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Atypical Neuroleptics & DM-a

Atypical Neuroleptics & DM-a - Diabetes...

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Diabetes & Schizophrenia Diabetes & Schizophrenia William Harper MD, FRCPC Endocrinology & Metabolism Assistant Professor of Medicine, McMaster University Dec 16, 2003. www.drharper.ca
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Case Case 38 male Paranoid Schizophrenia Meds: quetiapine 1 tab po bid clozapine 100 mg qAM, 200 mg qPM Psychosis refractory to other antipsychotics FHx DM ? Weight/BMI ? 1 month: polyuria, polydipsia 2 days: severe N/V, diarrhea, oliguria BG 53 mM, pH 6.95, AG 30 Creatinine 279, amylase 980
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Case Case Severe N/V esophageal tear Respiratory failure, hypotensive shock Received critical care: DKA, pancreatitis, ileus, ARF, pneumonia Ventilation, trach, Abtx, TPN, Insulin (IV SC) Quetiapine & clozapine stopped Haloperidol 1 mg IV bid
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Case Case 3 wk intensive care medical ward 1 wk later insulin stopped, normal BS Delusions/hallucinations recur: Haloperidol to 5 mg od symptoms persist 5 wk later trnsfr to psychiatric unit
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Case Case 1. Why did he develop diabetes and diabetic ketoacidosis? Do 2 nd Generation (Atypical) antipsychotics have adverse metabolic effects? 1. Could this metabolic decompensation have been predicted and prevented? 2. How should his psychotic symptoms be treated now?
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DKA risk factors DKA risk factors T1DM 1 st presentation Acute-illness Insulin omission (inappropriate sick-day management, noncompliance, Eating Disorders) T2DM During stress Ethnicity: African-American, Hispanic Extremes of age Poor glycemic control CSII
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Natural History Natural History of Type 2 Diabetes of Type 2 Diabetes Normal Impaired glucose tolerance Type 2 diabetes Time Insulin resistance Insulin production Glucose level β -cell dysfunction Henry. Am J Med 1998;105(1A):20S-6S.
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Mitochondrial Dysfunction & DM Mitochondrial Dysfunction & DM Gerald Shulman et al., Science 300:1140-2, May 2003.
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DKA: Pathophysiology DKA: Pathophysiology Glucose Pyruvate Acetyl-CoA Ketoacids Kreb’s + PFK Insulin fat cell TG FFA HSL Liver Cell Fatty Acyl-CoA Insulin - VLDL (TG) Glucagon Insulin + +
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DKA: Pathophysiology DKA: Pathophysiology Glucose Pyruvate Acetyl-CoA Ketoacids Kreb’s + PFK Insulin fat cell TG FFA HSL Liver Cell Fatty Acyl-CoA Insulin - VLDL (TG) Glucagon Insulin + +
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Schizophrenia & Diabetes Mellitus Schizophrenia & Diabetes Mellitus Many studies shown risk in schizophrenia: IGT, Insulin resistance Type 2 Diabetes mellitus 10% Schizophrenia > 6–8% general population Studies over several decades, predating both typical & atypical neuroleptics Many recent case reports/series: Treatment emergent DM (sometimes severe with DKA) Atypical > 1 st Generation Antipsychotics Alternative hypothesis: Worsening DM phenotype in schizophrenia population mirrors general population
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Year Number % of Cardiovascular Lower Limb New of People Population Hospitalization Amputation Dialysis/Yr 1996 1.2 mill. 4 80,000 6,000 1,500 2006 1.9 mill. 6 158,000 10,000 2,500 2016 2.7 mill. 7 228,000 15,000 3,500 Diabetes Mellitus (DM) in Canada Magnitude of the Problem Based on diagnosed diabetes.
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