Rheumatic manifestations of DM are the commonest of all described endocrine rheumatic manifestations. These manifestations have generally been under-recognized and poorly treated, compared to the other complications, such as neuropathy, nephropathy and retinopathy. These manifestations, involve not only the joints, but also the soft tissues and the bones. In 2004, the National Health Interview Survey in US determined that 58%of diabetic patients will develop functional disability.The percentage of diabetic patients with functional disability will increase as the number of diabetic patients increases.Recent data reveals that the prevalence of rheumatic manifestations in the hands and shoulders in patientswith type 1 or type 2 diabetes is 30%.3These manifestations are closely linked to age,4 prolonged disease duration,5,6 and vascular complications like retinopathy.7

1. Rheumatic Manifestations in Diabetes Mellitus Patients

2. Review Article
Rheumatic manifestations in diabetes mellitus patients
Meghnathi Bhowmik a
, Sundeep Upadhyaya b,
*
a
DNB Rheumatology Resident, Indraprastha Apollo Hospitals, New Delhi, India
b
Senior Consultant, Department of Rheumatology, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi, India
a r t i c l e i n f o
Article history:
Received 10 May 2013
Accepted 15 May 2013
Available online 6 June 2013
Keywords:
Diabetes mellitus
Rheumatic manifestations
Limited joint mobility
a b s t r a c t
The incidence of diabetes is increasing in most countries of the world and is a major public
health problem. Diabetology and rheumatology are two medical specialties that have much
in common, including the immuno-pathogenesis (Auto-immune for example) and share
many features. Diabetes affects the connective tissues in many ways and causes alter-
ations in the peri-articular and the musculo-skeletal systems. Patho-genetic mechanisms
for some of these conditions have not been studied and understood completely. Some of
them are considered intrinsic complications of diabetes; while in others, diabetes seems to
be a mere predisposition. In most cases, these manifestations are associated with func-
tional disability and pain, affecting the quality of life of the diabetic patient. The man-
agement of such clinical conditions requires multidisciplinary team effort to diagnose
them, since early diagnosis leads to a better outcome. This article reviews some clinical,
diagnostic, therapeutic and epidemiological aspects of these conditions.
Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
1. Introduction
Diabetes mellitus (DM) is a chronic metabolic condition char-
acterized by persistent hyperglycemia with resultant
morbidity and mortality related primarily to its associated
micro vascular and macro-vascular complications, which
share the phenotype of hyperglycemia.1
Factors contributing
to hyperglycemia include reduced insulin secretion, decreased
glucose utilization, and increased glucose production. The
metabolic dysregulation associated with DM causes secondary
pathophysiologic changes in multiple-organ systems. The two
broad categories of DM are designated as type 1 and type 2.
Type 1 DM is the result of complete or near-total insulin defi-
ciency. Type 2 DM is a heterogenous group of disorders char-
acterized by variable degrees of insulin resistance, impaired
insulin secretion, and increased glucose production.1
Rheumatic manifestations of DM are the commonest of all
described endocrine rheumatic manifestations. These mani
festations have generally been under-recognized and poorly
treated, compared to the other complications, such as neurop-
athy, nephropathy and retinopathy. These manifestations,
involve not only the joints, but also the soft tissues and the
bones. In 2004, the National Health Interview Survey in US
determined that 58% of diabetic patients will develop functional
disability.2
The percentage of diabetic patients with functional
disability will increase as the number of diabetic patients in-
creases. Recent data reveals that the prevalence of rheumatic
manifestations in the hands and shoulders in patients with type
1 or type 2 diabetes is 30%.3
These manifestations are closely
linked to age,4
prolonged disease duration,5,6
and vascular
complications like retinopathy.7
In contrast to various vascular complications of diabetes
mellitus (DM) that are life threatening, rheumatic manifesta-
tions lead to considerable morbidity. The micro vascular and
macro-vascular complications of DM have been studied
extensively, as opposed to the rheumatic complications which
* Corresponding author. Tel.: þ91 9818359408.
E-mail address: sundeepupadhyaya@hotmail.com (S. Upadhyaya).
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/apme
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 2 6 e1 3 3
0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.apme.2013.05.007

3. have been hitherto neglected. The data regarding the rheu-
matic and musculoskeletal manifestations are primarily
based on observational studies. Many authors have made an
attempt to classify rheumatic manifestations of DM in various
ways.3,8,9
The only proven association that has been reported to
occur exclusively among DM patients is diabetic muscle
infarction (DMI). The other rheumatic manifestations of DM
are also commonly found in various other diseases and are
not unique to DM. These manifestations are as follows: Syn-
dromes of limited joint mobility e limited joint mobility, dia-
betic hand syndrome (diabetic cheiroarthropathy/stiff hand
syndrome), adhesive capsulitis (frozen shoulder), trigger
finger (flexor tenosynovitis), dupuytren’s contractures, calcific
periarthritis, osteoarthritis; diffuse idiopathic skeletal hyper-
ostosis (DISH); neuropathic arthropathy (Charcot joints, dia-
betic osteoarthropathy), carpal tunnel syndrome, gout,
diabetic amyotrophy, reflex sympathetic dystrophy.10
The table below denotes the potential pathophysiologic
relationships that might be linked to these conditions (modi-
fied from “Rheumatic manifestations of diabetes mellitus.
Dorota Lebiedz-Odrebina, Jonathan Kay. Rheum Dis Clin N Am.
36(2010):681e699”).
2. Diabetic muscle infarction (DMI)
DMI is rare complication of DM, Angerwall et al first described
it as “Tumoriform focal muscular degeneration” in two dia-
betic patients way back in 1965.11
Since then many cases have
been reported and more than half of these patients had type 1
DM with a mean duration of 15 years.12,13
It presents with
acute onset of muscle pain and swelling. 80% of cases have
thigh muscle involvement, however isolated calf muscle,
simultaneous thigh and calf muscle and upper extremity
muscle involvement have also been described. A palpable
mass has also been reported. Recurrence in the same or
different group of muscle has been observed. The mean
mortality rate is 10% with DMI within 2 years of the initial
diagnosis, wherein mortality were predominantly due to the
macro-vascular complications.14
The typical clinical presentation and characteristic find-
ings on radiology, suggests the diagnosis of DMI. There is no
specific laboratory marker for DMI. Serum creatine kinase (CK)
levels were elevated in slightly fewer than half of those pa-
tients for whom a level was reported. MRI shows typically
isointense swelling on T1 weighted images and diffuse
heterogenous hyper intensity on T2 weighted images of the
affected muscle with surrounding subfascial and subcutane-
ous edema. Gadolinium contrast is not essential but if used
will show non-enhancing areas surrounded by peripheral
enhancement.15
Muscle biopsy is reserved for patients in
whom diagnosis is uncertain, with atypical presentation and
for those who do not improve with anti platelet or anti-
inflammatory therapy.16
Typical biopsy findings will reveal
muscle fiber necrosis, edema, phagocytosis of necrotic fibers,
granulation tissue and collagen deposition.
Patho-physiologically it has been suggested that reperfu-
sion injury after muscle ischemia resulted in muscle infarc-
tion, as almost all patients with DMI had microangiopathic
complications of DM. Also the theory of endothelial dysfunc-
tion in DM and the hypercoagulability resulting from alter-
nation of the coagulation- fibrinolytic system has been
proposed.17
But, due to the rarity of the condition, the asso-
ciation between antiphospholipid antibody syndrome and
DMI has not been proven.18
Differential diagnosis is made with myositis, venous
thrombosis, tumor and diabetic amyotrophy, adverse effect of
simvastatin, ruptured Baker’s cyst. The recommended man-
agement of this condition is symptomatic, with pain relief and
short-term immobilization as necessary. This condition tends
to resolve in most cases over a period of a few weeks. Opti-
mizing diabetic control is of paramount importance.19
Medical
therapy with antiplatelets and/or anti-inflammatory drugs is
recommended, but due to infrequent occurrence of this dis-
ease, there has not been any randomized controlled trial.
3. Upper limb manifestations
It mainly involves upper limb musculoskeletal structures and
it appears to be associated with the duration of diabetes, poor
metabolic control and presence of micro vascular complica-
tions.20
Each one of the following is explained as under:
“Stiff-hand syndrome” or Diabetic cheiroarthropathy
(derived from greek word “cheiros”, which means hand) is
characterized by hardened and stiff skin of the fingers and
palm and painless limitation of mobility of the small joints of
the hands. The prevalence is 8%e50% among patients with
diabetes, while only 4%e20% among individuals without
DM.21,22
Diabetic cheiroarthropathy is primarily a clinical
diagnosis and the imaging findings are nonspecific.23
There
two clinical signs which are indicative of the diagnosis are 1)
The prayer sign, in which, the patient is unable to approxi-
mate the palmar surface of the fingers when raising the hands
as if in prayer and 2) The tabletop sign, in which, when the
patient is asked to lay the palms flat on the tabletop, he is
unable to touch the palmar surface of the fingers to the table.
Limited mobility should be confirmed by demonstration of
loss of passive extension of the proximal interphalangeal and
metacarpophalangeal joints, which are less than 180
and less
Conditions
unique
to DM
Conditions more
frequent in DM
Conditions sharing
risk factors of DM
and metabolic
syndrome
Diabetic
muscle
Infarction
Limited joint mobility Diffuse Idiopathic
Skeletal Hyperostosis
(DISH)
Neuropathic arthropathy Gout
Stiff/Diabetic hand
syndrome
Osteoarthritis
Dupuytren’s contracture
Stenosing flexor
tenosynovitis/Trigger finger
Frozen shoulder/Shoulder
adhesive capsulitis
Calcific shoulder
periarthritis
Carpal tunnel syndrome
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 2 6 e1 3 3 127

4. than 60
respectively. The ultrasound findings of diabetic
cheiroarthropathy are the thickening of the flexor tendon
sheaths and subcutaneous tissues,23
and MRI shows the
thickening and enhancement of the flexor tendon sheaths.24
The early recognition of this disease is important since it
can be reversed by treatment and is a marker of other diabetic
micro-vascular complications. Rosenbloom et al25
showed in
his study that the prevalence of proteinuria and retinopathy
was of 11% in diabetic patients without diabetic cheiroarthr-
opathy versus 50% in diabetic patients with diabetic cheir-
oarthropathy. Therapeutic measures include non-steroidal
ant inflammatory drugs, physiotherapy and better glycemic
control. Surgery might be necessary to reduce pressure on
trapped nerves and improve sensation and discomfort,
although some residual problems may persist despite surgery.
Sorbinil, which was once used for treating cheiroarthropathy,
is no longer used due to side effects.
Trigger finger alsoknown asStenosingFlexor Tenosynovitis
is caused by the inflammation, fibrosis and thickening of
tendon sheaths, usually over a bony prominence or where it
crossed over as a pulley. It causes finger blocking in flexion with
the active extension failure. The middle and index fingers are
the most commonly involved. The classic presentation of
popping and locking of a trigger finger is usually sufficient for
making the diagnosis. Imaging for diagnostic purpose is not
recommended, with X-rays considered unnecessary in patients
without a history of inflammatory disease or trauma.26
The
prevalence of trigger finger ranges from 5% to 36% among pa-
tients with type 1 and 2 DM as compared with 2% in the general
population.27,28
The incidence of these disorders in diabetic
subjects has a stronger association with actual duration of the
diseaseand not with the glycemiccontrol.29
Treatment consists
in the modification of the routine activities of daily living in
order to avoid the triggering of the digits, non-steroidal anti-
inflammatory drugs, splinting, corticosteroid injection into
the tendon sheath and surgical release.30
Steroid use can again
disturb the glycemic control and multiple digits involvement
warrants surgical release for better relief of symptoms.
Dupuytren’s contracture (DC) is characterized by the
thickening and shortening of the palmar fascia, palmer or
digital nodules, causing a contracture in flexion of the affected
finger. In nondiabetic patients, the most affected fingers are
the ring and the little finger, but in individuals with DM, DC
mainly affect middle and ring fingers and the hand involve-
ment is frequently bilateral.31
The prevalence of DC in dia-
betes ranges between 20% and 63%, which is higher than
among subjects without diabetes by about 13%.6,21
DC is
associated with disease duration, long-term poor metabolic
and glycemic control and presence of micro vascular com-
plications.32
Diabetic cheiroarthropathy and DC may coexist
in the same patient.21
Treatment of DC includes topical
intralesional steroid injection, a good glycemic control,
physiotherapy, and for the refractory cases, surgery. Collage-
nase injection in the palmar fascia has been used recently,
and there was significant reduction in fixed flexion contrac-
tures as well as a marked improvement in range of motion.
Generalized hand stiffness has been observed after surgical
intervention.33
Therefore, collagenase injection, sourced from
clostridium histolyticum, is a good alternative to the surgical
treatment even though it is expensive.
4. Adhesive capsulitis of the shoulder
(Frozen shoulder syndrome, shoulder
periarthritis)
It is a condition characterized by an insidious and progressive
loss of active and passive mobility of glenohumeral joint,
presumably due to the capsular contraction,34
resulting in
pain and progressive restriction on abduction and external
rotation. In 1934, Codman first coined the term Frozen Shoulder;
later on Naviaser framed the term Adhesive Capsulitis to
describe the same condition. Natural course of the disease can
be divided into 3 phases: Pain, Stiffness and Recovery. This
condition is found in around 11e30% in diabetic patients,
which is considerably greater than in nondiabetics.21
Longer
duration of the disease and treatment with insulin was
associated with a larger percentage of shoulder calcification.35
The diagnosis of adhesive capsulitis is often one of exclusion.
Early in the disease process, adhesive capsulitis may clinically
appear similar to other shoulder conditions such as major
trauma, rotator cuff tear, rotator cuff contusion, labral tear,
bone contusion, subacromial bursitis, cervical or peripheral
neuropathy. If a history of these other conditions is negative
and if radiographs do not demonstrate osteoarthritis, then it
could be adhesive capsulitis.36
In idiopathic adhesive capsu-
litis, the joint capsule is thickened and adheres to the head of
the humerus, thereby reducing the glenohumeral joint vol-
ume. The treatment includes analgesics, physical therapy,
intra-articular corticosteroid injection into the glenohumeral
joint and subacromial bursa37
and kineto-therapy. Arthro-
scopic capsular release is used for refractory adhesive shoul-
der capsulitis and is preferred to open surgical release due to
shorter length of postoperative recovery.
5. Neuropathic osteoarthropathy (Charcot
osteoarthropathy, diabetic osteoarthropathy)
It is characterized in its early stages by acute inflammation
leading to bone and joint fractures, dislocation, instability and
gross deformities.38
It is a progressive and degenerative
arthropathy, which is associated with variety of diseases
involving neuropathy. In patients with diabetes, Charcot
osteoarthropathy is associated with a longstanding duration
of diabetes and peripheral neuropathy. The estimated preva-
lence among diabetic patients varies in the range of
0.08e13%.39
It most commonly involves the ankle, tarsome-
tatarsal, metatarsophalangeal and toe interphalangeal joints.
The disease is staged as below:
Stage 0 e (Inflammation), is characterized by erythema,
edema and heat but there are no structural changes visible on
plain X-ray.40
Stage 1 (Development) is characterized by bone resorption,
bone fragmentation, and joint dislocation. The swelling,
warmth, and redness persist, but there are also radiographic
changes such as evidence of debris formation at the articular
margins, osseous fragmentation, and joint disruption.
Stage 2 (Coalescence) involves bony consolidation, osteo-
sclerosis, and fusion after bony destruction. Absorption of
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 2 6 e1 3 3128

5. small bone fragments, fusion of joints, and sclerosis of the
bone are noticeable.
Stage 3 e (Reconstruction of the damaged joints and bone)
Healing and new bone formation occurs. Decrease in the
sclerosis and bony remodeling signify that the deformity
(subluxation, incongruity and dislocation) is permanent.41
It is important that the patient is put on early immobili-
zation and hence imaging studies should be obtained in the
early disease course itself. Radiological imaging aspects are
important in diagnosing Charcot neuroarthropathy, however,
they are not present in patients with stage 0 disease, for
which, magnetic resonance imaging and 111
ln-WBC scans are
used. However, the use of MRI offers the highest diagnostic
accuracy.42
It typically reveals ligamentous disruption, joint
deformity, center of signal enhancement within joints and the
subchondral bone.43
The goal of the treatment for acute or
quiescent Charcot neuroarthropathy should be to maintain
structural stability of the foot and ankle, to prevent skin ul-
ceration, and to preserve the plantigrade shape of the foot so
that prescription footwear can be used. Bisphosphonates can
significantly reduce the levels of the bone turnover, temper-
ature and pain, but the clinical benefit such as an earlier re-
turn to ambulation or radiographic improvement is weak at
best. Surgery is reserved for severe ankle and midfoot de-
formities that are susceptible to skin ulceration and that make
braces and orthotic devices difficult to use.44
6. Carpal tunnel syndrome (CTS)
It is a painful neuropathic disorder caused by the compression
of the median nerve between the carpal ligament and other
surrounding structures within the carpal tunnel. It is a form of
entrapmentneuropathy.Ithasbeenreportedinupto20percent
of diabetic patients, but the incidence rises to 75 percent in
those with limited joint mobility.45
CTS may be more common
in those with prediabetes.46
The presentation typically includes
pain and paresthesias of the thumb, index, and middle finger
and along the medial aspect of the ring finger. This also occa-
sionally is characterized by proximal irradiation, the O´ shaking
signO´ in which, there is disappearance of the symptoms after
vigorous flapping of the hands, the Tinel sign, wherein, per-
cussion ofthemedian nervetriggerspainresemblinganelectric
sensation along the course of the median nerve and the Phalen
test (wrist dorsiflexion) e the patient has to hold the hands
against each other in full palmar flexion, paresthesias begin-
ning between 30 and 120 s in this static position. One essential
parameter of the motor or sensory deficit is a pathological
change in motor or sensory conduction velocity evaluated with
the aid of electromyography. Treatment is either conservative
or surgical. The conservative therapy includes splinting, ste-
roids, activity modification, non-steroidal anti-inflammatory
drugs and vitamin B6 supplementation. Of the conservative
approaches, only splinting47
and steroids are supported with
evidence.48
Surgicalreleaseofthe carpaltunnelistypicallyused
in patients who fail to achieve an adequate relief with conser-
vative managements and for those with moderate to severe
symptoms.49
However, in diabetic patient the recuperation
after the surgical intervention is slower and less important.50
7. Diabetic amyotrophy
It is a condition occurring in type I and II DM, in which patients
develop severe aching or burning and lancinating pain in the
hip and thigh, followed by a weakness and wasting of the
thigh muscle and significant weight loss. It is associated with
poor glycemic control.51
The results of the electro-diagnostic
studies, which are often met, are consistent with the pres-
ence of a neurogenic lesion that involves lumbo-sacral roots,
plexus and peripheral nerves.52
This condition is most likely
caused by inflammatory, immune-mediated vascular radi-
culoplexopathy.53,54
The diagnosis is based on a clinical pre-
sentation, the presence of diabetes and neural studies. Good
functional recovery is expected within 2e3 years. Occasional
relapses can occur. Medical therapy includes immunosup-
pressive agents, such as cyclophosphamide and methyl-
prednisolone. Kifoyle et al studied the therapy with pulsed
methyl-prednisolone and noted a significant improvement in
pain and weakness in the majority of the patients.55
Although
these initial studies are encouraging, a Cochrane review
concluded that no evidence from randomized clinical trials
supports the use of immunotherapy treatment in lumbo-
sacral plexopathy.56
The treatment also consists in a good
glycemic control, physical therapy and occupational therapy.
8. Reflex sympathetic dystrophy and
complex regional pain syndrome (CRPS)
Reflex sympathetic dystrophy is a component of CRPS, which
is a neuropathic pain disorder with significant autonomic
features. CRPS is divided into CRPSeI (reflex sympathetic
dystrophy) and CRPS II (causalgia), which represent the
absence or the presence of documented nerve injury respec-
tively. CPRS I typically develops after a minor tissue trauma or
bone fracture and is associated with a predisposing condi-
tion.57
Predisposing conditions include DM and other endo-
crine disorders like hyperthyroidism, hyperparathyroidism
and metabolic disease such as type IV hyperlipidemia.58
It
presents with classic neuropathic pain characteristics that
includes allodynia, intense burning pain and hyperalgesia.
There is also local edema and changes suggestive of auto-
nomic involvement like altered sweating, skin color and skin
temperature in the affected region.
The International Association for Study of Pain (IASP)59
listed the diagnostic criteria for CRPS I. IASP defines CRSP 1
as I¨A variety of painful conditions following injury which ap-
pears regionally having a distal predominance of abnormal
findings, exceeding in both magnitude and duration the ex-
pected clinical course of the inciting event and often resulting
in significant impairment of motor function, and showing
variable progression over timeO´ . (Other 2 criteria sets
described below also use this definition.)
IASP 1994 consensus criteria includes the following:
1. Type 1 is a syndrome that develops after an initiating
noxious event.
2. Spontaneous occurrence of pain in the absence of an
external stimulus, allodynia (pain due to a mechanical or
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 2 6 e1 3 3 129

6. thermal stimulus that normally does not provoke pain), or
hyperalgesia (exaggerated response to a stimulus that is
normally painful) that is not limited to the territory of a
single peripheral nerve, and is disproportionate to the
inciting event.
3. There is or has been evidence of edema, skin blood flow
abnormality, or abnormal sudomotor (sweating) activity in
the region of the pain since the inciting event.
4. This diagnosis is excluded by the existence of conditions
that would otherwise account for the degree of pain and
dysfunction.
Criteria 2, 3 and 4 are necessary for a diagnosis of CRPS
type 1.
Bruehl60
and Veldman61
improved upon these criteria.
Bruehl criteria are as follows:
1. Continuing pain disproportionate to any inciting event.
2. Patient must report at least 1 symptom in each of the 4
following categories:
a) Sensory: reports of hyperesthesia
b) Vasomotor: reports of temperature asymmetry or skin
color changes or skin color asymmetry
c) Sudomotor/edema: reports of edema or sweating
changes or sweating asymmetry
d) Motor/trophic: reports of decreased range of motion or
motor dysfunction (weakness, tremor, dystonia) or
trophic changes (hair, nail, skin)
3. Must display at least 1 sign in 2 or more of the following
categories:
e) Sensory: evidence of hyperalgesia (to pinprick) or
allodynia (to light touch)
f) Vasomotor: evidence of temperature asymmetry or
skin color changes or asymmetry
g) Sudomotor/edema: evidence of edema or sweating
changes or sweating asymmetry
h) Motor/trophic: evidence of decreased range of motion
or motor dysfunction (weakness, tremor, dystonia) or
trophic changes (hair, nail, skin)
Veldman criteria are as follows:
1. Presence of 4 out of 5 symptoms:
a) Diffuse pain during exercise
b) Temperature differences between affected and unaf-
fected extremity
c) Color differences between affected and unaffected
extremity
d) Volume differences between affected and unaffected
extremity
e) Limitations in active range of movement of the
affected extremity
2. Occurrence or increase of symptoms during or after use
3. Symptoms in an area larger than the area of the primary
injury
While IASP criteria are non-specified, possibly not as
reproducible as Bruehl’s or Veldman’s criteria, they are cited
more widely in the literature, including treatment trials.62
The
treatment includes medical therapy, invasive procedures and
paramedical therapy. The medical therapy consists in analge-
sics, corticosteroids, oral muscle relaxants, bisphosphonates,
and calcium-channel blockers. Invasive treatment consists in
intravenous sympathetic blockade percutaneous sympathetic
blockade, surgical sympathectomy, spinal cord stimulation,
and amputation. Other paramedical interventions include
physiotherapy, occupational therapy, and psychological treat-
ment.63
Sympathetic nerve block seems to be unhelpful.
9. Diffuse idiopathic skeletal hyperostosis
(DISH) (Forestier’ disease)
It is characteristically associated with ligamentous calcifica-
tion and ossification of the ligaments and entheses. It typically
has a predilection for anterolateral aspect of the spinal col-
umn, sometimes leading to bony ankylosis. It has been
demonstrated that DISH is associated with diabetes mellitus
particularly with Type 2 DM. Hyperinsulinemia has been
suggested to play the pathophysiologic role and serves as a
link between DM, obesity and development of vertebral hy-
perostosis. Several other metabolic disturbances and
concomitant diseases have been suggested to be associated
with DISH including obesity, increased waist circumference,
hypertension, dyslipidemia, hyperuricaemia and the meta-
bolic syndrome.64e67
In one study, patients with DISH and
those with osteoarthritis had elevated levels of insulin and
growth hormone; however, the level of IGF-1 was higher in
patients with DISH than in those with osteoarthritis.68
Often
an asymptomatic condition, DISH, however may have
numerous clinical symptoms including pain, stiffness, limited
range of spinal motion and an increased susceptibility to un-
stable spinal fractures after trivial trauma. Cervical and lum-
bar segments of the spine are also frequently affected by DISH,
and clinical manifestations include dysphagia and airway
obstruction at cervical levels and radiculopathy.
The diagnosis of DISH is based mainly on radiologic fea-
tures. Radiographic criteria for the diagnosis proposed by
Resnick and Niwayama require the involvement of at least four
contiguous thoracic vertebral segments, typically described as
I¨flowing osteophytesO´ along the anterolateral aspects of those
four vertebrae, preservation of intervertebral disc spaces and
the absence of apophyseal joint degeneration or sacroiliac in-
flammatory changes.69
Later, Utsinger, in 1985 proposed a
revised diagnostic criterion that incorporated the involvement
of peripheral entheses. He suggested that symmetric periph-
eral enthesopathy and continuous ossification along with the
anterolateral aspect of the 2 or more contiguous vertebral
bodies support a probable diagnosis of DISH.70
Treatment is
generally symptomatic including NSAIDs, heat application,
analgesics,andphysiotherapy. Controlofassociatedmetabolic
disorders, may reduce the morbidities associated with these
disorders, may retard future cardiovascular disease and
possibly slow down the progression of soft tissue ossification.
Therapeutic interventions should also aim at a reduction of
insulin secretion and insulin resistance. Stretching and
strengthening exercises brings about an improvement in spi-
nal mobility but not in the pain associated with it.
Osteoporosis can either occur as a direct consequence of
the disease, or it can be treatment manifestation in diabetic
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 2 6 e1 3 3130

7. patients. The study done by of Nord Torndelag et al in Norway
showed significant increase of hip fracture among women
with type I DM compared with non-diabetic women (relative
risk ¼ 6.9, CI ¼ 2.2e21.6).71
Regarding type II diabetes, this
association is not very clear. It was demonstrated that the
thiazolidinediones, an oral hypoglycemic agent, causes a
reduction in bone mass and increase in risk to fracture.72
10. Gout
Monosodium urate crystals deposition in the joints due to
hyperuricemia results in gout. Several cross sectional studies
have studied and proved the co-relation between metabolic
syndrome, hyperuricemia and gout. The majority of patients
under excrete uric acid through the kidney, which results in
hyperuricemia and a small proportion of patients over pro-
duce uric acid. However the exact pathophysiological mech-
anism needs to be studied further. Strict glycemic control
would definitely go a long way in better control of the disease.
11. Osteoarthritis (OA)
OA is characterized by chronic joint pain and swelling due to
degenerative process. It usually involves the knee joint, hips,
spine and the first carpometacarpal joints.
OA has been said to be more common in diabetics with an
earlier age of onset as compared to nondiabetic, with more
severe joint destruction. There is often joint crepitus on ex-
amination and effusion or both. X-ray typically shows reduced
joint space, subchondral cyst and ostophytes. However
further studies are warranted due to scarcity of large database
studies.
12. Epidemiology of diabetes the India
scenario
Diabetes is pandemic in both developed and developing
countries. In 2000, there were an estimated 175 million people
with diabetes worldwide and by 2030; the projected estimate
of diabetes is 354 million.73
The greatest relative rise is pre-
dicted in the developing countries of the Middle Eastern
Crescent, Sub-Saharan Africa and the Indian subcontinent. By
the year 2030, over 85 percent of the world’s diabetic patients
will be in developing countries. Talking about India alone, the
prevalence of diabetes is expected to increase from
31.7 million in 2000e79.4 million in 2030.73
These estimates
are valid if the prevalence of obesity continues to remain the
same as it is at present. However, since the incidence of
obesity is rising at a rapid rate in developed as well as in the
developing countries, these projections could well be a gross
underestimation.
In the past 20 years, the rates of obesity have increased by a
multiple of three in developing countries the people have
adopted a Western lifestyle with over consumption of cheap,
energy dense food and decreased physical activity. The rela-
tionship between obesity and poverty is complex: being poor
in one of the world’s poorest countries is associated with
underweight and malnutrition, whereas being poor in a mid-
income country is associated with an increased risk of
obesity. A developing country like India faces the paradox of
families, in which the children are underweight and the adults
are overweight. This combination has been attributed by
some people to intrauterine growth retardation resulting in
low birth weight, which apparently confers a predisposition to
obesity later in life through the acquisition of a hefty pheno-
type that, when accompanied by rapid childhood weight gain,
is conducive to the development of insulin resistance and
metabolic syndrome.74
A national survey of diabetes conducted in six major cities
in India in the year 2000 has shown that the prevalence of
diabetes in urban Indian adults was 12.1%.75
The onset of
diabetes among Indians is about a decade earlier than their
western counterparts and this has been noted in Asian In-
dians in several studies.76
In the national survey 54.1% of
diabetes developed it in the most productive years of their
lives i.e. before the age of 50 years and they also had a higher
risk of developing chronic complications of diabetes.76,77
The
prevalence of type 2 diabetes is 4e6 times higher in the urban
areas as compared to rural areas. The prevalence of impaired
glucose tolerance (IGT) in the rural population is also high at
7e8%, which indicates presence of a genetic basis for type 2
diabetes in ethnic Indian population.78
This increasing prevalence will inevitably result in an
increasing prevalence of the diabetes and associated condi-
tions including rheumatic manifestations.
13. Pathophysiology
Insulin resistance is a feature common to both type 2 DM and
the metabolic syndrome. The onset of insulin resistance is
heralded by postprandial hyperinsulinemia, followed by
fasting hyperinsulinemia and, ultimately, hyperglycemia.
The pathophysiology of these rheumatic disorders in dia-
betic patients is not clear. It could be associated with con-
nective tissue disorders, such as the formation of abnormally
glycosylated end products or the impaired degradation of
byproducts, it could be indirectly related to the vasculopathy
and neuropathy commonly complicating the primary disease,
or finally, it could be attributed to a combination of factors.
Studies comparing the incidence of specific musculoskeletal
disorders between type 1 and type 2 diabetic patients did not
show significant differences between the two groups, despite
the substantial difference in the mean age of the patients in
the two groups. Most rheumatic complications seem to be
associated with the duration of DM and appear in diabetic
patients of younger age than their counterparts in the general
population. Rheumatic disorders in these patients are prob-
ably related to the long-term glycemic control of the diabetes.
However, no direct association could be proven with the
metabolic control of the disease. Keeping in mind the alarm-
ing rate at which the number of diabetic patients are on the
rise in a developing country like India, a low threshold for
recognizing and treating such conditions early on in the dis-
ease course will go a long way in changing the overall outcome
and also help in reducing a lot the morbidity associated with
diabetes.
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 1 2 6 e1 3 3 131

8. 14. Conclusion
Rheumatic manifestations in diabetes are primarily non-
inflammatory. The identification of characteristic rheumato-
logic manifestations of diabetes early may facilitate its man-
agement accordingly; on the other hand, presence of rheumatic
manifestations in a diabetic patient can serve as a marker for
poor glycemic control and presence of micro vascular compli-
cations like diabetic retinopathy. Most common are the upper
limb syndromes. It has been shown that limited joint mobility
and dupuytren contractures are more common than other
rheumatic manifestations.
Conflicts of interest
All authors have none to declare.
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