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, 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.
We herein report a patient with acute onset type 1 diabetes mellitus that developed three months after delivering a child with depletion of insulin secretion just after the onset. This patient was a ...32-year-old woman who recognized excessive thirst, polydipsia, polyuria and digestive symptoms. She visited the emergency room in our hospital, and her laboratory findings showed that her blood glucose level was 664 mg/dL, HbA1c 9.7 %, urine ketone bodies (3+), venous blood gas pH 7.018, fasting-serum C peptide 0.41 ng/mL, and islet cell antibody (ICA) 20 JDF units. We diagnosed her with autoimmune acute-onset type 1 diabetes with diabetic ketoacidosis (DKA). Her HLA-typing was DRB1*04: 05-DQB1*04: 01, which indicates susceptibility to Japanese type 1 diabetes. Her insulin secretion further deteriorated and was almost completely lost just 10 days after the onset. We considered her beta cell destruction to have been accelerated after the onset of acute-onset type 1 diabetes (autoimmune).
The patient was a 58-year-old woman with type 2 diabetes and obesity medicated by an SGLT2 inhibitor and biguanide. She had no medical history of diabetic ketoacidosis. She visited our emergency room ...with upper abdominal pain, vomiting, and diarrhea for four days despite discontinuing all oral hypoglycemic agents. Emergency upper gastrointestinal endoscopy revealed acute duodenitis. Blood and urine tests revealed that her blood glucose level was 211 mg/dL, HbA1c 8.2 %, urine ketone bodies (3+), and venous blood gas pH 7.291, indicating euglycemic DKA during treatment with an SGLT2 inhibitor. As both islet-related and thyroid-related auto-antibodies were positive, she was finally diagnosed with SPIDDM with Graves' disease. In this case, euglycemic DKA seems to have been caused by four factors: insufficient carbohydrate intake due to acute duodenitis, potential insulin insufficiencies due to SPIDDM, accelerated fat catabolism due to hyperthyroidism, and oral intake of an SGLT2 inhibitor.
A 23-year-old man was admitted to our hospital with a medical history of body weight reduction and hyperglycemic symptoms. His laboratory findings showed that his blood glucose level was 496 mg/dL, ...HbA1c 15.8 %, urine ketone bodies (3+), venous blood pH 7.15, and BMI 29.0 kg/m2. He was diagnosed with diabetic ketoacidosis (DKA) in June X. He neither consumed a lot of soft drinks nor had any virus infections. Islet-related autoantibodies were all negative, but his endogenous insulin secretion was remarkably low, and his serum C peptide level was 0.37 ng/mL. Tentatively, we diagnosed him with type 1B diabetes. His endogenous insulin secretion recovered rapidly after five months with insulin therapy, which allowed him to avoid insulin treatment for the following 10 months. However, he was hospitalized again with a diagnosis of diabetic ketosis (DK) with body weight gain in September X+1. Based on his clinical course, he was diagnosed with ketosis-prone diabetes. The results of glucagon and arginine load tests revealed that his endogenous insulin secretion was severely depressed at the onset of DKA and DK but recovered clearly after six months with the increase in endogenous glucagon secretion.
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.
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.
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).
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.
Fulminant type 1 diabetes is characterized by almost complete β‐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)
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