isotretinoin and Diabetes-Mellitus--Type-2

Latent autoimmune diabetes in adults (LADA) is the most common form of adult-onset autoimmune diabetes. Isotretinoin is a very effective treatment for severe acne. There are various reports on the effect of isotretinoin on autoimmunity. We present a case of LADA, probably related to isotretinoin treatment. To the best of our knowledge, this case was the second case of LADA that occurred after isotretinoin treatment. Here we discuss a hypothesis on the pathophysiology of how isotretinoin can induce LADA.. A 55-year-old female was diagnosed with type 2 diabetes mellitus (T2DM) one month after the end of a nine-month isotretinoin treatment period. At the time of diagnosis, the patient's fasting blood glucose level was 257 mg/dL and HbA1c level was 10.3%. Then, she was followed-up for T2DM for two years. Since the patient did not comply with classical T2DM characteristics and C-peptide level was 0.4 ng/ml (0.78-5.18), autoantibody test was performed. The patient was found positive for anti-glutamic acid decarboxylase antibody (>2000 IU/mL). Her oral antidiabetic drug treatment was discontinued and insulin degludec and insulin aspart therapy was started. Three months after this adjustment, HbA1c level decreased to 7.2%. Except 25-hydroxycholecalciferol which was low (10.9 ng/mL), all other laboratory parameters were within normal range.. Isotretinoin is known to have some immunomodulating effects. There are some case reports on the relationship between isotretinoin and autoimmune diseases. The negative immune environment that developed due to the long-standing moderate-severe VitD deficiency may have taken a turn toward autoimmunity upon isotretinoin treatment. This hypothesis on how isotretinoin can cause autoimmune diabetes needs to be validated.

Topics: Adult; Autoantibodies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Humans; Isotretinoin; Latent Autoimmune Diabetes in Adults; Middle Aged

Topics: Adrenal Cortex Hormones; Adult; Aged; Anti-Bacterial Agents; Breast Diseases; Colchicine; Diabetes Mellitus, Type 2; Drug Resistance; Female; Granuloma; Humans; Hypertension; Immunosuppressive Agents; Isotretinoin; Male; Pyoderma Gangrenosum; Remission Induction; Tacrolimus

We have previously reported that obesity-induced diabetes developed in high-fat diet (HFD)-fed BDF1 mice. This is caused by insufficient insulin response to an excess glucose load. In this study, we have shown that the enhanced expression of retinaldehyde dehydrogenase 3 (Raldh3) causes functional disorders of pancreatic islets in diabetic mouse models. In the pancreatic islets of HFD-induced diabetic BDF1 mice and spontaneously diabetic C57BL/KsJ(db/db) mice, gene expression analysis with oligonucleotide microarray revealed a significant increase in Raldh3 expression. Exposure to a culture medium containing a higher glucose concentration (25 mM) significantly increased Raldh3 expression in murine MIN6 and alphaTC1 clone 9 cells, which derived from the α and β-cells of pancreatic islets, respectively. Overexpression of Raldh3 reduced the insulin secretion in MIN6 cells, and surprisingly, increased the glucagon secretion in alphaTC1 clone 9 cells. Furthermore, the knockdown of Raldh3 expression with siRNA decreased the glucagon secretion in alphaTC1 clone 9 cells. Raldh3 catalyzes the conversion of 13-cis retinal to 13-cis retinoic acid and we revealed that 13-cis retinoic acid significantly reduces cell viability in MIN6 and alphaTC1 clone 9 cells, but not in cells of H4IIEC3, 3T3-L1, and COS-1 cell lines. These findings suggest that an increasing expression of Raldh3 deregulates the balanced mechanisms of insulin and glucagon secretion in the pancreatic islets and may induce β-cell dysfunction leading to the development of type 2 diabetes.

Topics: 3T3-L1 Cells; Animals; Chlorocebus aethiops; COS Cells; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Glucagon; Insulin; Insulin Secretion; Insulin-Secreting Cells; Islets of Langerhans; Isotretinoin; Mice; Mice, Inbred C57BL; Retinal Dehydrogenase

Topics: Arm; Diabetes Mellitus, Type 2; Granuloma Annulare; Humans; Isotretinoin; Leg; Male; Middle Aged