Insulin requirements during pregnancy in women with type 1 diabetes treated with insulin pump.

INTRODUCTION: Insulin requirement in women with Type 1 diabetes (T1DM) changes throughout pregnancy. The aim of this study was to determine the total change in insulin requirements and the effect of gestational weight gain (GWG) and pre-gestational BMI on insulin requirements during pregnancy in women with T1DM treated with continuous subcutaneous insulin infusion and continuous glucose monitoring. METHODS: This historical cohort study included all consecutive women with T1DM who were monitored during pregnancy at the high-risk pregnancy clinic at a tertiary medical center during April 2011-April 2019. One Way Repeated Measures ANOVA with Bonferroni adjustment was conducted to compare the effects of gestational age on insulin requirements and a Two Way Repeated Measures ANOVA was employed to test for the interaction between gestational age intervals and maternal BMI and GWG. RESULTS: Data regarding insulin requirements of 185 pregnancies were included in the analyses. There was a significant effect of gestational age on total insulin (Wilks' Lambda = 0.34, F(6,14) = 4.52, p = 0.009), basal insulin (Wilks' Lambda = 0.41, F(6,14) = 3.30, p = 0.031) and bolus insulin (Wilks' Lambda = 0.43, F(6,14) = 3.02, p = 0.041). Total insulin/kg requirements increased by 5.5% from 13-20 weeks to 20-26 weeks, 19% from 20-26 weeks to 26-33 weeks, and 17.4% from 26 to 33 weeks to delivery (p for trend = 0.009). Overall, insulin requirements increased by 42.1% from conception to delivery (p < 0.01). There was no significant main effect of maternal BMI or GWG on insulin requirements. CONCLUSIONS: There is a significant increase in insulin requirements per kg during pregnancy in women with T1DM who were treated with an insulin pump.

A Scoping Review Evaluating the Effect of SGLT-2 Inhibitors on Insulin Dose Requirements in Insulin-Dependent Patients With Type 2 Diabetes.

OBJECTIVE: Assess evidence describing the effect of Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors on total daily insulin (TDI) requirements in insulin-dependent patients with type 2 diabetes. DATA SOURCES: A scoping review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Protocols and Scoping Reviews (PRISMA-ScR) guidelines. The search was conducted in PubMed; citation mapping was completed in Web of Science. Filters for human studies, English language, and a publication date, from January 1, 2005 to April 12, 2021, were applied. STUDY SELECTION AND DATA EXTRACTION: Studies assessing insulin dose requirements with concurrent use of an SGLT2 inhibitor for patients with type 2 diabetes were included. DATA SYNTHESIS: Sixteen studies were included and demonstrated that addition of an SGLT2 inhibitor typically reduced TDI requirements. Insulin reductions were often statistically significant, occurring in studies evaluating (1) within subjects who received SGLT2 inhibitors, and (2) between subjects receiving SGLT2 inhibitors versus placebo. Compared with placebo, insulin dose reduction ranged from -0.72 to -19.2 units. However, studies were relatively small, not designed to assess TDI change, and some utilized fixed dose insulin protocols or empiric insulin dose reductions. CONCLUSIONS: Lowering insulin requirements may have benefits, such as decreased hypoglycemia risk, insulin resistance, and cost. Addition of an SGLT2 inhibitor may modestly reduce TDI requirements for patients with type 2 diabetes. Evidence indicating SGLT2 inhibitor use reduces TDI may lead to additional implementation in practice and inform future research. Further research is needed to clarify insulin type (i.e., basal or prandial) and degree of TDI reduction expected with addition of an SGLT2 inhibitor.

Outcome of bariatric surgery in patients with type 1 diabetes mellitus: our experience and review of the literature.

BACKGROUND: The beneficial effect of bariatric surgery (BS) in type 2 diabetes mellitus patients is well established. Conversely, little is known about the efficacy of BS in type 1 diabetes mellitus (T1DM) patients, despite the increasing prevalence of obesity in this population. METHODS: A retrospective review was carried out on a prospectively collected bariatric surgery registry of all patients undergoing BS at two university hospitals between 2010 and 2015. Patients with T1DM were identified, and detailed chart reviews were obtained. RESULTS: In this time period, we operated on thirteen patients with T1DM. Eight were female (61.5 %). Median age at time of surgery was 38 ± 8.3 (range 28-53) years. The procedures performed were laparoscopic sleeve gastrectomy (n = 10) and laparoscopic Roux-en-Y gastric bypass (n = 3). On median postoperative follow-up of 24 (range 2.5-51) months, mean body mass index significantly decreased from 39.9 ± 4.1 to 30.1 ± 3.9 kg/m2 (P < 0.0001) and insulin requirements were significantly reduced from 83.7 ± 40.4 to 45.7 ± 33.1 U/day (P < 0.01). However, there was no significant change in glycemic control assessed by HbA1C (P = 0.2). During the first months following surgery, three patients (21.4 %) experienced diabetic ketoacidosis, and four patients (28.6 %) reported more frequent episodes of hypoglycemia. CONCLUSIONS: Bariatric surgery in morbidly obese T1DM patients is an effective method for weight loss, leading to a remarkable improvement in insulin requirements. Larger prospective studies are still needed to confirm these findings, assess long-term effects of BS and better delineate its risk-to-benefit ratio in this growing population of morbidly obese patients with T1DM.

Effect of pregnancy on insulin requirements differs between type 1 and type 2 diabetes: A cohort study of 222 pregnancies.

BACKGROUND: Knowledge about expected insulin requirements during pregnancy, in women with pre-existing diabetes may assist clinicians to effectively respond to gestation-specific changes in glycemic pattern. Few studies have examined differences between type 1 (T1DM) and type 2 diabetes (T2DM). AIMS: To compare patterns of insulin requirements in pregnancy for women with pre-existing T1DM and T2DM. MATERIAL AND METHODS: A retrospective cohort study of 222 pregnancies was conducted in women with pre-existing diabetes, (67 with T1DM, 155 with T2DM). Total daily insulin dose (TID) at the end of each trimester, recorded as units and units per kilogram (median, 25th-75th percentile) as well as percentage increase in insulin dose per trimester were compared. RESULTS: Women with T1DM had higher insulin requirements in the first two trimesters than those with T2DM (0.69 (0.58-0.85) vs 0.36 (0.0-0.7) units/kg in first trimester; 0.80 (0.62-0.95) vs 0.61 (0.27-0.95) units/kg, P < 0.005) in second trimester), but requirements in late pregnancy were similar (0.97 (0.69-1.29) vs 0.95 (0.53-1.32) units/kg, P = 0.54). Women with T2DM needed much greater increases in insulin per trimester compared to T1DM (P < 0.001). Women with T1DM had a net fall in insulin requirements (3.7% in the first trimester and 4.1% in the late third trimester) while those with T2DM did not. CONCLUSIONS: This is the largest comparison study of insulin requirements in women with pre-existing diabetes, highlighting important trimester-specific differences between T1DM and T2DM to guide insulin titration during pregnancy. Our findings suggest a differential effect of pregnancy-mediated insulin resistance by type of diabetes.

Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes.

BACKGROUND: Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus (T2DM), that is, patients who have insulin resistance, obesity, and other cardiovascular risk factors, suggesting that the presence of glutamic acid decarboxylase (anti-GAD65), islet antigen 2 (anti-IA2), and zinc transporter 8 (anti-Zn8T) antibodies could have deleterious effects on beta cell function, causing failure and earlier requirement for insulin treatment. AIM: To evaluate anti-GAD65, anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of T2DM. METHODS: This was a case-control study in patients with clinically diagnosed with T2DM (68 cases and 64 controls with and without early insulin dependence respectively), male and female, aged 12-18 years. Somatometry, blood pressure, glucose, insulin, C-peptide, glycated hemoglobin A1c, and lipid profiles were assessed. ELISA was used to measure anti-GAD65, anti-IA2, and anti-Zn8T antibodies. Descriptive statistics, Pearson's χ 2 test, Student's t test, and logistic regression was performed. P < 0.05 was considered statistically significant. RESULTS: There were 132 patients (53.8% female), with a mean age was 15.9 ± 1.3 years, and there was a disease evolution time of 4.49 ± 0.88 years. The presence of anti-GAD65, anti-IA2, and anti-Zn8T positivity was found in 29.5%, 18.2%, and 15.9%, respectively. Dividing the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity: anti-GAD65 odds ratio (OR): 2.42 (1.112-5.303, P = 0.026); anti-IA2: OR: 1.55 (0.859-2.818, P = 0.105); and anti-Zn8T: OR: 7.32 (2.039-26.279, P = 0.002). CONCLUSION: Anti-GAD65 positivity was high in our study. Anti-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype, leading to an increased risk of early insulin dependence.

Impact of metabolic and bariatric surgery on weight loss and insulin requirements in type 1 and insulin-treated type 2 diabetes.

Metabolic and Bariatric Surgery (MBS) is effective in improving metabolic outcomes and reducing weight in patients with obesity and diabetes, with less explored benefits in type 1 diabetes (T1D). This study aimed to evaluate the impact of MBS on weight loss and insulin requirements in T1D patients compared to insulin-treated type 2 diabetes (T2D) patients over a 5-year period. This retrospective analysis included patients who underwent primary sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) with a confirmed preoperative diagnosis of either T1D or insulin-treated T2D. Primary endpoints focusing on weight loss and secondary outcomes assessing changes in insulin dosage and glycemic control. After 5 years, weight loss was similar across groups, with total weight loss at 14.2% for T1D and 17.6% for insulin-treated T2D in SG, and 22.6% for T1D vs. 26.8% for insulin-treated T2D in RYGB. Additionally, there was a significant reduction in median daily insulin doses from 140.5 units at baseline to 77.5 units at 1 year postoperatively, sustained at 90 units at 5 years. The differential impact of MBS procedure was also highlighted, where RYGB patients showed a more pronounced and enduring decrease in insulin requirements compared to SG.

Time course change of the insulin requirements during the perioperative period in hepatectomy and pancreatectomy by using an artificial pancreas STG-55.

Introduction: To investigate changes in insulin requirements over time in patients who underwent hepatectomy and pancreatectomy with perioperative glycemic control by an artificial pancreas (STG-55). Materials and methods: We included 56 patients (22 hepatectomies and 34 pancreatectomies) who were treated with an artificial pancreas in the perioperative period and investigated the differences in insulin requirements by organ and surgical procedure. Results: The mean intraoperative blood glucose level and total insulin doses were higher in the hepatectomy group than in the pancreatectomy group. The dose of insulin infusion increased in hepatectomy, especially early in surgery, compared to pancreatectomy. In the hepatectomy group, there was a significant correlation between the total intraoperative insulin dose and Pringle time, and in all cases, there was a correlation with surgical time, bleeding volume, preoperative CPR, preoperative TDD, and weight. Conclusions: Perioperative insulin requirements may be mainly dependent on the surgical procedure, invasiveness, and organ. Preoperative prediction of insulin requirements for each surgical procedure contributes to good perioperative glycemic control and improvement of postoperative outcomes.

Breastfeeding and insulin requirements in women with Type 1 diabetes mellitus in the first year postpartum.

AIMS: To explore whether breastfeeding affects postpartum insulin requirements, HbA1c levels, and pregnancy weight retention in women with Type 1 Diabetes Mellitus (T1DM). METHODS: This prospective study included 66 women with T1DM. The women were divided into two groups based on whether they were breastfeeding (BF) at 6 months postpartum (BFyes, n = 32) or not (BFno, n = 34). Mean daily insulin requirement (MDIR), HbA1c levels, and pregnancy weight retention at 5 time-points from discharge to 12 months postpartum were compared. RESULTS: MDIR increased by 35% from 35.7 IU at discharge to 48.1 IU at 12 months postpartum (p < 0.001). MDIR in BFyes and BFno were comparable, however in BFyes, MDIR were continuously lower compared to BFno. Postpartum HbA1c increased rapidly from 6.8% at 1 month to 7.4% at 3 months postpartum and settled at 7.5% at 12 months postpartum. The increase in HbA1c during the first 3 months postpartum was most pronounced in BFno (p < 0.001). Although neither were statistically significant, from 3 months postpartum HbA1c levels were highest in the BFno and BFno had a higher pregnancy weight retention compared to BFyes (p = 0.31). CONCLUSION: In women with T1DM, breastfeeding did not significantly affect postpartum insulin requirements, HbA1c levels or pregnancy weight retention in the first year after delivery.

Insulin Requirements During Severe COVID-19 Were Relatively Low in Japanese Patients With Type 2 Diabetes: Two Case Reports.

The global coronavirus disease 2019 (COVID-19) pandemic has caused myriad adverse effects on the pathology of other diseases. Numerous studies on COVID-19 have reported that, in patients with type 2 diabetes mellitus (T2DM) who have contracted severe COVID-19, glucose metabolism is exacerbated by multiple factors, such as severe inflammation, beta-cell dysfunction caused by the SARS-CoV-2 infection itself, corticosteroid therapy, vasopressor administration, and enteral or parenteral nutrition. Very high doses of insulin are often required in the acute phase of such patients; however, the factors that affect insulin requirements and to what extent remain unclear. A 50-year-old Japanese woman and a 67-year-old Japanese man, both with T2DM and obesity, were admitted to our hospital with severe COVID-19. Both patients required mechanical ventilation and were treated with dexamethasone and tocilizumab, an interleukin-6 (IL-6) receptor monoclonal antibody. Subcutaneous insulin injections failed to control the patients' hyperglycemia, requiring up to 1.83 and 1.81 units/kg/day of intravenous insulin, respectively. Insulin requirements were rapidly decreased with improvement of the respiratory condition, termination of dexamethasone, and discontinuation of tube feeding. Both patients were discharged with oral antidiabetic agents alone. We experienced two Japanese patients who achieved satisfactory glycemic control with a lower intravenous insulin dose than previous reports. Comparing the clinical factors with the previous literature, ethnic differences in insulin sensitivity and the administration of IL-6 receptor antibodies may have been related to the relatively low insulin requirements.

COVID-19 Pneumonia and Increased Insulin Requirement in Known Diabetic Patients: A Prospective Observational Study.

Background COVID-19-related critical illness affects multiple organs and causes a variety of metabolic derangements in the body's physiology that are not proven with the current level of evidence. Insulin resistance and deranged blood sugar control due to COVID-19 have been major problems when managing diabetic patients with hyperglycaemia when they are admitted with COVID-19 pneumonia. There is a lack of abundant literature to prove the excess insulin requirements of COVID-19 and to quantify their insulin needs scientifically. This study aims to quantify the degree of insulin dose increments in these patients. Materials and methods The study is a single-centre prospective observational study done in COVID-19 wards at a tertiary care hospital in India. The diabetic patients admitted with COVID-19 pneumonia between June 2020 and December 2020 were included in the study. Seventy-five patients with fair control of diabetes (HbA1C <7.5) were included in the study. Their average daily insulin requirement was calculated for the first seven days of admission. This was tabulated and compared to their baseline insulin requirement before being unwell due to COVID-19. A sub-group analysis was also done to show the relation between severity of illness and glycaemic dysregulation. Result Invariably, all patients were found to be hyperglycaemic on admission. Insulin need has increased to 1.5 to 2.5 times the baseline values in the first 24 hours of admission. This insulin dose requirement stayed high around the same levels for all seven days of observation. The average mean value of the daily insulin dose for the seven days of study was calculated to be 132 units. This is more than twice the mean baseline daily insulin requirement of 62 units during the pre-COVID-19 period. Subgroup analysis showed that the severe group had poor glycaemic control, requiring higher doses compared to their own baseline and also to the moderate group. Conclusion COVID-19 pneumonia significantly increases insulin resistance and insulin requirements during illness in fairly controlled known diabetic patients with insulin. Managing this COVID-19-induced hyperglycaemia requires 1.5 to 2.5 times the baseline insulin doses.

The relationship between falling insulin requirements and serial ultrasound measurements in women with preexisting diabetes: a prospective cohort study.

INTRODUCTION: A large fall in insulin requirements (FIR) in women with diabetes is associated with adverse clinical outcomes but previous studies have not examined its relation with serial ultrasound parameters. OBJECTIVE: To determine whether FIR is associated with alteration in umbilical artery Doppler parameters and fetal growth restriction (FGR) in women with preexisting diabetes. METHODS: Serial obstetric Doppler ultrasounds were conducted 2 weekly from 28 weeks gestation in women with Type 1 and Type 2 diabetes who were being treated with insulin. Estimated fetal weight (EFW), head circumference:abdominal circumference (HC:AC) ratio and umbilical artery doppler parameters (SD ratio) and pulsatility index (PI) were measured. Information on insulin dose was collected prospectively throughout pregnancy and women with FIR ≥ 15% were considered cases. Linear mixed effect models were used to assess the association between FIR and ultrasound parameters. RESULTS: One hundred and forty two women were included in the study (type 1 diabetes n = 41, type 2 diabetes n = 101). Thirty women demonstrated FIR ≥ 15%. There was no significant difference in the change of S/D ratio or PI over the third trimester in cases with FIR ≥ 15%, compared to the rest of the cohort, before or after adjusting for type of diabetes. Likewise there was no difference in EFW and HC:AC ratio with advancing gestation before or after adjusting for variables known to influence fetal growth. FGR rates (3.3 vs 8% p = 0.298) and high S/D ratio > 95% (13.3 vs 8%, p = 0.296) were similar between the two groups. CONCLUSIONS: FIR ≥ 15% was not associated with changes in placental flow or FGR however larger studies are needed to evaluate this further.

Insulin treatment of patients with gestational diabetes: does dosage play a role?

BACKGROUND AND OBJECTIVE: In nonpregnant patients high insulin requirements are associated with hypoglycemia and weight gain but not with improvement in glucose control. The effect of insulin requirement on maternal and neonatal outcomes in gestational diabetes mellitus (GDM) is yet unknown. METHODS: We conducted a retrospective cohort study of maternal and neonatal outcomes of pregnancy according to insulin requirements in women with GDM who were followed and delivered at the Yitzhak Shamir Medical Center between 2006 and 2016. The daily insulin dose in units per body weight was divided into quartiles and analyses were performed to compare the lowest, highest, and two middle quartiles. The primary outcome was a composite of any of the following: cesarean-section (CS), preeclampsia, macrosomia and large for gestational age (LGA) birth weight, neonatal intensive care unit admission, need for phototherapy, and neonatal hypoglycemia. RESULTS: Women were divided according to their insulin requirements as follows: 79 (24.8%) women who needed <0.13 IU/kg/day of insulin (insulin-sensitive group), 160 (50%) women who needed 0.14-0.42 IU/kg/day of insulin (comparison-group), and the rest who needed >0.43 IU/kg/day of insulin (insulin resistant group). There were no differences in the composite outcome between the groups (64.6, 61.3, and 69.6% for the insulin sensitive-, comparison- and resistant- groups, respectively, p = .44). Women in the insulin-resistant group had higher fasting glucose levels in the first trimester (91, 98 and 102 mg/dL for women in the insulin sensitive-, comparison- and insulin-resistant groups, respectively; p = .01). Women in the insulin-sensitive group had significantly better glycemic control (fasting glucose levels ≤90 mg/dL and 1-hour and 2-hour postprandial glucose levels ≤140 mg/dL and ≤120 mg/dL for more than 80% of measurements) than those in the insulin-resistant group (70.3 versus 29.9%; p < .001). The rate of CS was significantly higher in the insulin-resistant group (42.3 versus 24.1%; p = .03), but the rate of LGA birth weight was surprisingly higher in the insulin-sensitive group (29.5 versus 16.7%, p = .04). After controlling for confounders, women in the insulin-sensitive group had a decreased risk for CS in relation to the comparison group (OR = 0.46, 95%CI 0.23-0.9, p = .025). CONCLUSION: We found no association between insulin requirements and adverse composite outcome in women with GDM. However, those with higher insulin requirements have poorer glucose control and higher rates of CS than those with lower insulin requirements. Larger studies are needed to inquire short- and long-term outcomes of insulin requirements on fetal and maternal outcomes.

Continuous subcutaneous insulin infusion does not correspond with pregnancy outcomes despite better glycemic control as compared to multiple daily injections in type 1 diabetes - Significance of pregnancy planning and prepregnancy HbA1c.

OBJECTIVE: The aim of the study was to compare pregnancy outcomes with glycemic control, total increase in insulin requirement, and body weight gain in the women with Type 1 Diabetes Mellitus (T1DM) using continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). MATERIAL AND METHODS: This was a single center retrospective observational study involving 209 pregnant Caucasian women. Among the study participants, 95 subjects were treated with MDI and 114 patients were using CSII therapy. The primary outcomes were pregnancy results, while secondary ones were HbA1c, increase in daily dose of insulin (DDI), and body weight gain. RESULTS: At baseline, the CSII users were older (P = 0.0373), they were diagnosed with T1DM at a younger age (P = 0.047), and more often planned pregnancy (P = 0.032). A majority of the women were classified as class D, according to the White classification. Among the CSII users, a significantly higher proportion of the subjects in class B was noted than in the MDI users, with no differences in the proportion of the remaining White classes. Prepregnancy HbA1c was insignificantly lower in the CSII group, however, a significantly higher proportion of the CSII users reached the target value of HbA1c (P = 0.008). A prepregnancy daily dose of insulin (both total and per kg of body weight), body weight, and body mass index (BMI) did not differ between the groups. The 1st and 2nd trimester HbA1c was lower among the CSII users (6.83 ± 1.38 vs 7.52 ± 2.11%, P = 0.01 and 6.17 ± 0.9 vs 6.57 ± 1.12%, P = 0.009, respectively), while the 3rd trimester HbA1c as well as the total change in HbA1c were comparable. Neither DDI and body weight in concecutive trimesters, nor their total gestational increase, differed between the groups. The rate of pregnancy loss, such as abortions, fetal and neonatal death did not differ between the groups. As regards composite pregnancy loss, prepregnancy HbA1c was 8.41%±2.81% among the MDI cohort vs 7.22%±1.31% in the CSII users (P = 0.517). No differences were found in the gestational age at delivery, the mode of delivery, neonatal birth weight, the rate of macrosomy, LGA or SGA. A higher Apgar score was noted among the CSII users (8.63 ± 1.63 vs 8.03 ± 2.49%, P = 0.047), however, the proportion of neonates with an Apgar score lower than 7 points was similar. In the women planning pregnancy, as compared to the subjects who did not, HbA1c was significantly lower in the 1st trimester, together with a significantly higher rate of the women achieving the target HbA1c value during planning as well as in the 1st trimester. In the group of women planning pregnancy, significantly lower 1st trimester HbA1c and composite outcome of pregnancy loss were observed in the CSII users vs the MDI treated women. Lack of pregnancy planning and a high HbA1c level in the 1st trimester were independent predictors of both LGA (OR = 4.99 [95%CI 1.12-21.0], P = 0.033 and OR = 3.02 [95%CI 1.19-7.65], P = 0.019, respectively) and macrosomia (OR = 8.43 [95%CI 1.36-51.93], P = 0.021 and OR = 5.47 [95%CI 1.77-16.87], P = 0.003, respectively). CONCLUSIONS: The course of pregnancy and obstetric outcomes were not dependent on the mode of insulin delivery, but only on pregnancy planning and HbA1c in early pregnancy. Further studies are needed to explore more precise parameters describing both glycemic control in pregnant women as well as perinatal infant well-being.

Liraglutide-Induced Weight Loss May be Affected by Autonomic Regulation in Type 1 Diabetes.

The role of the autonomic nervous system in the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with type 1 diabetes is unknown. We assessed the association between autonomic function and weight loss induced by the GLP-1 RA liraglutide. Methods: Lira-1 was a randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of 1.8 mg liraglutide once-daily for 24 weeks in overweight patients with type 1 diabetes. Autonomic function was assessed by heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio), to the Valsalva maneuver and resting heart rate variability (HRV) indices. Associations between baseline the cardiovascular autonomic neuropathy (CAN) diagnosis (> 1 pathological non-resting test) and levels of test outcomes on liraglutide-induced weight loss was assessed by linear regression models. Results: Ninety-nine patients with mean age 48 (SD 12) years, HbA1c 70 (IQR 66;75) mmol/mol and BMI of 30 (SD 3) kg/m2 were assigned to liraglutide (N = 50) or placebo (N = 49). The CAN diagnosis was not associated with weight loss. A 50% higher baseline level of the 30/15 ratio was associated with a larger weight reduction by liraglutide of -2.65 kg during the trial (95% CI: -4.60; -0.69; P = 0.009). Similar significant associations were found for several HRV indices. Conclusions: The overall CAN diagnosis was not associated with liraglutide-induced weight loss in overweight patients with type 1 diabetes. Assessed separately, better outcomes for several CAN measures were associated with higher weight loss, indicating that autonomic involvement in liraglutide-induced weight loss may exist.

The importance of declining insulin requirements during pregnancy in patients with pre-gestational gestational diabetes mellitus.

OBJECTIVE: In patients with pre-gestational and gestational diabetes mellitus (GDM), insulin requirements often increase during the third trimester of pregnancy in order to maintain proper glycemic control. However, a fraction of patients demonstrate a significant decrease in insulin requirements in late gestation. We aimed to evaluate the clinical significance of decreasing insulin requirements in patients with pre-gestational diabetes and GDM with respect to fetal wellbeing and pregnancy outcome. STUDY DESIGN: We performed a retrospective cohort study in a single referral center for gestational diabetes between 1/2010 and 12/2014. Healthy pregnant women with pre-gestational diabetes and GDMA2 and a decrease of at least 30% in insulin requirements over a period of two weeks during the third trimester (group A) were compared to women with stable or increasing insulin requirements (group B). The primary outcome was a composite of situations associated with feto-placental dysfunction (fetal growth restriction, oligohydramnios and cesarean section due to category 2-3 monitor). Secondary outcomes were maternal oral glucose tolerance test (OGTT) results 6 weeks postpartum, neonatal intensive care unit (NICU) admission rates, Apgar scores ≤7 at 5min, arterial blood pH≤7.1, macrosomia, neonatal hypoglycemia and a composite adverse neonatal outcomes (defined as one or more of the following: respiratory morbidity, cerebral morbidity, phototherapy, need for blood transfusion, necrotizing enterocolitis or death). RESULTS: Group A consisted of 101 women and group B - of 203 women. There were no differences between the groups in demographic characteristics or diagnostic characteristics of diabetes. The frequency of conditions related to feto-placental dysfunction did not differ between the groups (7.9% vs. 8.4%, p=0.61). Secondary outcome measures also did not differ between the groups, regardless of insulin requirements. CONCLUSION: Decreasing insulin requirements during the third trimester are not associated with adverse perinatal outcome related to placental dysfunction.

Dynamics in insulin requirements and treatment safety.

AIMS: The majority of insulin users have elevated HbA1c. There is growing recognition that the low success rates are due to variations in insulin requirements. Thus, frequent dosage adjustments are needed. In practice, adjustments occur sporadically due to limited provider availability. We investigated intra-individual dynamics of insulin requirements using data from a service evaluation of the d-Nav® Insulin Guidance Service. This service facilitates automated insulin dosage adjustments, as often as needed, to achieve and maintain optimal glycemic balance. METHODS: Data were collected from subjects who have been using the service for more than a year. Events of considerable and persistent decrease in insulin requirements were identified by drops in total daily insulin ≥25%. RESULTS: Overall, 62 patients were studied over an average period of 2.1±0.5 (mean±standard deviation) years. Stability in HbA1c was attained after ~3 quarters at 7.4%±0.2% (57.4mmol/mol±1mmol/mol). Events were identified in 56.5% of the patients. On average, each affected patient had 0.8±0.4 events per year, lasting 9.7±6.6weeks, while total daily insulin dosage decreased by 41.4±13.4%. CONCLUSIONS: Our findings may call attention to a major contributing factor to hypoglycemia among insulin users. In reality, insulin dosage is seldom adjusted and thus transient periods of decrease in insulin requirements and overtreatment are usually overlooked.

Should metabolic surgery be offered in morbidly obese patients with type I diabetes?

BACKGROUND: Bariatric surgery has recently been endorsed as an effective treatment of type 2 diabetes (T2D) in severely obese patients. Little is known about its metabolic effects in type 1 diabetes (T1D). The objectives were to assess bariatric surgery outcomes in T1D obese patients who underwent either a biliopancreatic diversion (BPD) or a sleeve gastrectomy (SG) and who were matched with T2D obese patients requiring insulin therapy. The study setting was at a university-affiliated tertiary care center. METHODS: Through retrospective analysis of prospectively collected data, ten patients with T1D (7 BPD, 3 SG) were matched with 20 patients with T2D (14 BPD, 6 SG) according to age, gender, type of surgery, initial Body Mass Index and insulin requirements (1:2 matching). Weight loss, diabetes control, and remission of co-morbidities were compared. RESULTS: Mean follow-up was 55.1 months. Mean Excess BMI Loss% tended to be greater in T1D patients compared to T2D (77.1% versus 68.3%, P = .14). The remission and improvement rates of T2D were 55% and 45% versus 0% and 90% for T1D. The remission rate of T2D was significantly greater after BPD (71.43%) compared to SG (16.67%, P = .04). Insulin requirements were significantly reduced in both groups after surgery (T1D: .44 ±.24 versus 1.09 ±.7 units/kg/d, P = 0.03, T2D: .03 ±.12 versus .89 ±.77 units/kg/d, P = .0001). Remission rates of hypertension and dyslipidemia were similar for T1D and T2D (66.7% versus 62.5%, P = .63 and 88.9% versus 75%, P = .23). CONCLUSIONS: Even if metabolic surgery has limited effect on glycemic control in T1D, it improves insulin sensitivity and other co-morbidities. It should be considered as a therapeutic option in selected obese patients with metabolic syndrome and high cardio-vascular risk.

Use of continuous glucose monitoring to estimate insulin requirements in patients with type 1 diabetes mellitus during a short course of prednisone.

BACKGROUND: Insulin requirements to maintain normoglycemia during glucocorticoid therapy and stress are often difficult to estimate. To simulate insulin resistance during stress, adults with type 1 diabetes mellitus (T1DM) were given a three-day course of prednisone. METHODS: Ten patients (7 women, 3 men) using continuous subcutaneous insulin infusion pumps wore the Medtronic Minimed CGMS (Northridge, CA) device. Mean (standard deviation) age was 43.1 (14.9) years, body mass index 23.9 (4.7) kg/m(2), hemoglobin A1c 6.8% (1.2%), and duration of diabetes 18.7 (10.8) years. Each patient wore the CGMS for one baseline day (day 1), followed by three days of self-administered prednisone (60 mg/dl; days 2-4), and one post-prednisone day (day 5). RESULTS: Analysis using Wilcoxon signed rank test (values are median [25th percentile, 75th percentile]) indicated a significant difference between day 1 and the mean of days on prednisone (days 2-4) for average glucose level (110.0 [81.0, 158.0] mg/dl vs 149.2 [137.7, 168.0] mg/dl; p = .022), area under the glucose curve and above the upper limit of 180 mg/dl per day (0.5 [0, 8.0] mg/dl.d vs 14.0 [7.7, 24.7] mg/dl.d; p = .002), and total daily insulin dose (TDI) , (0.5 [0.4, 0.6] U/kg.d vs 0.9 [0.8, 1.0] U/kg.d; p = .002). In addition, the TDI was significantly different for day 1 vs day 5 (0.5 [0.4, 0.6] U/kg.d vs 0.6 [0.5, 0.8] U/kg.d; p = .002). Basal rates and insulin boluses were increased by an average of 69% (range: 30-100%) six hours after the first prednisone dose and returned to baseline amounts on the evening of day 4. CONCLUSIONS: For adults with T1DM, insulin requirements during prednisone induced insulin resistance may need to be increased by 70% or more to normalize blood glucose levels.