Unusual high blood glucose in ketoacidosis as first presentation of type 1 diabetes mellitus

in Endocrinology, Diabetes & Metabolism Case Reports
Authors:
Sebastian Hörber Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
German Center for Diabetes Research (DZD), München-Neuherberg, Germany

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Sarah Hudak Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany

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Martin Kächele Department of Internal Medicine, Medical Intensive Care Unit, University of Tübingen, Tübingen, Germany

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Dietrich Overkamp Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany

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Andreas Fritsche Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
German Center for Diabetes Research (DZD), München-Neuherberg, Germany

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Hans-Ulrich Häring Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
German Center for Diabetes Research (DZD), München-Neuherberg, Germany

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Andreas Peter Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
German Center for Diabetes Research (DZD), München-Neuherberg, Germany

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Martin Heni Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
German Center for Diabetes Research (DZD), München-Neuherberg, Germany

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Correspondence should be addressed to M Heni; Email: Martin.Heni@med.uni-tuebingen.de
Open access

Summary

Diabetic ketoacidosis is a life-threatening complication of diabetes mellitus. It usually occurs in patients with type 1 diabetes where it is typically associated with only moderately increased blood glucose. Here, we report the case of a 52-year-old female patient who was admitted to the emergency unit with severely altered mental status but stable vital signs. Laboratory results on admission revealed very high blood glucose (1687 mg/dL/93.6 mmol/L) and severe acidosis (pH <7) with proof of ketone bodies in serum and urine. Past history revealed a paranoid schizophrenia diagnosed 10 years ago and for which the patient was treated with risperidone for many years. Acute treatment with intravenous fluids, intravenous insulin infusion and sodium bicarbonate improved the symptoms. Further laboratory investigations confirmed diagnosis of autoimmune type 1 diabetes. After normalization of blood glucose levels, the patient could soon be discharged with a subcutaneous insulin therapy.

Learning points:

  • Diabetic ketoacidosis as first manifestation of type 1 diabetes can occur with markedly elevated blood glucose concentrations in elder patients.

  • Atypical antipsychotics are associated with hyperglycemia and an increased risk of new-onset diabetes.

  • First report of risperidone-associated diabetic ketoacidosis in new-onset type 1 diabetes.

  • Patients treated with atypical antipsychotics require special care and regular laboratory examinations to detect hyperglycemia and diabetic ketoacidosis.

  • In cases when the diagnosis is in doubt, blood gas analysis as well as determination of C-peptide and islet autoantibodies can help to establish the definite diabetes type.

Summary

Diabetic ketoacidosis is a life-threatening complication of diabetes mellitus. It usually occurs in patients with type 1 diabetes where it is typically associated with only moderately increased blood glucose. Here, we report the case of a 52-year-old female patient who was admitted to the emergency unit with severely altered mental status but stable vital signs. Laboratory results on admission revealed very high blood glucose (1687 mg/dL/93.6 mmol/L) and severe acidosis (pH <7) with proof of ketone bodies in serum and urine. Past history revealed a paranoid schizophrenia diagnosed 10 years ago and for which the patient was treated with risperidone for many years. Acute treatment with intravenous fluids, intravenous insulin infusion and sodium bicarbonate improved the symptoms. Further laboratory investigations confirmed diagnosis of autoimmune type 1 diabetes. After normalization of blood glucose levels, the patient could soon be discharged with a subcutaneous insulin therapy.

Learning points:

  • Diabetic ketoacidosis as first manifestation of type 1 diabetes can occur with markedly elevated blood glucose concentrations in elder patients.

  • Atypical antipsychotics are associated with hyperglycemia and an increased risk of new-onset diabetes.

  • First report of risperidone-associated diabetic ketoacidosis in new-onset type 1 diabetes.

  • Patients treated with atypical antipsychotics require special care and regular laboratory examinations to detect hyperglycemia and diabetic ketoacidosis.

  • In cases when the diagnosis is in doubt, blood gas analysis as well as determination of C-peptide and islet autoantibodies can help to establish the definite diabetes type.

Background

High blood glucose levels (>600 mg/dL/33.3 mmol/L) are a typical finding in hyperglycemic hyperosmolar syndrome, mostly seen in elderly patients with long-standing type 2 diabetes. It is characterized by high blood glucose, increased serum osmolarity and dehydration without significant ketoacidosis and therefore normal pH (1). In contrast, diabetic ketoacidosis (DKA) usually occurs in younger patients with type 1 diabetes and is associated with only moderate increased blood glucose (250–600 mg/dL/13.9–33.3 mmol/L) (2). DKA is defined by metabolic acidosis, high blood glucose, and the presence of ketone bodies in blood and urine. Reduced insulin effect due to markedly reduced or absent insulin secretion is the major cause for hyperglycemia in this condition. The inability of glucose to enter the cells leads to increased stimulation of lipolysis and subsequent accumulation of free fatty acids and significant amounts of ketone bodies (3). As a consequence, counter regulatory hormones, such as catecholamines, glucagon and cortisol are upregulated and act in direct opposition to insulin (4). Normally, elderly patients with very high blood glucose levels are considered to have type 2 diabetes and the high prevalence of type 2 diabetes in patients at that age makes it challenging to identify type 1 diabetes patients among them (5).

Risperidone is an atypical antipsychotic approved for the treatment of schizophrenia. It is long known that atypical antipsychotics are linked to hyperglycemia, new-onset of type 2 diabetes and in rare cases also with the development of diabetic ketoacidosis (6). Patients on atypical antipsychotic medication should therefore be considered as patients at high risk for diabetes and presumably also DKA.

Case presentation

A 52-year-old female patient was admitted to the emergency unit with severely altered mental status. The patient’s son reported that the patient complained of abdominal pain, nausea and vomiting for 2 days. The day before admission, the patient introduced herself to an ambulatory emergency service due to constant restlessness. They prescribed diazepam when needed. On admission to the emergency unit, the patient was somnolent. Vital signs revealed mild tachycardia (112/min), normal blood pressure (115/75 mmHg) and hyperventilation (Kussmaul breathing). Body temperature was normal. The patient was lean with a BMI of 21.7 kg/m2. Past history revealed no preexisting conditions, except for a paranoid schizophrenia diagnosed 10 years ago. Therefore, she has been treated with risperidone for many years. Family history was negative for diabetes and other relevant diseases.

Investigations

Initial laboratory results included (Fig. 1 and Table 1): a reduced blood pH of <7, a high serum anion gap (41 mEq/dL), markedly elevated blood glucose (1687 mg/dL/93.6 mmol/L), elevated lactate of 5.1 mg/dL and serum osmolality of 404 mosmol/kg. The urine sample was clearly positive for ketones and glucose. A drug screening was negative except for benzodiazepines. Serum beta-hydroxybutyrate was elevated and HbA1c was 12.2% (110 mmol/mol). C-peptide was decreased (77 pmol/L).

Figure 1
Figure 1

Arterial blood gas analysis. (A) Time course of the pH measurements for the first 2 days after admission. (B) Time course of the serum anion gap. Shown are values in mmol/L for the first 2 days after admission. The anion gap is calculated by subtracting the serum concentrations of chloride and bicarbonate from the concentrations of sodium and potassium.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2018, 1; 10.1530/EDM-18-0094

Table 1

Time course of arterial blood gas analyses and basic laboratory results.

Reference range Admission 1 h 2 h 4 h 8 h 16 h 24 h Day 3 Day 5
Blood gas analyses
 pH 7.35–7.45 <7.0 7.09 7.21 7.31 7.36 7.40 7.47
 Sodium (mmol/L) 136–148 125 130 144 146 146 150 151
 Potassium (mmol/L) 3.5–4.8 6.9 5.7 6.7 4.2 4.9 3.5 4.1
 Chloride (mmol/L) 96–110 78 80 107 109 111 115 116
 Bicarbonate (mmol/L) 22.0–26.0 4.8 5.8 7.8 8.3 11.4 16.3 24.1
 pO2 (mmHg) 65–100 94 125 122 129 112 109 92
 pCO2 (mmHg) 32.0–42.0 20 19.9 44 13.6 25.8 27.0 34.0
 Anion gap (mEq/L) 3–11 49.1 49.9 35.9 32.9 28.5 22.2 15.0
 Base excess (mmol/L) −3.0 to 3.0 −23.2 −21.5 −11.7 −19.3 −14.2 −7.5 0.1
 Glucose (mg/dL) 70–90 1687 1232 1059 890 837 845 806
Laboratory tests
 Hematocrit (%) 37.0–47.0 43.3 26.1 36.8
 Hemoglobin (g/dL) 12.0–16.0 13.2 9.7 12.8
 White cell count (per mm3) 4100–11 800 16 740 8700 5550
 Platelet count (103 per mm3) 150–450 319 137 218
 PT (INR) 0.9 1.1 1.0
 aPTT (s) Max. 40 27
Electrolytes (mmol/L)
 Sodium 136–148 124 148 140
 Potassium 3.5–4.8 6.5 4.1 4.1
 Calcium 2.1–2.6 2.4 2.0
 Phosphate 0.8–1.5 4.2 0.8 1.3
 Chloride 96–110 75 113 109
 Creatinine (mg/dL) 0.5–0.8 2.9 0.6 0.6
 GFR MDRD (mL/min * 1.73 m2) 80 ± 24 17 105.0 105.0
 C-reactive protein (mg/dL) Max. 0.5 0.4 1.4 0.34
 Creatin kinase (mg/dL) Max. 170 43 239 161
 Urea (mg/dL) 12–46 108 8
 Total cholesterol (mg/dL) 130–190 239
 Triglycerides (mg/dL) <200 111
 LDL cholesterol (mg/dL) <160 175
 HDL cholesterol (mg/dL) >45 51
 Total protein (g/dL) 6.5–8.5 4.3 7.2
 Albumin (g/dL) 3.0–5.0 2.9
 Alanine transaminase (U/L) Max. 34 15
 Alkaline phosphatase (U/L) 35–105 90
 Gamma-glutamyl transferase (U/L) Max. 40 14 9
 Lipase (U/L) Max. 60 80 40
 Lactate dehydrogenase (U/L) Max. 250 133 162
 Serum osmolality (mosmol/kg) 275–300 404 321
 TSH (mU/L) 0.5–4.4 0.93
 Cortisol (nmol/L) 130–630 3446 429
 Lactate (mg/dL) 0.5–2.2 5.1 1.6
 C-peptide (pmol/L) 140–830 77 114
 Glucose (mg/dL) 70–99 1687 331
 Glycosylated hemoglobin (%/IFCC) (mmol/mol) 4.5–6.2/26–44 12.2/110
 GAD antibodies (IU/mL) <5 135.0
 IA2 antibodies (IU/mL) <10 <0.8
 3-Hydroxy butyric acid (mg/dL) 3–9 1149 9
 Acetoacetic acid (mg/dL) <20 495 2

Numbers in bold were outside the reference range.

aPTT, activated partial thromboplastin time; BE, base excess; GAD, glutamic acid decarboxylase; GFR, glomerular filtration rate; HDL, high-density lipoprotein; IA, islet antigen; IFCC, international federation of clinical chemistry; INR, international normalized ratio; LDL, low-density lipoprotein; MDRD, modification of diet in renal disease; pCO2, partial pressure of CO2; pO2, partial pressure of O2; PT, prothrombin time; TSH, thyroid-stimulating hormone; U, units.

Treatment

Due to positive proof of benzodiazepine in urine and severely altered mental status, the treatment was first started with the benzodiazepine-antagonist flumazenil whereupon her condition improved only slightly. Though, she was simultaneously treated with intravenous fluids, intravenous insulin infusion and sodium bicarbonate under constant control of vital parameters, blood glucose, electrolytes and blood gas analyses.

Outcome and follow-up

Over the next 48 h, her general condition dramatically improved, blood glucose level fell and the anion gap normalized (Fig. 1 and Table 1). Immunological investigations revealed pancreatic autoantibodies against glutamic acid decarboxylase (GAD). In line with the markedly reduced C-peptide concentrations, we diagnosed type 1 diabetes. After normalization of blood glucose levels, the patient was transferred from the intensive care unit to the general ward and could soon be discharged from the hospital with a subcutaneous insulin injection therapy.

Discussion

Our patient clearly suffered from DKA due to newly diagnosed type 1 diabetes. Previously, auto-antibody-positive diabetes was sometimes also classified as latent autoimmune diabetes in the adult (LADA). Though, C-peptide concentrations were unusually low for this diabetes subtype (7), and the latest guidelines recommend classifying all cases of autoimmune diabetes as type 1 diabetes (8). Of notice, there is a lot of discussion in the field of diabetes subclassification lately, due to novel computational approaches on this topic (9). To our knowledge, our report is the first report about risperidone-associated DKA in new-onset type 1 diabetes. Several reviews addressed this rare and potentially detrimental side effect of atypical antipsychotics. Though, almost all previous reports are related to dysregulated glucose homeostasis in patients with type 2 diabetes (6, 10). A few studies focused on the mechanism of action to understand the pathogenesis of atypical antipsychotic-induced diabetes. Weight gain, as a typical side effect of this drug class, and insulin resistance is considered to be a main factor that drives the association of atypical antipsychotics with hyperglycemia (11). However, our patient was lean and weight gain alone can therefore not fully explain this association. There are some reports about other antipsychotics, like risperidone that was prescribed to our patient or aripiprazole, which have less effect on body weight (12). Of notice, these substances have also been linked to diabetes risk. Recently, one report even described a new diagnosed type 1 diabetes subject treated with olanzapine (13). The authors hypothesized that olanzapine led to a relevant hyperglycemia, thereby accelerating the onset type 1 diabetes. The precise underlying mechanisms, however, remain elusive.

The development of blood glucose concentrations, as high as in our patient, is very unusual in the context of DKA. It is possible that the blood glucose levels had increased to that enormous extent because the symptoms might have been masked by the diazepam that was prescribed the day before admission. Nevertheless, the development and the precise mechanism of such high glucose values with delayed clinical symptoms also remain unclear.

Conclusion

Very high blood glucose levels are often indicative for type 2 diabetes. However, in rare cases, the first manifestation of type 1 diabetes can also present with markedly elevated glucose (>1000 mg/dL/55.5 mmol/L). Failure to diagnose type 1 diabetes, especially in elderly patients, can have serious consequences due to initiation of inadequate treatment. In cases when the diagnosis is in doubt, blood gas analysis as well as determination of C-peptide and islet autoantibodies can help to establish the definite diabetes type. Furthermore, patients who are treated with atypical antipsychotics require special care and regular laboratory examinations to detect hyperglycemia and diabetic ketoacidosis.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding

The authors acknowledge support by the Deutsche Forschungsgemeinschaft and the Open Access Publishing Fund of the University of Tübingen. Part of this work was supported by a grant (01Gbib925) from the Federal Ministry of Education and Research (BMBF) to the German Centre for Diabetes Research (DZD e.V.).

Author contribution statement

Se H, Sa H, M K, D O and M H looked after the patient and wrote the report. A F, A P and H-U H reviewed the report. All authors approved the final version before submission.

References

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    Pasquel FJ & Umpierrez GE. Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. Diabetes Care 2014 37 31243131. (https://doi.org/10.2337/dc14-0984)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Kitabchi AE, Umpierrez GE, Miles JM & Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009 32 13351343. (https://doi.org/10.2337/dbib9-9032)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Lebovitz HE. Diabetic ketoacidosis. Lancet 1995 345 767772. (https://doi.org/10.1016/S0140-6736(95)90645-2)

  • 4

    Kitabchi AE, Umpierrez GE, Murphy MB & Kreisberg RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006 29 27392748. (https://doi.org/10.2337/dbib6-9916)

    • PubMed
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    • Export Citation
  • 5

    Thomas NJ, Jones SE, Weedon MN, Shields BM, Oram RA & Hattersley AT. Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK biobank. Lancet Diabetes Endocrinology 2017 6 122129. (https://doi.org/10.1016/S2213-8587(17)30362-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Guenette MD, Hahn M, Cohn TA, Teo C & Remington GJ. Atypical antipsychotics and diabetic ketoacidosis: a review. Psychopharmacology 2013 226 112. (https://doi.org/10.1007/s00213-013-2982-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Ahlqvist E, Storm P, Karajamaki A, Martinell M, Dorkhan M, Carlsson A, Vikman P, Prasad RB, Aly DM, Almgren P, et al.Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinology 2018 6 361369. (https://doi.org/10.1016/S2213-8587(18)30051-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in Diabetes-2018. Diabetes Care 2018 41 S13S27. (https://doi.org/10.2337/dc18-S002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Sladek R. The many faces of diabetes: addressing heterogeneity of a complex disease. Lancet Diabetes Endocrinology 2018 6 348349. (https://doi.org/10.1016/S2213-8587(18)30070-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Lipscombe LL, Austin PC, Alessi-Severini S, Blackburn DF, Blais L, Bresee L, Filion KB, Kawasumi Y, Kurdyak P, Platt RW, et al.Atypical antipsychotics and hyperglycemic emergencies: multicentre, retrospective cohort study of administrative data. Schizophrenia Research 2014 154 5460. (https://doi.org/10.1016/j.schres.2014.01.043).

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Alvarez-Jimenez M, Gonzalez-Blanch C, Vazquez-Barquero JL, Perez-Iglesias R, Martinez-Garcia O, Perez-Pardal T, Ramirez-Bonilla ML & Crespo-Facorro B. Attenuation of antipsychotic-induced weight gain with early behavioral intervention in drug-naive first-episode psychosis patients: a randomized controlled trial. Journal of Clinical Psychiatry 2006 67 12531260. (https://doi.org/10.4088/JCP.v67n0812)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Baptista T, ElFakih Y, Uzcategui E, Sandia I, Talamo E, Araujo de Baptista E & Beaulieu S. Pharmacological management of atypical antipsychotic-induced weight gain. CNS Drugs 2008 22 477495. (https://doi.org/10.2165/00023210-200822060-00003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Iwaku K, Otuka F & Taniyama M. Acute-onset Type 1 diabetes that developed during the administration of olanzapine. Internal Medicine 2017 56 335339. (https://doi.org/10.2169/internalmedicine.56.7010)

    • PubMed
    • Search Google Scholar
    • Export Citation

 

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  • Figure 1

    Arterial blood gas analysis. (A) Time course of the pH measurements for the first 2 days after admission. (B) Time course of the serum anion gap. Shown are values in mmol/L for the first 2 days after admission. The anion gap is calculated by subtracting the serum concentrations of chloride and bicarbonate from the concentrations of sodium and potassium.

  • 1

    Pasquel FJ & Umpierrez GE. Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. Diabetes Care 2014 37 31243131. (https://doi.org/10.2337/dc14-0984)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Kitabchi AE, Umpierrez GE, Miles JM & Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009 32 13351343. (https://doi.org/10.2337/dbib9-9032)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Lebovitz HE. Diabetic ketoacidosis. Lancet 1995 345 767772. (https://doi.org/10.1016/S0140-6736(95)90645-2)

  • 4

    Kitabchi AE, Umpierrez GE, Murphy MB & Kreisberg RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006 29 27392748. (https://doi.org/10.2337/dbib6-9916)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Thomas NJ, Jones SE, Weedon MN, Shields BM, Oram RA & Hattersley AT. Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK biobank. Lancet Diabetes Endocrinology 2017 6 122129. (https://doi.org/10.1016/S2213-8587(17)30362-5)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Guenette MD, Hahn M, Cohn TA, Teo C & Remington GJ. Atypical antipsychotics and diabetic ketoacidosis: a review. Psychopharmacology 2013 226 112. (https://doi.org/10.1007/s00213-013-2982-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Ahlqvist E, Storm P, Karajamaki A, Martinell M, Dorkhan M, Carlsson A, Vikman P, Prasad RB, Aly DM, Almgren P, et al.Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinology 2018 6 361369. (https://doi.org/10.1016/S2213-8587(18)30051-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in Diabetes-2018. Diabetes Care 2018 41 S13S27. (https://doi.org/10.2337/dc18-S002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Sladek R. The many faces of diabetes: addressing heterogeneity of a complex disease. Lancet Diabetes Endocrinology 2018 6 348349. (https://doi.org/10.1016/S2213-8587(18)30070-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Lipscombe LL, Austin PC, Alessi-Severini S, Blackburn DF, Blais L, Bresee L, Filion KB, Kawasumi Y, Kurdyak P, Platt RW, et al.Atypical antipsychotics and hyperglycemic emergencies: multicentre, retrospective cohort study of administrative data. Schizophrenia Research 2014 154 5460. (https://doi.org/10.1016/j.schres.2014.01.043).

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Alvarez-Jimenez M, Gonzalez-Blanch C, Vazquez-Barquero JL, Perez-Iglesias R, Martinez-Garcia O, Perez-Pardal T, Ramirez-Bonilla ML & Crespo-Facorro B. Attenuation of antipsychotic-induced weight gain with early behavioral intervention in drug-naive first-episode psychosis patients: a randomized controlled trial. Journal of Clinical Psychiatry 2006 67 12531260. (https://doi.org/10.4088/JCP.v67n0812)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Baptista T, ElFakih Y, Uzcategui E, Sandia I, Talamo E, Araujo de Baptista E & Beaulieu S. Pharmacological management of atypical antipsychotic-induced weight gain. CNS Drugs 2008 22 477495. (https://doi.org/10.2165/00023210-200822060-00003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Iwaku K, Otuka F & Taniyama M. Acute-onset Type 1 diabetes that developed during the administration of olanzapine. Internal Medicine 2017 56 335339. (https://doi.org/10.2169/internalmedicine.56.7010)

    • PubMed
    • Search Google Scholar
    • Export Citation