BACKGROUND: Mesenchymal stem cell infusion and vitamin D supplementation may have immunomodulatory actions that could prolong the preservation of residual insulin secretion in patients with type 1 diabetes (T1D). Intervention with these agents after onset of T1D could favor the development of a remission phase, with potential clinical impact. We aimed to compare the presence of clinical remission (CR), glycemic control and daily insulin requirement at 6, 12, 18, 24 and 36 months after the diagnosis of T1D using IDAA1c in patients who received therapy with adipose tissue-derived mesenchymal stem cell (ASC) infusion and vitamin D supplementation and a control group.
METHODS: This retrospective cohort study analyzed data from the medical records of patients with T1D diagnosed between 15 and 40 years. Partial CR was defined as an IDAA1c index < 9. Patients in the intervention group received an infusion of adipose tissued-derived mesenchymal stem cells (ASCs) within 3 months after diagnosis and supplementation with 2000 IU of cholecalciferol for 1 year, started on the day following the infusion. Partial CR was also determined using the ISPAD criteria, to assess its agreement with IDAA1c.
RESULTS: A total of 28 patients were evaluated: 7 in the intervention group (group 1) and 21 in the control group (group 2). All patients in group 1 evolved with partial CR while only 46.7% of patients in group 2 had this outcome. Group 1 had a higher frequency of CR when evaluated with IDAA1c and ISPAD criteria. The mean duration of CR varied between the two criteria. Although HbA1c was similar between groups during follow-up, group 1 had a lower total daily insulin requirement (p < 0.005) at all time points. At 36 months, group 1 used 49% of the total daily insulin dose used by group 2 with similar glycemic control.
CONCLUSIONS: The intervention with infusion of ASC + vitamin D supplementation was associated with partial CR at 6 months. Although there were no differences in CR established by the IDAA1c and ISPAD criteria after three years of follow-up, patients who underwent intervention had nearly the half insulin requirement of controls with conventional treatment, with similar glycemic control.
BACKGROUND: 37001514.0.0000.5257.

UNASSIGNED: An essential process affecting the course of type 1 diabetes (DM1) is the appearance and duration of clinical remission. One of the most important factors promoting the occurrence of remission is physical activity, due to increased activity of antioxidants, reduces insulin resistance and improves glucose transport. Maximal oxygen capacity (VO2max) is an objective measure of the body\'s aerobic capacity. To assess VO2max, oxygen uptake should be measured directly during the exercise test. The aim of the study was to evaluate the physical capacity in adults with DM1 and its relationship with the occurrence of partial clinical remission (pCR) during 2 years follow-up.
UNASSIGNED: The pCR was assessed by the following mathematical formula: A1c (%) + [4 × insulin dose (U/kg/d)]. The result ⩽9 indicates pCR. VO2max was assessed between 6th and 24th month of diabetes duration using an ergospirometer (COSMED K5 System), during an exercise test carried out on a cycloergometer (RAMP incremental exercise test).
UNASSIGNED: The study group consisted of 32 adults with DM1. People with pCR were proved to have higher VO2max level [36.0 (33.0-41.5) vs 30.9 (26.5-34.4) ml/min/kg, P = .009. Univariate and multivariate regression confirmed a significant association between VO2max and presence of pCR [AOR 1.26 (1.05-1.52), P = .015]. Duration of remission was longer among group with higher VO2max results [15 (9-24) vs 9 (0-12) months, P = .043]. The positive relationship was observed between diabetes duration and VO2max (rs = 0.484, P = .005). Multivariate linear regression confirms a significant association between remission duration and VO2max (ml/min/kg) (β = 0.595, P = .002).
UNASSIGNED: The higher VO2max, the better chance of partial clinical remission at 2 years of DM1 and longer duration of remission.
Better cardiorespiratory fitness increases the chance of partial clinical remission and prolongs remission duration in people with newly diagnosed type 1 diabetes. Introduction An essential process affecting the course of type 1 diabetes (DM1) is the appearance and duration of clinical remission. One of the most important factors promoting the occurrence of remission is physical activity, due to increased activity of antioxidants, reduces insulin resistance and improves glucose transport. Maximal oxygen capacity (VO2max) is an objective measure of the body’s aerobic capacity. To assess VO2max, oxygen uptake should be measured directly during the exercise test. The aim of the study was to evaluate the physical capacity in adults with DM1 and its relationship with the occurrence of partial clinical remission (pCR) during 2 years follow-up. Methods The pCR was assessed by the following mathematical formula: A1c (%) + [4 × insulin dose (U/kg/d)]. The result ⩽9 indicates pCR. VO2max was assessed between 6th and 24th month of diabetes duration using an ergospirometer (COSMED K5 System), during an exercise test carried out on a cycloergometer (RAMP incremental exercise test). Results The study group consisted of 32 adults with DM1. People with pCR were proved to have higher VO2max level [36.0 (33.0-41.5) vs 30.9 (26.5-34.4) ml/min/kg, P = .009. Univariate and multivariate regression confirmed a significant association between VO2max and presence of pCR [AOR 1.26 (1.05-1.52), P = .015]. Duration of remission was longer among group with higher VO2max results [15 (9-24) vs 9 (0-12) months, P = .043]. The positive relationship was observed between diabetes duration and VO2max (rs = 0.484, P = .005). Multivariate linear regression confirms a significant association between remission duration and VO2max (ml/min/kg) (β = 0.595, P = .002). Conclusions The higher VO2max, the better chance of partial clinical remission at 2 years of DM1 and longer duration of remission.

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The knowledge of the pathogenesis of type 1 diabetes mellitus (T1DM) continues to rapidly evolve. The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status. Not all individuals of T1DM progress in that specific sequence. We hereby present a case of T1DM with a classical third phase (honeymoon phase) and discuss the intricacies of this interesting phase along with a possible future promise of \"cure\" with the use of immunotherapies. We now know that the course of T1DM may not be in only one direction towards further progression; rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed. The third phase popularly called the \"honeymoon phase\", is of special interest as this phase is complex in its pathogenesis. The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive \"diabetes reversal\" in T1DM. Identifying this phase is therefore the key, with a lot of varying criteria having been proposed.

暂无摘要。

In type 1 diabetes (T1D), pancreatic beta cells are destroyed by the immune system, causing chronic hyperglycemia and micro and macrovascular complications. However, some people experience a \'honeymoon\' phase (or partial remission) after being diagnosed with type 1 diabetes. During this phase, a substantial amount of insulin is still produced by the pancreas, helping to reduce blood sugar levels and the requirement for external insulin. The clinical significance of this phase lies in the potential for pharmacological and non-pharmacological interventions during this time frame to either slow down or arrest beta-cell destruction. Clearly, we need to continue researching novel therapies like immunomodulatory agents, but we also need to look at potentially effective therapies with acceptable side effects that can serve as a complement to the medicines currently being studied. Physical activity and exercise, regardless of its type, is one of the factors its impact on the control of diabetes is being investigated and promising results have been achieved. Although there are still limited reports in this regard, there is some evidence to suggest that regular physical exercise could prolong the honeymoon period in both adults and children. In this review, having described the immune base of type 1 diabetes, we outline the benefits of exercise on the general health of individuals with T1D. Moreover, we centered on the honeymoon and current evidence suggesting the effects of physical activity and exercise on this phase duration.

Herein, we describe an unusually prolonged duration (31 months) of the clinical remission phase in a 22-year-old Italian man with new-onset type 1 diabetes. Shortly after the disease diagnosis, the patient was treated with calcifediol (also known as 25-hydroxyvitamin D3 or calcidiol), coupled with low-dose basal insulin, to correct hypovitaminosis D and to exploit the anti-inflammatory and immunomodulatory properties of vitamin D. During the follow-up period, the patient retained a substantial residual β-cell function and remained within the clinical remission phase, as evidenced by an insulin dose-adjusted glycated hemoglobin value <9. At 24 months, we detected a peculiar immunoregulatory profile of peripheral blood cells, which may explain the prolonged duration of the clinical remission sustained by calcifediol as add-on treatment to insulin.
We describe the case of a 22-year-old Italian man who was treated with a form of vitamin D called calcifediol shortly after the diagnosis of type 1 diabetes, which is an autoimmune condition leading to insulin deficiency and to the lifelong need for insulin therapy. Calcifediol was administered, coupled with low-dose insulin, to correct vitamin D insufficiency and to exploit the anti-inflammatory properties of vitamin D. During the follow-up period (31 months), the patient unexpectedly remained on once-daily insulin injection therapy and maintained near-normal blood glucose levels. These findings suggest that calcifediol administration may represent a valid add-on treatment to insulin, with the aim of reducing daily insulin requirements and improving glucose control in patients with recent-onset type 1 diabetes.

UNASSIGNED: The occurrence of partial remission (honeymoon phase) in type 1 diabetes (T1D) has been associated with a reduced risk of chronic microvascular complications of diabetes. We have published case reports showing that a combination therapy with the DPP-4 inhibitor sitagliptin plus vitamin D3 (VIDPP-4i) can prolong the honeymoon phase in patients with new-onset T1D. In the present case-control study, we investigated the frequency of occurrence of clinical remission (CR) in patients with new-onset T1D after VIDPP-4i treatment.
UNASSIGNED: In this case-control study, we collected data spanning 10 years from medical records of 46 patients (23 females) recently diagnosed with T1D. Overall, 27 participants with CR (insulin dose-adjusted glycated hemoglobin [IDAA1c] ≤ 9) at 12 or 24 months composed the case group, and 19 participants without CR served as the control group. Chi-square with Yates correction was used to analyze the association between VIDPP-4i use and CR, and odds ratio (OR) was used to determine the chance of CR due to VIDPP-4i treatment exposure.
UNASSIGNED: In all, 37 patients (80.4%) experienced CR at some time over 24 months. The mean CR duration was 13.15 ± 9.91 months. Treatment with VIDPP-4i was significantly associated with CR. At 24 months, the OR of CR after VIDPP-4i exposure was 9.0 (95% confidence interval [CI] 2.21-30.18, p = 0.0036). Additionally, 9 (33.6%) and 4 (14.8%) patients in the VIDPP-4i group experienced insulin-free CR at 12 and 24 months, respectively.
UNASSIGNED: Therapy with VIDPP-4i was associated with a higher frequency and duration of the honeymoon phase. Randomized controlled trials are needed to confirm these findings.

A \"honeymoon\" phase is a transient period of type 1 diabetes (T1D) remission, characterized by a significant reduction in insulin requirements and good glycemic control due to a temporary restoration of pancreatic β-cell function. This phenomenon occurs in about 60% of adults with this disease, is usually partial, and lasts for up to 1 year. We present a case of a 6-year complete remission of T1D in a 33-year-old man, the longest remission ever described in the literature to our knowledge. He was referred for presenting a 6-month history of polydipsia, polyuria, and weight loss of 5 kg. Laboratory studies confirmed the diagnosis of T1D (fasting blood glucose of 270 mg/dL; HbA1c of 10.6%, and positive antiglutamic acid decarboxylase), and the patient started intensive insulin therapy. After 3 months, a complete remission of the disease was assumed, he suspended insulin administration and since then, he has been under treatment with sitagliptin 100 mg daily, a low-carbohydrate diet, and regular aerobic physical activity. This work aims to highlight the potential role of these factors in delaying disease progression and preserving pancreatic β-cells when introduced at the time of presentation. More robust, prospective, and randomized studies will be needed to confirm its protective effect on the natural course of the disease and support its indication in adults with newly diagnosed T1D.

The publication of our recent randomized controlled trial (RCT) showing that vitamin D could protect the β-cells during the honeymoon phase of type 1 diabetes (T1D) has led to calls for guidance for vitamin D supplementation during the critical phase of type 1 diabetes. Prolonging the partial clinical remission (PR) phase of TID improves glycemic control and reduces long-term complications of T1D. This RCT randomized 36 children and adolescents to either receive vitamin D2 (ergocalciferol, given as 50,000 international units per week for 2 months and then every other week for 10 months) or a placebo. The results showed that vitamin D significantly decreased the temporal rise in both hemoglobin A1c at a mean rate of changes of 0.14% every 3 months versus 0.46% every 3 months for the placebo group (p=0.044); and in the functional marker of PR, the insulin-dose adjusted A1c at a mean rate of change of 0.30% every 3 months versus 0.77% every 3 months for the placebo group, (p=0.015). We recommend a baseline estimation of 25(OH)D concentration at the time of diagnosis of T1D, and to begin vitamin D supplementation if serum 25(OH)D concentration is <30 ng/mL, to maintain serum 25(OH)D concentrations between 30-60 ng/mL. If serum 25(OH)D concentration is >30 ng/mL, monitor vitamin D status with serial 25(OH)D estimations; and initiate vitamin D supplementation if serum 25(OH)D concentrations drop to <30 ng/mL. Continue vitamin D supplementation for at least one year to ensure optimal benefit from vitamin D supplementation during the partial clinical remission phase of type 1 diabetes.