New-onset Type 1 Diabetes Mellitus Research Articles

The Impact of COVID-19 Pandemic Lockdown on the Incidence of New-Onset Type 1 Diabetes and Ketoacidosis Among Saudi Children.

BackgroundOverburdened healthcare systems during the coronavirus disease (COVID-19) pandemic led to suboptimal chronic disease management, including that of pediatric type 1 diabetes mellitus (T1DM). The pandemic also caused delayed detection of new-onset diabetes in children; this increased the risk and severity of diabetic ketoacidosis (DKA). We therefore investigated the frequency of new-onset pediatric T1DM and DKA in Saudi Arabia during the COVID-19 pandemic and compared it to the same period in 2019.MethodsWe conducted a multicenter retrospective cohort study, including patients aged 1–14 years admitted with new-onset T1DM or DKA during the COVID-19 pandemic (March–June 2020) and the same period in 2019. We assessed factors including age, sex, anthropometric measures, nationality, duration of diabetes, diabetes management, HbA1c levels, glycemic control, cause of admission, blood gas levels, etiology of DKA, DKA complications, length of hospital stay, and COVID-19 test status.ResultDuring the lockdown, 106 children, compared with 154 in 2019, were admitted to 6 pediatric diabetes centers. Among the admissions, DKA was higher in 2020 than in 2019 (83% vs. 73%; P=0.05; risk ratio=1.15; 95% confidence interval, 1.04–1.26), after adjusting for age and sex. DKA frequency among new-onset T1DM and HbA1c levels at diagnosis were higher in 2020 than in 2019 (26% vs. 13.4% [P=<0.001] and 12.1 ± 0.2 vs. 10.8 ± 0.25 [P<0.001], respectively). Females and older patients had a higher risk of DKA.ConclusionThe lockdown implemented in Saudi Arabia has significantly impacted children with T1DM and led to an increased DKA frequency, including children with new-onset T1DM, potentially owing to delayed presentation.

Abnormal Functional Connectivity Density in New-Onset Type 1 Diabetes Mellitus Children: A Resting-State Functional Magnetic Resonance Imaging Study.

Type 1 diabetes mellitus (T1DM) causes cognitive changes in children, which may be due to deficits in brain functions. It is unclear whether T1DM children will have brain functional changes during the initial stage of the disease. We aimed to investigate the changes in the functional brain network topology in children with new-onset T1DM. In this study, 35 new-onset T1DM children and 33 age-, sex-matched healthy controls underwent resting-state fMRI. The whole brain functional connectivity density (FCD) analysis and seed-based functional connectivity (FC) analysis were performed to investigate the changes in functional brain networks in new-onset T1DM children when compared with the controls. Pearson correlational analysis was used to explore the correlation between FCD value of differential brain areas and clinical variables in T1DM children. Compared with the controls, children with new-onset T1DM exhibited significantly decreased FCDs of the right inferior temporal gyrus (ITG) and the right posterior cingulate cortex (PCC). In the subsequent FC analysis, decreased FC was found between right PCC and right cuneus and increased FC was found between right ITG and left orbital part of inferior frontal gyrus in children with new-onset T1DM compared to the controls. The FCD values of right ITG and PCC did not correlate with HbA1c, blood glucose level before imaging, and full-scale intelligence quotient (IQ) in T1DM children. These results revealed that T1DM affect the functional activity of the immature brain at the initial stage. These findings also indicate a decrease in regional brain function and abnormalities in temporal-frontal and limbic-occipital circuitry in children with new-onset T1DM, and highlight the effects of T1DM on children's brain networks involved in visual process and memory, which may contribute to the cognition impairments observed in children with T1DM.

Visoka prevalencija dijabetesne ketoacidoze kod mladih sa novootkrivenim tipom 1 djabetesa melitusa u Beogradu - desetogodišnje iskustvo tercijernog centra

Introduction/Aim: Diabetic ketoacidosis (DKA) is one of the most important causes of acute mortality in youth with type 1 diabetes mellitus (T1DM). Recently published data suggested worryingly high frequency of DKA at the onset of T1DM in Belgrade youth. The goal of this study was to assess the frequency of DKA at the onset of T1DM and the associated risk factors in Belgrade youth during the previous 10 years at a tertiary centre. Methods: Data were collected retrospectively from the medical records of all children with new-onset T1DM admitted to our centre during the study period between 1st January 2007 and 1st January 2017. Results: During the study period, a total of 501 subjects (233 girls and 268 boys) were diagnosed with new-onset T1DM, with a mean age of 9.55 ± 4.26 years, and mean pH at the time of diagnosis of 7.28 ± 0.14 (6.78-7.51). Girls with T1DM were younger compared to boys (9.05 ± 4.04 years vs. 9.98 ± 4.41 years, respectively, p 11 years (35%), although this difference was not statistically significant. Conclusion: There is an alarmingly high rate of DKA at the onset of T1DM in Belgrade youth with no significant differences between different age groups. These findings emphasize the need for intensive public health preventive actions aimed at early diagnosis of T1DM in all age groups.

Changes in platelet morphology indices in relation to duration of disease and glycemic control in children with type 1 diabetes mellitus

BackgroundThere is limited data on platelet alterations in children with type 1 diabetes mellitus (T1DM). We planned to study the effect of glycemic control and duration of T1DM on platelet morphology in children with T1DM. MethodsWe conducted an observational study on 260 children; 130 with T1DM (cases) and 130 healthy controls, in a tertiary care pediatric hospital. Platelet indices including Platelet count (PLT), Mean Platelet Volume (MPV), Platelet Distribution Width (PDW), Platelet-Large cell ratio (P-LCR), Plateletcrit (PCT) were measured, and their means were compared between cases and controls and various subgroups among the cases. ResultsThe MPV, PDW and P-LCR were significantly higher (p < 0.05) in cases when compared to controls and in children with suboptimal glycemic control compared to optimal control. PLT was considerably lower in cases compared to controls. In children with new-onset T1DM, only PDW was significantly raised when compared to controls. MPV and P-LCR had a significant positive correlation with duration of T1DM. ConclusionsChildren with T1DM have altered morphological parameter(s) which progress over time. Poor glycemic control is a significant risk factor for abnormal platelet indices.

Dipeptidyl peptidase-4 inhibitors (DPP-4i) combined with vitamin D3: An exploration to treat new-onset type 1 diabetes mellitus and latent autoimmune diabetes in adults in the future

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by destruction of pancreatic beta cells through cell injury caused primarily by cytotoxic T lymphocytes (CD8+). The pathophysiological basis of T1DM seems to be an imbalance between a reduced function of T regulatory lymphocytes and an increased inflammatory activity of Th17 lymphocytes caused by increased production of inflammatory cytokines, as IL-1β, IL-6, IL-17 and IFN-gamma due to environmental factors and genetic predisposition. The preservation of the reserve of beta cells in new-onset T1DM and latent autoimmune diabetes in adults (LADA) by immunomodulation in addition to the incretin effect seems to be possible with an association of DPP-4 inhibitors and vitamin D3. In this review, we discuss the effects of both drugs on the immune system and on beta cell function and their eventual additive effects in preserving the residual function of beta cells in new-onset T1DM and LADA.

A 20-year prospective follow-up study to evaluate the development of retinopathy and nephropathy after the onset of type 1 diabetes mellitus: Contribution of glycemic control and metabolic memory

To assess the time course of changes in the level of glycated hemoglobin (HbA1c) for 20 years after the onset of type 1 diabetes mellitus (T1DM) and to compare its correlation with the development of microvascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN). A total of 187 children with new-onset T1DM were registered in Moscow in 1994. During the 20-year follow-up study, these patients underwent regular check-ups at the Endocrinology Research Center, Ministry of Health of the Russian Federation, which included assessment of physical data, HbA1c 2-4 times a year, biochemical blood and albuminuria tests (once per year), and ophthalmologic examination (twice a year). A total of 155 people fully completed the 20-years follow-up study. During the 20-year follow-up period after the onset of T1DM, 86 of the 155 patients developed microvascular complications: DR and DN in 86 (55.5%) and 24 (15.5%) cases, respectively; while DR concurrent with DN were noted in 20 patients. By the time of their last visit, 69 (44.5%) patients had no evidence suggesting the presence of microvascular complications. The level of HbA1c at the onset of the disease in patients who later developed the complications was higher than in those without complications (10.2±0.6 and 8.5±0.2%, respectively (p = 0.003). The statistically significant differences in HbA1c levels between the groups persisted during subsequent 15 years of follow-up, averaging 9.2±1.5, 9.7±0.9, and 8.1±0.7% after 5, 10, and 15 years, respectively, in the complication group and 7.1±0.3, 8.1±0.4, and 7.2±0.2% in the non-complication group (p < 0.01). Over the last 5 years of the follow-up, the mean HbA1c level between the groups was not significantly different, which at the end of the 20-year follow-up period was 7.8±0.3 and 7.4±0.6%, respectively (p > 0.05). The mean duration of T1DM, in which DR developed, was 9.6±6.2, 11.0±2.0, and 13.6±4.6 years for the non-proliferative, pre-proliferative, and proliferative stages, respectively. That of T1DM, in which DN developed, was 11.8±0.6 years for microalbuminuria and 16.1±1.3 years for macroalbuminuria. The 20-year clinical follow-up of patients who had fallen ill with T1DM in childhood showed that diabetic microangiopathies developed with the long-term preservation of poor blood glucose control (BGC) starting at the onset of the disease. At the same time, the complications progressed to more severe stages, despite a clear trend toward better BGC. This may be suggestive of the negative metabolic memory phenomenon, which necessitates stable BGC, starting at the onset of the disease, for the prevention of microvascular complications.

Four-year clinical remission of type 1 diabetes mellitus in two patients treated with sitagliptin and vitamin D3.

SummaryType 1 diabetes mellitus (T1DM) is a chronic disease characterized by autoimmune destruction of pancreatic beta cells and inadequate insulin production. Remission criteria in T1DM take into account serum levels of C-peptide and glycosylated hemoglobin, as well as the dose of insulin administered to the patient. However, remission of T1DM lasting longer than 1 year is rare. We describe here the cases of two young women who presented with positive glutamic acid decarboxylase (GAD) antibody and classic clinical manifestations of T1DM. Both patients had a prior history of Hashimoto’s thyroiditis. They were initially treated with a basal-bolus regimen of insulin (glargine and lispro/glulisine). Once their blood glucose levels were controlled, they were started on oral sitagliptin 100 mg and vitamin D3 5000 IU daily. After this therapy, both patients achieved clinical diabetes remission for 4 years, along with a decrease in anti-GAD antibody levels. These benefits were probably associated with immunological effects of these medications. Inhibition of dipeptidyl peptidase 4 (DPP-4) in animal models deregulates Th1 immune response, increases secretion of Th2 cytokines, activates CD4+CD25+FoxP3+ regulatory T-cells and prevents IL-17 production. Vitamin D3 also activates CD4+CD25+FoxP3+ regulatory T-cells, and these medications combined can improve the immune response in patients with new-onset T1DM and probably promote sustained clinical remission.Learning points:The use of sitagliptin and vitamin D3 in patients with new-onset type 1 diabetes mellitus (T1DM) may help decrease the daily insulin requirement by delaying beta cell loss and improving endogenous insulin production.The use of sitagliptin and vitamin D3 in new-onset T1DM could help regulate the imbalance between Th17 and Treg cells.Age 14 years or above, absence of ketoacidosis and positive C-peptide levels in patients with T1DM are good criteria to predict prolonged T1DM remission.The determination of anti-GAD antibodies and C-peptide levels could be helpful in the follow-up of patients in use of sitagliptin and vitamin D3, which could be associated with prolonged T1DM clinical remission.

CDE Perspectives of Providing New-Onset Type 1 Diabetes Education Using Formal Vignettes and Simulation.

Purpose The purpose of this article is to describe the 4 Parent Education Through Simulation-Diabetes (PETS-D) nurse certified diabetes educators' (CDEs) perspectives of teaching parents of children with newly diagnosed type 1 diabetes mellitus (T1DM) early diabetes management skills using formal vignettes and a human patient simulator/human patient simulation (HPS) to augment/enhance the teaching-learning process. Methods A qualitative descriptive approach was used. Four CDEs were interviewed by phone about their teaching experiences. Meticulous notes were taken. Data were analyzed using qualitative content analysis. Results The vignettes (and use of HPS) provided structure, especially for parents who were struggling to learn. Certified diabetes educators described a short learning curve to master the use of the HPS manikin. Human patient simulation-enhanced education was described as helpful for teaching multiple caregivers about diabetes. Certified diabetes educators also described factors that affect parent learning, mechanical issues with the HPS, and additional space requirements for HPS-enhanced education. Conclusion Vignettes and HPS-enhanced education can successfully be used to educate parents of children with new-onset T1DM and were preferred by the CDEs when compared with previous teaching strategies. The results of this study support the use of both vignette-based and HPS-enhanced education when a child is newly diagnosed with T1DM. Further studies need to be done to see if these effects persist with different populations, during different stages of the disease, and for individuals with other chronic illnesses.

Predictive factors for prolonged remission after autologous hematopoietic stem cell transplantation in young patients with type 1 diabetes mellitus

Background aimsAutologous hematopoietic stem cell transplantation (auto-HSCT) followed by immunoablation is a promising therapy for type 1 diabetes mellitus (T1DM) treatment due to the immunosuppression and immunomodulation mechanisms. Indeed, a considerable number of patients have been able to discontinue insulin use with this treatment. However, nonresponse and relapse occur after auto-HSCT. It is important to select the patients who can potentially benefit from this treatment, but the factors that might influence the therapeutic outcome are unclear. The objective of this study was to explore the predictors for prolonged remission after auto-HSCT therapy. MethodsThe data for this study were extracted from an open-label prospective study, which was performed to treat new-onset T1DM patients with auto-HSCT. The 128 patients were categorized into insulin-free (IF) or insulin-dependent (ID) groups according to their response to treatment during the follow-up. We compared the baseline data of the two groups and explored possible prognostic factors and their odd ratios (ORs) with univariate analysis and multivariate logistic regression. Receiver operating characteristic curves (ROC) were performed to test the model discrimination function. ResultsDuring a follow-up of 28.5 ± 8.3 months, 71 of 128 patients in the IF group discontinued insulin use, whereas 57 of 128 patients in the ID group did not decrease their insulin dose or resumed insulin treatment after a transient remission. Multivariate logistic regression analysis demonstrated that prolonged remission was positively correlated with fasting C-peptide level (OR = 2.60, 95% confidence interval [CI]: 1.16–5.85) but negatively correlated with onset age (OR = 0.36, 95% CI: 0.14–0.88) and tumor necrosis factor-α levels (OR = 0.32, 95% CI: 0.14–0.73). ROC analysis confirmed the combined predictive function of these three variables (AUC = 0.739, 95% CI: 0.655–0.824). ConclusionsAge and fasting C-peptide and tumor necrosis factor-α levels were identified as possible predictors for prolonged remission following auto-HSCT therapy.

15-year incidence of diabetic ketoacidosis at onset of type 1 diabetes in children from a regional setting (Auckland, New Zealand).

We assessed the incidence of diabetic ketoacidosis (DKA) in children aged <15 years with newly diagnosed type 1 diabetes mellitus (T1DM) in the Auckland Region (New Zealand) in 1999–2013, in a retrospective review of a complete regional cohort. DKA and its severity were classified according to ISPAD 2014 guidelines. Of 730 children presenting with new-onset T1DM over the 15-year time period, 195 cases had DKA of any severity (27%). There was no change in the incidence of DKA or the proportion of children with severe DKA at presentation. The incidence of DKA among children aged <2.0 years (n = 40) was 53% compared to 25% for those aged 2–14 years (n = 690; p = 0.005). In children aged 2–14 years, increasing age at diagnosis was associated with greater likelihood of DKA at presentation (p = 0.025), with the odds of DKA increasing 1.06 times with each year increase in age. Non-Europeans were more likely to present in DKA than New Zealand Europeans (OR 1.52; p = 0.048). Despite a consistent secular trend of increasing incidence of T1DM, there was no reduction in the incidence of DKA in new-onset T1DM in the Auckland Region over time. Thus, it is important to explore ways to reduce DKA risk.

Validation d’un algorithme de détection de l’augmentation de la dose pour la consommation de médicaments psychotropes

There is limited data on platelet alterations in children with type 1 diabetes mellitus (T1DM). We planned to study the effect of glycemic control and duration of T1DM on platelet morphology in children with T1DM.We conducted an observational study on 260 children; 130 with T1DM (cases) and 130 healthy controls, in a tertiary care pediatric hospital. Platelet indices including Platelet count (PLT), Mean Platelet Volume (MPV), Platelet Distribution Width (PDW), Platelet-Large cell ratio (P-LCR), Plateletcrit (PCT) were measured, and their means were compared between cases and controls and various subgroups among the cases.The MPV, PDW and P-LCR were significantly higher (p < 0.05) in cases when compared to controls and in children with suboptimal glycemic control compared to optimal control. PLT was considerably lower in cases compared to controls. In children with new-onset T1DM, only PDW was significantly raised when compared to controls. MPV and P-LCR had a significant positive correlation with duration of T1DM.Children with T1DM have altered morphological parameter(s) which progress over time. Poor glycemic control is a significant risk factor for abnormal platelet indices.

Type 1 Diabetes Mellitus

1. Justin M. Gregory, MD* 2. Daniel J. Moore, MD, PhD† 3. Jill H. Simmons, MD‡ 1. *Pediatric Endocrinology Clinical Fellow, Ian Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, Nashville, TN. 2. †Assistant Professor of Pediatrics, Assistant Professor of Pathology, Microbiology, and Immunology, Ian Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, Nashville, TN. 3. ‡Assistant Professor of Pediatrics, Ian Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, Nashville, TN. * ADA: : American Diabetes Association DKA: : diabetic ketoacidosis HbA1c: : glycosylated hemoglobin I:C ratio: : insulin-to-carbohydrate ratio IV: : intravenous TDD: : total daily dose T1DM: : type 1 diabetes mellitus T2DM: : type 2 diabetes mellitus 1. All children with type 1 diabetes mellitus (T1DM) should have their blood sugar managed with basal-bolus insulin treatment by either multiple daily injections or an insulin pump. 2. All children with T1DM should have access to a pediatric endocrinologist with a diabetes management team with resources to support patients and families. 3. All children with T1DM should be monitored for symptoms and/or screened for commonly associated conditions such as thyroid and celiac disease. After completing this article, readers should be able to: 1. Recognize the presenting signs and symptoms of type 1 diabetes mellitus (T1DM). 2. Know the key principles of effective diabetes self-management and the diabetes care team’s role in facilitating effective self-management. 3. Know the acute and chronic complications of (T1DM). 4. Identify how different categories of insulin analogues are used in daily insulin regimens. True, it is a fight, but there is pleasure in the struggle. Victory comes to the courageous; and without courage and common sense, success awaits no one. I look upon the diabetic as charioteer and his chariot as drawn by three steeds named Diet, Insulin, and Exercise. It takes skill to drive one horse, intelligence to manage a team of two, but a man must be a very good teamster who can get all three to pull together.EP Joslin, 1933 Type 1 diabetes mellitus (T1DM) is a disorder of glucose homeostasis characterized by autoimmune destruction of the insulin-producing pancreatic β-cell that progressively leads to insulin deficiency and resultant hyperglycemia. If left untreated, insulin deficiency leads to progressive metabolic derangement, with worsening hyperglycemia, ketoacidosis, starvation, and death. In …

Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus

Effect of Cholecalciferol as Adjunctive Therapy With Insulin on Protective Immunologic Profile and Decline of Residual β-Cell Function in New-Onset Type 1 Diabetes Mellitus

To evaluate the effect of vitamin D3 on cytokine levels, regulatory T cells, and residual β-cell function decline when cholecalciferol (vitamin D3 administered therapeutically) is given as adjunctive therapy with insulin in new-onset type 1 diabetes mellitus (T1DM). An 18-month (March 10, 2006, to October 28, 2010) randomized, double-blind, placebo-controlled trial was conducted at the Diabetes Center of São Paulo Federal University, São Paulo, Brazil. Thirty-eight patients with new-onset T1DM with fasting serum C-peptide levels greater than or equal to 0.6 ng/mL were randomly assigned to receive daily oral therapy of cholecalciferol, 2000 IU, or placebo. Levels of proinflammatory and anti-inflammatory cytokines, chemokines, regulatory T cells, hemoglobin A1c, and C-peptide; body mass index; and insulin daily dose. Mean (SD) chemokine ligand 2 (monocyte chemoattractant protein 1) levels were significantly higher (184.6 [101.1] vs 121.4 [55.8] pg/mL) at 12 months, as well as the increase in regulatory T-cell percentage (4.55% [1.5%] vs 3.34% [1.8%]) with cholecalciferol vs placebo. The cumulative incidence of progression to undetectable (≤0.1 ng/mL) fasting C-peptide reached 18.7% in the cholecalciferol group and 62.5% in the placebo group; stimulated C-peptide reached 6.2% in the cholecalciferol group and 37.5% in the placebo group at 18 months. Body mass index, hemoglobin A1c level, and insulin requirements were similar between the 2 groups. Cholecalciferol used as adjunctive therapy with insulin is safe and associated with a protective immunologic effect and slow decline of residual β-cell function in patients with new-onset T1DM. Cholecalciferol may be an interesting adjuvant in T1DM prevention trials.

The association between ketoacidosis and 25(OH)-vitamin D3levels at presentation in children with type 1 diabetes mellitus

There is considerable evidence supporting the role of vitamin D deficiency in the pathogenesis of type 1 diabetes mellitus (T1DM). Vitamin D deficiency is also associated with impairment of insulin synthesis and secretion. There have been no formal studies looking at the relationship between 25(OH)-vitamin D(3) and the severity of diabetic ketoacidosis (DKA) in children at presentation with T1DM. To determine the relationship between measured 25(OH)-vitamin D(3) levels and the degree of acidosis in children at diagnosis with T1DM. Children presenting with new-onset T1DM at a tertiary children's hospital. 25(OH)-vitamin D(3) and bicarbonate levels were measured in children at presentation with newly diagnosed T1DM. Those with suboptimal 25(OH)-vitamin D(3) levels (<50 nmol/L) had repeat measurements performed without interim vitamin D supplementation. Fourteen of the 64 children had low 25(OH)-vitamin D(3) levels at presentation, and 12 of these had low bicarbonate levels (<18 mmol/L) (p = 0.001). Bicarbonate explained 20% of the variation in vitamin D level at presentation (partial r(2) = 0.20, p < 0.001) and ethnic background a further 10% (partial r(2) = 0.10, p = 0.002). The levels of 25(OH)-vitamin D(3) increased in 10 of the 11 children with resolution of the acidosis. Acid-base status should be considered when interpreting 25(OH)-vitamin D(3) levels in patients with recently diagnosed T1DM. Acidosis may alter vitamin D metabolism, or alternatively, low vitamin D may contribute to a child's risk of presenting with DKA.

Exendin-4 Improves Reversal of Diabetes in NOD Mice Treated with Anti-CD3 Monoclonal Antibody by Enhancing Recovery of β-Cells

Immune modulators can arrest loss of insulin secretion in type 1 diabetes mellitus (T1DM), but they have not caused permanent disease remission or restored normal insulin secretion. We tested whether exendin-4, a glucagon-like peptide-1 receptor agonist, would enhance remission of T1DM in NOD mice treated with anti-CD3 monoclonal antibody (mAb) and studied the effects of exendin-4 treatment on cellular and metabolic responses of beta-cells. Diabetic NOD mice treated with anti-CD3 mAb and exendin-4 had a higher rate of remission (44%) than mice treated with anti-CD3 mAb alone (37%) or exendin-4 (0%) or insulin or IgG alone (0%) (P < 0.01). The effect of exendin-4 on reversal of diabetes after anti-CD3 mAb was greatest in mice with a glucose level of less than 350 mg/dl at diagnosis (63 vs. 39%, P < 0.05). Exendin-4 did not affect beta-cell area, replication, or apoptosis or reduce the frequency of diabetogenic or regulatory T cells or modulate the antigenicity of islet cells. Reversal of T1DM with anti-CD3 mAb was associated with recovery of insulin in glucose transporter-2(+)/insulin(-) islet cells that were identified at diagnosis. Glucose tolerance and insulin responses improved in mice treated with combination therapy, and exendin-4 increased insulin content and insulin release from beta-cells. We conclude that treatment with glucagon-like peptide-1 receptor agonist enhances remission of T1DM in NOD mice treated with anti-CD3 mAb by enhancing the recovery of the residual islets. This combinatorial approach may be useful in treatment of patients with new-onset T1DM.