Syndromes of Extreme Insulin Resistance

Severe insulin resistance syndromes

“…However, circulating insulin concentration is dynamically variable, changing over time during the evolution of diabetes. In the research setting, other techniques to assess insulin resistance include the euglycemic clamp, considered the gold standard, and the simpler intravenous glucose tolerance test, which captures up to 90% of the variability as assessed by the clamp technique (10,11). In large-population epidemiology studies, an even simpler test, the homeostasis model assessment of insulin resistance index or the quantitative insulin sensitivity check index, can, despite limitations, evaluate insulin resistance and/or pancreatic responses.…”

“…In large-population epidemiology studies, an even simpler test, the homeostasis model assessment of insulin resistance index or the quantitative insulin sensitivity check index, can, despite limitations, evaluate insulin resistance and/or pancreatic responses. These tests may capture insulin resistance variability (up to 80% as calculated by the clamp technique) adequate for large epidemiology studies (10,12). Importantly, no universally accepted diagnostic biochemical criteria of severe insulin resistance in the clinical setting exist.…”

“…Mandibuloacral dysplasia. Mandibuloacral dysplasia (MAD) is a rare autosomal recessive syndrome identified in approximately 40 cases (10,73). It is characterized by craniofacial, skeletal, and cutaneous abnormalities, including mandibular and clavicular hypoplasia, birdlike face, joint contractures, dental anomalies, acroosteolysis, cutaneous pigmentation, and alopecia.…”

“…Acquired generalized lipodystrophy (AGL), or Lawrence syndrome, is a rare syndrome (approximately 80 patients) with female dominance (10,106) and develops in patients with a negative family history, usually during childhood or adolescence (73,116). Most patients with AGL demonstrate low leptin and markedly reduced adiponectin levels, which may associate with severe insulin resistance and related metabolic complications (117).…”

A new classification of diabetes mellitus – current approaches and challenges

“…The most common genetic risk factor is mutation in the LMNA gene. However, multiple genes have been identified to cause partial and generalized lipodystrophy syndromes (PPARG, BSCL2, AGPAT2) (40).…”