. 2022 Jan 31;13(2):337–343. doi: 10.1007/s13340-022-00570-5

Table 2.

Diagnostic criteria for genetic insulin resistance syndrome

Definition: a condition characterized by severe attenuation of insulin action as a result of insulin signaling defects due to genetic causes
A. Major signs 1. Hyperinsulinemia with no apparent cause of insulin resistance such as obesity or other conditions (fasting serum insulin level of > 30 μU/mL, although this value may depend on the course of treatment for diabetes)
B. Potential reference physical findings or clinical features 1. Juvenile-onset glucose intolerance 2. Acanthosis nigricans 3. Hypertrichosis 4. Polycystic ovary 5. Low birth weight 6. Intrauterine growth retardation, distinctive facial features, loss of subcutaneous fat, deformation of teeth and nails, and pineal hyperplasia in the case of Donohue syndrome and Rabson-Mendenhall syndrome 7. Distinctive facial features and Rieger anomaly in the case of PIK3R1 abnormalities (SHORT syndrome)
C. Differential diagnosis 1. Lipoatrophic diabetes
D. Genetic testing 1. Abnormalities of the insulin receptor gene (INSR) or of genes related to insulin receptor signaling (PIK3R1, AKT2, TBC1D4, PRKCE)
E. Diagnostic categories 1. Definite: meeting A, excluding diseases to be differentiated in C, and meeting D 2. Probable: meeting A, excluding diseases to be differentiated in C
F. Severity classification 1. Mild: does not require drug treatment for diabetes despite the presence of insulin resistance 2. Moderate: requires drug treatment for diabetes 3. Severe: requires insulin at ≥ 1 U/kg per day or injection of IGF-1 for treatment of diabetes

Definition: a condition characterized by severe attenuation of insulin action as a result of insulin signaling defects due to genetic causes

A. Major signs

1. Hyperinsulinemia with no apparent cause of insulin resistance such as obesity or other conditions (fasting serum insulin level of > 30 μU/mL, although this value may depend on the course of treatment for diabetes)

B. Potential reference physical findings or clinical features

1. Juvenile-onset glucose intolerance

2. Acanthosis nigricans

3. Hypertrichosis

4. Polycystic ovary

5. Low birth weight

6. Intrauterine growth retardation, distinctive facial features, loss of subcutaneous fat, deformation of teeth and nails, and pineal hyperplasia in the case of Donohue syndrome and Rabson-Mendenhall syndrome

7. Distinctive facial features and Rieger anomaly in the case of PIK3R1 abnormalities (SHORT syndrome)

C. Differential diagnosis

1. Lipoatrophic diabetes

D. Genetic testing

1. Abnormalities of the insulin receptor gene (INSR) or of genes related to insulin receptor signaling (PIK3R1, AKT2, TBC1D4, PRKCE)

E. Diagnostic categories

1. Definite: meeting A, excluding diseases to be differentiated in C, and meeting D

2. Probable: meeting A, excluding diseases to be differentiated in C

F. Severity classification

1. Mild: does not require drug treatment for diabetes despite the presence of insulin resistance

2. Moderate: requires drug treatment for diabetes

3. Severe: requires insulin at ≥ 1 U/kg per day or injection of IGF-1 for treatment of diabetes

If there are no special provisions in the diagnostic criteria, laboratory or clinical findings for any time period may be used for diagnosis. After the initiation of treatment, health care professionals may select the poorest conditions in the previous 6 months under appropriate medical management