Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Diabetes mellitus

Diabetes mellitus is characterizes by impared glucose metabolism due to inadequate insulin secretion or insulin resistance.

Epidemiology

The prevalence of type 1 diabetes remained nearly constant in the past decades. But the frequency of type 2 diabetes is still increasing and it reached 10% in some developed countries. Environmental factors contribute a lot to the development of type 2 diabetes but it is obvious that hereditary factors contribute too. This is especially true for late omplications of diabetes. These complications are an increasing health problem. Diabetic retinopathy is a common reason for aquired blindness and about 50% of patients on dialysis are diabetics.

Test Strategy

The type of diabetes has to be established first. In cases with not secure type 1 diabetes the possibility of MODY-diabetes should be checked. If this is not the case the estimation of molecular genetic risk factors can be considered.

Pathogenesis

Only in some few cases diabetes is caused by a monogenetic autosomal dominant form. In most cases diabetes is the result of a polygenetic disposition along with environmental influences. In these cases only risk factors can be defined by molecular testing.

Symptoms

Polyuria
Polyuria is an early symptom of diabetes mellitus. It is osmotic diuresis that results from poorly controled blood glucose.
Proteinuria
Microalbuminuria is an early symptom of renal damage in diabetes mellitus. In severe diabetic nephropathy proteinuria can reach the nephrotic range.

Systematic

Disturbances of glucose metabolism
Diabetes mellitus
Diabetic nephropathy
ACE
AGT
AKR1B1
Diabetic retinopathy
PON1
VEGFA
Gestational diabetes mellitus
MODY diabetes
MODY1 diabetes
HNF4A
MODY10 diabetes
INS
MODY11 diabetes
BLK
MODY12 diabetes
ABCC8
MODY13 diabetes
KCNJ11
MODY14 diabetes
APPL1
MODY2 diabetes
GCK
MODY3 diabetes
HNF1A
MODY4 diabetes
PDX1
MODY5 diabetes
HNF1B
MODY6 diabetes
NEUROD1
MODY7 diabetes
KLF11
MODY8 diabetes
CEL
MODY9 diabetes
PAX4
Mannose-binding protein deficiency
MBL2
Mitchell-Riley syndrome
RFX6
Partial lipodystrophy
Familial partial lipodystrophy type 2
LMNA
Familial partial lipodystrophy type 3
PPARG
Familial partial lipodystrophy type 4
PLIN1
Familial partial lipodystrophy type 5
CIDEC
Susceptibility to type 1 diabetes 01
PTPN22
TRPM6
Hereditary susceptibility to diabetes
IRS1
MAPK8IP1
PDX1
SH2B1
TBC1D1
Insulin resistance
CIDEC
Diabetes mellitus with insulin resistance and acanthosis nigricans
INSR
ENPP1
IRS1
IRS2
PPARG
MODY diabetes
MODY1 diabetes
HNF4A
MODY10 diabetes
INS
MODY11 diabetes
BLK
MODY12 diabetes
ABCC8
MODY13 diabetes
KCNJ11
MODY14 diabetes
APPL1
MODY2 diabetes
GCK
MODY3 diabetes
HNF1A
MODY4 diabetes
PDX1
MODY5 diabetes
HNF1B
MODY6 diabetes
NEUROD1
MODY7 diabetes
KLF11
MODY8 diabetes
CEL
MODY9 diabetes
PAX4
Mitochondrial diabetes
TRNE
TRNK
TRNL1
TRNS2
Neonatal diabetes mellitus
Leprechaunism
INSR
Mitchell-Riley syndrome
RFX6
Neonatal diabetes mellitus with congenital hypothyroidism
GLIS3
Pancreatogenic diabetes
Mitchell-Riley syndrome
RFX6
Pancreatic agenesis 1
PDX1
Pancreatic agenesis 2
PTF1A
Pancreatic agenesis and congenital heart defects
GATA6
Permanent neonatal diabetes mellitus
ABCC8
Developmental delay, epilepsy, and neonatal diabetes
KCNJ11
GCK
INS
KCNJ11
Phosphoribosylpyrophosphate synthetase superactivity
PRPS1
Wolcott-Rallison syndrome
EIF2AK3
Rabson-Mendenhall syndrome
INSR
Renal cysts and diabetes (RCAD)
HNF1B
Transient neonatal diabetes mellitus 1
HYMAI
PLAGL1
ZFP57
Transient neonatal diabetes mellitus 2
ABCC8
Transient neonatal diabetes mellitus 3
KCNJ11
X-linked immunodysregulation, polyendocrinopathy, and enteropathy
FOXP3
Noninsulin-dependent diabetes mellitus 1
CAPN10
Pancreatogenic diabetes
Mitchell-Riley syndrome
RFX6
Pancreatic agenesis 1
PDX1
Pancreatic agenesis 2
PTF1A
Pancreatic agenesis and congenital heart defects
GATA6
Severe obesity and type 2 diabetes
UCP3
Susceptibility to type 1 diabetes 01
PTPN22
Disturbed regulators of lipid and carbohydrate metabolism
Fasting plasma glucose trait loci
Hyperinsulinemic hypoglycemia
Hypoinsulinemic hypoglycemia

References:

1.

Fajans SS et al. (2001) Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young.

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2.

Horikawa Y et al. (2000) Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.

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3.

Ek J et al. (2001) Studies of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene in relation to insulin sensitivity among glucose tolerant caucasians.

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4.

Orphanet article

Orphanet ID 181371 [^]
5.

Wikipedia article

Wikipedia EN (Diabetes_mellitus) [^]
Update: May 9, 2019