A Case of Type 2 Diabetes Mellitus with Lung Cancer Suffered from Euglycemic Diabetic Ketosis Accompanied by Adrenal Insufficiency after Immune Checkpoint Inhibitors.

A 74-year-old patient with type 2 diabetes mellitus received basal-bolus insulin, insulin secretagogues, and sodium glucose transporter 2 (SGLT2) inhibitors. After immune checkpoint inhibitor treatment for lung cancer, he suffered from depressed consciousness with a urinary ketone body (3+). When all hypoglycemic treatments were discontinued, his serum blood glucose remained at 121 mg/dL. He was diagnosed with euglycemic diabetic ketosis. Endocrine loading tests revealed isolated adrenocorticotropic hormone (ACTH) deficiency as an immune-related adverse event. It was suggested that euglycemic diabetic ketosis was induced by the self-suspension of insulin and insulin secretagogues, adrenal insufficiency, SGLT2 inhibitors, and carbohydrate intake shortage.

Fulminant type 1 diabetes mellitus: a new class of type 1 diabetes.

Fulminant Type 1 diabetes is a novel subtype of Type 1 diabetes. In this disease, extremely rapid and almost complete beta-cell destruction occurs, resulting in nearly no residual insulin secretion even just after the onset. The number of patients presumably amounts to 5,000-7,000 in Japan. The involvement of both, genetic background and viral infection, has been suggested in the pathogenesis of this disease. Diagnostic criteria were established by a committee of the Japan Diabetes Society in 2004. Intensive insulin therapy is a standard therapy. We should pay special attention to early development of microvascular complications in fulminant Type 1 diabetes.

Expression of toll-like receptors in the pancreas of recent-onset fulminant type 1 diabetes.

Fulminant type 1 diabetes, established in 2000, is defined as a novel subtype of diabetes mellitus that results from remarkably acute and almost complete destruction of pancreatic beta cells at the disease onset. In this study, we aimed to clarify the pathogenesis of fulminant type 1 diabetes with special reference to insulitis and viral infection. We examined pancreatic autopsy samples from three patients who had died soon after the onset of disease and analyzed these by immunohistochemistry and in situ-hybridization. The results were that both beta and alpha cell areas were significantly decreased in comparison with those of normal controls. Mean beta cell area of the patients just after the onset was only 0.00256 % while that of normal control was 1.745 %. Macrophages and T cells-but no natural killer cells-had infiltrated the islets and the exocrine pancreas. Although both of them had massively infiltrated, macrophages dominated islet infiltration and were detected in 92.6 % of the patients' islets. Toll-like receptor (TLR) 3, a sensor of viral components, was detected in 84.7+/- 7.0 % of T cells and 62.7+/- 32.3 % of macrophages (mean+/- SD) in all three patients. TLR7 and TLR9 were also detected in the pancreas of all three patients. Enterovirus RNA was detected in beta-cell positive islets in one of the three patients by in situ-hybridization. In conclusion, our results suggest that macrophage-dominated insulitis rather than T cell autoimmunity contributes to beta cell destruction in fulminant type 1 diabetes.

Glycated albumin to glycated hemoglobin ratio is a sensitive indicator of blood glucose variability in patients with fulminant type 1 diabetes.

BACKGROUND: Since serum albumin is glycosylated more rapidly than hemoglobin, it is possible that the glycated albumin (GA) to HbA1c ratio (GA: HbA1c ratio) is potentially a more sensitive indicator of blood glucose excursion than HbA1c. The aim of the present study was to assess the clinical usefulness of GA: HbA1c ratio as a marker of daily glucose excursions in patients with type 1 diabetes according to the subtypes; acute onset type 1A, fulminant and slowly progressive type 1 diabetes. METHODS: Fifty-six outpatients with type 1 diabetes [16 fulminant, 20 acute-onset type 1A and 20 slowly progressive (SPIDDM)] were recruited consecutively. Each patient performed self-monitoring of blood glucose at seven points a day. The associations among the daily profile of glucose and GA, HbA1c, GA: HbA1c ratio were examined across and within the subtypes of type 1 diabetes. RESULTS: GA and GA: HbA1c ratio were each independently correlated with mean amplitude of glucose excursion (MAGE) in patients with type 1 diabetes (F=27.53, p<0.001 and F=13.02, p<0.001, respectively). GA: HbA1c ratio was significantly higher in fulminant type 1 diabetic patients than in SPIDDM patients (3.5 ± 0.2 vs. 3.2 ± 0.5, p=0.015) and it was independently associated with MAGE within fulminant type 1 diabetes (F=21.2, p<0.001). CONCLUSION: In conclusion, the present study demonstrated that GA: HbA1c ratio could be a better marker for glycemic variability than HbA1c in type 1 diabetes, especially in fulminant type 1 diabetes.

Endogenous insulin secretion even at a very low level contributes to the stability of blood glucose control in fulminant type 1 diabetes.

Fulminant type 1 diabetes is characterized by almost complete ß-cell destruction, resulting in scarce insulin secretion. In the present study, we aimed to clarify clinical features related to serum C-peptide levels measured by a high sensitivity method, chemiluminescent enzyme immunoassay, in 12 patients with fulminant type 1 diabetes. Serum C-peptide was detected (0.007-0.10 nmol/L) in four patients and was not detected in eight patients. A negative correlation was observed between serum C-peptide levels and daily dosages of insulin (P < 0.01). The patients with detectable C-peptide showed a significantly lower M-value than those without (P = 0.01). In conclusion, our present results suggest that even very low levels of endogenous insulin secreting capacity can improve daily dosages of insulin and stabilize blood glucose levels. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.0059.x, 2010).