Lucien Marchand

Screening of ZnT8 autoantibodies in the diagnosis of autoimmune diabetes in a large French cohort

AIM OF THE STUDY Evaluate the added value of screening anti-ZnT8 antibodies (ZnT8A) in addition to the classical anti-GAD (GADA) and anti-IA-2 (IA-2A) antibodies for the diagnosis of type-1 diabetes (T1D) within a large cohort of both children and adults. MATERIALS AND METHODS Retrospective 2-year study including 516 patients (215 children, 301 adults) who had blood tests at diabetes onset and/or for diabetes classification. ZnT8A, GADA, and IA-2A were analyzed in all samples. RESULTS Among those individuals included, 142 (28%) were ZnT8A-positive. A total of 228/516 suffered from T1D, of whom 110 (48%) were ZnT8A-positive and 166 (73%) GADA and/or IA-2A positive. When adding ZnT8A to GADA/IA-2A, 184 (81%) patients were positive for ≥1 Ab. Regarding the 122 patients at T1D onset, 75 (61%) were positive for ZnT8A and the proportion of patients with T1D with ≥1 Ab reached 89%. The highest prevalence of ZnT8A was observed in children aged 6-10years. Fourteen of the 124 patients positive for ZnT8A with a known clinical diagnosis suffered from a disease other than T1D. CONCLUSIONS ZnT8A should be included in routine evaluation at diabetes onset and is a valuable biological marker to classify newly-diagnosed diabetics. The predictive value in our high-risk subjects has to be confirmed.

Anti–Programmed Death 1 (PD-1) Antibodies and the Pancreas: A Diabetic Storm Ahead?

Nivolumab, a human IgG4 programmed death 1 (PD-1) immune checkpoint–inhibitor antibody, disrupts PD-1–mediated signaling and restores antitumor immunity (1). Many recent studies have emphasized the importance of anti–PD-1 antibodies to improve survival outcomes among patients with advanced melanoma or lung cancer. Several endocrinological side effects have been reported and a few patients developed insulin-requiring diabetes (2). Some …

Multiple autoantibodies at onset do not accurately predict long-term pancreatic beta-cell fate in a 13-year-old obese child with immediate insulin-requiring diabetes

iabetes (T2D) [1]. However, a significant number of patients ith long-standing disease remain insulin microsecretors [2] and ave a significant number of insulin-containing islets [3]. The onditions associated with persisting beta cells despite a hostile nvironment are largely unknown. Here we present an unusual bservation of a 13-year-old insulin-dependent obese child that llustrates the complexity of diabetes classification, and the grey one between T1D and T2D.

Comment on Jackson et al. Insulitis in Autoantibody-Positive Pancreatic Donor With History of Gestational Diabetes Mellitus. Diabetes Care 2017;40:723–725

We read with interest the article by Jackson et al. (1) illustrating mild insulitis in the pancreas of a 28-year-old lean Hispanic female with recent gestational diabetes mellitus (GDM) who died of anoxic encephalopathy of unknown etiology 32 days after cesarean delivery. She was positive for GAD antibody (GADA) and islet cell antibody, while autoantibodies against insulin, IA-2, and zinc transporter 8 (ZnT8A) were negative. This observation, as well as earlier studies (2), raises a possible role of …

Very high titres of ZnT8 autoantibodies at type 1 diabetes onset and presence of autoantibodies related to other autoimmune disorders

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since vendredi 13 avril 2018

Long-Term Effects of Continuous Subcutaneous Insulin Infusion on Glucose Control and Microvascular Complications in Patients With Type 1 Diabetes:

Background: We investigated the long-term effects of continuous subcutaneous insulin infusion (CSII) on glucose control and microvascular complications in patients with type 1 diabetes (T1D). Methods: A total of 157 patients (59 M/98 W; age 39.1 ± 14.8 years) with T1D who switched from multiple daily injections to CSII and used CSII for at least one year were included. HbA1c levels and status of microvascular complications before and while under CSII were analyzed, retrospectively. Results: The follow-up period was 4.0 ± 1.5 years. HbA1c significantly decreased from 8.4 ± 1.3 to 7.7 ± 1.3% (68 ± 14 to 61 ± 14 mmol/mol) after 1-year CSII and remained lower than pre-CSII levels during four years. Patients with pre-CSII HbA1c >8.0% (64 mmol/mol) showed significant improvement of HbA1c for four years, while those with pre-CSII HbA1c <8.0% showed no significant change. The prevalence of retinopathy, albuminuria, and chronic kidney disease (CKD) were respectively 39%, 12%, and 9% at CSII initiation. During follow-up, the incidence of retinopathy, albuminuria, and CKD were 3.6, 2.5 and 1.4/100 patient-years. Onset or progression of retinopathy occurred in 16 (27.1%) patients with diabetes duration >15 years, and in three (4.3%) patients with diabetes duration <15 years (P < .01). Conclusion: CSII was effective in improving HbA1c for up to four years, specifically in patients with HbA1c >8% (64 mmol/mol) prior to CSII. Incidence and progression rates of retinopathy and albuminuria were low, particularly in patients with a diabetes duration <15 years at CSII initiation. These results argue for not delaying a proposal of CSII initiation in T1D with sustained HbA1c >8% (64 mmol/mol).

Improvement of Glucose Control and Reduction of Hypoglycemia Following Intravenous Immune Globulins in a Child With Type 1 Diabetes and High Levels of Insulin Antibodies

Anti-insulin antibodies (AIA) usually have no impact on glucose control in type 1 diabetes (1). However, high titers of AIA with low/medium affinity for insulin may form unstable immune complexes resulting in high glucose variability (2). Corticosteroids, plasmapheresis, mycophenolate mofetil (3), and rituximab (4) have been tried to solve this issue. We report a case of interest owing to significant improvement following intravenous infusions of human immune globulins (IVIg). A lean 8-year-old Caucasian boy was diagnosed with type 1 diabetes 3 years before being referred to our clinic. No autoantibodies against islet antigens, GAD, IA2, or zinc transporter 8 were detected, but testing for AIA was not done at onset and no GCK , HNF1A , HNF4A , HNF1B , ABCC8 , KCNJ11, or INS gene mutations were found. Under multiple daily insulin injections or an insulin pump, high glucose variability included uncontrollable postmeal hyperglycemia and recurrent severe hypoglycemia in fasting/nighttime periods. Despite a sensor-augmented …