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    Home > Active Ingredient News > Endocrine System > Started with DKA but HbA1c is normal?

    Started with DKA but HbA1c is normal?

    • Last Update: 2021-04-14
    • Source: Internet
    • Author: User
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    Introduction: Although "fulminant type 1 diabetes" is relatively rare, it is often aggressive.

    How should this special subtype of diabetes be diagnosed and treated? Director Zhang Qianjin from the Endocrinology Department of Shuyang Hospital Affiliated to Xuzhou Medical University took the case as a guide and brought a lot of dry goods to everyone.

    Case sharing General situation: male, 27 years old, married, worker's chief complaint: repeated nausea and vomiting for 5 days.
    Current medical history: patient had nausea and repeated vomiting after "cold" 5 days ago.
    Stomach contents, accompanied by dry mouth, uncomfortable stool, and abdominal distension , Abdominal pain, considered "intestinal obstruction" for diagnosis and treatment in a Beijing hospital, checked RPG28mmol/l↑, and was recommended to be refused hospitalization.
    I took the train home 2 days ago.
    The symptoms of discomfort persisted and worsened, sometimes accompanied by deep and rapid breathing.
    I checked in 1 day ago.
    In a county hospital, check urine glucose+4↑, urine ketone body+3↑, RPG28.
    13mmol/l↑, arterial blood PH7.
    12↓, creatinine 234umol/L↑, CK766u/L↑, blood potassium 6.
    6mmol/L↑, diagnosis "DKA" was given treatments such as fluid rehydration and intravenous infusion of insulin, but the effect was poor.
    Today, "DM: DKA" is planned to be admitted to our department in the emergency department of our hospital.

    No fever, cough, sputum, chest pain, no diarrhea, unconsciousness, convulsions, no obvious polyuria, dry mouth, polydipsia and weight loss 5 days ago, poor appetite and sleep, stool unresolved for 5 days, recent months There was no significant change in weight.

    Past history: have a history of "chronic gastroenteritis", the specific circumstances are unknown, deny the history of "hypertension, hyperlipidemia, heart disease, stroke", deny the history of "thyroid, parathyroid, adrenal gland disease, celiac disease", deny hearing And abnormal vision.

    Family history: parents, brothers and children are healthy, deny family history of diabetes, deny other family history of genetic diseases.

    Physical examination: BP128/70mmHg, height 170cm, weight 65kg, BMI 22.
    5kg/㎡, withered, dehydrated appearance, deep breathing, pushed into the ward, no anemia appearance, black acanthosis (-), small thyroid gland, both lungs Coarse breath sounds, heart rate 110 beats/min, regular rhythm, flat and soft abdomen, mild tenderness around the umbilical cord, no muscle tension and rebound pain, untouched liver and spleen ribs, weakened bowel sounds, and no edema in both lower limbs.

    Outer hospital auxiliary examination ➤Blood routine: WBC16.
    97*109/l↑, N86.
    2%↑➤Urine routine: KET+3↑, GLU+4↑➤Blood biochemistry: RPG28.
    13mmol/l↑, Cr234umol/l↑, CK766u/l↑, K6.
    6mmol/l↑➤Arterial blood gas: PH7.
    12↓➤Infectious diseases: two and a half pairs of hepatitis B, hepatitis C antibody, syphilis antibody, HIV are all negative ➤ECG: atrial tachycardia➤CT of chest and abdomen: Gas in the intestinal cavity, no obvious abnormalities in both lungs, liver, gallbladder, spleen and pancreas.
    Diabetes to be diagnosed in the hospital.
    Diabetic ketoacidosis is hospitalized after oxygen inhalation, monitoring, active fluid rehydration, continuous insulin pumping, correction of electrolyte disorders, stomach protection, Prevention of infection and other treatments.

    The laboratory test results are shown in the table below.

    Figure 1-3 Plain CT scan of the upper abdomen + enhanced CT plain scan of the upper abdomen + enhanced: there is no abnormality in the pancreas.
    Why is HbA1c normal? What type of diabetes? Diagnosis: fulminant type 1 diabetes mellitus (FT1DM): DKA treatment plan: Novo Rui + Laitshi late follow-up: 1.
    HbA1c changes 2.
    Glucose tolerance combined with insulin and C peptide release test (13 after discharge) Month) Islet β-cell function damage is the core link in the occurrence of diabetes.
    All types of diabetes are based on different speeds and degrees of damage to islet β-cell function.
    If the speed and degree of islet β-cell function damage are classified, diabetes can be divided into Four categories: 1.
    Hyperacute diabetes—namely fulminant type 1 diabetes.
    The functional damage of pancreatic β-cells is calculated in days.
    The glucose metabolism may be completely normal one week ago and severe DKA will occur after one week, which damages pancreatic β-cells at a rapid rate.
    The degree is thorough, and the power is like a "cannon.
    "
    2.
    Acute Diabetes——Classic Type 1 Diabetes.
    The destruction strength should not be underestimated.
    The speed of pancreatic β cell function damage is calculated in months, which is like a "machine gun". 3.
    Subacute diabetes-that is, latent autoimmune diabetes in adults (LADA), the damage to pancreatic β-cell function is between the classic type 1 diabetes and type 2 diabetes, the speed is calculated in years, and the power is like a "rifle.
    "
    4.
    Chronic Diabetes—Classic Type 2 Diabetes, relatively speaking, is the mildest degree of injury.
    The speed is calculated in decades, and the power is like a "pistol.
    "
    Let's take a look at the power of the fighting disease in diabetes-fulminant type 1 diabetes! Fulminant Type 1 Diabetes 1.
    Definition Fulminant type 1 diabetes mellitus (FT1DM) was first reported by Imagawa in 2000.
    It refers to the rapid onset of the disease and the massive destruction of pancreatic β-cells in a short period of time, leading to severe hyperglycemia and DKA.
    A disease with metabolic disorders and no evidence of autoimmune reactions.

    FT1DM is a new subtype of type 1 diabetes, which occurs mostly in Asian countries, with the highest incidence in Japan, followed by South Korea and China, and rarely reported in European and American populations.

    The disease usually starts with ketosis or ketoacidosis, which is manifested as sudden onset, severe metabolic disorder, significant increase in blood sugar and normal or mild increase in glycosylated hemoglobin (HbA1c), which may be combined with rhabdomyolysis, acute renal failure, Severe complications such as cardiac arrest, cerebral edema, and multiple organ failure, if not diagnosed and rescued in time, often lead to death in a short period of time.

    In addition, due to the almost complete and irreversible damage of islet function, patients need long-term insulin replacement therapy, blood sugar fluctuates, and the risk of hypoglycemia increases significantly.

    Therefore, as an acute and critical illness in endocrine and metabolic diseases, FT1DM should arouse great attention.

    2.
    Epidemiology 1.
    Mostly sporadic; 2.
    The incidence is related to race, yellow people are larger than white people, so far there is no related report of black people onset; 3.
    The average age of onset is 39.
    1 years old, with 20 years old The above are many, and the age of onset of women is mostly younger than that of men; 4.
    There is no significant difference in the incidence of men and women, and the prevalence of men increases with age; 5.
    The incidence is related to pregnancy. 3.
    Etiology and pathogenesis The course of classic type 1A diabetes can be roughly divided into 6 stages of development: 1.
    Genetic susceptibility; 2.
    Environmental trigger; 3.
    Autoimmune activation; 4.
    Persistent metabolic abnormality; 5.
    Obvious Diabetes symptoms; 6.
    Insulin dependence.

    At present, it is believed that the main feature of FT1DM is the hyperacute and complete irreversible destruction of pancreatic β-cells, which generally rarely exceeds 1 week.
    Therefore, the natural course of FT1DM is significantly different from the natural course of classic type 1A diabetes.

    However, the etiology and pathogenesis of FT1DM are not yet fully understood, and it is believed that it may be related to factors such as genetics, environment (viral infection), autoimmunity and pregnancy.

    1.
    Genetic susceptibility (slidable) Studies have shown that HLA-Ⅱ gene polymorphism is related to the occurrence of FT1DM.

    HLA DR4-DQ4 is related to the onset of FT1DM patients in Japan, among which DRB1*0405-DQB1*0401, DQA1*0303-DQB1*0401 and DQA1*0302-DQB1*0303 appear more frequently.

    In addition, among Japanese patients, the susceptibility gene of GAD-Ab negative people is HLA DRB1*0405-DQB1*0401, and HLA DRB1*0901-DQB1*0303 genotype is more common in GAD-Ab positive and pregnancy-related FT1DM patients .

    For the Chinese population, HLA DQA1*0102-DQB1*0601 may be the susceptibility gene for FT1DM.

    The South Korean research results show that HLA-DRB1*0405-DQB1*0401 is significantly related to the onset of FT1DM.

    2.
    Virus infection Most FT1DM patients have a history of pre-infection within 2 weeks before onset, suggesting that viral infection may be related to the onset of disease.

    Existing reports suggest that common viruses are herpes simplex virus (HSV), human herpes virus 6 (HHV6), cytomegalovirus (CMV), Coxsackie virus, etc.
    ; suspicious viruses include mumps virus, parainfluenza virus, hepatitis A virus Wait. 3.
    Autoimmunity At the beginning of the discovery of FT1DM, since 11 patients with pancreatic islet autoantibodies were all negative, Imagawa et al.
    believed that it had nothing to do with autoimmunity and distinguished it from type 1A diabetes.

    However, follow-up studies found that some patients with GAD-Ab positive or with Graves’ disease or Hashimoto’s thyroiditis have lymphocyte infiltration in the pancreatic islet tissue, suggesting that immune factors are involved in the occurrence of FT1DM.

    Recent studies have found that the Toll-like receptor 9/interferon regulatory factor 7 (TLR9/IRF7) pathway is mainly involved in the pathogenesis of FT1DM through cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and forkhead transcription factor 3 (Foxp3) .

    4.
    Existing case reports in pregnancy show that pregnant women are a high-risk group for this disease.
    Almost all type 1 diabetes onset during pregnancy belongs to FT1DM, and it mostly occurs in the third trimester and within 2 weeks after delivery.

    At the same time, there are also reports of cases of FT1DM after 10 days of artificial abortion.

    The specific mechanism is unclear, and may be related to pregnancy-related hormones and metabolic changes.

    Therefore, FT1DM is currently divided into pregnancy-related FT1DM and non-pregnancy-related FT1DM.

    5.
    Drug allergy syndrome caused by some other drugs (carbamazepine, Mairudine, ibuprofen, etc.
    ) may be involved in the occurrence of FT1DM, and some antitumor drugs (such as uracil tegafur) may also cause FT1DM.

    4.
    Clinical features FT1DM often has a history of upper respiratory tract infection or gastrointestinal infection before the onset of FT1DM, the most common onset is DKA, the onset is rapid, and the condition is dangerous.
    Diabetic ketosis or DKA occurs within 1 week of the onset of typical hyperglycemia symptoms.
    At this time, fasting blood glucose is often ≥16mmol/l, HbA1c is normal or slightly elevated, generally <8.
    7%.
    At first diagnosis, pancreatic islet function is almost completely and irreversibly lost.
    About half of them are accompanied by disturbance of consciousness.
    Some patients may have liver, kidney, and heart.
    Multiple organ dysfunction such as striated muscle is manifested as increased liver enzymes, pancreatic enzymes and muscle enzymes.
    In severe cases, complications such as rhabdomyolysis, acute renal failure, cerebral edema and even cardiac arrest may occur.

    As for pregnancy-related FT1DM patients, their condition is more serious, and the incidence of miscarriage and stillbirth is extremely high.

    5.
    Diagnostic criteria Regarding the diagnosis of FT1DM, there is no uniform international standard.
    At present, the standard of the Japanese Diabetes Society (JDS) in 2012 is mostly referred to.

    1.
    Screening criteria a.
    Symptoms of hyperglycemia (more than three and one less), diabetic ketosis or DKA within 1 week; b.
    Fasting blood glucose ≥16mmol/l at the first diagnosis.

    2.
    Diagnostic criteria a.
    Diabetic ketosis or ketoacidosis occurs quickly (within about 1 week) after the appearance of hyperglycemia symptoms (test urine or blood ketones at the first diagnosis); b.
    The blood glucose level at the first diagnosis is ≥16.
    0mmol/L, And HbA1c<8.
    7% [U.
    S.
    National HbA1c Standardization Program (NGSP) standard]; c.
    Urinary C-peptide<10μg/d, or fasting serum C-peptide<0.
    3ng/ml (0.
    1nmol/L), after glucagon excitement Or C peptide peak value after eating <0.
    5ng/ml (0.
    17nmol/L).

    d.
    Other manifestations: ➤Islet autoantibodies, such as glutamate decarboxylase antibody (GAD-Ab), tyrosine phosphatase protein antibody (IA2-Ab), insulin autoantibody (IAA) are mostly negative; ➤Before insulin treatment , The course of the disease can be 1 to 2 weeks; ➤98% of patients can see elevated levels of pancreatin (amylase, lipase or elastase-1); ➤70% of patients can observe flu-like signs (fever, Upper respiratory tract symptoms, etc.
    ) or gastrointestinal symptoms (upper abdominal pain, nausea, vomiting, etc.
    ); ➤This disease can occur during pregnancy or within 2 weeks after delivery; ➤It may be related to human leukocyte antigen (HLA) DRB1*0405-DQB1* 0401 related.

    ——The first 3 criteria can be diagnosed as FT1DM, and those with other manifestations support the diagnosis.

    6.
    Differential diagnosis 1.
    T1DM (type 1A) 2.
    Atypical diabetes mellitus (ADM), namely T1DM (type 1B) 3.
    Other types of diabetes with negative islet autoantibodies a.
    Juvenile adult-onset diabetes (maturity) onset diabetes mellitus in young, MODY) b.
    Mitochondrial diabetes c.
    Wolfram syndrome 4.
    Acute pancreatitis 7.
    Treatment At present, the treatment of FT1DM is mainly based on individual case reports.
    According to its course of disease, it can be divided into acute treatment And long-term insulin replacement therapy.

    1.
    Acute treatment of FT1DM usually starts with ketosis and ketoacidosis, with rapid onset, severe metabolic disorder, and significant increase in blood sugar.

    The basic treatment principles are: once FT1DM is suspected, active rehydration, low-dose insulin intravenous drip, correction of electrolyte and acid-base balance, symptomatic and supportive treatment, prevention and treatment of complications should be given according to the principles of ketoacidosis treatment, and strict monitoring should be performed.
    Blood sugar, ketone bodies, liver and kidney function, pancreatic enzymes, muscle enzymes, etc.

    The main treatment methods include: fluid replacement, intravenous infusion of low-dose insulin, potassium supplementation, alkali supplementation and phosphate therapy.

    In addition, you need to pay attention to the following points: ➤ Make up the pre-estimated fluid loss within the first 24 hours, and evaluate whether the rehydration therapy is effective through hemodynamics (blood pressure, etc.
    ), volume, laboratory indicators, and clinical manifestations.

    ➤The disease has a sudden onset, severe metabolic disorder, and can cause serious complications or even death.
    Therefore, in the clinical diagnosis and treatment process, timely diagnosis and active rescue should be carried out: (1) Rapidly establish two intravenous channels, and continue intravenous infusion of insulin one way.
    , The other way for volume expansion or other anti-infective therapy; (2) Because the patient is severely dehydrated, and insulin absorption is poor, it is not recommended to use insulin pump therapy in the acute phase.

    ➤Pay attention to the possible occurrence of rhabdomyolysis and acute renal failure caused by patients: (1) Pay attention to whether the patient has muscle weakness, swelling and pain, and brown urine; (2) The level of blood creatine kinase is the most specific indicator of rhabdomyolysis.
    It is one of the routine testing items for this disease. ➤Patients with pregnancy-related FT1DM are more severely ill, and their HbA1c and arterial blood pH are also lower, which not only harms themselves but is also likely to cause stillbirth, shortening the time of hyperglycemia, timely correcting ketoacidosis and timely cesarean section may be The key to saving the fetus.

    2.
    Long-term insulin therapy.
    Due to the almost complete and irreversible destruction of pancreatic β cells in patients with FT1DM, patients with this disease have extremely poor pancreatic function, high blood sugar fluctuations, and low blood sugar.

    Therefore, after the condition is stable, long-term hypoglycemic treatment programs generally require fast-acting or ultra-short-acting insulin combined with medium-long-acting insulin for four subcutaneous intensive treatments or insulin pump treatment.

    8.
    Prognosis FT1DM progresses rapidly and the prognosis is poor.
    If timely diagnosis and treatment are not available, the risk of death is high.
    Therefore, clinicians should pay sufficient attention to early diagnosis and early treatment to reduce the disability and mortality rate.

    In patients with a clear diagnosis, it is difficult to control blood sugar during insulin treatment, and the risk of acute and chronic complications of diabetes is significantly increased.

    Studies have followed up patients with FT1DM for 5 years.
    The results show that the incidence of hypoglycemia and the risk of diabetic microvascular complications are significantly higher than those of autoimmune type 1 diabetes patients.
    Early detection, correct diagnosis and timely and appropriate treatment are available.
    Help improve the prognosis of patients.

    The author introduces Dr.
    Zhang Qianjin, director of the Department of Endocrinology, Shuyang Hospital Affiliated to Xuzhou Medical University, deputy chief physician, lecturer, postgraduate, deputy director of the Endocrinology Branch of the Suqian Medical Association, and deputy director of the Suqian Medical Association of Integrated Traditional Chinese and Western Medicine.
    Especially difficult, rare/rare diseases keep a keen interest, personal public account "endocrine regulator". References: [1] Imagawa A, Hanafusa T, Miyagawa J, et al.
    A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and absence of diabetes related antibodies [J].
    N Eng J Med, 2000, 342( 5):301-307.
    [2] Zhou Jian, Jia Weiping, Bao Yuqian, et al.
    A case of fulminant type 1 diabetes with rhabdomyolysis[J].
    Chinese Journal of Internal Medicine, 2007, 46(11):944-945.
    [3] Zhou Jian, Bao Yuqian, Li Ming, et al.
    Discussion on clinical features and treatment strategies of fulminant type 1 diabetes [J].
    Chinese Journal of Diabetes, 2009, 1(1): 34-38.
    [4] Ying Ling Wen, Ma Xiaojing, Zhou Jian.
    Research progress on the etiology and pathogenesis of fulminant type 1 diabetes[J].
    Chinese Journal of Diabetes, 2017, 9(2):139-142.
    [5] TsutsumiC, ImagawaA, IkegamiH, et al .
    Class Ⅱ HLA genotype in fulminant type 1 diabetes: A nationwide survey with reference to glutamic acid decarboxylase antibodies[J].
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    Clinical and immunogenetic characteristics of fulminant type 1 diabetes associated with pregnancy[J].
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    [7] ZhengC, ZhouZ, YangL, et al.
    Fulminant type 1 diabetes mellitus exhibits distinct clinical and autoimmunity features from classical type 1 diabetes mellitus in Chinese[J].
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    [8] Luo Shi, Ma Xiaoqian, Zhou Zhiguang, Et al.
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    [9] KwakSH, KimYJ, ChaeJ, et al.
    Association of HLA genotype and fulminant type 1 diabetes in Koreans[J].
    Genomics Inform, 2015, 13(4):126-131.
    [10] ImagawaA, HanafusaT, AwataT, et al.
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    J Diabetes Investig, 2012, 3(6):536-539.
    [8] Luo Fang, Ma Xiaoqian, Zhou Zhiguang, et al.
    Genetic characteristics of fulminant type 1 diabetes[J].
    Chinese Medical Journal, 2017, 97(8):561-563.
    [9] KwakSH, KimYJ, ChaeJ, et al.
    Association of HLA genotype and fulminant type 1 diabetes in Koreans[J].
    Genomics Inform, 2015, 13(4):126-131.
    [10] ImagawaA, HanafusaT, AwataT, et al.
    Report of the Committee of the Japan Diabetes Society on the research of fulminant and acute-onset type 1 diabetes mellitus: new diagnostic criteria of fulminant type 1 diabetes mellitus (2012)[J].
    J Diabetes Investig, 2012, 3(6):536-539.
    [8] Luo Fang, Ma Xiaoqian, Zhou Zhiguang, et al.
    Genetic characteristics of fulminant type 1 diabetes[J].
    Chinese Medical Journal, 2017, 97(8):561-563.
    [9] KwakSH, KimYJ, ChaeJ, et al.
    Association of HLA genotype and fulminant type 1 diabetes in Koreans[J].
    Genomics Inform, 2015, 13(4):126-131.
    [10] ImagawaA, HanafusaT, AwataT, et al.
    Report of the Committee of the Japan Diabetes Society on the research of fulminant and acute-onset type 1 diabetes mellitus: new diagnostic criteria of fulminant type 1 diabetes mellitus (2012)[J].
    J Diabetes Investig, 2012, 3(6):536-539.
    Report of the Committee of the Japan Diabetes Society on the research of fulminant and acute-onset type 1 diabetes mellitus: new diagnostic criteria of fulminant type 1 diabetes mellitus (2012)[J].
    J Diabetes Investig, 2012, 3(6): 536-539.
    Report of the Committee of the Japan Diabetes Society on the research of fulminant and acute-onset type 1 diabetes mellitus: new diagnostic criteria of fulminant type 1 diabetes mellitus (2012)[J].
    J Diabetes Investig, 2012, 3(6): 536-539.
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