*Małgorzata Godziejewska-Zawada, Katarzyna Szyfner
Rapid-onset type 1 diabetes mellitus in middle-aged and older persons
Szybko ujawniająca się cukrzyca typu 1 u osób starszych
Department of Endocrinology, Centre of Postgraduate Medical Education, Bielański Hospital, Warsaw
Head of Department: Professor Wojciech Zgliczyński, MD, PhD
Wstęp. U osób po 35. roku życia zazwyczaj rozpoznawana jest cukrzyca typu 2, dużo rzadziej cukrzyca typu LADA (ang. latent autoimmune diabetes in adults) – wolno (późno) ujawniająca się cukrzyca typu 1. W tej postaci cukrzycy, zgodnie z definicją, w początkowej fazie choroby przez 6 miesięcy lub dłużej można stosować leku doustne. Rzadko w grupie osób po 40. roku życia zdarza się piorunujący lub bardzo szybki początek cukrzycy typu 1, podobnie jak to często bywa u dzieci.
Cel pracy. Celem pracy była analiza przypadków szybko ujawniającej się cukrzycy typu 1, przyjmowanych do Kliniki w ciągu ostatnich 5 lat. Praca ma charakter opisowy.
Materiał i metody. W ocenie retrospektywnej odnaleziono 8 (osiem) przypadków szybko ujawniającej się cukrzycy typu 1 u osób po 40. roku życia, u których niezbędne było utrzymanie leczenia insuliną na zakończenie hospitalizacji lub niezbędne było wdrożenie insuliny do 2 miesięcy po zakończeniu hospitalizacji.
Nie znaleziono ewidentnych cech charakterystycznych, które mogłyby przepowiadać wczesną insulinozależność pacjentów, poza brakiem wyrównania przy próbie zmiany leczenia z insuliny na leki doustne.
Wnioski. W każdym przypadku chorego na cukrzycę powinniśmy myśleć o różnicowaniu choroby oraz zmieniać wstępnie przyjęte rozpoznanie, gdy przebieg choroby jest nietypowy. Do rozpoznania niezbędne jest wykonanie badań dodatkowych, głównie peptydu C, a w wybranych przypadkach przeciwciał anty-GAD. Niski poziom peptydu C potwierdza rozpoznanie cukrzycy typu 1 pod warunkiem wykonania badania po wstępnym wyrównaniu cukrzycy. Brak lub obecność chorób z autoagresji, zaburzeń lipidowych lub nadwagi nie są czynnikami różnicującymi cukrzycę typu 1 o szybkim początku u osób po 40 roku życia.
Introduction. Persons older than 35 years of age are usually diagnosed with type 2 diabetes mellitus and much less frequently with LADA (Latent Autoimmune Diabetes of Adults). According to the definition, initial stages of LADA can be treated with oral medications for 6 months or more. Very seldom, middle-aged or older patients (> 40 years of age) present with type 1 diabetes with characteristic abrupt or rapid onset, like in children or adolescents.
Aim. The aim of the study was to analyze cases of rapid-onset type 1 diabetes mellitus in patients admitted to the Endocrinology Unit within the past 5 years. The analysis was retrospective.
Material and methods. Retrospective analysis of cases of rapid-onset type 1 diabetes mellitus found in our Clinic in the past five years.
Results. We found eight cases of rapid-onset type 1 diabetes mellitus in patients older than 40 years of age in whom it was essential to continue insulin treatment after hospitalization or it was necessary to implement insulin within 2 months after hospitalization.
Conclusions. These cases show that there are no dogmas in diabetes. We should be watchful all the time and be ready to change the initial diagnosis if the course of the disease is atypical. Additional tests that are essential in establishing a diagnosis include C-peptide and, in some cases, anti-GAD autoantibody assays. A low level of C-peptide confirms a diagnosis of type 1 diabetes mellitus only when blood glucose is normalized after insulin therapy. The presented cases indicate that type 1 diabetes mellitus of a typical rapid course can be diagnosed after the age of 40 years and in the elderly and that, apart from insulin dependency, there are no evident features that distinguish type 1 diabetes, even with the rapid onset, from type 2 diabetes. This was a pilot study and that is why the study group was small. Collection of a greater number of data could possibly help find other typical features indicating rapid-onset type 1 diabetes mellitus in middle-aged and older patients.
Persons older than 35 years of age are usually diagnosed with type 2 diabetes mellitus and much less frequently with LADA (Latent Autoimmune Diabetes of Adults). According to the definition, initial stages of LADA can be treated with oral medications for 6 months or more. Very seldom, middle-aged or older patients (> 40 years of age) present with type 1 diabetes with characteristic abrupt or rapid onset, like in children. However, such cases do happen, and delayed diagnosis and improper therapy with oral medications in the early stage result in rapid beta cell exhaustion, C-peptide demise and very unstable disease course preventing effective therapy.
The aim of the study was to analyze cases of rapid-onset type 1 diabetes mellitus in patients admitted to the Endocrinology Unit within the past 5 years and to attempt to identify factors that can facilitate differential diagnosis.
MATERIAL AND METHODS
The evaluation involved patients admitted to the Endocrinology Unit with newly diagnosed diabetes within the past 5 years. The analysis included patients older than 40 years of age with type 1 diabetes who had to continue insulin therapy after hospitalization due to the impossibility to control diabetes with oral medications or had to start using insulin within 2 months post-hospitalization.
Eight persons met the criteria of rapid-onset type 1 diabetes mellitus. This group included three males and five females. Table 1 presents patient characteristics.
Tab. 1. Characteristics of patients with rapid-onset type 1 diabetes mellitus
|No||Initials||Sex||Age (years)||Weight (kg)||Height (m)||BMI (kg/m2)||HbA1c (%)||C-peptide (ng/ml)||Statin use||Arterial hypertension|
|average|| || ||58.62||69.46|| ||25.26||8.88||0.38||3/8||4/8|
*2 autoimmune diseases diagnosed after diabetes onset (hypothyroidism, vitamin B12 deficiency)
**anti-GAD antibodies > 2,000 IU/ml
***thyroid autoimmune disease diagnosed together with diabetes
The mean age at diagnosis of diabetes was 58.62 years. The oldest patient was 96 years old, and the youngest was 42.
Four patients (3 females and 1 male) had endocrine comorbidities (a disease of the thyroid gland), but they were diagnosed together with diabetes in only 1 case. In the remaining three patients, autoimmune conditions were identified within 1-5 years after the onset of diabetes. It was hypothyroidism in each case. Apart from hypothyroidism, 1 patient presented with vitamin B12 deficiency, and gastroscopy confirmed atrophic gastritis. There are no post-hospitalization data concerning the remaining patients.
The mean body mass index (BMI) amounted to 25.26 kg/m2. BMI was greater than 30 kg/m2 (obesity) in only 1 patient. Three patients needed statins to control blood lipid levels. All persons with lipid metabolism disorders had BMI over 25 kg/m2. The major irregularity in the lipid profile was increased LDL cholesterol level. Furthermore, 4 persons had arterial hypertension.
The typical features of patients with rapid-onset type 1 diabetes mellitus were as follows:
1. Significantly elevated blood glucose levels at admission (over 350 mg/dl) with signs of uncontrolled diabetes mellitus (increased thirst, polyuria, losing weight) and incommensurably only slightly raised HbA1c levels, which indicated a relatively recent onset of considerable hyperglycemia.
2. Very good and rapid reaction to insulin – control obtained within 1-3 days after insulin implementation.
3. An attempt to introduce oral medications ended with a failure – glucose concentration rose rapidly. The only exception was patient 2 who was discharged during an effective oral therapy, but glucose levels increased abruptly 5 weeks post-hospitalization (up to 350 mg/dl) and did not decrease in reaction to restrictive low-carbohydrate diet; the patient was re-admitted, treated with insulin, and had further tests conducted to differentiate the type of diabetes.
Rapid-onset type 1 diabetes mellitus in middle-aged and older persons could not be diagnosed on the basis of:
1. The presence of other autoaggressive conditions. An autoimmune disease was detected together with diabetes in only 1 case. In the remaining patients, autoimmune conditions were identified within 1-5 years after the onset of diabetes. There are no data concerning 2 patients who were not re-hospitalized.
2. The lack of lipid metabolism disorders or hypertension. Their presence did not exclude type 1 diabetes mellitus. The occurrence of lipid disorders and hypertension increases with age. That is why, their presence or absence in patients over 40 years of age does not determine the disease status.
3. Weight. Average BMI was higher than 25 kg/m2; one patient was obese. Healthy weight, particularly with BMI < 25 kg/m2, should prompt a differential diagnosis of diabetes, but research has shown that type 1 diabetes mellitus can also occur in overweight and obese individuals.
4. Age. The youngest patient that met the criteria was 42 years old, and the oldest – 95.
The most spectacular case of rapid-onset type 1 diabetes mellitus in individuals older than 40 years of age was a case of a 95-year-old patient admitted to Hospital due to freshly diagnosed diabetes with ketoacidosis and high glucose concentrations (glucose 1,211 mg/dl, with metabolic acidosis (pH 7.271, carbohydrates 16.8 mmol/l), hyperkalemia 5.7 mmol/l, corrected sodium 144 mmol/l, plasma osmolality 372 mOsm/kg H2O (normal range 280-300 mOsm/kg H2O)). Chest radiography revealed pneumonia. Additionally, the patient presented with hypertension, had had ischemic stroke 4 years before and had undergone right hip replacement surgery years before. Symptoms of hyperglycemia, in the form of weakness and urinary incontinence developed 4 days before hospitalization and, fortunately, were not ignored by the patient’s family. Despite high glucose levels and accompanying pneumonia, the patient’s condition was incommensurably good, and intravenous insulin (8 units per kg body weight per hour) led to a rapid normalization of glucose levels and enabled a change of treatment to 4 subcutaneous insulin injections. Initially, high glucose levels and acidosis were associated with newly diagnosed diabetes mellitus and pneumonia. It was assumed that the rapid improvement of the overall condition and quick normalization of blood glucose levels were caused by the simultaneous administration of insulin and antibiotics. Despite a very high glucose concentration at the beginning of inpatient treatment, glycated hemoglobin was relatively low – 8.0%. That is why, as pneumonia subsided, it was attempted to start oral therapy. However, each insulin discontinuation and an attempt to replace it with oral medications resulted in an abrupt increase in glucose levels and it was necessary to return to insulin therapy. In order to verify the type of diabetes, as glucose levels were regulated, blood was collected for C-peptide assay. It yielded the value of 0.12 ng/ml (normal range 1.1-4.4), which indicated type 1 diabetes and entailed the necessity of insulin therapy. Due to the clear clinical picture and an unambiguous C-peptide level that indicated insulin deficiency, anti-GAD antibody testing was deemed unnecessary in this and in the remaining cases. Although a positive result could undoubtedly confirm the autoimmune nature of diabetes in this 95-year-old patient, the negative result would not exclude such a diagnosis. The patient was discharged with insulin therapy of 4 injections.
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