Fulminant type 1 diabetes mellitus: a case report

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IOP Conference Series: Earth and Environmental Science

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To cite this article: E Yunir and Nenfiati 2018 IOP Conf. Ser.: Earth Environ. Sci. 125 012173

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Fulminant type 1 diabetes mellitus: a case report

E Yunir¹and Nenfiati^1*

1Division of Endocrinology and Metabolism,Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, CiptoMangunkusumo National General Hospital, Jakarta, Indonesia

*Corresponding author: [email protected]

Abstract. Type 1 diabetes mellitus is a metabolic disease caused by insulin deficiency that results from destruction of β-cells in the pancreas. Based on American Diabetes Association, there are two types of type 1 diabetes mellitus: type 1A (autoimmune) and 1B (idiopathic). In this case, we are presenting a new archetype of type 1 diabetes named fulminant type 1 diabetes mellitus. This disease results from quick destruction of β-cells byanautoimmune mechanism. The manifestation of this disease consists of unspecific flu-like symptoms, abdominal symptoms, to specific hyperglycemia symptoms such as fatigue, malaise, change in mental status that are attributable to high blood glucose and ketosis. Laboratory examination reveals high blood glucose, normal glycosylated hemoglobin, ketosis or ketoacidosis, potassium depletion and elevation of liver function tests. Treatment consists of intravenous infusion followed by insulin injection for blood glucose control, followed by treatment of metabolic derangements such as acid-base and electrolyte disorder.

1. Case presentation

A male, 27 years old, came with fatigue and dyspnea as a chief complaint that has been for one day.

The patient has complained to have a fever that suddenly spiked about four days ago, and has been given antibiotics in a clinic. About two days before fever, the patient was having an episode of fatigue, but no other complaints such as a cough, fever, and vomit. Aside from chief complaint, the patient was having urination more than usual, about ten times a day. Random blood glucose examination with blood glucose meter shows a level of 360 mg/dL, and 3 hours before admission, the patient had a series of vomit followed by lightheadedness and extreme fatigue. From physical examination, the patient was awoken, and having a normal body mass index with a weight of 67 kilograms and a height of 168 centimeters. Physical examination of eyes, neck, lungs, heart, abdomen are within normal range, but thestudy of extremities shows a minimal edema in the left lower extremity. Peripheral blood examination revealed elevated leukocyte count, metabolic acidosis with a pH level of 7,202 and declined C-peptide level. The patient was admitted to diabetic ketoacidosis and suspected type 1 diabetes mellitus, fulminant type. The patient was given glargine insulin at 21 units, and insulin aspart at 34 units. On follow-up at the hospital ward after ketoacidosis have been resolved (February 1^st, 2017), blood glucose was 131 mg/dL at night with 21 units of insulin glargine and 101 mg/dL at the following morning with 16 units of insulin aspart. On the next day (February 2^nd, 2017), blood glucose levels were 106 mg/dL at noon with 16 units of insulin aspart,an85 mg/dL at night with ten units of insulin glargine. At February 3^rd, 2017 blood glucose levels were 92 mg/dL at the morning without insulin and having an incidence of hypoglycemia after an injection of 16 units insulin aspartat noon (38 mg/dL).The midday and nighttime blood glucose were 62 and 207 with an injection of 16 units

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insulin aspart at noon and 21 units insulin glargine at night, respectively. On the third day (February 4^th, 2017), the patient was normoglycemic with a stable dose of 3 times, 12 units injection of insulin aspart and 21 units once daily injection of insulin glargine until discharge three days later.

2. Discussion

2.1. Definition

Type 1 diabetes mellitus is characterized by an absolute deficiency in insulin secretion due to thedestruction of β-cells in thepancreas. According to American Diabetes Association and the World Health Organization, type 1 diabetes is the autoimmune type (1A) and idiopathic type (1B). Type 1A diabetes was a result of thedestruction of β-cells by autoantibodies, while the exact cause of type 1B diabetes is not fully known. Nowadays, there is a new category of type 1 diabetes called fulminant type 1 diabetes because the disease progress rapidly and leaving a unique characteristic when blood examination is performed.[1] Fulminant type 1 diabetes is defined by a sudden onset of ketosis or ketoacidosis, no or decreased C-peptide secretion, and high level of plasma glucose accompanied with normal glycosylated hemoglobin level. These extremely abrupt characteristics happen within only a few days and rarely exceeds one week. Fulminant type 1 diabetes differs from type 1A diabetes in which it will take years to develop autoantibodies to the clinical onset of ketosis or ketoacidosis. From epidemiologic perspectives in Asia based on acase report, there are 20% of fulminant type 1 diabetes case amongst all of type 1 diabetes cases in Japan. In another research, an estimation of 5.000-7000 patients is having a fulminant type 1 diabetes mellitus in Japan, or about 19.4% of all type 1 diabetes mellitus, and 0.61% of all patients receiving insulin therapies. There were also evidences that pregnancy associated with fulminant type 1 diabetes mellitus. In Korea, there are about 7.1% of people with fulminant type 1 diabetes mellitus within all of thenewly diagnosed type 1 diabetes mellitus. In China, there are 53 reported cases from 24 hospitals, and 34,6% of cases associated with pregnancy.[1-4]

2.2. Pathophysiology

Pathogenesis of fulminant type 1 diabetes is around class II HLA susceptibility; even the exact mechanism is not known. There is a possibility that HLA molecule could interact with viruses and can cause fulminant type 1 diabetes. Among thevast array of viruses, enteroviruses,and herpes viruses seem to be frequently associated with fulminant diabetes, particularly human herpesvirus 6 (HHV-6), which can cause hypersensitivity syndrome and reactivation of HHV-6. It is also worth noting that IgA antibodies were significantly higher in patients with fulminant type 1A diabetes than in type 1A diabetes. Although viruses were said to be preceding this type of diabetes, immune reactions might also play a role in thedevelopment of the disease, mainly by the T-lymphocytes response to GAD.

Insulitis is observed in pancreas from deceased patients, but this finding does not warrant autoimmunity mediated that β-cells destruction. This type of autoimmunity can also affect theexocrine pancreas, as shown in theanimal model.[5]

2.3. Signs and symptoms

In fulminant type 1 diabetes, there are other symptoms which consist of thirst (93.7%), flu-like symptoms (71.7%), and abdominal symptoms (72.5%). Flu-like symptoms can manifest as fever (60%), sore throat (25.2%), and cough (12%), while the most common abdominal symptoms are nausea or vomiting (65.4%), upper abdominal pain (39.2%) and lower abdominal pain (11%). In some cases, the patients can experience a loss of consciousness ranging from drowsiness to coma, which is in about half of fulminant type 1 diabetes patients. Along with predictable symptoms, there has been a report of acardiopulmonary arrest in one patient with fulminant type 1 diabetes with a complaint of fatigue, and the patient was thought to have anunderlying cardiac disorder such as T-wave inversion or atrial fibrillation.[5]

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2.4. Laboratory findings

From laboratory findings, we could identify high blood plasma glucose with normal glycosylated hemoglobin because of the abrupt nature of the disease that caused by thequick destruction of β-cells, while glycosylated hemoglobin reflects an average in blood glucose over the period of 1-2 months.

Plasma ketone bodies are elevated (ketosis), and arterial blood gas had a pH below 7.35 in more than 90% patients with fulminant type 1 diabetes and ketoacidosis is usually seen at theonset of fulminant type 1 diabetes. Serum levels of exocrine pancreas enzymes such as amylase, elastase-1 and lipase are also elevated at the onset of fulminant type 1 diabetes. This elevation does not warrant pancreatitis, but in some cases, there will be a swelling of the pancreas that can be from CT-scan or abdominal echograms. Sodium and chloride levels are markedly lower,and potassium is higher. These electrolyte abnormalities are more severe than type 1A diabetes. The increment in AST and ALT levels can also be after starting insulin for treating patients, but the exact phenomenon is yet to be known.[1,2]These patients have negative islet cell antibodies (ICA), insulin autoantibody (IAA), anti-glutamic acid decarboxylase antibody (GADAb), and anti-insulinoma-associated antigen twoantibodies (IA-2Ab). In fulminant type 1 diabetes, the β-cells is only about 14,5% after 1-9 months of overt diabetes. Along with β-cells damage, there is damage in the α-cells portion about 33,1%, but this phenomenon was not with autoimmune type 1 diabetic patients.[1,5]

2.5. Treatment

Treatment in fulminant type 1 diabetes does not differ from autoimmune type 1 diabetes, which consists of intravenous infusion and regular insulin regiment. Once the acute phase of ketoacidosis can be managed, the patients can revert to daily or twice-daily injections with either very long-acting insulin together with twice or thrice daily doses at each meal with rapid-acting or regular insulin.[5]

3. Conclusion

Fulminant type 1 diabetes mellitus is a disease that centered around β-cells destruction by an autoimmunity process. It can be precipitated by viral infection, especially HHV-6 and enteroviruses.

Clinical characteristics of fulminant type 1 diabetes consist of high blood glucose, normal glycosylated hemoglobin level, thepresence of ketosis or ketoacidosis, abnormalities of potassium and ALT/AST level, and negative autoantibody examination such as ICA, IAA, GADAb, IA-2Ab.

Treatment in fulminant type 1 diabetes does not differ from another type 1 diabetes, which consists of glycemic control via the use of insulin (intravenous for initial therapy for diabetic ketoacidosis), intravenous infusion of isotonic saline, and corrections of acid-base and potassium abnormalities if the levels fall within therapeutic initiation range.

References

[1] Imagawa A and Hanafusa T 2006 Pathogenesis of fulminant type 1 diabetes Rev. Diabetic Stud.

3 169-77

[2] Park Y, Wintergerst K A and Zhou Z 2017 Immunological aspects of fulminant type 1 diabetes in Chinese Diabetes Metab. Res. Rev.

[3] Shibasaki S and Imagawa A 2012 Advanced in experimental medicine and biology Springer 20- 3

[4] Luo S, Zhang Z, Yang L, Yan X, Wang Z and Zheng C 2011 Fulminant type 1 diabetes: a collaborative clinical cases investigation in China Acta. Diabetol. 50 53-9

[5] Hanafusa T and Imagawa A 2007 Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners Nat. Clin. Pract. 3 36-45