Snapshot A 58-year-old male presents to his primary care physician for a routine checkup. He states that he has noticed some swelling of his ankles bilaterally but otherwise feels well. The patient has a 15-year history of diabetes mellitus. He takes metformin. His father died of a myocardial infarction at age 61. Routine labs are drawn. Urine dipstick is negative for protein. A spot urine microalbumin/creatinine ratio is elevated. (Diabetic nephropathy) Introduction Introduction demographics diabetes is 1 of the top 10 leading causes of death in the US majority of deaths in people with diabetes is due to cardiovascular disease Complications of Diabetes Short-Term Category Complication Pathogenesis Hyperglycemia Diabetic ketoacidosis (DKA) Hyperosmolar hyperglycemia state (HHS) Poor glycemic control Hypoglycemia Life-threatening hypoglycemia Secondary to therapy Long-Term Category Complication Pathogenesis Macrovascular Coronary artery disease (CAD) Peripheral arterial disease (PAD) Stroke Accelerated atherosclerosis due to chronic inflammation and injury to arterial walls Microvascular Diabetic retinopathy nonproliferative proliferative macular edema Diabetic nephropathy Diabetic neuropathy peripheral neuropathy central neuropathy cranial nerve III palsy Autonomic dysfunction gastroparesis impotence neurogenic bladder/overflow incontinence Diabetic foot Chronic hyperglycemia causes glycation of proteins and lipids resulting in impaired cell membrane function, osmotic damage, and tissue injury Immune dysfunction Urinary tract infections (UTIs) Rhinocerebral mucomycosis Pseudomonas malignant external otitis Hyperglycemic environment enhances virulence Lower secretions of inflammatory cytokines Decreased leukocyte adherence and chemotaxis Impaired neutrophil phagocytosis Other Necrobiosis lipoidica Non-alcoholic fatty liver disease (NAFLD) Diabetic Nephropathy Diabetic nephropathy pathogenesis glycosylation of basement membrane increased permeability and thickened glomerular basement membrane Presentation hypertension foamy urine signs of renal failure Studies urinalysis proteinuria microalbuminuria earliest sign progresses to nephrotic syndrome renal biopsy not necessary for diagnosis glomerular basement membrane thickening Kimmelstiel-Wilson nodules pathognomonic Treatment angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) regardless of blood pressure Diabetic Peripheral Neuropathy Peripheral neuropathy pathogenesis glycosylation of axon proteins Presentation progressive, symmetric “stocking-glove” loss of sensation, burning, or pain in distal lower extremities can progress to motor weakness and areflexia Studies monofilament test pinprick test Treatment pain management pregabalin or gabapentin serotonin norepinephrine receptor inhibitors (SNRIs) (i.e., duloxetine or venlafaxine) Complications diabetic foot Diabetic Foot Diabetic foot pathogenesis combination of vascular (poor circulation) and nerve (loss of sensation) damage Presentation painless ulcer most commonly on plantar metatarsal heads neuropathic arthropathy (Charcot foot) acute nontender, erythematous, swollen, and warm joint chronic joint or foot deformity most commonly collapse of tarsometatarsal joint and valgus angulation Imaging radiograph magnetic resonance imaging (MRI) if osteomyelitis is suspected Studies to rule out infection/osteomyelitis white blood cell count erythrocyte sedimentation rate C-reactive protein Treatment conservative immobilization and rest accommodative footwear wound care and dressing changes antibiotics indicated for infection surgery indicated for infection requiring debridement or osteomyelitis revascularization if underlying peripheral artery disease severe deformities Complications secondary infection cellulitis osteomyelitis spontaneous fractures Diabetic Gastroparesis Diabetic gastroparesis pathogenesis nerve damage leading to delayed gastric emptying Presentation nausea vomiting early satiety bloating constipation weight loss Imaging scintigraphy delayed gastric emptying endoscopy rule out obstructive lesion computed tomography (CT) rule out obstructive lesion Treatment prokinetics agents first-line metoclopramide alternatives domperidone erythromycin cisapride Complications risk of postprandial hypoglycemia Necrobiosis Lipoidica Necrobiosis lipoidica demographics majority associated with diabetes mellitus can also be associated with thyroid disease females > males pathogenesis collagen degeneration and lipid accumulation in skin Presentation pretibial skin lesions sharply demarcated, reddish-brown, or yellowish plaques with irregular margins and central sclerosis/atrophy Studies skin biopsy palisaded and interstitial granulomas in dermis and subcutaneous tissue necrobiosis of collagen infiltration of lymphocytes and plasma cells if no known history of diabetes mellitus or thyroid disorders, patient should be evaluated for these Treatment first-line high-potency topical steroid alternatives intralesional corticosteroid topical tacrolimus