Clinical factors associated with birth weight of infants born to pregnant women with diabetes.

We aimed to examine the clinical factors associated with the birth weight of infants born to Japanese pregnant women with diabetes. This retrospective observational study enrolled 204 Japanese women with singleton pregnancies with type 1 diabetes (n = 135) or type 2 diabetes (n = 69). We used multiple regression analyses to examine factors associated with birth weight standard deviation (SD) scores. In addition, we compared the clinical findings among the groups of mothers who gave birth to appropriate for gestational age infants (AGA group), large for gestational age infants (LGA group), and small for gestational age infants (SGA group). Multiple regression analyses showed that the birth weight SD score was positively associated with type 2 diabetes. In women with type 1 diabetes, the birth weight SD score was positively associated with glycated albumin levels and gestational weight gain and negatively associated with pre-pregnancy underweight. Only gestational weight gain was positively associated with birth weight SD scores in women with type 2 diabetes. Glycated hemoglobin levels, gestational weight gain, and triglyceride levels were significantly higher in the LGA group than in the AGA group. The SGA group showed significantly lower gestational weight gain and triglyceride levels than the AGA group. These results suggest that it is important to manage not only blood glucose levels but also pre-pregnancy body weight and gestational weight gain for appropriate fetal growth. The effects of clinical factors on infant birth weight may differ between patients with type 1 and those with type 2 diabetes.

The best outcomes for going through pregnancy with diabetes-Clinical features of four recipients of the Lilly Insulin 50-Year Award.

The Lilly Insulin 50-Year Award of Japan has been held since 2003. This Award is presented to people with diabetes based on their efforts in injecting insulin for 50 years. Among the 23 recipients of this Award in 2018, four were recognized because of their excellent efforts in receiving continuous treatment for diabetes mellitus before, during and throughout their life after pregnancy. This report focuses on the clinical features of these recipients with successful delivery of newborns at Tokyo Women's Medical University approximately 40-50 years ago. Three of the recipients [type 2 diabetes, n = 2 (cases 1 and 3); type 1 diabetes, n = 1 (case 4)] were treated before, during and after pregnancy, whereas one patient with type 2 diabetes (case 2) was only treated during pregnancy. Even though three recipients had a past history of stillbirth due to insufficient control of diabetes, all four recipients were directed to try to maintain normoglycemia before and during pregnancy, which resulted in the delivery of newborns without major events. The current ages of the recipients are 82, 78, 78 and 63 years old, respectively. No diabetic complications were observed in case 1. However, simple retinopathy occurred after ophthalmological treatment in case 3, and case 2 has received hemodialysis. Nevertheless, all of the patients have spent active lives with the confidence of successful delivery, even though none of the patient's HbA1c levels fell below 7% after delivery. The authors as their doctors are proud of the continuous efforts made by these four recipients to receive diabetes treatment before, during and after pregnancy. We therefore advocate "the best outcome for going through pregnancy with diabetes" to all diabetic patients who hope to become pregnant based on a planned pregnancy with the normalization of blood glucose.

Quantitative analysis of exercise among pregnant women with impaired glucose tolerance using pedometer data: An observational study.

AIMS: The aim of our study was to examine the feasibility of the use of a pedometer to quantify the amount of exercise and the relationship between the amount of exercise and carbohydrate metabolism in pregnant women with impaired glucose tolerance. METHODS: Seven pregnant women with impaired glucose tolerance (gestational diabetes: three, overt diabetes in pregnancy: one, pregestational diabetes type 2: three) were provided with pedometers. The relationship between pedometer data with blood glucose levels, maternal body weight, amount of insulin administered, blood hemoglobin A1c (HbA1c) levels, blood glycoalbumin levels and infant birth weight was investigated. RESULTS: When the 24-h-based data were examined, there was no correlation between the number of steps walked and blood glucose level immediately after walking, nor the average number of steps per day and the fasting blood glucose level in the next day. However, 4-week-based data showed that there was a negative correlation between the number of steps per day and the change in HbA1c level. Moreover, there was a negative correlation between the average number of steps per day and change in the maternal body weight. A 1-week-based data from five participants who were being administered insulin indicated that there was a negative correlation between the average number of steps per day and the total amount of insulin administered per day. CONCLUSION: Active application of pedometers is suggested to be feasible to improve metabolic control in pregnant women with glucose intolerance through the quantification of their exercise.

Changes in insulin requirements during pregnancy in Japanese women with type 1 diabetes.

AIMS: We investigated the changes in insulin requirements, and other relevant factors, in pregnant Japanese women with type 1 diabetes. METHODS: This retrospective observational study was conducted on 77 singleton pregnant women with type 1 diabetes, treated with multiple daily injections of insulin. We examined changes in daily insulin dose during pregnancy and defined the increased insulin doses as the ratio of maximum dose to the pre-pregnancy dose. The relationship between the increased insulin doses and maternal features or pregnancy outcomes was investigated. RESULTS: The insulin dose gradually increased during pregnancy, reaching a maximum dose that was 1.6 times of that prior to pregnancy, at 35 weeks of gestation. A negative significant correlation was observed between the insulin dose increases and duration of diabetes (p = 0.008). Greater increases in insulin doses were noted in women with multiparity, compared to nulliparity (p = 0.047). Multiple regression analyses revealed that shorter duration of diabetes was independently associated with the increases in insulin dose during pregnancy. CONCLUSIONS: Women with a longer duration of diabetes required smaller increases in insulin dose during pregnancy, suggesting that long diabetic duration may decrease placental function. Further investigations are needed to clarify the mechanisms that the duration of diabetes influences on insulin requirement during pregnancy.

The importance of nonstop treatment after delivery for pregnant women with type 2 diabetes.

BACKGROUND: There are no reports of very long follow-up studies of pregnant women with type 2 diabetes after delivery. Here we describe cases of Japanese women whom we treated for 20 to 50 years after deliveries to investigate the relationship between blood glucose control and diabetic complications. METHODS: In Japan, the prevalence of type 1 diabetes is very low, and we have very few long-term follow-up cases with type 1 diabetes. Therefore, we chose to describe subjects with type 2 diabetes only. We present data on a total of 80 deliveries, 68 cases, treated by one of us (Y.O.) for more than a 50-year period. They are divided into 4 groups based on duration of treatment after delivery: more than 50 years (1 delivery, 1 patient), 40 to 49 years (13 deliveries, 11 patients), 30 to 39 years (19 deliveries, 16 patients), and 20 to 29 years (47 deliveries, 40 patients). Their present average ages in these 4 groups are 77, 72.4, 65.9, and 55.5 years, respectively. Their average HbA1c levels at last visit, in May 2014, are 8.2%, 7.6%.,7.2%, and 8.3%, respectively. RESULTS: Despite elevated HbA1c levels, they had relatively few complications: 40% (no retinopathy), 43.8% (simple retinopathy), and 12.5% (treated with photocoagulation); 67.5% (no albuminuria), 26.3% (albuminuria), and 6.3% (treated with renal transplantation or hemodialysis). Therefore, even if glycemic control is not ideal, nonstop treatment of Japanese women for type 2 diabetes after deliveries is effective to prevent diabetic complications. CONCLUSIONS: Long-term attention to care of diabetes after pregnancy may be preventive of diabetic complications in other populations as well.

Assessment of predictors of insulin therapy in patients with gestational diabetes diagnosed according to the IADPSG criteria.

AIMS AND INTRODUCTION: It is helpful for both diabetologists and obstetricians to identify patients with gestational diabetes who require insulin therapy for glycemic control during pregnancy. The aim of the present study was to assess potential predictors of insulin requirement in patients with gestational diabetes. MATERIALS AND METHODS: One hundred thirteen patients with gestational diabetes [mean age 34.2 ± 4.5 years; pre-gestational body mass index (BMI), 23.6 ± 6.0 kg/m2] were included in this study. The associations between insulin requirement and the following factors were analyzed: clinical maternal characteristics, number of abnormal oral glucose tolerance test (OGTT) values, gestational age at diagnosis, plasma glucose levels measured during the OGTT, glycated hemoglobin (HbA1c) and glycated albumin levels, and serum C-peptide level before breakfast and 1 and 2 h after breakfast. RESULTS: Thirty-six patients (32 %) required insulin during pregnancy ("insulin group"); the remaining patients were treated with nutrition therapy ("nutrition group"). The insulin group had a higher pre-gestational BMI, higher fasting glucose level, higher area under the curve (AUC) for serum C-peptide level, higher HbA1c level, and a younger gestational age at diagnosis than the nutrition group (p < 0.05, all). Logistic regression analysis showed that the pre-gestational BMI, AUC for serum C-peptide level, and the HbA1c level were independent predictors for the insulin group (p < 0.05, all). CONCLUSIONS: The results suggest that a high insulin resistance and HbA1c level may be associated with insulin requirement in patients with gestational diabetes.

The over 50 year clinical course of a patient with slowly progressive type 1 diabetes (SPIDDM).

Type 1 diabetic patients who have endured their condition for prolonged periods are not uncommon, but there are few well-documented cases of type 2 diabetic patients with duration of over fifty years. In the present case study, we analyzed the history of a diabetic patient whose duration was 53 years. Her case was consequently diagnosed not as the common type 2 diabetes, but as the slowly progressive type 1 diabetes (SPIDDM) identified by Japanese medical researchers. The patient, now 73 years old, was first diagnosed with diabetes in 1953 when she was 17 years of age and started insulin injections. In 1962 she was referred to our hospital, and two years later she vaginally delivered a healthy baby (birth weight 3100 g) at the 40(th) week of gestation. She was the first case of a diabetic mother delivering an infant treated at Tokyo Women's Medical College Hospital. Her data shows that her C-peptide responses by meal tolerance test in 1978 was at least partly preserved though it decreased year by year. Her anti-GAD antibody was found to be positive in 2000 and remained so in 2009. This leads us to conclude that the etiology of her SPIDDM was most likely has insulin secretion exhaustion.

Studies of variations of the cyclin-dependent kinase inhibitor 1C and the cyclin-dependent kinase 4 genes in relation to type 2 diabetes mellitus and related quantitative traits.

CDK4 is involved in the regulation of body weight, pancreatic beta-cell proliferation, insulin responsiveness, and diabetes pathogenesis. CDK4 activity is inhibited by CDKN1C, which is regulated by insulin. In addition, CDKN1C plays an important role in beta-cell proliferation and is involved in the pathogenesis of the Beckwith-Wiedemann syndrome, a disorder characterized by neonatal hyperinsulinaemic hypoglycaemia and pre- and post-natal overgrowth. The aim of this study was to investigate if variations in the proximal promoter and the coding region of the CDKN1C and CDK4 genes are associated with type 2 diabetes or changes in related quantitative phenotypes among glucose-tolerant subjects. Mutation analyses of the two genes in 62 type 2 diabetic patients resulted in the discovery of seven variants of CDKN1C and two variants of CDK4. In a case-control study comprising 717 type 2 diabetic patients and 518 glucose-tolerant subjects the most frequent variants did not show any difference in allele frequencies between the type 2 diabetic patients and the control subjects. However, in two genotype-quantitative trait correlation studies involving 206 glucose-tolerant offspring of type 2 diabetic patients and 359 young, healthy subjects the CDKN1C del171APVA variant associated with increased birth weight (P=0.05 and P=0.05). Furthermore, the same variant tended to be associated with decreased basal glucose oxidation among 16 genotypically discordant dizygotic twins (P=0.03). In a genotype-quantitative trait study involving 500 middle-aged glucose-tolerant subjects the CDK4 IVS2-31G-->A variant was associated with an increased waist circumference (P=0.03) and waist-to-hip ratio (P=0.02) and altered fasting plasma glucose (P=0.03). However, these later findings could not be replicated in additional studies. In conclusion, variants in CDKN1C may contribute to the inter-individual variation in birth weight.