Microvascular Complications of Diabetes, Susceptibility to, 1

Alternative Names

  • Proliferative Retinopathy, Diabetic, Susceptibility to
  • Nonproliferative Retinopathy, Diabetic, Susceptibility to
  • Microvascular Complications of Diabetes, Susceptibility to
  • Microvascular Complications of Diabetes, Protection from
  • Nephropathy, Diabetic, Susceptibility to
  • End-Stage Renal Disease, Diabetic, Susceptibility to
  • Proliferative Retinopathy, Diabetic, Susceptibility to
  • Nonproliferative Retinopathy, Diabetic, Susceptibility to
  • Neuropathy, Diabetic, Susceptibility to
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Diabetes mellitus

OMIM Number

603933

Gene Map Locus

6p12

Description

Diabetic nephropathy is a serious complication of diabetes mellitus affecting 25-40% of patients with type 1 or type 2 diabetes within 20-25 years of the onset of the disease. However, the great majority of patients are those with type 2 diabetes. In this condition, the earliest clinical evidence of nephropathy is the appearance of low but abnormal levels of albumin in the urine. This stage is referred as microalbuminuria and patients with microalbuminuria are referred to as having incipient nephropathy. As the disease progress, patients reach to macroalbuminuria and, finally, end stage renal disease. About one third of patients with diabetic nephropathy progress to end stage renal disease. In addition, patients with diabetic nephropathy generally develop systemic hypertension. Several agents are used to delay the progression of diabetic nephropathy include beta blockers, calcium channel blockers, diuretics, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor antagonists (AIIRAs).

The exact cause of diabetic nephropathy is unknown, but several mechanisms have been postulated. Hyperglycemia increases the expression of transforming growth factor-beta (TGF-beta) in the glomeruli and of matrix proteins specifically stimulated by this cytokine. TGF-beta may contribute to both the cellular hypertrophy and enhanced collagen synthesis observed in persons with diabetic nephropathy. Also, hyperglycemia may activate protein kinase C, which may contribute to renal disease and other vascular complications of diabetes.

Molecular Genetics

Several genes have been shown to have association with diabetic nephropathy. The ACE gene obtained considerable interest because the treatment with ACE-inhibitors prevents and reduces progression of diabetic nephropathy and suppresses hepatic glucose production in type 2 diabetic patients. This gene is characterized by the presence (insertion [I]) or absence (deletion [D]) of a 287 bp Alu repeat sequence within intron 16. It was found that the presence of the DD genotype increased the risk of end-stage renal failure compared to other genotypes.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
603933.G.1.1United Arab Emirates Nephropathy; Type II diabetes mellitusNM_020859.3:c.168+52945C>AOsman et al. 2018 145 patients with di...

Other Reports

Bahrain

Al Arrayed et al. (2004) estimated the incidence of glomerular diseases in Bahrain by using 498 renal biopsies of patients with proteinuria, hematuria, and mild to moderate renal impairment during a period of 13 years (between January 1990 and December 2002) at a tertiary care hospital.Diabetic nephropathy was seen in 31.9% cases.

Al-Hermi et al. (2005) screened diabetic nephropathy (NDP) for all patients with T1DM of more than 5 years, who were diagnosed between years 1985 to 1995 and followed by pediatricians at Salmaniya Medical Complex, Kingdom of Bahrain. Diabetic nephropathy was diagnosed in 10 patients (31%), two with microalbuminuria (incipient nephropathy), and eight with proteinuria (clinical nephropathy). 

[See also: Saudi Arabia > Alsuwaida et al., 2007].

Kuwait

Al Sarraf et al. (2005) assessed the prevalence of diabetic nephropathy among diabetics in three primary health care centers in Kuwait. to be 22.1%, which was relatively low when compared to data from other countries. In the same patient group, the prevalence of microalbuminuria alone was found to be 11.1%. The factors independently associated with diabetic nephropathy were found to be aged between 50 and 60-years, duration of more than 5-years of diabetes, smoking, hypertension, and elevated serum Hb[A1c], HDL cholesterol, and triglyceride levels.

[Al Sarraf, Al Dhubaib AS, Al Banai DJ, El Shazly SK, Medhat K. Prevalence of diabetic nephropathy and associated factors in type 2 diabetes mellitus in primary health health care in kuwait. Bull Alex Fac Med. 2005; 41(4):583-91.]

Al-Zuabi et al. (2005) prospectively studied all newly diagnosed patients with type II DM in two clinics in Kuwait to look for diabetic retinopathy (DR). Of the 92 diabetic patients studied, seven were found to have DR (five of the females; overall average age-51 years). Al-Zuabi et al. (2005) considered the rate of DR (7.6%) to be low.

[See also: Saudi Arabia > Alsuwaida et al., 2007].

Oman

[See: Saudi Arabia > Alsuwaida et al., 2007].

Qatar

Rashed and Aboud (2004) reviewed the cases of 432 patients who received renal transplants (RT) between 1986 and 2002, 238 were Qatari nationals and 194, expatriates of mixed nationalities. Rashed and Aboud (2004) realized that diabetic nephropathy was the most common cause of end-stage renal disease among Qataris.

[See also: Saudi Arabia > Alsuwaida et al., 2007].

Saudi Arabia

Alsuwaida et al. (2007) found that the most common cause of end-stage renal failure in the Arabian Gulf Countries was diabetic nephropathy, closely followed by chronic glomerulonephritis. A total of 563 patients from 18 centers were included in the survey. These patients were undergoing chronic dialysis [hemodialysis (HD) or peritoneal dialysis (PD)] and their ages were 18 years or older. 

Shtir et al. (2016) sought to identify candidate genes with rare SNPs that confer a protective effect against Diabetic Retinopathy (DR).  To do so, 43 diabetics with no DR, 10-years after their diabetes diagnosis were enrolled as cases while the more common phenotype of diabetics with DR were recruited as controls.  Following whole exome sequencing, the combined multivariate and collapsing method helped identify three genes that reached genome-wide significance.  These were NME3, FASTK and LOC728699 (p=1.55x10-10, 3.21x10-8 and 6.23x10-10 respectively).  The alternate alleles in each of these genes was found to be more frequent in cases than controls, thereby suggesting that these SNPs provide a protective effect against DR in diabetes patients (Risk Ratio= 4.61, 3.18 and 3.26 respectively). 

United Arab Emirates

[See: Saudi Arabia > Alsuwaida et al., 2007].

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