Here we show the necessity of ß-arrestin recruitment for GIPR function, by combining in vitro pharmacological characterization of 47 GIPR variants with burden testing of clinical phenotypes and in vivo studies. Burden testing of variants with distinct ligand-binding capacity, Gs activation (cyclic adenosine monophosphate production) and ß-arrestin 2 recruitment and internalization shows that unlike variants solely impaired in Gs signalling, variants impaired in both Gs and ß-arrestin 2 recruitment contribute to lower adiposity-related traits. Endosomal Gs-mediated signalling of the variants shows a ß-arrestin dependency and genetic ablation of ß-arrestin 2 impairs cyclic adenosine monophosphate production and decreases GIP efficacy on glucose control in male mice. This study highlights a crucial impact of ß-arrestins in regulating GIPR signalling and overall preservation of biological activity that may facilitate new developments in therapeutic targeting of the GIPR system.

The risk of adverse pregnancy outcome after bariatric surgery: a nationwide register-based matched cohort study.

OBJECTIVE: The aim of this study was to describe the risk of adverse obstetric and neonatal outcome after bariatric surgery. STUDY DESIGN: Nationwide register-based matched cohort study of singleton deliveries after bariatric surgery during 2004-2010. Data were extracted from The Danish National Patient Registry and The Medical Birth Register. Each woman with bariatric surgery (exposed) was individually matched with 4 women without bariatric surgery (unexposed) on body mass index, age, parity, and date of delivery. Continuous variables were analyzed with the paired t test and binary outcomes were analyzed by logistic regression. RESULTS: We identified 339 women with a singleton delivery after bariatric surgery (84.4% gastric bypass). They were matched to 1277 unexposed women. Infants in the exposed group had shorter mean gestational age (274 vs 278 days; P < .001), lower mean birthweight (3312 vs 3585 g; P < .001), lower risk of being large for gestational age (adjusted odds ratio, 0.31; 95% confidence interval, 0.15-0.65), and higher risk of being small for gestational age (SGA) (adjusted odds ratio, 2.29; 95% confidence interval, 1.32-3.96) compared with infants in the unexposed group. No statistically significant difference was found between the groups regarding the risk of gestational diabetes mellitus, preeclampsia, labor induction, cesarean section, postpartum hemorrhage, Apgar score less than 7, admission to neonatal intensive care unit or perinatal death. CONCLUSION: Infants born after maternal bariatric surgery have lower birthweight, lower gestational age, 3.3-times lower risk of large for gestational age, and 2.3-times higher risk of SGA than infants born by a matched group of women without bariatric surgery. The impact on SGA was even higher in the subgroup with gastric bypass.

The impact of inter-laboratory glucose bias on the diagnosis of gestational diabetes mellitus: Comparison of common automated central laboratory methods.

BACKGROUND AND AIMS: The diagnosis of gestational diabetes mellitus (GDM) is based exclusively on glucose measurements, which are highly influenced by pre-analytical and analytical factors. Therefore, poor agreement across laboratories may affect the prevalence of GDM. We aimed to determine the inter-laboratory bias of glucose measurements and the impact on GDM prevalence. MATERIAL AND METHODS: A prospective cohort study of women (n = 110) referred for second-trimester GDM diagnostics using a 75 g oral glucose tolerance test. Maternal glucose was assessed from venous plasma at fasting, 1 h and 2 h. Venous blood were collected in Fluoride Citrate tubes and frozen. Samples were analyzed at five central laboratories using four different automated glucose Hexokinase methods and GDM prevalence was evaluated according to WHO2013 diagnostic criteria. RESULTS: Maximum inter-laboratory bias was 0.19, 0.30 and 0.27 mmol/L in fasting, 1 h and 2 h samples, respectively. GDM prevalence ranged 30.0-41.1% across laboratories. CONCLUSION: Inter-laboratory bias for mean venous glucose was low and within desirable limits. Nonetheless, the impact on GDM prevalence was considerable, which may inappropriately affect clinical practice.

Long-Term Follow-Up on Morbidity Among Women With a History of Gestational Diabetes Mellitus: A Systematic Review.

BACKGROUND: Gestational diabetes mellitus (GDM) complicates up to 10% of pregnancies and is a well-known risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease. Little is known about possible long-term risks of other diseases. BACKGROUND: The aim was to review the literature for evidence of associations with morbidity other than T2DM and cardiovascular disease and with long-term mortality. METHODS: A systematic review based on searches in Medline, Embase, and Cochrane Library until March 31, 2021, using a broad range of keywords. We extracted study characteristics and results on associations between GDM and disease occurrence at least 10 years postpartum, excluding studies on women with diabetes prior to pregnancy or only diabetes prior to outcome. The results are reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Newcastle-Ottawa Scale was used to assess risk of bias. RESULTS: We screened 3084 titles, 81 articles were assessed full-text, and 15 included in the review. The strongest evidence for an association was for kidney diseases, particularly in Black women. We found indication of an association with liver disease, possibly restricted to women with T2DM postpartum. The association between GDM and breast cancer had been studied extensively, but in most cases based on self-reported diagnosis and with conflicting results. Only sparse and inconsistent results were found for other cancers. No study on thyroid diseases was found, and no study reported on short-term or long-term mortality in women with a history of GDM. CONCLUSION: Given the frequency of GDM, there is a need for better evidence on possible long-term health consequences, in particular, studies based on comprehensive records of diagnosis of GDM and long-term health outcomes.

The influence of parental history of diabetes and offspring birthweight on offspring glucose metabolism in adulthood.

BACKGROUND: Links are well established between both family history of diabetes and reduced birthweight and increased risk of diabetes in adulthood. OBJECTIVES: 1) To investigate the influence of parental history of type 2 diabetes (T2DM) on offspring birthweight and adult offspring glucose tolerance status in non-diabetic offspring of patients with T2DM and 2) to study the associations of birthweight with measures of pancreatic beta-cell function and insulin sensitivity. DESIGN: Family cohort study. POPULATION: Offspring of patients with verified T2DM diagnosed after age 40 years with a spouse without known diabetes. METHODS: Oral glucose tolerance tests and frequently sampled intravenous glucose tolerance tests (FSIGT) in non-diabetic offspring. Birthweight and length obtained from birth records. RESULTS: Among 122 offspring with maternal history of T2DM, 14.8% had diabetes compared to 8.0% in 137 offspring with paternal history of diabetes, p=0.09. Offspring with maternal history of T2DM had a mean birthweight 196 g higher than offspring with paternal T2DM (3,651 ± 640 g (mean ± SD) vs. 3,456 ± 472g (p=0.01)). Non-diabetic offspring with birthweights in the lowest tertile had significantly higher plasma glucose levels after an oral glucose tolerance test (OGTT) [Area under the curve(glucOGTT) , mean (95%CI), 1 795 (1 725-1 866) vs. 1 683 (1 613-1 753) mmol/L/min, p=0.02], and lower insulin sensitivity index calculated from a frequently sampled intravenous glucose tolerance test - Si 9.60 [10(-5) (min*pmol/L)(-1) ] (8.23-10.97) vs. 11.79 (10.41-13.18), p=0.02 - in adulthood compared to offspring with birthweights in the upper tertile. CONCLUSIONS: Offspring with a family history of maternal T2DM have higher birthweights than those with paternal T2DM. Low birthweight associates with elevated plasma glucose levels after an oral glucose load and decreased insulin sensitivity in adulthood.

Further evidence that mutations in INS can be a rare cause of Maturity-Onset Diabetes of the Young (MODY).

BACKGROUND: Insulin gene (INS) mutations have recently been described as a common cause of permanent neonatal diabetes (PNDM) and a rare cause of diabetes diagnosed in childhood or adulthood. METHODS: INS was sequenced in 116 maturity-onset diabetes of the young (MODYX) patients (n = 48 Danish and n = 68 Czech), 83 patients with gestational diabetes mellitus (GDM), 34 type 1 diabetic patients screened negative for glutamic acid decarboxylase (GAD), and 96 glucose tolerant individuals. The control group was randomly selected from the population-based sampled Inter99 study. RESULTS: One novel heterozygous mutation c.17G>A, R6H, was identified in the pre-proinsulin gene (INS) in a Danish MODYX family. The proband was diagnosed at 20 years of age with mild diabetes and treated with diet and oral hypoglycaemic agent. Two other family members who carried the INS R6H were diagnosed with diabetes when 51 years old and with GDM when 27 years old, respectively. A fourth mutation carrier had normal glucose tolerance when 20 years old. Two carriers of INS R6H were also examined twice with an oral glucose tolerance test (OGTT) with 5 years interval. They both had a approximately 30% reduction in beta-cell function measured as insulinogenic index. In a Czech MODYX family a previously described R46Q mutation was found. The proband was diagnosed at 13 years of age and had been treated with insulin since onset of diabetes. Her mother and grandmother were diagnosed at 14 and 35 years of age, respectively, and were treated with oral hypoglycaemic agents and/or insulin. CONCLUSION: Mutations in INS can be a rare cause of MODY and we conclude that screening for mutations in INS should be recommended in MODYX patients.

[Post-partum hypoglycaemia in a child to a father with HNF4A diabetes].

Untreated hypoglycaemia in newborns may result in permanent cognitive damage, why early diagnosis and treatment is important. This case report describes a newborn girl, who developed hypoglycaemia, when she was two hours old despite early feeding. The father of the child had maturity-onset diabetes of the young Type 1, which is caused by an autosomal dominant inherited mutation in the HNF4A gene. Due to this, early blood glucose measurements were performed. The child was treated with extra feeding and recovered without any consequences. A later gene test showed, that the child was carrier of the mutation.