Complications of Diabetes

Dr.Debajyoti ChakrabortyPGT UnitII G.M.

DIABETIC NEPHROPATHY

Diabetic Glomerulopathy* (including diabetic tubulopathy) Renal artery stenosis Papillary necrosis Renal tubular acidosis Urinary tract infections CIN

Diabetic nephropathy

Diabetic nephropathy is the leading cause of ESRD in the United States and a leading cause of DM-related morbidity and mortality . Both microalbuminuria and macroalbuminuria in individuals with DM are associated with increased risk of cardiovascular disease. Individuals with diabetic nephropathy comm only have diabetic retinopathy .

DIABETIC GLOMERULOPATHY

Approximately one third of type 1 diabetic patients will have a

GFR higher than the upper normal range of age matched healthy nondiabetic subjects.

The degree of hyperfiltration is less in type 2 diabetic patients and reported lacking in some studies. The GFR elevation is

particularly pronounced in newly diagnosed diabetic patients and during other intervals with poor

metabolic control. Intensified insulin treatment and near-

normal blood glucose control reduce GFR toward normal levels after a period of days to weeks in both type 1 and type 2 diabetic

patients

Assess urine albumin excretion annually (B)◦ In type 1 diabetic patients with diabetes duration

of ≥5 years◦ In all type 2 diabetic patients at diagnosis

Measure serum creatinine at least annually (E)◦ In all adults with diabetes regardless of degree of

urine albumin excretion◦ Serum creatinine should be used to estimate GFR

and stage level of chronic kidney disease, if present

Screening(as per ADA 2013 guidelines)

.Under most circumstances untimed (‘‘spot’’) urine samples should be used to detect and monitor proteinuria in children and adults.

• It is usually not necessary to obtain a timed urine collection (overnight or 24-hour) for these evaluations in either children or adults.

• First morning specimens are preferred but random specimens are acceptable iffirst morning specimens are not available.

• In most cases screening with urine dipsticks is acceptable for detecting proteinuria. Patients with a positive dipstick test should undergo confirmation

of proteinuria by a quantitative measurement (ACR)within 3 months.

• Patients with two or more +ve quantitative tests temporally spaced by1to2weeks should be diagnosed as having persistent proteinuria and undergo furtherevaluation and management for ckd.

• Monitoring proteinuria in patients with chronic kidney disease should be performed using quantitative measurements.

KDOQI guidelines for screening of albuminuria

Kimmelstein wilson lesion

Light chain deposition disease Amyloidosis Nodules may occur in advanced stages of

subendothelial membranoproliferative or mesangiocapillary glomerulonephritis, also called membranoproliferative or mesangi- ocapillary glomerulonephritis type 1

Differential diagnosis based on HP appearance

a large majority of patients have albuminuria. Lack of albuminuria may occur in DN rarely but should prompt for search of alt. cause for altered RFT

the urinary sediment is characteristically unremarkable—i.e., there are usually no casts, no white blood cells, and no red blood cells—although red blood cells (2 to 15 /hpf) may be seen in up to 30% of patients , still active sediments are to be always suspected as a herald for other diseases

NDRD

Most common: interstitial nephritis>PIGN> memb.

Neph.>FSGS

the majority of patients have retinopathy before the onset of diabetic kidney disease. Lack of retinopathy in face of progressive renal injury must draw attention

as previously noted, the duration of the disease is also important; it is relatively unusual to diagnose diabetic nephropathy before 5 years of diabetes.

There are some novel markers for estimation of stage of ckd like cystatin based GFR, urinary glycoprotein, CYP24A1, MANBA, CUNB(gene

polymorphisms) but recent KDOQI guidelines have recommended that these are not required at present

to include in monitoring ckd pts.

eGFR Recommendation for monitoring of eGFR

All patients Yearly (rule out possibility of NDRD)

45-60 6 monthly

30-44 3 monthly

<30 Referal to nephrologist

<60 Evaluate for complications of CKD

According to Kdoqi guidelines every pt. s with stage3 & above should be evaluated for bone disease by routine measurements

of Ca2+ , PO43- , iPTH for evaluation of bone disease .

Microalbuminuria(30-299mg/d)

Lowering A1C to below or around 7% has been shown to reduce microvascular complications and, if implemented soon after the diagnosis of diabetes, is associated with long-term reduction in macrovascular disease (B)

Therefore, a reasonable A1C goal for many nonpregnant adults is <7% (B)

Providers might reasonably suggest more stringent A1C goals (such as <6.5%) for selected individual patients, if this can be achieved without significant hypoglycemia or other adverse effects of treatment (C)

Appropriate patients might include those with short duration of diabetes, long life expectancy, and no significant CVD (C)

ADA 2013 guideline recommendations regarding glycemic control & management of hypertension, use of antiplatelet therapy

Less stringent A1C goals (such as <8%) may be appropriate for patients with (B) History of severe hypoglycemia, limited life

expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions

• Consider aspirin therapy (75–162 mg/day) (C)As a primary prevention strategy in those with

type 1 or type 2 diabetes at increased cardiovascular risk (10-year risk >10%)

Includes most men >50 years of age or women >60 years of age who have at least one additional major risk factor

Family history of CVDHypertensionSmokingDyslipidemiaAlbuminuria

Use aspirin therapy (75–162 mg/day)◦ Secondary prevention strategy in those with

diabetes with a history of CVD (A) For patients with CVD and documented aspirin

allergy◦ Clopidogrel (75 mg/day) should be used (B)

Combination therapy with aspirin (75–162 mg/day) and clopidogrel (75 mg/day)◦ Reasonable for up to a year after an acute

coronary syndrome (B) Nonpregnant patient with modestly elevated (30-

299 mg/day) (C) or higher levels (≥300 mg/day) (A) of urinary albumin excretion◦ Use either ACE inhibitors or ARBs

Reduction of protein intake may improve measures of renal function (urine albumin excretion rate, GFR) (B)1. To 0.8–1.0 g/kg body wt per day in those

with diabetes, earlier stages of CKD2.To 0.8 g/kg body wt per day in later stagesof CKD

When ACE inhibitors, ARBs, or diuretics are used, monitor serum creatinine and potassium levels for the development of increased creatinine or changes in potassium (E)dm comp\1.docx

Reasonable to continue monitoring urine albumin excretion to assess both response to therapy and disease progression (E)

When estimated GFR is <60 mL/min/1.73 m2, evaluate and manage potential complications of CKD (E)

People with diabetes and hypertension should be treated to a systolic blood pressure goal of <140 mmHg (B)

Lower systolic targets, such as <130 mmHg, may be appropriate for certain individuals, such as younger patients, if it can be achieved without undue treatment burden (C)

Patients with diabetes should be treated to a diastolic blood pressure <80 mmHg (B)

For BP>120/80 lifestyle & dietary changes, if BP>140/80 drugs have to be introduced along with lifestyle changes & if ne essary multiple drugs have to be used to reach BP goal

In pregnant patients with diabetes and chronic hypertension, blood pressure target goals of 110–129/65–79 mmHg are suggested in interest of long-term maternal health and minimizing impaired fetal growth; ACE inhibitors, ARBs, contraindicated during pregnancy (E)

In the UKPDS, a reduction in BP from 154 to 144 mm Hg was associated with a

30% reduction in microalbuminuria

Diabetic Neuropathy

Patterns of Presentation of Diabetic Neuropathy

A pure or predominant motor polyneuropathy with few or no sensory

symptoms or signs is rarely due to diabetes and should trigger a search for alternative causes of weakness, such as motor neuron disease, primary muscle disease, spinal cord disease, or other

potentially treatable causes of peripheral neuropathy, such as chronic inflammatory

demyelinating polyneuropathy

Diabetic Neuropathy

Symmetric

1.Distal symmetric sensorimotor polyneuropathy

2. Autonomic neuropathy 3. Acute painful neuropathy 4. Hyperglycemic neuropathy

5. Treatment-induced neuropathy 6. Symmetric proximal lower extremity

neuropathy 7. CIDP

Asymmetric

Focal and multifocal

neuropathy 1. Cranial

neuropathy 2.Thoraco abdominal

neuropathy 3. Focal limb neuropathy 4. Diabetic amyotrophy

RISK FACTORS1.Hyperglycemia is now well established as a

risk factor in both patients with type 1 diabetes and patients with type 2 diabetes.

2.Age 3.Duration of diabetes,4. quality of metabolic control,5. height, 6. diabetic retinopathy,7. cigarette smoking, 8.high-density lipoprotein cholesterol, and 9.the presence of cardiovascular disease .

Most common type of Neuropathy in Dm pt.s as a whole is Distal symmetric sensorymotor neuropathy

Symmetric involvement in a length dependent manner giving rise to “glove & stocking” pattern, though an asymmetric pattern due to involvement of root or nerve m/b superimposed

Once developed this symm. Neuropathy is irreversible but may have intercurrent exacerbations with infections, depression

This variety is often associated with autonomic involvement In more severe cases, distal portions of thoracic intercostal

nerves are affected, producing an asymptomatic midline sensory loss in a teardrop distribution over the anterior thorax and abdomen that gradually spreads laterally . This thoracic and abdominal sensory loss differs from focal thoracic truncal radiculopathy in that it manifests as a painless, bilateral, symmetrical, and persistent form of neuropathy

Symmetric Peripheral Neuropathies

SFN involvement pattern Burning or lancinating

pain Hyperesthesia,

Paresthesia Loss of pain and

temperature sensation Dysautonomia Foot ulceration Loss of visceral pain Early in onset with

no/minimal Ncv abnormality

This pattern of isolated small fiber symptoms when involves U.limbs is known as “pseudosyringomyelia”

pattern

LFN involvement pattern Areflexia NCV test abnormal Loss of vibration & joint

position sense patients with

disproportionate large-fiber involvement may manifest muscle weakness, atrophy of the intrinsic foot muscles, and weakness of the extensors and flexors of the toes and ankles with foot drop. When these deficits are combined with proprioceptive deficit in the toes and feet, a “pseudotabetic” gait ataxia may result

Other symmetrical polyneuropathies

Features

Acute painful neuropathy •Diabetic neuropathic cachexia• Correlates poorly with severity of diabetes or presence of other diabetic microangiopathic complications.• Prognosis may be good in some patients, with gradual recovery over a period of months

Treatment induced neuropathy

•Starts with onset of t/t with insulin or OHA•Gradually improves over months, m/b reversible

Hyperglycemia induced neuropathy

•May occur in states of DKA/HONK •rapidly improve with control of hyperglycemia. •diffuse rather than distal distribution of paresthesias

Chronic inflammatory demyelinating neuropathy

• symmetric weakness with demyelination and conduction block on electromyography and demyelination on nerve biopsy. •The clinical progression is characteristically more rapid than that of diabetic polyneuropathy, weakness may be more prominent •there is often a satisfactory clinical response to immune modulation

This neuropathy typically occurs with a peak incidence in the fifth or sixth decade in patients with type 2 diabetes

The clinical picture is one of acute or subacute pain, weakness, and atrophy of the pelvic girdle and thigh musculature

Symptoms begin unilaterally but extend to the opposite extremity within weeks or months. Most patients have weight loss, and some appear cachectic.

subtle sensory symptoms and signs are commonly present. The knee jerk is nearly always reduced or absent on the affected side, whereas ankle jerks may be preserved unless compromised by a coexistent distal polyneuropathy.

The prognosis is usually good, with most patients showing resolution of pain followed later by gradual return of strength over a period of 6 to 18 months.

Diabetic amyotrophy

The finding of slow nerve-conduction velocities in femoral and distal nerves and of features of demyelination in nerve biopsy specimens in these patients indicates that “diabetic amyotrophy” is a form of diabetic neuropathy

Electromyography of patients with diabetic amyotrophy characteristically displays abundant fibrillations in the affected limb muscles and the paraspinal muscles. Nerve-conduction studies are unable to differentiate patients with diabetic amyotrophy from those with a generalized polyneuropathy.

Patients with unilateral and relatively focal pain and weakness seem to improve more rapidly and completely than patients with more widespread involvement.

CONTD.

Management of painful neuropathy

Fda apprvd

.

Intensive glycemic control Stop smoking & alcohol addiction Management of dyslipidemia α tocopherol can be used as antioxidant Aldose reductase inhibitors Supplementation with methylcobalamin

Other modalities of treatment

Autonomic neuropathy

Cardiovascular involvement

Orthostatic hypotension

g.i. involvemennt

Diabetic gastroparesis

Genitourinary involvement

Erectile dysfunction

Sudomotor

hyperhydrosis

Fludrocort &

Midodrine,

Erythromycin & domperi

done

PDE5 inh.

Topical anticholinergic & botulinu

m A

Rheumatological manifestations

Rheumatological manifestations of DM

Rheumatic syndromes uniquely or commonly

associated with diabetes mellitus

Adhesive capsulitis Shoulder-hand syndrome Diabetic hand syndrome

Dupuytren's disease Neuroarthropathy

Hyperostosis

Common rheumatological diseases associated with

diabetes

Osteoarthritis Gout and hyperuricemia Calcium pyrophosphate deposition arthropathy

Osteopenia Osteolysis of forefoot

Migratory osteolysis of hip & knee

The usual presentation is that of a patient with long-standing diabetes with complications present with an unilateral painless Jt. Swelling.

The foot is most commonly involved, followed in frequency by the ankle and knee. Rarely, upper extremity joints are involved.

Warmth and erythema may be present. When they are present, the differential diagnosis includes gout, pseudogout, osteomyelitis, or septic arthritis.

Typically, there are few systemic symptoms and no documented fever and leukocytosis.

“claw toe” arises as chronic motor neuropathy affects the small intrinsic muscles of the feet. When the larger muscles of the anterior tibial compartment are unopposed, subluxation of the proximal interphalangeal metatarsal joints may result, leading to a claw-toe appearance. This may lead to excessive pressure on the metatarsal heads and thus the tendency to form skin ulcers.

CHARCOT’S NEUROARTHROPATHY

phase manifestations

acute edema, localized warmth, erythema, and joint crepitus with range-of-motion examinationRadiographs are normal but MRI may suggest NA

coalescence skin temp. begins to equilibrate and jt. Crepitus diminishes. Plain radiographs will show resorption of osseous fragments and the laying down of new bone

Reconstruction / remodelling

This can eventually lead to a stable foot devoid of significant motion. Unfortunately, in many cases, the foot can be severely deformed, with obvious bony prominences susceptible to ulceration (e.g., the rocker-bottom foot)

Claw toe

Radiographically, there are destructive changes of the tarsometatarsal and metatarsophalangeal joints. Involvement of the tarsal and proximal metatarsal bones may occur and lead to osteoporosis, osteolysis, and bone fragmentation

Diagnostic criteria typically require the new bone formation to bridge four contiguous vertebral bodies in the absence of degenerative disc disease and the absence of inflammatory sacroiliac or facet joint changes

The condition is characterized by widespread new bone formation ,specifically the presence of new bone growth into the entheseal regions

Osseous changes are found around the acetabulum where fluffy new bone is formed, but similar changes around the knees and wrists have been documented.

DISH

Lateral view CXR

DISH changes are most characteristic in the thoracic spine, where uninterrupted

new bone may “flow” from one vertebra to another more prominent on the right side of the thoracic vertebra, thought to be a

consequence of the pressure effect of the left sided aorta. The presence of the

anterior longitudinal ligament over the anterior two thirds of the vertebral bodies dictates the distribution of the new bone

formation

SKIN INVOLVEMENT IN DIABETES

Patients with diabetes mellitus commonly suffer from a wide variety of cutaneous maladies. Estimates of the frequency of skin disease in people with diabetes range from 30% overall to 71% of patients with type 1 diabetes mellitus . While several skin conditions are specific to diabetes, most of them also occur in individuals without diabetes. The clinical manifestations and complications of skin disease are frequently more severe in the setting of diabetes

medicine\Joslin's Diabetes 14e.chm

ACANTHOSIS NIGRICANS:

Eruptive xanthoma: present as 1-4 mm papules on buttock and extensor

surface of extremities, indicates severe hypertriglyceridemia associated with

uncontrolled diabetes . Does’nt correlate with microvascular

complications

DIABETIC CHEIROPAT

HY:•Starts with

DIP of 5th finger gen.• Correlated with HbA1c

% & prevalence

of nephropath

y• Inversely correlated with insulin

therapy

Scleredema: Abrupt onset non pitting induration of skin. Skin

appears as smooth and waxy with dense dermal infiltration with

prominent follicular ostia , “peau –de- orange” appearance

Nephrogenic fibrosing

dermatopathy

Perforating dermatoses: umbillicated papules with

keratinized plaques, koebnerisation+ve

Fibroblast disorders

Sclerosing:

SclerodermaMorph

eaEosinophillic fasciti

slipodermatosclero

sis

Fibrosing:

Peyronies

disease

Dupuytrens contr.

Scleromucinosis

scleredema

Fibromucinosis:Scleromyxedema

Nefrogenic fibrosing dermatopathy

Toxic oil syndromeEosinophillia myalgia

syndrome

Fibrosclerosi

s:Juvenile hyaline

fibromatoses

Gingival fibromato

ses

Mucinosis:Pretibial myx.

Gen. myx.CTD

Degos disease

Necrobiosis lipoidica

Granuloma AnnulareGranuloma annulare (GA) is characterized by an annular configuration of flesh colored or pale red papule and plaques that occur in a localized or generalized (disseminated) pattern The lesions of GA may vary in size upto 5 cm . Localized GA is most characteristically located on the dorsa of the hands and feet. A single lesion is present in one half of patients with GA . The papules develop and enlarge slowly in a centrifugal fashion over a period of months to years. Generalized GA is characterized by a symmetrical eruption of hundreds of tiny papules, which can occur all over the body surface. Localized GA eventually undergoes spontaneous resolution usually within 2 years. Lesions often recur at the same site.

Diabetic dermopathy: small atrophied pink to brown skin

lesions over lower limbs which disappear on own

Bullous diabeticorum : painless, non pruritic bullae over lower limbs arising in

normal skin abruptly and heal spontaneously gen. without scarring

Gastrointestinal complications

DIARRHOEA in DIABETES

Delayed emptying of solid or nutrient meals is found in up to 50% of patients with type 1 diabetes and in 30% of patients with type 2 diabetes . However, the degree of delay for various constituents of food, i.e., liquids, digestible solids, and indigestible solids, is not the same. Simultaneous assessment of gastric emptying of liquids and digestible solids using dual markers (99Tc-labeled solid phase and 111In-labeled liquid phase) showed that indigestible solids are particularly delayed in persons with diabetes.

Diabetic Gastropathy

Patients have symptoms of anorexia, early satiety, and postprandial abdominal fullness and discomfort that resemble simple dyspepsia.

Vomiting of old food, however, is indicative of gastroparesis. Nausea and vomiting are common when gastric distention is associated with obstruction and vigorous gastric contractions.

In some patients, atonic dilation of the stomach, even when massive, may not be associated with nausea or vomiting.

Nausea and reflex vomiting may be elicited by the stimulation of the gastric afferents carried via vagal and sympathetic nerves to the vomiting center in the brainstem.

If gastric stasis and distention are primary causes of nausea and vomiting in diabetic gastroparesis, these symptoms should respond to gastric decompression by either vomiting or by insertion of a nasogastric tube.

Symptomatic diabetic gastropathy

Delayed emptying

Excitatory motor

neuropathy

Inhibitory motor

neuropathy

Normal gastric

emptying

Sensory hyperalges

ia

Fast gastric emptying

Fundal inhibitory

motor neuropathy

ProkineticsAvoid anti-Ach

Anti-Ach

Antiemeticsclonidi

ne

Anti- Ach

Erythromycin at a dose of 3 mg/kg bw i.v. every 8 hours can accelerate gastric emptying . When oral intake is resumed, treatment with oral 250 mg erythromycin t.i.d. for 2 weeks is worthwhile. Thereafter, the prokinetic effects of erythromycin are limited by Tachyphylaxis. Anecdotal findings suggest that erythromycin may be effective if courses are separated by a drug - free period (e.g. lasting 2 weeks).

Decompression of stomach using endoscopy with dislodging of bezoar if any.

Insulin theapy reqd.

Diabetic Gastroparesis Treatment

Others include:PTB test +veTraumatic foot woundUlceration>30 daysPrevious lower limb amputation

PEDIS: Perfusion, Extent (size), Depth (tissue loss), Infection, Sensation (neuropathy)

Classification system:

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