Risk factors of neonatal hypoglycemia in neonates born to mothers with gestational diabetes.

Hypoglycemia is one of the most significant problems in neonates born to mothers with gestational diabetes (GDM). This study aimed to identify novel predictors of hypoglycemia in neonates born to mothers with GDM. A total of 443 term singleton infants from mothers diagnosed with GDM and cared for at Keio University Hospital between January 2013 and December 2019 were included in this study. Neonatal hypoglycemia was defined as hypoglycemia of less than 47 mg/dL at 1 or 2 or 4 h after birth, according to previous studies. Among 443 full-term singleton neonates born to mothers with GDM, 200 developed hypoglycemia (45%). Gestational weight gain (GWG), HbA1c at 1st trimester, HbA1c at GDM diagnosis, and the incidence of insulin therapy in the neonatal hypoglycemia group were significantly higher than those in the non-neonatal hypoglycemia group (p = 0.016, p = 0.032, p = 0.011, and p = 0.017, respectively). Regarding the multiple regression analysis adjusted for nulliparity, GWG, and gestational weeks at delivery, the odds ratio for maternal HbA1c ≥5.2% at 1st trimester was 1.63 (p = 0.034), and maternal insulin therapy during pregnancy was 1.72 (p = 0.015). In conclusion, HbA1c in the 1st trimester and insulin therapy during pregnancy were good predictors of hypoglycemia in neonates born to GDM mothers, especially when their HbA1c was 5.2% or more. Further research will be necessary to improve the perinatal management of hypoglycemia.

Changes in glycemic variability, gastric emptying and vascular endothelial function after switching from twice-daily to once-weekly exenatide in patients with type 2 diabetes: a subpopulation analysis of the twin-exenatide study.

BACKGROUND: We investigated the changes in blood glucose fluctuation, gastric emptying, and vascular endothelial function by switching from an exenatide twice-daily formulation (BID) to a once-weekly formulation (QW) since the evaluation of postprandial glucose excursion and glycemic variability (GV) by continuous glucose monitoring (CGM) after switching was lacking. METHODS: Twenty-nine patients with type 2 diabetes treated with exenatide BID were included in this study and switched to exenatide QW for 24 weeks. GV assessed by CGM, gastric emptying (by 13 C-acetate breath test) and vascular endothelial function (by reactive hyperemia - peripheral arterial tonometry) were evaluated at baseline and 24 weeks after switching. RESULTS: HbA1c decreased significantly from the baseline to week 24, while postprandial glucose levels after breakfast and dinner significantly increased (both P <0.05). However, the increases in GV indices were modest and not statistically significant at week 24. Vascular endothelial function was also not significantly changed after switching (P >0.05). Gastric emptying was significantly accelerated at week 24 (Tmax 83.4 ± 12.1 min vs. 58.2 ± 16.4 min) (P <0.001) and correlated with increased postprandial glucose levels after breakfast and dinner (both P <0.05). CONCLUSIONS: Despite the increase in postprandial glucose associated with accelerated gastric emptying after switching from exenatide BID to QW, change in GV was modest and no significant deterioration in vascular endothelial function was observed after switching. These results support the superiority of treatment with exenatide QW over exenatide BID in clinical practice; however, attention should be paid to the monitoring and management of postprandial glucose levels when selecting exenatide QW. TRIAL REGISTRATION: Clinical trial registry number; UMIN000016390 and jRCTs031180320 . Approval date of Registry and the Registration: December 12, 2014.

Increased alpha cell to beta cell ratio in patients with pancreatic cancer.

The development of pancreatic cancer (PC) is associated with worsening of glucose tolerance. However, there is limited information about the effects of PC on islet morphology. The aim of this study was to elucidate changes in alpha and beta cell mass in patients with PC. We enrolled 30 autopsy cases with death due to PC (9 with diabetes; DM) and 31 age- and BMI-matched autopsy cases without PC (controls, 12 with DM). Tumor-free pancreatic sections were stained for insulin and glucagon, and fractional beta cell (BCA) and alpha cell area (ACA) were quantified. In addition, expression of de-differentiation markers, i.e., ALDH1A3 and UCN3, was qualitatively evaluated. The pancreas of subjects with PC showed atrophic and fibrotic changes. There was no significant difference in BCA in subjects with PC compared to controls (1.53 ± 1.26% vs. 0.95 ± 0.42%, p = 0.07). However, ACA and ACA to BCA ratio were significantly higher in subjects with PC compared to controls (2.48 ± 2.39% vs. 0.53 ± 0.26% and 1.94 ± 1.93 vs. 0.59 ± 0.26, respectively, both p < 0.001). Increased ACA to BCA ratio was observed in subjects with PC irrespective of the presence of DM. Qualitative evaluation of ALDH1A3 and UCN3 expression showed no significant difference between the groups. In conclusion, in subjects with PC, alpha to beta cell mass ratio is increased, which may contribute to the increased risk of worsening glucose metabolism. Further studies are warranted to elucidate the mechanisms of increased alpha to beta cell mass in patients with PC.

Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by reduced beta cell mass (BCM). However, it remains uncertain whether the reduction in BCM in type 2 diabetes is due to a decrease in size or number of beta cells. Our aim was to examine the impact of beta cell size and number on islet morphology in humans with and without type 2 diabetes. METHODS: Pancreas samples were obtained from 64 Japanese adults with (n = 26) and without (n = 38) type 2 diabetes who underwent pancreatectomy. Using pancreatic tissues stained for insulin, we estimated beta cell size based on beta cell diameter. Beta cell number was estimated from the product of fractional beta cell area and pancreas volume divided by beta cell size. The associations of beta cell size and number with islet morphology and metabolic status were examined. RESULTS: Both beta cell size (548.7 ± 58.5 vs 606.7 ± 65.0 µm3, p < 0.01) and number (5.10 × 108 ± 2.35 × 108 vs 8.16 × 108 ± 4.27 × 108, p < 0.01) were decreased in participants with type 2 diabetes compared with those without diabetes, with the relative reduction in beta cell number (37%) being greater than for beta cell size (10%). Beta cell number but not size was positively correlated with BCM in participants with and without type 2 diabetes (r = 0.97 and r = 0.98, both p < 0.01) and negatively correlated with HbA1c (r = -0.45, p < 0.01). CONCLUSIONS/INTERPRETATION: Both beta cell size and number were reduced in participants with type 2 diabetes, with the relative reduction in beta cell number being greater. Decrease in beta cell number appears to be a major contributor to reduced BCM in type 2 diabetes.

Inverse Association Between Fatty Liver at Baseline Ultrasonography and Remission of Type 2 Diabetes Over a 2-Year Follow-up Period.

BACKGROUND & AIMS: Improvement of fatty liver may be required for remission of type-2 diabetes. However, there is no longitudinal evidence on whether fatty liver reduces the chances for remission of type-2 diabetes. We investigated the association between fatty liver and remission of type-2 diabetes (the primary analysis), and also the association between improvement of fatty liver and remission of type-2 diabetes (the secondary analysis). METHODS: We collected data from 66961 people who underwent screening for type-2 diabetes from 2008 through 2016 at a single center in Japan. The primary analysis included 2567 patients with type-2 diabetes without chronic renal failure or a history of hemodialysis who underwent ultrasonography to detect fatty liver, all of whom had follow-up testing, including blood testing, for a median 24.5 months after the baseline ultrasonography. The secondary analysis included 1833 participants with fatty liver at baseline who underwent a second ultrasonography, and participants who had fatty liver at baseline but not at the second visit were considered to have had improvement of fatty liver. Remission of type-2 diabetes was defined as a fasting plasma glucose level below 126 mg/dL and an HbA1c level below 6.5% for more than 6 months without anti-diabetic drugs. Odds ratios (ORs) of remission of type-2 diabetes were estimated using logistic-regression models. RESULTS: A lower proportion of patients who had fatty liver detected by ultrasonography at baseline (8.7%, 167/1910) had remission of type-2 diabetes during the follow-up period than patients without fatty liver (13.1%, 86/657). Fatty liver at baseline was associated with a lower odds of remission of type-2 diabetes (multivariable-adjusted OR, 0.51; 95% CI, 0.37-0.72). A higher proportion of patients who had improvement of fatty liver had remission of type-2 diabetes (21.1%, 32/152) than patients with no improvement of fatty liver (7.7%, 129/1681). Improvement of fatty liver was associated with a higher odds of remission of type-2 diabetes (multivariable-adjusted OR, 3.08; 95% CI, 1.94-4.88). CONCLUSIONS: Over a follow-up period of approximate 2 years, remission of type-2 diabetes was less common in people with fatty liver detected by ultrasonography, and improvement of fatty liver was independently associated with type-2 diabetes remission.

Predictors of later insulin therapy for gestational diabetes diagnosed in early pregnancy.

Interventions for gestational diabetes mellitus (GDM), diagnosed in early pregnancy, have been a topic of controversy. This study aimed to elucidate factors that predict patients with GDM diagnosed before 24 gestational weeks (early GDM: E-GDM) who require insulin therapy later during pregnancy. Furthermore, we identified patients whose impaired glucose tolerance should be strictly controlled from early gestation onward. Women diagnosed with GDM were categorized based on the gestational age at diagnosis into E-GDM (n = 388) or late GDM (L-GDM, diagnosed after 24 weeks, n = 340) groups. Clinical features were compared between the groups, and the predictors for insulin therapy was evaluated in the E-GDM group. There were no significant between-group differences in terms of perinatal outcomes (e.g., gestational weeks at delivery, fetal growth, hypertensive disorder of pregnancy), with the exception of the Apgar score at 5 min. Moreover, there was no significant difference in the frequency of insulin therapy during pregnancy between the two groups. Using multiple logistic regression analysis, pre-pregnancy body mass index (BMI) ≥25 kg/m2, a family history of diabetes, and higher fasting plasma glucose (FPG), 1 h-plasma glucose (PG), and 2 h-PG values increased insulin therapy risk during pregnancy in the E-GDM group. Furthermore, since E-GDM patients with abnormal levels of FPG, as well as 1 h-PG or 2 h-PG, and those with pre-pregnancy BMI ≥25 kg/m2 and a family history of diabetes had a higher risk of later insulin therapy during pregnancy, they may require more careful follow-up in the perinatal period.

Associations of birthweight and history of childhood obesity with beta cell mass in Japanese adults.

AIMS/HYPOTHESIS: Low birthweight is associated with a high risk of diabetes, but there are no reports discussing birthweight and pancreatic tissues in humans. The purpose of this study was to examine the correlation between birthweight and beta and alpha cell mass in humans. METHODS: Sixty-four Japanese adults with and without diabetes who underwent pancreatectomy and were able to recall their weight history including birthweight were included. Pancreatic tissues were stained for insulin and glucagon, and fractional beta cell area (BCA) and alpha cell area (ACA) were quantified. Islet size and density and beta cell replication were also quantified and their associations with birthweight were evaluated. RESULTS: In participants without diabetes, there was a weak positive correlation between birthweight and BCA (R = 0.34, p = 0.03). The group with a history of childhood obesity, but not the group with a history of obesity in adulthood only, showed higher BCA compared with those without a history of obesity (1.78 ± 0.74% vs 0.99 ± 0.53%, p = 0.01), and the correlation coefficient between birthweight and BCA increased after excluding those with a history of childhood obesity (R = 0.51, p < 0.01). In those with diabetes, there was no correlation between birthweight and BCA. No correlation was found between birthweight and ACA in either those with or without diabetes. CONCLUSIONS/INTERPRETATION: Birthweight and beta, but not alpha, cell mass are positively correlated in non-diabetic adults, and a history of childhood obesity may affect beta cell mass. Graphical abstract.

Relationship between daily and visit-to-visit glycemic variability in patients with type 2 diabetes.

The aim of the study was to explore the relationship between daily glycemic variability (GV) and visit-to-visit glycemic variability (VVV) in patients with type 2 diabetes (T2DM). A total of 156 outpatients with T2DM who had undergone continuous glucose monitoring (CGM) for 5 days were included in this study. Indices of GV, i.e., standard deviation and coefficient of variation (CV) of glucose, mean amplitude of glycemic excursion (MAGE) and mean of the daily differences (MODD) were calculated from the CGM data. VVV was calculated as CV of HbA1c or glycated albumin (GA) from HbA1c or GA measured for 3 years. Relationships among clinical parameters, GV and VVV were evaluated. Age was positively, and BMI and C-peptide index were inversely correlated with GV such as CV glucose and MAGE, while BMI was positively correlated with VVV. Mean glucose rather than GV was correlated with VVV. In contrast, time in range (TIR, 70-180 mg/dL) was correlated with both mean HbA1c or GA and VVV. In conclusion, GV and VVV were differently correlated with clinical parameters and were hardly correlated with each other. TIR was correlated with both mean HbA1c and VVV, suggesting that efforts to achieve optimal TIR are practical strategies to reduce VVV in patients with T2DM.

Usefulness of the index calculated as the product of levels of fasting plasma glucose and hemoglobin A1c for insulinoma screening.

Hypoglycemia is the major symptom of insulinoma. Chronic and recurrent hypoglycemia leads to the disappearance of autonomic symptoms and persistence of non-specific symptoms alone, possibly contributing to the delayed diagnosis of insulinoma and accounting for several undiagnosed cases. We previously reported the usefulness of hemoglobin A1c (HbA1c) and glycated albumin as markers for early insulinoma screening; however, their diagnostic prediction performance and diagnostic performance were not satisfactory. We hypothesized that the product of fasting plasma glucose (FPG) and HbA1c levels (FPG × HbA1c index) is low in insulinoma, and this index may be a useful marker for screening. This cross-sectional multicenter study compared 82 insulinoma patients with 100 age-, sex-, and body mass index-matched controls with normal glucose tolerance based on 75-g oral glucose tolerance test. The FPG × HbA1c index was significantly lower in the insulinoma group than in the control group. Receiver operating curve analysis showed that the optimal cutoff point of the FPG × HbA1c index to diagnose insulinoma was 447.1, and the area under the curves (AUCs) of the FPG × HbA1c index and HbA1c were 0.998 and 0.966, respectively. The AUC of the index was significantly higher than that of HbA1c (p = 0.010). Conversely, no significant difference existed between the AUC of the FPG × HbA1c index and that of the FPG/fasting immunoreactive insulin index. Thus, in apparently healthy population, the product of FPG and HbA1c yields a useful index for insulinoma screening in terms of accuracy and versatility.

Signaling between pancreatic ß cells and macrophages via S100 calcium-binding protein A8 exacerbates ß-cell apoptosis and islet inflammation.

Chronic low-grade inflammation in the pancreatic islets is observed in individuals with type 2 diabetes, and macrophage levels are elevated in the islets of these individuals. However, the molecular mechanisms underlying the interactions between the pancreatic ß cells and macrophages and their involvement in inflammation are not fully understood. Here, we investigated the role of S100 calcium-binding protein A8 (S100A8), a member of the damage-associated molecular pattern molecules (DAMPs), in ß-cell inflammation. Co-cultivation of pancreatic islets with unstimulated peritoneal macrophages in the presence of palmitate (to induce lipotoxicity) and high glucose (to induce glucotoxicity) synergistically increased the expression and release of islet-produced S100A8 in a Toll-like receptor 4 (TLR4)-independent manner. Consistently, a significant increase in the expression of the S100a8 gene was observed in the islets of diabetic db/db mice. Furthermore, the islet-derived S100A8 induced TLR4-mediated inflammatory cytokine production by migrating macrophages. When human islet cells were co-cultured with U937 human monocyte cells, the palmitate treatment up-regulated S100A8 expression. This S100A8-mediated interaction between islets and macrophages evoked ß-cell apoptosis, which was ameliorated by TLR4 inhibition in the macrophages or S100A8 neutralization in the pancreatic islets. Of note, both glucotoxicity and lipotoxicity triggered S100A8 secretion from the pancreatic islets, which in turn promoted macrophage infiltration of the islets. Taken together, a positive feedback loop between islet-derived S100A8 and macrophages drives ß-cell apoptosis and pancreatic islet inflammation. We conclude that developing therapeutic approaches to inhibit S100A8 may serve to prevent ß-cell loss in patients with diabetes.

Usefulness of hemoglobin A1c and glycated albumin measurements for insulinoma screening: an observational case-control study.

BACKGROUND: Insulinoma represents hypoglycemia as a predominant symptom; the autonomic symptoms may be resolved by chronically recurrent hypoglycemia resulting in the persistence of non-specific symptoms alone. Therefore, it has been estimated that there are many patients in whom the disease takes longer to diagnose and has remained undiagnosed. Although some parameters exist for the definitive diagnosis of the disease, there are currently no indices for early screening. Indices of glycemic control, hemoglobin A1c (HbA1c), and glycated albumin (GA) may be useful for the screening of patients with insulinoma having chronic hypoglycemia because the values become low in such a condition. Because there are no articles that have reported the point, we examine the effective cutoff values of HbA1c and GA for the diagnosis of insulinoma in the present study. METHODS: In a multicenter cross-sectional study, 31 patients with insulinoma were included for comparison with 120 control subjects with normal glucose tolerance based on 75 g oral glucose tolerance tests whose characteristics were matched to the patients. The primary outcomes were optimal cutoff values of HbA1c and GA for the screening of insulinoma. RESULTS: HbA1c was significantly lower in the insulinoma group at 4.7 ± 0.4% compared to the healthy control group at 5.7 ± 0.3% (p < 0.001), and GA was significantly lower in the insulinoma group at 11.6 ± 1.8% compared to the healthy control group at 14.5 ± 1.0% (p < 0.001). According to a receiver operating characteristic (ROC) analysis, optimal cutoff values of HbA1c and GA for the diagnosis of insulinoma were 5.0 and 12.4%, respectively. Area under the curve values of HbA1c and GA were 0.970 and 0.929, respectively, showing no significant difference (p = 0.399). CONCLUSIONS: In the present study, HbA1c and GA values in patients with insulinoma were significantly lower compared to the healthy controls, and effective cutoff values for screening were shown in the diagnosis of insulinoma for the first time. HbA1c and GA can be useful indices for insulinoma screening. Because malignant insulinoma have a similar diagnostic process to that of benign insulinoma, these could be useful for malignant insulinoma.

Glycemic and metabolic features in gestational diabetes: singleton versus twin pregnancies.

A number of data on gestational diabetes mellitus (GDM) in singleton pregnancy is available, however, little is known about the glycemic characteristics of twin pregnancy with GDM. The aim of this study was to compare the severity of dysglycemia between twin and singleton pregnancies with GDM (T-GDM and S-GDM). We retrospectively analyzed pregnancies with GDM defined by the Japan Diabetes Society criteria (T-GDM, n = 20; S-GDM, n = 451) in our hospital. During the study period, women with GDM underwent self-monitoring of blood glucose measurements as well as dietary management. Insulin treatment was initiated when dietary treatment did not achieve the glycemic goal. The glycemic and metabolic characteristics were compared between T-GDM and S-GDM, as follows: gestational week at the diagnosis of GDM, 75 g oral glucose tolerance test (OGTT) results, HbA1c, insulin secretion (i.e. insulinogenic index [IGI] and Insulin Secretion-Sensitivity Index-2 [ISSI-2]), and insulin requirement before delivery. The rate of one abnormal OGTT value in T-GDM was similar to that in S-GDM (60% vs. 71%). There were no significant differences in gestational week and levels of HbA1c at diagnosis, levels of IGI and ISSI-2 between T-GDM and S-GDM (median, 20 weeks vs. 17 weeks, 5.0% vs. 5.2%, 0.58 vs. 0.71, 1.7 vs. 1.8, respectively). The rate of insulin treatment and a median dosage of insulin needed before delivery was comparable between the two groups (T-GDM vs. S-GDM: 45% vs. 32% and 14 vs. 13 unit/day). Our data suggested that the severity of dysglycemia in T-GDM was similar to that in S-GDM during pregnancy.

Lower serum total bilirubin concentration is associated with higher prevalence of gestational diabetes mellitus in Japanese pregnant women.

We aimed to clarify the pathophysiological significance of total bilirubin (TB) in gestational diabetes mellitus (GDM). This was a cross-sectional study that included 616 pregnant Japanese women (368 normal glucose tolerance [NGT] and 248 GDM). Serum TB concentration, homeostasis model assessment of insulin resistance (HOMA-IR), and other clinical parameters were compared in NGT and GDM women. TB concentration was also compared according to the number of abnormal OGTT values. Logistic regression analysis was used to evaluate the association between TB and GDM prevalence. A multiple linear regression model was used to evaluate the association between TB and HOMA-IR. TB concentrations were significantly lower in GDM women than in NGT women. This result did not change after adjustments for TB sampling timing were made. Out of 248 GDM women, the prevalences of 1- and 2/3- abnormal OGTT values (1- and 2/3-AV) GDM were 72.2% (n = 179) and 27.8% (n = 69), respectively. In the multiple comparisons, TB concentrations were significantly lower in women with 2/3-AV GDM than in women with NGT and 1-AV GDM. Multiple logistic regression analysis showed that TB was a significantly associated factor for 2/3-AV, but not for total GDM. HOMA-IR was significantly higher in GDM women than in NGT women. The univariate, but not multivariate, analysis showed that TB was a significantly associated factor for HOMA-IR. Our findings suggest that hypobilirubinemia may be involved in the pathogenesis of GDM.

Association between severity of obstructive sleep apnea and glycated hemoglobin level in Japanese individuals with and without diabetes.

Aim of this study was to examine the association between the severity of obstructive sleep apnea (OSA) and dysglycemia in Japanese individuals with and without type 2 diabetes (T2DM). We enrolled 115 individuals diagnosed with OSA with an apnea hypopnea-index (AHI) ≥ 20 in whom continuous positive airway pressure (CPAP) therapy was introduced (N = 115, 44 with T2DM, age 62 ± 11 years, BMI 27.0 ± 4.4 kg/m2 and AHI median 36.1; interquartile range 27.2-48.1). During admission, the severity of OSA was evaluated by polysomnography, and its association with glycated hemoglobin (HbA1c) level was examined. Continuous glucose monitoring (CGM) was also conducted during the admission in 94 individuals. Apnea-hypopnea index (AHI), non-rapid eye movement (REM) AHI, minimum peripheral capillary oxygen saturation (SpO2) and percentage of sleep time (%TST) with SpO2 < 90% were significantly associated with HbA1c level in total and non-diabetic individuals (all p < 0.05) but not in those with T2DM, the majority of whom were treated with anti-diabetic medications. The associations of the non-REM AHI and %TST with SpO2 < 90% with HbA1c level remained significant after adjustment for age, sex and BMI in non-diabetic and T2DM subjects treated with dietary therapy only. Mean glucose level, but not SD or coefficient of variation of glucose, assessed by CGM was significantly associated with AHI and non-REM AHI in non-diabetic subjects after adjustment for age, sex and BMI. In conclusion, the severity of OSA was associated with increased HbA1c level independently of BMI in Japanese individuals, especially in those without diabetes.

Association of common polymorphisms with gestational diabetes mellitus in Japanese women: A case-control study.

Gestational diabetes (GDM) and type 2 diabetes (T2DM) share part of pathomechanism and several T2DM susceptibility genes are demonstrated to be associated with GDM. No information on the genetics of GDM, however, was available in Japanese women. In this study, T2DM risk variants (45 single nucleotide polymorphisms [SNPs] from 36 genes) identified in previous studies were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in a cohort of 171 Japanese women with GDM and 128 normal glucose tolerance (NGT) diagnosed by the new International Association of Diabetes in Pregnancy Study Group criteria. Of 45 SNPs, three genetic variants were nominally associated with the development of GDM: rs266729 (p = 0.013, odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.10-2.23) in ADIPOQ, rs10811661 (p = 0.035, OR: 1.46, 95% CI: 1.03-2.08) in CDKN2A/2B, and rs9505118 (p = 0.046, OR: 1.41, 95% CI: 1.01-1.97) in SSR1-RREB1. There was a significant difference in the number of risk alleles of three variants between women with GDM and NGT (3.79 ± 1.33 vs. 3.05 ± 1.41, p = 6.0 × 10-6). In combined analysis of three genetic variants, women with five or more risk alleles had a 7.32-fold increased risk of GDM (p = 5.6 × 10-5, 95% CI: 4.54-11.96), compared with those having no more than one risk allele. Our results suggest several risk variants of T2DM had cumulative effects on the development of GDM in Japanese women.

Time-dependent changes in insulin requirement for maternal glycemic control during antenatal corticosteroid therapy in women with gestational diabetes: a retrospective study.

Though recommended for pregnant women at risk of preterm birth to improve perinatal outcomes, antenatal corticosteroid (ACS) treatment can cause maternal hyperglycemia, especially in cases of glucose intolerance. A standardized protocol for preventing hyperglycemia during ACS treatment remains to be established. We herein retrospectively investigated the time-dependent changes in insulin dose required for maternal glycemic control during ACS treatment in gestational diabetes (GDM). Twelve singleton pregnant women with GDM who received 12 mg of betamethasone intramuscularly twice 24 hours apart were included in this analysis. Of those, eight also received ritodrine hydrochloride for preterm labor. The blood glucose levels were maintained at 70-120 mg/dL with continuous intravenous infusion of insulin and nothing by mouth for 48 hours after the first betamethasone administration. After the first dose of betamethasone, the insulin dosage needed for glycemic control gradually increased and reached a maximum (6.6 ± 5.8 units/hr) at 10 hours, then, decreased to 4.1 ± 1.5 units/hr at 24 hours. Similar changes in the insulin requirement were found after the second betamethasone dose (the maximum insulin dosage: 5.5 ± 1.6 units/hr at 9 hours following the second administration). Women treated with ritodrine hydrochloride needed more insulin, than those without ritodrine hydrochloride treatment (130.8 ± 15.0 vs. 76.8 ± 15.2 units/day, respectively, p < 0.05). Our data indicated that the requirement for insulin is highest 9-10 hours after each dose of betamethasone. When GDM is treated with ACS, levels of blood glucose should be carefully monitored, especially in patients treated with ritodrine hydrochloride.

Postprandial C-Peptide to Glucose Ratio as a Marker of ß Cell Function: Implication for the Management of Type 2 Diabetes.

C-peptide is secreted from pancreatic ß cells at an equimolar ratio to insulin. Since, in contrast to insulin, C-peptide is not extracted by the liver and other organs, C-peptide reflects endogenous insulin secretion more accurately than insulin. C-peptide is therefore used as a marker of ß cell function. C-peptide has been mainly used to assess the presence of an insulin-dependent state for the diagnosis of type 1 diabetes. However, recent studies have revealed that ß cell dysfunction is also a core deficit of type 2 diabetes, and residual ß cell function is a key factor in achieving optimal glycemic control in patients with type 2 diabetes. This review summarizes the role of C-peptide, especially the postprandial C-peptide to glucose ratio which likely better reflects maximum ß cell secretory capacity compared with the fasting ratio in assessing ß cell function, and discusses perspectives on its clinical utility for managing glycemic control in patients with type 2 diabetes.