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diabetes mellitus

also see diabetes in the elderly Classification: 1) type 1 diabetes: insulin deficiency 2) type 2 diabetes: insulin resistance 3) gestational diabetes: insulin resistance 4) other types a) genetic defects in beta cell function - MODY syndrome - young person with strong family history & lean body type - no acanthosis nigricans or features of Cushings syndrome - normal C-peptide b) genetic defects in insulin action - type A insulin resistance - Leprechaunism - Rabon-Mendenhall syndrome - lipoatrophic diabetes c) diseases of the exocrine pancreas - pancreatitis - pancreatic cancer - cystic fibrosis - hemochromatosis - fibrocalculous pancreatopathy d) endocrinopathies - Cushing's disease - acromegaly - glucagonoma - pheochromocytoma - somatostatinoma - aldosteronoma e) drug-induced or chemically-induced - corticosteroids - niacin - diazoxide - chlorthalidone - encainide - ethacrynic acid - furosemide - growth hormone - oral contraceptives - thiazides - pentamidine - phenytoin - interferon-alfa - beta-adrenergic agonists - thyroxine - cyclosporine - tacrolimus - antiretroviral protease inhibitors - atypical antipsychotics (olanzapine, clozapine) - Vacor (rat poison) f) infections - CMV - congenital rubella g) rare forms of immune-mediated diabetes mellitus - Stiff man syndrome - anti-insulin receptor antibodies h) other genetic syndromes associated with diabetes mellitus - Down syndrome - Turner syndrome - Klinefelter syndrome - Prader-Willi syndrome - Lawrence-Moon-Biedl syndrome - myotonic dystrophy - Huntington chorea [1] - Wolfram syndrome 5) 5 clusters of adult-onset diabetes mellitus proposed [36] a) cluster 1 (6%) - severe autoimmune diabetes (formerly type 1 diabetes) - early-onset disease, relatively low BMI, & GADA-positive b) cluster 2 (18%) - severe insulin-deficient diabetes - GADA-negative but similar to cluster 1; lowest HOMA2-B scores c) cluster 3 (15%) - severe insulin-resistant diabetes - higher HOMA2-IR scores d) cluster 4 (22%) - mild obesity-related diabetes - obese, but not insulin resistant e) cluster 5 (39%) - mild age-related diabetes - older than other clusters, but largely similar to cluster 4 Epidemiology: - prevalence nearly doubled, 4.5% to 8.2% from 1995-2010 [4]; prevalence 10% (2014) [23] - prevalence of both type 1 diabetes & type 2 diabetes has increased among children & adolescents 2001-2009 [22] - prevalence of diabetes Aug 2021-Aug 2023 in U.S. 15.8% (overall), 18.0% (men), 13.7& (women), 3.6% age 20-39 years, 17.7& age 40-59, 27.3% age > 60, 24% of obese, 7% of normal weight, 28% of cases undiagnosed [49] - 11% of cases are undiagnosed [4] - men at greater risk of complications diabetes complications than women [48] Genetics: - genetic variation in SOD2 is associated with susceptibility to microvascular complications of diabetes mellitus Diagnostic criteria: 1) fasting blood sugar > 126 mg/dL on 2 separate occasions 2) random blood sugar > 200 mg/dL + symptoms of diabetes polyuria, polydyspia or blurred vision [1] 3) abnormal glucose tolerance test - 2 hour glucose > 200 mg/dL [1] 4) hemoglobin A1c >= 6.5% [2] 5) elevated fasting serum glucose + elevated HgbA1c from same specimen [1,39] * diagnostic criteria represent the approximate glycemic point at which the risk for retinopathy begins a steep ascent in relation to increasing plasma glucose Laboratory: - in new-onset diabetes mellitus, need to distinguish diabetes mellitus type 1 from diabetes mellitus type 2 - serology* a) serum islet cell antibodies - serum autoantibodies to beta-cell antigens b) anti-insulin antibody [6] c) anti-glutamic acid decarboxylase-2 - in early phases of diabetes mellitus type 1, patients may still secrete insulin, thus serum insulin & serum C-peptide are not useful [1] - 90% have measurable antibodies against specific beta-cell proteins at the time of diagnosis [46] - basic metabolic panel for serum glucose, serum creatinine (eGFR) - hemoglobin A1c - urine albumin/creatinine ratio - see ARUP consult [3] * diagnosis of type 1 diabetes is made on the basis of - serum islet cell antibodies - anti-glutamic acid decarboxylase-2 [1] Complications: - increased risk for cardiovascular disease a) coronary artery disease b) cerebrovascular disease c) peripheral vascular disease - increased risk of microvascular disease a) diabetic nephropathy b) diabetic retinopathy c) diabetic polyneuropathy [1] - increased mortality [14] - declines in all-cause & cause-specific mortality among adults with diabetes likely reflects improved prevention & treatment [38] - however, the total number of lives shortened by diabetes continues to increase because of the increase in diagnosis of diabetes among adults [38] - increased risk of geriatric syndromes [14,19,20] a) polypharmacy b) urinary incontinence c) falls in the elderly d) cognitive impairment e) depression f) chronic pain g) functional impairment h) disablity [14] - also see diabetes mellitus complication Differential diagnosis: 1) type 1 diabetes mellitus a) serum C peptide 1] below lower limit of detection or < 0.6 nM 5 min after 1 mg of IV glucagon 2] < 0.2 nM fasting 3] not useful in early phases of type 1 diabetes [1] b) positive serum islet cell antibodies in 80% of newly diagnosed type 1 diabetics c) positive anti-glutamic acid decarboxylase-2 d) recurrent ketoacidosis as endogenous insulin secretion is lost e) age < 35 years f) weight at or below ideal - not necessarily in early phases of type 1 diabetes [1] 2) type 2 diabetes mellitus 3) drug toxicity a) agents that interfere with insulin secretion 1] beta adrenergic agonists 2] calcium channel blockers 3] clonidine 4] thiazides 5] phenytoin 6] pentamidine b) agents that induce insulin resistance 1] glucocorticoids 2] estrogens 3] nicotinic acid 4) endocrine disorders a) Cushing's syndrome b) glucagonoma c) acromegaly d) pheochromocytoma e) aldosteronoma f) somatostatinoma g) thyrotoxicosis 5) chronic pancreatitis, pancreatectomy or pancreatic carcinoma 6) genetic abnormalities in proinsulin or insulin receptor Management: - see more specific type of diabetes mellitus - individuals the goals of treatment [14] - general goals of treatment [14] - control hyperglycemia & its symptoms - evaluation & treatment of complications of diabetes mellitus - optimizing general health status - American Diabetes Association recommends blood pressure target of < 130/80, in agreement with other organizations [1,43] - American Diabetes Association recommends LDL cholesterol < 70 mg/dL & < 55 mg/dL for high-risk patients [43] - take a break from prolonged sitting every 30 minutes [34 - risk of hypoglycemia is the most important factor in determining glycemic goals in the elderly [26] - sole use of sliding scale insulin should be avoided [26] - nutritional recommendations [8] - use of ACE inhibitors or ARBs not recommended for patients with normal blood pressure & urine albumin/creatinine < 30 mg/g & eGFR > 60 mL/min/1.73 m2 [1] - use of ACE inhibitors associated with better outcomes than use of ARBs [13] - self-management* - important part of diabetes care - annual self-management training is covered under Medicare part B - hospitalized patients with diabetes mellitus [1,40] - insulin for management of hospitalized patients - initiate insulin for blood glucose > 180 mg/dL with target of 140-180 mg/dL [40] - adequate nutritional intake: basal + prandial + correction insulin - poor nutritional intake or NPO: basal + correction insulin * only 7% of privately-insured, patients with newly diagnosed diabetes mellitus participate in American Diabetes Association recommended diabetes self-management education & training [24]

Interactions

disease interactions

Related

blood pressure & hypertension in diabetes diabetes in the elderly diabetes mellitus complication diabetes recognition program glycemic control hyperglycemia prediabetes

Useful

hypoglycemic agent

Specific

diabetes & deafness, maternally inherited; Ballinger-Wallace syndrome diabetes mellitus type 1 (insulin-dependent, juvenile) diabetes mellitus type 2 (insulin-resistant) diabetics who become pregnant gestational diabetes ketosis prone diabetes; flatbush diabetes, type 1B diabetes, atypical diabetes secondary diabetes mellitus

General

chronic endocrine disease chronic metabolic disease pancreatic disease

Database Correlations

OMIM 612634

References

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