Pathologic features of diabetic thick skin

Hanna, Wedad; Friesen, Dianne; Bombardier, C; Gladman, Dafna; Hanna, Amir

doi:10.1016/s0190-9622(87)70072-3

Cited by 77 publications

(26 citation statements)

References 19 publications

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“…Hyalinised and disorganised collagen can be found in thick diabetic skin (defined as an increase in whole skin thickness). Diabetic patients with and without thick skin showed a predominance of large collagen fibres in biopsies evaluated with electron microscopy [29]. Furthermore, enhanced collagen synthesis by cultured skin fibroblasts from Type 1 diabetic patients with diabetic nephropathy has been reported [30], which seems to agree with our results on tissue sections.…”

Section: Discussionsupporting

confidence: 92%

Extracellular matrix in human diabetic nephropathy: reduced expression of heparan sulphate in skin basement membrane

et al. 1998

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In Type 1 diabetes mellitus all tissues are exposed to hyperglycaemia, but only a subset (30±40 %) of diabetic patients develop diabetic kidney disease [1,2]. According to the Steno hypothesis, albuminuria and associated complications result from a genetic polymorphism of enzymes involved in the metabolism of heparan sulphate proteoglycans (HSPG) [2].HSPG consists of a core protein with heparan sulphate (HS) glycosaminoglycan side chains. Sulphate Diabetologia (1998) Summary In diabetic nephropathy, expression of glycosaminoglycan side chains of heparan sulphate proteoglycan in the glomerular basement membrane is reduced proportionally to the degree of proteinuria. We performed a cross-sectional study to evaluate whether non-vascular basement membranes also show a decrease in heparan sulphate side chain staining in patients with diabetic nephropathy. We evaluated the skin basement membrane for extracellular matrix components in the following groups: control subjects (n = 16); patients with Type 1 diabetes and normoalbuminuria (n = 17), microalbuminuria (n = 7), and macroalbuminuria (n = 16); patients with Type 1 diabetes and diabetic nephropathy undergoing renal replacement therapy (n = 13); and non-diabetic patients undergoing renal replacement therapy (n = 21). The following antibodies were used for this immunohistochemical study: monoclonal antibodies against the heparan sulphate side chain (JM403) and core protein (JM72) of the glomerular heparan sulphate proteoglycan; polyclonal antibodies against the core protein (B31); polyclonal antibodies against collagen types I, III, and IV, fibronectin, and laminin; and monoclonal antibodies against the noncollagenous domain of a1(collagen IV) and a3(collagen IV), against transforming growth factor b(2G7), and against advanced glycosylation end products (4G9). Expression of heparan sulphate side chains was reduced in the skin basement membrane of patients with overt diabetic nephropathy, of those with Type 1 diabetes undergoing renal replacement therapy, and those with non-diabetic renal failure. Increased intensity of staining was found for collagen type I and advanced glycosylation end products in patients with diabetic nephropathy. Changes in the extracellular matrix of the skin basement membrane seem to be similar to those in the glomerular basement membrane. These findings support the suggestion that patients with diabetic nephropathy also have altered heparan sulphate and collagen staining in extrarenal basement membranes. However, patients with non-diabetic renal failure also had reduced expression of heparan sulphate in the skin basement membrane, suggesting that this finding is not specific for diabetic nephropathy. [Diabetologia (1998) Keywords Advanced glycosylation end products, albuminuria, basement membrane, collagen, Type 1 diabetes mellitus, diabetic nephropathy, epidermodermal junction basement membrane zone, fibroblasts, heparitin sulphate, skin.Received: 13 November 1997 and in revised form: 10 February 1998Corresponding author: Dr. J. W. van de...

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Section: Discussionsupporting

confidence: 92%

Extracellular matrix in human diabetic nephropathy: reduced expression of heparan sulphate in skin basement membrane

et al. 1998

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“…In the mean time scleroderma-like changes of fingers and hands, [2][3][4], diabetic sclerodactyly [5], digital sclerosis [6] and diabetic thick skin were reported [7,8]. The incidence of skin thlckening and palpable induration of fingers was observed in up to 47% of children with IDDM [6,9], while joint contractures occurred in up to 38% [2,8,9] in depending on the duration of the disease [2,9,10]. Our two patients have suffered from LDDM for 23 and 25 years, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Histologically a hyperplasia of collagen fibers and an increase in collagen and glycosaminoglycans have also been found [13,14] In scleroderma-like lesions of IDDM Hama et al [8] described active fibroblasts and extensive collagen polymerization in the rough endopliismic reticulum of diabetic thick skin. Glucose excess seems to play an important role in diabetic skin.…”

Section: Discussionmentioning

confidence: 99%

Scleroderma‐like lesions in insulin‐dependent diabetes mellitus

Haustein

1999

Acad Dermatol Venereol

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We report on two patients (one female 42 years, one male 47 years) suffering from insulin-dependent diabetes mellitus (IDDM) for more than 20 years. Both patients exhibited sclerodactyly and sclerosis of the hands and lower arms as well as swelling and slight contracture of the distal interphalangeal joints. Interestingly, internal organs were not involved and autoantibodies characteristic for scleroderma were missing. Poor utilization and excess of glucose seem to be responsible for the activation of fibroblasts to produce abundant matrix proteins in the skin. Significant therapeutic improvement of the glucose metabolism was able to improve joint contractures or at least to stop the progression of skin changes in our patients. These skin changes should not be misdiagnosed as systemic sclerosis.

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“…The pathological features were further elucidated by Hanna et al (23). Diabetes patients with thick skin showed active fibroblasts and extensive collagen polymerization in the rough endoplasmic reticulum.…”

Section: Skin Changesmentioning

confidence: 99%

Limited Joint Mobility in Childhood Diabetes: Discovery, Description, and Decline

Rosenbloom

2013

The Journal of Clinical Endocrinology & Metabolism

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Context:The discovery of limited joint mobility (LJM) as the earliest clinically apparent complication of diabetes in children and adolescents nearly 40 years ago provided insights into the mechanism of diabetes complications.Results: LJM, due to periarticular connective tissue thickening and stiffness, varied from single joint involvement bilaterally to obvious hand deformity and limitation of movement of the spine. Thick, tight, waxy skin was apparent with more severe changes; biopsy indicated thickening of the dermis and epidermis with accumulation of collagen and loss of skin appendages. Substantial growth impairment was associated with all levels of LJM. Risk for microvascular disease over a 16-year period was actuarially increased nearly 4-fold by the presence of LJM. Long-term glycemic control influenced the onset of LJM; for every unit increase in average glycated hemoglobin from onset there was a 46% increase in the risk of LJM. Between 1976 -78 and 1998, the prevalence of LJM decreased from 30 to 7%, and the portion with moderate to severe changes decreased from 33 to 14%, with the disappearance of severely affected individuals. Furthermore, growth data markedly improved for those with and without LJM; 30% without LJM and 77% with LJM had been less than the 25th percentile for height, whereas the more contemporary group had 22% without LJM and 33% with LJM in this quartile. Conclusions:The elucidation of LJM as a novel and informative early complication of pediatric diabetes has provided insights into the evolution of the severe long-term complications of diabetes. The marked decrease in the frequency of LJM and statural deficit in children and youth with diabetes in the 20 years between the late 1970s and 1990s can be attributed to improved metabolic control of children and adolescents. The prevalence of LJM in a population may serve as a measure of quality of diabetes control. Discovery In the early 1970s, 3 older teenagers who had long-standing type 1 diabetes (T1D) were referred to the University of Florida pediatric diabetes clinic with striking limitation of extension and flexion of the interphalangeal (IP), metacarpophalangeal (MCP), wrist, elbow, and ankle joints-and in 2 of them, the spine-in association with short stature, thick, tight, waxy skin; delayed sexual maturation; and early microvascular complications (Figure 1) (1). Limitation appeared to be due to periarticular thickening and stiffness; radiography revealed normal joints and confirmed thickening of the periarticular tissues. These observations were followed by the description of milder manifestations in 28% of 229 campers with diabetes aged 7-18 years (2, 3). It is remarkable that these findings, particularly the more advanced changes, would not be described until more than half a century after the rescue and survival of children with T1D by insulin. DescriptionChanges were seen to begin in the MCP and proximal IP (PIP) joints of the little finger and extend radially; and in

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Pathologic features of diabetic thick skin

Cited by 77 publications

References 19 publications

Extracellular matrix in human diabetic nephropathy: reduced expression of heparan sulphate in skin basement membrane

Extracellular matrix in human diabetic nephropathy: reduced expression of heparan sulphate in skin basement membrane

Scleroderma‐like lesions in insulin‐dependent diabetes mellitus

Limited Joint Mobility in Childhood Diabetes: Discovery, Description, and Decline

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