Insulin Resistance Clinical Presentation
- Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD more...
The presentation of insulin resistance depends on the type and stage of the insulin-resistant state. Most patients have 1 or more clinical features of the insulin-resistant state. Many patients do not develop overt diabetes despite extreme insulin resistance. Other patients present with cases of severe hyperglycemia that require large quantities of insulin (>200 units); these people may manifest the classic symptoms of diabetes mellitus, such as polyuria, polydipsia, polyphagia, and weight loss.
Patients may present with the following:
Metabolic syndrome (syndrome X) – Note that a patient with the metabolic syndrome may be asymptomatic in spite of the presence of some, or even most, of the components of insulin resistance syndrome.
Obesity (most common cause of insulin resistance) or history or excessive body weight
Type 2 diabetes mellitus (chronic or acute [during severe decompensation] presentation [ie, the classic symptoms of diabetes])
A diagnosis of IGT or of IFG levels
History of biochemical abnormalities, such as dyslipidemia, detected during routine screening or workup for a cardiovascular disease
History of hypertension
Symptoms of coronary artery disease
Symptoms related to other macrovascular disease (eg, stroke, peripheral vascular disease)
Combination of hyperglycemia and virilization occurs in several syndromes of insulin resistance.
Type A, which affects young women, is characterized by severe hyperinsulinemia, usually present with obesity and features of hyperandrogenism.
Polycystic ovary syndrome (PCOS) - Patients usually present with infertility associated with anovulation; menstrual irregularity, typically chronic; and symptoms related to androgen excess, such as acne, frontal baldness, and hirsutism, but rarely features of virilization.
Type B syndrome - Some patients present with symptoms of hypoglycemia, such as sweating, tremulousness, irritability, and an altered level of consciousness. Hypoglycemia results from interaction between insulinomimetic antibodies and the insulin receptor. Some patients have insulin-binding antibodies directed against insulin, which, upon dissociation, can cause hypoglycemia. Symptoms related to immunologic disease (eg, arthralgia, swollen salivary glands, hair loss) may occur.
Other indicators of insulin-resistant states that may be elicited in the history include the following:
Leprechaunism - Abnormal facial appearance, early life growth retardation
Lipodystrophic states - Insulin resistance, usually during childhood, with progression to diabetes over several years
Werner syndrome - Features of premature aging
Rabson-Mendenhall syndrome - Dental and nail abnormalities, skin lesions
Pineal hypertrophic syndrome - Dental and nail abnormalities, sexual precocity
Alstrom syndrome - Childhood blindness, impaired hearing
Ataxia-telangiectasia - Movement disorder and symptoms related to immune deficiency, such as increased proneness to pulmonary infections
Myotonic dystrophy - Muscle weakness and visual symptoms (cataract)
In addition to elevated blood pressure (hypertension), the physical examination findings may include the features listed below.
Central obesity, not peripherally distributed fat, is a strong marker of insulin resistance syndrome. Waist or waist-to-hip ratio, height, weight, and body mass index (BMI) may indicate insulin resistance syndrome. This notion was supported by an Argentinian study that found waist circumference and BMI to be the anthropometric indexes that best correlate with the presence of insulin resistance.
The Argentinian investigators examined the association between insulin resistance and the following indexes: waist circumference, BMI, waist circumference/height, weight/(sitting height)(2), and waist circumference/sitting height of 625 children, 91 of whom were overweight and another 96 of whom were classified as obese.
Cardiovascular findings associated with insulin resistance may include the following:
Signs of heart disease
Peripheral vascular disease - Abnormalities in pulses and arterial wall
Stigmata of lipid disorders - Suggests the possibility of underlying hyperlipidemia
Premature arcus cornealis - Deposits of cholesterol and phospholipid
Xanthelasma - Indicates that lipid status should be investigated
Lipemia retinalis - Retinal vessels with milky, chylomicron-rich plasma commonly observed in acute, uncontrolled diabetes
Skin xanthomata - Eruptive xanthomas found most commonly on the buttocks
Tendon xanthomata - Usually over the patellar and Achilles tendon
Type A syndrome
Patients with type A syndrome are usually tall and have features of hirsutism and abnormalities of the female reproductive tract related to hyperandrogenism (eg, polycystic ovary syndrome [PCOS]). The patient may have either a thin or a muscular body build. Acral enlargement, a form of pseudoacromegaly, is not uncommon.
Acanthosis nigricans is common in patients with type A syndrome; it causes patchy, velvety brown hyperpigmentation plaques that are usually found in flexural areas, especially in the axillae and the nuchal region. Lesions may be due to the effect of high circulating levels of insulin on insulinlike growth factor (IGF) receptors in the skin. These eruptions have been reported in nearly one tenth of women evaluated for PCOS.
Acanthosis nigricans is found in a wide variety of clinical conditions that are associated with insulin resistance. It is occasionally a marker of malignant neoplasm.
Polycystic ovary syndrome
Patients with PCOS may have masculine habitus, such as coarse or greasy skin and acne, frontal alopecia, breast atrophy, hypertrophy of the clitoris, and obesity; varying degrees of hirsutism or virilization may be present. These manifestations are due to hyperandrogenism.
Type B syndrome (autoantibodies to insulin receptor)
Patients with type B syndrome usually have symptomatic diabetes mellitus, although ketoacidosis is unusual. Patients occasionally present with hypoglycemia. Agonist activity (hypoglycemia) or antagonist effect (insulin resistance) can occur, depending on the site of binding to the insulin receptor.
Other insulin-resistant states
Findings characteristic of other insulin-resistant states include the following:
Leprechaunism - Elfin appearance of the face, hirsutism, lack of subcutaneous fat, and thickened skin
Lipodystrophic states - Variable phenotypic expression (features include a total or partial lack of adipose tissue, metabolic dysfunction, such as abnormal glucose homeostasis, hypertriglyceridemia, and increased metabolic rate.)
Werner syndrome - Cataract, atrophic skin, and early osteopenia
Rabson-Mendenhall syndrome - Dystrophic nails, dental dysplasia, and acanthosis nigricans
Pineal hypertrophic syndrome - Early dentition with malformed teeth, hirsutism, thick nails, and skin dryness
Alstrom syndrome - Nerve deafness, hypogonadism (males), and retinal degeneration that results in blindness
Ataxia telangiectasia - Cerebellar ataxia, oculocutaneous telangiectases, immune deficiency, and increased proneness to pulmonary infections
Myotonic dystrophy - Weakness of limb and cranial muscles, cataract
Potential complications of insulin resistance include the following:
Acute metabolic complications, including severe hyperglycemia and hypoglycemia
Transient ischemic attack
Peripheral vascular disease
Renal disease 
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