DM: Complications Flashcards
What are the microvascular complications of DM? (3)
Retinopathy, nephropathy, neuropathy
What are the macrovascular complications of DM? (3)
Coronary heart disease, peripheral arterial disease, cerebrovascular disease
What are some of the nonvascular complications of DM?
Infections, skin changes, hearing loss, GI, GU, cataracts, glaucoma, etc
Which trial provided definitive proof that reduction in chronic hyperglycemia can prevent many complications of type 1 DM, and that intensive diabetes management substantially lowers HbA1c compared to conventional management?
Diabetes Control and Complications Trial (DCCT)
Type 1 DM
Which trial followed up the participants of the DCCT which showed that the initial separation in glycemic control disappeared on the subsequent follow-up of >18 years?
Epidemiology of Diabetes Intervention and Complications (EDIC) trial
The DCCT trial showed the improvement of glycemic control reduced the following complications by how much?
a. retinopathy
b. albuminuria
c. nephropathy
d. neuropathy
e. cardiovascular events
a. retinopathy - 47% reduction (7.7 additional years of vision)
b. albuminuria - 39% reduction
c. nephropathy - 54% reduction (5.8 additional years free from ESRD)
d. neuropathy - 60% reduction (5.6 years free from lower extremity amputations)
e. cardiovascular events - 42-57% reduction
Which trial showed that improved glycemic control reduced the complications of type 2 DM?
United Kingdom Prospective Diabetes Study (UKPDS)
Type 2 DM
The UKPDS showed that each percentage point reduction in HbA1c was associated with a ___% reduction in microvascular complications.
35%
Which trial studied Japanese individuals with type 2 DM randomized to either intensive glycemic control or standard therapy with insulin?
Kumamoto study
Legacy effect or Metabolic memory refers to
The positive impact of a period of improved glycemic control on later disease
Hypotheses on how DM complications develop
- Hyperglycemia leads to epigenetic changes that influence gene expression in affected cells
- Chronic hyperglycemia leads to formation of advanced glycosylation products which bind to specific cell surface receptor and/or the nonezymatic glycosylation of intra- and extracellular proteins, leading to cross-linking of proteins, accelerated atherosclerosis, glomerular dysfunction, endothelial dysfunction, and altered extracellular matrix composition
- Increases glucose metabolism via the sorbitol pathway related to enzyme aldose reductase
- Increases the formation of diacylglycerol, leading to activation of protein kinase C, which alters the transcription of genes
- Increases the flux through the hexosamine pathway, which generates fructose-6-phosphate, a substrate for O-linked glycosylation and proteoglycan production
Characteristics of nonproliferative diabetic retinopathy
Appears late in the first decade or early in the second decade of the disease
Retinal vascular microaneurysm, blot hemorrhages, and cotton-wool spots
Hallmark of proliferative diabetic retinopathy
Neovascularization
Most effective therapy for diabetic retinopathy
Prevention (intensive glycemic and blood pressure control)
Which medicine can reduce the progression of retinopathy?
Fenofibrate
True or false: Aspirin therapy (650mg/d) appears to influence the natural history of diabetic retinopathy.
False
How many percent of patients with diabetes develop diabetic nephropathy?
20-40% (hence there are additional genetic or environmental susceptibility factors)
Diabetic kidney disease refers to _______ and _________.
- Albuminuria
2. Reduced GFR (<60 ml/min/1.73m2)
True or false: Urinalysis can be used to screen for albuminuria in diabetes.
False. The urine protein measurement by routine urinalysis does not detect low levels of albumin excretion.
When should screening for albuminuria commence?
5 years after the onset of type 1 DM
At the time of diagnosis of type 2 DM
What medications can be given to reduce the albuminuria and the associated decline in GFR that accompanies it in individuals with DM?
ACE inhibitors or ARBs
ADA recommendation on the protein intake in individuals with diabetic kidney disease
0.8 mg/kg of body weight/day
What is the most common form of diabetic neuropathy?
Distal symmetric polyneuropathy (DSPN)
What is the characteristics of distal symmetric polyneuropathy?
Usually present at rest and worsens at night
When should annual screening for distal symmetric polyneuropathy begin?
5 years after diagnosis of type 1 DM
At the time of diagnosis of type 2 DM
What is the most commonly involved nerve in diabetic mononeuropathy?
Third cranial nerve (heralded by diplopia)
3 Agents that are FDA-approved for pain associated with diabetic neuropathy
Duloxetine
Pregabalin
Tapentadol (modest efficacy and poses addiction risk)
Most prominent GI symptoms in DM
Delayed gastric emptying (gastroparesis) and altered small- and large-bowel motility (nocturnal diarrhea alternating with constipation)
This was a double factorial randomized clinical trial comparing intensive vs. standard glycemic control, intensive versus standard blood pressure control and fenofibrate versus placebo against a background of statin treatment.
Action to Control Cardiovascular Risk in Type 2 Diabetes (ACCORD) trial (Not from Harrison’s)
Trial that studied a relatively homogeneous population of older men with poorly controlled T2DM and randomized them to intensive versus standard glucose control. Intensive treatment did not show significant improvement in complications. Legacy effect was not observed.
Veterans Affairs Diabetes Trial (VADT) (Not from Harrison’s)
Study that showed cardiovascular benefit with GLP-1 analog
SUSTAIN-6 (semaglutide)
Study that showed cardiovascular benefit with liraglutide
LEADER
Study that showed cardiovascular benefit with SGLT2 inhibitors
EMPA-REG (empagliflozin)
CANVAS (canagliflozin)
ADA recommendation on the use of aspirin in DM
- Consider the use of aspirin for primary prevention of coronary events in individuals with diabetes with an increased cardiovascular risk (>50 years with at least 1 risk factor such as hypertension, dyslipidemia, smoking, family history, or albuminuria)
- Aspirin is not recommended for primary prevention in those with a low cardiovascular risk (<50 years with no risk factors)
Most common pattern of dyslipidemia in DM
Hypertriglyceridemia (>150 mg/dL) and reduced HDL (<40 mg/dL in men, <50 in women)
ADA recommendations on statin therapy in diabetes
- All patients with diabetes and atherosclerotic cardiovascular disease should receive high-intensitiy statin therapy
- In patients aged 40-75 years, consider using moderate-intensity statin therapy (without additional risk factors), high intensity statin therapy (with additional risk factors)
- In patients <40 years and additional risk factors, consider moderate-intensity statin therapy
Combination therapy with a statin and a fibrate or niacin is NOT recommended with the EXCEPTION of a statin and ezetimibe and a statin in patients with recent acute coronary syndrome.
Target blood pressure in diabetes
<140/90 mmHg
May target <130/80 in younger individuals or those with increased CV risk
ADA recommendation on the treatment of hypertension in DM
All patients with diabetes and hypertension should be treated with an ACE inhibitor or an ARB initially.
Most common location of foot ulcers in type 2 DM
Great toe or metatarsophalangeal areas
Plantar surface of the foot
When should screening for lower extremity complications start?
In asymptomatic individuals >50 years og age who have diabetes and other risk factors (using ankle-brachial index)
In lower extremity complications, IV antibiotics should provide broad-spectrum coverage directed toward
Staphylococcus aureus
(Initial antimicrobial regimens include vancomycin + B-lactam/B-lactamase inhibitor or carbapenem OR vancomycin + a combination of a quinolone plus metronidazole)
What are the 2 most common skin manifestations of DM?
Xerosis and Pruritus
Describe the lesions of diabetic dermopathy
(Also termed pigmented pretibial papules or “diabetic skin spots”)
Begins as an erythematous macule or papule that evolves into an area of circular hyperpigmentation; result from minor mechanical trauma in the pretibial region; more common in elderly men with DM
What do you call the dermatologic manifestation of DM that occurs predominantly in young women, that usually begins in the pretibial region as an erythematous plaque or papules that gradually enlarge, darken, and develop irregular margins, with atrophic centers and central ulceration?
Necrobiosis lipoidica diabeticorum
What is type IV renal tubular acidosis?
Hyporeninemic hypoaldosteronism
